Interventional

Cardiology
Board Review
1400+ Questions and Answers
FOURTH EDITION
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Subjects: MESH: Cardiovascular Diseases—diagnosis | Cardiovascular Diseases—therapy |
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 To interventional fellows and colleagues everywhere for their
hard work and dedication to patient care; to my parents for
their infinite patience, love, and understanding; to my nephew
Rohin and to Suchandra, for her unconditional love and
support.
—DEBABRATA MUKHERJEE

To interventional fellows worldwide who will use this text to

expand their knowledge and advance our field … and to my
parents, wife, and sons who’ve taught me more about issues
of the heart than any cardiology text.
—RICHARD A. LANGE

To my parents, my wife, and my daughters—who inspire me to

keep learning—and to my innumerable mentors over the years
who have taught me the importance of guidance.

—SAURAV CHATTERJEE
 PREFACE

Insightful questions have been used throughout the ages as a metric to assess one’s knowledge,
but when coupled with carefully delivered answers, they can become a powerful teaching tool.
This book of questions and annotated answers covering the field of interventional cardiology is
meant to serve as a helpful resource for individuals preparing for the interventional
cardiovascular medicine board exam, as well as for clinicians who wish to perform an in-depth
self-assessment on individual topics or the full spectrum of cardiovascular medicine. The book
has many key features, which we believe will make the reader successful in passing the boards
and improving clinical practice.
Of foremost importance, the areas covered are relevant not only to the day-to-day practice of
interventional cardiology but have also been modified to fit the scope and content of the actual
board examination. The book begins with several chapters dedicated to the anatomy and
physiology associated with interventional cardiology and the pathobiology of atherosclerosis and
inflammation. This corresponds to 11% of the board examination, which targets material in the
basic sciences. The subsequent chapters focus on the essential interventional pharmacotherapy of
antiplatelets, anticoagulants, and other commonly used medications in the catheterization
laboratory and outpatient setting for patients with atherosclerosis. These chapters correspond to
the next 14% of the boards centering on pharmacology. 7% of the board examination is directed
toward imaging; and this book includes specific chapters on radiation safety, catheterization
laboratory equipment and technique, contrast agents, and intravascular ultrasound. The two
largest areas of the examination, each covering ~ 25% of the content, include case selection
management and procedural techniques. The book also now includes questions on catheter-based
management of noncoronary disease with 10% of board questions on this topic. This review
book dedicates several chapters to comprehensively cover these areas as well. Finally, we have
included chapters for the miscellaneous remaining areas covered by the board examination,
including peripheral vascular disease, cerebrovascular and structural heart interventions, ethics,
statistics, and epidemiology, as well as a chapter directed at improving test-taking skills.
Also essential to the quality and appropriateness of the questions and annotated answers is the
expertise of the chapter authors. We are fortunate to have assembled the “who’s who” of
academic interventional cardiology. The contributing authors from leading medical centers
around the world have over 10,000 articles cited in PubMed. We are greatly indebted to these
authors who are recognized both for their interventional expertise and for their teaching skills. In
the end, the true value of this textbook is not only the relevance of the questions and the
outstanding quality of the authors but also the value of the annotated answers. The text includes
more than 1,400 questions and over 400 figures and tables. The corresponding answers have
been appropriately detailed to provide relevant facts, information, and up-to-date journal
citations.
The practice of interventional cardiology is exciting, rewarding, and a privilege each of us
enjoys. Likewise, it has been our privilege to work with the superb contributors, our colleagues
in interventional cardiology, and Ms. Erin E. Hernandez and Ms. Ashley Fischer at Wolters
Kluwer for their editorial assistance. It is our personal hope that you will enjoy this book and that
it will be a valuable resource to you in passing the board examination and providing the highest
quality care possible to your patients.

Debabrata Mukherjee, MD
Richard A. Lange, MD, MBA
Saurav Chatterjee, MD
 CONTRIBUTORS

Mohammad H. Abbasi, MD
Fellow in Cardiovascular Medicine
Department of Cardiovascular Medicine
Cardiology Fellow
Heart, Vascular and Thoracic Institute
Cleveland Clinic Foundation
Cleveland, Ohio
Deepak Acharya, MD, MSPH
Professor of Medicine
Division of Cardiovascular Disease
University of Arizona College of Medicine
Division of Cardiology
Banner University Medical Center
Tucson, Arizona
Shikhar Agarwal, MD, MPH
Associate Interventional Cardiology and Structural Interventions
Department of Cardiology
Geisinger Medical Center
Danville, Pennsylvania
Vikas Aggarwal, MD, MPH
Senior Staff
Interventional Cardiology
Henry Ford Hospital
Detroit, Michigan
Muhammad Ajmal, MD
Adjunct Assistant Professor
Department of Cardiology
University of Arizona College of Medicine
Tucson, Arizona
Interventional Cardiologist
Department of Cardiology
 Great River Health
West Burlington, Iowa
Mahboob Alam, MBBS, FACC, FSCAI
Associate Professor of Medicine
Baylor College of Medicine
Houston, Texas
Mazen Albaghdadi, MD
Medical Director
Cardiac Catheterization Laboratory
Associate Program Director
Cardiology Fellowship
NCH Rooney Heart Institute
Naples, Florida
Salman S. Allana, MD
Assistant Professor
Division of Cardiology
Department of Medicine
University of Texas Southwestern Medical Center
Interventional Cardiologist
Division of Cardiology
Department of Medicine
William P. Clements Jr. University Hospital
Dallas, Texas
Mohammad Alqarqaz, MD, FACC
Interventional Cardiologist
Interventional Cardiology Fellowship Program Director
Clinical Assistant Professor
Henry Ford Hospital
Wayne State University
Detroit, Michigan
Zahid Amin, MD, MSCAI, FAHA
Director
Pediatric and Adult Congenital Cardiac Services
AdventHealth Orlando
Orlando, Florida
Anastasia L. Armbruster, PharmD
Professor
 Department of Pharmacy Practice
St. Louis College of Pharmacy
University of Health Sciences and Pharmacy in St. Louis
Cardiology Clinical Pharmacy Specialist
Department of Pharmacy
Missouri Baptist Medical Center
St. Louis, Missouri
Herbert D. Aronow, MD, MPH
Professor
Department of Medicine
College of Human Medicine, Michigan State University
East Lansing, Michigan
Medical Director
Heart & Vascular Services
Henry Ford Health
Detroit, Michigan
Shilpkumar Arora, MD, MPH
Fellow
Cardiology Division
Department of Medicine
Case Western Reserve University School of Medicine
University Hospitals Cleveland Medical Center
Cleveland, Ohio
Jayant Bagai, MD, MMHC, FACC, FSCAI
Associate Professor
Section of Interventional Cardiology
Division of Cardiovascular Medicine
Department of Medicine
Vanderbilt University Medical Center
Nashville, Tennessee
Sripal Bangalore, MD, MHA
Professor of Medicine
Division of Cardiology
Department of Medicine
NYU Grossman School of Medicine
Professor of Medicine
Director, Invasive and Interventional Cardiology
 Director, Complex Coronary Intervention
Interventional Director, Adult ECMO and MCS Program
Bellevue Hospital Center
Director of Research, Cardiac Catheterization Laboratory
Director, Cardiovascular Outcomes Group
NYU Langone Health
New York, New York
Mir Babar Basir, DO
Director, Acute Mechanical Circulatory Support
Division of Cardiology
Henry Ford Hospital
Detroit, Michigan
Craig J. Beavers, PharmD, FACC, FAHA, FCCP, BCCP, BCPS (AQ-Cardiology), CACP
Adjunct Associate Professor
Department of Pharmacy Practice and Science
University of Kentucky College of Pharmacy
Cardiovascular Clinical Pharmacist
Department of Pharmacy
University of Kentucky Healthcare
Lexington, Kentucky
Agastya D. Belur, MD
Fellow
Division of Cardiovascular Medicine
University of Louisville Hospital
Louisville, Kentucky
Mandeep Bhargava, MD
Staff Physician
Section of Cardiac Electrophysiology and Pacing
Department of Cardiovascular Medicine
Cleveland Clinic Foundation
Cleveland, Ohio
Dario Bongiovanni, MD, PhD
Senior Physician
Internal Medicine and Cardiology
Department of Internal Medicine I and Cardiology
University Hospital Augsburg
Augsburg, Germany
Emmanouil S. Brilakis, MD, PhD
Director, Center for Complex Coronary Interventions
Minneapolis Heart Institute
Minneapolis, Minnesota
Abel Casso, MD
Assistant Professor
Department of Cardiology
Mount Sinai Morningside
New York, New York
Saurav Chatterjee, MD
Director, Interventional Services and Cardiac Cath Lab
New York Community Hospital
Clinical Assistant Professor of Medicine
Zucker School of Medicine – Hofstra University
Hempstead, New York
Joaquin E. Cigarroa, MD, FACC, MSCAI
Director, Knight Cardiovascular Institute
Division Head of Cardiovascular Medicine
Melvin Judkins Professor of Cardiology
Professor of Medicine
Department of Medicine
Oregon Health and Sciences University
Portland, Oregon
Antonio Colombo, MD
Interventional Cardiologist
Department of Cardiology
Humanitas Research Hospital
Rozzano, Italy
Alan Dardik, MD, PhD
Professor of Surgery and Cellular and Molecular Physiology
Vice Chair, Department of Surgery
Surgery and Cellular and Molecular Physiology
Yale School of Medicine
New Haven, Connecticut
Attending Vascular Surgeon
Department of Surgery
VA Connecticut Healthcare Systems
 West Haven, Connecticut
Vishal Dhulipala, MD
Fellow in Interventional Cardiology
Department of Cardiology
Icahn School of Medicine at Mount Sinai
Fellow in Interventional Cardiology
Department of Cardiology
The Mount Sinai Hospital
New York, New York
Abhay Ashok Divekar, MBBS, MD, FSCAI, FPICS
Professor
Department of Pediatrics
University of Texas Southwestern Medical Center
Congenital Interventional Cardiologist
Department of Pediatrics
Children’s Medical Center Dallas
Dallas, Texas
Alok Kumar Dwivedi, PhD
Associate Professor
Division of Biostatistics & Epidemiology
Department of Molecular and Translational Medicine
Paul L. Foster School of Medicine
Texas Tech University Health Sciences Center El Paso
El Paso, Texas
Khady N. Fall, MD, MPH, RDCS
Director of Operations, Intravascular Imaging and Physiology
Columbia Interventional Cardiovascular Care
Program Manager, Intravascular Imaging & Physiology
NewYork-Presbyterian Hospital
New York, New York
Michael E. Farkouh, MD, MSc
Professor and Vice Chair
Department of Medicine
University of Toronto
Toronto, ON, Canada
Sareena George, MD
Endovascular Fellow
 Interventional Cardiology Department
Columbia University Irving Medical Center
New York, New York
Sachin S. Goel, MD, FACC, FSCAI
Assistant Professor
Department of Cardiology
Houston Methodist Academic Institute
Interventional Cardiologist and Medical Director
Structural Heart Interventions
Houston Methodist DeBakey Heart & Vascular Center
Houston Methodist Hospital
Houston, Texas
Sunny Goel, MD, FACC, FSCAI
Assistant Professor
Department of Cardiology
Icahn School of Medicine at Mount Sinai
New York, New York
Director, Structural Heart Disease
Mount Sinai South Nassau Hospital
Oceanside, New York
Timothy D. Henry, MD, FACC, MSCAI
Medical Director
The Carl and Edyth Lindner Center for Research and Education
The Carl and Edyth Lindner Family Distinguished Chair in Clinical Research
Director of Programmatic and Network Development
The Christ Hospital Health Network
Cincinnati, Ohio
Ashequl M. Islam, MD, MPH, FACC, FSCAI
Associate Chief, Division of Cardiology
Director of Strategic Development and Growth
Medical Director, Valvular Heart Disease Program
Baystate Heart and Vascular Program
Program Director, Interventional Cardiology Fellowship
Professor of Medicine and Surgery
Department of Medicine
University of Massachusetts Chan Medical School—Baystate
Associate Chief of Cardiology
 Baystate Health
Springfield, Massachusetts
Farouc A. Jaffer, MD, PhD
Director Coronary Intervention
Associate Professor of Medicine
Cardiology Division
Department of Medicine
Harvard Medical School
Massachusetts General Hospital
Boston, Massachusetts
Ankur Kalra, MD, FACP, FACC, FSCAI
Interventional Cardiologist
Franciscan Health
Lafayette, Indiana
Primary Investigator
Krannert Cardiovascular Research Center
Adjunct Clinical Associate Professor of Medicine
Indiana University School of Medicine
Indianapolis, Indiana
Sanjay Kaul, MD
Attending Cardiologist
Division of Cardiology
Cedars-Sinai Medical Center
Los Angeles, California
Jaikirshan Khatri, MD
Associate Professor
Department of Medicine
Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
Director of Complex Coronary Intervention Cardiovascular Medicine
Cleveland Clinic Foundation
Cleveland, Ohio
Sahil Khera, MD, MPH, FACC, FSCAI
Interventional Director, Structural Heart Program
Department of Medicine (Cardiology)
The Mount Sinai Hospital
New York, New York
Annapoorna S. Kini, MD, MRCP, FACC
 Zena and Michael A. Wiener Professor of Medicine
Department of Cardiology
Icahn School of Medicine at Mount Sinai
Director, Cardiac Catheterization Lab
Department of Cardiology
The Mount Sinai Hospital
New York, New York
Anoop N. Koshy, MBBS, PhD
Interventional & Structural Heart Cardiologist
Department of Cardiology
Austin Hospital
University of Melbourne
Melbourne, VIC, Australia
Ashish Kumar, MD
Resident
Department of Internal Medicine
Cleveland Clinic Akron General
Akron, Ohio
Amartya Kundu, MD, FACC, FSCAI
Interventional Cardiologist
UK Gill Heart & Vascular Institute
Assistant Professor of Medicine
Division of Cardiovascular Medicine
University of Kentucky
Lexington, Kentucky
Antonio Landi, MD
Cardiologist
Department of Cardiology
Cardiocentro Ticino Institute
Ente Ospedaliero Cantonale (EOC)
University of Italian Switzerland (USI)
Lugano, Switzerland
Richard A. Lange, MD, MBA
President and Dean
Paul L. Foster School of Medicine
Texas Tech University Health Sciences
Center El Paso
 El Paso, Texas
Azeem Latib, MD
Professor, Medicine (Cardiology)
Albert Einstein College of Medicine
Section Head (Interventional Cardiology)
Montefiore Einstein Center for Heart and Vascular Care
Montefiore Medical Center
Bronx, New York
Tetz C. Lee, MD, MPH
Resident Physician
Department of Internal Medicine
BronxCare Health System
Bronx, New York
Pier Pasquale Leone, MD, MSc
Cardiology Fellow
Department of Cardiology
Humanitas University
Milan, Italy
Visiting Cardiology Fellow
Department of Medicine, Interventional Cardiology
Montefiore Medical Center
Bronx, New York
Francesco Loizzi, MD
Physician
Attending in Cardiology
SS Annunziata Hospital, ASL TA
Taranto, Italy
Aaqib H. Malik, MD, MPH
Cardiologist
Westchester Medical Center
New York Medical College
Valhalla, New York
Anbukarasi Maran, MD, FSCAI, FACC
Associate Professor of Medicine
Director of Coronary CTO Program
Medical University of South Carolina
Ralph H. Johnson VA Medical Center
 Charleston, South Carolina
Verghese Mathew, MD
Director, Interventional Cardiology
Cardiology/Medicine
Swedish Hospital
NorthShore University HealthSystem
Chicago, Illinois
Roxana Mehran, MD, FACC, FAHA, MSCAI, FESC
Professor of Medicine in Cardiology and Population Health Science and Policy
Mount Sinai Endowed Professor in Cardiovascular Clinical Research and Outcomes
Director of Interventional Cardiovascular Research and Clinical Trials
Director of Women’s Heart and Vascular Center at Mount Sinai Fuster Heart Hospital
Department of Cardiology
Icahn School of Medicine at Mount Sinai
The Zena and Michael A. Wiener Cardiovascular Institute
New York, New York
Ari J. Mintz, DO
Assistant Professor
Department of Medicine
Columbia University Vagelos College of Physicians and Surgeons
Attending in Cardiology
Department of Medicine
Columbia University Irving Medical Center
NewYork-Presbyterian Hospital
New York, New York
Sergio A. Montano, Jr, MD, MA
Faculty
Department of Cardiology
NorthShore University Health System
Evanston, Illinois
George V. Moukarbel, MD
Professor of Medicine
Division of Cardiovascular Medicine
Department of Medicine
The University of Toledo Medical Center
Toledo, Ohio
Debabrata Mukherjee, MD
Chairman and Professor
Department of Internal Medicine
Paul L. Foster School of Medicine
Texas Tech University Health Sciences
Center El Paso
El Paso, Texas
Srihari S. Naidu, MD, FACC, FAHA, FSCAI
Professor of Medicine
Department of Medicine
New York Medical College
Director, Cardiac Catheterization Laboratory and Hypertrophic Cardiomyopathy Center
Department of Cardiology
Westchester Medical Center
Valhalla, New York
Sandeep Nathan, MD, MSc
Associate Professor of Medicine
Medical Director, Cardiac ICU
Co-Director, Cardiac Catheterization Laboratory
Section of Cardiology
University of Chicago Medicine
Chicago, Illinois
Eliano P. Navarese, MD, PhD
Head, Clinical Experimental Cardiology
Associate Professor
Clinical Interventional Cardiology
University of Sassari
Sardinia Island, Italy
Sahil A. Parikh, MD
Associate Professor of Medicine
Division of Cardiology, Department of Medicine
Center for Interventional Vascular Therapy
Columbia University Irving Medical Center
Director of Endovascular Services
Division of Cardiology, Department of Medicine
NewYork-Presbyterian Hospital
New York, New York
Nimai J. Patel, MD
Cardiovascular Disease Fellow
Department of Internal Medicine
McGovern Medical School at UTHealth Houston
Cardiovascular Disease Fellow
Department of Internal Medicine
Memorial Hermann Hospital
Houston, Texas
Timir K. Paul, MD, PhD, MPH, FACC, FSCAI, FAHA
Professor of Medicine
Program Director, Cardiology Fellowship
Clinical Medical Education
University of Tennessee Health Sciences Center at Nashville
Interventional Cardiologist
Saint Thomas Heart Institute
Ascension Saint Thomas Hospital West
Nashville, Tennessee
Ian Persits, DO, MS
Resident
Internal Medicine
Cleveland Clinic Foundation
Cleveland, Ohio
J. R. Exequiel T. Pineda, MD, PhD
Clinical Assistant Professor of Medicine
Division of Cardiology, Department of Medicine
University of Arizona College of Medicine
Banner University Medical Center
Tucson, Arizona
Sonal Pruthi, MD
Assistant Professor of Medicine
Division of Cardiology, Department of Medicine
Columbia University Irving Medical Centre
New York, New York
Rishi Puri, MD, PhD, FRACP
Associate Professor
Department of Cardiovascular Medicine
Staff Interventional Cardiologist
 Heart, Vascular & Thoracic Institute
Medical Director, Angiographic/IVUS Core Laboratories
Cleveland Clinic Lerner College of Case Western Reserve University
Cleveland, Ohio
Arman Qamar, MD, MPH
Interventional Cardiologist
Department of Interventional Cardiology
NorthShore University Health System
Evanston, Illinois
Louai Razzouk, MD, MPH
Professor of Medicine
NYU Grossman School of Medicine
Program Director, Interventional Cardiology Fellowship
Quality Officer, Cardiac Catheterization Lab (Tisch/Kimmel)
Division of Cardiology, Department of Medicine
NYU Langone Health
New York, New York
Frederic S. Resnic, MD, MSc
Professor of Medicine
Tufts University School of Medicine
Boston, Massachusetts
Chairman
Cardiovascular Medicine
Lahey Hospital and Medical Center
Burlington, Massachusetts
Mark Joseph Ricciardi, MD
Director, Interventional Cardiology and Structural Heart Disease
NorthShore Cardiovascular Institute
NorthShore University Health System
Evanston, Illinois
Partha Sardar, MD
Assistant Professor
Department of Medicine
Columbia University Irving Medical Center
Assistant Attending Physician of Medicine/Cardiology
NewYork-Presbyterian Hospital
New York, New York
Yasar Sattar, MD
Assistant Professor
Research Department
Texas Tech University
Odessa, Texas
Interventional Cardiology Fellow
Department of Cardiology
J.W. Ruby Memorial Hospital
Morgantown, West Virginia
Andrea Scotti, MD
Fellow
Cardiovascular Research Foundation
New York, New York
Fellow
Montefiore Einstein Center for Heart and Vascular Care
Montefiore Medical Center
Bronx, New York
Sanjum S. Sethi, MD, MPH
Assistant Professor of Medicine
Division of Cardiology, Department of Medicine
Columbia University Irving Medical Center
Attending Physician
Division of Cardiology
Department of Medicine
NewYork-Presbyterian Hospital
New York, New York
Madhan Shanmugasundaram, MD
Associate Professor of Medicine
Department of Cardiology
University of Arizona College of Medicine
Director of Cardiac Catheterization Lab
Cardiology/Interventional Cardiology
Banner University Medical Center
Tucson, Arizona
Abhishek Sharma, MD, FACC, FSCAI
Assistant Professor of Medicine
Director, Cardiac Catheterization Laboratory & Interventional Cardiology Program
 Director of Structural Heart Disease Program
Department of Medicine
Rutgers New Jersey Medical School
Newark, New Jersey
Timothy F. Simpson, MD, PharmD
Interventional Cardiologist
Legacy Health
Portland, Oregon
Amitoj Singh, MD
Fellow
Cardiovascular Medicine
Lahey Hospital and Medical Center
Burlington, Massachusetts
Daniel J. Snyder, MD
Physician
Division of Cardiology, Department of Medicine
Columbia University Irving Medical Center
NewYork-Presbyterian Hospital
New York, New York
Alessandro Spirito, MD
Fellow
Department of Cardiology
The Zena and Michael A. Wiener Cardiovascular Institute
Icahn School of Medicine at Mount Sinai
New York, New York
Jacqueline Tamis-Holland, MD, FAHA, FACC, FSCAI
Institute Director, Acute Cardiac Care
Interventional Cardiologist
Department of Cardiology
Cleveland Clinic, Heart, Vascular and Thoracic Institute
Cleveland, Ohio
Craig A. Thompson, MD, MMSc
System Director, Hartford Healthcare
Heart and Vascular Institute
Medicine/Cardiology
Hartford Healthcare
Hartford, Connecticut
Marco Valgimigli, MD, PhD
Adjunct Professor
Faculty of Biomedical Sciences
Università della Svizzera Italiana
Lugano, Switzerland
Deputy Chief of Cardiology
Department of Cardiology
Istituto Cardiocentro Ticino
Lugano, Switzerland
Saraschandra Vallabhajosyula, MD, MSc, FACP, FCCP, FCCM, FAHA, FACC, FSCAI
Assistant Professor of Medicine
Division of Cardiology, Department of Medicine
Warren Alpert Medical School of Brown University
Interventional and Critical Care Cardiology
Lifespan Cardiovascular Institute
Providence, Rhode Island
Dennis VanLoozen, MD
Interventional Pediatric Cardiologist
Department of Pediatric Cardiology
Cook Children’s Medical Center
Fort Worth, Texas
Joseph S. Van Tuyl, PharmD, BCCP
Associate Professor
Department of Pharmacy Practice
St. Louis College of Pharmacy
University of Health Sciences and Pharmacy in St. Louis
Cardiovascular Pharmacy Specialist
Department of Pharmacy
SSM Health St. Louis University Hospital
St. Louis, Missouri
Surendranath R. Veeram Reddy, MD
Professor
Department of Pediatrics
University of Texas Southwestern Medical Center
Director, Cardiac Catheterization and Interventional Laboratory
Medical Director, Single Ventricle/Fontan Program
Department of Pediatrics—Heart Center
 Children’s Medical Center
Dallas, Texas
Dhiran Verghese, MD
Chief Cardiology Fellow
Division of Cardiology
Department of Medicine
NCH Rooney Heart Institute
Naples, Florida
Mladen I. Vidovich, MD, FACC, FSCAI
Professor of Medicine
Division of Cardiology, Department of Medicine
University of Illinois at Chicago
Chief, Section of Cardiology
Jesse Brown VA Medical Center
Chicago, Illinois
Chair, VA Cardiology Field Advisory Board
Associate Editor, JACC Case Reports
Pedro Villablanca, MD, MSc
Interventional/Structural Cardiologist
Department of Medicine
Henry Ford Hospital
Detroit, Michigan
Birgit Vogel, MD
Assistant Professor of Medicine
Department of Cardiology
Icahn School of Medicine
Assistant Professor of Medicine
Department of Cardiology
Mount Sinai Fuster Heart Hospital
New York, New York
Sandra A. Weiss, MD, FACC
Attending, Interventional Cardiology
Medical Director, Cardiac ICU
Department of Cardiology
Christiana Care Hospital
Christiana Care Health System
Newark, Delaware
Christopher J. White, MD, MACC, MSCAI, FAHA, FESC, FACP
Professor and Chairman of Medicine and Cardiology
Ochsner Clinical School
University of Queensland
Brisbane, QLD, Australia
Medical Director
Centers of Excellence and Service Lines
Medical Director for Value Based Care
System Chair for Cardiovascular Diseases
Ochsner Health
New Orleans, Louisiana
Lina Ya’Qoub, MD
Fellow
Division of Cardiology
UCSF School of Medicine
San Francisco, California
Laura Young, MD
Clinical Instructor
Department of Interventional Cardiology
Cleveland Clinic Lerner College of Medicine
Associate Staff Physician
Department of Interventional Cardiology
Cleveland Clinic Foundation
Cleveland, Ohio
Firas Zahr, MD
Director, Interventional Cardiology
Lowell Edwards Professor of Cardiology
Knight Cardiovascular Institute
Oregon Health & Science University
Portland, Oregon
Thomas M. Zellers, MD
Professor Pediatrics
Pediatrics (Cardiology)
UT Southwestern Medical School
Pediatric Cardiologist
ACHD Cardiologist
Heart Center
 Children’s Health
Dallas, Texas
Robert S. Zilinyi, MD
Fellow
Division of Cardiology, Department of Medicine
Columbia University Irving Medical Center
NewYork-Presbyterian Hospital
New York, New York
 CONTENTS

Preface
Contributors

1 Vascular Biology and Metabolism

Alan Dardik

2 Anatomy and Physiology of Coronary Arteries

Richard A. Lange and Joaquin E. Cigarroa

3 Radiation Safety, Equipment, and Basic Concepts

Jayant Bagai

4 Inflammation and Arterial Injury

Dhiran Verghese, Mazen Albaghdadi, and Farouc A. Jaffer

5 Antiplatelet, Antithrombotic, and Thrombolytic Agents

Birgit Vogel, Alessandro Spirito, and Roxana Mehran

6 Pharmacogenomics and Drug-Drug Interactions

Craig J. Beavers

7 Antiarrhythmics, Inotropes, Sedatives, and Lipid-Lowering Agents

Anastasia L. Armbruster and Joseph S. Van Tuyl

8 Approach to Chest Pain

Richard A. Lange

9 Vasoactive Agents
Sandra A. Weiss and Sandeep Nathan

10 Guiding Catheter Selection for Coronary Interventions

Annapoorna S. Kini and Vishal Dhulipala

11 Intravascular Contrast Agents

Vikas Aggarwal and Nimai J. Patel
12 Elective Coronary Intervention
Tetz C. Lee, Abel Casso Dominguez, and Jacqueline E. Tamis-Holland

13 Percutaneous Coronary Intervention for Acute Coronary Syndrome

Shilpkumar Arora and Sachin S. Goel

14 Primary, Rescue, and Facilitated Angioplasty

J. R. Exequiel T. Pineda, Muhammad Ajmal, and Deepak Acharya

15 Periprocedural Myocardial Infarction, Embolic Protection, and

Thrombectomy
Timir K. Paul

16 Chronic Total Occlusion

Jaikirshan Khatri and Laura Young

17 Ostial and Bifurcation Lesions

Anbukarasi Maran

18 Long Lesions and Diffuse Disease

Daniel J. Snyder, Robert S. Zilinyi, Sonal Pruthi, Sareena George, Khady N. Fall, Ari J. Mintz, Sanjum S.
Sethi, and Sahil A. Parikh

19 Restenosis and Percutaneous Options

Abhishek Sharma and Sunny Goel

20 Atherectomy, Rotablation, and Laser

Mladen I. Vidovich

21 Stents and Stent Thrombosis

Antonio Landi, Francesco Loizzi, Dario Bongiovanni, and Marco Valgimigli

22 Drug-Eluting Stents and Drug-Coated Balloons

Pier Pasquale Leone, Antonio Colombo, and Azeem Latib

23 Saphenous Vein Graft Percutaneous Intervention

Salman S. Allana and Emmanouil S. Brilakis

24 Vascular Closure Devices

Amitoj Singh, George V. Moukarbel, and Frederic S. Resnic

25 Management of Intraprocedural and Postprocedural Complications

Saurav Chatterjee and Partha Sardar
26 Qualitative and Quantitative Angiography
Madhan Shanmugasundaram

27 Intracoronary Doppler and Pressure Monitoring

Yasar Sattar and Mahboob Alam

28 Intravascular Ultrasound and Optical Coherence Tomography

Dhiran Verghese, Agastya D. Belur, and Saraschandra Vallabhajosyula

29 Approach to Patient With Hemodynamic Compromise

Lina Ya’Qoub and Mir Babar Basir

30 Mechanical Circulatory Support

Ian Persits and Rishi Puri

31 Percutaneous Coronary Intervention in Diabetes and Chronic Kidney

Disease
Louai Razzouk, Eliano P. Navarese, Verghese Mathew, and Michael E. Farkouh

32 Endovascular Interventions for Peripheral Arterial Disease

Herbert D. Aronow, Mohammad Alqaraz, and Pedro Villablanca

33 Cerebrovascular Interventions
Christopher J. White

34 Acute Deep Vein Thrombosis/Pulmonary Embolism Interventions

Debabrata Mukherjee

35 Peripheral Venous Interventions

Debabrata Mukherjee

36 Mitral Valve Procedures

Timothy F. Simpson and Firas Zahr

37 Percutaneous Aortic Valve Procedures

Sergio A. Montano, Arman Qamar, and Mark Joseph Ricciardi

38 Percutaneous Tricuspid and Pulmonary Valve Procedures

Andrea Scotti, Dennis VanLoozen, Zahid Amin, and Azeem Latib

39 Congenital Heart Disease Interventions

Abhay Ashok Divekar, Thomas M. Zellers, and Surendranath R. Veeram Reddy

40 Patent Foramen Ovale and Atrial Septal Defect Closure

 Srihari S. Naidu and Aaqib H. Malik

41 Percutaneous Balloon Pericardiotomy for Pericardial Effusion

Amartya Kundu

42 Percutaneous Alcohol Septal Ablation for Hypertrophic Obstructive

Cardiomyopathy
Anoop N. Koshy and Sahil Khera

43 Left Atrial Appendage Closure

Mohammad H. Abbasi and Mandeep Bhargava

44 Chronic Ischemic Heart Disease

Ashequl M. Islam and Shikhar Agarwal

45 Non–ST-Segment Elevation ACS Guidelines

Craig A. Thompson

46 ACC/AHA Revascularization Guidelines

Sripal Bangalore

47 ST-Elevation Myocardial Infarction: ACC/AHA Guidelines

Mehmet Yildiz, James Jollis, and Timothy D. Henry

48 Ethical Issues and Risks Associated With Catheterization and

Interventional Procedures
Ashish Kumar and Ankur Kalra

49 Statistics Related to Interventional Cardiology Procedures

Alok Kumar Dwivedi and Sanjay Kaul

50 Approach to Interventional Boards and Test-Taking Strategies

Debabrata Mukherjee

Index
 ABBREVIATIONS

3D three-dimensional
AAA abdominal aortic aneurysm
ABI ankle-brachial index
ABIM American Board of Internal Medicine
ACAS Asymptomatic Carotid Atherosclerosis Study
ACC American College of Cardiology
ACCEL ACC extended learning
ACCF American College of Cardiology Foundation
ACE angiotensin-converting enzyme
ACEI angiotensin-converting enzyme inhibitor
ACEP American College of Emergency Physicians
ACGME Accredited Council for Graduate Medical Education
ACLS advanced cardiac life support
ACP American College of Physicians
ACS acute coronary syndrome
ACT activated clotting time
ACT acetylcysteine for contrast-induced nephropathy trial
ACUITY Acute Catheterization and Urgent Intervention Triage Strategy
ACVC acute cardiovascular care
AD advance directive
ADP adenosine diphosphate
ADR antegrade dissection and reentry
AEC automatic exposure control
AF atrial fibrillation
AHA American Heart Association
AI aortic insufficiency
AIVR accelerated idioventricular rhythm

AKI acute kidney injury

AL Amplatz left
ALARA as low as reasonably achievable
ALI acute limb ischemia
ALT alanine transaminase
AMI acute mesenteric ischemia
AMI acute myocardial infarction
AMICS acute myocardial infarction cardiogenic shock
AMISTAD-I Acute Myocardial Infarction Study of Adenosine
ANA antinuclear antibody
ANOCA angina with nonobstructive coronary arteries
AoO2 arterial oxygen content
AP ambulatory phlebectomy
AP anterior-posterior
ApoE apolipoprotein E
aPTT activated partial thromboplastin time
APV average peak velocity
AR Amplatz right
ARC Academic Research Consortium
ARFD acute renal failure requiring dialysis
ARMYDA atorvastatin for reduction of myocardial damage during angioplasty
ARNI angiotensin receptor neprilysin inhibitors
ARR absolute risk reduction
ARTIST Atherectomy for Treatment of Diffuse In-Stent Restenosis Trial
AS aortic stenosis
ASA acetylsalicylic acid
ASA atrial septal aneurysm
ASC agitated saline contrast
ASCVD atherosclerotic cardiovascular disease
ASD atrial septal defect
AST aspartate aminotransferase
AT as-treated

ATHOS-3 Angiotensin II for the Treatment of High-Output Shock

atm atmospheres
ATP adenosine triphosphate

AUC appropriate use criteria

AUC area under the ROC curve
AV aortic valve
AV arterio-venous
AV atrioventricular
AVA aortic valve area
AVF arteriovenous fistula
AVM arteriovenous malformation
AVP Amplatzer vascular plus
AVR aortic valve replacement
BARC Bleeding Academic Research Consortium
BARI bypass versus angioplasty revascularization investigation
BAV balloon aortic valvuloplasty
BCIS British Cardiovascular Intervention Society
BE balloon expandable
BID twice daily
BIMA bilateral internal mammary artery
BMI body mass index
BMS bare metal stent
BNP brain natriuretic peptide
BP blood pressure
BPH benign prostatic hyperplasia
bpm beats per minute
BRAVE-2 Beyond 12 Hours Reperfusion Alternative Evaluation-2
BRS bioresorbable stents
BSA body surface area
BUN blood urea nitrogen
BVS bioresorbable vascular scaffold
CABG coronary artery bypass graft
CAC coronary artery calcium
CAD coronary artery disease
CAM-ICU confusion assessment method for the ICU
cAMP cyclic adenosine monophosphate
CANTOS Canakinumab Antiinflammatory Thrombosis Outcome Study
CARAT Coronary Angioplasty and Rotablator Atherectomy Trial
CART controlled antegrade and retrograde tracking
CAS carotid artery stenting
CathPCI catheterization and percutaneous coronary intervention
CBC complete blood count
CCA common carotid artery
CCD charge-coupled device
CCS Canadian Cardiovascular Society
CCTA coronary computed tomography angiography
CCU coronary care unit
CDPs clinical decision pathways
CDT catheter-directed thrombolysis
CEA carotid endarterectomy
CEC circulating endothelial cells
CES cholesterol embolization syndrome
CFA common femoral artery
cFFR contrast fractional flow reserve
CFR coronary flow reserve
cGMP cyclic guanosine 3′-5′-monophosphate
CHD congenital heart disease
CHEER chest pain evaluation in the emergency room
CHF congestive heart failure
CI cardiac index
CI confidence interval
CICU cardiac intensive care unit

CIN contrast-induced nephropathy

CKD chronic kidney disease
CK-MB creatine kinase-MB
CLIA Clinical Laboratory Improvement Amendments
CLTI chronic limb-threatening ischemia
CMD coronary microvascular dysfunction
CME continuing medical education
CMR cardiovascular magnetic resonance
cMRI cardiac magnetic resonance imaging
CMS Centers for Medicare & Medicaid Services
CN calcific nodule
CNS central nervous system
CO cardiac output
COACT Coronary Angiography After Cardiac Arrest Trial
COAPT Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy
COBEST Covered versus Balloon Expandable Stent Trial

COLCOT Colchicine Cardiovascular Outcomes Trial

COPD chronic obstructive pulmonary disease
COPPS Colchicine for the Prevention of the Postpericardiotomy Syndrome
COR class of recommendation
COVADIS Coronary Vasomotor Disorders International Study
COX cyclooxygenase
CP chest pain
CPC cardiac progenitor cells
CPIC Clinical Pharmacogenetics Implementation Consortium
CPO cardiac power output
CPOT critical-care pain observation tool
CPR cardiopulmonary resuscitation
CrCl creatinine clearance
CREDO clopidogrel for the reduction of events during observation
CREST Carotid Revascularization Endarterectomy versus Stenting
CRP C-reactive protein
CRT-D cardiac resynchronization therapy-defibrillator
CSA cross-sectional area
CSO2 coronary sinus oxygen content
CSS Clinical Syntax score
cTn cardiac troponins
CT computed tomography
CTA computed tomographic angiography
CTEPH chronic thromboembolic pulmonary hypertension
CTFC corrected TIMI frame count
cTn conventional troponin
cTnI cardiac troponin I
cTnT cardiac troponin T
CTO chronic total occlusion
CTPA computed tomography pulmonary angiography
cTRA conventional transradial access
CVA cerebrovascular accident
CVD cardiovascular disease
CVP central venous pressure
CYP cytochromes P450
CYP2C19 cytochrome P450 2C19
D2B door-to-balloon
DAEDALUS Difference in Anti-restenotic Effectiveness of Drug-eluting stent and DCB
AngiopLasty for the occUrrence of coronary in-Stent restenosis
DAP dose area product
DAPT dual antiplatelet therapy
DAT dual antithrombotic therapy
DCA directional coronary atherectomy
DCB drug-coated balloon
DEB drug-eluting balloons
DECISION- Drug-Eluting Stent Implantation versus

CTO Optimal Medical Treatment in Patients with Chronic Total Occlusion

DES drug-eluting stent
DICOM Digital Imaging and Communication in Medicine
DK double kissing
DM diabetes mellitus
DNA deoxyribonucleic acid
DNR do not resuscitate
DOAC direct oral anticoagulant
DOREMI Dobutamine Compared with Milrinone
dPA diastolic pulmonary artery pressure
dPR diastolic pressure ratio
DREAM Dutch Randomized Endovascular Aneurysm Management
DRT device-related thrombus
DSA digital subtraction angiography
DSFab digoxin-specific antibody fragment
d-TGA d-transposition of great arteries
dTRA distal transradial access
DVT deep vein thrombosis
EAST Emory Angioplasty versus Surgery Trial
EBU extra back-up
ECA external carotid artery
ECG electrocardiogram
ECMO extracorporeal membrane oxygenation
ECPR ECMO-assisted CPR
ECST European Carotid Surgery Trial
ED emergency department
EDP end-diastolic pressure
EDRF endothelial-derived relaxing factor
EEM external elastic membrane
EEOC Equal Employment Opportunity Commission
EES everolimus-eluting stent
EF ejection fraction
EHIT endovenous heat-induced thrombosis
EKG electrocardiogram
ELCA excimer laser coronary atherectomy
EMERALD enhanced myocardial efficacy and recovery by aspiration of liberated debris
EMS emergency medical services
eNOS endothelial nitric oxide synthase
EP electrophysiologic
EPC endothelial progenitor cell
EPD embolic protection device
ER emergency room
ERS European Respiratory Society
ESC embryonic stem cells
ESC European Society of Cardiology
ESRD end-stage renal disease
ESSENCE efficacy and safety of subcutaneous enoxaparin in non–q wave coronary events
ESVS European Society for Vascular Surgery
EUCLID Examining Use of Ticagrelor in Peripheral Artery Disease
EURO CTO Evaluate the Utilization of Revascularization or Optimal Medical Therapy for
the Treatment of Chronic Total Coronary Occlusions
EuroSCORE European System for Cardiac Operative Risk Evaluation
EVAR endovascular aneurysm repair
FAUST Femoral Arterial Access with Ultrasound Trial
FDA Food and Drug Administration
FFR fractional flow reserve
FFR-CT fractional flow reserve computed tomography
FIRE FilterWire EX Randomized Evaluation
FMC first medical contact
FMD fibromuscular dysplasia
FOURIER Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects
with Elevated Risk
FOV field of view
FPD flat panel detector
FPS frames per second
FR femoral right
Fr French
FT fluoroscopy time
GC guide catheter
GDMT guideline–directed medical therapy
GERD gastroesophageal reflux disease
GFR glomerular filtration rate
GI gastrointestinal
GIK glucose-insulin-potassium
GLP-1 glucagon-like peptide-1
GP glycoprotein
GPI glycoprotein inhibitor
GRACE Global Registry of Acute Coronary Events
Gy gray
HBR high bleeding risk
HCM hypertrophic cardiomyopathy
HCTZ hydrochlorothiazide
HDL high-density lipoprotein
HF heart failure
HFA Heart Failure Association
HFpEF heart failure with preserved ejection fraction
HIT heparin-induced thrombocytopenia
HIV human immunodeficiency virus
HLA Human leukocyte antigen
HMG-CoA hydroxymethylglutaryl coenzyme A
HOCM high-osmolar contrast media
HOCM hypertrophic obstructive cardiomyopathy
HORIZONS Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial
Infarction
HPR high platelet reactivity
HPS Heart Protection Study
HR hazard ratio
HR heart rate
HRQoL health-related quality-of-life
HS hockey stick
hs-cTn high-sensitivity cardiac troponin
HSR high surgical risk
HTN hypertension
IA intra-arterial
IABP intra-aortic balloon pump
IART intra-atrial reentry tachycardia
iASD iatrogenic ASD

IC intracoronary
ICA internal carotid artery
ICAM intercellular cell adhesion molecule
ICD implantable cardioverter defibrillator
ICE intracardiac echocardiography
ICRP International Commission on Radiological Protection
ICS intermediate coronary stenosis
ICSS International Carotid Stenting Study
ICU intensive care unit
ID identification
IFDVT iliofemoral deep vein thrombosis
iFR instantaneous wave-free ratio
IgE immunoglobulin E
IHD ischemic heart disease
IL interleukin
IM internal mammary
IMA internal mammary artery
IMR index of microcirculatory resistance
INOCA ischemia but no obstructive coronary artery
INR international normalized ratio
IOCM iso-osmolar contrast media
IP infrapopliteal
IPA inhibition of platelet aggregation
iPSC induced pluripotent stem cells
IRA infarct-related artery
IRB Institutional Review Board
IRI ischemia-reperfusion injury
IRP interventional reference point
ISCHEMIA International Study of Comparative Health Effectiveness with Medical and
Invasive Approaches
ISHLT International Society for Heart and Lung Transplantation
ISR in-stent restenosis
ISTH International Society on Thrombosis and Haemostasis
ITT intention-to-treat
IV intravenous
IVBT intravascular brachytherapy
IVC inferior vena cava
IVL intravascular lithotripsy
IVUS Intravascular ultrasound
J joule
JL Judkins left
JR Judkins right
JVD jugular venous distention
JVP Jugular venous pressure
KAP KERMA area product
KDIGO The Kidney Disease: Improving Global Outcomes
KERMA kinetic energy released to matter
keV kiloelectron volt
kg kilogram
kVp kilovoltage peak
LA left atrial
LAA left atrial appendage

LAAC left atrial appendage closure

LAD left anterior descending
LAO left anterior oblique
LAST limited antegrade subintimal tracking
LBBB left bundle branch block
LCA left coronary artery
LCB left coronary bypass or left graft seeker
LCx left circumflex
LDH lactate dehydrogenase
LDL low-density lipoprotein
LDL-C low-density lipoprotein cholesterol
L-FABP -type fatty acid–binding protein
L

LFT liver function tests

LHC left heart catheterization
LIMA left internal mammary artery
LM left main
LMCA left main coronary artery
LMT left main trunk
LMWH low-molecular weight heparin
LOCM low-osmolar contrast media
LOE level of evidence
LSVC left-sided vena cava
LTA light transmission aggregometry
LV left ventricular
LVAD left ventricular assist device
LVEDP left ventricular end-diastolic pressure
LVEDV left ventricular end- diastolic volume
LVEF left ventricular ejection fraction
LVH left ventricular hypertrophy
LVOT left ventricular outflow tract
MA malignant arrhythmias
mA milliampere
MACCE major adverse cardiac and cerebrovascular events
MACE major adverse cardiovascular events
MAE major adverse events
MALEs major adverse limb events
MALS median arcuate ligament syndrome
MAP mean arterial pressure
MATRIX Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic
Implementation of AngioX
MBG myocardial blush grade
MCA middle cerebral artery
MCE myocardial contrast echocardiography
MCP monocyte chemoattractant protein-1
MCS mechanical circulatory support
MDCT multidetector computed tomography
MDR multidrug resistance
MERLIN Middlesbrough Early Revascularization to Limit Infarction
mg milligram
mGy milligray
MI myocardial infarction
MINOCA myocardial infarction with nonobstructive coronary artery disease
MK midkine
mL milliliter
MLA minimal lumen area
MLD minimal lumen diameter
mm millimeter
MMPs metalloproteinases
MONA morphine, oxygen, nitroglycerin, and aspirin
MP multipurpose
MPA main pulmonary artery
MR mitral regurgitation
MRA magnetic resonance angiography
MRI magnetic resonance imaging
MS mitral stenosis
MSA minimum stent area
MSC mesenchymal stem cells
mSv millisievert
mTOR mammalian target of rapamycin
MTS May-Thurner syndrome
MV main vessel
MVA microvascular angina
MVD multivessel disease
MVO2 myocardial oxygen consumption
MVP mitral valve prolapse
NAG N-acetyl-glucosaminidase
NASCET North American Symptomatic Carotid Endarterectomy Trial
NCDR National Cardiovascular Data Registry
NCEP National Cholesterol Education Program
NCRP National Council on Radiation Protection and Measurement
NET neutrophil extracellular traps
NIH neointimal hyperplasia
NNH number needed to harm
NNT number needed to treat
NO nitric oxide
NPC1L1 Niemann-Pick C1-like 1
NPH neutral protamine Hagedorn
NRC Nuclear Regulatory Commission
NSAID nonsteroidal anti-inflammatory drug
NSTE- non–ST-segment elevation acute coronary syndrome
ACS
NSTEMI non–ST-segment elevation myocardial infarction
NSVT nonsustained ventricular tachycardia
NTG nitroglycerine
NTR no-torque right
NYHA New York Heart Association
OA orbital atherectomy
OAT Occluded Artery Trial
OCT optical coherence tomography
OM obtuse marginal
OMT optimal medical therapy
OR odds ratio
OSA obstructive sleep apnea
OSHA Occupational Safety and Health Administration
OTW over-the-wire
PA plasminogen activator
PA pulmonary artery
Pa aortic pressure
PAA popliteal artery aneurysm
PAD peripheral arterial disease
PAF paroxysmal atrial fibrillation

PAH pulmonary arterial hypertension

PAI-1 plasminogen activator inhibitor-1
PAP PA pressure
PAPi pulmonary artery pulsatility index
PAR-1 protease activator receptor-1
PARIS patterns of non-adherence to anti-platelet regimen in stented patients
PASCAL PFO-Associated Stroke Causal Likelihood
PAV percent atheroma volume
PAVM pulmonary arteriovenous malformation
PB plaque burden
PBMA poly n-butyl methacrylate
PCDT pharmacomechanical CDT
PCI percutaneous coronary intervention
PCL poly(e-caprolactone)
PCP primary care provider
PCW pulmonary capillary wedge
PCWP pulmonary capillary wedge pressure
PD pharmacodynamic
Pd distal pressure
PDA patent ductus arteriosus
PDA posterior descending artery
PDS pericardial decompression syndrome
PE pulmonary embolism
PERT pulmonary embolism response team
PES paclitaxel-eluting stents
PET positron emission tomography
PEVA polyethylene-co-vinyl acetate
PFO patent foramen ovale
PFT pulmonary function test
PGA poly(glycolic acid)
PH pulmonary hypertension
PICSS PFO in Cryptogenic Stroke Study
PK pharmacokinetics
PKC protein kinase C
PLATO platelet inhibition and patient outcomes
PLC phospholipase C
PLE protein-losing enteropathy
PLLA poly-L-lactic acid
PLV posterior left ventricular
PM particulate matter
PMBV percutaneous mitral balloon valvuloplasty
PMH past medical history
PMT percutaneous mechanical thrombectomy
po by mouth
POBA plain balloon angioplasty
POSEIDON Prevention of Contrast Renal Injury with Different Hydration Strategies trial
POT proximal optimization technique
PP per-protocol
PPG pullback pressure gradient

PPI proton pump inhibitor

PPM permanent pacemaker
PR prevalence ratio
PR pulmonary regurgitation
PRESTIGE Prevention of Late Stent Thrombosis by an Interdisciplinary Global European
Effort
PRESTO Prevention of Restenosis with Tranilast and Its Outcome
PRIS propofol-related infusion syndrome
prn as needed
PROSPECT Providing Regional Observations to Study Predictors of Events in the Coronary
Tree
PROVE-IT/ Pravastatin or Atorvastatin Evaluation
TIMI 22 and Infection Therapy-Thrombolysis in Myocardial Infarction 22
PROXIMAL Proximal Protection during Saphenous Vein Graft Intervention
PSD peak skin dose
PT prothrombin time
PTA percutaneous transluminal angioplasty
PTCA percutaneous transluminal coronary angioplasty
PTS post thrombotic syndrome
PTSMA percutaneous transluminal septal myocardial ablation
PV peripheral vascular
PVA peripheral vascular angiography
PVC premature ventricular contractions
PVES popliteal vein entrapment syndrome
PVI peripheral vascular intervention
PVL pressure volume loop
PVR pulmonary valve replacement
PVR pulmonary vascular resistance
PY patient-years
QCA quantitative coronary angiography
QFR quantitative flow ratio
QoL quality of life
QTc corrected QT
R Roentgen
RA right atrial
RA rotational atherectomy
RAAS renin-angiotensin-aldosterone system
RAGE receptor for advanced glycation end products
RAID ranolazine implantable cardioverter-defibrillator
rANOVA repeated measures analysis of variance
RAO right anterior oblique
RAS renin-angiotensin-system
RASS Richmond Agitation Sedation Scale
RAUST Radial Artery access with Ultrasound Trial
RBBB right bundle branch block
RBC red blood cell
RC Rutherford Class
RCA right coronary artery
RCB right coronary bypass
rCFR relative coronary flow reserve
RCT randomized controlled trial
RD reference diameter
REDUCE- Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial
IT
RESOLVE Risk prEdiction of Side branch OccLusion in coronary bifurcation intervention
REVERSAL Reversal of Atherosclerosis with Aggressive Lipid Lowering trial
RFR relative flow reserve
RFR resting full-cycle ratio
RHC right heart catheterization
RI remodeling index
RIMA right internal mammary artery
RN registered nurse
ROC receiver operating characteristic
RoPE risk of paradoxical embolism
ROS reactive oxygen species
ROSC return of spontaneous circulation
RP retroperitoneal
rPDA right posterior descending artery
RPH retroperitoneal hematoma
RPM revolutions per minute
RR relative risk
RR respiratory rate
RRISC Reduction in Restenosis in Saphenous Vein Grafts with Cypher Sirolimus-
Eluting Stent trial
RSS residual SYNTAX score
RV right ventricular
RVAD right ventricular assist device
RVD reference vessel diameter
RVEDP right ventricular end-diastolic pressure
RVF right ventricular failure
RVMI right ventricular myocardial infarction
RVOT right ventricular outflow tract
RVOTO right ventricular outflow tract obstruction
RVSP right ventricular systolic pressure
SAFER Saphenous Vein Graft Angioplasty Free of Emboli Randomized
Sao2 oxygen saturation
SAPPHIRE Stenting and Angioplasty with Protection in Patients at High Risk for
Endarterectomy
SARS-CoV- Severe acute respiratory syndrome coronavirus 2
2
SAVED Saphenous VEin De novo
SAVR surgical aortic valve replacement
SB side branch
SBP systolic blood pressure
SCAD spontaneous coronary artery dissection
SCAI Society for Cardiovascular Angiography and Interventions
SCCM Society of Critical Care Medicine
sCD40L soluble CD40 ligand
SCI spinal cord ischemia
SD standard deviation
SE standard error
SES sirolimus-eluting stent
SET supervised exercise therapy
SFA superior femoral artery
SGLT2 sodium-glucose cotransporter 2
SI silent ischemia
SIHD stable ischemic heart disease
siRNA synthesized small interfering RNA
SIRS systemic inflammatory response syndrome

SKS simultaneous kissing stent

SMA superior mesenteric artery
SMC smooth muscle cell
SOAP II Sepsis Occurrence in Acutely Ill Patients II
SOB shortness of breath
sPA systolic pulmonary artery pressure
SPECT single photon emission computed tomography
SPM subintimal plaque modification
SRDL substantial radiation dose limits
SRT septal reduction therapy
SS spot stenting
ST stent thrombosis
STAR subintimal tracking and reentry
STEMI ST-segment elevation myocardial infarction
STR ST-segment resolution
STRATAS Study to Determine Rotablator and Transluminal Angioplasty Strategy
STRAW subintimal transcatheter withdrawal
STS Society of Thoracic Surgeons
Sv sievert
SVC superior vena cava
SVG saphenous vein graft
SVO2 mixed venous saturation
SVR systemic vascular resistance
SYC syncope
T1DM type 1 diabetes mellitus
T2DM type 2 diabetes mellitus
TAA thoracic aortic aneurysm
TAP T and small protrusion
TAPAS Thrombus Aspiration during Percutaneous Coronary Intervention in Acute
Myocardial Infarction Study
TAPSE tricuspid annular plane systolic excursion
TASC TransAtlantic Inter-Society Consensus
TASTE Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia
TAV total atheroma volume
TAVI transcatheter aortic valve implantation
TAVR transcatheter aortic valve replacement
TBI toe-brachial index
TCAR transcarotid artery revascularization
TCFA thin-cap fibroatheroma
TCL transcutaneous laser
TCR T-cell receptor
TdP torsades de pointes
TEE transesophageal echocardiogram
TEER transcatheter edge-to-edge repair
TF transfemoral
TFC TIMI frame count
TFPI tissue factor pathway inhibitor
TG triglycerides
ThCFA thick-cap fibroatheroma
THV transcatheter heart valves
TIA transient ischemic attack
TID transient ischemic dilation
TIMI thrombolysis in myocardial infarction
TLR target lesion revascularization
TMP TIMI myocardial perfusion
TMPG TIMI myocardial perfusion grade
TNF tumor necrosis factor
TnI troponin I
TnT troponin T
TOF tetralogy of Fallot
TOPAS Thrombolysis or Peripheral Arterial Surgery
TOSCA Total Occlusion Study of Canada
tPA tissue plasminogen activator
TPG transpulmonary gradient
TPVR transcatheter pulmonary valve replacement
TR tricuspid regurgitation
TS traditional stenting
TSH thyroid-stimulating hormone
TTE transthoracic echocardiogram
TV tricuspid valve
TVD triple vessel disease
TVP transvenous pacing
TVR target vessel revascularization
Tx Thromboxane
UA unstable angina
UFH unfractionated heparin
ULN upper limit of normal
UNOS United Network for Organ Sharing
URL upper reference limit
USAT ultrasound-assisted catheter-directed thrombolysis
USPSTF United States Preventive Services Task Force
VA-ECMO venoarterial extracorporeal membrane oxygenation
VASP vasodilator-stimulated phosphoprotein
VCAM vascular cell adhesion molecule
VCD vascular closure device
VE vascular endothelial
VF ventricular fibrillation
VH virtual histology
VKA vitamin K antagonists
VKOR vitamin K epoxide reductase
VL Voda left
VLDL very-low-density lipoprotein
VLST very late stent thrombosis
VPB ventricular premature beat
VSD ventricular septal defect
VSR ventricular septal rupture
VV-ECMO venovenous extracorporeal membrane oxygenation
WBC white blood cell
WFP wave-free period
WPB Weibel-Palade bodies
ZES zotarolimus-eluting stent
1 Vascular Biology and Metabolism

Alan Dardik

QUESTIONS

1.1 All of the following molecular pathways determine arterial or venous identity, EXCEPT:
A. Ephrin B2-EphB4
B. Notch 3-Dll4
C. Sonic hedgehog-VEGF A
D. COUP-TFII
E. Prox1

1.2 All of the following are a component of the shear stress receptor, EXCEPT:
A. PECAM-1
B. VE-cadherin
C. Akt1
D. VEGFR2
E. None of the above

1.3 All of the following are physiologic functions of elastin, EXCEPT:

A. Closure of the ductus arteriosus
B. Attracting T cells and macrophages to the injured artery
C. Inhibiting smooth muscle cell proliferation
D. Inhibiting smooth muscle cell migration
E. Inhibiting restenosis

1.4 All of the following are associated with plaque deposition in arteries, EXCEPT:
A. Arterial bifurcations
 B. Low shear stress
C. High shear stress
D. Oscillatory shear stress
E. Intimal thickening

1.5 Which of the following describes arterial remodeling to maintain constant flow despite
increases in atherosclerotic mass?
A. The Reynolds number
B. Poiseuille law
C. Glagov phenomenon
D. Laplace law
E. None of the above

1.6 All of the following cell types are considered candidates for cardiac regeneration,
EXCEPT:
A. Cardiac progenitor cells (CPC)
B. Mesenchymal stem cells (MSC)
C. Embryonic stem cells (ESC)
D. Reprogrammed fibroblasts
E. None of the above

1.7 Weibel-Palade bodies (WPB):

A. Were described in human cardiac biopsy specimens
B. Are found in lymphatic vessels
C. Contain P-selectin and von Willebrand factor
D. Are responsible for endocytosis of specific plasma proteins
E. Are found in lymphatic vessels and contain P-selectin and von Willebrand factor

1.8 Platelet margination in arterial vessels is associated with:

A. Low shear stress
B. High-velocity blood flow
C. Interactions with red blood cells
D. None of the above
E. All of the above

1.9 All of the following statements are true regarding fibrinolytic therapy, EXCEPT the
following:
 A. All available thrombolytic agents are serine proteases that cleave plasminogen into
plasmin
B. Fibrinolytic therapy is frequently performed by administration of tissue plasminogen
activator (tPA) that is used to convert prothrombin to its active form thrombin
C. Streptokinase is the most widely used fibrinolytic agent worldwide
D. Ischemic stroke within 3 months is an absolute contraindication for thrombolytic
treatment
E. It is used to treat ST-segment elevation myocardial infarction (MI) in many places
where acute percutaneous coronary intervention (PCI) is not an option

1.10 Heparin is thought to be useful in the treatment of patients with COVID-19 and elevated
D-dimer levels who do not have an increased risk of bleeding due to its actions that
include:
A. Inhibition of the formation of thrombosis
B. Inhibition of viral entry
C. Inhibition of cytokine storm
D. All of the above
E. None of the above

1.11 All of the following are appropriate treatments for type 2 heparin-induced
thrombocytopenia (HIT), EXCEPT:
A. Direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban)
B. Direct thrombin inhibitors (argatroban, bivalirudin, desirudin)
C. Indirect factor Xa inhibitors (danaparoid, fondaparinux)
D. Vitamin K antagonists (warfarin)
E. None of the above

1.12 Many patients with acute myocardial infarction (AMI) complicated by cardiac arrest or
cardiogenic shock receive PCI and dual antiplatelet therapy. Compared with clopidogrel,
those treated with a newer P2Y12 receptor inhibitor (ticagrelor or prasugrel) experience
a lower rate(s) of:
A. Major bleeding
B. Stent thrombosis
C. Early and 1-year mortality
D. All of the above
E. None of the above

1.13 In patients undergoing PCI, use of a bioresorbable stent in place of a drug-eluting stent is
associated with an increased risk of:
 A. Scaffold thrombosis
B. Scaffold restenosis
C. Target vessel failure
D. All of the above
E. None of the above

1.14 Coronary stent thrombosis in patients with COVID-19 may be due to

A. Increased risk of platelet aggregation and thrombus formation
B. COVID-19 cytokine storm
C. Increased risk of local microthromboembolism
D. All of the above
E. None of the above

1.15 Inflammation and redox stress are major contributing factors that increase the risk of
stent-related complications following PCI. Endothelial dysfunction following PCI may
be the result of:
A. Endothelial nitric oxide synthase (eNOS) uncoupling, with production of superoxide
rather than nitric oxide (NO)
B. Reduced bioavailability of NO due to its interaction with superoxide to form
peroxynitrite (ONOO−)
C. Increased reactive oxygen species—such as hydrogen peroxide, ONOO−, and lipid
peroxides—as a result of reduced glutathione peroxidase activity
D. All of the above
E. None of the above

1.16 Which of these factors is most likely responsible for the variability of efficacy noted in
patients taking low-dose aspirin to prevent arterial thrombotic events?
A. Genetic variation in metabolism
B. Insufficient acetylation of the entire platelet cyclooxygenase (COX) pool
C. Missed doses
D. None of the above
E. All of the above

1.17 In the patient with an AMI, ischemia-reperfusion injury (IRI) to the myocardium
following successful thrombolytic therapy or primary PCI can induce further myocyte
death. Which of the following adjuncts to PCI has been shown to limit the extent of IRI
and improve survival?
A. Therapeutic hypothermia
B. Therapeutic hyperoxemia
 C. Adenosine
D. Atorvastatin
E. None of the above

1.18 All of the following are considered nonclassical risk factors that contribute to the
development of cardiovascular inflammation, EXCEPT:
A. Sedentary lifestyle
B. Poor sleep quality
C. Noise and air pollution
D. Smoking
E. Psychosocial stress

1.19 Which of the following is NOT a mechanism of in-stent restenosis?

A. Elastic recoil
B. Negative remodeling
C. Intimal hyperplasia
D. Accumulation of foam cells
E. None of the above

1.20 Mammalian target of rapamycin (mTOR) inhibitors prevent restenosis by:

A. Associating with the immunophilin FK506 binding protein 12 (FKBP12)
B. Interfering with the phosphoinositide-3-kinase/Akt (PI3K/Akt) pathway
C. Arresting the cell cycle in the G1-S phase
D. Hindering vascular smooth muscle cell (SMC) proliferation, migration, and
dedifferentiation
E. All of the above

1.21 Balloon angioplasty does NOT cause:

A. Adventitial stretching
B. Dissection
C. Plaque fracture
D. Plaque apoptosis
E. Medial necrosis

1.22 Circulating endothelial cells (CEC):

A. Are a new potential biomarker for AMI
B. Have high circulating numbers in normal people
 C. Decrease in the serum with plaque rupture
D. Have no correlation with angiogenesis

1.23 Microvascular dysfunction secondary to diabetes:

A. Is different among patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM)
B. Occurs as a result of hyperglycemia-induced oxidative stress that leads to inflammation
and endothelial dysfunction
C. Increases NO bioavailability
D. Has no treatment

1.24 Hypertension causes damage to cardiac myocytes by all of the mechanisms, EXCEPT:
A. Myocardial hypertrophy due to increased load on the myocardium
B. Increased apoptosis due to the hyperactivity of the sympathoadrenal system or
increased load on the myocardium
C. Damage to cardiac myocytes’ cell membranes, which leads to an increase in membrane
permeability and release of cardiac troponins (CT)
D. eNOS resistance to activation
E. Activation of the renin-angiotensin-aldosterone system (RAAS)

1.25 Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower lipids via which of
the following mechanisms?
A. Inhibition of low-density lipoprotein (LDL) receptor degradation
B. Suppression of liver cholesterol synthesis via inhibition of 3-hydroxy-3-methylglutaryl-
CoA (HMG-CoA) reductase
C. Inhibition of cholesterol absorption
D. Upregulation of eNOS
E. All of the above

1.26 Which of the following is NOT a mechanism of action of PCSK9?

A. LDL receptor degradation
B. MHC-I receptor degradation
C. Reduced LDL receptor-T-cell receptor (TCR) cell surface complex in CD8+ T cells
D. Activation of the TLR4/NF-κB pathway
E. None of the above

1.27 Patients with homozygous familial hypercholesterolemia have defective LDL receptors
that lead to:
A. Increased plasma LDL at birth
 B. Heart attacks in early childhood
C. Increased HMG-CoA reductase activity
D. Defective receptor-mediated endocytosis
E. All of the above

1.28 The effects of statin drugs include:

A. Enhanced NO production, lowering blood pressure
B. Reduced IRI, reducing myocardial damage
C. Transformation of naive T lymphocytes from proinflammatory helper Th1 cells to anti-
inflammatory Th2 cells, protecting against immune injury
D. Mobilization of endothelial progenitor cells (EPC) from the bone marrow, and their
homing to ischemic areas, enhancing angiogenesis
E. All of the above

1.29 Which of the following statements is FALSE regarding paclitaxel?

A. Paclitaxel is an antiproliferative agent that stabilizes intracellular microtubules
B. Paclitaxel prevents mitosis in the G0-G1 and G2-M phases of the cell cycle
C. Paclitaxel is used to treat breast and ovarian cancer
D. Paclitaxel-covered stents are safe and effective to treat coronary artery disease
E. Paclitaxel-covered stents are the most commonly used stent currently used to treat
coronary artery disease

1.30 Anti-inflammatory therapy with canakinumab, a therapeutic monoclonal antibody

targeting interleukin-1β, in patients with previous MI and a high-sensitivity C-reactive
protein level, results in:
A. Increased serum high-sensitivity C-reactive protein levels
B. Reduced serum lipid levels
C. Reduced nonfatal MI, nonfatal stroke, or cardiovascular death
D. Reduced fatal infections
E. Reduced all-cause mortality

1.31 The NLRP3 inflammasome is activated by:

A. Extracellular adenosine triphosphate
B. Cholesterol crystals
C. Saturated fatty acids
D. Glucose
E. All of the above
1.32 Mechanisms by which sodium-glucose cotransporter 2 (SGLT2) inhibitors improve
outcome in heart failure with preserved ejection fraction (HFpEF) include:
A. Diuretic and natriuretic effects that improve volume status
B. Reducing cardiac glucose oxidation and increasing utilization of ketone bodies and
fatty acids to improve myocardial metabolism
C. Reducing interstitial myocardial fibrosis and decreasing cardiomyocytes’ stiffness to
improve left ventricular diastolic function
D. Promoting glucosuria and thus reducing serum glucose and lowering blood pressure
E. All of the above

1.33 Which of these factors is NOT a mechanism for clopidogrel resistance?

A. Increased function of CYP2C19
B. Concomitant treatment with proton pump inhibitors (PPIs)
C. Poor clopidogrel absorption
D. P2Y12 receptor polymorphisms

ANSWERS AND EXPLANATIONS

1.1 Answer E. Genetic determination of arteries and veins during embryogenesis is regulated
by the Ephrin-Eph system with Ephrin B2 determining arterial identity and EphB4
determining venous identity (Wang HU, Chen ZF, Anderson DJ. Molecular distinction
and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2
and its receptor Eph-B4. Cell. 1998;93(5):741-753. PMID: 9630219); associated Notch-
Dll4 (Lawson ND, Scheer N, Pham VN, et al. Notch signaling is required for arterial-
venous differentiation during embryonic vascular development. Development.
2001;128(19):3675-3683. PMID: 11585794) and sonic hedgehog-VEGF (Lawson ND,
Vogel AM, Weinstein BM. Sonic hedgehog and vascular endothelial growth factor act
upstream of the Notch pathway during arterial endothelial differentiation. Dev Cell.
2002;3(1):127-136. PMID: 12110173) determine arterial identity, and COUP-TFII (You
LR, Lin FJ, Lee CT, DeMayo FJ, Tsai MJ, Tsai SY. Suppression of Notch signalling by
the COUP-TFII transcription factor regulates vein identity. Nature. 2005;435(7038):98-
104. PMID: 15875024) determines venous identity. Lymphatic identity is determined by
Prox1 (Wigle JT, Oliver G. Prox1 function is required for the development of the murine
lymphatic system. Cell. 1999;98(6):769-778. PMID: 10499794).

1.2 Answer C. Fluid shear stress regulates vascular remodeling, cardiac development, and
atherogenesis; a mechanosensory complex comprising PECAM-1 (which directly
transmits mechanical force), vascular endothelial (VE) cell cadherin (which functions as
an adaptor), and VEGFR2 (which activates phosphatidylinositol-3-OH kinase) confer
responsiveness to flow (Tzima E, Irani-Tehrani M, Kiosses WB, et al. A
mechanosensory complex that mediates the endothelial cell response to fluid shear
 stress. Nature. 2005;437(7057):426-431. PMID: 16163360).

1.3 Answer B.Elastin is the dominant extracellular matrix protein deposited in the arterial wall
and can contribute up to 50% of its dry weight. Elastin is synthesized as tropoelastin
monomers and crosslinked to become organized into elastin polymers that form
concentric rings of elastic lamellae around the arterial lumen, alternating with rings of
smooth muscle cells, to provide arterial compliance. Loss of elastin is associated with
subendothelial proliferation and accumulation of vascular smooth muscle cells. Elastin
signals via a non-integrin, heterotrimeric G-protein-coupled pathway. Elastin is
associated with regulation of smooth muscle cells, not inflammatory cells such as T cells
or macrophages (Karnik SK, Brooke BS, Bayes-Genis A, et al. A critical role for elastin
signaling in vascular morphogenesis and disease. Development. 2003;130(2):411-423.
PMID: 12466207).

1.4 Answer C.Human autopsy studies showed the association of arterial bifurcations with lipid
deposition; these findings led to research showing that intimal thickening is associated
with nonlaminar hemodynamics (Zarins CK, Giddens DP, Bharadvaj BK, Sottiurai VS,
Mabon RF, Glagov S. Carotid bifurcation atherosclerosis. Quantitative correlation of
plaque localization with flow velocity profiles and wall shear stress. Circ Res.
1983;53(4):502-514. PMID: 6627609). Both low shear stress and oscillatory shear stress
enhance plaque formation (Ku DN, Giddens DP, Zarins CK, Glagov S. Pulsatile flow
and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque
location and low oscillating shear stress. Arteriosclerosis. 1985;5(3):293-302. PMID:
3994585), whereas high shear stress is atheroprotective. Low shear stress also
accelerates neointimal hyperplasia in vein grafts (Meyerson SL, Skelly CL, Curi MA, et
al. The effects of extremely low shear stress on cellular proliferation and neointimal
thickening in the failing bypass graft [Erratum in: J Vasc Surg. 2001;34(4):580]. J Vasc
Surg. 2001;34(1):90-97. PMID: 11436080).

1.5 Answer C.In 1987, Glagov reported the surprising finding that atherosclerotic arterial
lumen narrowing is not simply the result of enlargement of atherosclerotic lesions, but
the lumen area of atherosclerotic human coronaries remained constant until stenosis
exceeded 40%; at this point lumen diameter decreased, resulting in a restriction in flow
(Korshunov VA, Schwartz SM, Berk BC. Vascular remodeling: hemodynamic and
biochemical mechanisms underlying Glagov’s phenomenon. Arterioscler Thromb Vasc
Biol. 2007;27(8):1722-1728. PMID: 17541029). This phenomenon is known as adaptive
enlargement of arteries in response to plaque formation. The Reynolds number predicts
the occurrence of turbulent flow (NR = ρVd/η) based on fluid density (ρ, kg/L), flow
velocity (V, m/s), vessel diameter (d, cm), and blood viscosity (η, g/cm/s); values of NR
<2,000 predict laminar flow, whereas values of NR >3,000 predict turbulence. Poiseuille
law defines shear stress, the frictional force exerted by blood on the arterial wall, as τ =
4ηQ/πrlumen3, where η is blood viscosity (g/cm/s), Q (cm3/s) is volume blood flow, and
rlumen (cm) is lumen radius. Laplace law (T = Pr) postulates that tension (T) is
proportional to pressure (P) and rlumen.
1.6 Answer C. Undifferentiated cells, such as ESC and induced pluripotent stem cells (iPSC),
are not considered appropriate candidate cells for cardiac regeneration as they may give
rise to teratomas and may require immunosuppression. Furthermore, ESC are associated
with ethical questions due to their derivation from preimplantation embryos.
Differentiated cell types are thought to be superior to undifferentiated cell types for
cardiac regeneration, and several of these cells have entered clinical trials. CPC express
the receptor tyrosine kinase c-Kit and may induce regeneration of myocardial infarcts
and contribute to the formation of new myocardium and vessels. Bone marrow–derived
MSC have shown decreased arrhythmias and an improvement in some indices of
contractile function within 10 days of MI when used for cardiac regeneration.
Transdifferentiation of fibroblasts into cardiomyocytes using the Yamanaka factors (Oct-
4, Sox2, Klf4, and c-Myc) is an area of active research that is thought to have potential
for human therapy (Laflamme MA, Murry CE. Heart regeneration. Nature.
2011;473(7347):326-335. PMID: 21593865).

1.7 Answer C. WPB are small storage granules located in endothelial cells comprising the
intima of the heart and blood vessels. These bodies function to store two principal
molecules, P-selectin and von Willebrand factor. WPB allow VE cells to respond rapidly
to environmental changes by the secretion of factors that control hemostasis and
inflammation. In response to local vascular injury, endothelial cells rapidly change their
surface properties from nonadhesive (supporting unrestricted blood flow) to adhesive
(capturing circulating blood cells) by the secretion of major adhesion receptors for
platelets (von Willebrand factor) and leukocytes (P-selectin). WPB were discovered in
1964 via electron microscopic analyses of rat and human pulmonary arteries. WPB are
found in arteries, capillaries, veins, and the endocardium, but notably not in the
lymphatic vessels (Naß J, Terglane J, Gerke V. Weibel Palade bodies: unique secretory
organelles of endothelial cells that control blood vessel homeostasis. Front Cell Dev
Biol. 2021;9:813995. PMID: 34977047).

1.8 Answer C. The mechanical properties of blood cells create a segmented flowing fluid
whereby red blood cells concentrate in the vessel center and platelets marginate to the
near-wall region; collisions between the red blood cells and platelets help push the
platelets toward the vessel wall. Shear stress is highest near the wall of the blood vessel
and lowest in the center; conversely, velocity is maximal in the vessel center and
virtually zero near the wall (Lin J, Sorrells MG, Lam WA, Neeves KB. Physical forces
regulating hemostasis and thrombosis: vessels, cells, and molecules in illustrated review.
Res Pract Thromb Haemost. 2021;5(5):e12548. PMID: 34278188).

1.9 Answer B.During thrombosis, activated platelets convert circulating prothrombin to its
active form thrombin, which then converts fibrinogen into fibrin with the eventual
formation of a fibrin matrix. Endogenously or exogenously administered tPA converts
plasminogen into plasmin to initiate fibrinolysis. Streptokinase is the most widely used
fibrinolytic agent worldwide due to its relatively low cost with reasonable efficacy and
safety. Absolute contraindications to thrombolytic treatment include recent intracranial
hemorrhage, recent intracranial or spinal surgery, ischemic stroke within 3 months,
 possible aortic dissection, severe uncontrolled hypertension, and bleeding diathesis
(excluding menses). Although primary PCI is the preferred treatment for most patients
with acute ST-segment elevation MI, thrombolytic therapy may be recommended if
timely access to PCI is not available (Baig MU, Bodle J. Thrombolytic therapy. In:
StatPearls [Internet]. StatPearls Publishing; 2023. Updated September 8, 2022.
https://www.ncbi.nlm.nih.gov/books/NBK557411/).

1.10 Answer D. Clinical data suggest that unfractionated heparin or low-molecular-weight

heparin may decrease mortality in patients with COVID-19 with sepsis-induced
hypercoagulation through its anticoagulant, antiviral, and anti-inflammatory activities
(Wang P, Chi L, Zhang Z, Zhao H, Zhang F, Linhardt RJ. Heparin: an old drug for new
clinical applications. Carbohydr Polym. 2022;295:119818. PMID: 35989029).

1.11 Answer D.There are two types of HIT. Type-1 is a nonimmune disorder that results from
the direct effect of heparin on platelet activation: platelet count normalizes without the
need to discontinue heparin. Type-2 HIT is a drug-induced, immune-mediated
thrombocytopenia that typically occurs 4-10 days after exposure to heparin with the
development of HIT II antibodies (immunoglobulin G [IgG]) and creates a considerably
increased thrombosis risk for stroke and cardiac arrest. With type-2 HIT, all forms of
heparin should be immediately discontinued, heparin-coated catheters should be
immediately removed, and a non-heparin anticoagulant should be started to prevent
thrombosis. Vitamin K antagonists—such as warfarin—should be avoided in patients
with HIT until platelet count recovery because they cause depletion of protein C, which
may lead to venous limb gangrene; DOAC, direct thrombin inhibitors, and factor Xa
inhibitors are all guideline-recommended therapies for type-2 HIT (Fathi M. Heparin-
induced thrombocytopenia (HIT): identification and treatment pathways. Glob Cardiol
Sci Pract. 2018;2018(2):15. PMID: 30083545).

1.12 Answer C.Although newer P2Y12 inhibitors, such as ticagrelor or prasugrel, in these
patients are associated with lower rates of early and 1-year mortality than clopidogrel,
data on major bleeding and stent thrombosis are inconclusive. Newer P2Y12 inhibitors
have improved efficacy compared with clopidogrel alone; this is attributed to faster onset
of action, higher bioavailability, and predictable patient responsiveness, all of which
increase efficacy. Patients with AMI complicated by cardiac arrest or cardiogenic shock
have poor gastrointestinal absorption, splanchnic vasoconstriction from use of vasoactive
agents, hepatic and renal injury resulting in unpredictable bioavailability and
elimination, and use of cardiac and noncardiac organ support devices that influence the
volume of distribution (Patlolla SH, Kandlakunta H, Kuchkuntla AR, et al. Newer P2Y12
inhibitors vs clopidogrel in acute myocardial infarction with cardiac arrest or cardiogenic
shock: a systematic review and meta-analysis. Mayo Clin Proc. 2022;97(6):1074-1085.
PMID: 35662424).

1.13 Answer D.Bioresorbable stents can restore vessel integrity without leaving a metallic
structure in the vessel. However, a higher-than-expected rate of target vessel failure in
the ABSORB trials, mainly driven by a high rate of scaffold thrombosis and scaffold
 restenosis, has reduced enthusiasm for these stents. Newer generation bioresorbable
stents—with reduced strut thickness, improved mechanical structure, faster resorption
times, and better crossing profiles—may allow better clinical results in the future
(Gallinoro E, Almendarez M, Alvarez-Velasco R, Barbato E, Avanzas P. Bioresorbable
stents: is the game over? Int J Cardiol. 2022;361:20-28. PMID: 35577167).

1.14 Answer D. Stent thrombosis is a rare but usually catastrophic event, frequently associated
with large MI or death. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection activates inflammatory mechanisms (ie, cytokines) that potentially create a
prothrombotic environment (ie, increased platelet aggregation and thrombosis) that
increases the risk of local microthromboembolism and stent thrombosis (Skorupski WJ,
Grygier M, Lesiak M, Kałużna-Oleksy M. Coronary stent thrombosis in COVID-19
patients: a systematic review of cases reported worldwide. Viruses. 2022;14(2):260.
PMID: 35215853).

1.15 Answer D. Oxidative stress is generally defined as an imbalance between pro-oxidant

reactive oxygen species (ROS) and their antioxidant counterparts. Excessive production
of ROS such as superoxide, peroxynitrite (ONOO−), and hydrogen peroxide (H2O2) is
associated with the pathogenesis of several cardiovascular diseases, such as
atherosclerosis. In the vasculature, superoxide is the main ROS produced (Clare J, Ganly
J, Bursill CA, Sumer H, Kingshott P, de Haan JB. The mechanisms of restenosis and
relevance to next generation stent design. Biomolecules. 2022;12(3):430. PMID:
35327622).

1.16 Answer C. Although platelet inhibition with low-dose aspirin is effective in reducing
cardiovascular events in patients at elevated risk, MI and stroke can still occur on
treatment. Genetic variation in metabolism is insufficient to explain this variability in the
response to aspirin. Aspirin inhibits COX-1, depressing its ability to form thromboxane
(Tx) A2, which promotes vasoconstriction and platelet aggregation. Since platelets lack a
nucleus, they have minimal capacity to form new proteins from cytosolic RNA. Thus,
platelets exposed to aspirin are permanently inhibited, and the consequent inhibition of
platelet aggregation remains close to maximal for about 2 days after a single dose (ie,
≥325 mg). However, COX-1 activity needs to be inhibited almost completely (ie, >95%)
to suppress TxA2 below levels that effectively amplify platelet activation. This can make
reliable therapeutic inhibition with low-dose aspirin challenging. For example, formation
of peroxides and glycation products in patients with diabetes renders COX-1 somewhat
less susceptible to inhibition by aspirin. This may lead to considerable variability in the
response to aspirin with initial dosing. However, low doses of aspirin that may be
insufficient to acetylate the entire platelet COX-1 pool with initial dosing, at once,
eventually result in complete platelet inhibition if they are given repetitively.
Accordingly, extending the dosing interval—for example, by skipping more than an
occasional dose—can result in inadequate platelet inhibition (Fries S, Grosser T.
Mechanism of variability in the response to low dose aspirin. Clin Pharmacol Ther.
2022;111(4):740-742. PMID: 35167713).
1.17 Answer E.Although improvements in myocardial reperfusion, antiplatelet regimens, and
antithrombotic agents have occurred, no effective therapeutic strategy for preventing
myocardial reperfusion injury has been identified. Unsuccessful therapeutic strategies
have included adenosine, anti-inflammatory agents, statins, epoetin, sodium nitrite, and
glucose-insulin-potassium infusion (Hausenloy DJ, Yellon DM. Myocardial ischemia-
reperfusion injury: a neglected therapeutic target. J Clin Invest. 2013;123(1):92-100.
PMID: 23281415).

1.18 Answer D. Classic risk factors for inflammation are sex, age, smoking, genetic
predisposition, and blood cholesterol levels, whereas nonclassical risk factors such as
sterile inflammation (prior MI/stroke/rheumatoid arthritis), acute and chronic
psychosocial stress, noise and air pollution, poor sleep quality, and sedentary lifestyle all
contribute to inflammation and atherosclerosis. Exercise reduces cardiovascular risk via
multiple effects including on metabolism, antihypertension, and reduced leptin levels,
which limit proinflammatory leukocytes (Hinterdobler J, Schunkert H, Kessler T, Sager
HB. Impact of acute and chronic psychosocial stress on vascular inflammation. Antioxid
Redox Signal. 2021;35(18):1531-1550. PMID: 34293932).

1.19 Answer D.Elastic recoil leads to early lumen loss within 1 hour of the procedure. By
providing intravascular scaffolding, stents reduce the impact of elastic recoil and
negative remodeling on lumen area. However, intimal hyperplasia remains an important
limitation on the use of bare metal stents. Intimal hyperplasia is generally considered to
be a consequence of proliferation and migration of vascular smooth muscle cells,
whereas accumulation of foam cells contributes to primary atherosclerosis (Coolong A,
Kuntz RE. Understanding the drug-eluting stent trials. Am J Cardiol.
2007;100(5A):17K-24K. PMID: 17719349). The leading cause of restenosis is intimal
hyperplasia (Melnik T, Jordan O, Corpataux JM, Delie F, Saucy F. Pharmacological
prevention of intimal hyperplasia: a state-of-the-art review. Pharmacol Ther.
2022;235:108157. PMID: 35183591).

1.20 Answer E.Inhibition of the mTOR pathway is a conventional strategy to prevent

restenosis, as this signaling pathway is central in regulating the replication of
mammalian cells. mTOR inhibitors, such as sirolimus and everolimus, have been
investigated and used in clinics for restenosis prevention since the early 2000s (Melnik
T, Jordan O, Corpataux JM, Delie F, Saucy F. Pharmacological prevention of intimal
hyperplasia: a state-of-the-art review. Pharmacol Ther. 2022;235:108157. PMID:
35183591).

1.21 Answer D. Balloon angioplasty causes adventitial stretching, dissection of the wall, plaque
fracture, and ultimately medial necrosis (Giannopoulos S, Varcoe RL, Lichtenberg M, et
al. Balloon angioplasty of infrapopliteal arteries: a systematic review and proposed
algorithm for optimal endovascular therapy. J Endovasc Ther. 2020;27(4):547-564.
PMID: 32571125). Apoptosis does not typically occur with angioplasty and is thought to
be a mechanism of cryoplasty (Giannopoulos S, Varcoe RL, Lichtenberg M, et al.
Balloon angioplasty of infrapopliteal arteries: a systematic review and proposed
 algorithm for optimal endovascular therapy. J Endovasc Ther. 2020;27(4):547-564.
PMID: 32571125).

1.22 Answer A.CEC are noninvasive markers of vascular damage, remodeling, and
dysfunction; CEC concentrations are higher in patients with AMI compared with healthy
controls (Damani S, Bacconi A, Libiger O, et al. Characterization of circulating
endothelial cells in acute myocardial infarction. Sci Transl Med. 2012;4(126):126ra33.
PMID: 22440735) and correlate with plaque rupture (Li C, Wu Q, Liu B, et al. Detection
and validation of circulating endothelial cells, a blood-based diagnostic marker of acute
myocardial infarction. PLoS One. 2013;8(3):e58478. PMID: 23484031). CEC also
correlate with angiogenesis and may be a marker of some tumors.

1.23 Answer B.Patients with diabetes are frequently affected by coronary microvascular
dysfunction (CMD), a condition consisting of a combination of altered vasomotion and
long-term structural change to coronary arterioles leading to impaired regulation of
blood flow in response to changing cardiomyocyte oxygen requirements. Despite the
different pathogenesis of T1DM, T2DM, and other types of diabetes, all states of
hyperglycemia share the dysfunction of microvessels as a common chronic feature due
to the pronounced sensitivity of this vascular compartment to oxidative stress and the
inflammatory response to high circulating glucose levels. However, microangiopathy is
more precocious and frequent in the course of T2DM. The hallmark of diabetic
endothelial dysfunction is the loss of NO-dependent vasodilatory response due to
reduced activity or expression of eNOS and, to a greater extent, to scavenging
inactivation of NO by excess free radicals. Several new treatments are available,
including glucagon-like peptide-1 (GLP-1) receptor agonists and SGLT2 inhibitors
(Salvatore T, Galiero R, Caturano A, et al. Coronary microvascular dysfunction in
diabetes mellitus: pathogenetic mechanisms and potential therapeutic options.
Biomedicines. 2022;10(9):2274. PMID: 36140374).

1.24 Answer D. Hypertension activates major molecular pathways such as RAAS, endothelin,
NO signaling pathway, and oxidative stress in the development of vascular dysfunction
(de Oliveira MG, Nadruz W Jr, Mónica FZ. Endothelial and vascular smooth muscle
dysfunction in hypertension. Biochem Pharmacol. 2022;205:115263. PMID: 36174768).
As a marker of injury, the contribution of CT in the modern diagnosis of cardiovascular
diseases cannot be overestimated. Cardiac troponins are significant contributors due to
participating in the regulation of the contraction-relaxation of operating cardiac
myocytes. Mutations in the genes encoding CT lead to the pronounced disorders of
cardiac myocytes’ contraction-relaxation (hereditary cardiomyopathies), which are
clinically manifested by a group of symptoms of heart failure. Proteins CT-T and CT-I
are released from the cell into the blood during the ischemic necrosis of cardiac
myocytes, which can be used in the diagnosis of MI as well as a marker of hypertensive
cardiac injury (Chaulin AM. Cardiac troponins as biomarkers of cardiac myocytes
damage in case of arterial hypertension: from pathological mechanisms to predictive
significance. Life (Basel). 2022;12(9):1448. PMID: 36143484).
1.25 Answer A.PCSK9 inhibitors prevent PCSK9 from inhibiting LDL receptor degradation,
and thus increase LDL receptor numbers on the surface of hepatocytes, allowing
increasing update of plasma LDL. Inhibition of HMG-CoA reductase is the mechanism
of action of statin drugs; statins also upregulate eNOS to improve endothelial function,
an important benefit. Ezetimibe inhibits cholesterol absorption from the small intestine
leading to the reduction in intestinal cholesterol transmission to the liver, mainly
associated with the inhibition of the Niemann-Pick C1-like 1 (NPC1L1) protein (Dayar
E, Pechanova O. Targeted strategy in lipid-lowering therapy. Biomedicines.
2022;10(5):1090. PMID: 35625827).

1.26 PCSK9 shortens the half-life of cell surface receptors, such as LDL receptor,
Answer E.
VLDLR, and MHC-I, by escorting them into the lysosomal degradation pathway.
PCSK9 regulates the cell surface levels of the T-cell receptor and MHC-I, preventing
TCR activation that governs the antitumoral activity of CD8+ T cells. PCSK9 activates
the TLR4/NF-κB pathway via oxidized LDL receptor to promote vascular inflammation.
The many effects of PCSK9 suggest several potential functions for PCSK9 inhibitors
including reduced serum LDL cholesterol and atherosclerosis, reduced cancers and
metastasis, reduced viral infections and sepsis, and reduced allergies and inflammation
(Seidah NG, Prat A. The multifaceted biology of PCSK9. Endocr Rev. 2022;43(3):558-
582. PMID: 35552680).

1.27 Answer E. Studies of patients with familial hypercholesterolemia led to the discovery of
the LDL receptor by Goldstein and Brown in 1974, leading to new ways to think about
cholesterol metabolism. The LDL receptor discovery also introduced three general
concepts to cell biology: receptor-mediated endocytosis, receptor recycling, and
feedback regulation of receptors. The latter concept provides the mechanism by which
statins selectively lower plasma LDL, reducing heart attacks and prolonging life
(Goldstein JL, Brown MS. The LDL receptor. Arterioscler Thromb Vasc Biol.
2009;29(4):431-438. PMID: 19299327).

1.28 Answer E. In addition to inhibition of HMG-CoA reductase activity, statins have many
cardioprotective effects including modulation of vascular tone, endothelial permeability
and function, inhibition of complement injury, curbing of foam cell formation,
antioxidant and anti-inflammatory properties, and profibrinolytic and anticoagulant
activities. These effects lead to reduction of myocardial necrosis, myocardial
hypertrophy, blood pressure, and heart failure, as well as mobilization of EPC for repair,
angiogenic effects, and immunomodulation (Davignon J. The cardioprotective effects of
statins. Curr Atheroscler Rep. 2004;6(1):27-35. PMID: 14662105).

1.29 Answer E. Paclitaxel was originally isolated from the Pacific Yew tree (Taxus brevifolia)
and is an antiproliferative agent originally approved by the U.S. Food and Drug
Administration (FDA) in 1992. Paclitaxel-eluting stents were evaluated in the coronary
arteries in multiple trials, including the TAXUS, DELIVER, JACTAX, and BARDDS
trials, and paclitaxel-coated balloons were evaluated in the PICCOLETO, PEPCAD,
ISAR-DESIRE, PACCOCATH, and DEBUT trials. Paclitaxel-eluting stents fell out of
 favor due to reduced efficacy compared with next-generation drug-eluting stents rather
than any identified paclitaxel toxicity (Clare J, Ganly J, Bursill CA, Sumer H, Kingshott
P, de Haan JB. The mechanisms of restenosis and relevance to next generation stent
design. Biomolecules. 2022;12(3):430. PMID: 35327622). Paclitaxel-coated balloons are
not currently approved in the United States (Tuttle MK, Pompa JJ. A retrospective look
at paclitaxel use in the coronary arteries. Endovasc Today. Published September 2019.
Accessed July 18, 2023. https://evtoday.com/articles/2019-sept/a-retrospective-look-at-
paclitaxel-use-in-the-coronary-arteries).

1.30 Answer C. The CANTOS trial (supported by Novartis) tested the hypothesis that reducing
inflammation without changing lipid levels would reduce the risk of cardiovascular
disease. Treatment with canakinumab, a therapeutic monoclonal antibody targeting
interleukin-1β, in patients with previous MI and a high-sensitivity C-reactive protein
level, resulted in reduced serum high-sensitivity C-reactive protein and interleukin-6
levels, without a change in serum LDL cholesterol levels. Canakinumab (150 mg)
reduced by 15% nonfatal MI, nonfatal stroke, or cardiovascular death, the primary end
point of the study, but there was no reduction in all-cause mortality. Canakinumab was
associated with a higher incidence of fatal infection than was placebo (Ridker PM,
Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for
atherosclerotic disease. N Engl J Med. 2017;377(12):1119-1131. PMID: 28845751).

1.31 Answer E. The NLRP3 inflammasome is activated by a wide range of chemically unrelated
molecules reflecting cellular damage and metabolic stress, and inflammasome activation
leads to the release of proinflammatory cytokines such as interleukins-1β and -18. There
is increasing evidence that inflammasome activation plays an important role in the
development of cardiovascular disease, and that targeting inflammasome activation is an
exciting new therapeutic target for atherosclerosis, MI, ischemic stroke as well as heart
failure (Olsen MB, Gregersen I, Sandanger Ø, et al. Targeting the inflammasome in
cardiovascular disease. JACC Basic Transl Sci. 2021;7(1):84-98. PMID: 35128212).

1.32 Answer E. SGLT2 inhibitors are a new class of oral glucose–lowering agents that promote
glucosuria and thus reduce serum glucose and lower blood pressure. It is becoming more
widely believed that rather than a simple glucose-lowering effect, the cardioprotective
effect of SGLT2 inhibitors is a combined pathophysiologic process involving the heart,
kidney, vasculature, and even the whole body (Yang D, Zhang Y, Yan J, Liu M, An F.
SGLT-2 inhibitors on prognosis and health-related quality of life in patients with heart
failure and preserved ejection fraction: a systematic review and meta-analysis. Front
Cardiovasc Med. 2022;9:942125. PMID: 36158789). SGLT2 inhibitors are given a class
2A recommendation in the treatment of patients with HFpEF, and a class 1A
recommendation in the treatment of patients with heart failure with reduced ejection
fraction (HFrEF), in the 2022 American Heart Association (AHA) Guidelines for the
management of heart failure (Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022
AHA/ACC/HFSA guideline for the management of heart failure: a report of the
American College of Cardiology/American Heart Association Joint Committee on
Clinical Practice Guidelines [Erratum in: Circulation. 2022;145(18):e1033. Erratum in:
 Circulation. 2022;146(13):e185. Erratum in: Circulation. 2023;147(14):e674].
Circulation. 2022;145(18):e895-e1032. PMID: 35363499).

1.33 Answer A.The prevalence of high platelet reactivity (HPR) during clopidogrel treatment is
high. Hepatic activation of clopidogrel and conversion into an active metabolite is
essential for the inhibition of the P2Y12 receptor; the isoenzyme CYP2C19 is of
particular interest and is thought to explain 12%-15% of the variable response to
clopidogrel, and reduced function of CYP2C19 has been reported to increase the risk for
major adverse cardiovascular events (MACE). Drug interactions can also affect
clopidogrel response, including rifampicin, ketoconazole, and PPIs (Allen C, Dunn SP,
Macaulay TE, Mukherjee D. Clopidogrel-proton pump inhibitor interaction: a primer for
clinicians. Cardiovasc Hematol Disord Drug Targets. 2010;10(1):66-72. PMID:
20041840).
 Anatomy and Physiology of Coronary
2
Arteries

Richard A. Lange and Joaquin E. Cigarroa

QUESTIONS

2.1 An 80-year-old man is referred for coronary angiography for evaluation of retrosternal
pain at rest. Pressure recordings from the coronary catheter tip during its engagement in
the right coronary artery (RCA) ostium and withdrawal (see arrow, Figure Q2.1.1) into
the aorta indicate:

Figure Q2.1.1

A. Collateral coronary flow

B. Severe aortic stenosis
C. Anomalous origin of a coronary artery
D. Obstruction of antegrade coronary flow by the catheter

2.2 Which of the following projections allows the operator to visualize a proximal left
circumflex (LCx) stenosis optimally?
A. 30° right anterior oblique (RAO)
 B. 30° RAO, 30° cranial
C. 60° left anterior oblique (LAO), 30° cranial
D. 30° RAO, 30° caudal

2.3 A 45-year-old man with a bicuspid aortic valve is found to have a left-dominant coronary
circulation at cardiac catheterization. What is the incidence of this?
A. 90%
B. 50%
C. 30%
D. 10%

2.4 A 55-year-old man undergoes coronary angiography for evaluation of nonexertional chest
pain. The left lateral view of the left anterior descending (LAD) artery obtained during
diastole (panel A) and systole (panel B) is displayed in Figure Q2.4.2. He has:

Figure Q2.4.2 (With permission from Bauters C, Chmait A, Tricot O, et al. Images in cardiovascular medicine.
Coronary thrombosis and myocardial bridging. Circulation. 2002;105(1):130. PMID: 11772888.)

A. An eccentric atherosclerotic stenosis

B. Myocardial bridging
C. Prinzmetal angina
D. Coronary dissection

2.5 Each of the pressure-wire-based assessments utilizes the whole cardiac cycle for
evaluating the functional significance of a coronary stenosis, EXCEPT:
A. RFR (resting full-cycle ratio)
B. Rest Pd/Pa (Pd, distal pressure; Pa, aortic pressure)
 C. cFFR (contrast fractional flow reserve)
D. iFR (instantaneous wave-free ratio)

2.6 In a 30-year-old survivor of sudden cardiac death, left ventriculography in the 30° RAO
projection shows a “button” projecting from the aortic root (Figure Q2.6.3). This
suggests the patient has:

Figure Q2.6.3

A. Occlusion of the proximal RCA

B. Anomalous origin of the LCx artery
C. Pseudoaneurysm of the proximal ascending aorta
D. Coronary ectasia from Kawasaki disease

2.7 In routine clinical practice, the severity of coronary stenosis is estimated from visual
inspection of the coronary angiogram. Compared with quantitative coronary
angiography, such a visual estimation of coronary stenoses usually:
A. Provides similar results
B. Underestimates the severity of the stenosis by 35%
C. Underestimates the severity of the stenosis by 20%
D. Overestimates the severity of the stenosis by 20%

2.8 Impaired vasodilator reserve is first noted when the coronary luminal diameter narrowing
(ie, stenosis) is:
 A. 50%
B. 60%
C. 75%
D. 90%

2.9 What is a Kugel artery?

A. Anomalous origin of the LAD coronary artery from the pulmonary artery
B. Coronary arteriovenous fistula (AVF)
C. Conus artery branch
D. Right-to-right collateral (from proximal to distal RCA through the atrioventricular
[AV] node branch)

2.10 A 55-year-old woman with exertional chest pain and an abnormal myocardial perfusion
scan has a coronary angiogram that demonstrates a 50% stenosis of the mid-RCA. This
corresponds to a cross-sectional area narrowing of:
A. 50%
B. 60%
C. 75%
D. 90%

2.11 Which is TRUE of coronary blood flow?

A. Phasic coronary blood flow is more pronounced for diastolic compared with systolic
flow
B. The diastolic predominance is greater in the left coronary artery than in the RCA
C. With an epicardial stenosis, translesional pressure loss (ie, the aortic-coronary gradient)
will initially be evident in diastole
D. All of the above

2.12 In what percentage of individuals does the LCx coronary artery provide blood flow to the
sinoatrial node?
A. 10%
B. 40%
C. 60%
D. 90%

2.13 Which of the statements regarding coronary blood flow autoregulation is TRUE?
A. During exercise, the resistance of the coronary microvasculature increases
B. An epicardial stenosis increases epicardial resistance, which is compensated by an
 equivalent increase in microvascular resistance to maintain coronary autoregulation
C. When a coronary stenosis becomes “critical,” the compensation capacity of the
microvasculature is exhausted
D. The Bayliss phenomenon (ie, increased perfusion pressure causes reflex coronary
vasodilation) helps to maintain coronary autoregulation
E. A low coronary flow reserve (CFR) (<2 in adults) is diagnostic for abnormal
microvascular resistance

2.14 Which of the following is TRUE of the coronary venous system?

A. Veins and venules are innervated by sympathetic nerves
B. Venous volume increases with sympathetic stimulation
C. Veins dilate in response to local metabolic factor
D. Veins are constricted in the basal state

2.15 All the following are TRUE regarding coronary vascular resistance, EXCEPT:
A. Left ventricular (LV) hypertrophy can impair microcirculatory (R3) resistance
B. In the absence of stenosis, R1 (epicardial vessel) resistance is trivial
C. The R2 (prearteriolar) vessels are responsible for most of the total coronary resistance
D. The R3 (arteriolar and intramyocardial) vessels are regulated neurogenically and
locally

2.16 When assessing the functional significance of a coronary stenosis, which evaluation
requires hyperemia?
A. FFRangio (fractional flow reserve angiography)
B. iFR (instantaneous wave-free ratio)
C. cFFR (contrast FFR)
D. DPR (diastolic pressure ratio)
E. QFR (quantitative flow ratio)

2.17 Before placement of a catheter in the coronary sinus, a venogram is performed (Figure
Q2.17.4). What does the arrow denote?
Figure Q2.17.4 (With permission from Habib A, Lachman N, Christensenet KN, et al. The anatomy of the
coronary sinus venous system for the cardiac electrophysiologist. Europace. 2009;11:15-21. PMID:
19861386.)

A. A prominent Vieussens valve is visualized

B. The proximal coronary sinus has a thrombotic occlusion
C. The middle cardiac vein is seen coursing superiorly after emptying into the coronary
sinus
D. A persistent left superior vena cava (SVC) is visualized

2.18 The CORRECT formula for determining myocardial oxygen consumption (MVO2) from
the coronary arterial or venous flow (Q), arterial oxygen content (AoO2), and coronary
sinus oxygen content (CSO2) is:
A. MVO2 = Q/(AoO2 − CSO2)
B. MVO2 = (AoO2 − CSO2)/Q
C. MVO2 = Q × (AoO2 − CSO2)
D. Cannot calculate with the data provided

2.19 Which is TRUE of left heart dominance?

 A. The left main (LM) coronary artery is significantly longer in left-dominant patients
than in right-dominant patients
B. The prevalence is increased with bicuspid aortic valve
C. The posterior descending artery (PDA) arises from the LAD artery
D. Small branches from the dominant artery perfuse the sinoatrial node

2.20 In which of the following circumstances may the use of an LV-Ao pullback pressure
recording to assess aortic valve area yield inaccurate results?
A. Low (<35 mm Hg) transvalvular gradient
B. Atrial fibrillation
C. Immediately after left ventriculography
D. All of the above

2.21 A 50-year-old man with a left bundle branch block (LBBB) is referred for cardiac
catheterization to evaluate “atypical” chest pain because his noninvasive testing was
nondiagnostic. Coronary angiography demonstrates a 65% mid-LAD stenosis. You
decide to assess his iFR to determine the hemodynamic significance of his stenosis.
Which of the following best characterizes this assessment?
A. For measurement of iFR, adenosine intravenous (IV) (140 µg/kg/min) or intracoronary
(IC) (100 µg bolus) is preferable to regadenoson for achieving maximal hyperemia
B. Aortic and distal coronary artery pressures are compared during early diastole to obtain
iFR
C. An iFR of 0.85 is an indication for revascularization
D. An iFR of 0.90 is a contraindication to revascularization, as medical therapy is
effective in patients with this measurement

2.22 Coronary venous oxygen saturation is typically:

A. 30%
B. 50%
C. 65%
D. 80%

2.23 A 66-year-old woman presents to the emergency department with acute shortness of
breath and dizziness. She is noted to have a blood pressure of 90/60 mm Hg, a heart rate
of 35 bpm (beats per minute), elevated neck veins, and rales to the mid-lung fields. Her
electrocardiogram (ECG) shows an inferior ST-segment elevation myocardial infarction
(STEMI) and third-degree heart block. An echo shows a markedly decreased left
ventricular ejection fraction (LVEF) with inferior akinesis and anterior hypokinesis. She
is brought to the cardiac catheterization laboratory where a temporary transvenous
pacing is placed in the right ventricle and dobutamine is initiated prior to angiography.
 Catheterization revealed a 100% occlusion of the RCA and 60% proximal LAD stenosis.
Primary percutaneous coronary intervention (PCI) of the RCA is successful with
placement of a 3.0 × 20 mm drug-eluting stent (DES). To evaluate the “intermediate”
LAD stenosis you decide to:
A. Assess FFR after the dobutamine infusion is stopped because the increased contractility
alters FFR reliability
B. Assess FFR after the temporary pacing wire is discontinued, as changes in heart rate by
pacing may affect the accuracy of FFR measurement
C. Proceed with FFR without changing dobutamine infusion or pacing therapy, as neither
affects this measurement
D. Defer FFR and proceed directly to PCI of the proximal LAD stenosis, as FFR is
unreliable in the setting of an acute myocardial infarction (MI) due to microvascular
dysfunction

2.24 Which of these coronary anomalies is commonly associated with ischemic complications?
A. A RCA arising from the left sinus of Valsalva
B. Origin of the LCx from the right coronary sinus
C. A LM coronary artery arising from the noncoronary sinus
D. A RCA originating from the noncoronary sinus
E. All of the above

2.25 Which is TRUE of the normal endothelial layer of coronary arteries?

A. Endothelial cells produce and secrete von Willebrand factor
B. Endothelial cells secrete nitric oxide
C. Endothelial cells secrete matrix metalloproteinases
D. Endothelial cells secrete extracellular matrix components, such as elastin and
fibronectin
E. All of the above

2.26 Which is TRUE of the capillary vessels?

A. They consist of a single layer of endothelial cells
B. They lack the ability to change their diameter actively because they have no smooth
muscle cells
C. They have the largest cross-sectional and surface area of the vessels in the vasculature
D. All of the above

2.27 What percentage of the population is codominant with the PDA supplied by both the
RCA and the LAD artery?
A. 0%
 B. 10%-20%
C. 30%
D. 50%
E. 75%

2.28 Which of the following induces coronary arterial vasodilation?

A. Angiotensin II
B. Vasopressin
C. α-1 adrenergic receptor stimulation
D. β-2 adrenergic receptor stimulation
E. All of the above

2.29 Which of the following statements regarding the structure of coronary arteries is
CORRECT?
A. The media of all arteries is contained within a connective tissue layer called the internal
elastic lamina
B. At the point the epicardial arteries turn into the myocardium, they become more
muscular arteries with few if any elastic fibers
C. The media contains a network of small blood vessels (vasa vasorum), which is
responsible for the nutrition of the inner third of the artery
D. The internal elastic lamina contains nerves, which control the tone of the artery

2.30 In a normal subject at rest, coronary blood flow is what percentage of cardiac output?
A. 40%
B. 20%
C. 10%
D. 5%

2.31 Which of the following statements regarding the LM coronary artery is CORRECT?
A. The LM ostium lacks adventitia and has a greater portion of elastic tissue than other
segments of the coronary tree
B. Since the LM ostium has fewer elastic fibers, it is not subject to diseases affecting the
aortic wall, such as syphilitic aortitis, radiation-induced aortitis, and Takayasu arteritis
C. Trifurcation of the LM, with the third artery called the ramus intermedius, occurs in
10%-20% of the population
D. A high takeoff of the LM is associated with an increased risk of LM stenosis and
ischemia
E. Origin of the LM from the noncoronary cusp is associated with sudden cardiac death
 2.32 A 45-year-old woman developed acute-onset, severe substernal chest pain and anterior ST
elevation on her ECG following an intense argument with her son (Figures Q2.32.5A
and B). Arteriography demonstrated no significant coronary stenoses, and her left
ventriculogram is shown in Figure Q2.32.5C. She most likely has:

Figure Q2.32.5 (A, with permission from Witzke C, Lowe HC, Waldman H, Palacios IF. Images in
cardiovascular medicine. Transient left ventricular apical ballooning. Circulation. 2003;108(16):2014. PMID:
14568886.)

A. Prinzmetal angina
B. Myopericarditis
C. Dilated cardiomyopathy
D. Takotsubo cardiomyopathy

2.33 A 70-year-old woman presents with an acute inferior MI. Following primary PCI of an
 occluded RCA, coronary angiography shows persistent staining of the inferior
myocardium, with the blush persisting at the time of the next coronary injection (Figure
Q2.33.6). Using the thrombolysis in myocardial infarction (TIMI) myocardial perfusion
grade (TMPG) system, you would classify this as:

Figure Q2.33.6 (With permission from Gibson CM, Schömig A. Coronary and myocardial angiography:
angiographic assessment of both epicardial and myocardial perfusion. Circulation. 2004;109(25):3096-3105.
PMID: 15226226.)

A. TMPG 0
B. TMPG 1
C. TMPG 2
D. TMPG 3

2.34 A 71-year-old male smoker presents with chest pain. Coronary angiography reveals a
normal left coronary artery and severe stenoses in the proximal and mid-RCA (Figure
Q2.34.7A). Immediately following successful stenting of the RCA (Figure Q2.34.7B,
white and black arrows), the patient developed severe chest pain and marked anterior
ST-segment elevation (Figure Q2.34.7C). The most likely cause is:
Figure Q2.34.7 (With permission from Eichhöfer J, Curzen N. Images in cardiovascular medicine. Unexpected
profound transient anterior ST elevation after occlusion of the conus branch of the right coronary artery
during angioplasty. Circulation. 2005;111(9):e113-e114. PMID: 15753220.)

A. Microvascular obstruction
B. Occlusion of sinoatrial branch of the RCA
C. Transient occlusion of right ventricular branch of the RCA
D. Transient occlusion of the conus branch of the RCA

2.35 A 60-year-old man with previous coronary artery bypass surgery for LM disease
 undergoes coronary angiography for the evaluation of angina with minimal exertion
(Figure Q2.35.8), which demonstrates occlusion of the LM and a patent RCA. The
LAD, LCx, and ramus intermedius arteries are perfused via collaterals (solid black
arrow), the source (open arrow) of which is:

Figure Q2.35.8 (With permission from O’Leary EL, Garza L, Williams M, McCall D. Images in cardiovascular
medicine. Vieussens’ ring. Circulation. 1998;98(5):487-488. PMID: 9714100.)

A. Kugel artery
B. Aorta-coronary fistula
C. Anomalous origin of the LAD from the pulmonary artery (Bland-Garland-White
syndrome)
D. Large conus branch from RCA

2.36 To obtain a “spider view” to visualize the LM coronary artery as well as the proximal
LAD and LCx arteries optimally, the image intensifier should be positioned:
A. 50° LAO, 20° caudal
B. 30° RAO, 30° caudal
C. 50° LAO, 35° cranial
D. 15° RAO, 30° cranial
2.37 Which of the following are limitations of using CFR to assess the presence of a
significant epicardial stenosis?
A. Hyperemic flow is directly dependent on systemic blood pressure
B. Tachycardia decreases hyperemic flow, thus reducing CFR
C. The hyperemic and resting measurements are not performed simultaneously
D. CFR is not specific for epicardial stenosis
E. All of the above

2.38 The “abbreviated” form of the Gorlin formula (so-called Hakki equation: valve area (cm2)
= flow (L/min)/√peak-to-peak pressure gradient) is often used to estimate valve area in
patients with valvular stenosis referred for catheterization. It may be inaccurate in which
of the following circumstances?
A. Valve area <1.0 cm2
B. High cardiac output
C. Low transvalvular gradient
D. Bradycardia (heart rate <60 bpm) or tachycardia (heart rate >100 bpm)

2.39 Coronary blood flow velocity is:

A. Directly proportional to cross-sectional area of the artery
B. Directly proportional to vascular resistance
C. Directly proportional to blood flow
D. All of the above

ANSWERS AND EXPLANATIONS

2.1 Answer D. The pressure recording shows “ventricularization,” in which diastolic pressure
is reduced but systolic pressure is preserved. Normally, the catheter tip pressure and the
peripheral arterial pressure are similar. If a coronary ostial stenosis is present,
engagement of the catheter may obstruct antegrade blood flow and cause
ventricularization of the catheter pressure waveform (Pacold I, Hwang MH, Piao ZE, et
al. The mechanism and significance of ventricularization of intracoronary pressure
during coronary angiography. Am Heart J. 1989;118(6):1160-1166. PMID: 2589155).

2.2 Answer D. In the 30° RAO projection, one is looking down the atrioventricular (AV) plane,
in which the LCx artery resides. Because the proximal portion of the vessel is
foreshortened in this view, caudal angulation must be employed to unforeshorten it. With
the other angles listed, the proximal LCx is foreshortened or overlapped by other vessels.
2.3 Answer C.In the general population, only 10% of individuals are left dominant (ie, the
posterior descending artery (PDA) arises from the distal LCx artery), but 30% of
subjects with a bicuspid valve are left dominant (Hutchins GM, Nazarian IH, Bulkley
BH. Association of left dominant coronary arterial system with congenital bicuspid
aortic valve. Am J Cardiol. 1978;42(1):57-59. PMID: 677038).

2.4 Answer B. Not infrequently, the LAD will course beneath a muscle bundle on the
epicardial surface of the heart, resulting in its compression during ventricular systole;
this is known as myocardial bridging. It is usually an incidental finding of no
consequence, but rarely it has been associated with myocardial ischemia (Bauters C,
Chmait A, Tricot O, Lamblin N, et al. Images in cardiovascular medicine. Coronary
thrombosis and myocardial bridging. Circulation. 2002;105(1):130. PMID: 11772888).

2.5 Answer D.All the indices listed use the ratio between distal coronary pressure and aortic
pressure, but they differ regarding the phase of the cardiac cycle in which the
measurement takes place. In this way, they can be categorized into phase-specific versus
whole-cycle indices. Of the indices listed, only the iFR is phase specific, the others—
RFR, rest Pd/Pa, and cFFR—use the whole cardiac cycle.

2.6 Answer B.The most common coronary anomaly is origin of the LCx artery from the right
sinus of Valsalva. This can often be visualized during left ventriculography (30° RAO
projection) as a “dot” or “button” projecting from the aortic root as the LCx courses
posterior to the aorta (Page HL Jr, Engel HJ, Campbell WB, Thomas CS Jr. Anomalous
origin of the left circumflex coronary artery. Recognition, angiographic demonstration
and clinical significance. Circulation. 1974;50(4):768-773. PMID: 4417692; Ueyama K,
Ramchandani M, Beall AC Jr, Jones JW. Diagnosis and operation for anomalous
circumflex coronary artery. Ann Thorac Surg. 1997;63(2):377-381. PMID: 9033304).

2.7 Answer D. Visual estimation of coronary stenoses is subject to substantial operator

variability and a systematic form of “stenosis inflation,” in which the operator’s estimate
of diameter stenosis is approximately 20% greater than that measured by quantitative
coronary angiography (Stadius ML, Alderman EL. Coronary artery revascularization.
Critical need for, and consequences of, objective angiographic assessment of lesion
severity. Circulation. 1990;82(6):2231-2234. PMID: 2242544). Therefore, a stenosis that
measures 50% by quantitative angiography is typically called 70% by visual estimation.

2.8 Answer A. A 50% reduction in luminal diameter (hence, a 75% reduction in cross-sectional
area) is “hemodynamically significant,” in that it impairs CFR (ie, the 3- to 4-fold
augmentation in coronary flow in response to increased myocardial oxygen demands).
The ability to increase flow during vasodilator stimulus is first impaired when luminal
diameter is reduced by 50% and abolished when it is reduced by >70% (Uren NG, Melin
JA, De Bruyne B, Wijns W, Baudhuin T, Camici PG. Relation between myocardial
blood flow and the severity of coronary-artery stenosis. N Engl J Med.
1994;330(25):1782-1788. PMID: 8190154).
2.9 Answer D. A Kugel artery passes from either the proximal right or left coronary artery
along the anterior margin of the atrial septum to anastomose with the AV nodal branch
of the distal RCA to provide blood supply to the posterior circulation (Figure A2.9.9)
(Nerantzis CE, Marianou SK, Koulouris SN, et al. Kugel’s artery: an anatomical and
angiographic study using a new technique. Tex Heart Inst J. 2004;31(3):267-270. PMID:
15562847; Riseman JE, Josephs BN. Multiple lead electrocardiograms in angina
pectoris. Am Heart J. 1950;40(2):260-270. PMID: 15432287).

Figure A2.9.9

2.10 A 50% stenosis represents a 75% narrowing in cross-sectional area (Figure

Answer C.
A2.10.10).
 Figure A2.10.10

2.11 Answer D. Because of ventricular contraction, coronary blood flow occurs mainly during
diastole. Accordingly, phasic coronary blood flow is more pronounced for diastolic
compared with systolic flow. Flow in the left coronary artery has a greater diastolic
predominance than in the RCA because the compressive forces of the right ventricle are
less than those of the left ventricle. The diastolic predominance is greater in the left
coronary artery than in the RCA. At least 85% of coronary flow in the LAD occurs
during diastole, whereas the RCA blood flow is more or less equal in systole and
diastole. With an epicardial stenosis, the aortic-coronary gradient is initially evident in
diastole.

2.12 The sinus node artery originates from the LCx artery in 40% of individuals and
Answer B.
from the proximal RCA in 60%, regardless of whether the patient is right or left
dominant.

2.13 Answer C.During exercise or any other form of increased oxygen demand, the resistance
of the microvasculature decreases, allowing for an increased blood flow. Similarly, an
epicardial stenosis increases epicardial resistance, which is compensated by an
equivalent decrease in microvascular resistance. This results in a maintained total
resistance to blood flow and a preserved resting flow, with residual—albeit reduced—
CFR. When the stenosis becomes “critical,” the compensation capacity of the
microvasculature (ie, CFR) is exhausted. Hence, a lower CFR (<2 in adults) suggests
 that either the epicardial resistance is very high (ie, a critical epicardial stenosis is
present) or the microvascular resistance is abnormal, but it does not indicate which is
affected. The maintenance of constant resting coronary blood flow is referred to as
autoregulation. An example of an autoregulatory mechanism is the Bayliss phenomenon,
in which increased perfusion pressure causes reflex vasoconstriction.

2.14 Answer A.Like arterioles, veins and venules are innervated by sympathetic nerves, with
increased sympathetic tone resulting in venoconstriction and a decrease in venous
volume. Unlike arteries, the venous system is not regulated by local metabolic factors
and has little basal tone. Therefore, veins are generally in a dilated state.

2.15 Answer C.In the absence of stenoses, the R3 vessels (arteriolar and intramyocardial) are
responsible for 40%-50% of total coronary resistance, the R2 vessels (prearteriolar) are
responsible for 25%-35%, and the R1 (epicardial) vessels contribute little to coronary
resistance.

2.16 Answer C.cFFR is the lowest mean (noninstantaneous) Pd/Pa value obtained after IC
injection of a standard dose of radiographic contrast medium. Of the pressure-wire-based
evaluations, only cFFR requires hyperemia; resting measurements are used for iFR and
DPR. Both FFRangio and QFR are coronary angiography–based measurements and
neither requires hyperemia to evaluate the functional significance of a coronary lesion.
FFRangio is a resting, adenosine-free angiography-based index that uses a 3D
reconstruction of the coronary tree obtained from angiographic projections and a
proprietary computational fluid-dynamic model.
There is no difference in the ability to predict FFR when QFR is derived using resting
estimated contrast flow velocity or hyperemic estimated contrast flow velocity.

2.17 Answer A.The valve of Vieussens lies at the junction of the great cardiac vein and the
coronary sinus. Its position is marked by the vein of Marshall, which can be seen
coursing superiorly after emptying into the coronary sinus. In this particular patient, the
valve of Vieussens is preventing reflux of contrast material from the coronary sinus into
the great cardiac vein.

2.18 According to the Fick principle, the uptake of a substance (eg, oxygen or
Answer C.
MVO2) is the product of flow (Q) and the AV concentration difference of the substance
(AoO2 − CSO2). Therefore, MVO2 = Q × (AoO2 − CSO2).

2.19 Answer B. Approximately 5%-10% of the population are left heart dominant, with the PDA
originating from the LCx artery. There appears to be an increased prevalence of left heart
dominance in patients undergoing aortic valve replacement. Furthermore, the LM
coronary artery is significantly shorter in left-dominant individuals than those seen in
right heart–dominant patients; this may be evidence of a developmental relationship seen
in left heart–dominant patients between the LM coronary artery and aortic valve. Small
branches from the dominant artery perfuse the AV node (not the sinoatrial node).
2.20 Answer D. Assessment of the transvalvular aortic gradient with nonsimultaneous
measurement of LV and aortic pressures may be inaccurate when the transvalvular
gradient is low, if the systolic pressure is fluctuating (eg, with atrial fibrillation), or if
contrast material administered during left ventriculography causes depression of
ventricular systolic function and systemic vasodilation (Brogan WC III, Lange RA,
Hillis LD. Accuracy of various methods of measuring the transvalvular pressure gradient
in aortic stenosis. Am Heart J. 1992;123(4 Pt 1):948-953. PMID: 1550005).

2.21 Answer C.iFR is a measurement of the hemodynamic significance of a coronary artery

stenosis that relies on comparison of pressures during diastole in the absence of
hyperemia. It is measured during the wave-free period of mid to late diastole, when flow
during the cardiac cycle is the highest and the microcirculatory resistance is the lowest.
During this period, pressure and flow are linearly related, allowing pressure ratios to be
used to determine whether a flow-limiting lesion is present. Unlike in FFR assessment,
hyperemia is not required.
An iFR threshold of <0.9 has been proposed for revascularization based on the
RESOLVE study. The ADVISE studies took a different approach and proposed a hybrid
iFR-FFR approach, which involves performing revascularization for iFR <0.86, deferral
for iFR >0.93, and using FFR to guide revascularization if iFR is between 0.86 and 0.93.
This approach allowed a 95% classification agreement between the hybrid strategy and
FFR, while sparing 60% of patients from adenosine.

2.22 At rest, transmyocardial oxygen extraction is nearly maximal, with typical

Answer A.
coronary venous oxygen saturations of 25%-35%.

2.23 Answer C.Because each myocardial territory and its resistance bed serves as its own
control, FFR is a lesion-specific index. Unlike most other physiologic indexes, FFR has
a normal value of 1 for every patient and every coronary artery. FFR has high
reproducibility and low intraindividual variability. Furthermore, because FFR is
measured only at maximal hyperemia, it is independent of microcirculation, heart rate,
blood pressure, and other hemodynamic variables. De Bruyne and associates
demonstrated that in humans, FFR is independent of hemodynamic conditions (De
Bruyne B, Baudhuin T, Melin JA, et al. Coronary flow reserve calculated from pressure
measurements in humans. Validation with positron emission tomography. Circulation.
1994;89(3):1013-1022. PMID: 8124786). Changes in heart rate by pacing, contractility
by dobutamine infusion, and blood pressure by nitroprusside infusion did not alter FFR.
In an acute STEMI, FFR of most nonculprit lesions at a distance from the infarct-related
artery has been shown to be accurate (Ntalianis A, Sels JW, Davidavicius G, et al.
Fractional flow reserve for the assessment of nonculprit coronary artery stenoses in
patients with acute myocardial infarction. JACC Cardiovasc Interv. 2010;3(12):1274-
1281. PMID: 21232721). Hence, FFR measurement in the LAD can proceed reliably
without changing therapy.

2.24 Answer A.The course of an anomalous coronary artery, rather than the actual location of
the coronary ostium, is a major discriminating factor for the anomaly being benign or
associated with clinical complications such as angina, ventricular arrhythmias, syncope,
or sudden death. Adverse outcomes occur more frequently when the anomalous coronary
artery has a course that passes between the aorta and the pulmonary artery, or less
commonly via a septal pathway. The mechanism of ischemia, infarction, or sudden death
in this situation appears related to the shape of the coronary ostium of the anomalous
vessel rather than compression related to the interarterial course. A RCA arising from the
left sinus of Valsalva or the proximal LM almost invariably (>99%) will pass between
the aorta and pulmonary artery. The clinical course in these patients is variable, with
some having no symptoms or evidence of cardiac dysfunction and others having
complications including angina, MI, syncope, and sudden death. Anomalous coronary
origins of the LCx from the right coronary sinus, the LM from the noncoronary sinus,
and the right coronary from the noncoronary sinus do not typically result in passage of a
coronary artery between the aorta and pulmonary artery (Figure A2.24.11).
 Figure A2.24.11

2.25 Answer E. The endothelium is a metabolically active secretory tissue. Endothelial cells
secrete both vasodilator substances, such as prostacyclin, nitric oxide, and endothelial-
derived hyperpolarizing factors, and vasoconstrictor substances (endothelin and
vasoconstrictor prostanoids). Endothelial cells also produce and secrete von Willebrand
factor, factor VIII antigen, tissue factor, and tissue plasminogen activator, which have
important roles in coagulation and fibrinolysis. Moreover, endothelial cells secrete
certain structural components of the extracellular matrix, such as elastin,
glycosaminoglycans, and fibronectin, and, along with smooth muscle cells, matrix
metalloproteinases, which are critical in arterial remodeling.

2.26 Answer D. Capillaries are the smallest vessels in the vasculature with the largest cross-
sectional and surface area. The capillary wall consists of a single layer of endothelial
cells, thereby allowing the capillaries to act as the exchange vessels of the cardiovascular
system. Because they contain no smooth muscle cells, they lack the ability to change
their diameters.

2.27 Answer B.Seventy to 80% of the population is right heart dominant, with the PDA
originating from the RCA. Approximately 5%-10% of the population is left heart
dominant, with the PDA originating from the LCx artery, and about 10%-20% of the
population is codominant with the PDA supplied by both the LCx artery and RCA. A
“superdominant” LAD artery continuing as a PDA is an extremely rare coronary artery
anomaly.

2.28 Answer D. Stimulation of vascular β-2 adrenergic receptors causes vasodilation, whereas
 stimulation of α-1 adrenergic receptors causes vasoconstriction. Since β-2 receptors are
more sensitive to epinephrine, moderately elevated levels of circulating epinephrine
typically cause vasodilation, whereas higher levels cause α-1 receptor–mediated
vasoconstriction. Angiotensin II and vasopressin are potent vasoconstrictors.

2.29 Answer B. Large arteries have additional circumferential layers of elastic tissue within the
media and are thus referred to as elastic arteries. The epicardial coronary arteries are
elastic arteries, as are the carotids, cerebral arteries, and the aorta. However, at the point
the epicardial arteries turn into the myocardium, usually at a right angle from the parent
vessel, they become more muscular arteries with few if any elastic fibers. The media of
all arteries is contained within a connective tissue layer called the tunica adventitia, or
simply adventitia. The adventitia contains a network of small blood vessels (vasa
vasorum), which is responsible for the nutrition of the outer two-thirds of the artery. The
inner third of the artery derives nutrition by diffusion through the endothelium. The
adventitia also contains nerves, which control the tone of the artery.

2.30 Answer D.Coronary blood flow is approximately 250 mL/min, which represents 4%-5% of
cardiac output.

2.31 Answer A.The LM ostium lacks adventitia and has a greater portion of elastic tissue than
other segments of the coronary tree. This may account for some of the differences in
response to coronary interventions involving this segment of the LM. Since the LM
ostium technically lies within the wall of the aorta, it is subject to diseases affecting the
aortic wall, such as syphilitic aortitis, radiation-induced aortitis, and Takayasu arteritis.
Trifurcation of the LM has been reported in 37% of the general population (Levin DC,
Harrington DP, Bettmann MA, et al. Anatomic variations of the coronary arteries
supplying the anterolateral aspect of the left ventricle: possible explanation for the
“Unexplained” anterior aneurysm. Invest Radiol. 1982;17(5):458-462. PMID: 7141827).
A high takeoff of the LM is not generally felt to have any clinical significance. The
origin of the left coronary has been rarely observed from the noncoronary cusp but has
never been associated with symptoms or complications in this location.

2.32 Answer D.Takotsubo cardiomyopathy is characterized by systolic apical ballooning of the

ventricle with preservation of basal contraction. Excessive amounts of epinephrine
(endogenous or exogenous) are thought to cause it. The ventricular regional wall motion
abnormalities do not follow any particular coronary anatomic pattern and probably are
not a result of transient coronary arterial occlusion. The acute onset of severe chest pain
following emotional stress and the pattern of ventricular involvement are not
characteristic of myopericarditis.

2.33 Answer B.In the TMPG system, TMPG 0 represents minimal or no myocardial blush; in
TMPG 1, contrast material stains the myocardium, and the stain persists on the
subsequent injection; in TMPG 2, contrast material reaches the distal vessel lumen but
dissipates slowly; and in TMPG 3, normal vessel perfusion is noted (Gibson CM,
Schömig A. Coronary and myocardial angiography: angiographic assessment of both
 epicardial and myocardial perfusion. Circulation. 2004;109(25):3096-3105. PMID:
15226226).

2.34 Answer C.The post-PCI angiogram shows occlusion of the right ventricular branch of the
RCA. Anterior ST-segment elevation due to occlusion of a right ventricular RCA branch
has been reported previously and is thought to be a mirror image of right ventricular
ischemia. Occlusion of the sinoatrial branch of the RCA may cause dysrhythmias but not
anterior ST-segment elevation, and microvascular obstruction of the RCA would
typically cause inferior, rather than anterior, ST-segment alterations.

2.35 Answer D.The patient has a large (3.3-mm) conus branch off the RCA that passes upward
and over the right ventricular outflow tract to provide collateral flow to the LAD and
subsequently the other vessels of the left coronary artery system. This type of collateral
system is known as Vieussens ring.

2.36 Answer A.The LAO caudal view projects the LAD upward from the LM in the appearance
of a spider and permits improved visualization of the LM and the bifurcation.

2.37 Answer E. CFR—the ratio of maximal hyperemic blood flow to resting myocardial blood
flow—is obtained from successive (ie, nonsimultaneous) flow measurements. CFR can
be altered by changes in basal and hyperemic flows, both of which are influenced by
hemodynamics, loading conditions, hypertrophy, and contractility. Additionally,
tachycardia increases basal flow and decreases hyperemic flow, thus reducing CFR by
10% for each 15-beat increase in heart rate. A low CFR (<2 in adults) suggests that
either the epicardial resistance is very high (ie, a critical epicardial stenosis is present) or
the microvascular resistance is abnormal, but it does not indicate which is affected. In
clinical terms, CFR is best used to assess the microcirculation in the absence of
epicardial artery narrowings.

2.38 Answer D.At extremes of heart rate (<60 bpm or >100 bpm), the Hakki equation should
not be used to estimate valve area, as it may be inaccurate (Grishkin IuN. Effect of
ritmilen on myocardial refractility and cardiac impulse conduction in patients with
paroxysmal tachycardia. Kardiologiia. 1991;31(5):40-44. PMID: 1895645).

2.39 Answer C. Velocity (V) is proportional to blood flow (Q) and inversely proportional to the
cross-sectional area (A) of the artery and vascular resistance (R). This can be expressed
as V = Q/A. Since flow (Q) is proportional to the pressure gradient (ΔP) and inversely
proportional to resistance (Q = ΔP/R), then velocity (V) = ΔP/(A × R). Thus, blood flow
velocity (V) increases when the flow (Q) increases and decreases if the cross-sectional
area of the artery (A) or vascular resistance increases.
 Radiation Safety, Equipment, and
3
Basic Concepts

Jayant Bagai

QUESTIONS

3.1 Which of the following statements regarding radiation metrics and operator radiation
exposure is CORRECT when comparing transradial versus transfemoral cardiac
catheterizations (including diagnostic angiography and percutaneous coronary
intervention [PCI])?
A. Differences in fluoroscopy time (FT) and dose area product (DAP) between transradial
and transfemoral catheterizations account for all the differences in operator radiation
exposure between these procedures
B. Published data have shown higher radiation exposure during transradial PCI but not
transradial diagnostic coronary angiography
C. Operator experience does not lower higher operator radiation exposure during
transradial compared with transfemoral PCI
D. On average, operator radiation exposure is 50% higher for transradial compared with
transfemoral PCI

3.2 Which of the following statements regarding radiation dose is CORRECT?

A. Absorbed dose is the quantity of radiation that impinges on a tissue, is measured in
Gray (Gy), and varies as a function of depth from the beam entrance port
B. Effective dose takes into account differences in cancer risk between tissues and is a
measure of potential harm from cancer
C. The typical effective dose for a single-photon emission computed tomography
(SPECT) 99mTc sestamibi stress test using 30 mCi during both stress and rest is much
lower than that for diagnostic coronary angiography
D. Tissue weighting factors are applied during calculation of effective dose, and of all
tissues, the gonads have the highest susceptibility to cancer
3.3 Which of the following is INCORRECT regarding Air KERMA (AK [KERMA, Kinetic
Energy Released in MAterial])?
A. AK is a good measure of the dose absorbed by the body and thus the deterministic
effects of an external radiation beam
B. AK provides a precise estimate of the total skin dose at the point of entry of the beam
C. AK may underestimate the peak skin dose (PSD) in an obese patient
D. The interventional reference point (IRP) is commonly described as being 15 cm from
the isocenter toward the x-ray source and is assumed by the fluoroscope as the location
of the patient’s skin

3.4 Which of the following statements about the DAP or KERMA area product (KAP) is
CORRECT?
A. DAP is a good measure of the total amount of radiation delivered to the patient and
hence the stochastic risk
B. DAP can be lowered with the use of collimation
C. Assuming a 100 cm2 field at the patient’s skin, the National Council on Radiation
Protection and Measurement (NCRP) considers DAP ≥500 Gy·cm2 as a substantial
radiation dose level
D. All of the above

3.5 A medical student rotating in the cardiac catheterization lab asks you about the purpose of
and calculation of exposure from the two radiation dosimeters worn by you (Figure
Q3.5.1). What do you tell her?
 Figure Q3.5.1

A. The badges should be worn outside the lead apron at the collar level on the left side and
at the level of the waist
B. The waist level badge should be worn under the apron and the effective dose measured
by it should be <5% of the collar badge reading for a 0.5-mm lead equivalent apron
C. Patient exposure is roughly 100 times that of operator exposure
D. Based on the inverse square law, exposure to the circulator, who is at least 4 times the
distance from the primary operator, will be roughly 1/2 of the dose to the primary
operator

3.6 If the beam width is 10 cm and the dose rate 30 mGy/min at position A, in Figure Q3.6.2,
what is the dose rate at position B, which is twice the distance from the x-ray source?
 Figure Q3.6.2

A. 60 mGy/min
B. 15 mGy/min
C. 7.5 mGy/min
D. None of the above

3.7 The most optimal method to improve contrast between bone and soft tissues is by:
A. Increasing kilovoltage peak (kVp)
B. Decreasing kVp
C. Increasing milliampere (mA)
D. Decreasing mA
3.8 Image graininess or noise can be reduced by which of the following?
A. Increasing mA
B. Magnification
C. Steeper angles
D. Using digital subtraction angiography (DSA)

3.9 Which of the following statements is CORRECT regarding collimation (Figure Q3.9.3)?

Figure Q3.9.3

A. Collimation can reduce contrast and image-to-noise ratio because it can paradoxically
decrease mA and increase scatter
B. The dose per pulse delivered to the detector decreases when optimal collimation is used
 C. Collimation is of no value when using magnification
D. The collimator is an adjustable lead shutter attached to the beam exit port of the x-ray
source

3.10 Which of the following is CORRECT regarding magnification?

A. Detector area increases with magnification requiring a smaller number of photons to
maintain the same level of noise, which results in improved contrast
B. Using electronic magnification to decrease the field of view (FOV) from 25 to 12 cm
quadruples the patient dose rate (in mGy/s)
C. Geometric magnification can be achieved by lowering the detector and table as much
as possible to decrease the distance between the source and the detector
D. Geometric magnification can be achieved by raising the detector substantially above
the patient’s chest, which will also lower patient skin dose

3.11 Which of the following combinations of table and detector height results in the highest
patient dose and scatter to the operator (Figure Q3.11.4)?
 Figure Q3.11.4

A. Table low and detector low

B. Table high and detector high
C. Table high and detector low
D. Table low and detector high

3.12 Which of the following is INCORRECT regarding operator exposure?

A. Ceiling-suspended shields are most effective if they are positioned below the table in
front of the x-ray source and decrease radiation exposure to the operator’s head, neck,
and eyes
B. A short operator leaning forward receives significantly more radiation than a taller
operator standing straight
C. A pregnant female operator can continue to safely work in the cath lab, wearing at least
a 0.25-mm lead apron, due to the low scattered dose to the uterus as assessed with a
waist badge under the apron
D. Disposable radioabsorbent drapes have been shown to be of value in lowering operator
exposure but can increase patient dose if incorrectly positioned

3.13 Which of the following is true regarding stochastic events?

A. They occur above a certain threshold and their severity is proportional to the dose
absorbed
B. The probability of a stochastic event is thought to increase approximately linearly with
 dose
C. The likelihood of stochastic event will reach 100% at very large doses
D. Radiation-induced mutations of germ cells in exposed humans can be passed on to their
offspring

3.14 A patient underwent a complex PCI for a left circumflex chronic total occlusion (CTO). A
week following the procedure, the patient’s wife noted a rectangular area of redness over
the left side of his lower back, which was followed by development of a painful area of
flaking and peeling skin 1 month later. Nine months following the procedure, there
continues to be absence of hair growth and indurated skin over the area. Based on this
history, what must have been the expected cumulative AK recorded by the fluoroscope
after the CTO PCI to cause these skin changes?
A. 2-5 Gy
B. >15 Gy
C. 5-10 Gy
D. 10-15 Gy

3.15 The American College of Cardiology (ACC)/American Heart Association (AHA)/Society

for Cardiovascular Angiography and Interventions (SCAI) PCI guidelines provide a
class I recommendation to educate patients about the potential for a skin injury and
ensure appropriate follow-up within 30 days for patients with total AK at reference
point:
A. >2 Gy
B. >3 Gy
C. >4 Gy
D. >5 Gy

3.16 What is the ALARA (as low as reasonably achievable) principle of radiation safety based
on?
A. The linear-no threshold theory
B. The fact that there is no dose threshold below which radiation does not contribute to
cancer risk
C. The proportional increase in cancer risk as the patient is exposed to larger doses
D. All of the above

3.17 The solid organs that are most radiation-sensitive include which of the following?
A. Brain, salivary gland, skin, and bone cortex
B. Testes and ovaries
C. Bladder, esophagus, liver, and thyroid
 D. Bone marrow, colon, lung, stomach, and female breast

3.18 Which of the population groups is expected to have the highest lifetime attributable risk
of cancer incidence after radiation exposure?
A. Young women of reproductive age group
B. Males of age <15 years
C. Middle-aged male smokers with diabetes and high body mass index (BMI)
D. Female infants

3.19 Which of the following adjustments will lower the cumulative AK to the greatest extent
during a complex PCI?
A. Reducing fluoroscopy frame rate to 7.5 frames per second (fps)
B. Lowering cine acquisition rate to 10 fps
C. Beam spreading
D. Consistently using fluoro save

3.20 Operator and staff exposure limits based on the Nuclear Regulatory Commission (NRC)
for non-federal facilities are as follows:
A. 150 mSv to the lens of the eye, 50 mSv to the whole body, 500 mSv to the hands,
forearms, ankles, and feet per year. Cumulative lifetime dose less than 50 × (N − 18)
mSv, where N is the age of the provider
B. Less than 12.5 mSv or 1.25 rem to the whole body, head, and trunk or lenses of the eye
in any quarter of the year
C. Less than 20 mSv/year equivalent dose limit for the lens of the eye (averaged over 5
years) with no year exceeding 50 mSv
D. Less than 2.5 mSv/year equivalent dose limit for the lens of the eye

3.21 Which of the following statements is CORRECT (Figure Q3.21.5)?

Figure Q3.21.5 Depicts the energy spectra of x-rays produced by a typical cardiac fluoroscopy unit. Dashed
lines represent a change that has been made to the settings.

A. Increasing tube voltage increases the mean number of photons, and radiation dose is
more or less proportional to the square of the voltage
B. Patient dose is approximately 2,000 times higher than operator dose
C. Image noise is proportional to the square root of the detector dose
D. The dose per frame during cine acquisition is double that during standard-dose
fluoroscopy

3.22 With regard to DSA, which of the following is INCORRECT (Figure Q3.22.6)?

Figure Q3.22.6
 A. DSA allows use of a smaller volume of contrast for high-quality images compared with
unsubtracted imaging
B. Dose rates per frame are 6 times higher than for standard cine acquisition
C. DSA is excellent for reducing image noise
D. Frame rates used during DSA imaging are much lower compared with those used
during standard coronary cineangiography

3.23 To effectively decrease image noise, one can do which of the following?
A. Increase display contrast
B. Use last image hold instead of cine
C. Use collimation
D. Increase peak voltage (kVp)

3.24 To obtain the highest image sharpness and least geometric blur:
A. Use a small focal spot and low magnification
B. Use a small focal spot and high magnification
C. Use a large focal spot and low magnification
D. Use a large focal spot and high magnification

3.25 Which of the following is CORRECT?

A. The K-absorption edge refers to the abrupt decrease in absorption of x-ray photons
whose energy is just beyond the binding energy of the K-shell electrons of the
absorbing atom
B. The K-shell absorption edge of iodine is 70 keV
C. The K-shell binding energy of an element increases with its atomic number
D. X-ray photons that completely pass through the patient’s body without interaction
contribute to most of the image

3.26 Which of the following statements is INCORRECT?

A. Modern x-ray systems have become increasingly efficient such that almost 90% of the
electrical energy delivered to the tube is converted to x-rays
B. An aluminum filter is a mandatory requirement of x-ray systems to absorb low-energy
x-ray photons
C. Wedge filters are semitransparent copper shutters that reduce excessive brightness
caused by bordering lung tissue
D. An anteroposterior (AP) caudal projection is expected to result in a lower tertile of AK
compared with right anterior oblique (RAO) cranial
3.27 The NRC defines substantial radiation dose limits (SRDL) for PSD, AK, DAP, and FT as
follows:
A. PSD > 5 Gy, AK > 15 Gy, DAP > 500 Gy·cm2, FT > 60 min
B. PSD > 5 Gy, AK > 10 Gy, DAP > 1,000 Gy·cm2, FT > 60 min
C. PSD > 2 Gy, AK > 5 Gy, DAP > 1,000 Gy·cm2, FT > 120 min
D. PSD > 3 Gy, AK > 5 Gy, DAP > 500 Gy·cm2, FT > 60 min

3.28 With regard to patient radiation dose during endovascular interventions, which of the
following statements is INCORRECT?
A. Aortoiliac interventions result in significantly higher DAP compared with femoral and
below-knee interventions
B. Approximately 7% of endovascular interventions result in DAP >500 Gy·cm2
C. Elevated BMI does not have a significant impact on patient radiation dose during
endovascular interventions as compared with coronary interventions
D. Due to the relatively low radiation exposure during endovascular interventions,
counseling and follow-up are not usually required

3.29 Which of the following statements is INCORRECT?

A. The initial x-ray detector used was the fluoroscopic screen, followed by the image
intensifier and then the flat panel detector (FPD)
B. The most commonly used materials in FPDs are cesium and selenium
C. Image intensifiers for vascular imaging require substantially lower dose rates than
cardiac image intensifiers
D. One terabyte can store approximately 2,500 coronary angiograms in DICOM (Digital
Imaging and Communication in Medicine) format

3.30 Which of the following regarding fluoroscopy is INCORRECT?

A. During fluoroscopy at 15 fps and pulse width of 5 ms, the x-ray beam is on for only 5
ms out of the 66.7 ms duration of each frame, with the gap filled in using digital video
technology
B. As long as AK is monitored and reasonable, the operator can be sure that a particular
patient’s body part is not receiving an excessive skin dose
C. Digital techniques like recursive filtering can result in the appearance of a “ghost
coronary wire”
D. In the United States, Food and Drug Administration (FDA) regulations mandate the
maximum tabletop fluoroscopic dose rate at 88 mGy/min

ANSWERS AND EXPLANATIONS

3.1 Answer D.Transradial coronary angiography and PCI are associated with a 100% and 50%
increase in operator radiation exposure, respectively, compared with transfemoral
procedures. Increased transradial experience/expertise can allow operators to achieve FT
comparable to transfemoral procedures. However, the radiation exposure to a transradial
operator is disproportionately higher than the differences in FT and DAP between
transradial and transfemoral cardiac catheterization. Physicians received an average,
normalized, effective dose to their thorax of 77 µSv per transradial procedure versus 41
µSv when performing transfemoral catheterization, a statistically significant difference
(Lange HW, von Boetticher H. Randomized comparison of operator radiation exposure
during coronary angiography and intervention by radial or femoral approach. Catheter
Cardiovasc Interv. 2006;67(1):12-16. PMID: 16331696). The large RAD-MATRIX
study of 8,404 patients, a radiation substudy of the MATRIX (Minimizing Adverse
Hemorrhagic Events by Transradial Access Site and Systemic Implementation of
AngioX) trial, reported that compared with femoral access, radial access was associated
with a greater operator and patient radiation exposure when performed by expert
operators in current practice (Sciahbasi A, Frigoli E, Sarandrea A, et al. Radiation
exposure and vascular access in acute coronary syndromes: the RAD-matrix trial. J Am
Coll Cardiol. 2017;69(20):2530-2537. PMID: 28330794). After normalization of
operator radiation dose by FT or DAP, the difference remained significant. For every
100 transradial catheterizations performed, an operator receives an excess radiation dose
equal to six chest x-rays compared with the same procedures performed transfemorally.
This is postulated to be due to greater proximity to the x-ray tube and scatter from the
patient’s pelvic bones. Therefore, in addition to operator experience and technique, the
correct use of effective shielding, long tubing, and radiation safety practices is essential
to lower operator exposure.

3.2 Answer B. Effective dose is a measure of the estimated potential for the biological effect
(stochastic effect such as cancer) of a particular absorbed radiation dose on an organism.
It is calculated as the sum of the equivalent dose received by each organ multiplied by
the coefficient of radiation sensitivity (tissue weighting factor) of that organ. It is
measured in Sievert (Sv), such that an effective dose of 1 Sv is associated with the same
stochastic risk that accompanies an absorbed dose of 1 Gray (Gy). Effective dose is a
useful metric to compare the radiation dose of different procedures. The typical effective
dose of a 30 mCi/30 mCi 99mTc stress test is 18 mSv and is comparable to that of
diagnostic invasive coronary angiography (2-20 mSv). The bone marrow, colon, lung,
stomach, and breast have a tissue weighting factor of 0.12, which is higher than that of
the gonads (0.08). Absorbed dose is the concentration or intensity of radiation energy
that is deposited (not just impinging) per unit mass of tissue and is expressed in Gy,
which is the joules of energy deposited per kilogram of tissue.

3.3 Answer B.AK or Air KERMA is a parameter used to measure exposure from an external
radiation beam. It is the energy (in joules) that is released per kilogram of absorbing
material (which is air in medical x-ray applications). In fluoroscopy, AK is the amount
of energy per unit mass absorbed by air at the assumed location of the skin. The
fluoroscope assumes that the patient’s skin is located at the IRP, which is 15 cm from the
isocenter of rotation of the C-arm toward the x-ray source. In an obese patient, the skin
 may be much closer to the source than the IRP, which can result in underestimation of
the skin dose. While cumulative AK calculated by the fluoroscope is a reasonable
estimate of the risk of skin injury, the actual skin dose can vary due to the location of the
IRP, dose splitting caused by movement of the x-ray source, and scattered radiation that
is absorbed by the skin.

3.4 Answer D.DAP is the product of a beam’s KERMA and its cross-sectional area with units
of Gy·cm2. It is a measure of the total x-ray energy in a beam. It is the best dose metric
for estimating the stochastic risk to the patient and the amount of scatter that the operator
and room staff are exposed to. Collimation lowers the beam cross-sectional area without
affecting the beam strength and lowers DAP.

3.5 Answer B.Estimates of exposure are obtained using radiation monitors worn by medical
personnel. Ideally, two badges should be worn, one outside on the collar to measure the
dose to the head—H(col)—and one beneath the apron—H(u)—to determine the
radiation level that penetrates the lead apron. E (estimate) = 0.5 H(u) + 0.025 H(col).
Effective dose can also be estimated with a single badge worn on the collar. To denote
effective protection from the apron, the under-apron reading should be <5% of the collar
badge reading. Based on the inverse square law, doubling the distance from the source
will lower the dose rate by a factor of 4. Therefore, quadrupling the distance is expected
to lower the dose rate 8-fold. Standing 3 m from the x-ray tube affords similar protection
to wearing a lead apron.

3.6 Answer C.As mentioned in the answer to Question 3.5, radiation dose is proportional to
the inverse of the square of the distance from the x-ray source. Doubling the distance
will lower the dose by 4-fold, that is, from 30 to 7.5 mGy/min.

3.7 Answer B. Kilovoltage peak (kVp) is the peak potential applied to the x-ray tube, which
accelerates electrons from the cathode to the anode in radiography or computed
tomography. Tube voltage, in turn, determines the quality of the photons generated.
Increasing kVp produces high-energy x-rays that penetrate the patient’s body without
interacting with the tissues and are too energetic to be absorbed by the iodine in the
contrast. Raising kVp raises radiation dose but lowers contrast by decreasing differential
absorption between dense structures such as bone and light structures such as fat. Tube
voltage between 50 and 120 kVp provides the best compromise between contrast and
penetration. Increasing tube current (mA) increases the number of photons with no effect
on the energy spectrum of the x-rays. Larger, denser, and thicker body parts require
higher mA, but raising mA does not necessarily improve image contrast.

3.8 Answer A.Tube current (mA) is defined as the number of electrons accelerated across the
tube per unit time and determines the number of x-ray photons produced per unit time.
Image noise is produced by random variation in the number of x-ray photons striking the
detector, typically a decrease in their number (referred to as quantum mottle). Noise is
inversely proportional to the square root of the tube current. Increasing mA reduces
noise and graininess of the image. Magnification, steeper angles, and DSA are other
 causes of increased noise.

3.9 Answer D.A collimator is a lead shutter attached to the beam exit port on the x-ray tube. It
reduces the number of low-energy photons that reach the detector, which improves
contrast and signal-to-noise ratio. Without collimation the number of photons striking
the detector increases; this lowers mA and makes the image dark. In addition, when
collimation is used, a smaller detector area receives the beam, and DAP that is
proportional to the size of the imaged area decreases. With magnification, collimation is
useful, but it has no effect on the higher dose per pulse delivered in zoom modes.

3.10 Answer B. With electronic (detector size) magnification, image information from only a
small part of the detector is expanded to fill the display monitor. The number of photons
per pixel decreases, resulting in reduced contrast. This causes the automatic exposure
control (AEC) feature of the fluoroscope to increase the radiation output. Magnification
from a 25- to a 12-cm FOV can quadruple the dose rate (Anderson CM, Leidholdt EM
Jr. An Introduction to Fluoroscopic Safety. Department of Veterans Affairs course.
Version August 19, 2013). Geometric magnification is achieved by either moving the
detector further from the patient or by moving the patient closer to the x-ray source, such
that the detector is further away (not closer) to the source. Raising the detector
substantially above the patient causes beam divergence, which decreases the size of the
beam entrance port to the patient and increases the patient skin dose. The amount of
radiation to the staff also increases due to the effect of scatter.

3.11 Answer D. Lowering the table increases the patient dose, especially the (PSD), and raising
the detector high above the patient markedly increases the scatter of photons from the
divergent x-ray beam striking the table and the patient and also results in geometric
magnification that increases x-ray output (as explained in the answer to Question 3.10).
The operator’s primary source of exposure is the scattered x-ray photons as opposed to
the direct beam. Raising the table very high not only lowers patient skin exposure but
also increases the distance between the source and the detector. This lowers the detector
dose (inverse square law). The x-ray tube automatically increases kilovolt (kV) to
maintain the detector dose, which results in reduced image contrast. Best practices for
radiation safety call for raising the table as much as feasible and keeping the detector
close to the patient’s chest. This position can lower patient dose by a factor of 2.6
compared with a low table and high detector (Christopoulos G, Makke L,
Christakopoulos G, et al. Optimizing radiation safety in the cardiac catheterization
laboratory: a practical approach. Catheter Cardiovasc Interv. 2016;87(2):291-301.
PMID: 26526181).

3.12 Answer A. Ceiling-suspended shields should be positioned between the operator’s face and
the patient, instead of below the table. These shields protect the operator’s face from x-
rays that scatter after striking the table top and the patient’s body. Due to the effect of
scatter, shorter operators receive more radiation than taller operators, especially if they
are leaning forward. Standing on a step stool if feasible will lower their exposure.
Pregnant women can continue to safely work in the cath lab wearing protective lead, as
 the primary source of radiation to the fetus is scattered radiation from the woman’s
pelvic organs. For pregnant patients, a radiation dose of >0.1 Gy to the fetus can occur
with prolonged imaging of the abdomen/pelvis and in such cases postponing the
procedure should be discussed with the patient. Disposable radiation drapes have been
shown to lower operator exposure but can increase patient exposure if incorrectly
positioned in the imaging field (Musallam A, Volis I, Dadaev S, et al. A randomized
study comparing the use of a pelvic lead shield during trans-radial interventions:
threefold decrease in radiation to the operator but double exposure to the patient.
Catheter Cardiovasc Interv. 2015;85(7):1164-1170. PMID: 25510441).

3.13 Answer B. Stochastic effects are probabilistic effects that occur by chance. An extremely
rare stochastic effect is the development of cancer in an irradiated organ or tissue. The
probability of occurrence is typically proportional to the dose received. Stochastic effects
after exposure to radiation occur many years later (the latent period). These occur due to
radiation-induced damage to a cell’s DNA. While skin reactions have a threshold for
causation, there is no threshold for the development of a stochastic effect (the linear-no-
threshold theory). Excess cancer risk can be detected at a dose as small as 100 mSv in
adults and an even smaller dose in children. The relationship to dose is probabilistic but
the severity is not related to the dose. In other words, a cancer caused by a low dose of
radiation can be just as lethal as a cancer caused by a higher dose, but the more the
patient is exposed to radiation, the higher the chance of a cancer-causing mutation.
However, the probability of developing cancer does not reach 100% even at very high
doses. Fortunately, there is no convincing evidence in humans that mutations affecting
germ cells can be passed on to their offspring (Tatsukawa Y, Cologne JB, Hsu W, et al.
Radiation risk of individual multifactorial diseases in offspring of the atomic-bomb
survivors: a clinical health study. J Radiol Prot. 2013;33(2):281-293. PMID: 23482396).

3.14 The presence of desquamation (flaking/peeling of skin) within 4-8 weeks of the
Answer D.
procedure and prolonged skin atrophy suggest exposure to a PSD in the 10-15 Gy range.
Lower doses result in transient (2-5 Gy) or two-phase (5-10 Gy) erythema and temporary
or permanent epilation. Doses >15 Gy typically result in delayed skin necrosis due to
ischemia of the skin.

3.15 Answer D.The 2011 ACC/AHA PCI guidelines recommend that all patients who received
cumulative AK >5 Gy, as recorded by the fluoroscope, should be counseled on the
potential for skin injury. The physician should document the reason for the high dose,
whether multiple angles were used, and arrange for follow-up within 30 days. A phone
call may be sufficient with a visit scheduled if there is concern for injury. For doses >10
Gy, a physicist should calculate the actual skin dose and an in-person follow-up arranged
in 2-4 weeks, along with detailed documentation and prolonged follow-up. Cumulative
AK >15 Gy is a Joint Commission sentinel event. The physician and/or radiation safety
officer/medical physicist should contact hospital risk management within 24 hours. The
event should be reported to the Joint Commission and as needed to the appropriate State
Department of Health (Levine GN, Bates ER, Blankenship JC, et al. 2011
ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: executive
 summary: a report of the American College of Cardiology Foundation/American Heart
Association Task Force on Practice Guidelines and the Society for Cardiovascular
Angiography and Interventions. Catheter Cardiovasc Interv. 2012;79(3):453-495.
PMID: 22328235).

3.16 Answer D. The ALARA principle is based on the recommendation that x-ray exposure
should be “as low as reasonably achievable.” It is based on the linear-no-threshold
model, which means that there is no threshold below which radiation does not contribute
to risk and a linear relationship between dose and increased future risk of cancer.

3.17 Answer D. Bone marrow, colon, lung, stomach, and breast tissue have the highest
sensitivity to cancer risk from radiation exposure and are therefore ascribed a weighting
factor of 0.12 when calculating effective dose. The gonads have lower sensitivity with a
weighting factor of 0.08 followed by the bladder, esophagus, liver, and thyroid (0.04). In
comparison, radiation exposure to skin, bone cortex, brain, and salivary gland is much
less likely to result in cancer (Anderson CM, Leidholdt EM Jr. An Introduction to
Fluoroscopic Safety. Department of Veterans Affairs course. Version August 19, 2013).

3.18 Answer D. Females are more susceptible to radiation risk compared with males due to the
presence of more radiosensitive breast tissue. Because of a smaller body habitus, a
greater proportion of a child’s body is in proximity to the x-ray beam compared with an
adult. In addition, tissues of growing children have greater mitotic activity and, due to
the latent period for a stochastic event to occur, children are more likely to live long
enough to develop cancer than older adults (Hirshfeld JW Jr, Ferrari VA, Bengel FM.
2018 ACC/HRS/NASCI/SCAI/SCCT expert consensus document on optimal use of
ionizing radiation in cardiovascular imaging: best practices for safety and effectiveness.
Catheter Cardiovasc Interv. 2018;92(2):E35-E97. PMID: 30160063). Therefore, a
female infant exposed to fluoroscopy, especially repeatedly as for congenital heart
disease, is at much higher risk of developing cancer.

3.19 Answer A.The radiation dose during cineangiography is 10-60 times higher than during
fluoroscopy. Despite this, due to the limited number of cineangiographic sequences, the
majority of radiation exposure during PCI is due to fluoroscopy. Lowering fluoroscopic
frame rate from 15 to 7.5 fps was associated with a substantial reduction in patient DAP
during both diagnostic coronary angiography (26% relative risk [RR]; P = .0018) and
PCI (19% RR; P = .13) (Abdelaal E, Plourde G, MacHaalany J, et al. Effectiveness of
low rate fluoroscopy at reducing operator and patient radiation dose during transradial
coronary angiography and interventions. JACC Cardiovasc Interv. 2014;7(5):567-574.
PMID: 24746649).

3.20 Answer A.There are essentially three regulatory bodies that recommend upper limits for
operator radiation exposure—the U.S. Occupational Safety and Health Administration
(OSHA), NRC, and the International Commission on Radiological Protection (ICRP).
Most states in the United States use guidelines established by the NRC, as given in
option A. The limits specified by OSHA, for federal facilities, are stricter than for the
 NRC and are given in option B. ICRP limits in option C are less stringent than for the
NRC. A typical diagnostic coronary angiogram and routine PCI delivers an effective
dose of approximately 5 μSv to an operator standing 1 m from the x-ray source. An
operator performing 500 procedures per year, therefore, receives a total effective dose of
approximately 2.5 mSv/year. This is well below the recommended annual limit of 20
mSv as stated in option C.

3.21 Answer B.Patient effective dose is 2,000-fold higher than operator dose (~10 mSv for a
straightforward angiogram and PCI). Tube voltage determines the energy of the x-ray
photons produced. Tube current (mA) determines the number of photons generated.
Image noise is inversely proportional to the square root of the detector dose.
Cineangiography results in a dose per frame that is approximately 5 times higher than
the standard dose and 10 times higher than low-dose fluoroscopy.

3.22 Answer C. DSAs are highly susceptible to image noise as the subtraction process is
random, causing increased quantum mottle. For this reason, all the images are acquired
at a high dose per frame (1,200 nGy/frame compared with 200 nGy/frame for
cineangiography). Because of the high dose, DSA should be acquired at the lowest
clinically usable frame rate and duration as possible. The operator and staff should step
back and ideally be behind a lead shield or outside the room during image acquisition.

3.23 Answer C. Collimation reduces the number of scattered photons reaching the detector,
which do not contribute to the image but increase noise due to quantum mottle (random
variation in the number of photons striking different parts of the detector). It improves
image contrast and reduces noise. Increasing kV does not improve image noise but
lowers image contrast. On the other hand, increasing mA increases the dose reaching the
detector. This increases signal-to-noise ratio and image quality by lowering “graininess.”
It is better to use a lower kV to provide contrast when image graininess is less of a
concern. The “last image hold” feature on fluoroscopes is an FDA-mandated feature in
which the last image is displayed instead of the monitor turning blank after stepping of
the pedal. It has much lower quality than live fluoroscopy or cineangiography.

3.24 Answer A.Accelerated electrons are focused on to a focal spot on the rotating anode. The
smaller the focal spot, the sharper the image. Shorter pulse duration and higher pulse rate
also reduce blur from motion, such as in moving coronary arteries. The effect of the
focal spot size is impacted by the distance between the source and the patient and is
amplified by a greater distance (geometric magnification). Therefore, the sharpest image
is produced with a small focal spot and low geometric magnification and the least sharp
with a large focal spot and high geometric magnification (Balter S, Moscucci M.
Cineangiographic imaging, radiation safety and contrast agents. In: Mosscucci M.
Grossman and Baim’s Cardiac Catheterization, Angiography and Intervention. 9th ed.
Wolters Kluwer; 2021:19-44).

3.25 Answer C.The K-shell is the innermost shell of electrons surrounding an atomic nucleus
and these electrons can be ejected from their path when struck by so-called ionizing
 radiation such as x-rays at an energy above their binding energy. The K-absorption edge
refers to the abrupt increase in absorption of x-ray photons whose energy is just beyond
the binding energy of the K-shell electrons of the absorbing atom. The K-shell
absorption edge of iodine is 31 keV and it strongly absorbs x-photons in the range of 31-
70 keV. K-shell binding energy increases with the atomic number of the element. The
spectrum of x-rays created by increasing kV is further away from the region of maximal
iodine absorption. They reduce the differential penetration of photons by tissue and
iodine lowering image contrast. They pass through the tissues without interaction and do
not contribute to the image.

3.26 Answer A. Only 10% of the electrical energy from an x-ray tube is converted to x-rays and
the remainder is converted to heat. Aluminum filters absorb low-energy x-ray photons
before they enter the patient’s body to concentrate the x-ray beam just above the K-
absorption edge of the iodine in contrast media and are mandatory. Filters of different
thicknesses are selected by the machine’s automatic dose control to increase the
visibility of contrast while reducing patient dose (spectral shaping). Wedge filters should
be used to reduce the brightness caused by the decreased x-ray absorption of lung tissue
bordering the cardiac silhouette. Less steep projections such as AP caudal result in much
lower scatter and patient dose compared with steeper angles such as RAO cranial,
especially in obese patients.

3.27 Answer D. The NRCP defines SRDL as any of the following: PSD >3 Gy, AK >5 Gy, DAP
>500 Gy·cm2 (assuming a 100 cm2 field at the patient’s skin), FT >60 minutes. Initial
notification limits are AK >3 Gy, DAP >300 Gy·cm2, FT >30 minutes, with subsequent
notifications at AK = 1 Gy, DAP = 100 Gy·cm2, and FT = 15-minute increments
(Chambers CE, Fetterly KA, Holzer R, et al. Radiation safety program for the cardiac
catheterization laboratory. Catheter Cardiovasc Interv. 2011;77(4):546-556. PMID:
21254324).

3.28 Answer D. Proximal lesion intervention, such as aortoiliac, requires a larger FOV with
greater intervening bone and soft tissue and is the strongest predictor of patient exposure,
with mean DAP values 6 times higher compared with below-knee interventions. Other
predictors of high DAP are procedure duration, BMI, male gender, bifurcation lesions,
diabetes, and hypertension. Conversely, ipsilateral antegrade access is the strongest
predictor of lower DAP. Seven percent of endovascular interventions result in patient
exposure that exceeds the SRDL, specified by the NRCP (see answer to Question 3.27).
Radiation safety, patient education, and follow-up are of equal importance during
endovascular as for coronary interventions (Goldsweig AM, Kennedy KF, Abbott JD, et
al. Patient radiation dosage during lower extremity endovascular intervention. JACC
Cardiovasc Interv. 2019;12(5):473-480. PMID: 30846087).

3.29 Answer D.Vascular image intensifiers, which provide a larger FOV of 40 cm, require a
higher input dose compared with cardiac image intensifiers with a smaller FOV (17 cm).
The earliest x-ray detectors for coronary angiography were fluoroscopic screens,
followed by image intensifiers, and now FPDs. The so-called indirect FPDs first convert
 the x-ray beam from the patient to visible light with a cesium iodide scintillator and then
into a stream of electrons with a photocathode. A zinc cadmium scintillator then converts
the electron image to brighter visible light. The direct FPDs use a selenium layer to
directly convert x-rays into an electron signal, which is then digitized to an image. One
terabyte can store approximately 2,500 coronary angiograms displayed in a 512 × 512-
pixel matrix using the DICOM format (Balter S, Moscucci M. Cineangiographic
imaging, radiation safety and contrast agents. In: Mosscucci M. Grossman and Baim’s
Cardiac Catheterization, Angiography and Intervention. 9th ed. Wolters Kluwer;
2021:19-44).

3.30 Answer B.AK will not reflect a dangerously high PSD to a patient body part, for example,
an arm that is close to the x-ray tube. Severe skin injuries can occur if the patient’s hand
drops off the armrest and comes close to the x-ray tube. The typical duration of a single
x-ray pulse during fluoroscopy, also known as pulse width, is 5 ms. It is different from
the number of x-ray fps. Recursive filtering is a technology that combines the current
and preceding frames into an averaged image to reduce noise. This can result in the
appearance of a double image such as a double right coronary or coronary guidewire.
The maximal tabletop rate during fluoroscopy is set at 88 mGy/min (skin dose of ~0.1
Gy/min). A high dose or boost mode at 176 mGy/min can be used but is discouraged. It
produces an audible beep during operation to warn the operator (for instance, if turned
on in error) (Hirshfeld JW Jr, Ferrari VA, Bengel FM, et al. 2018
ACC/HRS/NASCI/SCAI/SCCT expert consensus document on optimal use of ionizing
radiation in cardiovascular imaging: best practices for safety and effectiveness. Catheter
Cardiovasc Interv. 2018;92(2):E35-E97. PMID: 30160063).
4 Inflammation and Arterial Injury

Dhiran Verghese, Mazen Albaghdadi, and Farouc

A. Jaffer

QUESTIONS

4.1 All of the following have proven anti-inflammatory effect after percutaneous coronary
intervention (PCI), EXCEPT:
A. Atorvastatin
B. Abciximab
C. Canakinumab
D. Nitrates

4.2 Which of the following statements is TRUE regarding peripheral arterial disease (PAD)?
A. Elevated C-reactive protein (CRP) is associated with an increased risk of coronary
artery disease (CAD), but not of PAD
B. Cigarette smoking and diabetes are not reliable predictors of developing PAD
C. Patients with rheumatoid arthritis are at higher risk of PAD than those without
D. The rate of CAD is similar in patients with and without PAD

4.3 Which of the following statements are TRUE regarding in-stent restenosis (ISR)?
A. Acute coronary syndrome (ACS) at presentation is an independent predictor of
recurrent ISR at follow-up
B. Diabetes mellitus is a risk factor for ACS but is not associated with increased rates of
ISR
C. Bioresorbable scaffolds have shown to lower the rates of ISR
D. More potent antiproliferative agents, such as everolimus, have no effect on 1-year rates
of ISR
4.4 Which of the following treatment options is TRUE regarding the American College of
Cardiology/American Heart Association (ACC/AHA) guideline recommendations for
the management of ISR?
A. PCI with everolimus-based drug-eluting stent (DES) is a Class IIIB recommendation
for the treatment of single-layer ISR
B. Coronary artery bypass graft (CABG) is preferred over PCI for recurrent ISR
C. Intravascular coronary imaging with intravascular ultrasound (IVUS) or optical
coherence tomography (OCT) is not recommended in ISR due to higher rates of
complications
D. Plain balloon angioplasty (POBA) is an alternative treatment option for single-layer
ISR

4.5 A 68-year-old female patient with diabetes mellitus and current daily smoker presents to
the hospital with chest pain that started 3 hours ago and is associated with shortness of
breath and dizziness. Electrocardiogram (ECG) shows ST-segment depression in leads
II, III, and aVF. Her blood pressure (BP) is noted to be 85/50, and high-sensitivity
troponin is noted to be 3205 ng/mL. Initial lab work demonstrates creatinine of 1.8
mg/dL, hemoglobin of 12.4 g/dL, white blood count (WBC) of 12.1, and lactate of 3.2
mmol/L. Which of the following statements is TRUE regarding this patient?
A. PCI of the nonculprit lesion along with the culprit lesion in the same initial setting is
associated with better outcomes than culprit-only PCI
B. The systemic inflammatory response syndrome (SIRS) that results from cardiogenic
shock is associated with a higher mortality in Society for Cardiovascular Angiography
and Interventions (SCAI) stage C or D, but not in SCAI stage A or B
C. In acute myocardial infarction (AMI) associated with cardiogenic shock, the
deleterious effects of SIRS are primarily mediated by elevated nitric oxide levels
D. SIRS occurring during cardiogenic shock is not associated with increased CRP levels

4.6 Which inflammatory biomarker participates in the causal pathway leading to MI and
cardiovascular events?
A. CRP
B. Interleukin-1 (IL-1)
C. Serum amyloid A
D. Pro-BNP

4.7 Which of the following inflammation-related molecules mediates the initial association of
leukocytes with platelets and facilitates tethering and rolling of leukocytes along the
endothelium?
A. P-selectin
B. β2 integrin
 C. IL-8
D. MCP-1

4.8 Which of the following statements on mechanism of pathophysiology of stent restenosis

versus balloon angioplasty restenosis is TRUE?
A. Negative remodeling does not play a role in restenosis after balloon angioplasty
B. Stented arteries have a larger initial lumen gain compared to arteries after balloon
angioplasty
C. Late lumen loss is lower in stented arteries compared to arteries after balloon
angioplasty
D. The rates of ISR and lesion restenosis treated by balloon angioplasty are similar

4.9 After balloon angioplasty or stent placement, elevation of which of the inflammatory
markers is associated with restenosis?
A. CD11b
B. CD40
C. Serum amyloid A
D. High-sensitivity troponin

4.10 A 67-year-old patient presents to the clinic 3 weeks after a DES was implanted with
complaints of severe pruritic rash and hives. She was started on dual-antiplatelet therapy
(DAPT) with aspirin, ticagrelor, and atorvastatin. What is the best recommendation?
A. Consider switching ticagrelor to clopidogrel or prasugrel and switching the class of
statin, start oral antihistamines and oral steroids
B. Undergo immediate coronary angiography for possible stent thrombosis
C. Stop P2Y12 inhibitor and continue antiplatelet therapy with only aspirin
D. Continue medications and start antihistamines

4.11 A 57-year-old female patient with a past medical history significant for diabetes,
hypertension, and Hodgkin lymphoma status post mantle radiation about 15 years earlier
presents to the emergency department for acute chest pain. ECG demonstrates normal
sinus rhythm with no significant ST-segment changes. High-sensitivity troponin is noted
to be 2,500 at presentation and peaked at 7,500. The left anterior descending (LAD)
artery demonstrated diffuse moderate stenosis. The angiogram of the right coronary
artery (RCA) is shown in Figure Q4.11.1. Which of the following statements is TRUE?
 Figure Q4.11.1

A. The arterial narrowing seen with radiation is often very distal

B. Women have higher rates of cardiovascular events and mortality compared with men
with radiation–induced cardiovascular disease
C. The most common valvulopathy in these patients is aortic stenosis (AS)
D. CABG is usually the preferred treatment option for revascularization compared to PCI

4.12 A 65-year-old male patient presents 2 years after PCI of the LAD. He underwent coronary
angiography for anginal symptoms refractory to guideline–directed medical therapy.
Optical tomography and histology images are shown in Figure Q4.12.2. What is the
most likely mechanism underlying his recurrent symptoms?
Figure Q4.12.2 (Top: OCT image; Bottom from Otsuka F, Byrne RA, Yahagi K, et al. Neoatherosclerosis:
overview of histopathologic findings and implications for intravascular imaging assessment. Eur Heart J.
2015;36(32):2147-2159. Figure 8.)
 A. Neoatherosclerosis
B. Neointimal hyperplasia
C. Stent malapposition
D. Discontinuation of DAPT

4.13 Which of the following is FALSE regarding stent thrombosis?

A. Delayed reendothelization after stent implantation causes higher rates of very late stent
thrombosis (VLST) with first-generation DES as compared to bare-metal stents (BMS)
B. Stent malapposition is a significant cause of early stent thrombosis
C. Late stent malapposition occurs due to positive remodeling of the artery
D. Thinner stent struts are associated with decreased stent thrombosis

4.14 Which of the following is TRUE regarding glycoprotein IIb/IIIa receptor inhibitors?
A. They decrease restenosis rates
B. They lower the rates of stent thrombus by lowering thrombus burden
C. They decrease platelet aggregation and the incidence of periprocedural myonecrosis
D. They are routinely indicated for patients presenting with non–ST-segment elevation-
ACS undergoing PCI

4.15 OCT is performed on a patient 18 months after DES placement for stable angina. Which
of the following findings is shown in Figure Q4.15.3?

Figure Q4.15.3 (From Mintz GS, Matsumura M, Ali Z, Maehara A. Clinical utility of intravascular imaging: past,
present, and future. JACC Cardiovasc Imaging. 2022;15(10):1799-1820. Figure 11.)

A. Stent underexpansion
 B. Stent malapposition
C. Neointimal hyperplasia
D. Stent thrombosis

4.16 A 43-year-old woman was admitted to the emergency department with anginal chest pain.
An ECG revealed ST-segment depressions in leads V2-V6. Emergency coronary
angiography was performed, and a severe stenosis was noted in the proximal LAD
artery. Balloon dilatation was performed with a suboptimal result. Unexpected near-total
occlusion and persistent dye staining developed of the proximal LAD after ballooning
was complete. IVUS was performed, which is shown in Figure Q4.16.4. What is the
next best course of action?

Figure Q4.16.4 Maehara A, Mintz GS, Bui AB, Castagna MT, Walter OR, Pappas C, Pinnow EE, Pichard AD,
Satler LF, Waksman R, Suddath WO, Laird JR Jr, Kent KM, Weissman NJ. Incidence, morphology,
angiographic findings, and outcomes of intramural hematomas after percutaneous coronary interventions:
an intravascular ultrasound study. Circulation. 2002;105(17):2037-42. doi:
10.1161/01.cir.0000015503.04751.bd. PMID: 11980682.

A. Stent placement
 B. Cutting balloon followed by stent deployment
C. Use of rotational atherectomy followed by stent deployment
D. Remove wires and manage medically

4.17 A 76-year-old male patient with end-stage renal disease (ESRD), diabetes, hypertension,
and hyperlipidemia presents to the hospital with chest pain. ECG demonstrated ST-
segment elevation in V3-V5. Patient underwent coronary angiography and stent
placement in the proximal to mid-LAD artery. Post-PCI, an IVUS pullback is shown in
Figure Q4.17.5 (distal-to-proximal). What is the best next step in the management of the
patient?
Figure Q4.17.5 (From Räber L, Mintz GS, Koskinas KC, et al. Clinical use of intracoronary imaging. Part 1:
guidance and optimization of coronary interventions. An expert consensus document of the European
Association of Percutaneous Cardiovascular Interventions [published correction appears in Eur Heart J.
2019;40(3):308]. Eur Heart J. 2018;39(35):3281-3300. Figure 4.)

A. Medical management
B. Referral for CABG
C. Stent deployment
D. Fractional flow reserve to better delineate functional flow at the lesion site

4.18 A 56-year-old female patient who is undergoing cardiac catheterization requests that you
use ticagrelor and not clopidogrel after stent placement. Which of the following
statements regarding ticagrelor as compared to clopidogrel is TRUE?
A. Ticagrelor has similar rates of stent thrombosis compared to clopidogrel
B. Ticagrelor decreases ischemic cardiovascular events compared to clopidogrel in
patients with stable coronary syndromes undergoing PCI
C. Ticagrelor has a delayed onset on action for platelet inhibition compared to clopidogrel
D. Ticagrelor does not suppress post-PCI inflammation beyond that of clopidogrel

4.19 Which of the following is the most common mechanism of ACS?

A. Plaque erosion
B. Plaque rupture
C. Calcific nodule (CN)
 D. Thrombus formation

4.20 Which of the following is TRUE regarding coronary artery inflammation and injury post-
MI?
A. There is no association between persistently high levels of CRP following PCI and 1-
year mortality risk
B. Cardiac macrophages recruited post-MI consist of a homogeneous population
C. In women with ischemia but no obstructive coronary artery (INOCA) disease, there is
no association between cardiomyocyte injury and worse coronary vascular dysfunction
D. Stent deployment with struts in contact with media or lipid core contributes to arterial
inflammation and injury

4.21 Which of the following is TRUE regarding plaque erosion and plaque rupture?
A. Plaque erosion demonstrates abundance of HLA-positive macrophages and T cells at
the site of erosion
B. Eroded plaques are rich in proteoglycans and smooth muscle cells at the luminal
surface
C. Thrombi on the eroded plaque are rich in fibrin and CRP
D. Plaque erosion is the predominant etiology of ACS

4.22 A 53-year-old male patient who is a current smoker undergoes angiography for stable
angina. There is diffuse nonobstructive disease on the angiogram. Which of the
following individual features noted on intravascular imaging is NOT considered high
risk for injury and is NOT associated with increased rate of future events?
A. A thin-cap fibroatheroma
B. Small minimal luminal area
C. High plaque burden
D. A thick calcified plaque

4.23 A 76-year-old patient presents to the hospital for an ACS. Angiography demonstrated an
RCA culprit lesion, and they underwent stent placement in the RCA. An IVUS image of
a nonculprit lesion is shown in Figure Q4.23.6. Which of the following statements is
TRUE regarding the plaque depicted in this image?
Figure Q4.23.6 (From Xu Y, Mintz GS, Tam A, et al. Prevalence, distribution, predictors, and outcomes of
patients with calcified nodules in native coronary arteries: a 3-vessel intravascular ultrasound analysis from
Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT).
Circulation. 2012;126(5):537-545.).

A. It is more common in men

B. It is more often seen in younger individuals less than 50 years
C. It is associated with intraplaque hemorrhage
D. It is the most common cause of ACS

4.24 Assuming similar guideline–directed medical therapy, which of the following statements
is TRUE regarding DES and BMS?
A. Everolimus-eluting stents (EES) exhibit lower rates of acute stent thrombosis and
similar rates of late stent thrombosis, as compared to first-generation DES
B. First-generation DES have higher rates of late stent thrombosis compared to BMS
C. First-generation DES have lower rates of acute and late thrombosis compared to BMS
D. First-generation DES have lower rates of acute stent thrombosis and similar rates of
late stent thrombosis compared to BMS

4.25 Which of the following is TRUE regarding bioresorbable stents (BRS)?

A. BRS have a lower risk of early stent thrombosis compared to second-generation DES
B. Coronary vasomotility after BRS scaffold resorption is higher compared to DES
 C. Long-term positive coronary remodeling is more pronounced for BRS compared to
DES
D. BRS are associated with lower rates of target vessel revascularization compared to
DES

ANSWERS AND EXPLANATIONS

4.1 Answer D. Statins, abciximab, and canakinumab have shown to reduce inflammatory
markers post-MI. Abciximab lowered CRP and IL-6 in the evaluation of 7E3 for the
prevention of ischemic complications (EPIC) trial. Canakinumab was noted to lower IL-
6 in the canakinumab antiinflammatory thrombosis outcome study (CANTOS) trial.
Statins have anti-inflammatory effects that extend beyond the culprit lesion treated and
have shown to have higher benefit in patients with higher CRP levels in the JUPITER
trial. Nitrates do not exert effects via the inflammatory pathway (EPIC Investigators. Use
of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in
high-risk coronary angioplasty. N Engl J Med. 1994;330(14):956-961. PMID: 8121459;
Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab
for atherosclerotic disease. N Engl J Med. 2017;377(12):1119-1131. PMID: 28845751;
Chan AW, Bhatt DL, Chew DP, et al. Relation of inflammation and benefit of statins
after percutaneous coronary interventions. Circulation. 2003;107(13):1750-1756. PMID:
12665489; Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular
events in men and women with elevated C-reactive protein. N Engl J Med.
2008;359(21):2195-2207. PMID: 18997196).

4.2 Answer C. CRP has been shown to be associated with PAD in multiple studies. In the
Physician Health Study, the relative risk of developing PAD in men with CRP >2.1
mg/L was 2-fold higher than men in the lowest quartile of CRP. Similarly, the
relationship between CRP and PAD has been demonstrated in healthy women. Cigarette
smoking is one of the strongest risk factors for developing PAD. Patients with diabetes
are at significantly higher risk for PAD. The prevalence of CAD in patients with PAD is
very high, ranging above 43%. Inflammation associated with autoimmune diseases
including rheumatoid arthritis and systemic lupus erythematosus has been shown to
contribute to an increased risk of PAD in these conditions (Ridker PM, Cushman M,
Stampfer MJ, et al. Plasma concentration of C-reactive protein and risk of developing
peripheral vascular disease. Circulation. 1998;97(5):425-428. PMID: 9490235;
Bloemenkamp DG, van den Bosch MA, Mali WP, et al. Novel risk factors for peripheral
arterial disease in young women. Am J Med. 2002;113(6):462-467. PMID: 12427494;
Brevetti G, Giugliano G, Brevetti L, et al. Inflammation in peripheral artery disease.
Circulation. 2010;122(18):1862-1875. PMID: 21041698).

4.3 Answer A. Patients with ISR who present with an ACS have higher rates of major adverse
cardiac events and recurrent ISR at follow-up as noted in the prevention of restenosis
with tranilast and its outcome (PRESTO) trial. Bioresorbable scaffolds have been noted
 to be associated with higher rates of ISR compared to contemporary second-generation
DES. Hyperinsulinemia and metabolic alterations noted in patients with diabetes
accelerate neointimal hyperplasia, leading to ISR. Newer iterations of DES have
demonstrated excellent long-term thrombotic safety and reduced the incidence of ISR
(Giustino G, Colombo A, Camaj A, et al. Coronary in-stent restenosis: JACC state-of-
the-art review. J Am Coll Cardiol. 2022;80(4):348-372. PMID: 35863852; Assali AR,
Moustapha A, Sdringola S, et al. Acute coronary syndrome may occur with in-stent
restenosis and is associated with adverse outcomes (the PRESTO trial). Am J Cardiol.
2006;98(6):729-733. PMID: 16950172; Dangas GD, Claessen BE, Caixeta A, et al. In-
stent restenosis in the drug-eluting stent era. J Am Coll Cardiol. 2010;56(23):1897-1907.
PMID: 21109112; Cassese S, Byrne RA, Ndrepepa G, et al. Everolimus-eluting
bioresorbable vascular scaffolds versus everolimus-eluting metallic stents: a meta-
analysis of randomised controlled trials. Lancet. 2016;387(10018):537-544. PMID:
26597771; Madhavan MV, Kirtane AJ, Redfors B, et al. Stent-related adverse events >1
year after percutaneous coronary intervention. J Am Coll Cardiol. 2020;75(6):590-604.
PMID: 32057373).

4.4 Answer B.Intravascular coronary imaging is essential to characterize the mechanism and
substrate of ISR. In cases where the significance of ISR is unclear, fractional flow
reserve or nonhyperemic pressure measures can be used to determine physiologic
significance of the stenosis. DES with EES or sirolimus-eluting stents have shown to be
associated with the lowest rates of restenosis and target vessel revascularization. PCI
with everolimus-based DES is a Class IA recommendation for the treatment of single-
layer ISR. CABG may be the preferred approach in recurrent ISR as well as in left main
(LM) ISR and diffuse ISR if the anatomy is suitable, and patients are good surgical
candidates. Another option with recurrent ISR may be brachytherapy. POBA has proven
to be inferior to other options due high recurrence of ISR (Giustino G, Colombo A,
Camaj A, et al. Coronary in-stent restenosis: JACC state-of-the-art review. J Am Coll
Cardiol. 2022;80(4):348-372. PMID: 35863852; Lawton JS, Tamis-Holland JE,
Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery
revascularization: a report of the American College of Cardiology/American Heart
Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol.
2022;79(2):e21-e129. PMID: 34895950; Siontis GC, Stefanini GG, Mavridis D, et al.
Percutaneous coronary interventional strategies for treatment of in-stent restenosis: a
network meta-analysis. Lancet. 2015;386(9994):655-664. PMID: 26334160).

4.5 Answer C. The CULPRIT-SHOCK trial showed worse outcomes with multivessel PCI in
patients with AMI and cardiogenic shock. The 2021 ACC/AHA revascularization
guidelines recommend against routine PCI of nonculprit lesions in the same setting in
patients with AMI and shock. SIRS is frequently observed among patients with MI
complicated by cardiogenic shock and contributes to worsening shock and multiorgan
failure. SIRS is associated with worse outcomes across all SCAI stages of shock. Release
of cardiac cytokines leads to elevated levels of the pro-inflammatory cytokines IL-6 and
CRP, which are independently associated with mortality. Inflammatory cytokines
upregulate nitric oxide synthase, leading to high levels of nitric oxide and thus causing
systemic vasodilation, inhibition of myocardial contractility, and refractory hypotension
 (Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for
coronary artery revascularization: a report of the American College of
Cardiology/American Heart Association Joint Committee on Clinical Practice
Guidelines. J Am Coll Cardiol. 2022;79(2):e21-e129. PMID: 34895950; Jentzer JC,
Lawler PR, van Diepen S, et al. Systemic inflammatory response syndrome is associated
with increased mortality across the spectrum of shock severity in cardiac intensive care
patients. Circ Cardiovasc Qual Outcomes. 2020;13(12):e006956. PMID: 33280435;
Hochman JS. Cardiogenic shock complicating acute myocardial infarction: expanding
the paradigm. Circulation. 2003;107(24):2998-3002. PMID: 12821585).

4.6 Answer B.High levels of CRP are associated with an increased cardiovascular risk, and
lowering CRP associates with clinical benefit in many instances. Although CRP predicts
cardiovascular risk, Mendelian randomization studies do not support a direct causal role
for CRP. Interventional trials have demonstrated upstream drivers of CRP, in particular
IL-1 to be involved in the causal pathway, leading to MI, stroke, and major
cardiovascular events (Ridker PM, Koenig W, Kastelein JJ, Mach F, Lüscher TF. Has
the time finally come to measure hsCRP universally in primary and secondary
cardiovascular prevention? Eur Heart J. 2018;39(46):4109-4111. PMID: 30452612).

4.7 Answer A. P-selectin is expressed by platelets and endothelial cells and plays a critical role
in the tethering and rolling of leukocytes to endothelium. This is followed by firm
adhesion and transmigration, which is dependent on integrin class of adhesion
molecules. IL-8 plays a critical role in recruitment of leukocytes to areas of vascular
inflammation. The cytokine MCP-1 participates in the recruitment of monocytes,
basophils, and T cells (Welt FG, Rogers C. Inflammation and restenosis in the stent era.
Arterioscler Thromb Vasc Biol. 2002;22(11):1769-1776. PMID: 12426203; Zarbock A,
Ley K, McEver RP, Hidalgo A. Leukocyte ligands for endothelial selectins: specialized
glycoconjugates that mediate rolling and signaling under flow. Blood.
2011;118(26):6743-6751. PMID: 22021370).

4.8 Answer B. Negative remodeling and neointimal hyperplasia contribute to restenosis after
balloon angioplasty, with negative remodeling contributing significantly more. Stented
arteries have a much larger lumen gain due to the rigid scaffolding that prevents negative
remodeling, and studies have shown a larger luminal area and lower restenosis in stented
arteries. However, late loss (lumen immediately after follow-up minus lumen at follow-
up) is greater in stented arteries than in arteries undergoing balloon angioplasty (Welt
FG, Rogers C. Inflammation and restenosis in the stent era. Arterioscler Thromb Vasc
Biol. 2002;22(11):1769-1776. PMID: 12426203; Hoffmann R, Mintz GS, Dussaillant
GR, et al. Patterns and mechanisms of in-stent restenosis. A serial intravascular
ultrasound study. Circulation. 1996;94(6):1247-1254. PMID: 8822976; Mintz GS,
Popma JJ, Pichard AD, et al. Arterial remodeling after coronary angioplasty: a serial
intravascular ultrasound study. Circulation. 1996;94(1):35-43. PMID: 8964115;
Fischman DL, Leon MB, Baim DS, et al. A randomized comparison of coronary-stent
placement and balloon angioplasty in the treatment of coronary artery disease. Stent
Restenosis Study Investigators. N Engl J Med. 1994;331(8):496-501. PMID: 8041414).
4.9 Answer A.CD11b is a leukocyte-specific receptor expressed on monocyte/macrophages,
granulocytes, and natural killer cells. Upregulation of CD11b levels is associated with
adverse clinical events and restenosis. Elevated CD11b levels from intracoronary
samples proximal and distal to the angioplasty site as well as systemic venous levels
were found to be linked to restenosis. CD40 ligand, a transmembrane protein on T cells
and activated platelets, interacts with vascular cells, resulting in a variety of
inflammatory responses. Circulating matrix metalloproteinases (MMPs) have recently
been identified as a potential marker of developing ISR (Mickelson JK, Lakkis NM,
Villarreal-Levy G, et al. Leukocyte activation with platelet adhesion after coronary
angioplasty: a mechanism for recurrent disease? J Am Coll Cardiol. 1996;28(2):345-353.
PMID: 8800108; Neumann FJ, Ott I, Gawaz M, et al. Neutrophil and platelet activation
at balloon-injured coronary artery plaque in patients undergoing angioplasty. J Am Coll
Cardiol. 1996;27(4):819-824. PMID: 8613609; Rhein P, Mitlohner R, Basso G, et al.
CD11b is a therapy resistance- and minimal residual disease-specific marker in precursor
B-cell acute lymphoblastic leukemia. Blood. 2010;115(18):3763-3771. PMID:
20228269).

4.10 Answer A. The initial course of action should include switching the class of medications as
the presentation could be from an allergy to one of the medications. DES
hypersensitivity reaction can also be a cause of her symptoms and should be considered
if there is no improvement of symptoms with the initial approach. The RADAR study
demonstrated that both the metallic (nickel) and nonmetallic (polymer) components in
the stent can induce DES hypersensitivity. Hypersensitivity to stent components is
associated with late and very late stent restenosis and stent thrombosis. Referral to an
allergy consultant is also reasonable in this situation (Virmani R, Guagliumi G, Farb A,
et al. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-
eluting stent: should we be cautious? Circulation. 2004;109(6):701-705. PMID:
14744976; Chioncel V, Andrei CL, Brezeanu R, et al. Some perspectives on
hypersensitivity to coronary stents. Int J Gen Med. 2021;14:4327-4336. PMID:
34408475).

4.11 Answer B. Radiation-induced cardiovascular disease typically occurs 10-30 years after
treatment. The major risk factor for cardiovascular events is the total dose of radiation,
with a dose above 30 Gy/m2 considered a high dose. Radiation causes endothelial injury
in the coronary arteries that leads to a pro-inflammatory state, oxidative stress, and
cytokine release. The arterial narrowing seen with radiation is often very proximal and
involves the coronary ostia. The most common valvulopathy associated with radiation–
induced cardiovascular disease is aortic insufficiency. Surgical aortic valve replacement
(AVR) has shown to have worse outcomes in this population with a matched cohort
study, noting a significant increased 6-year mortality (48% vs 7%; P < .001). A 2020
meta-analysis demonstrated transcatheter aortic valve replacement (TAVR) as a safe
treatment option for radiation-induced AS, with similar 30-day mortality compared to
control patients with AS. Women have higher mortality than men with radiation–induced
cardiovascular disease, although reasons are still unclear. CABG can be complicated due
to a hostile chest from radiation, fibrotic stenosed arterial/venous conduits preventing
them from being viable grafts, concomitant radiation–induced lung fibrosis, and
 significant thoracic aortic calcification precluding safe clamping. Because of the
aforementioned reasons, PCI is usually preferred in patients with radiation-induced CAD
(Donnellan E, Masri A, Johnston DR, et al. Long-term outcomes of patients with
mediastinal radiation-associated severe aortic stenosis and subsequent surgical aortic
valve replacement: a matched cohort study. J Am Heart Assoc. 2017;6(5):e005396.
PMID: 28476874; Zafar MR, Mustafa SF, Miller TW, et al. Outcomes after transcatheter
aortic valve replacement in cancer survivors with prior chest radiation therapy: a
systematic review and meta-analysis. Cardiooncology. 2020;6:8. PMID: 32685198;
Belzile-Dugas E, Eisenberg MJ. Radiation-induced cardiovascular disease: review of an
underrecognized pathology. J Am Heart Assoc. 2021;10(18):e021686. PMID:
34482706).

4.12 Answer B. The OCT and histologic images demonstrate substantial homogeneous
neointimal hyperplasia within the stent. Histologically, neointimal hyperplasia is
characterized by smooth muscle cell proliferation embedded in a collagen-rich
extracellular matrix. Neoatherosclerosis, on the other hand, has a heterogeneous
composition on OCT with in-stent necrotic core, fibrous cap, lipid, or calcific
accumulation. Histologically, neoatherosclerosis is characterized by an accumulation of
lipid-laden foamy macrophages with or without necrotic core formation and/or
calcification. Stent malapposition has been associated with late stent thrombosis and is
characterized by stent struts that are unopposed to the intimal layer of the vessel. It has
been more than 1 year since stent implantation, and discontinuation of DAPT is well
accepted at this time frame (Giustino G, Colombo A, Camaj A, et al. Coronary in-stent
restenosis: JACC state-of-the-art review. J Am Coll Cardiol. 2022;80(4):348-372.
PMID: 35863852; Shlofmitz E, Iantorno M, Waksman R. Restenosis of drug-eluting
stents: a new classification system based on disease mechanism to guide treatment and
state-of-the-art review. Circ Cardiovasc Interv. 2019;12(8):e007023. PMID: 31345066).

4.13 Answer B.Stent malapposition is rarely a cause of acute stent thrombosis. Late stent
malapposition resulting from outward arterial wall expansion (positive remodeling)
appears more commonly with DES and has been associated with late stent thrombosis
and VLST. First-generation DES reduced acute and early stent thrombosis rates;
however, reendothelization was significantly delayed with DES when compared to BMS,
which likely underlies the higher rates of VLST with first-generation DES. Thinner stent
struts over the years have lowered the rate of stent thrombosis.

4.14 Answer C. Glycoprotein IIb/IIIa receptor inhibitors decrease platelet aggregation, lower
periprocedural myonecrosis, and improve 30-day outcomes in the BMS era, although
increased significant bleeding rates. In the era of more potent oral antiplatelet agents,
IIb/IIIa antagonists are generally reserved for patients with large thrombus burden or no-
reflow attributable to distal embolization of thrombus. While the EPIC trial
demonstrated abciximab to lower CRP and IL-6, there are no data to support similar
reduction of inflammatory markers with the use of tirofiban or eptifibatide. Furthermore,
none of the glycoprotein IIb/IIIa receptor inhibitors have shown to reproducibly lower
neointimal hyperplasia, ISR, or stent thrombosis (Lawton JS, Tamis-Holland JE,
 Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery
revascularization: executive summary: a report of the American College of
Cardiology/American Heart Association Joint Committee on Clinical Practice
Guidelines. Circulation. 2022;145(3):e4-e17. PMID: 34882436; EPIC Investigators. Use
of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in
high-risk coronary angioplasty. N Engl J Med. 1994;330(14):956-961. PMID: 8121459).

4.15 Answer B. The OCT image demonstrates stent struts that are unapposed to the intima,
demonstrating malapposition of the stent between 11 o’clock and 7 o’clock. Late
acquired malapposition is the most common finding in very late (>1 year) stent
thrombosis. Acute malapposition of <0.4 mm with longitudinal extension <1 mm does
not require intervention as spontaneous neointimal integration is anticipated. However,
in larger volumes of malapposition, especially in the setting of symptomatic late ISR, or
stent thrombosis, intervention might be necessary (Mintz GS, Matsumura M, Ali Z, et al.
Clinical utility of intravascular imaging: past, present, and future. JACC Cardiovasc
Imaging. 2022;15(10):1799-1820. PMID: 36202460).

4.16 Answer B. The image shows an intramural hematoma of the coronary wall between 10
o’clock and 3 o’clock. The use of a cutting balloon will allow for fenestration and
evacuation of blood from the subintimal space into the lumen. This maneuver will permit
appropriate sizing and optimal expansion of a stent, which should be deployed as the
next step. Stenting without prior evacuation of the hematoma could lead to an undersized
stent, increasing the risk of ISR. Furthermore, direct stenting could worsen the situation
by propagating the hematoma forward and jeopardizing flow. Atherectomy is reserved
for calcified lesions and could be dangerous in the setting of a dissection. Medical
management would not be optimal for this patient with a near-total occlusion of the
LAD.

4.17 Answer C.The IVUS images (Figure A4.17.7) demonstrate injury of the proximal LAD
proximal to the deployed stent, with a dissection flap (arrow) and intramural hematoma
(asterisk).
 Figure A4.17.7

Given extension into the media (arrowhead), the patient will need an intervention with
stenting of the edge dissection. Small edge dissections do not need any further
intervention. A recent consensus document classified large treatable intravascular
imaging dissections as those that have a lateral extension >60o, longitudinal extension of
>2 mm, or involvement of the medial or adventitial layers (Räber L Mintz GS, Koskinas
KC, et al. Clinical use of intracoronary imaging. Part 1: guidance and optimization of
coronary interventions. An expert consensus document of the European Association of
Percutaneous Cardiovascular Interventions. Eur Heart J. 2018;39(35):3281-3300.
PMID: 29790954).

4.18 Answer D. Ticagrelor and prasugrel have not been studied for long-term clinical outcomes
in patients with stable ischemic heart disease undergoing PCI. In patients with ACS,
ticagrelor reduced the rate of the composite end point of death from vascular causes, MI,
or stroke. In the PLATO (Platelet Inhibition and Patient Outcomes) trial, ticagrelor
reduced stent thrombosis rates. However, compared to clopidogrel, a positive impact on
arterial injury and inflammation has not yet been demonstrated for ticagrelor or prasugrel
(Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with
acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057. PMID: 19717846).

4.19 Answer B.Plaque rupture remains the predominant cause of ACS, and a thin-cap
fibroatheroma is the most common precursor. Furthermore, intravascular imaging has
demonstrated that plaque ruptures are more common than anticipated and most do not
lead to ACS. After plaque rupture, the next most common etiology of ACS is plaque
 erosion, and the incidence of plaque erosion has been increasing in part related to
increased use of statins that is altering the underlying plaque biology. Loss of endothelial
lining with an intact or absent fibrous cap is a histopathologic hallmark of plaque erosion
(Fahed AC, Jang IK. Plaque erosion and acute coronary syndromes: phenotype,
molecular characteristics and future directions. Nat Rev Cardiol. 2021;18(10):724-734.
PMID: 33953381).

4.20 Answer D. Patients who have elevated CRP (>2 mg/L) immediately after PCI and at 30-
days post-PCI have been at a significantly higher risk for MI and all-cause mortality at 1
year. The CANTOS and colchicine cardiovascular outcomes trial (COLCOT) trials have
demonstrated the potential role of anti-inflammatory therapy post-PCI that may lower
this residual risk and improve outcomes; however, further studies need to validate these
results. In women with INOCA disease, cardiomyocyte injury represented by elevated
high-sensitivity troponin levels has shown to be associated with worse vascular function
on invasive coronary vascular testing as demonstrated in the WISE-CVD study.
Macrophages recruited post-MI participate in wound healing and are heterogeneous
spanning broad phenotypes between classic pro-inflammatory M1 and anti-inflammatory
M2 macrophages. Stent-mediated arterial injury determines adverse healing response
and may increase the risk of restenosis. Injury of the media or lipid core penetration by
stent struts increases the inflammatory response and associates with worse outcomes
(Kalkman DN, Aquino M, Claessen BE, et al. Residual inflammatory risk and the impact
on clinical outcomes in patients after percutaneous coronary interventions. Eur Heart J.
2018;39(46):4101-4108. PMID: 30358832; Al Badri A, Wei J, Quesada O, et al.
Coronary vascular function and cardiomyocyte injury: a report from the WISE-CVD.
Arterioscler Thromb Vasc Biol. 2020;40(12):3015-3021. PMID: 33028098); Holmes DR
Jr, Savage M, LaBlanche JM, et al. Results of Prevention of REStenosis with Tranilast
and its Outcomes (PRESTO) trial. Circulation. 2002;106(10):1243-1250. PMID:
33028098; Peet C, Ivetic A, Bromage DI, Shah AM. Cardiac monocytes and
macrophages after myocardial infarction. Cardiovasc Res. 2020;116(6):1101-1112.
PMID: 31841135).

4.21 Answer B. Plaque rupture is the most common cause of ACS, followed by plaque erosion.
Autopsy studies have shown significant differences in the composition of atherosclerotic
plaques. Plaque rupture, not erosion, has an abundance of HLA-DR–positive
macrophages and T cells. In contrast, plaque erosion demonstrates neutrophil infiltration
and neutrophil extracellular traps (NETs) and is rich in proteoglycans, smooth muscle
cells with only sparsely distributed macrophages, and T cells. The thrombus overlying
ruptured plaques is rich in fibrin and CRP. Thrombi on eroded plaques consist
predominantly of platelets (Kolte D, Yonetsu T, Ye JC, et al. Optical coherence
tomography of plaque erosion: JACC focus seminar part 2/3. J Am Coll Cardiol.
2021;78(12):1266-1274. PMID: 34531028; Farb A, Burke AP, Tang AL, et al. Coronary
plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis
in sudden coronary death. Circulation. 996;93(7):1354-1363. PMID: 8641024; Kolodgie
FD, Burke AP, Farb A, et al. Differential accumulation of proteoglycans and hyaluronan
in culprit lesions: insights into plaque erosion. Arterioscler Thromb Vasc Biol.
2002;22(10):1642-1648. PMID: 12377743).
4.22 Answer D. Multiple studies have assessed various plaque types with the goal of identifying
vulnerable plaques and vulnerable patients. In the PROSPECT I and PROSPECT II
studies and the ATHEROMA project, among several others, predictors of clinical events
included a large plaque burden, thin-cap fibroatheroma, large lipidic arc, and necrotic
core. Minimal luminal area is a strong predictor for future events. Thick calcified
plaques can pose difficulties to stenting when seen at the site of culprit obstructive
lesions, especially when subintimal. However, nonobstructive calcified plaques are
considered more stable than lipid-rich plaques (Stone GW, Maehara A, Lansky AJ, et al.
A prospective natural-history study of coronary atherosclerosis. N Engl J Med.
2011;364(3):226-235. PMID: 21247313; Cheng JM, Garcia-Garcia HM, de Boer SP, et
al. In vivo detection of high-risk coronary plaques by radiofrequency intravascular
ultrasound and cardiovascular outcome: results of the ATHEROREMO-IVUS study. Eur
Heart J. 2014;35(10):639-647. PMID: 24255128).

4.23 The IVUS image (Figure A4.23.8) demonstrates a CN protruding into the
Answer C.
lumen with a typical concave pattern (arrow).

Figure A4.23.8

The most common cause of ACS is plaque rupture (60%-65%), followed by plaque
erosion (30%), and a smaller portion (5%) are caused by CNs. CNs have the greatest
ratio of calcification to plaque area among all vulnerable plaque subtypes. It is associated
with healed fibroatheroma and intraplaque hemorrhage. CNs more often occur in older
(>60) patients with similar rates in men and women and are associated with diabetes and
 chronic kidney disease (Torii S, Sato Y, Otsuka F, et al. Eruptive calcified nodules as a
potential mechanism of acute coronary thrombosis and sudden death. J Am Coll Cardiol.
2021;77(13):1599-1611. PMID: 33795033; Xu Y, Mintz GS, Tam A, et al. Prevalence,
distribution, predictors, and outcomes of patients with calcified nodules in native
coronary arteries: a 3-vessel intravascular ultrasound analysis from Providing Regional
Observations to Study Predictors of Events in the Coronary Tree (PROSPECT).
Circulation. 2012;126(5):537-545. PMID: 22744975).

4.24 Answer B. EES have a thin 81-μm strut cobalt-chromium backbone and a novel polymeric
drug carrier. Large randomized trials and meta-analyses have demonstrated superiority
of second-generation EES-based DES, as compared to first-generation DES and BMS,
for both acute stent thrombosis and late stent thrombosis.
First-generation DES lowered the incidence of early stent thrombosis; however, there
was an observed increased risk of late stent thrombosis and restenosis, likely due to
hypersensitivity, drug toxicity, and persistence of the durable polymer, which impaired
arterial healing (Serruys PW, Ong AT, Piek JJ, et al. A randomized comparison of a
durable polymer everolimus-eluting stent with a bare metal coronary stent: the SPIRIT
first trial. EuroIntervention. 2005;1(1):58-65. PMID: 19758878; Palmerini T, Biondi-
Zoccai G, Della Riva D, et al. Stent thrombosis with drug-eluting and bare-metal stents:
evidence from a comprehensive network meta-analysis. Lancet. 2012;379(9824):1393-
1402. PMID: 22445239).

4.25 Answer C. The Multicenter GHOST-EU registry and a meta-analysis of all trials of BRS
showed an increased risk of early stent thrombosis and VLST. The most likely
mechanism is due to the thicker struts and “scaffold dismantling” (reabsorption of
incompletely endothelialized struts), need for more aggressive lesion preparation, and
poorer radial strength. The 5-year results of the ABSORB trial demonstrated that the
outward remodeling was more significant and frequent for BRS compared to metal
stents. Dilation of the BRS-stented segment to intracoronary nitroglycerin was similar to
segments stented with DES in the ABSORB trial. BRS was associated with higher rates
of target vessel revascularization (Mukherjee D. Device thrombosis with bioresorbable
scaffolds. N Engl J Med. 2017;376(24):2388-2389. PMID: 28402239; Serruys PW,
Katagiri Y, Sotomi Y, et al. Arterial remodeling after bioresorbable scaffolds and
metallic stents. J Am Coll Cardiol. 2017;70(1):60-74. PMID: 28662808; Capodanno D,
Gori T, Nef H, et al. Percutaneous coronary intervention with everolimus-eluting
bioresorbable vascular scaffolds in routine clinical practice: early and midterm outcomes
from the European multicenter GHOST-EU registry. EuroIntervention.
2015;10(10):1144-1153. PMID: 25042421; Sorrentino S, Giustino G, Mehran R, et al.
Everolimus-eluting bioresorbable scaffolds versus everolimus-eluting metallic stents. J
Am Coll Cardiol. 2017;69(25):3055-3066. PMID: 28412389).
 Antiplatelet, Antithrombotic, and
5
Thrombolytic Agents

Birgit Vogel, Alessandro Spirito, and Roxana

Mehran

QUESTIONS

5.1 A 78-year-old woman presents with unstable angina. She takes medication for
hypertension and hypercholesterolemia and has a history of a minor spontaneous
intracranial hemorrhage 2 years ago. She undergoes percutaneous coronary intervention
(PCI) with a single drug-eluting stent implantation in the mid–right coronary artery.
There are no other significant coronary lesions. Which is the most appropriate
antithrombotic regimen post PCI for this patient?
A. Aspirin plus prasugrel for 6 months, followed by aspirin monotherapy
B. Aspirin plus ticagrelor for 12 months, followed by aspirin monotherapy
C. Aspirin plus clopidogrel for 6 months, followed by aspirin monotherapy
D. Aspirin plus clopidogrel for 12 months, followed by aspirin monotherapy

5.2 A 65-year-old man presents to the emergency department with acute chest pain. He is
overweight (body mass index [BMI] 29 kg/m2), has non-insulin-dependent type 2
diabetes, and had gastric bleeding requiring transfusion and endoscopic clipping 3
months ago. The electrocardiogram (ECG) shows nonspecific T-wave changes, and
high-sensitive troponin T is elevated. The coronary angiogram reveals a 90% stenotic
lesion of the mid–left anterior descending artery involving the first diagonal branch,
requiring treatment of the bifurcation with two drug-eluting stents. Treatment is started
with aspirin 81 mg daily and ticagrelor 90 mg twice daily. You are discharging the
patient after an uncomplicated postprocedural hospital course. Since the gastric bleeding,
the patient has been taking a proton pump inhibitor. Which antithrombotic strategy do
you recommend?
A. Continuation of current regimen and clinical reevaluation 3 months after discharge
B. Immediate discontinuation of aspirin and continuation of ticagrelor monotherapy for 9
 months
C. Continuation of current regimen for 12 months
D. Aspirin 81 mg daily plus clopidogrel 75 mg daily for 12 months

5.3 For which of the following antithrombotic drugs a specific reversal agent has been shown
to be effective in restoring hemostasis?
A. Factor Xa inhibitors (rivaroxaban, edoxaban, apixaban, enoxaparin)
B. Dabigatran
C. Ticagrelor
D. All of the above

5.4 The neurologist contacts you for advice on the reversal of oral anticoagulation therapy. A
63-year-old woman with arterial hypertension and treatment with rivaroxaban 20 mg
daily has been diagnosed with acute spontaneous intracranial hemorrhage. The patient
has a history of atrial fibrillation and underwent elective noncomplex PCI 13 months
ago. The neurologist wants to reverse the effect of rivaroxaban. What do you
recommend?
A. Discontinuation of rivaroxaban only. There is no reversal agent for rivaroxaban
B. Discontinuation of rivaroxaban and reversal with andexanet alfa and activated
prothrombin complex concentrates
C. Discontinuation of rivaroxaban and reversal with tranexamic acid
D. Discontinuation of rivaroxaban and hemoadsorption

5.5 The anesthesiologist contacts you regarding a 76-year-old patient on dual antiplatelet
therapy for an elective PCI with drug-eluting stent implantation in his proximal right
coronary artery 3 weeks ago, who now presents with a displaced femoral fracture
needing a nondeferrable surgical intervention. The orthopedist and anesthesiologist
would like to discontinue the P2Y12 inhibitor and ask whether you agree. What is your
recommendation?
A. Discontinue the P2Y12 inhibitor and restart it at the latest 48 hours after the procedure
B. Discontinue the P2Y12 inhibitor and consider bridging with intravenous (IV) heparin
C. Discontinue aspirin
D. Discontinue the P2Y12 inhibitor and consider bridging with cangrelor or a small-
molecule glycoprotein (GP) IIb/IIIa inhibitor

5.6 A 68-year-old patient on vitamin K antagonist for atrial fibrillation is referred to the
catheterization laboratory for stable angina with a positive stress test. The angiogram
shows two-vessel disease amenable to PCI, and the patient undergoes successful
implantation of three drug-eluting stents. The patient has mild impaired renal function
(estimated glomerular filtration rate 40 mL/min/1.73 m2) and has tolerated the vitamin K
antagonist well until now. What is the most appropriate antithrombotic therapy for this
 patient?
A. Vitamin K antagonist, aspirin, and clopidogrel for 1 month with discontinuation of
clopidogrel thereafter
B. Vitamin K antagonist, aspirin, and clopidogrel for 1 month with discontinuation of
aspirin thereafter
C. Direct oral anticoagulant, aspirin, and clopidogrel for 1 month with discontinuation of
aspirin thereafter
D. Direct oral anticoagulant, aspirin, and clopidogrel for 1 month with discontinuation of
clopidogrel thereafter

5.7 A 56-year-old woman on rivaroxaban 20 mg daily due to a segmental pulmonary

embolism that occurred 10 weeks ago has been admitted for acute dyspnea and chest
discomfort. The ECG shows T-wave inversion in the anterior leads, and troponin is
elevated. A triple-rule-out computed tomography (CT) angiography at this time excludes
pulmonary embolism and aortic dissection, whereas it reveals a subocclusive thrombotic
lesion of the proximal left anterior descending artery, confirmed by coronary
angiography. The patient undergoes PCI with implantation of three drug-eluting stents.
The patient has mild impaired renal function (estimated glomerular filtration rate 40
mL/min/1.73 m2). Which antithrombotic strategy is most appropriate?
A. Rivaroxaban 15 mg daily, aspirin 81 mg daily, and clopidogrel 75 mg daily for 1
month with clinical reevaluation afterward
B. Rivaroxaban 15 mg daily plus clopidogrel 75 mg daily for 12 months
C. Rivaroxaban 20 mg daily plus clopidogrel 75 mg daily for 12 months
D. Discontinuation of rivaroxaban and treatment with aspirin 81 mg daily plus clopidogrel
75 mg daily for 1 month with clinical reevaluation afterward

5.8 In patients without indication for chronic oral anticoagulation and no recent PCI, what is
the most appropriate antithrombotic therapy after transcatheter aortic valve replacement
(TAVR)?
A. Dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor for 6 months, followed by
aspirin alone
B. Aspirin alone
C. Rivaroxaban 10 mg daily plus aspirin for 3 months, followed by aspirin alone
D. A direct oral anticoagulant plus clopidogrel for 3 months, followed by aspirin alone

5.9 An 82-year-old woman underwent successful TAVR for symptomatic aortic stenosis.
Before the procedure, she was taking a vitamin K antagonist due to atrial fibrillation.
With regard to the latter, she tolerated the treatment well, and international normalized
ratio (INR) values were in the therapeutic range most of the time. She has no
comorbidities except for anemia due to chronic iron deficiency (hemoglobin 10 g/dL),
which was comprehensively investigated with no specific underlying reason identified.
 The nurse practitioner calls you to confirm the antithrombotic therapy at discharge. What
do you recommend?
A. Continue the vitamin K antagonist
B. Continue the vitamin K antagonist and add aspirin for 3-6 months
C. Replace the vitamin K antagonist with a direct oral anticoagulant
D. Triple therapy with vitamin K antagonist, P2Y12 inhibitor, and aspirin for 1 month,
and dual therapy with vitamin K antagonist plus aspirin thereafter

5.10 The emergency medical service contacts you about a 72-year-old woman with suspected
acute coronary syndrome who is now transported to a PCI-capable hospital for
evaluation. The patient is a smoker and overweight. The ECG does not show ST-
segment elevations. Treatment with aspirin and IV unfractionated heparin has already
been initiated, and you are asked about P2Y12 inhibitor loading. What is your
recommendation?
A. Loading with ticagrelor 180 mg
B. Loading with clopidogrel 600 mg
C. Single dose of clopidogrel 75 mg or ticagrelor 90 mg
D. No P2Y12 inhibitor administration at this time

5.11 A general practitioner asks your opinion about the antiplatelet treatment of a patient who
underwent PCI at your institution 1 year ago. At that time, the 62-year-old man
presented with a very late stent thrombosis of a first-generation drug-eluting stent
implanted 5 years before in the mid–left anterior descending artery. The lesion was
treated with a second-generation drug-eluting stent. The patient has insulin-dependent
type 2 diabetes, which is not well controlled, and stable peripheral artery disease. During
the first year, he had two episodes of self-limiting epistaxis and no ischemic
complications with dual antiplatelet therapy with aspirin and ticagrelor. What is your
recommendation?
A. Stop aspirin and continue with ticagrelor monotherapy
B. Continue the current treatment
C. Stop ticagrelor and continue with aspirin monotherapy
D. Continue aspirin and replace ticagrelor with clopidogrel

5.12 A 59-year-old male smoker who is overweight (BMI 32 kg/m2) and with frequent angina
during physical activity is admitted to the cardiology department for an elective coronary
angiography. The coronary CT angiography detected an intermediate (50%-70%)
stenosis of the mid–right coronary artery. The nurse asks whether any medication has to
be administered before the patient is transferred to the catheterization laboratory. The
patient has been taking aspirin and a statin since he received the results of the coronary
CT angiography. What is your recommendation?
A. Loading with clopidogrel 300 mg
 B. IV heparin
C. No further treatment at this time
D. A and B

5.13 A 67-year-old African American woman with type 2 diabetes underwent elective
implantation of three drug-eluting stents for a long lesion (60 mm) of the proximal left
circumflex (LCx) artery in the setting of stable ischemic heart disease. In addition to
aspirin, which antiplatelet agent would you recommend for the next 6 months?
A. Clopidogrel 75 mg daily
B. Prasugrel 5 mg daily
C. Ticagrelor 90 mg twice daily
D. Prasugrel 10 mg daily

5.14 A 59-year-old patient presented with acute coronary syndrome and underwent PCI with
drug-eluting stent implantation in the proximal left anterior descending artery 5 months
ago. Since then, he has been taking aspirin 81 mg daily and prasugrel 10 mg daily. The
patient needs to undergo hip replacement surgery because of chronic pain that severely
limits his ability to walk. According to the orthopedic surgeon, the intervention cannot
be performed on ongoing dual antiplatelet treatment. What is your recommendation with
regard to antithrombotic therapy?
A. Surgery is reasonable at this time but allow for discontinuation of prasugrel 7 days
prior to surgery and restart 48 hours thereafter
B. Delay surgery to allow for full 6 months of dual antiplatelet therapy after PCI before
discontinuing prasugrel
C. Delay surgery to allow for full 12 months of dual antiplatelet therapy after PCI before
discontinuing prasugrel
D. Surgery is reasonable at this time but allow for discontinuation of aspirin 7 days prior
to surgery and restart 48 hours thereafter

5.15 In 2019, the Bleeding Academic Research Consortium (BARC) defined criteria to
identify patients at high bleeding risk (HBR). What is the expected rate of major
bleeding (ie, BARC 3 or 5 bleeding) at 1 year in patients deemed as HBR?
A. ≥2%
B. >6%
C. ≥4%
D. >8%

5.16 A patient with type 2 diabetes, non–ST-segment elevation myocardial infarction (non-
STEMI), and three-vessel disease is referred for coronary artery bypass graft surgery.
The patient received a loading dose of ticagrelor 180 mg in the ambulance 6 hours ago.
The patient is hemodynamically stable. The cardiac surgeon would like to discuss the
 best strategy to reduce the risk of bleeding associated with coronary artery bypass graft
surgery in this patient. What do you recommend?
A. Surgery deferral for 5 days
B. Immediate platelet transfusion and surgery the same day
C. Bentracimab and surgery the same day
D. B and C

5.17 An 80-year-old patient with STEMI received fibrinolytic therapy because primary PCI
was not immediately available and the transfer to a hospital with PCI capability was
anticipated to be >120 minutes from the initial presentation. Upon arrival at the PCI-
capable hospital 3 hours later, the patient was referred to rescue PCI due to evidence of
failed reperfusion. What is the most appropriate P2Y12 inhibitor regimen at this time?
A. Ticagrelor 180 mg followed by a maintenance dose of 90 mg twice a day
B. Ticagrelor 90 mg followed by a maintenance dose of 90 mg twice a day
C. Prasugrel 60 mg followed by a maintenance dose of 5 mg daily
D. Clopidogrel 300 mg followed by a maintenance dose of 75 mg daily

5.18 A patient with a history of heparin-induced thrombocytopenia is brought to the

catheterization laboratory for primary PCI. What agent is an acceptable alternative for
anticoagulation during PCI?
A. Fondaparinux
B. Bivalirudin
C. Argatroban
D. B or C

5.19 An 82-year-old patient with chronic kidney disease and a history of gastrointestinal
bleeding requiring a blood transfusion 3 months ago presents now with STEMI for
primary PCI. This patient is considered HBR according to the Academic Research
Consortium HBR criteria. In addition to choosing radial over femoral artery access, what
may be a reasonable anticoagulation strategy as an alternative to unfractionated heparin
to reduce bleeding risk?
A. Bivalirudin IV bolus of 0.75 mg/kg followed by 1.75 mg/kg/h IV infusion during PCI
and for 2-4 hours afterward with GP IIb/IIIa inhibitor use reserved for thrombotic
complications during PCI
B. Argatroban IV bolus of 350 mg/kg followed by 15 mg/kg/min IV infusion during PCI
C. Enoxaparin IV bolus of 0.5-0.75 mg/kg and GP IIb/IIIa inhibitor use reserved for
thrombotic complications during PCI
D. Bivalirudin IV bolus of 0.75 mg/kg followed by 1.75 mg/kg/h IV infusion and routine
GP IIb/IIIa inhibitor use reserved for thrombotic complications during PCI
5.20 A 53-year-old male with stable angina and positive stress echocardiography undergoes
coronary angiography, which shows multivessel coronary artery disease with left main
artery stenosis. The patient undergoes coronary artery bypass surgery with left internal
mammary artery to left anterior descending artery, saphenous vein graft (SVG) to first
diagonal, SVG to first obtuse marginal artery and sequential graft to first left
posterolateral branch, and SVG to right posterior descending artery. Which
antithrombotic agent in combination with acetylsalicylic acid (ASA) 81 mg may improve
vein graft patency compared with ASA 81 mg alone?
A. Prasugrel 5 mg daily
B. Clopidogrel 75 mg daily
C. Rivaroxaban 2.5 mg twice daily
D. A and B

5.21 Based on the recent Scientific Statement from the American Heart Association (AHA) for
the contemporary diagnosis and management of patients with myocardial infarction with
nonobstructive coronary artery disease (MINOCA), which is NOT a correct
recommendation for antithrombotic treatment?
A. Spontaneous coronary artery dissection: aspirin, consider clopidogrel
B. Coronary artery spasm: consider aspirin
C. Coronary embolism/thrombus: antiplatelet or anticoagulant therapy
D. Plaque disruption: aspirin, consider clopidogrel/ticagrelor

5.22 In the COMPASS trial, a strategy with rivaroxaban 2.5 mg twice daily plus aspirin
compared with aspirin alone in patients with stable atherosclerosis was associated with
reduced cardiovascular death, myocardial infarction, or stroke. Conversely, the rate of
major bleeding was higher in the group treated with rivaroxaban 2.5 mg twice daily plus
aspirin. What was the risk of the composite net-clinical-benefit outcome of
cardiovascular death, stroke, myocardial infarction, fatal bleeding, or symptomatic
bleeding into a critical organ?
A. 7.1% for rivaroxaban plus aspirin versus 5.9% for aspirin alone
B. 4.7% for rivaroxaban plus aspirin versus 5.9% for aspirin alone
C. 2.1% for rivaroxaban plus aspirin versus 5.9% for aspirin alone
D. 5.8% for rivaroxaban plus aspirin versus 5.9% for aspirin alone

5.23 A 56-year-old male patient with a past medical history of active smoking, hypertension,
and hyperlipidemia presents with symptomatic peripheral artery disease and undergoes
revascularization of the distal superficial femoral artery. Based on recent evidence, what
is the most beneficial antithrombotic regimen for this patient in terms of acute limb
ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke,
or death from cardiovascular causes?
A. Aspirin 81 mg daily plus apixaban 5 mg twice daily with or without clopidogrel 75 mg
 daily (up to 6 months)
B. Aspirin 81 mg daily plus apixaban 5 mg daily with or without clopidogrel 75 mg daily
(up to 6 months)
C. Aspirin 81 mg daily plus rivaroxaban 2.5 mg twice daily with or without clopidogrel
75 mg daily (up to 6 months)
D. Aspirin 81 mg daily plus rivaroxaban 2.5 mg daily with or without clopidogrel 75 mg
daily (up to 6 months)

5.24 The TWILIGHT trial found that among high-risk patients who underwent PCI and
completed 3 months of ticagrelor-based dual antiplatelet therapy, ticagrelor monotherapy
was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus
aspirin, with no higher risk of death, myocardial infarction, or stroke. What was the
prevalence of patients with STEMI in this trial?
A. 41%
B. 0%
C. 12%
D. 100%

5.25 A 68-year-old female patient with a past medical history of hypertension, hyperlipidemia,
prediabetes, chronic kidney disease stage III, and s/p stroke 2 years ago presents to the
emergency department with chest discomfort since a few days and worsening shortness
of breath on exertion. The ECG shows ST-segment depressions in the precordial leads.
Her initial laboratory findings show a creatinine of 2.1 mg/dL and troponin I of 2.04
ng/mL. The patient is urgently taken to the catheterization laboratory and undergoes PCI
for severely calcified lesions in the proximal left anterior descending artery and the
proximal LCx. Which antiplatelet therapy is most appropriate for this patient?
A. Loading with aspirin 325 mg and clopidogrel 600 mg followed by aspirin 81 mg daily
and clopidogrel 75 mg daily
B. Loading with aspirin 325 mg and prasugrel 60 mg followed by aspirin 81 mg daily and
prasugrel 10 mg daily
C. Loading with aspirin 325 mg and ticagrelor 180 mg followed by ASA 81 mg daily and
ticagrelor 90 mg twice daily
D. Loading with aspirin 325 mg and prasugrel 60 mg followed by aspirin 81 mg daily and
prasugrel 5 mg daily

5.26 Which of the following statements about bivalirudin is NOT correct?

A. Bivalirudin is a direct thrombin inhibitor
B. There is no antidote for bivalirudin
C. The half-life of bivalirudin is approximately 55 minutes
D. Bivalirudin is eliminated renally
5.27 A 72-year-old female patient with chronic kidney disease (estimated glomerular filtration
rate 40 mL/min/1.73 m2) and a history of gastrointestinal bleeding 1 year ago undergoes
primary PCI for STEMI and is started on dual antiplatelet therapy with aspirin 81 mg
daily and prasugrel 10 mg daily. The treating physician is concerned about the risk of
bleeding in this patient and considers de-escalation from prasugrel 10 mg to prasugrel 5
mg or to clopidogrel 75 mg daily. What strategies have been investigated to inform de-
escalation?
A. Genotype testing
B. Multiplate analyzer testing after switching to clopidogrel for 1 week
C. VerifyNow P2Y12 assay
D. All of the above

5.28 Which of the following statements about cangrelor is NOT correct?

A. Reaches its maximum concentration in 2 minutes
B. Half-life is approximately 3-6 minutes
C. Non-thienopyridine analogue of adenosine triphosphate
D. Renal adjustment is needed

5.29 Which of the following studies did NOT investigate an aspirin-free strategy in patients
after PCI?
A. DAPT
B. STOPDAPT-2
C. TWILIGHT
D. SMART-CHOICE

5.30 According to the PARIS (Patterns of Non-Adherence to Anti-Platelet Regimen in Stented

Patients) risk score, which of the following factors are risk factors for bleeding AND
ischemic events in patients after PCI?
A. Current smoking
B. Age
C. Chronic kidney disease defined as an estimated glomerular filtration rate of <60
mL/min/1.73 m2
D. A and C

ANSWERS AND EXPLANATIONS

5.1 Answer C.According to the criteria for HBR issued by the Academic Research Consortium
(Urban P, Mehran R, Colleran R, et al. Defining high bleeding risk in patients
undergoing percutaneous coronary intervention. Circulation. 2019;140(3):240-261.
 PMID: 31116032), the patient is at HBR due to her age (≥75 years) and the history of
intracranial hemorrhage. In addition, the recurrence of an ischemic event in this scenario
is not a major concern in the absence of comorbidities increasing this risk (eg, type 2
diabetes) and because she underwent noncomplex PCI. Due to the history of intracranial
hemorrhage, prasugrel and ticagrelor are contraindicated, and based on the HBR, a
shorter (6-month) dual antiplatelet therapy with aspirin and clopidogrel is preferred.

5.2 Answer A.Since the patient has several risk factors for recurrent ischemic events (type 2
diabetes, presentation with acute coronary syndrome, PCI of bifurcation with double
stenting), treatment with a potent P2Y12 inhibitor should be preferred. The risk of a
recurrent gastrointestinal hemorrhage is moderate, given the prior endoscopic clipping
and the concomitant therapy with a proton pump inhibitor. However, the clinical course
is uncertain, and the most appropriate decision is to continue the current regimen and
reevaluate the patient 3 months after discharge. If the patient tolerates the treatment well
and has no recurrent ischemic events, aspirin can be discontinued 3 months after
discharge to reduce the risk of bleeding complications (Lawton JS, Tamis-Holland JE,
Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery
revascularization: a report of the American College of Cardiology/American Heart
Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol.
2022;79(2):e21-e129. PMID: 34895950). Discontinuation of aspirin at the time of
hospital discharge after acute coronary syndrome has not been investigated in
randomized controlled trials in patients without chronic oral anticoagulation.

5.3 Answer D. Over the last years, andexanet alfa (ANNEXA-4 study), idarucizumab (RE-
VERSE AD study), and bentracimab (REVERSE-IT study) were investigated in clinical
trials and were shown to be effective in restoring hemostasis and reversing the effect of
factor Xa inhibitors, dabigatran, and ticagrelor, respectively. The first two are already
available for clinical use, whereas the effect of bentracimab is currently being assessed in
a large clinical trial.

5.4 Answer B.Andexanet alfa is a specific reversal agent that neutralizes the anticoagulant
effects of both direct and indirect factor Xa inhibitors. In the ANNEXA-4 study,
andexanet alfa reduced anti–factor Xa activity and restored hemostasis in patients with
acute major bleeding associated with either apixaban or rivaroxaban. Given the bleeding
severity, activated prothrombin complex concentrates can be concomitantly
administered, even though their effectiveness in restoring hemostasis varies with the
quantity of unbound rivaroxaban metabolites.
Hemoadsorption is a promising method of reversal of antithrombotic medications,
whose effect is currently investigated in two ongoing randomized controlled trials and is
not yet available for clinical use.

5.5 Answer D. The orthopedist and anesthesiologist are worried about the risk of
periprocedural bleeding, which would be reduced by discontinuing the P2Y12 inhibitor
rather than aspirin. However, the patient is at high risk for thrombotic complications (ie,
stent thrombosis), given that PCI with stent implantation was less than 1 month ago. For
 these reasons, P2Y12 inhibitor discontinuation with bridging with cangrelor or a small-
molecule GP IIb/IIIa inhibitor, depending on the lapse of time until surgical intervention,
is the best option. Bridging with heparin to decrease ischemic events is not
recommended.

5.6 Answer C. Five large randomized controlled trials demonstrated the superiority of direct
oral anticoagulants over vitamin K antagonists in reducing bleeding events after PCI. In
particular, the AUGUSTUS trial showed that the continuation of aspirin beyond 1 month
is associated with an increased risk of bleeding and similar rates of ischemic events
compared to dual therapy with apixaban and clopidogrel. Nevertheless, one should note
that none of these trials were large enough to detect small but potentially meaningful
differences in the incidence of ischemic events.

5.7 Answer A. The duration of “triple therapy” with an oral anticoagulant, clopidogrel, and
aspirin should be reduced to a minimum to limit the risk of bleeding. However, the
patient has an increased thrombotic risk (presentation with acute coronary syndrome,
PCI of proximal left anterior descending artery, and implantation of three stents) and no
risk factors for bleeding except for anticoagulation therapy. Therefore, the immediate
discontinuation of aspirin is not recommended. Since the pulmonary embolism occurred
only 10 weeks before PCI, discontinuation of rivaroxaban is premature. The patient
should undergo additional investigations (eg, thrombophilia screening), and the
indication to long-term antithrombotic therapy should be reevaluated after that.
Rivaroxaban can be safely reduced from 20 to 15 mg with concomitant antiplatelet
therapy or in case of estimated glomerular function below 45 mL/min/1.73 m2
(Angiolillo DJ, Bhatt DL, Cannon CP, et al. Antithrombotic therapy in patients with
atrial fibrillation treated with oral anticoagulation undergoing percutaneous coronary
intervention: a North American perspective: 2021 update. Circulation. 2021;143(6):583-
596. PMID: 33555916).

5.8 Answer B. Data from the most recently published POPular-TAVI trial (Brouwer J,
Nijenhuis VJ, Delewi R, et al. Aspirin with or without clopidogrel after transcatheter
aortic-valve implantation. N Engl J Med. 2020;383(15):1447-1457. PMID: 32865376)
suggest lower risk of bleeding and similar risk of ischemic events with a strategy of
single antiplatelet therapy with low-dose aspirin alone versus dual antiplatelet therapy
with aspirin plus clopidogrel in patients with no indication for anticoagulation and/or
recent PCI. In patients with aspirin allergy, clopidogrel monotherapy is preferred. In
GALILEO, routine use of rivaroxaban after TAVR in patients without an indication for
oral anticoagulation was associated with worse outcomes, including increased risk of
death, increased risk of major bleeding events, and no reduction in thromboembolic
events, resulting in a Class III recommendation for harm in recent guidelines.

5.9 Answer A.In patients with an indication for oral anticoagulation and no recent PCI, no
additional antiplatelet therapy is indicated after TAVR. Routine replacement of vitamin
K antagonist with a direct oral anticoagulant is not recommended in the context of
TAVR, especially if the therapy is well tolerated and INR values are in the therapeutic
 range.

5.10 Answer D.The optimal timing of P2Y12 inhibitor administration in the setting of suspected
acute coronary syndrome is still a matter of debate. Pretreatment, defined as the
administration of a P2Y12 inhibitor loading dose before assessment of the coronary
anatomy, may prevent early ischemic events but may unnecessarily expose the patient to
an increased risk of bleeding if coronary artery disease is not confirmed. The evidence in
favor of this practice is limited to the CURE trial, which may not reflect current practice
with a prolonged time interval between clopidogrel administration and coronary
angiography and a low proportion of patients undergoing PCI. More recent evidence
(ACCOAST, DUBIUS, and ISAR-REACT 5) suggested potential bleeding harm
associated with pretreatment and failed to demonstrate any ischemic benefit in patients
with non–ST-segment elevation acute coronary syndrome. Therefore, routine
pretreatment is not supported by recent evidence in patients with non–ST-segment
elevation acute coronary syndrome.

5.11 Answer B.The patient is at high risk for recurrent stent-related and non–stent-related
coronary ischemic events based on his uncontrolled type 2 diabetes and prior in-stent
restenosis. The risk of bleeding is low as the two episodes of self-limiting epistaxis are
not considered relevant bleeding (Urban P, Mehran R, Colleran R, et al. Defining high
bleeding risk in patients undergoing percutaneous coronary intervention. Circulation.
2019;140(3):240-261. PMID: 31116032). Therefore, continuing dual antiplatelet therapy
is reasonable to reduce the ischemic risk. Clopidogrel monotherapy for chronic
maintenance has been compared with aspirin monotherapy in a recent randomized
controlled trial conducted in a South Korean population (HOST-EXAM). Further
evidence is needed before recommending this regimen. Given the absence of relevant
side effects from ticagrelor, there is no reason at this time to switch to clopidogrel.

5.12 Answer C.Pretreatment with a P2Y12 inhibitor or IV administration of heparin in patients

with stable coronary artery disease in which the indication for PCI has not yet been
confirmed is not recommended. Indeed, this strategy would expose the patient to an
unnecessary risk of bleeding in case the PCI is not performed. In this case, even though
the CT angiography showed intermediate stenosis, the indication for PCI has yet to be
confirmed.

5.13 Answer A. In patients with stable ischemic heart disease undergoing PCI, the use of potent
P2Y12 inhibitors is currently not recommended due to the associated increased risk of
clinically relevant bleeding and an uncertain benefit in terms of ischemic events.
Even though the patient has a higher risk for recurrent ischemic events because of
concomitant type 2 diabetes and the complexity of the PCI, aspirin plus clopidogrel is
the recommended treatment. Ongoing randomized controlled trials are comparing dual
antiplatelet therapy with a potent P2Y12 inhibitor versus clopidogrel in patients
presenting with chronic coronary syndrome and undergoing complex PCI.
5.14 Answer B.Despite the chronic pain with severe limitations in walking, the abovementioned
surgery is considered deferrable. According to the 2016 American College of Cardiology
(ACC)/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in
Patients With Coronary Artery Disease (Levine GN, Bates ER, Bittl JA, et al. 2016
ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients
with coronary artery disease: a report of the American College of Cardiology/American
Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol.
2016;68(10):1082-1115. PMID: 27036918), after drug-eluting stent implantation, dual
antiplatelet therapy discontinuation for a deferrable noncardiac surgery is considered safe
after 6 months from PCI, even in patients who underwent complex PCI or who presented
with acute coronary syndrome. Before 6 months, deferrable surgery may be considered.
In the case described, the risks of dual antiplatelet therapy discontinuation outweigh the
benefit of immediate surgery (symptom reduction). Deferring surgery to allow for 12
months of dual antiplatelet therapy is unnecessary in this case, in which chronic pain
severely limits the patient’s ability to walk.

5.15 Answer C. Among HBR patients, the expected rate of major bleeding at 1-year after PCI is
at least 4% and of intracranial bleeding 1%. Dedicated bleeding avoidance strategies are
recommended in patients considered as HBR.

5.16 Answer A.Bentracimab, a selective reversal agent of ticagrelor, showed promising results
in phase 2 and one phase 3 clinical trials. However, there are currently no therapies
approved for clinical use to reverse the effect of ticagrelor. The effectiveness of platelet
transfusion to restore platelet function in patients with an ongoing hemorrhage related to
antiplatelet therapy is uncertain, especially when the active metabolites of antiplatelet
drugs are still present at therapeutic concentrations in the bloodstream. There is no
evidence endorsing platelet transfusion in patients without active bleeding undergoing
surgery. The optimal timing of coronary artery bypass surgery in non-STEMI is a matter
of debate. However, evidence supports the safety of deferring coronary artery bypass
graft surgery, with some studies suggesting even increased mortality with early surgery
(within 24 hours).

5.17 Answer D. Current guidelines recommend a loading dose of 300 mg of clopidogrel,

followed by 75 mg daily in patients undergoing PCI within 24 hours after fibrinolytic
therapy to reduce ischemic events based on the PCI-CLARITY study. Clopidogrel is the
only P2Y12 inhibitor studied in patients immediately after administration of fibrinolytic
therapy. In patients of younger age (<75 years) and low bleeding risk, a loading dose of
600 mg clopidogrel or even the administration of ticagrelor may be a reasonable
alternative (Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI
guideline for coronary artery revascularization: a report of the American College of
Cardiology/American Heart Association Joint Committee on Clinical Practice
Guidelines. J Am Coll Cardiol. 2022;79(2):e21-e129. PMID: 34895950).

5.18 Answer D.Heparin-induced thrombocytopenia is caused by the formation of antibodies

that bind to a complex of heparin and platelet factor 4 and cause platelet activation.
 Argatroban and bivalirudin are direct thrombin inhibitors and do not interact with
platelet factor 4. Based on their different mechanism of action, argatroban and
bivalirudin are acceptable alternative anticoagulants for use in patients with heparin-
induced thrombocytopenia. Fondaparinux is no longer recommended as the only
anticoagulant in PCI because of a higher incidence of guide catheter thrombosis (Lawton
JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary
artery revascularization: a report of the American College of Cardiology/American Heart
Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol.
2022;79(2):e21-e129. PMID: 34895950).

5.19 Answer A. The decreased bleeding risk associated with bivalirudin was often attributed to
the routine use of GP IIb/IIIa inhibitors in the unfractionated heparin groups of
randomized clinical trials. The recently published BRIGHT-4 trial compared bivalirudin
with a post-PCI high-dose infusion for 2-4 hours versus unfractionated heparin
monotherapy with GP IIb/IIIa inhibitor use reserved for procedural thrombotic
complications in both groups. Compared with heparin monotherapy, bivalirudin
significantly reduced the 30-day composite of all-cause mortality or BARC types 3-5
major bleeding. The high-dose post-PCI bivalirudin infusion is meant to mitigate the risk
of stent thrombosis occurring within the first few hours after PCI associated with abrupt
discontinuation of bivalirudin after the procedure.

5.20 Answer C. There is evidence from smaller studies and meta-analyses that suggests
improved vein graft patency with clopidogrel in addition to aspirin compared with
aspirin alone in patients with stable ischemic heart disease, which is why current
guidelines give a IIb recommendation for adding clopidogrel to aspirin for 12 months
after coronary artery bypass graft surgery. More recently, a large meta-analysis of four
randomized controlled trials found that adding ticagrelor to aspirin was associated with a
significantly improved vein graft patency in patients after coronary artery bypass graft
surgery. However, dual antiplatelet therapy, regardless of which P2Y12 inhibitor is used,
compared with aspirin alone, is associated with an increased risk of bleeding. Therefore,
individualized decision-making considering bleeding and ischemic risk in patients with
stable ischemic heart disease after coronary artery bypass graft surgery should be
applied. Rivaroxaban was ineffective at improving bypass graft patency rates in the
COMPASS-CABG substudy.

5.21 Answer B.The Scientific Statement from the AHA for the contemporary diagnosis and
management of patients with myocardial infarction in the absence of obstructive
coronary artery disease does not recommend antithrombotic treatment in patients with
diagnosed coronary spasm. Selective/empirical therapies are mentioned for the other
ischemic presentations as listed in options A, C, and D. The document emphasizes the
importance of an accurate diagnosis to initiate the appropriate (antithrombotic) treatment
(Tamis-Holland JE, Jneid H, Reynolds HR, et al. Contemporary diagnosis and
management of patients with myocardial infarction in the absence of obstructive
coronary artery disease: a scientific statement from the American Heart Association.
Circulation. 2019;139(18):e891-e908. PMID: 30913893).
5.22 Answer B. Compared with aspirin monotherapy, the combination of rivaroxaban 2.5 mg
twice daily plus aspirin resulted in significantly fewer net-clinical-benefit events defined
as a composite of cardiovascular death, stroke, myocardial infarction, fatal bleeding, or
symptomatic bleeding into a critical organ (4.7% for rivaroxaban plus aspirin vs 5.9%
for aspirin alone; hazard ratio [HR], 0.80 [95% confidence interval (CI), 0.70-0.91], P =
.0005). This result was primarily driven by preventing adverse efficacy events,
particularly stroke and cardiovascular mortality, whereas severe bleedings were less
frequent and with less clinical impact. The net clinical benefit was particularly favorable
in high-risk subgroups and those with multiple risk characteristics (Steffel J, Eikelboom
JW, Anand SS, et al. The COMPASS trial: net clinical benefit of low-dose rivaroxaban
plus aspirin as compared with aspirin in patients with chronic vascular disease.
Circulation. 2020;142(1):40-48. PMID: 32436455).

5.23 Answer C. Evidence from the VOYAGER-PAD study (Bonaca MP, Bauersachs RM,
Anand SS, et al. Rivaroxaban in peripheral artery disease after revascularization. N Engl
J Med. 2020;382(21):1994-2004. PMID: 32222135) suggests that a regimen of aspirin
with versus without rivaroxaban 2.5 mg twice daily reduced the incidence of the
composite outcome of acute limb ischemia, amputation for vascular causes, myocardial
infarction, ischemic stroke, or cardiovascular death in patients with symptomatic
peripheral artery disease who had undergone lower extremity revascularization. In either
group, 51% of patients were taking clopidogrel for up to 6 months. Apixaban was not
tested in patients after lower extremity revascularization.

5.24 Answer B. Presentation with STEMI was an exclusion criterion in TWILIGHT. Therefore,
findings of this trial cannot be extrapolated to this group of patients. Other key exclusion
criteria included cardiogenic shock, ongoing long-term treatment with oral
anticoagulants, or contraindication to aspirin or ticagrelor.

5.25 Answer C.This patient underwent PCI for acute coronary syndrome. Current guidelines
(Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for
coronary artery revascularization: a report of the American College of
Cardiology/American Heart Association Joint Committee on Clinical Practice
Guidelines. J Am Coll Cardiol. 2022;79(2):e21-e129. PMID: 34895950) include a Class
IIa recommendation for the use of ticagrelor or prasugrel in preference to clopidogrel to
reduce ischemic events, including stent thrombosis. As this patient has a history of
stroke, prasugrel is contraindicated and therefore, ticagrelor should be given.

5.26 Answer C.Option C is not correct, as bivalirudin has an even shorter half-life of
approximately 25 minutes in patients with normal renal function or mild renal
impairment. All the other options are correct. Bivalirudin provides predictable
anticoagulation by inactivating free and clot-bound thrombin, prohibiting thrombin-
mediated platelet activation and aggregation. It is eliminated renally (Reed MD, Bell D.
Clinical pharmacology of bivalirudin. Pharmacotherapy. 2002;22(6 Pt 2):105S-111S.
PMID: 12064567).
5.27 Answer D.In the POPular Genetics study, a CYP2C19 genotype–guided strategy for the
selection of the P2Y12 inhibitor was noninferior to standard treatment with ticagrelor or
prasugrel at 12 months with respect to thrombotic events and resulted in a lower
incidence of bleeding. In the TROPICAL-ACS study, multiplate analyzer testing after
switching from prasugrel to clopidogrel for 1 week informed the decision whether
clopidogrel or prasugrel should be administered and was noninferior to standard
treatment with prasugrel at 1 year after PCI in terms of net clinical benefit. In the A-
MATCH study, the VerifyNow P2Y12 assay was used to assess platelet function and
inform de-escalation from prasugrel 10 mg to prasugrel 5 mg. Compared with the
standard-dose prasugrel, the de-escalation strategy showed a higher chance of being
within the therapeutic window and a lower tendency toward bleeding episodes.
Nevertheless, routine platelet function testing or genotype testing to adjust antiplatelet
therapy is not currently recommended by international guidelines.

5.28 Answer D. Cangrelor is a non-thienopyridine analogue of adenosine triphosphate, a

reversible antagonist of the platelet P2Y12 receptor. Cangrelor reaches its maximum
concentration in 2 minutes, and after stopping the infusion, restoration of normal platelet
function is achieved within 60 minutes. Cangrelor is given as an IV bolus of 30 mg/kg
followed by continuous infusion of 4 mg/kg/min for at least 2 hours or the duration of
PCI, whichever is longer. No renal adjustment is needed (Capodanno D, Milluzzo RP,
Angiolillo DJ. Intravenous antiplatelet therapies (glycoprotein IIb/IIIa receptor inhibitors
and cangrelor) in percutaneous coronary intervention: from pharmacology to indications
for clinical use. Ther Adv Cardiovasc Dis. 2019;13:1753944719893274. PMID:
31823688).

5.29 Answer A.The DAPT trial is the earliest of the above-listed trials and investigated
prolonging dual antiplatelet therapy beyond 12 months. The reduction of ischemic events
with this strategy came at the expense of higher bleeding risk. Recently, a strategy of
dropping aspirin and continuing P2Y12 inhibitor therapy after a short duration of dual
antiplatelet therapy has emerged as an approach to reduce bleeding while preserving the
ischemic benefit in patients after PCI. All trials listed in options B-D investigated this
strategy and showed promising results.

5.30 Answer D. Using data from the PARIS registry, separate risk scores were developed to
predict coronary thrombotic events and major bleeding events (Baber U, Mehran R,
Giustino G, et al. Coronary thrombosis and major bleeding after PCI with drug-eluting
stents: risk scores from PARIS. J Am Coll Cardiol. 2016;67(19):2224-2234. PMID:
27079334). Independent predictors of coronary thrombotic events included acute
coronary syndrome, prior revascularization, type 2 diabetes renal dysfunction, and
current smoking. Independent predictors of major bleeding included older age, BMI,
triple therapy at discharge, anemia, current smoking, and renal dysfunction. Only active
smoking and renal dysfunction emerged as common contributors to both events.
 Pharmacogenomics and Drug-Drug
6
Interactions

Craig J. Beavers

QUESTIONS

6.1 Which of the following genotypes represents the wild type for the CYP2C19 enzyme?
A. *1/*1
B. *1/*2
C. *2/*2
D. *3/*3

6.2 The drug interaction between P2Y12 inhibitors and morphine administered to patients
with acute coronary syndrome is due to a delay in which pharmacokinetic process?
A. P2Y12 inhibitor absorption
B. P2Y12 inhibitor distribution
C. P2Y12 inhibitor metabolism
D. P2Y12 inhibitor excretion

6.3 Ticagrelor is a substrate of which CYP enzyme?

A. 2C19
B. 2D6
C. 3A4
D. 1A2

6.4 Which of the following best describes a strategy when pharmacogenetic testing is
performed for a specific drug-gene interaction?
A. Retrospective
B. Reactive
 C. Preemptive
D. Prospective

6.5 A 56-year-old Asian male is admitted for ST-segment elevation myocardial infarction
(STEMI) and undergoes primary percutaneous coronary intervention (PCI) with stent
placement to the proximal left anterior descending (LAD) artery. He receives a 600 mg
clopidogrel loading dose and is placed on clopidogrel 75 mg daily. During the hospital
admission, pharmacogenetic testing is completed, which shows the patient has
CYP2C19*2/*3. Which one of the following is the best assessment and action to
recommend for this patient?
A. Rapid CYP2C19 metabolism; increase clopidogrel to 300 mg once daily
B. Normal CYP2C19 metabolism; continue clopidogrel 75 mg daily
C. Intermediate CYP2C19 metabolism; continue current management
D. Poor CYP2C19 metabolism; discontinue clopidogrel and initiate ticagrelor 90 mg twice
daily

6.6 Which of the following best describes an interaction that occurs when the pharmacologic
effects of one medication are altered by another medication in a combination regimen?
A. Pharmacokinetic
B. Pharmacodynamic
C. Pharmaceutical
D. Pharmacogenomic

6.7 Which of the following genes has been associated with simvastatin-induced muscle-
related symptoms?
A. CYP2C19
B. VKORC1
C. GRK5
D. SLCO1B1

6.8 Which of the following proton pump inhibitors should be avoided in the patient taking
clopidogrel?
A. Dexlansoprazole
B. Omeprazole
C. Pantoprazole
D. Rabeprazole

6.9 Which of the following enzymes that metabolizes warfarin can be linked to most of the
genetic variability in warfarin response?
 A. CYP3A4
B. CYP1A2
C. VKORC1
D. GRK5

6.10 Patients taking verapamil (ie, a strong CYP3A4 inhibitor) or diltiazem (ie, a moderate
CYP3A4 inhibitor) should be prescribed which statin agent to avoid potential
interactions?
A. Atorvastatin
B. Simvastatin
C. Rosuvastatin
D. Lovastatin

6.11 A 60-year-old Asian female underwent PCI and drug-eluting stent implantation 3 days
ago. Today she returns to the catheterization laboratory for evaluation of new sudden-
onset severe chest pressure. Her current drugs include lisinopril 20 mg daily,
rosuvastatin 10 mg daily, aspirin 81 mg daily, and clopidogrel 75 mg daily. She attests to
taking all of her medications as prescribed. Angiography confirms acute stent
thrombosis. Which of the following genotypes is this patient most likely to have?
A. CYP2C19*1/*1
B. CYP2C19*2/*2
C. CYP2C19*1/*2
D. CYP2C19*1/*3

6.12 The combination/overlap of an angiotensin-converting enzyme inhibitor (ACE-I) and an

angiotensin receptor–neprilysin inhibitor (ARNI) is likely to increase the risk of
angioedema via pharmacodynamic interaction. When switching a patient from an ACE-I
to an ARNI, what is the appropriate washout period to observe in order to avoid the risk
of angioedema with combined use of these agents?
A. 12 hours
B. 24 hours
C. 36 hours
D. 48 hours

6.13 Which of the following patient genetic profiles for warfarin metabolism would warrant an
initial warfarin dose reduction of 15%-30%?
A. CYP2C9*1/*1, non-African ancestry
B. CYP2C9*1/*1, African ancestry
C. CYP2C9*1/*5, non-African ancestry
 D. CYP2C9*1/*5, African ancestry

6.14 A 65-year-old patient was admitted to the hospital following successful resuscitation from
a ventricular fibrillation cardiac arrest due to an acute anterior myocardial infarction
(MI). A transthoracic echocardiogram prior to discharge revealed apical akinesis and a
large left ventricular thrombus. The patient’s medication includes amiodarone, lisinopril,
ticagrelor, aspirin, carvedilol, rosuvastatin, pantoprazole, and empagliflozin. Warfarin is
planned to be started with a goal international normalized ratio (INR) of 2-3. Which of
the following medications prompts you to start warfarin at a lower dose?
A. Amiodarone
B. Empagliflozin
C. Pantoprazole
D. Rosuvastatin

6.15 Which of the following phenotypic profiles would warrant the starting dose of
rosuvastatin to be ≤20 mg?
A. SLCO1B1 increased function, ABCG2 decreased function
B. SLCO1B1 increased function, ABCG2 normal function
C. SLCO1B1 normal function, ABCG2 poor function
D. SLCO1B1 decreased function, ABCG2 decreased function

6.16 An 80-year-old female patient (weight 66 kg) with a history of chronic kidney disease
(serum creatinine 1.7 mg/dL; creatinine clearance [CrCl] ~28 mL/min) reports to her 1-
month follow-up after transthoracic aortic valve replacement. She has developed new-
onset symptomatic atrial fibrillation with a heart rate of 100-120 beats/min despite
treatment with metoprolol succinate 200 mg. You decide to initiate amiodarone and
replace her antiplatelet therapy with an anticoagulant. Which of the following would be
the optimal anticoagulant in this patient?
A. Dabigatran 75 mg twice daily
B. Apixaban 2.5 mg twice daily
C. Edoxaban 30 mg daily
D. Warfarin, goal INR 2-3

6.17 Which of the following organizations provides clinicians with practice guidelines based
on gene/drug pairs?
A. American Society for Clinical Pharmacology and Therapeutics
B. Food and Drug Administration
C. National Institutes of Health
D. Clinical Pharmacogenetics Implementation Consortium
6.18 You are evaluating a patient for PCI for treatment of symptomatic chronic angina. In a
discussion with the patient, you determine that they have not been treated with
nitrates/nitroglycerin. Home medications include aspirin 81 mg daily, amlodipine 10 mg
daily, metoprolol 100 mg twice daily, atorvastatin 80 mg daily, metformin 1,000 mg
twice daily, tadalafil 5 mg daily, sitagliptin 100 mg daily, and sertraline 100 mg daily.
Which of the following medications should be discontinued prior to starting isosorbide
mononitrate?
A. Metformin
B. Sertraline
C. Sitagliptin
D. Tadalafil

6.19 Metoprolol and carvedilol are metabolized by CYP2D6, and their plasma concentrations
are expected to be increased in phenotypically poor metabolizers. Which of the
following interacting medications is a CYP2D6 strong inhibitor (ie, mimics the
phenotype of a CYP2D6 poor metabolizer), necessitating additional heart rate and blood
pressure monitoring?
A. Bupropion
B. Colchicine
C. Fexofenadine
D. Semaglutide

6.20 You are managing a 60-year-old patient with diabetes, heart failure, and reduced left
ventricular function (ejection fraction 30%) resulting from an anterior MI treated with
primary PCI (ie, drug-eluting stent placement). The patient is receiving atorvastatin,
aspirin, ticagrelor, lisinopril, and carvedilol. You would also like to initiate eplerenone.
Before starting therapy, you should consider stopping agents that would increase the
chance of which adverse event?
A. Alopecia
B. Hyperkalemia
C. Hyperglycemia
D. Tremor

6.21 According to the Clinical Pharmacogenetics Implementation Consortium (CPIC)

guidelines, what is the best recommendation regarding statin use for a patient who has a
low-density lipoprotein (LDL) cholesterol of 250 mg/dL and SLCO1B1 poor transporter
phenotype?
A. Avoid all statins
B. Administer simvastatin 20 mg daily
C. Administer simvastatin 40 mg daily
D. Administer rosuvastatin 40 mg daily
6.22 A 27-year-old man has a medical history that includes STEMI status post coronary stent
placement. The patient, who lives on a fixed income, receives a new diagnosis of atrial
fibrillation requiring anticoagulation based on his CHA2DS2-VASc score. His current
regimen includes aspirin, atorvastatin, clopidogrel, lisinopril, and metoprolol. His
genotype shows CYP2C19*1/*17 (rapid metabolizer), CYP2C9*1/*2 (intermediate
metabolizer), and VKORC1 AA (increased sensitivity). Given his medical history and
pharmacogenetic test results, which one of the following is best to recommend for this
patient?
A. Rivaroxaban 15 mg daily, ticagrelor 90 mg twice daily, aspirin 81 mg daily
B. Apixaban 5 mg twice daily, clopidogrel 75 mg daily, stop aspirin
C. Warfarin 5 mg daily, ticagrelor 90 mg twice daily, stop aspirin
D. Dabigatran 75 mg twice daily, clopidogrel 75 mg daily, aspirin 81 mg daily

6.23 Patients who are taking cardiovascular medications that are substrates of CYP3A4 (eg,
statins, apixaban, ticagrelor) should avoid large quantities of which of the following?
A. Orange juice
B. Bananas
C. Grapefruit juice
D. Spinach

6.24 Which of the following direct-acting oral anticoagulants has an interaction with
dronedarone requiring a dose adjustment of the anticoagulant in patients with reduced
CrCl?
A. Apixaban
B. Dabigatran
C. Edoxaban
D. Rivaroxaban

6.25 A patient has arrived at your catheterization laboratory for management of a STEMI. The
patient’s past medical history includes seizure disorder for which the patient takes
phenytoin. Which of the following antiplatelet agents should be avoided in the
management of this patient after coronary intervention?
A. Aspirin
B. Clopidogrel
C. Prasugrel
D. Ticagrelor

6.26 Which of the following best describes the role of the CPIC guidelines?
 A. Use the CPIC guidelines to determine which clinical scenarios warrant CYP2C19
testing to guide antiplatelet therapy
B. Use the CPIC guidelines to help clinicians determine whether clopidogrel is a
reasonable treatment
C. Use the CPIC guidelines to help determine whether Clinical Laboratory Improvement
Amendments (CLIA) certification is necessary for pharmacogenetic testing in the
context of dual antiplatelet therapy
D. Use the CPIC guidelines to determine the usefulness and cost-effectiveness of
pharmacogenetic testing

6.27 You are working with your clinical pharmacist to establish pharmacogenomic testing in
your practice. You decide to use a commercial laboratory that offers single-gene and
multigene panel–based tests for both reactive and preemptive purposes. Which one of the
following best describes the most appropriate and feasible usability of test results from
reactive and preemptive genotyping?
A. Preemptive testing is called just-in-case testing because the results can be used in the
future
B. Preemptive testing is called just-in-time testing because the results can be used
immediately
C. Reactive testing is called just-in-case testing because the results can be used in the
future
D. Reactive testing is called just-in-time testing because the results can be used in the
future

6.28 Cilostazol is a substrate of which enzyme system and should not be administered
concomitantly with strong inhibitors and inducers of this system?
A. CYP2D6
B. CYP3A4
C. CYP2C19
D. CYP2C9

6.29 A drug interaction that leads to competition for binding sites on serum proteins that
results in drug displacement describes an impact to which pharmacokinetic principle?
A. Absorption
B. Distribution
C. Metabolism
D. Excretion

6.30 It is appropriate to administer a loading dose of which of the following antiplatelet agents
during cangrelor infusion?
 A. None; all must be given after the cangrelor infusion is discontinued
B. Clopidogrel
C. Prasugrel
D. Ticagrelor

ANSWERS AND EXPLANATIONS

6.1 Answer A. The wild type for the CYP2C19 enzyme is denoted as *1/*1, and patients with
this genotype are normal metabolizers. Patients who have the *1/*2 genotype are
considered to have one normal functioning allele and one nonfunction or loss-of-function
allele; they would be considered intermediate metabolizers. Patients with either *2/*2 or
*3/*3 carry two nonfunction alleles and are considered to be poor metabolizers (CPIC.
Clopidogrel and CYP2C19. https://cpicpgx.org/guidelines/guideline-for-clopidogrel-and-
cyp2c19; 2022).

6.2 Answer A.Morphine delays gastric peristalsis, which can impact the absorption of orally
administered P2Y12 inhibitors. The other three answer choices are pharmacokinetic
processes that would not be impacted by coadministration of these two drugs
(Giannopoulos G, Deftereos S, Kolokathis F, et al. P2Y12 receptor antagonists and
morphine: a dangerous liaison? Circ Cardiovasc Interv. 2016;9(9):e004229. PMID:
27586412).

6.3 Answer C. Ticagrelor is a known substrate of CYP3A4, which means agents that are strong
inducers of CYP3A4 (eg, carbamazepine) increase the metabolism of ticagrelor and
hence reduce its plasma concentration and bioavailability. Conversely, agents that inhibit
CYP3A4 (eg, ritonavir) slow the metabolism of ticagrelor and increase its exposure and
effects. It should be noted that clopidogrel is metabolized by CYP2C19, which is also
impacted by drug interactions and genetic factors (https://labels.fda.gov).

6.4 Answer B. Reactive testing is performed when needed to assess a specific drug-gene
interaction. With reactive testing, the physician orders the pharmacogenomic test when
they are about to prescribe a drug with pharmacogenomic guidelines. In
pharmacogenomics, the other form of testing strategy is preemptive, which is when
testing is done for the entire genomic profile before the results are needed. With
preemptive testing, patients have genetic testing using a pharmacogenomic panel prior to
any clinical decisions. The terms retrospective and prospective are not used in the
pharmacogenomic paradigm.

6.5 Answer D. Clopidogrel must be metabolized by CYP2C19 to produce the active metabolite
that inhibits platelet aggregation. A person who has a genotype of *2/*3 is likely to be a
poor metabolizer. Thus, clopidogrel treatment may be less effective, or ineffective, given
the inability to produce the active metabolite via the CYP2C19 metabolic pathway.
 Based on the CPIC, it would be advisable to select a different P2Y12 inhibitor (CPIC.
Clopidogrel and CYP2C19. https://cpicpgx.org/guidelines/guideline-for-clopidogrel-and-
cyp2c19; 2022).

6.6 Answer B. A pharmacodynamic interaction occurs when the pharmacologic effect of

medication is altered by another medication in a combination regimen; an example
would be the addition of an ACE-I to a potassium-sparing diuretic increasing the risk of
hyperkalemia. A pharmacokinetic interaction occurs when one medication alters the
absorption, distribution, metabolism, or elimination of another medication. A
pharmaceutical interaction is a physical or chemical incompatibility that may be of
benefit or detriment. Pharmacogenomics occurs when genotypic differences alter
metabolism (Niu J, Straubinger RM, Mager DE. Pharmacodynamic drug-drug
interactions. Clin Pharmacol Ther. 2019;105(6):1395-1406. PMID: 30912119).

6.7 Answer D. Variation in the SLCO1B1 gene has been associated with a diverse array of
statin-associated muscle symptoms with simvastatin. Variation in CYP2C19 impacts
clopidogrel metabolism, VKORC1 impacts warfarin, and GRK5 impacts β-blockers
(CPIC. https://cpicpgx.org; 2022).

6.8 Answer B.Omeprazole is an inhibitor of CYP2C19, which is the primary enzyme

responsible for metabolism of clopidogrel to an active metabolite; thus, it should be
avoided in the patient taking clopidogrel. The other proton pump inhibitors have limited
or no interaction with CYP2C19 and would be appropriate to use in a patient taking
clopidogrel (https://labels.fda.gov).

6.9 Answer C.Genetic variation in VKORC1 has been implicated in ~25% of variation in
warfarin response. The other genes have limited or no gene variation that contributes to
warfarin response (Magavern EF, Kaski JC, Turner RM, et al. The role of
pharmacogenomics in contemporary cardiovascular therapy: a position statement from
the European Society of Cardiology Working Group on Cardiovascular
Pharmacotherapy. Eur Heart J Cardiovasc Pharmacother. 2022;8(1):85-99. PMID:
33638977).

6.10 Answer C. Given that these two agents are inhibitors of CYP3A4, it is ideal to select a
statin that is not dependent on this pathway for metabolization. Of the options, only
rosuvastatin does not use a CYP3A4 pathway (eg, rosuvastatin is metabolized mainly by
CYP2C9) and should be selected to avoid interaction and reduce risk for statin-
associated muscle events. Other statins not significantly metabolized by CYP3A4
include fluvastatin and pravastatin (https://labels.fda.gov).

6.11 Option B is correct based on the patient’s diagnosis of stent thrombosis despite
Answer B.
appropriate clopidogrel therapy. Clopidogrel must be metabolized by CYP2C19 to
produce the active metabolite that inhibits platelet aggregation. CYP2C19*1/*1 is the
wild-type allele, which would not impact clopidogrel metabolism. Patients with the
 CYP2C19*2/*2 are poor metabolizers. Patients who have the *1/*2 or *1/*3 are
considered to have one normal function allele and one nonfunction or loss-of-function
allele; they would be considered intermediate metabolizers. The prevalence of the *2 and
*3 alleles varies by ethnicity. In Caucasian, Black, and Asian population, the proportion
of patients who carry at least one copy of *2 is 25%, 30%, and 40%-50% respectively,
while the proportion for *3 is <1%, <1%, and 7%, respectively (CPIC. Clopidogrel and
CYP2C19. https://cpicpgx.org/guidelines/guideline-for-clopidogrel-and-cyp2c19; 2022).

6.12 Answer C.Per the package labeling, when switching from an ACE-I to an ARNI, a 36-hour
washout period should be strictly observed given the risk of angioedema with combined
use of these agents. This washout period does not apply to the patient who is switching
from an angiotensin receptor blocker to an ARNI, as the currently approved ARNI (ie,
sacubitril/valsartan) already includes valsartan (https://labels.fda.gov).

6.13 African American populations contain known or putative poor-metabolizer

Answer D.
CYP2C9 alleles (CYP2C9*5, CYP2C9*6, and CYP2C9*11) that are rarely found in
European American populations. Based on the CPIC recommendations, patients who
have a CYP2C9*5 allele and are of African ancestry should receive an initial warfarin
dose reduction. Patients with *1/*1 have the wild-type or normal genotype and normal
metabolism of warfarin, so no dose adjustment is indicated (ie, making A and B wrong
answers) (CPIC. https://cpicpgx.org; 2022).

6.14 Answer A.Amiodarone is known to inhibit multiple enzymes, including CYP2C9, which
can lead to an increased anticoagulation effect with warfarin. Hence, this warrants the
administration of lower doses of warfarin and close monitoring of the INR. The other
agents listed do not have a major interaction with warfarin and do not warrant a change
in dosing practice (https://labels.fda.gov).

6.15 Answer C. SLCO1B1 gene facilitates the hepatic uptake of statins. Decreased SLCO1B1
function—inherited through genetic variability or acquired through drug-mediated
inhibition—can markedly increase systemic exposure to statins. Similarly, ABCG2
encodes an efflux transporter that affects the disposition of rosuvastatin with reduced
ABCG2 function raising plasma concentration of rosuvastatin as a result of decreased
intestinal efflux. Based on the genetic polymorphisms, functions of these alleles may be
increased, normal, decreased, or poor. Based on the CPIC guidance, patients who have a
phenotype of poor function or either SLCO1B1 or ABCG2 should receive ≤20 mg of
rosuvastatin as a starting dose: if both are poor functioning, then the starting dose of
rosuvastatin should be ≤10 mg. Patients who have SLCO1B1 increased and ABCG2
decreased function (option A), SLCO1B1 increased and ABCG2 normal function (option
B), SLCO1B1 decreased and ABCG2 decreased function (option D) all allow the
prescribed desired dose (CPIC. https://cpicpgx.org; 2022).

6.16 Answer B.The most optimal agent for this patient would be apixaban given its safety in
this older patient with chronic renal disease and the lack of drug-drug interaction with
amiodarone via the P-glycoprotein (P-gp) transporter. P-gp is one of the drug
 transporters that determines the uptake and efflux of a range of drugs. Both dabigatran
and edoxaban are P-gp substrates, and amiodarone is an inhibitor of P-gp. Accordingly,
both dabigatran and edoxaban should be avoided, if possible, due to amiodarone’s
inhibition of P-gp and the potential for increased bleeding. Amiodarone and the patient’s
renal function will make maintaining a therapeutic INR challenging if warfarin is
administered (https://labels.fda.gov).

6.17 Answer D. The CPIC is an international consortium whose goal is to address the barriers to
clinical implementation of pharmacogenetic tests by creating and posting freely
available, peer-reviewed, evidence-based, updatable, and detailed clinical practice
guidelines. The other organizations support or endorse CPIC but do not offer this
guidance (CPIC. https://cpicpgx.org; 2022).

6.18 Answer D.Irrespective of the indication for use of a phosphodiesterase-5 enzyme inhibitor
(eg, erectile dysfunction, benign prostate hyperplasia, pulmonary hypertension), its
concomitant use with all forms of nitrates, regularly or intermittent, is contraindicated.
Nitrate-mediated vasodilation is markedly exaggerated and prolonged with
phosphodiesterase-5 enzyme inhibitors. All other medications the patient is receiving are
safe to use with nitrates (https://labels.fda.gov).

6.19 Answer A.Bupropion is considered a strong CYP2D6 inhibitor and would provide a
phenotypic profile similar to a poor metabolizer. It would be warranted to avoid these β-
blockers, in favor of bisoprolol or atenolol, or provide additional monitoring. The other
agents would not demonstrate this issue (https://labels.fda.gov; Magavern EF, Kaski JC,
Turner RM, et al. The role of pharmacogenomics in contemporary cardiovascular
therapy: a position statement from the European Society of Cardiology Working Group
on Cardiovascular Pharmacotherapy. Eur Heart J Cardiovasc Pharmacother.
2022;8(1):85-99. PMID: 33638977).

6.20 Answer B.Eplerenone is a potassium-sparing diuretic via its aldosterone receptor–blocking

actions. Thus, it would be ideal to screen and avoid or stop agents that also increase the
risk of hyperkalemia (eg, potassium supplements, nonsteroidal anti-inflammatory agents,
and sulfamethoxazole and trimethoprim [SMP/TMZ]). There is no major risk of the
other adverse events listed (https://labels.fda.gov).

6.21 Answer D. SLCO1B1 polymorphism is associated with simvastatin-induced myopathy. It is

not a class effect; hence, other statins can be used, making option “A” incorrect.
Although low-dose simvastatin can be used, it is not potent enough to achieve adequate
LDL cholesterol lowering in this patient. High-dose simvastatin would put the patient at
risk of statin-associated muscle side effects. Thus, the best option would be rosuvastatin
given its high potency and limited impact by the SLCO1B1 polymorphism (CPIC.
https://cpicpgx.org; 2022; Magavern EF, Kaski JC, Turner RM, et al. The role of
pharmacogenomics in contemporary cardiovascular therapy: a position statement from
the European Society of Cardiology Working Group on Cardiovascular
Pharmacotherapy. Eur Heart J Cardiovasc Pharmacother. 2022;8(1):85-99. PMID:
 33638977).

6.22 Answer B. Triple therapy, based on expert consensus and guidelines, should ideally be
avoided, thus eliminating options “A” and “D” as answer. Compared to therapy
consisting of an anticoagulant and a single antiplatelet agent, triple therapy is associated
with increased bleeding risks without superior efficacy. Current evidence also does not
support the use of more potent P2Y12 inhibitors—such as ticagrelor—when an
anticoagulant is recommended. Based on the patient’s pharmacogenetic profile,
metabolism of clopidogrel to its active metabolite would not be impaired; hence, it
should be an effective antiplatelet agent. Lastly, given the patient’s warfarin phenotype
(ie, increased sensitivity to VKORC1 requiring lower initial and maintenance dosing of
warfarin), it would be prudent to use a direct oral anticoagulant (DOAC), making option
“B” the most suitable answer (CPIC. https://cpicpgx.org; 2022; Kumbhani DJ, Cannon
CP, Beavers CJ, et al. 2020 ACC expert consensus decision pathway for anticoagulant
and antiplatelet therapy in patients with atrial fibrillation or venous thromboembolism
undergoing percutaneous coronary intervention or with atherosclerotic cardiovascular
disease: a report of the American College of Cardiology Solution Set Oversight
Committee. J Am Coll Cardiol. 2021;77(5):629-658. PMID: 33250267).

6.23 Answer C. Some grapefruit juice constituents inhibit CYP3A4. Thus, grapefruit juice
should be avoided with these medications to reduce the risk of adverse events with this
interaction. The other food choices listed do not affect CYP3A4 (https://labels.fda.gov).

6.24 Answer B.Dronedarone can increase the blood levels and effects of dabigatran. Dabigatran
is metabolized by the P-gp transporter, and dronedarone inhibits this transporter. Thus,
concomitant administration of dronedarone leads to an increase in dabigatran plasma
concentration. In the patient receiving dronedarone, the labeling recommends the
dabigatran dose be reduced to 75 mg twice daily in those with CrCl 30-50 mL/min and
avoided in those with CrCl <30 mL/min (https://labels.fda.gov).

6.25 Answer D. CYP3A enzymes participate in the elimination of ticagrelor and the
bioactivation of clopidogrel and prasugrel. Strong CYP3A4 inducers substantially reduce
ticagrelor exposure and may decrease the efficacy of ticagrelor; hence, their concomitant
use should be avoided. Phenytoin is considered a strong CYP3A4 inducer and should not
be prescribed concomitantly with ticagrelor. Strong induction of CYP3A4 does not
interfere with the antiplatelet efficacy of clopidogrel or prasugrel, and aspirin is not a
substrate for CYP3A4 (https://labels.fda.gov).

6.26 Answer B.The CPIC guidelines provide recommendations on how test results should be
translated into prescribing actions. The CPIC guidelines do not determine when a test
should be performed and do not offer information on CLIA requirements or financial
value of testing (CPIC. https://cpicpgx.org; 2022).

6.27 Answer A. Pharmacogenetic testing can be done preemptively or reactively. Preemptive

 testing is conducted before a disease is symptomatic and a drug with pharmacogenetic
information is prescribed. The results can then be integrated into patients’ health records,
making this information available at the point of care in the future. Thus, preemptive
testing is called just-in-case testing, where the test is done before any need for
pharmacologic treatment and the results are there for future use. Reactive testing is
performed when needed to assess a specific drug-gene interaction. Reactive panel testing
refers to tests administered after the first disease is diagnosed and drug therapy is
indicated, but before the treatment is initiated. Hence, it is not for future use (Weitzel
KW, Cavallari LH, Lesko LJ. Preemptive panel-based pharmacogenetic testing: the time
is now. Pharm Res. 2017;34(8):1551-1555. PMID: 28466392).

6.28 Answer B.Cilostazol is a substrate of CYP3A4, and it should not be prescribed

concomitantly with strong CYP3A4 inhibitors or inducers to prevent bleeding or reduced
cilostazol efficacy (https://labels.fda.gov).

6.29 Answer B. Any competition for binding sites on serum proteins between drugs, resulting in
displacement, would impact the drugs’ distribution. For example, valproic acid may
displace warfarin from its protein binding sites resulting in the redistribution of warfarin
in its free active form and leading to a rapid increase in INR. Additionally, valproate has
the potential to inhibit warfarin metabolism via inhibition of CYP2C9, leading to
increased plasma concentrations of warfarin (https://labels.fda.gov).

6.30 Answer D.Cangrelor binds to and competes for the same platelet receptor site as
clopidogrel and prasugrel; they should not be administered during the cangrelor infusion
since they will not be effective. Conversely, ticagrelor binds to a different receptor site
than cangrelor (ie, it is noncompetitive) and can be administered during cangrelor
infusion (https://labels.fda.gov).
 Antiarrhythmics, Inotropes, Sedatives,
7
and Lipid-Lowering Agents

Anastasia L. Armbruster and Joseph S. Van Tuyl

QUESTIONS

7.1 A 62-year-old man presents to the emergency department (ED) with shortness of breath
that has progressively worsened over the past month. He recently noticed his legs were
swollen, and his weight has increased 10 pounds in the past week. His past medical
history (PMH) is significant for hypertension and heart failure with reduced ejection
fraction (HFrEF): left ventricular ejection fraction (LVEF) 30% 6 months ago. The
patient’s home medications include metoprolol succinate, furosemide,
sacubitril/valsartan, and spironolactone. The patient is afebrile with the following vital
signs: blood pressure (BP) 112/76 mm Hg, heart rate (HR) 125 beats per minute (bpm),
respiratory rate (RR) 20 breaths per minute, and pulse oximetry oxygen saturation (SaO2)
94% on room air. Lung examination reveals diffuse rales on auscultation. A physical
examination reveals 2+ pitting edema on both lower extremities and jugular venous
distention (JVD). An electrocardiogram (ECG) reveals atrial fibrillation with a rapid
ventricular rate. In addition to optimizing his volume status, which intravenous (IV)
agent is best to manage this patient’s arrhythmia?
A. Amiodarone
B. Diltiazem
C. Esmolol
D. Sotalol

7.2 A 68-year-old woman is admitted to the hospital for dofetilide initiation. Her PMH
includes atrial fibrillation and hypertension. A baseline ECG is obtained, and the
corrected QT (QTc) interval is measured at 380 ms. Her current medications include
lisinopril 20 mg daily, hydrochlorothiazide (HCTZ) 25 mg daily, and apixaban 5 mg
twice daily. Current laboratory values include serum creatinine 0.9 mg/dL (creatinine
clearance [CrCl] using actual body weight 66 mL/min), potassium 4.2 mEq/L, and
magnesium 2.0 mEq/L. Which of the following is necessary prior to initiating dofetilide
 500 µg BID?
A. Replete potassium
B. Discontinue HCTZ
C. Obtain second ECG to confirm QTc interval
D. Replete magnesium

7.3 A 54-year-old man with diabetes mellitus, hypertension, and hyperlipidemia presents to a
clinic and reports palpitations and shortness of breath for the past week. His ECG shows
atrial fibrillation with a rapid ventricular response. A transthoracic echocardiogram
demonstrates normal left ventricular function and no valvular abnormalities. Apixaban 5
mg twice daily and metoprolol tartrate 50 mg twice daily are initiated. The patient
returns 1 month later with continued palpitations and shortness of breath. After
discussing rhythm control with the patient, it is determined to initiate a class 1c
antiarrhythmic agent. Which of the following is the most appropriate next step prior to
initiation?
A. Invasive coronary angiography
B. Transesophageal echocardiogram
C. Exercise myocardial perfusion study
D. Cardiac magnetic resonance imaging study

7.4 A patient has been successfully managed on amiodarone 400 mg daily for the past 6
months for suppression of ventricular arrhythmias. Today, the patient reports increased
feelings of fatigue and cold intolerance for the past month. Which of the following
would correlate with the adverse effect she is likely experiencing?
A. Low thyroid-stimulating hormone (TSH); high T4
B. Elevated TSH; low T4
C. Abnormal chest x-ray
D. Low vitamin D level

7.5 A 47-year-old woman presents to the ED with new-onset atrial flutter. Vital signs include
BP 102/66 mm Hg and HR 135 bpm. On ECG, her QTc is measured at 320 ms. A
transthoracic echocardiogram is obtained, and her estimated LVEF is 45%. Pertinent
laboratory values include serum creatinine 0.9 mg/dL, potassium 2.9 mEq/L, and
magnesium 2.1 mg/dL. The decision to administer ibutilide is made. Which of the
following increases the risk of torsades de pointes (TdP) in this patient?
A. Corrected QT
B. Left ventricular ejection fraction
C. Serum potassium level
D. Serum magnesium level
7.6 An 80-year-old woman presents with altered mental status and vomiting. Her daughter
reports that the patient has had decreased oral intake over the past week. Current vital
signs include BP 82/52 mm Hg and HR 42 bpm. An ECG demonstrates second-degree
atrioventricular (AV) nodal block and bigeminy. Pertinent laboratory values include
serum creatinine 3.6 mg/dL (baseline 1.2 mg/dL), potassium 5.7 mEq/L, and digoxin 3.5
ng/mL. Which of the following is most appropriate to recommend at this time?
A. Phenylephrine
B. Digoxin-specific antibody fragment
C. Dopamine
D. Calcium gluconate

7.7 A 61-year-old female is admitted to the hospital for recurrent implantable cardioverter-
defibrillator (ICD) shocks. She has a history of nonischemic cardiomyopathy (LVEF
20%), cardiac resynchronization therapy-defibrillator (CRT-D) device placement, stage 4
chronic kidney disease, and hypothyroidism. Interrogation of the ICD reveals sustained
ventricular tachycardia that persisted despite antitachycardia pacing and required three
defibrillations before the arrhythmia was terminated. Relevant laboratory parameters
include serum potassium 4.1 mEq/L, magnesium 2.0 mg/dL, serum creatinine 2.5 mg/dL
(estimated CrCl 21 mL/min), and TSH 3.42 mIU/L. Current medications include
empagliflozin 10 mg daily, levothyroxine 25 µg daily, metoprolol succinate 100 mg
daily, sacubitril/valsartan 24/26 mg twice daily, and torsemide 20 mg twice daily. In this
patient, which medication is best to suppress recurrent, appropriate ICD shocks?
A. Lidocaine
B. Amiodarone
C. Sotalol
D. Ranolazine

7.8 Which of the following is TRUE regarding medication administration during cardiac
arrest secondary to pulseless ventricular tachycardia?
A. Epinephrine should be administered as soon as possible to facilitate return of
spontaneous circulation (ROSC)
B. Amiodarone is superior to lidocaine for achievement of ROSC
C. Antiarrhythmic medications should be administered after initial defibrillation attempts
fail to achieve ROSC
D. Procainamide is superior to amiodarone to facilitate ROSC

7.9 A 53-year-old man presents to the ED via ambulance with complaints of progressive
shortness of breath over the past week. During his transfer, he received a single
defibrillation for ventricular fibrillation. Upon arrival, vital signs include BP 98/60 mm
Hg and HR 100 bpm. His extremities are cool to the touch. A transthoracic
echocardiogram reveals an LVEF of 15%. A right heart catheterization is performed with
the following findings: pulmonary capillary wedge pressure (PCWP) 32 mm Hg and
 cardiac index 1.6 L/min/m2. Which medication is most appropriate in this patient?
A. Dobutamine
B. Epinephrine
C. Milrinone
D. Vasopressin

7.10 A 57-year-old patient presents with cardiogenic shock following an acute right coronary
artery occlusion. A transthoracic echocardiogram confirms right ventricular (RV)
dysfunction. Following reperfusion therapy, the patient remains hypotensive with central
venous pressure 10 mm Hg. Which vasoactive agent is most appropriate in this patient?
A. Phenylephrine
B. Dobutamine
C. Milrinone
D. Epinephrine

7.11 Which vasoactive agent is recommended in patients with hypertrophic obstructive

cardiomyopathy (HOCM) experiencing hypotension?
A. Dopamine
B. Dobutamine
C. Phenylephrine
D. Norepinephrine

7.12 A 59-year-old man is brought to the cardiac catheterization lab following a positive stress
test. Fifteen minutes into the procedure, the patient becomes profoundly hypotensive,
tachycardiac, and hypoxemic. Inspiratory stridor is noted by one of the staff members.
Which agent should be administered acutely to prevent additional compromise?
A. Epinephrine administered intravenously
B. Epinephrine administered subcutaneously
C. Norepinephrine
D. Dopamine

7.13 A 71-year-old male is admitted to the cardiac intensive care unit (ICU) for management
of cardiogenic shock and hypoxic respiratory failure. The patient is receiving fentanyl
and dexmedetomidine for analgesia and sedation while mechanically ventilated, and
dobutamine, epinephrine, and vasopressin are infusing to augment cardiac output (CO)
and mean arterial pressure. Vital signs include BP 92/66 mm Hg and HR 98 bpm. The
SaO2 is 96% on a fraction of inspired oxygen (FIO2) 40%, and an arterial blood gas reveals
a pH 7.21, PaO2 82 mm Hg, PaCO2 39 mm Hg, and HCO3 19 mEq/L. Serum lactate
increased from 2.3 to 4.9 mmol/L over the past 24 hours. Which medication may be
contributing to elevated serum lactate?
 A. Dexmedetomidine
B. Dobutamine
C. Epinephrine
D. Vasopressin

7.14 A 36-year-old male is admitted to the cardiac ICU after experiencing TdP secondary to an
intentional overdose of citalopram. IV magnesium supplementation was initiated by the
primary team; however, TdP recurred thrice in the past 6 hours, with each recurrence
successfully terminated with defibrillations. An ECG recorded after the most recent
episode records an HR 62 bpm and QTc 620 ms. Which strategy is best to prevent TdP
recurrence?
A. Procainamide
B. Lidocaine
C. Isoproterenol
D. Amiodarone

7.15 A 62-year-old male is transported to the ED after being resuscitated for out-of-hospital
cardiac arrest secondary to an ST-segment elevation myocardial infarction (STEMI) for
which the patient receives a drug-eluting stent (DES) to the proximal left anterior
descending artery. The patient becomes hypotensive and febrile after percutaneous
coronary intervention with BP 88/42 mm Hg and temperature 101.1 °F. A right heart
catheterization reveals the following hemodynamic parameters: right atrial pressure 14
mm Hg, PCWP 25 mm Hg, CO 4.9 L/min, cardiac index 2.0 L/min/m2, and systemic
vascular resistance 702 dynes s/cm5. Relevant laboratory parameters include white blood
cell (WBC) count 13.2 cells/mm3, serum lactate 4.5 mmol/L, and mixed venous oxygen
saturation (SvO2) 60%. Which vasoactive medication is most appropriate to optimize
hemodynamics in this patient?
A. Dobutamine
B. Milrinone
C. Epinephrine
D. Norepinephrine

7.16 A 78-year-old female is transported to the ED with dyspnea on exertion and altered
mentation. Her PMH includes hypertension and paroxysmal atrial fibrillation. Home
medications include amlodipine 10 mg daily, apixaban 5 mg twice daily, and bisoprolol
5 mg daily. Pertinent physical exam findings include bilateral rales and cool extremities
bilaterally. Initial vital signs include BP 84/42 mm Hg, HR 109 bpm, RR 24 bpm, SpO2
90% on bilevel positive airway pressure (BiPAP) (FIO2 60%), and temperature 99.1 °F.
Relevant laboratory parameters include serum creatinine 2.2 mg/dL (baseline 1.1
mg/dL), WBC 8.2 cells/mm3, and lactate 3.9 mmol/L. An ECG shows sinus tachycardia,
and a chest x-ray reveals bilateral interstitial opacities. A transthoracic echocardiogram
reveals the following: LVEF 55%, AV peak velocity 4.4 m/s, AV mean gradient 42 mm
 Hg, AV area 0.9 cm2, and stroke volume index 48 mL/m2. Which vasoactive medication
is best to initiate?
A. Milrinone
B. Dobutamine
C. Phenylephrine
D. Dopamine

7.17 A 71-year-old man with diabetes mellitus and a history of revascularization for peripheral
artery disease (PAD) was initiated on ezetimibe 10 mg/day 4 months ago in addition to
atorvastatin 80 mg/day. His low-density lipoprotein cholesterol (LDL-C) today is 82
mg/dL. Which one of the following is best to optimize this patient’s medical regimen?
A. Maintain current therapy
B. Add bempedoic acid
C. Change to rosuvastatin 40 mg/day
D. Add evolocumab

7.18 A patient presents to the clinic following triple vessel coronary artery bypass graft
(CABG) surgery 2 months ago. She was discharged on rosuvastatin 5 mg 3 times per
week due to her previous history of partial statin intolerance. Her LDL-C obtained in the
office is 99 mg/dL. She is not interested in self-administering injectables or increasing
her dose or frequency of rosuvastatin. Which of the following is most appropriate to
initiate to achieve her LDL-C target of <55 mg/dL?
A. Bempedoic acid
B. Alirocumab
C. Inclisiran
D. Ezetimibe

7.19 A 55-year-old man presents with questions regarding cardiovascular risk reduction after
his friend died of a heart attack. He has hypertension and reports his mother had a heart
attack at the age of 60 years. His 10-year atherosclerotic cardiovascular disease
(ASCVD) risk is 7.3%. Which of the following steps is most appropriate?
A. Obtain biomarkers or a coronary artery calcium score
B. Initiate atorvastatin 40 mg
C. Initiate simvastatin 20 mg
D. Initiate ezetimibe 10 mg

7.20 A 48-year-old woman with type 2 diabetes mellitus (for 10 years) presents to the clinic
for follow-up. Current medications include lisinopril 10 mg/day, HCTZ 25 mg/day, and
atorvastatin 10 mg/day. Her 10-year ASCVD risk is estimated at 7.5% and plasma LDL-
C is measured at 110 mg/dL. Which of the following is most appropriate to reduce her
 risk of ASCVD events?
A. Continue current therapy
B. Increase atorvastatin to 40 mg
C. Add ezetimibe 10 mg
D. Add aspirin 81 mg

7.21 A 49-year-old male presents to the clinic for a routine follow-up of stable ischemic heart
disease. The patient has a history of non–ST-segment elevation acute coronary syndrome
(NSTE-ACS) with a DES placement to the right coronary artery (4 months ago), type 2
diabetes mellitus, and hypertension. Current medications include aspirin 81 mg daily,
carvedilol 12.5 mg twice daily, losartan 25 mg daily, metformin 500 mg twice daily,
prasugrel 10 mg daily, and rosuvastatin 40 mg daily. A fasting lipid panel reveals total
cholesterol 135 mg/dL, high-density lipoprotein cholesterol (HDL-C) 44 mg/dL, LDL-C
51 mg/dL, and triglycerides 202 mg/dL. Relevant laboratory parameters include an
aspartate aminotransferase (AST) 29 IU/L, alanine transaminase (ALT) 26 IU/L, and
hemoglobin A1C 6.8%. Which change to pharmacologic therapy is most appropriate?
A. Change rosuvastatin 40 mg daily to atorvastatin 80 mg daily
B. Add ezetimibe
C. Add evolocumab
D. Add icosapent ethyl

7.22 A 66-year-old man presents to the clinic following his recent STEMI 2 months ago (DES
to right coronary artery). Other relevant PMH includes diabetes mellitus and
hypertension. Current medications include aspirin 81 mg daily, ticagrelor 90 mg twice
daily, metoprolol tartrate 25 mg twice daily, metformin 1,000 mg twice daily, lisinopril
20 mg daily, and rosuvastatin 20 mg daily. At the time of his acute coronary syndrome
(ACS), he was not receiving statin therapy and his plasma LDL-C was reported as 155
mg/dL. In clinic today, a fasting lipid panel reports his LDL is 70 mg/dL. Which of the
following is the most appropriate next step?
A. No changes, repeat lipid panel in 12 months
B. Add ezetimibe
C. Add evolocumab
D. Change rosuvastatin to atorvastatin

7.23 A 57-year-old female is admitted to the hospital with unstable angina. Her PMH includes
a two-vessel CABG, PAD with a stent to the right common iliac artery, hypertension,
type 2 diabetes mellitus, and gout. Current medications include allopurinol 200 mg daily,
aspirin 81 mg daily, atorvastatin 80 mg daily, clopidogrel 75 mg daily, heparin 12
units/kg/h IV continuous infusion, liraglutide 1.2 mg SQ (subcutaneous) daily,
metformin 1,000 mg twice daily, metoprolol tartrate 50 mg twice daily, and ramipril 10
mg daily. A fasting lipid panel reveals total cholesterol 178 mg/dL, HDL-C 37 mg/dL,
LDL-C 111 mg/dL, and triglycerides 148 mg/dL. Which lipid-lowering therapy is most
 appropriate to add at discharge?
A. Evolocumab
B. Ezetimibe
C. Icosapent ethyl
D. Inclisiran

7.24 A 68-year-old male with no PMH is admitted to the hospital with acute-onset, substernal
chest pain that occurred at rest. The ECG reveals ST depressions in leads II, III, and
aVF. Serial cardiac troponin I values are collected upon presentation and every 6 hours
following and include 0.02, 0.123, and 0.957 ng/mL. A fasting lipid panel reveals total
cholesterol 223 mg/dL, HDL-C 55 mg/dL, LDL-C 70 mg/dL, and triglycerides 489
mg/dL, and a hemoglobin A1C is 10.1%. Which antihyperlipidemic therapy is best to
initiate at this time?
A. Atorvastatin 80 mg daily
B. Rosuvastatin 10 mg daily
C. Icosapent ethyl 2 g twice daily
D. Fenofibrate 45 mg daily

7.25 A 38-year-old woman is admitted to the ICU after an out-of-hospital cardiac arrest
secondary to ventricular fibrillation. The patient is mechanically ventilated and receiving
fentanyl and midazolam for analgesia and sedation. She is receiving targeted temperature
management, but shivering persists despite therapy with acetaminophen and buspirone.
Cisatracurium is to be administered to control shivering. Which statement is TRUE
regarding analgesia and sedation during cisatracurium use?
A. Deep sedation is required prior to cisatracurium administration
B. Light sedation is required prior to cisatracurium administration
C. Cisatracurium has analgesic and sedative properties
D. Fentanyl and midazolam should be discontinued after cisatracurium initiation

7.26 A 45-year-old woman is in the cardiac ICU with cardiogenic shock secondary to acute
decompensated heart failure. The patient was intubated on day 1 of the hospitalization
and has received analgesia and sedation with fentanyl and propofol, respectively, since
the initiation of mechanical ventilation. Dobutamine was initiated at 5 µg/kg/min upon
admission, and the infusion rate was decreased to 2.5 µg/kg/min by day 2 of the
hospitalization. Mean arterial pressure and CO declined on day 3, necessitating up-
titration of dobutamine to 10 µg/kg/min and initiation of epinephrine. On day 4, while
the patient is receiving dobutamine, epinephrine, and norepinephrine for hemodynamic
support, laboratory data reveal a worsening lactic acidosis, rhabdomyolysis, and renal
failure. Which medication could be causing the worsening clinical status of the patient?
A. Fentanyl
B. Epinephrine
 C. Propofol
D. Dobutamine

7.27 A 49-year-old man is transported to the ED with a STEMI. While in the cardiac
catheterization lab, the patient becomes hypoxic and requires mechanical ventilation to
maintain adequate arterial oxygenation. Current vitals include BP 102/74 mm Hg, HR 94
bpm, RR 25 bpm, and SaO2 86% on BiPAP with FIO2 60%. Relevant laboratory
parameters include serum potassium 5.7 mEq/L, creatinine 1.6 mg/dL, AST 48 IU/L, and
ALT 55 IU/L. The patient is administered fentanyl for analgesia. Which induction agent
and neuromuscular blocking agent are most appropriate to facilitate rapid sequence
intubation in this patient?
A. Etomidate, succinylcholine
B. Etomidate, rocuronium
C. Ketamine, succinylcholine
D. Propofol, rocuronium

7.28 A 63-year-old female with a history of nonischemic cardiomyopathy is admitted to the

cardiac ICU in cardiogenic shock secondary to severe mitral regurgitation. The patient is
mechanically ventilated with an FIO2 40% and positive end–expiratory pressure (PEEP) of
10 cm H2O and maintaining an SaO2 of 98%. Relevant medications include milrinone
0.25 µg/kg/min intravenously, furosemide 15 mg/h intravenously, fentanyl 100 mg/h
intravenously, and midazolam 4 mg/h intravenously. A Richmond Agitation Sedation
Scale (RASS) score has been consistently recorded at −3, and the Critical-Care Pain
Observation Tool (CPOT) is 0. Which strategy is best to manage analgesia and sedation
in this patient?
A. Decrease fentanyl infusion rate
B. Increase fentanyl infusion rate
C. Decrease midazolam infusion rate
D. Maintain midazolam infusion rate

7.29 A patient is mechanically ventilated and receiving fentanyl and midazolam for analgesia
and sedation. Respiratory function has improved, and ventilator settings are minimal in
preparation for extubation. However, the patient has a positive Confusion Assessment
Method for the ICU (CAM-ICU) score and becomes agitated when sedation is
decreased. The ongoing agitation is preventing liberation from the ventilator. Which
strategy is best to facilitate extubation?
A. Start haloperidol
B. Change midazolam to dexmedetomidine
C. Start quetiapine
D. Discontinue fentanyl
7.30 Which statement regarding the interaction between morphine and oral P2Y12 inhibitors is
TRUE?
A. Morphine may delay absorption of clopidogrel and prolong the duration of residual
platelet reactivity
B. Morphine increases the risk of cardiovascular mortality in patients with an ACS
C. Morphine delays onset of antiplatelet activity after clopidogrel administration via
CYP2C19 inhibition
D. Morphine does not affect the onset of antiplatelet activity after ticagrelor or prasugrel
administration

ANSWERS AND EXPLANATIONS

7.1 Answer A. In patients with HFrEF presenting with new-onset atrial fibrillation and
worsening heart failure, control of a rapid ventricular rate is important. Amiodarone is
considered safe in patients with HFrEF, while other rate control therapies (ie, diltiazem,
esmolol, and sotalol) may worsen heart failure due to negative inotropic effects. When
utilizing amiodarone in this setting, patients’ risk of stroke should be addressed in the
event cardioversion to sinus rhythm occurs.

7.2 Answer B. Use of HCTZ is contraindicated in patients receiving dofetilide, as it increases

plasma levels of dofetilide (by decreasing renal clearance) and decreases serum levels of
potassium, thus increasing the risk of QTc prolongation. It is important to maintain
serum potassium and magnesium levels to decrease the risk of torsade de pointes in
patients receiving dofetilide.

7.3 Answer C. Vaughan Williams class 1c antiarrhythmic agents (ie, flecainide, propafenone)
are effective for the management of atrial fibrillation but are contraindicated in the
presence of structural heart disease, including obstructive coronary disease. Based on the
patient’s risk factors, it is necessary to rule out obstructive coronary disease prior to the
initiation of flecainide or propafenone.

7.4 Answer B. Amiodarone is associated with the development of both hypothyroidism and
hyperthyroidism due to the iodine modality found in the structure. The patient is
reporting symptoms consistent with hypothyroidism and should receive screening for
thyroid abnormalities. Amiodarone-induced hypothyroidism often occurs earlier in
treatment course and is more likely to occur in patients of older age and women.

7.5 Answer C. Ibutilide is an effective cardioversion agent, especially in patients with recent
onset atrial flutter. To reduce the risk of TdP, ibutilide should be avoided in patients with
QTc prolongation, marked hypokalemia, and an LVEF ≤30%. This patient has a normal
QT interval, marked hypokalemia, mildly reduced LVEF, and normal serum magnesium
level. Patients should undergo continuous ECG monitoring for at least 4 hours following
 ibutilide administration to monitor for TdP.

7.6 Answer B.This patient presents with severe digoxin toxicity and is exhibiting symptoms
(hyperkalemia, AV block, vomiting, and altered mental status) consistent with toxicity.
Administration of digoxin-specific antibody fragment (DSFab) is appropriate based on
the severity of symptoms and elevated digoxin level. Hyperkalemia will likely resolve
with the administration of DSFab.

7.7 Answer B.Amiodarone is safe to administer to patients with heart failure with reduced
LVEF and effective in suppressing recurrent, appropriate ICD shocks. According to the
2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular
Arrhythmias and the Prevention of Sudden Cardiac Death, amiodarone or sotalol can be
beneficial (COR [class of recommendation] IIa, LOE [level of evidence] B-R) in patients
with nonischemic cardiomyopathy and an ICD who experience spontaneous ventricular
arrhythmias or recurrent appropriate shocks despite optimal device programming and
treatment with a β blocker. However, sotalol is contraindicated in patients with an
estimated CrCl <40 mL/min, and the patient’s CrCl is 21 mL/min. The patient’s
hypothyroidism is well controlled, but the TSH will need ongoing monitoring during
amiodarone therapy. Lidocaine may be considered as an add-on therapy for patients with
recurrent ventricular arrhythmias despite treatment with amiodarone, but it requires IV
administration. Ranolazine failed to decrease the composite risk of death or ventricular
tachycardia or fibrillation requiring appropriate ICD therapy when compared with
placebo in the Ranolazine Implantable Cardioverter-Defibrillator (RAID) trial; therefore,
ranolazine is not an appropriate initial therapy to suppress appropriate ICD shocks.

7.8 Answer C. Although no clinical trials have assessed the effect of timing of antiarrhythmic
medication administration on clinical outcomes in out-of-hospital cardiac arrest, study
protocols routinely stipulate that antiarrhythmic medications be administered after
defibrillations fail to achieve ROSC. Therefore, the 2020 AHA Guidelines for
Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommend the
administration of either amiodarone or lidocaine after initial defibrillation attempts fail to
achieve ROSC. The updated guideline recommends either amiodarone or lidocaine to
improve ROSC and survival to hospital admission, whereas prior guideline statements
prioritized amiodarone use over lidocaine in pulseless ventricular tachycardia or
ventricular fibrillation. There are insufficient data to recommend procainamide
administration during cardiac arrest. In addition, defibrillations and antiarrhythmic
therapy should be prioritized over epinephrine in pulseless ventricular tachycardia or
ventricular fibrillation, but rapid epinephrine administration is appropriate during
pulseless electrical activity or asystole.

7.9 Answer C.An inotrope is indicated in this patient with hemodynamic findings of low
cardiac index combined with elevated PCWP (ie, cardiogenic shock) to augment CO and
improve end-organ perfusion. A preferred inotrope has not been identified in clinical
studies and is frequently left to clinician preference. Due to stimulation of β-1 receptors
by dobutamine with resultant increased HR and risk of cardiac arrhythmia, milrinone is
 preferred in this patient following the development of ventricular fibrillation requiring
defibrillation. Epinephrine is an inotropic agent, but unlike milrinone and dobutamine, it
increases systemic vascular resistance (afterload) that may be deleterious in this patient
with markedly depressed left ventricular function. Vasopressin acts through the
vasopressin 1 receptors to cause vasoconstriction and raises mean arterial pressure. It
does not have any inotropic effects and causes reduction in HR and CO. Vasopressin is
used as a second-line vasopressor in septic shock, but evidence for its use in cardiogenic
shock is lacking. There have been no randomized control trials on vasopressin use in
cardiogenic shock.

7.10 Answer C.Management of patients in cardiogenic shock secondary to acute RV failure is

focused on the optimization of right-sided filling pressures and reducing RV afterload.
Agents that reduce preload, slow HR, or decrease contractility should be used with
caution. Inotropes that reduce cardiac filling pressure by reducing afterload—such as
milrinone—are preferred. If treatment is limited by hypotension, norepinephrine can be
added for additional support. Milrinone is more effective at reducing afterload than
dobutamine, and epinephrine increases afterload. Phenylephrine is a vasoconstrictor with
no inotropic properties.

7.11 Answer C.Acute hypotension in patients with HOCM should focus on maximizing preload
and afterload while avoiding increases in contractility or HR. Phenylephrine is
recommended over other agents due to its vasoconstrictive properties: phenylephrine is a
vasoconstrictor with no positive inotropic or chronotropic properties.

7.12 This patient is experiencing anaphylactic shock with hemodynamic

Answer A.
compromise. Epinephrine is the drug of choice for treating severe anaphylactic reactions.
IV administration provides a rapid onset of action and avoids erratic absorption from
subcutaneous sites. IV administration is typically reserved for patients experiencing
shock. Additional supportive medications—including high-dose steroids, antihistamines,
histamine-2 receptor blockers, and aggressive fluid resuscitation—should be
administered following the administration of epinephrine.

7.13 Answer C. The patient has an elevated serum lactate despite achieving a mean arterial
pressure greater than 65 mm Hg and adequate oxygenation with mechanical ventilation.
Epinephrine may increase serum lactate via stimulation of β-2 adrenergic receptors on
skeletal muscle with increased aerobic glycolysis: the increase in lactic acid production
occurs under aerobic conditions. Therefore, serum lactate may not be a consistently
reliable laboratory parameter to monitor to assess end-organ perfusion during
epinephrine administration. None of the other medications is a known cause of elevated
serum lactate.

7.14 Answer C.According to the 2017 AHA/ACC/HRS Guideline for Management of Patients
With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death, atrial or
ventricular pacing or isoproterenol is recommended to increase HR to suppress recurrent
TdP despite magnesium replacement in the setting of a prolonged QTc and bradycardia
 (COR I, LOE B-NR). Medications that cause QTc prolongation are ineffective in
suppression of TdP secondary to a prolonged QTc, so amiodarone is an inappropriate
medication to suppress TdP. Although procainamide may be considered for termination
of hemodynamically stable, sustained ventricular tachycardia with a pulse, there are no
data to suggest that procainamide suppresses TdP. Lidocaine is also not recommended
for TdP suppression.

7.15 Answer D. The patient has evidence of mixed shock with a low cardiac index, high PCWP,
and low systemic vascular resistance. Although a pure inotropic agent (ie, dobutamine)
or an inodilator (ie, milrinone) may be appropriate to administer for cardiogenic shock
after coronary revascularization for myocardial infarction, neither medication alone is
expected to cause vasoconstriction to increase systemic vascular resistance and mean
arterial pressure. Both norepinephrine and epinephrine are predominantly vasopressors
with positive inotropy, although positive inotropic effects are comparatively less than
dobutamine or milrinone. Although epinephrine causes greater positive inotropy than
norepinephrine, epinephrine increases the risk of refractory cardiogenic shock after
myocardial infarction compared with norepinephrine, and both medications achieve
similar augmentation of cardiac index. Therefore, norepinephrine is the most appropriate
vasoactive medication to administer to optimize cardiovascular hemodynamics in this
patient.

7.16 Answer C. The patient is in cardiogenic shock secondary to severe aortic stenosis with a
preserved LVEF. Cardiogenic shock in the setting of severe aortic stenosis is considered
afterload dependent; therefore, vasopressors should be preferred over inotropic
medications to improve mean arterial pressure and end-organ perfusion, according to the
2017 AHA Scientific Statement on Contemporary Management of Cardiogenic Shock.
Phenylephrine is an α-1 adrenergic agonist that is preferred in this setting. Although
dopamine may be an α-1 adrenergic agonist at high doses, dopamine increases the risk of
atrial tachyarrhythmias, including atrial fibrillation. It would not be preferred in this
patient with paroxysmal atrial fibrillation, despite the absence of atrial fibrillation on the
most recent ECG. If the LVEF were reduced, then dobutamine or milrinone may be
preferred to augment CO, improve mean arterial pressure, and maintain end-organ
perfusion.

7.17 Answer D. This patient is considered very high risk for future coronary events due to one
major ASCVD event (PAD with prior revascularization), plus multiple high-risk
conditions (age ≥65 years, diabetes mellitus). The 2022 ACC ECDP Role of Nonstatin
Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic
Cardiovascular Disease Risk recommends the addition of a proprotein convertase
subtilisin/kexin type 9 serine protease (PCSK9) inhibitor in patients receiving maximally
tolerated statin therapy plus ezetimibe who are not achieving an LDL-C ≤55 mg/dL.
Additionally, evolocumab has been shown to reduce the risk of major limb events in
patients with PAD. There is no benefit from changing from one high-intensity statin
therapy to another (ie, from atorvastatin 80 mg/day to rosuvastatin 40 mg/day).
Bempedoic acid is FDA (U.S. Food and Drug Administration) approved for the
 treatment of adults with heterozygous familial hypercholesterolemia or established
ASCVD who require additional lowering of LDL-C. Bempedoic acid may also be an
effective oral therapeutic option for lipid lowering in patients who cannot tolerate statins
to reduce the composite risk of cardiovascular mortality, nonfatal myocardial infarctions,
nonfatal stroke, or coronary revascularization, but the estimated LDL-C reduction from
bempedoic acid alone (approximately 25%) is insufficient to achieve the target LDL-C

7.18 Answer C. This patient still requires significant LDL reduction and is unable to tolerate
additional statin therapy. Inclisiran works by targeting the PCSK9 enzyme; however, as
opposed to PCSK9 inhibitors, which are antibodies that inhibit circulating PCSK9,
inclisiran is a chemically synthesized small interfering RNA (siRNA) molecule that
reduces the production of PCSK9 through gene silencing. Inclisiran is administered by a
clinician rather than self-administered like PCSK9 inhibitors. It offers a robust LDL
reduction (45%-52%) and is administered once every 6 months following the initial
dose, followed by a dose at day 90, making it a feasible option for patients who refuse to
self-administer or may struggle with compliance. Cardiovascular outcome data with
inclisiran are forthcoming. Bempedoic acid is an orally administered lipid-lowering
agent that lowers LDL-C by an additional 15%-20% in patients already taking a statin
medication. Bempedoic acid reduces the composite risk of cardiovascular mortality,
nonfatal myocardial infarctions, nonfatal stroke, or coronary revascularization in patients
with a history of myocardial infarction and intolerant of statins. Randomized clinical
trials support the prescription of ezetimibe as an add-on agent or alternative therapy in
statin-intolerant patients or among those with suboptimal LDL-C reductions on a statin
monotherapy; however, in combination therapy with statins, ezetimibe would result in
only a 25% additional LDL-C lowering.

7.19 Answer A.The 10-year risk for ASCVD is categorized as low risk (<5%), borderline risk
(5%-7.4%), intermediate risk (7.5%-19.9%), and high risk (≥20%). As outlined in the
2018 Cholesterol Clinical Practice Guidelines, patients with intermediate risk should
undergo a risk discussion with their provider, which includes the assessment of risk
enhancers. The patient reported one risk enhancer (premature ASCVD in mother), and
additional assessment with biomarkers or a coronary artery calcium score would provide
additional insight prior to initiation of statin therapy.

7.20 Answer B. Patients with diabetes mellitus and an LDL 70-189 mg/dL are indicated for a
moderate-intensity statin. While this patient is already receiving a moderate-intensity
statin, her LDL remains above 100 mg/dL, indicating the change to a high-intensity
statin should be considered. Her estimated ASCVD risk of ≥7.5% combined with the
duration of her diabetes mellitus (diabetes risk enhancer) also supports the increase to a
high-intensity statin.

7.21 Answer D.The patient has hypertriglyceridemia with serum triglycerides 202 mg/dL
despite at least 6 weeks of high-intensity statin therapy after a recent ACS. Per the 2021
ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk
Reduction in Patients with Persistent Hypertriglyceridemia, icosapent ethyl may be
 considered, in addition to maximally tolerated statin therapy, in patients with clinical
ASCVD who are achieving a goal LDL-C and have persistent hypertriglyceridemia with
triglycerides 150-500 mg/dL. In patients with clinical ASCVD on maximally tolerated
statin therapy, icosapent ethyl decreased the risk of the composite end point of
cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary
revascularization, or unstable angina in the REDUCE-IT (Reduction of Cardiovascular
Events With Icosapent Ethyl-Intervention Trial) study. Since the patient is achieving a
goal LDL-C ≤55 mg/dL, further LDL-C reduction with ezetimibe or evolocumab is
unlikely to significantly decrease the risk of recurrent ASCVD events; therefore, the
addition of neither ezetimibe nor evolocumab is necessary in this patient. Changing
rosuvastatin to atorvastatin (ie, from one high-intensity statin to another) is unlikely to
improve hypertriglyceridemia or further reduce the risk of recurrent ASCVD events.

7.22 Answer B.This patient is considered very high risk due to one major ASCVD event (ACS
in the past 12 months), plus multiple high-risk conditions (age ≥65 years, diabetes
mellitus, and hypertension). The 2022 ACC Expert Consensus Decision Pathway on the
Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of
Atherosclerotic Cardiovascular Disease Risk recommends ezetimibe as the initial
nonstatin therapy in patients receiving maximally tolerated statin therapy who are not
achieving an LDL ≤55 mg/dL. Either ezetimibe or a PCSK9 inhibitor may be considered
to decrease the LDL-C to goal and reduce the risk of recurrent ASCVD events. Factors
favoring ezetimibe use over a PCSK9 inhibitor include <25% LDL-C reduction to
achieve the goal LDL-C, cost considerations, <3 months since ACS, ease of
administration (oral vs self-injection), and patient preference. Since a 25% LDL-C
reduction from 70 mg/dL will achieve the target LDL-C of ≤55 mg/dL, ezetimibe may
be reasonably justified over a PCSK9 inhibitor. Switching high-intensity statins (ie, from
rosuvastatin to atorvastatin) is of no benefit.

7.23 Answer A. Per the 2022 ACC Expert Consensus Decision Pathway on the Role of
Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of
Atherosclerotic Cardiovascular Disease Risk recommendations, the patient is at very
high risk of recurrent ASCVD events; therefore, the patient has a goal LDL-C of ≤55
mg/dL. The current LDL-C (111 mg/dL) is more than twice the goal. A PCSK9
monoclonal antibody is considered appropriate to achieve the goal LDL-C and reduce
the composite risk of cardiovascular death, myocardial infarction, stroke, hospitalization
for unstable angina, or coronary revascularization, according to the FOURIER (Further
Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated
Risk) trial. Inclisiran may be considered in patients with poor adherence or intolerance to
PCSK9 monoclonal antibodies who do not achieve goal LDL-C reduction with
maximally tolerated statin therapy. Inclisiran is proven to decrease LDL-C; however, its
effect on cardiovascular morbidity and mortality has not yet been determined, although
trials to assess these are ongoing. Since the anticipated LDL-C reduction with ezetimibe
(25%) or bempedoic acid (17%-18%) is not expected to decrease the LDL-C to ≤55
mg/dL, neither medication should be preferred over a PCSK9 inhibitor. Since the patient
has not achieved the goal LDL-C and does not have persistent hypertriglyceridemia,
pharmacologic options that target LDL-C reduction should be prioritized over icosapent
 ethyl.

7.24 Answer A. The patient is experiencing a non–ST-elevated myocardial infarction

(NSTEMI). According to the 2014 AHA/ACC Guideline for the Management of Patients
with Non–ST-Elevation Acute Coronary Syndromes, high-intensity statin therapy should
be initiated in all patients with NSTE-ACS and no contraindications to use (COR I, LOE
A). This recommendation is applicable regardless of plasma LDL-C concentration.
Rosuvastatin 10 mg daily is a moderate-intensity statin and is an inferior option
compared with atorvastatin 80 mg daily which is the dose of atorvastatin proven to
decrease the composite risk of death from any cause, myocardial infarction, unstable
angina requiring hospitalization, coronary revascularization, or stroke in patients with
ACS enrolled in the PROVE-IT/TIMI 22 (the Pravastatin or Atorvastatin Evaluation and
Infection Therapy-Thrombolysis in Myocardial Infarction 22) trial. Although the patient
has elevated plasma triglycerides, high-intensity statin therapy should be initiated prior
to pharmacologic options to target serum triglycerides. In addition, uncontrolled diabetes
mellitus is a known cause of hypertriglyceridemia, and treatment of underlying causes of
hypertriglyceridemia is necessary before initiating pharmacologic therapy, according to
the 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk
Reduction in Patients with Persistent Hypertriglyceridemia. If the patient has persistent
hypertriglyceridemia after achieving a target LDL-C on maximally tolerated statin
therapy, then icosapent ethyl may be considered to decrease the risk of recurrent
ASCVD events.

7.25 Answer A.Neuromuscular blocking agents (eg, cisatracurium, rocuronium, vecuronium) do

not provide analgesia or sedation, and RASS and CPOT monitoring are unreliable during
administration of neuromuscular blocking agents. Thus, the Clinical Practice Guidelines
for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient recommend
achieving deep sedation prior to administration of neuromuscular blocking agents and
maintaining analgesic and sedative medications throughout the neuromuscular blockade.

7.26 Answer C. Propofol-related infusion syndrome (PRIS) typically manifests after 48 hours of
sedation with propofol at doses exceeding 4 mg/kg/h and is typified by a constellation of
clinical findings including metabolic acidosis, rhabdomyolysis, renal failure, and
increasing inotrope and vasopressor requirement. Management of overt PRIS requires
immediate discontinuation of propofol infusion and supportive management, including
hemodialysis, hemodynamic support, and extracorporeal membrane oxygenation in
refractory cases. Although epinephrine is known to cause lactic acidosis due to agonism
of β-2 adrenergic receptors on skeletal muscle, epinephrine is not implicated in a risk of
renal failure or rhabdomyolysis. Neither dobutamine nor fentanyl has been implicated in
this clinical syndrome.

7.27 Answer B.Fentanyl was administered to the patient to provide analgesia in anticipation of
rapid sequence intubation. Etomidate has minimal hemodynamic effects and is not
expected to decrease BP, so it may be administered safely for induction prior to
neuromuscular blockade. Succinylcholine is contraindicated in this patient due to the
 presence of hyperkalemia with a serum potassium 5.7 mEq/L. Therefore, rocuronium is
the neuromuscular blocking agent safest to administer to this patient. Ketamine is
considered hemodynamically neutral, unless catecholamine reserve has been exhausted,
and provides analgesia; however, since the patient already received fentanyl for
analgesia, an induction agent that provides analgesia is unnecessary. Propofol may
decrease BP more than either etomidate or ketamine and is generally not preferred in
patients with lower BP and at risk of hemodynamic instability.

7.28 Answer C. According to the Clinical Practice Guidelines for the Prevention and
Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in
Adult Patients in the ICU, light sedation should be provided to mechanically ventilated
patients to decrease time to extubation and ICU length of stay. The CPOT score of 0
indicates adequate analgesia, so the fentanyl dose can be maintained at the current
infusion rate to maintain pain control. A RASS score of −3 is indicative of deep
sedation; the goal RASS for light sedation is 0 to −2. Therefore, the midazolam infusion
rate should be decreased to achieve light sedation.

7.29 Answer B.Dexmedetomidine is recommended in patients with ongoing delirium that

prevents ventilator weaning or extubation, per the Clinical Practice Guidelines for the
Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and
Sleep Disruption in Adult Patients in the ICU. Benzodiazepines, such as midazolam, are
a known risk factor for delirium and should be minimized or avoided, if possible, to
decrease the risk of delirium and prevent worsening delirium. Atypical antipsychotic
medications (ie, quetiapine) and haloperidol are not recommended for routine use to treat
delirium due to lack of clinical benefit, unless the patient experiences significant
psychological distress (eg, fearfulness, hallucinations). Adequate analgesia is appropriate
in patients with delirium, and fentanyl should be maintained for analgesia.

7.30 Answer A. Morphine is associated with delayed absorption of clopidogrel, ticagrelor, and
prasugrel and a prolonged duration of high residual platelet reactivity. The mechanism of
the drug-drug interaction is hypothesized to be secondary to delayed gastric emptying
and a subsequent delayed absorption of oral P2Y12 inhibitors; each of the P2Y12
inhibitors is almost completely absorbed in the intestine. The clinical effect of the
interaction between morphine and oral P2Y12 inhibitors has not been confirmed with
prospective, randomized controlled trials, although there may be an association between
morphine use and worse cardiovascular outcomes in analyses of large registries.
8 Approach to Chest Pain

Richard A. Lange

QUESTIONS

8.1 A 39-year-old woman without risk factors for coronary artery disease (CAD) presents to
the emergency department (ED) with acute chest pain of 6 hours duration. A 12-lead
electrocardiogram (ECG) is normal, and serum cardiac troponin levels obtained on
presentation and 4 hours later are undetectable. Urgent diagnostic testing should include:
A. Coronary calcium scan
B. Routine exercise stress test
C. Myocardial perfusion scan
D. Coronary angiography
E. None of the above

8.2 The most common symptom in women ultimately diagnosed with acute coronary
syndrome (ACS) is:
A. Fatigue
B. Shortness of breath
C. Nausea
D. Chest pain
E. Lightheadedness

8.3 Patients with acute chest pain who benefit the most from cardiac imaging and noninvasive
testing are those:
A. At low pretest risk of obstructive CAD
B. At intermediate risk of obstructive CAD
C. At high pretest risk of obstructive CAD
D. With previous PCI
8.4 A 45-year-old man presents to your clinic for evaluation of right parasternal chest pain
that began 3 days ago. It is nonexertional, unrelenting, nonradiating, and worsened with
movement and deep breathing. The patient denies associated shortness of breath, nausea,
vomiting, or palpitations. The best descriptor of this patient’s chest pain is:
A. Atypical
B. Cardiac
C. Possibly cardiac
D. Noncardiac
E. None of the above

8.5 A 60-year-old woman presents to the ED with 2 hours of substernal chest pressure. Prior
to obtaining an ECG and serum cardiac troponin levels, you assess her risk factors and
establish that she also has new-onset epigastric symptoms and palpitations. Which is
TRUE of women with cardiac chest pain?
A. Traditional risk score tools often underestimate risk in women and misclassify them as
having nonischemic chest pain
B. Women commonly present with chest pain symptoms similar to men
C. Women have a greater prevalence of other symptoms than men (ie, epigastric
symptoms; palpitations; and discomfort in the jaw, neck, arms, or interscapular)
D. Women have more cardiovascular risk factors than men
E. All of the above

8.6 A 55-year-old woman presents with acute-onset tachycardia, dyspnea, and chest pain with
inspiration. On examination, she has clear lung fields, a friction rub over the anterior
chest on inspiration, and no murmurs or gallops. A 12-lead ECG is obtained (Figure
Q8.6.1). The most likely source of her chest pain is:
Figure Q8.6.1

A. Acute myocardial infarction (MI)

B. Pericarditis
C. Pneumonia
D. Pulmonary embolism
E. Myocarditis

8.7 A 69-year-old man with a history of diabetes, cigarette smoking, and elevated cholesterol
presents to your office with acute-onset substernal chest pressure, diaphoresis, and
shortness of breath of 2 hours duration. You perform a 12-lead ECG that is
nondiagnostic. What is the most appropriate next step?
A. Have patient drive to the nearest ED immediately
B. Obtain a blood sample for cardiac troponin measurement
C. Record supplemental electrocardiographic leads V7-V9 to rule out posterior MI
D. Repeat 12-lead ECG in 1 hour
E. Refer for urgent myocardial perfusion scan

8.8 A 72-year-old woman presents to the ED with 3 hours of chest pain. The preferred blood
biomarker for rapid detection (or exclusion) of myocardial injury is:
A. Cardiac troponin I (cTnI)
B. Cardiac troponin T (cTnT)
C. High-sensitivity cardiac troponin (hs-cTn)
 D. Creatine kinase MB (CK-MB)
E. High-sensitivity myoglobin

8.9 For which of the patient scenarios would coronary computed tomographic angiography
(CCTA) be the diagnostic test of choice for evaluation of chest pain?
A. Low pretest likelihood of CAD
B. Intermediate-high pretest likelihood of CAD and <65 years
C. Intermediate-high pretest likelihood of CAD and >65 years
D. Intermediate-high pretest likelihood of CAD and suspected to have more obstructive
CAD
E. None of the above

8.10 You are evaluating a 60-year-old male patient with acute chest pain suggestive of ACS
that began at least 3 hours before ED arrival. He has a normal ECG and a single hs-cTn
concentration that is below the limit of detection. Which of the following is TRUE for
this patient?
A. Myocardial injury is reasonably excluded
B. Serial 12-lead ECGs should be obtained for the next 8 hours
C. A repeat hs-cTn should be obtained in 3 hours to exclude myocardial injury
D. Myocardial perfusion imaging should be obtained to exclude myocardial injury
E. None of the above

8.11 A 73-year-old woman with acute chest pain has suspected ACS. You consider obtaining
serial troponins to exclude myocardial injury. What are the recommended time intervals
for repeat measurements after the initial troponin sample collection (time zero)?
A. 1-3 hours for both high-sensitivity (hs-cTn) and conventional troponin (cTn) assays
B. 3-6 hours for both hs-cTn and cTn assays
C. 1-3 hours for hs-cTn and 3-6 hours for cTn assays
D. 1-3 hours for cTn and 3-6 hours for hs-cTn assays
E. Serial troponins are not necessary

8.12 Clinical decision pathways (CDPs) are generally used to help guide disposition of the
patient presenting with chest pain and consider previous test results to decrease
unnecessary testing. Accordingly, the “warranty period” for a normal coronary
angiogram is:
A. 1 year
B. 2 years
C. 5 years
D. 10 years
8.13 Which variable is used in chest pain risk scores to assess whether individuals are at low,
intermediate, or high risk for index visit acute MI and 30-day major adverse
cardiovascular events (MACE)?
A. Serum cardiac troponin level
B. Patient age
C. Patient history
D. Previous cardiac imaging
E. All of the above

8.14 A 55-year-old man with no known CAD risk factors presents to the ED at midnight with
chest discomfort of 4 hours duration. The initial ECG and hs-cTn are normal. What is the
most appropriate next step in his management?
A. Admit for 24-hour observation
B. Admit overnight for stress test in the morning
C. Serial ECG and troponin levels for 3-6 hours
D. Urgent coronary artery calcium score
E. Discharge home

8.15 A 75-year-old man presents with substernal chest pressure that occurred at rest and lasted
30 minutes. Four months previously, he had a myocardial perfusion scan with
pharmacologic stress that showed evidence of moderate ischemia. He was placed on
appropriate antianginal and antiplatelet therapy. The next step in his evaluation should
include:
A. Invasive coronary angiography
B. Coronary artery calcium score
C. Dobutamine stress echo
D. Stress myocardial perfusion scan
E. Fractional flow reserve computed tomography (FFR-CT)

8.16 A 45-year-old woman with type 1 diabetes mellitus and hypertriglyceridemia has new-
onset substernal chest pressure occurring at rest with associated shortness of breath.
Which of the following would prompt you to recommend invasive coronary angiography
in this patient rather than stress imaging?
A. New ischemic changes on the 12-lead ECG
B. Elevated serum troponin level
C. New-onset left ventricular systolic dysfunction (LVEF <40%)
D. A high-risk score on a CDP
E. All of the above
8.17 The most common cause of chest pain in patients >80 years old presenting to the ED is:
A. Nonspecific chest pain
B. Coronary atherosclerosis
C. Congestive heart failure
D. Acute MI
E. Pneumonia

8.18 A 63-year-old woman is brought to your office by her husband because she is
experiencing crushing substernal chest pain of 1 hour duration with associated nausea,
diaphoresis, and shortness of breath. Your next step is:
A. Contact emergency medical services (EMS) for immediate transfer to the ED
B. Obtain a 12-lead ECG
C. Draw blood for cardiac troponin measurement
D. To avoid delay, instruct the husband to take her immediately to the ED
E. None of the above

8.19 A 58-year-old man with stage 4 chronic kidney disease and severe peripheral arterial
disease is referred to you for noninvasive imaging to assess the presence and extent of
CAD. His baseline 12-lead ECG shows sinus tachycardia and increased QRS voltage in
the precordial leads. What is the most appropriate noninvasive test?
A. Exercise stress test
B. Nuclear stress test
C. Stress cardiovascular magnetic resonance (CMR) imaging
D. CCTA

8.20 A 35-year-old woman with severe hypercholesterolemia (plasma cholesterol >500 mg/dL)
is in her first trimester of pregnancy when she develops acute-onset chest pain at rest
with nonspecific ST changes. Which cardiac test would you recommend?
A. Coronary angiography
B. Nuclear stress test
C. Stress echocardiogram
D. CCTA
E. Stress CMR

8.21 Which is/are TRUE regarding CDPs used in chest pain protocols?
A. They help avoid admission or further testing in up to 40% of eligible patients
B. Although sensitive in detecting ACS, they have low sensitivity for detecting 30-day
MACE
 C. The patient’s history, examination, and 12-lead ECG provide the necessary clinical
information
D. Since it assesses acute chest pain risk, it is not influenced by previous cardiac test
results
E. All of the above

8.22 In the patient with chest pain who is recommended for a noninvasive evaluation, when is
CCTA favored over stress imaging?
A. Patient >65 years old
B. Pursuing an ischemia-guided management approach
C. Suspicion of anomalous coronary artery
D. High likelihood of microvascular dysfunction
E. All of the above

8.23 Which of the following statements regarding diagnostic testing is TRUE for the patient
with stable chest pain who needs an imaging study?
A. Exercise testing is preferred over pharmacologic stress
B. Positron emission tomography (PET) has better diagnostic and prognostic performance
than single-photon emission computed tomography (SPECT)
C. Candidates for elective coronary angiography may be safely triaged using CCTA or
noninvasive stress testing
D. CCTA has similar effectiveness near term (at ~2-3 years) to stress testing
E. All of the above

8.24 A 55-year-old woman presents to the ED with 4 hours of chest pain without ECG changes
or elevation in serum hs-cTn levels. Eighteen months ago, she had a normal CCTA.
Which of the following is the most appropriate management?
A. Discharge home
B. Admit for 24-hour observation with serial high-sensitivity cardiac troponin
C. Perform stress test before ED discharge
D. Schedule outpatient coronary computed tomography (CT) within 30 days
E. Schedule outpatient stress test within 30 days

8.25 A 70-year-old man with a history of type 2 diabetes mellitus, hyperlipidemia, and
cigarette smoking presents to the ED with 30 minutes of chest pain at rest. His 12-lead
ECG and initial hs-cTnI are normal. Three months ago, he had a stress SPECT
myocardial perfusion imaging that was mildly abnormal. Optimal management in this
patient may include all the following, EXCEPT:
A. CCTA prior to ED discharge
 B. Stress SPECT myocardial perfusion imaging before ED discharge
C. Bedside transthoracic echocardiogram
D. Admission to an observation unit

ANSWERS AND EXPLANATIONS

8.1 Answer E.For patients with acute (or stable) chest pain determined to be low risk (ie,
noncardiac chest pain, no risk factors for coronary disease, no ischemic changes, and
normal serum cardiac troponin levels), urgent diagnostic testing for suspected CAD is
not needed. Noninvasive testing (ie, coronary calcium scan, routine exercise stress test,
or myocardial perfusion scan [options A-C]) may be performed electively as an
outpatient, if indicated. Coronary angiography is rarely indicated in low-risk individuals
and never urgently.

8.2 Chest pain is the dominant and most frequent symptom for both men and
Answer D.
women ultimately diagnosed with ACS. Women may be more likely than men to present
with accompanying symptoms, such as nausea, fatigue, and shortness of breath.
However, chest pain remains the predominant symptom reported by women diagnosed
with ACS, occurring with a frequency equal to men.

8.3 Answer B.Patients with acute chest pain who are at intermediate risk of obstructive CAD
benefit the most from cardiac imaging and testing. Noninvasive testing does not provide
significant additional predictive value to individuals at low or high risk of obstructive
CAD.

8.4 Answer D.The location, chronicity, lack of associated symptoms, and worsening with
movement are consistent with costochondritis, a noncardiac condition. None of the
features suggests a cardiac or possible cardiac origin. Chest pain should not be described
as atypical because it is not helpful in determining the cause and can be misinterpreted as
benign in nature. Instead, chest pain should be described as cardiac, possibly cardiac, or
noncardiac because these terms are more specific to the potential underlying diagnosis.
Properly defining chest pain is a level 1 class (strength) of recommendation (COR)
according to the 2021 Guideline for the Evaluation and Diagnosis of Chest Pain.

8.5 Answer E.Multiple studies have shown that men and women are equally likely to present
with chest pain; however, women are more likely to have other associated symptoms (ie,
epigastric symptoms; palpitations; and discomfort in the jaw, neck, arms, or between the
shoulder blades) and a greater prevalence of cardiovascular risk factors. Unfortunately,
traditional risk score tools and physician assessments often underestimate risk in women
and misclassify them as having nonanginal chest pain.

8.6 Answer D. Tachycardia and dyspnea are present in >90% of patients with pulmonary
 embolism. The typical ECG findings associated with pulmonary embolism are present,
including sinus tachycardia, S1Q3T3 pattern (S wave in lead I indicating a rightward
shift of QRS axis with Q wave and T inversion in lead III). The inspiratory rub is
supportive of this diagnosis. Chest pain and friction rub with inspiration are not
characteristic for acute MI. The chest pain associated with pericarditis is worse in the
supine position and does not change with respiration (option B). Although an inspiratory
rub may occur with pneumonia, the absence of fever and normal breath sounds make this
unlikely (option C). The absence of fever, heart failure symptoms, and an S3 gallop
make myocarditis (option E) unlikely.

8.7 Answer C. In this high-risk individual, a normal ECG may be associated with left
circumflex occlusion and posterior wall ischemia, which is often “electrically silent”;
therefore, posterior leads (V7-V9 ECG leads) should be considered when such lesions
are suspected (Class 2a recommendation, level of evidence [LOE] B). Patients with acute
chest pain who are evaluated in the office setting and determined to be intermediate-to-
high clinical suspicion for ACS should be transferred to the nearest ED (option A) after
the supplemental ECG is acquired. The transfer should not be delayed to await results of
cardiac troponin levels (option B), a repeat ECG in 1 hour (option D), or other diagnostic
tests (ie, myocardial perfusion scan) (option E). Patients with acute chest pain should be
transported to the ED by trained emergency medical service personnel: one in 300
patients with chest pain transported to the ED by private vehicle suffers a cardiac arrest
en route.

8.8 Answer C.In patients presenting with acute chest pain, hs-cTn is the preferred biomarker
because it enables more rapid detection or exclusion of myocardial injury and increases
diagnostic accuracy. The sensitivity and negative predictive values are greater with hs-
cTn compared with conventional cTn assays. In addition, the time interval from the onset
of chest pain to a detectable concentration at patient presentation is shorter with hs-cTn,
affording more rapid rule-in and rule-out algorithms. With the availability of cTn, CK-
MB isoenzyme and myoglobin are not useful for the diagnosis of acute myocardial
injury.

8.9 Answer B. No testing is indicated in the individual with a low pretest likelihood of CAD
(option A). Conversely, stress testing is indicated in individuals with intermediate-high
pretest likelihood of CAD who are ≥65 years (option C) or suspected to have more
obstructive CAD (option D). CCTA is preferred in those <65 years or suspected of
having less obstructive CAD.

8.10 Answer A.For patients with acute chest pain, a normal ECG, and symptoms suggestive of
ACS that began at least 3 hours before ED arrival, a single hs-cTn concentration that is
below the limit of detection on initial measurement (time zero) is reasonable to exclude
myocardial injury (Class 2a recommendation). Cardiac biomarkers are more sensitive
than serial ECGs and myocardial perfusion imaging for detecting acute myocardial
injury. Repeat hs-cTn would be indicated if the chest pain is of short duration, but a
normal hs-cTn in the setting of prolonged chest pain is alone sufficient to exclude
 myocardial injury.

8.11 Answer C.Important differences exist in the performance of hs-cTn and cTn assays. For
example, hs-cTn assays may be used to guide disposition by repeat sampling at 1, 2, or 3
hours from ED arrival using the pattern of rise or fall (ie, δ) and the repeat value itself,
based on assay-specific diagnostic thresholds. When using cTn assays, the sampling
timeframe is extended to 3-6 hours from the presentation. Both recommendations are
Class 1 indications for patients with acute chest pain and suspected ACS (not including
ST-segment elevation myocardial infarction [STEMI]).

8.12 Answer B.Previous test results should always be considered in the evaluation of patients
with acute chest pain once ACS has been ruled out (Class 1 recommendation). In those
with recent coronary angiography (within the previous 2 years) and normal findings who
do not have biomarker evidence of acute myocardial injury, further testing is of limited
value, provided imaging was of sufficient quality and symptoms are unchanged.

8.13 Answer E. Chest pain risk scores provide a summative assessment combining clinical
information, such as age, ST-segment changes on ECG, history (symptoms and CAD
risk factors), previous cardiac imaging, and cTn, to estimate a patient’s probability of
ACS or risk of 30-day MACE.

8.14 Answer E.There is no evidence to support routine admission or cardiac testing for patients
with chest pain who are low risk (30-day risk of death or MACE <1%), although
outpatient coronary artery calcium scanning can provide additional information for
longer-term risk stratification.

8.15 Answer A. In patients who have evidence of moderate or severe ischemia on previous
stress testing, who were not revascularized, and who present with acute chest pain,
additional noninvasive stress testing is unlikely to result in any change in management.
Such patients are assumed to have significant flow-limiting CAD and can proceed
directly to an invasive evaluation if coronary revascularization is consistent with the
goals of care (Class 1 recommendation, LOE C).

8.16 Answer E. All are Class 1 indications for invasive coronary angiography according to the
2021 Guideline for the Evaluation and Diagnosis of Chest Pain. Patients with symptoms
suggestive of ACS who are at high risk of short-term MACE include those with new
ischemic changes on the ECG, troponin-confirmed acute myocardial injury, new-onset
left ventricular systolic dysfunction (ejection fraction <40%), newly diagnosed
moderate-severe ischemia on stress imaging, and/or a high-risk score on a CDP. Invasive
coronary angiography is indicated for patients with confirmed ACS based on a robust
body of randomized trial evidence and clinical practice guideline indications.

8.17 Answer A. Although patients >75 years account for 33% of all cases of ACS, alternative
diagnoses are still more common than a cardiac cause of chest pain at presentation. The
 top causes of chest pain in older patients presenting to the ED are nonspecific chest pain
(>50%), coronary atherosclerosis (8%), congestive heart failure (~6%), acute MI (~4%),
and pneumonia (~3%). Nevertheless, the priorities for the patient presenting to the ED
with chest pain are (i) rapid initiation of optimal management in patients with life-
threatening conditions such as ACS, aortic dissection, and pulmonary embolism, as well
as nonvascular syndromes (eg, esophageal rupture, tension pneumothorax) and (ii)
deliberate therapy for those with less critical illness.

8.18 Answer B. In all patients who present with acute chest pain regardless of the setting (ie,
clinic or ED), an ECG should be acquired and reviewed for STEMI within 10 minutes of
arrival (option B); if an ECG is unavailable in the office setting, the patient should be
referred to the ED so one can be obtained (Class 1 recommendation). Transferring
patients with chest pain to the ED without a prehospital ECG results in an avoidable
delay in readiness of the ED and reperfusion teams to implement optimally timed
reperfusion therapy. Patients with ACS or other life-threatening causes of acute chest
pain seen in the office setting should be transported urgently to the ED, ideally by EMS
(option A); one in 300 patients with chest pain transported to the ED by private vehicle
suffers a cardiac arrest en route (option D). Delayed transfer to the ED for determination
of cardiac troponins (option C) or other diagnostic testing beyond the ECG in the office
setting can be detrimental and should be avoided.

8.19 Answer B. Exercise stress testing (option A) is not suitable for patients with peripheral
artery disease and abnormal ST changes on resting ECG (ie, >0.5-mm ST depression,
left ventricular hypertrophy, left bundle branch block). Reduced glomerular filtration rate
(GFR [<30 mL/min/1.73 m2]) is a contraindication to stress CMR, which requires
gadolinium as the imaging agent (option C). Severe renal impairment is also a
contraindication to CCTA, which uses contrast material that may worsen renal function.

8.20 Answer C.Imaging using ionizing radiation during pregnancy or postpartum while
breastfeeding should generally be avoided, even though radiation risk to the fetus is
considered to be very small. For a test deemed clinically necessary, the lowest effective
dose of ionizing radiation should be used, including considerations for tests with no
radiation exposure (eg, echocardiography). Although CMR does not use ionizing
iodinated contrast, the use of gadolinium contrast with CMR stress should be
discouraged in pregnancy. If contrast is needed for a postpartum woman (ie, coronary
angiography is recommended), breastfeeding may continue because <1% of iodinated
contrast is excreted into the breast milk and absorbed into the infant’s gastrointestinal
tract.

8.21 Answer A.In patients presenting with acute chest pain and suspected ACS, CDPs should
categorize patients into low-, intermediate-, and high-risk strata to facilitate disposition
and subsequent diagnostic evaluation (Class 1 recommendation, LOE B). CDPs help
avoid admission or further testing in 21%-43% of eligible patients (option A) while
maintaining high sensitivity for detection of acute myocardial injury and 30-day MACE
(option B). Chest pain risk scores provide a summative assessment combining clinical
 information, such as age, ST-segment changes on ECG, symptoms, CAD risk factors,
and cTn or hs-cTn. All CDPs generally involve single or serial cTn measurement (option
C). Previous test results should always be considered in the evaluation of patients with
acute chest pain once ACS has been ruled out (option D). In those with recent cardiac
testing and normal findings who do not have biomarker evidence of acute myocardial
injury, further testing is of limited value.

8.22 Answer C. CCTA is favored over stress imaging in younger patients (<65 years old), when
wanting to assess both obstructive and nonobstructive CAD, when anomalous coronary
artery is a consideration (option C), and when an assessment of the aorta or pulmonary
arteries is indicated. Conversely, stress imaging should be utilized in older patients (≥65
years old) (option A), when pursuing an ischemia-guided management (option B) or
when microvascular dysfunction is suspected (option D). CCTA is preferable in those
<65 years and not on optimal preventive therapies, while stress testing may be
advantageous in those >65 years because they have a higher likelihood of ischemia and
obstructive CAD.

8.23 Answer E. In patients selected for stress imaging who are able to exercise, exercise testing
is preferred over pharmacologic stress (option A) to improve the diagnostic and
prognostic information of the test and to collect data on the hemodynamic or
symptomatic response to exercise. PET has improved diagnostic and prognostic
performance than SPECT (option B), especially when quantitative assessment of
myocardial blood flow can be performed. Several randomized trials compared the
effectiveness of CCTA versus direct referral to coronary angiography, with initial CCTA
associated with lower cost but similar 1-year MACE rates (death, ACS, stroke,
urgent/emergency coronary revascularization, or cardiac hospitalization). Randomized
trials comparing the effectiveness of CCTA versus stress testing report similar near-term
effectiveness (at ~2-3 years of follow-up).

8.24 Answer A. According to the 2021 Guideline for the Evaluation and Diagnosis of Chest
Pain, in patients with acute chest pain and suspected ACS who are deemed low risk
(<1% 30-day risk of death or MACE), it is reasonable to discharge home without
admission or urgent cardiac testing (Class 2a recommendation, LOE B). For patients
with acute chest pain, a normal ECG, and symptoms suggestive of ACS that began at
least 3 hours before ED arrival, a single hs-cTn concentration that is below the limit of
detection on initial measurement is reasonable to exclude myocardial injury (option A).
There is no evidence to support routine admission (option B) or cardiac testing (option
C) for patients with chest pain who are low risk. Furthermore, there is no evidence that
stress testing or cardiac imaging within 30 days of the index ED visit in these low-risk
patients improves their outcomes (options D and E). Finally, in patients with recent
cardiac testing (CCTA or coronary angiography within the past 2 years) and normal
findings who do not have biomarker evidence of acute myocardial injury, further testing
is of limited value.

8.25 Answer B. This patient falls into an intermediate-risk group. For intermediate-risk patients
 with acute chest pain, transthoracic echocardiography (option C) is recommended as a
rapid, bedside test to establish baseline ventricular and valvular function, evaluate for
wall motion abnormalities, and to assess for pericardial effusion (Class 1
recommendation). Management in an observation unit (option D) is reasonable to
shorten the length of stay and lower cost relative to an inpatient admission (Class 2a
recommendation, LOE option B). With a previously inconclusive or mildly abnormal
stress test in the past year, CCTA is recommended (option A), avoiding the potential for
inconclusive results if the same type of test is repeated (option B) and enabling a more
definitive rule out of obstructive CAD. In the ED evaluation of patients with acute chest
pain, CCTA contributes to a reduced time to diagnosis and prompt discharge, without
impacting safety (ie, no difference in death, repeat ED visits, or ACS over 1-6 months of
follow-up) compared with a standard evaluation including stress testing.

SUGGESTED READINGS
Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR
guideline for the evaluation and diagnosis of chest pain: a report of the American College of
Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J
Am Coll Cardiol. 2021;78(22):e187-e285. PMID: 34709879
Hemal K, Pagidipati NJ, Coles A, et al. Sex differences in demographics, risk factors,
presentation, and noninvasive testing in stable outpatients with suspected coronary artery
disease: insights from the PROMISE trial. JACC Cardiovasc Imaging. 2016;9(4):337-346.
PMID: 27017234
Hsia RY, Hale Z, Tabas JA. A national study of the prevalence of life-threatening diagnoses in
patients with chest pain. JAMA Intern Med. 2016;176(7):1029-1032. PMID: 27295579
Lichtman JH, Leifheit EC, Safdar B, et al. Sex differences in the presentation and perception of
symptoms among young patients with myocardial infarction: evidence from the VIRGO
Study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients).
Circulation. 2018;137(8):781-790. PMID: 29459463
9 Vasoactive Agents

Sandra A. Weiss and Sandeep Nathan

QUESTIONS

9.1 A 54-year-old man with a history of chronic nonischemic cardiomyopathy status post
biventricular implantable cardioverter defibrillator (ICD) with ejection fraction (EF)
25% on the most recent echo from 6 months prior presents to the emergency department
with worsening shortness of breath, nausea, and decreased urination over the preceding 5
days. Vital signs show blood pressure is 85/64 mm Hg, heart rate is 102 bpm, pulse
oximetry is 95%. He is fully oriented with crackles audible on pulmonary exam. Cardiac
exam is slightly tachycardic, with a 3/6 holosystolic murmur at the apex that radiates to
the axilla and an audible S3 gallop. There is slight discomfort on palpation of the right
upper quadrant. Lower extremities are cool with 2+ pitting edema but no cyanosis. Labs
reveal a sodium of 131 mmol/L, potassium of 4.8 mmol/L, bicarbonate of 18 mg/dL,
creatinine of 2.5 mg/dL (baseline 0.8), lactate of 4.3 mmol/L, aspartate transaminase
(AST) 105 units/L, alanine transaminase (ALT) 97 units/L, total bilirubin 1.8 mg/dL,
pro–B-type natriuretic peptide (pro-BNP) 25,000 pg/mL. Complete blood count (CBC)
is within normal limits. Based on this presentation, which of the following statements is
TRUE?
A. The patient is demonstrating Society of Cardiovascular Angiography and Interventions
(SCAI) class B shock and can be managed with diuresis alone
B. An initial choice of therapy should include norepinephrine with possible escalation to
intra-aortic balloon pump if there is no improvement in clinical status
C. Milrinone should be considered first-line therapy in this situation
D. Phenylephrine is contraindicated in this situation because of the potential for reflex
tachycardia
E. Dobutamine should not be used in this patient because there is evidence of acute
kidney injury

9.2 The primary mechanism of action of norepinephrine is:

A. Pure α-receptor effect to raise mean arterial pressure (MAP)
 B. Inhibition of the degradation of cyclic adenosine monophosphate (cAMP) to increase
intracellular calcium and contractility
C. α1-receptor >> β1-receptor activity to increase MAP and inotropy
D. Activation of the V1 receptors to increase systemic vascular resistance (SVR) and
mean arterial blood pressure
E. Nonselective α- and β-receptor activity that increases chronotropy, inotropy, and MAP

9.3 A 55-year-old man with a history of poorly controlled hypertension presents to his local
emergency department with complaints of searing pain between his scapula that began 3
hours prior to presentation. He is having difficulty finding a comfortable position on the
stretcher and appears diaphoretic and in moderate distress. Vitals reveal a blood pressure
of 230/125 mm Hg on the right arm, 140/78 mm Hg on the left arm, heart rate 110 bmp,
oxygen saturation 96% on room air. On exam, he is mildly tachycardic with a 1/4
diastolic murmur, lung exam is clear, abdomen is nonacute. Right radial pulse is 2+, left
radial pulse is diminished and delayed, and bilateral pedal pulses are only found by
Doppler and demonstrate a monophonic waveform. Chest x-ray demonstrates a widened
mediastinum. Lab work reveals a normal CBC, sodium 138 mmol/L, potassium 5.4
mmol/L, CO2 18 mmol/L, blood urea nitrogen (BUN) 55 mg/dL, and creatinine 1.8
mg/dL. Chest computed tomography (CT) demonstrates an aortic dissection beginning at
the sinotubular junction with extension into the arch and ostium of the left subclavian
artery. The next steps in the management of this patient should include all of the
following EXCEPT:
A. The patient should be started on intravenous (IV) esmolol as soon as possible
B. The goal of IV therapy is to reduce systolic blood pressure to 100-120 mm Hg within
20 minutes and attain heart rates <60 beats per minute (bpm)
C. The patient should be given hydralazine 10 mg IV with the goal of reducing systolic
blood pressure by 25% in the first hour
D. This condition is considered a surgical emergency and a stat CT surgical consultation
should be conducted
E. IV nitroprusside or clevidipine is a reasonable alternative or adjunct to treatment

9.4 You are asked to perform angiography on a 67-year-old woman with a history of type 2
diabetes mellitus who presented with sudden-onset chest discomfort and found to have
elevated troponin-I consistent with non–ST-segment elevation myocardial infarction
(NSTEMI). Imaging of the left system is achieved without difficulty, revealing a
stenosis, visually estimated to be 95% severity, in the proximal left anterior descending
(LAD) artery with angiographic features suggestive of plaque rupture with residual
thrombus and thrombolysis in myocardial infarction (TIMI) II flow in the vessel. You
encounter difficulty engaging the right coronary artery (RCA) with a Judkins right
catheter from the right radial approach as the catheter would repeatedly disengage from
the ostium, requiring repeated attempts before you are ultimately successful.
Angiography reveals a focal 90% ostial stenosis without reflux of contrast. There is
evidence of pressure dampening on the transducer with engagement of the artery. The
 remainder of the vessel appears to be free of angiographic disease. After removal of the
catheter from the RCA ostium, what would be the next most appropriate step?
A. Prepare to undergo multivessel percutaneous intervention of the LAD and RCA,
starting with the left anterior descending artery as this subtends a larger quantity of
myocardium
B. Prepare to undergo multivessel percutaneous intervention of the LAD and RCA,
starting with the RCA because it appears more hemodynamically significant based on
pressure dampening on the transducer
C. Wait 1-2 minutes before repeating angiography of the RCA with the Judkins right
catheter
D. Calculate a SYNTAX score and consult cardiothoracic surgery for considering
coronary artery bypass grafting as the patient has evidence of two-vessel disease
inclusive of the proximal LAD
E. Reengage the right coronary with an alternative catheter, possibly with side holes, and
inject intracoronary nitroglycerin

9.5 Treatment to relieve coronary artery vasospasm seen following balloon dilation of a
significant lesion in the left anterior descending artery include intracoronary injection of
all of the following EXCEPT:
A. Sodium nitroprusside
B. Verapamil
C. Acetylcholine
D. Nitroglycerin
E. Nicardipine

9.6 A 38-year-old woman without significant medical history is being evaluated for
progressive shortness of breath, mild exertional chest discomfort, and one episode of
syncope when climbing the stairs 2 weeks prior to presentation. Physical exam is
remarkable for clear lungs, mild tachycardia, right-sided S3, and positive right
ventricular (RV) heave. A chest x-ray is unremarkable, lab work including human
immunodeficiency virus (HIV) serology is within normal limits. An electrocardiogram
(ECG) reveals sinus tachycardia with right-axis deviation. Echo demonstrates normal left
ventricular (LV) size and function, mild mitral regurgitation, severe tricuspid
regurgitation, and severe RV enlargement with significant reduction in RV function.
Short-axis view shows a “D sign.” Pulmonary function test is normal and CT chest rules
out pulmonary embolism. You are concerned for possible primary pulmonary
hypertension (PH) and you schedule the patient for right heart catheterization with
vasodilator study. Left ventricular end-diastolic pressure (LVEDP) is 8 mm Hg. Which
vasodilator regimen would be appropriate at this time?
A. Inhaled nitric oxide at 80 parts per million and 90% O2 for 10 minutes
B. Diltiazem 10 mg IV bolus, followed by 5 mg/h IV infusion
 C. Nitroglycerin 10-50 μg/min as a continuous infusion
D. Inhaled iloprost 5 μg delivered over 15 minutes
E. Adenosine up to a maximum dose of 500 μg/kg/min

9.7 All of the following statements regarding intra-arterial (IA) cocktail used during radial
artery catheterization are true EXCEPT:
A. The IA cocktail typically consists of nitroglycerin 100-200 μg combined with a non-
dihydropyridine calcium channel blocker
B. The IA cocktail can be repeated, if needed, during the procedure to prevent radial
artery spasm
C. The primary benefits of the antispasm cocktail are to prevent femoral conversion and
radial artery occlusion
D. Nonpharmacologic interventions such as forearm heating and reactive hyperemia can
produce local vasodilation when pharmacologic agents are contraindicated
E. The use of IA verapamil exerts only local effects so dose adjustments are not necessary
in patients with hypotension, bradycardia, or severe aortic stenosis (AS)

9.8 A 55-year-old woman with a history of diabetes and tobacco use presents to the
emergency department with complaints of chest pain while mowing the lawn over the
last 4 months. Today she experienced similar symptoms upon waking, prompting her
presentation. Vitals and exam are unremarkable. Lab work, including troponin T, is
normal. Initial ECG does not demonstrate any ST-/T-wave changes. While ambulating to
the rest room, she has another episode of pain, and an ECG now demonstrates 0.5-1.0
mm of ST-segment depressions in the anterior leads. Out of concern for unstable angina,
you perform a cardiac catheterization, which demonstrates no obstructive coronary
disease, although vessels are diffusely small. What is the next most appropriate step?
A. Perform a measure of fractional flow reserve (FFR) by placing a pressure wire into the
left anterior descending artery and instilling IV adenosine at a rate of 140 μg/kg/min
B. Refer her for an exercise single-photon emission computed tomography (SPECT) study
C. Order a cardiac magnetic resonance imaging (MRI) to diagnose myocarditis
D. Perform a measure of coronary flow reserve (CFR) by placing a pressure wire into the
left anterior descending artery and instilling IV adenosine at a rate of 140 μg/kg/min
E. No further cardiac testing is needed. Refer her to a gastroenterologist for evaluation of
reflux disease

9.9 A patient presents to the hospital with near syncope and shortness of breath. As part of the
workup, an echocardiogram is performed, which demonstrates an left ventricular
ejection fraction of 30%. A right heart catheterization is performed. In which of the
following scenarios would it be most appropriate to initiate a dobutamine infusion at 5
μg/kg/min?

HR (bpm) MAP (mm Hg) RAP (mm Hg) mPAP (mm Hg) CI (L/min/m2) SVR (dynes s/cm5) PCWP (mm Hg)
A. 120 55 2 18 4.0 700 10
B. 90 75 15 38 1.6 1,700 30
C. 120 55 15 38 1.6 1,700 30
D. 90 75 5 18 3.4 1,000 10
CI, cardiac index; HR, heart rate; MAP, mean arterial pressure; mPAP, mean pulmonary artery pressure; PCWP, pulmonary capillary wedge
pressure; RAP, right atrial pressure; SVR, systemic vascular resistance.

9.10 Regarding the pharmacologic and vasodilatory properties of the nitrodilator compounds,
nitroglycerin and sodium nitroprusside, which of the following statements is correct?
A. Sodium nitroprusside is an inorganic prodrug that promotes selective coronary
vasodilation
B. Nitroglycerin requires conversion in the body to nitric oxide, which serves as an
arterial and venous dilator with coronary vasodilation primarily occurring in the
epicardial vessels, incurring minimal risk of coronary steal
C. Thiocyanate toxicity secondary to sodium nitroprusside treatment can occur in the
setting of renal insufficiency and typically occurs within the first 12-24 hours
D. Both nitroglycerin and sodium nitroprusside require the presence of aldehyde
dehydrogenase and/or other specific thiol-containing compounds for nitric oxide
generation

9.11 Vasopressor agents and inotropes are used, alone or in combination, for the medical
stabilization of patients with acute decompensated heart failure and/or cardiogenic
shock. Which of the following therapeutic profiles of commonly utilized agents is
correct?
A. Dopamine is an endogenous catecholamine that demonstrates differential effects on
adrenergic and dopaminergic receptors at escalating doses. At low doses (0.5-3
μg/kg/min), dopamine binds β1-adrenergic receptors that results in increased inotropy
and cardiac contractility as well as mild increase in systemic vascular resistance. At
intermediate doses (3-10 μg/kg/min), there is stimulation of D1 and D2 dopaminergic
receptors, increasing flow to the coronary, cerebral, renal, and mesenteric vascular
beds. At high doses (10-20 μg/kg/min), the predominant effect is peripheral
vasoconstriction mediated by α1-adrenergic stimulation
B. Norepinephrine is synthesized endogenously from dopamine and is a potent α1-
adrenergic agonist with minimal β1-activity that, when administered in cardiogenic
shock, increases systolic and diastolic blood pressure with minimal impact on cardiac
output
C. Milrinone is a synthetic catecholamine that increases the level of cAMP by inhibiting
intracellular breakdown, resulting in increased myocardial contractility, and is an
effective inotrope in the setting of decompensated heart failure
D. Levosimendan is a calcium-sensitizing agent used outside the United States, which
achieves both enhanced myocardial contractility and arterial and venous vasodilation
via calcium sensitization of contractile proteins and direct binding to cell surface
 inotrope receptors

9.12 The phase 3 Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial
evaluated the impact of adding angiotensin II to background therapy vasopressor agents,
which would improve blood pressure in patients with catecholamine-resistant,
vasodilatory shock states. Which of the following statements is NOT TRUE regarding
this therapy?
A. Patients with vasodilatory shock who were receiving more than 0.2 μg/kg/min body
weight of norepinephrine (or the equivalent dose of another vasopressor) were
randomized to receive infusions of either angiotensin II or placebo
B. The primary outcome variable of mean arterial pressure (MAP) response at 3 hours
(defined as MAP >75 mm Hg or higher or an increase in MAP from baseline of at least
10 mm Hg without an increase in baseline vasopressor therapy) was reached by more
patients in the angiotensin II group than in the control group
C. Serious adverse events also occurred more frequently (to a statistically significant
degree) in the angiotensin II group than in the control group
D. Death by day 28 post-randomization occurred equally in both groups

9.13 Pharmacologic support with inotrope or catecholamine vasopressors remains the most
often utilized strategy for the initial management of cardiogenic shock. The
pharmacologic profiles of commonly used agents such as dopamine, norepinephrine,
dobutamine, and milrinone vary greatly, and preferential use of one over the others is
often guided by individual experience or institutional preference/protocols. Which of the
following statements regarding the recently published Dobutamine Compared with
Milrinone (DOREMI) trial is correct?
A. The DOREMI trial utilized a modified crossover design that randomized patients with
cardiogenic shock to receive either dobutamine or milrinone, after failing another
(different) vasoactive agent
B. The trial exclusively recruited adult (>18 years) patients in SCAI shock stages D-E
C. As in the intra-aortic balloon pump (IABP) SHOCK II trial, nearly half of the patients
had sustained cardiac arrest with resuscitation prior to randomization
D. The DOREMI trial randomly assigned patients meeting trial criteria for cardiogenic
shock and/or clinical evidence of systemic and/or pulmonary congestion despite use of
vasodilators and/or diuretics, to receive either dobutamine or milrinone at a dose
determined using a standardized dosing scale

9.14 In the DOREMI trial that studied the impact of choice of inotrope on outcomes in
cardiogenic shock, which of the following statements regarding the cohort studied and
clinical outcomes is correct?
A. The two treatment groups differed with respect to the proportion of SCAI Stage D/E
shock and baseline left ventricular function
B. There was no difference between treatment groups with respect to the occurrence of the
 primary end point (in-hospital death from any cause, resuscitated cardiac arrest, need
for cardiac transplantation or mechanical circulatory support, nonfatal myocardial
infarction [MI], transient ischemic attack [TIA]/stroke, or initiation of renal
replacement therapy)
C. While there was no difference between the two arms with respect to the composite
primary end point, the secondary end point of in-hospital death was lower in the
dobutamine arm
D. Clearance of lactate was more rapid in patients randomized to milrinone

9.15 Shock states can be broadly divided by etiology into cardiogenic, septic (or distributive),
and hypovolemic. At the time of initial evaluation, it may be difficult to determine the
primary mechanism of shock, and indeed, multiple etiologies may coexist in the same
patient. The ideal choice of vasopressor in shock remains a matter of some controversy
and is largely driven by individual preference and treatment setting. Which of the
following statements regarding the Sepsis Occurrence in Acutely Ill Patients II (SOAP
II) trial is NOT CORRECT?
A. The trial included 1,679 patients with shock who were randomized to receive either
dopamine or norepinephrine infusions after a trial of volume resuscitation unless there
was objective evidence of fluid overload
B. Overall, there was no significant difference in the rate of death at 28 days between the
dopamine- and norepinephrine-treated cohorts
C. In patients with cardiogenic shock, a subgroup analysis found that dopamine (vs
norepinephrine) was associated with an increased rate of death at 28 days
D. Subgroup analysis found norepinephrine was associated with a greater number of
arrhythmic events than dopamine

9.16 An 89-year-old man with calcific aortic stenosis (AS) is referred for transcatheter aortic
valve replacement (TAVR) and was deemed to be appropriate on the basis of high
surgical risk, frailty, and limited rehabilitation potential. Transthoracic echocardiography
was performed and demonstrated a heavily calcified tricuspid aortic valve with leaflet
restriction, a peak aortic gradient by Doppler of 92 mm Hg, and a mean gradient of 61
mm Hg. The calculated aortic valve area (AVA) using the continuity equation was 0.55
cm2, consistent with critical AS. There was also noted to be severe left ventricular (LV)
hypertrophy most notably affecting the interventricular septum and posterobasal
segment. The LV cavity size was small and LV function was hyperdynamic with a
midcavitary gradient of 9-10 mm Hg at baseline. After remaining pre-TAVR evaluation
was completed, the patient underwent TAVR via transfemoral implantation of a 23 mm
Sapien transcatheter heart valve with nominal deployment and 90/10 placement by
aortography. The starting blood pressure pre-deployment was 131/62 mm Hg and heart
rate 92 bpm. Immediately following deployment, the patient is noted to be hypotensive
at 62/40 mm Hg and tachycardic to 120-130 bpm with a regular narrow complex rhythm.
After ruling out access site bleeding, pericardial effusion, coronary occlusion, and aortic
root rupture, what maneuvers are most likely to elucidate and treat the condition?
 A. A bolus of IV epinephrine to increase myocardial contractility
B. Immediate electrical cardioversion
C. IV fluids and cardiac imaging to evaluate the intracavitary gradient
D. Norepinephrine drip to increase vascular tone

9.17 Which of the following choices represents the correct dosing ranges for the listed
catecholamine vasopressors or inotropes as they are used in decompensated heart failure
or cardiogenic shock?
A. Dopamine 2.5-20 μg/min IV
B. Dobutamine 2.5-20 mg/kg/min IV
C. Norepinephrine 0.01-3 μg/kg/min
D. Milrinone 50 mg/kg IV bolus then 0.375-0.75 μg/kg/min IV infusion (renal adjustment
necessary)

9.18 While routine use of IABP failed to reduce infarct size in patients with anterior MI
without cardiogenic shock (CRISP AMI study) or reduce 30-day mortality in patients
with advanced stages of cardiogenic shock (IABP SHOCK II trial), there has been
renewed interest in the use of IABP in acute decompensated heart failure without overt
shock, in lieu of vasoactive agents. Based on recent randomized trial data comparing
primary IABP support versus inotropes in decompensated heart failure, which of the
following statements is correct?
A. In decompensated, non–acute coronary syndrome (ACS) heart failure with low output
states, primary support with IABP (vs inotropic support with dobutamine or
enoximone) resulted in a greater short-term improvement in mixed venous saturation
(SVO2) and more negative fluid balance with no IABP-related serious adverse events
B. Short-term IABP support is associated with significantly higher 30-day survival as
compared with inotropic support in decompensated heart failure
C. Primary IABP support in heart failure without shock (vs inotropic support) is
associated with short-term improvement in cardiac power output (CPO) and also
increased vascular complications
D. Inotropic support with dobutamine/enoximone more rapidly resulted in diuresis and
improved SVO2 than a primary IABP strategy

9.19 Coronary “no-reflow phenomenon” is a descriptive term that refers to sluggish or

stagnant flow in a coronary artery following percutaneous coronary intervention (PCI)
despite a patent epicardial vessel. Myocardial tissue hypoperfusion results from
microvascular obstruction and confers a higher risk of MI and death. Pharmacologic
intervention is most commonly utilized in the cardiac catheterization laboratory once no-
reflow has occurred. Which of the following statements regarding agents commonly
used to treat no-reflow is NOT accurate?
A. Platelet glycoprotein inhibitors (GPIs; abciximab, eptifibatide, tirofiban) irreversibly
 bind with the adenosine diphosphate (ADP) P2Y12 receptor, thus interfering with the
activation state of the platelet surface glycoprotein (Gp) IIb/IIIa receptor
B. Adenosine promotes smooth muscle relaxation and reduces oxygen free radical
formation
C. Sodium nitroprusside is a nitrodilator that activates guanylate cyclase and serves as a
nitric oxide donor
D. Nicardipine is a dihydropyridine calcium channel blocker that may be administered in
50-200 μg intracoronary (IC) boluses

9.20 Adenosine vasodilates the coronary microcirculation and small-scale studies have
suggested that it may confer ischemic protection in patients undergoing STEMI. The
AMISTAD-I (Acute Myocardial Infarction Study of Adenosine) and AMISTAD-II trials
evaluated various dosing regiments of IV adenosine in STEMI patients receiving
fibrinolytics or undergoing primary PCI. Which of the following statements regarding
the AMISTAD-I and -II trials is INCORRECT?
A. The AMISTAD-I trial of 236 thrombolytic-treated patients found a significant 33%
relative reduction in infarct size with a 3-hour adenosine infusion (70 g/kg/min)
compared with control treatment
B. Efficacy in AMISTAD-I was limited to the cohort of patients presenting with anterior
STEMI with a trend toward more adverse events in the nonanterior STEMI patients
C. In the large-scale AMISTAD-II trial of anterior STEMI patients undergoing
reperfusion therapy, infarct size was reduced with the higher dose protocol of 70
μg/kg/min adenosine infusion
D. In AMISTAD-II, high-dose but not low-dose (50 μg/kg/min) adenosine infusion was
associated with a reduction in the primary endpoint of new congestive heart failure
(CHF) beginning >24 hours after randomization, or the first rehospitalization for CHF,
or death from any cause within 6 months

ANSWERS AND EXPLANATIONS

9.1 Answer B. The patient is demonstrating SCAI class C cardiogenic shock, defined as
hypoperfusion, often coupled with hypotension, and requiring one intervention
(pharmacologic or mechanical) beyond volume resuscitation. Patients often have
evidence of volume overload (rales, lower extremity edema, elevated BNP) and cool
extremities. There is often evidence of acute kidney injury and elevated liver function
tests (LFTs), and lactate levels will be >2 mmol/L. SCAI class B shock would manifest
as volume overload, but signs of hypoperfusion such as acute kidney injury and elevated
lactate, as seen in this patient, would not be present. Although the phosphodiesterase
inhibitor milrinone is a reasonable agent for inotropy, its lucitropy and resulting afterload
reduction may not be well tolerated in a patient who is already hypotensive.
Additionally, the drug is cleared by renal excretion so it must be used with extreme
 caution, if at all, in the setting of acute renal dysfunction as this could promote prolonged
hypotension. Unlike milrinone, however, dobutamine is hepatically metabolized and can
be used safely in patients with renal dysfunction in the right clinical setting. Although
the effect on α-receptors would improve hypotension, phenylephrine is inappropriate in
this setting because an unopposed increase in afterload would harm a patient whose SVR
is already markedly elevated. Further, it has no β1 affect so reflex tachycardia would not
be expected. Although norepinephrine would also act on the α-receptors to improve
hypotension, its additional effects on β1-receptors would increase contractility, coronary
blood flow, and end-organ perfusion, making norepinephrine a better choice for initial
therapy. If no clinical improvement occurs, the patient would be classified as SCAI class
D shock with need for vasoactive escalation or institution of mechanical support such as
an IABP (Overgaard CB, Dzžavík V. Inotropes and vasopressors—review of physiology
and clinical use in cardiovascular disease. Circulation. 2008;118(10):1047-1056. PMID:
18765387).

9.2 Answer C. Option A is consistent with the mechanism of action for phenylephrine that
produces unopposed vasoconstriction, making it a good agent for pure vasodilatory
shock. Option B is how milrinone acts to increase contractility. Its additional lucitropy
effect also reduces afterload, with the combined effect of increasing forward flow from
the heart and reducing SVR. This is an ideal agent for patients who require increased
cardiac output who are not hypotensive. Option D describes the mechanism of action for
vasopressin, which like phenylephrine primarily increased blood pressure without a
primary effect on heart rate or contractility. It is also frequently used in the setting of
septic shock. Option E describes the mechanism of action for epinephrine. Its strong
effect on chronotropy and inotropy makes it an ideal agent in cardiogenic shock.
Norepinephrine is similar to endogenous catecholamines produced by the adrenal gland
and sympathetic nervous system. While its α-receptor effect acts to increase MAP
through powerful vasoconstriction, its mixed action on the β1-receptor also significantly
increases contractility, making it an ideal agent in patients with cardiogenic shock who
cannot tolerate pure afterload reduction in the setting of hypotension (Overgaard CB,
Dzžavík V. Inotropes and vasopressors—review of physiology and clinical use in
cardiovascular disease. Circulation. 2008;118(10):1047-1056. PMID: 18765387).

9.3 Answer C.This patient is experiencing an acute type A aortic dissection. He presents with
typical symptoms and physical exam findings including discrepancy in upper and lower
extremity pulses. The dissection extends into the left subclavian with associated
reduction in left arm blood pressure/pulse, into the iliac arteries with reduced pedal
pulses, and affects the aortic valve with associated diastolic murmur of aortic
insufficiency. This is considered a surgical emergency and immediate consultation with
an experienced cardiothoracic surgeon should be sought. As many as 40% of patients
with type A dissections die prior to presentation, but of those that make it to the hospital,
mortality increases by 1%-3% per hour of surgical delay. Type A aortic dissection is
considered a form of hypertensive emergency that requires aggressive blood pressure
reduction above and beyond standard treatment. Without evidence of stroke,
preeclampsia, or dissection, the treatment of hypertensive emergency is to lower blood
 pressure by 25% in the first hour, to <160/110 mm Hg in hours 2-6, and then to normal
in the subsequent 24-48 hours. Although this can be achieved by continuous IV infusion,
this can also often be accomplished by bolus dosing of medications such as hydralazine.
However, this is inadequate treatment in the setting of aortic dissection that requires
immediate reduction in blood pressure to systolic 100-120 mm Hg in the first 20-60
minutes with the use of IV medications, β-blockers in particular given their ability to
reduce shear stress across the damaged aorta. Alternative or adjective medications often
include IV sodium nitroprusside and/or clevidipine (Evangelista A, Isselbacher EM,
Bossone E, et al. Insights from the International Registry of Acute Aortic Dissection: a
20-year experience of collaborative clinical research. Circulation. 2018;137(17):1846-
1860. PMID: 29685932).

9.4 Answer E.Although the stenosis in the ostial RCA may be atherosclerotic in origin, the
description is also consistent with coronary artery spasm induced by aggressive and
repeated catheter manipulation. This can be effectively treated with introduction of
intracoronary nitroglycerin to release the spasm and help define if this lesion requires
intervention. In this case, instilling 200-300 μg of IC nitroglycerin should eliminate
catheter-associated spasm and thus clarify the etiology of the stenosis. While waiting 1-2
minutes to reengage and repeat angiography may be sufficient to demonstrate relief of
spasm, but this may neither be long enough (spasm can persist for 5-30 minutes), and
repeat attempts with the same catheter may introduce the same trauma and potentially
lead to worse complications such as dissection. If the stenosis was not relieved by
nitroglycerin, then consideration for optimal mode or revascularization based on
SYNTAX score and medical history, and assuming PCI is pursued, interventional
sequencing would be appropriate.

9.5 Answer C.The treatment of choice for coronary artery vasospasm is the use of an
intracoronary vasodilator. Although acetylcholine can lead to coronary artery dilation,
because it is an endothelium-dependent agent, it can exert the opposite effect leading to
vasoconstriction in the setting of endothelial derangement, such as can be seen in
coronary artery disease or endothelial disruption from balloon angioplasty. Sodium
nitroprusside, nitroglycerin, and the calcium channel blockers such as verapamil,
diltiazem, and nicardipine are all endothelial-independent vasodilators and do not require
an intact endothelium to exert their vasodilator effect.

9.6 Answer A. The patient has signs and symptoms consistent with severe PH (RV heave on
exam, RV dysfunction/enlargement with pressure and volume overload [D sign] on echo,
exertional syncope), and with high clinical suspicion for primary process (ruled out left
heart dysfunction [group 2 PH], chronic lung disease [group 3], chronic thromboembolic
pulmonary hypertension [CTEPH; group 4]), a right heart catheterization is appropriate.
Once normal LVEDP is confirmed, use of a pulmonary vasodilator is the next most
appropriate step. A short-acting agent with minimal side effects is ideal. The longer half-
life of calcium channel blockers such as diltiazem and verapamil, especially with the
potential for systemic hypotension limiting necessary maximal dose titration, limits the
usefulness of these agents. Nicardipine, with its shorter half-life, could be used, but
 immediate-release formulation has been associated with stroke and death. Prostacyclins
including IV epoprostenol and inhaled iloprost (class IIb) have been successfully used in
high-volume centers, but access and cost can prove limiting. Adenosine can also be used
(class IIb), but small studies have found this agent to be less sensitive and specific for the
diagnosis of vasoreactive PH compared to the gold standard, inhaled nitric oxide (class
IIa), which is the best agent to use during right heart catheterization (Maron BA. Revised
definition of pulmonary hypertension and approach to management: a clinical primer. J
Am Heart Assoc. 2023;12(8):e029024. PMID: 37026538).

9.7 Answer E.The use of radial artery access for percutaneous procedures has dramatically
reduced vascular complications compared with the femoral approach, with additional
benefits of reduced bleeding complications, reduced mortality in certain populations, and
increased patient comfort and satisfaction. However, the radial approach has a steep
learning curve and is met with increased need for femoral conversation due to arterial
tortuosity, radial artery spasm, and radial artery occlusion. To increase procedural
success via the radial approach, the radial “cocktail” has been routinely utilized to reduce
spasm and subsequent occlusion, typically consisting of 100-200 μg of IA nitroglycerin
in addition to a non-dihydropyridine calcium channel blocker (eg, verapamil 5 mg),
although dihydropyridine agents such as nicardipine have been used effectively. This
cocktail can be repeated between catheter exchanges, assuming hemodynamics allow.
However, IA administration can have systemic effects including hypotension and
bradycardia, and therefore should be used with caution, or at reduced dose, in patients
with hypotension, inferior MI, severe bradycardia, or severe AS. In these circumstances,
nonpharmacologic therapies such as local heat can prove beneficial.

9.8 Answer D. The patient has hallmark features of microvascular angina (MVA, alternatively
syndrome X and INOCA), defined as typical angina despite angiographically normal
coronary arteries. Symptoms are typically triggered by coronary microvascular
dysfunction and tend to occur in postmenopausal women with traditional cardiac risk
factors such as diabetes and tobacco use. Establishing the diagnosis of MVA requires
clinical features consistent with the diagnosis along with objective documentation of
myocardial ischemia (eg, ST depressions on ECG when ambulating to rest room), the
absence of obstructive epicardial coronary disease by angiography, and findings
consistent with the diagnosis by provocative intracoronary testing (eg, CFR). CFR is the
ratio of maximal hyperemic blood flow measured after infusion of a coronary vasodilator
(adenosine) to resting coronary blood flow. Maximal coronary blood flow should be at
least 2.5 times that measured at rest. When there is no significant epicardial stenosis, a
CFR <2-2.5 suggests abnormal microvascular response to vasodilators. In this scenario,
the next appropriate step would be to perform CFR to confirm the diagnosis of MVA.
FFR would not be helpful because FFR solely assesses epicardial stenoses and
eliminates the contribution of microvascular disease in its assessment. Although one
could do an exercise SPECT as part of the initial diagnostic approach, it is not
uncommon to have provokable symptoms with a bland perfusion study, possibly because
the ischemia is patchy or limited to the subendocardium. Suspicion for myocarditis is
low as the patient has had symptoms for several months, so a cardiac MRI would be of
limited utility. Lastly, typical angina with provokable ischemic change on ECG points
 heavily to a cardiac diagnosis, making referral to gastroenterology inappropriate.

9.9 Answer B.The best use for the purely inotropic medications like dobutamine and milrinone
is when a patient is normotensive to hypertensive but hemodynamics suggests low
output. The latter is characterized by high filling pressure, low cardiac index, high
systemic vascular resistance (SVR), and clinical/laboratory markers of poor end-organ
perfusion. Dobutamine is a β-agonist, with the β1 effect acting to increase
inotropy/cardiac output and the β2 effect acting to reduce afterload and thereby SVR.
Both will result in improved end-organ and renal perfusion, leading to improved diuretic
response and reduction in filling pressures. The β1 effect can induce tachycardia and
arrhythmias, so starting heart rate and underlying ectopy should be taken into
consideration before medication initiation. Option B best highlights this clinical setting.
Option A, with evidence of hypotension and tachycardia, low filling pressures, and low
SVR, is more consistent with septic shock where inotropes would be contraindicated.
Option D is most consistent with a normal hemodynamic profile where inotropes would
not be indicated. Option C also suggests a low output state, but unlike option B, this
patient has hypotension consistent with cardiogenic shock and afterload reduction may
cause a further deleterious drop in blood pressure. In this clinical situation, the best agent
would not be an inotrope, but rather a pressor such as norepinephrine with or without
mechanical support.

9.10 Answer B. Nitrodilators comprise a class of compounds that relax vascular smooth muscle
via direct or indirect generation of nitric oxide, which in turn activates soluble guanylyl
cyclase to form cyclic guanosine 3′-5′-monophosphate (cGMP). Sodium nitroprusside is
an inorganic prodrug that spontaneously releases nitric oxide and serves as a potent
vasodilator for both arteries and veins, rather than selectively affecting the coronary
arteries. Nitroprusside is metabolized to cyanide ions and cyanmethemoglobin, with
cyanide subsequently converting to thiocyanate. Thiocyanate toxicity, while relatively
rare, tends to be more likely in the setting of renal insufficiency and prolonged (>72
hours) infusions, rather than within the first 12-24 hours. As noted, of the two
compounds, only nitroglycerin requires enzymatic activation in the body prior to
generation of nitric oxide. Organic nitrates such as nitroglycerin dilate both venous and
arterial beds, resulting in decreased cardiac preload, thereby reducing ventricular wall
stress and myocardial oxygen demand. Coronary dilation occurs to a large degree in the
epicardial vessels without significant risk of coronary steal. Nitroglycerin, unlike sodium
nitroprusside, requires aldehyde dehydrogenase and/or other specific thiol-containing
compounds for biologic activation and generation of nitric oxide (Ranadive SM, Eugene
AR, Dillon G, Nicholson WT, Joyner MJ. Comparison of the vasodilatory effects of
sodium nitroprusside vs. nitroglycerin. J Appl Physiol (1985). 2017;123(2):402-406.
PMID: 28572495).

9.11 Dopamine is an endogenous catecholamine and the precursor to endogenously

Answer B.
generated norepinephrine. Dopamine binds a variety of receptors throughout the body in
a dose-dependent fashion: At low doses (0.5-3 μg/kg/min) dopamine binds D1 and D2
dopaminergic receptors and increases flow to the coronary, cerebral, renal, and
 mesenteric vascular beds. At intermediate doses (3-10 μg/kg/min), dopamine binds to β1-
adrenergic receptors, which results in increased inotropy and cardiac contractility as well
as mild increase in SVR. At high doses (10–20 μg/kg/min), the predominant effect is
peripheral vasoconstriction mediated by α1-adrenergic receptor stimulation.
Norepinephrine is synthesized endogenously from dopamine and is a potent α1-
adrenergic agonist with minimal β1-activity, which, when administered in cardiogenic
shock, increases systolic and diastolic blood pressures with minimal impact on cardiac
output. Milrinone is the most commonly utilized phosphodiesterase 3 inhibitor (not
catecholamine) that increases intracellular level of cAMP by inhibiting its breakdown,
resulting in increased myocardial contractility and vasodilation, thus reducing preload,
afterload, and SVR. Levosimendan is a calcium-sensitizing agent that increases
myocardial contractility via calcium sensitization of contractile proteins and arterial and
venous vasodilation through opening of adenosine triphosphate (ATP)-dependent
potassium channels (not via direct binding to cell surface inotrope receptors) (Overgaard
CB, Dzžavík V. Inotropes and vasopressors—review of physiology and clinical use in
cardiovascular disease. Circulation. 2008;118(10):1047-1056. PMID: 18765387).

9.12 Answer C. The ATHOS-3 trial evaluated the impact of synthetic human angiotensin II
(LJPC-501, an identical amino acid sequence replicate of endogenous angiotensin II) or
saline placebo on patients with vasopressor-resistant distributive/vasodilatory shock in
whom cardiogenic shock was ruled out with hemodynamic assessment. Patients with
vasodilatory shock who were receiving more than 0.2 μg/kg/min body weight of
norepinephrine (or the equivalent dose of another vasopressor) were included in this
study. The primary end point of MAP response at 3 hours (defined as MAP >75 mm Hg
or higher or an increase in MAP from baseline of at least 10 mm Hg without an increase
in baseline vasopressor therapy) was reached by more patients in the angiotensin II
group than in the control group (69.9% vs 23.4%, odds ratio, 7.95; 95% confidence
interval [CI] 4.76-13.3; P < .001) without an excess of serious adverse events (60.7% of
the patients in the angiotensin II group vs 67.1% in the placebo group). Death by 28 days
occurred in a comparable proportion of both groups (46% in the angiotensin II vs 54% in
the placebo group; hazard ratio, 0.78; 95% CI, 0.57-1.07; P = .12). The authors
concluded that angiotensin II was effective in increasing blood pressure in vasopressor-
resistant patients with vasodilatory shock (Khanna A, English SW, Wang XS, et al.
Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med.
2017;377(5):419-430. PMID: 28528561).

9.13 Answer D.The DOREMI trial sought to understand if the initial choice of inotropic support
in cardiogenic shock without out-of-hospital cardiac arrest impacted clinical outcomes.
A total of 192 participants with a clinical diagnosis of cardiogenic shock and systolic
blood pressure <90 mm Hg with end-organ dysfunction or evidence of systemic and/or
pulmonary congestion despite use of vasodilators and/or diuretics (among other
inclusion criteria) were randomly assigned to receive either dobutamine or milrinone at a
dose determined using a standardized dosing scale. Patients with SCAI shock stages B-E
were included and patients suffering out-of-hospital cardiac arrest were excluded from
the study. In either treatment group, <10% of patients suffered resuscitated in-hospital
 cardiac arrest. The primary outcome was a very broad composite of in-hospital death
from any cause, resuscitated cardiac arrest, need for cardiac transplantation or
mechanical circulatory support, nonfatal MI, TIA or stroke, or initiation of renal
replacement therapy. The conclusion of this study was that in patients with cardiogenic
shock, no significant difference between milrinone and dobutamine was found with
respect to the primary composite outcome or important secondary outcomes (which were
individual components of the primary outcome) (Mathew R, Di Santo P, Jung RG, et al.
Milrinone as compared with dobutamine in the treatment of cardiogenic shock. N Engl J
Med. 2021;385(6):516-525. PMID: 34347952).

9.14 Answer B.The DOREMI trial sought to understand if the initial choice of inotropic support
in cardiogenic shock without out-of-hospital cardiac arrest impacted clinical outcomes.
A total of 192 participants with a clinical diagnosis of cardiogenic shock and systolic
blood pressure <90 mm Hg with end-organ dysfunction or evidence of systemic and/or
pulmonary congestion despite use of vasodilators and/or diuretics (among other
inclusion criteria) were randomly assigned to receive either dobutamine or milrinone at a
dose determined using a standardized dosing scale. The distribution of shock stages was
very similar between treatment arms, which were well balanced with respect to other
baseline variables as well. There was no difference between treatment groups with
respect to the occurrence of the primary end point or any of the key components of the
primary end point that comprised the secondary end points. While 30-day mortality was
numerically lower in dobutamine-treated patients, in-hospital mortality did not differ nor
did other key biochemical, hemodynamic, or clinical measures (Mathew R, Di Santo P,
Jung RG, et al. Milrinone as compared with dobutamine in the treatment of cardiogenic
shock. N Engl J Med. 2021;385(6):516-525. PMID: 34347952; Supplementary appendix:
milrinone versus dobutamine in the treatment of cardiogenic shock.
https://www.nejm.org/doi/suppl/10.1056/NEJMoa2026845/suppl_file/nejmoa2026845_appendix.pdf

9.15 Answer D. The SOAP II trial was a large multicenter randomized clinical trial conducted in
Europe in which 1,679 adult patients presenting with a diagnosis of shock requiring
vasopressor support after an initial trial of volume resuscitation (at least 1,000 mL of
crystalloids or 500 mL of colloids, unless there was objective hemodynamic evidence of
volume overload) were randomized to first-line treatment with IV dopamine or
norepinephrine. If blood pressure could not be maintained with maximal doses of initial
agent, the protocol allowed for the addition of open-label norepinephrine, epinephrine, or
vasopressin. The primary outcome was the rate of death at 28 days following
randomization and was not different between the dopamine- and norepinephrine-treated
patients. Subgroup analyses found that dopamine was associated with a higher incidence
of arrhythmic events in the overall cohort and a higher rate of death at 28 days in patients
with cardiogenic shock (De Backer D, Biston P, Devriendt J, et al. Comparison of
dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362(9):779-
789. PMID: 20200382).

9.16 Answer C.In the setting of a well-placed TAVR valve and once any rare but potentially
catastrophic complications of TAVR such as large-bore access bleeding, cardiac
 tamponade, coronary occlusion, and aortic root disruption have all quickly been ruled
out, worsening of the patient’s dynamic intracavitary gradient must be evaluated and
treated. This phenomenon, termed “suicide left ventricle,” is the most likely condition in
this case given the existing gradient at baseline, hyperdynamic LV systolic function and
significant LV hypertrophy. The physiology of this dynamic condition is akin to
hypertrophic obstructive cardiomyopathy. As the condition is precipitated by sudden
relief of the fixed LV obstruction (critical AS) in the setting of an intracavitary gradient
and hypercontractility, hypovolemia and maneuvers that result in increased inotropy will
immediately worsen the hypotension. Electrical cardioversion is not indicated as there is
no evidence of a malignant arrhythmia or loss of AV synchrony; the elevated heart rate
most likely represents physiologically driven sinus tachycardia. Treatment for suicide
LV should focus on volume correction/resuscitation, slowing down the heart rate, and
decreasing inotropy if possible (Suh WM, Witzke CF, Palacios IF. Suicide left ventricle
following transcatheter aortic valve implantation. Catheter Cardiovasc Interv.
2010;76(4):616-620. PMID: 20506145).

9.17 Answer C. The standard dosing for the agents listed are: dopamine 2.5-20 μg/kg/min IV,
dobutamine 2.5-20 μg/kg/min IV, norepinephrine 0.01-3 μg/kg/min IV, and milrinone 50
μg/kg IV bolus then 0.375-0.75 μg/kg/min IV infusion (renal adjustment necessary)
(Overgaard CB, Dzžavík V. Inotropes and vasopressors—review of physiology and
clinical use in cardiovascular disease. Circulation. 2008;118(10):1047-1056. PMID:
18765387).

9.18 Answer A. Routine use of IABP support in acute MI and cardiogenic shock has fallen out
of favor in US and European practice guidelines on the basis of various negative clinical
trials. While inotrope-supported diuresis has been the standard approach in
decompensated heart failure without shock, there have now been over a dozen studies
investigating the use of IABP in this patient cohort (Baldetti L, Pagnesi M, Gramegna M,
et al. Intra-aortic balloon pumping in acute decompensated heart failure with
hypoperfusion: from pathophysiology to clinical practice. Circ Heart Fail.
2021;14(11):e008527. PMID: 34706550). A small, well-designed randomized trial by
den Uil and colleagues studied patients admitted with decompensated, non-ACS heart
failure with low output and volume overload, and randomized them to a strategy of 50
mL IABP support versus inotropic support with dobutamine/enoximone. IABP support
was associated with improvement in SVO2 at 3 hours compared with the inotrope
strategy, as well as improvement in CPO, N-terminal-proBNP proportional change,
cumulative fluid balance, and change in dyspnea severity score at 48 hours, with no
IABP-related serious adverse effects. Thirty-day mortality was 23% in the IABP group
versus 44% in the inotrope group (P = NS). The ongoing Altshock-II trial seeks to
expand these observations to acute decompensated heart failure patients with cardiogenic
shock.

9.19 Answer A. Platelet glycoprotein inhibitors (GPIs) are commonly used in the setting of no-
reflow occurring in primary PCI for STEMI due to the presumed association with
platelet-rich thrombus that has embolized to the microvasculature. Platelet GPIs block
 the final common pathway for platelet aggregation by interfering with binding of soluble
fibrinogen to the αIIb/β3 integrin (Gp IIb/IIIa receptor). Abciximab binds irreversibly to
the Gp IIb/IIIa receptor, whereas the small-molecule, synthetic agents tirofiban and
eptifibatide bind reversibly. Adenosine is a purine nucleoside base that binds to
purinergic receptors found abundantly throughout the body. When administered IC,
adenosine effects smooth muscle relaxation and also exerts weak antiplatelet properties
and mitigation of free radical formation. Sodium nitroprusside is a nitrodilator that
activates guanylate cyclase and serves as a nitric oxide donor. Nitroprusside may be
administered IC in 50-200 μg boluses, with little systemic hypotension. Nicardipine is a
dihydropyridine calcium channel blocker that promotes coronary vasodilation when
administered locally. Bolus doses of 50-200 μg are injected directly into the affected
coronary bed, while larger doses (0.5-1 mg) are given IV to acutely treat hypertension
(Caiazzo G, Musci RL, Frediani L, et al. State of the art: no-reflow phenomenon.
Cardiol Clin. 2020;38(4):563-573. PMID: 33036718).

9.20 Answer D.The AMISTAD-I trial of 236 thrombolytic-treated patients did indeed find a
significant 33% relative reduction in infarct size with a 3-hour adenosine infusion (70
g/kg/min) compared with control treatment, but also noted that efficacy of the therapy
was limited to anterior STEMI patients with a trend toward more adverse events in the
non–anterior STEMI patients. The subsequent AMISTAD-II trial enrolled 2,228 patients
with evolving anterior STEMI receiving thrombolysis or primary angioplasty and
randomized to a 3-hour infusion of either adenosine 50 or 70 μg/kg/min or placebo. The
primary endpoint of new CHF beginning >24 hours after randomization, or the first
rehospitalization for CHF, or death from any cause within 6 months was not significantly
reduced in the pooled adenosine groups or either the 50 or 70 μg/kg/min groups,
analyzed separately. The pooled adenosine group did trend, however, toward a smaller
median infarct size compared with the placebo group, and infarct size was reduced with
the 70 μg/kg/min adenosine infusion group with fewer adverse events noted in this group
of patients (Ross AM, Gibbons RJ, Stone GW, et al. AMISTAD-II Investigators. A
randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an
adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J
Am Coll Cardiol. 2005;45(11):1775-1780. PMID: 15936605).
 Guiding Catheter Selection for
10
Coronary Interventions

Annapoorna S. Kini and Vishal Dhulipala

QUESTIONS

10.1 A 65-year-old Dutch pianist is having a diagnostic angiogram through left femoral arterial
access. With a Judkins left (JL)4 catheter, you cannot engage the left main coronary
artery due to significant prolapse of the catheter in the ascending aorta. What is the next
best step?
A. Exchange to JL3.5
B. Exchange to JL4.5
C. Exchange to XB3.5
D. Perform a nonselective injection in the aorta

10.2 You have planned to perform a staged percutaneous coronary intervention (PCI) of mid–
right coronary artery (RCA) chronic total occlusion (CTO) in a 56-year-old female
through a femoral approach. As per the diagnostic angiogram, the takeoff of the RCA is
anterior in the right coronary cusp. Which of the following guide catheters would
provide the most optimal guide support and coaxiality?
A. 3DRC
B. JR4
C. AL
D. FR3.5

10.3 As you are intervening on the patient in Question 2, you see the invasive diastolic
pressure drop from 80 to 40 mm Hg. Which of the following is the most likely next step?
A. Adjust the guiding catheter
B. Aspirate at least 20 mL of blood to remove the thrombus in the catheter
C. Flush the catheter with saline to treat air embolism
 D. Remove the guide catheter and check the sheath pressure

10.4 You plan to intervene on an 80%-90% ostial RCA stenosis. Which one of the following
guide catheters is preferred to increase procedural success and decrease complications?
A. AL1
B. MPA
C. FR3.5
D. JR4

10.5 In a patient with possible severe aortic (AO) stenosis, which is the preferred way of
measuring left ventricular (LV) and AO gradient?
A. 5F femoral sheath for AO pressure and 4F pigtail for LV pressure
B. Dual arterial access, one for AO pressure and the other for a pigtail catheter for LV
pressures
C. Pullback of a single 5F Judkins right (JR) catheter from the left ventricle to the aorta
D. Use a Langston catheter

10.6 A 70-year-old female patient presents with a lateral wall ST-elevation myocardial
infarction (STEMI). While obtaining the right radial access, you feel mild spasms while
advancing the sheath that is relieved by the radial cocktail. Which choice of catheters is
more appropriate in this case?
A. JR followed by JL diagnostic or left-sided guide catheter
B. Ikari left catheter
C. Cross over to femoral access and use a JL and JR catheter
D. Cross over to left radial access

10.7 A 75-year-old male patient with a history of coronary artery bypass graft (CABG) is in
the cath lab for a diagnostic angiogram due to exertional chest pain and anterior ischemia
noted on stress perfusion imaging. You plan to use the right femoral access and are
trying to image the left internal mammary artery (LIMA) graft with a JR catheter. Which
of the following maneuvers is safe and will help you in navigating from the arch of the
aorta?
A. Counterclock the catheter and advance the catheter over a wire
B. Clock the catheter and advance the catheter
C. Counterclock the catheter and advance the catheter
D. Clock the catheter and advance the catheter over a wire

10.8 After performing an atherotomy with a cutting balloon and percutaneous transluminal
coronary angioplasty (PTCA) to tortuous distal RCA, it was hard to deliver a long stent
into the lesion with an Amplatz left (AL) guide. Which of the below equipment with be
 the next best step in this scenario?
A. Using a Turnpike catheter
B. Venture catheter
C. Change to internal mammary (IM) guide catheter
D. Using a guide extension catheter
E. Finecross microcatheter

10.9 Severely calcified proximal left anterior descending (LAD) artery is planned to be
intervened with a 6F voda left (VL) guide catheter. The vessel size is 3.5 mm. What is
the maximum size of Rota-burr that can be accommodated per the manufacturer’s
labeling?
A. 1.25 mm
B. 1.5 mm
C. 1.75 mm
D. 2.0 mm

10.10 A 79-year-old woman has a diagnostic angiogram through 5F Slender radial access, and
her radial artery is noted to be of small caliber based on ultrasound imaging prior to
arterial access. Now she will need an intervention to be performed for proximal LAD
stenosis. Which is the least invasive option?
A. Crossover to femoral access and 6F system
B. Exchange to 6F Slender sheath
C. Image left radial artery with ultrasound for potential access
D. Exchange to a 6.5F Sheathless Eaucath system

10.11 You have diagnosed a bifurcation lesion of distal RCA with medina 1,1,1 distribution and
plan to intervene with a mini-crush strategy through femoral access. After intravascular
ultrasound (IVUS) imaging, you plan to size 2.5 and 2.25 mm stents. What is the
appropriate guide catheter size to deliver the balloons and stents?
A. 5F
B. 6F
C. 7F
D. 8F

10.12 Which of the following statements is INCORRECT regarding a 45 cm sheath?

A. It helps in settings with tortuous aorta and iliac arteries
B. It provides more support for the guide catheter
C. It conveys bias to the guide catheter
D. A Vascade closure device can be deployed through it at the end of the procedure
10.13 Of the below-mentioned guide catheters, which is the correct decreasing order of support
they provide for an intervention of the left coronary system?
A. EBU > Voda L > JL
B. EBU > JL > Voda L
C. Voda L > JL > EBU
D. JL > Voda L > EBU

10.14 You plan to intervene on a distal LAD lesion through a LIMA graft. After obtaining the
right femoral access, which is the appropriate guide catheter for this setting?
A. 5F 90 cm LIMA guide catheter
B. 6F 90 cm LIMA guide catheter
C. 5F 100 cm LIMA guide catheter
D. 6F 100 cm LIMA guide catheter

10.15 A 67-year-old male with chronic kidney disease (CKD) stage 3 was found to have ostial
RCA stenosis and dampening while obtaining a diagnostic angiogram. The lesion looks
intermediate, and you plan to perform a fractional flow reserve (FFR). Which of the
below statements is FALSE?
A. Side-hole catheter increases the chances of contrast-induced nephropathy
B. Side-hole catheters transduce a better pressure waveform from the tip of the catheter
C. Side-hole catheters do not necessari