Acute Myocardial Ischaemia Terminology,

Pathophysiology and Recognition

Table of Contents
 Preface
 Introduction
 Terminology
 Unstable Angina (UA)
 Myocardial Infarction
 Myocardial infarction with non obstructive coronary arteries (MINOCA)
 Myocardial infarction in the Intensive Care Unit
 Pathophysiology Of AMI
 Understanding the underlying mechanisms
 Pathophysiology of the complications and sequelae of Myocardial
Infarction
 Understanding normal coronary artery anatomy
 Cardiogenic Shock
 Recognition of AMI
 Clinical features of ischaemic chest pain
 Triage and early risk stratification
 Immediate management of ACS
 On going physical examination
 Investigations
 Risk Scoring Systems
 Conclusion
Acute myocardial ischaemia Terminology, Pathophysiology
and Recognition

Update 2022

Authors
Jose Alfonso Rubio Mateo Sidron MD, Intensive Care Unit. Hospital Universitario
12 de octubre, Madrid.
Patricia Marquez Lozano MD, Cardiology Service. Hospital Infanta Cristina.
Badajoz. Spain
Sara Helena De Miguel Martin MD, Intensive Care Unit. Hospital de Villalba. Madrid.
Spain
Eduardo Morales Sorribas MD, Intensive Care Unit. Hospital Sanitas-La Moraleja.
Madrid. Spain

Reviewers
Sameer Jog MD, Consultant Intensivist, Deenanath Mangeshkar Hospital and
Research Center. Pune 411004, India,

Editors
Jan Bakker MD, PhD, FCCM, FCCP, Assistant Professor Dept of Pulmonology and
Critical Care, New York University; Adjunct Professor Dept of Pulmonology and
Critical Care, Columbia University, New York, United States; Professor Dept of
Intensive Care Adults, Erasmus MC Rotterdam, The Netherlands; Professor

Executive Editor
Nathan D. Nielsen MD, MSc, Associate Professor, Division of Pulmonary, Critical
Care and Sleep Medicine, University of New Mexico School of Medicine,
Albuquerque, United States; Editorial Board and Sepsis Section Editor, ESICM
Academy

First Edition 2019

Authors
Jose Alfonso Rubio Mateo Sidron MD, Intensive Care Unit. Hospital Universitario
12 de octubre, Madrid.
 Patricia Marquez Lozano MD, Cardiology Service. Hospital Infanta Cristina.
Badajoz. Spain
Sara Helena De Miguel Martin MD, Intensive Care Unit. Hospital de Villalba. Madrid.
Spain
Eduardo Morales Sorribas MD, Intensive Care Unit. Hospital Sanitas-La Moraleja.
Madrid. Spain

Reviewers
Daniel Caeiro MD, Cardiac Intensive Care Unit. Centro Hospitalar Vila Nova de
Gaia/Espinho, Porto, Portugal
Robert von Arx MD, University Hospital Bern, Switzerland

Section Editor
Jan Bakker MD, PhD, FCCM, FCCP, Assistant Professor Dept of Pulmonology and
Critical Care, New York University; Adjunct Professor Dept of Pulmonology and
Critical Care, Columbia University, New York, United States; Professor Dept of
Intensive Care Adults, Erasmus MC Rotterdam, The Netherlands; Professor

CoBaTrICE Mapping Contributors

Cristina Santonocito MD, Dept. of Anesthesia and Intensive Care, IRCSS-ISMETT-
UPMC, Palermo, Italy
Victoria Anne Bennett MD, MBBS, FFICM, FRCA, Anaesthetic and Intensive care
registrar, University Hospital Lewisham, London, United Kingdom

Co-Ordinating Editor
Joana Berger Estilita MD, Department of Anaesthesiology and Intensive Care,
Salem Spital, Hirslanden Medical Group; Institute for Medical Education, University of
Bern, Bern, Switzerland

Executive Editor
Mo Al-Haddad MBChB, FRCA, FFICM, EDIC, MSc (Clinical Education),
Consultant in Critical Care and Anaesthesia, Queen Elizabeth University Hospital
Honorary Professor at the University of Glasgow

Intended Learning Outcomes

Acute myocardial ischaemia Terminology, Pathophysiology

and Recognition
 1. Review the latest definition, causes and pathophysiology of acute coronary
syndrome
2. Recognise how to confirm a diagnosis of acute coronary syndrome with the use
of the contemporary detection strategies
3. Demostrate how to manage acute coronary syndrome with the latest strategies
4. Recognise the evidence based secondary prevention strategy in acute
coronary syndrome.
5. Distinguish between myocardial injury and myocardial infarction (MI)
6. Distinguish between acute myocardial injury with/without myocardial ischaemia
and chronic myocardial injury
7. Define and differentiate UA, NSTEMI, and STEMI.
8. Distinguish between acute myocardial injury related to either acute coronary
athero-thrombosis (MI type 1) or to an imbalance between myocardial oxygen
supply/demand secondary to underlying stressor(s) (MI type 2)
9. Distinguish between procedural related myocardial injury and procedural
related myocardial infarction (MI types 4a or 5)
10. Discuss the pathophysiology of acute coronary syndromes describing the role
of atherosclerotic plaque, platelets, and the coagulation system.
11. Describe the therapy for acute coronary syndromes (aspirin, thrombolytic
therapy, etc.) in terms of the underlying pathophysiology
12. Explain the complications of acute myocardial infarction
13. Define the mechanisms of heart failure and cardogenic shock in coronary artery
disease
14. Triage, identify and activate immediate management strategies of patients with
suspected ACS
15. Apply algorithm diagnostic to rule in/out ACS (ECG, biomarkers and imaging
techniques) and confirm a diagnosis of AMI
16. Distinguish ST-segment elevation MI (STEMI) and non-STEMI by different
prognosis and treatment strategy
17. Detect ACS and distinguish the types of myocardial infarction that can occur in
critically ill patients
18. Discuss the role of primary PCI in the management of AMI and appropriate
pharmacotherapy
19. Establish risk stratification models (clinical, ischemic and bleeding) of STEMI
and non-SETMI
eModule Information

Relevant Competencies from CoBaTrICE

Acute myocardial ischaemia Terminology, Pathophysiology

and Recognition

1.1 Adopts a structured and timely approach to the recognition, assessment and
stabilisation of the acutely ill patient with disordered physiology
1.4 Triages and prioritises patients appropriately, including timely admission to
ICU.
2.1 Obtains a history and performs an accurate clinical examination
2.2 Undertakes timely and appropriate investigations
2.4 Performs electrocardiography (ECG / EKG) and interprets the results
2.9 Monitors and responds to trends in physiological variables.
2.10 Integrates clinical findings with laboratory investigations to form a differential
diagnosis.
3.1 Manages the care of the critically ill patient with specific acute medical
conditions
3.3 Recognises and manages the patient with circulatory failure.
4.1 Prescribes drugs and therapies safely.
5.1 Administers oxygen using a variety of administration devices
11.6 Critically appraises and applies guidelines, protocols and care bundles
12.1 Communicates effectively with patients and relatives
12.2 Communicates effectively with members of the health care team
12.3 Maintains accurate and legible records / documentation
12.4 Involves patients (or their surrogates if applicable) in decisions about care
and treatment
12.7 Collaborates and consults; promotes team-working
12.8 Ensures continuity of care through effective hand-over of clinical information
1. Introduction

The most obvious effect of coronary artery disease (CAD) is the compromise on the
oxygenation of the myocardial cells, which leads to an entity known as ischemic heart
disease. CAD cause approximately one third of all deaths in persons above 35 years old.

In its acute form, it initially presents as a particularly serious condition known as acute
coronary syndrome (ACS) and represents a group of medical conditions with different
stages of a continuum that may be indistinguishable at presentation to emergency
departments. They share similar pathogenic mechanisms, being the common link the
rupture of a vulnerable coronary atherosclerotic plaque and the formation of the
intracoronary thrombus.

ACS account for nearly 2 million hospitalizations annually in the United States, and if
patients who die before reaching the hospital are included, the mortality may be as high
as 25%.

The ACS is a major challenge time-dependent process where time is muscle. The
existence of a well-organized network for rapid assistance from the moment it occurs and
transfers to the appropriate hospital is essential. The monitoring of the diagnostic and
therapeutic process based on guidelines of clinical practice, following local protocols and
applied by a multiprofessional team of doctors, nurses and technicians, where ICU staff
should participate, are the best guarantee of the best results.

After being treated in the Emergency Department, and some of them go through the
hemodynamics laboratory, many of these high risk patients are in current practice finally
admitted to the Intensive Care Unit (ICU) / Coronary Care Unit under the responsibility
and direct supervision of the intensivist physician depending on the local health
organization.

 Note
The management of acute coronary syndromes (ACS) is evolving rapidly

The management of patients with ACS is changing and evolving rapidly. The advances
achieved in recent years in the knowledge of pathophysiological mechanisms of the ACS
have meant in practice to have new drugs and procedures that have improved the
diagnostic process and treatment, achieving better short and long term results. At the
same time, the intensivist doctor is faced with new complex situations and difficult
decisions to obtain the best risk/benefit ratio that requires an updated knowledge of the
disease and its management. This is generally drawn from multicentre studies of patients
presenting to emergency departments or chest pain/coronary unit. In patients already
admitted to the ICU, ACS is a difficult diagnosis to make as there are often multiple
possible causes for a raised troponin or ECG changes and there is often a lack of clinical
history to put these results into context. In addition, establishing the type of myocardial
infarction and reason for the troponin rise is especially important in patients admitted to
the ICU for its implications in the treatment and prognosis.

 Note
Patients with ACS are at high risk

In text References

(Reed, Rossi and Cannon 2017; Werns 2019; Carroll, Mount and Atkinson 2016; Fuster et
al. 1992)

 References
Reed GW, Rossi JE, Cannon CP, Acute myocardial infarction., 2017,
PMID:27502078
Werns S, Acute Coronary Syndromes and Acute Myocardial Infarction.,
Elsevier, 2019, Philadelphia, ISBN: 9780323446761
Carroll I, Mount T, Atkinson D, Myocardial infarction in intensive care units: A
systematic review of diagnosis and treatment., 2016, PMID:28979516
Fuster V, Badimon L, Badimon JJ, Chesebro JH., The pathogenesis of
coronary artery disease and the acute coronary syndromes (1)., 1992,
PMID:1727977
2. Terminology

ACS has evolved as a useful operational term that refers to a spectrum of conditions
compatible with acute myocardial ischemia and/or infarction that are usually due to an
abrupt reduction in coronary blood flow.

These syndromes are almost always caused by acute rupture or erosion of pre-existing
coronary artery atherosclerotic plaque, leading to acute thrombus formation, closure of
coronary arteries and impaired myocardial oxygen supply.

The underlying rationale is that regional myocardial hypoperfusion and ischaemia lead to
a cascade of events including myocardial dysfunction and cell death, early releasable
cytosolic pool biomarkers (troponin -cTn- and creatine kinase MB isoform -CK MB-) into
the blood stream from stressed cardiomyocytes.

ACS has traditionally been classified into Q-wave or transmural myocardial infarction,
non-Q-wave or no transmural myocardial infarction (NQMI), and unstable angina (UA).
This classification refers to a later phase in the evolution of the clinical process.

In initial assistance it is more useful to use the classification based on the initial
electrocardiogram. Patients are divided into three groups:

(1) those with ST– elevation (STEMI) on the presenting or subsequent 12-lead ECGs
(2) those without ST elevation on the presenting or subsequent 12-lead ECGs but
with enzyme evidence of myocardial damage (non–ST elevation MI or NSTEMI), and
(3) those with UA.

The importance of this classification lies in the fact that the initial ECG changes coincide
with current treatment strategies: STEMI benefit from immediate reperfusion. In contrast
fibrinolytic agents should not be used in NSTEMI.

2. 1. Unstable Angina (UA)

UA is considered to be present in patients with ischemic symptoms suggestive of an ACS
and no elevation in troponins, with or without electrocardiogram changes indicative of
ischemia (eg, ST segment depression or transient elevation or new T wave inversion).
Myocardial infarction differs from unstable angina, which is usually precipitated by
increased myocardial oxygen demand (e.g. exertion, fever, tachycardia) with background
coronary artery narrowing (limitation of oxygen supply).

Stable exertional angina results from an imbalance in myocardial oxygen supply and
demand, in this case brought on by increased demand (e.g. exertion, fever, tachycardia)
with a limitation oxygen supply (coronary artery narrowing).

In UA, the patient experiences ischaemic type chest pain, which is of recent origin, is
more frequent, severe, or prolonged than the patient’s usual angina; is more difficult to
control with drugs; or is occurring at rest or on minimal exertion.

In text References

(Ford, Corcoran and Berry 2018)

 References
Ford TJ, Corcoran D, Berry C, Stable coronary syndromes: pathophysiology,
diagnostic advances and therapeutic need., 2018, PMID:29030424

2. 2. Myocardial Infarction
An updated classification of myocardial infarction has been recently published that takes
into account the setting in which ACS has been diagnosed (see table 1). This
differentiation is extremely important in severe acute illness or postoperative settings
admitted to the ICU, as trial data obtained in different settings may or may not be fully
applicable.

Detection of an elevated cTn value above the 99th percentile upper reference limit (URL)
is defined as myocardial injury. The injury is considered acute if there is a rise and/or fall
of cTn values.

Although elevated cTn values reflect injury to myocardial cells, they do not indicate the
underlying pathophysiological mechanisms, and myocardial ischaemic or non-ischaemic
conditions associated with increased cTn values are presented in Table 1.

This is important in ICU setting because many causes of myocardial injury are common in
critical ill patients.

Table 1: Causes of Myocardial Injury. Reproduced from: Thygesen K,

Alpert JS, Jaffe AS, et al., 2018
 Myocardial injury related to acute myocardial ischaemia
Atherosclerotic plaque disruption with thrombosis

Myocardial injury related to acute myocardial ischaemia

because of oxygen supply/demand imbalance
Reduced myocardial perfusion, e.g.
Coronary artery spasm, microvascular dysfunction
Coronary embolism
Coronary artery dissection
Sustained bradyarrhythmia
Hypotensive or shock
Respiratory failure
Severe anaemia
Increased myocardial oxygen demand, e.g.
Sustained tachyarrhythmia
Severe hypertension with or without left ventricular
hypertrophy

Other causes of myocardial injury

Cardiac conditions, e.g.
Heart failure
Myocarditis
Cardiomyopathy (any type)
Takotsubo syndrome
Coronary revascularization procedure
Cardiac procedure other tan revascularization
Catheter ablation
Defibrillator shocks
Cardiac contusion
Systemic conditions, e.g.
Sepsis, infectious disease
Chronic kidney disease
Stroke, subarachnoid haemorrhage
Infiltrative disease, e.g. amyloidosis, sarcoidosis
Chemotherapeutic agents
Critically ill patients
Strenuous exercise

The clinical definition of AMI denotes the presence of acute myocardial injury in the setting
of evidence of acute myocardial ischaemia.
The diagnosis of AMI relies on criteria established by a committee grouping the European
Society of Cardiology (ESC), the American College of Cardiology (ACC), the American
Heart Association (AHA), and the World Heart Federation (WHF). Indeed, according to the
Fourth Universal Definition, AMI is a clinical event consequent to the death of cardiac
myocytes (myocardial necrosis) that is caused by ischemia (as opposed to other
aetiologies). According to this definition, spontaneous myocardial infarction (also known
as Type 1) occurs in cases of detection of a rise and/or fall of cardiac biomarker values
(preferably cardiac troponin) with at least one value above the 99th percentile upper
reference limit (URL) and with at least one of the following: symptoms of ischemia,
ischemic ECG changes, identification of an intracoronary thrombus by angiography, or
imaging evidence of new loss of viable myocardium or a new regional wall motion
abnormality.

The other types of myocardial infarction identified according to the Fourth Universal
Definition are as follows: Type 2, myocardial infarction due to ischemic blood
supply/demand imbalance; Type 3, cardiac death presumed to be caused by myocardial
infarction when markers of myocardial injury are unavailable; Type 4a, myocardial
infarction associated with percutaneous coronary intervention (arbitrary defined by
elevation of biomarker values higher than five times 99th percentile URL in patients with
normal baseline values or a rise of values over 20% if the baseline values are elevated
but stable or falling); Type 4b, myocardial infarction related to stent thrombosis; Type 4c,
caused by restenosis associated with percutaneous coronary intervention and Type 5,
myocardial infarction associated to coronary artery bypass grafting (arbitrary defined by
elevation of biomarker values over 10 times the 99th percentile URL in patients with
normal baseline values) (Table 2).

Table 2: Clinical classification of different types of myocardial infarction

Type Classification Description

Myocardial infarction (MI) caused by
atherothrombotic coronary artery
Type 1
disease and usually precipitated by
atherosclerotic plaque disruption.
MI in a context of a mismatch between
oxygen supply and demand (eg.
Type 2
Coronary artery spasm, anaemia,
arrhythmias or hypotension).
 Sudden cardiac death with symptoms
suggestive of myocardial ischaemia
accompanied by presumed new
Type 3 ischemic changes or ventricular
fibrillation, but die before biomarkers
can be obtained. Is detected by autopsy
examination.
MI after percutaneous coronary
Type 4a
intervention (< 48 h).
MI associated with stent thrombosis as
Type 4b
documented by angiography or autopsy.
MI associated with restenosis after
Type 4c
percutaneous coronary intervention.
MI associated with coronary artery
Type 5
bypass grafting (<48h).

Differentiating between Type 1 and 2 MI is very important in Critical Care setting: dual
antiplatelet therapy is only indicated in Type 1 MI. Factors that point to a diagnosis of Type
2 MI include presence of another definitive diagnosis known to be associated with an
increase in troponin levels.

A conceptual model to facilitate the clinical distinction between acute ischaemic

myocardial injury with or without an acute atherothrombotic event (Type 1 or Type 2 MI)
vs. conditions without acute ischaemic myocardial injury is displayed in Figure 1

Figure 1: A model for interpreting myocardial

injury. Reproduced from: Thygesen K, Alpert JS,
Jaffe AS, et al., 2018.

Figure 1: A model for interpreting myocardial injury. Ischaemic thresholds vary

substantially in relation to the magnitude of the stressor and the extent of underlying
cardiac disease. MI = myocardial infarction; URL = upper reference limit. (a) Stable
denotes ≤ 20% variation of troponin values in the appropriate clinical context. (b)
Ischaemia denotes signs and/or symptoms of clinical myocardial ischaemia.

In text References

(Thygesen et al. 2018)

 References
Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD;
ESC Scientific Document Group., Fourth universal definition of myocardial
infarction (2018)., 2018, PMID:30165617

2. 3. Myocardial infarction with non obstructive coronary

arteries (MINOCA)
It is increasingly recognized that there is a group of MI patients with no angiographic
obstructive CAD (≥ 50% diameter stenosis in a major epicardial vessel), and the term
myocardial infarction with non-obstructive coronary arteries (MINOCA) has been coined
for this entity.

 Note
For MINOCA keep in mind that other aetiologies for the symptoms and changes in
ECG and cardiac biomarkers must be evaluated.

In text References

(Pasupathy et al. 2015; Agewall et al. 2017)

 References
Pasupathy S, Air T, Dreyer RP, Tavella R, Beltrame JF, Systematic review of
patients presenting with suspected myocardial infarction and nonobstructive
coronary arteries., 2015, PMID:25587100
Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, Caforio AL, De
Caterina R, Zimarino M, Roffi M, Kjeldsen K, Atar D, Kaski JC, Sechtem U,
Tornvall P, WG on Cardiovascular Pharmacotherapy., ESC working group
position paper on myocardial infarction with non-obstructive coronary arteries.,
2017, PMID:28158518
2. 4. Myocardial infarction in the Intensive Care Unit
The pathophysiology of infarction in many ICU patients is probably different to that of
ACS. Studies suggest that, in the presence of severe ischaemia, left main disease and
triple-vessel disease are common and that ischaemia is secondary to oxygen supply and
demand problems (Type 2 MI) rather than thrombosis.

Some elevation of cTn values may reflect Type 2 MI due to underlying CAD and increased
myocardial oxygen demand, whereas in other patients, Type 1 MI may occur because of
plaque disruption leading to thrombosis in a coronary artery. However, other patients may
have elevated cTn values and marked decreases in ejection fraction (EF) due to sepsis
caused by endotoxin, with myocardial function recovering completely with normal EF once
the sepsis is treated.

It is frequently challenging for the clinician caring for a critically ill patient to decide on a
plan of action when the patient has elevated cTn values.

Furthermore the clinical presentation is often different and establishing the diagnosis and
weighting the relevance of elevated biomarkers can be challenging. Clinical judgement
should be employed to decide whether further evaluation for CAD or structural heart
disease is indicated.

 Note
in association with ECG and serial cTn levels, consider the use of
echocardiography to identify regional wall motion abnormality (RWMA) for
diagnosis of AMI in ICU setting.

In text References

(Mazzarelli and Hollenberg. 2017; Bradley P. Sppelt. 2019)

 References
Mazzarelli J, Hollenberg S., Acute Coronary Syndromes: Therapy., 2017,
ISBN:9780323376389
Bradley P. Sppelt I., Acute cardiac syndromes, investigations and
interventions., 2019, ISBN:97807020722215
3. Pathophysiology Of Acute Myocardial Ischaemia,
Infraction and Cardiogenic Shock
The majority of patients with acute MI have coronary artery atheroma. ACS usually results
from the formation of either totally or partially occluding thrombus upon disrupted, fissured
or eroded atheromatous plaque.

3. 1. Understanding the underlying mechanisms

MI is caused mainly by atherothrombotic coronary artery disease (CAD) and usually
precipitated by atherosclerotic plaque disruption (rupture or erosion) of a major epicardial
vessel. Often termed vulnerable plaques, atherosclerotic plaques tend to have a thin
fibrous cap over a central core of foam cells, lipids, and necrotic debris. Exposure of this
subendothelial matrix of vulnerable plaques to circulating blood leads to platelet adhesion
and activation, thrombin generation, thrombus formation, coronary blood flow obstruction
and myocardial cell death due to prolonged ischaemia.

The first ultrastructural changes are seen as early as 10–15 min after the onset of
ischaemia. It can take hours before myocyte necrosis evolves and progresses from the
subendocardium to the subepicardium. The time course to transmural myocardial
infarction may be prolonged by increased collateral flow and reduced determinants of
myocardial oxygen consumption. Timely implementation of reperfusion therapy, when
appropriate, reduces ischaemic injury to the myocardium.

The exact cause of plaque rupture or fissuring is unknown. Inflammatory processes with
activation of metalloproteinases that degrade collagen in the fibrous cap and inhibit
synthesis of new collagen and acute hemodynamic stress are synergistically associated
with increased adrenergic tone and are considered important triggers of plaque rupture.
Lipid-lowering agents may stabilise plaque not only by lowering plaque cholesterol but
also through lipid-independent (‘pleiotropic’) anti-inflammatory effects.

3. 1. 1. Pathophysiology correlated with presenting syndrome

The relative burden of atherosclerosis and thrombosis in the culprit lesion varies greatly,
and the dynamic thrombotic component may lead to total occlusion of an artery, typically
leading to ST-segment elevation myocardial infarction (STEMI), or partial non-occlusive
thrombus of the vessel leading to non–ST-segment elevation myocardial infarction
(NSTEMI).
NSTEMI and Unstable Angina are usually caused by an imbalance between myocardial
oxygen supply and demand, which may be due to one or more of the following causes:

Non-occlusive thrombus developing on a pre-existing plaque (the most frequent

cause). Arterial inflammation or infection can predispose to plaque rupture.
Dynamic obstruction – spasm of an epicardial artery or intramural vasoconstriction.
Progressive coronary narrowing without spasm or thrombus. May be due to
progressive atherosclerosis or restenosis after a PCI.
Secondary UA (‘demand ischaemia’). Patients with chronic atherosclerotic narrowing
are subjected to increased myocardial oxygen demand (fever, tachycardia) or
reduced oxygen delivery (hypotension, anaemia).

Development of thrombus upon eroded plaque results from:

1. platelet adherence and activation, and

2. coagulation pathway activation.

Platelets aggregate to form ”white thrombus”, however this thrombus is seldom totally
occluding. Activation of coagulation pathways by exposed lipid and fibrin, as well as by the
now-activate platelets, leads ultimately to thrombin activation and the laying-down of fibrin
clot. Red cells are enmeshed in this so-called ”red thrombus” complex, which surrounds
the white thrombus.

These processes have immediate relevance to treatment:

Antiplatelet agents prevent platelet adherence, which limits and even reverses the
development of “white thrombus” these agents may target the adenosine diphoshate
(ADP) receptor (e.g. clopiogrel, prasugrel, ticagrelor) or may inhibit cyclo-oygenase
and synthesis of thromboxane A2 (e.g. aspirin), but it fails to block platelet activation
by thrombin, ADP and collagen
Fibrinolytic agents lyse “red thrombus” but are not active against “white thrombus”
Antithrombin agents (eg heparins) may limit thrombin activation. Current thrombolytic
agents lyse fibrin and red cell thrombus, but paradoxically may increase surface
thrombin activation
Totally occluding thrombus causes myocardial necrosis and is often accompanied by
ST-segment elevation (STE) on the ECG
If thrombus is largely white thrombus, with minimal or non-occlusive may cause USA
or MI, especially if spasm or distal embolisation of thrombus occurs non-occlusive
plaque it is indicative of unstable plaque and is strongly associated with reinfarction
and death in following months.
3. 2. Pathophysiology of the complications and sequelae of
Myocardial Infarction
Ischaemic necrosis results in cellular disruption, loss of function, thinning and softening of
the affected myocardium with an increase in ventricular compliance. As fibrosis takes
place compliance is decreased. With time, there is often expansion of the infarcted
segment and compensatory hypertrophy of unaffected myocardial cells is also known as
ventricular remodelling.

After an AMI, mechanical problems that result from dysfunction or disruption of critical
myocardial structures may occur portending a significantly worse outcome.

After an AMI, mechanical problems that result from dysfunction or disruption of critical
myocardial structures may occur portending a significantly worse outcome.

Cardiogenic shock usually results from extensive loss of left ventricle contractile
function.
Severe ischemia or infarction can lead to papillary muscle dysfunction or rupture,
resulting in mitral valve regurgitation of varying severity.
Ventricular septal defects may occur with extensive anterior and inferior wall
infarction.
Acute free wall rupture is a catastrophic event presenting with severe hypotension.
Right ventricle infarction may lead to decreased compliance and decreased systolic
function thus causing venous congestion and low cardiac output.
In the long term, the left ventricle will undergo a transformation of its size and shape
through a process known as negative remodelling, this adversely affects left
ventricular function and can eventually lead to chronic heart failure.

Additionally, a wide diversity of potentially life-threatening cardiac dysrhythmias may result

from electrical instability due to ischemia, conduction disturbances, and excessive
sympathetic stimulation that occurs during the course of AMI.

Infarct size determines:

left ventricular systolic and/or diastolic function impairment

stroke volume decrease
ventricular filling pressure rise leads to pulmonary congestion and hypotension that
may impair coronary perfusion pressures and exacerbate the myocardial ischaemia
3. 3. Understanding normal coronary artery anatomy
The main arteries of the heart are the:

Left main coronary artery which divides soon after its origin into:
Left anterior descending coronary artery (LAD)
Circumflex coronary artery (LCX)
Right coronary artery (RCA)

 Note

Remember, anatomy of the coronary vessels is highly variable between people

A detailed understanding of coronary anatomy is not necessary, but will significantly

improve the understanding of patients experiencing infarction. It is vital if you are involved
in the care of postoperative CABG (Coronary artery bypass grafting) patients.

 Think
Review the anatomy of the coronary vessels in any textbook and try to relate
anatomy, ECG changes, angiographic findings and clinical presentation when
reviewing any patient. See also table ‘Localisation of infarct using
electrocardiogram’.

 Think
about the Acute Coronary Syndrome in relation to the gender and the aging process
and in special situations (e.g. cocaine abuse and in pregnant women).

3. 4. Cardiogenic Shock
3. 4. 1. Etiology
Acute MI dysfunction due to acute occlusion of one or more coronary arteries with
subsequent LV due to ischaemic myocardium or necrosis is the most common clinical
entity leading to cardiogenic shock. As many as 81% of patients presenting with CS had
an underlying acute coronary syndrome (ACS), although up to 30% of the CS can present
in patients with a smaller infarction and previously chronic HF.

Cardiogenic shock complicates about 7–10% of STEMI and about 2–3% of NSTEMI.
While sometimes present at admission, shock most often does not arise until some hours
later. The median time after STEMI for the occurrence of shock is in the range of 5–6
hours. Shock complicating UA or NSTEMI seems to occur at a later time period, with a
median of 76 and 94 hours, respectively.

 Note
A high index of suspicion and rapid echocardiography are required for diagnosis of
CS.

In general, a loss of > 40% of functional myocardium is required to cause CS. However,
mechanical complications, such as acquired ventricular septal defect (VSD), free wall
rupture (FWR), and papillary muscle rupture or dysfunction, with subse-quent ischaemic
mitral regurgitation (MR), also contribute to CS after AMI 20. The causes of CS have been
described with an incidence of 78.5% for LV failure, 3.9% for VSD, 6.9% for ischaemic
MR, 2.8% for right ventricular (RV) failure, and 1.4% for cardiac tamponade.

In general, the underlying pathophysiology is a profound depression of myocardial

contractility, resulting in a vicious and potentially deleterious spiral of reduced cardiac
output, low blood pressure, further coronary ischaemia, and subsequent reduction in
contractility and cardiac output. This cycle may lead to death, if not interrupted by
adequate treatment. This classic paradigm also includes compensatory, although
pathological, systemic vasoconstriction that occurs in response to a depression of cardiac
function and ineffective stroke volume.

Although ineffective stroke volume is the inciting event, inadequate circulatory

compensation may also contribute to shock.

Extremity and vital organ hypoperfusion is the hallmark of CS. Compensatory

mechanisms by vasoconstriction lead to an intermittent improvement in the coronary and
peripheral perfusion, at the cost of an increased afterload. However, vasoconstriction can
be counterbalanced by systemic inflammation, leading to subsequent pathologic
vasodilatation that occurs frequently with increasing shock duration.

Endothelial and inducible nitric oxide (NO) synthase may play a major role in the
production of high NO levels, along with peroxynitrite, which has a negative inotropic
effect and is cardiotoxic. Other inflammatory mediators such as interleukins and tumor
necrosis factor can also contribute to systemic vasodilation and have been associated
with mortality in CS.

In addition, bleeding and transfusions of stored blood products may also contribute to
inflammation induced by alterations in erythrocyte NO biology.

 Note
Cardiogenic shock may complicate myocardial infarction - remember the vicious
cycle of cardiogenic shock

Challenge
Review the following diagram (Figure 2) and article relating to the pathogenesis of
cardiogenic shock. Work through the diagram to understand the inexorably progressive
nature of cardiogenic shock. Try and relate it to the clinical findings and investigation
abnormalities that one might find.

3. 4. 2. Downward spiral of Cardiogenic Shock

Figure 2: Downward spiral of Cardiogenic Shock.

Esicm Academy 2019

In Chapter References

(van Diepen et al. 2017; Van Herck et al. 2015; Kolte et al. 2014; Thiele et al. 2010; van
Diepen 2018; Crossman 2004; Reynolds and Hochman. 2008; Vahdatpour, Collins and
Goldberg 2019)

 References
van Diepen S, Katz JN, Albert NM, Henry TD, Jacobs AK, Kapur NK, Kilic A,
Menon V, Ohman EM, Sweitzer NK, Thiele H, Washam JB, Cohen MG;
American Heart Association Council on Clinical Cardiology; Council on
Cardiovascular and Stroke Nursing; Council on Qu, Contemporary
Management of Cardiogenic Shock: A Scientific Statement From the American
Heart Association., 2017, PMID:28923988
Van Herck JL, Claeys MJ, De Paep R, Van Herck PL, Vrints CJ, Jorens PG,
Management of cardiogenic shock complicating acute myocardial infarction.,
2015, PMID:25624526
Kolte D, Khera S, Aronow WS, Mujib M, Palaniswamy C, Sule S, Jain D, Gotsis
W, Ahmed A, Frishman WH, Fonarow GC., Trends in incidence, management,
and outcomes of cardiogenic shock complicating ST-elevation myocardial
infarction in the United States., 2014, PMID:24419737
Thiele H, Allam B, Chatellier G, Schuler G, Lafont A., Shock in acute
myocardial infarction: the Cape Horn for trials?, 2010, PMID:20610640
van Diepen S, Norepinephrine as a First-Line Inopressor in Cardiogenic Shock:
Oversimplification or Best Practice?, 2018, PMID:29976292
Crossman DC, The pathophysiology of myocardial ischaemia., 2004,
PMID:15084567
Reynolds HR, Hochman JS., Cardiogenic shock: current concepts and
improving outcomes., 2008, PMID:18250279
Vahdatpour C, Collins D, Goldberg S, Cardiogenic Shock., 2019,
PMID:30947630
4. Recognition, Immediate Measures and Risk Stratification
of the Patient with Acute Myocardial Ischaemia
Diagnosis of ACS is particularly challenging, due to numerous cardiac and noncardiac
potentially life-threatening causes and comorbidities that can mimic it. Every patient with
chest pain should rapidly have a comprehensive evaluation including assessment of
symptoms at presentation, clinical history and examination of the cardiovascular system,
standard 12-lead ECG, and evaluation of serum markers of myocardial injury. When AMI
is diagnosed, risk stratification based on the data obtained during the initial workup is a
next step to predict the risk of adverse events and guide optimal treatment (Figure 3)

Figure 3: Guide optimal treatment. Esicm

Academy 2019.

 Note

ECG is important for the recognition of acute ischaemia. In patients with suspected
ACS it should be acquired and interpreted promptly (i.e. target within 10 min). A
very low threshold should be used to determine whether an ECG is necessary,
since presentations may be atypical.

ACS is often associated with dynamic changes in ECG waveform and serial ECG
acquisition can provide critical information, particularly if the ECG at initial presentation is
not diagnostic.

4. 1. Clinical features of ischaemic chest pain

The diagnosis of suspected myocardial ischaemia is usually made on the basis of clinical
history and ECG. It is important to realize that the clinical presentation can often be
atypical or silent in the intensive care setting.

In text References
(Carroll, Mount and Atkinson 2016; Booker et al. 2003; Guest et al. 1995; Ko et al. 2013)

Initial patient assessment is directed to accurately characterize the patient’s discomfort

and identify its location, duration, aggravating, and relieving factors.
Patients with myocardial ischaemia can present with:

Chest pain or pressure

Syncope
Palpitations
Dyspnoea
Sudden death.
Abdominal pain

Typically the pain of myocardial infarction is:

Severe
Constant
Retrosternal
Spreading across the chest. May radiate to the throat and jaw, down the ulnar aspect
of both arms or to the interscapular area.
Duration > 20 minutes.
Sweating, nausea, pallor, dyspnoea and anxiety often present.

 Note

Focus your history. A high index of suspicion is necessary in the ICU

 Note
Prodromal symptoms of myocardial ischaemia occur in 20–60% of patients in the
days preceding the infarct.

Assessment of clinical symptoms alone is insufficient for risk stratification and severity of
pain does not usually correlate with the extent of infarction

The pain of unstable angina may be similar, although it’s often milder. Features indicating
myocardial ischaemia may include:

Waxing and waning.

Often reproducible upon minimal exertion or with emotion
Often associated with autonomic symptoms.

The pain may sometimes be atypical in terms of location or perception. It may be:
• Epigastric
• Confined to jaw, arms, wrists or interscapular region
• Perceived as burning or as a “pressure”
• Sharp or stabbing in nature (uncommon)
• Reproduced by chest pressure (uncommon) in some patients.
Pain may not be the pre-eminent symptom and in many patients nausea and vomiting,
collapse, dyspnoea and diaphoresis may be more troublesome symptoms.

 Note
Skill is required to elicit warning symptoms in some patients, especially women and
the elderly.

In some patients, myocardial infarction may occur without any symptoms (silent
presentation) and are less likely to receive definitive treatment. For example patients with
diabetes mellitus can have only minimal or no symptoms.

In text References
(Chiariello and Indolfi. 1996)

Failure in the differential diagnosis of myocardial infarction may have life-threatening

consequences:

Aortic dissection
Pulmonary embolism.
Pericarditis

 Note

History taking and physical examination are crucial but... do not delay specific
treatment.

A targeted review for other significant patient’s medical history should aim at identifying
problems including usual medical treatment, cardiovascular risk factors, previous
cardiovascular disease, other conditions affecting the oxygen supply–demand ratio or
acting as ischemia precipitants and those relevant to thrombolysis, anticoagulation and
angiography.

It will help you appreciate the importance of obtaining a time efficient but accurate history
if you prepare your own checklist with the items prioritised. In the next ten patients with
chest pain you see and determine how relevant and useful your list proves to be.
Especially develop skills in determining features of acute coronary syndromes.

 Note
Recognition of the variable symptoms of acute coronary syndrome is crucial.
However, symptoms alone are not sufficiently specific to allow accurate risk
stratification and treatment selection for patients with ACS. Special test are
required.

 Note
Develop skills to get a good history of acute and chronic cardiac disease
In text References
(Boon. 2019)

 References
Carroll I, Mount T, Atkinson D, Myocardial infarction in intensive care units: A
systematic review of diagnosis and treatment., 2016, PMID:28979516
Booker KJ, Holm K, Drew BJ, Lanuza DM, Hicks FD, Carrigan T, Wright M,
Moran J., Frequency and outcomes of transient myocardial ischemia in
critically ill adults admitted for noncardiac conditions., 2003, PMID:14619356
Guest TM, Ramanathan AV, Tuteur PG, Schechtman KB, Ladenson JH, Jaffe
AS., Myocardial injury in critically ill patients. A frequently unrecognized
complication., 1995, PMID:7783306
Ko Y, Park C, Kim W, Jeong B, Suh G, Lim S, Kwon J, Jeon K, Coronary artery
disease in patients clinically diagnosed with myocardial infarction in the
medical intensive care unit, 2013,
https://www.sciencedirect.com/science/article/abs/pii/S0883944113000063
Chiariello M, Indolfi C., Silent myocardial ischemia in patients with diabetes
mellitus., 1996, PMID:8925575
Boon N., Cardiovascular and physical examination., 2019,
ISBN:9780198784906

4. 2. Triage and early risk stratification

The clinical presentation of myocardial ischaemia is most often acute chest discomfort. It
is essential that initial assessment and management are rapid but methodical according to
the institutional protocols for triaging and managing patients who present with symptoms
suggestive of myocardial ischaemia.

Initial examination should include assessment of hemodynamic and respiratory status and
a screening neurologic evaluation.

Heart rate, arterial blood pressure, auscultation of the lung and peripheral pulses
palpation are essential parts of physical examination.

Patients with severe infarction and extensive myocardial injury often show signs of
autonomic activation (pallor, sweating, agitation) as well as heart failure symptoms and
even cardiogenic shock may be apparent and are associated with particular poor
outcome.

Right ventricular infarction results in hypotension and marked elevation of the jugular
venous pressure.
Early risk stratification of acute and persistent chest pain suggestive of myocardial
ischaemia is based on simple criteria:

History, clinical symptoms and signs

ECG
Biochemical markers (serial)

 Note

Other investigations (e.g. echocardiography) are required in certain situations.

Early triage thus allows some patients to be diagnosed as having:

STEMI
NSTEMI
Non-coronary chest pain (including potential life-threatening conditions such as aortic
dissection, pulmonary embolism, and oesophageal rupture) or
Stable angina suitable for outpatient management

See Risk scoring systems  for further details

 Note
Identify patients with non-cardiac chest pain and with stable angina.

4. 3. Immediate management of ACS

If acute coronary syndrome (ACS) is the leading suspected differential diagnosis,
immediate and rapid clinical evaluation of a patient complaining of chest pain, includes
non-invasive blood pressure measurement, pulse oximetry and continuous ECG
monitoring.

Delay in initiating therapy is associated with worsening outcome. Immediate treatment

and management is critical and include:

12-lead ECG within 10 minutes after first medical contact (Table 3). The ECG should
be repeated at 15 to 30-minute intervals if the initial study is not diagnostic but the
patient remains symptomatic and high clinical suspicion for ACS persists.
ECG, arterial pressure and SpO2 continuous monitoring.
Oxygen should be administered via facemask or nasal cannula when blood oxygen
saturation is < 90% or if the patient is in respiratory distress.
 Venous access (reserve right arm for radial access during the ICP). Blood is drawn
for cardiac biomarkers (high sensitive cardiac troponin if available), biochemical and
haematological work-up including indices of coagulation and renal function,
Intravenous nitrates must be considered (intravenous are more effective than
sublingual nitrates), their dose should be titrated upwards until symptoms are
relieved. Beyond symptom control, there is no indication for nitrate treatment.
Sublingual nitroglycerin should be administered at a dose of 0.4mg every five minutes
for a total of three doses, after which an assessment of blood pressure and pain relief
should guide the need for a more effective intravenous nitroglycerin (intravenous are
more effective than sublingual nitrates). Doses should be titrated upwards until
symptoms are relieved. Once the symptoms are controlled nitrates are removed. Side
effects include hypotensive reactions and a hypotensive bradycardic response
(Bezold-Jarisch Reflex). All patients should be questioned about the use of
phosphodiesterase-5 inhibitors. Nitrates are contraindicated if these drugs have been
used in the previous 24-48 hours because of the propensity to cause potentially
severe hypotension. Extreme care should also be taken before giving nitrates in the
setting of an inferior myocardial infarction with possible involvement of the right
ventricle. In these setting nitrates can cause severe hypotension.
Analgesia if nitroglycerin and lessening of anxiety are not sufficient. Consider
intravenous morphine (2-4 mg). Repeat doses with increments of 2 to 8 mg, at 5 to 15
minute intervals may be given for pain relief.
Aspirin 160 - 325 mg should be chewed and swallowed on arrival, followed by a daily
oral dose of ≤100 mg. In the ISIS-2 study this reduced mortality by 23% compared
with placebo.
A platelet P2Y12 receptor blocker (Clopidogrel, Ticagrelor or Prasugrel) is indicated in
patients with AMI (STEMI and NSTEMI) depending on the estimated risk and
therapeutic strategy chosen.
Beta-adrenergic blockers should be used in patients without evidence of heart failure
or hypotension/cardiogenic shock in the first 24 hours. According to the
COMMIT/CCS2 trial, the largest placebo-controlled trial ever performed with beta
blockers in acute MI, it seems reasonable to defer intravenous beta blockers in
patients who are hemodynamically compromised in whom mortality may actually be
increased by such therapy. Once the patient is stable, an oral beta-blocker can be
started with gradual up titration to the maintenance doses.
Pulmonary oedema, if present, is treated with upright posture, intravenous
furosemide, intravenous nitroglycerin and CPAP or non-invansive ventilation.

 Note

Decisions can usually be made with readily available clinical data

In patients with ST-segment elevation or evidence of new (or presumed new) left or right
bundle branch block (LBBB o RBBB) a decision about how to reopen the occluded
coronary artery should be made expeditiously.

In text References
(No authors 1988; Valgimigli et al. 2018; Mateos et al. 2015)

 Note
Decisions can usually be made with readily available clinical data

In patients with ST-segment elevation or non-interpretable ST-segments on the ECG such

as those with evidence of new (or presumed new) left bundle branch block (LBBB) or
ventricular pacing, a decision about how to reopen the occluded coronary artery should be
made expeditiously, preferably through a primary PCI strategy.

 Note
Rapidly evolving area of medicine

Reperfusion therapy is indicated in all patients with symptoms of ischaemia of ≤ 12 h

duration and persistent ST-segment elevation. A primary PCI strategy is recommended
over fibrinolysis within indicated timeframes.

If timely primary PCI cannot be performed after STEMI diagnosis, fibrinolytic therapy is
recommended within 12 h of symptom onset in patients without contraindications (Table 3)

In the absence of ST-segment elevation, a primary PCI strategy is indicated in patients

with suspected ongoing ischaemic symptoms suggestive of MI and at least one of the
following criteria present:

Haemodynamic instability or cardiogenic shock

Recurrent or ongoing chest pain refractory to medical treatment
Life-threatening arrhythmias or cardiac arrest
Mechanical complications of MI
Acute heart failure
Recurrent dynamic ST-segment or T- wave changes, particularly with intermittent ST-
segment elevation.

In patients with time from symptom onset >12 h, a primary PCI strategy is indicated in the
presence of ongoing symptoms suggestive of ischaemia, haemodynamic instability, or life-
threatening arrhythmias.

Table 3: Summary of important time targets in acute STEMI. From Ibanez et al., 2018
 Time
Intervals
targets
Maximum time from FMC to ECG and diagnosis ≤10 min
Maximum expected delay from STEMI diagnosis to primary PCI (wire
crossing) to choose primary PCI strategy over fibrinolysis (if this target ≤120 min
time cannot be met, consider fibrinolysis)
Maximum time from STEMI diagnosis to wire crossing in patients
≤ 60 min
presenting at a primary PCI hospitals
Maximum time from STEMI diagnosis to wire crossing in transferred
≤ 90 min
patients
Maximum time from STEMI diagnosis to bolus or infusion start of
≤10 min
fibrinolysis in patients unable to meet primary PCI target times
Time delay from start of fibrinolysis to evaluation of its efficacy (success
60 – 90 min
or failure)
Time delay from start of fibrinolysis to angiography (if fibrinolysis is
2 – 24 h
successful)

Abbreviations:

ECG= electrocardiogram
FMC= first medical contact
PCI = percutaneous coronary intervention
STEMI = ST-segment elevation myocardial infarction.

 Note

Risk profiling in acute myocardial infarction

High risk can be defined by clinical features (presentation in congestive heart failure),
haemodynamic criteria (SBP <100 mmHg, HR >100 bpm), size of infarction (anterior ST
elevation >2 mm in two or more contiguous leads), RV involvement, or LV dysfunction (EF
<35%).

In text References

(Ibanez et al. 2018; Andersen et al. 2003; Keeley, Boura and Grines. 2003; O'Gara et al.
2013)

 References
No authors listed, Randomised trial of intravenous streptokinase, oral aspirin,
both, or neither among 17,187 cases of suspected acute myocardial infarction:
ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative
Group., 1988, PMID:2899772
Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Jüni P,
Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M,
Steg PG, Windecker S, Zamorano JL, Levine GN; ESC Scientific Document
Group; ESC Committee for Practice, 2017 ESC focused update on dual
antiplatelet therapy in coronary artery disease developed in collaboration with
EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease
of the European Society of Cardiology (ESC) and of the European , 2018,
PMID:28886622
Mateos A, García-Lunar I, García-Ruiz JM, Pizarro G, Fernández-Jiménez R,
Huertas P, García-Álvarez A, Fernández-Friera L, Bravo J, Flores-Arias J,
Barreiro MV, Chayán-Zas L, Corral E, Fuster V, Sánchez-Brunete V, Ibáñez B,
METOCARD-CNIC Investigators., Efficacy and safety of out-of-hospital
intravenous metoprolol administration in anterior ST-segment elevation acute
myocardial infarction: insights from the METOCARD-CNIC trial., 2015,
PMID:25129820
Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H,
Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A,
Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P,
Widimský P; ESC Scientific Document Gr, 2017 ESC Guidelines for the
management of acute myocardial infarction in patients presenting with ST-
segment elevation: The Task Force for the management of acute myocardial
infarction in patients presenting with ST-segment elevation of the European
Socie, 2018, PMID:28886621
Andersen HR, Nielsen TT, Rasmussen K, Thuesen L, Kelbaek H, Thayssen P,
Abildgaard U, Pedersen F, Madsen JK, Grande P, Villadsen AB, Krusell LR,
Haghfelt T, Lomholt P, Husted SE, Vigholt E, Kjaergard HK, Mortensen LS;
DANAMI-2 Investigators., A comparison of coronary angioplasty with fibrinolytic
therapy in acute myocardial infarction., 2003, PMID:12930925
Keeley EC, Boura JA, Grines CL., Primary angioplasty versus intravenous
thrombolytic therapy for acute myocardial infarction: a quantitative review of 23
randomised trials., 2003, PMID:12517460
O'Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA,
Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM,
Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-
Holland JE, Tommaso CL, Tracy CM, Woo YJ,, 2013 ACCF/AHA guideline for
the management of ST-elevation myocardial infarction: a report of the
American College of Cardiology Foundation/American Heart Association Task
Force on Practice Guidelines., 2013, PMID:23247304
4. 4. On going physical examination
A more detailed physical examination is undertaken but should not delay immediate
treatment. It is often insensitive and non-specific but is aimed at:

Diagnosing specific complications.

Excluding alternative diagnoses, both cardiovascular (e.g. pericarditis, aortic
dissection) as well as non-cardiac (pulmonary embolism, pleuro-pneumonia, gastric
ulcer, pancreatitis, cholecystitis).

Distended jugular veins signal right ventricular diastolic pressure elevation, and the
appearance of pulmonary crackles (in the abscense of pulmonary disease) indicate left
ventricular filling pressures. See the ESICM module on heart failure  for further
information.

A systolic bulge occasionally can be palpated on the precordium in the area of the apex of
the heart, representing contact of an ischaemic dyskinetic segment of the left ventricle
with the chest wall. Auscultation of the precordium during an ischaemic episode may
reveal the presence of a fourth heart sound (indicative of a non-compliant left ventricle).

 Note
Patients should be examined to exclude shock and left ventricular failure

Left ventricular failure is associated with higher mortality and is suggested by the
presence of pulmonary crackles, tachypnoea, tachycardia, and a S3 gallop. A third heart
sound (S3) usually indicates a large infarction with extensive muscle damage.

A systolic murmur of mitral regurgitation may be present and result from a papillary
muscle dysfunction or left ventricle dilatation. A pansystolic murmur may also be due to an
acute ventricular septal defect due to septal rupture.

Physical examination is also important to exclude alternative diagnoses and to suggest

further investigations. A friction rub may indicate the presence of pericarditis. Unequal arm
pressures should raise the suspicion of aortic dissection. Cardiac tamponade may present
with a low cardiac output state and elevated neck vein pulsations, which move
paradoxically during respiratory cycle. Hypoxaemia, hypotension and a clear lung
examination should raise the suspicion of pulmonary embolism.

 Note
 Patients should have targeted examination to exclude other relevant medical
(especially respiratory and neurological) problems

 Note
Cardiogenic shock presents as hypotension, oliguria and features of low cardiac
output and is associated with a particularly poor outcome.

Cardiogenic shock may occasionally be present with evidence of hypoperfusion but

without hypotension. Cardiogenic shock may not develop until hours after the onset of
symptoms and regular examination is therefore required.

In text References
(Goldberg et al. 2009; Jeger et al. 2007)


What are the clinical features of right ventricular infarction and why is
it important to make this diagnosis?

COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER

 With right ventricular infarction, there may be marked elevation of the

jugular venous pressure (JVP), usually with clear lungs and low or normal
wedge pressure. Recognition of RV infarction is important because
decreasing filling pressures in this setting may precipitate hypotension and,
conversely, hypotension may respond to judicious fluid administration.

In text References

(Pöss et al. 2017; Albulushi et al. 2018)

 References
Goldberg RJ, Spencer FA, Gore JM, Lessard D, Yarzebski J., Thirty-year
trends (1975 to 2005) in the magnitude of, management of, and hospital death
rates associated with cardiogenic shock in patients with acute myocardial
infarction: a population-based perspective., 2009, PMID:19237658
Jeger RV, Lowe AM, Buller CE, Pfisterer ME, Dzavik V, Webb JG, Hochman
JS, Jorde UP; SHOCK Investigators., Hemodynamic parameters are
prognostically important in cardiogenic shock but similar following early
 revascularization or initial medical stabilization: a report from the SHOCK Trial.,
2007, PMID:17951622
Pöss J, Köster J, Fuernau G, Eitel I, de Waha S, Ouarrak T, Lassus J, Harjola
VP, Zeymer U, Thiele H, Desch S, Risk Stratification for Patients in Cardiogenic
Shock After Acute Myocardial Infarction., 2017, PMID:28408020
Albulushi A, Giannopoulos A, Kafkas N, Dragasis S, Pavlides G, Chatzizisis
YS, Acute right ventricular myocardial infarction., 2018, PMID:29902098

4. 5. Investigations
4. 5. 1. Electrocardiography
The ECG 12 standard leads is considered the initial single most important test for
diagnosing and guiding the emergency treatment of MI, and should be acquired and
interpreted promptly (i.e. target within 10 min) after first medical contact.

Pre-hospital ECGs reduce the time to diagnosis and treatment, and can facilitate a
strategy for immediate reperfusion therapy. When coupled with communication of STEMI
diagnosis and preferential transport to a PCI-capable hospital, has been shown to result in
rapid reperfusion times and excellent clinical outcomes.

Initial ECGs may reveal significant ST-segment elevation (STEACS) or that lack
significant ST-segment elevation (NSTEACS). In addition serial ECGs may give
information about localization, size and guide possible therapies.

Acute myocardial ischaemia is often associated with dynamic changes in ECG waveform
and serial ECG acquisition can provide critical information,

Acute and complete occlusion of a coronary artery usually leads to serial EGC changes in
leads subtending the area of ischaemia, where the number of leads involved broadly
reflects the extent of myocardium involved, the height of initial ST segment changes is
correlated with the degree of ischaemia and acute resolution of STEACS correlates well
with reperfusion acute and early changes where STEACS is present identifies patients in
whom reperfusion therapy may interrupt, prevent or minimise myocardial necrosis.

You can review the use of the electrocardiogram and ECG interpretation in the following
references.

In text References
(Zimetbaum and Josephson. 2003)

4. 5. 1. 1. ECG changes of AMI

ECG changes of AMI often evolve in a characteristic pattern. Acute and complete
occlusion of a coronary artery usually leads to serial ECG changes in leads subtending
the area of ischaemia. All clinicians should recognise these changes and their variations
(Figure 4)

Hyperacute (0-20 minutes) tall, peaking T-waves and progressive upward coving and
elevation of ST-segments. Increased hyperacute T wave amplitude, with prominent
symmetrical T waves in at least two contiguous or more anatomically leads, is an early
sign that may precede the elevation of the ST-segment.

Acute (minutes to hours) persisting STE, gradual loss of R-wave in the infarcted area ST-
segments begin to fall and there is progressive inversion of T-waves

Early (hours to days) loss of R-wave and development of pathological Q-waves in area of
ischaemia. Return of ST-segments to baseline. Persistence of T-wave inversion

Indeterminate (days to weeks) pathological Q-waves with persisting T-wave inversion.

ST-segments normalise (unless there is aneurysm)

Old (weeks to months) persisting pathological Q-waves with normalised ST-segments and
T-waves.

Figure 4: ECG changes of AMI. Esicm Academy

2019.

Changes above are 'stereotyped'. ECG changes in clinical practice are highly variable in
their occurrence and combinations. Patients may progress more rapidly through these
stages. Successful revascularisation may interrupt these changes and prevent or
minimise myocardial necrosis.

 Note
If the ECG is equivocal or does not show evidence to support the clinical suspicion
of MI, ECGs should be repeated and, when possible compared with previous
recordings.

 Note
It is vital that clinicians identify acute changes and ST-segment elevation so that
early reperfusion strategies can be initiated.

4. 5. 1. 2. Pattern of ECG changes

The pattern of ECG changes may give a guide to the area and extent of infarction. The
number of leads involved broadly reflects the extent of myocardial injury.

Acute myocardial ischaemia is often associated with dynamic changes in ECG waveform
and serial ECG acquisition can provide critical information, particularly if the ECG at initial
presentation is non-diagnostic. If this is the case, the 12 lead ECG with fixed electrodes
should be repeated (eg, at 15- to 30-minute intervals during the first hour), especially if
symptoms recur.

Continuous computer-assisted with 12-lead ECG monitoring (if available) to detect

dynamic ECG changes may be a reasonable alternative in patients whose initial ECG is
nondiagnostic or with persistent or recurrent symptoms and who are at risk of ACS. Serial
or continuous ECG recordings may be helpful in determining reperfusion or re-occlusion
status. Reperfusion is usually associated with a large and prompt reduction in ST-
segment elevation.

A normal ECG may also be associated with left circumflex or right coronary artery
occlusions, which can be electrically silent or be associated with ST segment depressions
in the anterior leads (in which case posterior electrocardiographic leads V7 to V9 and
right-sided leads (V3R to V4R) may be helpful (Table 4)

 Note
Some patients with an acute coronary occlusion may have an initial ECG without
ST-segment elevation, and be denied for urgent reperfusion therapy, resulting in a
larger infarction and worse outcomes.

Table 4: ECG monitoring recommendations for the initial diagnosis

12-lead ECG recording and interpretation is indicated as soon as

possible at the point of First Medical Contact, with a maximum target
delay of 10 min.
ECG monitoring with defibrillator capacity is indicated as soon as
possible in all patients with suspected STEMI
The use of additional posterior chest wall leads (V7–V9) in patients
with high suspicion of posterior MI (circumflex occlusion) and anterior
ST segment depression should be considered.
The use of additional right precordial leads (V3R and V4R) in
patients with inferior MI should be considered to identify concomitant
RV infarction.

Review this ECG from the Arrhythmia module. What changes are
present and what is their relevance? (Figure 5)

Figure 5:

COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER


The first ECG displays inferior infarction of recent onset. There is no
evidence of posterior extension. The Arrhythmia module states this case
illustrates an acute inferior wall myocardial infarction with an ST score (the
total amount, in millimetres, of ST elevation in the inferior leads II, III, aVF)
of more than 7 mm, indicating an extensive myocardial infarction. The
additional recording of lead V4R would have been of help in identifying the
presence of right ventricular myocardial infarction. If this were a clinical
concern, echocardiography would be useful diagnostically and would also
likely assist in ongoing management. Right ventricular involvement, as
diagnosed by V4R, does suggest proximal or RCA (Right coronary artery)
occlusion but the real reason to record V4R is not so much to determine
where the RCA is occluded but rather to get a sense of whether there is
RV infarction, with its distinctive physiology.

Review of all leads may thus suggest the coronary territory involved, the presence of right
ventricular myocardial infarction and risk of developing AV nodal block. The latter was
already present in this patient – indicating the proximal location of the obstruction in the
right coronary artery, leading to a large inferior wall infarction with right ventricular
involvement. When high-degree AV nodal block occurs in acute myocardial infarction, the
in-hospital mortality rate is two and one-half times that of inferior myocardial infarction
without high-degree AV block. This patient should be referred for primary percutaneous
coronary intervention.

Review this ECG from the Arrhythmia module. What changes are
present and what is their relevance? (Figure 6)

Figure 6:

COMPLETE TASK THEN CLICK TO REVEAL THE ANSWER


The second ECG displays LBBB complicating anterior myocardial
infarction. New or presumed new LBBB is an indication for reperfusion
therapy. Lack of a previous ECG should not be a reason to withhold such
therapy when the clinical setting suggests myocardial infarction.

Where there is uncertainty, echocardiography may confirm a regional wall motion

abnormality. Angiography can also be diagnostic and may allow for definitive
revascularisation (which may be superior to thrombolysis in this setting). The Arrhythmia
module states this case illustrates an acute anterior myocardial infarction complicated by
a left bundle branch block. The development of bundle branch block during the acute
phase of myocardial infarction indicates extensive anterior wall infarction, and early death
may occur because of pump failure and ventricular tachycardia or fibrillation. The finding
of a bundle branch block as a complication of anterior wall infarction calls for aggressive
treatment. This patient should be referred for primary percutaneous coronary intervention
(PCI). Development of second or third degree heart block in association with bundle
branch block during anterior MI necessitates temporary pacing.

In text References
(Sgarbossa, Birnbaum and Parrillo. 2001; Smith et al. 2012)

Electrocardiographic manifestations suggestive of acute myocardial ischaemia include (in

the absence of left ventricular hypertrophy and bundle branch block):
 ST-elevation: New ST-elevation at the J-point in two or more anatomically contiguous
leads with the cut-point ≥ 1 mm (1 mm = 0.1 mV) in all leads other than leads V2–V3
where the following cut-points apply: ≥ 2mm in men > 40 years; ≥ 2.5 mm in men ≤ 40
years, or ≥ 1.5 mm in women regardless of age.
Patients with ACS but without significant ST-segment elevation probably have active,
non-occluding thrombus. ECGs in these patients may be normal or display ST-
segment depression, T-wave inversion or normalisation of previous inverted waves.
Patients who present with ischaemic chest pain and a non-diagnostic initial ECG
supplemental leads, as well as serial ECG recordings, should be deployed with a very
low threshold. Recording of V7, V8 and V9 leads is strongly recommended in patients
with high clinical suspicion of acute circumflex occlusion (e.g. initial ECG non-
diagnostic or ST-segment depression in leads V1–V3 may be suggestive of
inferobasal myocardial ischaemia (previously termed posterior infarction))
Patients with inferior and suspected right ventricular infarction, leads aVR or V1 may
exhibit ST-segment elevation ≥ 1 mm. The early recording of right precordial leads
V3R and V4R should be performed
The presence of ST depression ≥ 1 mm in eight or more surface leads (inferolateral
ST depression), coupled with ST-segment elevation in aVR and/or V1, suggests
multivessel ischemia or left main coronary artery obstruction, particularly if the patient
presents with haemodynamic compromise.

 Note
Remember, anatomy of the coronary vessels is highly variable between people

Patients with clinical suspicion of ongoing myocardial ischaemia and left bundle branch
block (LBBB) should be managed in a way similar to STEMI patients, regardless of
whether the LBBB is previously known (Table 5)

Patients with new right bundle branch block (RBBB) have a poor prognosis. Therefore, a
primary PCI strategy (emergent coronary angiography and PCI if indicated) should be
considered when persistent ischaemic symptoms occur in the presence of RBBB.

In text References
(Wang et al. 2018)

Other ECG signs associated with acute myocardial ischaemia include cardiac
arrhythmias, intraventricular bundle branch blocks, atrioventricular conduction delays and
loss of precordial R wave amplitude (Table 5).

Table 5: Atypical ECG signs that should prompt PCI strategy in patients
with ongoing symptoms consistent with myocardial ischemia
 Bundle branch block
Criteria used to improve the diagnostic accuracy of STEMI in LBBB
Concordant ST-segment elevation ≥ 1 mm in leads with a
positive complex
Concordant ST-segment depression ≥ 1 mm inV1-V3
Discordant ST-segment elevation ≥ 5 mm in leads with a
negative QRS complex

The presence of RBBB may confound the diagnosis of STEM

Ventricular pacing rhythm
During RV pacing, the ECG also show LBBB and the above rules
also apply for the diagnosis of myocardial infarction during pacing;
however, they are less specific
Isolated posterior myocardial infarction
Isolated ST depression ≥ 0.5 mm in leads V1-V3 and ST-segment
elevation (≥ 0.5 mm) in posterior chest Wall leads V7-V9
Ischaemia due to left main coronary artery occlusion or
multivessel disease
ST depression ≥ 1 mm in eight or more surface leads, coupled with
ST-segment elevation in aVR and/or V1, suggest left main or left
main equivalent-coronary obstruction, or severe three vessel
ischemia

4. 5. 1. 3. Localisation of infarct using electrocardiogram

It is usual to use the ECG in initial clinical assessments to localise the area of myocardial
ischaemia. The pattern of lead involvement may assist with localisation of the MI (Table
6). There is a reasonable correlation between the site of infarction as defined by the ECG,
the occluded coronary artery, and the infarcted region of myocardium according to
coronary anatomy.

Table 6: Infarct localisation and ECG

Area of ECG
Infarct-related artery
infarction leads
RCA (right coronary artery) or
Inferior II, III, AVF
posterolateral branch of Cx
Anterior V2, V3, V4 LAD or diagonal branch of LAD
I, aVL, V5,
Lateral Cx
V6
 Posterolateral branch of Cx or
Tall R wave
True posterior Posterior Descending Branch of
in V1
RCA
Septal V1-V3 LAD or diagoinal branch of LAD
Anterolateral I, aVL, V2-V6 Proximal LAD
II, III, aVF, I, Proximal Cx or large RCA in right
Inferolateral
aVL, V5, V6 dominant system
Right ventricular V3R, V4R RCA

Abbreviations:

RCA= Right Coronary Artery

LAD= Left Anterior Descending Coronary Artery
Cx= Circumflex Coronary Artery
LV= Lateral Ventricular Artery

In text References
(Zimetbaum and Josephson. 2003; Sanaani et al. 2017)

You will find examples of ECGs on the following websites.

ECG Wave-Maven 
ECG Library 
ECG Learning Center 
Life in the Fast Lane 

 Note
Clinicians should be aware of conditions in which the ECG may mimic ischaemia so
that inappropriate therapy is not given.

 Note
ECGs should always be interpreted in clinical context

The ECG by itself is often insufficient to diagnose acute myocardial ischaemia or

infarction, since ST deviation may be observed in other conditions, such as:

Pericarditis
Left ventricular hypertrophy
Left ventricular aneurysm (persisting ST-segment elevation following older infarction)
Brugada Syndrome (ST-segment elevation in V1-V3 + RBBB)
Pulmonary embolism (ST-segment elevation V1- V3)
 Wolff–Parkinson–White Syndrome
Conduction defects
Metabolic disturbance
Drug toxicity
Normal variant
Subarachnoid haemorrhage
Apical ballooning syndrome (Takotsubo syndrome)

In text References
(Wang, Asinger and Marriott. 2003; Karve, Bossone and Mehta. 2007; Pollak and Brady
2012)

Apical ballooning syndrome (Takotsubo or ‘broken-heart syndrome’) is characterised by

precordial ST-segment elevation, apical ballooning on echocardiography with sparing of
basal segments, but normal vessels on angiography. It may follow the onset of recent
severe mental or physical stress and may cause up to 1–2% of STEMI. It has been
particularly associated with post-menopausal females and failure to recognise it may lead
to inappropriate therapy. Angiography is needed for definitive diagnosis (normal vessels
with absence of thrombus) although echocardiography has highly suggestive features. It
is being increasingly recognised in the setting of acute severe illness in intensive care.

In text References
(Tsuchihashi et al. 2001; Prasad 2007; Templin et al. 2015)

4. 5. 2. Biochemical markers
When myocardial injury occurs a variety of biochemical compounds are released into the
blood (Figure 7)

The cardiac troponin (cTN) complex has three isoforms, two (cTnT and cTnI) of which are
exclusiely expressed (highly specific for cTnI) in cardiac myocytes. Acute myocardial
injury produces an initial release of troponin within the cell cytosol. Diffusion of this
cytosolic troponin allows detection in blood samples approximately 4-6 hours post injury
with a peak usually at 12-24 hours. In acute injury there is a gradual return to normal
within 7-14 days. This long tail on levels is key to the diagnosis of patients who present
late.

Increase of the enzyme creatine kinase (CK) and its dimeric isoform CK-MB are less
sensitive and less specific, but trace amounts are generally present in blood and, as these
enzymes are also present in other tissues (muscle and brain subunits), their rising values
may reflect other conditions such as trauma or surgery. After an AMI, CK and CK-MB start
increasing within 4 to 6 hours, peak within 18 to 24 hours, and remain elevated for 48 to
72 hours.
 Figure 7: Biochemical compounds released when
myocardial injury occurs. Esicm Academy 2019.

The cTnI and cTnT are the preferred biomarkers for the evaluation of myocardial injury,
and high-sensitivity (hs)-cTn assays recently introduced in routine practice are
recommended for routine clinical use over conventional non-hs-cTn assays and are the
gold standard for the confirmation of myocardial necrosis

If a cTn assay is not available, the best alternative is CK-MB measured by a mass assay.

Myocardial injury is defined as being present when blood levels of cTn are increased
above the 99th percentile upper reference limit (URL). The injury may be acute, as
evidenced by a newly detected dynamic rising and/or falling pattern of cTn values above
the 99th percentile URL, or chronic, in the setting of persistently elevated cTn levels.
Although elevated cTn values reflect injury to myocardial cells, they do not indicate the
underlying pathophysiological mechanisms.

However, regardless of the mechanism, acute myocardial injury, when associated with a
rising and/or falling pattern of cTn values with at least one value above the 99th percentile
URL and caused by sudden myocardial ischaemia, is designated as an acute MI.

The demonstration of a rising and/or falling pattern is needed to distinguish acute injury
from chronic conditions associated with structural heart disease that can have chronic
increases of cTn values. To establish the diagnosis of an acute MI, a rise and/or fall in cTn
values with at least one value above the 99th percentile URL is essential and required,
coupled with a high clinical and/or ECG likelihood of myocardial ischaemia and to
establish early the diagnosis of acute MI.

Blood samples for the measurement of cTn should be drawn on first assessment
(designated as 0h) and repeated 3 – 6 h later, or earlier with hs-cTn assays. The hs-cTn
assays shorten the time to diagnosis in many patients to within 1 - 3 h of onset of
symptoms, but some may rule in late (6 h)

 Note
biomarkers should be evaluated in relation to the time of onset of the symptoms
Some patients with acute myocardial injury presenting late after the onset of acute MI (>
12 – 18 h) and who are on the downslope of the time-concentration curve may require
longer periods of time for a changing pattern to be detected. Therefore, the absence of
significant changes in a serial determination of cTn does not rule out acute myocardial
injury if the clinical context is compatible.

Patients with symptoms suggestive of unstable angina may have increased hs-cTn values
as a result of coexistent structural heart disease. The triage of these patients can only be
accomplished based on clinical evaluation.

With the implementation of cTn and hs-cTn assays, the frequency of unstable angina will
decrease and the diagnosis of NSTEMI will increase. The magnitude of these changes
using hs-cTn assays has been reported in the range of 18 – 30%.

There is a strong correlation between troponin level, intracoronary thrombus and amount
of threatened or ischaemic myocardium and is a strong predictor of risk.

 Note
Other causes of myocardial injury can elevate troponin

Myocardial ischaemic or non-ischaemic conditions associated with increased cTn do not

differentiate the cause of the myocardial injury, thus clinical context must always be
considered. An increased cTn value above the 99th percentile URL, with or without a
dynamic change of values, or in the absence of clinical evidence of ischaemia, should
prompt a search for other diagnoses associated with myocardial injury:

Congestive heart failure

Coronary vasospam
Cardiac Trauma
Miocarditis/pericarditis
Pulmonary embolism
Postcardiac surgery
Cardioversion
Cardiopulmonary resuscitation
Sepsis and criticially ill patients
End stage renal disease
Arrythmias
Stroke
Epileptic seizures

Elevation can be caused by different clinical situations that can coexist in a single patient
and triage can only be accomplished based on the context of a complete clinical
evaluation.
  Note
Elevated of biomarkers levels should be taken as evidence of myocardial injury
and, only in the correct setting, as confirmation of MI

Elevated troponin levels are also common in ICU populations. Although initially
considered as ‘false positives’, many of these are now thought to be reflective of disease
processes which secondarily involve the myocardium or induce a supply–demand
mismatch e.g. vasoconstrictor use, overwhelming bacterial sepsis, multiple organ failure,
renal failure and cerebrovascular catastrophes.

 Think
of the mechanism of elevation of troponin following thrombus formation upon
unstable plaque and in ICU populations. Why might causes of elevation, prognostic
value and treatments be different in different patient populations? Think about the
population from which the evidence base for your treatment plan was derived, the
degree to which that evidence base applies in a given case, and the risks and
benefits for your individual patient.

In text References
(Twerenbold et al. 2017; Thygesen et al. 2012; Jarolim. 2015; Fromm RE 2007; McLean,
Huang and Salter 2008; Thygesen et al. 2008)

4. 5. 3. Imaging Techniques
Non-invasive imaging plays many important roles in patients with known or suspected MI.
The underlying rationale is that regional myocardial hypoperfusion and ischaemia lead to
a cascade of events including myocardial dysfunction, cell death, and healing by fibrosis

The role of noninvasive imaging is centered on the diagnosis and characterization of

myocardial injury in MI.

Imaging techniques can be useful in the diagnosis of acute MI because of the ability to
detect wall motion abnormalities or loss of viable myocardium in the presence of elevated
cardiac biomarker values.

If biomarkers have been measured at appropriate times and are normal, this excludes
acute MI and takes precedence over the imaging criteria.

Normal function practically excludes significant MI, but a small MI cannot be ruled out.

Commonly used imaging techniques in acute and prior MI are echocardiography, MPS
using SPECT or PET, CMR, and computed tomography (CT).

4. 5. 3. 1. Echocardiography
The strength of echocardiography is the combined assessment of cardiac structure and
function, in particular myocardial thickness, thickening/thinning, and motion. Regional wall
motion abnormalities (RWMA) are seen almost immediately after onset when > 20%
transmural myocardial thickness is affected. It also allows detection of non-coronary
cardiac pathologies known to cause chest pain, e.g. acute pericarditis, severe aortic
stenosis, and hypertrophic cardiomyopathy among others

The technique is useful in diagnosing mechanical complications in patients with AMI and
haemodynamic compromise (shock) or other potentially fatal entities such as acute aortic
dissection or massive pulmonary embolism where the clinical presentation might be
similar to that seen with AMI.
The easy availability and versatility of transthoracic echocardiography make this imaging
modality the technique of choice at bedside for the evaluation of patients with suspected
MI

Two-dimensional transthoracic echocardiograhy with colour Doppler has good clinical

utility as a non invasive investigation during admission for an ACS. Its primary role is in
assessing the degree of regional and global ventricular function.

Regional function analysis includes evaluation of both wall thickening and wall motion
toward the left ventricular center. Myocardial segments with abnormal contractility
coexisting with areas of normal contractile myocardium are highly suggestive of ischemic
heart disease. On the other hand, areas of thinned and akinetic myocardium and a dilated
LV suggest scarred or chronically hypoperfused myocardium.

Detects RWMAs, which can help confirm or exclude the diagnosis of MI in the small
percentage of cases where diagnosis is uncertain (e.g. late presentation, left bundle
branch block) although clinical context is required to determine the timing of infarction.
RWMA and loss of wall thickening with contraction are often present in these cases if due
to ischaemia, whereas their absence suggests that ischaemia is not acute.or is not
significant.

Echocardiography provides a bedside assesment of right and left (RV and LV function and
infarct size, and can also confirm right ventricular infarction. It is particularly useful in the
diagnosis of complications of MI, including acute mitral regurgitation, myocardial rupture,
including ventricular septal defect, pericardial effusion and infarct expansion. Assesment
of valvular heart disease is also of paramount importance: Valvular heart disease can be a
complication of MI and can contribute to the patient clinical instability. Echocardiography
can thus aid in decision making whether the patient is a candidate for surgical
revascularization as combined surgery (CABG plus valvular repair/replacement) may be
appropriate. It is also useful for excluding aortic dissection or pericardial effusion.
Furthermore it is a useful additional tool or alternative to Pulmonary Artery Catheter (PAC)
to evaluate the resolution and/or improvement of cardiogenic shock or myocardial
stunning and to help guide volume therapy.

Transoesophageal echocardiograhy has an increasing role in the therapy of cardiogenic

shock and complicated myocardial infarction and is very useful in ICU setting.

Echocardiographic contrast agents permit the more accurate diagnosis of regional wall
motion abnormalities, and tissue Doppler and strain imaging allow quantification of global
and regional myocardial function.

Stress echocardiography (2-10 days after MI) can assess myocardial viability and
distinguish non-viable myocardium from stunned myocardium.

In text References
(Reynolds and Hochman. 2008; Prastaro et al. 2017)

4. 5. 3. 2. Other non-invasive techniques

Other imaging techniques such as nuclear medicine (myocardial perfusion with (positron
emission tomography (PET) or single, photon emission computed tomography (SPECT)),
cardiovascular magnetic resonance (CMR), and coronary computed tomography
angiography (CCTA) are used.

There is evidence of the value of CCTA in the diagnosis of coronary artery disease in
patients with low-to- intermediate risk and normal cTn at the time of admission to the
chest pain unit, and the use of CMR to define the etiology of the myocardial injury.

CMR is the modality of choice for late-presentation MI due to its ability to detect
subendocardial scarring and differentiate ischemic cardiomyopathy from nonischemic
cardiomyopathy, based on the late enhancement pattern when gadolinium is used as
contrast agent. It is also very useful to assess presence of viable myocardium which may
benefit from revascularization procedures like PCI of CABG surgery.

4. 5. 3. 3. Coronary Angiography and Left Ventriculography

Coronary angiograhy will also allow detection of other coronary artery disease and an
assessment of function It is the gold standard for the diagnosis and often treatment of
CAD coronary angiograhy and will usually identify a culprit artery subtending an area of
regional wall motion abnormality and additionally may allow definitive treatment of this
abnormality.

 References
Reynolds HR, Hochman JS., Cardiogenic shock: current concepts and
improving outcomes., 2008, PMID:18250279
Sgarbossa EB, Birnbaum Y, Parrillo JE., Electrocardiographic diagnosis of
acute myocardial infarction: Current concepts for the clinician., 2001,
PMID:11275913
Smith SW, Dodd KW, Henry TD, Dvorak DM, Pearce LA, Diagnosis of ST-
elevation myocardial infarction in the presence of left bundle branch block with
the ST-elevation to S-wave ratio in a modified Sgarbossa rule., 2012,
PMID:22939607
Wang J, Luo H, Kong C, Dong S, Li J, Yu H, Chu Y, Prognostic value of new-
onset right bundle-branch block in acute myocardial infarction patients: a
systematic review and meta-analysis., 2018, PMID:29576967
Zimetbaum PJ, Josephson ME., Use of the electrocardiogram in acute
myocardial infarction., 2003, PMID:12621138
Sanaani A, Yandrapalli S, Jolly G, Paudel R, Cooper HA, Aronow WS,
Correlation between electrocardiographic changes and coronary findings in
patients with acute myocardial infarction and single-vessel disease., 2017,
PMID:28936441
Wang K, Asinger RW, Marriott HJ., ST-segment elevation in conditions other
than acute myocardial infarction., 2003, PMID:14645641
Karve AM, Bossone E, Mehta RH., Acute ST-segment elevation myocardial
infarction: critical care perspective., 2007, PMID:17964359
Pollak P, Brady W, Electrocardiographic patterns mimicking ST segment
elevation myocardial infarction., 2012, PMID:23102035
Tsuchihashi K, Ueshima K, Uchida T, Oh-mura N, Kimura K, Owa M,
Yoshiyama M, Miyazaki S, Haze K, Ogawa H, Honda T, Hase M, Kai R, Morii I;
Angina Pectoris-Myocardial Infarction Investigations in Japan., Transient left
ventricular apical ballooning without coronary artery stenosis: a novel heart
syndrome mimicking acute myocardial infarction. Angina Pectoris-Myocardial
Infarction Investigations in Japan., 2001, PMID:11451258
Prasad A, Apical ballooning syndrome: an important differential diagnosis of
acute myocardial infarction, 2007, PMID:17283269
Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M,
Cammann VL, Sarcon A, Geyer V, Neumann CA, Seifert B, Hellermann J,
Schwyzer M, Eisenhardt K, Jenewein J, Franke J, Katus HA, Burgdorf C,
Schunkert H, Moeller C, Thiele H, Bauersachs J, Clinical Features and
Outcomes of Takotsubo (Stress) Cardiomyopathy., 2015, PMID:26332547
Twerenbold R, Boeddinghaus J, Nestelberger T, Wildi K, Rubini Gimenez M,
Badertscher P, Mueller C, Clinical Use of High-Sensitivity Cardiac Troponin in
Patients With Suspected Myocardial Infarction., 2017, PMID:28818210
 Thygesen K, Mair J, Giannitsis E, Mueller C, Lindahl B, Blankenberg S, Huber
K, Plebani M, Biasucci LM, Tubaro M, Collinson P, Venge P, Hasin Y, Galvani
M, Koenig W, Hamm C, Alpert JS, Katus H, Jaffe AS; Study Group on
Biomarkers in Cardiology of ESC Work, How to use high-sensitivity cardiac
troponins in acute cardiac care., 2012, PMID:22723599
Jarolim P., High sensitivity cardiac troponin assays in the clinical laboratories.,
2015, PMID:25252753
Fromm RE Jr, Cardiac troponins in the intensive care unit: common causes of
increased levels and interpretation., 2007, PMID:17205004
McLean AS, Huang SJ, Salter M, Bench-to-bedside review: the value of
cardiac biomarkers in the intensive care patient., 2008, PMID:18557993
Thygesen K, Alpert JS, Jaffe AS, White HD., Diagnostic application of the
universal definition of myocardial infarction in the intensive care unit., 2008,
PMID:18787447
Prastaro M, Pirozzi E, Gaibazzi N, Paolillo S, Santoro C, Savarese G, Losi MA,
Esposito G, Perrone Filardi P, Trimarco B, Galderisi M, Expert Review on the
Prognostic Role of Echocardiography after Acute Myocardial Infarction., 2017,
PMID:28477781

4. 6. Risk Scoring Systems

A number of scoring systems have been developed to predict patient risk after myocardial
infarction. Risk stratification using a combination of comorbidities, clinical features,
electrocardiography and biochemical markers allows for rapid estimation of the risk of an
adverse outcome and provides optimal guidance of treatment to prevent both ischemic
and bleeding events. Evolving risk assessment can similarly be used to determine the
most appropriate level of care and monitoring.

4. 6. 1. Killip Classification
This is not a rigorous risk score, but a very rapid and effective system of risk assessment
of patients with myocardial infarction. Class I includes individual with no clinical signs of
heart failure, Class II includes those with rales or crackles in the lungs, a third heart
sound, and elevated jugular venous pressure, Class III are patients with frank, acute
pulmonary edema, and Class IV are those with cardiogenic shock or severe hypotension.

4. 6. 2. Grace Scoring System

The Global Registry of Acute Coronary Events (GRACE) score was developed from an
international registry with a population of patients across the entire spectrum of ACS. It is
composed of the following items: age, heart rate, systolic blood pressure, serum
creatinine, Killip class, cardiac arrest at admission, elevation of markers of myocardial
injury, ST-segment deviation. Patients with GRACE score over 140 have high risk of in-
hospital mortality, whereas values between 109 and 140 identify those with an
intermediate risk. Grace risk score has been use to estabilish the need and optimal timing
for invasive stratification.

Figure 8:Grace risk score

4. 6. 3. TIMI Scoring System

4. 6. 3. 1. Non-STEMI:
The thrombolysis in myocardial infarction (TIMI) risk score is a well-validated scoring
system used to predict the 14-day risk of death, myocardial infarction, or urgent
revascularization in patients with NSTEMI. It is composed of seven independent
predictors.

To calculate the score, a value of 1 is assigned when each variable was present and 0
when it was absent:

Age ≥65 years

Presence of at least three risk factors for coronary heart disease (CHD)
Prior coronary stenosis of ≥50 percent
Presence of ST segment deviation on admission ECG
At least two anginal episodes in prior 24 hours
Elevated serum cardiac biomarkers
Use of aspirin in prior seven days
A higher TIMI score correlated significantly with increased number of events (all-cause
mortality, new or recurrent myocardial infarction or severe recurrent ischemia requiring
revascularization):

Score of 0/1– 4.7 percent

Score of 2 – 8.3 percent
Score of 3 – 13.2 percent
Score of 4 – 19.9 percent
Score of 5 – 26.2 percent
Score of 6/7– 40.9 percent

Figure 9:TIMI Risk score for UA/NSTEMI. Esicm

Academy 2019

4. 6. 3. 2. STEMI:
A TIMI risk score predicting 30-day adverse events in patients with STEMI has been
developed as well, and includes different variables.

In STEMI patients, the TIMI risk score is based upon data of 15000 patients with an
STEMI eligible for fibrinolytic therapy. It is calculate with the sum of eight predictors of
mortality:

Age ≥75 years – 3 points

Age 65 to 74 years – 2 points
History of diabetes, hypertension, or angina – 1 point
Systolic blood pressure <100 mmHg – 3 points
Heart rate >100/min– 2 points
Killip class II to IV – 2 points
Weight <67 kg – 1 point
Anterior ST elevation or left bundle branch block – 1 point
Time to reperfusion therapy >4 hours – 1 point

Mortality increase as the value is higher, as can be seen in figure 10.

 Figure 10: TIMI Risk score for STEMI. Esicm
Academy 2019

4. 6. 4. CRUSADE
Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes
with Early Implementation of the ACC/AHA Guidelines (CRUSADE) Bleeding Score
quantifies risk for in-hospital major bleeding across all post-admission treatments,
enhancing baseline risk assessment for Non-ST Elevated Myocardial Infarction (NSTEMI)
care.

The CRUSADE bleeding Score combines 8 readily available variables (baseline

haematocrit, creatinine clearance, female sex, diabetes, peripheral vascular disease,
signs of heart failure, systolic blood pressure, and heart rate on admission) into a
validated bleeding risk Score (range 1 to 100 points). The risk of bleeding increases
progressively with the CRUSADE score.

This Score stratifies baseline bleeding risk across quintiles:

Very low risk (Score ≤20)

Low risk (21 to 30)
Moderate risk (31 to 40)
High risk (41 to 50)
Very high risk (≥50).

In CRUSADE, observed rates of major in-hospital bleeding across quintiles of risk were
3.1% (very low risk), 5.5% (low risk), 8.6% (moderate risk), 11.9% (high risk), and 19.5%
(very high risk). By providing an estimation of baseline risk of bleeding, application of the
CRUSADE bleeding Score will better equip providers to consider the safety and efficacy
implications of various treatment strategies for a patient with non–STEMI.

In text References

(Poldervaart et al. 2017; Hall et al. 2018; Subherwal et al. 2009; Fox et al. 2006; Antman
et al. 2000; Morrow et al. 2000; Subherwal et al. 2009)
 References
Poldervaart JM, Langedijk M, Backus BE, Dekker IMC, Six AJ, Doevendans
PA, Hoes AW, Reitsma JB, Comparison of the GRACE, HEART and TIMI score
to predict major adverse cardiac events in chest pain patients at the
emergency department., 2017, PMID:27810290
Hall M, Bebb OJ, Dondo TB, Yan AT, Goodman SG, Bueno H, Chew DP,
Brieger D, Batin PD, Farkouh ME, Hemingway H, Timmis A, Fox KAA, Gale CP,
Guideline-indicated treatments and diagnostics, GRACE risk score, and
survival for non-ST elevation myocardial infarction., 2018, PMID:30202849
Subherwal S, Bach RG, Chen AY, Gage BF, Rao SV, Newby LK, Wang TY,
Gibler WB, Ohman EM, Roe MT, Pollack CV Jr, Peterson ED, Alexander KP.,
Baseline risk of major bleeding in non-ST-segment-elevation myocardial
infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina
patients Suppress ADverse outcomes with Early implementation of the
ACC/AHA Guidelines) Bleeding Score., 2009, PMID:19332461
Fox KA, Dabbous OH, Goldberg RJ, Pieper KS, Eagle KA, Van de Werf F,
Avezum A, Goodman SG, Flather MD, Anderson FA Jr, Granger CB., Prediction
of risk of death and myocardial infarction in the six months after presentation
with acute coronary syndrome: prospective multinational observational study
(GRACE)., 2006, PMID:17032691
Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G,
Mautner B, Corbalan R, Radley D, Braunwald E., The TIMI risk score for
unstable angina/non-ST elevation MI: A method for prognostication and
therapeutic decision making., 2000, PMID:10938172
Morrow DA, Antman EM, Charlesworth A, Cairns R, Murphy SA, de Lemos JA,
Giugliano RP, McCabe CH, Braunwald E., TIMI risk score for ST-elevation
myocardial infarction: A convenient, bedside, clinical score for risk assessment
at presentation: An intravenous nPA for treatment of infarcting myocardium
early II trial substudy., 2000, PMID:11044416
Subherwal S, Bach RG, Chen AY, Gage BF, Rao SV, Newby LK, Wang TY,
Gibler WB, Ohman EM, Roe MT, Pollack CV Jr, Peterson ED, Alexander KP.,
Baseline risk of major bleeding in non-ST-segment-elevation myocardial
infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina
patients Suppress ADverse outcomes with Early implementation of the
ACC/AHA Guidelines) Bleeding Score., 2009, PMID:19332461
5. Conclusion
Acute myocardial infarction (AMI) and Unstable Angina (UA) are often clinically
indistinguishable at presentation; hence the acute coronary syndrome (ACS) terminology.
About 10% of patients presenting with an ACS have ST-segment elevation. The diagram
below summarises the diagnostic categorisation (Figure 11).

Figure 11: On the left: typical lesion of unstable angina. On the

right: typical lesion of acute myocardial infarction. From Davies MJ,
2000.

 Important
Not all patients subsequently proven to have myocardial necrosis exhibit ECG
changes. A normal ECG does not exclude AMI.

Clinical examination, along with echocardiography, is very important to exclude alternative

diagnoses as well as to detect complications of myocardial infarction.

STEMI patients should be considered for reperfusion strategies depending on their time of
presentation. Patients with ACS without ST elevation are classified as unstable angina or
NSTEMI depending on their biomarker level. Early risk stratification and prognostication
with clinically validated scoring systems, utilising history, physical examination, ECG
findings and biomarkers are effective means of directing and escalating therapy.

In text References

(Davies 2000)

 References
Davies MJ, The pathophysiology of acute coronary syndromes., 2000,
PMID:10677422

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