Papers by Andrew Civitello
Asaio Journal, Jul 1, 2013
Journal of Heart and Lung Transplantation, 2008
BACKGROUND For patients with persistent cardiogenic shock refractory to intraaortic balloon pump ... more BACKGROUND For patients with persistent cardiogenic shock refractory to intraaortic balloon pump (IABP) support, there are only limited means of resuscitation and bridging to surgical left ventricular assist device (LVAD) implantation. Extracorporeal membrane oxygenation and emergency surgical approaches have been attempted but are associated with significant morbidity and mortality. We evaluated the efficacy of a percutaneous left ventricular assist device (PVAD) as a bridge to LVAD implantation in patients in cardiogenic shock refractory to IABP and pressor support. METHODS Between May 2003 and April 2006, at our institution, 18 patients in severe refractory cardiogenic shock received a PVAD as a bridge to LVAD placement or orthotopic heart transplantation. Six patients had ischemic cardiomyopathy, and 12 had nonischemic cardiomyopathy. At the time of PVAD placement, 17 were receiving IABP support, and 10 were undergoing cardiopulmonary resuscitation. RESULTS The mean duration of PVAD support was 4.2 +/- 2.5 days. During this time, the cardiac index improved from 0.86 +/- 0.66 to 2.50 +/- 0.93 liters/min/m2 (p < 0.001), systolic blood pressure improved from 72 +/- 11 to 98 +/- 15 mm Hg (p = 0.001), and systemic mixed venous oxygenation improved from 37 +/- 7 to 62 +/- 6 mm Hg (p < 0.001). We terminated life support in 4 of the 18 patients before LVAD placement; 14 were successfully bridged to LVAD or heart transplantation. The mortality rate was 27% at 30 days and 33% at 6 months. There were no PVAD-associated deaths. CONCLUSION In patients with terminal hemodynamic collapse, PVAD support is an effective bridging therapy to LVAD and appears to be a viable alternative to other invasive methods of support.
Genomics, Jun 1, 1990
The Lesch-Nyhan (LN) syndrome is a genetically lethal human neurological disease that results fro... more The Lesch-Nyhan (LN) syndrome is a genetically lethal human neurological disease that results from mutations that inactivate the hypoxanthine phosphoribosyltransferase (HPRT) gene. The elucidation of the complete DNA sequence of the human HPRT gene locus has enabled the construction of multiple oligonucleotide primer sets for the simultaneous in uitro amplification of all nine HPRT exons. The multiplex polymerase chain reaction provides a facile assay for the detection of HPRT exon deletions and the reaction products can be analyzed by direct automated fluorescent DNA sequencing to identify subtle alterations in the gene. Alterations have been identified in the HPRT genes from 15 independent LN cases, and 10 LN family studies were performed. The sequencing method uses solid supports and is sufficiently simple and sensitive to be a favored approach for LN diagnosis. LN heterozygotes can be diagnosed without reference to the affected male. In addition, these procedures will be useful for somatic mutagenesis studies.
Journal of Heart and Lung Transplantation, Apr 1, 2019
Purpose: Vascular endothelial growth factor (VEGF) has been implicated in gastrointestinal angiod... more Purpose: Vascular endothelial growth factor (VEGF) has been implicated in gastrointestinal angiodysplasias (GIADs). Bevacizumab (Avastin) is a humanized monoclonal antibody against VEGF and confers potent antiangiogenic properties. We sought to examine the safety and efficacy of intravenous bevacizumab in a small group of LVAD patients with refractory GI bleeding due to GIADs. Methods: We conducted a pilot study between January, 2017 and March, 2018 at a large institution to examine the efficacy and safety of intravenous bevacizumab administration in patients supported with continuous flow LVAD who presented with refractory GIADs-related bleeding, defined as endoscopy-proven GIADs that failed both conventional medical and endoscopic therapies. We assessed response to therapy based on changes in number of GI bleeding hospitalizations, blood transfusions, and scoping procedures. Results: Five LVAD patients (mean age 67 years, all male, all HeartMate II) with refractory GIADs-associated bleeding were treated with intravenous bevacizumab for a total of 8 cycles according to our institutional protocol. The median (interquartile range [IQR]) of follow up while on LVAD was 11.0 (2.6, 25.5) and 11.2 (10.2, 13.5) months pre and post bevacizumab initiation, respectively. Intravenous bevacizumab administration resulted in a remarkable decrease in the annual number of blood transfusions (45.
Journal of Heart and Lung Transplantation, Apr 1, 2019
Results: Of the 82 patients, 46 (56%) had a score < 21, while 36 (44%) had a score ≥ 21. There we... more Results: Of the 82 patients, 46 (56%) had a score < 21, while 36 (44%) had a score ≥ 21. There were no differences in baseline characteristics including age (58 vs 56, p=0.5), gender (Male: 85% vs 72%, p=0.2), INTER-MACS class (3 vs 3, p=0.9), EF (18% vs 17%, p=0.4), GFR (71 vs 66, p=0.4), median days on LVAD support (138 vs 164, p=0.9), or device type. There was no difference in the composite outcome of death or readmission for HF, bleeding, infection, or stroke [Figure 1], or any of the individual components between those with SIPAT scores < 21 versus ≥ 21. Conclusion: Unlike cardiac transplant, the SIPAT score was not predictive of medical outcomes in patients undergoing LVAD therapy. A patient's underlying biologic effects may influence outcomes more than their psychosocial aspects. Prospective studies should be considered to further explore the validity of the SIPAT score in patients undergoing LVAD implantation.
The Annals of Thoracic Surgery, Mar 1, 2012
After discontinuation of cardiopulmonary bypass, central venous pressure was 12 to 14 mm Hg. The ... more After discontinuation of cardiopulmonary bypass, central venous pressure was 12 to 14 mm Hg. The patient was extubated 18 hours later without further neurologic deterioration. Neurologic rehabilitation with physical, occupational, and speech therapy was initiated. Anticoagulation was maintained with aspirin and warfarin, with a target international normalized ratio of 2.0 to 2.5. Histologic examination of the implant left ventricular muscle core demonstrated no lymphocyte infiltration. Serial postoperative echocardiograms showed no improvement in left ventricular function. Device performance remained optimal except for occasional suction alarms that resolved with increased oral fluid intake. Device speed was left at 2,450 RPM with flows of 3.8 to 4.2 L/min. On postimplantation day 19 she was transferred to a rehabilitation facility. Twelve days later at the time of discharge to home, her aphasia was nearly resolved and she had improved strength and was walking with assistance. Her swallowing studies had normalized and she was eating a regular diet. Brief readmission was prompted by occasional light-headed sensations after walking. Subsequent right heart catheterization showed low atrial filling pressures. Pump speed was reduced from 2,450 to 2,400 RPM with symptom resolution. On postimplantation day 60, a suitable donor was identified and she underwent successful device explantation and cardiac transplantation.
Kidney360, Mar 31, 2022
Durable and temporary mechanical circulatory support (MCS) use is growing for a range of cardiova... more Durable and temporary mechanical circulatory support (MCS) use is growing for a range of cardiovascular indications. Kidney dysfunction is common in persons evaluated for or receiving durable or temporary MCS, and portends worse outcomes. This kidney dysfunction can be due to preexisting kidney chronic kidney disease (CKD), acute kidney injury (AKI) related to acute cardiovascular disease necessitating MCS, AKI due to cardiac procedures, and due to acute and chronic MCS effects and complications. Durable MCS, with implantable continuous flow pumps, is used for long-term support in advanced HF refractory to guideline directed medical and device therapy, either permanently or as a bridge to heart transplantation. Temporary MCS-encompassing in this review intra-aortic balloon pumps (IABPs), axial flow pumps, centrifugal flow pumps, and venoarterial ECMO-is used for diverse situations: high risk percutaneous coronary interventions (PCI), acute decompensated heart failure (HF), cardiogenic shock, and resuscitation following cardiac arrest. The wide adoption of MCS makes it imperative to improve understanding of the effects of MCS on kidney health/function, and of kidney health/ function on MCS outcomes. The complex structure and functions of the kidney, and the complex health states of individuals receiving MCS, makes investigations in this area challenging, and current knowledge is limited. Fortunately, the increasing nephrology toolbox of non-invasive kidney health/ function assessments may enable development and testing of individualized management strategies and therapeutics in the future. We review technology, epidemiology, pathophysiology, clinical considerations, and future directions in MCS and nephrology.
Artificial Organs, May 16, 2022
BackgroundHyponatremia is associated with adverse outcomes in heart failure and after cardiac sur... more BackgroundHyponatremia is associated with adverse outcomes in heart failure and after cardiac surgery. We hypothesized that hyponatremia is associated with poorer short‐term and longer term survival in patients after continuous‐flow left ventricular assist device (CF‐LVAD) placement.MethodsWe reviewed a single‐center database of patients who received a CF‐LVAD during 2012–2017. Sodium (Na) values obtained within 14 days before CF‐LVAD insertion were averaged; patients (n = 332) were divided into hyponatremia (mean Na &lt;135 mEq/L; n = 160; 48.2%) and normonatremia groups (mean Na 135–145 mEq/L; n = 172; 51.8%). Patients requiring preoperative dialysis or pump exchange were excluded. We compared outcomes between preoperative hyponatremia and normonatremia groups.ResultsThe two groups’ baseline characteristics were similar, although hyponatremia patients more often had preoperative mechanical circulatory support (44.4% vs. 31.4%, p = 0.002). Although hyponatremic and normonatremic patients did not differ in 30‐day mortality (7.5% vs. 6.5%, p = 0.7), preoperative hyponatremia was associated with greater 5‐year mortality (61% vs. 44%, p = 0.03). On binary logistic regression analysis, the strongest independent predictors of late mortality were hyponatremia (odds ratio [OR] 1.88, 95% CI [1.07–3.31], p = 0.02), older age (OR 1.03, 95% CI [1.01–1.05], p = 0.01), and elevated mean right atrial pressure/pulmonary capillary wedge pressure ratio (OR 4.69, 95% CI [1.76–12.47], p = 0.002).ConclusionsHyponatremia was not associated with greater early mortality but was associated with poorer late survival. The optimal timing of LVAD implantation in relation to hyponatremia, and whether correcting hyponatremia perioperatively improves long‐term survival, should be investigated.
Journal of Heart and Lung Transplantation, Feb 1, 2004
VEGF-C has previously been shown to promote lympangiogenesis and mild angiogenesis. The aim of th... more VEGF-C has previously been shown to promote lympangiogenesis and mild angiogenesis. The aim of ths study was to investigate angiogenic potential of VEGF-C in ischaemic porcine heart model. Fifteen lanrace piglets were subjected to ameroid-induced gradual occlusion of the left circumflex artery. All animal treatment were performed conforming the 1991 revision of "Guiding Principles in the Care and Use of Animals"(American Physiological association). Three weeks after ameroid placement, 99Tc-sestamibi gated SPECT during rest and stress, in vivo angiography and gamma camera mounted dual head coincidence detection imaging were performed and the pigs were randomized to receive adeno (ad) VEGF-C (n ϭ 6) or control adLacZ (n ϭ 5). Four weeks later the examinations were repeated. At that time, in vivo angiography showed significantly greater collateral development in the (ad) VEGF-C group localized in the treatment area (p Ͻ 0,05) compared to the control group. Histology revealed more capillary vessels in the (ad) VEGF-C group versus control animals (p Ͻ 0,03).Coincidence detection imaging of 18F-FDG metabolism suggested improved myocardial viability in the treatment group compared to control animals (p ϭ 0,054). SPECT perfusion imaging showed no difference between the groups. VEGF-C induces subtle, but statistically significant collateral formation in the ischaemic porcine heart model. The results suggest also better recognition of minor ischaemic changes in the myocardium using PET coincidence imaging versus SPECT.
Automated DNA Sequencing and Analysis, 1994
American journal of human genetics, 1991
Tandemly reiterated sequences represent a rich source of highly polymorphic markers for genetic l... more Tandemly reiterated sequences represent a rich source of highly polymorphic markers for genetic linkage, mapping, and personal identification. Human trimeric and tetrameric short tandem repeats (STRs) were studied for informativeness, frequency, distribution, and suitability for DNA typing and genetic mapping. The STRs were highly polymorphic and inherited stably. A STR-based multiplex PCR for personal identification is described. It features fluorescent detection of amplified products on sequencing gels, specific allele identification, simultaneous detection of independent loci, and internal size standards. Variation in allele frequencies were explored for four U.S. populations. The three STR loci (chromosomes 4, 11, and X) used in the fluorescent multiplex PCR have a combined average individualization potential of 1/500 individuals. STR loci appear common, being found every 300-500 kb on the X chromosome. The combined frequency of polymorphic trimeric and tetrameric STRs could be ...
The Journal of Thoracic and Cardiovascular Surgery, 2019
Objective: The effects of having a lower left ventricular end-diastolic dimension before HeartMat... more Objective: The effects of having a lower left ventricular end-diastolic dimension before HeartMate II (Thoratec Corp, Pleasanton, Calif) left ventricular assist device implantation remain unclear. We analyzed our single-center data on HeartMate II implantation to determine whether having a lower left ventricular end-diastolic dimension preoperatively was associated with inferior outcomes. Methods: From November 2003 to March 2016, 393 patients with chronic heart failure underwent primary HeartMate II implantation. We compared the preoperative left ventricular end-diastolic dimension and associated survival outcomes of these patients to determine the left ventricular end-diastolic dimension cutoff for worse overall survival. Then, we compared the preoperative demographics, stroke rate, and mortality of patients with a left ventricular end-diastolic dimension above the cutoff for worse survival with those of patients with a left ventricular end-diastolic dimension below the cutoff. Results: A Cox multivariate regression model showed that low left ventricular end-diastolic dimension was an independent predictor of mortality (hazard ratio, 1.49; P ¼ .02). The Contal and O'Quigley method showed that overall survival postimplantation was decreased in patients with a left ventricular end-diastolic dimension less than 6.0 cm (n ¼ 91). Kaplan-Meier analysis confirmed that the left ventricular end-diastolic dimension less than 6.0 cm group had lower overall survival than the left ventricular end-diastolic dimension 6.0 cm or greater group (P ¼ .04). Furthermore, a competing-risk analysis showed that postoperative stroke was more common in the left ventricular end-diastolic dimension less than 6.0 cm group than in the left ventricular end-diastolic dimension 6.0 cm or greater group (P <.01). Conclusions: Overall survival was decreased and postoperative stroke was increased in HeartMate II recipients with a preoperative left ventricular end-diastolic dimension less than 6.0 cm. Future research should determine the left ventricular end-diastolic dimension cutoff values for safely implanting other support devices, and device designs should be improved to better accommodate the needs of patients with a limited left ventricle size.
The Journal of Heart and Lung Transplantation, 2018
on temporary MCS, median waiting time to transplant reduced from 29 days to 10 days (p= 0.04). Th... more on temporary MCS, median waiting time to transplant reduced from 29 days to 10 days (p= 0.04). Thirty-day post-transplant survival rates were similar for super-urgent (N= 25), urgent (N= 53) and non-urgent (N= 25) transplants carried out since October 2016, at 88.0%, 87.9% and 91.8% respectively (p= 0.9). Conclusion: Prioritising the most clinically urgent patients on the heart transplant waiting list reduces waiting time for the sickest patients with no negative impact on post-transplant outcomes. Close monitoring is needed to ensure the new super-urgent tier is preserved for those most in need.
Circulation, 2020
Introduction: Cardiovascular disease (CVD) is the leading cause of mortality in the United States... more Introduction: Cardiovascular disease (CVD) is the leading cause of mortality in the United States, leading to one in four deaths. The role of inherited susceptibility to CVD is well established, from rare monogenic disorders to polygenic traits. For many of these conditions, guidelines exist for medical interventions and other preventative care that can improve outcomes and quality of life. Methods: We developed a comprehensive genetic screen, "HeartCare", consisting of a 158 gene panel evaluating 1) Mendelian conditions including cardiomyopathies, aortopathies, arrhythmias, and dyslipidemias, 2) a coronary artery disease polygenic risk score (PRS), 3) variants in the LPA gene encoding Lipoprotein(a) that are an independent risk factor for atherosclerotic CVD events, and 4) pharmacogenetic (PGx) variants contributing to simvastatin-induced myopathy and warfarin metabolism. After sequencing in a CAP/CLIA certified laboratory, results were returned to the ordering physician ...
Resuscitation, 2017
BACKGROUND Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a widely used form of me... more BACKGROUND Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a widely used form of mechanical circulatory support in patients with refractory cardiogenic shock. A common drawback of this modality is a resultant increase in left ventricular afterload. OBJECTIVES The purpose of this meta-analysis was to examine the efficacy and safety of left ventricular unloading strategies during VA-ECMO in adult patients with cardiogenic shock. METHODS The authors performed a systematic search of studies examining left ventricular unloading during VA-ECMO in Medline, EMBASE, and the Cochrane library. The primary outcome was all-cause mortality. Secondary outcomes included limb ischemia, bleeding, need for renal replacement therapy, multiorgan failure, stroke or transient ischemic attack, and hemolysis. RESULTS Of 2,221 publications identified, 17 observational studies met the inclusion criteria. In total, outcomes in 3,997 patients were included with 1,696 (42%) receiving a concomitant left ventricular unloading strategy while on VA-ECMO (intra-aortic balloon pump 91.7%, percutaneous ventricular assist device 5.5%, pulmonary vein or transseptal left atrial cannulation 2.8%). There were 2,412 deaths (60%) in the total cohort. Mortality was lower in patients with (54%) versus without (65%) left ventricular unloading while on VA-ECMO (risk ratio: 0.79; 95% confidence interval: 0.72 to 0.87; p < 0.00001). Hemolysis was higher in patients who underwent VA-ECMO with left ventricular unloading. Otherwise, secondary outcomes were not demonstrably different in patients treated with VA-ECMO with versus without left ventricular unloading. CONCLUSIONS In observational studies, left ventricular unloading was associated with decreased mortality in adult patients with cardiogenic shock treated with VA-ECMO. In the absence of prospective randomized data, left ventricular unloading may be considered for appropriately selected patients undergoing VA-ECMO support.
Stroke, 2018
Background: The development of stroke while on continuous flow left ventricular assist device (CF... more Background: The development of stroke while on continuous flow left ventricular assist device (CF-LVAD) remains a source of significant morbidity and mortality. The ability to risk stratify these patients can improve postoperative management. Objective: To describe the overall experience of cerebrovascular accidents in CF-LVAD patients at a large volume tertiary center and compare the utility of CHADS 2 , CHA 2 DS 2 -VASc, and R 2 CHADS 2 scores. Methods: A retrospective analysis of 522 patients (524 CF-LVADs: HeartMate-II=402; Heartware=122), between 2003 and 2016, was conducted. Post-operative heparin for 2-3 days, warfarin (goal INR 2-3), and 80-325mg aspirin were administered daily. Cerebrovascular vascular accident (CVA) was defined as any focal or global deficit with positive imaging. The CHADS 2 , R 2 CHADS 2 and CHA 2 DS 2 -VASc scores were calculated. Baseline characteristics and risk assessment scores were compared between patients with ischemic CVA (ICVA) and no CVA (nCVA...
The Journal of invasive cardiology, 2006
OBJECTIVES: We describe our experience in using the TandemHeart percutaneous ventricular assist d... more OBJECTIVES: We describe our experience in using the TandemHeart percutaneous ventricular assist device (pVAD) during high-risk percutaneous coronary intervention (PCI). BACKGROUND: Coronary artery bypass grafting (CABG) is the preferred treatment for disease in an unprotected left main coronary artery or left main equivalent. However, severe comorbidities may preclude surgery in some patients. In these cases, PCI is also often a high-risk procedure. The pVAD is designed to provide circulatory support during high-risk PCI. METHODS AND RESULTS: We used the pVAD for hemodynamic support during PCI in 5 consecutive patients who were ineligible for CABG because of severe comorbidities. In all 5 cases, the device was inserted and support initiated without complications. Percutaneous revascularization was successfully performed with pVAD support (approximately 3 L/minute). Four patients were supported for an average of 107 minutes, the pVAD being withdrawn shortly after PCI; all 4 patients ...
Acute Coronary Syndromes The Trial: SYMPHONY II Presenter:Kristin Newby, Duke University Medical ... more Acute Coronary Syndromes The Trial: SYMPHONY II Presenter:Kristin Newby, Duke University Medical Center, Durham, NC. The study: A randomized trial of sibrafiban (an oral glycoprotein [GP] IIb/IIIa antagonist) in patients with acute coronary syndromes. The study was originally designed to include 8400 patients, but it was terminated prematurely by the sponsor (unilaterally) after the negative results of SYMPHONY. At the time the trial was terminated, a total of 6671 patients had been enrolled. To qualify, patients had to present within 7 days with an acute coronary syndrome and be stabilized. They were then randomized to receive aspirin (80 mg every 12 hours), sibrafiban (high dose), or sibrafiban (low dose) plus aspirin (80 mg every 12 hours). The primary end point was the composite of death, myocardial infarction (MI), or severe recurrent ischemia. Secondary end points included the incidence of coronary ischemic events, reversible coronary ischemia, coronary revascularization, reho...
Journal of Artificial Organs, 2021
Renal replacement therapy (RRT) after continuous flow left ventricular assist device (CF-LVAD) im... more Renal replacement therapy (RRT) after continuous flow left ventricular assist device (CF-LVAD) implantation significantly affects patients’ quality of life and survival. To identify preoperative prognostic markers in patients requiring RRT after CF-LVAD implantation, we retrospectively reviewed data from patients who underwent implantation of a CF-LVAD at our institution during 2012–2017. Patients who required preoperative RRT were excluded. Preoperative and operative characteristics, as well as survival and adverse events, were compared between 74 (22.2%) patients requiring any duration of postoperative RRT and 259 (77.8%) not requiring RRT. Patients requiring RRT experienced more postoperative complications than patients who did not, including respiratory failure necessitating tracheostomy (35.7% vs 2.5%, p < 0.001), reoperation for bleeding (34.3% vs 11.7%, p < 0.001), and right heart failure necessitating perioperative mechanical circulatory support (32.4% vs 6.9%, p < 0.001). Patients requiring postoperative RRT also had poorer survival at 30 days (74.7% vs 98.8%), 6 months (48.2% vs 95.1%), and 12 months (45.3% vs 90.2%) (p < 0.001). Significant predictors of RRT after CF-LVAD implantation included urine proteinuria (odds ratio [OR] 3.6, 95% confidence interval [CI] [1.7–7.6], p = 0.001), estimated glomerular filtration rate < 45 mL/min/1.73 m2 (OR 3.4, 95% CI [1.5–17.8], p = 0.004), and mean right atrial pressure to pulmonary capillary wedge pressure ratio ≥ 0.54 (OR 2.6, 95% CI [1.3–5.], p = 0.01). Of the 74 RRT patients, 11 (14.9%) recovered renal function before discharge, 36 (48.6%) still required RRT after discharge, and 27 (36.5%) died before discharge. We conclude that preoperative renal and right ventricular dysfunction significantly predict postoperative renal failure and mortality after CF-LVAD implantation.
European Journal of Heart Failure, 2020
Decreased systolic function is a central factor in HFrEF. OM is a myotrope and a selective cardia... more Decreased systolic function is a central factor in HFrEF. OM is a myotrope and a selective cardiac myosin activator that improves cardiac function. The GALACTIC-HF trial evaluates the effect of OM on outcomes in patients with chronic HF.
Uploads
Papers by Andrew Civitello