The End of Endomyocardial Biopsy?: A Practical Guide for Noninvasive Heart Transplant Rejection Surveillance.

Noninvasive heart transplant rejection surveillance using gene expression profiling (GEP) to monitor immune activation is widely used among heart transplant programs. With the new development of donor-derived cell-free DNA (dd-cfDNA) assays, more programs are transitioning to a predominantly noninvasive rejection surveillance protocol with a reduced frequency of endomyocardial biopsies. As a result, many practical questions arise that potentially delay implementation of these valuable new tools. The purpose of this review is to provide practical guidance for clinicians transitioning toward a less invasive acute rejection monitoring protocol after heart transplantation, and to answer 10 common questions about the GEP and dd-cfDNA assays. Evidence supporting GEP and dd-cfDNA testing is reviewed, as well as guidance on test interpretation and future directions.

Utilization of COVID-19 positive donors for Heart transplantation and associated short-term outcomes.

BACKGROUND: The safety and efficacy of using COVID-19 positive donors in heart transplantation (HT) are increasingly relevant, but not well established. The present study evaluated the characteristics and utilization of such donors and associated post-HT outcomes. METHODS: All adult (≥18 years old) potential donors and HT recipients in the United States from April 21, 2020 to March 31, 2022 were included. Donor COVID-19 status was defined by the presence (or absence) of any positive test within 21 days of organ recovery. Donor and recipient characteristics and post-HT outcomes, including a primary composite of death, graft failure, and re-transplantation, were compared by donor COVID-19 status. RESULTS: Of 967 COVID-19(+) potential donors, 19.3% (n = 187) were used for HT compared to 26.7% (n = 6277) of COVID-19(-) donors (p < 0.001). Transplanted COVID-19(+) vs COVID-19(-) donors were younger, but otherwise were similar. Recipients of hearts from COVID-19+ vs COVID-19(-) donors less frequently received pre-HT inotropes (24.1% vs 31.7%, p = 0.023) and ventricular assist device therapy (29.7% vs 36.8%, p = 0.040). There were no significant differences in any post-HT outcome by donor COVID-19 status, including the primary composite outcome at 90 days (5.4% vs 5.6%, p = 0.91). Among COVID-19(+) donors, the presence of a subsequent negative test prior to transplant was not associated with posttransplant outcomes. CONCLUSIONS: Our results suggest that carefully selected COVID-19 positive donors may be used for HT with no difference in short-term post-transplant outcomes. Additional data regarding donor and recipient treatments and impact of vaccination should be collected to better inform our use of organs from COVID(+) donors.

Noninvasive Physiologic Assessment of Cardiac Allograft Vasculopathy Is Prognostic for Post-Transplant Events.

BACKGROUND: Cardiac allograft vasculopathy (CAV) causes impaired blood flow in both epicardial coronary arteries and the microvasculature. A leading cause of post-transplant mortality, CAV affects 50% of heart transplant recipients within 10 years of heart transplant. OBJECTIVES: This analysis examined the outcomes of heart transplant recipients with reduced myocardial blood flow reserve (MBFR) and microvascular CAV detected by 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging. METHODS: A total of 181 heart transplant recipients who underwent PET to assess for CAV were included with a median follow-up of 4.7 years. Patients were classified into 2 groups according to the total MBFR: >2.0 and ≤2.0. Microvascular CAV was defined as no epicardial CAV detected by PET and/or coronary angiography, but with an MBFR ≤2.0 by PET. RESULTS: In total, 71 (39%) patients had an MBFR ≤2.0. Patients with an MBFR ≤2.0 experienced an increased risk for all outcomes: 7-fold increase in death or retransplantation (HR: 7.05; 95% CI: 3.2-15.6; P < 0.0001), 12-fold increase in cardiovascular death (HR: 12.0; 95% CI: 2.64-54.12; P = 0.001), and 10-fold increase in cardiovascular hospitalization (HR: 10.1; 95% CI: 3.43-29.9; P < 0.0001). The 5-year mean survival was 302 days less than those with an MBFR >2.0 (95% CI: 260.2-345.4 days; P < 0.0001). Microvascular CAV (adjusted HR: 3.86; 95% CI: 1.58-9.40; P = 0.003) was independently associated with an increased risk of death or retransplantation. CONCLUSIONS: Abnormal myocardial blood flow reserve, even in the absence of epicardial CAV, identifies patients at a high risk of death or retransplantation. Measures of myocardial blood flow provide prognostic information in addition to traditional CAV assessment.

Evolving Characteristics of Heart Transplantation Donors and Recipients: JACC Focus Seminar.

Although the burden of end-stage heart failure continues to increase, the number of available organs for heart transplantation (HT) remains inadequate. The HT community has been challenged to find ways to expand the number of donor hearts available. Recent advances include use of hearts from donors infected with hepatitis C virus as well as other previously underutilized donors, including those with left ventricular dysfunction, of older age, and with a history of cocaine use. Concurrently, emerging trends in HT surgery include donation after circulatory death, ex vivo normothermic heart perfusion, and controlled hypothermic preservation, which may enable procurement of organs from farther distances and prevent early allograft dysfunction. Contemporary HT recipients have also evolved in light of the 2018 revision to the U.S. heart allocation policy. This focus seminar discusses recent trends in donor and recipient phenotypes and management strategies for successful HT, as well as evolving areas and future directions.

COVID-19 therapeutics and outcomes among solid organ transplant recipients during the Omicron BA.1 era.

Treatment outcomes associated with the use of novel COVID-19 therapeutics in solid organ transplant recipients (SOTR) are not well described in the literature. The objective of this analysis was to characterize 30-day hospitalization and other key secondary endpoints experienced by outpatient SOTR with mild-moderate COVID-19 treated with nirmatrelvir/ritonavir (NR), sotrovimab, or no SARS-CoV-2 specific treatment. This IRB-approved, retrospective study included 154 SOTR with a documented positive SARS-CoV-2 infection between December 16, 2021 and January 19, 2022 (a predominant Omicron BA.1 period in New York City). Patients who received NR (N = 28) or sotrovimab (N = 51) experienced a lower rate of 30-day hospitalization or death as compared to those who received no specific treatment (N = 75) (p = .009). A total of three deaths occurred, all among patients who initially received no specific treatment prior to hospitalization. These results suggest a role for SARS-CoV-2 specific agents in the treatment of SOTR with COVID-19, and that there does not appear to be any difference in effectiveness when comparing NR versus sotrovimab.

Vaccines, Antibodies and Donors: Varying Attitudes and Policies Surrounding COVID-19 and Heart Transplantation.

INTRODUCTION: There are varied opinions in the United States regarding many aspects of care related to COVID-19. The purpose of this study was to examine the opinions of health care personnel and the policies of heart transplant centers concerning practices for the prevention and treatment of COVID-19 in donors and recipients of heart transplants. METHODS: Two anonymous, electronic web-based surveys were developed: 1 was administered to health care personnel through a mailing list maintained by the Heart Failure Society of America (HFSA); another was administered to U.S. medical adult and pediatric heart transplant (HT) program directors. Individual and group e-mails were sent with an embedded link to the respective surveys in February 2022. RESULTS: A total of 176 individuals (8.6%) responded to the survey administered through the HFSA. Of medical directors of transplant programs, 78 (54% response rate) completed a separate survey on their centers' policies. Although 95% (n = 167) of individuals indicated vaccination against COVID-19 should be required prior to HT, only 67% (n = 52) of centers mandated that practice. Similarly, 61% of individuals thought vaccination should be required prior to HT for caregivers, but only 13% of transplant centers mandated caregiver vaccination. Of the centers, 63% reported considering donors despite histories of recent COVID-19 infection (within 3 months), and 47% considered donors with current positive polymerase chain reaction tests. Regarding post-transplant care, only 22% of programs routinely measured antibodies to COVID-19, and 71% used tixagevimab/cilgavimab (Evusheld) for pre-exposure prophylaxis. CONCLUSIONS: There were significant differences between individual preferences and centers' practices with respect to COVID-19 management of candidates for and recipients of HT. Additionally, there was wide variation in policies among centers, reflecting the need for further study to inform consistent guidance and recommendations across centers to optimize equitable care for this high-risk patient population.

The Prevalence of Palliative Care Consultation in Deceased COVID-19 Patients and Its Association with End-of-Life Care.

Background: During the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City, COVID-19 hospitalization was associated with high mortality. It is unknown how palliative care was utilized in this context. Objectives: To describe the frequency of palliative care consultation and its association with end-of-life care for deceased patients with COVID-19. Methods: Adults who were admitted to our institution between February 23, 2020, and April 21, 2020, and died from COVID-19 were included. The primary outcome was the frequency of palliative care consultation. Secondary analyses included the association of palliative care consultation with code status at the time of death, life-sustaining treatments, mechanical ventilation, invasive procedures, intensive care unit (ICU) admissions, and length of hospital stay. Results: The 203 patients were 61% male with median age 76 (interquartile range [IQR] 67-84) years. Palliative care was consulted for 113 patients (56%). At baseline, they were less independent in instrumental activities of daily living (28 patients, 26.1%, vs. 47 patients, 49.0%, p < 0.01) and had more do-not-resuscitate orders (35 patients, 32.7%, vs. 11 patients, 11.5%, p < 0.01). Palliative care consultation was associated with fewer invasive procedures (0, IQR 0-2, vs. 2, IQR 0-3, p < 0.01), less mechanical ventilation (32 patients, 29.9% vs. 65 patients, 67.7%, p < 0.01), and fewer ICU admissions (33 patients, 30.8% vs. 69 patients, 71.9%, p < 0.01). Palliative care was associated with shorter ICU stays (0 days, IQR 0-4, vs. 4 days, IQR 0-12, p < 0.01), whereas hospital stays did not differ significantly (8 days, IQR 5-12.5, vs. 10 days, IQR 5-16.3, p = 0.15). Conclusion: Palliative care was consulted for roughly half of deceased patients with COVID-19 and those patients were less likely to undergo invasive procedures or life-sustaining treatments and spent less time in the ICU at the end of life.

Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19.

The coronavirus disease 2019 (COVID-19) can result in a hyperinflammatory state, leading to acute respiratory distress syndrome (ARDS), myocardial injury, and thrombotic complications, among other sequelae. Statins, which are known to have anti-inflammatory and antithrombotic properties, have been studied in the setting of other viral infections, but their benefit has not been assessed in COVID-19. This is a retrospective analysis of patients admitted with COVID-19 from February 1st through May 12th, 2020 with study period ending on June 11th, 2020. Antecedent statin use was assessed using medication information available in the electronic medical record. We constructed a multivariable logistic regression model to predict the propensity of receiving statins, adjusting for baseline sociodemographic and clinical characteristics, and outpatient medications. The primary endpoint includes in-hospital mortality within 30 days. A total of 2626 patients were admitted during the study period, of whom 951 (36.2%) were antecedent statin users. Among 1296 patients (648 statin users, 648 non-statin users) identified with 1:1 propensity-score matching, statin use is significantly associated with lower odds of the primary endpoint in the propensity-matched cohort (OR 0.47, 95% CI 0.36-0.62, p < 0.001). We conclude that antecedent statin use in patients hospitalized with COVID-19 is associated with lower inpatient mortality.

Gender Differences in Publication Authorship During COVID-19: A Bibliometric Analysis of High-Impact Cardiology Journals.

Background The purpose of this study was to examine gender differences in authorship of manuscripts in select high-impact cardiology journals during the early coronavirus disease 2019 (COVID-19) pandemic. Methods and Results All manuscripts published between March 1, 2019 to June 1, 2019 and March 1, 2020 to June 1, 2020 in 4 high-impact cardiology journals (Journal of the American College of Cardiology, Circulation, JAMA Cardiology, and European Heart Journal) were identified using bibliometric data. Authors' genders were determined by matching first name with predicted gender using a validated multinational database (Genderize.io) and manual adjudication. Proportions of women and men first, co-first, senior, and co-senior authors, manuscript types, and whether the manuscript was COVID-19 related were recorded. In 2019, women were first authors of 176 (22.3%) manuscripts and senior authors of 99 (15.0%) manuscripts. In 2020, women first authored 230 (27.4%) manuscripts and senior authored 138 (19.3%) manuscripts. Proportions of woman first and senior authors were significantly higher in 2020 compared with 2019. Women were more likely to be first authors if the manuscript's senior author was a woman (33.8% for woman first/woman senior versus 23.4% for woman first/man senior; P<0.001). Women were less likely to be first authors of COVID-19-related original research manuscripts (P=0.04). Conclusions Representation of women as key authors of manuscripts published in major cardiovascular journals increased during the early COVID-19 pandemic compared with similar months in 2019. However, women were significantly less likely to be first authors of COVID-19-related original research manuscripts. Future investigation into the gender-disparate impacts of COVID-19 on academic careers is critical.

Admission Cardiac Diagnostic Testing with Electrocardiography and Troponin Measurement Prognosticates Increased 30-Day Mortality in COVID-19.

Background Cardiovascular involvement in coronavirus disease 2019 (COVID-19) is common and leads to worsened mortality. Diagnostic cardiovascular studies may be helpful for resource appropriation and identifying patients at increased risk for death. Methods and Results We analyzed 887 patients (aged 64±17 years) admitted with COVID-19 from March 1 to April 3, 2020 in New York City with 12 lead electrocardiography within 2 days of diagnosis. Demographics, comorbidities, and laboratory testing, including high sensitivity cardiac troponin T (hs-cTnT), were abstracted. At 30 days follow-up, 556 patients (63%) were living without requiring mechanical ventilation, 123 (14%) were living and required mechanical ventilation, and 203 (23%) had expired. Electrocardiography findings included atrial fibrillation or atrial flutter (AF/AFL) in 46 (5%) and ST-T wave changes in 306 (38%). 27 (59%) patients with AF/AFL expired as compared to 181 (21%) of 841 with other non-life-threatening rhythms (P<0.001). Multivariable analysis incorporating age, comorbidities, AF/AFL, QRS abnormalities, and ST-T wave changes, and initial hs-cTnT ≥20 ng/L showed that increased age (HR 1.04/year), elevated hs-cTnT (HR 4.57), AF/AFL (HR 2.07), and a history of coronary artery disease (HR 1.56) and active cancer (HR 1.87) were associated with increased mortality. Conclusions Myocardial injury with hs-cTnT ≥20 ng/L, in addition to cardiac conduction perturbations, especially AF/AFL, upon hospital admission for COVID-19 infection is associated with markedly increased risk for mortality than either diagnostic abnormality alone.

Indications for and Findings on Transthoracic Echocardiography in COVID-19.

BACKGROUND: Despite growing evidence of cardiovascular complications associated with coronavirus disease 2019 (COVID-19), there are few data regarding the performance of transthoracic echocardiography (TTE) and the spectrum of echocardiographic findings in this disease. METHODS: A retrospective analysis was performed among adult patients admitted to a quaternary care center in New York City between March 1 and April 3, 2020. Patients were included if they underwent TTE during the hospitalization after a known positive diagnosis for COVID-19. Demographic and clinical data were obtained using chart abstraction from the electronic medical record. RESULTS: Of 749 patients, 72 (9.6%) underwent TTE following positive results on severe acute respiratory syndrome coronavirus-2 polymerase chain reaction testing. The most common clinical indications for TTE were concern for a major acute cardiovascular event (45.8%) and hemodynamic instability (29.2%). Although most patients had preserved biventricular function, 34.7% were found to have left ventricular ejection fractions ≤ 50%, and 13.9% had at least moderately reduced right ventricular function. Four patients had wall motion abnormalities suggestive of stress-induced cardiomyopathy. Using Spearman rank correlation, there was an inverse relationship between high-sensitivity troponin T and left ventricular ejection fraction (ρ = -0.34, P = .006). Among 20 patients with prior echocardiograms, only two (10%) had new reductions in LVEF of >10%. Clinical management was changed in eight individuals (24.2%) in whom TTE was ordered for concern for acute major cardiovascular events and three (14.3%) in whom TTE was ordered for hemodynamic evaluation. CONCLUSIONS: This study describes the clinical indications for use and diagnostic performance of TTE, as well as findings seen on TTE, in hospitalized patients with COVID-19. In appropriately selected patients, TTE can be an invaluable tool for guiding COVID-19 clinical management.

The Prognostic Value of Electrocardiogram at Presentation to Emergency Department in Patients With COVID-19.

OBJECTIVE: To study whether combining vital signs and electrocardiogram (ECG) analysis can improve early prognostication. METHODS: This study analyzed 1258 adults with coronavirus disease 2019 who were seen at three hospitals in New York in March and April 2020. Electrocardiograms at presentation to the emergency department were systematically read by electrophysiologists. The primary outcome was a composite of mechanical ventilation or death 48 hours from diagnosis. The prognostic value of ECG abnormalities was assessed in a model adjusted for demographics, comorbidities, and vital signs. RESULTS: At 48 hours, 73 of 1258 patients (5.8%) had died and 174 of 1258 (13.8%) were alive but receiving mechanical ventilation with 277 of 1258 (22.0%) patients dying by 30 days. Early development of respiratory failure was common, with 53% of all intubations occurring within 48 hours of presentation. In a multivariable logistic regression, atrial fibrillation/flutter (odds ratio [OR], 2.5; 95% CI, 1.1 to 6.2), right ventricular strain (OR, 2.7; 95% CI, 1.3 to 6.1), and ST segment abnormalities (OR, 2.4; 95% CI, 1.5 to 3.8) were associated with death or mechanical ventilation at 48 hours. In 108 patients without these ECG abnormalities and with normal respiratory vitals (rate <20 breaths/min and saturation >95%), only 5 (4.6%) died or required mechanical ventilation by 48 hours versus 68 of 216 patients (31.5%) having both ECG and respiratory vital sign abnormalities. CONCLUSION: The combination of abnormal respiratory vital signs and ECG findings of atrial fibrillation/flutter, right ventricular strain, or ST segment abnormalities accurately prognosticates early deterioration in patients with coronavirus disease 2019 and may assist with patient triage.

Trends in US Heart Transplant Waitlist Activity and Volume During the Coronavirus Disease 2019 (COVID-19) Pandemic.

IMPORTANCE: Solid organ transplants have declined significantly during the coronavirus disease (COVID-19) pandemic in the US. Limited data exist regarding changes in heart transplant (HT). OBJECTIVE: To describe national and regional trends in waitlist inactivations, waitlist additions, donor recovery, and HT volume during COVID-19. DESIGN, SETTING, AND PARTICIPANTS: This descriptive cross-sectional study used publicly available data from the United Network for Organ Sharing and US Centers for Disease Control and Prevention, using 8 prespecified United Network for Organ Sharing regions. Adult (18 years or older) HT candidates listed and deceased donors recovered between January 19 to May 9, 2020. EXPOSURES: COVID-19 pandemic. MAIN OUTCOMES AND MEASURES: Changes in waitlist inactivations, waitlist additions, deceased donor recovery, and transplant volumes from the pre-COVID-19 (January 19-March 15, 2020) to the COVID-19 era (March 15-May 9, 2020). Density mapping and linear regression with interrupted time series analysis were used to characterize changes over time and changes by region. RESULTS: During the COVID-19 era, there were 600 waitlist inactivations compared with 343 during the pre-COVID era (75% increase). Waitlist additions decreased from 637 to 395 (37% reduction). These changes were most profound in the Northeast and Great Lakes regions with high rates of COVID-19. Deceased donor recovery decreased by 26% from 1878 to 1395; the most significant decrease occurred in the North Midwest despite low COVID-19 prevalence. Heart transplant volumes were significantly reduced across all regions except the Northwest. The largest decrease was seen in the Northeast where COVID-19 case rates were highest. From the pre-COVID-19 era to the COVID-19 era, there was significant regional variation in waitlist additions (eg, 69% decrease in the Northeast vs 8.5% increase in the South Midwest; P < .001) and deceased donor recovery (eg, 41% decrease in North Midwest vs 16% decrease in South Midwest; P = .02). CONCLUSIONS AND RELEVANCE: Heart transplant volumes have been significantly reduced in recent months, even in regions with a lower prevalence of COVID-19 cases. This has been accompanied by increased waitlist inactivations, decreased waitlist additions, and decreased donor recovery. Future studies are needed to determine if the COVID-19 pandemic is associated with changes in waitlist mortality.

Considerations for Heart Failure Care During the COVID-19 Pandemic.

The coronavirus-2019 (COVID-19) infection pandemic has affected the care of patients with heart failure (HF) who have contracted COVID-19 as well as those without COVID-19 who have been impacted by the restructuring of health care delivery. Patients with HF and other cardiovascular comorbidities are at risk for severe disease and complications of infection. Similarly, COVID-19 has been demonstrated to cause myocarditis and may be implicated in new-onset cardiomyopathy. During this pandemic, special considerations are needed for patients with advanced HF, including those supported by durable left ventricular assist devices (LVADs) and heart transplant recipients. The purpose of this review is to summarize emerging data regarding the development of HF secondary to COVID-19 infection in patients with advanced HF and the implications of the pandemic for care of uninfected patients with HF.