Arrhythmia and Survival Outcomes Among Black Patients and White Patients With a Primary Prevention Defibrillator.

BACKGROUND: Black Americans have a higher risk of nonischemic cardiomyopathy (NICM) than White Americans. We aimed to evaluate differences in the risk of tachyarrhythmias among patients with an implantable cardioverter-defibrillator (ICD). METHODS: The study population comprised 3895 ICD recipients in the United States enrolled in primary prevention ICD trials. Outcome measures included ventricular tachyarrhythmia (VTA), atrial tachyarrhythmia (ATA), ICD therapies, VTA burden (using Andersen-Gill recurrent event analysis), death, and the predicted benefit of the ICD. All events were adjudicated blindly. Outcomes were compared between self-reported Black patients versus White patients with cardiomyopathy (ischemic and NICM). RESULTS: Black patients were more likely to be female (35% versus 22%) and younger (57±12 versus 62±12 years) with a higher frequency of comorbidities. In NICM, Black patients had a higher rate of first VTA, fast VTA, ATA, and appropriate and inappropriate ICD therapy (VTA ≥170 bpm, 32% versus 20%; VTA ≥200 bpm, 22% versus 14%; ATA, 25% versus 12%; appropriate therapy, 30% versus 20%; and inappropriate therapy, 25% versus 11%; P<0.001 for all). Multivariable analysis showed that Black patients with NICM experienced a higher risk of all types of arrhythmia or ICD therapy (VTA ≥170 bpm, hazard ratio [HR] 1.71; VTA ≥200 bpm, HR 1.58; ATA, HR 1.87; appropriate therapy, HR 1.62; inappropriate therapy, HR 1.86; P≤0.01 for all), higher burden of tachyarrhythmias or therapies (VTA, HR 1.84; appropriate therapy, HR 1.84; P<0.001 for both), and a higher risk of death (HR 1.92; P=0.014). In contrast, in ischemic cardiomyopathy, the risk of all types of tachyarrhythmia, ICD therapy, or death was similar between Black patients and White patients. Both Black patients and White patients derived a significant and similar benefit from ICD implantation. CONCLUSIONS: Among patients with NICM with an ICD for primary prevention, Black patients compared with White patients had a high risk and burden of VTA, ATA, and ICD therapies with a lower survival rate. Nevertheless, the overall benefit of the ICD was maintained and was similar to that of White patients.

Heart Failure Subtypes and Cardiomyopathies in Women.

Heart failure affects over 2.6 million women and 3.4 million men in the United States with known sex differences in epidemiology, management, response to treatment, and outcomes across a wide spectrum of cardiomyopathies that include peripartum cardiomyopathy, hypertrophic cardiomyopathy, stress cardiomyopathy, cardiac amyloidosis, and sarcoidosis. Some of these sex-specific considerations are driven by the cellular effects of sex hormones on the renin-angiotensin-aldosterone system, endothelial response to injury, vascular aging, and left ventricular remodeling. Other sex differences are perpetuated by implicit bias leading to undertreatment and underrepresentation in clinical trials. The goal of this narrative review is to comprehensively examine the existing literature over the last decade regarding sex differences in various heart failure syndromes from pathophysiological insights to clinical practice.

Outcomes of heart transplant recipients with prior left ventricular assist device associated stroke.

BACKGROUND: Left ventricular assist devices (LVADs) improve survival in patients with end-stage heart failure but are associated with ischemic stroke and intracranial hemorrhage (ICH). The impact of LVAD-associated stroke on transplant candidacy and outcomes has not been characterized. METHODS: Adult patients undergoing LVAD implantation at Cleveland Clinic between 2004 to 2021 were reviewed and patients who developed ischemic stroke or ICH were identified. Post-transplant survival analysis was performed between patients with LVAD-associated stroke vs. without. RESULTS: 917 patients had an LVAD implantation of whom 244 (median age 57, 79% male) underwent subsequent transplant including 25 with prior LVAD-associated stroke. The 1- and 2-year survival after transplant in patients with LVAD-associated stroke were 100% and 95% respectively, compared with 92% and 90% in patients without stroke (p=0.156; p=0.323) Similarly, there was no difference in stroke incidence at 1- and 2 years after transplant between patients with LVAD-associated stroke (4% and 5%) and those without prior stroke (5% and 6%, p = 0.884; p=0.744). CONCLUSIONS: In this single-center retrospective study, patients with LVAD-associated stroke were significantly less likely to undergo heart transplant, but those who underwent heart transplant had similar post-transplant outcomes as patients without history of LVAD-associated stroke. Given the similar outcomes seen in this population, history of LVAD-associated stroke should not be viewed as an absolute contraindication to subsequent heart transplant.

Genetic and Phenotypic Landscape of Peripartum Cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) occurs in ≈1:2000 deliveries in the United States and worldwide. The genetic underpinnings of PPCM remain poorly defined. Approximately 10% of women with PPCM harbor truncating variants in TTN (TTNtvs). Whether mutations in other genes can predispose to PPCM is not known. It is also not known if the presence of TTNtvs predicts clinical presentation or outcomes. Nor is it known if the prevalence of TTNtvs differs in women with PPCM and preeclampsia, the strongest risk factor for PPCM. METHODS: Women with PPCM were retrospectively identified from several US and international academic centers, and clinical information and DNA samples were acquired. Next-generation sequencing was performed on 67 genes, including TTN, and evaluated for burden of truncating and missense variants. The impact of TTNtvs on the severity of clinical presentation, and on clinical outcomes, was evaluated. RESULTS: Four hundred sixty-nine women met inclusion criteria. Of the women with PPCM, 10.4% bore TTNtvs (odds ratio=9.4 compared with 1.2% in the reference population; Bonferroni-corrected P [P*]=1.2×10-46). We additionally identified overrepresentation of truncating variants in FLNC (odds ratio=24.8, P*=7.0×10-8), DSP (odds ratio=14.9, P*=1.0×10-8), and BAG3 (odds ratio=53.1, P*=0.02), genes not previously associated with PPCM. This profile is highly similar to that found in nonischemic dilated cardiomyopathy. Women with TTNtvs had lower left ventricular ejection fraction on presentation than did women without TTNtvs (23.5% versus 29%, P=2.5×10-4), but did not differ significantly in timing of presentation after delivery, in prevalence of preeclampsia, or in rates of clinical recovery. CONCLUSIONS: This study provides the first extensive genetic and phenotypic landscape of PPCM and demonstrates that predisposition to heart failure is an important risk factor for PPCM. The work reveals a degree of genetic similarity between PPCM and dilated cardiomyopathy, suggesting that gene-specific therapeutic approaches being developed for dilated cardiomyopathy may also apply to PPCM, and that approaches to genetic testing in PPCM should mirror those taken in dilated cardiomyopathy. Last, the clarification of genotype/phenotype associations has important implications for genetic counseling.

The Impact of Health Care Disparities on Patients With Heart Failure.

Heart failure (HF) remains a condition associated with high morbidity, mortality, and associated costs. Although the number of medical and device-based therapies available to treat HF are expanding at a remarkable rate, disparities in the risk for incident HF and treatments delivered to patients are also of growing concern. These disparities span across racial and ethnic groups, socioeconomic status, and apply across the spectrum of HF from stage A to stage D. The complexity of HF risk and treatment is further impacted by the number of patients who experience the downstream impact of social determinants of health. The purpose of this document is to highlight the known health care disparities that exist in the care of patients with HF and to provide a context for how clinicians and researchers should assess both biological and social determinants of HF risk in vulnerable populations. Furthermore, this document provides a framework for future steps that can be used to help diminish inequalities in access and clinical outcomes over time, and offer solutions to help decrease disparities within HF care.

Increased Opportunities for Transplantation for Women in the New Heart Allocation System.

BACKGROUND: Historically, women have had less access to advanced heart failure therapies, including temporary and permanent mechanical circulatory support and heart transplantation (HT), with worse waitlist and post-transplant survival compared with men. This study evaluated for improvement in sex differences across all phases of HT in the 2018 allocation system. METHODS AND RESULTS: The United Network for Organ Sharing registry was queried to identify adult patients (≥18 years) listed for HT from October 18, 2016, to October 17, 2018 (old allocation), and from October 18, 2018, to October 18, 2020 (new allocation). The outcomes of interest included waitlist survival, pretransplant use of temporary and durable mechanical circulatory support, rates of HT, and post-transplant survival. There were 15,629 patients who were listed for HT and included in this analysis; 7745 (2039 women, 26.3%) in the new and 7875 patients (2074 women, 26.3%) in the old allocation system. When compared with men in the new allocation system, women were more likely to have lower priority United Network for Organ Sharing status at time of transplant, and less likely to be supported by an intra-aortic balloon pump (27.1% vs 32.2%, P < .001), with no difference in the use of venoarterial extracorporeal membrane oxygenation (5.5% vs 6.3%, P = .28). Despite these findings, when transplantation was viewed in the context of risk for death or delisting, the cumulative incidence of transplant within 6 months of listing was higher in women than men in the new allocation system (62.4% vs 54.9%, P < .001) with no differences in post-transplant survival. When comparing women in the old with the new allocation system, the distance traveled for organ procurement was 187.5 ± 207.0 miles vs 272.8 ± 233.7 miles (P < .001). CONCLUSIONS: Although the use of temporary mechanical circulatory support in women remains lower than in men in the new allocation system, more women are being transplanted with comparable waitlist and post-transplant outcomes as men. Broader sharing may be making its greatest impact on improving transplant opportunities for women.

Racial and Ethnic Disparities Persist in the Current Era of Pediatric Heart Transplantation.

BACKGROUND: Previous studies have demonstrated that children in the United States who were of racial and ethnic minorities have inferior waitlist and post-heart transplant (HT) outcomes. Whether these disparities still exist in the contemporary era of increased ventricular assist device use remains unknown. METHODS: All children (age <18 years) in the Scientific Registry of Transplant Recipients database listed for HT from December 2011 to February 2019 were included and were separated into 5 races/ethnicities: Caucasian, African American, Hispanic, Asian, and Other. Differences in clinical characteristics and survival among children of different racial/ethnic groups were compared at listing and at HT. RESULTS: The waitlist cohort consisted of 2134 (52.2%) Caucasian, 840 (20.5%) African American, 808 (19.8%) Hispanic, 161 (3.9%) Asian, and 146 children of Other races (3.6%). At listing, Asian children mostly had cardiomyopathy (70.8%), whereas Caucasian children had congenital heart disease (58.7%). African American children were most likely to be listed as Status 1A and to have renal dysfunction and hypoalbuminemia at listing. African American and Hispanic children were most likely to be on Medicaid. After multivariable analysis, it was found that only African American children were at increased risk for waitlist mortality as compared to Caucasian children (adjusted hazard ratio = 1.25; P = 0.029). Post-HT, there were no disparities in early and midterm graft survival among groups, but African American children had increased numbers of rejection episodes compared to Caucasian and Hispanic children. CONCLUSION: African American children continue to experience increased waitlist mortality and have increased rejection episodes post-HT. Studies exploring barriers to health care access and implicit bias as reasons for these disparities need to be conducted.

Dynamic Assessment of Pulmonary Artery Pulsatility Index Provides Incremental Risk Assessment for Early Right Ventricular Failure After Left Ventricular Assist Device.

BACKGROUND: The pulmonary artery pulsatility index (PAPi) has been studied to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation, but only as a single time point before LVAD implantation. Multiple clinical factors and therapies impact RV function in pre-LVAD patients. Thus, we hypothesized that serial PAPi measurements during cardiac intensive care unit (CICU) optimization before LVAD implantation would provide incremental risk stratification for early RVF after LVAD implantation. METHODS AND RESULTS: Consecutive patients who underwent sequential pulmonary artery catherization with cardiac intensive care optimization before durable LVAD implantation were included. Serial hemodynamics were reviewed retrospectively across the optimization period. The optimal PAPi was defined by the initial PAPi + the PAPi at optimized hemodynamics. RVF was defined as need for a right ventricular assist device or prolonged inotrope use (>14 days postoperatively). Patients with early RVF had significantly lower mean optimal PAPi (3.5 vs 7.5, P < .001) compared with those who did not develop RVF. After adjusting for established risk factors of early RVF after LVAD implantation, the optimal PAPi was independently and incrementally associated with early RVF after LVAD implantation (odds ratio 0.64, 95% confidence interval 0.532-0.765, P < .0001). CONCLUSIONS: Optimal PAPi achieved during medical optimization before LVAD implantation provides independent and incremental risk stratification for early RVF, likely identifying dynamic RV reserve.

Disparities in heart and lung transplantation.

PURPOSE OF REVIEW: Cardiothoracic transplantation is the definitive therapy for end-stage heart and lung disease. In service to this population, disparities in access and care must be simultaneously understood and addressed. RECENT FINDINGS: There are sex, race, geographic, age, and underlying disease disparities in both heart and lung transplantation. Women have reduced waitlist survival but improved posttransplant survival when compared with men for both heart and lung transplantation. Black patients have worse outcome compared with other races postheart transplant. Geographic disparities impact the likelihood of receiving heart or lung transplant and the growing number of patients with advanced age seeking transplant complicates discussions on survival benefit. Finally, underlying disease has affected outcomes for both heart and lung transplant and now are incorporated into the allocation system. SUMMARY: Though heart and lung transplantation have several existing disparities, it remains to be seen how advancements in medical technology, changes in donor organ allocation policies, and growing experience in patient selection will impact these concerns.

Sex Differences in Advanced Heart Failure Therapies.

This in-depth review of sex differences in advanced heart failure therapy summarizes the existing literature on implantable cardioverter defibrillators, biventricular pacemakers, mechanical circulatory support, and transplantation with a focus on utilization, efficacy/clinical effectiveness, adverse events, and controversies. One will learn about the controversies regarding efficacy/clinical effectiveness of implantable cardioverter defibrillators and understand why these devices should be implanted in women even if there are sex differences in appropriate shocks. Individuals will learn about the sex differences with biventricular pacemakers with respect to ventricular remodeling and reduction in heart failure hospitalizations/mortality, as well as, possible mechanisms. We will demonstrate sex differences in heart transplantation and waitlist survival. Despite similar survival for women and men with left ventricular assist devices, there are sex differences in adverse events. These devices do successfully bridge women and men to transplant, yet women are less likely than men to have a left ventricular assist at time of listing and time of transplantation. Finally, one will learn about the concerns regarding poor outcome for men who receive female donor hearts and discover this may not be due to sex, but rather size. More research is needed to better understand sex differences and further improve advanced heart failure therapy for both women and men.

Successful management of COVID-19 and associated coagulopathy in a patient with durable left ventricular assist device.

Patients with durable left ventricular assist devices pose special problems for management in the setting of COVID-19 infection. We describe the successful management of a 44-year-old man with severe COVID-19 infection and HeartMate 3 left ventricular assist device. His course was complicated by cytokine storm and COVID-19-associated coagulopathy. We describe our institutional protocol for managing COVID-19 infection in patients on mechanical circulatory support, focusing on the need for a thoughtful, multidisciplinary approach.

Variables of importance in the Scientific Registry of Transplant Recipients database predictive of heart transplant waitlist mortality.

The prelisting variables essential for creating an accurate heart transplant allocation score based on survival are unknown. To identify these we studied mortality of adults on the active heart transplant waiting list in the Scientific Registry of Transplant Recipients database from January 1, 2004 to August 31, 2015. There were 33 069 candidates awaiting heart transplantation: 7681 UNOS Status 1A, 13 027 Status 1B, and 12 361 Status 2. During a median waitlist follow-up of 4.3 months, 5514 candidates died. Variables of importance for waitlist mortality were identified by machine learning using Random Survival Forests. Strong correlates predicting survival were estimated glomerular filtration rate (eGFR), serum albumin, extracorporeal membrane oxygenation, ventricular assist device, mechanical ventilation, peak oxygen capacity, hemodynamics, inotrope support, and type of heart disease with less predictive variables including antiarrhythmic agents, history of stroke, vascular disease, prior malignancy, and prior tobacco use. Complex interactions were identified such as an additive risk in mortality based on renal function and serum albumin, and sex-differences in mortality when eGFR >40 mL/min/1.73 m. Most predictive variables for waitlist mortality are in the current tiered allocation system except for eGFR and serum albumin which have an additive risk and complex interactions.

Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies.

Background Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin. Methods In 172 women with peripartum cardiomyopathy, we sequenced 43 genes with variants that have been associated with dilated cardiomyopathy. We compared the prevalence of different variant types (nonsense, frameshift, and splicing) in these women with the prevalence of such variants in persons with dilated cardiomyopathy and with population controls. Results We identified 26 distinct, rare truncating variants in eight genes among women with peripartum cardiomyopathy. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than that in a reference population of 60,706 persons (4.7%, P=1.3×10(-7)) but was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients [17%], P=0.81). Two thirds of identified truncating variants were in TTN, as seen in 10% of the patients and in 1.4% of the reference population (P=2.7×10(-10)); almost all TTN variants were located in the titin A-band. Seven of the TTN truncating variants were previously reported in patients with idiopathic dilated cardiomyopathy. In a clinically well-characterized cohort of 83 women with peripartum cardiomyopathy, the presence of TTN truncating variants was significantly correlated with a lower ejection fraction at 1-year follow-up (P=0.005). Conclusions The distribution of truncating variants in a large series of women with peripartum cardiomyopathy was remarkably similar to that found in patients with idiopathic dilated cardiomyopathy. TTN truncating variants were the most prevalent genetic predisposition in each disorder.

Heart Failure with Reduced Ejection Fraction in Women: Epidemiology, Outcomes, and Treatment.

There are millions of people affected by heart failure with reduced ejection fraction (HFrEF) as diagnosed with ejection fraction 40% or less by imaging. Established therapies have been proven through clinical trials on lifestyle interventions, medications, and devices for HFrEF to improve quality of life, heart function, and survival. Although there are more men than women suffering with HFrEF, there are no prospectively proven, sex-specific guideline therapies because women have been underrepresented in clinical trials. Current recommendations for medications in women with HFrEF are described in this article.

Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial.

BACKGROUND: The Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts. The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital. We aimed to assess the clinical outcomes of the Organ Care System compared with standard cold storage of human donor hearts for transplantation. METHODS: We did this prospective, open-label, multicentre, randomised non-inferiority trial at ten heart-transplant centres in the USA and Europe. Eligible heart-transplant candidates (aged >18 years) were randomly assigned (1:1) to receive donor hearts preserved with either the Organ Care System or standard cold storage. Participants, investigators, and medical staff were not masked to group assignment. The primary endpoint was 30 day patient and graft survival, with a 10% non-inferiority margin. We did analyses in the intention-to-treat, as-treated, and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT00855712. FINDINGS: Between June 29, 2010, and Sept 16, 2013, we randomly assigned 130 patients to the Organ Care System group (n=67) or the standard cold storage group (n=63). 30 day patient and graft survival rates were 94% (n=63) in the Organ Care System group and 97% (n=61) in the standard cold storage group (difference 2·8%, one-sided 95% upper confidence bound 8·8; p=0·45). Eight (13%) patients in the Organ Care System group and nine (14%) patients in the standard cold storage group had cardiac-related serious adverse events. INTERPRETATION: Heart transplantation using donor hearts adequately preserved with the Organ Care System or with standard cold storage yield similar short-term clinical outcomes. The metabolic assessment capability of the Organ Care System needs further study. FUNDING: TransMedics.

Infectious Myocarditis on FDG-PET Imaging Mimicking Sarcoidosis.

Cardiac positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) is often used for the diagnosis of cardiac involvement in sarcoidosis. Areas of segmental perfusion defects coupled with FDG uptake are considered to represent active inflammation. However, these findings may be associated with other inflammatory myocardial diseases. We describe a case of tuberculous myocarditis with imaging findings mimicking those found in cardiac sarcoidosis.

Early pandemic in-hospital outcomes and mortality risk factors in COVID-19 solid organ transplant patients.

Background: Solid organ transplant (SOT) recipients with COVID-19 have a higher risk of mortality than those without COVID-19. However, it is unclear how SOT patient outcomes compare to the general population without SOT who contract COVID-19. Methods: We used the National Inpatient Sample from January to December 2020 to investigate inpatient outcomes seen in SOT recipients after contracting COVID-19 compared to nontransplant patients. We identified our study sample using ICD-10 CM and excluded those <18 years of age and those with dual organ transplants. Inpatient outcomes were compared in SOT and non-SOT COVID cohorts, and we further evaluated predictors of mortality in the SOT with COVID population. Results: Out of the 1,416,445 COVID-19 admissions included in the study, 8315 (0.59%) were single SOT recipients. Our analysis that adjusted for multiple baseline characteristics and comorbidities demonstrated that COVID-19 in SOT patients was associated with higher rates of acute kidney injury (adjusted odds ratio [aOR] 2.34, 95% confidence interval [CI] 1.81-3.02, P < 0.01), lower rates of acute respiratory distress syndrome (aOR 0.68, 95% CI 0.54-0.85, P < 0.01), and similar rates of cardiac arrest, pulmonary embolism, circulatory shock, cerebrovascular events, and in-hospital mortality. Age >65 was associated with mortality in SOT patients. Conclusion: In this nationally representative sample, SOT patients presenting with COVID-19 experienced similar rates of mortality compared to those without SOT. SOT patients were more likely to develop acute kidney injury. Further research is needed to understand the complex relationship between transplant patient outcomes and COVID-19.

A comparison of quality-adjusted life years in older adults after heart transplantation versus long-term mechanical support: Findings from the SUSTAIN-IT study.

BACKGROUND: The quality-adjusted life year (QALY) measures disease burden and treatment, combining overall survival and health-related quality of life (HRQOL). We estimated QALYs in 3 groups of older patients (60-80 years) with heart failure (HF) who underwent heart transplantation (HT, with pre-transplant mechanical circulatory support [HT MCS] or HT without pre-transplant MCS [HT Non-MCS]) or long-term MCS (destination therapy). We also identified factors associated with gains in QALYs through 24 months follow-up. METHODS: Of 393 eligible patients enrolled (10/1/15-12/31/18) at 13 U.S. sites, 161 underwent HT (n = 68 HT MCS, n = 93 HT Non-MCS) and 144 underwent long-term MCS. Survival and HRQOL data were collected through 24 months. QALY health utilities were based on patient self-report of EQ-5D-3L dimensions. Mean-restricted QALYs were compared among groups using generalized linear models. RESULTS: For the entire cohort, mean age in years closest to surgery was 67 (standard deviation, SD: 4.7), 78% were male, and 83% were White. By 18 months post-surgery, sustained significant differences in adjusted average ± SD QALYs emerged across groups, with the HT Non-MCS group having the highest average QALYs (24-month window: HT Non-MCS = 22.58 ± 1.1, HT MCS = 19.53 ± 1.33, Long-term MCS = 19.49 ± 1.3, p = 0.003). At 24 months post-operatively, a lower gain in QALYs was associated with HT MCS, long-term MCS, a lower pre-operative LVEF, NYHA class III or IV before surgery, and an ischemic or other etiology of HF. CONCLUSIONS: Determination of QALYs may provide important information for policy makers and clinicians to consider regarding benefits of HT and long-term MCS as treatment options for older patients with HF.