Eligibility and Projected Benefits of Rapid Initiation of Quadruple Therapy for Newly Diagnosed Heart Failure.

BACKGROUND: U.S. nationwide estimates of the proportion of patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) eligible for quadruple medical therapy, and the associated benefits of rapid implementation, are not well characterized. OBJECTIVES: This study sought to characterize the degree to which patients newly diagnosed with HFrEF are eligible for quadruple medical therapy, and the projected benefits of in-hospital initiation. METHODS: Among patients hospitalized for newly diagnosed HFrEF in the Get With The Guidelines-Heart Failure registry from 2016 to 2023, eligibility criteria based on regulatory labeling, guidelines, and expert consensus documents were applied for angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitor therapies. Of those eligible, the projected effect of quadruple therapy on 12-month mortality was modeled using treatment effects from pivotal clinical trials utilized by the AHA/ACC/HFSA Guideline for the Management of Heart Failure, and compared with observed outcomes among patients treated with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blockers. RESULTS: Of 33,036 patients newly diagnosed with HFrEF, 27,158 (82%) were eligible for quadruple therapy, and 30,613 (93%) were eligible for ≥3 components. From 2021 to 2023, of patients eligible for quadruple therapy, 15.3% were prescribed quadruple therapy and 41.5% were prescribed triple therapy. Among Medicare beneficiaries eligible for quadruple therapy, 12-month incidence of mortality was 24.7% and HF hospitalization was 22.2%. Applying the relative risk reductions in clinical trials, complete implementation of quadruple therapy by time of discharge was projected to yield absolute risk reductions in 12-month mortality of 10.4% (number needed to treat = 10) compared with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blocker, and 24.8% (number needed to treat = 4) compared with no GDMT. CONCLUSIONS: In this nationwide U.S. cohort of patients hospitalized for newly diagnosed HFrEF, >4 of 5 patients were projected as eligible for quadruple therapy at discharge; yet, <1 in 6 were prescribed it. If clinical trial benefits can be fully realized, in-hospital initiation of quadruple medical therapy for newly diagnosed HFrEF would yield large absolute reductions in mortality.

Differences in Donor Heart Acceptance by Race and Gender of Patients on the Transplant Waiting List.

Importance: Barriers to heart transplant must be overcome prior to listing. It is unclear why Black men and women remain less likely to receive a heart transplant after listing than White men and women. Objective: To evaluate whether race or gender of a heart transplant candidate (ie, patient on the transplant waiting list) is associated with the probability of a donor heart being accepted by the transplant center team with each offer. Design, Setting, and Participants: This cohort study used the United Network for Organ Sharing datasets to identify organ acceptance with each offer for US non-Hispanic Black (hereafter, Black) and non-Hispanic White (hereafter, White) adults listed for heart transplant from October 18, 2018, through March 31, 2023. Exposures: Black or White race and gender (men, women) of a heart transplant candidate. Main Outcomes and Measures: The main outcome was heart offer acceptance by the transplant center team. The number of offers to acceptance was assessed using discrete time-to-event analyses, nonparametrically (stratified by race and gender) and parametrically. The hazard probability of offer acceptance for each offer was modeled using generalized linear mixed models adjusted for candidate-, donor-, and offer-level variables. Results: Among 159 177 heart offers with 13 760 donors, there were 14 890 candidates listed for heart transplant; 30.9% were Black, 69.1% were White, 73.6% were men, and 26.4% were women. The cumulative incidence of offer acceptance was highest for White women followed by Black women, White men, and Black men (P < .001). Odds of acceptance were less for Black candidates than for White candidates for the first offer (odds ratio [OR], 0.76; 95% CI, 0.69-0.84) through the 16th offer. Odds of acceptance were higher for women than for men for the first offer (OR, 1.53; 95% CI, 1.39-1.68) through the sixth offer and were lower for the 10th through 31st offers. Conclusions and Relevance: The cumulative incidence of heart offer acceptance by a transplant center team was consistently lower for Black candidates than for White candidates of the same gender and higher for women than for men. These disparities persisted after adjusting for candidate-, donor-, and offer-level variables, possibly suggesting racial and gender bias in the decision-making process. Further investigation of site-level decision-making may reveal strategies for equitable donor heart acceptance.

Racial and Ethnic Disparities in Ambulatory Heart Failure Ventricular Assist Device Implantation and Survival.

BACKGROUND: Durable left ventricular assist devices (VADs) improve survival in eligible patients, but allocation has been associated with patient race in addition to presumed heart failure (HF) severity. OBJECTIVES: This study sought to determine racial and ethnic differences in VAD implantation rates and post-VAD survival among patients with ambulatory HF. METHODS: Using the INTERMACS (Interagency Registry of Mechanically Assisted Circulatory Support) database (2012-2017), this study examined census-adjusted VAD implantation rates by race, ethnicity, and sex in patients with ambulatory HF (INTERMACS profile 4-7) using negative binomial models with quadratic effect of time. Survival was evaluated using Kaplan-Meier estimates and Cox models adjusted for clinically relevant variables and an interaction of time with race/ethnicity. RESULTS: VADs were implanted in 2,256 adult patients with ambulatory HF (78.3% White, 16.4% Black, and 5.3% Hispanic). The median age at implantation was lowest in Black patients. Implantation rates peaked between 2013 and 2015 before declining in all demographic groups. From 2012 to 2017, implantation rates overlapped for Black and White patients but were lower for Hispanic patients. Post-VAD survival was significantly different among the 3 groups (log rank P = 0.0067), with higher estimated survival among Black vs White patients (12-month survival: Black patients: 90% [95% CI: 86%-93%]; White patients: 82% [95% CI: 80%-84%]). Low sample size for Hispanic patients resulted in imprecise survival estimates (12-month survival: 85% [95% CI: 76%-90%]). CONCLUSIONS: Black and White patients with ambulatory HF had similar VAD implantation rates but rates were lower for Hispanic patients. Survival differed among the 3 groups, with the highest estimated survival at 12 months in Black patients. Given higher HF burden in minoritized populations, further investigation is needed to understand differences in VAD implantation rates in Black and Hispanic patients.

Nurturing Diverse Generations of the Medical Workforce for Success With Authenticity: An Association of Black Cardiologists' Roundtable.

The COVID-19 pandemic exposed the consequences of systemic racism in the United States with Black, Hispanic, and other racial and ethnic diverse populations dying at disproportionately higher rates than White Americans. Addressing the social and health disparities amplified by COVID-19 requires in part restructuring of the healthcare system, particularly the diversity of the healthcare workforce to better reflect that of the US population. In January 2021, the Association of Black Cardiologists hosted a virtual roundtable designed to discuss key issues pertaining to medical workforce diversity and to identify strategies aimed at improving racial and ethnic diversity in medical school, graduate medical education, faculty, and leadership positions. The Nurturing Diverse Generations of the Medical Workforce for Success with Authenticity roundtable brought together diverse stakeholders and champions of diversity and inclusion to discuss innovative ideas, solutions, and opportunities to address workforce diversification.

Assessing Heuristic Bias During Care for Patients Hospitalized for Heart Failure: Get With The Guidelines-Heart Failure.

BACKGROUND: Heuristic biases are increasingly recognized, and potentially modifiable, contributors to patient care and outcomes. Left digit bias is a cognitive bias where continuous variables are categorized by their left-most digit. The impact of this heuristic bias applied to patient age on quality of care in heart failure has not been explored. METHODS: We examined participants admitted from 2005 to 2021 in the Get With The Guidelines-Heart Failure registry. To create 2 naturally randomized groups, isolating the effect of left digit bias, we dichotomized patients into those discharged within 60 days prior to their 80th birthday (N=4238) and those discharged within 60 days after their 80th birthday (N=4329). We performed multivariable logistic regression to assess the association between discharge date relative to 80th birthday and several in-hospital quality metrics and in-hospital outcomes. Among Medicare participants (N=2759), we performed adjusted Cox regression to analyze the relationship between discharge date and risk of 1-year mortality or readmission. RESULTS: Among 8567 patients, 50.4% were female, 73% were non-Hispanic White, and 42.9% had an ejection fraction ≤40%. Discharge date relative to 80th birthday was not associated with numerous in-hospital quality metrics or in-hospital outcomes on unadjusted or adjusted logistic regression. Among Medicare beneficiaries, there was no association between discharge date and risk of mortality or readmission at 1-year postdischarge (hazard ratio, 1.03 [95% CI, 0.95-1.12]; P=0.52). CONCLUSIONS: In a large registry of patients hospitalized for heart failure, we did not detect a left digit bias' with respect to age at discharge, which resulted in differential quality of care or outcomes.

Representation matters: a call for inclusivity and equity in heart failure clinical trials.

The burden of heart failure remains substantial worldwide, and heart failure with reduced ejection fraction (HFrEF) affects approximately half of this population. Despite this global prevalence of HFrEF, the majority of contemporary clinical trials in HFrEF have underenrolled individuals from minoritized sex, gender, race, ethnicity, and socioeconomic groups. Moreover, significant disparities in access to HFrEF treatment and outcomes exist across these same strata. We provide a call to action for the inclusion of diverse populations in HFrEF clinical trials; catalogue several barriers to adequate representation in HFrEF clinical trials; and propose strategies to broaden inclusivity in future HFrEF trials.

Circulating microRNAs in cellular and antibody-mediated heart transplant rejection.

BACKGROUND: Noninvasive monitoring of heart allograft health is important to improve clinical outcomes. MicroRNAs (miRs) are promising biomarkers of cardiovascular disease and limited studies suggest they can be used to noninvasively diagnose acute heart transplant rejection. METHODS: The Genomic Research Alliance for Transplantation (GRAfT) is a multicenter prospective cohort study that phenotyped heart transplant patients from 5 mid-Atlantic centers. Patients who had no history of rejection after transplant were compared to patients with acute cellular rejection (ACR) or antibody-mediated rejection (AMR). Small RNA sequencing was performed on plasma samples collected at the time of an endomyocardial biopsy. Differential miR expression was performed with adjustment for clinical covariates. Regression was used to develop miR panels with high diagnostic accuracy for ACR and AMR. These panels were then validated in independent samples from GRAfT and Stanford University. Receiver operating characteristic curves were generated and area under the curve (AUC) statistics calculated. Distinct ACR and AMR clinical scores were developed to translate miR expression data for clinical use. RESULTS: The GRAfT cohort had a median age of 52 years, with 35% females and 45% Black patients. Between GRAfT and Stanford, we included 157 heart transplant patients: 108 controls and 49 with rejection (50 ACR and 38 AMR episodes). After differential miR expression and regression analysis, we identified 12 miRs that accurately discriminate ACR and 17 miRs in AMR. Independent validation of the miR panels within GRAfT led to an ACR AUC 0.92 (95% confidence interval [CI]: 0.86-0.98) and AMR AUC 0.82 (95% CI: 0.74-0.90). The externally validated ACR AUC was 0.72 (95% CI: 0.59-0.82). We developed distinct ACR and AMR miR clinical scores (range 0-100), a score ≥ 65, identified ACR with 86% sensitivity, 76% specificity, and 98% negative predictive value, for AMR score performance was 82%, 84% and 97%, respectively. CONCLUSIONS: We identified novel miRs that had excellent performance to noninvasively diagnose acute rejection after heart transplantation. Once rigorously validated, the unique clinical ACR and AMR scores usher in an era whereby genomic biomarkers can be used to screen and diagnose the subtype of rejection. These novel biomarkers may potentially alleviate the need for an endomyocardial biopsy while facilitating the initiation of targeted therapy based on the noninvasive diagnosis of ACR or AMR.