BACKGROUND:Rare variant genetics have been associated with peripartum cardiomyopathy (PPCM), but the role of genetics remains unsettled. The study sought to compare dilated cardiomyopathy (DCM) genetic risk in first-degree relatives (FDRs) of female patients (probands) with DCM or PPCM to gain causal inference, and to assess DCM-relevant rare variant prevalence in DCM/PPCM probands and population controls. METHODS:Clinical and genetic data were analyzed from the DCM Precision Medicine Study. Risk of DCM or partial DCM, where partial DCM was defined as left ventricular enlargement or a left ventricular ejection fraction of <50%, was estimated in 665 FDRs from 452 female probands, all of whom had been pregnant; 67 had PPCM and 385 had DCM; prevalence of pathogenic, likely pathogenic, or uncertain significance variants was estimated among probands. RESULTS:The risk of DCM/partial DCM for FDRs of PPCM probands was similar to that for FDRs of DCM probands (hazard ratio, 0.77 [95% CI, 0.47-1.28]). Estimated DCM prevalence among the lowest-risk FDRs of non-Hispanic European ancestry probands with PPCM (7.0% [95% CI, 0%-14.1%] females, 9.0% [95% CI, 1.6%-16.3%] males) exceeded population estimates from a UK Biobank study (0.30% females, 0.63% males). Estimated prevalences of a pathogenic, likely pathogenic, or uncertain significance variant among African ancestry and European ancestry probands with PPCM were 55.4% (95% CI, 33.1%-77.7%) and 66.0% (95% CI, 38.6%-93.3%), respectively. The estimated prevalence of pathogenic/likely pathogenic variants among European ancestry PPCM probands (26.6% [95% CI, 12.6%-40.6%]) exceeded a population estimate from a UK Biobank study (0.6%). CONCLUSIONS:The risk of DCM/partial DCM among FDRs was similar regardless of whether their probands had PPCM or DCM. Also, DCM-relevant rare variant findings for females with PPCM or DCM were similar and greater than in population controls, suggesting a similar causal basis for PPCM and DCM. These findings underscore the need for genetic evaluations in all patients with PPCM. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037632.

Data regarding cardiogenic shock (CS) from safety-net hospitals serving socioeconomically-disadvantaged patients are limited. In addition, little is known regarding long-term outcomes and management of heart failure-related CS (HF-CS), a population potentially especially vulnerable to adverse social determinants of health (SDOH). A single-center retrospective cohort study of patients with Stage C, D, or E CS at a public safety-net hospital between 2017 and 2023 was performed. Management and outcomes were compared between patients with HF-CS and myocardial infarction-CS (AMI-CS). The primary outcome was survival through 2 years. The cohort included 378 patients (median age 57y, 44% Black race, 35% Hispanic ethnicity, 81% HF-CS, 19% AMI-CS); 23% received mechanical circulatory support. Thirty-day mortality was lower among patients with HF-CS than AMI-CS (16% vs 28%; HR 0.50 [95% CI 0.30 to 0.84], p = 0.01]). In contrast, mortality from 31 days through 2 years was higher after HF-CS (45% vs 22%, HR 1.94 [1.11 to 3.38], p = 0.02). At long-term follow-up, 53% of survivors were on beta blockers and 32% on no guideline-directed medical therapies. Eighteen patients (5%) received transplant or left ventricular assist device, all of whom had HF-CS and survived through available follow up (median 2.3y [0.9 to 4.0]). In conclusion, in a large safety-net hospital serving a diverse population with adverse SDOH, HF-CS was much more common than AMI-CS, with lower short-term but higher long-term mortality in HF-CS. Use of advanced therapies was low, with favorable survival among patients who received these. These results highlight the importance of expanding access to specialized heart failure care for socially vulnerable patients with CS.

BACKGROUND:Previous studies have speculated that a viral infection may act as a trigger in the development of idiopathic dilated cardiomyopathy (DCM) among individuals genetically at risk. This study aims to describe the frequency of patients with DCM who reported experiencing symptoms of flu-like illness before their DCM diagnosis and to examine if this experience modified the association between genetics and DCM. METHODS:We analyzed data from the family-based cross-sectional DCM Study conducted between 2016 and 2021. Self-reported symptoms of flu-like illness proximal to DCM diagnosis were obtained from patient interviews. Exome sequencing identified rare variants (pathogenic, likely pathogenic, or variant of uncertain significance) in DCM genes. In a case-only design, logistic mixed models were used to examine if flu-like illness modified the effect of these rare variants on DCM risk. Firth logistic regression was used to examine if flu-like illness modified the effect of each of 13 400 141 common autosomal variants (minor allele frequency ≥1%) on DCM risk. RESULTS:Of 1164 patients with DCM, 30.2% reported symptoms of flu-like illness proximal to DCM diagnosis. The percentage of patients with antecedent flu-like illness by variant classification was 30.0% for pathogenic/likely pathogenic, 29.6% for variant of uncertain significance only, and 30.0% for no pathogenic/likely pathogenic/variant of uncertain significance. Antecedent flu-like illness was not found to modify the effect of carrying any pathogenic, likely pathogenic, or variant of uncertain significance variants on DCM risk (interaction relative risk, 0.9 [95% CI, 0.7-1.3]). However, significant modification of the effect of rs2102158 (3q24) by antecedent flu-like illness (P=2.74×10-8) was identified by case-only genome-wide association study. CONCLUSIONS:Approximately one-third of patients with DCM experienced flu-like illness symptoms before DCM diagnosis. We did not find evidence that a flu-like illness modified the effect of rare variants on DCM risk; however, our genome-wide association study analysis suggested that flu-like illness may modify the effect of a common variant on DCM risk. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037632.

Pheochromocytoma is a rare cause of nonischemic cardiomyopathy with a variable clinical presentation. We report 2 cases in which the diagnosis of pheochromocytoma was not initially recognized during evaluation of a reduced left ventricular ejection fraction, despite some potential clues. Following diagnosis, largely driven by incidental detection of an adrenal mass, targeted treatment with surgical resections led to successful outcomes. One patient maintained left ventricular ejection fraction >55% for more than 15 years. These cases emphasize that in patients with new-onset nonischemic cardiomyopathy who have either a relapsing/remitting pattern of left ventricular ejection fraction or evidence of catecholamine excess, pheochromocytoma should be considered. With appropriate diagnosis and targeted treatment, successful and durable recovery of cardiac function is possible.

BACKGROUND:Donor-recipient size matching is a key factor in donor selection for heart transplantation (HT). One approach uses predicted heart mass (PHM), derived from the Multi-Ethnic Study of Atherosclerosis (MESA). We sought to examine whether predicted left ventricular mass (PLVM) derived from the Dallas Heart Study (DHS) is associated with post-transplant outcomes. METHODS:The study cohort included participants without pre-existing cardiac disease in the DHS who had cardiac MRIs (n = 1746). A PLVM model was derived by linear regression. The DHS PLVM and MESA PHM were tested for correlation. The associations of the DHS PLVM and the MESA PHM with 1-year mortality post-HT were assessed in the United Network for Organ Sharing Registry in 3 eras: era 1: 1/1/2011-12/31/2014; era 2: 1/1/2015-10/17/2018; and era 3: 10/18/2018-12/31/2021). A pre-specified threshold for low donor-to-recipient mass ratio (< 0.86) was used in Kaplan-Meier survival estimation and univariate and multivariable Cox proportional hazard models. RESULTS:The DHS cohort had a median age of 43 (IQR 36-52) years, 49% male, 40% Black, and 18% Hispanic ethnicity. The DHS PLVM was highly correlated with the MESA PHM: r = 0.96; P < 0.001. In era 1, a low donor-to-recipient mass ratio according to the DHS PLVM was associated with increased 1-year mortality rates (log-rank P < 0.001) as was the MESA PHM (log rank P = 0.002). However, in eras 2 and 3, a low donor-to-recipient mass ratio by either the DHS PLVM or MESA PHM was not associated with increased 1-year mortality rates. CONCLUSION:PLVM was highly correlated with PHM. A low donor-to-recipient mass ratio, whether assessed by PLVM or PHM, was associated with 1-year mortality post-HT in a historical era but not in the current era under the new allocation system. These findings suggest that other factors may be contributing to donor selection and mortality risk in the modern era.

BACKGROUND:To better define the importance of the amyloidogenic p.V142I TTR allele across the life span of a carrier, we leveraged data from All of Us to provide a generalizable assessment of the population-level burden of cardiovascular risk and estimate the age at disease onset. METHODS:We included self-identifying Black participants in All of Us who provided genomic data (N=77 767). The exposure of interest was p.V142I TTR carrier status (N=2213). Outcomes included incident heart failure (HF), atrial fibrillation, and carpal tunnel syndrome. RESULTS:The median (interquartile range) age at enrollment was 56 (42-64) years. For the subset with genetic ancestry data (N=50 516), the p.V142I TTR carrier frequency was 3.5% (N=1771) among those with African ancestry. After adjustment for age and traditional risk factors, p.V142I TTR carrier status was associated with a greater risk of HF (odds ratio, 1.56 [95% CI, 1.22-1.99]; P=0.001), atrial fibrillation (odds ratio, 1.3 [95% CI, 1.08-1.90]; P=0.013), and carpal tunnel syndrome (odds ratio, 1.94 [95% CI, 1.43-2.63]; P<0.001).The risks increased in the sixth decade of life. In carriers, the attributable risk of the variant for HF, atrial fibrillation, and carpal tunnel syndrome was 27%, 26%, and 43%, respectively. While traditional HF risk factors did not modify the association of carrier status with HF (P-interaction >0.05 for all), their presence substantially augmented the risk of HF over a lifetime. CONCLUSIONS:p.V142I TTR carriers are at an increased risk of HF and atrial fibrillation, beginning during the sixth decade of life. HF risk rises in a dose-dependent manner with other nonamyloid-related HF risk factors, highlighting the importance of aggressive treatment of HF risk factors among carriers. These observations also confirm the clinical relevance of the p.V142I TTR variant for individuals of African ancestry and underscore the importance of efforts to increase diagnoses, implement TTR-targeted therapies, and evaluate screening strategies for variant transthyretin cardiac amyloidosis.

Introduction:Heart failure (HF) is a leading cause of hospitalization and mortality worldwide, emphasizing the critical role of optimal medical therapy (OMT) in improving patient outcomes. Despite extensive research, most scientific evidence regarding HF is gathered and studied in developed countries, leaving substantial knowledge gaps regarding HF in Latin America and the Caribbean. Objective:To characterize the sociodemographic and clinical profiles of HF patients and to assess their adherence to OMT in the Americas. Methods:The AMERICCAASS Registry is a prospective, observational, multicenter study, including patients aged 18 and older, both hospitalized and ambulatory, and diagnosed with HF. Sociodemographic and clinical data were collected from the first 2,500 patients to characterize the study population. Adherence to OMT was subsequently evaluated according to left ventricular ejection fraction (LVEF). Results:Among the 2,500 patients in the study, 36% were hospitalized and 64% were ambulatory. The median ages of the patients were 66.9 (hospitalized) and 66.3 years (ambulatory). Males made up 60.8% of hospitalized and 59.3% of ambulatory patients. The majority had HF with reduced LVEF (≤40%): 60.7% for hospitalized and 58.5% for ambulatory. The New York Heart Association (NYHA) functional class II predominated among ambulatory patients (67.9%), while NYHA functional class III predominated among hospitalized patients (46.6%). Only 21% of patients with reduced LVEF were receiving quadruple therapy, whereas 12.3% of patients with mildly reduced LVEF (41-49%) were on this treatment. Conclusion:The findings demonstrate that the sociodemographic and clinical profiles of HF patients in the Americas are broadly consistent with international reports. However, the low use of OMT observed in this population underscores gaps in adherence to current guidelines. These results highlight the need for targeted strategies to improve pharmacological treatment adherence to optimize health outcomes in this region.