Bon Secours Heart & Vascular Institute

Background: Evidence of the diverse genetic architecture of dilated cardiomyopathy (DCM) continues to emerge and requires reassessment of the clinical relevance of implicated disease genes. Building on the 2019-2020 Clinical Genome Resource (ClinGen) evaluation, the DCM Gene Curation Expert Panel (GCEP) reconvened in 2024-2025 to conduct a reassessment of genes in DCM. Methods: The ClinGen semi-quantitative clinical validity classification framework was applied with specifications to DCM to classify genes into categories based upon strength of published evidence for a DCM phenotype. Previously curated genes were reassessed and newly reported gene-disease-mode of inheritance (MOI) relationships, termed ?curations,? were evaluated. Results: Sixty-eight genes were evaluated, inclusive of 72 unique gene-disease-MOI relationships across 51 previously evaluated and 17 newly assessed genes. Thirty-five curations were classified as high evidence (16 Definitive, 10 Strong, 9 Moderate), increasing by 16 from the prior assessment. Nine newly assessed genes were classified as high evidence, including BAG5, FLII, LMOD2, MYLK3, MYZAP, NRAP, PPA2, PPP1R13L, and RPL3L. Twelve genes (11 newly appraised) were rated as high evidence with an autosomal recessive (AR) MOI. Five re-evaluated genes from 2019-2020 had clinically significant changes in classification. Except for JPH2, for which curation was modified to separate autosomal dominant (-AD) and -AR MOI curations, clinically significant changes involved upgrades from low to high evidence categories (PLEKHM2, PRDM16, TBX20, TNNI3K), demonstrating the robustness of the ClinGen gene curation process over time. An additional 29 gene-disease-MOI curations were classified as Limited, including six newly evaluated genes and one new MOI for a previously evaluated gene, MYBPC3-AR; four were classified as No Known Disease Relationship, and four remained Disputed. Four previously evaluated genes were curated for both AD and AR MOIs, including JPH2 (AD-Strong, AR-Limited), LDB3 (AD-Limited, AR-Strong), MYBPC3 (AD-Limited, AR-Limited), and TNNI3 (AD- and AR- Strong). Conclusions: With substantial new evidence, the genetic architecture of DCM has rapidly expanded. This updated assessment of genes reported in DCM yielded 35 high evidence curations, an increase from 19 only five years ago. The results of this evidence-based evaluation process informs clinical interpretation of genetic information in the care of DCM patients and families.

Background: Racial and gender disparities in heart transplant access and outcomes were well documented prior to 2018. On October 18, 2018, the United Network for Organ Sharing (UNOS) implemented a revised Adult Heart Allocation Policy aimed at improving equity. This study examines whether such disparities have persisted in the post-policy era. Method: A retrospective cohort study was conducted using data from the United States TriNetX platform, which aggregates records from 66 healthcare organizations. Heart transplant recipients from 2018 to 2023 were identified and stratified by gender and race. Propensity score matching was used to balance baseline characteristics between groups. The primary outcome was all-cause mortality, while secondary outcomes included heart failure and all-cause hospitalization, transplant rejection, sepsis and end-stage renal disease. Hazard ratios were calculated using Cox proportional hazards models. Results: Between 2018 and 2023, a total of 2,569 heart transplant recipients were identified, including 1,862 males (72.5%) and 707 females (27.5%). The racial distribution included 1,414 White (55.0%), 722 African American (28.1%), 216 Hispanic (8.4%), and 56 Asian (2.2%) patients. No significant differences in mortality were observed across sex or racial groups. However, female recipients had significantly higher risks of adverse outcomes compared to males, including heart failure (HR = 1.59, 95% CI: 1.11–2.28), transplant rejection (HR = 1.26, 95% CI: 1.09–1.46), and rehospitalization (HR = 1.21, 95% CI: 1.07–1.38). African American recipients experienced a significantly lower rate of transplant rejection compared to White recipients (HR = 0.72, 95% CI: 0.62–0.84, p < 0.001). There were no statistically significant differences in heart failure hospitalization, ESRD, or all-cause hospitalization among racial groups. Conclusions: The findings suggest that while disparities in heart transplant outcomes have improved since the 2018 allocation policy change, significant gaps remain. Female recipients continue to face higher risks of adverse outcomes, and although racial differences in mortality were not observed, certain disparities—such as in transplant rejection rates—persist. These results highlight progress toward equity but underscore the need for continued efforts to eliminate sex- and race-based differences in post-transplant outcomes fully.

Background: Despite widespread use of the Impella 5.5 to support patients with cardiogenic shock (CS), the identification of patient profiles that benefit the most from this intervention remains a challenge. Understanding the clinical and hemodynamic characteristics associated with successful outcomes is crucial for optimizing patient selection and management. Methods: Using data from a comprehensive registry of 508 patients, we evaluated clinical stabilization among those receiving Impella 5.5 for CS. Clinical stabilization was defined as weaning from the Impella 5.5 without escalation to additional mechanical circulatory support and discharge from the hospital alive, or bridging to durable heart replacement therapy (HT or LVAD) without further escalation of support. Results: Of the 508 patients analyzed, 30.7%(N=156) achieved clinical stabilization. The mean age of the cohort was 58.4±12.6 years, with 83.7% being male. Heart failure-related cardiogenic shock (HF-CS) was present in 69.5% of the patients. No significant demographic differences were observed between the stabilization and deterioration groups (p>0.05). Patients who stabilized were more likely to have HF-CS (p<0.001) and lower incidence of out-of-hospital cardiac arrest (OHCA)(p<0.001). Higher pulmonary artery pressure (mPAP, p=0.02) and pulmonary capillary wedge pressure (PCWP, p<0.001) were significant predictors of stabilization. The presence of implantable cardioverter-defibrillators (ICDs) was more common in stabilized patients (p=0.01). Major complications such as stroke (stabilization:3.8%, deterioration:6.1%, p=0.3), limb ischemia (stabilization:1.9%, deterioration:7.4%, p=0.02), and bleeding requiring surgery (stabilization:7.7%, deterioration:12.8%, p=0.09) were observed. Notably, bleeding requiring transfusion was significantly higher in the deterioration group (41.5% vs. 30.1%,p=0.02). The median duration from Impella 5.5 insertion to heart recovery or discharge was 15.1 days (IQR:7.7-29.1 days). Conclusions: Among patients with CS supported with the Impella 5.5, those with HF-CS, higher pulmonary pressures, and the presence of ICDs are more likely to achieve clinical stabilization. Significant complications, including bleeding and limb ischemia, remain a concern and require careful management. This study highlights the importance of detailed pre-implant hemodynamic assessment and suggests that targeted management strategies based on these predictors could improve patient outcomes.