Sarcomere gene variants are a key cause of hypertrophic cardiomyopathy (HCM), and have been associated with worse prognosis. However, it is unclear how comorbidities influence clinical trajectories, the timing of events, and causes of death in sarcomeric and nonsarcomeric HCM.

Cardiomyocytes, as highly specialized and differentiated somatic cells, possess a limited capacity for renewal. Neonatal rodents possess the ability to regenerate cardiomyocytes after injury; however, this regenerative capacity declines rapidly with cardiomyocyte maturation, suggesting an inhibitory network between cellular maturation and cardiomyocyte proliferation. Maturing cardiomyocytes undergo a metabolic shift from predominantly glycolysis in the neonatal state to increased fatty acid oxidation in the mature state, which poses a barrier to cardiomyocyte proliferation and cardiac regenerative repair. YAP, a transcriptional cofactor regulated by the Hippo signaling pathway, promotes cardiac regenerative repair. We investigated the role of YAP in mediating metabolic remodeling to overcome the cardiomyocyte proliferation barrier and enable cardiac regenerative repair after heart injury.

Aortic valve calcification increases leaflet stiffness and contributes to the development of calcific aortic valve disease. The molecular and cellular mechanisms underlying calcification remain unclear. Here, we aimed to investigate the role of PRMT3 (protein arginine methyltransferase 3) in valvular calcification and calcific aortic valve disease progression.

Right ventricular failure drives both morbidity and mortality in pulmonary arterial hypertension (PAH), but the mechanism of transition from compensated right ventricle (cRV) to decompensated RV (dRV) is unknown, and some PAH patients develop dRV faster than others.

Myocardial ischemia/reperfusion (I/R) injury is a common and severe clinical complication in patients with ischemic heart disease after reperfusion therapy. Effective therapeutic strategies for myocardial I/R injury remain limited. Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. However, the mechanisms underlying ferroptosis in myocardial I/R injury are not fully understood.

Background: Angiography-derived fractional flow reserve (Angio-FFR) is an emerging tool for guiding percutaneous coronary intervention (PCI). Its uptake and outcomes compared to pressure wire (PW)-based assessment in the US are unknown. Methods: We conducted a cohort study of US Medicare beneficiary data from 1 January 2019 to 31 December 2024. Propensity score matching (1:3) of Angio-FFR to PW was performed in patients who underwent PCI during the same procedure, and separately among those who did not undergo PCI during the same procedure. The primary outcome was the cumulative incidence of major adverse cardiovascular events (MACE) through 2 years, including all-cause death, myocardial infarction (MI) and repeat revascularization. Secondary outcomes included individual MACE components, 30-day acute kidney injury and 30-day major bleeding. Falsification endpoints (hospitalization for pneumonia and hip fracture) were used to assess unmeasured confounding. Results: Of 466,535 angiograms that included intra-procedural physiologic assessment, 1.00% (N=4,672) used Angio-FFR. Annual use increased from 0.47% in 2019 to 3.85% in 2024. Among PCI patients, 1,591 Angio-FFR and 4,773 PW matched PCI patients had similar MACE rates through 2 years (24.8% vs 23.5%; HR 1.01, 95% CI 0.85 - 1.20). Secondary outcomes and falsification endpoints were not significantly different. In non-PCI patients, 2,532 Angio-FFR and 7,596 PW matched patients also had similar MACE through 2 years (24.1% vs 23.9%; HR 0.97, 95% CI 0.84 - 1.11). Conclusions: Angio-FFR usage in the US is modest but increasing. Angio-FFR guidance during angiography versus PW was associated with comparable outcomes through 2 years.

Background: Although guidelines recommend invasive management for non-ST-elevation myocardial infarction (NSTEMI), there is considerable variability in the application of these recommendations across different hospitals, reflecting a lack of standardized clinical pathways and highlighting ongoing uncertainty in real-world practice. We sought to describe site-level variability in the use and timing of invasive angiography for NSTEMI and their association with in-hospital outcomes. Methods: Using NCDR Chest Pain-MI registry data (2019-2024), the rates and timing of invasive coronary angiography, if any, were characterized among patients with NSTEMI. Hierarchical logistic regression models were created to describe hospital-level variability in management using median odds ratios (MORs), adjusted for patient and site characteristics. Inverse probability weighting was used to estimate the association between treatment strategy and in-hospital outcomes. Results: We included 287,275 patients with Type-1 NSTEMI from 541 hospitals (age 67.6±13.3 years, 36.4% women). Invasive coronary angiography was performed in 87.1%, of whom 56.9% within 24 hours. Among those treated invasively, 66.1% received percutaneous coronary intervention. Older patients with more comorbidities were paradoxically more likely to receive conservative management or delayed intervention (>24 hours). Site-level variability for invasive strategy (vs. conservative) was large [MOR 2.85 (2.64-3.10)], as was early invasive treatment [MOR 1.67 (1.62-1.74)], particularly on weekends/holidays [MOR 1.89 (1.81-1.98)]. The use of any invasive strategy was associated with lower in-hospital mortality versus conservative management [weighted OR 0.36 (0.31-0.42)]. This finding was consistent across all baseline risk categories (P-interaction <0.001). Conclusions: Patients with Type-1 NSTEMI and higher-risk clinical profiles were not consistently prioritized to undergo early invasive management with substantial variability across hospitals. Invasive management was associated with lower in-hospital mortality compared with conservative treatment. Future randomized studies in the modern PCI era are needed to confirm our findings, and identify which patients benefit most and when intervention should occur.

Moderate and severe tricuspid regurgitation (TR) is associated with poor outcomes, yet current grading systems do not fully capture circulatory heterogeneity. We investigate the relationship of cardiac index (CI) with rest-exercise hemodynamics, metabolic and inflammatory profiles, and clinical outcomes in moderate and severe TRs.