Desmin is a muscle-specific intermediate filament protein crucial for maintaining cardiomyocyte structural integrity, connecting multiprotein complexes and organelles. Although DES mutations are known to cause various (cardio)myopathies, many rare variants remain classified as variants of uncertain significance.

Self-expandable valves are emerging complements to balloon-expandable valves for transcatheter pulmonary valve replacement in dysfunctional right ventricular outflow tracts, though their safety and efficacy remain underexplored. We aim to compare patient characteristics and outcomes of self-expandable valves and balloon-expandable valves in transcatheter pulmonary valve replacement.

Right heart catheterization plays a pivotal role in the preprocedural evaluation of patients considered for transcatheter tricuspid valve edge-to-edge repair. This study aimed to explore the potential impact of hemodynamic parameters obtained through right heart catheterization on patient-centered outcomes.

Background: MODULAR ATP (antitachycardia pacing), a multicenter, international trial, assesses a modular cardiac rhythm management system (mCRM): a subcutaneous implantable cardioverter-defibrillator (S-ICD) in wireless communication with a leadless pacemaker (LP) capable of pace-terminating ventricular tachycardia (VT). Methods: Enrolees had one or more clinical risk factors for VT and did not require chronic pacing. Complications included pre-specified major LP system- and procedure-related complications, and any complication related to the LP, S-ICD, implantation, or study protocol. Survival analysis was performed to identify complication-free rates, therapy delivery, and all-cause mortality. Results: The 297 patients enrolled had an ejection fraction 35±13%, 43% secondary prevention indications, and 59% with prior ventricular arrhythmias (VA). Of 286 patients undergoing LP implantation (100% success), 251 patients completed 12-month follow-up. Mortality rate was 6%, with none related to the implant procedure. Median follow-up duration was 23.4 months (interquartile range: 17.9-28.1). The LP major complication-free rate was 97.2%, exceeding the performance goal. The overall LP+S-ICD system-related complication-free rate was 88.5%. Appropriate tachyarrhythmia-therapy (ATP+shock) rates were 14.4% and appropriate shock rates were 8.5%. Inappropriate total tachyarrhythmia therapy was 9.5% of which 8.5% were shocks. ATP was 67.3% successful in terminating VA episodes and accelerated VAs in 10.1% of episodes. Overall therapy burden (ATP+shock) was 96/100 patient-years of which 44/100 patient-years was for shock delivery. Conclusions: One-year outcomes of the first modular pacing-defibrillator system reveal low system and LP complication rates and good ATP efficacy rates suggesting that the mCRM is a viable alternative to single-chamber ICDs using low-energy pacing capability without the need for transvenous leads.

The clinical effects of sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor, on anthracycline-induced cardiotoxicity remain unknown. Experimental evidence suggests cardioprotective properties. This study evaluated the efficacy of sacubitril-valsartan in reducing cardiotoxicity in patients with increased cardiac troponin I concentrations during anthracycline chemotherapy.

The rapid advancement of genomic and precision medicine has expanded the role of genetics and genomics in the diagnosis, risk stratification, and management of cardiovascular diseases. With the decreasing cost and increasing accessibility of genetic testing, its clinical utility continues to expand, necessitating updated policies to ensure equitable access, appropriate regulatory oversight, and ethical data stewardship. This policy statement by the American Heart Association provides a framework addressing key policy areas, including equitable implementation of genetic testing, the impact of federal regulations, data privacy concerns, reimbursement for genetic counseling services, and the integration of emerging technologies such as artificial intelligence in cardiovascular genomics into clinical practice. This policy statement underscores the importance of strategic investments in biobanking and genomic research across all populations to enhance variant interpretation and to improve risk prediction models. In addition, it highlights the evolving landscape of pharmacogenomics, polygenic risk scores, and precision public health approaches to cardiovascular disease prevention. By advocating for a multidisciplinary approach that bridges scientific innovation, clinical application, and policy development, this policy statement aims to optimize the benefits of genetic and genomic testing while mitigating disparities and ethical challenges in its implementation.

Background: The Lead EvaluAtion for Defibrillation and Reliability (LEADR) trial evaluated the small-diameter (4.7Fr), lumenless, integrated bipolar OmniaSecure defibrillation lead. The trial exceeded primary safety and efficacy objective thresholds, demonstrating favorable efficacy at implant and a low rate of complications. Three-year term outcomes of the LEADR trial assessing the OmniaSecure lead are reported here. Methods: The LEADR trial is a prospective, multicenter, single-arm clinical trial. Patients with an indication for de novo ICD/CRT-D were implanted with the OmniaSecure lead in standard right ventricle (RV) locations and followed at prespecified intervals. The lead was evaluated for safety, efficacy, and reliability through final follow-up. Results: There were 643/657 patients (97.9%) successfully implanted with the OmniaSecure lead with a mean follow-up of 32.4 ± 9.1 months (26% female, 61.9 ± 12.9 years). Pacing capture threshold, pacing impedance, and R-wave amplitudes remained stable throughout. There was a 96.5% freedom from major study lead-related complications at 3 years. At 3 years, 22.3% of patients received appropriate therapies, i.e., shock and/or anti-tachycardia pacing (ATP), with a 75.4% ATP efficacy. Inappropriate shock rate was 2.7% and 5.9% at 1 and 3 years, respectively. Conclusions: The final results of the LEADR trial demonstrated 3-year term safety, efficacy, and reliability of the OmniaSecure lead, emphasizing the potential utility of this lead in a wide variety of patients.

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder that increases risk for premature coronary artery disease and has accessible and effective interventions. The Dutch lipid clinic network is currently the most used diagnostic criterion; however, genetic sequencing provides a definitive diagnosis of FH. The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify individuals who were genotype positive for FH.

Pathogenic variants in ALPK3 (α-protein kinase 3), an atypical α‑kinase acting as a sarcomeric M-band scaffold, cause cardiomyopathy with severity linked to zygosity. We present a comprehensive review with systematic curation of peer-reviewed clinical and experimental reports through June 9, 2025, encompassing 156 patient-level variants and all published preclinical models. Biallelic loss-of-function variants lead to severe, often lethal cardiomyopathy with prenatal or early onset presentation and extracardiac involvement. Heterozygous protein-truncating variants, defined as nonsense or frameshift (resulting from insertion/deletion events or splicing mutations), explain ≈1% to 4% of adult hypertrophic cardiomyopathy, often with apical/septal hypertrophy, right ventricular involvement, fibrosis, and risk of progression. ALPK3 lacks catalytic activity and maintains sarcomeric proteostasis by scaffolding MYOMs (myomesins), MuRF (muscle ring-finger protein) E3 ligases, and SQSTM1 (sequestosome-1)/p62. Loss of this scaffolding function displaces MYOMs, drives thick‑filament protein aggregation, and precipitates severe contractile dysfunction in human induced pluripotent stem cell-derived cardiomyocytes and multiple mouse models. Therapeutic proof‑of‑concept has now been achieved on 2 fronts: (1) pharmacological correction of sarcomeric hypercontractility with the myosin inhibitor mavacamten and (2) durable phenotypic rescue in global knockout mice using an adeno-associated virus-delivered miniALPK3 gene‑replacement construct. Together, these data position ALPK3 cardiomyopathy as a compelling target for precision medicine. Early genetic diagnosis, genotype-tailored surveillance, and focused development of gene-replacement or editing strategies, potentially combined with modulators of the ALPK3-MuRF proteostatic axis, offer a realistic path to disease-modifying therapy for this once enigmatic condition.

Drug-coated balloons (DCBs) are now a Food and Drug Administration--approved treatment option for the management of in-stent restenosis (ISR) based on superior outcomes compared with plain old balloon angioplasty (POBA) alone. However, the efficacy of DCB compared with drug-eluting stent (DES; repeat stenting) for ISR is uncertain, with prior studies showing inferiority of DCB. We aimed to compare the outcomes of DES, DCB, or POBA in patients with coronary ISR.

The role of cardiac magnetic resonance (CMR) quantification of tricuspid regurgitation (TR) to identify high-risk patients with TR remains poorly defined. The aim of this study was to assess the prognostic relevance of TR quantification and of its consequences by CMR in a large real-world cohort.

Cardiorespiratory fitness is an integrative measure of cardiometabolic health and predictor of survival, yet little is known about its molecular underpinnings. Small molecule metabolites and lipids are increasingly recognized as exercise-stimulated signaling molecules and candidate molecular transducers of cardiorespiratory fitness.

Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive disease caused by the deposition of transthyretin as amyloid in the myocardium. Current therapies may slow disease progression but do not clear existing deposits. Coramitug is a humanized monoclonal antibody that targets misfolded transthyretin, designed to promote clearance of transthyretin amyloid through antibody-mediated phagocytosis.

The high-dose inactivated influenza vaccine (HD-IIV) has demonstrated superior protection against a range of hospitalization endpoints versus standard-dose inactivated influenza vaccine (SD-IIV), but its effectiveness against specific cardiovascular (CV) outcomes and in those with pre-existing CV disease (CVD) is not well elucidated.