Clonal hematopoiesis encompasses diverse somatic mutations in hematopoietic cells, ranging from age-related expansions to mutations acquired after cytotoxic therapy, with implications for hematologic malignancy and cardiovascular disease. We characterize the spectrum of patients referred to cardiology for clonal hematopoiesis, including incidental detection during cytopenia or cancer predisposition workup, coexisting malignancy, and posttherapy surveillance. High-risk features, large clone size, multiple mutations, and specific driver genes interact with traditional cardiovascular risk factors to influence ischemic events. Contextualizing clonal hematopoiesis by detection setting, genotype, and clinical history informs individualized cardiovascular evaluation and risk mitigation, guiding mechanistically targeted preventive strategies and trial design.

Despite antiplatelet therapy, some patients remain at high ischemic risk because of drug nonresponsiveness or high residual platelet reactivity. We aimed to target an orphan platelet GPCR (G protein-coupled receptor) from the OR (olfactory receptor) family as a novel antithrombotic strategy.

We hypothesized that quantification of coronary atherosclerotic plaque burden by artificial intelligence-guided quantitative computed tomography can identify patients who derive outcome benefit from lipid-lowering medication (LLM).

Nationally, there has been a rise in the number of children and adolescents with congenital and acquired heart disease presenting with acute decompensated heart failure. Compared with adults, these children have increased morbidity and mortality and use significantly more health care resources once admitted. Currently, there is little guidance on how to assess, manage, and create successful discharge plans for children presenting with acute decompensated heart failure. Given that this population represents an intersection among emergency medicine, cardiology, surgery, critical care, and psychology, a guidance document for the comprehensive management of this high-risk population is needed. This scientific statement reflects the state of current evidence and highlights important knowledge gaps in this domain.

Although emerging evidence supports 3-dimensional myocardial activation during atrial fibrillation (AF), human studies remain limited. We thus characterized the endocardial and epicardial left atrial posterior wall (LAPW) in humans to assess the prevalence of asynchronous endocardial-epicardial LAPW conduction during AF.

Catheter ablation for atrial fibrillation is a widely used rhythm-control strategy, yet its role in reducing thromboembolic risk and enabling oral anticoagulation (OAC) discontinuation remains uncertain. This meta-analysis aims to comprehensively synthesize and evaluate randomized controlled trial evidence supporting long-term antithrombotic strategies in patients with atrial fibrillation undergoing catheter ablation.

Right ventricular (RV) dysfunction is a key predictor of outcomes in pulmonary hypertension (PH), substantially contributing to illness and death. As PH progresses, increased pulmonary vascular resistance places chronic pressure overload on the right ventricle. Initially, the right ventricle adapts through hypertrophic remodeling, thickening the heart wall to maintain cardiac output. Over time, this adaptive phase shifts to maladaptive remodeling, marked by RV dilation, fibrosis, stiffness, and decoupling from the pulmonary artery, known as RV-pulmonary arterial uncoupling. This uncoupling reflects the inability of the right ventricle to sustain contractility against elevated afterload, ultimately leading to right heart failure, the primary cause of death in late-stage PH. Awareness of RV dysfunction has grown, extending beyond PH and pulmonary arterial hypertension to systemic conditions, such as heart failure with preserved ejection fraction, congenital heart disease, COVID-19, and complications of left ventricular assist device implantation. Research is increasingly focused on understanding the molecular and hemodynamic drivers of RV failure, including inflammation and altered cellular signaling. Innovations in imaging and biomarker discovery are improving the detection of maladaptive RV remodeling. Promising treatments, such as the activin signaling inhibitor sotatercept, may reduce pulmonary vascular resistance and support RV recovery. Further work is needed to enhance RV function and prevent failure. This review summarizes current knowledge on RV dysfunction in PH, emphasizing its mechanisms, clinical relevance, and therapeutic potential. Recognizing the right ventricle as a central therapeutic target may lead to more personalized, effective interventions and improved patient outcomes in PH and related conditions.

TMEM43 (transmembrane protein 43) is a ubiquitously expressed 4-transmembrane-protein localized in the endoplasmic reticulum and nuclear lamina. The missense mutation TMEM43-p.S358L causes fully penetrant ARVC5 (arrhythmogenic right ventricular cardiomyopathy type 5) especially in males. The TMEM43 function of the protein and the pathomechanisms of TMEM43-p.S358L remain poorly understood. We analyzed carrier-derived human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), human myocardial tissue from TMEM43-wild-type, and TMEM43-p.S358L and identified differentially interacting proteins. Here we provide evidence for a novel pathomechanism contributing to the onset of ARVC5.

Remapping studies have evaluated chronic lesion durability of the first-generation pentaspline pulsed field ablation (PFA) catheter that did not have integrated electroanatomical mapping. By invasive remapping, this first-in-human study evaluated the durability of lesions facilitated by the integration of the navigation-enabled pentaspline PFA catheter and mapping system in patients with atrial fibrillation.