Primary aldosteronism (PA) carries excess cardiovascular risk not fully explained by hemodynamic load. While aldosterone promotes fibroblast activation experimentally, in vivo evidence linking adrenocortical activity with myocardial remodeling remains limited. This study integrated CXCR4 (C-X-C chemokine receptor type 4)-targeted 68Ga-Pentixafor positron emission tomography (PET)/magnetic resonance and FAP (fibroblast activation protein)-targeted 68Ga-FAPI-04 PET/cardiac magnetic resonance to evaluate the adrenal-cardiac axis in PA.

Metabolic disturbances are key contributors to myocardial ischemia-reperfusion (I/R) injury, yet the underlying molecular mechanisms remain largely unclear. RND3, a cytosolic small GTPase known to antagonize ROCK1 (Rho-associated coiled-coil kinase 1), has been implicated in several cardiovascular disorders. However, its mitochondrial localization and functional role in cardiac energy metabolism and I/R injury remain unknown.

Heart rate (HR) is a key prognostic factor after myocardial infarction (MI), but its relevance in the modern reperfusion era is uncertain. We aim to evaluate the association between HR and β-blocker interruption on cardiovascular outcomes.

Pulmonary hypertension (PH) is a progressive, life-threatening disease characterized primarily by pulmonary vascular remodeling in which endothelial dysfunction plays a vital role. However, the molecular factors contributing to this pathological process remain incompletely understood. Through proteomic analysis of hypoxia-treated human pulmonary artery endothelial cells, we identified serine hydroxymethyltransferase 2 (SHMT2) as a potential target in PH, but its role in disease pathogenesis and the underlying mechanisms remain unclear.

Heart failure is a leading cause of morbidity and mortality worldwide, particularly among the growing elderly population. In degenerative aging and autoimmune diseases, the cytoplasmic leak of mitochondrial DNA, resulting from mitochondrial cristae compromise, triggers persistent low-grade cellular inflammation through activation of the cGAS (cyclic GMP [guanosine monophosphate]-AMP [adenosine monophosphate] synthase)-STING (stimulator of interferon genes) pathway and the IFN-I (type I interferon) response. However, how and whether mitochondrial architectural components and cardiomyocyte inflammation drive cardiac aging and failure are not yet well understood.

The "2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome" retires, replaces, and expands upon the "2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults." The primary intended audience for this guideline is clinicians who care for patients across the spectrum of cardiovascular-kidney-metabolic syndrome, an interrelated condition characterized by the interconnections among metabolic risk factors (including obesity and type 2 diabetes), chronic kidney disease, and cardiovascular disease.

Current clinical practice guidelines for the primary prevention of cardiovascular disease recommend risk assessment to align the type and intensity of preventive efforts with an individual's risk. The 2025 American Heart Association/American College of Cardiology guideline for the prevention, detection, evaluation, and management of high blood pressure in adults and the 2026 American Heart Association/American College of Cardiology guideline on the management of dyslipidemia incorporate quantitative risk assessment, recommending the PREVENT (Predicting Risk of Cardiovascular Disease Events) equations to guide initiation and intensification of antihypertensive and lipid-lowering therapies, respectively. Given the growing awareness of the clustering of cardiovascular-kidney-metabolic risk factors along with the expanding armamentarium of cardioprotective therapies for obesity, diabetes, and chronic kidney disease, a harmonized approach that comprehensively assesses and addresses risk across these interconnected conditions is needed. The 2026 American Heart Association/American College of Cardiology guideline for the prevention, detection, evaluation, and management of cardiovascular-kidney-metabolic syndrome provides recommendations for the use of the PREVENT equations with outcome-specific risk thresholds for staging, detection of subclinical cardiovascular disease, and decision-making regarding initiation and intensification of cardiovascular-kidney-metabolic therapies. This approach integrates predicted risk (using PREVENT-CVD [cardiovascular disease], PREVENT-ASCVD [atherosclerotic cardiovascular disease], and PREVENT-HF [heart failure]) with the relative risk reduction expected from treatment for each outcome to estimate the expected benefit (ie, absolute risk reduction) from drug therapy. This scientific statement details the rationale for using outcome-specific PREVENT equations, the evidence base for selected risk thresholds, and the potential population-level impact of these recommendations. This scientific statement also offers practical guidance for applying risk assessment as the first step in shared decision-making and for addressing gaps in awareness, risk communication, and optimal implementation of evidence-based preventive therapies to improve outcomes in individuals with or at risk for cardiovascular-kidney-metabolic syndrome.

Heart failure with preserved ejection fraction (HFpEF) has become the most prevalent type of heart failure, a condition characterized by impaired diastolic function and elevated left ventricular stiffness. TPM1 (tropomyosin 1), a crucial part of the thin filament in cardiomyocytes, has multiple alternative exons. However, the impact of TPM1 alternative splicing (AS) in HFpEF remains unclear.

GDF2 (encoding BMP9) variants have been described in pulmonary arterial hypertension (PAH) and hereditary hemorrhagic telangiectasia, as well as a few BMP10 variants in PAH. The purpose of the present study was to develop a functional assay capable of discriminating benign from pathogenic variants and to characterize the underlying molecular mechanisms responsible for their loss of function.

The relationship between fetal aortic valvuloplasty procedural volume and outcomes is crucial to understand whether regionalization should be advised worldwide. This study utilizes the International Fetal Cardiac Intervention Registry to examine the relationship between center volume for fetal aortic valvuloplasty and outcome metrics including procedure success, complications, and fetal death.

Global Vhl knockout results in vascular defects and early lethality, limiting our knowledge of von Hippel-Lindau/HIF (hypoxia-inducible factor) signaling in coronary vessel formation and homeostasis. The hypoxia pathway has been implicated in cardiovascular diseases characterized by inflammation and vascular remodeling, such as atherosclerosis, but its involvement in Kawasaki disease (KD) remains unknown. Coronary artery dilation and vessel rupture are the most serious complications of KD. However, the molecular mechanisms underlying these cardiac events are not fully understood. We investigated the role of the von Hippel-Lindau/HIF pathway in cardiovascular pathology and its relevance to KD.

Performance and transferability of contemporary polygenic risk scores (PRS) for atherosclerotic cardiovascular disease phenotypes may vary across PRS methods, training data, and trait ascertainment.

Congenital heart disease (CHD), the most common birth defect and a leading cause of infant mortality, is frequently linked to dysregulated Notch signaling. However, the role of the Notch transcriptional coactivator Mastermind-like 1 (MAML1) in CHD pathogenesis and the underlying molecular mechanism remain unclear.

Arrhythmogenic cardiomyopathy (ACM) is an inherited disease that is characterized by lethal ventricular arrhythmias stemming from myocyte dysfunction. ACM is associated with considerable subepicardial fibrosis and inflammation with right ventricle predominance. Most cases of gene-positive ACM are caused by a desmosome protein mutation, with plakophilin-2 (Pkp2) mutations being the most common. We hypothesized that Pkp2-deficiency in epicardium-derived cells (EPDCs) contributes to fibro-inflammatory signaling and ACM pathogenesis.

GWASs (genome-wide association studies) have advanced our understanding of coronary artery disease (CAD) genetics and enabled the development of polygenic risk scores (PRSs) for estimating genetic risk based on common variant burden. However, GWASs have limitations in analyzing rare variants due to insufficient statistical power, thereby constraining PRS performance.

Although the prognostic utility of positron emission tomography (PET) myocardial flow reserve (MFR) is well established, emerging data suggest that reduced subendocardial flows also predict adverse outcomes. However, the incremental value of subendocardial MFR (MFRSE) beyond transmural MFR (MFRTM) remains unclear.

The EARLY TAVR trial demonstrated that early transcatheter aortic valve replacement (TAVR) was superior to clinical surveillance (CS) in asymptomatic severe aortic stenosis. The relative impact of early TAVR versus a CS strategy by age is unknown.

Complete revascularization is superior to culprit lesion-only percutaneous coronary intervention (PCI) in reducing ischemic events in patients with ST-segment-elevation myocardial infarction and multivessel disease. However, the relationship between the extent of revascularization and the benefits of a complete revascularization strategy remains unclear. The aim of this substudy of the COMPLETE trial was to evaluate how the degree of anatomic completeness of revascularization, measured by the core laboratory-derived modified residual SYNTAX score (R'SS), relates to major cardiovascular events.

During the 18-month CENTRAL (Effect of Weight-Loss Diet Strategies and Exercise on Dynamics of Body Fat Depots and Metabolic Rate) and DIRECT-PLUS (Effects of Green-Mediterranean Diet via the Gut-Fat-Brain Axis) randomized controlled trials, participants achieved considerable reductions in abdominal and ectopic fat. We examined the long-term postintervention cardiometabolic profile associated with these changes.

Innovation in the treatment of ascending aorta and arch pathology with novel catheter-based and hybrid procedures has driven the need for a strategy to guide their safe application. The ARCH-ARC (Aortic Arch Academic Research Consortium) was established to pragmatically develop consistent clinical end points and to standardize definitions for use in studies of these new technologies. The ARCH-ARC team, consisting of independent international specialists in cardiac surgery, vascular surgery, vascular medicine, cardiology, neurology, radiology, and clinical trials, along with US Food and Drug Administration, industry, and contract research organization representatives, held virtual meetings from 2021 to 2025. Consensus was used to identify appropriate clinical end points and to standardize definitions of end points for endovascular, hybrid, and open surgical procedures in clinical trials in the ascending aorta and arch. Drawing on previous ARC work in cardiac, neurological, renal, and bleeding end points, the ARCH-ARC focused on definitions and end points related to aortic arch-specific anatomy, pathology, and procedures and clinical, device, and imaging. The adoption of the ARCH-ARC consensus definitions and end points will provide a template for consistent adjudication and event reporting and facilitate comparisons of clinical research studies involving devices for ascending aorta and arch pathology.