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.

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.

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.

Weight loss and weight loss maintenance are prominent topics of discussion for clinicians and health professionals involved in treatment to reduce obesity and the risk of cardiovascular disease. Because physical activity is a key component of comprehensive obesity treatment, this scientific statement summarizes the role of physical activity in promoting weight loss, weight loss maintenance, and cardiometabolic health, complementing lifestyle, pharmacological, and surgical-based weight loss intervention strategies. Independently of weight loss, physical activity and exercise programs improve major cardiometabolic risk factors, including hypertension, insulin resistance, and dyslipidemia, which are highly prevalent in patients with overweight or obesity. As a single treatment modality, physical activity and exercise programs are unlikely to result in clinically meaningful weight loss (ie, at least 5% loss of initial body weight) unless aerobic physical activity levels are exceptionally high. When combined with diet-induced negative energy balance, obesity medication, or surgical treatment, increased physical activity can augment total weight loss and improve cardiometabolic outcomes. Because clinicians and health professionals play a pivotal role in fostering and sustaining patients' health goals, this scientific statement also provides an overview of evidence-based strategies for targeted weight loss counseling and for leveraging digital technology, particularly to engage patients and achieve realistic physical activity goals.

Familial hypercholesterolemia (FH) is an inherited disorder characterized by lifelong elevated LDL-C (low-density lipoprotein cholesterol) and increased risk for premature myocardial infarction. FH research has focused on European populations and, consequently, estimates of global FH burden primarily reflect this ancestry, with limited data available from other groups.

While clinical benefits of guideline-directed medical therapy in patients with heart failure (HF) are well established, acute hemodynamic changes after initiation of these agents are not well described. Wireless pulmonary artery pressure (PAP) monitoring using implantable sensors is ideally suited to determine changes in pressure following medication titration.

Cardiac sarcoidosis (CS) is an enigmatic disorder characterized by unexplained patchy, sterile granulomas intermixed with preserved myocardium and fibrotic regions without granuloma. CS causes arrhythmias, sudden cardiac death, and heart failure. The mechanisms producing this remarkable histopathology and disease progression remain unexplained.

The heart transplant allocation system is evolving in response to increasing demand for donor organs, technological advances, and changes in medical decision-making. In this evolving landscape, the historical focus of allocating donor hearts to the "sickest patients first" principle may warrant periodic reassessment and thoughtful safeguards to ensure responsible stewardship and fairness. It is important to note that ethical considerations are central to frontline transplantation cardiologists and cardiothoracic surgeons, who must balance their role in advocating for their individual patients while aligning with allocation policies designed to benefit all recipients equitably. The goals of this scientific statement are (1) to raise awareness of ethical principles in heart transplantation, (2) to review ethical implications of the past and current allocation systems, and (3) to encourage clinicians and stakeholders to address ethical issues that will provide the foundation for future allocation systems.

Bisphenol F (BPF) is a common substitute for bisphenol A and the most prevalent bisphenol compound in diverse plastic manufacturing applications. However, the potential toxicity of BPF remains largely unexplored. This study investigates the effects of BPF on the cardiovascular system and intestinal barrier.

Lipoprotein(a) [Lp(a)] is a risk factor for coronary heart disease. Whether baseline Lp(a) identifies higher risk patients who derive more benefit from evolocumab is not established in a population without prior myocardial infarction (MI) or stroke.

Heart failure with reduced ejection fraction (HFrEF) is characterized by impaired contractility and high mortality. Dysregulation of intracellular ion (ie, Na+/H+ and Ca2+) cycling underlies reduced cardiac contractility. The mechanisms linking myocardial stress to this ion dysregulation remain incompletely understood. Although the metabolic transcription factor SREBP1 (sterol regulatory element-binding protein 1) remodels cardiac metabolism, its role in HFrEF without metabolic comorbidities, particularly regarding ion handling, remains undefined.

Metabolic remodeling, marked by maladaptive shifts in substrate use and energy production, is a hallmark of pathologic cardiac hypertrophy. Yet the mechanisms linking stress signaling to impaired myocardial glucose oxidation remain incompletely defined. Sam68 (Src-associated in mitosis, 68 kDa; also known as KHDRBS1 [KH domain-containing, RNA-binding, signal transduction-associated protein 1]), a STAR (signal transduction and activation of RNA) family RNA-binding protein, has not previously been implicated in cardiac metabolic control.

Cardiac intensive care units are specialized, high-acuity, and resource-intensive environments for the care of critically ill patients with cardiovascular disease. Over the past 60 years, medical and interventional therapeutic advances have improved survival and reduced the risk of life-threatening arrythmias in many common cardiovascular conditions. Nonetheless, some hospitals have maintained historical cardiac intensive care admission practices, resulting in admissions of low-acuity patients who could otherwise be cared for in a telemetry-equipped hospital ward environment. These triage practices may be partially attributable to a lack of guidance from international societies on contemporary cardiac intensive care admission standards. In this scientific statement, we propose cardiac intensive care triage practice standards for common cardiovascular conditions, summarize available prediction scores, and outline priorities for future health services research in this field.