The mechanisms behind endocardial entanglement and resultant delamination during left bundle branch area pacing, as well as potential solutions, have not been fully demonstrated in the human heart.

Guideline-directed medical therapy (GDMT) is central to the care of heart failure with reduced ejection fraction, yet no standard metric exists to quantify its implementation.

Preeclampsia affects approximately 1 in 10 pregnancies, leading to severe complications and long-term health risks for both mother and offspring. While the etiology remains unclear, preeclampsia has been linked to both autoimmunity and the timing of menarche.

The AMEND implant is a semi-rigid closed D-shaped annuloplasty ring deployed through a transvenous transeptal approach. It is aimed to affect selective anteroposterior dimensional reduction, improving leaflet coaptation, and reduce mitral regurgitation (MR). We report the 6-month outcomes of the first cohort treated.

Addressing the rising burden of stroke in low-income countries will require pragmatic and scalable interventions targeting major risk factors. Under routine care settings, <10% of adults living with hypertension ever achieve blood pressure control, accentuating risks for adverse vascular events. The effectiveness of mobile health-centered, nurse-led interventions for the control of hypertension among patients with recent stroke in a resource-limited African setting is unknown.

Transcatheter mitral valve-in-valve replacement is an established therapy for intermediate and high-risk patients with degenerated bioprostheses, but restricted transcatheter valve (THV) expansion within rigid surgical frames and elevated gradients have raised durability concerns. This study aimed to evaluate midterm outcomes of mitral valve-in-valve patients according to THV expansion and sizing strategy.

In general, females have lower aortic valve calcium (AVC) scores compared with males of similar age, and the AVC score threshold for diagnosing severe aortic stenosis (AS) is lower for females. We examined whether the association of AVC with the long-term risk of clinically significant AS differed for females compared with males.

Hypercholesterolemia and a high-fat diet promote 2 macrophage subtypes involved in atherosclerosis by inducing lipid droplet accumulation in foamy macrophages (FMs) and inflammatory activation in non-foamy macrophages (NFMs). MicroRNAs are key regulators of macrophage function; for instance, miR-10a-5p reduces atherosclerosis and improves mitochondrial health in FMs, whereas miR-155-5p accelerates atherosclerosis by impairing efferocytosis. miR-147-3p is upregulated by inflammatory stimuli in macrophages and in atherosclerotic lesions, suggesting a role in NFMs.

Exercise unmasks limitations in multi-organ system reserve capacity characteristic of heart failure with preserved ejection fraction (HFpEF). However, the metabolic and genetic underpinnings of exercise deficits, and their cumulative contribution to HFpEF severity and prognosis, remain incompletely understood.

Physician compensation models in the United States are diverse, shaped by practice settings, specialties, and institutional factors. A notable shift in academic medical centers has been the transition from salary-based compensation to relative value unit (RVU)-based models. While this shift may align compensation with clinical productivity and facilitate budgetary planning, it has profound implications for physician satisfaction, burnout, and clinical practice, particularly in primarily cognitive/nonprocedural based specialties like advanced heart failure (AHF). This article explores the benefits and drawbacks of the RVU model, with a focus on its application in AHF care. The RVU system, designed to measure physician work, practice expenses, and malpractice risk, is associated with efficiency incentives but also risks prioritizing quantity over quality, especially in multidisciplinary fields like AHF. Patients with AHF often have multiple comorbidities requiring extensive management and care coordination across multiple subspecialties, outside of the work effort captured by a clinic visit. The RVU model may undervalue the comprehensive, longitudinal care AHF specialists provide. Through a detailed examination of inpatient and outpatient AHF management, we argue that the RVU model may inadequately capture the full scope of AHF care, which may contribute to systemic challenges, physician burnout, and a decline in interest in AHF subspecialty training. Hence, we call for a reconsideration of AHF physician compensation and productivity measurement that more accurately reflects the full breadth of comprehensive AHF care.

Although adeno-associated virus (AAV) gene-replacement therapy is a potentially transformative therapy for severe genetic diseases, its cardiac immunotoxicity may challenge broad clinical use.

Cardiac imaging and in particular transthoracic echocardiography and computed tomography play a major role in the selection of the patients for surgical or transcatheter aortic valve replacement, for the assessment or procedural success and early prosthetic valve hemodynamics following aortic valve replacement, and for the evaluation and follow-up of the prosthetic valve structure and function in the longer-term, which is key to demonstrate the valve durability. The purpose of this review article is thus to present the role of cardiac imaging, and particularly transthoracic echocardiography and computed tomography, in: (1) patient selection for intervention; (2) assessment of procedural and device success, and of intended performance of the valve; and (3) assessment of the long-term success, valve durability, and prognosis, for clinical trials of intervention in patients with aortic stenosis. Transthoracic echocardiography is the primary imaging modality to detect and stage bioprosthetic valve dysfunction. However, multimodality imaging, including transesophageal echocardiography and computed tomography, is often necessary to determine the cause of bioprosthetic valve dysfunction and make the differential diagnosis between prosthesis-patient mismatch, structural valve deterioration, thrombosis, pannus, or endocarditis. The clinical trials in the field of structural heart disease, and particularly in the field of aortic valve intervention, include imaging end points as part of the primary or key secondary end points. Standardized methods and definitions should be applied to adjudicate these imaging end points, and ideally, these trial end points should be analyzed by independent imaging core labs.

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 mutation TMEM43-p.S358L causes ARVC5 (arrhythmogenic right ventricular cardiomyopathy type 5). The TMEM43 function 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. We provide evidence for a novel pathomechanism contributing to ARVC5.