Circulation

BackgroundThe comparative roles of triglyceride-rich lipoproteins (TRLs) and low-density lipoproteins (LDLs) in abdominal aortic aneurysm (AAA) pathogenesis are unclear. ObjectivesTo evaluate the putative causal role of TRLs in AAA, quantify the relative effect on AAA risk ("aneurysmogenicity") of TRL vs LDL particles, and prioritize lipid-lowering drug targets for AAA prevention and treatment. MethodsWe performed summary-level and individual-level Mendelian randomization (MR) analyses. Geneti...

Heart failure with preserved ejection fraction (HFpEF) affects over 30 million people and lacks disease-modifying therapies. Although genomic-led drug discovery increases success by more than 2.6-fold, HFpEF genomic discovery remains constrained by imprecise phenotyping in biobanks, with only two loci identified to date. Biobanks lack HFpEF diagnostic codes and echocardiograms, yet HFpEF diagnosis exists along a continuum and is inherently probabilistic, presenting an opportunity for multimodal ...

Congenital heart disease (CHD) occurs in over half of individuals with 22q11.2 deletion syndrome (22q11.2DS) and the types of lesions range from mild to severe. To determine the basis of variation in cardiac phenotypes we analyzed demographic data from 3,016 unrelated individuals with 22q11.2DS from centers in the Northeast US, Canada, Europe, South America, Israel and Australia. Most individuals in this cohort had a 3 million base pair hemizygous deletion between low copy repeat, LCR22 A-D (87....

BACKGROUNDPeak oxygen uptake (pVO2) is a strong, independent predictor of adverse cardiovascular outcomes, supporting cardiopulmonary exercise testing as a primary end point assessing efficacy of novel drug therapies in obstructive hypertrophic cardiomyopathy (oHCM) clinical trials. However, characterizing changes in pVO2 that patients perceive as beneficial or meaningful (ie, minimal important difference [MID]) has not been determined. METHODSData from patients with symptomatic oHCM enrolled i...

BackgroundHDL particles can carry microRNAs (miRNAs), capable of regulating gene expression connected to HDL functions. Despite links to some cardiovascular risk factors, miRNA association with incident acute myocardial infarction (AMI) remains unclear. ObjectivesOur aim was to elucidate the association between HDL-bound miRNAs (HDL-miRNAs) and incident AMI using a non-targeted approach in a population-based study. MethodsWe conducted a case-cohort study including 247 participants from the REG...

Heart failure with preserved ejection fraction (HFpEF) is an increasingly common cause of morbidity and mortality in older adults that is driven by cardiac and non-cardiac mechanisms. Physical rehabilitation improves frailty and functional capacity in HFpEF, though underlying mechanisms remain less clear. We quantified >5,000 circulating proteins across two randomized clinical trials of rehabilitation in HFpEF (REHAB-HF, SECRET-II), identifying proteins associated with prognostic measures of phy...

BackgroundAdvances in wearable devices and machine-learning-based ECG analysis enable highly accurate detection of atrial fibrillation (AF) outside traditional clinical settings, leading to increasing identification of asymptomatic AF. However, the prognostic significance of AI-detected asymptomatic AF and its implications for downstream cardiovascular risk remain unclear. In contrast to clinically diagnosed AF, evidence guiding risk stratification and further evaluation in this population is li...

Background and AimsAccurate classification of mitral stenosis (MS) remains a significant clinical challenge. This study aimed to develop an artificial intelligence (AI) framework to automatically detect clinically significant MS from echocardiography. MethodsWe developed EchoNet-MS, an open-source end-to-end integrated approach combining video based convolutional neural networks to assess MS severity and differentiate rheumatic etiology from echocardiography and validated its performance across...

BackgroundArtificial intelligence (AI) has emerged as a promising tool for interpreting 12-lead electrocardiograms (ECGs), with the potential to enhance diagnostic accuracy for arrhythmia detection. However, published studies vary widely in methodology and validation strategy, warranting a quantitative synthesis of diagnostic performance. MethodsA systematic review and meta-analysis was conducted according to the PRISMA-DTA 2018 guidelines and registered in PROSPERO (CRD420251027264). Searches ...

Background and aims Iron deficiency (ID) and myocardial iron depletion (MID) are causally linked to heart failure (HF) in the general population and in preclinical models. ID is common amongst pregnant women, but its impact on cardiac adaptations to pregnancy is unknown. This study examines that impact, and its potential relevance to peripartum cardiomyopathy (PPCM). Methods. We provided female mice with iron-replete or iron-deficient diets, and monitored cardiac function and morphology longitud...

BackgroundEchocardiography (echo) is a cornerstone of pediatric cardiology, yet access to expert interpreters is limited worldwide, particularly in low-resource and rural settings. Artificial intelligence (AI) offers a mechanism to broadly deliver expert-level precision and standardize measurements, yet AI for comprehensive automated measurements in pediatric and congenital heart disease (CHD) echo remains underdeveloped. MethodsWe created EchoFocus-Measure, an AI platform that automatically ex...

We performed a systematic review and meta-analysis of randomized controlled trials evaluating glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus placebo in adults with heart failure (HF), searching PubMed, Cochrane CENTRAL, and ClinicalTrials.gov through February 2026. The primary outcome was the composite of cardiovascular death and first HF hospitalization. Random-effects meta-analysis used restricted maximum likelihood estimation with Hartung-Knapp-Sidik-Jonkman adjustment. We inclu...

BackgroundEmbolic stroke of undetermined source (ESUS) is associated with a high risk of recurrence. However, randomized trials have not shown superiority of anticoagulation over aspirin in unselected patients. Atrial cardiomyopathy (AtCM) may identify a high-risk ESUS phenotype. We investigated whether multimodal AtCM markers distinguish ESUS from controls and predict adverse clinical outcomes. MethodsIn this prospective single-center study, consecutive ESUS patients and age- and sex-matched c...

BackgroundAcute myocarditis is typically self-limiting and resolves spontaneously in most cases. However, ventricular arrhythmias (VA) complications, which may be life-threatening are associated with higher rates of in-hospital complications and mortality. Catheter ablation is occasionally required for acute myocarditis associated ventricular tachycardia (VT), but data on its procedural use and outcomes, in this setting, remain limited. We aimed to determine the prevalence of VA among patients h...

ObjectivesTo identify unique echocardiographic signatures associated with TTR+ carrier status preceding onset of cardiac amyloidosis. BackgroundCarrier status for the most common pathogenic TTR variant in the United States, Val142Ile (V142I), found in 4% of African Americans (AA) and 1% of Hispanic/Latino (H/L) individuals, confers a 40-60% lifetime risk of developing variant transthyretin amyloidosis (ATTRv), including cardiac amyloidosis (CA) and heart failure (HF). Myocardial amyloid deposit...

BACKGROUNDConventional electrocardiography (ECG) has limited diagnostic accuracy for detecting coronary artery disease (CAD) in patients with stable chest pain. Advanced electrocardiography (A-ECG) may improve diagnostic performance. The study aimed to derive, externally validate, and prognostically validate an explainable A-ECG score for detecting CAD on coronary computed tomography angiography (CCTA). METHODSParticipants attending an outpatient rapid access chest pain clinic (RACC) underwent ...

BackgroundIn patients with atrial fibrillation (AF) and stable coronary artery disease beyond 1 year after percutaneous coronary intervention (PCI), oral anticoagulant monotherapy is guideline-recommended; however, its efficacy and safety in patients with complex PCI remain uncertain. MethodsWe conducted a post-hoc analysis of the randomized ADAPT AF-DES trial comparing NOAC monotherapy versus NOAC plus clopidogrel in AF patients [≥]12 months after second- or third-generation drug-eluting st...

Background and AimsDespite advances in reperfusion and medical therapy, survivors of acute myocardial infarction (AMI) remain at risk for adverse left ventricular remodeling (LVR), a precursor to heart failure. Building on prior work outlining 12-month biomarker trajectories linked to early ventricular dysfunction, we aimed to assess whether these circulating biomarkers predict long-term adverse LVR. MethodsWe prospectively enrolled 155 patients experiencing their first AMI. Clinical, biochemic...

Structured AbstractO_ST_ABSBackgroundC_ST_ABSGuideline recommendations for infective endocarditis (IE) prophylaxis have narrowed significantly over the past decade. However, these recommendations are derived from adult data and may not adequately account for the unique risk factors for IE in pediatric and congenital heart disease (CHD) patients with cardiac implantable electronic devices (CIEDs). ObjectiveTo characterize contemporary IE cases and prophylaxis practices among members of the Pedia...

BackgroundThe molecular drivers distinguishing valvular heart disease-associated atrial fibrillation (VHD-AF) from other AF etiologies remain poorly defined, with prior transcriptomic studies largely focused on non-valvular AF. MethodsWe performed RNA sequencing on peripheral blood mononuclear cells (PBMCs) from 15 patients with VHD-AF and 15 age- and sex-matched healthy controls. Bioinformatic analyses identified differentially expressed genes (DEGs), enriched pathways, and protein-protein int...