Circulation

BackgroundPeripartum cardiomyopathy (PPCM) is a life-threatening condition. Despite rising incidence, outcomes have not improved. This study evaluated national inpatient trends, disparities, and independent risk factors for PPCM. MethodsUsing the National Inpatient Sample (2016-2020), we analyzed adults ([≥]18 years) hospitalized between 10 and 42 weeks of gestation. Among 18,844,715 patients, 4,475 had PPCM. We performed uni- and multivariate logistic regression analysis of risk factors for...

IntroductionPeripartum cardiomyopathy (PPCM) is a life-threatening pregnancy-associated cardiomyopathy characterized by left ventricular systolic dysfunction. Due to its relative rarity, risk factors are not well established, and a validated risk score is lacking. MethodsWe conducted a retrospective cohort study, analyzing 317,892 deliveries between January 2014-December 2024. PPCM cases were identified by individual clinical chart review and echocardiographic validation. Multivariate logistic ...

BackgroundNaV1.5 channels, encoded by SCN5A, are essential for the genesis and shaping of the cardiac action potential (AP). Gain-of-function (GoF) variants in SCN5A are associated with long QT syndrome (LQTS), whereas loss-of-function (LoF) mutations are linked with Brugada syndrome. MOG1 is an integral part of the NaV1.5 channelosome, increasing both current and membrane expression of NaV1.5. Two LoF variants in MOG1 (E61X and E83D) cause Brugada Syndrome in patients, but no association with L...

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...

BackgroundRight heart failure (RHF) leads to an elevation in central venous pressure and causes hepatic congestion. Apolipoprotein M (ApoM), a hepatocyte-derived lipocalin bound to high-density lipoprotein, transports sphingosine-1-phosphate (S1P), which maintains vascular integrity and modulates inflammation. Although low ApoM predicts adverse outcomes in heart failure (HF), its role in RHF is unclear. We sought to investigate the impact of RHF on circulating ApoM, its prognostic value in RHF m...

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...

BackgroundAccurate etiologic classification of mitral valve (MV) is essential for guiding clinical management but remains dependent on expert visual interpretation. Despite advances in artificial intelligence (AI)-based quantitative analysis, automated morphologic interpretation under routine imaging conditions remains limited. ObjectivesTo develop and validate a deep learning (DL) framework for multiclass classification for major MV etiologies using a limited routine transthoracic echocardiogr...

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...

BackgroundDelayed or missed diagnosis of congenital heart disease (CHD) contributes to excess pediatric mortality worldwide. Echocardiography (echo) is central to diagnosing and triaging CHD, yet expert interpretation remains a scarce and maldistributed global resource. Artificial intelligence (AI) offers the potential to democratize diagnostics and extend expert-level interpretation beyond large academic centers, but its application in CHD remains underexplored. MethodsWe developed EchoFocus-C...

BackgroundArtificial intelligence (AI)-derived electrocardiographic aging (ECG-aging) has been found to be associated with the risk of atrial fibrillation (AF). ObjectivesWe aimed to assess the causal association between the discrepancy in AI-predicted electrocardiographic age and chronological age (AI-ECG age gap) and AF risk. MethodsWe analyzed 12-lead ECGs in UK Biobank to derive the AI-ECG age gap using our latest AI-based age prediction model. Associations between measured ECG-aging and g...

BackgroundCardiovascular and cerebrovascular risks of SARS-CoV-2 infection and mRNA vaccination remain incompletely defined and lacking comparative outcomes such as sex-specific vulnerabilities. MethodsUsing the TriNetX Research Network (December 2020-December 2024), we identified four mutually exclusive cohorts: uninfected/unvaccinated (naive), infected/unvaccinated, vaccinated-only, and infected/vaccinated (hybrid immunity). We compared 50 prespecified cardiovascular, cerebrovascular, and mor...