Journal of the American Heart Association

Background: The manifestations of cardiovascular disease (CVD) among people with HIV (PWH) differ by region globally. While HIV disease is associated with increased atherosclerotic CVD risk in the global North, non-ischemic heart failure (HF) is more common in sub-Saharan Africa, the global HIV epicenter. We estimated the effect of treated HIV on the frequency and phenotype of HF and its cardiac precursors in South Africa (SA). Methods: In an observational study, we recruited PWH on antiretroviral therapy (ART), age [≥]40 years and people without HIV (PWoH) with similar distributions of age, sex, ethnicity, and hypertension, from a community clinic in Khayelitsha (Cape Town, SA). Procedures included a clinical assessment, echocardiography (Echo), and b-type natriuretic peptide (BNP) measure. Echo parameters defined structural abnormalities, left ventricle (LV) filling pressure, and LV systolic and diastolic dysfunction (DD). HF was defined by symptoms and/or BNP [≥]35pg/mL and LV dysfunction, subcategorized as reduced, mildly reduced, or preserved ejection fraction (HFrEF, HFmrEF, and HFpEF). Comparisons by HIV status were adjusted for age, sex, hypertension, smoking, obesity, diabetes, elevated LDL-cholesterol, and hazardous alcohol use. Results: Between September 2022 and August 2025, we enrolled 1008 PWH and 500 controls [median (Q1-Q3) age 48 years (43-53), 77% female]. Among PWH and controls respectively, 37% and 39% had hypertension, 21% and 25% were current smokers, 40% and 45% were obese, and 9% and 17% had diabetes. LV systolic dysfunction (1%) and HFrEF (1%) were rare, and undiagnosed HFpEF (8%) was the predominant HF phenotype. Compared to controls, PWH had higher odds of elevated LV mass index (LVMI) (OR 2.1; 95%CI 1.5-3.0) and DD (OR 1.4; 95%CI 1.0-2.0). Risk for elevated LVMI and DD was greatest among women with HIV, who also had an increased risk for undiagnosed HFpEF (OR 1.9; 95%CI 1.2-3.2), compared to women without HIV; effects which were not seen among men (p=0.051 for HIV*Sex interaction). Conclusions: In a peri-urban SA community with a high burden of cardiometabolic risk factors, the frequency of abnormal structural and functional cardiac precursors of HFpEF was greater amongst ART-treated PWH. This was most pronounced amongst women with HIV, who also had increased risk of undiagnosed HFpEF.

Background: Most approaches to suicide risk assessment consider clinical conditions as independent risk factors, potentially overlooking prognostic information in the order in which conditions accumulate. We applied temporal sequence mining to linked claims and mortality data to identify ordered clinical diagnostic trajectories associated with suicide death. Results: The cohort included 3 647 059 insured Maryland residents aged 10 years or older with available claims records in the Maryland Suicide Data Warehouse from January 1, 2016, to December 31, 2020, among whom 768 suicide deaths were ascertained through medical examiner linkage. Sequential pattern mining of ICD-10-CM diagnoses grouped into Clinical Classifications Software Refined categories identified 89 221 candidate sequences, of which 1 816 remained significantly associated with suicide death in time-varying Cox models. Adjusted hazard ratios (AHRs) ranged from 2.4 to 134.1. Two-thirds of significant trajectories ended in physical conditions, and approximately half crossed from psychiatric to physical endpoints. Among suicide decedents, 62% were exposed to at least 1 significant sequence (median, 16 per case); median sequence duration was 18.7 months, and median time from completion to death was 13.1 months. In landmark analyses, among patients with depression who later developed suicidal ideation (n = 26 356), the path through anxiety, then anemia, was associated with higher risk (AHR, 4.6; 95% CI, 2.2-9.5), whereas the anxiety-only path was not (AHR, 1.3; 95% CI, 0.8-2.1). Among patients with anxiety who later developed hypertension (n = 149 215), the path through history of self-harm was associated with higher risk (AHR, 32.0; 95% CI, 16.6-61.6). Associations were generally consistent across sex and age. Conclusions: Temporal ordering of clinical conditions may carry prognostic information for suicide death. Clinical trajectories incorporating physical illness within psychiatric sequences identified higher-risk groups. These findings suggest that opportunities for risk detection may extend beyond psychiatric settings and that suicide risk signals may be fragmented across care settings and not apparent within isolated encounters.

Abstract Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular benefit in type 2 diabetes and obesity, with recent observational data suggesting favorable associations after transcatheter aortic valve replacement. Whether similar associations exist after surgical aortic valve replacement (SAVR) is unknown. Methods: Retrospective propensity-matched cohort analysis using the TriNetX U.S. Collaborative Network. Adults with type 2 diabetes or obesity (BMI [≥]30 kg/m2) undergoing SAVR were categorized by GLP-1 RA exposure (any use within 3 months before through 1 year after SAVR) versus no use. One-to-one matching was performed on 44 covariates. Primary outcomes were 1-year all-cause mortality, heart failure, acute kidney injury, acute myocardial infarction, cerebral infarction, and atrial fibrillation. Sensitivity analyses included 30-day landmark restriction and falsification outcomes. Results: After matching, 1,984 patients were retained per cohort. GLP-1 RA use was associated with lower 1-year risks of all-cause mortality (4.8% vs 10.4%; HR, 0.44; 95% CI, 0.34-0.56), acute kidney injury (6.9% vs 10.1%; HR, 0.65; 95% CI, 0.49-0.85), myocardial infarction (3.0% vs 5.1%; HR, 0.57; 95% CI, (0.40-0.82), heart failure (11.3% vs 15.7%; HR, 0.68; 95% CI, (0.51-0.90), and atrial fibrillation or flutter (10.1% vs 13.9%; HR, 0.69; 95% CI, 0.54-0.90; all P[≤]006). Cerebral infarction did not differ. In landmark analysis, mortality, heart failure, and acute kidney injury associations persisted; myocardial infarction and atrial fibrillation associations were attenuated. Falsification outcomes were null. Conclusions: Perioperative GLP-1 RA use was associated with lower 1-year cardiovascular event rates after SAVR. These hypothesis-generating findings support prospective randomized investigation.

Background: Infants with critical congenital heart disease (CHD) are at high risk for abnormal brain development and later neurodevelopmental impairment. We hypothesized that the trajectory of perioperative whole-brain network development would predict neurodevelopmental outcomes in early childhood. Methods: This prospective longitudinal cohort of neonates with critical CHD (n = 97) underwent preoperative and/or postoperative brain MRI with diffusion imaging. Whole-brain network measures were derived from structural connectomes. Neurodevelopment was assessed between 1 and 4 years using the Bayley Scales of Infant and Toddler Development. Results: White matter injury was associated with slower perioperative growth in global efficiency (p = 0.013), a measure of network integration, whereas cardiac physiology was not associated with network development. Infants with greater perioperative increases in global efficiency had higher cognitive (p = 0.001), language (p < 0.001), and motor (p = 0.008) scores. For each 1-standard deviation increase in the trajectory of global efficiency, cognitive scores increased by 8.2 points (95% CI, 3.64-12.78), independent of brain injury and socioeconomic factors. Conclusion: In infants with critical CHD, longitudinal whole-brain network development was associated with neurodevelopment across multiple domains. Early network development may represent a candidate biomarker of neurodevelopmental risk and resilience in this population.

Background Myocardial remodeling precedes symptomatic heart failure, which is important to detect early. We assessed feasibility and clinical correlates of a novel integrated assessment of myocardial remodeling in a large rural cohort in the Southeastern United States. Methods Echoes were obtained with AI assistance (Caption guidance) in 3100 adults in the NHLBI-funded RURAL cohort study. Of those, 1895 had quantifiable global longitudinal strain (GLS), left ventricular mass (LVM), and left atrial volume (LAV). LV-LA Health was based on a simple count of sex-specific abnormalities (0-3), indexed to body surface area (BSA) or height (Table 1). Relationships with demographics and risk factors were compared with Spearman correlation and Mantel-Haenszel tests, with moderate and severe results combined. Results Median (IQR) age was 49 (40-58). Impaired LV-LA Health is common even in a low PREVENT cardiovascular (CV) risk population (median 10-year risk 3.3%; 25th, 75th 1.2,7.2) with preserved ejection fraction (EF; 60%; 57,62). The prevalence of abnormalities differed greatly by indexing method: 18.2% with BSA (15.1% mild; 3.1% mod/severe) vs 51% with height (38.3% mild; 12.7% mod/severe) (Figure 1). LV-LA impairment increased with age, PREVENT CV risk score and cardiovascular risk factors (hypertension, diabetes, dyslipidemia, obesity); all p<0.001. Impairment was more common in Black vs White people (p<0.001) and differed by sex only with height indexation. Conclusions A novel LV-LA health composite of routinely acquired echocardiographic measures identifies substantial subclinical cardiac remodeling in a middle-aged rural community cohort, not detected by PREVENT score or ejection fraction. This is the first application of this framework in a large, unselected community sample. Indexation method affects prevalence, with BSA likely underestimating risk in adiposity-enriched populations. Findings suggest a high rural burden and longitudinal evaluation with future CV events is ongoing.

Aims This multicenter study aims to compare outcomes of total aortic arch replacement (TAR) using the frozen elephant trunk (FET) technique in patients with and without heritable thoracic aortic disease (HTAD) and to assess whether HTAD influences postprocedural adverse aortic events (AAEs). Methods From 06/2007 to 05/2024, aortic databases from 13 European centers were screened for HTAD patients undergoing TAR with FET. All consecutive dissection and aneurysm non-HTAD patients from the four core centers served as comparator. The primary outcome was AAE, a composite of diameter progression, distal stent graft induced new entry (dSINE), malperfusion, rupture and pseudoaneurysm at 5 years after FET implantation. Results Of 2739 FET patients, 196 (7.2%) were diagnosed with HTAD. The control group consisted of 867 non-HTAD FET patients. Marfan syndrome was the most common condition (72%), followed by Loeys-Dietz syndrome (11%), vascular Ehlers-Danlos syndrome (5.6%) and Turner syndrome (2.0%). Seventeen (8.8%) patients were diagnosed with ns-HTAD. At 5 years 46 (24%) AAEs occurred in the HTAD group, 169 (20%) in the non-HTAD group (p=0.2). Diameter progression was the most common event (10% vs. 12%; p=0.6), followed by dSINE (5.8% vs. 4.5%; p=0.5), malperfusion (4.2% vs. 3.3%; p=0.5), rupture (2.1% vs. 0.7%; p=0.09) and pseudoaneurysm (0.5% vs. 0.2%; p=0.5). Conclusions The FET technique appears safe and effective for acute and chronic aortic disease in HTAD patients, with outcomes comparable to non-HTAD cases and no increase in graft-related complications, challenging traditional concerns about stent graft use in genetically mediated aortic disease.

Background: Red cell distribution width (RDW), a readily available hematological parameter reflecting erythrocyte size heterogeneity, has been increasingly recognized as a prognostic marker in congestive heart failure (CHF), with elevated levels independently associated with adverse outcomes. However, RDW-derived composite indices-particularly the RDW-to-platelet ratio (RPR) and RDW-to-hemoglobin ratio (RHR), which integrate inflammatory, hemostatic, and oxygen-delivery pathways-remain largely unexplored in CHF populations. Whether these indices provide incremental prognostic value beyond RDW alone in critically ill patients with CHF has not been established. Methods: This retrospective cohort study included 30,409 participants from the MIMIC-IV and eICU-CRD databases. Multivariable logistic regression, restricted cubic spline (RCS) analysis, and subgroup analyses were employed to evaluate the associations between RDW, RDW-derived indices (RPR and RHR), and in-hospital mortality in patients with congestive heart failure. Results: Based on a pooled cohort of 30,409 patients with CHF from the MIMIC-IV and multi-center eICU-CRD databases (15,983 and 14,426, respectively), 16,295 (53.6%) were male and 14,114 were female, with a median age of 71.7 years. The mean RDW was 16.0 {+/-} 2.5, and the overall in-hospital mortality rate was 12.6%. Higher RDW quintiles were associated with progressively increased in-hospital mortality. In the fully adjusted model, RDW, RPR, and RHR were all significantly associated with increased in-hospital mortality, with adjusted odds ratios (ORs) of 2.46 (95% CI: 2.17-2.79) for RDW, 1.55 (95% CI: 1.38-1.73) for RPR, and 2.43 (95% CI: 2.09-2.82) for RHR. Sensitivity analyses using restricted cubic splines demonstrated that the association between RDW and RHR with in-hospital mortality was linear (P for nonlinearity > 0.05), whereas that for RPR exhibited a non-linear pattern (P = 0.02 for non-linearity). Conclusions. Elevated RDW, RPR, and RHR were independently associated with increased in-hospital mortality in patients with congestive heart failure. Notably, RPR exhibited a non-linear threshold association with in-hospital mortality.

Background World Symposium on Pulmonary Hypertension (WSPH) Group 2 pulmonary hypertension (PH) is a clinically integrated phenotype attributed to left heart disease, whereas pre- versus post-capillary classification is operationalized primarily by pulmonary capillary wedge pressure (PCWP). Although current recommendations emphasize contextual interpretation and provocative testing for intermediate PCWP values, the relationship between PCWP-based classification and underlying phenotype has not been systematically evaluated. We aim to quantify phenotype-hemodynamic discordance across the PCWP spectrum and evaluate a staged physiology-guided framework incorporating inhaled nitric oxide (iNO), ventricular geometry, and provocative testing. Methods We studied 1,032 participants from the NHLBI-sponsored PVDOMICS cohort with multidisciplinary adjudicated phenotypes integrating clinical, imaging, physiologic, and hemodynamic data. Stage-specific PCWP thresholds classified pre- versus post-capillary physiology at rest, during iNO, and during provocation (fluid challenge or invasive cardiopulmonary exercise testing [iCPET]). Echocardiographic right ventricular-to-left ventricular (RV/LV) ratio was evaluated as a marker of ventricular interdependence. Restricted cubic spline and staged concordance analyses defined certainty-based PCWP ranges and incremental diagnostic yield. Results Adjudicated Group 2 phenotype was present in 37.0% of participants. Resting PCWP demonstrated good discrimination (AUC 0.86), but substantial bidirectional phenotype-hemodynamic discordance persisted across intermediate PCWP ranges. At a resting PCWP of 12 mmHg, 25% of participants classified as pre-capillary had adjudicated Group 2 PH, whereas at 18 mmHg, 35% classified as post-capillary remained discordant non-Group 2. Concordance did not approach 90% until PCWP values were <9 mmHg or >24 mmHg. Dynamic testing incrementally improved concordance within these overlap zones. Nearly half of adjudicated Group 2 PH participants (46.5%) were not identified by resting PCWP alone; incorporation of iNO and provocative testing increased cumulative Group 2 identification by 63.4% and improved sensitivity from 79.9% to 83.7%. Model discrimination improved from an AUC of 0.863 to 0.908 (likelihood-ratio P<0.001). iNO increased PCWP in discordant Pre/G2 participants, unmasking latent left-sided limitation, while lowering PCWP in discordant Post/NonG2 participants, consistent with ventricular interdependence. RV/LV ratio [&ge;]0.94 reduced discordant Post/NonG2 classification by 70.5%, and incorporation of PCWP/cardiac output slope improved physiologic specificity during exercise. Conclusions Group 2 PH is a dynamic, load-dependent phenotype inadequately characterized by resting PCWP alone. Intermediate PCWP values represent continuous probabilities of bidirectional discordance rather than discrete diagnostic states. A staged physiology-guided approach integrating iNO, ventricular geometry, and provocative testing improves concordance between hemodynamic classification and clinically integrated phenotype assignment.

Background Totally endoscopic aortic root (AR) surgery via right anterior minithoracotomy (RAMT) may reduce surgical trauma and accelerate recovery compared with full sternotomy (FS). However, the approach is technically demanding due to limited access and anatomical complexity. This study compares early clinical outcomes and quality of life (QoL) after RAMT versus FS to evaluate the feasibility and safety of the totally endoscopic approach. Methods This single-center, retrospective study included 149 patients underwent AR surgery via RAMT (n=74) or FS (n=75) between January 2021 and March 2026. Patients with aortic dissection, infective endocarditis, redo surgery, concomitant procedures, or arch replacement were excluded. Operative outcomes, postoperative recovery, 30-day and 1-year mortality were analyzed. QoL was assessed using the Short Form-8 (SF-8) questionnaire. Results The median age was 60.0 years, and 79.9% of patients were male. Bentall procedure was performed in 84.6% of patients, 15.4% underwent a David procedure. Compared with FS-AR, RAMT-AR was associated with shorter median operative time (147.0 vs. 178.0 min; p<0.001), lower median chest drainage volume (650.0 vs. 850.0 mL; p<0.001), and shorter median ICU stay (24.0 vs. 25.0 h; p=0.008) and hospital stay (6.0 vs. 8.0 days; p=0.028). Overall, 30-day and 1-year mortality was 0.7%. SF-8 analysis demonstrated significantly higher physical and mental component scores in RAMT-AR patients. Conclusion In specialized centers, totally endoscopic AR surgery via RAMT is a safe and feasible minimally invasive approach associated with favorable early outcomes and a potential benefit in postoperative physical and mental QoL by reducing surgical trauma.

Background: Machine learning models trained on population health surveys offer scalable tools for cardiovascular screening, but recurring methodological weaknesses undermine their credibility and equity: data leakage from synthetic oversampling, qualitative rather than quantitative explainability evaluation, and the absence of demographic fairness auditing at the clinical operating threshold. Methods: We present EXHEART, a leakage-free stacked ensemble pipeline trained on BRFSS 2015 (n = 253,680) and validated on BRFSS 2020 (n = 319,795; temporal transport and retrain) and a clinical cardiovascular examination dataset (n = 68,730). The pipeline combines XGBoost, LightGBM, Random Forest, and a multi-layer perceptron as base learners with 5-fold out-of-fold logistic regression stacking and Platt scaling calibration. A quantitative SHAP-LIME consistency framework, based on Kendall-tau rank correlation and Jaccard overlap, accompanies a decision-curve analysis, a subgroup-stratified SHAP interaction analysis, and an intersectional fairness audit (Sex x Age x Income) with threshold-shifting mitigation and a frontier of the fairness-utility trade-off. The framework also adds cross-instrument fairness-disparity attribution, an empirical diagnostic that provides evidence on whether an observed subgroup disparity is more consistent with a measurement-induced or a substantive explanation by re-validating it on a dataset that measures the same clinical construct objectively. On heart disease, this diagnostic associates 89% of the sex TPR gap (95% CI [0.65, 0.99]) with the self-reported survey outcome rather than with a substantive risk difference. Results: On BRFSS 2015, EXHEART achieves AUC-ROC = 0.850, AUPRC = 0.371, Brier score = 0.071, and reduces ECE by 96% (0.256 to 0.011) via Platt scaling. Global SHAP-LIME rank agreement is moderate-to-strong (Kendall-tau = 0.580, Spearman-rho = 0.818) with a substantial top-3 divergence (Jaccard@3 = 0.200), where Stroke flips from SHAP rank 8 to LIME rank 1. The Sex TPR gap is 0.124 at the screening threshold; intersectional Sex x Age disparities reach 0.649 among adequately-powered cells, 5.2x the single-attribute gap. Temporal transport to BRFSS 2020 collapses sensitivity from 0.776 to 0.267, while retraining restores AUC = 0.840 and ECE = 0.012. On clinical examination data, the Sex TPR gap collapses to 0.014; the attribution test indicates this gap is instrument-dependent, consistent with a measurement or outcome-definition explanation rather than a substantive risk difference. Cross-domain SHAP analysis identifies four instrument-independent CVD risk factors and two major portability failures. Conclusions: EXHEART combines three practices that population-scale cardiovascular classifiers usually apply in isolation: leakage-free training with calibrated probabilities, a test of whether the model's explanations are stable, and a fairness audit that examines intersecting subgroups rather than single attributes. Bringing them together proved worthwhile. The intersectional audit revealed disparities that single-attribute auditing missed, and the cross-instrument comparison indicated that much of the sex gap reflects how the outcome is measured in survey data rather than a substantive difference in risk. The temporal transport findings indicate that deployed BRFSS models warrant periodic monitoring and retraining to maintain clinical utility. EXHEART is a retrospective methodological evaluation on public de-identified data; it is not validated for direct clinical decision-making, diagnosis, or treatment recommendation without prospective clinical validation.

Background: Epic Cosmos is a relatively new centralized electronic health record dataset with high potential utility in perinatal epidemiologic research. Objectives: The study objectives were to develop replicable steps to create longitudinal, linked maternal-infant cohorts in Cosmos, assess completeness of key variables, evaluate potential selection bias with restrictions for longitudinal healthcare encounters, and provide an example epidemiologic analysis. Methods: We created maternal-infant cohorts by starting with live births during 2023-2024 recorded in the BirthFact data table and joining with additional data tables as needed. We selected and created variables for perinatal characteristics, common comorbidities, and routinely measured vital signs and laboratory values, and assessed variable completeness. We sequentially restricted the birth cohort for maternal-infant linkage and longitudinal healthcare from first-trimester prenatal care encounter through infant follow-up care within 12 weeks post-discharge from birth hospitalization. Finally, we conducted an example analysis of the association between high systolic blood pressure in the first trimester ([&ge;]140 mm Hg) and later onset of preeclampsia among those with chronic hypertension. Results: The total linked birth cohort included 2,624,186 pregnancies. Completeness was >90% for most variables assessed but was 77% for racial and ethnic group and 76% for body mass index at delivery. Characteristics of the cohort were similar to those reported for the entire United States birth population based on birth certificate data, including similar regional and racial-ethnic composition. Longitudinal cohort restriction requiring linked records from first trimester prenatal care through infant follow-up care reduced the cohort size to 509,148 pregnancies. However, restriction had minimal effects on cohort characteristics. In the example analysis, high systolic blood pressure was associated with increased risk of preeclampsia among those with chronic hypertension (aRR: 1.26; 95% CI: 1.22, 1.30). Conclusions: This study provides a rigorous and reproducible approach to creating longitudinal, linked maternal-infant cohorts in Epic Cosmos and the analytical findings suggest high data quality and representativeness.

Background: Maternal mental health problems are common after prenatal diagnosis of congenital heart disease (CHD), with long-term implications for child and family wellbeing. HEARTPrep is a prenatal psychosocial intervention with three self-paced modules and corresponding telehealth sessions, delivered during pregnancy via mobile app to improve mental health and wellbeing for mothers expecting a baby with CHD. This proof-of-concept study evaluated the feasibility of HEARTPrep and examined maternal mental health and psychosocial functioning throughout participation. Methods: Participants were mothers receiving care for a fetal CHD diagnosis within one health system. Feasibility was assessed via rates of enrollment and completion. Mothers completed 4-item PROMIS questionnaires assessing anxiety, depression, and social isolation and reported self-efficacy and hope on a weekly basis throughout HEARTPrep. Results: Of 34 recruited mothers, 29 (85%) enrolled and two were subsequently not eligible (delivery prior to participation, change in fetal diagnosis), resulting in a final sample of 27 mothers. The majority (n = 22, 81%) completed all three telehealth sessions and Modules 1 (n = 22, 81%) and 2 (n = 19, 70%), with just over half (n = 14, 52%) completing Module 3 prior to delivery. Mean PROMIS depression T-scores decreased from 57.5 to 52.9, and 48% of mothers had a decrease in depression scores exceeding the meaningful change threshold (half standard deviation). The percentage of mothers reporting high self-efficacy increased from 19% to 48%. Conclusions: HEARTPrep is feasible and corresponds with reduced maternal depression and increased self-efficacy, supporting proof-of-concept. A randomized controlled trial is needed to determine whether HEARTPrep improves outcomes compared to a control group.

Background Blood pressure (BP) regulation in individuals with sickle cell disease (SCD) is influenced by a complex interplay of genetic and physiological factors. While SCD has traditionally been associated with lower BP, there is an increased risk of hypertension. Emerging BP research suggests significant heterogeneity across genotypes, age groups, and sex. Objectives: This study investigated the longitudinal effects of population-level characteristics and continuous clinical and laboratory predictors on systolic (SBP) and diastolic blood pressure (DBP) in individuals with SCD, with emphasis on the interactions between baseline and predicted blood pressure slopes over time. Methods We retrospectively analyzed longitudinal data from a cohort of 2,739 patients with diverse SCD genotypes. Descriptive statistics were documented across sex, age range, genotype, health status and relative systemic hypertension risk categories (rHTN-risk). Linear mixed-effects models provided estimates of fixed- and random-effects of baseline BP and of time-related BP effects, respectively. Post-estimation margins provided contrasts of baseline-adjusted BP means and of pre-specified time effects on BP patterns. Results Males had significantly higher baseline SBP ({beta} = 6.64, p < 0.001) but lower baseline DBP ({beta} = -2.61, p < 0.001) compared with age-matched HbSS females. Baseline SBP was more unstable compared with baseline DBP and baseline DBP was more predictive of future BP trends than baseline SBP. Genotype was a consistent predictor of DBP (p < 0.05), but not of SBP. Similarly, we observed increased risks of relative diastolic hypertension across most genotypes, while the prevalence and magnitude of systolic hypertension was lower across all genotype compared with HbSS. Conclusions Blood pressure trajectories in SCD patients are not uniform and are significantly related to genotype, age group and sex over time. Baseline diastolic levels were less heterogenous and exhibited clear upward trajectories over time. These findings support the need for patient-specific BP surveillance in the care and management of SCD.

This cross-sectional study aimed to examine the prevalence of alcohol use and its sociodemographic correlates among adults with cardiovascular disease (CVD). We analyzed data from two large US cohorts: the All of Us Research Program (2017-2023) and the National Health and Nutrition Examination Survey (NHANES, 1999-2016). Both CVD diagnosis and past-year alcohol consumption were self-reported. Risky drinking was defined as exceeding moderate drinking or binge drinking (All of Us), or moderate/heavy drinking (NHANES). Multivariable logistic regression was used to exam associations with sociodemographic and lifestyle factors. Among 32,788 current drinkers with CVD in the All of Us cohort, 15% exceeded moderate drinking thresholds and 26% reported binge drinking. Older age, female sex, and higher socioeconomic status were inversely associated with risky drinking, while smoking was positively associated. In NHANES, moderate drinking rose from 47.3% to 57.2% and heavy drinking from 6.7% to 7.2%. Moderate/heavy drinking was positively associated with age <65 but inversely with age [&ge;]65. Higher education and income were linked to moderate drinking, while current smoking was strongly associated with heavy drinking. These results highlight the need to integrate holistic screening for alcohol use, tobacco use, and social context into routine cardiovascular care.

Background: In atrial fibrillation (AF), cerebral microbleed (CMB) burden guides anticoagulation decisions, yet AF is itself inconsistently associated with CMBs, a paradox unexplained by frameworks that treat CMBs as a unitary marker of small vessel disease. We hypothesized that the white matter hyperintensity (WMH) context in which CMBs arise modifies their vascular meaning, and that this context-dependence underlies the inconsistent AF-CMB association. Methods: From a multicenter Korean stroke registry, we analyzed 5,735 first-ever ischemic stroke patients imaged at nine centers using susceptibility-weighted MRI. WMH volume and CMB count were extracted by validated deep learning pipelines. Patients were cross-classified by age-adjusted WMH residual (median split) and CMB count (2) into four groups. The AF-CMB association was estimated by multivariable logistic regression within each WMH stratum with formal interaction testing. Spatial CMB distribution was analyzed against the Automated Anatomical Labeling atlas. Results: In the full cohort (mean age 69.5 years; 57.7% male), AF was not associated with CMBs (OR 1.04; 95% CI 0.87-1.25). Stratification yielded divergent estimates: the adjusted AF OR was 1.46 (1.11-1.93; P = 0.007) in the WMH-low stratum and 0.95 (0.73-1.22; P = 0.665) in the WMH-high stratum, with significant interaction (OR 0.56; P < 0.001). The discordant phenotype (low WMH, high CMB; 8.9%) was enriched for AF (28.0%) and showed fronto-temporal cortical predominance with deep structure sparing. AF independently reduced the proportion of deep CMBs (IRR 0.80; P = 0.040). The interaction was preserved across prespecified sensitivity analyses. Conclusions: The AF-CMB association is confined to patients with low WMH burden relative to age and is accompanied by a topographically distinct CMB distribution. Clinical assessment of small vessel disease based on WMH alone may overlook a CMB phenotype linked to AF.

Background and Purpose: Hemorrhagic transformation (HT) is a serious complication of endovascular thrombectomy (EVT), yet dedicated prediction models for young adults are lacking. We aimed to develop and externally validate a simplified risk score for HT in young adults with acute ischemic stroke undergoing EVT. Methods: This multicenter retrospective study included patients aged 18 to 49 years with acute anterior circulation large vessel occlusion who underwent EVT. The primary outcome was any HT within 24 hours after EVT. Multivariable logistic regression was used to identify independent predictors of HT, from which the NO?PAIN Score was derived. External validation was performed in an independent cohort of 138 patients. Results: Among 598 patients in the derivation cohort, HT occurred in 176 (29.4%). Five independent predictors were identified: admission NIHSS, number of thrombectomy passes, atrial fibrillation, alcohol consumption, and mTICI grade. The mTICI grade demonstrated a non-linear, inverted U-shaped relationship with HT risk, peaking at partial recanalization. The NO-PAIN Score showed acceptable discrimination in both the derivation (C-index, 0.737; optimism-corrected C-index, 0.748) and external validation cohorts (C-index, 0.726), with satisfactory calibration. Conclusions: The NO-PAIN Score is a simple risk prediction tool for HT after EVT in young adults with acute anterior circulation large vessel occlusion. It may assist in individualized risk stratification in this population.

BACKGROUND: Coronary artery disease (CAD) and Impaired Cognitive (IC) disease share sociodemographic, genetic, and clinical factors, but the association of IC with statin use in CAD remains unclear. OBJECTIVES: To determine the association between IC and statin use in CAD based on APO (e) genotype, sex, and lipid levels. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective study of AllofUS (AoU) participants with CAD (Age [&ge;]60 yrs) enrolled from 2017 to 2023. We defined CAD as having a history of angina/myocardial infarction/chronic ischemic heart disease or having percutaneous coronary intervention/CABG, and IC defined as mild cognitive impairment or all cause dementia, using ICD/SNOMED codes. MEASURES: We assessed the association between IC and statin use using logistic regression analysis, while adjusting for clinical factors, sociodemographics, and APO (e) genotypes before and after propensity score matching. We further performed stratified analysis by sex, and APO (e) genotypes. We finally assessed the association between IC and statin users, based magnitude on the change in lipid levels before CAD and after IC (TC: Total cholesterol, LDL: low density lipoprotein, HDL: High Density Lipoprotein). Significance was defined at p < 0.05. RESULTS: The cohort included 22,089 participants with CAD and 1343 with IC. Thirty-nine percent of participants were females, 77% were European, 13% were African American, and 9% were of Admixed American ancestry. The proportion of IC was higher (6.8% vs 3.5%, p<0.001) in statin users (n=17,191) vs non-statin users (n=4,898). IC was significantly associated with statin use (OR:1.70;1.40-2.10, p = 4.9e-7) after adjustment for clinical factors, sociodemographics, and APO (e) genotypes. After propensity-score matching between IC and CAD, we observed an association between IC and statin use (OR:1.55;1.24-1.94, p =1e-4). In stratified analysis, the association between IC and statin use was strongest in the APO e3/e3 group (OR:2.04;1.53-2.75, p = 1e-6), and in females (OR:2.20;1.60-3.06, p = 2.e-6) compared to males (OR:1.43;1.10-1.90, p = 0.01). We finally observed an increased magnitude of association between IC and statin users having higher HDL increase (> 10 mg/dl: OR:1.95;1.44-2.66, p=1e-5) as compared to statin users with lesser HDL increase (<=; 10mg/dl: OR:1.61;1.22-2.15, p=8e-4). CONCLUSION: In the AllofUS cohort, IC was significantly associated with statin use in CAD participants. We observed the strongest association in the APO e3/e3 group, among females, and with a greater increase in HDL levels in statin users.

Abstract Background: Heart Failure is a complex clinical syndrome of growing public health concern in sub-Saharan Africa, yet the data from Sierra Leone are absent. The aim of the study is to characterise the clinical profile, etiological and temporal trends of hospitalised HF patients at Choithrams Memorial Hospital (CMH), Freetown, Sierra Leone, to confirm specific management strategies. Methods: This single-center, retrospective observational cohort study analysed data on HF patients (>18years) admitted at the CMH between January 2021 to 31 December 2025. The clinical definition of HF was based on the Framingham criteria and the European Society of Cardiology (ESC) guidelines , including standard echocardiographic parameters. All variables, including patients demographics, HF. phenotype, aetiology, medical history and hospital outcomes were extracted from the digital record. Non-parameteric tests, multivariable logistic regression to identify variables associated with etiology, Wilcoxon rank-sum test to compare groups and Kruskal-Wallis test to analyse trends over time were utilised. Result: A total of 765 patients were included in the study, with a median age of 53 years (IQR 42-61) and male predominance of 55.3%. Patients with recurrent HF (60.9%) were more common than those with de novo HF (39.1%), were older (54 years vs 53 years), had a higher comorbidity burden (34% vs 4%, p < 0.001), and presented with a cold-wet hemodynamic profile (18.4% vs 8.4%, p < 0.001). HFrEF (61.3%) was the most predominant phenotype, though HFpEF increased with age. Dilated Cardiomyopathy (37.0%), Hypertensive Heart Disease (31.2%) and Valvular Heart Failure (17.1%) were the leading etiologies, while ischemic heart disease (6.3%) was relatively uncommon. A majority of the patients were referred (77.9%), and 50.8% presented with NYHA IV. The strongest independent predictor for HF was hypertensive heart disease [AOR = 17.81; C.I 95%: (3.13-48.76), p <0.001]. An analysis of the trends in etiologies and demographics over the five-year period demonstrated no significant changes (all p-values > 0.05 for age, sex, aetiology, and most comorbidities). Conclusion: HF affects the younger adult population in Sierra Leone and is mainly caused by DCM and HHD. The late case presentations, the high prevalence of recurrent HF, and the associated high burden of comorbidities emphasize an urgent need to develop and implement improved strategies for the prevention, early detection, and long-term management of HF within Sierra Leone's healthcare system.

Background: Aortic stenosis (AS) is a progressive valvular disease associated with poor prognosis once symptoms develop, yet routine echocardiographic screening is impractical. While artificial intelligence (AI)-based electrocardiogram (ECG) models have shown promise for AS detection, it remains unclear whether they primarily reflect conventional left ventricular hypertrophy (LVH) voltage criteria or capture additional ECG features. Methods and Results: We developed a deep learning model using 244,816 ECGs from 51,713 patients across six academic institutions in Japan (CLIDAS database). AS labels were derived from inpatient Diagnosis Procedure Combination (DPC) codes. The model achieved an area under the receiver operating characteristic curve (AUC) of 0.849 (95% confidence interval 0.832-0.865) in the independent test cohort, with consistent performance across institutions, sex, and age. At a threshold of 0.1, sensitivity was 79.1%, specificity was 73.9%, and negative predictive value (NPV) was 98.0%. Conventional LVH voltage criteria (Sokolow-Lyon AUC 0.706; Cornell AUC 0.692) showed lower performance, and adding them to the AI model conferred no incremental benefit (AUC 0.849 vs. 0.847). Gradient-weighted class activation mapping (Grad-CAM) revealed predominant attention around QRS complexes in limb leads, beyond regions typically assessed in LVH evaluation. Conclusions: This multicenter AI-ECG model demonstrated strong discrimination for AS and captured ECG features beyond conventional LVH voltage criteria. The high NPV supports its use as a rule-out pre-screening tool.

Background Cardiovascular-kidney-metabolic (CKM) syndrome integrates adiposity, metabolic risk, kidney dysfunction, and cardiovascular disease in a prevention-oriented framework. National estimates across 1999-2023 NHANES and future burden remain limited. Methods We analyzed US adults aged 20 years from 11 NHANES cycles, 1999-2000 through August 2021-August 2023. CKM stage 0-4 was assigned using harmonized examination, laboratory, medication, and questionnaire data. Prevalence was survey-weighted and standardized to the 2010 US Census adult population. Decade trends used survey-weighted logistic regression adjusted for age, sex, and race and ethnicity. Exploratory 2040 and 2050 projections combined NHANES prevalence models with US Census projections under population-aging-only, trend-continuation, and risk-improvement scenarios. Results Among 62,890 eligible adults, 62,888 had sufficient CKM data. In 2021-2023, age-standardized prevalence was 87.9% (95% CI, 86.5%-89.4%) for CKM stage 1 and 62.0% (95% CI, 60.1%-63.8%) for stages 2-4. Stage 2 accounted for 50.1% (95% CI, 48.2%-51.9%) and stages 3-4 for 11.9% (95% CI, 11.0%-12.7%). From 1999-2000 to 2021-2023, any CKM increased by 4.6 percentage points (95% CI, 2.4 to 6.9; P<0.001), whereas stages 2-4 changed by 2.1 percentage points (95% CI, 5.1 to 0.8; P=0.156). In adjusted decade models, any CKM increased (OR, 1.28; 95% CI, 1.19-1.38; P<0.001), while stages 2-4 showed no significant linear trend (OR, 0.95; 95% CI, 0.89-1.01; P=0.084). Excess adiposity and diabetes increased, dyslipidemia declined, and hypertension, chronic kidney disease, and clinical cardiovascular disease were stable. With population aging alone, projected stages 2-4 burden rose from 164.8 million adults in 2023 to 193.7 million in 2050; under risk improvement, it was 147.7 million. Conclusions CKM syndrome remained highly prevalent among US adults. Although later stages did not increase significantly, population aging may expand the absolute care burden unless broad risk improvement occurs.