BMC Cardiovascular Disorders

Background Sedentary behavior (SB) has been associated with cardiovascular disease risk, independent of physical activity (PA) and sleep. However, the effect of replacing SB with PA or sleep on atrial fibrillation (AF) risk remains unclear. Methods We studied 86,096 participants from the United Kingdom Biobank (UKB) and 5,777 from the United States (US) REasons for Geographic And Racial Differences in Stroke (REGARDS) prospective cohort studies who were free of AF at baseline and had valid accelerometry data. The two cohorts were included to evaluate the consistency of associations across distinct populations in the UK and the US, two regions with a high burden of AF. Daily time spent in light PA (LPA), moderate to vigorous PA (MVPA), and SB were derived from accelerometer recordings; sleep was accelerometer-derived in UKB and self-reported in REGARDS. Incident AF was identified using ICD-10 codes (I48.x) listed as either a primary diagnosis, secondary diagnosis, or cause of death through hospital and death registry data linkage in UKB and in a follow-up visit through electrocardiogram and self-reported medical history in REGARDS. Isotemporal substitution models were used to examine replacing 30 minutes of SB with LPA or MVPA in both cohorts and with sleep in UKB on the outcome of incident AF. Results Among the UKB participants [57% female, mean age 56.0 (SD 7.8) years, 98% White race], 4,035 AF cases were identified during a median of 7.9 years of follow-up. Replacing 30 minutes of SB with PA was associated with a slightly lower risk of AF in the minimally adjusted models but the associations were attenuated after full adjustment (LPA: HR 0.99, 95% CI 0.95-1.02; MVPA: HR 1.00, 95% CI 0.99-1.02). The REGARDS participants had an average age of 63 (SD 8.3) years, 55% female, 31% Black and 69% White adults, with 486 AF cases identified. Fully adjusted substitution of 30 minutes of SB with MVPA was associated with lower AF odds (OR 0.80, 95% CI 0.63-1.01), whereas LPA showed no association. In UKB, replacing SB with sleep was not associated with AF risk. The magnitude of the association of MVPA substitution with AF appeared stronger among REGARDS participants aged [&ge;]65 years and those reporting <7 hours/day of sleep. Conclusion Replacing SB with moderate or higher intensity PA may decrease AF risk. In REGARDS, these substitutions appeared to benefit older individuals and those reporting shorter sleep duration. These findings highlight the potential benefit of reducing sedentarism to lower AF burden, warranting validation in future studies.

Abstract Background The SYNTAX score (SS) quantifies the severity and complexity of coronary artery lesions and serves as an independent predictor of major adverse cardiovascular events and mortality in patients with acute coronary syndrome (ACS). However, few studies have examined the association between SS and in-hospital cardiac arrest (IHCA) in this population. Therefore, this study aims to elucidate the relationship between SS and the incidence of IHCA in patients with ACS. Methods This study consecutively enrolled 3,224 patients undergoing percutaneous coronary intervention (PCI). Logistic regression and restricted cubic spline (RCS) analyses were employed to examine the association between SS and the incidence of IHCA. Participants were stratified into three groups based on SS: Group T1 (SS ? 10, N = 1,097), Group T2 (10 < SS ? 18, N = 1,089), and Group T3 (SS > 18, N = 1,038). The primary endpoint was the incidence of IHCA. Results The overall incidence of IHCA was 4% (N=147). After adjusting for covariates, SS was significantly associated with the incidence of IHCA in ACS patients treated with PCI (OR = 1.0400; 95% confidence interval (CI) = 1.0200?1.0700; p < 0.001). Compared with the T1 group, the T3 group exhibited an increased risk of IHCA (OR = 2.1800; 95% CI = 1.2900?3.6900; p = 0.0040). Subgroup analyses revealed that, after covariate adjustment, patients with ST-segment elevation myocardial infarction (STEMI) had an increased risk of IHCA (OR = 1.0700; 95% CI = 1.0300?1.1100; p < 0.001). Similarly, both patients with diabetes mellitus (DM) (OR = 1.0400; 95% CI = 1.000?1.0700; p = 0.0270) and those without DM (OR = 1.0600; 95% CI = 1.0200?1.1000; p = 0.0020) showed an increased risk. Furthermore, elderly patients (?60 years) (OR = 1.0300; 95% CI = 1.0100?1.0700; p = 0.0210) and non-elderly patients (<60 years) (OR = 1.0500; 95% CI = 1.000?1.1000; p = 0.0470) had an increased risk, as did male patients (OR = 1.0500; 95% CI = 1.0200?1.0700; p = 0.0020). RCS analysis indicated a dose-response relationship between IHCA incidence and SS (nonlinear p-value = 0.906), with the risk of IHCA increasing when SS exceeded 23.975. Incorporating SS into the baseline risk model improved the predictive value for IHCA incidence in ACS patients undergoing PCI (Net reclassification improvement [NRI]: 0.3537 [0.1906?0.5167], p < 0.001; Integrated discriminant improvement [IDI]: 0.0104 [0.0025?0.0183], p = 0.0097). Conclusions Among patients with ACS undergoing PCI, SS is significantly associated with the incidence of IHCA. Consequently, SS may serve as an effective predictor of IHCA in this population.

Background: Sleep-disordered breathing (SDB) is an established adverse prognostic factor in heart failure (HF). Sleep apnea-specific hypoxic burden (SASHB), which reflects the duration and depth of respiratory event-related oxygen desaturation, has shown stronger prognostic value than the apnea-hypopnea index (AHI) in general populations and patients with coronary artery disease. However, its clinical utility in patients hospitalized due to acute HF remains unclear. Objectives: This study evaluated the prognostic value of SASHB in patients hospitalized for acute HF and compared its performance with AHI for risk stratification and identification of patients who may benefit from positive airway pressure (PAP) therapy. Methods: This post hoc analysis included 230 patients from a prospective single-center observational cohort of adults hospitalized for acute HF. The primary analysis included 178 patients who did not receive PAP treatment. Associations of SASHB and AHI with the composite endpoint of cardiovascular death or rehospitalization for worsening HF were evaluated using Cox proportional hazards models. Model improvement after adding SASHB or AHI to a model including established clinical risk factors was assessed using changes in the C index and Brier score, reflecting changes in model discrimination and prediction error, respectively. In the full cohort, the interaction between PAP treatment and SDB metrics was evaluated using the g-formula. Results: During a median follow-up of 3.7 years, 58 of 178 patients (32.6%) reached the composite endpoint. Both SASHB and AHI were independently associated with the composite outcome after multivariable adjustment. However, only SASHB consistently predicted outcomes across analyses and improved model performance beyond established prognostic factors (bootstrap {Delta} C index, 0.020 [95% CI: 0.008 - 0.031]; bootstrap {Delta} Brier score, - 0.007 [95% CI: - 0.014 to - 0.001]), whereas AHI did not. In the analysis including PAP-treated patients, both SASHB and AHI showed interaction with PAP treatment. Conclusions: In patients hospitalized for acute HF, SASHB showed a consistent independent association with adverse clinical outcomes and provided additional prognostic information beyond AHI. SASHB may improve risk stratification and may help identify patients who are more likely to benefit from PAP therapy.

Background: Growth differentiation factor 15 (GDF-15) has emerged as a prognostic biomarker in patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). Our study evaluated the temporal evolution of GDF-15 in the acute phase and its association with recurrent ischemic events. Methods: Serum samples were collected from patients with NSTE-ACS at admission and at 1 and 3 hours after admission. GDF-15 levels, along with other prognostic biomarkers, NT-proBNP and hs-cTnT, were measured. Spearman rank-correlation coefficients and linear regression models were used to identify the variables associated with GDF-15 levels at admission and with their temporal changes. Associations between GDF-15 and clinical outcomes were evaluated using Cox proportional hazards models. To assess incremental prognostic value, the areas under the curve (AUC) were calculated for each model. Results: GDF-15 levels showed a slight increasing trend within 3 hours of admission. The 1-hour change in GDF-15 was correlated with hs-cTnT changes. Increased 1-hour GDF-15 levels, compared with the admission levels, were associated with a higher risk of recurrent ischemic events during the 1-year follow-up (1.9% vs. 17.5%, P =0.019) and were an independent predictor after adjusting for established clinical variables and biomarkers (adjusted hazard ratio, 1.71 (1.28 to 228.75), P =0.03). Furthermore, serial measurements of GDF-15 provided additional prognostic information beyond traditional risk factors. Conclusions: Serial measurements of GDF-15 of NSTE-ACS patients provided independent and incremental prognostic value for predicting recurrent ischemic events. These findings support the potential utility of GDF-15 as a dynamic biomarker for early risk stratification in the acute management of NSTE-ACS.

Background: The systemic immune-inflammation index (SII) is a routinely available blood-derived marker with potential prognostic relevance after coronary artery bypass grafting (CABG). We evaluated associations between preoperative SII and postoperative outcomes. Methods: PubMed, Embase, Scopus and Web of Science were searched to 1 October 2026, with supplementary searches through 14 October 2026. Peer-reviewed observational studies evaluating preoperative SII in adults undergoing CABG were eligible. Methodological quality was assessed using the Newcastle-Ottawa Scale. Compatible categorical associations and exploratory adjusted continuous mortality effects were pooled separately using restricted maximum-likelihood random-effects models; other findings were summarized descriptively. Results: Thirty-one reports were included, with an aggregate sample of 30,976 and possible cohort overlap; five contributed to meta-analysis. Two off-pump cohorts comprising 1,378 patients and 180 atrial-fibrillation events yielded an imprecise crude association with postoperative atrial fibrillation (OR 1.60, 95%CI 0.53-4.82; I2=68%). An exploratory crude synthesis indicated greater intra-aortic balloon pump use with higher SII (OR 2.45, 95%CI 1.16-5.18; I2=51%). Two cohorts with differing follow-up yielded an exploratory adjusted mortality HR of 1.11 (95% Wald CI 1.05-1.18) per study-specific SD increase in log-SII. In one 624-patient cohort, high SII was associated with postoperative acute kidney injury after adjustment (OR 3.35, 95% CI 2.25-4.97).Apparent atrial-fibrillation discrimination varied (AUC 0.587-0.946). Conclusions: Preoperative SII showed associations with selected adverse outcomes after CABG, supporting further evaluation as an accessible prognostic marker. Its incremental value beyond established clinical risk models requires validation. Keywords: Systemic immune-inflammation index; Coronary artery bypass grafting; Atrial fibrillation; Prognosis; Systematic review

IntroductionCirculating proteins may augment prognostic scores and provide mechanistic insights for cardiovascular disease. Their role for adding precision to predicting response to therapeutic exercise training is less certain. Older adults with HF frequently experience geriatric syndromes, which may influence response to a rehabilitation intervention (RI). We sought to determine if the functional benefits of a 12-week tailored, structured, and progressive multidomain physical RI program in older adults, following a HF admission, could be estimated by pre-intervention levels of proteins. MethodsHospitalized adults age [&ge;] 60 years with HF were randomized to 12-week multidimensional (aerobic, strength, balance, flexibility) physical therapist-led RI versus attention control (AC). Outcomes included change in the short physical performance battery (SPPB) and 6-minute walk distance (6MWD). At pre-intervention and 12-weeks, 92 circulating proteins associated with CVD and inflammation were measured. Using linear regression, LASSO and ensemble tree-based approaches for flexible feature selection, proteins were selected for stratification of treatment response. Decision trees were developed to incorporate a multi-protein approach to optimize stratification of treatment response (effect measure modifiers [EMM]) for both functional outcomes. Differences in 12-week temporal changes based on RI vs AC and mediation analysis were used to assess possible causal roles for these proteins. ResultsBaseline proteomic data was available in 243/349 participants (69.6%). For SPPB, 2 proteins (GP6, ST2), and for 6MWD, 3 proteins (ALCAM, Gal-4, PECAM-1) were selected as EMMs. For SPPB, a decision tree with ST2 followed by GP6 level identified a differential 12-week improvement in score for RI vs AC from -0.8 (95%CI -1.9, 0.2) to 2.1 (95%CI 1.5, 2.7). For 6MWD, the optimized decision tree was based only on ALCAM with a differential 12-week improvement in score for RI vs AC from 10m (95%CI -17m, 36m) to 85m (95%CI 56m, 113m). However, none of the EMM proteins were mediators of change for the functional outcomes. ConclusionsCirculating proteins related to CVD and inflammation (GP6, ST2, ALCAM) stratify a successful functional response to the REHAB-HF rehabilitation program in older adults following HF hospitalization. Further investigation is needed to identify proteins associated with a causal role for rehabilitation benefits.

Background. Information is lacking about everyday psychological states of individuals with a recent myocardial infarction (MI) and whether they influence outcomes. We investigated real world psychological experiences and their association with subsequent cardiovascular events in survivors of an MI. Methods. We studied 287 individuals [&le;] 60 years of age within 8 months from an MI. At the baseline visit, we assessed sociodemographic and clinical factors, and administered a battery of psychological scales of depression, anxiety, anger, perceived stress and social support. Participants underwent a 7-day home monitoring of mood and stress using ecological momentary assessments, and a momentary negative affect (MNA) score, integrating daily mean ratings of sadness, anxiety, anger, distress and loneliness, was calculated. Participants were followed for a median time of 28 months. The study endpoint was a composite index of major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal MI, stroke or hospitalizations for heart failure. Cox proportional hazards models adjusted for sociodemographic and clinical factors. Results. The mean age of the sample was 51 years, and 43% of participants were women. Each standard deviation increase in MNA was significantly associated with a 60% increased risk of MACE (95% confidence interval (CI), 20% to 100%), irrespective of adjustment for sociodemographic factors and clinical characteristics. The association was similar in women and men. Momentary positive mood and momentary perceived stress were not associated with MACE. The MNA score showed a larger independent contribution to MACE compared to the combined battery of baseline psychological assessments and the association was independent of baseline history of depression. Conclusion. Among individuals after MI, moment-to-moment negative affect during one week of monitoring in daily life is a powerful predictor of subsequent cardiovascular events. A prospective evaluation of negative mood during everyday living could represent a novel strategy to uncover residual risk after MI.

Background: Pacing-induced cardiomyopathy (PICM) is a major complication of chronic right ventricular pacing and develops in up to 25% of patients. Reliable prediction of PICM may facilitate individualized pacing strategy selection; however, currently available approaches demonstrate limited discriminative performance. This study aimed to develop and validate machine learning (ML) models for predicting PICM in patients with atrioventricular block (AVB) underlying heart failure with mildly reduced or preserved ejection fraction. Methods: In this multicenter prospective study derived from the RISK-PICM registry (January 2002 to January 2026), 125 patients with AVB who underwent pacemaker implantation were analyzed. PICM was defined as a ?10% reduction in left ventricular ejection fraction (LVEF) resulting in an LVEF <50%. Four ML algorithms, including logistic regression, support vector machine, random forest, and XGBoost, were trained using stratified 4-fold cross-validation with hyperparameter optimization and model discrimination was evaluated. Results: PICM developed in 41 patients (32.8%) during a median follow-up of 4.8 years. Male sex, pre-implant minimum QTc interval, and post-implant maximum QRS duration were significantly associated with PICM in univariable Cox regression. XGBoost achieved the highest discriminative performance (AUROC 0.831; sensitivity 0.805; specificity 0.845). Feature importance analysis identified baseline LVEF and post-implant maximum QRS duration as the most influential features. Model-derived risk stratification significantly differentiated high-risk and low-risk groups on Kaplan-Meier analysis (P < 0.001). Conclusions: ML-based models, particularly XGBoost, demonstrated clinically meaningful performance for PICM and may support individualized pacing strategy selection in patients with AVB and underlying heart failure with mildly reduced or preserved ejection fraction.

Background: Patients with heart failure (HF) experience high mortality, yet survival estimates remain challenging. Available prognostic tools commonly predict survival beyond 1-year, limiting goals of care discussions and enrollment on palliative care programs. The objective of this project was to develop a novel prognostic score to better predict 6-month mortality. Methods: Patients with HF admitted to the St. Boniface Hospital (Winnipeg, Canada) between January 1, 2019 and January 1, 2024 were identified. Patient characteristics, imaging parameters, laboratory values, and functional assessments (Palliative Performance Scale; PPSv2) were collected. Patients were randomly divided into development (80%) and validation (20%) cohorts. Penalized LASSO regression was used to select variables most predictive of 6-month mortality in the development cohort. Retained variables were incorporated into a multivariable logistic regression model to derive the CARDIO-PAL score, the performance of which was assessed in the holdout validation cohort. Results: Characteristics were similar between the development (n = 2036) and validation (n = 508) cohorts, with 6-month mortality rates of 29% and 31%, respectively. 8 candidate variables were retained: age (adjusted odds ratio [aOR] 1.01), PPSv2 (aOR 2.08), systolic blood pressure (aOR 1.14), discontinued use of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (aOR 2.58), beta-blocker (aOR 1.59), and mineralocorticoid receptor antagonist (aOR 2.67), right ventricular systolic pressure (aOR 2.06), and urea (aOR 2.13). The CARDIO-PAL score demonstrated good discrimination, with an area under the curve of 0.80 (95% confidence interval 0.75 - 0.84) and good calibration (slope 0.84, intercept -0.04). 6-month mortality across low, intermediate, and high-risk groups was 2%, 15%, and 54%, respectively. Conclusion: The CARDIO-PAL score is a novel tool to predict 6-month mortality in HF inpatients. A collaborative approach integrating CARDIO-PAL with other prognostic scores and serial clinical assessments has the potential to promote patient-centered care and improve referral to palliative care programs.

Background: Aortic stenosis (AS) is a valvular heart disease which imposes chronic pressure overload on the left ventricle (LV). Although LV remodelling may regress following aortic valve replacement, the molecular determinants of reverse remodelling remain poorly understood. This study develops a machine learning-based model using myocardial microRNA (miRNA) expression profiles to predict LV mass normalization one year after valve replacement. Methods: Consensus selection combining Random Forest and Bayesian Network analyses was applied to miRNA sequencing data from LV biopsies of 12 matched patient pairs with AS. Selected miRNAs were qPCR quantified in an extended cohort of 89 AS patients and incorporated into predictive models. Sex-stratified analyses were performed. Model robustness was assessed using bootstrap resampling and cross-validation. Candidate miRNAs and target genes were evaluated in LV from a murine model of pressure overload induced by transverse aortic constriction (TAC). Results: The combined Random Forest-Bayesian Network approach identified a three-miRNA signature (miR-517a-3p, miR-122b-5p, and miR-4683) associated with LV mass normalization after valve replacement. Validation in an extensive cohort demonstrated good overall discrimination and achieved its highest performance in women (AUC >0.80). Functional analyses identified drebrin (DBN1) as a putative target of miR-517a-3p and supported its potential involvement in pressure overload-induced cardiac remodelling. Conclusion: Random Forest and Bayesian Network integrated analyses enabled the identification of a myocardial miRNA signature with sex-dependent predictive value for reverse cardiac remodelling after aortic valve replacement. Functional validation supports the relevance of selected miRNAs and their downstream targets, highlighting their potential as biomarkers and candidate regulators of myocardial recovery.

Background: Tirzepatide and semaglutide improve functional status and heart failure (HF) events in patients with obesity and HF with preserved ejection fraction. Tirzepatide has been associated with greater control of cardiometabolic risk factors in patients with obesity compared to semaglutide. Whether tirzepatide is associated with lower risk of new-onset HF than semaglutide in patients with obesity is underexplored. Methods: A retrospective cohort study was conducted using data pooled from the TriNetX platform. Patients with obesity who initiated therapy with tirzepatide or semaglutide during the period Jun 4, 2021 to Aug 13, 2026 were identified and 1:1 propensity-score matched to produce two study cohorts. The one-year incidence of new-onset HF was calculated and compared between the two cohorts. Secondary outcomes included new-onset systolic HF, new-onset diastolic heart failure, new-onset atrial fibrillation or flutter, all-cause mortality, and hospital encounters. Cox proportional hazards models were fitted to calculate hazard ratios (HR) along with 95% confidence intervals (CI). Results: Two well-matched cohorts (N=424,269 in each) were formed. The incidence of new-onset HF was lower in the tirzepatide group (1.0% vs. 1.3%; absolute risk difference -0.3%, 95% CI -0.35 to -0.26; HR 0.9, 95% CI 0.86[boxh]0.93). The tirzepatide group were also at lower risk of all-cause mortality (HR, 95% CI: 0.8, 0.77[boxh]0.91) and new-onset systolic HF (0.8, 0.79[boxh]0.92). All other secondary outcomes occurred at similar rates in both study groups. Conclusion: Among patients with obesity, tirzepatide therapy was associated with lower risk of new-onset HF compared to semaglutide although the effect sizes were modest.

Introduction: In hypertrophic cardiomyopathy (HCM), wall stress and subclinical myocardial injury related in part to pathological hypercontractility, which in turn are associated with worse outcomes. Cell-free DNA (cfDNA) is released from cardiomyocytes (cfDNA-CM) through irreversible cellular injury and death. We investigated the feasibility of quantifying cfDNA-CM and its relationship to HCM patient characteristics. Methods: We analyzed 57 plasma samples from stable patients with HCM and 10 plasma samples from patients with acute myocardial infarction (AMI). Plasma cfDNA was isolated from both groups. Whole genome bisulfite sequencing (WGBS) libraries were generated and sequenced with short-read sequencing. Methylation patterns were used for tissue deconvolution analysis and cell-specific cfDNA quantification. Results: Yields of cfDNA (p = 0.003) and cfDNA-CM (p = 0.002) fractions were higher in AMI controls than HCM, supporting the validity of the assay. Within the HCM cohort, the median cfDNA yield was 12.22 ng [IQR: 7.77, 18.94]. The cfDNA-CM fraction in this cohort ranged from 0% to 6.4% of total cfDNA. Higher cfDNA-CM tertiles were associated with higher body mass index (BMI, p=0.001), a greater prevalence of BMI 30 kg/m2 (p<0.001), and a higher prevalence of obstructive sleep apnea (p=0.038). No significant differences were observed in other demographic, genetic, and laboratory characteristics. Higher cfDNA-CM tertile was numerically associated with higher New York Heart Association (NYHA) functional class and left ventricular outflow tract (LVOT) obstruction, while circulating biomarkers of wall stress (NT-proBNP) and myocardial injury (troponin) did not differ across tertiles (p=0.83 and p=0.29, respectively). Conclusion: Isolation and quantification of cfDNA as well as detection of cfDNA-CM in chronic stable patients with HCM are feasible. Higher cfDNA-CM fraction was associated with increasing BMI and cardiometabolic comorbidity burden. The absence of association with traditional circulating biomarkers suggests that cfDNA-CM may reflect a distinct domain of myocardial health, injury, and adverse remodeling.

BackgroundObstructive sleep apnea (OSA) is a highly prevalent sleep disorder. Major risk factors include obesity, older age, and male sex. Given the well-established association between OSA and cardiovascular disease, markers of cardiovascular health derived from electrocardiography (ECG) may help identify individuals with undiagnosed OSA. This study evaluated whether 12-lead ECG features improve machine learning-based prediction of OSA beyond established clinical factors. MethodsWe conducted a retrospective cohort study of individuals who underwent diagnostic sleep studies at the University of Kansas Health System Sleep Disorders Center (2004-2025) and had a 12-lead ECG acquired within one year. Standard ECG features (intervals, amplitudes, voltage-time integrals, morphology descriptors) were extracted from the representative beat. Latent representations were derived using two variational autoencoder (VAE) models pretrained on >1 million ECGs: a 30-dimensional representative-beat VAE and a 90-dimensional full 10-second ECG VAE. Three LightGBM models were trained: clinical factors only (age, sex, weight, height, body mass index [BMI], Epworth sleepiness scale [ESS]), ECG features only, and a combined model. Feature selection and hyperparameter tuning were performed separately for each model within a 5-fold cross-validation scheme. The outcome was moderate-to-severe OSA (AHI[&ge;]15 events/h), evaluated by AUROC (bootstrapped 95% CI) in a 10% holdout test set. ResultsThe dataset included 7,699 individuals (52.2% women, mean age 58.0 {+/-} 14.2 years, BMI 33.6{+/-}8.2 kg/m{superscript 2}, ESS 8.8{+/-}5.1; 36.4% with moderate-to-severe OSA) Training AUROC (95% CI) was 0.71 (0.66-0.76) for the combined model, versus 0.65 (0.59-0.70) for the clinical-only model and 0.66 (0.61-0.72) for the ECG-only model. Holdout test AUROC was 0.78 (combined), 0.69 (clinical-only), and 0.71 (ECG-only). Feature importance identified age, BMI, weight, ECG VAE latent variables, height, sex, and P-wave voltage-time integral as relevant contributor to the predictions. ConclusionsLatent ECG features extracted by VAE improve prediction of moderate-to-severe OSA when combined with clinical factors.

HIV infection significantly elevated the odds of cardiovascular diseases, including myocardial fibrosis. We aimed to determine the difference of late gadolinium enhancement (LGE), extracellular volume (ECV), T1, and T2 using cardiac magnetic resonance imaging (CMR) in patients living with HIV (PLWH) and healthy controls. The databases Scopus, Web of Science, Embase, and PubMed were searched systematically using relevant keywords. STATA version 17 was used for meta-analysis using random effect and fixed effect models for heterogeneous and non-heterogeneous analyses. An overall number of 13 studies were included in the current analysis involving 1425 PLWH and 766 healthy controls. PLWH showed significantly higher LGE (OR: 5.47, 95% CI: 1.90-15.64, p<0.001) and ECV (mean difference: 1.46, 95% CI: 0.21-2.71, p=0.02) compared to controls. However, differences in Left Ventricular Ejection Fraction (LVEF) were not significant (mean difference: -1.41, 95% CI: -2.81- -0.01, p=0.05). There were no meaningful disparities in pro B-type natriuretic peptide (BNP) values (mean difference: 8.67, 95% CI: 0.04-17.29, p=0.05) or T2 values (mean difference: 0.91 ms, 95% CI: -1.04-2.86, p=0.36), but T1 values were significantly higher in PLWH (mean difference: 13.78 ms, 95% CI: 9.16-18.40, p<0.001). In meta regression, LGE was correlated with nadir CD4 (z=-3.41, p-value<0.001). In addition, ECV was correlated with white race (Z=-3.97, p-value<0.001), Hepatitis C (Z=-2.08, p-value=0.037), and smoking (Z=2.05, p-value=0.041). HIV is related to a significantly elevated rate of myocardial fibrosis, and factors such as lower nadir CD4, white race, hepatitis C, and smoking were correlated with hepatitis C. Keywords: Myocardial fibrosis, HIV, AIDS, Cardiovascular diseases, Heart failure

BACKGROUND: Because of the high mortality rate associated with fulminant myocarditis (FM), there is limited evidence regarding the prognostic efficacy of endomyocardial biopsy (EMB). In this study, we aimed to evaluate the influence of EMB in the early phase after admission on treatment and prognosis in FM using a large-scale nationwide registry in Japan. METHODS: Patients with FM who required catecholamine or mechanical circulatory support between 2012 and 2017 from 235 hospitals across Japan were included. The primary outcome of death or heart transplantation within 90 days according to performance of early EMB were determined using Kaplan-Meier and Cox regression analyses. Factors associated with performance of early EMB, and subsequent medical treatment were analyzed. RESULTS: The median age of 736 patients with clinical FM was 56 years, and 407 patients (55%) received EMB. Most EMB (89%) were performed during the early phase (within 5 days of admission) and 63% were performed on the first day of admission. The prognosis of FM patients who underwent EMB was more favorable than that of those who did not based on the landmark analysis (log-rank test, P=0.04). Factor analysis demonstrated that FM patients who underwent EMB had a lower left ventricular ejection fraction, higher incidence of cardiogenic shock on admission, and higher rate of early mechanical circulatory support, as well as early initiation of corticosteroids and guideline-directed medical therapy (GDMT) for heart failure. Absence of any GDMT was associated with a less favorable prognosis on multivariate analysis (hazard ratio, 4.34 [95% CI, 3.14?6.01]; P<0.0001). CONCLUSIONS: Although performing EMB in the early phase after admission depends on disease severity in FM patients, it is associated with early initiation of advanced medical treatment and may contribute to improving the prognosis.

Observational studies suggest an association between COVID-19 and acute myocardial infarction (AMI), however, whether this relationship is causal remains unclear. We conducted a multi-ancestry Mendelian randomization (MR) study across European, East Asian, South Asian, and African populations, evaluating three COVID-19 phenotypes: very severe COVID-19, hospitalized COVID-19, and general infection association with AMI. GWAS summary statistics were obtained from the COVID-19 Host Genetics Initiative Round 7 and UK Biobank/Biobank Japan for AMI. Inverse-variance weighted (IVW) MR was the primary method, with fixed- or random-effects models selected according to heterogeneity test. MR-Egger, weighted median and weighted mode were conducted as sensitivity analyses. In European ancestry, genetic liability to very severe COVID-19 and hospitalized COVID-19 was slightly inversely associated with AMI risk, but without statistical significances across sensitivity analyses. Hospitalized COVID-19 showed a suggestive but non-significant inverse association in South Asian ancestry. No significant associations were identified in East Asian or African ancestries. Our findings did not support a robust causal association between COVID-19 susceptibility or severity and AMI risk across ancestries, suggesting that the observed cardiovascular burden may be driven more by acute pathophysiological mechanisms than shared genetic architecture.

Objective This study aimed to develop and validate a predictive model for sleep disorders in young and middle-aged adults with anemia, providing evidence for early identification, risk stratification, and individualized sleep management. Methods Data in the NHANES were analyzed and randomly divided into development and validation cohorts. LASSO regression was used to screen optimal predictors in the development cohort, followed by univariate and multivariate logistic regression to identify independent predictors and construct a nomogram. Model performance was evaluated using receiver operating characteristic curves, calibration curves, Brier scores, and decision curve analysis. Results The weighted prevalence of sleep disorders among young and middle-aged adults with anemia was 10.19%. Multivariate logistic regression identified seven independent predictors: sex, monocyte count, asthma, overweight, arthritis, congestive heart failure, and hypertension. The model showed good discrimination, with area under the curve values of 0.817 in the development cohort and 0.791 in the validation cohort. Calibration was satisfactory, with Brier scores of 0.074 and 0.075, respectively. Decision curve analysis indicated favorable clinical net benefit in both cohorts. Conclusion The proposed predictive model demonstrated good discrimination, calibration, and may help healthcare providers identify young and middle-aged adults with anemia who are at high risk for sleep disorders.

Background: Ascending thoracic aortic aneurysm (ATAA) is characterized by progressive biomechanical remodeling that is incompletely captured by maximum aortic diameter. The relationships between age, sex, aortic valve phenotype (BAV vs TAV), and aneurysmal mechanics remains incompletely understood. Methods: Ascending aortic specimens from 54 patients undergoing elective ATAA repair were evaluated. Biaxial testing quantified Green strain and local stiffness at membrane tensions of 60 and 120 N/m. Opening angle was used to assess circumferential residual stress and stretch. Associations with age were evaluated using Pearson correlations, and differences between sex and valve phenotype were also explored. Multivariable linear regression models including age, sex, and valve phenotype were used to evaluate their adjusted associations with each mechanical outcome. Results: Increasing age was associated with increased local stiffness and reduced Green strain and remained the strongest determinant of biaxial mechanical properties after adjustment. Compared with tricuspid aortic valve specimens, BAV specimens exhibited lower Green strain together with lower local stiffness. Females demonstrated greater Green strain in unadjusted analyses; however, after adjustment, sex remained associated only with longitudinal Green strain at 60 N/m. None of the evaluated clinical characteristics consistently explained opening angle or residual stretch. Conclusions: Age was the predominant clinical determinant of biaxial mechanical remodeling in ATAA, whereas valve phenotype demonstrated selective associations and sex contributed comparatively little after adjustment. Circumferential residual stress appeared largely independent of these clinical characteristics, suggesting that residual stress and biaxial mechanics capture complementary aspects of aneurysmal remodeling.

Aims: Premature coronary artery disease (PCAD) lacks specific molecular drivers, and the role of immunosenescence is unclear. We investigated whether aging-related gene dysregulation in T cells contributes to PCAD. Methods: We combined bulk transcriptomics of PBMCs from 12 PCAD patients and 21 controls, single-cell RNA sequencing of PBMCs and human atherosclerotic plaques, weighted gene co-expression network analysis, gene perturbation network analysis, and molecular docking. Results: KRAS was identified as a hub gene intersecting PCAD-associated genes and aging-related genes. Single-cell analysis showed KRAS upregulation predominantly in effector CD8+ T cells, which exhibited the highest senescence scores that were further elevated in disease. Network perturbation of KRAS strongly impacted the cell killing pathway. KRAS-high effector CD8+ T cells were detected in coronary and carotid plaques, displaying enhanced cytotoxicity, exhaustion, and senescence features. Additionally, a candidate small molecule was computationally predicted to bind inactive KRAS. Conclusions: Elevated KRAS expression in senescent, cytotoxic CD8+ T cells is associated with PCAD, bridging immunosenescence and premature atherosclerosis. This finding provides a novel biomarker candidate and potential therapeutic entry point, awaiting further functional validation.

BackgroundMacitentan is a dual endothelin receptor antagonist used in pulmonary arterial hypertension (PAH) and has also been studied in other forms of pulmonary hypertension (PH). Evidence across PH phenotypes has been heterogeneous. This study aims to evaluate the efficacy and safety of macitentan compared with concurrent control therapies across PH phenotypes and to explore whether treatment effects differ according to PH classification. MethodsPubMed, Embase, and the Cochrane database were searched from inception through June 2026. Randomized and non-randomized comparative studies of patients with PH receiving macitentan were eligible. Prespecified efficacy outcomes were 6-minute walk distance (6MWD), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), and cardiac index; prespecified safety outcomes included mortality and adverse events. Random-effects meta-analyses were performed using mean differences (MDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes. ResultsFourteen studies met the eligibility criteria. Macitentan was associated with a greater reduction in PVR (MD, -134.50 dyn.s.cm; 95% CI, -226.10 to -42.86) and an increase in cardiac index (MD, 0.44 L/min/m; 95% CI, 0.22 to 0.67). No statistically significant difference was observed for 6MWD (MD, 5.04 m; 95% CI, -15.06 to 25.14) or mPAP (MD, -2.70 mmHg; 95% CI, -6.46 to 1.05). In pooled safety analyses, mortality was lower and risks of anemia, peripheral edema, and discontinuation due to adverse events were higher with macitentan. Heterogeneity and the small number of studies within several phenotype-specific analyses limited the precision of subgroup findings. ConclusionsMacitentan-containing therapy was associated with favorable changes in selected hemodynamic outcomes but not with a statistically significant improvement in 6MWD or mPAP. The safety findings were characterized by higher risks of anemia, peripheral edema, and treatment discontinuation. These results should be interpreted in the context of differences in PH phenotype, dose, comparator, study design, and outcome measurement.