BMC Cardiovascular Disorders

BackgroundAccumulating evidence indicates that moderate exercise may reduce the incidence of Stanford type A aortic dissection (TAAD), but the specific mechanisms remain unclear. This study aims to identify exercise-related biomarkers in TAAD patients and to investigate their underlying mechanisms. MethodsTranscriptome data related to TAAD and exercise-related genes were obtained from publicly available databases. Candidate biomarkers for TAAD were identified through an integrative approach incorporating differential expression analysis, machine learning, and expression level assessment, leading to the construction of a diagnostic model. Subsequently, functional enrichment, immune infiltration, regulatory network analysis, and computational drug prediction were conducted to systematically investigate the pathological mechanisms and translational potential of the indentified biomarkers. ResultsABCA3 and SCN4B were identified as exercise-related biomarkers in TAAD progression. A nomogram incorporating these two biomarkers exhibited strong diagnostic performance for identifying the disease. Functional enrichment analysis revealed potential involvement of these biomarkers in disease progression through pathways including circadian rhythm regulation and ribosome biosynthesis. Additionally, immune cells like M1 macrophages and naive B cells, as well as regulatory factors including hsa-miR-1343-3p and XIST, were found to be involved in this process. Finally, zonisamide and MRS1097 were identified through computation prediction as potential therapeutic drugs. ConclusionABCA3 and SCN4B were identified as exercise-related biomarkers associatied with TAAD and represent potential valuable targets for both diagnosis and treatment strategies.

BACKGROUND: Observational studies have suggested an association between obstructive sleep apnea (OSA) and myocardial infarction (MI), but whether this relationship is causal or largely reflects shared risk factors remains unclear. METHODS AND RESULTS: We performed a 2-sample Mendelian randomization (MR) analysis to evaluate the causal effect of OSA on MI. Summary statistics for OSA were obtained from FinnGen, and MI data were obtained from the UK Biobank, with external validation using CARDIoGRAMplusC4D. Mediation MR was used to assess 13 potential mediators, and a 6-step multivariable MR framework was applied to estimate the direct effect of OSA after sequential adjustment for potential confounders. Reverse MR was conducted to test possible reverse causality. Genetically predicted OSA liability was associated with increased MI risk (odds ratio [OR] per log-OR increase, 1.0024 [95% CI, 1.0010-1.0039]; P=0.001). Body mass index (BMI) was the strongest mediator, explaining 35.94% of the association (P=0.030), whereas systolic blood pressure (SBP) showed minimal mediation (0.28%; P=0.678). In stepwise multivariable MR, the OSA-MI association was attenuated after adjustment for BMI and SBP (P=0.156), suggesting partial confounding by shared cardiometabolic risk. In a model including SBP and atrial fibrillation (AF), AF remained independently associated with MI (P=0.004), whereas OSA showed only a marginal direct effect (P=0.050). Reverse MR found no evidence that MI influenced OSA risk. CONCLUSIONS: These findings support a causal association between OSA and MI and suggest that this relationship may be mediated in part through obesity-related and arrhythmia-related pathways. AF may represent an important intermediate component of OSA-related cardiovascular risk beyond traditional hemodynamic factors. Keywords: obstructive sleep apnea; myocardial infarction; Mendelian randomization; mediation analysis; obesity.

Background | Angina with nonobstructive coronary arteries (ANOCA) is a heterogeneous condition encompassing distinct endotypes representing different underlying pathophysiological mechanisms. Endothelial dysfunction is considered a central hallmark of ANOCA. However, studying patient-derived endothelial cells (ECs) remains challenging due to the limited availability of disease-specific endothelial samples. We therefore aimed to assess the feasibility of isolating and culturing ECs from catheterization material obtained during routine coronary function testing in ANOCA patients. Methods | Catheterization material was collected from 79 ANOCA patients (84% female, age 58{+/-}10 years) undergoing coronary function testing. ECs were isolated, expanded and characterized using immunostaining, flow cytometry, gene expression profiling and functional assays. Results | EC isolation was successful in 43% of cases and resulted in 34 primary EC cultures that were expanded up to passage 10. Isolation success was independent of clinical or procedural characteristics. Isolated cells exhibited typical EC morphology and expressed EC markers confirmed by immunostaining, flow cytometry and gene expression analyses. EC marker gene expression remained largely stable over passages. However, stress- and defense-related gene expression programs increased over time, while proliferation-related processes decreased. Functional assays demonstrated that the coronary catheterization-derived ECs showed typical properties of wound healing, angiogenesis, activation responses upon stimuli and monocyte adhesion. Conclusions | This study demonstrates the feasibility of isolating and expanding ECs directly from catheterization material collected during routine coronary function testing in ANOCA patients. These patient-derived ECs retain characteristic endothelial features and functionality. This approach offers primary EC cultures to study the mechanisms underlying endothelial dysfunction in ANOCA.

PurposeObstructive sleep apnea (OSA) is a common comorbidity in heart failure (HF) patients with prevalence increasing as HF severity worsens. While CPAP/BiPAP has been shown to reduce disease burden and mortality in the general HF population, it is unclear whether these benefits extend to patients with left ventricular assist devices (LVADs). We sought to determine whether OSA affects long-term survival in newly implanted LVAD patients and whether CPAP/BiPAP treatment confers mortality benefits. MethodsThis single-center retrospective study included patients who underwent LVAD implantation between January 2007 and February 2022. Recipients were stratified by OSA status (OSA vs No-OSA), and those with OSA were further categorized based on CPAP/BiPAP compliance. Comparative statistics and Kaplan-Meier survival analyses were performed, with log-rank tests used to compare groups and assess survival differences. A Cox proportional hazards model was conducted to evaluate the association between risk factors and survival among patients with OSA and No-OSA. ResultsBefore LVAD implantation, patients with OSA had higher body mass index, hypertension, and a higher rate of implantable cardioverter-defibrillator placement than those without OSA. OSA was not associated with increased postoperative complications. Although survival did not differ significantly between OSA and No-OSA patients (p=0.33), CPAP/BiPAP-compliant OSA patients had significantly better survival than noncompliant patients (p=0.0099). ConclusionsLVAD patients with OSA who consistently use CPAP/BiPAP have better survival than those who do not. CPAP/BiPAP is a simple, low-risk treatment that can reduce mortality in this population. Therefore, increased perioperative screening for OSA should be considered for patients receiving LVADs. Multicenter studies are needed to confirm our findings further.

Abstract Background: ST-elevation myocardial infarction (STEMI) is reported to be a leading cause of mortality worldwide. While cardiac troponins are the gold standard for myocardial injury detection but creatine kinase-MB (CK-MB) and total creatine phosphokinase (CPK) retain prognostic use in resource-limited settings. Objective: To evaluate the prognostic significance of admission CK-MB and CPK levels in STEMI patients and to assess their association with hematological parameters for integrated risk stratification. Methods: This cross-sectional study enrolled 15 consecutive STEMI patients from the Punjab Institute of Cardiology, Lahore, during January 2024. Comprehensive laboratory analysis including cardiac biomarkers (CK-MB, CPK, troponin-I, LDH), complete blood count, renal function, serum electrolytes, and metabolic parameters, was performed on admission. Pearson correlation and comparative statistical analyses were also conducted to assess the relationships between cardiac biomarkers and hematological indices. Results: The cohort includes 15 patients (mean age 50.1 +/- 12.2 years; 73.3% male). Cardiac biomarker elevation was prevalent: CK-MB was elevated in 12/15 (80%), CPK was elevated in 12/15 (80%), with concordant elevation in 11/15 (73.3%), which indicates extensive myocardial necrosis. Troponin-I showed the highest elevation rate at 13/15 (86.7%). Hematological abnormalities included anemia (60%), WBC elevation (53.3%), and RBC reduction (40%). Random glucose averaged 150.80 +/- 63.55 mg/dL, with 66.7% highlighted the hyperglycemia. Remarkably, electrolyte balance was preserved in all of the patients (0% sodium, potassium, and bicarbonate abnormalities), indicating maintained homeostasis. Pearson correlation analysis revealed a significant correlation between CK-MB and CPK (r = 0.615, p = 0.0126), while correlations between cardiac biomarkers and hematological parameters were weak (p > 0.05). Risk stratification identified 53.3% of patients as high-risk who required intensive management. Conclusions: CK-MB and CPK demonstrate significant concordance and retain prognostic value in STEMI patients, particularly in resource-limited settings where troponin access may be constrained. While troponin-I remains the most sensitive biomarker, combined assessment of conventional cardiac enzymes supports reliable evaluation of myocardial injury. Hematological parameters reflect systemic response but show limited correlation with cardiac biomarkers.

Background: Socioeconomic factors impact cardiovascular health. We investigated the association between patient education level and incident heart failure (HF), acute myocardial infarction (AMI), and stroke following a first hospitalization with atrial fibrillation (AF). Methods: In this nationwide retrospective cohort study using linked Swedish national registers, we included all patients receiving a diagnosis of AF while hospitalized in Sweden from 1995 through 2008; categorized education level as primary, secondary, or academic; and followed patients for up to five years. Outcomes were first hospitalization for HF, AMI, or stroke. Associations were assessed using sex-stratified Cox proportional hazards models adjusted for age, calendar year of AF diagnosis, and measures of comorbidity burden (Charlson Comorbidity Index) and thromboembolic risk (CHA2DS2VA score). Results: The cohort comprised 263,172 patients (mean age 72.5 {+/-} 10.4 years; 56.2% male). Compared with primary education, secondary and academic education attainment were associated with lower adjusted risk of HF and AMI in both females and males. For HF, adjusted hazard ratios (HR) were 0.96 (95% CI 0.93 - 1.00) for secondary and 0.82 (95% CI 0.77 - 0.87) for academic education for females and 0.93 (95% CI 0.90 - 0.96) and 0.76 (95% CI 0.72 - 0.80), respectively, for males. For AMI, adjusted HRs were 0.89 (95% CI 0.85 - 0.93) and 0.71 (95% CI 0.65 - 0.78) for females and 0.91 (95% CI 0.87 - 0.94) and 0.75 (95% CI 0.71 - 0.80) for males. For stroke, lower adjusted risk was observed only in the academic education group. Baseline comorbidity burden and thromboembolic risk were higher in lower education groups. Conclusions: Education level was inversely associated with risk of incident HF and AMI over five years, while the association with stroke risk was weaker. Documenting education level may help identify patients at increased risk who could benefit from careful monitoring and optimized preventive care.

Abstract Aims: While traditional anthropometric indices are established cardiovascular predictors, their prognostic value for incident infective endocarditis (IE) remains undefined. Methods: We included 386,859 participants (mean age 57.0 years; 52.9% female) from the UK Biobank between 2006 and 2010 with standardized baseline data on BMI, waist circumference (WC), waist-to-height ratio (WhtR), and the triglyceride-glucose (TyG) index.Multivariable Cox proportional hazard models with restricted cubic splines were used to estimate the hazard ratio (HR) of these indices, adjusting for demographic and clinical risk factors. Results: Over 16.87 median years (25th, 16.02; 75th, 17.60 percentile) of follow-up, there were a total of 1,124 incident IE events. During the follow-up period, 38,342 total deaths were recorded, of which 8,524 were cardiovascular disease (CVD)-related.Overall, compared to individuals with normal weight and baseline metabolic indices, those in the fourth quartile of WC, WHtR, and TyG index exhibited the highest risk of incident IE. Compared to other metabolic indices, WC (HR = 1.53, 95% CI 1.23?1.90,P < 0.001) and WHtR (HR = 1.46, 95% CI 1.20?1.78,P < 0.001) demonstrated higher relative increases in risk associated with IE. Furthermore, the risk of IE was significantly elevated among the younger population with abdominal obesity and concomitant diabetes. However, no significant increase in IE risk was observed among participants with pre-existing valvular heart disease (P = 0.796). Conclusion: Compared with BMI, higher WC and WHtR were robustly associated with increased risk of IE, even after adjusting for traditional risk factors. Furthermore, the risk of IE was markedly elevated among younger individuals with abdominal obesity and diabetes.

Background. Patients with heart failure and reduced ejection fraction (HFrEF) commonly show signs of systemic inflammation. Interleukin-1 (IL-1) is a pro-inflammatory cytokine, known to modulate cardiac function. We aimed to determine the effects of treatment with anakinra, recombinant IL-1 receptor antagonist (IL-1Ra), on plasma IL-1Ra levels. Methods. We measured IL-1Ra levels at baseline and longest available follow-up to 24 weeks in 63 patients (44 males, 40 self-identified Black-Americans) with recent hospitalization for HFrEF, and systemic inflammation (C reactive protein [CRP] levels >2 mg/L) who were assigned to anakinra (N=42 [66.7%]) or placebo (N=21 [33.3%]) as part of the REDHART2 clinical trial (NCT0014686). Cardiorespiratory fitness was measured as peak oxygen consumption (peak VO2). Results. Baseline plasma IL-1Ra levels were 380 pg/ml (290 to 1046). On-treatment IL-1Ra levels were significantly higher in the patients treated with anakinra vs placebo (3,994 pg/ml [3,372 to 5,000] vs 492 pg/ml [304 to 1370], P<0.001). The longest available follow-up was 6 weeks in 10 patients (15.9%), 12 weeks in 12 patients (19%) and 24 weeks in 41 patients (65.1%). On-treatment IL-1Ra levels and interval change in IL-1Ra showed a modest inverse correlation with on-treatment CRP levels (R=-0.269, P=0.033 and R=-0.355, P=0.004, respectively) and no statistically significant correlations with peak VO2 values (P>0.05). Conclusions. Patients with recently decompensated HFrEF and systemic inflammation treated with recombinant IL-1Ra, anakinra, have a significant several-fold increase in plasma IL-1Ra levels. On-treatment IL-1Ra levels however show only a modest correlation with CRP levels and not with peak VO2.

Introduction: Accurate stratification of hard atherosclerotic cardiovascular disease (ASCVD) risk remains challenging despite advances in prevention. Liver function biomarkers (LFBs), particularly gamma - glutamyl transferase (GGT), have been linked to cardiovascular outcomes, yet their contribution to hard ASCVD risk prediction is not well defined. Methods: This study analyzed data from the National Health and Nutrition Examination Survey (NHANES, 2005 - 2018) to assess cross - sectional associations between LFBs and 10 - year hard ASCVD risk estimated by the ACC/AHA Pooled Cohort Equations. Multivariable regression, restricted cubic splines, and mediation analyses were applied to examine independent and dose - response relationships. External validation was performed in the China Health and Retirement Longitudinal Study (CHARLS) and NHANES using machine learning models (CoxBoost, Naive Bayes and Random Forest). Results: Among 5,731 NHANES participants, GGT showed an independent linear association with hard ASCVD risk (P - trend = 0.003), partly mediated by systolic blood pressure (44.8%), HbA1c (19.0%), and high density lipoprotein cholesterol (13.4%). Machine learning (ML) models incorporating GGT, alkaline phosphatase (ALP), and globulin alongside traditional risk factors improved predictive accuracy, with Naive Bayes achieving an AUC of 0.751 in NHANES validation. Conclusions: GGT is an independent and biologically plausible biomarker of hard ASCVD risk, acting through cardiometabolic pathways. Incorporating LFBs into risk prediction models, particularly with machine learning, enhances risk stratification and may facilitate early identification of high - risk individuals.

Sex specific differences in stroke are recognized. Whether differences in incident stroke risk persists in recent periods needs further elucidation to aid public health preventive efforts. Aim: To determine long-term sex specific trends in stroke and stroke risk factors at different epochs among Framingham Heart Study participants. Methods: We examined age-adjusted 10-year stroke incidence using Cox regression in women and men in five epochs: 1962-1969 (epoch 1, reference), 1971-1976 (epoch 2), 1987-1991 (epoch 3), 1998-2005 (epoch 4), 2015-2021 (epoch 5). We compared stroke incidence by sex across epochs, estimated decade-wise linear trends overall and by sex. We compared risk factors in successive epochs to the first, and estimated sex-specific trends in risk factors. Interactions between baseline risk factors with epoch and trends were assessed by sex. Secondary analyses were repeated in participants <60 years old. Results: Incident stroke occurred in 4.5% (178/3996) in epoch 1, 3.9% (227/5786) in epoch 2, 3.9% (199/5137) in epoch 3, 2.7% (207/7642) in epoch 4, 2.2% (119/5534) in epoch 5. Men had higher risk of incident stroke in each epoch with significant difference in epochs 2 (HR 1.41, 95% CI [1.08, 1.84]) and 4 (HR 1.46, 95% CI [1.11, 1.91]) overall, and in epoch 4 (HR 2.13, 95% CI [1.17, 3.87]) among those <60 years. Stroke incidence declined by 16% per decade in men (HR 0.84, 95% CI [0.79, 0.89]) and 19% per decade in women (HR 0.81, 95% CI [0.76, 0.86]). Among those <60 years, stroke incidence declined by 22% per decade in women (HR 0.78, 95% CI [0.67, 0.95]). Hypertension declined by 8% per decade in women only ([OR] 0.92, 95% CI [0.90, 0.94]), while Atrial fibrillation and diabetes increased in both. Conclusion: Stroke incidence continues to decline in recent periods for women and men. Among participants <60 years, decline was observed only in women, possibly related to decline in hypertension in women.

Background: Chronic conditions such as hypertension can significantly disrupt daily life and emotional wellbeing. The interaction between patients' perceptions, adherence to antihypertensive medication and quality of life (QoL) remains underexplored outside structured clinical settings. Objectives: To capture unprompted patient perspectives and assess whether hypertension affects QoL and to investigate if patient reported experiences are associated with self-reported antihypertensive medication adherence. Methods: Social media listening (SML) study analyzing 86,368 anonymized posts from individuals with hypertension in 12 countries, collected between January 2022 and May 2024. Posts from 11 countries (n=81,368) were analyzed using artificial intelligence-enabled natural language processing. Posts from China (n=5,000) were analyzed separately using a harmonized framework. Quantitative and qualitative methods assessed variations by country, age, and gender, and associations between emotional expression and antihypertensive medication adherence. Results: Across the 11-country core sample, 45% of posts mentioned at least one QoL impact, most commonly worry/anxiety (11%). Impacts varied across countries. Among 8,096 posts with age identified, individuals <40 years reported emotional balance impacts in 28% of posts versus 22% among those aged 40+. Work/Education impacts were mentioned in 17% of posts by those <40 years vs 12% in 40+. Among 7968 posts explicitly referencing adherence, expressed worry was associated with stricter adherence (62% association score), as were structured routines (79% score), home monitoring (77%), dietary changes (77%), and exercise (71%). In contrast, sadness/depression was associated with inconsistent adherence (71%), as were forgetfulness (79%), side effects (73%), and cost/insurance concerns (65%). Conclusions: These results emphasize the importance of the psychological and emotional impact of hypertension, including on adherence to medication regimens, reinforcing the value of a holistic approach to patient care.

Backgound: Accurate assessment of diastolic function and left ventricular (LV) filling pressure is central to heart failure diagnosis and risk stratification. Contemporary guideline algorithms rely on complex parameters that are not consistently available in routine clinical practice. Objective: To compare the diagnostic and prognostic performance of the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) and 2025 ASE guidelines with a deep learning model based on routinely acquired echocardiographic variables. Methods: This study evaluated the guideline-based algorithms and a deep learning model in participants from the Atherosclerosis Risk in Communities (ARIC) cohort (n=5450) for prognostication and two invasive hemodynamic validation cohorts from the United States (n=83) and Japan (n=130) for detection of elevated left ventricular filling pressure. Results: In the ARIC cohort, the deep learning model demonstrated superior prognostic performance compared with the 2016 and 2025 guidelines (C-index: 0.676 vs. 0.638 and 0.602, respectively; both p<0.001). Similar findings were observed among participants with preserved ejection fraction (C-index: 0.660 vs. 0.628 and 0.590; both p<0.001), with improved performance compared with the H2FPEF score (C-index: 0.660 vs. 0.607; p<0.001). In the US hemodynamic validation cohort, the deep learning model showed higher diagnostic performance than the 2025 guidelines (AUC: 0.879 vs. 0.822; p=0.041) and similar performance compared with the 2016 guidelines (AUC: 0.879 vs. 0.812; p=0.138). In the Japanese hemodynamic validation cohort, the deep learning model outperformed both guidelines (AUC: 0.816 vs. 0.634 and 0.694; both p<0.05). Conclusions: A deep learning model leveraging routinely available echocardiographic parameters demonstrated improved diagnostic and prognostic performance compared with contemporary guideline-based approaches, potentially offering a scalable alternative for assessing diastolic function and left ventricular filling pressures.

Background: The prevalence of heart failure (HF) is increasing worldwide, and rehospitalizations due to exacerbations remain a major clinical and economic burden. Beyond medical triggers, insufficient patient understanding and inadequate self-management often contribute to recurrent admissions. The Kurume-HEARTS program was developed to provide regular planned hospitalizations incorporating structured education, cardiac rehabilitation, and medication adjustment for patients with recurrent HF. Objective: To retrospectively evaluate the clinical and economic impact of the Kurume-HEARTS program. Methods: We enrolled consecutive patients with recurrent HF hospitalizations who underwent the program at Kurume University Hospital between January 2020 and October 2025. Outcomes compared planned versus unplanned hospitalizations within the same patients. Co-primary endpoints were total hospitalization cost and total length of stay per person-year. Secondary endpoints included per-hospitalization cost, length of stay, unplanned and planned admission frequency, and NT-proBNP levels at admission. Results: Of 31 screened patients, 20 with recurrent heart failure were included. During a median follow-up of 27.1 months, 135 hospitalizations occurred (69 unplanned and 66 program-based). Total hospitalization cost per person-year was significantly lower during the Kurume-HEARTS program than during unplanned hospitalizations, while length of stay per person-year tended to be shorter. Per-admission cost and length of stay were significantly lower with the program, without differences in admission frequency. NT-proBNP levels at admission were higher during unplanned hospitalizations, indicating greater clinical instability. Conclusions: The Kurume-HEARTS program can help reduce the cost and hospitalization length of unplanned admissions by enabling earlier intervention and structured inpatient management.

STRUCTERED ABSTRACTO_ST_ABSBACKGROUNDC_ST_ABSCoronary artery bypass graft (CABG) is a widely performed procedure for coronary artery disease (CAD), yet its association with Impaired Cognition (IC), i.e., mild-cognitive impairment or all-cause dementia, while accounting for APO ({varepsilon}) genotype, remains unclear. METHODSWe analyzed AllofUS participants with CAD (Age[&ge;]60 yrs) from 2017-2023. We defined CAD as a history of angina/myocardial infarction/chronic ischemic heart disease or having percutaneous coronary intervention/CABG, and IC as mild cognitive impairment or all-cause dementia using ICD/SNOMED codes. We performed logistic regression analyses to assess the association between CABG and IC, adjusting for clinical factors (age, sex, hypertension, diabetes, hyperlipidemia, depression, stroke, smoking, alcohol use, statin/antihypertensive/antidiabetic use), social determinants (self-reported race/ethnicity, income, employment), and APO ({varepsilon}) genotypes. We further performed stratified analyses across APO ({varepsilon}) genotypes ({varepsilon}2/{varepsilon}2, {varepsilon}2/{varepsilon}3 {varepsilon}3/{varepsilon}3, {varepsilon}2/{varepsilon}4, {varepsilon}3/{varepsilon}4, {varepsilon}4/{varepsilon}4). We defined significance at p [&le;] 0.05. RESULTSWe included 22,349 with CAD and identified 908 with IC after CAD till 2023. 40% were females, 70% were White, 12% were Black, and 9% were Hispanic. The proportion of IC was higher (5.1% vs 3.5%, p=1e-08) in CABG (n=8,135) vs non-CABG (n=14,214). After adjusting for clinical factors, social determinants, and APO ({varepsilon}) genotypes, CABG (1.23;1.06-1.41, p = 0.005) was associated with IC. In APO ({varepsilon}) stratified analysis, the association of CABG with IC was strongest in the APO {varepsilon}2/{varepsilon}3 group (1.91;1.21-3.02, p = 0.005). CONCLUSIONIn the AllofUS cohort, we observed an association between CABG and IC in CAD participants, with the strongest association in the APO {varepsilon}2/{varepsilon}3 group. Key MessageO_ST_ABSWhat is already known on this topicC_ST_ABSCoronary artery disease (CAD) and Impaired Cognitive (IC) disease, i.e., mild cognitive impairment and all-cause dementia, share genetic, sociodemographic, and clinical factors, including cardiovascular conditions like coronary artery bypass grafting (CABG) procedure. What this study addsWe observed an association between CABG and IC in CAD participants after adjusting for sociodemographic, clinical factors, and APO ({varepsilon}) effects. Further, when CAD participants were stratified across APO ({varepsilon}) groups, CABG was significantly associated with IC in the APO {varepsilon}2/{varepsilon}3 group. How this study might affect research, practice or policyOur observations highlight the role of APO ({varepsilon}) genotype evaluation in CAD patients for IC risk assessment.

Background Poor physical function has been associated with higher cardiovascular disease (CVD) risk. However, the association between physical function and atrial fibrillation (AF) remains understudied. The comprehensive investigation of the association between physical function and incident AF risk could highlight a novel target for AF prevention. Methods A total of 4,803 participants without diagnosed AF from the Atherosclerosis Risk in Communities (ARIC) Study cohort with physical function assessed in 2011-2013 were studied. Physical function was measured using Short Physical Performance Battery (SPPB), 4-meter walk time, and grip strength. Hospital discharge codes and death certificates were used to ascertain incident AF through 2022, and through 2020 for participants from Jackson. Cox regression was used to assess the association between physical function and incident AF risk, adjusting for multiple covariates. Z-score transformations were performed to identify the physical function measure most strongly associated with incident AF risk, and SPPB component analysis was performed to identify the most influential SPPB component. Results Mean age of the study participants was 75.1 {+/-} 5.0 years, with 41.2% being male participants and 22.2% being black participants. During a median follow-up of 9.2 years, there were 809 incident AF events. SPPB (HR: 0.93, 95% CI: 0.90-0.96, per 1-point increase) and grip strength (HR: 0.87, 95% CI: 0.78-0.96, per 10kg increase) were inversely associated with incident AF risk, while 4-meter walk time (HR: 1.08, 95% CI: 1.03-1.13, per 1-second increase) was positively associated with incident AF risk. SPPB had the strongest association with incident AF risk. Within SPPB, only the chair stand component was significantly associated with incident AF risk. Conclusions The findings suggest that better physical function is associated with reduced incident AF risk, with higher SPPB having the strongest association. Given the modifiable nature of physical function, these findings highlight a potential novel target for AF prevention in aging populations.

Aims: Dynamic left ventricular outflow tract obstruction (LVOTO) is a hemodynamically significant complication following transcatheter aortic valve replacement (TAVR) that remains difficult to predict with conventional transthoracic echocardiography (TTE). We examined whether a deep learning (DL) model developed for LVOTO detection in hypertrophic cardiomyopathy (HCM) could predict post-TAVR LVOTO from pre-TAVR TTE in patients with severe aortic stenosis (AS). Methods and Results: In this retrospective study of 302 consecutive patients undergoing TAVR for severe AS, a pre-trained DL model was applied to pre-TAVR TTE to generate a patient-level DL index of LVOTO (DLi-LVOTO; range 0-100). Post-TAVR LVOTO was defined as a peak pressure gradient [&ge;]30 mmHg on follow-up TTE. Logistic regression and receiver operating characteristic analyses assessed the association and discriminative performance of DLi-LVOTO. Pre-TAVR LVOTO was present in 32 patients (10.6%) and post-TAVR LVOTO in 35 (11.6%). Follow-up TTE was performed at a median of 47 days (IQR 37-63) after TAVR, with the majority of TTE (216 of 302, 71.5%) performed within 2 months. DLi-LVOTO was significantly higher in patients with LVOTO at both pre- and post-TAVR TTE (all p<0.001). In multivariable analysis, DLi-LVOTO remained independently associated with post-TAVR LVOTO even after adjusting for conventional TTE parameters and pre-TAVR LVOTO (adjusted OR 1.29, 95% CI 1.06-1.56 per 10-score increase, p=0.011), with an AUROC of 0.78 (95% CI 0.72-0.85). Among patients without pre-TAVR LVOTO, DLi-LVOTO retained independent predictive value (adjusted OR 1.56, 95% CI 1.19-2.06, p=0.001; AUROC 0.84, 95% CI 0.77-0.91). Conclusion: A DL model originally trained in HCM patients independently predicts post-TAVR LVOTO from pre-TAVR TTE, including in patients without pre-existing LVOTO, suggesting it captures hemodynamic features beyond conventional echocardiographic assessment.

Background: Resting electrocardiogram (ECG) is not currently recommended as part of cardiovascular disease (CVD) risk assessment, although accumulating evidence suggests a potential role. Objective: To examine the association between ECG abnormalities and incident CVD events as assessed by the 2023 Predicting Risk of Cardiovascular Disease Events (PREVENT) equations. Design: Secondary data analysis from the REasons for Geographic And Racial Differences in Stroke (REGARDS) prospective cohort, including study participants without a baseline CVD. Exposure: ECG abnormalities were classified by Minnesota Code (MC) as normal, any minor, or major abnormality at baseline (2003-2007). Outcome: Participants were followed for expert adjudicated incident CVD events through December 31, 2021. Results: Among 19,173 participants (mean age at baseline of 63.7 years; 57.8% were female). According to the PREVENT risk equations, 39.4% were classified as <7.5% 10-year risk CVD risk, 44.6% as 7.5-20% risk, and 16.0% as >20% risk. Overall, 47.0% had normal ECG, 44.0% had any minor abnormality, and 9.0% had any major abnormality. During follow-up, CVD events occurred in 12.4% of participants with normal ECG, 17.0% of those with any minor abnormality, and 25.4% of those with any major abnormality. Compared to those without ECG abnormality, the adjusted HR for incident CVD were 1.19 (95% CI 1.10-1.29) for any minor abnormality, and 1.53 (1.36-1.72) for any major ECG abnormality. In the <7.5% risk group, 43.6% had at least one ECG abnormality; in this risk group compared to those without ECG abnormality, the HR for incident CVD associated with any major ECG abnormality, present in 5.0% of the <7.5% risk group, was 1.87 (95% CI 1.34-2.62), The HR for any minor ECG abnormalities, present in 38.6% was 1.13 ( 95% CI 0.93 - 1.37). Conclusion: ECG abnormalities were associated with risk of CVD events across PREVENT risk groups. A substantial proportion of low-risk participants (according to the PREVENT equation) had ECG abnormalities and associated elevated risk. This supports the potential for using ECG to identify a subgroup of low-risk patients who may benefit from more aggressive primary prevention especially with major ECG abnormalities. Addition of electrocardiographic evaluation to the PREVENT risk equations may improves cardiovascular risk discrimination.

Background and Aims: Acute myocarditis (AM) is a T cell-mediated myocardial disease with clinical manifestations ranging from mild chest pain to cardiogenic shock. Reliable biomarkers to stratify patients and guide therapy are currently lacking. In particular, the extent of the dysregulation of inflammatory pathways, and the impact on myocardial dysfunction, remain elusive. Methods: Serum analyses were performed in prospectively recruited AM patients (n = 103) from two independent cohorts. Multimodal data integration combining profiling of cytokine and chemokine dysregulation with clinical biomarkers was used to define clinical phenotypes with distinct inflammatory signatures. Machine-learning and regression models were applied to determine biomarkers that indicate clinical severity. Results: Immuno-proteomic profiling revealed conserved inflammatory patterns across AM cohorts, dominated by T cell-related cytokines and chemokines. In addition, AM patients showed dysregulation of fibroblast-derived cytokines, including hepatocyte growth factor (HGF), bone morphogenic protein 4 (BMP4) and the BMP4 inhibitors Gremlin-1 (GREM1) and Gremlin-2 (GREM2). Data integration and unsupervised clustering revealed two immuno-clinical phenotypes, linking T cell activation and fibroblast dysregulation to disease severity. Machine learning-based analysis identified CXCL10, GREM2 and LVEF as critical parameters for stratifying disease severity. Conclusions: These findings highlight a systemic T cell activation signature as diagnostic hallmark of AM. In addition, dysregulation of fibroblast-derived tissue cytokines serves as an indicator for distinct immuno-clinical phenotypes in myocardial inflammatory disease. Thus, the clinically relevant link between T cell-driven immune activation, myocardial inflammation and fibroblast-driven remodelling provides a versatile set of parameters to identify severe manifestations of AM.

Background: Insulin resistance (IR) and obesity are key drivers of atrial fibrillation (AF). However, the comparative predictive value of the Triglyceride-Glucose (TyG) index versus composite indices combining IR and anthropometric measures such as TyG-BMI, TyG-Waist Circumference (TyG-WC), and Waist-to-Height Ratio (WHtR) remains undefined. We aimed to evaluate these associations and the modifying effect of genetic susceptibility. Methods: We analyzed 293,318 UK Biobank participants free of AF at baseline. Hazard ratios (HRs) were estimated using Cox proportional hazards models, and non-linearity was assessed using restricted cubic splines. Incremental predictive value was evaluated via Net Reclassification Improvement (NRI). Interactions with AF Polygenic Risk Scores (PRS) were examined. Results: During follow-up, 22,707 incident AF cases occurred. While the TyG index was associated with AF in unadjusted models, this association was nullified after full adjustment. In contrast, composite indices (TyG-BMI, TyG-WC) and WHtR showed robust, positive associations (WHtR HR per SD: 1.30, 95% CI 1.28-1.32). Spline analysis identified non-linear threshold effects (e.g., WHtR inflection at 0.556). Adding WHtR or TyG-BMI to baseline models significantly improved risk reclassification (NRI ~10.3-11.8%, P<0.001), whereas TyG alone did not (P=0.73). Elevated metabolic risk increased AF incidence across all genetic categories, with significant interactions suggesting greater relative impact in low-genetic risk groups. Conclusions: Composite indices integrating central obesity and insulin resistance are superior to the TyG index alone in predicting incident AF. The identification of specific risk thresholds and genetic interactions highlights "metabolic health" as a crucial, modifiable target for AF prevention.

Introduction: Spontaneous coronary artery dissection (SCAD) is frequently accompanied by persistent symptoms of unknown pathogenesis after the index event. Autonomic dysfunction is a plausible mechanism for these but has not been systematically characterized. We quantified antecedent and contemporary autonomic symptoms in survivors of SCAD and examined their associations with cardiac and extra-cardiac symptoms and health-related quality of life. Methods: This cross-sectional study recruited 227 volunteers from multiple countries with a self-reported history of SCAD. Participants completed validated patient-reported measures, including the Composite Autonomic Symptom Score-31 (COMPASS-31), Anxiety Sensitivity Index-3 (ASI-3), and EuroQol-5 Dimension-5L (EQ-5D-5L). They also completed an internally derived retrospective autonomic predisposition score assessing symptoms during adolescence and early adulthood. Results: Participants were predominantly female (97.8%), median age 53 (47-58) years, and were surveyed a median of 3 (1-5) years after their index SCAD event. 21.6% reported SCAD recurrence. Moderate autonomic symptom burden (COMPASS-31 20) was present in 56.4% and severe burden (40) in 16.3%. History of antecedent autonomic symptoms was the strongest independent predictor of contemporary autonomic symptom burden after adjustment for demographic and clinical covariates (=0.514; P <0.001). Greater autonomic symptom burden independently predicted lower EQ-5D health utility (=0.150; P=0.029) and was associated with the ASI-3 physical concerns (=0.232; P <0.001), but not social concerns domain. Autonomic symptoms were not associated with SCAD recurrence. Conclusion: Symptoms of autonomic dysregulation are common in survivors of SCAD and are associated with reduced quality of life. Their association with antecedent dysautonomic features during adolescence and early adulthood suggests a longstanding predisposition, the significance of which warrants further evaluation.