BMC Cardiovascular Disorders

BackgroundDilated cardiomyopathy (DCM) is a leading cause of heart failure, with 30-50 % of cases attributed to familial inheritance. Mutations in RNA-binding motif protein 20 (RBM20) account for 3-5 % of cases and are associated with severe DCM and ventricular arrhythmias. However, the role of RBM20 mutations in atrial cardiomyopathy (AtCM) and atrial fibrillation (AF) remains underexplored. This study investigates the effects of the RBM20-R636Q mutation on atrial electrophysiology and evaluates sodium-glucose co-transporter (SGLT) inhibitors as potential therapeutics. ResultsRbm20-R636Q mice exhibited atrial remodeling, including hypertrophy, left atrial enlargement, and shortened action potential duration at 90% repolarization (APD90). Compared with RBM20-knockout and laminopathy models, RBM20-R636Q mice showed distinct reductions in Ito / IKur without changes in IK,sus or IK,tail currents, alongside TASK-1 potassium current upregulation and alterations of ICaL. SGLT inhibitors (sotagliflozin, empagliflozin, dapagliflozin) reduced AP inducibility and partially restored APD90, with effects comparable to lidocaine, suggesting a role in modulating peak sodium currents. ConclusionsRBM20 mutations contribute to atrial remodeling, promoting AtCM and AF. SGLT inhibitors demonstrate therapeutic potential by modulating atrial electrophysiology and reducing arrhythmogenesis, offering a promising strategy for managing RBM20-related cardiac disorders. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/711772v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@1bf3b44org.highwire.dtl.DTLVardef@1cc2ee1org.highwire.dtl.DTLVardef@19e8f6org.highwire.dtl.DTLVardef@10da900_HPS_FORMAT_FIGEXP M_FIG C_FIG

BackgroundAtrial fibrillation (AF), the most common sustained arrhythmia, is driven by electrical and structural remodelling, including altered ion channel expression. The atrial-specific potassium channel TASK-1 regulates action potential duration (APD) and is differentially expressed in AF and left ventricular dysfunction, but the mechanisms controlling its expression are not well understood. ObjectiveThis study examines whether the transcription factor ETV1 regulates TASK-1 and contributes to atrial electrical remodelling. MethodsAtrial tissue from patients with and without AF was analysed to assess the relationship between ETV1 and TASK-1 (KCNK3) expression. In HL-1 cardiomyocyte-like cells and native fibroblasts, ETV1 activity was reduced using pharmacological inhibition or siRNA-mediated knockdown. TASK-1 expression, TASK-1 current, and APD at 90% repolarization were measured. Pacing experiments tested activity-dependent TASK-1 regulation. Direct transcriptional regulation was evaluated using ChIP-qPCR and ChIP-seq to detect ETV1 binding at the KCNK3 promoter. ResultsETV1 and TASK-1 levels were positively correlated in human atrial tissue. In HL-1 cells and fibroblasts, ETV1 inhibition or knockdown decreased TASK-1 expression and current and selectively prolonged APD90. Pacing-induced upregulation of TASK-1 was prevented by ETV1 inhibition, indicating a protective effect against pro-arrhythmic remodelling. ChIP-qPCR and ChIP-seq confirmed direct ETV1 binding to the KCNK3 promoter. ConclusionETV1 directly regulates TASK-1 expression and contributes to atrial electrical remodelling, identifying ETV1 as a potential upstream therapeutic target in AF. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/711402v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1498239org.highwire.dtl.DTLVardef@1049e15org.highwire.dtl.DTLVardef@2685a2org.highwire.dtl.DTLVardef@10f6a74_HPS_FORMAT_FIGEXP M_FIG C_FIG Translational perspectiveAtrial fibrillation is sustained by maladaptive electrical remodelling that remains insufficiently addressed by current rhythm-control therapies. Direct inhibition of individual ion channels has shown efficacy but is limited by phenotype dependence and proarrhythmic risk. The present data identify ETV1 as an upstream transcriptional regulator of the atrial-specific potassium channel TASK-1. Modulation of ETV1 reduced TASK-1 expression, prolonged atrial repolarisation, and prevented tachycardia-induced electrical remodelling in vitro. Targeting ETV1 may therefore represent a disease-modifying strategy that intervenes earlier in the remodelling cascade than conventional antiarrhythmic drugs. This approach could enable phenotype-guided therapy in atrial cardiomyopathy, particularly in patients with preserved ventricular function, and warrants validation in translational large-animal and clinical studies.

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.

BackgroundIncidence and recurrence of atrial fibrillation (AF) is associated with several lifestyle risk factors. Lifestyle and risk factor modification (LRFM) clinics could have a role in comprehensively addressing AF from a holistic patient-centred approach to improve clinical outcomes. MethodsWe performed a systematic review and meta-analysis of randomised controlled trials (RCTs) evaluating the role of LRFM clinics compared with usual care (UC) in patients with AF. The primary endpoint was atrial arrhythmia recurrence. Secondary endpoints were AF and heart failure (HF) related hospitalisation, cardiovascular death, stroke or transient ischaemic attack (TIA), and quality-of-life (QOL). ResultsA total of eleven RCTs with a total of 3364 patients were included (five RCTs performed in the context of AF ablation). Mean age was 58-73 years, 30% were female and 18% had persistent AF. Duration of follow-up ranged from 3-24 months. LRFM clinics significantly reduced the primary endpoint of arrhythmia recurrence compared with UC after catheter ablation (OR 0.34, 95% CI 0.23-0.51, p<0.001, I2=0%). LRFM clinics also reduced AF-related hospitalisation (OR 0.70, 95%CI 0.51-0.98, p=0.04, I2=21%) and improved QOL (mean improvement on Short Form 36 Questionnaire 8.90, 95% CI 7.6.91-10.90, p<0.001). There was no difference between LRFM clinics and UC for HF-related hospitalisation (p=0.16), cardiovascular deaths (p=0.79) or stroke/TIA (p=0.83). ConclusionIn this meta-analysis of RCTs, LRFM clinics reduced AF recurrence after ablation, reduced AF-related hospitalisation and improved QOL. This study supports a comprehensive multidisciplinary lifestyle risk modification model of care to improve clinical outcomes in patients with AF.

BackgroundGuideline-directed medical therapy (GDMT) has been shown to improve mortality and/or symptoms in heart failure with reduced ejection fraction (HFrEF). Medical devices also play an important role in improved quality of life and overall symptom relief for HFrEF patients. Baroreflex Activation Therapy (BAT) increases parasympathetic nervous system activity by stimulating the carotid baroreceptors, thereby reducing symptoms. Herein, we analyzed the effects of BAT on hospitalization, atrial arrhythmia (AA), and ventricular arrhythmia (VA) rates. MethodsA retrospective cohort study was conducted consisting of HFrEF patients treated with BAT at Keck Hospital of USC between 11/2014 and 11/2022. We compared median pre-BAT hospitalization, AA, and VA rates to post-BAT rates at both 6- and 12-months using Wilcoxon Signed Rank tests. ResultsAmong 31 patients on BAT, 38.7% met criteria for receiving all four GDMT classes for at least 12 months prior to BAT. Among these, 91.7% had an implantable cardioverter defibrillator (ICD) implanted for [&ge;]12 months pre- and post-BAT. Average pre- vs. post-BAT all-cause hospitalization rates were significantly different only at 12 months [1.3 {+/-} 1.4 vs 0.3 {+/-} 0.9, respectively (p=0.05)]. Borderline significant pre-post comparisons were noted including decreased VA rate at both 6 and 12 months and increased AA rate at 12-months (p=0.06 for all). ConclusionIn HFrEF patients on full GDMT, BAT was associated with a significant reduction in hospitalization rates at 12 months. There were no significant changes in AA or VA rates.

BackgroundKetone bodies have shown potential to improve cardiac metabolism and function in patients with heart failure (HF). ObjectiveTo evaluate the effects of exogenous ketone-based interventions on cardiac function in patients with HF or related cardiometabolic risk factors. MethodsWe conducted a systematic review based on a search of MEDLINE, EMBASE, CINAHL, Cochrane Library, and Scopus from inception to January 2025. Eligible studies included randomized controlled trials evaluating exogenous ketones (oral ketones or ketone infusions) compared to placebo in adults with HF or patients with risk factors for HF including type 2 diabetes mellitus, hypertension, or coronary artery disease. Paired reviewers independently screened and identified hits at title-and-abstract and full-text levels to determine eligibility and extracted data from eligible studies. Random-effects meta-analysis was performed. Effects of interventions were summarized as mean differences (MD). Risk of bias was assessed using Cochrane RoB 2.0 tool. Certainty of evidence was evaluated using the GRADE (grading of recommendations assessment, development and evaluation) approach. ResultsOut of 565 unique records, 22 full-text articles were reviewed, and 8 studies met inclusion criteria. Exogenous ketone administration increased left ventricular ejection fraction (LVEF) (MD = 3.94, 95% CI 2.18-5.70, p = 0.001), cardiac output (CO) (MD = 1.11 L/min, 95% CI 0.55-1.67, p = 0.002), heart rate (4.85 bpm, 95% CI 2.24-7.46, p = 0.003), and stroke volume (SV) (MD = 10.21 mL, 95% CI 4.06-16.35, p = 0.005). Pulmonary capillary wedge pressure (PCWP) decreased (MD = -0.93 mmHg, 95% CI -1.44 to -0.43, p = 0.003), while mean arterial pressure showed no change (MD = -1.37 mmHg, 95% CI -3.53 to 0.79, p = 0.18). ConclusionsExogenous ketone-based therapies are associated with improvements in hemodynamic markers of cardiac function, including increases in LVEF, CO, and SV, along with a reduction in PCWP. These findings suggest that ketone supplementation may offer clinical benefits for patients with HF or vascular disease.

BackgroundCoronary artery tortuosity (CAT) is often viewed as a benign angiographic finding; however, emerging evidence suggests its potential hemodynamic significance, particularly in non-atherosclerotic cardiomyopathies such as Takotsubo syndrome (TS). ObjectivesThis study aimed to investigate the prevalence and hemodynamic implications of CAT in patients diagnosed with Takotsubo cardiomyopathy (TCM) and to evaluate the association between the severity of tortuosity and myocardial injury markers, recovery of ventricular function, and other clinical variables. MethodsA retrospective review of 100 patients with TCM from the Baptist Memorial Hospital network (2015-2025) was conducted. Tortuosity severity was quantified using angiographic criteria per Eleid et al. (2014). Associations between CAT and biochemical or echocardiographic parameters were evaluated using multiple linear regression and non-parametric tests. ResultsCAT was highly prevalent (85.1%) in this TCM cohort, with a mean tortuosity index of 3.26--significantly higher than in general angiography populations. No significant correlations were found between tortuosity severity and peak troponin levels (p = .588) or ejection fraction (EF) at presentation (p = .820). Full EF recovery (55-65%) at [&ge;]3 months occurred in 70.7% of patients and was not significantly associated with prior cardiomyopathy, coronary artery tortuosity index or baseline troponin levels. ConclusionsCAT appears markedly more prevalent among patients with TCM, although its severity does not correlate with biomarker elevation or EF recovery. These findings suggest that coronary tortuosity may contribute to the hemodynamic environment predisposing to TS, without directly determining the extent of myocardial dysfunction or recovery.

BackgroundTricuspid transcatheter edge-to-edge repair (TEER) can induce an acute annuloplasty effect. While this has a therapeutic benefit, the mechanisms driving the reduction in annular size remain unclear. ObjectivesWe quantify the annular force induced by TEER in vitro in whole porcine heart preparations. We explore the impact of clipping different leaflet pairs on the TEER-induced annular forces. MethodsWe performed 49 interventions in 13 porcine hearts using a MitraClip XT. The clip was implanted between either the anterior-septal (AS), anterior-posterior (AP), or posterior-septal (SP) leaflet pairs. We also considered two-clip interventions between the combination of the AS-AP, AS-PS, or AP-PS leaflet pairs. For each intervention, we measured the right ventricular pressure, transvalvular flow rate, and force at eight locations around the annulus. ResultsTEER induced significant inward-pulling forces on the annulus. The maximum force was induced following an AS-PS two-clip intervention. A single AS clip induced the largest force among the one-clip interventions. Furthermore, the AP and AS-AP interventions induced the smallest annular forces. ConclusionsThe magnitude of the TEER-induced force depends on the intervention and number of clips implanted.

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.

Subclinical rheumatic valvular disease is a significant yet underdiagnosed contributor to the global rheumatic heart disease (RHD) burden. Early detection through population screening is essential to prevent its progression to severe RHD. Rhythm changes and prolongations of PR and QTc intervals in the ECG are described in the advanced RHD cases. However, these parameters were not yet studied in asymptomatic RHD. We aimed to investigate the potential of ECG biomarkers for screening RHD in asymptomatic schoolchildren. ECG tracings from 611 schoolchildren aged 10 to 20 years were selected from a cohort screened for RHD in four schools in an RHD-endemic region. Confirmatory diagnoses were based on echocardiographic findings, where 564 (F=326, M=238) were healthy, and 47 (F=28, M=19) were positive for RHD (24 borderline RHD and 23 definite RHD). Independent, blinded reviewers manually annotated the ECGs and PR interval (PR), P-wave dispersion (PWd), and the ratio between the P-wave duration and PR interval (Pw/PR) were analyzed. The mean age of the study cohort at diagnosis was 16.1 {+/-} 2.5 years, and 58% of the participants were females. Atrial fibrillation was seen in 8% (n=4), and prolonged PR in 2% (n=1) of RHD-positive cases. The mean {+/-} std for normals vs RHD is (PR, 138{+/-}19 vs 150{+/-}19), (Pw/PR, 0.75{+/-}0.06 vs 0.71{+/-}0.07), and (PWd, 49{+/-}14 vs 56{+/-}17). The PR (p<0.001), Pw/PR (p<0.001), and PWd (p=0.008) showed a significant difference between healthy and RHD-positive subjects. The PR was increased consistently with severity across age groups above and below 16 years. The PR, PWd, and Pw/PR can serve as non-invasive biomarkers for the screening of RHD in at-risk schoolchildren. Monitoring alterations in these markers at an early stage of RHD is crucial for enabling prompt management and follow-up. It is thus evident that ECG can support an intermittent ambulatory RHD screening in resource-limited settings.

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.

BackgroundAdvances in wearable devices and machine-learning-based ECG analysis enable highly accurate detection of atrial fibrillation (AF) outside traditional clinical settings, leading to increasing identification of asymptomatic AF. However, the prognostic significance of AI-detected asymptomatic AF and its implications for downstream cardiovascular risk remain unclear. In contrast to clinically diagnosed AF, evidence guiding risk stratification and further evaluation in this population is limited. We therefore investigated the association between AI-detected asymptomatic AF and incident cardiovascular outcomes in a large population-based cohort. MethodsWe applied a validated open-source ECG-based deep learning model for atrial fibrillation detection (AI-AF) to 12-lead ECG recordings from participants in the UK Biobank. Participants with AI-detected AF on ECG and no prior clinical AF diagnosis were classified as asymptomatic AF (c). Kaplan-Meier curves and log-rank tests were used to compare the incidence of ischemic stroke and major adverse cardiovascular events (MACE: myocardial infarction, ischemic stroke, or cardiovascular death) across AF subgroups. Cox proportional hazards models were used to evaluate the association between AI-AF risk and incident MACE, adjusting for age, sex, current smoking, systolic blood pressure, total and HDL cholesterol, and prevalent type 2 diabetes. Follow-up was administratively censored at 6 years. ResultsThe study included 96,531 participants with mean [SD] age of 65 [8] years; 52% female; median follow-up [IQR] of 4.7 [1.6-7.2] years. ECG data were available for 64,029 participants and an additional 32,502 participants with clinically diagnosed atrial fibrillation (AF) without ECG recordings were included. Among participants without prior clinical AF and with available ECGs, 2,399 were classified as asympAF based on AI detection, while 58,879 were AF-free. Over 6 years of follow-up, the incidence of ischemic stroke was significantly higher in participants with asympAF compared with AF-free individuals (1.5% vs 0.52%, p = 7x10-7) and significantly lower than in participants with clinically diagnosed AF (1.5% vs 3.4%, p = 2x10-5). Similar patterns were observed for myocardial infarction and cardiovascular death. Using a more liberal AI-AF threshold corresponding to a 15% false-positive rate (asympAF15) yielded consistent findings: participants classified as asympAF15 had a 62% higher risk of incident MACE in adjusted Cox PH models (hazard ratio 1.6, 95% CI 1.2-2.2) over six years. ConclusionAI-detected asymptomatic AF identified individuals at elevated risk of ischemic stroke and major adverse cardiovascular events. As ischemic stroke is a hallmark complication of atrial fibrillation, these findings support the hypothesis that AI-ECG models may capture subclinical AF-related risk not detected by conventional clinical assessment. This approach may help extend the window for preventive interventions in populations without clinically diagnosed AF.

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.

Structured AbstractO_ST_ABSBackgroundC_ST_ABSVericiguat and sacubitril/valsartan both modulate the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signaling pathway and may improve myocardial function in patients with heart failure. ObjectivesTo compare the effects of vericiguat, sacubitril/valsartan, and their combination on left ventricular function and clinical outcomes in heart failure with nonpreserved ejection fraction patients. MethodsIn this retrospective real-world study, patients were classified into three groups: vericiguat added to guideline-directed medical therapy (vericiguat group), sacubitril/valsartan-based therapy (sacubitril/valsartan group), and combined sacubitril/valsartan plus vericiguat therapy (add-vericiguat group). Changes in left ventricular ejection fraction ({Delta}LVEF), in stroke volume ({Delta}SV), and in log-transformed N-terminal pro-B-type natriuretic peptide ({Delta}Log10 NT-pro BNP) from baseline to 1 year were evaluated. Clinical outcomes were also assessed. ResultsAt 1 year, LVEF significantly improved in both the vericiguat group (p = 0.02) and the sacubitril/valsartan group (p < 0.001). There was no significant difference in {Delta}LVEF between these two groups (p = 0.25). In contrast, the add-vericiguat group demonstrated a significantly greater improvement in {Delta}LVEF compared with the vericiguat group alone (p = 0.01). ConclusionsIn a real-world setting, vericiguat was associated with improvements in left ventricular function comparable to those of sacubitril/valsartan, and combination therapy provided incremental benefits. Vericiguat may serve as an alternative or adjunctive treatment option, particularly in patients unable to tolerate or maintain angiotensin receptor-neprilysin inhibitor therapy.

BACKGROUNDDilated cardiomyopathy (DCM) presents a highly heterogeneous spectrum, including a familial subset with elevated arrhythmic risk. Traditional demographic and imaging markers, such as late gadolinium enhancement, have been inadequate for identifying high-risk patients before arrhythmic events. Remodelling of the interventricular septum--central to ventricular mechanics and conduction--may offer improved risk stratification. OBJECTIVESTo identify differences in left ventricular (LV) morphology between arrhythmic and idiopathic dilated cardiomyopathy (aDCM vs iDCM), and to identify LV remodeling patterns that link to adverse outcomes. METHODSThree-dimensional LV shape models were constructed from end diastolic cardiovascular magnetic resonance images of 102 individuals subdivided by their idiopathic or arrhythmic subgroup allocation. A statistical shape model was built using principal component analysis. A linear discriminant analysis determined shape features of the arrhythmic subgroup and increased composite arrhythmic outcome of sudden cardiac death, aborted sudden cardiac death, and sustained ventricular tachycardia. RESULTSThe idiopathic DCM group displayed larger mass, length, diameter, mass to volume ratio, and a mild spiral pattern of thicker septal walls (p=0.004). The arrhythmic DCM group displayed a more conical (wider basal and mid wall to apical diameter) LV, and the lack of the spiral septal morphology was the most significant feature (p=0.006) to identify subjects that had the composite arrhythmic outcome. CONCLUSIONThe LV morphology derived suggests a differentiation of arrhythmic DCM patients beyond size, function and LGE presence. This was distinctive and captured shape features that suggest alternate mechanisms for arrhythmic risk linked to a pattern of remodeling. Graphical AbstractAssessing LV morphology signature of arrhythmic DCM phenotype O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/26346514v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1f47f7aorg.highwire.dtl.DTLVardef@dd5d08org.highwire.dtl.DTLVardef@106ef07org.highwire.dtl.DTLVardef@36eb76_HPS_FORMAT_FIGEXP M_FIG C_FIG

BackgroundScreening for atherosclerosis focuses on identifying Standard Modifiable Risk Factors (SMuRFs), including diabetes, hypertension, hyperlipidaemia, and smoking. PurposeTo compare the extracardiac thoracoabdominal atherosclerotic plaque burden, as measured by computed tomography angiography (CTA), among heart transplant candidates with ischemic or non-ischemic cardiomyopathy (ICM, NICM), and evaluate potential associations between plaque burden and SMuRFs. MethodsThis retrospective study identified heart transplant candidates with ICM or NICM matched for age and sex, undergoing thoracoabdominal CTA. Patients were classified as with SMuRFs or SMuRF-less. Extracardiac thoracoabdominal non-calcified and calcified atherosclerotic plaque was classified as present or absent across 78 arterial segments per patient. ResultsAmong included patients (n=167, median [interquartile range] age 58 [53-63] years, 16% female, 51% NICM), 40 patients (24%) were SMuRF-less (ICM: 16/82 (20%), NICM: 24/85 (28%), age 56 [50-67] years). Overall, out of 13,026 arterial segments analysed, 1,746 (13%) were affected by atherosclerotic plaque (9 [4-15] segments per patient). ICM had a higher total plaque burden than NICM (11 [7-18] vs 6 [3-11] segments per patient, p<0.001). SMuRF-less patients showed no difference in non-calcified, calcified, or total plaque burden compared to patients with SMuRFs, among all patients (ICM+NICM, p>0.17) and within the ICM and NICM groups, respectively (p>0.30). ConclusionsThe burden of extracardiac thoracoabdominal atherosclerotic plaque is higher among heart transplant candidates with ICM. However, it does not differ between SMuRF-less or those with SMuRFs, regardless of underlying ICM or NICM. The prevalence of SMuRFs is not an effective marker to determine the need to screen for extracardiac atherosclerotic plaque among heart transplant candidates. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/26347056v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1aff6b1org.highwire.dtl.DTLVardef@16cfb07org.highwire.dtl.DTLVardef@1d4894corg.highwire.dtl.DTLVardef@81e9d3_HPS_FORMAT_FIGEXP M_FIG C_FIG

BackgroundEmbolic stroke of undetermined source (ESUS) is associated with a high risk of recurrence. However, randomized trials have not shown superiority of anticoagulation over aspirin in unselected patients. Atrial cardiomyopathy (AtCM) may identify a high-risk ESUS phenotype. We investigated whether multimodal AtCM markers distinguish ESUS from controls and predict adverse clinical outcomes. MethodsIn this prospective single-center study, consecutive ESUS patients and age- and sex-matched controls without known cardiac disease were enrolled and followed for [&ge;]12 months. All participants underwent clinical assessment, measurement of NT-proBNP, 12-lead ECG, and transthoracic echocardiography. The primary endpoint was a composite of all-cause death, recurrent stroke, transient ischemic attack, myocardial infarction, or newly detected atrial fibrillation. Cox regression analyses identified independent predictors and optimal cutoff values. ResultsThe study included 103 ESUS patients (mean age 70.6{+/-}13.3 years) and 123 controls. Compared with controls, ESUS patients had higher NT-proBNP levels, more frequent advanced interatrial block (IAB), and impaired left atrial function. Over a mean follow-up of 470{+/-}205 days, 29 ESUS patients experienced the primary endpoint. Independent predictors were NT-proBNP >420 pg/mL, advanced IAB, E' [&le;]9 cm/s, left atrial volume index [&ge;]29 mL/m{superscript 2}, and left atrial ejection fraction <50%. A risk score incorporating these variables identified a high-risk ESUS subgroup ([&ge;]3 factors) in which >50% experienced a cardiovascular event within 1 year. ConclusionsAtCM features are common in ESUS and strongly associated with adverse outcomes. A multimodal assessment incorporating NT-proBNP, ECG, and echocardiography identifies a high-risk ESUS subgroup that merits targeted evaluation in future anticoagulation trials.

BackgroundInflammation plays a key role in atrial fibrillation (AF) pathogenesis. The empirical dietary inflammatory potential (EDIP) score predicts circulating inflammatory biomarkers and adverse cardiac outcomes, but its association with incident AF is unclear. This study aimed to examine the relationship between EDIP score and AF risk. MethodsParticipants from the Atherosclerosis Risk in Communities (ARIC) free of baseline AF who completed a validated food frequency questionnaire were included. Correlation of EDIP with inflammatory biomarkers (factor VIII, fibrinogen, von Willebrand factor, and C-reactive protein) was examined at baseline. Incident AF was ascertained using electrocardiograms, hospital records, and death certificates. Cox proportional hazards models estimated hazard ratios of AF across EDIP quantiles and per SD increase, adjusting for sociodemographic and cardiovascular risk factors. ResultsAmong 8,277 participants (54.1 years old, 51.3% women, 80% white), higher EDIP score correlated with circulating inflammatory biomarkers at baseline. Over a median 24.2 years of follow-up, 1,453 had incident AF (incident rate 8.6 per 1,000 person-years). Compared with the most anti-inflammatory diet (EDIP Q1), the most pro-inflammatory diet (EDIP Q5) was associated with increased AF risk (HR 1.21; 95% CI 1.03-1.43). Sex-stratified analyses showed a stronger association in men (HR 1.43; 95% CI 1.14-1.79), while no significant association was observed in women. ConclusionsPro-inflammatory dietary patterns are independently associated with higher AF risk in a middle-aged cohort. These findings would support incorporating dietary inflammatory load into AF risk stratification. Clinical Perspective What Is New?O_LIHigher Empirical Dietary Inflammatory Potential (EDIP) scores, indicating a more pro inflammatory diet, were associated with an increased long-term risk of atrial fibrillation (AF) in a large, biracial, community-based cohort followed for over two decades. C_LIO_LISex stratified analyses revealed a significant sex difference: higher EDIP scores were consistently associated with increased AF risk in men, whereas no significant association was observed in women, suggesting sex-specific susceptibility to EDIP. C_LIO_LIObesity modified the association between EDIP and AF, with the strongest risk observed among individuals with BMI [&ge;]30, while an inverse or attenuated association was seen among normal weight participants. C_LI What Are the Clinical Implications?O_LIDietary inflammatory load may serve as a meaningful and modifiable upstream AF risk factor, complementing conventional cardiovascular risk assessment, particularly in men and individuals with obesity. C_LIO_LIIncorporating dietary pattern assessment into routine AF risk stratification may help identify individuals who could benefit most from targeted lifestyle interventions. C_LIO_LIPublic health and clinical prevention strategies promoting anti-inflammatory dietary patterns (e.g., increased intake of fruits, vegetables, and whole grains; reduced intake of processed meats and refined carbohydrates) could meaningfully reduce AF incidence. C_LIO_LIRecognition of sex specific differences in AF pathways reinforces the need for personalized preventive strategies, as diet inflammation mechanisms appear to influence AF development more prominently in men. C_LI

BackgroundAtrial fibrillation and flutter (AF/AFL) represent a major global public health challenge, contributing significantly to stroke, heart failure, and cardiovascular mortality. While previous studies have documented a rising AF/AFL burden, comprehensive comparisons of long-term trends and forecasts across regions--particularly benchmarking China against Southeast Asia, Europe, and global averages--remain limited. This study aims to quantify the AF/AFL burden across these regions from 1990 to 2021 and project trends to 2050. MethodsUsing data from the Global Burden of Disease Study 2021, we analysed the burden of AF/AFL from 1990 to 2021 in China, Southeast Asia, Europe, and globally. We examined incidence, prevalence, mortality, and disability-adjusted life years (DALYs). Advanced analytical methods, including Joinpoint regression, age-period-cohort modelling, decomposition analysis, Frontier analysis and Bayesian forecasting were employed to assess trends, drivers, and projections to 2050. FindingFrom 1990 to 2021, China experienced the most rapid increase in age-standardized incidence rate (ASIR) globally (AAPC +0.16%), with incident cases rising to 916,180, accounting for 20.43% of the global total. In contrast, Europe saw a slight decline in ASIR, while the global ASIR remained stable. China also recorded the largest increase in age-standardized prevalence rate (ASPR), whereas Europes ASPR declined. Despite rising incidence, China achieved the sharpest reduction in age-standardized mortality rate (ASMR; AAPC -0.45%), while Southeast Asias ASMR increased (AAPC +0.76%), and Europe maintained the highest ASMR globally. Frontier analysis highlighted Chinas rapid efficiency improvements in mortality reduction relative to its SDI, outperforming several high-income European countries. Projections to 2050 suggest Chinas ASIR and ASPR will continue to rise, whereas Europes are forecast to decline. Southeast Asia faces persistently increasing mortality, and global aggregates mask significant regional heterogeneity. ConclusionAF/AFL burdens are increasingly driven by population aging and metabolic risks, with heterogeneous mortality trends reflecting regional disparities in healthcare access and prevention. China s success in reducing mortality despite rising incidence highlights the impact of improved anticoagulation and stroke prevention, yet unchecked prevalence growth signals future complications. Southeast Asia s rising mortality underscores urgent needs for equitable resource allocation, while Europes stagnant burden reflects challenges in aging populations. Globally, prioritising primordial prevention--such as metabolic risk control--alongside targeted screening and gender-specific interventions, is critical to mitigating AF/AFL-related morbidity and mortality. Future efforts should integrate digital health technologies and address structural barriers to optimize care efficiency worldwide. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSPrior to undertaking this analysis, we systematically reviewed the existing epidemiological literature on atrial fibrillation and atrial flutter (AF/AFL), with a particular emphasis on global and regional comparative studies. Our searches covered PubMed, Embase, Web of Science, the Cochrane Library, and the Global Burden of Disease (GBD) repository from January 1990 to December 2023, without language restrictions. Key terms included "atrial fibrillation," "atrial flutter," "global burden," "epidemiology," "trend," and "GBD." We included studies providing representative estimates of AF/AFL burden and excluded small-sample or non-age-standardized reports. Previous analyses indicated a rising global AF/AFL burden, largely due to population aging and improved detection. However, comprehensive assessments capturing temporal dynamics, risk drivers, and forecasting across major world regions--especially benchmarking China, Southeast Asia, and Europe against global patterns--remained limited. Most studies focused on isolated regions or short spans, lacking integrative multidimensional approaches such as age-period-cohort modeling, decomposition, or Bayesian forecasting. Added value of this studyThis study provides a comprehensive and comparative assessment of the atrial fibrillation and atrial flutter (AF/AFL) burden across China, Southeast Asia, Europe, and globally from 1990 to 2021, utilizing the latest GBD 2021 data and advanced statistical methodologies, including Joinpoint regression, age-period-cohort modeling, Bayesian forecasting, decomposition analysis, and data envelopment frontier analysis. Our analysis reveals significant regional disparities against a backdrop of global stability: while the global age-standardized incidence rate (ASIR) remained stable (52{middle dot}51 in 1990 vs. 52{middle dot}12 in 2021), China experienced the most rapid increase worldwide (ASIR rising from 42{middle dot}63 to 44{middle dot}92), with a substantial number of new cases (916,180), accounting for 20{middle dot}43% of the global total (4,484,926 cases). In contrast, Europe recorded a slight decline in ASIR. China also demonstrated the most pronounced increase in prevalence globally, while Europes age-standardized prevalence rate (ASPR) declined and the global rate remained largely unchanged. Notably, China achieved a significant reduction in mortality (age-standardized mortality rate [ASMR] declining from 4{middle dot}93 to 4{middle dot}33) despite rising incidence, sharply contrasting with Southeast Asia, where ASMR increased from 2{middle dot}94 to 4{middle dot}06 (estimated annual percentage change +1{middle dot}07%)--trends potentially associated with structural challenges in Southeast Asia--while Europe maintained the highest ASMR globally (5{middle dot}10 in 2021) despite interventions. We further identified key drivers: population growth and aging accounted for the majority of the case increase in China, consistent with global demographic trends, while metabolic risk factors accelerated this trend. Gender and age analyses revealed a global pattern of later-life predominance in women and earlier onset in middle-aged groups, particularly pronounced in China. Our projections to 2050 indicate a continued rise in ASIR and ASPR in China, reinforcing its significant and growing contribution to the global AF/AFL burden, whereas other regions face divergent challenges--Southeast Asia is projected to experience persistently increasing mortality pressure, while Europe must address persistently high disability-adjusted life year (DALY) rates, masking mortality gains in an aging population. Implications of all the available evidenceThe collective evidence from this study and previous research underscores that AF/AFL remains a critical and growing public health challenge worldwide, characterized by heterogeneous patterns across regions when viewed against the global aggregate. Chinas success in reducing mortality within a rising incidence environment highlights the potential of enhanced clinical management and stroke prevention, yet its unchecked prevalence growth--especially among younger cohorts--signals a looming surge in complications absent strengthened primary prevention, a concern mirrored in many developing economies. Southeast Asias rising mortality underscores urgent needs for improved access to anticoagulation and rhythm control, while Europes stagnant burden reflects challenges in managing an aging population efficiently. These findings advocate for regionally tailored strategies that align with global frameworks but address local disparities--integrating primordial prevention (e.g., metabolic risk control) with early detection, gender-specific treatment, and equitable resource allocation. Future research should prioritize mechanistic studies of AF/AFL subtypes, real-world intervention assessments, and the integration of digital health technologies for scalable screening and management, thereby informing coordinated global actions to mitigate the evolving burden of AF/AFL.