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

Background: Higher METS-IR has been shown to be associated with a higher risk of major adverse cardiovascular events, but data are lacking regarding cardiac arrhythmias. Objectives: The aim of this study was to assess the association between METS-IR and atrial fibrillation/flutter, ventricular arrhythmia and bradyarrhythmia. Methods: Data from the Atherosclerosis Risk in Communities study spanning 1987 to 2013 was utilized for this analysis. METS-IR scores were assessed at baseline (1987-1989) and arrhythmia episodes were identified using ICD-9 codes. Multivariate-adjusted Cox proportional hazard models were constructed to evaluate the relationship between METS-IR and arrhythmia risk, with dose-response analyses conducted. In addition, we analyzed the predictive value of METS-IR for arrhythmias. Results: Over a mean follow-up of 21.9 years, 2493 cases of AF, 688 cases of bradyarrhythmia, and 1315 cases of ventricular arrhythmia were recorded. Each interquartile range increase in METS-IR was associated with a 49% higher risk of atrial fibrillation(P<0.001), 29% higher risk of bradyarrhythmia(P<0.001), and 42% higher risk of ventricular arrhythmia(P<0.001). After correction for relevant confounders, the METS-IR index was significantly and positively associated with the risk of new-onset atrial fibrillation, bradyarrhythmia, and ventricular arrhythmia (P overall<0.05, P for non-linearity>0.05). Most of the results of the subgroup analyses were not significantly different. The inclusion of METS-IR in the base model improves the predictive value of the risk of arrhythmogenesis. Conclusions: There is a significant association between METS-IR and increased risk of arrhythmias.

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.

OBJECTIVEThis study aimed to explore the role and underlying mechanism of microRNA-128 (miR-128) in regulating vascular remodeling in spontaneously hypertensive rats (SHRs), focusing on its targeting of peroxisome proliferator-activated receptor {gamma} (PPAR-{gamma}) and modulation of the Toll-like receptor 4/nuclear factor-{kappa}B (TLR4/NF-{kappa}B) inflammatory pathway. METHODSAll experimental procedures were approved by the Animal Care and Use Committee of Fujian Medical University. In vivo, ten-week-old male SHRs were randomly assigned to three groups: renal denervation (RDN, n=6), sacubitril/valsartan (Sac/Val, n=6), and Sham (n=6). Age-matched Wistar-Kyoto (WKY) rats served as normotensive controls (n=6).Eight weeks after intervention, mesenteric arteries were harvested for histological, functional, and molecular analyses. Serum miR-128 levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The expression levels of key proteins in the vascular wall were assessed via immunofluorescence (IF), immunohistochemistry (IHC), and Western blotting (WB). Bioinformatics analysis and RNA sequencing (RNA-seq) were employed to identify core genes and signaling pathways associated with hypertension-induced pathological inflammation. RESULTSIn vivo, in the SHR sham-operated group, elevated blood pressure, severe vascular remodeling, and impaired vasodilatory function were observed, accompanied by downregulated miR-128 expression and upregulated TLR4/NF-{kappa}B signaling activity (all p < 0.0001).RDN postoperative, miR-128 expression was significantly restored, which in turn inhibited the TLR4/NF-{kappa}B pathway, reduced the production of pro-inflammatory cytokines (including IL-1{beta}, IL-6, and TNF-), and ameliorated vascular dilation dysfunction in SHRs (all p < 0.0001). Mechanistically, miR-128 negatively regulated the TLR4/NF-{kappa}B signaling pathway while upregulating the expression of PPAR-{gamma} (p < 0.05). CONCLUSIONRDN not only exerts a hypotensive effect but also improves hypertensive vascular remodeling. miR-128 inhibits excessive inflammation in vascular smooth muscle cells and alleviates vascular remodeling in SHRs via the PPAR-{gamma}/TLR4/NF-{kappa}B axis. These findings identify miR-128 as a potential therapeutic target for RDN in the treatment of hypertension, providing a novel regulatory strategy for the precision management of cardiovascular diseases.

Background: Atrial Fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide, representing the primary cardiac etiology of stroke. In recent years, direct oral anticoagulants (DOACs) have shown favorable results in terms of efficacy and safety in the prevention of thromboembolism in patients with AF. TROMBIX-DZ study investigated the safety and efficacy of rivaroxaban in routine clinical settings in response to the need for real-world evidence on the use of DOACs. Methods: We carried a national, multicenter, prospective, observational cohort study to evaluate the safety and efficacy of rivaroxaban in Algerian patients with atrial fibrillation. Patients were followed-up at 3 months intervals for 1 year. The primary outcome of this study was to evaluate the safety of rivaroxaban, reported as the frequency of treatment-emergent serious adverse events (SAEs); Secondary outcomes assessed the frequency of thromboembolic events, adverse events (AEs), and treatment persistence. Results: TROMBIX-DZ enrolled 398 eligible patients with AF from 19 specialized public and private cardiology centers across different regions in Algeria. The mean age was 70.5 {+/-} 11.94. 71.9% of patients received once daily rivaroxaban 20mg, and 28.1% received the 15mg dose. The most common comorbidities included, hypertension (77.1%), diabetes (28.6%) and heart failure (25.4%), prior strokes and TIA (8.8%), and prior major bleeding (3.1%). The mean CHA2DS2-VASc score was 3.147 {+/-} 1.3, and the mean HAS-BLED score was 1.682 {+/-} 1.198; 14.06% of patients had Creatinine clearance < 50 ml/min. A total of 5.77% had treatment-emergent AE, and 1.76% had treatment-emergent SAE. The incidence rate (events per 100 patient-years) of treatment-emergent major bleeding events, treatment-emergent thromboembolic events and all-cause death during the study period were 2.1, 0.9, and 4.18, respectively. Treatment persistence was 75.88% at the end of the study. Conclusion: TROMBIX-DZ study, the first cohort in the Maghreb region, provides important insights into the safety and efficacy of rivaroxaban in Algerian population with atrial fibrillation receiving standard medical care. Rates of major bleeding and stroke were low and broadly consistent with previous international real-world registries. Trial registration number: Clinicaltrial.gov: (NCT06184204). Keywords: Direct oral anticoagulants, Rivaroxaban, Atrial fibrillation, Major bleeding, Stroke, Thromboembolism, The Maghreb region, Real-world.

Background: Postoperative atrial fibrillation (POAF) affects up to 50% of cardiac surgery patients and is linked to higher morbidity, longer hospital stays and increased thromboembolic risk. Early identification of at-risk patients remains challenging. Calcitonin (CT), a hormone with anti-fibrotic effects, may serve as a novel biomarker. Methods: In 491 patients undergoing elective cardiac surgery, baseline serum CT was measured preoperatively using CT-specific enzyme-linked immunosorbent assay (ELISA). Patients with pre-existing AF were excluded. Associations between CT levels and POAF incidence and onset were evaluated using logistic regression, Cox proportional hazards models, and Kaplan-Meier analysis. Results: Among 248 patients with detectable CT levels, 88 patients developed POAF. Higher baseline CT was independently associated with lower risk of POAF (OR 0.68 per 5 pg/ml increase; 95% CI 0.51-0.89; P = 0.009) and delayed arrhythmia onset (adjusted HR 0.941; 95% CI 0.898-0.980, P = 0.0026) after adjusting for covariates. Kaplan-Meier analysis demonstrated a graded relationship between increasing CT levels and reduced cumulative incidence of POAF. In this cohort, baseline CT showed greater discriminative ability than CRP and BNP, although overall model performance remained moderate. Conclusion. Higher preoperative circulating CT levels are associated with reduced risk and delayed onset of POAF following cardiac surgery. These findings suggest that calcitonin may have the potential as a biomarker for perioperative risk stratification in POAF. Given the observational design and single-centre setting, further validation in independent cohorts and studies integrating mechanistic insights are warranted.

BackgroundAortic stenosis (AS) carries a high mortality risk if left untreated. Transcatheter aortic valve implantation (TAVI) has emerged as a primary treatment modality for many patients with severe AS. Observational data suggest that renin-angiotensin system (RAS) inhibitor use following TAVI are associated with lower risk, but with divergent reported effects and limited statistical power for specific cardiovascular outcome. This study aimed to assess the association between RAS inhibitor use and clinical outcomes after TAVI. MethodsA systematic literature search was conducted in EMBASE and PubMed. Eligible studies included those reporting on RAS inhibitor use in TAVI populations. The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, myocardial infarction (MI), cerebrovascular events, and heart failure (HF) hospitalization. ResultsNine observational studies including 36,015 patients were included. RAS inhibitor use was associated with lower odds of all-cause mortality (OR 0.74, 95% CI 0.70- 0.78), cardiovascular mortality (OR 0.62, 95% CI 0.55-0.72), cerebrovascular events (OR 0.59, 95% CI 0.47-0.74), and HF hospitalization (OR 0.84, 95% CI 0.77-0.92). No clear association was observed for MI (OR 0.95, 95% CI 0.59-1.53). ConclusionsRAS inhibitor use was associated with favorable clinical outcomes following TAVI. However, these findings are based on observational data, which are subject to residual confounding. Randomized controlled trials are needed to clarify the clinical utility of RAS inhibitors in this setting.

Background: A growing burden of cardiovascular risk factors has raised cardiovascular disease-related mortality in Sub-Saharan Africa (SSA), driving higher prevalence of heart failure with reduced ejection fraction (HFrEF) and its complication with atrial fibrillation (AF). No prospective study has examined AF's clinical impact on HFrEF in SSA. Aim: To determine AF prevalence in HFrEF, describe HFrEF-AF clinical characteristics, and determine AF's impact on mortality. Methods: In this prospective observational study at a tertiary hospital in Johannesburg, 136 HFrEF patients were enrolled and categorised as HFrEF- SR (sinus rhythm) or HFrEF-AF. Baseline clinical characteristics and biochemistry were recorded. Comprehensive echocardiography including left atrial strain by 2D speckle-tracking was performed. Median follow-up was 30.6 months. Results: AF was present in 28 patients (21%). The mean age was 58.7 {+/-} 14.9 years (52.9% male) and differed between groups (p < 0.001). Hypertensive heart disease was the leading cause of HFrEF (36%). Compared with SR, HFrEF-AF patients had poorer health status (KCCQ 27 [16-43] vs 45 [32-60], p < 0.001) and lower left atrial strain (26.2 {+/-} 11.3%, p < 0.001). Guideline-directed medical therapy was suboptimal in the AF group: anticoagulation use was higher than SR (60% vs 9.5%, p < 0.001) but overall inadequate; HFrEF-AF patients received lower median doses of carvedilol (15.6 mg vs 25 mg, p = 0.002) and enalapril (10 mg vs 20 mg, p = 0.004), and fewer received spironolactone (50% vs 75.3%, p = 0.013). Survival was significantly lower in HFrEF-AF (0.41 [0.22-0.61]) versus SR (0.73 [0.61-0.82], p < 0.001). Independent predictors of mortality included prior stroke, lower TAPSE and KCCQ, and higher E/e' and heart rate. Conclusion: AF is common among HFrEF patients in this SSA cohort (though lower than in high-income countries) and associates with worse clinical status, suboptimal therapy, and higher mortality.

AimsWhile traditional anthropometric indices are established cardiovascular predictors, their prognostic value for incident infective endocarditis (IE) remains undefined. MethodsWe 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. ResultsOver 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). ConclusionCompared 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. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/26351534v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@a281e7org.highwire.dtl.DTLVardef@fe7fb0org.highwire.dtl.DTLVardef@7108a1org.highwire.dtl.DTLVardef@edb9a5_HPS_FORMAT_FIGEXP M_FIG C_FIG

ObjectivesTo evaluate the therapeutic potential of BMP-7 mRNA-lipid nanoparticle formulation in attenuating cardiac fibrosis and improving function in non-ischemic heart failure, and to assess its impact on endothelial phenotype and function under pro endothelial-to-mesenchymal transition (EndMT) conditions. BackgroundDespite advances in neurohormonal blockade, heart failure (HF) progression remains driven in part by fibrotic remodeling. Endothelial-to-mesenchymal transition (EndMT) has emerged as a contributor to myocardial fibrosis, while recent work suggests endothelial phenotypic plasticity may also participate in myocardial recovery. Bone morphogenetic protein-7 (BMP-7) is a known anti-fibrotic regulator, but effective therapeutic delivery strategies remain limited. MethodsA patent pending, custom-designed BMP-7 mRNA formulated in lipid nanoparticles (AET-1978) was administered subcutaneously in a murine model of non-ischemic HF induced by L-NAME and angiotensin II. Cardiac function and fibrosis were assessed by echocardiography and histology. In an invitro EndMT model, human umbilical vascular endothelial cells (HUVECs) were treated with BMP-7 mRNA and endothelial and mesenchymal morphology, and markers were assessed along with endothelial functional tests. ResultsAET-1978 therapy significantly improved left ventricular systolic and diastolic function and reduced myocardial fibrosis compared with untreated HF mice, without evidence of renal or hepatic toxicity. In vitro, BMP-7 mRNA delivery restored endothelial morphology, suppressed EndMT-associated mesenchymal and profibrotic marker expression while preserving nitric oxide production, lipoprotein uptake, and angiogenic capacity of the HUVECs. ConclusionsA novel formulation of BMP-7-mRNA-LNP called AET-1978 represents a novel, transient, non-integrating strategy to attenuate fibrotic remodeling and improve cardiac function in heart failure, with supportive evidence of being anti endothelial to mesenchymal transition. HighlightsO_LIA novel BMP-7 mRNA-lipid nanoparticle formulation delivered as a subcutaneous injection attenuated myocardial fibrosis and improved systolic and diastolic function in a murine model of non-ischemic heart failure. C_LIO_LIBMP-7 mRNA therapy preserved endothelial phenotype and suppressed endothelial-to-mesenchymal transition in an in vitro platform of human umbilical vascular endothelial cells. C_LIO_LIBMP-7 mRNA therapy preserved endothelial function including restoration of nitric oxide production, lipoprotein uptake, and angiogenic capacity in vitro. C_LIO_LIThis study introduces AET-1978, a transient, non-integrating mRNA therapeutic platform, as a novel approach to target residual fibrotic pathways in heart failure using a clinically scalable delivery route. C_LI

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.

BackgroundST-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. ObjectiveTo 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. MethodsThis 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. ResultsThe 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. ConclusionsCK-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.

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

BackgroundLeft atrial appendage closure (LAAC) and direct oral anticoagulants (DOACs) have emerged as alternatives to warfarin for stroke prevention in atrial fibrillation (AF). However, recent trials have shown variable results igniting the debate on this topic. MethodsWe performed a systematic review and network meta-analysis (NMA) of RCTs comparing LAAC, DOACs, and warfarin in patients with AF. The primary efficacy outcome was ischemic stroke or systemic embolism (IS/SE) and the primary bleeding outcome was hemorrhagic stroke (HS). Secondary outcomes included net adverse clinical events (NACE) and major or clinically relevant bleeding (MCRB). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using a random-effects model. ResultsTen RCTs (LAAC: 6 trials; DOAC: 8 trials; warfarin: 6 trials) enrolling 78,594 patients fulfilled the inclusion criteria. There were no significant differences for the primary efficacy outcome of IS/SE among the 3 strategies. However, when compared with warfarin, both DOACs (OR 0{middle dot}43, 95% CI 0{middle dot}34-0{middle dot}54) and LAAC (OR 0{middle dot}34, 95% CI 0{middle dot}18-0{middle dot}63) reduced the primary safety outcome of HS, with no significant difference between them (OR 0{middle dot}79, 95% CI 0{middle dot}44-1{middle dot}3). For NACE, both DOACs (OR 0{middle dot}87, 95% CI 0{middle dot}83-0{middle dot}91) and LAAC (OR 0{middle dot}85, 95% CI 0{middle dot}73-0{middle dot}99) were superior to warfarin, with similar performance between them (OR 0{middle dot}98, 95% CI 0{middle dot}84-1{middle dot}13). For MCRB, DOACs were superior to warfarin (OR 0{middle dot}79, 95% CI 0{middle dot}63-0{middle dot}99), while LAAC showed a non-significant trend towards benefit. ConclusionIn this meta-analysis of RCTs with data from over 78,000 patients, LAAC and DOACs significantly reduced NACE driven by lower hemorrhagic stroke and provided equivalent IS/SE protection compared with warfarin, making LAAC a potential viable alternative to oral anticoagulation in appropriately selected AF patients. FundingNone.

Background Depression and anxiety are prevalent among cardiovascular disease (CVD) patients and significantly worsen clinical outcomes, increasing complications, recurrent events, and healthcare costs. Evidence shows that psychological stress, depression, and anxiety elevate CVD risk, while post-discharge nurse-led telephone follow-up has demonstrated benefits in patient support and symptom management. Little is known about its impact on mental health. Objective The aim of this study was to evaluate the effects of implementing the "nurse telephone follow-up" project on depression, anxiety and stress levels among cardiovascular patients. Methods An experimental study was conducted with 60 randomly selected patients from the Coronary Care Unit (CCU) department of a hospital in Iran, who were divided into two groups: an intervention group and a control group. The educational intervention was administered within two weeks after discharge. Data were collected via the Depression Anxiety Stress Scale (DASS-21). Descriptive analysis, Mann?Whitney and Wilcoxon tests, Generalized Estimating Equations (GEE) regression, and Spearmans correlation were used for data analysis. Results The mean age of the patients was 57.43 {+/-} 15.33 years. While no significant difference was found between the intervention and control groups in terms of depression, anxiety, or stress (p>0.05), the depression score decreased by 1.53 points, and the anxiety score decreased by 1.18 points after the intervention. Furthermore, an increase in patients ejection fraction (EF) score was associated with a 0.1 decrease in both depression and anxiety levels. No significant relationship was found between stress and any variables. Conclusions The results of this study suggest that psychological and therapeutic interventions may help reduce depression and anxiety in patients with cardiovascular diseases. However, this requires further detailed evaluation and additional studies. The potential link between improved cardiac function and reduced psychological symptoms could be effective in designing more comprehensive treatments for these patients.

BackgroundAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are frequently associated with cardiac complications, including myocardial injury and right ventricular dysfunction. However, the mechanisms linking pulmonary injury to cardiac dysfunction remain incompletely understood. In this study, we investigated ventricular mitochondrial respiratory function during the acute phase of bleomycin-induced ALI. MethodsALI was induced in male and female rats by intratracheal bleomycin (2.5 mg/kg); saline served as a control. Circulating cardiac troponin I (cTnI) was measured as an indicator of myocardial injury. Mitochondrial respiration was assessed in permeabilized ventricular fibers using high-resolution respirometry (HRR). The mitochondrial respiration rate of the H9C2 cardiomyoblast cell line was performed using Seahorse Xfe96 Cell Mitochondrial Stress Test. Cells were treated with pro-inflammatory cytokine cocktails (PRO; IL1{beta} plus TNF plus IL6), anti-inflammatory cytokine cocktails (ANTI; IL4 plus IL10), a mixture of PRO and ANTI (BOTH), and (-)-norepinephrine (NE) in either hypoxic (1% oxygen) or normoxic conditions. ResultsBleomycin-induced ALI increased circulating cTnI levels in male rats, indicating early cardiac stress following lung injury. Mitochondrial respiration in the LV appeared to show modest alterations, with preserved oxidative phosphorylation (OXPHOS) and electron transport (ET) capacity. In contrast, the RV of male animals demonstrated marked reductions in absolute respiratory flux and substrate-supported OXPHOS capacity, indicating impaired mitochondrial oxidative capacity. Female animals exhibited greater preservation of mitochondrial respiratory function, particularly in the RV, with higher OXPHOS capacity and greater Complex I gain than males. H9C2 cells treated with PRO showed a significant increase in uncoupled respiration following 6- and 24-hour incubation periods, under normoxic conditions. Maximal respiration and spare respiratory capacity were increased following 24-hours under hypoxia. No significant changes were observed following treatment with NE alone and in combination with PRO under normoxia or hypoxia for 24 hours. ConclusionsALI induces ventricle-specific and sex-dependent alterations in cardiac mitochondrial bioenergetics, with pronounced impairment in males and relative mitochondrial resilience in females. In H9C2 cardiomyoblasts, short-term exposure (6-24 hours) to pro-inflammatory cytokines enhances uncoupled mitochondrial respiration under normoxic conditions, while short-term hypoxic exposure independently increases maximal respiration and spare respiratory capacity.

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.

BackgroundPoor 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. MethodsA 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. ResultsMean 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. ConclusionsThe 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. What is KnownO_LIPhysical function has been associated with cardiovascular diseases, however, the relationship between physical function and incident atrial fibrillation (AF) remains understudied. C_LI What the Study AddsO_LIThis study found that better Short Physical Performance Battery (SPPB), 4-meter walk time, and grip strength were all independently associated with reduced risk of incident AF. C_LIO_LIIn this study, higher SPPB was most strongly associated with reduced risk of incident AF, implying the importance of multi-domain measures of physical function. C_LIO_LIThis study found that within SPPB, higher chair stand component score was the only component significantly associated with reduced risk of incident AF, highlighting the critical role of muscle strength in the association between physical function and risk of incident AF. C_LIO_LIThe results suggest that physical function may be a novel modifiable target for AF prevention. C_LI