BMC Cardiovascular Disorders

AbstractO_ST_ABSBackgroundC_ST_ABSThis study aims to explore the causal relationships between inflammatory cytokines (ICs), metabolites, and the risk of arrhythmia through Mendelian Randomization (MR) analysis. MethodsThe causal associations were analyzed using five different MR analysis methods. Additionally, reverse MR analysis was performed to assess the impact of arrhythmias on these ICs and their metabolites. ResultsThe MR analysis revealed that Oncostatin-M receptor (OSM) was significantly associated with an increased risk of arrhythmia (OR = 1.0812, p < 0.05), along with other ICs such as CXCL11 (OR = 1.0586), SIRT2 (OR = 1.0521), and FGF5 (OR = 1.0520). Five were positively correlated with arrhythmia risk, including X-22776 (OR = 1.071, p = 0.022) and tricosanoylsphingomyelin (OR = 1.066, p = 0.035).Mediation analysis demonstrated that FGF5 influences arrhythmia risk through its metabolite 1-palmitoyl-2-oleoyl-GPE, with a mediated effect accounting for 5.1% of the total effect. ConclusionsOur findings suggest that specific ICs and metabolites contribute to the pathogenesis of arrhythmia. In particular, FGF5 and its metabolite 1-palmitoyl-2-oleoyl-GPE are implicated in increased arrhythmia risk, highlighting potential metabolic targets for therapeutic intervention.

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

BackgroundThe Endothelial Activation and Stress Index (EASIX) reflects endothelial dysfunction and has prognostic value in cardiovascular diseases. This study investigates the association between EASIX and all-cause mortality in critically ill atrial fibrillation (AF) patients. MethodsUsing MIMIC-IV (v3.1) data, 4722 AF patients were stratified by EASIX quartiles. Cox regression, Kaplan-Meier curves, and restricted cubic spline (RCS) models assessed mortality risk at 7, 30, 180, and 365 days. Subgroup analyses evaluated consistency. ResultsEASIX was significantly associated with increased mortality at all time points. The Kaplan-Meier survival curve shows that as the EASIX quartile increases, the 7-day, 30-day, 180-day, and 365-day mortality rates of AF patients significantly increase. RCS analyses showed that there was a significant non-linear relationship between EASIX and the 7-day, 30-day, 180-day, and 365-day mortality rates of patients with AF. The Cox analysis before and after adjusting for confounding factors showed that EASIX was an independent risk factor for 7-day, 30-day, 180-day, and 365-day all-cause mortality in AF patients. Subgroup analyses further indicated the robustness of these results. ConclusionsEASIX levels are significantly correlated with all-cause mortality at 7, 30, 180, and 365 days in patients with AF, and endothelial dysfunction plays an important role in poor prognosis in AF patients.

BackgroundAtrial fibrillation (AF) is the most prevalent tachycardia. The major injuries caused by AF are systemic embolism and heart failure. Although AF therapies have evolved substantially in recent years, the success rate of sinus rhythm maintenance is relatively low. The reason is the incomplete understanding of the AF mechanisms. Material and methodIn this study, profiles were downloaded from the GEO database (GSE79762). Bioinformatic analysis was used to identify differentially expressed genes (DEGs). GO analysis and KEGG analysis were performed to identify the most enriched terms and pathways. A protein-protein interaction network was constructed to determine regulatory genes. Key modules and hub genes were identified by MOCDE and cytoHubba. Transcription factors (TFs) were predicted by PASTAA. ResultsSeventy-seven up-regulated DEGs and 236 downregulated DEGs were identified. In the GO biological process, cellular components, and molecular function analysis, positive regulation of cell migration, anchoring junction and cell adhesion molecule binding were the most significant enrichment terms. The Hippo signaling pathway was the most significantly enriched pathway. In the PPI network analysis, we found that Class A/1 (rhodopsin-like receptors) may be the critical module in AF. Ten hub genes were extracted, including 4 upregulated genes and 6 downregulated genes. CXCR2, TLR4 and CXCR4 may play critical roles in AF. In TF prediction, we found that Irf-1 may be implicated in AF. ConclusionOur study found that the CXCR4, TLR4, CXCR2; Hippo signaling pathway; and class A/1 (rhodopsin-like receptors) modules may play critical roles in AF occurrence and maintenance. This may provide novel targets for AF treatment.

BackgroundVirtual evaluation of medical therapy through human-based modelling and simulation can accelerate and augment clinical investigations. Treatment of the most common cardiac arrhythmia, atrial fibrillation (AF), requires novel approaches. ObjectivesTo prospectively evaluate and mechanistically explain novel pharmacological therapies for atrial fibrillation through in-silico trials, considering single and combined SK and K2P channel block. MethodsA large cohort of 1000 virtual patients was developed for simulations of AF and pharmacological action. Extensive calibration and validation with experimental and clinical data support their credibility. ResultsSustained AF was observed in 654 (65%) virtual patients. In this cohort, cardioversion efficacy increased to 82% (534 of 654) through combined SK+K2P channel block, from 33% (213 of 654) and 43% (278 of 654) for single SK and K2P blocks, respectively. Drug-induced prolongation of tissue refractoriness, dependent on the virtual patients ionic current profile, explained cardioversion efficacy (atrial refractory period increase: 133.0{+/-}48.4 ms for combined vs. 45.2{+/-}43.0 and 71.0{+/-}55.3 for single SK and K2P block, respectively). Virtual patients cardioverted by SK channel block presented lower K2P densities, while lower SK densities favoured the success of K2P channel inhibition. Both ionic currents had a crucial role on atrial repolarization, and thus, a synergism resulted from the polypharmacological approach. All three strategies, including the multi-channel block, preserved atrial electrophysiological function (i.e., conduction velocity and calcium transient dynamics) and thus, its contractile properties (safety). ConclusionIn-silico trials identify key factors determining efficacy of single vs combined SK+K2P channel block as effective and safe strategies for AF management.

BackgroundMental illness was identified associated with high risk of cardiovascular diseases (CVDs). However, few studies focused on the effect of personality traits, the causal relationships remain unknown. Here, we use mendelian randomization (MR) analyses to evaluate the causal association between mood instability (mood swings) and 5 common CVDs. MethodsLarge genome-wide association studies (GWAS) of mood swings (n= 373733) and 5 CVDs from two independent cohorts respectively including coronary artery disease (CAD) (n= 766053), myocardial infarction (MI) (n= 596436), heart failure (HF) (n= 1185501), atrial fibrillation (AF) (n= 2169833) and stroke (n = 627558). We performed a range of bidirectional two-sample MR and related sensitive analysis including MR-Egger regression, MR-PRESSO global test and "Leave-one-out" method. A Bonferroni-corrected significance level of p < 0.01 (0.05/5) was identified to be statistically significant, while p < 0.05 was considered to indicate suggestive evidence. Moreover, multivariable MR (MVMR) and mediation analyses were also conducted to adjust confounding factors as well as found potential mediators. ResultsThis MR analyses revealed the significant causal effects of mood swings on CAD (OR = 1.45, 95% CI 1.24-1.71; P = 5.52e-6), MI (OR = 1.60, 95% CI 1.32-1.95; P = 1.77e-6), HF (OR = 1.42, 95% CI 1.12-1.71; P = 2.32e-6) and stroke (OR = 1.48, 95% CI 1.19-1.83; P = 3.46e-4). However, no causal effects of mood swings on AF (P=0.16) were found. In the reverse MR, no causal relationships were observed. Additionally, hypertension may mediate the causal pathway from mood swings to CAD (proportion of mediation effect in total effect: 39.60%, 95% CI: 19.31%-59.89%), MI (35.37%, 95% CI: 17.10%-53.65%), HF (43.19%, 95% CI: 20.68%-65.69%) and stroke (55.47%, 95% CI: 27.00%-83.95%). ConclusionMood instability (mood swings) causally resulted in CAD, MI, HF and stroke, and these causal effects may be partly mediated by hypertension.

BackgroundOn the one hand, the coronary slow flow phenomenon (CSFP) may cause recurrence of chest pain, prompting medical examinations and further healthcare expenses, and on the other side, it can result in myocardial infarction, ventricular arrhythmia, and sudden cardiac death. ObjectivesDue to the lack of agreement on the optimal treatment for CSFP, we decided to examine the effectiveness of sildenafil in this context. MethodsWe assessed the eligibility of 196 CSFP patients to participate in a 12-week, triple-blind, randomized, placebo-controlled study for receiving either 50 mg daily oral sildenafil or placebo. We evaluated the efficacy of sildenafil based on exercise tolerance test parameters, severity of angina, adverse effects, and major adverse cardiovascular events. ResultsTwenty eligible patients were randomly allocated in a 1:1 ratio to two groups. Sildenafil demonstrated significant efficacy in improving angina severity, with all recipients achieving a Class I angina severity, contrasting with a 40% attainment in the placebo group (P=0.011). Notably, Sildenafil induced statistically significant reductions in systolic and diastolic blood pressure, unlike the placebo group. Although a reduction in the QT interval favored Sildenafil (-21 millisecond vs +3 milliseconds), statistical significance was not reached (P=0.09 vs. P=0.67). Moreover, Sildenafil markedly improved Duke Treadmill Score (DTS) (P=0.005), while the placebo group showed non-significant improvement. Concurrently, the Sildenafil group exhibited significant enhancements in functional capacity (METs) and maximum heart rate during exercise testing compared to the placebo group. ConclusionsWe suggest that a daily low dose of sildenafil could be a valuable therapeutic option for CSFP. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/24301510v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@168d767org.highwire.dtl.DTLVardef@15d806org.highwire.dtl.DTLVardef@19846corg.highwire.dtl.DTLVardef@144d9c9_HPS_FORMAT_FIGEXP M_FIG C_FIG

AimThis study aimed to develop a refined classification of atrial fibrillation (AF) according to comprehensive risk factors to identify patients at high-risk for poor prognosis and their life expectancy. MethodA total of 7,391 participants aged 40-69 with AF at baseline, from UK Biobank, were classified into five clusters, based on seven clustering variables including age and six risk factor categories (metabolic disease, respiratory disease, cardiovascular disease, renal/immune-mediated disease, mental health disease, acute illness). Difference in the risk of death and major complications, as well as reductions in life expectancy, among clusters were estimated. Replication was done in 2,399 participants with newly diagnosed AF within two years after baseline. ResultsFive distinct AF clusters were identified: acute illness-related, mental health-related, cardiovascular disease-related, immune-and-renal disease-related, and respiratory-and- metabolic disease-related AF. Patients with respiratory-and-metabolic disease-related AF had the highest risk of death, acute myocardial infarction, heart failure, and cerebral ischemic stroke, while those with acute illness-related AF had the lowest corresponding risk. In addition, compared with individuals with acute illness-related AF, those with respiratory-and- metabolic disease-related and mental health-related AF had the top 2 greatest loss of life expectancy. Furthermore, genetic variants for AF had different effect among the five clusters. Replication analysis confirmed the result stability. ConclusionA novel AF classification was developed, which provided insights into varying life expectancy and risks of death and complications among AF subgroups with distinct characteristics. It offers a practical approach for identifying high-risk patients, which might help to tailor precise interventions for AF management.

BackgroundAtrial fibrillation (AF) is considered the most common supraventricular arrhythmia in patients undergoing coronary artery bypass graft (CABG). The predictive value of the SYNTAX score for post-CABG new-onset AF incidence has not been clearly evaluated. This study aimed to assess this association in patients undergoing isolated on-pump CABG. MethodThis study was done in a single-center, randomized, and observational setting. A total of 133 patients undergoing on-pump isolated CABG who were older than 18 years and had sinus rhythm were enrolled. Demographic variables of patients were recorded, and the SYNTAX score was measured for the participants. The multivariate logistic regression model was applied to identify the predictors of post-CABG new-onset AF. ResultsThe logistic regression model showed that SYNTAX score of more than 28.25 (p-value= 0.001; OR= 14.25, 95% CI= 2.90_70.11), hypertension (p-value=0.02; OR = 6.59, 95% CI = 1.23_34.57), and calcium channel blocker consumption (p-value=0.02; OR = 8.05, 95% CI = 1.43_45.42) are predictors of new-onset AF after on-pump CABG. ConclusionThis study demonstrated that patients with higher SYNTAX scores in coronary angiography are more likely to develop new-onset AF after isolated on-pump CABG.

BackgroundNicorandil acts as a potassium channel opener, however its cardio protective benefit is still uncertain. This meta-analysis was conducted with the objective of evaluating the efficacy of nicorandil in improving cardiovascular outcomes in acute coronary syndrome. Main BodyA total of 24 RCTs with 1640 patients in the nicorandil group and 1592 patients in the control group were identified following PRISMA guidelines till November 2019 and were matched for inclusion and exclusion criteria. The following search strings and MESH terms were used: "nicorandil", "ACS", "MACE". Following this, nicorandil was evaluated for its efficacy and safety outcomes. RevMan 5.3 was used for appropriate statistical tests. Fixed and Random Effect Model Test were used and p<0.05 was considered statistically significant. ResultsAdministration of nicorandil was found to be associated with a significant decrease in MACE (RR = 0.686, 95% CI = 0.509-0.925, p=0.013), no-reflow phenomenon (RR =0.395, 95% CI = 0.266-0.588, p<0.001) and worsening of HF (RR =0.441, 95% CI = 0.221-0.882, p=0.021). It was also associated with significant improvement in LVEF (SMD= 0.637, 95% CI= 0.0972 to 1.177, p=0.021) and significant lowering of cTFC (SMD= -0.216, 95% CI= -0.428 to -0.0041, p=0.046) ConclusionsNicorandil does indeed exert a cardio protective effect by improving cardiovascular outcomes. There is a significant decrease in occurrences of MACE and worsening of HF. There is also significant improvement in LVEF.

BackgroundPericarditis is a relatively rare disease with a global burden. Despite its strong association with adverse cardiovascular outcomes, identification of patients at risk of future heart failure or arrhythmic events is difficult. In the following study, automated electrocardiogram (ECG) were used to predict new onset ventricular tachycardia/fibrillation (VT/VF), atrial fibrillation (AF) and heart failure with reduced ejection fraction (HF) in an Asian cohort of pericarditis patients. MethodsConsecutive patients admitted to a single tertiary center in Hong Kong, China, for a diagnosis of pericarditis between 1st January 2005 and 31st December 2019 with baseline ECG measurements were included. Patients with existing AF or HF were excluded. The follow-up period was until the 31st December 2020, or death. Cox regression was applied to identify significant predictors of the primary outcomes (incident VT/VF, AF or HF). ResultsA total of 874 patients were included. The cohort was 57% male and had a median age of 59 (IQR: 50-70) years old. During follow-up, 57 patients (6.5%), 156 (17.8%) and 168 (19.2%) suffered from VT/VF, AF and HF, respectively. Cox regression identified baseline VT/VF, terminal angle of the QRS vector in the transverse plane, mean QRS duration and mean QTc intervals as significant predictors of incident VT/VF events, with only the former most maintaining significance in multivariate analysis. In contrast, baseline age, prior diagnoses of hypertension, initial angle and magnitude of the QRS vector in the transverse plane, P-wave and QRS axis in the frontal plane, ST segment axis in the frontal and horizontal planes, mean PT interval, mean PR segment duration and QTc intervals were all univariate predictors of incident AF, albeit only baseline age and initial angel of the QRS vector in the transverse plane retained significance after multivariate adjustment. As it pertains to new-onset HF, several clinical and electrocardiographic parameters demonstrated an association with HF in univariate analysis, with prior diagnosis of HT or DM, initial QRS angle in transverse plane, I 40 in horizontal axis, ST-segment axis in the horizontal plane, T-wave frontal axis and atrial rate, of which, except for prior diagnosis of DM, I40 in horizontal axis and T-wave frontal axis, all variables showcased significant relationships in multivariate analysis InterpretationAF and HF are relatively common complications VT/VF occurs less frequently in the context of pericarditis. Different clinical and ECG predictors of these outcomes were identified. Future studies are still needed to evaluate their use for risk stratification in the clinical setting.

AimsThe BTB and CNC homology 1 (BACH1) transcription factor is a repressor of heme oxygenase-1 (HMOX1), a pivotal enzyme involved in antioxidant response and iron recycling. Here we investigated whether pharmacological modulation of the BACH1 by hemin impacts on antioxidant responses and reparative angiogenesis in a mouse model of myocardial infarction (MI). Methods and resultsIn vitro studies on vascular cells showed hemin treatment downregulates BACH1 gene and protein expression and upregulates HMOX1. This axis was confirmed to be modulated in the murine infarcted heart, with BACH1 being upregulated, and HMOX1 downregulated compared to sham. Treatment with hemin every 3 days for 28 days post-MI significantly decreased BACH1 and increased HMOX1 protein expression, though no decrease in oxidative stress markers was detected. Hemin treated mice showed increases in both capillary and arteriole density, and reduced iron accumulation compared with controls. Furthermore, echocardiology measurements showed hemin treatment induced significant improvements in left ventricular wall thickness, and cardiac function as indicated by increased ejection fraction, fractional shortening, and stroke volume measurements. ConclusionHemin has therapeutic potential to improve revascularisation and cardiac function in the heart post-MI.

BackgroundAtrial fibrillation (AF) is surprisingly common in patients with obstructive hypertrophic cardiomyopathy (oHCM) and is associated with significant symptoms and poor survival. Globally accepted models for AF detection are yet to be established. We aimed to investigate the relationship between heart rate variability (HRV) and AF in patients with oHCM. MethodsWe enrolled 1112 consecutively recruited patients with oHCM, including 158 and 954 patients with and without AF, respectively. The HRV variables mainly included the standard deviation of the mean R-R intervals (SDNN), root mean squared successive difference (rMSSD), and percentage of cycles differing from the preceding one by > 50 ms (pNN50). The SDNN, rMSSD, and pNN50 were transformed into binary variables underlying the cutoff for AF detection (termed SDNN_cutoff, rMSSD_cutoff, and pNN50_cutoff, respectively). ResultsThe mean age of this cohort was 48.94 {+/-} 12.37 years, and 451 patients were females. The patients with AF were older, more likely to have palpitations, had a larger left atrial diameter and lower left ventricular outflow gradient, and a significantly higher SDNN, rMSSD, and pNN50 than those without AF. In multivariable logistic regression analysis, pNN50_cutoff was independently associated with AF (odds ratio: 7.86, 95% confidence interval [CI]: 4.25-14.7), while the model including pNN50_cutoff had the largest area under the curve (0.736; 95% CI: 0.690-0.782) and the lowest Akaike information criterion (774). ConclusionHRV was associated with a higher incidence of AF. Among the HRV variables, pNN50_cutoff (cutoff value = 43.5) may be a good predictor of AF in patients with oHCM.

BackgroundGrowing evidence are showing beneficial effects of sodium glucose transport protein 2 inhibitors (SGLT2i) in treatment of heart failure, but underlying neurogenic mechanism remains unclear. In this study the effect of empagliflozin (EM) on sympatho-excitation and potential neurogenic mechanism for EMs therapeutic effects on cardiac remodeling were studied. MethodsDeoxycorticosterone acetate (DOCA)-salt and high-salt (8%) diet (HSD) mouse models were utilized. Single-cell RNA sequencing was used to explore the mechanism by which SGLT2 inhibitors improve cardiac remodeling in hypertension. Meanwhile, blood samples were collected from hospitalized patients diagnosed with heart failure to verify the results of animal studies. ResultsIn DOCA-salt or HSD treated mice, EM was associated with a protective, blood pressure-independent effect on cardiac remodeling. Both DOCA-salt and HSD induced sympatho-excitation, together with neuronal hyper-activity in the pre-autonomic regions of brain, and these were blunted in mice with EM co-treatment. Additionally, single-nucleus RNA sequencing using hypothalami indicated that cellular interplays among the vessels, microglia and inhibitory neurons were involved in the disease- and EM-associated actions. Further analysis of microglia pinpointed a close involvement of peripheral immune activation in disease-associated state transformation of microglia, during DOCA-salt or HSD treatment, including increased lymphocytes count and plasma level of interferon-{gamma}. Differentially expressed genes in neurons highlighted that EM abolished disease-associated upregulation of protein ubiquitination, which might support imbalance of presympathetic excitatory/inhibitory tones, and vasopressin production. In patients blood samples, EM was associated with significant elevation of hematocrit value in all groups, and reduction of lymphocytes counts in the patients with high NT-proBNP value (> 2550 pg/mL, no diuretic co-treatment). ConclusionsOur data provide a neuro-immune pathway by which EM blunts disease-associated cardiac sympathetic tone and hypertrophic remodeling.

BackgroundThe role of immune cells in the pathogenesis of ischaemic heart failure (IHF) is well-established. However, identifying key diagnostic candidate genes in patients with IHF remains a challenge. Therefore, this study aimed to use bioinformatics and machine learning algorithms to identify potential diagnostic genes for IHF. MethodsTwo IHF datasets were obtained from the GEO database, and key genes for IHF were identified using Limma and WGCNA. Functional enrichment analysis was performed to explore the potential mechanisms of IHF. Next, we used three machine learning algorithms, namely LASSO, RF, and SVM-REF, to identify immune-related diagnostic genes for IHF. ssGSEA enrichment analysis was also completed. To assess the diagnostic value of the identified genes, we developed nomogram and validated them on additional GEO datasets. Finally, an immune infiltration analysis was conducted using the CIBERSORT algorithm to explore immune cell dysregulation in IHF. ResultsOur analysis yielded a total of 92 key genes associated with IHF. Enrichment analysis revealed that the mechanisms underlying IHF are mostly associated with immunity and inflammation. Using the machine learning algorithms, we identified four IHF diagnostic genes, namely RNASE2, MFAP4, CHRDL1, and KCNN3. We constructed nomogram and validated the diagnostic value of these genes on additional GEO datasets. The results showed that these four genes had high diagnostic value (AUC value of 0.961). Furthermore, our immune infiltration analysis revealed the presence of three dysregulated immune cells in IHF, namely Macrophages M2, Monocytes, and T cells gamma delta. ConclusionIn summary, our study identified four potential diagnostic candidate genes for IHF by using bioinformatics and machine learning algorithms. We also explored the potential molecular mechanisms of IHF and the immune cell infiltration environment of the failing myocardium. These findings provide new insights into the pathogenesis, diagnosis, and treatment of IHF.

BackgroundVenous congestion (VC) sets in weeks before visible clinical decompensation, progressively increasing cardiac strain and leading to acute heart failure (HF) decompensation. Currently, the field lacks a universally acknowledged gold standard and early detection methods for VC. MethodsUsing data from the GEO database, we identified VCs impact on HF through key genes using Limma and STRING databases. The potential mechanisms of HF exacerbation were explored via GO and KEGG enrichment analyses. Diagnostic genes for acute decompensated HF were discovered using LASSO, RF, and SVM-REF machine learning algorithms, complemented by single-gene GSEA analysis. A nomogram tool was developed for the diagnostic models evaluation and application, with validation conducted on external datasets. ResultsOur findings reveal that VC influences 37 genes impacting HF via 8 genes, primarily affecting oxygen transport, binding, and extracellular matrix stability. Four diagnostic genes for HFs pre-decompensation phase were identified: SMOC2, OGN, FCN3, and SERPINA3. These genes showed high diagnostic potential, with AUCs for each gene exceeding 0.9 and a genomic AUC of 0.942. ConclusionsOur study identifies four critical diagnostic genes for HFs pre-decompensated phase using bioinformatics and machine learning, shedding light on the molecular mechanisms through which VC worsens HF. It offers a novel approach for clinical evaluation of acute decompensated HF patient congestion status, presenting fresh insights into its pathogenesis, diagnosis, and treatment.

BackgroundObesity is considered a significant risk factor for numerous cardiovascular conditions. The prevalence of atrial fibrillation (AF) is elevated among patients with obesity. Weight loss has been shown to reverse cardiac remodelling, leading to lower recurrence of AF despite the better prognosis in obese patients. MethodsWe utilized the National Inpatient Sample 2016-2019 to extract patients [&ge;]18 years of age admitted with AF as the primary diagnosis based on ICD 10 codes. We performed univariate and multivariate regression analysis for known coronary risk factors. We divided patients based on their body mass index (BMI), and our primary outcomes were determining the odds of electrical cardioversion (ECV) and cardiac ablation (CA) due to AF. ResultsThe analysis included 1,625,809 weighted patients. Patients include underweight (6.66%), normal BMI (4.03), overweight (6.51%), obesity class I (20.65%), obesity class II (21.45%), and obesity class III (40.7). After multivariate regression analysis, patients with obesity class I, II, or III had higher odds of ECV, irrespectively of coronary risk factors (OR 1.3, 95% CI 1.25-1.37, OR 1.3, 95% CI 1.32-1.43, OR 1.3, 95% CI1.29-1.38, respectively, with statistically significant P values). However, underweight or normal BMI patients had fewer odds of ECV (OR 0.5 95%CI 0.49-0.61 and OR 0.6 95%CI 0.58-0.74, respectively, with P values <0.001). Meanwhile, there was no statistical significance between a BMI and the odds of CA. ConclusionOur study highlights the significant impact of BMI on managing AF, particularly regarding ECV. Patients in higher BMI categories (obesity class I to III) had increased odds of undergoing ECV, suggesting obesity influences treatment approaches and outcomes in AF management. Interestingly, BMI did not affect the likelihood of CA, indicating a complex relationship between body weight and AF treatment modalities warranting further investigation.

BackgroundThis study aimed to investigate the causal relationship between coronary artery bypass grafting (CABG) and atrial fibrillation (AF) using Mendelian Randomization (MR) and a retrospective cohort from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. MethodsWe performed two-sample MR analysis using GWAS summary statistics (UK Biobank and EBI) to identify genetic instruments for CABG, followed by sensitivity analyses (MR-Egger, weighted median) to validate causality. Concurrently, 1, 835 ICU patients from MIMIC-IV were analyzed via multivariable logistic regression to assess CABG-AF association, stratified by age, hemodynamic, and coagulation profiles. ResultsMR analysis demonstrated a robust causal effect of CABG on AF (IVW OR=1.8, P=2.33x10-), corroborated by cohort data showing doubled AF risk post-CABG (OR=2.1, 95% CI:1.4-3.1, P<0.001). Subgroups with autonomic instability (low heart/respiratory rates) or coagulopathy (INR>2.5) exhibited heightened susceptibility. ConclusionCABG independently elevates AF risk via autonomic, inflammatory, and hemostatic pathways, necessitating tailored perioperative monitoring and prophylactic interventions.

AimsRed blood cell distribution width/albumin ratio (RAR) is a novel parameter associated with inflammation. Previous studies have not focused on the role of RAR in the incidence and long-term prognosis of chronic heart failure (CHF). This study included three cohorts, two prospective and one retrospective study. The aim was to investigate the value of RAR in the incidence of CHF and the long-term prognosis of CHF. MethodsThree cohorts were investigated, including MIMIC, NHANES, and JHDH. The included patients of MIMIC, NHANES, and JHDH were 22,672 from 2001-2012, 60,754 from 1999-2020, and 15,102 from 2021-2022, respectively. According to whether the patients have CHF-related risk factors, the patients were classified into non-CHF, pre-CHF, and CHF groups. The median follow-up time of MIMIC and NHANES was 364 days and 62 months. Logistic regression, Cox regression, restricted cubic spline (RCS), and Kaplan-Meier (KM) curves were used to analyze the value of RAR in CHF patients. ResultIn NHANES, the CHF prevalence in quartiles of RAR (Q1, Q2, Q3, and Q4) were 8.88%, 16.86%, 27.65%, and 46.61%, respectively. MIMIC and JHDH showed a similar trend. Among the non-CHF and CHF patients, the odds ratio (OR) was 1.45 (JHDH 95% CI 1.33-1.58) and 1.93 (NHANES 95% CI 1.41-2.65). In NHANES, the RAR OR value of Q2, Q3 and Q4 were 2.02(CI 1.19-3.43), 3.24(CI 1.95-5.39), and 4.95(CI 2.44-10.02) compared with Q1, respectively. And the OR was 1.05 (MIMIC 95% CI 1.02-1.07) in pre-CHF and CHF patients. The CHF mortality showed an adjusted hazard ratio (HR) is 1.12 (MIMIC 95% CI 1.1-1.14) and 2.26 (NHANES 95% CI 1.52-3.36). KM demonstrates that higher RAR (>3.4 in NHANES and >5.06 in MIMIC) prognoses lead to poor survival in CHF patients. CHF mortality in the 19th quartile of the RAR was 1.4 times higher than in the first quartile, compared with 1.22 times in the red blood cell distribution width (RDW). The 19-quartile mortality curves of the RAR were more stable than RDW and albumin (ALB). ConclusionRAR is an independent risk factor for incidence and all-cause long-term mortality in CHF patients. The predictive value of RAR for all-cause mortality in CHF is superior to ALB and RDW. RAR may be a potential clinical indicator for future treatment of CHF.

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.