Right ventricular pacing (RVP) is associated with the progression of tricuspid regurgitation (TR). Left bundle branch area pacing (LBBAP) has been considered a more physiological procedure. Hence, we aimed to investigate the TR variation and associated clinical outcomes after LBBAP implantation. We retrospectively analyzed 492 patients receiving a new pacemaker implantation between 2018 January and 2024 December, consisting of 241 patients with LBBAP and 251 patients with RVP. Primary outcomes were the deterioration or regression of TR grade, and the progression of tricuspid regurgitation pressure gradient (TRPG). During a mean follow-up period of 2.17 ± 0.87 years, the LBBAP group had a lower incidence of TRPG progression (P = 0.010), and a higher incidence of TR regression (P = 0.016) compared with the RVP group. Kaplan–Meier survival curve analysis revealed that the LBBAP group had a lower cumulative incidence of TRPG progression compared with the RVP group (Log-rank test, P = 0.023). Furthermore, the patients with TRPG progression had a higher cumulative incidence of heart failure hospitalization compared with those without TRPG progression (Log-rank test, P < 0.001). Only in patients with heart failure with reduced ejection fraction, the incidence of TR progression was lower in the LBBAP group than the RVP group (P = 0.019). In this study, we found that LBBAP, compared with RVP, may prevent TRPG progression, have the benefit of TR improvement, and decrease TR progression in patients with heart failure with reduced ejection fraction, probably leading to decrease heart failure hospitalization.

Background Right ventricular (RV) pacing can induce metabolic and structural alterations in left ventricular (LV) myocardium, including lipid accumulation, glycogen depletion, and increased endoplasmic reticulum (ER) stress. This study evaluated protective effects of atorvastatin on RV pacing–induced metabolic dysfunction. Methods Fifteen male Lanyu miniature pigs were randomized into sham control (n = 5), RV pacing (n = 5), and RV pacing with atorvastatin treatment (n = 5) groups. RV pacing was achieved via ventricular lead implantation at the RV outflow tract, followed by complete atrioventricular block, with ventricular pacing maintained for at least 80 beats/min in dual-chamber, dual-sensing, dual-response, rate-responsive mode to provide atrial-synchronous ventricular pacing while allowing atrial sensing or pacing. The RV pacing with atorvastatin treatment group received atorvastatin (40 mg/d) starting 2 weeks before surgery until euthanasia at 6 months. Metabolic, histologic, and molecular parameters were assessed in LV myocardial tissue. Results Compared with sham controls, RV pacing significantly increased myocardial lipid accumulation, with higher triglyceride (2.43 ± 0.17 vs 1.74 ± 0.14 μg/mg, P < 0.01) and diacylglycerol (2902 ± 567.7 vs 977.5 ± 182.5 μg/mg, P < 0.01) levels, and significantly reduced glycogen content (0.09 ± 0.03 vs 0.21 ± 0.03 μg/mg, P < 0.05). ER stress markers binding immunoglobulin protein and cleaved caspase-9 were markedly increased in the RV pacing group (P < 0.0001). Atorvastatin significantly reduced lipid accumulation (triglycerides: 1.83 ± 0.08 μg/mg; P < 0.05), ER stress, and apoptosis, but did not significantly restore glycogen levels. Conclusions RV pacing induces lipid accumulation, glycogen loss, and increased ER stress in the LV myocardium. Atorvastatin partially mitigated these effects by normalizing fatty acid metabolism and reducing ER stress and apoptosis, suggesting a potential role in attenuating early/subclinical RV pacing–induced metabolic remodelling.

The optimal ablation strategy beyond pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF) remains unclear. This study evaluated the outcomes of PVI optimized using complex fractionated atrial electrograms (CFAE) and high-frequency mapping in patients with persistent AF. From March 2022 to December 2023, 55 patients undergoing first-time AF ablation were enrolled. Group 1 included 32 patients with paroxysmal AF, and Group 2 included 23 with persistent or long-standing persistent AF. All patients underwent PVI; in Group 2, additional ablation was guided by CFAE and high-frequency mapping when sinus rhythm was not restored or if inducible atrial tachyarrhythmias were present. Group 2 had higher rates of prior stroke (26.1

Background: Radiofrequency catheter ablation for atrial fibrillation (AF) restores sinus rhythm, but late recurrence is common. Left atrial (LA) size is a known predictor of AF recurrence, but the prognostic value of early post-ablation LA remodeling remains underexplored. Objective: We aimed to evaluate whether pre-ablation and early post-ablation LA volume index (LAVI) predict late atrial tachyarrhythmia recurrence after AF ablation. Methods: This is a retrospective single-center study of adults undergoing their first radiofrequency ablation for AF between January 2013 and December 2021. LA volume was measured by transthoracic echocardiography and indexed to body surface area to derive LAVI within one week before ablation and at 6 and 12 months after the procedure. The 6-month echocardiographic assessment was prespecified as the primary early post-ablation time point because it occurs beyond the 3-month blanking period and captures early structural remodeling during routine follow-up. Early recurrence was defined as atrial tachyarrhythmia occurring within 3 months after ablation, and late recurrence (LR) as any atrial tachyarrhythmic event thereafter. Multivariable Cox proportional hazards models were used to identify independent predictors of LR. Results: Among 408 patients with at least one year of follow-up, 157 (38.5%) experienced LR. Age and sex were similar between recurrence and non-recurrence groups (60.7 ± 9.8 vs. 59.9 ± 0.8 years; 56.1% vs. 64.1% male). Recurrence was associated with a higher prevalence of atrial flutter and persistent AF, higher pre-ablation and post-ablation LAVI, and lower post-ablation left ventricular ejection fraction. In multivariable analysis, atrial flutter, persistent AF, and LAVI, measured both before and after ablation, were independent predictors of LR. In receiver operating characteristic analysis, pre-ablation LAVI demonstrated modest discrimination for LR (AUC = 0.622; 95% CI 0.563–0.681; p < 0.001), with an optimal cut-off of 41.6 mL/m2, while post-ablation LAVI showed similar performance (AUC = 0.597; 95% CI 0.532–0.662; p = 0.003), with a cut-off of 38.6 mL/m2. Overall, discrimination was modest (AUC < 0.65), limiting LAVI as a standalone predictor. Conclusions: Elevated LAVI measured before and early after AF ablation independently predicts LR. Limited post-ablation LA reverse remodeling, reflected by persistently increased LAVI, is associated with unfavorable long-term rhythm outcomes. Serial assessment of LAVI may enhance post-ablation risk stratification.

RATIONALE:Stroke prevention in patients with non-valvular atrial fibrillation who cannot tolerate long-term anticoagulation remains a major clinical challenge. Left atrial appendage occlusion (LAAO) offers an alternative strategy to reduce thromboembolic risk, but device-related thrombus (DRT) formation can undermine its protective benefit. Although most DRT occur early, late thrombus formation related to minimal peri-device leak (PDL) is increasingly recognized. Understanding this rare but serious complication is crucial for optimizing long-term post-LAAO management. PATIENT CONCERNS:A 65-year-old male with prior ischemic stroke presented to the emergency department 10 months after LAAO with acute dizziness but no neurological deficits. DIAGNOSES:Transesophageal echocardiography and cardiac computed tomography angiography revealed a large thrombus (3.8 × 2.4 cm) on the Watchman device with minimal PDL, consistent with massive late DRT. INTERVENTIONS:The patient was started on high-intensity warfarin therapy (international normalized ratio: 2.5-3.5) for anticoagulation. Clopidogrel was temporarily discontinued to reduce bleeding risk. OUTCOMES:After 2 months of warfarin therapy, repeat cardiac imaging confirmed complete thrombus resolution. The patient remained neurologically intact without embolic complications. LESSONS:Even minimal PDL can serve as a nidus for significant late thrombus formation, particularly in patients with interrupted anticoagulation. This case highlights the importance of continued long-term imaging surveillance after LAAO and individualized anticoagulation strategies. Clinicians should maintain vigilance for late DRT, especially in high-risk patients, and consider extended follow-up protocols to optimize outcomes.

Background: Left atrial (LA) myopathy from interventricular dyssynchrony often precedes atrial fibrillation (AF) in atrioventricular block (AVB) patients with frequent right ventricular (RV) pacing, but the role of statin therapy in preventing LA myopathy and associated arrhythmias remains debated. Objectives: This study investigated the mechanisms of LA myopathy and the clinical outcomes of statin therapy in AVB patients with permanent pacemakers (PPMs). Methods: The study comprised an animal, cell, and clinical cohort study. In the animal study, 12 Lanyu miniature pigs were divided into sham control, RV pacing, and RV pacing plus atorvastatin groups to assess cardiac effects over six months. The cellular study used HL-1 atrial myocytes to evaluate fibrosis and protein expression after cyclic stretching. The clinical study included 2338 AVB patients with PPM, comparing statin and non-statin groups for AF incidence and outcomes using inverse probability of treatment weighting (IPTW). Results: In the animal model, atorvastatin did not affect LA size, function, or fibrosis. The cellular study showed increased fibrosis markers in both stretch and stretch plus atorvastatin groups compared to controls. In the PPM cohort, statin use did not significantly impact LA size, AF incidence (p=0.731), or CV mortality (p=0.129) over five years, but it was associated with significantly lower all-cause mortality (p=0.004) after IPTW adjustment. Conclusion: Statins do not appear to improve LA myopathy or reduce the incidence of associated atrial arrhythmias in the AVB population with PPMs.

Background: Long-term right ventricular pacing (RVP) can cause electrical and mechanical dyssynchrony, resulting in adverse outcomes. Recently, left bundle branch area pacing (LBBAP) has emerged as a physiological pacing modality and is considered a promising alternative. To date, the long-term outcomes of LBBAP compared with RVP, particularly with respect to sex differences, remain unclear. Methods: Between January 2017 and July 2024, 1211 patients who underwent de novo pacemaker implantation were enrolled and categorized into RVP (n = 789) and LBBAP (n = 422). The primary outcome was a composite of all-cause mortality, heart failure hospitalization (HFH), and pacing-induced cardiomyopathy (PICM). Propensity score matching (PSM) was employed to minimize the selection bias and achieve comparability among the study population. A post hoc power analysis based on the observed effect size and sample size showed a power of 80%, confirming sufficient sensitivity to detect group differences. Results: After PSM, 764 patients were analyzed. The mean age of the patients was 74.6 ± 10.5 years in RVP and 74.5 ± 9.8 years in LBBAP, respectively, and 52.3% patients were male. Patients with LBBAP had a lower incidence of the primary outcome (8.6% vs. 24.6%, p < 0.001), HFH (2.6% vs. 13.6%, p < 0.001), and all-cause mortality (6.5% vs. 13.9%, p < 0.001) compared with RVP. There were no significant differences in the clinical outcomes, including the primary outcome, HFH and all-cause mortality, between the sexes in the group with either RVP or LBBAP. However, during a 2-year follow-up period for survival analysis, male patients with LBBAP had a significant lower incidence of all the endpoints, whereas female patients with LBBAP had a lower incidence of HFH [HR 0.14 (95% CI 0.06–0.32), p = 0.001] compared with those with RVP. Conclusions: Regardless of sex, patients with LBBAP had a lower risk of poor clinical outcomes, including HFH and all-cause mortality, compared to those with RVP. Moreover, compared with RVP, LBBAP decreased the risks of all the major endpoints in male patients and the risk of HFH particularly in female patients. Further research is needed to establish the sex-specific responses to LBBAP.

Background/Objectives: The objectives of this study were to determine whether the early initiation of cardiac rehabilitation (CR) within 6 weeks of discharge improves long-term outcomes in patients hospitalized for acute heart failure (HF) and to evaluate whether baseline lysyl oxidase-like 2 (LOXL2) levels affect the response to CR. Methods: We prospectively enrolled patients with acute HF who completed a structured Heart Failure Disease Management Program between January 2019 and July 2022. Participants were categorized into an early-CR group (initiating supervised CR within 6 weeks post-discharge and continuing a home-based program) or a non-CR group. The primary outcome was all-cause mortality. The secondary outcomes included HF rehospitalization and changes in scores on the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) at 6 and 12 months. A post hoc analysis was conducted to stratify patients by baseline LOXL2 levels in order to assess differential CR effects in relation to the severity of cardiac fibrosis. Results: Out of 162 patients, 34 participated in early CR. After 1:1 propensity score matching, each group contained 33 patients. Over a median follow-up of 2.85 years, the early-CR group experienced lower all-cause mortality (0 vs. 87.2 events per 1000 patient-years; rate difference: -0.087). A subgroup analysis revealed the greatest benefit among patients with LOXL2 levels > 200 pg/mL (0 vs. 172.3 events per 1000 patient-years; rate difference: -0.172). Conclusions: Early post-discharge CR was associated with improved survival in patients with acute HF. The survival benefit was more pronounced in patients with an elevated level of LOXL2, suggesting its potential role as a biomarker for fibrosis-guided CR strategies. Health systems seeking scalability may consider embedding exercise-based and biomarker-guided CR programs within clinical networks early on to improve access while advancing patient-centered care. Further randomized trials are warranted to confirm these findings.

Aim To evaluate whether initiation of cardiac rehabilitation (CR) within 6 weeks improves long-term outcomes of patients with acute heart failure (HF). Methods Patients with acute HF who participated in an HF disease management program from January 2019 to July 2022 were prospectively enrolled. Eligible patients were divided into two groups: early CR (and continued home-based CR during the follow-up period) and non-CR. The primary outcome was all-cause mortality. Secondary outcomes were rehospitalisation for recurrent HF and changes in 12-item Kansas City Cardiomyopathy Questionnaire scores from baseline to 6 months and 1 year. A post-hoc analysis stratified by lysyl oxidase-like 2 (LOXL2) levels assessed CR benefits for patients with cardiac fibrosis. Results Of 162 patients, 34 received early CR. The non-CR group was older (median age: 58.5 vs. 53.0 years, p=0.022) and had higher N-terminal pro-B-type natriuretic peptide levels (4552.5 vs. 1275.0 pg/mL, p=0.002). Propensity score matching yielded 33 patients per group. Over 2.85 years, the early CR group had lower all-cause mortality (0 vs. 87.16 events per 1000 patient-years, rate difference: -0.087 [95% confidence interval {CI}: -0.143 to -0.031], p=0.002). Patients with LOXL2 >200 pg/mL benefited the most (0 vs. 172.3 events per 1000 patient-years, rate difference: -0.172 [95% CI: -0.299 to -0.046], p=0.008). Conclusion Early post-discharge exercise-based CR was associated with reduced all-cause mortality in patients with acute HF. Patients with more severe cardiac fibrosis, indicated by higher LOXL2 levels, derived greater benefits from the CR program. Large-scale trials are needed to validate these findings. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial The study protocol was registered at ClinicalTrials.gov (identifier: [NCT03782337][1]). ### Funding Statement This work was supported by a program grant from the Chang Gung Medical Foundation [grant number: CMRPG8P0061]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was conducted in accordance with the principles embodied in the Declaration of Helsinki and was approved by the Institutional Review Board (IRB) of Chang Gung Medical Foundation (IRB approval number: 201801077B0C506). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data underlying this article will be shared on reasonable request to the corresponding author. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03782337&atom=%2Fmedrxiv%2Fearly%2F2025%2F05%2F01%2F2025.04.28.25326610.atom

ObjectiveEarly rhythm control has demonstrated clinical benefits even among patients with persistent atrial fibrillation. However, some patients continue to experience recurrent atrial tachyarrhythmias despite undergoing catheter ablation and treatment with antiarrhythmic drugs. This study aimed to assess the efficacy of digoxin in restoring sinus rhythm among patients with recurrent atrial tachyarrhythmias after catheter ablation and ongoing medical therapy.MethodsBetween 1 January 2013 and 1 September 2023, a total of 194 patients underwent catheter ablation for persistent atrial fibrillation. Among these, 96 (49.5%) patients experienced recurrence of atrial tachyarrhythmia during follow-up after catheter ablation. Of these, 12 patients with sustained arrhythmias despite at least 1 month of treatment with antiarrhythmic drugs and rate-control medications were treated with digoxin. Patients who achieved sinus rhythm after digoxin administration were categorized as the digoxin-effective group, and those who did not were classified as the non-digoxin-effective group. Clinical characteristics, medications, and echocardiographic parameters were compared between the two groups.ResultsAmong the 12 patients analyzed (mean age: 66 ± 7 years; 3 males and 9 females), 7 (58.3%) achieved sinus rhythm after digoxin administration. Patients in the digoxin-effective group exhibited significantly smaller left atrial sizes than those in the non-digoxin-effective group (39.2 ± 3.3 mm vs. 46.8 ± 2.6 mm, p = 0.017). Most recurrences in the digoxin-effective group were atrial tachycardia episodes (5/7, 71.4%). The median duration from digoxin initiation to sinus rhythm restoration was 49 days (range: 21-210 days). No serious adverse effects occurred.ConclusionsDigoxin effectively restored sinus rhythm in selected patients experiencing recurrent atrial tachyarrhythmias after catheter ablation and ongoing medical therapy, particularly among those with smaller left atrial sizes. Further research is warranted to validate these findings and explore the underlying mechanisms.

Background The light-dark (LD) cycle regulates circadian rhythms that influence cardiac function and autonomic regulation. However, the impact of LD cycle disturbances on cardiac electrophysiology and gene expression remains unclear. This study investigated how disrupted light exposure affects cardiac rhythm, function, and gene expression in mice. Methods Eight-week-old C57BL/6 J mice were exposed to either a normal LD cycle (12 h light/12 h dark, NLD) or a disrupted LD cycle (24 h light for 3 days/24 h dark for 4 days, DLD) for 12 and 24 weeks. Monthly electrocardiographic (ECG) and echocardiographic assessments were performed. Gene expression related to circadian regulation, mitochondrial function, and cardiac remodeling was analyzed. Results DLD mice exhibited transient weight gain and persistent cardiac hypertrophy. ECG analysis showed shortened RR intervals, prolonged QTc intervals (weeks 4 and 8), and widened QRS duration (week 16). Heart rate variability analysis indicated sustained sympathovagal imbalance (increased LF/HF ratio). Echocardiography revealed early cardiac remodeling with increased left ventricular outflow tract velocity, pressure gradient, and internal diameter. Gene analysis showed early Per2 and Nr1d1 dysregulation, followed by Bmal1, Clock, Rora, and Rorc downregulation and Nr1d1 upregulation at 24 weeks. Mitochondrial dysfunction, fibrosis, and inflammation markers were also dysregulated. Conclusion Chronic LD disruption leads to circadian misalignment, autonomic imbalance, and cardiac remodeling, potentially contributing to adverse cardiovascular outcomes. Translational relevance This model simulates circadian disruption in shift workers and individuals with irregular sleep patterns, highlighting prolonged circadian misalignment may elevate cardiovascular risk and the importance of circadian health in cardiovascular prevention strategies.

Atrial fibrillation (AF) is a leading cause of stroke, heart failure, and cardiovascular morbidity, yet its pathophysiology remains incompletely understood. Among various molecular regulators, microRNAs (miRNAs) have emerged as promising biomarkers for AF detection and burden monitoring. However, the optimal sample type for miRNA analysis remains unclear, posing a challenge for biomarker standardization. This study aimed to assess whether miRNA expression profiles remain consistent across plasma and blood cells, with a focus on identifying miRNAs with a strong predictive potential for AF burden. This exploratory study recruited patients diagnosed with sick sinus syndrome who had undergone permanent pacemaker implantation. Participants were stratified into three groups based on AF status: no AF (n = 2), paroxysmal AF (PaAF; n = 2), and persistent AF (PerAF; n = 2) for white blood cell (WBC) samples, and pooled plasma samples from no AF (n = 3 pools) and PerAF (n = 3 pools). Using an miRNA microarray analysis, miR-1-3p was consistently downregulated in both WBC and plasma samples of patients with AF, showing significant decreases (fold-change in WBC: PaAF 0.22, PerAF 0.20; plasma PerAF 0.28) and highlighting its potential as a circulating biomarker for AF burden. Additional differentially expressed miRNAs, including miR-451a and miR-382-5p, exhibited sample-dependent variations, underscoring the importance of validating miRNA expression across multiple biological compartments. The study highlights the need for mechanistic investigations to determine whether miR-1-3p directly contributes to AF pathogenesis or serves as a downstream consequence of atrial remodeling. These findings reinforce the potential of miR-1-3p as a reliable circulating biomarker for AF, offering new avenues for non-invasive monitoring and risk stratification. Future research should explore the role of miR-1-3p in AF-related molecular pathways and its applicability as a therapeutic target.

Background/Objectives: Left atrial appendage (LAA) morphology has been implicated in atrial fibrillation (AF) recurrence following catheter ablation. However, the predictive value of specific anatomical shapes remains unclear. We aimed to evaluate the association between distinct LAA morphologies and AF recurrence post-ablation. Methods: In this retrospective, single-center study, 463 patients with AF undergoing first-time catheter ablation were included. Pre-ablation contrast-enhanced cardiac computed tomography was performed to classify LAA morphology into chicken-wing, windsock, cauliflower, and cactus types. Patients were followed for one year, with AF recurrence defined as documented atrial tachyarrhythmia episodes lasting more than 30 s occurring between 3 and 12 months post-procedure. Clinical, anatomical, and procedural factors were analyzed using multivariable logistic regression to identify independent predictors of recurrence. Results: Among the four morphologies, the windsock-type LAA had the highest recurrence rate at 48.3%, significantly greater than chicken-wing (25.2%), cauliflower (20.8%), and cactus (18.2%) types (p = 0.017). Multivariable analysis confirmed windsock morphology as an independent predictor for AF recurrence (adjusted OR = 2.720, 95% CI: 1.209–6.118; p = 0.016). Additionally, persistent AF (adjusted OR = 1.748, 95% CI: 1.075–2.842; p = 0.024) and antiarrhythmic drug use in the blanking period (adjusted OR = 2.862, 95% CI: 1.689–4.849; p < 0.001) independently increased the risk of recurrence. Conclusions: Windsock-type LAA morphology significantly predicts increased AF recurrence following catheter ablation, underscoring the importance of morphological assessment in ablation planning. Individualized strategies targeting high-risk LAA morphologies may enhance procedural success and reduce AF recurrence. Future prospective studies are warranted to validate these findings.

AimsThis study aimed to evaluate the prevalence of cognitive impairment among patients with acute heart failure (AHF), its prognosis, and the effects of cardiac rehabilitation (CR) on these patients' outcomes.MethodsOverall, 247 consecutive AHF patients (median age, 60 years; males, 78.5%) were evaluated from March 2015 to May 2021. Patients received an AHF disease management program coordinated by an HF specialist nurse and underwent a Luria-Nebraska Neuropsychological battery-screening test (LNNB-S) assessment during admission. Cognitive impairment was defined as an LNNB-S score ≥10. Patients who underwent at least one session of phase II CR and continued with the home-based exercise program were considered to have received CR. The primary endpoint was composite all-cause mortality or readmission after a 3.30-year follow-up (interquartile range, 1.69–5.09 years).ResultsCognitive impairment occurred in 53.0% and was associated with significantly higher composite endpoint, all-cause mortality, and readmission rates (p=<0.001, 0.001, and 0.015, respectively). In the total cohort, 40.9% of patients experienced the composite endpoint. Multivariate analysis showed that the peak VO2 was a significant predictor of the composite endpoint. After adjustment, CR significantly decreased the event rate of the composite endpoint and the all-cause mortality in patients with cognitive impairment (log-rank p= 0.024 and 0.009, respectively). However, CR did not have a significant benefit on the composite endpoint and the all-cause mortality in patients without cognitive impairment (log-rank p=0.682 and 0.701, respectively).ConclusionCognitive impairment is common in AHF patients and can lead to poor outcomes. CR is a standard treatment to improve prognosis.

Although there is a link between obstructive sleep apnea (OSA) and atrial fibrillation (AF) and numerous investigations have examined the mechanism of AF development in OSA patients, which includes cardiac remodeling, inflammation, and gap junction-related conduction disorder, there is limited information regarding the differences between the sexes. This study analyzes the impact of sex differences on the expression of cardiac remodeling, inflammatory cytokines, and gap junctions in patients with OSA and AF. A total of 154 individuals diagnosed with sleep-related breathing disorders (SRBDs) were enrolled in the study and underwent polysomnography and echocardiography. Significant OSA was defined as an apnea–hypopnea index (AHI) of ≥15 per hour. Exosomes were purified from the plasma of all SRBD patients and incubated in HL-1 cells to investigate their effects on inflammatory cytokines and GJA1 expression. The differences in cardiac remodeling and expression of these biomarkers in both sexes were analyzed. Of the 154 enrolled patients, 110 patients were male and 44 patients were female. The LA sizes and E/e’ ratios of male OSA patients with concomitant AF were greater than those of control participants and those without AF (all p < 0.05). Meanwhile, female OSA patients with AF had a lower left ventricular ejection fraction than those OSA patients without AF and control subjects (p < 0.05). Regarding the expression of inflammatory cytokines and GJA1, the mRNA expression levels of GJA1 were lower and those of IL-1β were higher in those male OSA patients with AF than in those male OSA patients without AF and control subjects (p < 0.05). By contrast, mRNA expression levels of HIF-1α were higher in those female OSA patients with and without AF than in control subjects (p < 0.05). In conclusion, our study revealed sex-specific differences in the risk factors and biomarkers associated with AF development in patients with OSA.

Cardiovascular diseases (CVDs) stand as a predominant global health concern, introducing vast socioeconomic challenges. In addressing this pressing dilemma, enhanced diagnostic modalities have become paramount, positioning electrochemical biosensing as an instrumental innovation. This comprehensive review navigates the multifaceted terrain of CVDs, elucidating their defining characteristics, clinical manifestations, therapeutic avenues, and intrinsic risk factors. Notable emphasis is placed on pivotal diagnostic tools, spotlighting cardiac biomarkers distinguished by their unmatched clinical precision in terms of relevance, sensitivity, and specificity. Highlighting the broader repercussions of CVDs, there emerges an accentuated need for refined diagnostic strategies. Such an exploration segues into a profound analysis of electrochemical biosensing, encapsulating its foundational principles, diverse classifications, and integral components, notably recognition molecules and transducers. Contemporary advancements in biosensing technologies are brought to the fore, emphasizing pioneering electrode architectures, cutting-edge signal amplification processes, and the synergistic integration of biosensors with microfluidic platforms. At the core of this discourse is the demonstrated proficiency of biosensors in detecting cardiovascular anomalies, underpinned by empirical case studies, systematic evaluations, and clinical insights. As the narrative unfolds, it addresses an array of inherent challenges, spanning intricate technicalities, real-world applicability constraints, and regulatory considerations, finally, by casting an anticipatory gaze upon the future of electrochemical biosensing, heralding a new era of diagnostic tools primed to revolutionize cardiovascular healthcare.

AbstractBackgroundFew clinical studies of atrial fibrillation (AF) have focused on Asian patients; data are lacking on current mapping and ablation strategies in the Asia Pacific region (APAC).ObjectiveThe HD Mapping Observational Study (NCT04022954) was designed to characterize electroanatomic mapping (EAM) with market‐released high‐density mapping (HDM) catheters in subjects with AF in APAC.MethodsSubjects undergoing HDM and indicated for radiofrequency ablation (RFA) to treat AF were prospectively enrolled in APAC. Data included mapping strategy and ablation targets. EAM was performed using one of two commercially available HDM catheters (Advisor™ HD Grid, Sensor Enabled™, Abbott [GRID] or Inquiry™ AFocus II™ Double Loop, Abbott [DL]). Procedure‐related adverse events were collected.ResultsTwo hundred subjects were enrolled at 15 centers: 164 with symptomatic paroxysmal (PAF) and 36 with symptomatic persistent (PersAF) AF for de novo ablation. GRID and DL were used in 186 and 14 cases, respectively. All subjects underwent voltage mapping, with conservative thresholds (low voltage ≤0.5 mV and very low voltage/electrical scar ≤0.1 mV) used in 60.2% and 35.4% of maps, respectively. Focal impulses, rotors, complex fractionated electrograms, and other substrate targets were each searched for in <3% of subjects. Median time to generate a map was 9.0 (Q1: 5.0, Q3: 13.0) minutes. Ablation strategy included pulmonary vein (PV) isolation in all, and non‐PV triggers in 75/200 (37.5%) subjects. Five serious adverse events were reported.ConclusionsThe study demonstrated an efficient strategy with the feasibility and safety of using HDM during AF ablation procedures in APAC.

A previous study showed that high-glucose (HG) conditions induce mitochondria fragmentation through the calcium-mediated activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) in H9C2 cells. This study tested whether empagliflozin could prevent HG-induced mitochondria fragmentation through this pathway. We found that exposing H9C2 cells to an HG concentration decreased cell viability and increased cell apoptosis and caspase-3. Empagliflozin could reverse the apoptosis effect of HG stimulation on H9C2 cells. In addition, the HG condition caused mitochondria fragmentation, which was reduced by empagliflozin. The expression of mitochondria fission protein was upregulated, and fusion proteins were downregulated under HG stimulation. The expression of fission proteins was decreased under empagliflozin treatment. Increased calcium accumulation was observed under the HG condition, which was decreased by empagliflozin. The increased expression of ERK 1/2 under HG stimulation was also reversed by empagliflozin. Our study shows that empagliflozin could reverse the HG condition, causing a calcium-dependent activation of the ERK 1/2 pathway, which caused mitochondria fragmentation in H9C2 cells.

Background Metabolic disorder is noted for pacing‐induced cardiomyopathy. The benefits of His bundle pacing over right ventricular (RV) pacing in preventing pacing‐induced cardiomyopathy from a metabolic perspective are yet to be fully understood. Method and Results Three pig groups were established for this study: sham control, RV pacing (RV pacing for 6 months), and His pacing (RV pacing for 6 months, followed by His bundle pacing for 3 months). Complete atrioventricular block was created in the last 2 groups. Left ventricular function and dyssynchrony were assessed via echocardiography, while proteins linked to metabolism, endoplasmic reticulum stress, and inflammation in left ventricular myocardium were examined. The RV pacing group had significantly more left ventricular mechanical dyssynchrony compared with the other groups. The RV pacing group exhibited triglyceride and diacylglycerol accumulation in cardiomyocytes and higher expression of binding immunoglobulin protein and tumor necrosis factor‐α than the other groups. Additionally, the expression of CD36 was activated, while the expression of hormone‐sensitive lipase was downregulated in the RV pacing group compared with the His pacing and sham control groups. Furthermore, the expressions of GLUT4 and pyruvate dehydrogenase were higher in the RV pacing group than the sham control and His pacing groups. Notably, the abnormal fatty acid and glucose metabolic pathways in the left ventricular myocardium during RV pacing could be corrected by His bundle pacing. Conclusions His bundle pacing can mitigate the abnormal metabolism disorders, endoplasmic reticulum stress, and inflammation induced during RV pacing and may contribute to the superiority of conduction system pacing over RV pacing in reducing heart failure hospitalization.