BACKGROUND:Clinical and experimental studies have suggested that sodium-glucose cotransporter type-2 inhibitors (SGLT2i) may exert a preventive effect against doxorubicin (Dox)-induced heart failure; however, the underlying mechanisms remain incompletely understood. This study aimed to investigate whether empagliflozin (Emp) protects against Dox-induced cardiotoxicity by preserving transverse tubule (t-tubule) structure and improving Ca2+ handling. METHODS:Adult male C57BL/6 mice were randomly assigned to four groups: Control, Emp-only, Dox-only, and Dox+ Emp. Emp was administered to the Emp-only and Dox+ Emp groups at 10 mg/kg/day, and Dox was administered to the Dox-only and Dox+ Emp groups at a cumulative dose of 15 mg/kg. Cardiac function was assessed by echocardiography. T-tubule ultrastructure and Ca2+ handling were evaluated using confocal microscopy and IonOptix imaging. Protein expression was analyzed by western blotting. RESULTS:Dox-treated mice exhibited increased left ventricular dilatation and impaired cardiac function, both of which were attenuated in the Dox + Emp group. Dox induced blunted and dyssynchronous sarcoplasmic reticulum Ca2+ release, characterized by reduced amplitude and delayed Ca2+ transients, as well as increased Ca2+ spark frequency. These abnormalities were significantly ameliorated by Emp treatment. In addition, Emp effectively prevented Dox-induced t-tubule loss and disorganization. Emp also ameliorated Dox-induced alterations in JPH2, BIN1, Ca2+/calmodulin-dependent protein kinase II (CaMKII), and CaMKII-dependent phosphorylation of RyR2, leading to improved synchronous Ca2+ release, enhanced Ca2+ transient amplitude, and reduced Ca2+ sparks frequency. CONCLUSIONS:Dox-induced cardiotoxicity is associated with severe t-tubule remodeling and impaired Ca2+-handling. Emp prevents Dox-induced structural and functional remodeling of t-tubule and improves Ca2+-handling, thereby exerting cardioprotective effects in mice. These findings provide structural-level mechanistic insight into Emp-mediated cardioprotection and support the potential of Emp as a preventive strategy against Dox-induced cardiotoxicity.

BACKGROUND:Catheter ablation restores sinus rhythm in atrial fibrillation (AF), but long-term cardiovascular risk remains incompletely defined. The prognostic value of high-sensitivity C-reactive protein (hs-CRP) after ablation is uncertain. OBJECTIVE:This study aimed to investigate the association between preprocedural hs-CRP levels and long-term cardiovascular outcomes after AF ablation. METHODS:We analyzed 4612 patients with nonvalvular AF undergoing first-time radiofrequency ablation in the prospective Chinese Atrial Fibrillation Registry (2011-2023), with a median follow-up of 5.0 years. Baseline hs-CRP was measured using a high-sensitivity immunoturbidimetric assay and analyzed as log-transformed continuous values and tertiles. The primary endpoint was a composite of cardiovascular death and ischemic stroke. Secondary endpoints included life-threatening bleeding, AF recurrence, and cardiovascular readmission. Cox models adjusted for demographic factors, comorbidities, AF type, and medications. RESULTS:Higher baseline hs-CRP was independently associated with an increased risk of the primary endpoint (adjusted hazard ratio, 1.21; 95% confidence interval, 1.10-1.33; P < .001) with a significant dose-response relationship across tertiles. The association was stronger in patients aged <65 years (interaction P = .006) and remained significant in patients without AF recurrence (hazard ratio, 1.26; P = .006). Elevated hs-CRP was also associated with a higher risk of cardiovascular readmission. Associations with life-threatening bleeding and AF recurrence were weaker. CONCLUSION:Preprocedural hs-CRP independently predicts long-term cardiovascular death and ischemic stroke after AF ablation, even in patients without recurrence. These findings support inflammation-based risk stratification beyond rhythm outcomes.

BACKGROUND:Ethanol infusion of the vein of Marshall (EIVOM) improves outcomes in atrial fibrillation (AF) ablation. However, its association with delayed pericardial effusion (PE)-specifically its incidence, clinical features, and mechanism-remains poorly defined. OBJECTIVES:This study sought to investigate the risk of delayed PE associated with EIVOM and characterize its clinical profile, management, and outcomes. METHODS:This study analyzed 15,101 patients with persistent AF from the China-AF Registry, stratified into an EIVOM group (n = 8,151) and a non-EIVOM group (n = 6,950). The primary endpoint was delayed PE, defined as newly detected PE >10 mm occurring ≥7 days after ablation and resulting in rehospitalization. Propensity score overlap weighting was applied to balance baseline covariates between groups. RESULTS:Delayed PE occurred in 0.17% of the total cohort, with a higher incidence in the EIVOM group compared with the non-EIVOM group (0.25% vs 0.07%). EIVOM was an independent risk factor for delayed PE (overlap-weighted HR: 3.18; 95% CI: 1.15-8.74; P = 0.025). Delayed PE in the EIVOM group tended to manifest late (median 38 days vs 14 days), with large effusion size and severe systemic inflammation. Management in the EIVOM group frequently required invasive intervention (17 of 20 [85%]). Notably, 20% (4 of 20) of patients with EIVOM-related delayed PE experienced recurrence post-discharge, requiring prolonged management. CONCLUSIONS:EIVOM is associated with an increased risk of delayed PE, characterized by late onset, systemic inflammation, frequent need for invasive management, and high recurrence risk. These findings support the need for extended echocardiographic monitoring beyond the standard postprocedural period.

AIMS:Pericardiocentesis is usually completed under fluoroscopy. The electroanatomic mapping (EAM) system allows visualizing puncture needle tip (NT) while displaying the electrogram recorded from NT, making it possible to obtain epicardial access (EA) independent of fluoroscopy. This study was designed to establish and validate a technique by which EA is obtained under guidance of three-dimensional (3D) EAM combined with NT electrogram. METHODS AND RESULTS:3D shell of the heart was generated, and the NT was made trackable in the EAM system. Unipolar NT electrogram was continuously monitored. Penetration into pericardial sac was determined by an increase in NT potential amplitude and an injury current. A long guidewire of which the tip was also visible in the EAM system was advanced to confirm EA. Epicardial access was successfully obtained without complication in 13 pigs and 22 patients. In the animals, NT potential amplitude was 3.2 ± 1.0 mV when it was located in mediastinum, 5.2 ± 1.6 mV when in contact with fibrous pericardium, and 9.8 ± 2.8 mV after penetrating into pericardial sac (all P ≤ 0.001). In human subjects, it measured 1.54 ± 0.40 mV, 3.61 ± 1.08 mV, and 7.15 ± 2.88 mV, respectively (all P < 0.001). Fluoroscopy time decreased in every 4-5 cases (64 ± 15, 23 ± 17, and 0 s for animals 1-4, 5-8, 9-13, respectively, P = 0.01; 44 ± 23, 31 ± 18, 4±7 s for patients 1-7, 8-14, 15-22, respectively, P < 0.001). In five pigs and seven patients, EA was obtained without X-ray exposure. CONCLUSION:By tracking NT in the 3D EAM system and continuously monitoring the NT electrogram, it is feasible and safe to obtain EA with minimum or no fluoroscopic guidance.

Background: Ibrutinib, a potent Bruton’s tyrosine kinase inhibitor with marked efficacy against hematological malignancies, is associated with the heightened risk of atrial fibrillation (AF). Although ibrutinib-induced AF is linked to enhanced oxidative stress, the underlying mechanisms remain unclear. Objective: This research aimed to explore the molecular mechanism and regulatory target in ibrutinib-induced AF. Methods: We performed in vivo electrophysiology studies using ibrutinib-treated mice, and then employed proteomic and single-cell transcriptomic analyses to identify the underlying targets and mechanisms. The effects of A-kinase anchoring protein 1 (AKAP1) depletion on mitochondrial quality surveillance (MQS) were evaluated using both in vivo and ex vivo AKAP1 overexpression models. Results: Atrial AKAP1 expression was significantly reduced in ibrutinib-treated mice, leading to inducible AF, atrial fibrosis, and mitochondrial fragmentation. These pathological changes were effectively mitigated in an overexpression model of ibrutinib-treated mice injected with an adeno-associated virus carrying Akap1. In ibrutinib-treated atrial myocytes, AKAP1 down-regulation promoted dynamin-related protein 1 (DRP1) translocation into mitochondria by facilitating DRP1 dephosphorylation at Ser637, thereby mediating excessive mitochondrial fission. Impaired MQS was also suggested by defective mitochondrial respiration, mitochondrial metabolic reprogramming, and suppressed mitochondrial biogenesis, accompanied by excessive oxidative stress and inflammatory activation. The ibrutinib-mediated MQS disturbance can be markedly improved with the inducible expression of the AKAP1 lentiviral system. Conclusions: Our findings emphasize the key role of AKAP1-mediated MQS disruption in ibrutinib-induced AF, which explains the previously observed reactive oxygen species overproduction. Hence, AKAP1 activation can be employed to prevent and treat ibrutinib-induced AF.

Background Cancer has become significant comorbidity in patients with atrial fibrillation (AF). However, little is known about the efficacy and safety of AF ablation, the first-line rhythm control strategy, in patients with cancer. This study aims to evaluate the incidence and risk of AF recurrence and safety endpoints in patients with cancer compared to the non-cancer group after ablation.Methods From August 2011 to December 2020, we consecutively enrolled cancer patients in the China-AF cohort. We used propensity score matching (1:3) to select the control group and assessed the risk of AF recurrence and adverse events after ablation in cancer patients using a multivariable Fine and Gray competing risk model.Results A total of 203 patients with cancer were enrolled and 21 of them were active cancer, with a median follow-up of 12.3 months. The cumulative incidence of AF recurrence was comparable between patients with and without cancer (43.8% vs. 51.1%; p = .88). No difference in the risk of AF recurrence, thromboembolism, major bleeding, and mortality was observed after adjusting confounders. Active cancer was not associated with an increased risk of AF recurrence compared to the stable disease (SHR = 1.32; 95% CI 0.72-2.43; p = .46). Cancer was associated with a low risk of cardiovascular hospitalization (SHR, 0.54; 95% CI, 0.36-0.81; p = .01). Subgroup analysis found that hematological malignancy was associated with a high risk of AF recurrence (SHR, 5.68; 95% CI, 3.00-10.8; p < .001).Conclusions This study suggests that catheter ablation could be feasible for rhythm control of AF patients with concomitant cancer.

Background & aims The individual effect of working schedule on survival in the hypertensive population has not been adequately studied. Shiftworkers are also prone to unhealthy lifestyles like pro-inflammatory diet. Therefore, we assessed the effect of shift work and its joint association with dietary inflammatory potential on mortality risk among the large US nationally representative sample of adult hypertensive population. Methods Data were from a nationally representative prospective cohort among US hypertensive population (n = 3680; weighted population, 54,192,988). The participants were linked to the 2019 public-access linked mortality archives. The working schedule were self-reported using the Occupation Questionnaire Section. Dietary inflammatory index (DII) scores were equally calculated using the 24-hour dietary recall (24 h) interviews. Multivariable Cox proportional hazards regression models were used to estimate hazard ratio and 95% confidence intervals (95%CI) for survival of hypertension individuals by work schedule and dietary inflammatory potential. The joint effect of work schedule and dietary inflammatory potential was then examined. Results Among the 3680 hypertension individuals (39.89% female [n = 1479] and 71.42% white [n = 1707]; weighted mean [SE] age, 47.35 [0.32] years), 592 individuals reported shift work status. 474 (10.76%) reported shift work status with pro-inflammatory dietary pattern (DII scores > 0). 118 (3.06%) reported shift work status with anti-inflammatory dietary pattern (DII scores < 0). 646 (19.64%) reported a non-shift working schedule with anti-inflammatory dietary pattern, while 2442 (66.54%) reported non-shift working schedule with pro-inflammatory dietary pattern. After a median follow-up of 11.67 years (140 months), 317 deaths (cardiovascular diseases (CVD), 65; cancer, 104) were registered. Cox regression analysis showed that shift work was associated with higher risk of all-cause mortality (hazard ratio [HR], 1.48; 95% CI, 1.07–2.06) compared with non-shift workers. In the joint analysis, shift work status combined with pro-inflammatory dietary pattern was associated with the highest all-cause mortality risk. Moreover, adopting the anti-inflammatory diet significantly attenuates the deleterious effect of shift work on mortality risk. Conclusions In this large representative sample of adults with hypertension in the U.S., the combination of shift work status with pro-inflammatory dietary pattern was highly prevalent and was associated with the highest risks of death from all causes.

Tyrosine kinase inhibitors (TKIs) are a novel category of antitumor agents with remarkable efficacy in extending patient survival. However, clinical use of TKIs has been hindered by the major adverse effect of atrial fibrillation (AF). Recent studies have revealed that TKIs induce metabolic alterations and remodeling in cardiomyocytes, thus perturbing energy metabolism. Specifically, mitochondrial dysfunction and shifts in cardiac substrate utilization have been implicated in the mechanisms underlying TKI-induced AF. In light of these findings, this article reviews the energy metabolism-associated pathways involved in TKI-induced AF, identifies precise therapeutic targets for managing this condition, and discusses evidence that may contribute to the development of novel TKIs without cardiac adverse effects.

Atrial fibrillation ablation procedures have become a focus of research among electrophysiologists, with the aim of increasing success rates while minimizing complications. One major concern is phrenic nerve injury (PNI). Despite advancements in ablation strategies, equipment, and monitoring methods, the incidence of PNI during these procedures remains substantial, particularly during cryoballoon ablation, which has a reported PNI incidence of 3.5%. This review examines recent studies, to provide a comprehensive overview of PNI mechanisms, clinical features, prognosis, and methods for prevention during ablation.

OBJECTIVE:This study aimed to evaluate the feasibility of real-time visualization and mapping of the right phrenic nerve (RPN) by using intracardiac echocardiography (ICE) during atrial fibrillation (AF) ablation. BACKGROUND:RPN injury is a complication associated with the ablation of AF. Multiple approaches are currently being used to prevent and detect RPN injuries. However, none of these approaches can directly visualize the RPN in real-time during the ablation procedure. METHODS AND RESULTS:The RPN was detected using ICE. The RPN and its adjacent structures were analysed. The relationship between the RPN's distance from the superior vena cava (SVC) and its pacing capture threshold was quantified. The safety of SVC isolation guided by the ICE-visualized RPN was evaluated. Thirty-eight people were enrolled in this study. The RPN was visualized by ICE in 92% of patients. It ran through the space between the SVC and the mediastinal pleura and had a 'straw'-like appearance upon ICE imaging. The course of the RPN was close to the SVC (minimum 1.0 ± 0.4 mm) and the right superior pulmonary vein (minimum 14.1 ± 7.3 mm). There was a positive linear correlation between the RPN's capture threshold and its distance from the SVC (Spearman's correlation coefficient = 0.728, < 0.001). SVC isolation was guided by the RPN; none of the patients developed an RPN injury. CONCLUSIONS:RPN can be visualized by ICE in most patients, thus providing a novel approach for the real-time detection of RPN during AF ablation.

Objective: To investigate the timing of pericardial drainage catheter removal and restart of the anticoagulation in patients with atrial fibrillation (AF) suffered from perioperative pericardial tamponade during atrial fibrillation catheter ablation and uninterrupted dabigatran. Methods: A total of 20 patients with pericardial tamponade, who underwent AF catheter ablation with uninterrupted dabigatran in Beijing Anzhen Hospital from January 2019 to August 2021, were included in this retrospective analysis. The clinical characteristics of enrolled patients, information of catheter ablation procedures, pericardial tamponade management, perioperative complications, the timing of pericardial drainage catheter removal and restart of anticoagulation were analyzed. Results: All patients underwent pericardiocentesis and pericardial effusion drainage was successful in all patients. The average drainage volume was (427.8±527.4) ml. Seven cases were treated with idarucizumab, of which 1 patient received surgical repair. The average timing of pericardial drainage catheter removal and restart of anticoagulation in 19 patients without surgical repair was (1.4±0.7) and (0.8±0.4) days, respectively. No new bleeding, embolism and death were reported during hospitalization and within 30 days following hospital discharge. Time of removal of pericardial drainage catheter, restart of anticoagulation and hospital stay were similar between patients treated with idarucizumab or not. Conclusion: It is safe and reasonable to remove pericardial drainage catheter and restart anticoagulation as soon as possible during catheter ablation of atrial fibrillation with uninterrupted dabigatran independent of the idarucizumab use or not in case of confirmed hemostasis.

炎症在多种心血管疾病的发生发展中起重要作用,抗炎治疗一直是攻克心血管疾病的研究热点.秋水仙碱作为经典的抗炎药物,近年来在心血管病领域内研究颇丰,本文综述了秋水仙碱在心包炎、心包切开术后综合征、恶性心包积液、冠心病(冠状动脉粥样硬化性心脏病)以及心房颤动等疾病的临床与基础研究进展,发现秋水仙碱可以有效抑制心血管疾病的炎症进展,从而对心包炎、冠心病以及术后心房颤动等起到一定疗效,但较多的不良反应限制了其在临床广泛使用,所以还需要进一步研究帮助临床工作者进行最优的临床决策.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of glucose-lowering agents that have improved clinical outcomes in patients with heart failure; however, their therapeutic mechanisms remain elusive. Although contradictory results have been reported, it has been proposed that improving Na+ homeostasis may be the underlying mechanism of action of SGLT2 inhibitors in heart failure treatment. This study explored whether empagliflozin ameliorates Na+ and Ca2+ handling disorders induced by ouabain in an Na+-dependent manner. Isolated ventricular myocytes of mice were incubated with ouabain to establish a cellular model of Na+ overload. Effects of empagliflozin on Na+ and Ca2+ handling were evaluated using an ionOptix system and a confocal microscope. Distinct cytosolic Na+ levels were established by incubating different ouabain concentrations (10, 50, and 100 μmol/L). In the absence of ouabain, 1 μmol/L empagliflozin had a negligible impact on Na+ and Ca2+ handling in ventricular myocytes. Ouabain (50 μmol/L) significantly enhanced cytosolic Na+ levels and dysregulated Ca2+ handling, including an increased Ca2+ transient amplitude, elevated Ca2+ content in the sarcoplasmic reticulum, and enhanced spontaneous Ca2+ release normalized by treatment with 1 μmol/L empagliflozin within 10 min. All Na+ and Ca2+ handling abnormalities induced by ouabain were reversed by 1 μmol/L empagliflozin. The efficacy of empagliflozin was more potent at higher cytosolic Na+ levels. Pretreatment with the Na+/H+ exchanger (NHE) inhibitor (1 μmol/L cariporide) abolished the effects of empagliflozin. Empagliflozin ameliorates ouabain-induced Na+ and Ca2+ handling disorders in a cytosolic Na+-dependent manner, potentially by inhibiting the NHE.

Background: Post-cardiac procedure atrial fibrillation (PCP-AF) is a significant medical problem. Inflammation is one of the key factors in the pathogenesis of PCP-AF. As a classical anti-inflammatory drug, colchicine may prevent the occurrence of PCP-AF. This meta-analysis of 12 randomized controlled trials (RCTs) analyzed the feasibility and safety of colchicine for the prevention of PCP-AF. Methods: PubMed, EMBASE, Web of Science, the Cochrane Library, and Google Scholar were retrieved for RCTs on the efficacy of colchicine in preventing atrial fibrillation. The primary endpoint was the diagnosis of PCP-AF, which includes cardiac surgery or pulmonary vein isolation. Evaluation was performed with estimated odds ratios (OR) and 95% confidence intervals (CI). Results: In this meta-analysis, 12 RCTs were selected and a total of 2297 patients were included. Colchicine therapy was associated with a reduced incidence of PCP-AF both in post-cardiac surgery (OR: 0.62; 95% CI: 0.49-0.78, p < 0.0001, I-2 = 0%), and in post-pulmonary vein isolation (OR: 0.43; 95% CI: 0.30-0.62, p < 0.0001, I-2 = 0%). Colchicine therapy was associated with increased side effects (OR: 2.81; 95% CI: 1.96-4.03, p < 0.00001, I-2 = 26%). Conclusion: Colchicine can effectively prevent post-cardiac operative atrial fibrillation and relapse of atrial fibrillation after pulmonary vein isolation (PVI). However, colchicine can also increase the incidence of side effects, mainly gastrointestinal adverse events. More studies are needed to find a more appropriate treatment dose and time.

Background The impact of elevated resting heart rate on early-stage renal dysfunction, manifesting as microalbuminuria, in hypertension is unclear. This study aimed to analyze the association between resting heart rate and microalbuminuria in patients with hypertension according to their blood pressure status. In addition, the effect of antihypertensive agents on this relationship was evaluated. Methods and Results We searched the National Health and Nutrition Examination Survey for eligible participants from 2009 to 2018. Data on key parameters such as age, sex, blood pressure, heart rate, albumin creatinine ratio, and medication were collected for analysis. Subsequently, participants were classified according to the heart rate quartile and blood pressure status for subgroups assessment. A total of 5,692 participants were enrolled in this study. After adjusting the confounding factors, there was a linear association between resting heart rate and microalbuminuria in patients with hypertension (OR 1.184 [per 1 SD]; 95% CI: 1.101, 1.274; P < 0.001). However, the association between elevated resting heart rate and microalbuminuria was not significant in patients with uncontrolled hypertension (OR 1.092 [per 1 SD]; 95% CI: 0.935, 1.275; P = 0.269). The OR of the indirect effect of β-blockers on the risk of microalbuminuria incidence through heart rate was 0.926 (95% CI: 0.895, 0.956), while the direct effect was 1.374 (95% CI: 1.138, 1.662, P = 0.010). Similarly, dihydropyridine calcium channel blockers were associated with a higher prevalence of microalbuminuria (OR 1.300, 95% CI: 1.058, 1.597, P = 0.013), but the association between non-dihydropyridine calcium channel blockers and microalbuminuria was not significant (OR 1.207, 95% CI: 0.737, 1.978, P = 0.454). Conclusion Elevated resting heart rate is associated with a high risk of microalbuminuria in untreated patients and patients with controlled hypertension. Although there is a linear association between heart rate and microalbuminuria, the use of β-blockers exhibits a significantly increase in the prevalence of microalbuminuria in hypertension. Likewise, dihydropyridine calcium channel blockers may increase the risk of microalbuminuria in hypertension.

Current knowledge on the dynamic changes of corrected QT (QTc) before, during, and after an atrial fibrillation (AF) episode is limited. It remains controversial which of the presently available formulas performs the best in calculating QTc during AF. This study was designed to explore whether an AF attack would affect QTc and to determine the performance of 6 available formulas in correcting QT before, during, and after AF. A total of 101 patients with Holter-documented paroxysmal AF were enrolled. QT interval before, during, and after AF was measured and corrected to heart rate (HR) by using Bazett, Fridericia, Framingham, Hodges, Dmitrienko, and RTHa formulas. In 40 patients, QTc under AF was compared with under sinus rhythm (SR) with identical HR. Although QT was significantly longer before AF and after AF compared with during AF; there was no difference in QTc between SR and AF with identical HR regardless of the formulas used. QTc calculated by the Framingham formula showed excellent homogeneity with a mean delta difference of -0.2 +/- 41.6 ms (before AF vs AF) and -6.6 +/- 35.4 ms (after AF vs AF), respectively. QTc corrected by the Bazett formula (before AF vs AF -38.7 +/- 52.3 ms; after AF vs AF -42.6 +/- 46.9 ms) yielded significant heterogeneity among the 3 time points. In conclusion, AF does not influence QTc. The Framingham formula accurately corrects QT without being affected by the AF episode. The Bazett formula significantly overestimated QTc during AF. Published by Elsevier Inc.

Abstract Background  Left ventricular thrombus (LVT) is a common complication of dilated cardiomyopathy (DCM), causing morbidity and mortality. Methods  This study retrospectively analyzed patients with DCM from January 2002 to August 2020 in Beijing Anzhen Hospital. Clinical characteristics were compared between the LVT group and the age and sex 1:4 matched with the LVT absent group. The receiver operator characteristic (ROC) curve was plotted to evaluate the diagnostic value of D-dimer predicting LVT occurrence in DCM. Results  A total of 3,134 patients were screened, and LVT was detected in 72 (2.3%) patients on echocardiography. The patients with LVT had higher D-dimer, fibrinogen, and lower systolic blood pressure than those without LVT. The ejection fraction (EF) was lower and left ventricular end-systolic diameter was larger in the LVT group. Severe mitral regurgitation (MR) was more common in the LVT absent groups. The prevalence of atrial fibrillation was lower in the LVT group. The ROC curve analysis yielded an optimal cut-off value of 444 ng/mL DDU (D-dimer units) for D-dimer to predict the presence of LVT. Multivariable binary logistic regression analysis revealed that EF (OR = 0.90, 95% CI = 0.86–0.95), severe MR (OR = 0.19, 95% CI = 0.08–0.48), and D-dimer level (OR = 15.4, 95% CI = 7.58–31.4) were independently associated with LVT formation. Conclusion  This study suggested that elevated D-dimer levels (>444 ng/mL DDU) and reduced EF were independently associated with increased risk of LVT formation. Severe MR could decrease the incidence of LVT.

Background There exist sex differences in the clinical profile, management, and outcome of atrial fibrillation (AF). Catheter ablation of AF has become a first-line therapy and has markedly made headway over the recent decades. Little is known about sex differences and temporal trends in hospitalization for catheter ablation of AF in the real-world setting. Methods We retrospectively retrieved medical records of patients at Beijing Anzhen Hospital between January 2005 and December 2019. The patients undergoing catheter ablation of AF were enrolled. Demographical and clinical data were compared between sexes. The temporal trends of sex differences were evaluated. Results We identified 13502 male patients (66.8%) and 6713 female patients (33.2%). The number of patients undergoing AF ablation had remarkably increased over time, but no sex differences were observed (p=0.17). The median age of women was five years older than that of men (p < 0.001). The median time of in-hospital stay for the women decreased from 11 days to 4 days and for the men from 9 to 4 days. In-hospital mortality was 0.03% and 0.01% for women and men, respectively, with no significant difference between sexes. The women were more likely to have a comorbid diagnosis of hypertension and heart failure than men (p < 0.001). The CHA2DS2-VA score was higher in women than in men (1.64 vs. 1.28, p < 0.001). The temporal trend in the score increased in women from 1.17 to 1.81 (p < 0.001) and in men from 0.91 to 1.41 (p < 0.001). The percentage of patients with CHA2DS2-VA score ≥2 was higher in women than in men (49.8% vs. 35.8%, p < 0.001), and the temporal trend of this sex gap was nearly doubled (8.0% in 2005–2007 vs. 15.5% in 2017–2019, p=0.03). Conclusions Safety of catheter ablation for AF was comparable in both sexes. In contrast, the women showed a higher CHA2DS2-VA score than men. The percentage of patients with CHA2DS2-VA score ≥2 increased more quickly in women than in men. Furthermore, sex-specific research is warranted to reduce this sex disparity.

BackgroundEvidence for the role of the CACNA1C gene, which encodes for the α-subunit of the cardiac L-type calcium channel CaV1.2, as a cause of the BrS3 variant of Brugada syndrome (BrS) is contradictory.ObjectiveThe purpose of this study was to define in a large BrS cohort the yield of molecular screening and to test whether appropriate patient selection could improve clinical utility.MethodsA total of 709 patients were included in this study. BrS probands (n = 563, consecutively referred) underwent CACNA1C sequencing. Two matched cohorts where defined: discovery cohort (n = 200) and confirmation cohort (n = 363). In addition, the clinical phenotypes of a matched SCN5A-positive BrS cohort (n = 146) were included for comparative genotype-phenotype correlation.ResultsIn the discovery cohort, we identified 11 different rare variants in 9 patients; 10 of the variants (5%) were considered potentially causative based on their frequency in the general population. However, American College of Medical Genetics criteria were unable to classify the majority (80%) of them, which eventually were labeled as variants of unknown significance (VUS). Functional studies revealed a loss of function for 9 variants, pointing to a prevalence of CACNA1C causative variants in 4% of the discovery cohort. Genotype-phenotype correlation showed that pathogenic variants are significantly more frequent in patients with shorter QTc (12.9% vs 2.2% in patients with QTc <390 ms).ConclusionCACNA1C is an infrequent but definitive cause of BrS typically associated with short QT. Functional studies are highly relevant to improve variant interpretation.