BACKGROUND:Premature ventricular complexes (PVCs) originating from the proximal left anterior fascicle (LAF) can be eliminated safely from the right coronary cusp (RCC). OBJECTIVE:This study was performed to evaluate a new mapping and ablation strategy for proximal LAF-PVCs under the guidance of electrocardiographic characteristics. METHODS:Proximal LAF-PVCs were defined as PVC-QRS with prominent inferior frontal plane QRS axis, right bundle branch block pattern, and with QRS duration difference (between PVC and sinus rhythm) <15 ms. The study group consisted of consecutive patients with proximal LAF-PVCs, which were prospectively mapped and ablated from only the RCC. The control group consisted of patients with proximal LAF-PVCs, which were mapped from the left ventricle and RCC before ablation from within the RCC was successful. RESULTS:There were 24 and 8 patients in the study and control groups, respectively. For the study group, after mapping from only the RCC, proximal LAF-PVCs were eliminated with ablation from the RCC alone (2.5 ± 0.7 lesions). Mapping time (9.3 ± 5.8 min vs 27.9 ± 6.8 min, P < .001), and procedure time (43.8 ± 7.5 min vs 61.0 ± 6.9 min, P < .001) of the study group were shorter than that of the control group. Long-term success rates and electrocardiographic characteristics were similar between groups. CONCLUSION:Under the guidance of electrocardiographic characteristics, this new mapping and ablation strategy (from the RCC alone) is a simple, safe, and effective method for elimination of proximal LAF-PVCs.

Background:The triglyceride-glucose (TyG) index and Systemic Inflammatory Response Index (SIRI) are markers of insulin resistance and inflammation, respectively, and are each independently associated with mortality. Their combined prognostic value is not well established. This study aimed to investigate the association between combined categories of TyG and SIRI and cardiovascular (CVD) and all-cause mortality. Methods:We included 11,010 participants from the NHANES 1999-2010. All analyses accounted for the complex survey design. We employed Cox models, restricted cubic splines, and time-dependent ROC analyses. The incremental predictive value of the combined categories was assessed using the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results:A TyG threshold of 8.64 (linear association) and an SIRI threshold of 0.63 (L-shaped association) were identified. Compared to the low-risk group (TyG ≤ 8.64 and SIRI≤0.63), participants with both TyG > 8.64 and SIRI>0.63 had a 68% higher risk of CVD mortality (HR = 1.68, 95% CI: 1.08-2.61, P = 0.021) and a 52% higher risk of all-cause mortality (HR = 1.52, 95% CI: 1.21-1.91, P < 0.0001). Adding the combined categories to a model of traditional risk factors significantly improved reclassification for CVD mortality (NRI = 0.15, P < 0.05). Subgroup and sensitivity analyses supported the robustness of the findings. Conclusions:Concurrently high TyG and SIRI identifies individuals at significantly increased mortality risk. This simple, threshold-based stratification may serve as a practical tool for cardiovascular risk assessment.

This study was performed to evaluate the current status and to analyze the associated factors of intraoperative pain experience during radiofrequency ablation of atrial fibrillation (AF) with conscious sedation and analgesia. This cross-sectional observational study employed convenience sampling of AF patients underwent their first radiofrequency ablation. General information questionnaire, intraoperative status sheet, Wong-Baker faces pain rating scale, hospital anxiety and depression scale, and the Connor-Davidson Resilience Scale were employed for data collection and analysis. A total of 428 patients (mean age 66.5 ± 9.6years; 59.8

BACKGROUND:Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation, although the optimal site for ablation remains controversial. METHODS AND RESULTS:We reported a 52- year-old woman with the third paroxysmal AF ablation. Mapping showed that the ostial PV ， but not the PV antrum ，was isolated. During circumferential PV antrum ablation, the atrial arrhythmias were eliminated. The roof line and superior vena cava isolation was empirically performed. During the 84-month follow-up, she was free of arrhythmias without antiarrhythmics. CONCLUSION:Isolation of the PV antrum, which was easily to be identify by image integration, should be checked and achieved for patients with AF recurrence after "successful and durable ostial PVI". CLINICAL TRIAL REGISTRATION STATEMENT:No clinical trial registration number is applicable.

Abstract. Atrial fibrillation (AF) is one of the most commonly sustained cardiac arrhythmias, which increases the risk of ischemic stroke, heart failure, and death. Although great progress has been achieved in the treatment of AF, a proportion of patients are refractory to treatment with anti-arrhythmics or experience AF recurrence and progression. Accumulating evidence identifies diabetes mellitus (DM) as an independent risk factor for AF, indicating that glucose-lowering medications may be effective for the treatment of AF. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a relatively new class of anti-diabetes agents, may therefore offer an alternative therapeutic strategy for AF. While several reviews support the cardiovascular benefits of SGLT2i, few publications have specifically focused on their effects on AF. This review comprehensively summarizes existing clinical studies valuating the impact of SGLT2i on new-onset AF in DM patients without AF, AF recurrence risk in DM patients with AF, and associated poor prognosis. In addition, data derived from animal models exploring the influence of SGLT2i on the inducibility, incidence, and duration of AF, as well as the underlying molecular mechanisms, are summarized. The cumulative evidence suggests that the use of SGLT2i considerably reduces the risk of new-onset AF, AF recurrence, and AF-related complications. The potential underlying mechanisms involve regulation of ion exchange channels and energy metabolism, and inhibition of oxidative stress, mitochondrial dysfunction, inflammation, apoptosis, and fibrosis. Further studies should be carried out to verify these beneficial effects by integrating the studies with negative results and to further explore other mechanisms that explain the benefits of SGLT2i.

BackgroundLeft bundle branch area pacing (LBBAP) has emerged as a physiological pacing strategy. LBBAP has been predominantly performed using the lumen-less lead.ObjectivesThis study aims to explore the efficacy and safety of LBBAP performed with stylet-driven leads (SDL) via site-selective pacing catheter (SSPC) sheaths.MethodsWe evaluated consecutive 79 patients undergoing LBBAP using standard stylet-driven active leads via SSPC sheaths. Pacing parameters (threshold, R-wave amplitude, impedance), QRS morphology and duration, left ventricular activation time in lead V5 and complication rates were analyzed. Postoperative measurements of lead parameters and complications were recorded at 1, 3, 6, and 12 months.ResultsLBBAP was successfully achieved in 69 of the 79 patients (87.3%), with 7742 leads via SSPC sheaths, with 52 patients (65.8%) showing visible left bundle branch potentials. Mean paced QRS duration and left ventricular activation time in lead V5 were 111.1 ± 27.2 ms and 69.0 ± 11.7 ms. Intraoperative electrode parameters for SDL-LBBAP, including pacing threshold (0.8 ± 0.2 V at 0.4 ms), impedance (792.5 ± 140.7 ohms), and sensing amplitude (14.0 ± 5.9 mV), remained stable during the 12 month follow up. Intraoperative ventricular septal perforation occurred in six patients (7.6%), with no subsequent persistent ventricular septal defects. Procedural time and fluoroscopy exposure time were lower in the latter 39 patients, declining markedly as operator experience accumulated.ConclusionsThe application of SDL in LBBAP is safe and feasible, with excellent success rates and stable long term electrical performance.

Mitochondrial dysfunction is increasingly recognized as a pivotal driver of cardiomyocyte apoptosis and cardiac deterioration following myocardial infarction (MI). This study identifies a significant upregulation of DDX60 in cardiomyocytes under hypoxic conditions. Elevated DDX60 levels enhance mitochondrial function and attenuate cardiomyocyte apoptosis in vitro, whereas its knockdown induces the opposite effects. In vivo, cardiomyocyte-specific DDX60 knockout markedly exacerbates mitochondrial dysfunction and apoptosis, accelerating post-MI cardiac remodeling and functional decline. Furthermore, we found that Arl2 knockdown partially negates the protective effects of DDX60 overexpression on ATP production and apoptosis. Conversely, adeno-associated virus-9 (AAV9)-mediated Arl2 overexpression partially restores cardiac function, reduces infarct size, and rescues mitochondrial integrity in DDX60 CKO mice post-MI. Mechanistically, DDX60 forms a translational complex with eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) that enhances Arl2 mRNA translation, a process essential for mitochondrial homeostasis. Collectively, these findings establish DDX60 as a key regulator of cardioprotection post-MI by enhancing Arl2 translation, highlighting its potential as a therapeutic target for ischemic heart disease.

Introduction and Aims: Craniofacial and upper airway development are closely associated with obstructive sleep apnea (OSA). This study aimed to analyse craniofacial and upper airway characteristics in adults with severe obesity and OSA to better understand the disease. Methods: Ninety-four severely obese patients (BMI ≥ 35) underwent polysomnography (PSG) and lateral cephalograms to assess craniofacial and upper airway morphology. Cephalometric and airway measurements were analysed combined with PSG findings to evaluate craniofacial and airway features in severe OSA patients. Results: The study included 50 males and 44 females, with a mean age of 33.05 years and an average apnea-hypopnea index (AHI) of 52.22 events/h. Males had significantly higher AHI, neck circumference (NC), waist circumference, and arousal index, along with lower average and minimal oxygen saturation levels compared to females. Cephalometric analysis showed that males had greater mandibular ramus length and Sella-to-condyle vertical distance. Cross-correlation analysis indicated significant associations between AHI and both NC and the mandibular plane to Sella-Nasion line measurement. The Frankfurt horizontal plane to Nasion–Pogonion plane was correlated with BMI, NC, and waist circumference. Hyoid bone position was linked to tongue volume, Y-axis angle, pharyngeal airway space, facial height, and lip length. Tongue volume correlated with mandibular ramus length, upper anterior tooth angle, and upper lip length. Snoring index was associated with pharyngeal airway space and tongue height, while pharyngeal airway space width was related to oxygen saturation levels. Conclusion: Severe obese individuals, particularly males, experience more severe OSA symptoms. A complex interplay exists between OSA, craniofacial morphology, and airway structure. Clinical Relevance: Craniofacial and dental features are consistent in severe obese OSA patients, suggesting that obesity-related fat accumulation has a greater impact on respiratory function than skeletal structure or dental alignment.

BackgroundAtrial fibrillation (AF) and tricuspid regurgitation (TR) frequently coexist and mutually worsen each other. However, the long-term effects of functional tricuspid regurgitation (FTR) on AF recurrence and the improvement of TR after radiofrequency catheter ablation (RFCA) remain unclear.MethodsThis retrospective, single-center observational study involved 1,690 patients with persistent atrial fibrillation (PsAF) who underwent AF ablation between January 2012 and June 2022. 153 paients with significant FTR were propensity matching 153 patients with no or mild FTR based on age, body mass index, and mitral regurgitation (MR) severity. Patients were followed up for at least 1 year. Procedural success was defined as freedom from any atrial tachyarrhythmia (>30 s) after the 3-month blanking period, off antiarrhythmic drugs. Significant FTR was defined as moderate to severe TR. Significant TR improvement was defined as a reduction in TR severity by ≥2 grades from pre- to post-ablation.ResultsAmong the observational cohort, 153 patients (9.1%) had significant FTR, the severity of which correlated with female sex, AF duration, atrial/ventricular remodeling, and NT-proBNP levels. During the 12-month follow-up, the procedural success rate was 67.6% (207/306). RFCA significantly reduced the proportion of RA and RV enlargement (P < 0.001), and improved the severity of FTR (P < 0.001). Logistic regression analyses showed that AF recurrence [odds ratio (OR) 18.244, 95% CI 7.500–52.427, P < 0.001]) was the strongest independent risk factor for non-significant TR improvement after ablation. After a mean follow-up of 5.3 ± 3.7 years, the overall procedural success rate was 47.4% (145/306). The overall success rate was significantly lower in patients with significant FTR compared to those with no or mild FTR (37.3% VS 57.5%, P < 0.001). A comparable difference was observed between ventricular FTR and no or atrial FTR (27.1% VS 53.4%, P < 0.001).ConclusionsSignificant FTR was an independent predictor of AF recurrence in patients with PsAF undergoing RFCA. The long-term success was poor in the subgroups of significant FTR and those with ventricular FTR. Furthermore, successful RFCA was associated with significantly improved FTR in patients with PsAF.

Acute ischemic stroke (AIS) during radiofrequency ablation of premature ventricular complexes (PVC) patients was rarely reported. This is the first case report on AIS during catheter ablation of PVC that highlighted that AIS could be encountered in some patients resulting from repeated retrograde transaortic manipulation with excessive contact force.

Doxorubicin (Dox) is a potent chemotherapeutic agent commonly used in cancer treatment. However, cardiotoxicity severely limited its clinical application. To address this challenge, a novel self-assembled nanomedicine platform, PMDDH, is developed for the co-delivery of Dox and metformin, an antidiabetic drug with cardioprotective and anti-tumor properties. PMDDH integrates metformin into a polyethyleneimine-based bioactive excipient (PMet), with Dox intercalated into double-stranded DNA and a hyaluronic acid (HA) coating to enhance tumor targeting. The PMDDH significantly improves the pharmacokinetics and tumor-targeting capabilities of Dox, while metformin enhances the drug's anti-tumor activity by downregulating programmed cell death ligand 1 (PD-L1) and activating the AMP-activated protein kinase (AMPK) signaling pathway. Additionally, the DNA component stimulates the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, which synergizes with Dox-induced immunogenic cell death (ICD) to promote a robust anti-tumor immune response. PMDDH markedly reduces Dox-induced cardiotoxicity by preserving mitochondrial function, reducing reactive oxygen species (ROS) production, and inducing protective autophagy in cardiomyocytes. These findings position PMDDH as a promising dual-function nanomedicine that enhances the anti-tumor efficacy of Dox while minimizing its systemic toxicity, offering a safer and more effective alternative for cancer therapy.

Abnormal cardiac fibrosis is the main pathological change of post-myocardial infarction (MI) heart failure. Although the E3 ubiquitin ligase FBXL8 is a key regulator in the cell cycle, cell proliferation, and inflammation, its role in post-MI ventricular fibrosis and heart failure remains unknown. FBXL8 was primarily expressed in cardiac fibroblasts (CFs) and remarkably decreased in CFs treated by TGFβ and heart subjected to MI. The echocardiography and histology data suggested that adeno-associated viruses (AAV9)-mediated FBXL8 overexpression had improved cardiac function and ameliorated post-MI cardiac fibrosis. In vitro, FBXL8 overexpression prevented TGFβ-induced proliferation, migration, contraction, and collagen secretion in CFs, while knockdown of FBXL8 demonstrated opposite effects. Mechanistically, FBXL8 interacted with Snail1 to promote Snail1 degradation through the ubiquitin–proteasome system and decreased the activation of RhoA. Moreover, the FBXL8ΔC3 binding domain was indispensable for Snail1 interaction and degradation. Ectopic Snail1 expression partly abolished the effects mediated by FBXL8 overexpression in CFs treated by TGFβ. These results characterized the role of FBXL8 in regulating the ubiquitin-mediated degradation of Snail1 and revealed the underlying molecular mechanism of how MI up-regulated the myofibroblasts differentiation-inducer Snail1 and suggested that FBXL8 may be a potential curative target for improving post-MI cardiac function.

BACKGROUND:Transseptal catheterization is critical for atrial fibrillation (AF) ablation but risks thromboembolism. Transseptal sheaths (TSS) were suggested for continuous heparinized saline solution flush. The safety and effectiveness of a simple TSS management to reduce sheath-associated thrombus development risk was investigated. METHODS:AF patients who underwent radiofrequency ablation with the simple TSS management were studied under a retrospective multi-center observation study and a prospective single-center observation study. TSS and dilators were washed and perfused with high concentration heparinized saline (20 u/mL). Immediately after two successful transseptal punctures, activated clotting time ≥300 s was maintained by heparin infusion. TSS aspiration with negative suction and re-perfusion with high concentration heparinized saline (20 u/mL) was performed for the remaining procedure before and after catheter withdrawal. RESULTS:A total of 4765 AF patients underwent 5367 ablation procedures were enrolled in the retrospective study, involving 156 (2.9% per procedure) complications. No acute stroke occurred during all the procedures. Perioperative thromboembolic complications occurred in 10 (0.21%) patients and in 10 (0.19%) procedures. Thromboembolic complications occurred within 24 h, between 24-48 h, and after 48 h post-procedure in six, two, and two patients, respectively. In the prospective observation study, neither sheath- nor catheter-associated thrombus were detected by the intracardiac echocardiography during all 127 procedures, without any perioperative thromboembolic complications. No hemorrhagic cerebrovascular complication was encountered in both observational studies. CONCLUSION:For AF radiofrequency ablation, it was safe and effective for TSS high concentration heparinized saline infusion only. This approach could avoid sheath-associated thrombus for interventional procedures.

This study aimed to evaluate the safety and short-term effect of contemporaneous surgeries (bariatric surgery plus uvulopalatopharyngoplasty [UPPP]) in the treatment of morbid obesity comorbid with severe obstructive sleep apnea (OSA). A retrospective cohort study was performed to identify patients with obesity and severe OSA who underwent laparoscopic sleeve gastrectomy (LSG) with or without UPPP surgeries between December 2019 and December 2021 in our center. Patients were divided into 2 groups according to different surgical methods (contemporaneous group [LSG with UPPP] vs LSG-only group). Data about surgical safety, OSA remission, and effectiveness of weight loss were collected and analyzed between the 2 groups before and 12 months after surgery. A total of 101 patients were included in this study (contemporaneous group [LSG with UPPP], n = 42 vs LSG only group, n = 59). There was no significant difference in surgical safety between the 2 groups, and both OSA and obesity were significantly improved at 12.5 ± 2.1 months postoperative follow-up. The apnea-hypopnea index decreased from 68.7 ± 30.4 events/h to 10.2 ± 7.0 events/h in the contemporaneous group (P < .001) and from 64.7 ± 26.2 events/h to 18.9 ± 9.8 events/h in the LSG group (P < .001). Moreover, the apnea-hypopnea index decreased to below 5 events/h in 50

Background Radiofrequency catheter ablation (RFCA) for long-standing persistent atrial fibrillation (LSP-AF) remains challenging, especially in patients with very long atrial fibrillation (AF) duration. Objective To evaluate the long-term outcomes of RFCA in patients with LSP-AF lasting ≥ 3 years, and to identify predictors for AF recurrence. Methods This retrospective study included 151 patients with LSP-AF undergoing first-time RFCA. Procedure was performed with wide antral pulmonary vein isolation (PVI) based individualized ablation strategy, guided by ablation index (AI). Patients were followed up for ≥ 18 months, and recurrence predictors were determined. Results Enrolled patients (mean persistent AF duration: 7.6 ± 5.2 years) had a mean age of 65.3 ± 9.2 years and the median left atrial diameter (LAD) was 45.0 (42.0-49.0) mm. PVI was achieved in all, followed by modified left posterior wall isolation (PWI) in 147 patients. Additional ablation after PWI was performed in 88 patients. During the 18-month follow-up, the overall success rate was 74.2%. Multivariate analysis identified AF duration (HR 1.078; 95% CI 1.020-1.139; P = 0.007), LAD (HR 1.069; 95% CI 1.010-1.132; P = 0.022), and pre-procedure CRP (HR 1.063; 95% CI 1.010-1.117; P = 0.018) as independent predictors of AF recurrence. Among patients with PVI and PWI, those without empirical additional ablation (EAA) had a lower but not statistically significant recurrence rate (18.6%) than those with EAA (31.8%, P = 0.076). Conclusion Among LSP-AF patients, the long-term efficacy of AI-guided RFCA is acceptable, especially in selected patients. However, EAA after PVI and PWI may be unhelpful. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by National Natural Science Foundation of China, grant number 82370324, Clinical Research Plan of SHDC (SHDC2023CRD008), Zunyi Science and Technology Bureau (2018-191), Clinical Research Plan of Shanghai General Hospital (CCTR-2022B09). ### 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: Ethical approval was granted by the Ethics Committee of Shanghai general hospital. 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 figure was created by SPSS 25.0 (IBM Corp., Armonk, NY, USA) and GraphPad Prism (version 8.0).

A 58-year-old woman was referred for atrial flutter ablation after atrial fibrillation ablation. Linear and reinforcement mitral isthmus ablation failed to terminate the perimitral flutter. During vein of Marshall ethanol infusion (VOMEI), the flutter was terminated and followed by left atrial appendage (LAA) isolation. Voltage mapping showed that a large low voltage area was created in the superior and anterior wall of left atrium. During the waiting time, the LAA activation recovered. It would be necessary to keep in mind that VOMEI would lead to uncontrolled lesion of left atrium.