Background: Loss-of-function mutations in the SCN5A gene, which encodes for the predominant cardiac NaV isoform, NaV1.5, result in either deficiency in the channel expression or function. Impaired NaV1.5 expression and function underlie reduced peak Na+ current (INa) and result in ventricular conduction velocity slowing, predisposing the heart to conduction block and ventricular arrhythmias clinically associated with Brugada syndrome (BrS). Recently, a missense mutation in NaV1.5 selectivity filter (DEKA motif), K1419E (DEEA), has been identified in patients with BrS. Despite early characterization of mutations in selectivity filter of other NaV isoforms, little is known about the impact of DEEA on NaV1.5 function as well as on cardiac electrophysiology.
Objectives: In this study, we generated a mouse heterozygous for NaV1.5 DEEA to characterize the mutation and investigate the outcome of this functionally deficient NaV1.5 variant on cardiac electrophysiology and arrhythmias.
Methods: Patch clamp electrophysiology studies were conducted in Chinese hamster ovary cells expressing the DEEA variant, along with immunolabeling, voltage optical mapping, and in vivo electrocardiography studies in a DEEA murine model of BrS.
Results: A heterologous expression system and isolated cardiomyocytes revealed lower current density and unchanged NaV1.5 expression in DEEA vs wild type (DEKA). On the organ level, optical mapping revealed conduction velocity slowing in DEEA hearts, which was accentuated by flecainide, resulting in in vivo ventricular arrhythmias.
Conclusions: Overall, to our knowledge, we provide the first mechanistic insight into the proarrhythmic consequences of a functionally deficient BrS mutation in NaV1.5.
{"title":"Selectivity Filter Mutation in Na<sub>V</sub>1.5 Promotes Ventricular Tachycardia.","authors":"Zoja Selimi, Mikhail Tarasov, Xiaolei Meng, Patrícia Dias, Bianca Moise, Haiyan Liu, Omer Cavus, Drew Nassal, Rengasayee Veeraraghavan, Przemysław B Radwański","doi":"10.1016/j.jacep.2025.12.033","DOIUrl":"10.1016/j.jacep.2025.12.033","url":null,"abstract":"<p><strong>Background: </strong>Loss-of-function mutations in the SCN5A gene, which encodes for the predominant cardiac Na<sub>V</sub> isoform, Na<sub>V</sub>1.5, result in either deficiency in the channel expression or function. Impaired Na<sub>V</sub>1.5 expression and function underlie reduced peak Na<sup>+</sup> current (I<sub>Na</sub>) and result in ventricular conduction velocity slowing, predisposing the heart to conduction block and ventricular arrhythmias clinically associated with Brugada syndrome (BrS). Recently, a missense mutation in Na<sub>V</sub>1.5 selectivity filter (DEKA motif), K1419E (DEEA), has been identified in patients with BrS. Despite early characterization of mutations in selectivity filter of other Na<sub>V</sub> isoforms, little is known about the impact of DEEA on Na<sub>V</sub>1.5 function as well as on cardiac electrophysiology.</p><p><strong>Objectives: </strong>In this study, we generated a mouse heterozygous for Na<sub>V</sub>1.5 DEEA to characterize the mutation and investigate the outcome of this functionally deficient Na<sub>V</sub>1.5 variant on cardiac electrophysiology and arrhythmias.</p><p><strong>Methods: </strong>Patch clamp electrophysiology studies were conducted in Chinese hamster ovary cells expressing the DEEA variant, along with immunolabeling, voltage optical mapping, and in vivo electrocardiography studies in a DEEA murine model of BrS.</p><p><strong>Results: </strong>A heterologous expression system and isolated cardiomyocytes revealed lower current density and unchanged Na<sub>V</sub>1.5 expression in DEEA vs wild type (DEKA). On the organ level, optical mapping revealed conduction velocity slowing in DEEA hearts, which was accentuated by flecainide, resulting in in vivo ventricular arrhythmias.</p><p><strong>Conclusions: </strong>Overall, to our knowledge, we provide the first mechanistic insight into the proarrhythmic consequences of a functionally deficient BrS mutation in Na<sub>V</sub>1.5.</p>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12952376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-05DOI: 10.1016/j.jacep.2026.01.006
Atul Verma, Monica Lo, Christopher E Woods, Ayman A Hussein, Alok Gambhir, Sri Sundaram, Prashanthan Sanders, David DeLurgio, Stavros E Mountantonakis, Petr Neuzil, Joaquin Osca, Amar Trivedi, Peter Loh, Hugh Calkins, David Strouse, Gian-Battista Chierchia, Brett Atwater, Jonathan Kalman, Helmut Puererfellner, Antonio Dello Russo, Ramin Davoudi, Richard Schilling, Wenjiao Lin, Amber Miller, Emily Jesser, Dhanunjaya Lakkireddy
Background: A novel balloon-in-basket catheter integrated into a mapping system may advance pulsed field ablation (PFA) of atrial fibrillation (AF) with demonstrated deeper lesions, less hemolysis, and promising initial clinical experience.
Objectives: The goal of this study was to assess the 1-year clinical outcomes of the balloon-in-basket PFA system.
Methods: The multicenter VOLT-AF IDE Clinical Study enrolled patients with symptomatic, paroxysmal (PAF), and persistent AF (PeAF) . Pulmonary vein isolation (PVI) was performed with the investigational system. The primary effectiveness endpoint was acute PVI and 12-month freedom from atrial arrhythmia, antiarrhythmic escalation/initiation, cardioversion, or repeat ablation. The primary safety endpoint was device- and/or procedure-related serious adverse events within 7 days of any ablation. Follow-up consisted of 12-lead electrocardiograms at discharge, 3 months, and 12 months; biweekly and symptomatic transtelephonic monitoring; and 24-hour Holter monitoring at 12 months.
Results: Of the 392 patients enrolled, 335 were main cohort patients (57 roll-ins), and 320 were treated (165 PAF and 155 PeAF). Their mean age was 65 ± 11 years, and the mean CHA2DS2-VASc score was 2.3 ± 1.6. Left atrial catheter dwell time was 44.1 ± 18.1 minutes (including a 20-minute wait). A mean of 4.6 ± 0.9 applications were delivered per vein. Primary effectiveness was 81.1% (95% CI: 74.3%-86.3%) in PAF and 63.3% (95% CI: 55.1%-70.4%) in PeAF. Freedom from documented arrhythmia recurrence was 84.2% in the PAF group and 67.8% in the PeAF group. Primary safety events occurred in 1.9% of patients, with none in the PAF group. During redo ablation in 19 patients, 78.5% of pulmonary veins remained durably isolated.
Conclusions: This multicenter trial reports high PVI-based effectiveness of the novel balloon-in-basket PFA device with excellent safety.(VOLT-AF IDE Clinical Study; NCT06223789).
{"title":"Balloon-in-Basket Pulsed Field Ablation for Pulmonary Vein Isolation: One-Year Outcomes of the VOLT-AF IDE Study.","authors":"Atul Verma, Monica Lo, Christopher E Woods, Ayman A Hussein, Alok Gambhir, Sri Sundaram, Prashanthan Sanders, David DeLurgio, Stavros E Mountantonakis, Petr Neuzil, Joaquin Osca, Amar Trivedi, Peter Loh, Hugh Calkins, David Strouse, Gian-Battista Chierchia, Brett Atwater, Jonathan Kalman, Helmut Puererfellner, Antonio Dello Russo, Ramin Davoudi, Richard Schilling, Wenjiao Lin, Amber Miller, Emily Jesser, Dhanunjaya Lakkireddy","doi":"10.1016/j.jacep.2026.01.006","DOIUrl":"https://doi.org/10.1016/j.jacep.2026.01.006","url":null,"abstract":"<p><strong>Background: </strong>A novel balloon-in-basket catheter integrated into a mapping system may advance pulsed field ablation (PFA) of atrial fibrillation (AF) with demonstrated deeper lesions, less hemolysis, and promising initial clinical experience.</p><p><strong>Objectives: </strong>The goal of this study was to assess the 1-year clinical outcomes of the balloon-in-basket PFA system.</p><p><strong>Methods: </strong>The multicenter VOLT-AF IDE Clinical Study enrolled patients with symptomatic, paroxysmal (PAF), and persistent AF (PeAF) . Pulmonary vein isolation (PVI) was performed with the investigational system. The primary effectiveness endpoint was acute PVI and 12-month freedom from atrial arrhythmia, antiarrhythmic escalation/initiation, cardioversion, or repeat ablation. The primary safety endpoint was device- and/or procedure-related serious adverse events within 7 days of any ablation. Follow-up consisted of 12-lead electrocardiograms at discharge, 3 months, and 12 months; biweekly and symptomatic transtelephonic monitoring; and 24-hour Holter monitoring at 12 months.</p><p><strong>Results: </strong>Of the 392 patients enrolled, 335 were main cohort patients (57 roll-ins), and 320 were treated (165 PAF and 155 PeAF). Their mean age was 65 ± 11 years, and the mean CHA<sub>2</sub>DS<sub>2</sub>-VASc score was 2.3 ± 1.6. Left atrial catheter dwell time was 44.1 ± 18.1 minutes (including a 20-minute wait). A mean of 4.6 ± 0.9 applications were delivered per vein. Primary effectiveness was 81.1% (95% CI: 74.3%-86.3%) in PAF and 63.3% (95% CI: 55.1%-70.4%) in PeAF. Freedom from documented arrhythmia recurrence was 84.2% in the PAF group and 67.8% in the PeAF group. Primary safety events occurred in 1.9% of patients, with none in the PAF group. During redo ablation in 19 patients, 78.5% of pulmonary veins remained durably isolated.</p><p><strong>Conclusions: </strong>This multicenter trial reports high PVI-based effectiveness of the novel balloon-in-basket PFA device with excellent safety.(VOLT-AF IDE Clinical Study; NCT06223789).</p>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-03DOI: 10.1016/j.jacep.2025.12.030
Amneet Sandhu, Li Qin, Vincenzo B Polsinelli, Karl E Minges, James V Freeman, Sana M Al-Khatib, Adrienne Walker, Steven M Bradley, P Michael Ho, Wendy S Tzou, Paul D Varosy, Paul L Hess
Background: Despite a common rhythm control strategy, use and safety of atrial fibrillation (AF) ablation pursued urgently among inpatients has not been adequately characterized.
Objectives: This study sought to describe the use and safety of urgent AF ablation, defined as an ablation pursued among inpatients hospitalized for a nonprocedural indication.
Methods: Using the National Cardiovascular Data Registry AFib Ablation Registry, patients who underwent AF ablation from January 1, 2016, to June 30, 2023, were stratified by urgent or elective ablation. Factors, trends, and in-hospital complication rates associated with urgent AF ablation were analyzed.
Results: Among 140,051 patients who underwent index AF ablation, 2,714 (1.9%) were conducted as urgent and 137,337 (98.1%) as elective procedures. Those undergoing urgent ablation had higher rates of comorbidities including: diabetes (30.6% vs 20.4%; P < 0.0001), coronary artery disease (30.8% vs 22.7%; P < 0.0001), and heart failure (47.1% vs 20.8%; P < 0.0001). Urgent AF ablation was more often used among Black patients (OR: 1.68; 95% CI: 1.41-2.0) and those presenting to the procedure in AF (OR: 1.73; 95% CI: 1.36-2.20). A higher hospital volume of AF ablations (OR [per 100 cases]: 1.22; 95% CI: 1.20-1.25) was associated with a higher odds of urgent ablation. Urgent AF ablation increased over the study period (0.5% to 2.0%; P < 0.0001) and the adjusted procedure-related complication rate was significantly higher compared with elective ablation (4.9% vs 2.4%; P < 0.0001).
Conclusions: The rate of urgent inpatient AF ablation has increased over time. Compared with elective ablation, patients who underwent urgent AF ablation had more comorbid conditions, particularly heart failure, with a higher rate of risk-adjusted, procedure-related complications.
背景：尽管有常见的心律控制策略，但在住院患者中迫切进行心房颤动（AF）消融的使用和安全性尚未得到充分的描述。目的：本研究旨在描述紧急房颤消融的使用和安全性，定义为住院患者因非程序性指征进行的消融。方法：使用国家心血管数据登记处房颤消融登记，将2016年1月1日至2023年6月30日接受房颤消融的患者按紧急或选择性消融进行分层。分析紧急房颤消融相关的因素、趋势和院内并发症发生率。结果：在140,051例接受指数房颤消融的患者中，2,714例（1.9%）作为紧急手术，137,337例（98.1%）作为选择性手术。接受紧急消融的患者有更高的合并症发生率，包括：糖尿病（30.6% vs 20.4%, P < 0.0001）、冠状动脉疾病（30.8% vs 22.7%, P < 0.0001）和心力衰竭（47.1% vs 20.8%, P < 0.0001）。急诊房颤消融更常用于黑人患者（OR: 1.68; 95% CI: 1.41-2.0）和房颤患者（OR: 1.73; 95% CI: 1.36-2.20）。较高的房颤消融住院量（OR[每100例]:1.22;95% CI: 1.20-1.25）与较高的紧急消融几率相关。在研究期间，紧急房颤消融增加（0.5%至2.0%,P < 0.0001），调整后的手术相关并发症发生率明显高于选择性消融（4.9% vs 2.4%, P < 0.0001）。结论：急诊住院房颤消融率随着时间的推移而增加。与选择性消融相比，接受紧急房颤消融的患者有更多的合并症，特别是心力衰竭，风险调整后的手术相关并发症发生率更高。
{"title":"Use and Safety of Urgent vs Elective Catheter Ablation of Atrial Fibrillation in the United States.","authors":"Amneet Sandhu, Li Qin, Vincenzo B Polsinelli, Karl E Minges, James V Freeman, Sana M Al-Khatib, Adrienne Walker, Steven M Bradley, P Michael Ho, Wendy S Tzou, Paul D Varosy, Paul L Hess","doi":"10.1016/j.jacep.2025.12.030","DOIUrl":"https://doi.org/10.1016/j.jacep.2025.12.030","url":null,"abstract":"<p><strong>Background: </strong>Despite a common rhythm control strategy, use and safety of atrial fibrillation (AF) ablation pursued urgently among inpatients has not been adequately characterized.</p><p><strong>Objectives: </strong>This study sought to describe the use and safety of urgent AF ablation, defined as an ablation pursued among inpatients hospitalized for a nonprocedural indication.</p><p><strong>Methods: </strong>Using the National Cardiovascular Data Registry AFib Ablation Registry, patients who underwent AF ablation from January 1, 2016, to June 30, 2023, were stratified by urgent or elective ablation. Factors, trends, and in-hospital complication rates associated with urgent AF ablation were analyzed.</p><p><strong>Results: </strong>Among 140,051 patients who underwent index AF ablation, 2,714 (1.9%) were conducted as urgent and 137,337 (98.1%) as elective procedures. Those undergoing urgent ablation had higher rates of comorbidities including: diabetes (30.6% vs 20.4%; P < 0.0001), coronary artery disease (30.8% vs 22.7%; P < 0.0001), and heart failure (47.1% vs 20.8%; P < 0.0001). Urgent AF ablation was more often used among Black patients (OR: 1.68; 95% CI: 1.41-2.0) and those presenting to the procedure in AF (OR: 1.73; 95% CI: 1.36-2.20). A higher hospital volume of AF ablations (OR [per 100 cases]: 1.22; 95% CI: 1.20-1.25) was associated with a higher odds of urgent ablation. Urgent AF ablation increased over the study period (0.5% to 2.0%; P < 0.0001) and the adjusted procedure-related complication rate was significantly higher compared with elective ablation (4.9% vs 2.4%; P < 0.0001).</p><p><strong>Conclusions: </strong>The rate of urgent inpatient AF ablation has increased over time. Compared with elective ablation, patients who underwent urgent AF ablation had more comorbid conditions, particularly heart failure, with a higher rate of risk-adjusted, procedure-related complications.</p>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The effect of atrial fibrillation (AF) catheter ablation on neurocognitive function is debated.
Objectives: This study sought to investigate changes in cognitive function and brain imaging after AF ablation.
Methods: Patients undergoing AF catheter ablation were screened. Participants underwent assessments of neurocognitive function using the Cambridge Neuropsychological Test Automated Battery before and 3 and 6 months after ablation. Patients with AF managed by drug therapy served as a control group. A subset of patients underwent brain magnetic resonance imaging before and 6 months after the procedure, where cerebral blood flow (CBF) and bilateral hippocampal volume (HV) were assessed.
Results: One hundred forty-five patients, 94 in the ablation group and 51 in the control group (aged 64 ± 11 years, 70% men, 41% with paroxysmal AF), were studied. Changes in neurocognitive function tests scores were not significantly different between groups. Arrhythmia recurrence and AF type (paroxysmal or persistent) did not significantly affect the outcome. In the magnetic resonance imaging subgroup (51 patients: ablation 42 and control 9), change in CBF (ΔCBF) and proportional change in HV were significantly different between groups (+46 mL/min [IQR: -17 to +111] vs -45 mL/min [IQR: -70 to +9], P = 0.007; +0.1% [IQR: -1.1 to +0.8] vs -1.0% [IQR: -2.0 to +0.1], P = 0.043; for ablation vs control, respectively). Those with ΔCBF more than +35 mL/min had greater improvements in memory and new learning score than those with ΔCBF less than +35 mL/min (+2 [IQR: -0.5 to +5] vs 0 [IQR: -3 to +3], P = 0.048).
Conclusions: In this study, AF ablation did not significantly affect neurocognitive function at the 6-month follow-up. Compared with drug therapy, ablation was associated with greater changes in CBF and HV, and patients with CBF improvement, regardless of treatment assignment, showed improved performance in memory and new learning.
{"title":"Neurocognitive Function, Cerebral Blood Flow, and Hippocampal Volume After Catheter Ablation of Atrial Fibrillation.","authors":"Tasuku Yamamoto, Yoshihide Takahashi, Shunsuke Takagi, Ryo Kitabayashi, Sayuri Ishii, Genichi Sugihara, Jun Oyama, Shinsuke Miyazaki, Masahiko Goya, Akihiro Hirakawa, Hidehiko Takahashi, Tetsuo Sasano","doi":"10.1016/j.jacep.2025.12.037","DOIUrl":"https://doi.org/10.1016/j.jacep.2025.12.037","url":null,"abstract":"<p><strong>Background: </strong>The effect of atrial fibrillation (AF) catheter ablation on neurocognitive function is debated.</p><p><strong>Objectives: </strong>This study sought to investigate changes in cognitive function and brain imaging after AF ablation.</p><p><strong>Methods: </strong>Patients undergoing AF catheter ablation were screened. Participants underwent assessments of neurocognitive function using the Cambridge Neuropsychological Test Automated Battery before and 3 and 6 months after ablation. Patients with AF managed by drug therapy served as a control group. A subset of patients underwent brain magnetic resonance imaging before and 6 months after the procedure, where cerebral blood flow (CBF) and bilateral hippocampal volume (HV) were assessed.</p><p><strong>Results: </strong>One hundred forty-five patients, 94 in the ablation group and 51 in the control group (aged 64 ± 11 years, 70% men, 41% with paroxysmal AF), were studied. Changes in neurocognitive function tests scores were not significantly different between groups. Arrhythmia recurrence and AF type (paroxysmal or persistent) did not significantly affect the outcome. In the magnetic resonance imaging subgroup (51 patients: ablation 42 and control 9), change in CBF (ΔCBF) and proportional change in HV were significantly different between groups (+46 mL/min [IQR: -17 to +111] vs -45 mL/min [IQR: -70 to +9], P = 0.007; +0.1% [IQR: -1.1 to +0.8] vs -1.0% [IQR: -2.0 to +0.1], P = 0.043; for ablation vs control, respectively). Those with ΔCBF more than +35 mL/min had greater improvements in memory and new learning score than those with ΔCBF less than +35 mL/min (+2 [IQR: -0.5 to +5] vs 0 [IQR: -3 to +3], P = 0.048).</p><p><strong>Conclusions: </strong>In this study, AF ablation did not significantly affect neurocognitive function at the 6-month follow-up. Compared with drug therapy, ablation was associated with greater changes in CBF and HV, and patients with CBF improvement, regardless of treatment assignment, showed improved performance in memory and new learning.</p>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-03DOI: 10.1016/j.jacep.2026.01.001
Beatriz Castello-Branco, Bruno Wilnes, Jakub Sroubek, Koji Higuchi, Justin Lee, Ayman Hussein, Walid Saliba, Mohamed Kanj, Tyler Taigen, Arwa Younis, Mandeep Bhargava, Oussama Wazni, André A L Carmo, Pasquale Santangeli
Background: Percutaneous epicardial access has been increasingly adopted in clinical practice, particularly for ventricular tachycardia ablation. "Dry" epicardial puncture (Dry-EPI) carries a considerable risk of access-related complications, even with modified techniques. Pericardial carbon dioxide insufflation (EpiCO2) has emerged as a promising alternative, potentially enhancing safety by increasing anatomical clearance between pericardial layers.
Objectives: This study compared the safety and efficacy of EpiCO2 vs traditional Dry-EPI techniques through systematic review, meta-analysis, and meta-regression.
Methods: PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane databases were searched using medical subject heading terms "epicardial access," "carbon dioxide insufflation," "complications," and similar key words. Random-effects meta-analyses of proportions and means, subgroup analyses, and meta-regressions were conducted.
Results: One hundred nineteen studies (8,784 procedures) were included; most (95.0%) were of moderate or high quality. Ventricular tachycardia ablation was the main access indication (n = 7,178). EpiCO2 was used in 493 procedures (5.6%) and Dry-EPI in 8,291 (94.4%). Among 5,786 Dry-EPI cases with specified needle type, 5,184 (89.6%) used a large-bore needle and 602 (10.4%) a micropuncture needle. EpiCO2 was associated with significantly fewer complications requiring surgery compared with Dry-EPI (0.24% [95% CI: 0.00-0.93] vs 1.55% [95% CI: 1.27-1.86], P < 0.010), large-bore needle (0.24% [95% CI: 0.00%-0.93%] vs 1.58% [95% CI: 1.23-1.97], P < 0.010), and micropuncture (0.24 [95% CI: 0.00-0.93] vs 1.66% [95% CI: 0.60-3.17], P = 0.020). Inadvertent ventricular puncture was also lower with EpiCO2 compared with Dry-EPI (0.28% [95% CI: 0.00-1.00] vs 3.17% [95% CI: 2.36-4.10], P < 0.010).
Conclusions: Compared with Dry-EPI, EpiCO2 was associated with significantly lower risk of inadvertent ventricular puncture and complications requiring surgery, supporting broader clinical adoption.
背景：经皮心外膜通路在临床实践中越来越多地被采用，特别是室性心动过速消融。“干式”心外膜穿刺（Dry- epi）即使采用改良的技术，也有相当大的准入相关并发症风险。心包二氧化碳注入（EpiCO2）已成为一种有希望的替代方法，通过增加心包层之间的解剖间隙，可能提高安全性。目的：本研究通过系统评价、meta分析和meta回归比较了EpiCO2与传统Dry-EPI技术的安全性和有效性。方法：检索PubMed/MEDLINE、Embase、Scopus、Web of Science和Cochrane数据库，使用医学主题词“心外膜通路”、“二氧化碳吸入”、“并发症”和类似关键词。进行了随机效应的比例和均值荟萃分析、亚组分析和荟萃回归。结果：纳入了119项研究（8,784例手术）；大多数（95.0%）为中等或高质量。室性心动过速消融是主要的适应症（n = 7178）。EpiCO2用于493例（5.6%），Dry-EPI用于8291例（94.4%）。5786例指定针型的Dry-EPI病例中，5184例（89.6%）使用大孔针，602例（10.4%）使用微孔针。与Dry-EPI （0.24% [95% CI: 0.00-0.93] vs 1.55% [95% CI: 1.27-1.86], P < 0.010）、大孔径针头（0.24% [95% CI: 0.00- 0.93%] vs 1.58% [95% CI: 1.23-1.97], P < 0.010）和微穿刺（0.24 [95% CI: 0.00-0.93] vs 1.66% [95% CI: 0.60-3.17], P = 0.020）相比，EpiCO2需要手术的并发症明显减少。与Dry-EPI相比，使用EpiCO2的意外心室穿刺率也较低（0.28% [95% CI: 0.00-1.00] vs 3.17% [95% CI: 2.36-4.10], P < 0.010）。结论：与Dry-EPI相比，EpiCO2与意外心室穿刺和需要手术的并发症的风险显著降低相关，支持更广泛的临床应用。
{"title":"Safety of Carbon Dioxide-Facilitated vs Conventional Epicardial Access: Systematic Review and Meta-Analysis.","authors":"Beatriz Castello-Branco, Bruno Wilnes, Jakub Sroubek, Koji Higuchi, Justin Lee, Ayman Hussein, Walid Saliba, Mohamed Kanj, Tyler Taigen, Arwa Younis, Mandeep Bhargava, Oussama Wazni, André A L Carmo, Pasquale Santangeli","doi":"10.1016/j.jacep.2026.01.001","DOIUrl":"https://doi.org/10.1016/j.jacep.2026.01.001","url":null,"abstract":"<p><strong>Background: </strong>Percutaneous epicardial access has been increasingly adopted in clinical practice, particularly for ventricular tachycardia ablation. \"Dry\" epicardial puncture (Dry-EPI) carries a considerable risk of access-related complications, even with modified techniques. Pericardial carbon dioxide insufflation (EpiCO<sub>2</sub>) has emerged as a promising alternative, potentially enhancing safety by increasing anatomical clearance between pericardial layers.</p><p><strong>Objectives: </strong>This study compared the safety and efficacy of EpiCO<sub>2</sub> vs traditional Dry-EPI techniques through systematic review, meta-analysis, and meta-regression.</p><p><strong>Methods: </strong>PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane databases were searched using medical subject heading terms \"epicardial access,\" \"carbon dioxide insufflation,\" \"complications,\" and similar key words. Random-effects meta-analyses of proportions and means, subgroup analyses, and meta-regressions were conducted.</p><p><strong>Results: </strong>One hundred nineteen studies (8,784 procedures) were included; most (95.0%) were of moderate or high quality. Ventricular tachycardia ablation was the main access indication (n = 7,178). EpiCO<sub>2</sub> was used in 493 procedures (5.6%) and Dry-EPI in 8,291 (94.4%). Among 5,786 Dry-EPI cases with specified needle type, 5,184 (89.6%) used a large-bore needle and 602 (10.4%) a micropuncture needle. EpiCO<sub>2</sub> was associated with significantly fewer complications requiring surgery compared with Dry-EPI (0.24% [95% CI: 0.00-0.93] vs 1.55% [95% CI: 1.27-1.86], P < 0.010), large-bore needle (0.24% [95% CI: 0.00%-0.93%] vs 1.58% [95% CI: 1.23-1.97], P < 0.010), and micropuncture (0.24 [95% CI: 0.00-0.93] vs 1.66% [95% CI: 0.60-3.17], P = 0.020). Inadvertent ventricular puncture was also lower with EpiCO<sub>2</sub> compared with Dry-EPI (0.28% [95% CI: 0.00-1.00] vs 3.17% [95% CI: 2.36-4.10], P < 0.010).</p><p><strong>Conclusions: </strong>Compared with Dry-EPI, EpiCO<sub>2</sub> was associated with significantly lower risk of inadvertent ventricular puncture and complications requiring surgery, supporting broader clinical adoption.</p>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Electrocardiographic Patterns and Ablation Approaches in Ventricular Arrhythmias Arising From the Inferoseptal Process of the Left Ventricle.","authors":"Ryuichi Usui, Yuka Oda, Yuki Komatsu, Kikuya Uno, Akihiko Nogami","doi":"10.1016/j.jacep.2026.01.004","DOIUrl":"https://doi.org/10.1016/j.jacep.2026.01.004","url":null,"abstract":"","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-20DOI: 10.1016/j.jacep.2025.09.041
Andreas A. Boehmer MD , Moritz Rothe MD , Jason G. Andrade MD , Lilli Wiedenmann BSc , Pascal Spork BSc , Katia Y. Schneider BSc , Elena Nussbaum BSc , Christoph Keim MD , Peter Weiss MD , Bianca C. Dobre MD , Sebastian Feickert MD , Christian Ruckes PhD , Katia Dyrda MD , Bernhard M. Kaess MD , Stanley Nattel MD , Joachim R. Ehrlich MD
Background
Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) are both associated with increased morbidity and mortality. Ablation-based rhythm control, particularly using radiofrequency ablation with disparate strategies, has demonstrated clinical benefit. However, prospective data evaluating a pulmonary vein isolation (PVI)-only strategy in HFrEF are lacking, and no studies have directly compared ablation efficacy between patients with and without HFrEF.
Objectives
This study sought to assess whether a PVI-only approach using cryoballoon ablation in patients with HFrEF (LVEF ≤40%) is noninferior to PVI-only in patients without HFrEF regarding rhythm control efficacy, and to describe safety outcomes.
Methods
We conducted a prospective, investigator-initiated, single-center, noninferiority, observational study with propensity score matching. The primary efficacy endpoint was the first documented recurrence of any atrial arrhythmia after a 90-day blanking period. Safety endpoints included death, cerebrovascular events, and procedure-related adverse events.
Results
A total of 1,420 patients (paroxysmal and persistent AF) underwent PVI. With propensity score matching, 1,044 patients were analyzed in a 1:5 ratio. Over a mean follow-up of 2 years, the primary efficacy endpoint occurred in 76 (43.7%) of 174 patients with HFrEF and in 379 (43.6%) of 870 without HFrEF (HR: 1.01; 95% CI: −∞ to 1.24; P = 0.005 for noninferiority). The incidence of all-cause mortality was numerically higher in patients with HFrEF (6.3% vs 3.4%; P = 0.07), while rates of procedure-related safety events were similar between groups (2.9% vs 4.1%; P = 0.53).
Conclusions
In patients with AF undergoing ablation, a PVI-only approach shows noninferior rhythm control efficacy and comparable procedural safety in patients with HFrEF compared with those without HFrEF. (Cryoballoon Pulmonary Isolation for Atrial Fibrillation With Heart Failure [POLAR-HF]; NCT04461691)
背景：心房颤动（AF）和心力衰竭伴射血分数降低（HFrEF）都与发病率和死亡率增加相关。以消融为基础的节律控制，特别是使用不同策略的射频消融，已经证明了临床益处。然而，评估仅肺静脉隔离（PVI）治疗HFrEF策略的前瞻性数据缺乏，也没有研究直接比较有和无HFrEF患者的消融疗效。目的：本研究旨在评估在HFrEF （LVEF≤40%）患者中使用低温球囊消融的纯pvi方法在节律控制效果方面是否优于非HFrEF患者的纯pvi方法，并描述安全性结果。方法：我们进行了一项前瞻性、研究者发起、单中心、非劣效性、倾向评分匹配的观察性研究。主要疗效终点是在90天的空白期后首次记录的任何心房心律失常复发。安全性终点包括死亡、脑血管事件和手术相关不良事件。结果：共有1420例（阵发性和持续性房颤）患者接受了PVI治疗。倾向评分匹配，1044例患者以1:5的比例进行分析。在平均2年的随访中，174例HFrEF患者中有76例（43.7%）出现主要疗效终点，870例无HFrEF患者中有379例（43.6%）出现主要疗效终点（HR: 1.01； 95% CI: -∞至1.24；非劣效性P < 0.001）。HFrEF患者的全因死亡率在数字上更高（6.3% vs 3.4%; P = 0.07），而手术相关安全事件的发生率在两组之间相似（2.9% vs 4.1%; P = 0.53）。结论：在接受消融治疗的房颤患者中，与无HFrEF的患者相比，HFrEF患者仅采用pvi入路具有良好的心律控制效果和相当的手术安全性。低温球囊肺隔离治疗心房颤动合并心力衰竭[极地hf]； contemporary medicine; 2011 - 12
{"title":"Pulmonary Vein Isolation Only for Atrial Fibrillation With Heart Failure (POLAR-HF)","authors":"Andreas A. Boehmer MD , Moritz Rothe MD , Jason G. Andrade MD , Lilli Wiedenmann BSc , Pascal Spork BSc , Katia Y. Schneider BSc , Elena Nussbaum BSc , Christoph Keim MD , Peter Weiss MD , Bianca C. Dobre MD , Sebastian Feickert MD , Christian Ruckes PhD , Katia Dyrda MD , Bernhard M. Kaess MD , Stanley Nattel MD , Joachim R. Ehrlich MD","doi":"10.1016/j.jacep.2025.09.041","DOIUrl":"10.1016/j.jacep.2025.09.041","url":null,"abstract":"<div><h3>Background</h3><div>Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) are both associated with increased morbidity and mortality. Ablation-based rhythm control, particularly using radiofrequency ablation with disparate strategies, has demonstrated clinical benefit. However, prospective data evaluating a pulmonary vein isolation (PVI)-only strategy in HFrEF are lacking, and no studies have directly compared ablation efficacy between patients with and without HFrEF.</div></div><div><h3>Objectives</h3><div>This study sought to assess whether a PVI-only approach using cryoballoon ablation in patients with HFrEF (LVEF ≤40%) is noninferior to PVI-only in patients without HFrEF regarding rhythm control efficacy, and to describe safety outcomes.</div></div><div><h3>Methods</h3><div>We conducted a prospective, investigator-initiated, single-center, noninferiority, observational study with propensity score matching. The primary efficacy endpoint was the first documented recurrence of any atrial arrhythmia after a 90-day blanking period. Safety endpoints included death, cerebrovascular events, and procedure-related adverse events.</div></div><div><h3>Results</h3><div>A total of 1,420 patients (paroxysmal and persistent AF) underwent PVI. With propensity score matching, 1,044 patients were analyzed in a 1:5 ratio. Over a mean follow-up of 2 years, the primary efficacy endpoint occurred in 76 (43.7%) of 174 patients with HFrEF and in 379 (43.6%) of 870 without HFrEF (HR: 1.01; 95% CI: −∞ to 1.24; <em>P</em> = 0.005 for noninferiority). The incidence of all-cause mortality was numerically higher in patients with HFrEF (6.3% vs 3.4%; <em>P =</em> 0.07), while rates of procedure-related safety events were similar between groups (2.9% vs 4.1%; <em>P =</em> 0.53).</div></div><div><h3>Conclusions</h3><div>In patients with AF undergoing ablation, a PVI-only approach shows noninferior rhythm control efficacy and comparable procedural safety in patients with HFrEF compared with those without HFrEF. (Cryoballoon Pulmonary Isolation for Atrial Fibrillation With Heart Failure [POLAR-HF]; <span><span>NCT04461691</span><svg><path></path></svg></span>)</div></div>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":"12 2","pages":"Pages 264-273"},"PeriodicalIF":7.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-24DOI: 10.1016/j.jacep.2025.10.005
Raquel Neves MD , Lia Crotti MD, PhD , Sahej Bains BS , J. Martijn Bos MD, PhD , Dan Ye MD , Federica Dagradi MD , Giulia Musu BSc , Federica Spiezia MD , Matteo Pedrazzini BSc , Fulvio L.F. Giovenzana MD , Paolo Cerea MD , John R. Giudicessi MD, PhD , Peter J. Schwartz MD, FHRS , Michael J. Ackerman MD, PhD
Background
Pathogenic/likely pathogenic variants in the KCNH2-encoded Kv11.1 potassium channel cause type 2 long QT syndrome (LQT2). Despite the updated 2015 American College of Medical Genetics (ACMG) variant interpretation guidelines, the burden of KCNH2 variants of uncertain significance (VUS) in patients evaluated for long QT syndrome (LQTS) remains ∼30%. Previously, we developed and validated phenotype-enhanced (PE) ACMG variant adjudication for type 1 long QT syndrome.
Objectives
The purpose of this study was to determine whether a PE-ACMG variant classification approach can reduce the VUS burden in patients with clinically suspected LQT2.
Methods
Retrospective analysis was performed on 209 unique missense variants within KCNH2 from 2 LQTS specialty centers. Each variant was categorized based on the classification on the initial genetic test reports. Subsequently, all VUS were re-adjudicated with the use of a PE-ACMG framework that incorporates the patient’s phenotype using the LQTS clinical diagnostic Schwartz score plus 2 LQT2-defining features: 1) biphasic/notches T waves; and 2) LQTS-triggered events during emotional stress or auditory stimuli.
Results
In total, 69/209 (33%) unique KCNH2 variants were classified as VUS based on their initial genetic test report. Mean Schwartz score for patients with a VUS was 3.6, and 41 patients (29%) had a score over 3.5. After PE-ACMG adjudication, 31/69 variants (45%) were upgraded to pathogenic, 18 (26%) to likely pathogenic, and 11 (16%) were downgraded to benign variants. Only 9 of 69 variants (13%) remained VUS. Overall, the VUS burden decreased from 69 of 209 (33%) to 9/209 (4%; P < 0.0001).
Conclusions
Phenotype-guided variant adjudication significantly decreased the VUS burden of LQT2 case–derived KCNH2 missense variants from 2 LQTS specialty centers. There is clear value in incorporating LQT2-specific phenotype/clinical data to aid in the interpretation of KCNH2 missense variants identified during LQTS genetic testing, thereby facilitating prompt initiation of LQT2-guided therapy and cascade testing of appropriate relatives.
{"title":"A Phenotype-Enhanced Variant Classification Framework to Decrease the Burden of Variants of Uncertain Significance in Type 2 Long QT Syndrome","authors":"Raquel Neves MD , Lia Crotti MD, PhD , Sahej Bains BS , J. Martijn Bos MD, PhD , Dan Ye MD , Federica Dagradi MD , Giulia Musu BSc , Federica Spiezia MD , Matteo Pedrazzini BSc , Fulvio L.F. Giovenzana MD , Paolo Cerea MD , John R. Giudicessi MD, PhD , Peter J. Schwartz MD, FHRS , Michael J. Ackerman MD, PhD","doi":"10.1016/j.jacep.2025.10.005","DOIUrl":"10.1016/j.jacep.2025.10.005","url":null,"abstract":"<div><h3>Background</h3><div>Pathogenic/likely pathogenic variants in the <em>KCNH2</em>-encoded Kv11.1 potassium channel cause type 2 long QT syndrome (LQT2). Despite the updated 2015 American College of Medical Genetics (ACMG) variant interpretation guidelines, the burden of KCNH2 variants of uncertain significance (VUS) in patients evaluated for long QT syndrome (LQTS) remains ∼30%. Previously, we developed and validated phenotype-enhanced (PE) ACMG variant adjudication for type 1 long QT syndrome.</div></div><div><h3>Objectives</h3><div>The purpose of this study was to determine whether a PE-ACMG variant classification approach can reduce the VUS burden in patients with clinically suspected LQT2.</div></div><div><h3>Methods</h3><div>Retrospective analysis was performed on 209 unique missense variants within <em>KCNH2</em> from 2 LQTS specialty centers. Each variant was categorized based on the classification on the initial genetic test reports. Subsequently, all VUS were re-adjudicated with the use of a PE-ACMG framework that incorporates the patient’s phenotype using the LQTS clinical diagnostic Schwartz score plus 2 LQT2-defining features: 1) biphasic/notches T waves; and 2) LQTS-triggered events during emotional stress or auditory stimuli.</div></div><div><h3>Results</h3><div>In total, 69/209 (33%) unique KCNH2 variants were classified as VUS based on their initial genetic test report. Mean Schwartz score for patients with a VUS was 3.6, and 41 patients (29%) had a score over 3.5. After PE-ACMG adjudication, 31/69 variants (45%) were upgraded to pathogenic, 18 (26%) to likely pathogenic, and 11 (16%) were downgraded to benign variants. Only 9 of 69 variants (13%) remained VUS. Overall, the VUS burden decreased from 69 of 209 (33%) to 9/209 (4%; <em>P</em> < 0.0001).</div></div><div><h3>Conclusions</h3><div>Phenotype-guided variant adjudication significantly decreased the VUS burden of LQT2 case–derived KCNH2 missense variants from 2 LQTS specialty centers. There is clear value in incorporating LQT2-specific phenotype/clinical data to aid in the interpretation of <em>KCNH2</em> missense variants identified during LQTS genetic testing, thereby facilitating prompt initiation of LQT2-guided therapy and cascade testing of appropriate relatives.</div></div>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":"12 2","pages":"Pages 350-359"},"PeriodicalIF":7.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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