Pub Date : 2025-12-01DOI: 10.1016/j.jacep.2025.07.018
Pranav Rekapalli MD , Alireza Oraii MD , Jonathan Heintz MS , Sanjay Dixit MD , Andrew E. Epstein MD , David S. Frankel MD , Matthew Hyman MD, PhD , David Lin MD , Timothy Markman MD , Steven R. Messé MD , Saman Nazarian MD, PhD , Brett Cucchiara MD , Robert D. Schaller DO , Vincent Y. See MD , Wei Yang PhD , Scott E. Kasner MD , Francis E. Marchlinski MD , Rajat Deo MD, MTR
Background
Clinical guidelines recommend cardiac rhythm monitoring in post-stroke patients.
Objectives
This study sought to assess the prevalence and significance of nonsustained ventricular tachycardia (NSVT) in patients who have had an ischemic stroke or transient ischemic attack (TIA).
Methods
The CAMPS (Cardiac Ambulatory Monitoring Post Stroke) study was composed of post-stroke or TIA patients who were referred for ambulatory cardiac rhythm monitoring. Between 2019 and 2023, 752 patients completed cardiac monitoring within 1 year of the ischemic event. We evaluated the association between the presence of NSVT and the risk of subsequent stroke, cardiac events, or death.
Results
Patients were monitored for a mean of 19 ± 7 days, and NSVT was observed in 164 patients (22%). Compared with patients who did not have NSVT, those with NSVT were older, more likely to be male, smoke, and have a higher prevalence of coronary heart disease. Patients with NSVT had a higher risk of subsequent stroke (HR: 2.65; 95% CI: [1.74-4.02]), cardiac events (HR: 2.25; 95% CI: [1.40-3.64]), and death (HR: 1.87; 95% CI: [1.12-3.15]). These estimates remained significant after adjustment for demographics and clinical factors: subsequent stroke (HR: 2.50; 95% CI: [1.59-3.93]), cardiac events (HR: 1.86; 95% CI: [1.11-3.11]), and death (HR: 1.90; 95% CI: [1.09-3.31]). In this exploratory analysis, a higher NSVT burden was associated with increased risk of adverse events.
Conclusions
NSVT in patients with recent stroke or TIA is independently associated with a 2- to 3-fold increased risk of subsequent stroke, cardiac events, and death after controlling for demographics and clinical factors.
{"title":"Detection and Significance of Nonsustained Ventricular Tachycardia in a Post-Stroke Population","authors":"Pranav Rekapalli MD , Alireza Oraii MD , Jonathan Heintz MS , Sanjay Dixit MD , Andrew E. Epstein MD , David S. Frankel MD , Matthew Hyman MD, PhD , David Lin MD , Timothy Markman MD , Steven R. Messé MD , Saman Nazarian MD, PhD , Brett Cucchiara MD , Robert D. Schaller DO , Vincent Y. See MD , Wei Yang PhD , Scott E. Kasner MD , Francis E. Marchlinski MD , Rajat Deo MD, MTR","doi":"10.1016/j.jacep.2025.07.018","DOIUrl":"10.1016/j.jacep.2025.07.018","url":null,"abstract":"<div><h3>Background</h3><div>Clinical guidelines recommend cardiac rhythm monitoring in post-stroke patients.</div></div><div><h3>Objectives</h3><div>This study sought to assess the prevalence and significance of nonsustained ventricular tachycardia (NSVT) in patients who have had an ischemic stroke or transient ischemic attack (TIA).</div></div><div><h3>Methods</h3><div>The CAMPS (Cardiac Ambulatory Monitoring Post Stroke) study was composed of post-stroke or TIA patients who were referred for ambulatory cardiac rhythm monitoring. Between 2019 and 2023, 752 patients completed cardiac monitoring within 1 year of the ischemic event. We evaluated the association between the presence of NSVT and the risk of subsequent stroke, cardiac events, or death.</div></div><div><h3>Results</h3><div>Patients were monitored for a mean of 19 ± 7 days, and NSVT was observed in 164 patients (22%). Compared with patients who did not have NSVT, those with NSVT were older, more likely to be male, smoke, and have a higher prevalence of coronary heart disease. Patients with NSVT had a higher risk of subsequent stroke (HR: 2.65; 95% CI: [1.74-4.02]), cardiac events (HR: 2.25; 95% CI: [1.40-3.64]), and death (HR: 1.87; 95% CI: [1.12-3.15]). These estimates remained significant after adjustment for demographics and clinical factors: subsequent stroke (HR: 2.50; 95% CI: [1.59-3.93]), cardiac events (HR: 1.86; 95% CI: [1.11-3.11]), and death (HR: 1.90; 95% CI: [1.09-3.31]). In this exploratory analysis, a higher NSVT burden was associated with increased risk of adverse events.</div></div><div><h3>Conclusions</h3><div>NSVT in patients with recent stroke or TIA is independently associated with a 2- to 3-fold increased risk of subsequent stroke, cardiac events, and death after controlling for demographics and clinical factors.</div></div>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":"11 12","pages":"Pages 2647-2655"},"PeriodicalIF":7.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040199","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 : 2025-12-01DOI: 10.1016/j.jacep.2025.07.014
Matteo Castrichini MD , Raquel Neves MD , Ramin Garmany PhD , Thomas Allison PhD , Michael J. Ackerman MD, PhD , John R. Giudicessi MD, PhD
Background
Arrhythmogenic cardiomyopathy (ACM) is characterized by fibrofatty myocardial replacement and increased arrhythmic risk. Although exercise exacerbates desmosomal ACM, the prognostic significance of arrhythmias during exercise stress tests (ESTs) remains unclear.
Objectives
The goal of this study was to determine the impact of ventricular arrhythmia observed during peak exercise and/or recovery EST phases on the risk of major ventricular arrhythmia (MVA) events in patients with desmosomal ACM.
Methods
A retrospective review of 904 patients with ACM was used to identify those with a pathogenic/likely pathogenic variant in DSC2, DSG2, DSP, JUP, and PKP2. After exclusion of patients with no EST data, demographic and electrocardiographic data were extracted from the medical record. The arrhythmic burden (premature ventricular complexes [PVCs], couplet, bigeminy, nonsustained VT, sustained VT, ventricular fibrillation, and PVCs per minute) during each EST phase (baseline, peak, and early and late recovery) were reviewed and correlated with MVA outcomes (sudden cardiac arrest, sustained VT, and appropriate implantable cardioverter-defibrillator therapies).
Results
A total of 326 ESTs from 147 patients (89 PKP2 [60%], 45 DSP [31%], 10 DSG2 [7%], and 3 DSC2 [2%]) were included. PKP2-ACM patients exhibited increased PVCs per minute (P < 0.001), bigeminy (P < 0.001), couplets (P < 0.001), and nonsustained VT (P < 0.001) during recovery. Recovery phase arrhythmias in PKP2-ACM patients were associated with a higher risk of MVA events (HR: 10.580; P = 0.003), a pattern absent in other genotypes (HR: 1.037; P = 0.973). This association remained significant in multivariable analysis (adjusted HR: 3.851; P = 0.040).
Conclusions
PKP2-ACM patients display a distinct recovery phase arrhythmic profile predictive of MVA events, emphasizing the importance of EST in risk stratification and management. Future studies are needed to validate these findings and ascertain the additive value of EST beyond established risk factors.
背景：心律失常性心肌病（ACM）以纤维脂肪心肌替代和心律失常风险增加为特征。尽管运动加剧了桥粒体ACM，但运动应激试验（ESTs）中心律失常的预后意义尚不清楚。目的：本研究的目的是确定在运动高峰和/或EST恢复期观察到的室性心律失常对桥粒体ACM患者发生主要室性心律失常（MVA）事件的影响。方法：对904例ACM患者进行回顾性分析，以确定DSC2、DSG2、DSP、JUP和PKP2的致病/可能致病变异。在排除无EST数据的患者后，从病历中提取人口统计学和心电图数据。每个EST阶段（基线、峰值、早期和晚期恢复）的心律失常负荷（室性早搏、室性早搏、双相、非持续性室性心动过速、室性颤动和每分钟室性早搏）与MVA结果（心脏骤停、持续性室性心动过速和适当的植入式心律转复除颤器治疗）相关。结果：147例患者共纳入326条ESTs （PKP2 89条[60%]，DSP 45条[31%]，DSG2 10条[7%]，DSC2 3条[2%]）。PKP2-ACM患者在恢复期间表现为每分钟室性早搏数增加（P < 0.001）、双心室（P < 0.001）、联心室（P < 0.001）和非持续性VT （P < 0.001）。PKP2-ACM患者的恢复期心律失常与MVA事件的高风险相关（HR: 10.580; P = 0.003），其他基因型患者没有这种模式（HR: 1.037; P = 0.973）。在多变量分析中，这种关联仍然显著（调整后的HR: 3.851; P = 0.040）。结论：PKP2-ACM患者表现出明显的恢复期心律失常特征，可预测MVA事件，强调EST在风险分层和管理中的重要性。未来的研究需要验证这些发现，并确定EST的附加价值超出既定的危险因素。
{"title":"Diagnostic and Prognostic Significance of Exercise Stress Testing in Desmosomal Arrhythmogenic Cardiomyopathy","authors":"Matteo Castrichini MD , Raquel Neves MD , Ramin Garmany PhD , Thomas Allison PhD , Michael J. Ackerman MD, PhD , John R. Giudicessi MD, PhD","doi":"10.1016/j.jacep.2025.07.014","DOIUrl":"10.1016/j.jacep.2025.07.014","url":null,"abstract":"<div><h3>Background</h3><div>Arrhythmogenic cardiomyopathy (ACM) is characterized by fibrofatty myocardial replacement and increased arrhythmic risk. Although exercise exacerbates desmosomal ACM, the prognostic significance of arrhythmias during exercise stress tests (ESTs) remains unclear.</div></div><div><h3>Objectives</h3><div>The goal of this study was to determine the impact of ventricular arrhythmia observed during peak exercise and/or recovery EST phases on the risk of major ventricular arrhythmia (MVA) events in patients with desmosomal ACM.</div></div><div><h3>Methods</h3><div>A retrospective review of 904 patients with ACM was used to identify those with a pathogenic/likely pathogenic variant in <em>DSC2</em>, <em>DSG2</em>, <em>DSP</em>, <em>JUP</em>, and <em>PKP2</em>. After exclusion of patients with no EST data, demographic and electrocardiographic data were extracted from the medical record. The arrhythmic burden (premature ventricular complexes [PVCs], couplet, bigeminy, nonsustained VT, sustained VT, ventricular fibrillation, and PVCs per minute) during each EST phase (baseline, peak, and early and late recovery) were reviewed and correlated with MVA outcomes (sudden cardiac arrest, sustained VT, and appropriate implantable cardioverter-defibrillator therapies).</div></div><div><h3>Results</h3><div>A total of 326 ESTs from 147 patients (89 PKP2 [60%], 45 DSP [31%], 10 DSG2 [7%], and 3 DSC2 [2%]) were included. PKP2-ACM patients exhibited increased PVCs per minute (<em>P</em> < 0.001), bigeminy (<em>P</em> < 0.001), couplets (<em>P</em> < 0.001), and nonsustained VT (<em>P</em> < 0.001) during recovery. Recovery phase arrhythmias in PKP2-ACM patients were associated with a higher risk of MVA events (HR: 10.580; <em>P</em> = 0.003), a pattern absent in other genotypes (HR: 1.037; <em>P</em> = 0.973). This association remained significant in multivariable analysis (adjusted HR: 3.851; <em>P</em> = 0.040).</div></div><div><h3>Conclusions</h3><div>PKP2-ACM patients display a distinct recovery phase arrhythmic profile predictive of MVA events, emphasizing the importance of EST in risk stratification and management. Future studies are needed to validate these findings and ascertain the additive value of EST beyond established risk factors.</div></div>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":"11 12","pages":"Pages 2633-2643"},"PeriodicalIF":7.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000491","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 : 2025-12-01DOI: 10.1016/j.jacep.2025.07.015
Thomas A. Dewland MD , David G. Rosenthal MD , Edward P. Gerstenfeld MD , Melvin M. Scheinman MD , Alvaro Alonso MD, PhD , Elsayed Z. Soliman MD, MS , Lin Yee Chen MBBS, MS , David S. Siscovick MD, MPH , Nona Sotoodehnia MD , John S. Gottdiener MD , Bruce M. Psaty MD, PhD , Susan R. Heckbert MD, PhD , Phyllis K. Stein PhD , Gregory M. Marcus MD, MAS
Background
The anatomical distribution of spontaneous ventricular ectopy and the risk of heart failure associated with premature ventricular contraction (PVC) location has not been studied outside the narrow group of individuals presenting for arrhythmia-related clinical care.
Objectives
This study sought to describe the epidemiology of PVC site of origin and to determine whether PVC anatomical location is independently associated with incident heart failure risk.
Methods
Ambulatory adults without prevalent heart failure were identified from the CHS (Cardiovascular Health Study) and the ARIC (Atherosclerosis Risk in Communities Study) cohorts. Anatomical PVC location was assessed by 2 expert reviewers using baseline 12-lead electrocardiogram (ECG) morphology.
Results
Among 20,590 participants, 427 (2.1%) demonstrated at least 1 PVC on baseline ECG. Ventricular ectopy was localized to the left ventricle in 49% of participants, outflow tract in 27%, right ventricle in 22%, and epicardium in 2%. Over a mean follow-up of 19.2 years, ventricular ectopy on baseline ECG was associated with an increased adjusted risk of heart failure (HR: 1.43; 95% CI: 1.20 to 1.70; P < 0.001). Adjusted risk of incident heart failure was highest for PVCs arising from the epicardium (HR: 2.98; 95% CI: 1.12 to 7.95; P = 0.029) and the left ventricle (HR: 1.59; 95% CI: 1.30 to 1.94; P < 0.001).
Conclusions
In a large population-based cohort, ventricular ectopy was most frequently localized to the left ventricle. Individuals with ectopy arising from the left ventricle and from epicardial locations experienced a higher likelihood of incident heart failure compared with those without PVCs or those with PVCs from other locations.
背景：自发性室性异位的解剖分布以及与室性早搏（PVC）位置相关的心力衰竭风险，除了接受心律失常相关临床护理的狭窄人群外，尚未得到研究。目的：本研究旨在描述PVC起源部位的流行病学，并确定PVC解剖位置是否与发生心力衰竭的风险独立相关。方法：从CHS（心血管健康研究）和ARIC（社区动脉粥样硬化风险研究）队列中确定无普遍心力衰竭的门诊成年人。2位专家使用基线12导联心电图（ECG）形态学评估解剖性PVC位置。结果：在20,590名参与者中，427名（2.1%）在基线心电图上显示至少1例PVC。49%的参与者发生左心室异位，27%发生外流道，22%发生右心室，2%发生心外膜。在平均19.2年的随访中，基线心电图上的心室异位与心力衰竭调整风险增加相关（HR: 1.43; 95% CI: 1.20 ~ 1.70; P < 0.001）。心外膜（HR: 2.98; 95% CI: 1.12 ~ 7.95; P = 0.029）和左心室（HR: 1.59; 95% CI: 1.30 ~ 1.94; P < 0.001）引起的室性早搏发生心力衰竭的调整后风险最高。结论：在一个以人群为基础的队列中，心室异位最常局限于左心室。与没有室性早搏或其他部位室性早搏的患者相比，左心室和心外膜位置异位的患者发生心力衰竭的可能性更高。
{"title":"Premature Ventricular Contraction Location and Incident Heart Failure","authors":"Thomas A. Dewland MD , David G. Rosenthal MD , Edward P. Gerstenfeld MD , Melvin M. Scheinman MD , Alvaro Alonso MD, PhD , Elsayed Z. Soliman MD, MS , Lin Yee Chen MBBS, MS , David S. Siscovick MD, MPH , Nona Sotoodehnia MD , John S. Gottdiener MD , Bruce M. Psaty MD, PhD , Susan R. Heckbert MD, PhD , Phyllis K. Stein PhD , Gregory M. Marcus MD, MAS","doi":"10.1016/j.jacep.2025.07.015","DOIUrl":"10.1016/j.jacep.2025.07.015","url":null,"abstract":"<div><h3>Background</h3><div>The anatomical distribution of spontaneous ventricular ectopy and the risk of heart failure associated with premature ventricular contraction (PVC) location has not been studied outside the narrow group of individuals presenting for arrhythmia-related clinical care.</div></div><div><h3>Objectives</h3><div>This study sought to describe the epidemiology of PVC site of origin and to determine whether PVC anatomical location is independently associated with incident heart failure risk.</div></div><div><h3>Methods</h3><div>Ambulatory adults without prevalent heart failure were identified from the CHS (Cardiovascular Health Study) and the ARIC (Atherosclerosis Risk in Communities Study) cohorts. Anatomical PVC location was assessed by 2 expert reviewers using baseline 12-lead electrocardiogram (ECG) morphology.</div></div><div><h3>Results</h3><div>Among 20,590 participants, 427 (2.1%) demonstrated at least 1 PVC on baseline ECG. Ventricular ectopy was localized to the left ventricle in 49% of participants, outflow tract in 27%, right ventricle in 22%, and epicardium in 2%. Over a mean follow-up of 19.2 years, ventricular ectopy on baseline ECG was associated with an increased adjusted risk of heart failure (HR: 1.43; 95% CI: 1.20 to 1.70; <em>P</em> < 0.001). Adjusted risk of incident heart failure was highest for PVCs arising from the epicardium (HR: 2.98; 95% CI: 1.12 to 7.95; <em>P</em> = 0.029) and the left ventricle (HR: 1.59; 95% CI: 1.30 to 1.94; <em>P</em> < 0.001).</div></div><div><h3>Conclusions</h3><div>In a large population-based cohort, ventricular ectopy was most frequently localized to the left ventricle. Individuals with ectopy arising from the left ventricle and from epicardial locations experienced a higher likelihood of incident heart failure compared with those without PVCs or those with PVCs from other locations.</div></div>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":"11 12","pages":"Pages 2623-2632"},"PeriodicalIF":7.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080614","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}
Patients who have an ischemic stroke (IS) with an oral anticoagulant (OAC) have a high recurrence rate of IS. There is insufficient data on left atrial appendage closure (LAAC) for patients with nonvalvular atrial fibrillation (AF) who have had an IS despite OAC.
Objectives
The objectives of this study were to compare the clinical outcomes of the patients after LAAC based on IS risk.
Methods
This study was retrospective observational study from the OCEAN-LAAC (Optimized Catheter Valvular Intervention–Left Atrial Appendage Closure) registry. Nonvalvular AF patients who underwent LAAC were divided into 3 groups: a control group with no IS history, a group having a previous IS despite an OAC, and a group having a previous IS without OAC. The coprimary endpoints were cardiovascular (CV) death and IS.
Results
We included 1,418 patients (median CHA2DS2-VASc 5.0, HAS-BLED 3.0) undergoing LAAC. The previous history of IS was noted in 503 (35.4%), and 346 patients were under an OAC. During the median follow-up period of 367 days, no differences in CV death rate were observed among the 3 groups (previous IS despite OAC, subdistribution HR [sHR]: 1.78; 95% CI: 0.87-3.64; previous IS without OAC, sHR: 1.45; 95% CI: 0.59-3.55). The incidence of IS after LAAC was predominantly higher in the previous IS despite OAC group (sHR: 2.62; 95% CI: 1.17-5.86; Gray’s test: P = 0.02; previous IS without OAC: sHR: 1.24; 95% CI: 0.36-4.28; Gray’s test: P = 0.70).
Conclusions
The patients after LAAC who have had an IS despite OAC did not differ in CV death but were at higher risk of IS even after LAAC.
{"title":"Left Atrial Appendage Closure for Patients With a History of Ischemic Stroke Despite Oral Anticoagulant","authors":"Tadatomo Fukushima MD , Masato Fukunaga MD , Akihiro Isotani MD , Miho Nakamura MD , Kenichi Ishizu MD , Shinichi Shirai MD , Masahiko Asami MD , Mitsuru Sago MD , Shuhei Tanaka MD , Ryuki Chatani MD , Daisuke Hachinohe MD , Toru Naganuma MD, PhD , Yohei Ohno MD, PhD , Tomoyuki Tani MD , Hideharu Okamatsu MD , Yusuke Watanabe MD, PhD , Masaki Izumo MD, PhD , Mike Saji MD, PhD , Shingo Mizuno MD , Hiroshi Ueno MD, PhD , Kentaro Hayashida MD, PhD","doi":"10.1016/j.jacep.2025.07.021","DOIUrl":"10.1016/j.jacep.2025.07.021","url":null,"abstract":"<div><h3>Background</h3><div>Patients who have an ischemic stroke (IS) with an oral anticoagulant (OAC) have a high recurrence rate of IS. There is insufficient data on left atrial appendage closure (LAAC) for patients with nonvalvular atrial fibrillation (AF) who have had an IS despite OAC.</div></div><div><h3>Objectives</h3><div>The objectives of this study were to compare the clinical outcomes of the patients after LAAC based on IS risk.</div></div><div><h3>Methods</h3><div>This study was retrospective observational study from the OCEAN-LAAC (Optimized Catheter Valvular Intervention–Left Atrial Appendage Closure) registry. Nonvalvular AF patients who underwent LAAC were divided into 3 groups: a control group with no IS history, a group having a previous IS despite an OAC, and a group having a previous IS without OAC. The coprimary endpoints were cardiovascular (CV) death and IS.</div></div><div><h3>Results</h3><div>We included 1,418 patients (median CHA<sub>2</sub>DS<sub>2</sub>-VASc 5.0, HAS-BLED 3.0) undergoing LAAC. The previous history of IS was noted in 503 (35.4%), and 346 patients were under an OAC. During the median follow-up period of 367 days, no differences in CV death rate were observed among the 3 groups (previous IS despite OAC, subdistribution HR [sHR]: 1.78; 95% CI: 0.87-3.64; previous IS without OAC, sHR: 1.45; 95% CI: 0.59-3.55). The incidence of IS after LAAC was predominantly higher in the previous IS despite OAC group (sHR: 2.62; 95% CI: 1.17-5.86; Gray’s test: <em>P</em> = 0.02; previous IS without OAC: sHR: 1.24; 95% CI: 0.36-4.28; Gray’s test: <em>P</em> = 0.70).</div></div><div><h3>Conclusions</h3><div>The patients after LAAC who have had an IS despite OAC did not differ in CV death but were at higher risk of IS even after LAAC.</div></div>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":"11 12","pages":"Pages 2715-2728"},"PeriodicalIF":7.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080590","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 : 2025-11-28DOI: 10.1016/j.jacep.2025.10.030
Eduardo Martinez-Gomez, Konstantinos C Siontis
{"title":"Ablation in Heart Failure: The Case for Simplicity.","authors":"Eduardo Martinez-Gomez, Konstantinos C Siontis","doi":"10.1016/j.jacep.2025.10.030","DOIUrl":"https://doi.org/10.1016/j.jacep.2025.10.030","url":null,"abstract":"","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145742615","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 : 2025-11-21DOI: 10.1016/j.jacep.2025.10.005
Raquel Neves, Lia Crotti, Sahej Bains, J Martijn Bos, Dan Ye, Federica Dagradi, Giulia Musu, Federica Spiezia, Matteo Pedrazzini, Fulvio L F Giovenzana, Paolo Cerea, John R Giudicessi, Peter J Schwartz, Michael J Ackerman
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, Lia Crotti, Sahej Bains, J Martijn Bos, Dan Ye, Federica Dagradi, Giulia Musu, Federica Spiezia, Matteo Pedrazzini, Fulvio L F Giovenzana, Paolo Cerea, John R Giudicessi, Peter J Schwartz, Michael J Ackerman","doi":"10.1016/j.jacep.2025.10.005","DOIUrl":"https://doi.org/10.1016/j.jacep.2025.10.005","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-11-21","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号