Heart rhythm最新文献

英文中文

Habitual sleep duration and QT variability index: Correlates of ventricular repolarization lability and all-cause mortality 习惯性睡眠时间和QT变异性指数：心室复极不稳定性和全因死亡率的相关性。

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Heart rhythm

Pub Date : 2026-01-01 DOI: 10.1016/j.hrthm.2025.08.029

Phabiola Herrera MD , Soroosh Solhjoo PhD , Darko Stefanovski PhD , Jeffrey J. Goldberger MD , Mark C. Haigney MD , Naresh M. Punjabi MD, PhD

Background

Habitually short and long sleep duration have been associated with adverse cardiovascular outcomes, but their potential effects on ventricular repolarization lability are unknown. The QT variability index (QTVI) is a validated electrocardiographic measure of ventricular repolarization lability that predicts sudden cardiac death and all-cause mortality.

Objective

This study aimed to characterize associations among habitual sleep duration, QTVI, and all-cause mortality.

Methods

Data from 1123 adults in the Sleep Heart Health Study without sleep-disordered breathing were analyzed. Self-reported habitual sleep duration was categorized as ≤5, 6, 7, 8 (reference), or ≥9 h/night. QTVI was derived from a single-lead electrocardiogram during in-home polysomnography. Associations between sleep duration and QTVI were examined using robust linear regression. Proportional hazards regression was used to assess the association between QTVI and all-cause mortality.

Results

Both short (≤5 hours) and long sleep duration (≥9 hours) were associated with higher QTVI than 8 hours of habitual sleep after adjustment for demographic and clinical covariates (ΔQTVI = 0.18; 95% confidence interval [CI] 0.05–0.31; ΔQTVI = 0.15; 95% CI 0.02–0.28, respectively). Higher QTVI predicted greater mortality risk, with the highest quartile associated with more than double the risk (hazard ratio 2.14; 95% CI 1.45–3.17). The QTVI–mortality association varied by sleep duration (P = .04 for interaction), with the strongest effect in those reporting ≤5 hours of sleep (hazard ratio 3.12; 95% CI 1.85–5.26).

Conclusion

In adults without sleep-disordered breathing, short and long habitual sleep duration were associated with increased ventricular repolarization lability. Elevated QTVI independently predicted all-cause mortality, particularly in short sleepers, suggesting that sleep duration may influence electrophysiological vulnerability and arrhythmic risk.

背景：短睡眠时间和长睡眠时间与不良心血管结局有关。但它们对心室复极稳定性的潜在影响尚不清楚。QT变异性指数（QTVI）是一种有效的心室复极不稳定性的心电图测量方法，可预测心源性猝死和全因死亡率。目的：探讨习惯性睡眠时间、QTVI和全因死亡率之间的关系。方法：对1123名无睡眠呼吸障碍的成人的睡眠心脏健康研究数据进行分析。自我报告的习惯性睡眠时间分为≤5、6、7、8（参考）或≥9小时/夜。QTVI来源于家庭多导睡眠描记术中的单导联心电图。睡眠时间与QTVI之间的关系采用稳健线性回归进行检验。比例风险回归评估了qtvi与死亡率的关系，并纳入了睡眠时长与qtvi的相互作用项。结果：与人口统计学和临床协变量调整后的8小时相比，短睡眠（≤5小时）和长睡眠（≥9小时）与更高的QTVI相关（ΔQTVI=0.18, 95% CI 0.05-0.31； ΔQTVI=0.15, 95% CI 0.02-0.28）。较高的QTVI预示着更高的死亡风险，最高的四分位数与两倍以上的风险相关（HR=2.14, 95% CI 1.45-3.17）。qtvi与死亡率的关联因睡眠时长而异（相互作用p=0.04），在报告睡眠≤5小时的患者中影响最大（HR=3.12, 95% CI 1.85-5.26）。结论：在没有睡眠呼吸障碍的成年人中，短时间和长时间的习惯性睡眠与心室复极不稳定性增加有关。QTVI升高独立预测全因死亡率，特别是短睡眠者，这表明睡眠时间可能影响电生理脆弱性和心律失常风险。

{"title":"Habitual sleep duration and QT variability index: Correlates of ventricular repolarization lability and all-cause mortality","authors":"Phabiola Herrera MD , Soroosh Solhjoo PhD , Darko Stefanovski PhD , Jeffrey J. Goldberger MD , Mark C. Haigney MD , Naresh M. Punjabi MD, PhD","doi":"10.1016/j.hrthm.2025.08.029","DOIUrl":"10.1016/j.hrthm.2025.08.029","url":null,"abstract":"<div><h3>Background</h3><div>Habitually short and long sleep duration have been associated with adverse cardiovascular outcomes, but their potential effects on ventricular repolarization lability are unknown. The QT variability index (QTVI) is a validated electrocardiographic measure of ventricular repolarization lability that predicts sudden cardiac death and all-cause mortality.</div></div><div><h3>Objective</h3><div>This study aimed to characterize associations among habitual sleep duration, QTVI, and all-cause mortality.</div></div><div><h3>Methods</h3><div>Data from 1123 adults in the Sleep Heart Health Study without sleep-disordered breathing were analyzed. Self-reported habitual sleep duration was categorized as ≤5, 6, 7, 8 (reference), or ≥9 h/night. QTVI was derived from a single-lead electrocardiogram during in-home polysomnography. Associations between sleep duration and QTVI were examined using robust linear regression. Proportional hazards regression was used to assess the association between QTVI and all-cause mortality.</div></div><div><h3>Results</h3><div>Both short (≤5 hours) and long sleep duration (≥9 hours) were associated with higher QTVI than 8 hours of habitual sleep after adjustment for demographic and clinical covariates (ΔQTVI = 0.18; 95% confidence interval [CI] 0.05–0.31; ΔQTVI = 0.15; 95% CI 0.02–0.28, respectively). Higher QTVI predicted greater mortality risk, with the highest quartile associated with more than double the risk (hazard ratio 2.14; 95% CI 1.45–3.17). The QTVI–mortality association varied by sleep duration (<em>P</em> = .04 for interaction), with the strongest effect in those reporting ≤5 hours of sleep (hazard ratio 3.12; 95% CI 1.85–5.26).</div></div><div><h3>Conclusion</h3><div>In adults without sleep-disordered breathing, short and long habitual sleep duration were associated with increased ventricular repolarization lability. Elevated QTVI independently predicted all-cause mortality, particularly in short sleepers, suggesting that sleep duration may influence electrophysiological vulnerability and arrhythmic risk.</div></div>","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":"23 1","pages":"Pages e42-e48"},"PeriodicalIF":5.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144951803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cardioneural ablation: Toward achieving uniformity in nomenclature, procedural approaches, and outcome measures 心神经消融术：在命名、手术方法和结果测量上实现统一。

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Heart rhythm

Pub Date : 2026-01-01 DOI: 10.1016/j.hrthm.2025.09.022

Wei-Hsin Chung MD , Duc Do MD , Muhammed Ibrahim Erbay MD , Olujimi A. Ajijola MD, PhD, FHRS

The cardiac autonomic nervous system plays a pivotal role in regulating heart function through a complex network of extrinsic and intrinsic components, including ganglionated plexi (GPs). Cardioneuroablation (CNA), a novel therapeutic approach targeting GPs, has emerged as a treatment for cardio-inhibitory vasovagal syncope and select atrioventricular block cases. However, heterogeneity in anatomical nomenclature, GP identification techniques, ablation strategies, and procedural end points limits standardization. Although methods such as high-frequency stimulation, electroanatomic mapping, and anatomical guidance are used to localize GPs, each has limitations. CNA has demonstrated favorable short-term outcomes; however, concerns regarding long-term efficacy, reinnervation, and safety—particularly related to ventricular arrhythmia risk—remain. This review critically reviews the studies from the basic science of the cardiac autonomic nervous system to the latest clinical outcomes, highlighting the need for unified terminology, patient selection criteria, procedural techniques, and the necessity for long-term, multicenter studies to optimize CNA’s safety and effectiveness.

心脏自主神经系统通过包括神经节丛（gp）在内的一个由外在和内在成分组成的复杂网络，在调节心脏功能方面起着关键作用。心神经消融术（CNA）是一种针对GPs的新型治疗方法，已被用于治疗心脏抑制性血管迷走神经性晕厥和部分房室传导阻滞病例。然而，解剖学命名法、GPs识别技术、消融策略和手术终点的异质性限制了标准化。虽然高频刺激、电解剖成像和解剖引导等方法用于定位GPs，但每种方法都有局限性。CNA已显示出良好的短期疗效，但对长期疗效、神经再生和安全性，特别是室性心律失常风险的担忧仍然存在。本文回顾了从心脏自主神经系统的基础科学到最新临床结果的研究，强调了统一术语、患者选择标准、操作技术的必要性，以及长期、多中心研究优化CNA安全性和有效性的必要性。

{"title":"Cardioneural ablation: Toward achieving uniformity in nomenclature, procedural approaches, and outcome measures","authors":"Wei-Hsin Chung MD , Duc Do MD , Muhammed Ibrahim Erbay MD , Olujimi A. Ajijola MD, PhD, FHRS","doi":"10.1016/j.hrthm.2025.09.022","DOIUrl":"10.1016/j.hrthm.2025.09.022","url":null,"abstract":"<div><div>The cardiac autonomic nervous system plays a pivotal role in regulating heart function through a complex network of extrinsic and intrinsic components, including ganglionated plexi (GPs). Cardioneuroablation (CNA), a novel therapeutic approach targeting GPs, has emerged as a treatment for cardio-inhibitory vasovagal syncope and select atrioventricular block cases. However, heterogeneity in anatomical nomenclature, GP identification techniques, ablation strategies, and procedural end points limits standardization. Although methods such as high-frequency stimulation, electroanatomic mapping, and anatomical guidance are used to localize GPs, each has limitations. CNA has demonstrated favorable short-term outcomes; however, concerns regarding long-term efficacy, reinnervation, and safety—particularly related to ventricular arrhythmia risk—remain. This review critically reviews the studies from the basic science of the cardiac autonomic nervous system to the latest clinical outcomes, highlighting the need for unified terminology, patient selection criteria, procedural techniques, and the necessity for long-term, multicenter studies to optimize CNA’s safety and effectiveness.</div></div>","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":"23 1","pages":"Pages e75-e83"},"PeriodicalIF":5.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rapid direct mapping of the superior vena cava using an extended circular array pulsed field catheter to identify sinus node activation prior to ablation 使用扩展圆形阵列脉冲场导管快速直接测绘上腔静脉以识别消融前窦结激活。

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Heart rhythm

Pub Date : 2026-01-01 DOI: 10.1016/j.hrthm.2025.09.031

Akiko Kodama MD, Suguru Nishiuchi MD, PhD, Kojiro Hattori MD, Taiki Masuyama MD, Kenichi Kaseno MD, PhD, Shingo Yoshimura MD, Takehito Sasaki MD, Kohki Nakamura MD, PhD, Shigeto Naito MD, PhD

引用次数: 0

Table Of Content 目录表

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Heart rhythm

Pub Date : 2026-01-01 DOI: 10.1016/S1547-5271(25)03097-8

引用次数: 0

Advancing heart rhythm care in challenging times 在挑战时代推进心律护理

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Heart rhythm

Pub Date : 2026-01-01 DOI: 10.1016/j.hrthm.2025.11.011

Mina K. Chung MD, FHRS

引用次数: 0

Demonstration of dual AV nodal pathways in patients with supraventricular tachycardia 室上性心动过速患者双房室结通路的证明

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Heart rhythm

Pub Date : 2026-01-01 DOI: 10.1016/j.hrthm.2025.09.025

Pablo Denes MD, MPH

引用次数: 0

A leadless pericardial pacemaker 无铅心包起搏器。

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Heart rhythm

Pub Date : 2026-01-01 DOI: 10.1016/j.hrthm.2025.01.036

Yaniv Bar-Cohen MD, FHRS , Michael J. Silka MD , Allison C. Hill MD, FHRS , Mark Shwayder MD , Jay D. Pruetz MD , Lynlee Stevey-Rindenow DVM , Raymond Peck , Samuel Kohan , Gerald E. Loeb MD

Background

Cardiac pacemakers have complications related to long pacemaker leads, subcutaneous pockets, and endovascular hardware.

Objective

We report on the development of a leadless micropacemaker for percutaneous implantation into the pericardial space.

Methods

Percutaneous implantations of a micropacemaker system were performed in 15 pigs through subxiphoid access to the pericardial space. In our concept phase, 10 implants were performed with iterative changes to the design and implantation techniques until a design was reached for a viable device. In the study phase, a viable device was implanted in 5 pigs and observed during 8 weeks.

Results

At the completion of the concept phase, a prototype micropacemaker device was fabricated that met 3 mandatory system requirements: can be safely and reproducibly implanted percutaneously into the pericardial space; does not migrate after implantation; and successfully captures the myocardium at implantation and during long-term follow-up (up to 8 weeks). The prototype device was successfully and safely implanted into all 5 pigs in the study phase. These 5 animals survived to the 8-week end point without complications. Ventricular capture threshold calculations at implantation were a median 0.43 V at 0.4 ms (range, 0.05–0.75 V at 0.4 ms). At 8 weeks of follow-up, median capture thresholds were 2.8 V at 0.4 ms (total range, 2.2–7.1 V).

Conclusion

A novel pericardial micropacemaker system allows minimally invasive implantation of a leadless cardiac pacemaker without entering the vascular space. We provide proof of concept of this design with encouraging follow-up data.

背景：心脏起搏器的并发症与起搏器导线过长、皮下袋和血管内硬件有关：我们报告了一种经皮植入心包腔的无引线微型起搏器的开发情况：方法：通过剑突下进入心包腔，在 15 头猪身上经皮植入了微型起搏器系统。在概念阶段，我们对设计和植入技术进行了反复修改，直到设计出可行的装置，共进行了十次植入。在研究阶段，我们在五头猪身上植入了可行的装置，并对其进行了为期 8 周的长期跟踪：在概念阶段完成后，微型起搏器原型装置制作完成，该装置符合三个强制性系统要求：1.)2.) 植入后不会移位；以及 3.）在植入和长期随访（长达 8 周）期间成功捕获心肌。在研究阶段，原型装置成功、安全地植入了所有五头猪体内。这五只动物均存活至 8 周终点，未出现并发症。植入时的心室捕获阈值计算中值为 0.43 V @ 0.4 ms（范围为 0.05 - 0.75 V @ 0.4 ms）。随访 8 周时，中位捕获阈值为 2.8 V @ 0.4 ms（总范围为 2.2 - 7.1 V）：结论：新型心包微起搏器系统可在不进入血管空间的情况下以微创方式植入无引线心脏起搏器。我们提供了这一设计的概念验证和令人鼓舞的后续数据。

{"title":"A leadless pericardial pacemaker","authors":"Yaniv Bar-Cohen MD, FHRS , Michael J. Silka MD , Allison C. Hill MD, FHRS , Mark Shwayder MD , Jay D. Pruetz MD , Lynlee Stevey-Rindenow DVM , Raymond Peck , Samuel Kohan , Gerald E. Loeb MD","doi":"10.1016/j.hrthm.2025.01.036","DOIUrl":"10.1016/j.hrthm.2025.01.036","url":null,"abstract":"<div><h3>Background</h3><div>Cardiac pacemakers have complications related to long pacemaker leads, subcutaneous pockets, and endovascular hardware.</div></div><div><h3>Objective</h3><div>We report on the development of a leadless micropacemaker for percutaneous implantation into the pericardial space.</div></div><div><h3>Methods</h3><div>Percutaneous implantations of a micropacemaker system were performed in 15 pigs through subxiphoid access to the pericardial space. In our concept phase, 10 implants were performed with iterative changes to the design and implantation techniques until a design was reached for a viable device. In the study phase, a viable device was implanted in 5 pigs and observed during 8 weeks.</div></div><div><h3>Results</h3><div>At the completion of the concept phase, a prototype micropacemaker device was fabricated that met 3 mandatory system requirements: can be safely and reproducibly implanted percutaneously into the pericardial space; does not migrate after implantation; and successfully captures the myocardium at implantation and during long-term follow-up (up to 8 weeks). The prototype device was successfully and safely implanted into all 5 pigs in the study phase. These 5 animals survived to the 8-week end point without complications. Ventricular capture threshold calculations at implantation were a median 0.43 V at 0.4 ms (range, 0.05–0.75 V at 0.4 ms). At 8 weeks of follow-up, median capture thresholds were 2.8 V at 0.4 ms (total range, 2.2–7.1 V).</div></div><div><h3>Conclusion</h3><div>A novel pericardial micropacemaker system allows minimally invasive implantation of a leadless cardiac pacemaker without entering the vascular space. We provide proof of concept of this design with encouraging follow-up data.</div></div>","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":"23 1","pages":"Pages 194-202"},"PeriodicalIF":5.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Validation of QT interval measurement using an implantable cardiac monitor with remote monitoring: The multicenter QT-ICM study 使用植入式心脏监护仪远程监测QT间期测量的验证：多中心QT- icm研究。

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Heart rhythm

Pub Date : 2026-01-01 DOI: 10.1016/j.hrthm.2025.07.039

Domenico Maria Carretta MD , Vincenzo Russo MD, PhD , Gerardo Nigro MD, PhD , Orlando Munciguerra MD , Fabio Franculli MD , Gennaro Vitulano MD , Miguel Viscusi MD , Vincenzo Coscia MD , Francesca Maria Carretta MD , Andrea Spadaro Guerra MSc , Paola Napoli MSc , Daniele Giacopelli PhD , Mario Volpicelli MD

引用次数: 0

Steerable vs fixed-curve sheaths in left atrial appendage occlusion: First US experience 左心耳闭塞的可操纵与固定曲线鞘：美国的首次经验。

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Heart rhythm

Pub Date : 2026-01-01 DOI: 10.1016/j.hrthm.2025.07.038

Jalaj Garg MD, FACC, FESC, FHRS , Makoto Nagahama MD , Esteban Arevalo MD , Kuldeep Shah MD , Davendra Ramsingh MD , Ravi Mandapati MD , Dhanunjaya Lakkireddy MD , Rahul Bhardwaj MD

引用次数: 0

Myocardial PKG1α dysregulation contributes to ventricular tachycardia pathogenesis in type 2 diabetes and metabolic syndrome 心肌cGMP-PKG1α异常参与2型糖尿病和代谢综合征室性心动过速发病

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Heart rhythm

Pub Date : 2026-01-01 DOI: 10.1016/j.hrthm.2025.08.032

Xuehong Cao MD, PhD , Yali Zhang PhD , Audrey Tripp BA , Rachel Steinhauer MD , Pei-wen Liu MS , Mark J. Aronovitz BA , Greg L. Martin BS , Bo Wang MD , Abdullah Alissa MD , Mossab Aljuaid MD , Justin Ho MS , Tina Phan MD , Christopher Madias MD , Robert M. Blanton MA, MD , Jonas B. Galper MD, PhD

Background

Type 2 diabetes mellitus (DMII) and metabolic syndrome (MBS) increase ventricular arrhythmia and sudden cardiac death risk.

Objective

This study aimed to identify mechanisms through which DMII and MBS promote ventricular tachycardia (VT).

Methods

We performed programmed ventricular stimulation on leptin receptor mutant (Db/Db) mice with DMII; high-fat, high-sucrose (HFHS) diet–fed mice with MBS; and cyclic guanosine monophosphate (cGMP)-dependent protein kinase 1 alpha (PKG1α) leucine zipper mutant (LZM) mice, which have neither DMII nor MBS but have disrupted PKG1α signaling.

Results

Programmed ventricular stimulation induced VT in Db/Db and HFHS diet–fed mice. Both models demonstrated autonomic dysfunction and decreased cGMP owing to decreased cardiac parasympathetic responsiveness. Conversely, cGMP augmentation with soluble guanylate cyclase stimulation (riociguat) or phosphodiesterase 5 inhibition (sildenafil) reduced VT inducibility. PKG1α LZM mice had normal autonomic responsiveness, but excess VT. Left ventricular tissue from HFHS diet–fed and LZM mice demonstrated hyperactivated glycogen synthase kinase-3 beta (GSK3β). GSK3β inhibition with TWS119 abolished inducible VT in all 3 models. Sarcoplasmic reticulum Ca²⁺ reuptake was delayed in cardiomyocytes (CMs) from all 3 models, reflected by increased time constant of cytoplasmic Ca²⁺ decline, tau. TWS119 reversed this effect. Phospholamban, which when unphosphorylated inhibits sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2a–mediated Ca²⁺ reuptake from the cytosol, was hypophosphorylated in HFHS diet–fed and LZM mice, which was reversed by TWS119. CMs from HFHS diet–fed mice displayed increased frequency of early afterdepolarizations, further supporting Ca²⁺ dyshomeostasis. cGMP augmentation with riociguat/sildenafil prevented afterdepolarizations in HFHS CMs.

Conclusion

In DMII and MBS, reduced PKG1α signaling drives GSK3β hyperstimulation, calcium dyshomeostasis, and VT. Pharmacologic modulation of these pathways opposes VT pathogenesis.

背景：ii型糖尿病（DMII）和代谢综合征（MBS）增加室性心律失常和心源性猝死的风险。目的：确定DMII和MBS促进室性心动过速（VT）的机制。方法：我们对患有DMII的瘦素受体突变（Db/Db）小鼠、患有MBS的高脂高糖（HFHS）喂养小鼠和既没有DMII也没有MBS的cgmp依赖性蛋白激酶1α (PKG1α)亮氨酸zipper突变（LZM）小鼠进行程序性心室刺激（PVS），但PKG1α信号被破坏。结果：PVS诱导Db/Db和hfhs喂养小鼠VT。两种模型均表现出自主神经功能障碍和cGMP降低，原因是心脏副交感神经反应性降低。相反，用可溶性鸟苷酸环化酶刺激（riociguat）或磷酸二酯酶5抑制（西地那非）增强cGMP可降低VT诱导性。PKG1α LZM小鼠具有正常的自主神经反应性，但HFHS和LZM小鼠过量的VT. LV组织表现出高激活的糖原合成酶激酶3β (GSK3β)。用TWS119抑制GSK3β可使3种模型的诱导型VT消失。肌浆网Ca2+再摄取在所有3种模型的心肌细胞（CM）中都延迟，反映在细胞质Ca2+下降的时间常数tau增加。TWS119逆转了这一效应。磷蛋白（PLB）在未磷酸化时抑制肌浆/内质网Ca2+ atp酶2a （SERCA2a）介导的Ca2+从细胞质再摄取，在hfhs喂养和LZM小鼠中被低磷酸化，被TWS119逆转。hfhs喂养小鼠的CMs显示早期后去极化（EADs）频率增加，进一步支持Ca2+失衡。用瑞西奎特/西地那非增强cGMP可预防HFHS CMs中的EADs。结论：在DMII和MBS中，cGMP-PKG1α信号的减少可驱动GSK3β过度刺激、钙平衡失调和室速。这些途径的药理调节可对抗室速的发病机制。

{"title":"Myocardial PKG1α dysregulation contributes to ventricular tachycardia pathogenesis in type 2 diabetes and metabolic syndrome","authors":"Xuehong Cao MD, PhD , Yali Zhang PhD , Audrey Tripp BA , Rachel Steinhauer MD , Pei-wen Liu MS , Mark J. Aronovitz BA , Greg L. Martin BS , Bo Wang MD , Abdullah Alissa MD , Mossab Aljuaid MD , Justin Ho MS , Tina Phan MD , Christopher Madias MD , Robert M. Blanton MA, MD , Jonas B. Galper MD, PhD","doi":"10.1016/j.hrthm.2025.08.032","DOIUrl":"10.1016/j.hrthm.2025.08.032","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes mellitus (DMII) and metabolic syndrome (MBS) increase ventricular arrhythmia and sudden cardiac death risk.</div></div><div><h3>Objective</h3><div>This study aimed to identify mechanisms through which DMII and MBS promote ventricular tachycardia (VT).</div></div><div><h3>Methods</h3><div>We performed programmed ventricular stimulation on leptin receptor mutant (Db/Db) mice with DMII; high-fat, high-sucrose (HFHS) diet–fed mice with MBS; and cyclic guanosine monophosphate (cGMP)-dependent protein kinase 1 alpha (PKG1α) leucine zipper mutant (LZM) mice, which have neither DMII nor MBS but have disrupted PKG1α signaling.</div></div><div><h3>Results</h3><div>Programmed ventricular stimulation induced VT in Db/Db and HFHS diet–fed mice. Both models demonstrated autonomic dysfunction and decreased cGMP owing to decreased cardiac parasympathetic responsiveness. Conversely, cGMP augmentation with soluble guanylate cyclase stimulation (riociguat) or phosphodiesterase 5 inhibition (sildenafil) reduced VT inducibility. PKG1α LZM mice had normal autonomic responsiveness, but excess VT. Left ventricular tissue from HFHS diet–fed and LZM mice demonstrated hyperactivated glycogen synthase kinase-3 beta (GSK3β). GSK3β inhibition with TWS119 abolished inducible VT in all 3 models. Sarcoplasmic reticulum Ca<sup>2+</sup> reuptake was delayed in cardiomyocytes (CMs) from all 3 models, reflected by increased time constant of cytoplasmic Ca<sup>2+</sup> decline, tau. TWS119 reversed this effect. Phospholamban, which when unphosphorylated inhibits sarcoplasmic/endoplasmic reticulum Ca<sup>2+</sup> ATPase 2a–mediated Ca<sup>2+</sup> reuptake from the cytosol, was hypophosphorylated in HFHS diet–fed and LZM mice, which was reversed by TWS119. CMs from HFHS diet–fed mice displayed increased frequency of early afterdepolarizations, further supporting Ca<sup>2+</sup> dyshomeostasis. cGMP augmentation with riociguat/sildenafil prevented afterdepolarizations in HFHS CMs.</div></div><div><h3>Conclusion</h3><div>In DMII and MBS, reduced PKG1α signaling drives GSK3β hyperstimulation, calcium dyshomeostasis, and VT. Pharmacologic modulation of these pathways opposes VT pathogenesis.</div></div>","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":"23 1","pages":"Pages e49-e61"},"PeriodicalIF":5.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144951806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

首页上一页

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Heart rhythm

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀