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Performance and Safety of the Extravascular Implantable Cardioverter-Defibrillator Through Long-Term Follow-Up: Final Results From the Pivotal Study. 血管外植入式心律转复除颤器长期随访的性能和安全性:关键研究的最终结果
IF 37.8 1区 医学
Circulation Pub Date : 2024-09-26 DOI: 10.1161/circulationaha.124.071795
Paul Friedman,Francis Murgatroyd,Lucas V A Boersma,Jaimie Manlucu,Bradley P Knight,Nicolas Clémenty,Christophe Leclercq,Anish Amin,Béla Merkely,Ulrika Birgersdotter-Green,Joseph Yat Sun Chan,Mauro Biffi,Reinoud Elwin Knops,Gregory Engel,Ignacio Muñoz Carvajal,Laurence M Epstein,Venkata Sagi,Jens Brock Johansen,Maciej Sterliński,Clemens Steinwender,Troy Hounshell,Richard Abben,Amy E Thompson,Yan Zhang,Christopher Wiggenhorn,Sarah Willey,Ian Crozier,
{"title":"Performance and Safety of the Extravascular Implantable Cardioverter-Defibrillator Through Long-Term Follow-Up: Final Results From the Pivotal Study.","authors":"Paul Friedman,Francis Murgatroyd,Lucas V A Boersma,Jaimie Manlucu,Bradley P Knight,Nicolas Clémenty,Christophe Leclercq,Anish Amin,Béla Merkely,Ulrika Birgersdotter-Green,Joseph Yat Sun Chan,Mauro Biffi,Reinoud Elwin Knops,Gregory Engel,Ignacio Muñoz Carvajal,Laurence M Epstein,Venkata Sagi,Jens Brock Johansen,Maciej Sterliński,Clemens Steinwender,Troy Hounshell,Richard Abben,Amy E Thompson,Yan Zhang,Christopher Wiggenhorn,Sarah Willey,Ian Crozier,","doi":"10.1161/circulationaha.124.071795","DOIUrl":"https://doi.org/10.1161/circulationaha.124.071795","url":null,"abstract":"BACKGROUNDSubsternal lead placement of the extravascular implantable cardioverter-defibrillator (EV ICD) permits both defibrillation at thresholds similar to those seen with transvenous ICDs and effective antitachycardia pacing (ATP), while avoiding the vasculature and associated complications. The global Pivotal study has shown the EV ICD system to be safe and effective through 6 months, but long-term experience has yet to be published. We aim to report the performance and safety of the EV ICD system throughout the study.METHODSThe EV ICD Pivotal study was a prospective, global, single-arm, pre-market clinical study. Individuals with a class I or IIa indication for a single-chamber ICD per guidelines were enrolled. Freedom from major system- or procedure-related complications, as well as appropriate and inappropriate therapy rates, were assessed through 3 years using the Kaplan-Meier method. Anti-tachycardia pacing success was calculated using simple proportions.RESULTSAn implant was attempted in 316 patients [25.3% female, 53.8±13.1 years old, 81.6% primary prevention, LVEF 38.9%±15.4%]. Of 299 patients with a successful implant, 24 experienced 82 spontaneous arrhythmic episodes that were appropriately treated with either ATP only (38, 46.3%), shock only (34, 41.5%), or both (10, 12.2%) for a Kaplan-Meier-estimated rate of first any appropriate therapy of 9.2% at 3 years. Antitachycardia pacing was successful in 77.1% (37/48) of episodes, and ATP usage significantly increased from discharge to last follow-up visit (P<0.0001). Shock therapy was successful in 100% (27/27) of discrete, spontaneous ventricular arrhythmias. The inappropriate shock rates at 1 and 3 years were 9.8% and 17.5%, respectively, with P-wave oversensing the predominant cause. No major intraprocedural complications were reported and the estimated freedom from system- or procedure-related major complications was 91.9% at 1 year and 89.0% at 3 years. The most common major complications were lead dislodgement (10 events; n=9 patients, 2.8%), postoperative wound or device pocket infection (n=8, 2.5%), and device inappropriate shock delivery (n=4, 1.3%). Twenty-four system revisions were performed as a result of major complications related to the EV ICD system or procedure.CONCLUSIONSFrom implant to study completion, the EV ICD Pivotal study demonstrated that a single integrated system with an extravascular lead placed in the substernal space maintains high ATP success, effective defibrillation, and a consistent safety profile.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328761","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}
引用次数: 0
Associations of "Weekend Warrior" Physical Activity With Incident Disease and Cardiometabolic Health. 周末战士 "体育锻炼与突发疾病和心脏代谢健康的关系。
IF 37.8 1区 医学
Circulation Pub Date : 2024-09-26 DOI: 10.1161/circulationaha.124.068669
Shinwan Kany,Mostafa A Al-Alusi,Joel T Rämö,James P Pirruccello,Timothy W Churchill,Steven A Lubitz,Mahnaz Maddah,J Sawalla Guseh,Patrick T Ellinor,Shaan Khurshid
{"title":"Associations of \"Weekend Warrior\" Physical Activity With Incident Disease and Cardiometabolic Health.","authors":"Shinwan Kany,Mostafa A Al-Alusi,Joel T Rämö,James P Pirruccello,Timothy W Churchill,Steven A Lubitz,Mahnaz Maddah,J Sawalla Guseh,Patrick T Ellinor,Shaan Khurshid","doi":"10.1161/circulationaha.124.068669","DOIUrl":"https://doi.org/10.1161/circulationaha.124.068669","url":null,"abstract":"BACKGROUNDAchievement of guideline-recommended levels of physical activity (≥150 minutes of moderate-to-vigorous physical activity per week) is associated with lower risk of adverse cardiovascular events and represents an important public health priority. Although physical activity commonly follows a \"weekend warrior\" pattern, in which most moderate-to-vigorous physical activity is concentrated in 1 or 2 days rather than spread more evenly across the week (regular), the effects of physical activity pattern across a range of incident diseases, including cardiometabolic conditions, are unknown.METHODSWe tested associations between physical activity pattern and incidence of 678 conditions in 89 573 participants (62±8 years of age; 56% women) of the UK Biobank prospective cohort study who wore an accelerometer for 1 week between June 2013 and December 2015. Models were adjusted for multiple baseline clinical factors, and P value thresholds were corrected for multiplicity.RESULTSWhen compared to inactive (<150 minutes moderate-to-vigorous physical activity/week), both weekend warrior (267 total associations; 264 [99%] with lower disease risk; hazard ratio [HR] range, 0.35-0.89) and regular activity (209 associations; 205 [98%] with lower disease risk; HR range, 0.41-0.88) were broadly associated with lower risk of incident disease. The strongest associations were observed for cardiometabolic conditions such as incident hypertension (weekend warrior: HR, 0.77 [95% CI, 0.73-0.80]; P=1.2×10-27; regular: HR, 0.72 [95% CI, 0.68-0.77]; P=4.5×10-28), diabetes (weekend warrior: HR, 0.57 [95% CI, 0.51-0.62]; P=3.9×10-32; regular: HR, 0.54 [95% CI, 0.48-0.60]; P=8.7×10-26), obesity (weekend warrior: HR, 0.55 [95% CI, 0.50-0.60]; P=2.4×10-43, regular: HR, 0.44 [95% CI, 0.40-0.50]; P=9.6×10-47), and sleep apnea (weekend warrior: HR, 0.57 [95% CI, 0.48-0.69]; P=1.6×10-9; regular: HR, 0.49 [95% CI, 0.39-0.62]; P=7.4×10-10). When weekend warrior and regular activity were compared directly, there were no conditions for which effects differed significantly. Observations were similar when activity was thresholded at the sample median (≥230.4 minutes of moderate-to-vigorous physical activity/week).CONCLUSIONSAchievement of measured physical activity volumes consistent with guideline recommendations is associated with lower risk for >200 diseases, with prominent effects on cardiometabolic conditions. Associations appear similar whether physical activity follows a weekend warrior pattern or is spread more evenly throughout the week.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324872","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}
引用次数: 0
Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial. 萨库比特利/缬沙坦治疗小儿心力衰竭(PANORAMA-HF):一项随机、多中心、双盲试验。
IF 37.8 1区 医学
Circulation Pub Date : 2024-09-25 DOI: 10.1161/circulationaha.123.066605
Robert Shaddy,Michael Burch,Paul F Kantor,Susan Solar-Yohay,Tania Garito,Sijia Zhang,Michele Kocun,Chad Mao,Antoinette Cilliers,Xu Wang,Charles Canter,Joseph Rossano,Gonzalo Wallis,Jondavid Menteer,Linda Daou,Jacek Kusa,Kursat Tokel,Daniel Dilber,Zhuoming Xu,Tingting Xiao,Nancy Halnon,Kevin P Daly,Matthew J Bock,Warren Zuckerman,Tajinder P Singh,Manisha Chakrabarti,Aviva Levitas,Michele Senni,Giorgia Grutter,Gi Beom Kim,Jinyoung Song,Hyoung Doo Lee,Ching Kit Chen,Joan Sanchez-de-Toledo,Yuk Law,Suthep Wanitkun,Yanqin Cui,Rui Anjos,Timur Mese,Damien Bonnet
{"title":"Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.","authors":"Robert Shaddy,Michael Burch,Paul F Kantor,Susan Solar-Yohay,Tania Garito,Sijia Zhang,Michele Kocun,Chad Mao,Antoinette Cilliers,Xu Wang,Charles Canter,Joseph Rossano,Gonzalo Wallis,Jondavid Menteer,Linda Daou,Jacek Kusa,Kursat Tokel,Daniel Dilber,Zhuoming Xu,Tingting Xiao,Nancy Halnon,Kevin P Daly,Matthew J Bock,Warren Zuckerman,Tajinder P Singh,Manisha Chakrabarti,Aviva Levitas,Michele Senni,Giorgia Grutter,Gi Beom Kim,Jinyoung Song,Hyoung Doo Lee,Ching Kit Chen,Joan Sanchez-de-Toledo,Yuk Law,Suthep Wanitkun,Yanqin Cui,Rui Anjos,Timur Mese,Damien Bonnet","doi":"10.1161/circulationaha.123.066605","DOIUrl":"https://doi.org/10.1161/circulationaha.123.066605","url":null,"abstract":"BACKGROUNDSacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD).METHODSChildren with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro-B-type natriuretic peptide) was an exploratory end point.RESULTSA total of 375 children (mean age, 8.1±5.6 years; 52% female) were randomized to sacubitril/valsartan (n=187) or enalapril (n=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47-0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72-1.14]; P=0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children.CONCLUSIONSIn this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks.REGISTRATIONURL: https://www.clinicaltrials.gov; Unique identifier: NCT02678312.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321111","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}
引用次数: 0
Effect of Delayed Remote Ischemic Preconditioning on Acute Kidney Injury and Outcomes in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial. 延迟远程缺血预处理对心脏手术患者急性肾损伤和预后的影响:随机临床试验
IF 37.8 1区 医学
Circulation Pub Date : 2024-09-25 DOI: 10.1161/circulationaha.124.071408
Ping Jia,Qiang Ji,Zhouping Zou,Qi Zeng,Ting Ren,Weize Chen,Zhixin Yan,Daoqi Shen,Yang Li,Fangyuan Peng,Ying Su,Jiarui Xu,Bo Shen,Zhe Luo,Chunsheng Wang,Xiaoqiang Ding
{"title":"Effect of Delayed Remote Ischemic Preconditioning on Acute Kidney Injury and Outcomes in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial.","authors":"Ping Jia,Qiang Ji,Zhouping Zou,Qi Zeng,Ting Ren,Weize Chen,Zhixin Yan,Daoqi Shen,Yang Li,Fangyuan Peng,Ying Su,Jiarui Xu,Bo Shen,Zhe Luo,Chunsheng Wang,Xiaoqiang Ding","doi":"10.1161/circulationaha.124.071408","DOIUrl":"https://doi.org/10.1161/circulationaha.124.071408","url":null,"abstract":"BACKGROUNDRemote ischemic preconditioning (RIPC) has 2 time windows for organ protection: acute and delayed. Previous studies have mainly focused on the organoprotective effects of acute RIPC. We aimed to determine whether delayed RIPC can reduce the occurrence of acute kidney injury (AKI) and postoperative complications in patients undergoing cardiac surgery.METHODSThis prospective, single-center, double-blind, randomized controlled trial involved 509 patients at high risk for AKI who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass. Patients were randomized to receive RIPC (4 cycles of 5-minute inflation and 5-minute deflation on 1 upper arm with a blood pressure cuff) 24 hours before surgery or a sham condition (control group) that was induced by 4 cycles of 5-minute inflation to a pressure of 20 mm Hg followed by 5-minute cuff deflation. The primary end point was the incidence of AKI within the prior 7 days after cardiac surgery. The secondary end points included renal replacement therapy during hospitalization, change in urinary biomarkers of AKI and markers of myocardial injury, duration of intensive care unit stay and mechanical ventilation, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90.RESULTSA total of 509 patients (mean age, 65.2±8.2 years; 348 men [68.4%]) were randomly assigned to the RIPC group (n=254) or control group (n=255). AKI was significantly reduced in the RIPC group compared with the control group (69/254 [27.2%] versus 90/255 [35.3%]; odds ratio, 0.68 [95% CI, 0.47-1.00]; P=0.048). There were no significant between-group differences in the secondary end points of perioperative myocardial injury (assessed by the concentrations of cardiac troponin T, creatine kinase myocardial isoenzyme, and NT-proBNP [N-terminal pro-brain natriuretic peptide]), duration of stay in the intensive care unit and hospital, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90.CONCLUSIONSAmong high-risk patients undergoing cardiac surgery, delayed RIPC significantly reduced the occurrence of AKI.REGISTRATIONURL: https://www.chictr.org.cn; Unique identifier: ChiCTR2000035568.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321420","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}
引用次数: 0
Core Components of Cardiac Rehabilitation Programs: 2024 Update: A Scientific Statement From the American Heart Association and the American Association of Cardiovascular and Pulmonary Rehabilitation. 心脏康复计划的核心内容:2024 年更新:美国心脏协会和美国心血管与肺康复协会的科学声明》(Core Components of Cardiac Rehabilitation Programs: 2024 Update: A Scientific Statement From the American Heart Association and the American Association of Cardioascular and Pulmonary Rehabilitation)。
IF 35.5 1区 医学
Circulation Pub Date : 2024-09-24 DOI: 10.1161/CIR.0000000000001289
Todd M Brown, Quinn R Pack, Ellen Aberegg, LaPrincess C Brewer, Yvonne R Ford, Daniel E Forman, Emily C Gathright, Sherrie Khadanga, Cemal Ozemek, Randal J Thomas
{"title":"Core Components of Cardiac Rehabilitation Programs: 2024 Update: A Scientific Statement From the American Heart Association and the American Association of Cardiovascular and Pulmonary Rehabilitation.","authors":"Todd M Brown, Quinn R Pack, Ellen Aberegg, LaPrincess C Brewer, Yvonne R Ford, Daniel E Forman, Emily C Gathright, Sherrie Khadanga, Cemal Ozemek, Randal J Thomas","doi":"10.1161/CIR.0000000000001289","DOIUrl":"https://doi.org/10.1161/CIR.0000000000001289","url":null,"abstract":"<p><p>The science of cardiac rehabilitation and the secondary prevention of cardiovascular disease has progressed substantially since the most recent American Heart Association and American Association of Cardiovascular and Pulmonary Rehabilitation update on the core components of cardiac rehabilitation and secondary prevention programs was published in 2007. In addition, the advent of new care models, including virtual and remote delivery of cardiac rehabilitation services, has expanded the ways that cardiac rehabilitation programs can reach patients. In this scientific statement, we update the scientific basis of the core components of patient assessment, nutritional counseling, weight management and body composition, cardiovascular disease and risk factor management, psychosocial management, aerobic exercise training, strength training, and physical activity counseling. In addition, in recognition that high-quality cardiac rehabilitation programs regularly monitor their processes and outcomes and engage in an ongoing process of quality improvement, we introduce a new core component of program quality. High-quality program performance will be essential to improve widely documented low enrollment and adherence rates and reduce health disparities in cardiac rehabilitation access.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307190","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}
引用次数: 0
Assays of Variant Effect and Automated Patch Clamping Improve KCNH2-LQTS Variant Classification and Cardiac Event Risk Stratification. 变异效应测定和自动膜片钳改善了 KCNH2-LQTS 变异分类和心脏事件风险分层。
IF 35.5 1区 医学
Circulation Pub Date : 2024-09-24 DOI: 10.1161/CIRCULATIONAHA.124.069828
Matthew J O'Neill, Chai-Ann Ng, Takanori Aizawa, Luca Sala, Sahej Bains, Annika Winbo, Rizwan Ullah, Qianyi Shen, Chek-Ying Tan, Krystian Kozek, Loren R Vanags, Devyn W Mitchell, Alex Shen, Yuko Wada, Asami Kashiwa, Lia Crotti, Federica Dagradi, Giulia Musu, Carla Spazzolini, Raquel Neves, J Martijn Bos, John R Giudicessi, Xavier Bledsoe, Eric R Gamazon, Megan C Lancaster, Andrew M Glazer, Bjorn C Knollmann, Dan M Roden, Jochen Weile, Frederick Roth, Joe-Elie Salem, Nikki Earle, Rachael Stiles, Taylor Agee, Christopher N Johnson, Minoru Horie, Jonathan Skinner, Michael J Ackerman, Peter J Schwartz, Seiko Ohno, Jamie I Vandenberg, Brett M Kroncke
{"title":"Assays of Variant Effect and Automated Patch Clamping Improve <i>KCNH2</i>-LQTS Variant Classification and Cardiac Event Risk Stratification.","authors":"Matthew J O'Neill, Chai-Ann Ng, Takanori Aizawa, Luca Sala, Sahej Bains, Annika Winbo, Rizwan Ullah, Qianyi Shen, Chek-Ying Tan, Krystian Kozek, Loren R Vanags, Devyn W Mitchell, Alex Shen, Yuko Wada, Asami Kashiwa, Lia Crotti, Federica Dagradi, Giulia Musu, Carla Spazzolini, Raquel Neves, J Martijn Bos, John R Giudicessi, Xavier Bledsoe, Eric R Gamazon, Megan C Lancaster, Andrew M Glazer, Bjorn C Knollmann, Dan M Roden, Jochen Weile, Frederick Roth, Joe-Elie Salem, Nikki Earle, Rachael Stiles, Taylor Agee, Christopher N Johnson, Minoru Horie, Jonathan Skinner, Michael J Ackerman, Peter J Schwartz, Seiko Ohno, Jamie I Vandenberg, Brett M Kroncke","doi":"10.1161/CIRCULATIONAHA.124.069828","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.069828","url":null,"abstract":"<p><strong>Background: </strong>Long QT syndrome is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by <i>KCNH2</i>. Variant classification is difficult, often because of lack of functional data. Moreover, variant-based risk stratification is also complicated by heterogenous clinical data and incomplete penetrance. Here we sought to test whether variant-specific information, primarily from high-throughput functional assays, could improve both classification and cardiac event risk stratification in a large, harmonized cohort of <i>KCNH2</i> missense variant heterozygotes.</p><p><strong>Methods: </strong>We quantified cell-surface trafficking of 18 796 variants in <i>KCNH2</i> using a multiplexed assay of variant effect (MAVE). We recorded KCNH2 current density for 533 variants by automated patch clamping. We calibrated the strength of evidence of MAVE data according to ClinGen guidelines. We deeply phenotyped 1458 patients with <i>KCNH2</i> missense variants, including QTc, cardiac event history, and mortality. We correlated variant functional data and Bayesian long QT syndrome penetrance estimates with cohort phenotypes and assessed hazard ratios for cardiac events.</p><p><strong>Results: </strong>Variant MAVE trafficking scores and automated patch clamping peak tail currents were highly correlated (Spearman rank-order ρ=0.69; n=433). The MAVE data were found to provide up to pathogenic very strong evidence for severe loss-of-function variants. In the cohort, both functional assays and Bayesian long QT syndrome penetrance estimates were significantly predictive of cardiac events when independently modeled with patient sex and adjusted QT interval (QTc); however, MAVE data became nonsignificant when peak tail current and penetrance estimates were also available. The area under the receiver operator characteristic curve for 20-year event outcomes based on patient-specific sex and QTc (area under the curve, 0.80 [0.76-0.83]) was improved with prospectively available penetrance scores conditioned on MAVE (area under the curve, 0.86 [0.83-0.89]) or attainable automated patch clamping peak tail current data (area under the curve, 0.84 [0.81-0.88]).</p><p><strong>Conclusions: </strong>High-throughput <i>KCNH2</i> variant MAVE data meaningfully contribute to variant classification at scale, whereas long QT syndrome penetrance estimates and automated patch clamping peak tail current measurements meaningfully contribute to risk stratification of cardiac events in patients with heterozygous <i>KCNH2</i> missense variants.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307250","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}
引用次数: 0
Circulating Autoantibodies Targeting TREK-1 in Patients With Short-Coupled Ventricular Fibrillation. 短耦合室颤患者体内针对TREK-1的循环自身抗体
IF 35.5 1区 医学
Circulation Pub Date : 2024-09-24 DOI: 10.1161/CIRCULATIONAHA.124.070284
Jin Li, Alexandre Janin, Mona Patoughi, Nathalie Gaudreault, Lenke Kis, Hamid Moha Ou Maat, Yohan Bossé, Christian Steinberg
{"title":"Circulating Autoantibodies Targeting TREK-1 in Patients With Short-Coupled Ventricular Fibrillation.","authors":"Jin Li, Alexandre Janin, Mona Patoughi, Nathalie Gaudreault, Lenke Kis, Hamid Moha Ou Maat, Yohan Bossé, Christian Steinberg","doi":"10.1161/CIRCULATIONAHA.124.070284","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.070284","url":null,"abstract":"<p><strong>Background: </strong>Short-coupled ventricular fibrillation (SCVF) is increasingly being recognized as a distinct primary electrical disorder and cause of otherwise unexplained cardiac arrest. However, the pathophysiology of SCVF remains largely elusive. Despite extensive genetic screening, there is no convincing evidence of a robust monogenic disease gene, thus raising the speculations for alternative pathogeneses. The role of autoimmune mechanisms in SCVF has not been investigated so far. The objective of this study was to screen for circulating autoantibodies in patients with SCVF and assess their role in arrhythmogenesis.</p><p><strong>Methods: </strong>This is a prospective, single-center, case-control study enrolling cardiac arrest survivors diagnosed with SCVF or idiopathic ventricular fibrillation (IVF) between 2019 and 2023 at the Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval Inherited Arrhythmia Clinic in Canada. Plasma samples were screened for autoantibodies targeting cardiac ion channels using peptide microarray technology. Identified target autoantibodies were then purified from pooled plasma samples for subsequent cellular electrophysiological studies.</p><p><strong>Results: </strong>Fourteen patients with SCVF (n=4 [29%] female patients; median age, 45 years [36, 58]; n=14 [100%] non-Hispanic White) and 19 patients with idiopathic ventricular fibrillation (n=8 [42%] female patients; median age, 49 years [38, 57]; n=19 [100%] non-Hispanic White) were enrolled in the study and compared with 38 (n=20 [53%] female subjects; median age, 45 years [29, 66]; n=36 [95%] non-Hispanic White) sex-, age- and ethnicity-matched healthy controls. During the study period, 11 (79%) SCVF probands experienced ventricular fibrillation recurrence after a median of 4.3 months (interquartile range, 0.3-20.7). Autoantibodies targeting cardiac TREK-1 (TWIK [tandem of pore-domains in a weakly inward rectifying potassium channel]-related potassium channel 1 were identified in 7 (50%) patients with SCVF (<i>P</i>=0.049). Patch clamp experiments demonstrated channel-activating properties of anti-TREK-1 autoantibodies that are antagonized by quinidine in both HEK293 cells and human induced pluripotent stem cell-derived cardiomyocytes.</p><p><strong>Conclusions: </strong>Patients with SCVF harbor circulating autoantibodies against the cardiac TREK-1 channel. Anti-TREK-1 autoantibodies not only present the first reported biomarker for SCVF, but our functional studies also suggest a direct implication in the arrhythmogenesis of SCVF.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307189","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}
引用次数: 0
2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM 非心脏手术围手术期心血管管理指南:美国心脏病学会/美国心脏协会临床实践指南联合委员会报告》。
IF 37.8 1区 医学
Circulation Pub Date : 2024-09-24 DOI: 10.1161/cir.0000000000001285
Annemarie Thompson,Kirsten E Fleischmann,Nathaniel R Smilowitz,Lisa de Las Fuentes,Debabrata Mukherjee,Niti R Aggarwal,Faraz S Ahmad,Robert B Allen,S Elissa Altin,Andrew Auerbach,Jeffrey S Berger,Benjamin Chow,Habib A Dakik,Eric L Eisenstein,Marie Gerhard-Herman,Kamrouz Ghadimi,Bessie Kachulis,Jacinthe Leclerc,Christopher S Lee,Tracy E Macaulay,Gail Mates,Geno J Merli,Purvi Parwani,Jeanne E Poole,Michael W Rich,Kurt Ruetzler,Steven C Stain,BobbieJean Sweitzer,Amy W Talbot,Saraschandra Vallabhajosyula,John Whittle,Kim Allan Williams
{"title":"2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.","authors":"Annemarie Thompson,Kirsten E Fleischmann,Nathaniel R Smilowitz,Lisa de Las Fuentes,Debabrata Mukherjee,Niti R Aggarwal,Faraz S Ahmad,Robert B Allen,S Elissa Altin,Andrew Auerbach,Jeffrey S Berger,Benjamin Chow,Habib A Dakik,Eric L Eisenstein,Marie Gerhard-Herman,Kamrouz Ghadimi,Bessie Kachulis,Jacinthe Leclerc,Christopher S Lee,Tracy E Macaulay,Gail Mates,Geno J Merli,Purvi Parwani,Jeanne E Poole,Michael W Rich,Kurt Ruetzler,Steven C Stain,BobbieJean Sweitzer,Amy W Talbot,Saraschandra Vallabhajosyula,John Whittle,Kim Allan Williams","doi":"10.1161/cir.0000000000001285","DOIUrl":"https://doi.org/10.1161/cir.0000000000001285","url":null,"abstract":"AIMThe \"2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery\" provides recommendations to guide clinicians in the perioperative cardiovascular evaluation and management of adult patients undergoing noncardiac surgery.METHODSA comprehensive literature search was conducted from August 2022 to March 2023 to identify clinical studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.STRUCTURERecommendations from the \"2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery\" have been updated with new evidence consolidated to guide clinicians; clinicians should be advised this guideline supersedes the previously published 2014 guideline. In addition, evidence-based management strategies, including pharmacological therapies, perioperative monitoring, and devices, for cardiovascular disease and associated medical conditions, have been developed.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321030","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}
引用次数: 0
NT-proBNP and Cardiac Troponin I, but Not Cardiac Troponin T, Are Associated With 7-Year Changes in Cardiac Structure and Function in Older Adults: The ARIC Study. NT-proBNP和心肌肌钙蛋白I(而非心肌肌钙蛋白T)与老年人心脏结构和功能的7年变化有关:ARIC研究
IF 35.5 1区 医学
Circulation Pub Date : 2024-09-24 DOI: 10.1161/CIRCULATIONAHA.124.069735
Peder L Myhre, Brian Claggett, Christie M Ballantyne, Ron C Hoogeveen, Elizabeth Selvin, Kunihiro Matsushita, Dalane Kitzman, Suma Konety, Thomas Mosley, Amil M Shah
{"title":"NT-proBNP and Cardiac Troponin I, but Not Cardiac Troponin T, Are Associated With 7-Year Changes in Cardiac Structure and Function in Older Adults: The ARIC Study.","authors":"Peder L Myhre, Brian Claggett, Christie M Ballantyne, Ron C Hoogeveen, Elizabeth Selvin, Kunihiro Matsushita, Dalane Kitzman, Suma Konety, Thomas Mosley, Amil M Shah","doi":"10.1161/CIRCULATIONAHA.124.069735","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.069735","url":null,"abstract":"<p><strong>Background: </strong>Higher circulating concentrations of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) are associated with left ventricular remodeling and with incident heart failure. The associations of these cardiac biomarkers with changes in cardiac structure and function over time are uncharacterized.</p><p><strong>Methods: </strong>Among 2006 participants in the ARIC prospective cohort study (Atherosclerosis Risk in Communities) who were free of overt cardiovascular disease and underwent echocardiography at study visits 5 (2011- 2013) and 7 (2018-2019), we assessed the associations of NT-proBNP, hs-cTnT, and hs-cTnI concentrations at visit 5 with changes in left ventricular structure and function between visits 5 and 7 (≈7-year change) using multivariable linear regression with the biomarkers modeled as restricted cubic splines. Models were adjusted for age, sex, race, body mass index, smoking, diabetes, hypertension, and renal function at visit 5; blood pressure and heart rate at both visits; and the baseline value of the echocardiographic parameter of interest.</p><p><strong>Results: </strong>Mean±SD age was 74±4 years at visit 5; 61% were women; and 23% were Black adults. Median (25th-75th percentile) concentrations at visit 5 of NT-proBNP, hs-cTnT, and hs-cTnI were 87 ng/L (50-157 ng/L), 9 ng/L (6-12 ng/L), and 2.6 ng/L (1.9-3.9 ng/L). In adjusted models, elevated baseline concentrations of NT-proBNP and hs-cTnI were significantly associated with 7-year decline in left ventricular systolic function (ejection fraction, longitudinal and circumferential strain) and worsening diastolic indices. In contrast, elevated baseline concentrations of hs-cTnT were not significantly associated with 7-year changes in cardiac structure, systolic function, or diastolic function (all <i>P</i>>0.05).</p><p><strong>Conclusions: </strong>Higher concentrations of NT-proBNP and hs-cTnI, but not hs-cTnT, were associated with greater declines in left ventricular function over ≈7 years in late life independently of traditional cardiovascular risk factors.AQ.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307191","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}
引用次数: 0
Bone Morphogenetic Protein 9 Protects Against Myocardial Infarction by Improving Lymphatic Drainage Function and Triggering DECR1-Mediated Mitochondrial Bioenergetics. 骨形态发生蛋白 9 通过改善淋巴排泄功能和触发 DECR1 介导的线粒体生物能量代谢保护心肌梗死。
IF 35.5 1区 医学
Circulation Pub Date : 2024-09-24 DOI: 10.1161/CIRCULATIONAHA.123.065935
Zikun Duan, Zhouqing Huang, Wei Lei, Ke Zhang, Wei Xie, Hua Jin, Maolan Wu, Ningrui Wang, Xiaokun Li, Aimin Xu, Hao Zhou, Fan Wu, Yulin Li, Zhuofeng Lin
{"title":"Bone Morphogenetic Protein 9 Protects Against Myocardial Infarction by Improving Lymphatic Drainage Function and Triggering DECR1-Mediated Mitochondrial Bioenergetics.","authors":"Zikun Duan, Zhouqing Huang, Wei Lei, Ke Zhang, Wei Xie, Hua Jin, Maolan Wu, Ningrui Wang, Xiaokun Li, Aimin Xu, Hao Zhou, Fan Wu, Yulin Li, Zhuofeng Lin","doi":"10.1161/CIRCULATIONAHA.123.065935","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.123.065935","url":null,"abstract":"<p><strong>Background: </strong>BMP9 (bone morphogenetic protein 9) is a member of the TGF-β (transforming growth factor β) family of cytokines with pleiotropic effects on glucose metabolism, fibrosis, and lymphatic development. However, the role of BMP9 in myocardial infarction (MI) remains elusive.</p><p><strong>Methods: </strong>The expressional profiles of BMP9 in cardiac tissues and plasma samples of subjects with MI were determined by immunoassay or immunoblot. The role of BMP9 in MI was determined by evaluating the impact of BMP9 deficiency and replenishment with adeno-associated virus-mediated BMP9 expression or recombinant human BMP9 protein in mice.</p><p><strong>Results: </strong>We show that circulating BMP9 and its cardiac levels are markedly increased in humans and mice with MI and are negatively associated with cardiac function. It is important to note that BMP9 deficiency exacerbates left ventricular dysfunction, increases infarct size, and augments cardiac fibrosis in mice with MI. In contrast, replenishment of BMP9 significantly attenuates these adverse effects. We further demonstrate that BMP9 improves lymphatic drainage function, thereby leading to a decrease of cardiac edema. In addition, BMP9 increases the expression of mitochondrial DECR1 (2,4-dienoyl-CoA reductase 1), a rate-limiting enzyme involved in β-oxidation, which, in turn, promotes cardiac mitochondrial bioenergetics and mitigates MI-induced cardiomyocyte injury. Moreover, DECR1 deficiency exacerbates MI-induced cardiac damage in mice, whereas this adverse effect is restored by the treatment of adeno-associated virus-mediated DECR1. Consistently, DECR1 deletion abrogates the beneficial effect of BMP9 against MI-induced cardiomyopathy and cardiac damage in mice.</p><p><strong>Conclusions: </strong>These results suggest that BMP9 protects against MI by fine-tuning the multiorgan cross-talk among the liver, lymph, and the heart.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307188","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}
引用次数: 0
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