Alessio Gasperetti, Richard T Carrick, Alexandros Protonotarios, Brittney Murray, Mikael Laredo, Iris van der Schaaf, Ronald H Lekanne, Petros Syrris, Douglas Cannie, Crystal Tichnell, Chiara Cappelletto, Marta Gigli, Kristen Medo, Ardan M Saguner, Firat Duru, Nisha A Gilotra, Stefan Zimmerman, Robyn Hylind, Dominic J Abrams, Neal K Lakdawala, Julia Cadrin-Tourigny, Mattia Targetti, Iacopo Olivotto, Maddalena Graziosi, Moniek Cox, Elena Biagini, Philippe Charron, Michela Casella, Claudio Tondo, Momina Yazdani, James S Ware, Sanjay K Prasad, Leonardo Calò, Eric D Smith, Adam S Helms, Sophie Hespe, Jodie Ingles, Harikrishna Tandri, Flavie Ader, Giovanni Peretto, Stacey Peters, Ari Horton, Jess Yao, Sven Dittmann, Eric Schulze-Bahr, Maria Qureshi, Katelyn Young, Eric D Carruth, Chris Haggerty, Victoria N Parikh, Matthew Taylor, Luisa Mestroni, Arthur Wilde, Gianfranco Sinagra, Marco Merlo, Estelle Gandjbakhch, J Peter van Tintelen, Anneline S J M te Riele, Perry M Elliott, Hugh Calkins, Cynthia A James
{"title":"Clinical features and outcomes in carriers of pathogenic desmoplakin variants","authors":"Alessio Gasperetti, Richard T Carrick, Alexandros Protonotarios, Brittney Murray, Mikael Laredo, Iris van der Schaaf, Ronald H Lekanne, Petros Syrris, Douglas Cannie, Crystal Tichnell, Chiara Cappelletto, Marta Gigli, Kristen Medo, Ardan M Saguner, Firat Duru, Nisha A Gilotra, Stefan Zimmerman, Robyn Hylind, Dominic J Abrams, Neal K Lakdawala, Julia Cadrin-Tourigny, Mattia Targetti, Iacopo Olivotto, Maddalena Graziosi, Moniek Cox, Elena Biagini, Philippe Charron, Michela Casella, Claudio Tondo, Momina Yazdani, James S Ware, Sanjay K Prasad, Leonardo Calò, Eric D Smith, Adam S Helms, Sophie Hespe, Jodie Ingles, Harikrishna Tandri, Flavie Ader, Giovanni Peretto, Stacey Peters, Ari Horton, Jess Yao, Sven Dittmann, Eric Schulze-Bahr, Maria Qureshi, Katelyn Young, Eric D Carruth, Chris Haggerty, Victoria N Parikh, Matthew Taylor, Luisa Mestroni, Arthur Wilde, Gianfranco Sinagra, Marco Merlo, Estelle Gandjbakhch, J Peter van Tintelen, Anneline S J M te Riele, Perry M Elliott, Hugh Calkins, Cynthia A James","doi":"10.1093/eurheartj/ehae571","DOIUrl":null,"url":null,"abstract":"Background and Aims Pathogenic variants in the desmoplakin (DSP) gene are associated with the development of a distinct arrhythmogenic cardiomyopathy phenotype not fully captured by either dilated cardiomyopathy (DCM), non-dilated left ventricular cardiomyopathy (NDLVC), or arrhythmogenic right ventricular cardiomyopathy (ARVC). Prior studies have described baseline DSP cardiomyopathy genetic, inflammatory, and structural characteristics. However, cohort sizes have limited full clinical characterization and identification of clinical and demographic predictors of sustained ventricular arrhythmias (VAs), heart failure (HF) hospitalizations, and transplant/death. In particular, the relevance of acute myocarditis-like episodes for subsequent disease course is largely unknown. Methods All patients with pathogenic/likely pathogenic (P/LP) DSP variants in the worldwide DSP-ERADOS Network (26 academic institutions across nine countries) were included. The primary outcomes were the development of sustained VA and HF hospitalizations during follow-up. Fine–Gray regressions were used to test association between clinical and instrumental parameters and the development of outcomes. Results Eight hundred patients [40.3 ± 17.5 years, 47.5% probands, left ventricular ejection fraction (LVEF) 49.5 ± 13.9%] were included. Over 3.7 [1.4–7.1] years, 139 (17.4%, 3.9%/year) and 72 (9.0%, 1.8%/year) patients experienced sustained VA and HF episodes, respectively. A total of 32.5% of individuals did not fulfil diagnostic criteria for ARVC, DCM, or NDLVC; their VA incidence was 0.5%/year. In multivariable regression, risk features associated with the development of VA were female sex [adjusted hazard ratio (aHR) 1.547; P = .025], prior non-sustained ventricular tachycardia (aHR 1.721; P = .009), prior sustained VA (aHR 1.923; P = .006), and LVEF ≤ 50% (aHR: 1.645; P = .032), while for HF, they were the presence of T-wave inversion in 3+ electrocardiogram leads (aHR 2.036, P = .007) and LVEF ≤ 50% (aHR 3.879; P < .001). Additionally, 70 (8.8%) patients experienced a myocardial injury episode at presentation or during follow-up. These episodes were associated with an increased risk of VA and HF thereafter (HR 2.394; P < .001, and HR 5.064, P < .001, respectively). Conclusions Patients with P/LP DSP variants experience high rates of sustained VA and HF hospitalizations. These patients demonstrate a distinct clinical phenotype (DSP cardiomyopathy), whose most prominent risk features associated with adverse clinical outcomes are the presence of prior non-sustained ventricular tachycardia or sustained VA, T-wave inversion in 3+ leads on electrocardiogram, LVEF ≤ 50%, and myocardial injury events.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":null,"pages":null},"PeriodicalIF":37.6000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Heart Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/eurheartj/ehae571","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
Background and Aims Pathogenic variants in the desmoplakin (DSP) gene are associated with the development of a distinct arrhythmogenic cardiomyopathy phenotype not fully captured by either dilated cardiomyopathy (DCM), non-dilated left ventricular cardiomyopathy (NDLVC), or arrhythmogenic right ventricular cardiomyopathy (ARVC). Prior studies have described baseline DSP cardiomyopathy genetic, inflammatory, and structural characteristics. However, cohort sizes have limited full clinical characterization and identification of clinical and demographic predictors of sustained ventricular arrhythmias (VAs), heart failure (HF) hospitalizations, and transplant/death. In particular, the relevance of acute myocarditis-like episodes for subsequent disease course is largely unknown. Methods All patients with pathogenic/likely pathogenic (P/LP) DSP variants in the worldwide DSP-ERADOS Network (26 academic institutions across nine countries) were included. The primary outcomes were the development of sustained VA and HF hospitalizations during follow-up. Fine–Gray regressions were used to test association between clinical and instrumental parameters and the development of outcomes. Results Eight hundred patients [40.3 ± 17.5 years, 47.5% probands, left ventricular ejection fraction (LVEF) 49.5 ± 13.9%] were included. Over 3.7 [1.4–7.1] years, 139 (17.4%, 3.9%/year) and 72 (9.0%, 1.8%/year) patients experienced sustained VA and HF episodes, respectively. A total of 32.5% of individuals did not fulfil diagnostic criteria for ARVC, DCM, or NDLVC; their VA incidence was 0.5%/year. In multivariable regression, risk features associated with the development of VA were female sex [adjusted hazard ratio (aHR) 1.547; P = .025], prior non-sustained ventricular tachycardia (aHR 1.721; P = .009), prior sustained VA (aHR 1.923; P = .006), and LVEF ≤ 50% (aHR: 1.645; P = .032), while for HF, they were the presence of T-wave inversion in 3+ electrocardiogram leads (aHR 2.036, P = .007) and LVEF ≤ 50% (aHR 3.879; P < .001). Additionally, 70 (8.8%) patients experienced a myocardial injury episode at presentation or during follow-up. These episodes were associated with an increased risk of VA and HF thereafter (HR 2.394; P < .001, and HR 5.064, P < .001, respectively). Conclusions Patients with P/LP DSP variants experience high rates of sustained VA and HF hospitalizations. These patients demonstrate a distinct clinical phenotype (DSP cardiomyopathy), whose most prominent risk features associated with adverse clinical outcomes are the presence of prior non-sustained ventricular tachycardia or sustained VA, T-wave inversion in 3+ leads on electrocardiogram, LVEF ≤ 50%, and myocardial injury events.
期刊介绍:
The European Heart Journal is a renowned international journal that focuses on cardiovascular medicine. It is published weekly and is the official journal of the European Society of Cardiology. This peer-reviewed journal is committed to publishing high-quality clinical and scientific material pertaining to all aspects of cardiovascular medicine. It covers a diverse range of topics including research findings, technical evaluations, and reviews. Moreover, the journal serves as a platform for the exchange of information and discussions on various aspects of cardiovascular medicine, including educational matters.
In addition to original papers on cardiovascular medicine and surgery, the European Heart Journal also presents reviews, clinical perspectives, ESC Guidelines, and editorial articles that highlight recent advancements in cardiology. Additionally, the journal actively encourages readers to share their thoughts and opinions through correspondence.