Clinical features and outcomes in carriers of pathogenic desmoplakin variants.

Autor:	Gasperetti A; Division of Cardiology, Department of Medicine, Johns Hopkins University, 601 North Caroline St., Baltimore, MD 21287, USA.; Department of Genetics, University Medical Center Utrecht, University of Utrecht, The Netherlands.; Department of Medicine, Division of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Carrick RT; Division of Cardiology, Department of Medicine, Johns Hopkins University, 601 North Caroline St., Baltimore, MD 21287, USA., Protonotarios A; UCL Institute of Cardiovascular Science, London, UK., Murray B; Division of Cardiology, Department of Medicine, Johns Hopkins University, 601 North Caroline St., Baltimore, MD 21287, USA., Laredo M; Institut de Cardiologie, Sorbonne Université, AP-HP, IHU-ICAN, Groupe Hospitalier Pitié-Salpêtrière, Paris, France., van der Schaaf I; Department of Medicine, Division of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Lekanne RH; Department of Medicine, Division of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Syrris P; UCL Institute of Cardiovascular Science, London, UK., Cannie D; UCL Institute of Cardiovascular Science, London, UK., Tichnell C; Division of Cardiology, Department of Medicine, Johns Hopkins University, 601 North Caroline St., Baltimore, MD 21287, USA., Cappelletto C; Division of Cardiology, Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina and University of Trieste, Trieste, Italy., Gigli M; Division of Cardiology, Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina and University of Trieste, Trieste, Italy., Medo K; University of Colorado Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Saguner AM; Department of Cardiology, Arrhythmia Unit, University Heart Center, University Hospital Zurich, Zurich, Switzerland.; Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of Zurich, 8952 Schlieren, Switzerland., Duru F; Department of Cardiology, Arrhythmia Unit, University Heart Center, University Hospital Zurich, Zurich, Switzerland.; Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of Zurich, 8952 Schlieren, Switzerland., Gilotra NA; Division of Cardiology, Department of Medicine, Johns Hopkins University, 601 North Caroline St., Baltimore, MD 21287, USA., Zimmerman S; Division of Cardiology, Department of Medicine, Johns Hopkins University, 601 North Caroline St., Baltimore, MD 21287, USA., Hylind R; Center for Cardiovascular Genetics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA., Abrams DJ; Center for Cardiovascular Genetics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA., Lakdawala NK; Brigham and Women's Hospital Cardiovascular Medicine, Boston, MA, USA., Cadrin-Tourigny J; Cardiovascular Genetics Center, Montreal Heart Institute, Université de Montréal, Montréal, QC, Canada., Targetti M; Department of Experimental and Clinical Medicine, University of Florence, Meyer Children Hospital and Careggi University Hospital, Florence, Italy., Olivotto I; Department of Experimental and Clinical Medicine, University of Florence, Meyer Children Hospital and Careggi University Hospital, Florence, Italy., Graziosi M; Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Italy., Cox M; Department of Cardiology, University Medical Centre Groningen, Groningen, The Netherlands., Biagini E; Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Italy., Charron P; Institut de Cardiologie, Sorbonne Université, AP-HP, IHU-ICAN, Groupe Hospitalier Pitié-Salpêtrière, Paris, France., Casella M; Department of Clinical, Special and Dental Sciences, Cardiology and Arrhythmology Clinic, University Hospital 'Ospedali Riuniti', Marche Polytechnic University, Ancona, Italy., Tondo C; Dept. of Clinical Electrophysiology & Cardiac Pacing, Centro Cardiologico Monzino, IRCCS, Milan, Italy.; Dept. of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy., Yazdani M; National Heart and Lung Institute and MRC London Institute of Medical Sciences, Imperial College London, London, UK.; Royal Brompton & Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK., Ware JS; National Heart and Lung Institute and MRC London Institute of Medical Sciences, Imperial College London, London, UK.; Royal Brompton & Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK., Prasad SK; National Heart and Lung Institute and MRC London Institute of Medical Sciences, Imperial College London, London, UK.; Royal Brompton & Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK., Calò L; Department of Cardiology, Policlinico Casilino, Rome, Italy., Smith ED; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, USA., Helms AS; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, USA., Hespe S; Centre for Population Genomics, Garvan Institute of Medical Research, and UNSW Sydney, Sydney, Australia., Ingles J; Centre for Population Genomics, Garvan Institute of Medical Research, and UNSW Sydney, Sydney, Australia., Tandri H; Division of Cardiology, Department of Medicine, Johns Hopkins University, 601 North Caroline St., Baltimore, MD 21287, USA., Ader F; APHP Sorbonne Université, DMU BioGem, UF de cardiogénétique et myogénétique moléculaire et cellulaire, 75013 Paris, France.; Université Paris Cité, UFR de Pharmacie, UP Biochimie, 75006 Paris, France., Peretto G; Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Hospital, Milan, Italy., Peters S; Royal Melbourne Hospital, Melbourne 3050, Victoria, Australia., Horton A; Royal Melbourne Hospital, Melbourne 3050, Victoria, Australia., Yao J; Royal Melbourne Hospital, Melbourne 3050, Victoria, Australia., Dittmann S; Department of Cardiovascular Medicine, Institute for Genetics of Heart Diseases, University Hospital Münster, Münster, Germany., Schulze-Bahr E; Department of Cardiovascular Medicine, Institute for Genetics of Heart Diseases, University Hospital Münster, Münster, Germany., Qureshi M; The Heart Institute, Geisinger, Danville, PA, USA., Young K; The Heart Institute, Geisinger, Danville, PA, USA., Carruth ED; The Heart Institute, Geisinger, Danville, PA, USA., Haggerty C; The Heart Institute, Geisinger, Danville, PA, USA.; Department of Translational Data Science and Informatics, Geisinger, Danville, PA, USA., Parikh VN; Stanford Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA., Taylor M; University of Colorado Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Mestroni L; University of Colorado Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Wilde A; Department of Cardiology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.; Amsterdam Cardiovascular Sciences, Heart Failure and Arrhythmias, Amsterdam, The Netherlands., Sinagra G; Institut de Cardiologie, Sorbonne Université, AP-HP, IHU-ICAN, Groupe Hospitalier Pitié-Salpêtrière, Paris, France., Merlo M; Division of Cardiology, Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina and University of Trieste, Trieste, Italy., Gandjbakhch E; Institut de Cardiologie, Sorbonne Université, AP-HP, IHU-ICAN, Groupe Hospitalier Pitié-Salpêtrière, Paris, France., van Tintelen JP; Department of Genetics, University Medical Center Utrecht, University of Utrecht, The Netherlands.; Netherlands Heart Institute, Utrecht, The Netherlands., Te Riele ASJM; Department of Medicine, Division of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.; Netherlands Heart Institute, Utrecht, The Netherlands., Elliott PM; UCL Institute of Cardiovascular Science, London, UK., Calkins H; Division of Cardiology, Department of Medicine, Johns Hopkins University, 601 North Caroline St., Baltimore, MD 21287, USA., James CA; Division of Cardiology, Department of Medicine, Johns Hopkins University, 601 North Caroline St., Baltimore, MD 21287, USA.
Jazyk:	angličtina
Zdroj:	European heart journal [Eur Heart J] 2024 Sep 17. Date of Electronic Publication: 2024 Sep 17.
DOI:	10.1093/eurheartj/ehae571
Abstrakt:	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. (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)
Databáze:	MEDLINE
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