A novel tool for arrhythmic risk stratification in desmoplakin gene variant carriers.

Autor:	Carrick RT; Division of Cardiology, Department of Medicine, Johns Hopkins University, 601 North Caroline St., Baltimore, MD 21287, USA., 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, Utrecht, The Netherlands.; Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Protonotarios A; Inherited Cardiovascular Diseases Unit, St Bartholomew's Hospital, 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, Institut de Cardiologie, Paris, France., van der Schaaf I; Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Dooijes D; Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Syrris P; Inherited Cardiovascular Diseases Unit, St Bartholomew's Hospital, UCL Institute of Cardiovascular Science, London, UK., Cannie D; Inherited Cardiovascular Diseases Unit, St Bartholomew's Hospital, 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., Gilotra NA; 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, University of Trieste, Trieste, Italy., Medo K; Department of Medicine, Division of Cardiology, 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., Duru F; Department of Cardiology, Arrhythmia Unit, University Heart Center, University Hospital Zurich, Zurich, Switzerland., Hylind RJ; Center for Cardiovascular Genetics, Boston Children's Hospital, Boston, MA, USA., Abrams DJ; Center for Cardiovascular Genetics, Boston Children's Hospital, Boston, MA, USA., Lakdawala NK; Center for Advanced Heart Disease, 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, Careggi University Hospital, Florence, Italy., Olivotto I; Department of Experimental and Clinical Medicine, University of Florence, Meyer Children Hospital, Careggi University Hospital, Florence, Italy., Graziosi M; Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, 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, Bologna, Italy., Charron P; Institut de Cardiologie, Sorbonne Université, AP-HP, IHU-ICAN, Groupe Hospitalier Pitié-Salpêtrière, Institut de Cardiologie, Paris, France., Compagnucci P; Cardiology and Arrhythmology Clinic, University Hospital 'Ospedali Riuniti', Ancona, Italy., Casella M; Cardiology and Arrhythmology Clinic, University Hospital 'Ospedali Riuniti', Ancona, Italy.; Department of Clinical, Special and Dental Sciences, Marche Polytechnic University, Ancona, Italy., Conte G; Department of Cardiology, Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland., Tondo C; Department of Clinical Electrophysiology and Cardiac Pacing, Centro Cardiologico Monzino, Cen, IRCCS, University of Milan, Milan, Italy.; Department of Biochemical, Surgical and Dentist Sciences, University of Milan, Milan, Italy., Yazdani M; Department of Cardiology, National Heart and Lung Institute and and MRC London Institute of Medical Sciences, London, United Kingdom.; Royal Brompton & Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK., Ware JS; Department of Cardiology, National Heart and Lung Institute and and MRC London Institute of Medical Sciences, London, United Kingdom.; Royal Brompton & Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK., Prasad SK; Department of Cardiology, National Heart and Lung Institute and and MRC London Institute of Medical Sciences, London, United Kingdom.; 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, UNSW Sydney, Sydney, Australia., Ingles J; Centre for Population Genomics, Garvan Institute of Medical Research, 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; UF de Cardiogénétique et Myogénétique Moléculaire et Cellulaire, APHP Sorbonne Université, DMU BioGem, 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; Department of Cardiology, Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia., Horton A; Department of Cardiology, Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia., Yao J; Department of Cardiology, Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia., Schulze-Bahr E; Department of Cardiovascular Medicine, Institute for Genetics of Heart Diseases, University Hospital Münster, Münster, Germany., Dittman S; Department of Cardiovascular Medicine, Institute for Genetics of Heart Diseases, University Hospital Münster, Münster, Germany., Carruth ED; Department of Translational Data Science and Informatics, Geisinger, Danville, PA, USA., Young K; Department of Translational Data Science and Informatics, Geisinger, Danville, PA, USA., Qureshi M; Department of Translational Data Science and Informatics, Geisinger, Danville, PA, USA., Haggerty C; Department of Translational Data Science and Informatics, Geisinger, Danville, PA, USA.; The Heart Institute, 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; Department of Medicine, Division of Cardiology, University of Colorado Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Mestroni L; Department of Medicine, Division of Cardiology, 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 UMC Location University of Amsterdam, Amsterdam, The Netherlands., Sinagra G; Division of Cardiology, Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina, University of Trieste, Trieste, Italy., Merlo M; Division of Cardiology, Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina, University of Trieste, Trieste, Italy., Gandjbakhch E; Institut de Cardiologie, Sorbonne Université, AP-HP, IHU-ICAN, Groupe Hospitalier Pitié-Salpêtrière, Institut de Cardiologie, Paris, France., van Tintelen JP; Department of Genetics, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.; Netherlands Heart Institute, Utrecht, The Netherlands., Te Riele ASJM; Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.; Netherlands Heart Institute, Utrecht, The Netherlands., Elliott P; Inherited Cardiovascular Diseases Unit, St Bartholomew's Hospital, 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., Wu KC; 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 Aug 21; Vol. 45 (32), pp. 2968-2979.
DOI:	10.1093/eurheartj/ehae409
Abstrakt:	Background and Aims: Pathogenic desmoplakin (DSP) gene variants are associated with the development of a distinct form of arrhythmogenic cardiomyopathy known as DSP cardiomyopathy. Patients harbouring these variants are at high risk for sustained ventricular arrhythmia (VA), but existing tools for individualized arrhythmic risk assessment have proven unreliable in this population. Methods: Patients from the multi-national DSP-ERADOS (Desmoplakin SPecific Effort for a RAre Disease Outcome Study) Network patient registry who had pathogenic or likely pathogenic DSP variants and no sustained VA prior to enrolment were followed longitudinally for the development of first sustained VA event. Clinically guided, step-wise Cox regression analysis was used to develop a novel clinical tool predicting the development of incident VA. Model performance was assessed by c-statistic in both the model development cohort (n = 385) and in an external validation cohort (n = 86). Results: In total, 471 DSP patients [mean age 37.8 years, 65.6% women, 38.6% probands, 26% with left ventricular ejection fraction (LVEF) < 50%] were followed for a median of 4.0 (interquartile range: 1.6-7.3) years; 71 experienced first sustained VA events {2.6% [95% confidence interval (CI): 2.0, 3.5] events/year}. Within the development cohort, five readily available clinical parameters were identified as independent predictors of VA and included in a novel DSP risk score: female sex [hazard ratio (HR) 1.9 (95% CI: 1.1-3.4)], history of non-sustained ventricular tachycardia [HR 1.7 (95% CI: 1.1-2.8)], natural logarithm of 24-h premature ventricular contraction burden [HR 1.3 (95% CI: 1.1-1.4)], LVEF < 50% [HR 1.5 (95% CI: .95-2.5)], and presence of moderate to severe right ventricular systolic dysfunction [HR 6.0 (95% CI: 2.9-12.5)]. The model demonstrated good risk discrimination within both the development [c-statistic .782 (95% CI: .77-.80)] and external validation [c-statistic .791 (95% CI: .75-.83)] cohorts. The negative predictive value for DSP patients in the external validation cohort deemed to be at low risk for VA (<5% at 5 years; n = 26) was 100%. Conclusions: The DSP risk score is a novel model that leverages readily available clinical parameters to provide individualized VA risk assessment for DSP patients. This tool may help guide decision-making for primary prevention implantable cardioverter-defibrillator placement in this high-risk population and supports a gene-first risk stratification approach. (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)
Databáze:	MEDLINE
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