Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study.

Autor:	Jansen M; Department of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; Department of Cardiology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; Netherlands Heart Institute, Utrecht, the Netherlands; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart). Electronic address: m.jansen-48@umcutrecht.nl., de Brouwer R; Netherlands Heart Institute, Utrecht, the Netherlands; Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands., Hassanzada F; Department of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart)., Schoemaker AE; Department of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart)., Schmidt AF; Department of Cardiology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart); Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom; Department of Cardiology, University Medical Centre Amsterdam, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Heart Failure and Arrhythmias, University Medical Centre Amsterdam, Amsterdam, the Netherlands., Kooijman-Reumerman MD; Department of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart)., Bracun V; Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands., Slieker MG; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart); Department of Pediatric Cardiology, University Medical Centre Utrecht, Utrecht University, the Netherlands., Dooijes D; Department of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart)., Vermeer AMC; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart); Department of Human Genetics, University Medical Centre Amsterdam Amsterdam, University of Amsterdam, Amsterdam, the Netherlands., Wilde AAM; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart); Department of Cardiology, University Medical Centre Amsterdam, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Heart Failure and Arrhythmias, University Medical Centre Amsterdam, Amsterdam, the Netherlands., Amin AS; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart); Department of Cardiology, University Medical Centre Amsterdam, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Heart Failure and Arrhythmias, University Medical Centre Amsterdam, Amsterdam, the Netherlands., Lekanne Deprez RH; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart); Department of Human Genetics, University Medical Centre Amsterdam Amsterdam, University of Amsterdam, Amsterdam, the Netherlands., Herkert JC; Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands., Christiaans I; Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands., de Boer RA; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart); Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands; Department of Cardiology, Thorax Center, Erasmus University Medical Center, Erasmus University Rotterdam, Rotterdam, the Netherlands., Jongbloed JDH; Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands., van Tintelen JP; Department of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; Netherlands Heart Institute, Utrecht, the Netherlands; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart)., Asselbergs FW; Department of Cardiology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart); Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom; Department of Cardiology, University Medical Centre Amsterdam, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Heart Failure and Arrhythmias, University Medical Centre Amsterdam, Amsterdam, the Netherlands; Health Data Research UK and Institute of Health Informatics, University College London, London, United Kingdom., Baas AF; Department of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart).
Jazyk:	angličtina
Zdroj:	JACC. Heart failure [JACC Heart Fail] 2024 Jan; Vol. 12 (1), pp. 134-147. Date of Electronic Publication: 2023 Aug 09.
DOI:	10.1016/j.jchf.2023.07.007
Abstrakt:	Background: MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene. Objectives: This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies. Methods: In this multicenter cohort study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients. Results: In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age <12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95% CI: 1.15-3.04; P = 0.012) and at age ≤1 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95% CI: 4.81-93.20; P < 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95% CI: 1.09-5.50; P = 0.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95% CI: 1.15-2.87; P = 0.010) and at age ≤5 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95% CI: 5.16-291.88; P < 0.001). Conclusions: MYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at <12 years. Competing Interests: Funding Support and Author Disclosures This work was supported by the Netherlands Cardiovascular Research Initiative with the support of the Dutch Heart Foundation. Dr Jansen has received support from the Netherlands Cardiovascular Research Initiative with the support of the Dutch Heart Foundation (CVON2014-40 DOSIS, DCVA [Dutch Cardiovascular Alliance] 2020B005 DoubleDose) and from the Dutch Heart Foundation (Dekker 2015T041). Dr Christiaans has received support from the Netherlands Cardiovascular Research Initiative with the support of the Dutch Heart Foundation (CVON2015-12 e-Detect). Dr de Boer has received support from the Netherlands Cardiovascular Research Initiative with the support of the Dutch Heart Foundation (CVON2014-40 DOSIS, DCVA 2020B005 DoubleDose). Dr van Tintelen has received support from the Netherlands Cardiovascular Research Initiative with the support of the Dutch Heart Foundation (CVON2014-40 DOSIS, DCVA 2020B005 DoubleDose and CVON2015-12 e-Detect). Dr Asselbergs has received support from the Netherlands Cardiovascular Research Initiative with the support of the Dutch Heart Foundation (CVON2014-40 DOSIS, DCVA 2020B005 DoubleDose and CVON2015-12 e-Detect) and from the UCL Hospitals NIHR Biomedical Research Centre. Dr Baas has received support from the Netherlands Cardiovascular Research Initiative with the support of the Dutch Heart Foundation (CVON2014-40 DOSIS, DCVA 2020B005 DoubleDose and CVON2015-12 e-Detect) and from the Dutch Heart Foundation (Dekker 2015T041). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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