TY - JOUR
T1 - Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies
T2 - Results From a Dutch Multicenter Cohort Study
AU - Jansen, Mark
AU - de Brouwer, Remco
AU - Hassanzada, Fahima
AU - Schoemaker, Angela E.
AU - Schmidt, Amand F.
AU - Kooijman-Reumerman, Maria D.
AU - Bracun, Valentina
AU - Slieker, Martijn G.
AU - Dooijes, Dennis
AU - Vermeer, Alexa M. C.
AU - Wilde, Arthur A. M.
AU - Amin, Ahmad S.
AU - Lekanne Deprez, Ronald H.
AU - Herkert, Johanna C.
AU - Christiaans, Imke
AU - de Boer, Rudolf A.
AU - Jongbloed, Jan D. H.
AU - van Tintelen, J. Peter
AU - Asselbergs, Folkert W.
AU - Baas, Annette F.
N1 - Publisher Copyright: © 2024 American College of Cardiology Foundation
PY - 2024/1
Y1 - 2024/1
N2 - 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.
AB - 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.
KW - MYH7
KW - cardiomyopathy
KW - myosin
KW - penetrance
KW - prognosis
KW - screening
UR - http://www.scopus.com/inward/record.url?scp=85171742798&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jchf.2023.07.007
DO - https://doi.org/10.1016/j.jchf.2023.07.007
M3 - Article
C2 - 37565978
SN - 2213-1779
VL - 12
SP - 134
EP - 147
JO - JACC: Heart Failure
JF - JACC: Heart Failure
IS - 1
ER -