TY - JOUR
T1 - Natural History of MYH7-related Dilated Cardiomyopathy
AU - de Frutos, Fernando
AU - Ochoa, Juan Pablo
AU - Navarro-Peñalver, Marina
AU - Baas, Annette
AU - Bjerre, Jesper Vandborg
AU - Zorio, Esther
AU - Méndez, Irene
AU - Lorca, Rebeca
AU - Verdonschot, Job Aj
AU - García-Granja, Pablo Elpidio
AU - Bilinska, Zofia
AU - Fatkin, Diane
AU - Fuentes-Cañamero, M Eugenia
AU - García-Pinilla, José M
AU - García-Álvarez, María I
AU - Girolami, Francesca
AU - Barriales-Villa, Roberto
AU - Díez-López, Carles
AU - Lopes, Luis R
AU - Wahbi, Karim
AU - García-Álvarez, Ana
AU - Rodríguez-Sánchez, Ibon
AU - Rekondo-Olaetxea, Javier
AU - Rodríguez-Palomares, José F
AU - Gallego-Delgado, María
AU - Meder, Benjamin
AU - Kubanek, Milos
AU - Hansen, Frederikke G
AU - Restrepo-Córdoba, María Alejandra
AU - Palomino-Doza, Julián
AU - Ruiz-Guerrero, Luis
AU - Sarquella-Brugada, Georgia
AU - Perez-Perez, Alberto José
AU - Bermúdez-Jiménez, Francisco José
AU - Ripoll-Vera, Tomas
AU - Rasmussen, Torsten Bloch
AU - Jansen, Mark
AU - Sabater-Molina, Maria
AU - Elliot, Perry M
AU - Garcia-Pavia, Pablo
AU - European Genetic Cardiomyopathies Initiative Investigators
N1 - Copyright © 2022. Published by Elsevier Inc.
PY - 2022/10/11
Y1 - 2022/10/11
N2 - Background: Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. Objectives: We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. Methods: We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. Results: At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. Conclusions: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare.
AB - Background: Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. Objectives: We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. Methods: We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. Results: At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. Conclusions: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare.
U2 - 10.1016/j.jacc.2022.07.023
DO - 10.1016/j.jacc.2022.07.023
M3 - Article
C2 - 36007715
SN - 0735-1097
VL - 80
SP - 1447
EP - 1461
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 15
ER -