Emery-Dreifuss muscular dystrophy Type 1 is associated with a high risk of malignant ventricular arrhythmias and end-stage heart failure.

Abstract

BACKGROUND AND AIMS:

Emery-Dreifuss muscular dystrophy (EDMD) is caused by variants in EMD (EDMD1) and LMNA (EDMD2). Cardiac conduction defects and atrial arrhythmia are common to both, but LMNA variants also cause end-stage heart failure (ESHF) and malignant ventricular arrhythmia (MVA). This study aimed to better characterize the cardiac complications of EMD variants.

METHODS:

Consecutively referred EMD variant-carriers were retrospectively recruited from 12 international cardiomyopathy units. MVA and ESHF incidences in male and female variant-carriers were determined. Male EMD variant-carriers with a cardiac phenotype at baseline (EMDCARDIAC) were compared with consecutively recruited male LMNA variant-carriers with a cardiac phenotype at baseline (LMNACARDIAC).

RESULTS:

Longitudinal follow-up data were available for 38 male and 21 female EMD variant-carriers [mean (SD) ages 33.4 (13.3) and 43.3 (16.8) years, respectively]. Nine (23.7%) males developed MVA and five (13.2%) developed ESHF during a median (inter-quartile range) follow-up of 65.0 (24.3-109.5) months. No female EMD variant-carrier had MVA or ESHF, but nine (42.8%) developed a cardiac phenotype at a median (inter-quartile range) age of 58.6 (53.2-60.4) years. Incidence rates for MVA were similar for EMDCARDIAC and LMNACARDIAC (4.8 and 6.6 per 100 person-years, respectively; log-rank P = .49). Incidence rates for ESHF were 2.4 and 5.9 per 100 person-years for EMDCARDIAC and LMNACARDIAC, respectively (log-rank P = .09).

CONCLUSIONS:

Male EMD variant-carriers have a risk of progressive heart failure and ventricular arrhythmias similar to that of male LMNA variant-carriers. Early implantable cardioverter defibrillator implantation and heart failure drug therapy should be considered in male EMD variant-carriers with cardiac disease.

• Authors: Douglas E Cannie, Petros Syrris, Alexandros Protonotarios, Athanasios Bakalakos, Jean-François Pruny, Raffaello Ditaranto, Cristina Martinez-Veira, Jose M Larrañaga-Moreira, Kristen Medo, Francisco José Bermúdez-Jiménez, Rabah Ben Yaou, France Leturcq, Ainhoa Robles Mezcua, Chiara Marini-Bettolo, Eva Cabrera, Chloe Reuter, Javier Limeres Freire, José F Rodríguez-Palomares, Luisa Mestroni, Matthew R G Taylor, Victoria N Parikh, Euan A Ashley, Roberto Barriales-Villa, Juan Jiménez-Jáimez, Pablo Garcia-Pavia, Philippe Charron, Elena Biagini, José M García Pinilla, John Bourke, Konstantinos Savvatis, Karim Wahbi, Perry M Elliott
• Journal: European heart journal (Eur Heart J) Vol. 44 Issue 48 Pg. 5064-5073 (Dec 21 2023) ISSN: 1522-9645 [Electronic] England
• PMID: 37639473 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.

Topics

• Humans
• Male
• Female
• Middle Aged
• X-Linked Emery-Dreifuss Muscular Dystrophy (complications)
• Retrospective Studies
• Arrhythmias, Cardiac (epidemiology, genetics, complications)
• Heart Diseases (complications)
• Muscular Dystrophy, Emery-Dreifuss (complications, genetics, pathology)
• Heart Failure (etiology, complications)
• Mutation