Prevalence and clinical outcomes of dystrophin‐associated dilated cardiomyopathy without severe skeletal myopathy
María Alejandra Restrepo-Córdoba, Karim Wahbi, Anca Florian, Juan Jiménez‐Jáimez, Luisa Politano, Michael Arad, Vicente Climent, Ana García‐Álvarez, Rasmus Borup Hansen, José M. Larrañaga‐Moreira, Miloš Kubánek, Luís R. Lopes, Andrea Ros, Ruxandra Jurcuţ, Torsten B. Rasmussen, Luis Ruiz‐Guerrero, Regina Pribe‐Wolferts, Julián Palomino-Doza, Zofia T. Bilińska, José F. Rodríguez‐Palomares, Rosa Laura E. van Loon, María Teresa Basurte Elorz, Giovanni Quarta, María Robledo Iñarritu, Job A.J. Verdonschot, Tanya Stojkovic, Zornitsa Shomanova, Francisco Bermúdez-Jiménez, Alberto Palladino, Dov Freimark, Ana García‐Álvarez, Paloma Jordà, Fernándo Domínguez, Juan Pablo Ochoa, Francesca Girolami, Ramón Brugada, Benjamin Meder, Roberto Barriales‐Villa, Jens Mogensen, Pascal Laforêt, Ali Yılmaz, Perry Elliott, Pablo García‐Pavía, for the European Genetic Cardiomyopathies Initiative Investigators (see online supplementary Appendix S1)
Abstract
AIMS: Dilated cardiomyopathy (DCM) associated with dystrophin gene (DMD) mutations in individuals with mild or absent skeletal myopathy is often indistinguishable from other DCM forms. We sought to describe the phenotype and prognosis of DMD associated DCM in DMD mutation carriers without severe skeletal myopathy. METHODS AND RESULTS: At 26 European centres, we retrospectively collected clinical characteristics and outcomes of 223 DMD mutation carriers (83% male, 33 ± 15 years). A total of 112 individuals (52%) had DCM at first evaluation [n = 85; left ventricular ejection fraction (LVEF) 34 ± 11.2%] or developed DCM (n = 27; LVEF 41.3 ± 7.5%) after a median follow-up of 96 months (interquartile range 5-311 months). DCM penetrance was 45% in carriers older than 40 years. DCM appeared earlier in males and was independent of the type of mutation, presence of skeletal myopathy, or elevated serum creatine kinase levels. Major adverse cardiac events (MACE) occurred in 22% individuals with DCM, 18% developed end-stage heart failure and 9% sudden cardiac death or equivalent. Skeletal myopathy was not associated with survival free of MACE in patients with DCM. Decreased LVEF and increased left ventricular end-diastolic diameter at baseline were associated with MACE. Individuals without DCM had favourable prognosis without MACE or death during follow-up. CONCLUSIONS: DMD-associated DCM without severe skeletal myopathy is characterized by incomplete penetrance but high risk of MACE, including progression to end-stage heart failure and ventricular arrhythmias. DCM onset is the major determinant of prognosis with similar survival regardless of the presence of skeletal myopathy.