Restrepo-Cordoba Maria A, Wahbi Karim, Florian Anca R, Jiménez-Jáimez Juan, Politano Luisa, Arad Michael, Climent-Paya Vicente, Garcia-Alvarez Ana, Hansen Rasmus B, Larrañaga-Moreira José M, Kubanek Milos, Lopes Luis R, Ros Andrea, Jurcut Ruxandra, Rasmussen Torsten B, Ruiz-Guerrero Luis, Pribe-Wolferts Regina, Palomino-Doza Julian, Bilinska Zofia, Rodríguez-Palomares José F, Van Loon Rosa L E, Basurte Elorz María Teresa, Quarta Giovanni, Robledo Iñarritu Maria, Verdonschot Job A J, Stojkovic Tanya, Shomanova Zornitsa, Bermudez-Jimenez Francisco, Palladino Alberto, Freimark Dov, García-Álvarez Maria I, Jorda Paloma, Dominguez Fernando, Ochoa Juan Pablo, Girolami Francesca, Brugada Ramon, Meder Benjamin, Barriales-Villa Roberto, Mogensen Jens, Laforêt Pascal, Yilmaz Ali, Elliott Perry, Garcia-Pavia Pablo
Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
Eur J Heart Fail. 2021 Aug;23(8):1276-1286. doi: 10.1002/ejhf.2250. Epub 2021 Jun 9.
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.
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.
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.
在患有轻度或无骨骼肌病的个体中，与肌营养不良蛋白基因（DMD）突变相关的扩张型心肌病（DCM）通常与其他形式的DCM难以区分。我们试图描述在无严重骨骼肌病的DMD突变携带者中，DMD相关DCM的表型和预后。
在26个欧洲中心，我们回顾性收集了223名DMD突变携带者（83%为男性，年龄33±15岁）的临床特征和结局。共有112名个体（52%）在首次评估时患有DCM [n = 85；左心室射血分数（LVEF）34±11.2%] 或在中位随访96个月（四分位间距5 - 311个月）后发生DCM（n = 27；LVEF 41.3±7.5%）。年龄大于40岁的携带者中DCM的外显率为45%。DCM在男性中出现得更早，且与突变类型、骨骼肌病的存在或血清肌酸激酶水平升高无关。22%的DCM患者发生了主要不良心脏事件（MACE），18%发展为终末期心力衰竭，9%发生心源性猝死或相当于心源性猝死的事件。在患有DCM的患者中，骨骼肌病与无MACE的生存情况无关。基线时LVEF降低和左心室舒张末期直径增加与MACE相关。无DCM的个体在随访期间无MACE或死亡，预后良好。
无严重骨骼肌病的DMD相关DCM的特点是外显率不完全，但发生MACE的风险高，包括进展为终末期心力衰竭和室性心律失常。DCM的发病是预后的主要决定因素，无论是否存在骨骼肌病生存情况相似。
