- 作者：Marta Diegoli PhD ; † ; ; Maurizia Grasso PhD ; Valentina Favalli BME ; Alessandra Serio MD ; Fabiana Isabella Gambarin MD ; Catherine Klersy MD‡ ; ; Michele Pasotti MD ; Emanuela Agozzino MD ; Laura Scelsi MD§ ; ; Alessandra Ferlini MD ; PhD ; Oreste Febo MD¶ ; ; Giovanni Piccolo MD# ; Luigi Tavazzi MD ; Jagat Narula MD ; PhD† ; † ; ; Eloisa Arbustini MD ; arbustini@smatteo.pv.it"" rel=""nofollow
- 关键词：congestive heart failure ; dystrophin ; heart transplantation ; serum creatine phosphokinase ; X-linked dilated cardiomyopathy
- 刊名：Journal of the American College of Cardiology
- 出版年：2011
- 出版时间：23 August 2011
- 年：2011
- 卷：58
- 期：9
- 页码：925-934
- 全文大小：3212 K
Objectives
We sought to describe the diagnostic work-up, phenotype, and long-term evolution of dilated cardiomyopathy (DCM) associated with Dystrophin (DYS) defects.Background
X-linked DCM associated with DYS defects can be clinically indistinguishable from other types of DCM.
Methods
The series comprises 436 consecutive male patients diagnosed with DCM. Patients underwent endomyocardial biopsy (EMB). Genetic testing employed multiplex polymerase chain reaction and multiple ligation dependent probe assay for deletions and direct sequencing of the 79 exons and flanking regions of the gene for point mutations or small rearrangements.
Results
We identified DYS defects in 34 of 436 patients (7.8 % ) (onset age 34 ± 11 years, age range 17 to 54 years); 30 had proven X-linked inheritance. The 2 phenotypes included DCM with mild skeletal myopathy and/or increased serum creatine phosphokinase (n = 28) or DCM only (n = 6). The EMB showed defective dystrophin immunostain. The DYS defects consisted of 21 in-frame deletions and 11 out-of-frame deletions as well as 1 stop and 1 splice-site mutation. During a median follow-up of 60 months (interquartile range: 11.25 to 101.34 months) we observed 17 events, all related to heart failure (HF) (median event-free survival: 83.5 months). Eight patients (23 % ) underwent transplantation, and 9 (26 % ) died of HF while waiting for transplantation. Eight patients received an implantable cardioverter-defibrillator, although none had device intervention during a median follow-up of 14 months (interquartile range: 5 to 25 months). No patient died suddenly, suffered syncope, or developed life-threatening ventricular arrhythmias.
Conclusions
DYS-related DCM should be suspected in male patients with increased serum creatine phosphokinase (82 % ) and X-linked inheritance. The disease shows a high risk of end-stage HF but a lower risk of life-threatening arrhythmias.