Risk Factors for Cardiac Causes of Death in Males with Duchenne Muscular Dystrophy

Abstract

Purpose As survival and neuromuscular function in Duchenne Muscular Dystrophy (DMD) have improved with glucocorticoid therapy and advances in respiratory care, the proportion of cardiac deaths is increasing. Little is known about risk factors for cardiac causes of death in this population. Methods We conducted a retrospective cohort study of 436 males with DMD followed at 17 centers across North America, from January 1, 2005-December 31, 2015, and sought to identify risk factors for cardiac causes of death, including sudden cardiac death and progressive heart failure. Those dying of cardiac causes were compared to those who died of non-cardiac causes and to those alive at study end. Results There were 29 (6.8%) deaths during the study period at a median age of 19 (IQR: 15-31) years; 8 (27.6%) cardiac (SCD, n=5 and progressive HF, n=3) and 21 non-cardiac (respiratory failure, n=8, multi-organ failure, n=3, stroke, n=1, and other/unknown, n=9). Age at death did not differ based on cause; cardiac 18 (IQR: 15.5-24) years vs. non-cardiac 19 (IQR: 16.5-23) years, p=0.68, but those living were significantly younger (14.9 (IQR: 11.0-19.1) years vs. those who died of cardiac (p=0.03) and non-cardiac (p=0.002) causes). Genetic testing was available for 15/29 deceased (52%) and 292/379 (77%) of those living with all deceased having a deletion, however this did not differ from those living (228/292 (78%), p=0.13). Current or past steroid use was significantly lower in those dying of cardiac causes compared to those living (2/8 (25%) vs. 304/378 (80.4%), p=0.001). Ejection fraction (EF) at study end/death was significantly lower for those dying of cardiac causes compared to those living (mean 37.5% ±12.8 vs. 54.5% ±10.8, p=0.01) but not compared to those dying of non-cardiac causes (37.5% ±12.8 vs. 41.2% ± 19.3, p=0.58). Fractional shortening (FS) was also lower in those dying of cardiac causes compared to those living (mean 18.5% ±10.2 vs. 29.6% ±7.7, p=0.03) but not compared to those dying of non-cardiac causes (18.5% ±10.2 vs. 23.4 % ±9.2, p=0.3). Conclusion In a large cohort of males with DMD, approximately 1/3rd of deaths were from a cardiac cause. Lack of steroid use was associated with cardiac causes of death, while systolic dysfunction was associated with death from any cause. Future studies are needed to define optimal medical management of systolic dysfunction in males with DMD with hopes of extending survival.