Predictors of Death in Adults With Duchenne Muscular Dystrophy–Associated Cardiomyopathy

Abstract

BackgroundDuchenne muscular dystrophy (DMD) is frequently complicated by development of a cardiomyopathy. Despite significant medical advances provided to DMD patients over the past 2 decades, there remains a group of DMD patients who die prematurely. The current study sought to identify a set of prognostic factors that portend a worse outcome among adult DMD patients.Methods and ResultsA retrospective cohort of 43 consecutive patients was followed in the adult UT Southwestern Neuromuscular Cardiomyopathy Clinic. Clinical data were abstracted from the electronic medical record to generate baseline characteristics. The population was stratified by survival to time of analysis and compared with characteristics associated with death. The DMD population was in the early 20s, with median follow‐up times over 2 years. All the patients had developed a cardiomyopathy, with the majority of the patients on angiotensin‐converting enzyme inhibitors (86%) and steroids (56%), but few other guideline‐directed heart failure medications. Comparison between the nonsurviving and surviving cohorts found several poor prognostic factors, including lower body mass index (17.3 [14.8–19.3] versus 25.8 [20.8–29.1] kg/m2, P<0.01), alanine aminotransferase levels (26 [18–42] versus 53 [37–81] units/L, P=0.001), maximum inspiratory pressures (13 [0–30] versus 33 [25–40] cmH2O, P=0.03), and elevated cardiac biomarkers (N‐terminal pro‐brain natriuretic peptide: 288 [72–1632] versus 35 [21–135] pg/mL, P=0.03].ConclusionsThe findings demonstrate a DMD population with a high burden of cardiomyopathy. The nonsurviving cohort was comparatively underweight, and had worse respiratory profiles and elevated cardiac biomarkers. Collectively, these factors highlight a high‐risk cardiovascular population with a worse prognosis.

Life expectancy at birth in Duchenne muscular dystrophy: a systematic review and meta-analysis

“…We estimated the pooled median life expectancy at birth in patients with DMD who did not receive ventilatory support to be 19.0–19.4 years, notably lower than corresponding estimates for patients receiving ventilatory support (29.9–31.8 years). These findings are consistent with reports of causes of death in DMD, which for recent cohorts are more frequently related to cardiac, as opposed to respiratory, involvement [ 28 , 29 ]. That survival varies between ventilated and non-ventilated groups of patients was also evident from our synthesis of data derived from samples where an undisclosed proportion of patients were ventilated.…”

“…The outcomes of this meta-analysis highlight several topics of importance for clinical and health policy. First, because of reductions in mortality from respiratory involvement, treatment of cardiac-related complications, especially cardiomyopathy, is expected to now become one of the most pressing challenges in the medical management of the aging DMD population [4,28,29]. Second, given the progressive accumulation of disability and morbidity associated with the disease, as life expectancy improves, additional efforts should be made to help maintain and promote patient quality of life, in particular mental well-being in advanced stages of the disease (where patients approach a state of full paralysis).…”

Progressive left ventricular dysfunction and myocardial fibrosis in Duchenne and Becker muscular dystrophy: a longitudinal cardiovascular magnetic resonance study

“…We found that most patients with DMD or BMB had an elevated level of serum troponin T at baseline, probably reflecting latent and progressive myocardial damage, and that those with elevated levels of plasma BNP were more likely to have a substantial LGE. BNP or N-terminal pro-BNP is the most widely used biomarker for the detection and management of heart failure, which may be useful for risk stratification in pediatric outpatients [22] and in patients with DMD [23]. Our…”

Duchenne Muscular Dystrophy: recent advances in protein biomarkers and the clinical application

“…Biomarker in both patients and DMD models [95,109,110]. The use of membrane sealant in dystrophic dogs to ameliorate cardiac injury resulted in decrease of TNNI3 [111].…”