The association between cardiac involvement and long‐term clinical outcomes in patients with Duchenne muscular dystrophy

Abstract

Aims Despite advances in contemporary cardiopulmonary therapies, cardiomyopathy remains the leading cause of death in patients with Duchenne muscular dystrophy (DMD). Also, the long-term clinical outcomes of patients with DMD and cardiomyopathy is unknown. This study investigated long-term clinical outcomes and their associated factors in patients with late-stage DMD. Methods and results A total of 116 patients with late-stage DMD (age > 15 years) were enrolled in this retrospective study. All enrolled patients were followed up at a single tertiary referral hospital. LV systolic dysfunction was dichotomously defined as reduced [left ventricular ejection fraction (LVEF) ≤ 40%] vs. preserved [>40%] based on the initial echocardiographic result. The primary endpoint was all-cause death. The secondary endpoint was a composite event defined as death or unexpected hospitalization due to cardiovascular reasons including chest pain, dyspnoea, and generalized oedema. The patients were divided into preserved (n = 84, 72.4%) and reduced LVEF groups (n = 32, 27.6%). The mean age was 20.8 ± 5.9 years, the mean disease duration, 8.8 ± 3.7 years, and the mean follow-up duration, 1708 ± 659 days. For primary endpoint, the reduced LVEF group showed a lower rate of overall survival (Reduced LVEF vs. Preserved LVEF; 81.3% vs. 98.8%, log-rank P = 0.005). In the multivariable Cox regression analysis, brain-natriuretic peptide (BNP) level (adjusted hazard ratio [HR] 1.088, 95% confidence interval [CI] 1.019-1.162, P = 0.011) and diuretic use (adjusted HR 9.279, 95%CI 1.651-52.148, P = 0.011) were significant predictors of all-cause death in patients with DMD. For the secondary endpoint, the reduced LVEF group had a lower rate of freedom from composite events than the preserved LVEF group (65.6% vs. 86.9%, log-rank P = 0.005). In the multivariable Cox regression analysis, BNP level (adjusted HR 1.057, 95%CI 1.005-1.112, P = 0.032) and diuretic use (adjusted HR 4.189, 95% CI 1.704-10.296, P = 0.002) were significant predictors of the composite event in patients with DMD. Conclusions Patients with DMD and reduced LVEF had worse clinical outcomes than those with preserved LVEF. BNP level and diuretic use were associated with adverse clinical outcomes in patients with late-stage DMD, irrespective of LVEF.

Cardiomyopathy as cause of death in Duchenne muscular dystrophy: a longitudinal observational study

“…In an adult DMD population treated in a tertiary HMV centre and in collaboration with a multidisciplinary care team, the cause of death was explained as cardiac in >50% in patients with known cause of death, and lower LVEF as a marker of more severe cardiomyopathy was associated with earlier death. This finding is consistent with reports from other large centres [ 15 , 22 , 23 ].…”

Wireless Pulmonary Artery Pressure Monitor Implantation in a Patient with Duchenne Muscular Dystrophy

“…Additionally, there are no comprehensive studies describing the progression of laboratory biomarkers of disease progression such as natriuretic peptides. Existing case series suggest modified “normal values” may be needed in DMD, as appreciable rises may be a late finding [ 4 ]. Similarly, in our case, persistently low nt-BNP values (100–150 pg/mL) and “stably” depressed left ventricular systolic dysfunction (LVEF 40% ± 2%) had provided false reassurance that his symptoms were driven by respiratory progression rather than heart.…”

Cardiac atrial pathology in Duchenne muscular dystrophy

“…Cardiac disease becomes initially manifest by diffuse extracellular matrix expansion followed by ventricular fibrosis (as visualized by late gadolinium enhancement [LGE]) in the mid‐teenage years 2,3 . Progression of this process culminates in the development of widespread left ventricular fibrofatty replacement, severe ventricular dysfunction, and heart failure 4,5 . Although these ventricular level changes have been well described, there is very limited description of atrial changes in DMD, with only scattered case reports describing potential disease involvement 6 …”

“…2,3 Progression of this process culminates in the development of widespread left ventricular fibrofatty replacement, severe ventricular dysfunction, and heart failure. 4,5 Although these ventricular level changes have been well described, there is very limited description of atrial changes in DMD, with only scattered case reports describing potential disease involvement. 6 In addition to cardiac changes, magnetic resonance imaging and magnetic resonance spectroscopy data have shown near universal fibrofatty replacement of all skeletal muscles with time.…”