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. 2018 Mar 3;5(1):e000783.
doi: 10.1136/openhrt-2018-000783. eCollection 2018.

Progressive left ventricular dysfunction and long-term outcomes in patients with Duchenne muscular dystrophy receiving cardiopulmonary therapies

Mary Wang  1 , David J Birnkrant  2 , Dennis M Super  2 , Irwin B Jacobs  2 , Robert C Bahler  2
Affiliations

Progressive left ventricular dysfunction and long-term outcomes in patients with Duchenne muscular dystrophy receiving cardiopulmonary therapies

Mary Wang et al. Open Heart. .

Abstract

Objective: To describe the natural history of cardiomyopathy in patients with Duchenne muscular dystrophy (DMD) who are receiving contemporary therapies.

Methods: This is a single-institution retrospective cohort study of 57 patients aged >15 years with DMD. Serial digital echocardiograms were performed over a median follow-up of 8 years. Left ventricular dysfunction (LVD) was defined as shortening fraction (SF) <29% plus focal wall motion abnormalities. Therapies included ACE inhibitors, beta-blockers and assisted ventilation.

Results: The SF declined progressively in 53/57 patients (93%). LVD occurred in 40 of 57 patients (70%), with variable age at onset (median 18 years, IQR 14-21.5 years). Rate of SF decline (-1.51%±1.16%/year) was variable and unrelated to genotype. However, survival was shorter for patients with LVD onset at age <18 years vs onset at ≥18 years (death at 21.1±2.5 years vs 33.1±4.4 years; P<0.001). Death occurred in 27/57 (47%) patients at a median age of 26.3 years (IQR 20.6-31.5). Death was preceded by LVD in 22/27 patients (81%), 15 (68%) of whom developed class 4 heart failure (CHF). Time from CHF to death was brief (median 8.0 months).

Conclusion: Despite contemporary therapies, SF declined progressively in almost all patients. Age at onset of LVD and age at death were variable and unrelated to genotype; however, survival was shortened for patients with LVD onset at age <18 years. Death was usually preceded by LVD. CHF was a sentinel event, with death occurring shortly thereafter.

Keywords: cardiomyopathy; duchenne muscular dystrophy; dystrophin genotype; echocardiography; heart function.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Flow chart of patient cohort.
Figure 2
Figure 2
Plots of shortening fraction (SF) versus age for patients with identical genotypes. Patients with deletion of exon 44 (solid lines) or deletion of exon 51 (dotted lines) exhibit variability in the age when the SF falls below 29% (solid horizontal line) even when having identical genotypes. Subsequently, the SF continues to decline at similar rates.
Figure 3
Figure 3
(A) Survival for those with deletion of exon 44 (n=9) versus the remaining cohort (n=48). The survival curves are similar, although the duration of follow up was less for those with a deletion of exon 44. The median survival time for the entire cohort was 31.7 years (95% CI 27.4 to 36.0 years). (B) Survival of patients with onset of LVD at age <18 years (n=18) vs age ≥18 years (n=22). Death occurred at an earlier age if LVD developed at age <18 years (P<0.001). The slopes of the survival curves appeared similar. (C) Survival after onset of LVD in patients with (n=15) and without (n=25) CHF. The development of CHF reduced the survival time (P=0.005). (D) Survival after onset of CHF (n=15). Survival was brief after onset of CHF. CHF, class 4 heart failure; LVD, left ventricular dysfunction.
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