Myocardial fibrosis burden predicts left ventricular ejection fraction and is associated with age and steroid treatment duration in duchenne muscular dystrophy

J Am Heart Assoc. 2015 Mar 26;4(4):e001338. doi: 10.1161/JAHA.114.001338.

Abstract

Background: Patients with Duchenne muscular dystrophy exhibit progressive cardiac and skeletal muscle dysfunction. Based on prior data, cardiac dysfunction in Duchenne muscular dystrophy patients may be influenced by myocardial fibrosis and steroid therapy. We examined the longitudinal relationship of myocardial fibrosis and ventricular dysfunction using cardiac magnetic resonance in a large Duchenne muscular dystrophy cohort.

Methods and results: We reviewed 465 serial cardiac magnetic resonance studies (98 Duchenne muscular dystrophy patients with ≥4 cardiac magnetic resonance studies) for left ventricular ejection fraction (LVEF) and presence of late gadolinium enhancement (LGE), a marker for myocardial fibrosis. LVEF was modeled by examining LGE status, myocardial fibrosis burden (as assessed by the number of LGE-positive left ventricular segments), patient age, and steroid treatment duration. An age-only model demonstrated that LVEF declined 0.58 ± 0.10% per year. In patients with both LGE-negative and LGE-positive studies (n=51), LVEF did not decline significantly over time if LGE was absent but declined 2.2 ± 0.31% per year when LGE was present. Univariate modeling showed significant associations between LVEF and steroid treatment duration, presence of LGE, and number of LGE-positive left ventricular segments; multivariate modeling showed that LVEF declined by 0.93 ± 0.09% for each LGE-positive left ventricular segment, whereas age and steroid treatment duration were not significant. The number of LGE-positive left ventricular segments increased with age, and longer steroid treatment duration was associated with lower age-related increases.

Conclusion: Progressive myocardial fibrosis, as detected by LGE, was strongly correlated with the LVEF decline in Duchenne muscular dystrophy patients. Longer steroid treatment duration was associated with a lower age-related increase in myocardial fibrosis burden.

Keywords: cardiomyopathy; magnetic resonance imaging; morbidity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Child
  • Disease Progression
  • Fibrosis / etiology
  • Glucocorticoids / therapeutic use*
  • Heart / drug effects
  • Heart / physiopathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Muscular Dystrophy, Duchenne / complications
  • Muscular Dystrophy, Duchenne / drug therapy
  • Muscular Dystrophy, Duchenne / pathology*
  • Muscular Dystrophy, Duchenne / physiopathology
  • Myocardium / pathology*
  • Prednisone / therapeutic use
  • Pregnenediones / therapeutic use
  • Retrospective Studies
  • Stroke Volume / physiology
  • Young Adult

Substances

  • Glucocorticoids
  • Pregnenediones
  • deflazacort
  • Prednisone