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

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.

Figure 1.

LVEF vs age. LGE‐negative studies are marked in green, and LGE‐positive studies are marked in red. The studies for each individual patient are linked with a colored line. Dashed lines are upper and lower 95th CIs of predicted mean LVEF. LVEF declined 0.58±0.10% per year in an age‐only model, accounting for correlated values within patients. LGE indicates late gadolinium enhancement; LVEF, left ventricular ejection fraction.

Figure 2.

LVEF vs time after t_LGE. This figure demonstrates LVEF vs t_LGE for patients with at least 1 LGE‐negative study followed by at least 1 LGE‐positive study (LGE−/+ group). LGE‐negative studies are marked in green, and LGE‐positive studies are marked in red. The studies for each individual patient are linked with a colored line. Dashed lines are upper and lower 95th CIs of predicted mean LVEF. LVEF remained stable over time if patients were LGE negative but declined by 2.2±0.31% per year if patients were LGE positive. LGE indicates late gadolinium enhancement; LVEF, left ventricular ejection fraction; t_LGE, time after development of LGE.

Figure 3.

LVEF vs number of left ventricular segments positive for LGE. LGE‐negative studies are marked in green, and LGE‐positive studies are marked in red. The studies for each individual patient are linked with a colored line. Dashed lines are upper and lower 95th CIs of predicted mean LVEF. Each additional LGE‐positive LV segment was associated with an LVEF decline of 0.93±0.09%. LGE indicates late gadolinium enhancement; LV, left ventricular; LVEF, left ventricular ejection fraction.

Figure 4.

Number of LGE‐positive LV segments vs patient age. This figure demonstrates the number of LGE‐positive LV segments related to age. The points for each patient are connected with a colored line. LGE indicates late gadolinium enhancement; LV, left ventricular.