Prevalence and distribution of late gadolinium enhancement in a large population of patients with Duchenne muscular dystrophy: effect of age and left ventricular systolic function.

Kan N Hor,Linda H Cripe,Subha V Raman,D Woodrow Benson,Wojciech Mazur,Michael D Taylor,Robert O'Donnell,John L Jefferies,Hussein R Al-Khalidi

doi:10.1186/1532-429x-15-107

Abstract

BackgroundDuchenne muscular dystrophy (DMD), an X-linked disorder affects approximately 1 in 5000 males, is universally associated with heart disease. We previously identified myocardial disease by late gadolinium enhancement (LGE) in DMD subjects at various stages of disease, but the true prevalence is unclear. Cardiovascular magnetic resonance (CMR) is well established for both assessment of ventricular function and myocardial fibrosis by LGE. We sought to establish i) prevalence and distribution of LGE in a large DMD population and ii) relationship among LGE, age, LVEF by CMR and current living status.MethodsCurrent living status, demographic and CMR data including ventricular volumes, LVEF and LGE from 314 DMD patients undergoing evaluation at a single large tertiary referral center were analyzed.Results113 of 314 (36%) of DMD subjects showed LGE positivity with prevalence increasing from 17% of patients <10 years to 34% of those aged 10–15 years and 59% of those >15 years-old. Patients with LVEF ≥55% were LGE positive in 30% of cases; this increased to 84% for LVEF <55%. LGE was more prevalent in the free wall (531/1243, 42.7%) vs. septal segments (30/565, 5.3%). Patients with septal involvement were significantly older and had lower LVEF than those with isolated free wall LGE. Ten percent (11/113) patients who had LGE died 10.8 months after CMR. Only one patient from the LGE negative group died. Patients who died had higher heart rate, larger left ventricular volume and mass, greater number of positive LGE segment and increase incident of septal LGE compared to those who remained alive.ConclusionIn DMD patients, LGE occurs early, is progressive and increases with both age and decreasing LVEF. Segmentally, the incidence of the number of positive LGE segments increase with age and lower LVEF. Older patients and those who died during the study period had more septal LGE involvement. The current studies suggest that the time course and distribution of LGE-positivity may be an important clinical biomarker to aid in the management of DMD-associated cardiac disease.

Highlights

Duchenne muscular dystrophy (DMD), an X-linked disorder affects approximately 1 in 5000 males, is universally associated with heart disease
left ventricular ejection fraction (LVEF) was lower and indexed left ventricular end-diastolic volume (LVEDV/Body surface area (BSA)) and mass (LVM/BSA) were significantly larger for late gadolinium enhancement (LGE) positive compared to LGE negative patients suggesting more advanced heart disease (Table 1)
Patients who died during the study period were older (19.5 ± 5.9 vs 14.7 ± 4.8 years, p = 0.003), had higher heart rates (110 ± 21 vs 96 ± 13.9 bpm, p = 0.003), larger ventricular volume (128.2 ±46.2 vs 73.1 ± 16.9 mL/m2, p < 0.0001), ventricular mass (69 ± 11.8 vs 51 ± 12.5 g/m2, p < 0.0001), lower LVEF (32 ±13.9 vs 59.7 ± 7.5 percent, p < 0.0001) and greater number of positive LGE segments (9.6 ± 4.2 vs 4.5 ± 2.4, p < 0.0001) compared to those who remained alive (Table 2)

Summary

Introduction

Duchenne muscular dystrophy (DMD), an X-linked disorder affects approximately 1 in 5000 males, is universally associated with heart disease. Cardiovascular magnetic resonance (CMR) is well established for both assessment of ventricular function and myocardial fibrosis by LGE. Duchenne muscular dystrophy (DMD), an X-linked recessive disorder affecting approximately 1 in 5000 males is the most common inherited muscular dystrophy [1,2,3]. The disease results from mutations in the gene for dystrophin, a sarcolemmal protein, that is abundant in both cardiac and skeletal muscle [4]. Progressive skeletal muscle weakness results in loss of ambulation between 7 and 13 years of age [5,6]. DMD-associated cardiac disease is progressive and results in global ventricular systolic dysfunction, often with minimal ventricular dilation [14]. End-stage cardiac pathology includes cardiomyocyte hypertrophy, atrophy and fibrosis [15,16,17]

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