Myocardial late gadolinium enhancement is associated with clinical presentation in Duchenne muscular dystrophy carriers

Paul Wexberg, Marion Avanzini, Julia Mascherbauer, Stefan Pfaffenberger, Birgit Freudenthaler, Reginald Bittner, Günther Bernert, Franz Weidinger, Paul Wexberg, Marion Avanzini, Julia Mascherbauer, Stefan Pfaffenberger, Birgit Freudenthaler, Reginald Bittner, Günther Bernert, Franz Weidinger

Abstract

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive disease that occurs in males leading to immobility and death in early adulthood. Female carriers of DMD are generally asymptomatic, yet frequently develop dilated cardiomyopathy. This study aims to detect early cardiac manifestation in DMD using cardiovascular magnetic resonance (CMR) and to evaluate its association with clinical symptoms.

Methods: Clinical assessment of DMD carriers included six minutes walk tests (6MWT), blood analysis, electrocardiography, echocardiography, and CMR using FLASH sequences to detect late gadolinium enhancement (LGE). T1-mapping using the Modified Look-Locker Inversion recovery (MOLLI) sequence was performed quantify extracellular volume (ECV).

Results: Of 20 carriers (age 39.47 ± 12.96 years) 17 (89.5 %) were clinically asymptomatic. ECV was mildly elevated (29.79 ± 2.92 %) and LGE was detected in nine cases (45 %). LGE positive carriers had lower left ventricular ejection fraction in CMR (64.36 ± 5.78 vs. 56.67 ± 6.89 %, p = 0.014), higher bothCK (629.89 ± 317.48 vs. 256.18 ± 109.10 U/l, p = 0.002) and CK-MB (22.13 ± 5.25 vs. 12.11 ± 2.21 U/l, p = 0.001), as well as shorter walking distances during the 6MWT (432.44 ± 96.72 vs. 514.91 ± 66.80 m, p = 0.037). 90.9 % of subjects without LGE had normal pro-BNP, whereas in 66.7 % of those presenting LGE pro-BNP was elevated (p = 0.027). All individuals without LGE were in the NYHA class I, whereas all those in NYHA classes II and III showed positive for LGE (p = 0.066).

Conclusions: Myocardial involvement shown as LGE in CMR occurs in a substantial number of DMD carriers; it is associated with clinical and morphometric signs of incipient heart failure. LGE is thus a sensitive parameter for the early diagnosis of cardiomyopathy in DMD carriers.

Trial registration: Clinicaltrials.gov, NCT01712152 Trial registration: October 19, 2012. First patient enrolled: September 27, 2012 (retrospectively registered).

Keywords: Cardiomyopathy; Cardiovascular magnetic resonance; Duchenne muscular dystrophy; T1-mapping.

Figures

Fig. 1
Fig. 1
Diffuse myocardial fibrosis. Short-axis view (inversion-recovery gradient-echo) depicting diffuse myocardial fibrosis in two carriers of DMD. Note the patchy pattern of LGE along the lateral and inferolateral wall

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