Prognostic impact of left ventricular noncompaction in patients with Duchenne/Becker muscular dystrophy — Prospective multicenter cohort study,☆☆

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Abstract

Background

The reported prevalence of left ventricular noncompaction (LVNC) varies widely and its prognostic impact remains controversial. We sought to clarify the prevalence and prognostic impact of LVNC in patients with Duchenne/Becker muscular dystrophy (DMD/BMD).

Methods

We evaluated the presence of LNVC in patients with DMD/BMD aged 4–64 years old at the study entry (from July 2007 to December 2008) and prospectively followed-up their subsequent courses (n = 186). The study endpoint was all-cause death and the presence of LVNC was blinded until the end of the study (median follow-up: 46 months; interquartile range: 41–48 months).

Results

There were no significant differences in baseline characteristics between patients with LVNC (n = 35) and control patients without LVNC (n = 151), with the exception of LV function. Patients with LVNC showed, in comparison with patients without LVNC, a significant negative correlation between age and LVEF (R =  0.7 vs. R =  0.4) at baseline; and showed a significantly greater decrease in absolute LVEF (− 8.6 ± 4.6 vs. − 4.3 ± 4.5, p < 0.001) during the follow-up. A worse prognosis was observed in patients with LVNC (13/35 died) than in patients without LVNC (22/151 died, Log-rank p < 0.001). Multivariate Cox analysis revealed that LVNC is an independent prognostic factor (relative hazard 2.67 [95% CI: 1.19–5.96]).

Conclusion

LVNC was prevalent in patients with DMD/BMD. The presence of LVNC is significantly associated with a rapid deterioration in LV function and higher mortality. Neurologists and cardiologists should pay more careful attention to the presence of LVNC.

Introduction

Left ventricular (LV) noncompaction (LVNC) is a rare cardiomyopathy that is characterized by the presence of persistent trabecular meshwork and deep intertrabecular recesses, which are secondary to the arrest of myocardial maturation [1], [2], [3], [4]. The World Health Organization listed LVNC as an unclassified cardiomyopathy in 1995, and The American Heart Association classified the condition into a genetic cardiomyopathy in 2006 [5], [6]. Increased awareness of LVNC among cardiologists, as well as improved imaging technologies, has led this previously poorly recognized condition to become a widely recognized cardiomyopathy [7]. Although knowledge concerning LVNC continues to increase, the reported prevalence varies widely and its prognostic impact remains controversial since most studies conducted to date have been retrospective and lacked adequate controls [4], [8]. On the other hand, studies have shown that neuromuscular diseases are most frequently (reported prevalence of neuromuscular diseases was 66% and 82%) associated with LVNC [3], [8], [9], [10].

Dystrophin defects cause Duchenne muscular dystrophy (DMD) and its milder variant, Becker muscular dystrophy (BMD). These X-linked recessive myopathies are caused by mutations in the dystrophin gene that lead to a fragile cytoskeleton of muscle cells [11]. Patients with DMD/BMD develop progressive systemic muscle weakness, which leads to a premature death that is primarily caused by its cardiac involvement [12]. The objective of the current multicenter cohort study was to clarify the prevalence and prognostic impact of LVNC in common neuromuscular diseases (DMD/BMD) without intervention bias.

Section snippets

Study design and patients

A total of 224 male patients with DMD/BMD from 4 neuromuscular centers; namely, Niigata National Hospital (Niigata, Japan), Shimoshizu National Hospital (Chiba, Japan), Hakone National Hospital (Kanagawa, Japan), and The University of Tokyo Hospital (Tokyo, Japan) were invited to participate. Experienced neurologists diagnosed DMD/BMD following the assessment of clinical manifestations, physical examinations, family history, increase in serum creatine kinase, muscle pathology, and dystrophin

Baseline characteristics and the diagnosis of LVNC

LVNC was diagnosed in 19% (35 of 186) of the patients. Although some patients showed limited image quality, the echocardiographic variables and the presence of LVNC could be evaluated by expert echo-cardiologists in all patients. There were no significant baseline differences in the distributions of DMD/BMD type, age, blood pressure, heart rate, ventilator use, oxygen use, and medications administered between patients with and without LVNC (Table 1). However, echocardiographic findings,

Discussion

This cohort study revealed 3 findings: 1) patients with DMD/BMD had a high prevalence of LVNC, 2) the presence of LVNC was associated with a significantly greater decrease in LVEF than control patients without LVNC, and 3) the presence of LVNC was independently associated with a poorer prognosis.

The reported prevalence of LVNC varies considerably. The prevalence among patients referred to echocardiography laboratories has been reported to range between 0.014% and 1.26% [14], [17], [18]. In two

Conclusion

LVNC was prevalent in patients with DMD/BMD. Moreover, the presence of LVNC by itself was profoundly associated with a rapid deterioration in LV function and a higher mortality rate. Therefore, neurologists and cardiologists should pay more careful attention to the presence of LVNC.

Acknowledgments

The authors gratefully acknowledge the valuable assistance of S. Nukaga, M. Chigira (Department of Laboratory Medicine, The University of Tokyo Hospital), N. Fukuda (Takasaki General Medical Center, Gunma), and H Yamagata (Department of Cardiology, The University of Tokyo) with reviewing the echocardiographic images and data management; M. Terashima and N. Koyama (Cardiovascular Imaging Clinic Iidabashi, Tokyo) for their review of the cardiac magnetic resonance images; Y. Kuroiwa, Y. Izumi

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    All the authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

    ☆☆

    No financial support for this study was provided.

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