Discussion

Cardiomyopathy is a common complication during early adolescence in Duchenne muscular dystrophy, but its progression is insidious without specific symptoms. It is universally accepted that dystrophic cardiomyopathy progresses with age. Inevitable ongoing myocyte death triggers an inflammatory cascade that induces muscle degeneration in both skeletal muscles and heart.^{Reference Nitahara-Kasahara, Takeda and Okada1} The typical clinical manifestations of heart failure are frequently unrecognised due to the patient’s severely limited voluntary activity as a result of progressive muscle weakness and wasting. Common early clinical presentation of dystrophic cardiomyopathy includes resting sinus tachycardia and/or mild left ventricular systolic dysfunction by echocardiogram.^{Reference Meyers and Townsend2} Early recognition and initiation of cardioprotective treatment are integral in attenuating this gradual but progressive cardiac complication in Duchenne muscular dystrophy.^{Reference Viollet, Thrush, Flanigan, Mendell and Allen3} To the best of our knowledge, this is the first reported case of dystrophic cardiomyopathy presenting with unexpected sudden cardiac arrest due to ventricular fibrillation at 7 years of age with no evidence of advanced heart failure. Patchy septal and subepicardial myocardial fibrosis with no evidence of acute inflammation was demonstrated by MRI despite relatively well-preserved left ventricular systolic function by prior echocardiogram.

In Duchenne muscular dystrophy patients, myocardial fibrosis has been shown to increase with age and left ventricular dysfunction,^{Reference Tandon, Villa and Hor4} representing an independent predictor of ventricular arrhythmias, adverse cardiac remodelling, and death.^{Reference Florian, Ludwig and Engelen5} In 74 patients (14.2 ± 4.2 years of age) who underwent MRI, 24 patients (32.4%) showed myocardial fibrosis indicated by positive late gadolinium enhancement, where fibrosis positive cohort was significantly older than without (16.6 ± 4.4 vs. 13.0 ± 3.6, p < 0.001).^{Reference Puchalski, Williams and Askovich6} However, Silva et al. studied cardiac MRI in eight Duchenne patients (7 to 18 years of age) and demonstrated myocardial fibrosis in six patients (75%), including a 7-year-old male with normal left ventricular systolic function.^{Reference Silva, Meira and Gurgel Giannetti7} Unlike other genetic cardiomyopathies, myocardial fibrosis can precede ventricular dysfunction or dilatation in Duchenne muscular dystrophy.

This is a very unusual case within a spectrum of dystrophic cardiomyopathy, as no responsible genetic mutation was identified by whole exome sequence. Other contributing factors, such as acute myocarditis or drugs, were denied. Lethal ventricular arrhythmia and sudden cardiac death have been reported with end-stage cardiomyopathy and advanced heart failure in Duchenne muscular dystrophy,^{Reference Groh8} but not at this young age with preserved left ventricular systolic function.

Fibrosis of the conduction system has been reported by pathologic examination of dystrophic hearts.^{Reference Nomura and Hizawa9} However, these cases were all end-stage cardiomyopathy with severe left ventricular dysfunction and myocardial fibrosis. In mdx mice, the mouse model for human Duchenne muscular dystrophy, Fauconnier et al. demonstrated the occurrence of ventricular arrhythmia due to abnormal intracellular calcium homeostasis via dysfunctional sarcoplasmic reticulum without overt histopathological phenotype of advanced cardiomyopathy.^{Reference Fauconnier, Thireau and Reiken10} Unknown intracellular ion channel abnormalities might have been involved in this case. Further studies are warranted to answer this question.

In summary, we reported a very rare case of a patient with Duchenne muscular dystrophy who unexpectedly developed ventricular fibrillation at age 7 as a first cardiac manifestation of cardiomyopathy with MRI findings of prominent myocardial fibrosis. Although the underlying mechanism of lethal ventricular arrhythmia in this patient remains undetermined, this case may represent an extreme spectrum of dystrophic cardiomyopathy and suggests the importance of early detection of subclinical cardiomyopathy even in asymptomatic preadolescent Duchenne children.