Dystrophinopathy should be considered in adolescent males with nonischemic cardiomyopathy and heart failureHeart failure treatment shows promise for a boy with muscular dystrophy

BackgroundDuchenne muscular dystrophy (DMD) can involve the myocardium and progress to cardiomyopathy and heart failure; however, diagnosis is frequently delayed because initial clinical manifestations are often atypical. In adolescent males presenting with nonischemic cardiomyopathy of unclear etiology, early integration of a coherent evidence chain spanning neuromuscular clues, multimodality imaging, and genetic testing is pivotal for etiologic clarification and optimization of long-term management.Case summaryThe patient was a 17-year-old adolescent male who presented repeatedly with chest tightness, fatigue, and reduced exercise tolerance. During the first hospitalization in September 2025, evaluation revealed left atrial and left ventricular enlargement with impaired systolic function (LVEF ∼44%). Laboratory testing showed marked hyperCKemia (CK 1,451 U/L), mildly elevated hs-cTnT (0.033 μg/L), and concomitant transaminase elevation. Coronary computed tomography angiography demonstrated no significant stenosis, with only a superficial myocardial bridge in the mid–left anterior descending artery. According to the original clinical cardiac magnetic resonance report, multifocal patchy late gadolinium enhancement was described predominantly in a subepicardial distribution, together with a trabeculated/noncompaction-like left ventricular morphology. During the second hospitalization in November 2025, focused neuromuscular assessment uncovered a long-standing progressive proximal weakness (EMG-supported), linking the cardiac phenotype to dystrophinopathy (positive Gower's sign, calf pseudohypertrophy, and waddling gait), and electromyography supported a myopathic process; transthoracic echocardiography showed improvement of LVEF to 50%. At the third hospitalization in December 2025, the dominant issues were hyperglycemia with proteinuria (HbA1c 7.7% and UACR ∼389 mg/g), while echocardiography documented further recovery of LVEF to 55%. Genetic testing identified a DMD variant (NM_004006.3:c.1351G>T, p.Asp451Tyr), and Sanger sequencing confirmed hemizygosity in the proband and heterozygosity in his mother. Taken together, the convergent clinical, imaging, electrophysiologic, and genetic findings established the diagnosis of DMD-associated cardiomyopathy. Under guideline-directed heart failure therapy and multidisciplinary care, the patient demonstrated longitudinal improvement in cardiac function (LVEF ∼44% → 50% → 55%).ConclusionIn adolescent males with nonischemic cardiomyopathy and/or heart failure of unclear etiology—particularly when accompanied by hyperCKemia or suspected myogenic transaminase elevation—dystrophinopathy should be considered early in the differential diagnosis. A diagnostic “closed loop” can be achieved by integrating cardiac phenotyping, neuromuscular examination, electromyography, family history, and confirmatory genetic testing, while guideline-directed heart failure therapy and proactive family-based care (including cardiac surveillance of female carriers) should be initiated in parallel to improve long-term outcomes.