Hypertrophic cardiomyopathy — a leading cause of sudden cardiac death in young adults and a driver of progressive heart failure — has long lacked disease-modifying therapies that address its structural roots. A new mechanistic approach targeting copper dysregulation may offer a path toward reversing the cardiac remodeling that defines this condition, potentially broadening the therapeutic toolkit beyond symptom management.
This multicentre, randomized, placebo-controlled Phase 2 trial enrolled 154 adults with hypertrophic cardiomyopathy, requiring a minimum left ventricular wall thickness of 15 mm and including patients across New York Heart Association functional classes I through III. Participants received trientine dihydrochloride at 400 mg twice daily or placebo for 52 weeks. The primary endpoint was change in left ventricular mass indexed to body surface area, measured via cardiovascular magnetic resonance — a sensitive and reproducible structural metric. The mean participant age was approximately 53 years, with a median maximum wall thickness of 20 mm, reflecting a moderately to severely affected cohort. Notably, patients across the full range of left ventricular outflow tract gradients were eligible, including those without significant obstruction — a population historically underserved by available treatments.
The mechanistic rationale here is distinct and worth unpacking. Trientine operates on a dual copper pathway: it facilitates intracellular copper I ion trafficking to support mitochondrial function, while chelating the loosely bound copper II ions implicated in profibrotic signaling. Prior preclinical work demonstrated reductions in both left ventricular hypertrophy and myocardial fibrosis, suggesting the compound may address two of the three core pathophysiological features of hypertrophic cardiomyopathy simultaneously. This positions trientine conceptually apart from myosin inhibitors like mavacamten, which primarily target contractile dysfunction. As a Phase 2 trial, this work is appropriately hypothesis-testing rather than confirmatory, and full efficacy data from the complete cohort will determine whether structural regression was achieved. If positive, this copper-modulation framework could represent a genuinely novel mechanistic avenue for cardiomyopathy treatment.