231P Efficacy of tranilast in preventing exacerbating cardiac function and death from heart failure in muscular dystrophy patients with advanced-stage heart failure: a single-arm, open-label, multicenter study

Transient receptor potential cation channel subfamily V member 2 (TRPV2) functions as a stretch-sensitive calcium channel, with overexpression in the sarcolemma of skeletal and cardiac myocytes leading to detrimental calcium influx, triggering muscle degeneration. In our previous pilot study, we showed that tranilast, a TRPV2 inhibitor, reduced brain natriuretic peptide (BNP) levels in two patients with muscular dystrophy (MD) and advanced heart failure. Building on this, we performed a single-arm, open-label, multicenter study herein to evaluate the safety and efficacy of tranilast in the treatment of advanced heart failure in MD patients. This study involved 18 MD patients with BNP levels > 100 pg/mL, despite receiving standard cardioprotective therapy. Tranilast was administered orally at a dose of 100 mg, three times daily. We published earlier the primary endpoint, the change in the logarithm of BNP level from baseline to 28 weeks (short-term treatment). All 15 patients who completed the short-term treatment consented to be enrolled in long-term therapy for an additional 116 weeks. After all participants completed the long-term treatment, we assessed TRPV2 expression on the peripheral blood mononuclear cell surfaces, cardiac events, total mortality, left ventricular fractional shortening, BNP, human atrial natriuretic peptide, cardiac troponin T, creatine kinase, pinch strength, and quality of life. Two patients died, and one withdrew during the long-term period. The survival rate was 80.7%, and no cardiac deaths were reported. Despite the presence of progressive disease, the cardiac indices remained stable, and only BNP levels at 144 weeks showed significant changes. Notably, TRPV2 expression decreased throughout the study period. The findings suggest that tranilast can inhibit TRPV2 expression for an extended period and is effective in preventing the worsening of cardiac function and subsequent death from heart failure.