Temporal evolution of the heart failure phenotype in Barth syndrome and treatment with elamipretide.

Barth syndrome (BTHS) is a rare genetic disorder caused by pathogenic variants in TAFAZZIN leading to reduced remodeled cardiolipin (CL), a phospholipid essential to mitochondrial function and structure. Cardiomyopathy presents in most patients with BTHS, typically appearing as dilated cardiomyopathy (DCM) in infancy and evolving to hypertrophic cardiomyopathy (HCM) resembling heart failure (HF) with preserved ejection fraction (HFpEF) in some patients ≥12 years. Elamipretide localizes to the inner mitochondrial membrane where it associates with CL, improving mitochondrial function, structure and bioenergetics, including ATP synthesis. Numerous preclinical and clinical studies in BTHS and other forms of HF have demonstrated that elamipretide improves left ventricular relaxation by ameliorating mitochondrial dysfunction, making it well suited for therapeutic use in adolescent and adult patients with BTHS.