Project leader: Prof. dr. J. van der Velden (VUMC)
Funded by: ZonMW and the Dutch Heart Foundation
Extra energy for hearts with a genetic defect: ENERGY trial.
Clinical problem: Hypertrophic cardiomyopathy (HCM) is the most frequent and lethal genetic heart disease. It is caused by mutations in sarcomeric proteins, the building blocks of the heart. Individuals are at high-risk for ventricular arrhythmias and sudden cardiac death, or develop cardiomyopathy at a young age. The current treatment options are insufficient to prevent the disease.
In the ENERGY trial we will investigate if metabolic therapy reverses the reduced myocardial efficiency in asymptomatic mutation carriers. This trial is based on our preclinical and clinical studies, which revealed that 1) mutant proteins cause an energetic deficiency of the heart and 2) this energetic deficit is already observed in human mutation carriers without cardiomyopathy. The mutation-induced energy deficiency of the heart causes hypertrophy and dysfunction of the heart.
Approach: We will treat asymptomatic mutation carriers with metabolic therapy or placebo and measure cardiac efficiency at baseline and after 4 months of treatment.
Impact: Our study will establish if energy deficiency represents a novel HCM drug target before onset of cardiac hypertrophy. This phase II clinical trial builds proof for a multicenter phase III clinical trial to study if metabolic therapy prevents cardiac hypertrophy, acute cardiac arrest and development of cardiomyopathy in asymptomatic mutation carriers.