Trimetazidine Therapy in Hypertrophic Cardiomyopathy

Overview

Hypertrophic cardiomyopathy (HCM) is a common inherited heart condition that causes breathlessness, chest pain and fatigue. There are few treatments available. The investigators have recently shown that a drug called perhexiline reduced symptoms and improved exercise capacity in patients with HCM. This change appears to be driven by alterations in myocardial energy metabolism. The aim of this trial is to test a similar drug, trimetazidine, in a group of symptomatic patients with non-obstructive HCM. HYPOTHESIS: trimetazidine will improve symptoms, peak oxygen consumption, cardiac function and arrhythmia burden in medically refractory symptomatic patients with non-obstructive HCM.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common inherited disorder of heart muscle affecting 1 in 500 individuals worldwide. It is associated with arrhythmias, heart failure and sudden death in young people. In the majority of patients, HCM is caused by mutations in genes encoding cardiac contractile proteins. It has been hypothesised that excessive sarcomeric energy consumption is an important and early factor in the pathophysiology of HCM. Therefore modulation of myocardial metabolism presents a novel target for improving myocardial performance and symptoms in patients with HCM. Trimetazidine is an anti-anginal agent which like perhexiline reduces fatty acid oxidation and increases glucose oxidation, thus increasing the efficiency of energy production. Trimetazidine has been shown to significantly improve exercise performance in patients with stable angina, ischaemic and non ischaemic cardiomyopathy, either as monotherapy or in combination with beta-blockers or calcium channel blockers, DESIGN: A single centre prospective randomised, double blind, placebo-controlled, trial of trimetazidine therapy. DOSING: 20 mg Trimetazidine or Placebo three times daily for three months METHODS: The following assessments will be made at baseline and after 3 months treatment: history and physical examination, Minnesota heart failure questionnaire, fasting blood tests, electrocardiogram, echocardiogram, cardiopulmonary exercise test, six minute walk test, 24 hour ECG Holter monitor.