Trimetazidine Therapy and Exercise Capacity in Nonobstructive HCM

Study Questions:

What is the impact of trimetazidine hydrochloride on exercise capacity in patients with symptomatic, medically refractory, nonobstructive hypertrophic cardiomyopathy (HCM)?

Methods:

Symptomatic adults with nonobstructive HCM (left ventricular outflow tract [LVOT] obstruction <50 mm Hg) receiving stable medical therapy were randomized to trimetazidine or placebo. The primary endpoint was peak oxygen consumption (VO2). Secondary endpoints included: 1) symptom burden; 2) 6-minute walk distance; 3) biomarkers including B-type natriuretic peptide (BNP), proBNP, and troponin; 4) systolic and diastolic function on echocardiography; and 5) ventricular ectopy.

Results:

Study recruitment could not be completed at the end of the enrollment period despite an extension. Overall, 26 patients were randomized to trimetazidine and 23 received placebo. After adjusting for baseline peak VO2, patients receiving trimetazidine had a lower peak VO2 at the end of 3 months. However, this change was small and unlikely to be of clinical significance. Patients receiving trimetazidine covered a shorter 6-minute walk distance. There was no change in symptoms, systolic or diastolic echocardiographic parameters, biomarker levels, or difference in ventricular ectopy burden.

Conclusions:

Trimetazidine did not improve exercise capacity in patients with nonobstructive HCM.

Perspective:

HCM is characterized by inefficient energy production within the myocardium. Existing medical therapies with negative chronotropic agents such as beta-blockers and calcium channel blockers are frequently ineffective in symptomatic patients with nonobstructive HCM. Accordingly, trimetazidine, a direct inhibitor of β oxidation of fatty acids, can improve energy efficiency by inhibiting cardiac fatty acid oxidation. This study aimed to examine the efficacy of trimetazidine on exercise capacity in patients with nonobstructive HCM. Compared to patients receiving placebo, trimetazidine did not have any impact on exercise capacity in this population. Six-minute walk distance was lower in the trimetazidine group, and all other secondary endpoints including symptom burden were no different compared to placebo. However, the study was unable to complete recruitment despite an extension in enrollment period making it underpowered. While the medication was safely tolerated, its role in management of nonobstructive HCM patients with symptoms is not clarified by this study.

Clinical Topics: Arrhythmias and Clinical EP, Dyslipidemia, Heart Failure and Cardiomyopathies, Noninvasive Imaging, EP Basic Science, SCD/Ventricular Arrhythmias, Lipid Metabolism, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound

Keywords: Biological Markers, Calcium Channel Blockers, Cardiomyopathy, Hypertrophic, Diastole, Echocardiography, Fatty Acids, Heart Failure, Myocardium, Natriuretic Peptide, Brain, Oxygen Consumption, Systole, Trimetazidine, Troponin, Ventricular Premature Complexes


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