Abstract 3713: Metabolic Modulation With Perhexiline Corrects Energy Deficiency and Improves Exercise Capacity in Symptomatic Hypertrophic Cardiomyopathy
Background: Patients with hypertrophic cardiomyopathy (HCM) exhibit myocardial energetic impairment, but a causative role for this energy deficiency in the pathogenesis of HCM remains unproven. We hypothesized that the metabolic modulator, perhexiline, would ameliorate myocardial energy deficiency and thereby improve diastolic function and exercise capacity. .
Methods: Forty six consecutive patients with symptomatic exercise limitation (peak oxygen consumption - peak VO2 <75% of predicted) due to non-obstructive HCM (mean age 55±0.26 years old) were randomized to perhexiline (n=25) or placebo (n=21). Myocardial energetics (PCr/γATP ratio) measured by 31P magnetic resonance spectroscopy, left ventricular diastolic filling [heart rate normalized time to peak filling nTTPF] at rest and during exercise using radionuclide ventriculography, peak VO2, symptoms and quality of life were assessed at baseline and at the end of the study (4.6±1.8 months).
Results: Perhexiline improved the PCr/γATP ratio (from 1.27±0.02 to 1.73±0.02; p=0.003) and normalised the abnormal prolongation of nTTPF between rest and exercise (δnTTPF - 0.01±0.005 vs + 0.11±0.008 sec; p=0.03). These changes were accompanied by improvement in peak VO2 (22.2±0.2 to 24.29±0.2 ml/kg/min; p=0.003) and symptoms (NYHA class by 0.8 units p <0.001) (all p values ANCOVA).
Conclusions: Modulation of myocardial metabolism with perhexiline in patients with HCM ameliorates cardiac energetic impairment, corrects diastolic dysfunction and increases exercise capacity. This study supports the hypothesis that energy deficiency contributes to the pathogenesis and provides a rationale for further consideration of metabolic therapies in HCM