Left ventricular hypertrophy and myocardial protection with perhexiline during cardiac surgery

Myocardial protective strategies during cardiac surgery continue to improve yet they remain imperfect. Patients with left ventricular hypertrophy (LVH) are considered to be at greater risk of myocardial injury post cardiac surgery. Perhexiline is an anti-anginal agent known to modulate myocardial metabolism towards a more efficient glucose metabolic pathway. This metabolic modulation may improve myocardial protection. In this thesis I present a multi-centre double-blind randomised placebo controlled trial evaluating the role of perhexiline as an adjunct to standard myocardial protection in patients with LVH secondary to aortic stenosis undergoing an aortic valve replacement. Perhexiline does not augment myocardial protection. Magnetic Resonance Spectroscopy based energetic studies, echocardiographic and functional assessments in a homogenous patient cohort show no added benefit with perhexiline therapy in LVH. Therefore perhexiline should be limited to those patients refractory to maximum medical therapy. Metabolomic assessment of LVH has shown no change in the metabolomic profile within the myocardium. However any changes that do exist may be subtle. In LVH there is an increased activity of some innate cardioprotective mechanistic pathways in patients that do not sustain a low cardiac output episode post cardiac surgery. Further examination of these cardioprotective regulators is warranted