Abozguia, Khalid (2010)
Ph.D. thesis, University of Birmingham.
Despite major advances in therapies, chronic heart failure (CHF) and hypertrophic cardiomyopathy (HCM) are still associated with significant morbidity and mortality. These patients often have a significant limitation in their exercise capacity. We showed that there are widespread abnormalities of both systolic and diastolic function in HCM patients. These abnormalities contribute significantly to exercise limitation observed in these patients. Furthermore, we showed that HCM manifest a myocardial energy defieciency which was accompanied by a slowing of the energy-dependent early diastolic LV active relaxation during exercise. The present study supports the hypothesis that HCM is, at least in part, a disease of energy deficiency. Consistent with this hypothesis, we showed that metabolic modulation by perhexiline augmented myocardial energetics, and normalised diastolic ventricular filling which translated into significant subjective (improved symptoms) and objective (increased exercise capacity [peak VO2]) clinical improvement in HCM patients. These findings suggest that metabolic modulators, such as perhexiline, have the potential role in the management of patients with symptomatic non obstructive HCM, a condition for which there are currently limited therapeutic options. However, large scale longterm studies are still required to examine the effects of these agents on morbidty and mortality in these patients.
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