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Metabolic alterations in patients with heart disease

Abozguia, Khalid (2010)
Ph.D. thesis, University of Birmingham.

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Abstract

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.

Type of Work:Ph.D. thesis.
Supervisor(s):Frenneaux, Michael and Gammage, Michael
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:Department of Cardiovascular Medicine
Subjects:R Medicine (General)
Institution:University of Birmingham
ID Code:690
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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