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Role of Perhexiline in Hypertrophic Cardiomyopathy

Professor Joseph Selvanayagam, Institution: Flinders University

2020 Vanguard Grant

Years funded: 2021-2022


Hypertrophic cardiomyopathy (HCM) is an inherited condition that results in an abnormally thickened heart muscle. It is the most common inherited heart muscle condition affecting up to 1 in 200 of the general population. The genetic mutation (or ‘spelling mistake’ in the genes) leads to inefficient heart muscle contraction as it affects the genes that code for the heart muscle proteins usually critical to cardiac contraction. The inefficient heart muscle contraction over time is thought to lead to heart muscle thickening which then leads to symptoms such as chest pain, shortness of breath, dizziness, fainting episodes or palpitations. Occasionally, the disease may cause sudden death. The thickness of the heart muscle is the one of the most important predictors of symptoms in patients with HCM.

Treatment of HCM has focused on relief of symptoms by drugs such as ß-blockers which slow the heart rate and improve heart function. However, symptom relief is often incomplete and there is no evidence on the benefit of ß-blockers or related medications to reverse abnormal heart muscle thickening. Perhexiline, a drug currently used safely as an anti-anginal agent, increases the energy efficiency of the heart. As energy depletion of cardiac muscle cells is thought to be the principal driver of increased muscle thickness in HCM, and Perhexiline improves energy efficiency in the heart, there are plausible reasons (not yet tested) that it may reduce heart muscle thickness as well as improve patient symptoms. We aim to study the effects of Perhexiline treatment on heart muscle thickness in symptomatic HCM patients. If our study is positive, it would lead to the design of a definitive clinical trial that would address the question of whether Perhexiline use reduces heart failure and sudden death events in HCM patients.

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