Role of Perhexiline in Hypertrophic Cardiomyopathy
Status:
Recruiting
Trial end date:
2022-08-01
Target enrollment:
Participant gender:
Summary
Hypertrophic Cardiomyopathy (HCM) is the most common inherited heart muscle condition
affecting up to 1 in 200 of the general population. It results from mutations in genes
encoding components of the contractile apparatus in the heart muscle cell (myocyte). These
mutations result in increased energy cost of force production for the myocyte which then
cumulatively causes a myocardial energy deficit. This myocardial energy deficit is then
thought to lead to cardiac hypertrophy ('left ventricular hypertrophy' or LVH) in HCM.
LVH leads to impairments in heart muscle function, heart muscle oxygenation and microvascular
blood flow and is the chief driver of patient symptoms in HCM. These symptoms consist of
chest pain, shortness of breath, dizziness, fainting episodes or palpitations. Occasionally,
the disease may cause sudden cardiac death (SCD). HCM is the most common cause of SCD in
young people including competitive athletes. In addition, HCM has been found to result in
significant global deterioration in health-related quality of life.
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 LVH.
Perhexiline, a potent carnitine palmitoyl transferase-1 (CPT-1) inhibitor shifts myocardial
metabolism to more efficient glucose utilisation and rectifies impaired myocardial
energetics. It is currently used to treat angina in patients with coronary artery disease.
There is some preliminary evidence that Perhexiline may aid in the improvement of symptoms in
patients with HCM. However, the effect of any form of therapy on potential regression of LVH
in HCM remains unexplored.
In this randomised double-blind placebo-controlled trial, the investigators will use state of
the art cardiac imaging, principally advanced echocardiography and Cardiovascular Magnetic
Resonance (CMR) to study the effects of perhexiline on LVH, cardiac function, and oxygenation
in symptomatic patients with HCM. The investigators hypothesize that perhexiline will
favourably reduce LVH and improve myocardial oxygenation by improving myocardial energetics,
and that these putative morphological and functional changes can be accurately measured
utilizing echocardiography and CMR. If this pilot study supports the hypothesis, then it will
pave the way for a major randomised controlled trial to definitely determine the role of
Perhexiline in HCM.