Perhexiline Therapy in Heart Failure With Preserved Ejection Fraction Syndrome
Perhexiline Therapy in Heart Failure With Preserved Ejection Fraction Syndrome
Up to half of all patients with clinical features of heart failure are found to have normal
 heart pumping function. Recently the investigators have shown that a drug called perhexiline
 markedly improved exercise capacity and symptoms in patients with heart failure associated
 with impaired cardiac pump function. In this proposal the investigators will assess whether
 perhexiline has beneficial effects in patients with heart failure and a normal heart pumping
 function.
Up to 50% of patients with symptoms of heart failure have a preserved left ventricular
 ejection fraction (HFpEF syndrome). Current therapy for systolic heart failure is targeted at
 inducing vasodilation and counteracting neuro-endocrine activation. There is a lack of a
 corresponding evidence base for the treatment of HEpEF. We have previously shown that
 perhexiline, an agent that increases the efficiency of energy production by shifting
 substrate utilization from free fatty acids towards glucose, was highly effective in
 improving exercise capacity, symptoms and cardiac function in patients with systolic heart
 failure. We have also recently shown that energy deficiency plays a major role in the
 pathophysiology of HFpEF. In this proposal we therefore aim to investigate the effectiveness
 of perhexiline in 70 HFpEF patients, in a 3 month randomised, double-blind, controlled trial.
 An interim analysis is planned after 20 patients.
Inclusion Criteria:

 -  HFpEF will be defined as:

 -  Clinical features consistent with heart failure

 -  LVEF ≥ 50%, with no evidence of significant valvular disease

 -  No hypertrophic cardiomyopathy, and no evidence of pericardial constriction

 -  Peak VO2 < 80% predicted, with RER>1 and with a pattern of gas exchange on
 metabolic exercise testing indicating a cardiac cause for limitation)

 -  Patients recruited will be in sinus rhythm

 Exclusion Criteria:

 -  BMI >35

 -  Objective evidence of lung disease on formal lung function testing

 -  Reversible myocardial ischaemia on contrast-enhanced myocardial stress
 Echocardiography, and no evidence of exercise-induced mitral regurgitation (>2+)

 -  Impaired hepatic function; known hypersensitivity to perhexiline