Diastolic Heart Failure
Conditions
Keywords
diastolic dysfunction, cardiac energetics, perhexiline, magnetic resonance spectroscopy
Brief summary
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.
Detailed description
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.
Interventions
DRUGPerhexiline
100mg o bd for 3 months
DRUGPlacebo
Placebo one tablet bd for 3 months
Sponsors
University of Aberdeen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Peak oxygen consumption (Vo2max) | 3 months |
Secondary
| Measure | Time frame |
|---|---|
| Symptomatic Status (Modified Minnesota Living with Heart Failure Questionnaire) | 3 Months |
| Resting myocardial energetics by cardiac MR spectroscopy (MRS) | 3 months |
| Resting and exercise diastolic function (nuclear studies) | 3 months |
| Indirect measures of resting LVEDP (tissue Doppler E/Ea) | 3 months |
| Global LV Ejection Fraction (MRI / nuclear studies) | 3 months |
Countries
United Kingdom
Outcome results
None listed