Heart failure with preserved ejection fraction (HFpEF) is a common and serious complication of obesity and type 2 diabetes (T2D). HFpEF occurs when the heart muscle unable to relax efficiently to pump the blood around the body. This leads to fluid build-up, breathlessness and inability to tolerate physical exertion. People who develop HFpEF do less well because treatment options are limited. Pilot data in patients with obesity and diabetes and a small number of patients with HFpEF have shown improvements in exercise capacity and reversal of changes in the heart and blood vessels. This study will assess if this is achievable in a multi-ethnic cohort of patients with established HFpEF. A total of 63 adults will be invited and allocate by chance into two groups: 1) 12-weeks of a low calorie diet or 2) Standard care and health advice on how to lose weight followed by the option to have the low calorie diet after 12-weeks. The study will determine if weight loss over 12 weeks can improve heart function, symptoms and ability to exercise. Additionally, participants' views on changing their diet and how this has impacted their symptoms will be sought during the study in an optional interview. This will help guide treatments planning in the future to get maximum benefits, and to individualize support to patients from different cultural backgrounds.
Established clinical diagnosis of heart failure with preserved ejection fraction HFpEF (EF>45%) made by a cardiologist or a primary care physician with heart failure expertise, or a heart failure nurse
Clinically stable for ≥ 3 months (no admissions to hospital)
Obesity (BMI ≥30kg/m2 if white European or ≥27kg/m2 if Asian, Middle Eastern or Black ethnicity)
Age ≥18
Inability to walk/undertake 6-minute walk test
Inability to follow a low-energy MRP
HFpEF due to infiltrative cardiomyopathy (cardiac amyloidosis or sarcoidosis), genetic hypertrophic cardiomyopathy, restrictive cardiomyopathy/pericardial disease or congenital heart disease.
Recovered EF (previous EF < 40%) unless reduced EF was in context of tachycardia induced cardiomyopathy (eg AF/Aflutter).
Parallel
Low calorie meal replacement plan
DrugMeal replacement diet containing \~850 kcal/day (40% protein, 50% carbohydrate, 10% fat) supplied by Counterweight® (www.counterweight.org).The meal replacement plan will comprise of 3-4 meal packs/day (to equate to 850 kcal) with sweet and savoury options, and an allowance of 100ml semi-skimmed milk or a non-dairy alternative.
Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy
Diagnostic testCMR scanning performed on a 3T MRI scanner. Standardised protocol incorporating cine functional assessment to determine LV mass, systolic function and left atrial volumes; global systolic strain and diastolic strain rates will be assessed by tagging and with tissue tracking analysis from cine images, adenosine rest and stress myocardial perfusion to assess reserve index and qualitative perfusion defects, aortic distensibility to measure aortic stiffness, delayed contrast enhancement for assessment of LV fibrosis and evidence of previous myocardial infarction. Myocardial and liver triglyceride content will be assessed using the modified Hepafat® sequence or 1H MR spectroscopy at the inter ventricular septum. Additional imaging will be undertaken for quantification of visceral adiposity and subcutaneous adipose tissue. Cardiac 31P magnetic resonance spectroscopy imaging to assess cardiac muscle energetics according to a standardised operating procedure.
Transthoracic echocardiography
Diagnostic testComprehensive transthoracic echocardiography, including: tissue Doppler indices of diastolic filling, exclusion of valvular abnormalities, assessment of LV size and function
Blood test
Diagnostic testCollection of blood samples from each participant to characterise the participant's health status and fibroinflammatory markers.
Electrocardiogram
Diagnostic testAn ECG will be obtained to assess for baseline rhythm.
Accelerometery
Diagnostic testAccelerometer (GeneActiv) measured daily activity levels continuously for 7 consecutive days.
6 minute walk test (6MWT)
Diagnostic testSupervised 6MWT will be performed with symptom assessment using dyspnoea scale (Borg's).
Skeletal muscle strength using handgrip strength
Diagnostic testSkeletal muscle strength will be measured using hand grip strength
Assessment of quality of life and heart failure symptoms
Other interventionQuality of life and HF symptoms will be assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) questionnaire, which is used as a standardised measure of self-reported health status, and HF symptoms and is considered to have a good discriminatory power and validity
Assessment of sarcopenia
Other interventionParticipants will be assessed for presence of sarcopenia using the Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls (SARC-F) questionnaire. It is a robust tool for diagnosis of sarcopenia and prediction poor physical function, with excellent specificity in multimorbid individuals.
Assessment of frailty
Other interventionFrailty will be assessed using the Edmonton Frail Scale (EFS). The EFS is a multidimensional frailty assessment which assesses multiple domains of frailty including functional independence, social support, cognition, medication use, and mood.
Qualitative interview
Other interventionParticipants in the MRP and control groups will be invited to attend a focused semi-structured, 1-2-1 interview aimed to elicit barriers and enablers to the MRP and describe their perspective on the relationship between healthy eating and health interview during the 12-week visit. Participants who complete or drop out will be eligible. Inclusion of participants in the control arm will allow us to compare the experiences of MRP versus health coaching and detect any specific issues people face when trying to introduce lifestyle changes themselves.
Change in the distance walked during 6 minute walk test (6MWT)
The primary outcome measure is a change in the distance walked on 6MWT measured in meters
Beneficial reverse cardiovascular remodelling
CMR-derived measures of cardiovascular remodelling defined as left ventricular mass/volume ratio
Change in physical activity levels
Improvement in physical activity will be determined by change in daily activity as determined accelerometery
Change in upper limb muscle power
Change in muscle power will be determined by handgrip strength
Improvement in exercise tolerance
This will be assessed by change in Borg dyspnoea scale during 6MWT
Click on the lead sponsor to view all of their trials.
University of Leicester
Lead sponsor
University of Oxford
Collaborator
University of Manchester
Collaborator
University of Leeds
Collaborator
