The Effect of Weight Loss Through Lifestyle Interventions in Patients With Heart Failure With Preserved Ejection Fraction-A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) accounts for >50% of heart failure cases and is associated with significant morbidity and health system burden. To date, there have been limited treatment options proven to improve outcomes in these patients, with sodium glucose co-transporter 2 (SGLT2) inhibitors the first class of drug to demonstrate significant clinical benefits, including reductions in heart failure hospitalisation. Obesity is associated with all forms of heart failure and has been linked with worse clinical outcomes. Numerous reviews support the benefits of weight loss in heart failure, more specifically in patients with heart failure with reduced ejection fraction. However, the evidence in HFpEF patients is less clear. With limited pharmacotherapy options and growing support for weight loss in patients with HFpEF, this systematic review and meta-analysis aims to examine the effects of lifestyle interventions on weight loss and other health outcomes in patients with HFpEF.

Methods: Web of Science, Embase, Scopus, and PubMed databases were searched to identify relevant studies up to February 2023. Included studies were randomised controlled trials (with a duration of four weeks or more) of lifestyle interventions conducted in adults with HFpEF that reported weight loss. Outcomes of interest were body weight, body mass index (BMI), blood pressure (systolic and diastolic), aerobic capacity (6-minute walk distance), New York Heart Association (NYHA) Functional Classification, self-reported health quality of life (Minnesota Living with Heart Failure Questionnaire; MLHFQ), and N-terminal pro B-Type Natriuretic Peptide (NT-proBNP) levels. Review Manager software was used to conduct random effect meta-analyses, forest plots were generated for each outcome, and between-study heterogeneity was estimated using the I² test statistic. Risk-of-bias assessment used the Cochrane risk-of-bias tool, and the certainty of the evidence was assessed using GRADE.

Results: From 2,282 records identified, six studies with a total of 375 participants, between three to six months in duration, were included in this systematic review and meta-analysis. Lifestyle interventions consisted of diet only, exercise only, combination of diet and exercise, and education and exercise. Over a mean follow-up of 4.5 months, pooled effects of the interventions were associated with a reduction in body weight of >5kg (weight mean difference (WMD): -5.30 kg; 95% CI: -8.72 to -1.87; p=0.002), and a reduction in resting systolic (WMD: -2.98 mmHg; 95% CI: -4.20 to -1.76; p<0.001) and diastolic blood pressure (WMD: -4.51 mmHg; 95% CI: -8.39 to -0.64; p=0.02) compared with those who received usual care. Interventions also improved 6-minute walk distance (WMD: 43.63 m; 95% CI: 22.28 to 64.97; p<0.001), NYHA class (WMD: -0.54; 95% CI: -0.75 to -0.33; p<0.001), and MLHFQ score (WMD: -17.77; 95% CL: -19.00 to -16.53; p<0.001).

Conclusion: In patients with HFpEF, lifestyle intervention was associated with a significant reduction in body weight and had favourable effects on blood pressure, aerobic capacity, NYHA class, and health-related quality of life. Further research is needed in this population to examine the feasibility and durability of weight loss interventions and to examine the potential impact on hard clinical endpoints.

Keywords: HFpEF; Heart failure; Meta-analysis; Weight loss.