BMJ Open. 2026 Mar 26;16(3):e113093. doi: 10.1136/bmjopen-2025-113093.
ABSTRACT
INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) represents a common subtype of heart failure, accounting for approximately 50% of all heart failure cases. It is characterised by a left ventricular ejection fraction of ≥50%, alongside persistent symptoms and signs of heart failure. The pathophysiology of HFpEF is complex and multifactorial, involving mechanisms such as hypertension, coronary artery disease, left ventricular dysfunction, right ventricular impairment, systemic inflammation and metabolic abnormalities. Although pharmacological therapies play a central role in the management of HFpEF, non-pharmacological interventions have also demonstrated potential in improving patients' symptoms and quality of life. However, there remains no consensus regarding which non-pharmacological approach is most effective. This study will aim to systematically compare the efficacy of different non-pharmacological therapies in patients with HFpEF by conducting a systematic review and network meta-analysis.
METHODS AND ANALYSIS: We will systematically search the following electronic databases from their inception to 14 February 2026: PubMed, MEDLINE, Embase, the Cochrane Library, Web of Science, Chinese databases China National Knowledge Infrastructure (CNKI) and SinoMed. The search will be restricted to studies published in English or Chinese. The primary outcomes will comprise all-cause and cardiovascular mortality, together with heart failure-related rehospitalisation. Pairwise meta-analyses will be performed using RevMan V.5.3 (The Cochrane Collaboration, Copenhagen, Denmark), while network meta-analyses will be conducted using ADDIS V.1.16.6 (Drugis, Groningen, The Netherlands) and Stata V.16.1 (StataCorp) within a Bayesian framework employing Markov chain Monte Carlo methods to compare the relative efficacy of different non-pharmacological therapies. To ensure transitivity assumptions are met, we will conduct separate network meta-analyses for lifestyle and behavioural interventions (exercise training, dietary interventions and multidisciplinary management), device-based and surgical interventions (interatrial shunts, implantable haemodynamic monitors, cardiac contractility modulation and splanchnic nerve ablation), and a full network including all modalities. To ensure accuracy and reliability, study screening, data extraction, risk of bias assessment and certainty of evidence evaluation will be carried out independently by two reviewers. We will assess the risk of bias in individual studies with the Cochrane Risk of Bias tool and evaluate the certainty of evidence using both the Grading of Recommendations, Assessment, Development and Evaluations framework and the Confidence in Network Meta-Analysis tool.
ETHICS AND DISSEMINATION: Ethical approval is not required for this study, as it is a systematic review of previously published literature. The findings will be submitted for publication in a peer-reviewed journal and/or presented at relevant academic conferences.
PROSPERO REGISTRATION NUMBER: CRD420251165545.
PMID:41887649 | DOI:10.1136/bmjopen-2025-113093