Effects of empagliflozin on cardiac structure, function and biomarkers in patients with heart failure with preserved ejection fraction: study protocol for a randomised, placebo-controlled prospective trial

Heart failure (HF) with preserved ejection fraction (HFpEF) has become the main type of HF worldwide. Although large randomised controlled studies have demonstrated the beneficial effects of sodium-glucose cotransporter 2 inhibitors among patients with HFpEF, the mechanisms remain unclear. Basic research suggests that empagliflozin inhibits myocardial fibrosis. Myocardial extracellular volume (ECV) can be calculated using cardiac MRI (CMRI), which can reflect the degree of diffuse myocardial fibrosis. Studies show that empagliflozin can reduce ECV and left ventricular mass (LVM) assessed by CMRI in patients with diabetes with coronary heart disease and patients without diabetes with HF with reduced ejection fraction. However, whether empagliflozin reduces ECV and LVM among patients with HFpEF is unclear. This study intends to use CMRI to evaluate ECV and LVM, combined with echocardiography and an assessment of related biomarkers, to determine whether empagliflozin can improve myocardial fibrosis and left ventricular remodelling in patients with HFpEF. This report describes the study design of a prospective, multicentre, randomised, double-blind, placebo-controlled and parallel-group clinical study. A total of 180 participants with HFpEF aged 40-80 years old who meet the inclusion and exclusion criteria will be randomly divided into an empagliflozin treatment group or a placebo control group. The empagliflozin treatment group will receive 10 mg of empagliflozin per day for 6 months in addition to guideline-directed medical treatment, while the control group will receive placebo oral administration with guideline-directed medical therapy for 6 months. The primary outcomes are ECV and LVM changes measured by CMRI after 6 months of treatment. The study design is approved by the ethical committee of Beijing Hospital (2022BJYYEC-070-02). The trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn). The trial results will be published in peer-reviewed journals and conferences. Chinese Clinical Trial Registry (ChiCTR2200060862).