Empagliflozin in improving exercise tolerance in HFpEF: study protocol for an open-label, randomized controlled study

INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) constitutes nearly half of patients with heart failure, but there is still a lack of treatment options to improve prognosis. Empagliflozin is a new hypoglycemic medication classified as sodium glucose cotransporter 2 inhibitors (SGLT2i); nonetheless, its effects on exercise tolerance in HFpEF remain ambiguous. Additional clinical studies are necessary to clarify the effect of SGLT2i in HFpEF. This study aims to evaluate the efficacy and safety of empagliflozin on exercise tolerance in patients with heart failure with preserved ejection fraction without diabetes, using cardiopulmonary exercise testing. METHODS AND ANALYSIS: This study is a single-center, open-label, randomized controlled trial. We will randomly (1:1) assign 86 patients with an ejection fraction of more than 40% and class II-III heart failure to receive empagliflozin (10 mg once daily) or to maintain their original treatment regimen. The treatment duration will be 12 weeks. The primary endpoint is the evaluation of changes in peak oxygen uptake (peak VO2) after a 12-week period using cardiopulmonary exercise testing (CPET). The secondary endpoints encompassed additional parameters of CPET and echocardiography, N-terminal pro-B-type natriuretic peptide level, alanine aminotransferase level, aspartate transaminase level, estimated glomerular filtration rate level, New York Heart Association functional classification, and scores from the Minnesota Living with Heart Failure Questionnaire. Safety events associated with empagliflozin and CPET will be monitored. DISCUSSION: We used peak oxygen uptake, the gold standard for assessing exercise tolerance, to evaluate the efficacy and safety of empagliflozin in treating non-diabetic patients with HFpEF. The improvement in quality of life of heart failure patients by SGLT2i will be objectively assessed. TRIAL REGISTRATION: www.chictr.org.cn (ChiCTR2300072908). Registered on 04 July 2023.