Impact of SGLT2 inhibitors on functional outcomes in heart failure patients according to the aetiology

Exercise intolerance is a significant symptom of heart failure with reduced ejection fraction (HFrEF) and is associated with poor outcomes. While sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiovascular benefits, their impact on functional capacity remains debated. This study aimed to assess the effects of SGLT2i on exercise capacity and quality of life in patients with ischemic and non-ischemic HFrEF. Patients with a recent diagnosis of HFrEF and stable clinical status, referred to a heart failure unit, were prospectively enrolled. Exercise capacity was evaluated using the six-minute walk test (6MWT), and quality of life with the Minnesota Living with Heart Failure Questionnaire (MLHFQ) both at baseline and after 6 months. Patients were stratified by etiology and analyzed according to SGLT2i use. A total of 462 patients were included (275 non-ischemic, 187 ischemic); 86 (18.6%) received SGLT2i (45 non-ischemic, 41 ischemic). At 6 months, SGLT2i treatment significantly improved 6MWT in non-ischemic patients (+31.9 m, <i>p</i> = 0.005), but not in ischemic patients (+9.0 m, <i>p</i> = 0.411; <i>P-interaction = 0.034</i>). MLHFQ scores improved similarly in both groups, with no significant differences related to SGLT2i use. SGLT2i improved exercise capacity only in non-ischemic HFrEF patients, suggesting a differential response based on etiology.