Effect of sodium-related glucose transporter 2 -Inhibitors on exercise capacity in heart failure patients with reduced ejection fraction, does etiology matter?

Abstract

Abstract Introduction Recently sodium-related glucose transporter 2 (SGLT2) inhibitors were found to improve cardiovascular outcomes significantly, however their effects on exercise capacity are yet unclear. Aim To assess in patients with heart failure with reduced ejection fraction (HFrEF), if etiology may have a role in treatment response to SGLT2-I and exercise improvement. Methods We included patients with a recent diagnosis of HF with ejection fraction ≤ 40%, between June 2014 and September 2022. An exhaustive initial evaluation was performed with laboratory tests, echocardiography, and exercise tolerance test, performing a 6-minute-walking test (6MWT). Patients were reassessed after 6 months, prior treatment optimization. Finally, patients were divided according to the HF etiology into ischemic and non-ischemic, comparing the results between the patients who received SGLT2-i and those who did not. Results Among the 462 patients included (275 non-ischemic and 187 ischemic; mean age 64.1 ±14.0 vs 61.9 ± 19.8 years, women 27.5% vs 15.8%), 45 and 41 patients respectively, received treatment with SGLT2-i. In both groups, patients who received SGLT2-i, had a significant higher prevalence of hypertension, dyslipidemia, and diabetes mellitus (Non-ischemic: hypertension 68.9 % vs 50.9%, p = 0.02; dyslipidemia 42.2% vs 25.8%, p= 0.02; diabetes mellitus 55.6% vs 28.3 %, p <0.001; Ischemic: hypertension 68.3% vs 50.3%, p = 0.04, dyslipidemia 75.6% vs 47.9, p< 0.02, diabetes mellitus 78% vs 38.4% p<0.001) and were as well treated with ARNI on a higher percentage (Non-ischemic 35.6% vs 13.9% p< 0.001, Ischemic: 39% vs 17.8%, p = 0.004). In the non-ischemic group, patients treated with SGLT2-i had a higher mean age (68.2±12.2 vs 63.3±14.3; p = 0.03). No other differences were observed between the baseline characteristics and the treatment. Treatment with SGLT2-i improved performance in 6MWT (+32.5 m [95% CI 10.7-54.4]) only in non-ischemic group while no differences have been found in ischemic patients. Conclusions Treatment with SGLT2-inhibitors has been associated with an improvement in exercise ability at six months only in patients with HFrEF of non-ischemic etiology whereas in patients with ischemic etiology it has not shown improvement in functional capacity. Our study suggests that, in clinical setting, non-ischemic patients may have a greater benefit with SGLT2-inhibitors treatment in term of exercise capacity.