Impact of SGLT2i Use on Functional Capacity in Heart Failure

Abstract

<h3>Purpose</h3> Recently published trials have shown benefit for patients with heart failure with reduced or preserved ejection fraction with the addition of sodium glucose co-transporter 2 inhibitors (SGLT2i) to optimal medical therapy (OMT). Outcomes are limited to readmission and mortality but fail to elucidate a benefit in functional capacity. Data regarding the impact of SGLT2i on hemodynamic optimization has not demonstrated benefit in heart failure patients. The impact of SGLT2i on peak oxygen consumption measured by cardiopulmonary stress testing (CPET) has only been evaluated in animal models. Our aim was to evaluate the physiological impact of SGLT2i in the advanced heart failure population. <h3>Methods</h3> We performed a retrospective study between August 1, 2020 and August 15, 2021 to evaluate all patients with heart failure (preserved or reduced ejection fraction) undergoing CPET. Pre and post CPET were required after initiation of SGLT2i or after OMT. The SGLT2i group was compared to matched controls on OMT. <h3>Results</h3> A total of 13,213 patients were on SGLT2i during our study period. Of those, 2,063 (16%) had a diagnosis of heart failure with a total of 96 patients with CPET. 46 of these (48%) patients were in the SGLT2i group and 50 (52%) were matched controls on OMT. Median LVEF was 33% (IQR 25-40) in the SGLT2i group and 38% (IQR 25 -50) in the OMT group, p=0.10. Median duration between baseline and follow-up CPET in SGLT2i group was 352 days and 437 days in the OMT group, p=0.06. Pre and post comparison between OMT and SGLT2i was not different for exercise time (p=0.09), VE/VCO2 (p=0.11), RER (p=0.45), METS (p=0.25) or NYHA class (p=0.28). Less ARNI use (29 vs. 39, p=0.05), higher A1C (6.5 vs 5.7, p=0.01), similar GFR (65 vs 63, p=0.25) and less hypotensive blood pressure response at peak exercise (p<0.01) was noted in the SGLT2i group. Estimated GFR was not impacted by SGLT2i use (p=0.21) There was no significant difference in VO2 max at baseline (p=0.18) or follow-up (p=0.19) between the two groups. Change in VO2 max after SGLT2i was not significant (p=0.31). <h3>Conclusion</h3> The pluripotent mechanism of SGLT2i effect in heart failure is not clearly understood. Current outcomes have limited focus on readmission and mortality. Our data suggest that SGLT2i use does not improve functional capacity in heart failure. Optimization with SGLT2i is potentially due to a predominant effect on neurohormonal modulation and diuretic effect in addition to OMT.