The Effect of SGLT2 Inhibitor Therapy on Endothelial Progenitor Cell Function in Patients With Heart Failure.

Abstract

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been shown to reduce the risk of cardiovascular mortality and hospitalizations in patients with heart failure (HF) with preserved or reduced ejection fraction (HFpEF or HFrEF). The mechanism for this benefit is not clear. Endothelial progenitor cells (EPCs) are bone marrow-derived cells able to differentiate into functional endothelial cells and participate in endothelial repair. The aim of this study was to evaluate the effect of SGLT-2 inhibitors on the level and function of EPCs in patients with HF. We enrolled 20 patients with symptomatic HF, 12 with HFrEF and 8 with HFpEF (aged 73.3 ± 10.2 years, 95% men). Blood samples were drawn at 2 time points: baseline and ≥3 months after initiation of SGLT-2 inhibitor therapy. Circulating EPC levels were evaluated by expression of vascular endothelial growth factor receptor-2 (VEGFR-2), CD34, and CD133 by flow cytometry. EPC colony forming units (CFUs) were quantified after 7 days in culture. The proportion of cells that coexpressed VEGFR-2 and CD34 or VEGFR-2 and CD133 was higher following 3 months of SGLT-2 inhibitors [0.26% (interquartile range, IQR 0.10-0.33) versus 0.55% (IQR 0.28-0.91), P = 0.002; 0.12% (IQR 0.07-0.15) versus 0.24% (IQR 0.15-0.39), P = 0.001, respectively]. EPC CFUs were also increased following SGLT-2 inhibitor treatment [23 (IQR 3.7-37.8) versus 79.4 (IQR 25.1-110.25) colonies/10 6 cells, P = 0.0039]. In patients with symptomatic HF, both HFpEF and HFrEF, treatment with SGLT-2 inhibitors is associated with an increase in the level and function of circulating EPCs. This augmentation in EPCs may be a contributing mechanism to the clinical benefit of SGLT-2 inhibitors in patients with HF.