Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are currently a standard therapy for patients with heart failure with reduced ejection fraction (HFrEF). This study aims to assess the effects of Dapagliflozin on exercise capacity, cardiac biomarkers, fluid retention, renal and pulmonary function.
Methods: We prospectively enrolled stable HFrEF outpatients (left ventricular ejection fraction, LVEF<40%, New York Heart Association, NYHA, class II or III) eligible for SGLT2i and performed serial cardiopulmonary exercise tests (CPET), pulmonary function tests (spirometry and diffusing capacity of the lungs for carbon monoxide, DLCO), laboratory and echocardiographic assessments before and after 6 months of treatment, to evaluate effects on exercise capacity, ventricular remodelling, cardiac biomarkers, fluid retention, renal and pulmonary function. Results: 49 patients (86% males, age 64±12 years) on optimal medical therapy (84% on sacubitril/valsartan; 98% on β-blockers, 84% on MRAs) were evaluated. We observed an increase in LVEF (32.8±7.1 vs. 35.5±8.3%; 0.001) and a reduction in left ventricular end-diastolic (EDV) and end-systolic (ESV) volumes (EDV: 209±83 vs. 199± 77 mL, p=0.004; ESV: 143±73 vs. 133± 68 mL, 0.001). There were no significant changes in peak oxygen uptake, while ventilatory efficiency during exercise (VE/VCO2 slope) showed a significant improvement (fig.1). Hemoglobin (Hb) and hematocrit levels improved, while renal function sodium and potassium levels remained stable, as did blood urea nitrogen, while BNP, NT-proBNP, ST2, and hs-TNI did not reach statistical significance in this sub-population. NYHA functional class improved, together with a significant decrease of MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) score, from 3.9% to 2.7% with a positive impact on 2-year prognosis. Conclusion: Medium-term treatment with Dapagliflozin demonstrated beneficial effects on LV remodelling, ventilatory efficiency and functional status. An improvement in VE/VCO2 slope and MECKI score paralleled with an enhancement in echocardiographic parameters and NYHA class was observed. Our study did not detect medium-term effects on spirometry values, DLCO, fluid retention and NT-proBNP. These results suggest that some favourable effects could unfold over a longer period of time. Further studies with longer follow up are desirable to assess Dapagliflozin effects even in such a well-treated HF population.
