EFFECTS OF DAPAGLIFLOZIN ON EXERCISE CAPACITY, RESPIRATORY FUNCTION, BIOMARKERS, SLEEP APNEA, AND LEFT VENTRICULAR REMODELING IN PATIENTS WITH HEART FAILURE: A PROSPECTIVE, SINGLE CENTER, NON RANDOMIZED STUDY

Background: Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has become a cornerstone in the management of heart failure with reduced ejection fraction (HFrEF). Its clinical efficacy is well-established, primarily attributed to its effects on diuresis and hemodynamic unloading. However, despite its widespread use and therapeutic success, the precise mechanisms through which dapagliflozin exerts its beneficial effects remain incompletely understood. Current research is focused on elucidating the broader physiological pathways involved. Given the complexity of its actions, a more comprehensive understanding of its multifaceted effects will require detailed, multidomain assessments, spanning metabolic, cardiovascular, and renal functions. Methods: A single prospective cohort of stable HFrEF patients was studied in two parallel, complementary investigations. The first focused on exercise capacity, cardiac remodelling, fluid status, and conventional biomarkers. The second investigated alveolar-capillary membrane function through surfactant protein-B (proSP-B), gas exchange, and sleep-disordered breathing. Evaluations were performed at baseline, 2–4 weeks, and after 6 months of treatment with dapagliflozin 10 mg/day. Results: Among 75 patients enrolled, 67 completed full follow-up. Dapagliflozin improved left ventricular ejection fraction (LVEF), reduced cardiac volumes and pulmonary artery pressures, and enhanced ventilatory efficiency (VE/VCO₂ slope). Haemoglobin increased significantly, while peakVO₂, natriuretic peptides, and spirometry remained unchanged. DLCO and its subcomponents (Dm and Vcap) were stable, yet a significant reduction in circulating proSP-B was observed, suggesting improved alveolar-capillary membrane integrity. Central sleep apnoea frequency decreased in affected patients, with no impact on obstructive events or total apnoea burden. Conclusions: In this multidimensional evaluation of a single HFrEF cohort, dapagliflozin showed concordant benefits on cardiac remodelling, ventilatory efficiency, haemoglobin, and alveolar-capillary membrane health, despite unchanged peakVO₂ and pulmonary function. These findings reinforce dapagliflozin’s complex therapeutic profile, involving both hemodynamic and non-hemodynamic mechanisms.