Improvements of cardiac function and metabolic parameters by sodium-glucose cotransporter 2 inhibitors with no significant effects on sympathetic or parasympathetic activity in chronic heart failure

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated significant cardiovascular benefits, including reductions in hospitalizations and mortality among patients with heart failure (HF). However, the mechanisms underlying these benefits, particularly their effects on autonomic nervous system activity, remain incompletely understood. This single-center, prospective observational study included 11 patients with chronic HF who were newly initiated on SGLT2 inhibitors. Sympathetic nerve activity was assessed using 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy, while parasympathetic activity was evaluated via heart rate recovery during cardiopulmonary exercise testing (CPET) conducted at baseline and three months post-treatment initiation. Echocardiographic and laboratory parameters were also analyzed. After three months of treatment, no significant changes were observed in MIBG-derived heart-to-mediastinum (H/M) ratios, washout rates, or heart rate recovery following exercise. Echocardiographic assessment revealed significant improvements in cardiac function. Laboratory findings demonstrated reductions in uric acid and HbA1c levels, improved liver function, and increased erythropoietin levels, while NT-proBNP exhibited a non-significant downward trend. Notably, free carnitine levels decreased significantly, possibly indicating enhanced energy metabolism within the failing myocardium. In patients with chronic HF, SGLT2 inhibitors had no significant effect on autonomic nervous system activity within the first three months of treatment. However, significant improvements in cardiac function and metabolic parameters were observed, supporting their cardioprotective role.

Keywords: CPET; Heart failure; Heart rate; MIBG; SGLT2 inhibitor.