Aims: Leptin has recently been related to myocardial remodeling leading to ventricular hypertrophy and heart failure (HF). With the emergence of new medical therapies targeting cardiac remodeling, there needs to be a better understanding of leptin’s metabolic pathways. Neprilysin inhibition has favorable effects on cardiac remodeling and was shown to decrease the morbidity and mortality in patients with reduced systolic cardiac function. Neprilysin itself promotes adipogenesis suggesting a positive feedback loop effects on leptin signaling. We aimed to investigate the effects of neprilysin inhibition on leptin pathways and its potential positive impacts on the clinical status of HF patients.

Methods: 34 patients with chronic heart failure with reduced ejection fraction (HFrEF) of ischemic (n = 14) and non-ischemic (n = 20) origin (mean LVEF 30.38 %, SD 8.35; mean NYHA 2.38, SD 0.6; n = 23 male) were prospectively included. Serum concentrations of leptin, NT-proBNP, LDL and total cholesterol were measured at baseline and approximately 6 months after beginning of therapy with sacubritril/valsartan. Additional, pericardial adipose tissue (PAT) was measured in transthoracic echocardiography, parasternal long and short-axis views. The difference of values (Δ) was calculated.

Results: After the initiation of treatment with sacubitril/valsartan the serum concentration of leptin and LVEF increased significantly (table). The clinical condition of the patients improved, accordingly the decreased NYHA Class. We found a negative correlation between Δ leptin and Δ NYHA Class (r = -0.383; p = 0.025). Although PAT did not change significantly, we found a negative correlation between Δ PAT and Δ LVEF (r = -0.400; p = 0.019).