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Background Heart Failure with reduced ejection fraction (HFrEF) has a life time risk about 20% among adults aged 40 years or older and a 5-year mortality rate about 60% [1,2]. However novel therapies have shown to improve this outcome. One novel agent are angiotensin receptor-neprilysin inhibitors (ARNIs) that increase the BNP levels via inhibiting neprilsyin [3]. This has beneficial effects on heart failure by reducing preload, inflammation and fibrosis. Neprilysin also interacts with leptin and is known to correlate with the incidence and progression of heart failure if chronically elevated [4]. Furthermore beneficial affects of ARNI therapy on glucose metabolism were reported in a post-hoc analysis of the PARADIGM-HF trial [5]. In this study we aim to investigate the effect of ARNI therapy on the fat metabolism markers leptin and on the glucose metabolism marker fructosamin. Methods In total, we included 74 patients with HFrEF with ischemic (N=37) and non-ischemic (n=37) origin in the present study. The mean NYHA class was II–III, the mean BMI 28 (SD 6.3). Patients had well established heart failure therapy before starting ARNI therapy with sacubitril/valsartan. 88% of patients were on ACE-inhibitors, 86% on beta blockers and 68% on mineralocorticoid receptor antagonists. Serum samples were obtained and analyzed for leptin, fructosamin and pBNP before and 3–6 month after ARNI therapy. The clinical parameters LVEF and NYHA class were assessed before and 3–6 month after ARNI therapy. Results Baseline leptin level was 15.0 (SD 17.2), baseline fructosamin level was 370.1 (SD 167.7) and baseline pBNP level was 1494.9 (SD 1281.4). Under therapy a significant improvement of ejection fraction from 29,8% to 37,5% (7,7 SD 8,5 P≤0.001), an improvement of NYHA stadium from 2.46 (SD 0.62) to 1.96 (SD 0.63, p=0.005) and a significant decrease of pBNP (562.1 SD 1256.4, p=0.018) was found. Along with that, a significant increase in leptin levels (3.6 SD 8.85, p=0.012) and a significant increase in fructosamine levels (93.5 SD 160.6, p=0.013) was shown. Conclusion Under therapy with ARNI we showed a sufficient therapy response with improvement of ejection fraction and decrease of pBNP in line with literature. Surprisingly metabolism biomarkers did significantly worsen under the first three to six month after new ARNI therapy. To distinguish between a side effect of ARNI therapy or consequence of heart failure itself further investigations are needed. Funding Acknowledgement Type of funding sources: None.

Aims Leptin has recently been related to myocardial remodeling in animal experimentation studies on heart failure (HF). Furthermore, leptin has been reported to be related to diastolic dysfunction, however only in healthy population. With the emergence of new medical therapies targeting cardiac remodeling, there needs to be a better understanding of the metabolic pathways involving leptin. Our study aims to investigate leptin's correlation to parameters of systolic and diastolic heart function, as well as epicardial and pericardial adipose tissue (EAT and PAT) in heart failure (HF) patients. Methods The study included 51 patients with chronic heart failure with reduced ejection fraction (HFrEF) of ischemic (n=22) and non-ischemic (n=29) origin (NYHA II-III, mean EF 29.56%, SD 8.1; mean BMI 28.08, SD 5.8). Serum concentrations of leptin, NT-proBNP, HbA1c, LDL, and total cholesterol were also measured. Global longitudinal strain (GLS) and other LV function parameters were assessed in transthoracic echocardiography, as well as EAT and PAT in parasternal long and short-axis views. Results We found a significant correlation between leptin serum concentration and epicardial, as well as pericardial adipose tissue (EAT r=0.336, p=0.030; PAT r=0.565, p Conclusion We provide evidence of serum leptin correlation to remodeling parameters, as well as epicardial and pericardial fat tissue in HF patients. Whether leptin has positive effects on reversing or preventing remodeling in heart failure, needs further investigation. Correlation of leptin vs. GLS Funding Acknowledgement Type of funding source: None