{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T20:00:40Z","timestamp":1773432040336,"version":"3.50.1"},"reference-count":63,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T00:00:00Z","timestamp":1682294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>(1) Background: Heart failure with reduced ejection fraction (HFrEF) remains a major health burden. Angiotensin-Receptor-Neprilysin-Inhibitors (ARNIs) are an established HFrEF therapy which increases natriuretic peptide levels by inhibiting neprilysin. Leptin is a lipid metabolism parameter, which is also involved in glucose metabolism and is suggested to correlate with HF burden. While the hormone also seems to interact with neprilysin, potential associations with ARNI therapy have not been investigated yet. (2) Methods: To study this issue, we measured levels of leptin and fructosamine in consecutive 72 HFrEF patients before initiation of ARNI therapy and 3\u20136 months after initiation of therapy in two European centers. Biomarker levels were correlated with clinical parameters including ejection fraction, LVEF, and NYHA class. (3) Results: During a follow-up of up to 6 months, clinical parameters improved significantly (LVEF: 30.2 \u00b1 7.8% to 37.6 \u00b1 10.0%, (p &lt; 0.001) and a significant improvement of the mean NYHA class with initial 32 patients in NYHA III or IV and 8 patients in NYHA class III\/IV during the follow up (p &lt; 0.001). The initial NT-proBNP levels of 2251.5 \u00b1 2566.8 pg\/mL significantly improved to 1416.7 \u00b1 2145 pg\/mL, p = 0.008) during follow up. ARNI therapy was also associated with an increase in leptin levels (17.5 \u00b1 23.4 \u00b5g\/L to 22.9 \u00b1 29.3, p &lt; 0.001) and furthermore, affected glucose metabolism indicated by elevation of fructosamine values (333.9 \u00b1 156.8 \u00b5mol\/L to 454.8 \u00b1 197.8 \u00b5mol\/L, p = 0.013). (4) Conclusion: while in the early phase of therapy, ARNI promotes clinical improvement of HFrEF, and it also seems to affect fat and glucose parameters, indicating significant metabolic implications of this therapy regime.<\/jats:p>","DOI":"10.3390\/jcm12093083","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T03:04:08Z","timestamp":1682305448000},"page":"3083","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of Angiotensin Receptor-Neprilysin Inhibitors (ARNIs) on the Glucose and Fat Metabolism Biomarkers Leptin and Fructosamine"],"prefix":"10.3390","volume":"12","author":[{"given":"Bernhard","family":"Ohnewein","sequence":"first","affiliation":[{"name":"Department for Internal Medicine II, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zornitsa","family":"Shomanova","sequence":"additional","affiliation":[{"name":"Department of Cardiology I, Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera","family":"Paar","sequence":"additional","affiliation":[{"name":"Department for Internal Medicine II, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Topf","sequence":"additional","affiliation":[{"name":"Department for Internal Medicine II, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Jirak","sequence":"additional","affiliation":[{"name":"Department for Internal Medicine II, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2626-3098","authenticated-orcid":false,"given":"Lukas","family":"Fiedler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiology, Nephrology and Intensive Care Medicine, Hospital Wiener Neustadt, 2700 Wiener Neustadt, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Granitz","sequence":"additional","affiliation":[{"name":"Department for Internal Medicine II, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Van Almsick","sequence":"additional","affiliation":[{"name":"Department of Cardiology I, Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4386-8533","authenticated-orcid":false,"given":"Dilvin","family":"Semo","sequence":"additional","affiliation":[{"name":"Department of Cardiology I, Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2386-6707","authenticated-orcid":false,"given":"Naufal","family":"Zagidullin","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases, Bashkir State Medical University, Lenin str., 3, 450008 Ufa, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna-Maria","family":"Dieplinger","sequence":"additional","affiliation":[{"name":"Institute for Nursing Science and Practice, Paracelsus Medical University, 5020 Salzburg, Austria"},{"name":"Medical Faculty, Johannes Kepler University Linz, 4040 Linz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juergen","family":"Sindermann","sequence":"additional","affiliation":[{"name":"Department of Cardiology I, Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Reinecke","sequence":"additional","affiliation":[{"name":"Department of Cardiology I, Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uta C.","family":"Hoppe","sequence":"additional","affiliation":[{"name":"Department for Internal Medicine II, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7676-3942","authenticated-orcid":false,"given":"Rudin","family":"Pistulli","sequence":"additional","affiliation":[{"name":"Department of Cardiology I, Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas J.","family":"Motloch","sequence":"additional","affiliation":[{"name":"Department for Internal Medicine II, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart 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