{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T23:52:07Z","timestamp":1788825127880,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Heart failure (HF) is categorized arbitrarily based on the left ventricular ejection fraction (LVEF) in HF with reduced (HFrEF; LVEF &lt; 40%), mildly reduced (HFmrEF; LVEF 40\u201349%), or preserved ejection fraction (HFpEF; LVEF \u2265 50%). In this opinion paper, based on (patho)physiological considerations, we contend that the neurohormonal overactivity syndrome (NOHS), which is present in all symptomatic HF patients irrespective of their LVEF, not only contributes to the development of signs and symptoms but it is also a major determinant of patients\u2019 outcomes. In this regard, NHOS is the only currently available treatment target in HF and should be combatted in most patients with the combined use of diuretics and neurohormonal inhibitors (\u03b2-blockers, angiotensin receptor-neprilysin inhibitor\/angiotensin-converting enzyme inhibitors\/angiotensin receptor blockers, mineralocorticoid antagonists, and sodium-glucose co-transporter 2 inhibitors). Unfortunately, despite the advances in therapeutics, HF mortality remains high. Probably machine learning approaches could better assess the multiple and higher-dimension interactions leading to the HF syndrome and define clusters of HF treatment efficacy.<\/jats:p>","DOI":"10.3390\/life13010250","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T02:10:32Z","timestamp":1673921432000},"page":"250","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Neurohormonal Overactivity Syndrome in Heart Failure"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9439-3946","authenticated-orcid":false,"given":"Andrew","family":"Xanthopoulos","sequence":"first","affiliation":[{"name":"Department of Cardiology, University General Hospital of Larissa, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7159-2478","authenticated-orcid":false,"given":"John","family":"Skoularigis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University General Hospital of Larissa, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6433-4016","authenticated-orcid":false,"given":"Filippos","family":"Triposkiadis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University General Hospital of Larissa, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1002\/ejhf.1858","article-title":"Epidemiology of heart failure","volume":"22","author":"Groenewegen","year":"2020","journal-title":"Eur. 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