{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T08:46:42Z","timestamp":1777970802805,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health (Ricerca Corrente)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Heart failure (HF) is a syndrome characterized by signs and symptoms resulting from structural or functional cardiac abnormalities, confirmed by elevated natriuretic peptides or evidence of congestion. HF patients are classified according to left ventricular ejection fraction (LVEF). Worsening HF (WHF) is associated with increased short- and long-term mortality, re-hospitalization, and healthcare costs. The standard treatment of HF includes angiotensin-converting enzyme inhibitors, angiotensin receptor\u2013neprilysin inhibitors, mineralocorticoid-receptor antagonists, beta-blockers, and sodium-glucose-co-transporter 2 inhibitors. To manage systolic HF by reducing mortality and hospitalizations in patients experiencing WHF, treatment with vericiguat, a direct stimulator of soluble guanylate cyclase (sGC), is indicated. This drug acts by stimulating sGC enzymes, part of the nitric oxide (NO)\u2013sGC\u2013cyclic guanosine monophosphate (cGMP) signaling pathway, regulating the cardiovascular system by catalyzing cGMP synthesis in response to NO. cGMP acts as a second messenger, triggering various cellular effects. Deficiencies in cGMP production, often due to low NO availability, are implicated in cardiovascular diseases. Vericiguat stimulates sGC directly, bypassing the need for a functional NO-sGC-cGMP axis, thus preventing myocardial and vascular dysfunction associated with decreased sGC activity in heart failure. Approved by the FDA in 2021, vericiguat administration should be considered, in addition to the four pillars of reduced EF (HFrEF) therapy, in symptomatic patients with LVEF &lt; 45% following a worsening event. Cardiac rehabilitation represents an ideal setting where there is more time to implement therapy with vericiguat and incorporate a greater number of medications for the management of these patients. This review covers vericiguat\u2019s metabolism, molecular mechanisms, and drug\u2013drug interactions.<\/jats:p>","DOI":"10.3390\/jcm13144209","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T09:14:53Z","timestamp":1721380493000},"page":"4209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["New Therapeutics for Heart Failure Worsening: Focus on Vericiguat"],"prefix":"10.3390","volume":"13","author":[{"given":"Patrizia","family":"Russo","sequence":"first","affiliation":[{"name":"Department of Human Sciences and Promotion of the Quality of Life, San Raffaele University; Via di Val Cannuta 247, 00166 Rome, Italy"},{"name":"Clinical and Molecular Epidemiology, IRCCS San Raffaele Roma, Via di Val Cannuta 247, 00166 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0776-3601","authenticated-orcid":false,"given":"Laura","family":"Vitiello","sequence":"additional","affiliation":[{"name":"Department of Human Sciences and Promotion of the Quality of Life, San Raffaele University; Via di Val Cannuta 247, 00166 Rome, Italy"},{"name":"Clinical and Molecular Epidemiology, IRCCS San Raffaele Roma, Via di Val Cannuta 247, 00166 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Milani","sequence":"additional","affiliation":[{"name":"Department of Human Sciences and Promotion of the Quality of Life, San Raffaele University; Via di Val Cannuta 247, 00166 Rome, Italy"},{"name":"Clinical and Molecular Epidemiology, IRCCS San Raffaele Roma, Via di Val Cannuta 247, 00166 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2624-9213","authenticated-orcid":false,"given":"Maurizio","family":"Volterrani","sequence":"additional","affiliation":[{"name":"Department of Human Sciences and Promotion of the Quality of Life, San Raffaele University; Via di Val Cannuta 247, 00166 Rome, Italy"},{"name":"Cardiology Rehabilitation Unit, IRCCS San Raffaele Roma, Via della Pisana 235, 00163 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe M. C.","family":"Rosano","sequence":"additional","affiliation":[{"name":"Department of Human Sciences and Promotion of the Quality of Life, San Raffaele University; Via di Val Cannuta 247, 00166 Rome, Italy"},{"name":"Cardiology, San Raffaele Cassino Hospital, Via Gaetano di Biasio, 1, 03043 Cassino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1823-2195","authenticated-orcid":false,"given":"Carlo","family":"Tomino","sequence":"additional","affiliation":[{"name":"Scientific Direction, IRCCS San Raffaele Roma, Via di Val Cannuta 247, 00166 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3833-6717","authenticated-orcid":false,"given":"Stefano","family":"Bonassi","sequence":"additional","affiliation":[{"name":"Department of Human Sciences and Promotion of the Quality of Life, San Raffaele University; Via di Val Cannuta 247, 00166 Rome, Italy"},{"name":"Clinical and Molecular Epidemiology, IRCCS San Raffaele Roma, Via di Val Cannuta 247, 00166 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100527","DOI":"10.1016\/j.ajpc.2023.100527","article-title":"The AHA\/ACC\/HFSA 2022 Heart Failure Guidelines: Changing the Focus to Heart Failure Prevention","volume":"15","author":"Abovich","year":"2023","journal-title":"Am. 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