{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:03:25Z","timestamp":1785402205098,"version":"3.56.0"},"reference-count":55,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["PNRR-POC-2023-12378186 CUP I73C24000330006"],"award-info":[{"award-number":["PNRR-POC-2023-12378186 CUP I73C24000330006"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PNRR-POC-2023-12378186 CUP I73C24000330006"],"award-info":[{"award-number":["PNRR-POC-2023-12378186 CUP I73C24000330006"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vericiguat is currently indicated for patients with heart failure with reduced ejection fraction (HFrEF) following recent clinical worsening, based on evidence demonstrating a reduction in cardiovascular death or heart failure hospitalization in a high-risk population. While this positioning is clinically justified, it may underestimate the broader pathophysiological context in which soluble guanylate cyclase (sGC) stimulation may be relevant, particularly in phases of persistent biological activation following apparent clinical stabilization. In routine practice, acute coronary syndromes (ACS), acute heart failure (AHF), and chronic HFrEF are approached as distinct clinical entities. However, these conditions often represent sequential manifestations of a continuous disease trajectory driven by persistent endothelial dysfunction, impaired nitric oxide\u2013sGC\u2013cyclic guanosine monophosphate (NO\u2013sGC\u2013cGMP) signaling, and residual vascular risk. In this perspective, we revisit the mechanistic and clinical rationale for vericiguat and propose a reframing of its therapeutic role. Its greatest utility may lie in patients with recently worsening HFrEF who remain biologically vulnerable after stabilization. Extension of this concept to post-ACS populations remains hypothesis-generating and is not supported by direct clinical evidence. This \u201cpost-stabilization vulnerable state\u201d represents a clinically recognizable yet insufficiently targeted phase, characterized by ongoing biological activation despite apparent clinical improvement. Adopting a continuum-based view of cardiovascular disease may improve alignment between pathophysiology and treatment, refine patient selection, and inform future trial design focused on this early post-event window. Importantly, this perspective is hypothesis-generating and reflects an effort to align emerging mechanistic insights with clinical trajectory, rather than to extend current indications beyond the available evidence base.<\/jats:p>","DOI":"10.3390\/ijms27125301","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:53:10Z","timestamp":1781247190000},"page":"5301","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vericiguat in the Post-Stabilization Phase of HFrEF: Targeting Residual Risk Across the Ischemia\u2013Decompensation Continuum"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3464-1645","authenticated-orcid":false,"given":"Beata","family":"Krasi\u0144ska","sequence":"first","affiliation":[{"name":"Department of Hypertensiology, Angiology, and Internal Medicine, Poznan University of Medical Sciences, \u00bd D\u0142uga Street, 61-848 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calogera","family":"Pisano","sequence":"additional","affiliation":[{"name":"Department of Research, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Specialized Therapies), 90127 Palermo, Italy"},{"name":"Department of Precision Medicine in Medical Surgical and Critical Area (Me.Pre.C.C.), University of Palermo, 90134 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1787-552X","authenticated-orcid":false,"given":"Roberta","family":"Vazzana","sequence":"additional","affiliation":[{"name":"Department of Research, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Specialized Therapies), 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7141-2561","authenticated-orcid":false,"given":"Giuseppe Maria","family":"Raffa","sequence":"additional","affiliation":[{"name":"Department of Research, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Specialized Therapies), 90127 Palermo, Italy"},{"name":"Department of Precision Medicine in Medical Surgical and Critical Area (Me.Pre.C.C.), University of Palermo, 90134 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5478-3245","authenticated-orcid":false,"given":"Mariusz","family":"Kowalewski","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Center of Postgraduate Medical Education, Central Clinical Hospital of the Ministry of Interior, 02-507 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6563-0877","authenticated-orcid":false,"given":"Krzysztof J.","family":"Filipiak","sequence":"additional","affiliation":[{"name":"The Centre of Postgraduate Medical Education, 99\/103 Marymoncka Street, 01-813 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw","family":"Bartkowski","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery and Transplantology, Poznan University of Medical Sciences, \u00bd D\u0142uga Street, 61-848 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2798-1959","authenticated-orcid":false,"given":"Zbigniew","family":"Krasi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Vascular, Endovascular Surgery, Angiology and Phlebology, Poznan University of Medical Science, \u00bd Dluga Street, 61-848 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Suwalski","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Center of Postgraduate Medical Education, Central Clinical Hospital of the Ministry of Interior, 02-507 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Koziarska","sequence":"additional","affiliation":[{"name":"University Clinical Hospital, 49 Przybyszewskiego Street, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9643-2697","authenticated-orcid":false,"given":"Vincenzo","family":"Nuzzi","sequence":"additional","affiliation":[{"name":"Department of Clinical Cardiology and Heart Failure, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3383-9657","authenticated-orcid":false,"given":"Paolo","family":"Manca","sequence":"additional","affiliation":[{"name":"Department of Clinical Cardiology and Heart Failure, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7265-7613","authenticated-orcid":false,"given":"Gennaro","family":"Galasso","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery, and Dentistry, University of Salerno, 84084 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8080-2764","authenticated-orcid":false,"given":"Tomasz","family":"Urbanowicz","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery and Transplantology, Poznan University of Medical Sciences, \u00bd D\u0142uga Street, 61-848 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/ehf2.14857","article-title":"2024 update in heart 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