{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:26:58Z","timestamp":1790191618948,"version":"4.1.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":744,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:00:00Z","timestamp":1700611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Persistent symptoms despite guideline-directed medical therapy (GDMT) and poor tolerance of GDMT are hallmarks of patients with advanced heart failure (HF) with reduced ejection fraction (HFrEF). However, real-world data on GDMT use, dose, and prognostic implications are lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We included 699 consecutive patients with HFrEF and at least one \u2018I NEED HELP\u2019 marker for advanced HF enrolled in a multicentre registry. Beta-blockers (BB) were administered to 574 (82%) patients, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor\u2013neprilysin inhibitors (ACEi\/ARB\/ARNI) were administered to 381 (55%) patients and 416 (60%) received mineralocorticoid receptor antagonists (MRA). Overall, \u226550% of target doses were reached in 41%, 22%, and 56% of the patients on BB, ACEi\/ARB\/ARNI and MRA, respectively. Hypotension, bradycardia, kidney dysfunction and hyperkalaemia were the main causes of underprescription and\/or underdosing, but up to a half of the patients did not receive target doses for unknown causes (51%, 41%, and 55% for BB, ACEi\/ARB\/ARNI and MRA, respectively). The proportions of patients receiving BB and ACEi\/ARB\/ARNI were lower among those fulfilling the 2018 HFA-ESC criteria for advanced HF. Treatment with BB and ACEi\/ARB\/ARNI were associated with a lower risk of death or HF hospitalizations (adjusted hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.48\u20130.84, and HR 0.74, 95% CI 0.58\u20130.95, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In a large, real-world, contemporary cohort of patients with severe HFrEF, with at least one marker for advanced HF, prescription and uptitration of GDMT remained limited. A significant proportion of patients were undertreated due to unknown reasons suggesting a potential role of clinical inertia either by the prescribing healthcare professional or by the patient. Treatment with BB and ACEi\/ARB\/ARNI was associated with lower mortality\/morbidity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3081","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T03:04:51Z","timestamp":1699326291000},"page":"327-337","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Guideline-Directed Medical Therapy in Severe Heart Failure with Reduced Ejection Fraction: An Analysis from the HELP-HF Registry"],"prefix":"10.1093","volume":"26","author":[{"given":"Daniela","family":"Tomasoni","sequence":"first","affiliation":[{"name":"Institute of Cardiology, ASST Spedali Civili, Department of Medical and Surgical specialties, Radiological Sciences and Public Health, University of Brescia , Brescia ,","place":["Italy"]},{"name":"Division of Cardiology, Department of Medicine, Karolinska Institutet, and Heart and Vascular and Neuro Theme, Karolinska University Hospital , Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Pagnesi","sequence":"additional","affiliation":[{"name":"Institute of Cardiology, ASST Spedali Civili, Department of Medical and Surgical specialties, Radiological Sciences and Public Health, University of Brescia , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Colombo","sequence":"additional","affiliation":[{"name":"Institute of Cardiology, ASST Spedali Civili, Department of Medical and Surgical specialties, Radiological Sciences and Public Health, University of Brescia , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Chiarito","sequence":"additional","affiliation":[{"name":"Humanitas Research Hospital IRCCS , Rozzano ,","place":["Italy"]},{"name":"Department of Biomedical Sciences, Humanitas University , Pieve Emanuele ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Stolfo","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste , Trieste ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Baldetti","sequence":"additional","affiliation":[{"name":"Cardiac Intensive Care Unit, IRCCS San Raffaele Scientific Institute , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo Mario","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Institute of Cardiology, ASST Spedali Civili, Department of Medical and Surgical specialties, Radiological Sciences and Public Health, University of Brescia , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Adamo","sequence":"additional","affiliation":[{"name":"Institute of Cardiology, ASST Spedali Civili, Department of Medical and Surgical specialties, Radiological Sciences and Public Health, University of Brescia , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Maggi","sequence":"additional","affiliation":[{"name":"Institute of Cardiology, ASST Spedali Civili, Department of Medical and Surgical specialties, Radiological Sciences and Public Health, University of Brescia , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo Maria","family":"Inciardi","sequence":"additional","affiliation":[{"name":"Institute of Cardiology, ASST Spedali Civili, Department of Medical and Surgical specialties, Radiological Sciences and Public Health, University of Brescia , Brescia 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Universitaria Giuliano Isontina (ASUGI), University of Trieste , Trieste ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto Maria","family":"Cappelletti","sequence":"additional","affiliation":[{"name":"Cardiac Intensive Care Unit, IRCCS San Raffaele Scientific Institute , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Rosano","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Centre for Clinical and Basic Research, IRCCS San Raffaele Pisana , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Sinagra","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste , Trieste 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