{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:07:04Z","timestamp":1768464424625,"version":"3.49.0"},"reference-count":27,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Utilization of heart failure (HF) guideline\u2010directed medical therapy (GDMT) to target doses is suboptimal, with studies citing adverse effects (AEs), physiological factors, and therapeutic inertia as potential contributing factors. The objective of our study was to explore tolerability and GDMT titration\u2010limiting AEs in a specialized heart failure optimization program implemented at our institution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied the baseline characteristics of 254 patients who successfully completed our program and analyzed the frequency and severity of the four most common GDMT\u2010related AEs: hypotension, bradycardia, hyperkalemia, and renal dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients who achieved target doses were younger, more likely to have nonischemic HF, less likely to have a recent HF\u2010related hospitalization, had less coronary artery disease, and were more likely to be obese. Multivariate analyses revealed significant associations between beta blocker suboptimal dosing (&lt;\u200950% of target dose) and older age (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.0\u20131.07; <jats:italic>p<\/jats:italic>\u2009=\u20090.031), presence of atrial fibrillation (OR: 2.57; 95% CI: 1.18\u20135.58; <jats:italic>p<\/jats:italic>\u2009=\u20090.017), and absence of hypertension (OR: 0.39; 95% CI: 0.17\u20130.89; <jats:italic>p<\/jats:italic>\u2009=\u20090.025). For angiotensin converting enzyme inhibitors\/angiotensin II receptor blockers\/angiotensin receptor neprilysin inhibitors, suboptimal dosing was associated with the presence of atrial fibrillation (OR: 2.08; 95% CI: 1.04\u20134.17; <jats:italic>p<\/jats:italic>\u2009=\u20090.039). Of the patients who completed the program, 59.1% encountered at least one AE that hindered the titration to target GDMT doses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings highlight the complexities of GDMT optimization within a specialized program and the need for standardized definitions of GDMT\u2010related AEs and management strategies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/clc.70179","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T10:49:38Z","timestamp":1752576578000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tolerability and Adverse Effects in a Specialized Heart Failure Guideline\u2010Directed Medical Therapy Optimization Program"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0606-817X","authenticated-orcid":false,"given":"Claudia Mae","family":"Velasco","sequence":"first","affiliation":[{"name":"Penn State College of Medicine Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gladys","family":"Baksh","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Heart &amp; Vascular Institute Penn State Hershey Medical Center Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Haydo","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Heart &amp; Vascular Institute Penn State Hershey Medical Center Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Reesor","sequence":"additional","affiliation":[{"name":"Penn State College of Medicine Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Boehmer","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Heart &amp; Vascular Institute Penn State Hershey Medical Center Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omaima","family":"Ali","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Heart &amp; Vascular Institute Penn State Hershey Medical Center Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/clc.23664"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.3081"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.14559"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.04.070"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.02.015"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.37765\/ajmc.2022.88844"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.122.026187"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.15420\/cfr.2021.34"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2023.02.011"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.3757"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurpra.2024.105108"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001063"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(87)90171-8"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs337"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2022.11.026"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2021.12.004"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.14163"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2795"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2378"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2283"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2022.08.009"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.0640"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.3214"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2252"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2020.04.019"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2020.05.011"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2019.02.001"}],"container-title":["Clinical Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/clc.70179","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T13:03:38Z","timestamp":1753707818000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/clc.70179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":27,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/clc.70179"],"URL":"https:\/\/doi.org\/10.1002\/clc.70179","archive":["Portico"],"relation":{},"ISSN":["0160-9289","1932-8737"],"issn-type":[{"value":"0160-9289","type":"print"},{"value":"1932-8737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2025-05-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70179"}}