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Multimorbid patients are under-represented in clinical trials; therefore, the effect of multimorbidity clustering on the prognosis of HF patients remains unknown. We evaluated the prevalence of multimorbidity clusters among consecutively registered hospitalized HF patients and assessed whether GDMT attenuated outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We examined 1924 hospitalized HF patients with reduced left ventricular ejection fraction (&amp;lt;50%) in a multicentre registry (West Tokyo HF Registry: WET-HF). Ten comorbid conditions in the WET-HF were abstracted: coronary artery disease, atrial fibrillation, stroke, anaemia, chronic obstructive pulmonary disease, renal dysfunction, obesity, hypertension, dyslipidaemia, and diabetes. Patients were divided into three groups (0\u20132: n = 451; 3\u20134: n = 787; and \u22655: n = 686) based on the number of comorbid conditions. The primary composite endpoint was all-cause mortality and HF rehospitalization. The most prevalent comorbidities were renal dysfunction (67.9%), hypertension (66.0%), and anaemia (53.8%). Increased comorbidity was associated with increased adverse outcomes [3\u20134: hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.13\u20131.77, P = 0.003; \u22655: HR 2.12, 95%CI 1.69\u20132.65, P &amp;lt; 0.001; and reference: 0\u20132] and lower GDMT prescription rate (0\u20132: 69.2%; 3\u20134: 57.7%; and \u22655: 57.6%). GDMT was associated with decreased adverse outcomes; this association was maintained even as the comorbidity burden increased but tended to weaken (0\u20132: HR 0.53, 95%CI 0.35\u20130.78; P = 0.001; 3\u20134: HR 0.82, 95%CI 0.65\u20131.04, P = 0.095; and \u22655: HR 0.81, 95%CI 0.65\u20131.00, P = 0.053; P for interaction = 0.156).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Comorbidity clusters were prevalent and associated with poorer outcomes. GDMT remained beneficial regardless of the comorbidity burden but tended to weaken with increasing comorbidity burden. Further research is required to optimize medical care in these patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.13954","type":"journal-article","created":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T09:30:09Z","timestamp":1652434209000},"page":"2500-2510","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Multimorbidity, Guideline-Directed Medical Therapies, and Associated Outcomes Among Hospitalized Heart Failure Patients"],"prefix":"10.1093","volume":"9","author":[{"given":"Shinsuke","family":"Takeuchi","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyorin University Hospital , 6-20-2 Shinkawa, Mitaka, 181-8611 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kohno","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyorin University Hospital , 6-20-2 Shinkawa, Mitaka, 181-8611 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Goda","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyorin University Hospital , 6-20-2 Shinkawa, Mitaka, 181-8611 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Keio University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Kawana","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, Stanford University , Stanford, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Saji","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sakakibara Heart Institute , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Nagatomo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, National Defense Medical College , Saitama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Nishihata","sequence":"additional","affiliation":[{"name":"Department of Cardiology, St. Lukes International Hospital , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Takei","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tokyo Saiseikai Central Hospital , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Saitama Medical University, International Medical Center , Saitama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Soejima","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyorin University Hospital , 6-20-2 Shinkawa, Mitaka, 181-8611 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Kohsaka","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Keio University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sakakibara Heart Institute , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"West Tokyo Heart Failure Registry Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,13]]},"reference":[{"key":"2026012114142854600_ehf213954-bib-0001","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1001\/jama.2020.10262","article-title":"Heart failure with reduced ejection fraction: a review","volume":"324","author":"Murphy","year":"2020","journal-title":"JAMA"},{"key":"2026012114142854600_ehf213954-bib-0002","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1161\/CIR.0b013e31829e8807","article-title":"2013 ACCF\/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation\/American Heart Association Task Force on practice guidelines","volume":"128","author":"Yancy","year":"2013","journal-title":"Circulation"},{"key":"2026012114142854600_ehf213954-bib-0003","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ejhf.592","article-title":"2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). 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