{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T11:49:54Z","timestamp":1783511394038,"version":"3.55.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,11,6]],"date-time":"2022-11-06T00:00:00Z","timestamp":1667692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2022,11,6]],"date-time":"2022-11-06T00:00:00Z","timestamp":1667692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01HL130204"],"award-info":[{"award-number":["U01HL130204"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01HL130163"],"award-info":[{"award-number":["U01HL130163"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014588","name":"Sanofi Pasteur","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014588","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01HL130204"],"award-info":[{"award-number":["U01HL130204"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01HL130163"],"award-info":[{"award-number":["U01HL130163"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014588","name":"Sanofi Pasteur","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014588","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Influenza vaccination is associated with reduced cardiopulmonary morbidity and mortality among patients with heart failure or recent myocardial infarction. The immune response to vaccination frequently results in mild adverse reactions (AR), which leads to vaccine hesitancy. This post hoc analysis explored the association between vaccine-related AR and morbidity and mortality in patients with high-risk cardiovascular disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>The INVESTED trial randomized 5260 patients with recent heart failure hospitalization or acute myocardial infarction to high-dose trivalent or standard-dose quadrivalent inactivated influenza vaccine. We examined the association between vaccine-related AR and adverse clinical outcomes across both treatment groups in propensity-adjusted models. Among 5210 participants with available information on post-vaccination symptoms, 1968 participants (37.8%) experienced a vaccine-related AR. Compared to those without AR, post-vaccination AR, most commonly injection site pain (60.3%), were associated with lower risk for the composite of all-cause death or cardiopulmonary hospitalization (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.75\u20130.92, p\u2009&amp;lt;\u20090.001), cardiopulmonary hospitalizations (HR 0.85 [95% CI 0.76\u20130.95], p\u2009=\u20090.003), all-cause death (HR 0.77 [95% CI 0.62\u20130.96], p\u2009=\u20090.02), cardiovascular hospitalizations (HR 0.88 [95% CI 0.78\u20130.99], p\u2009=\u20090.03) and non-cardiopulmonary hospitalizations (HR 0.80 [95% CI 0.69\u20130.92], p\u2009=\u20090.003). While mild (76.4%) and moderate (20.6%) AR were most common and together associated with lower risk for the primary outcome (HR 0.81 [95% CI 0.74\u20130.90], p\u2009&amp;lt;\u20090.001), severe AR (2.9%) were related to increased risk (HR 1.68 [95% CI 1.17\u20132.42], p\u2009=\u20090.005).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Mild to moderate post-vaccination reactions after influenza vaccine were associated with reduced risk of cardiopulmonary hospitalizations and all-cause mortality in patients with high-risk cardiovascular disease, while severe reactions may indicate increased risk. Mild to moderate AR to influenza vaccination may be a marker of immune response and should not deter future vaccinations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2716","type":"journal-article","created":{"date-parts":[[2022,11,6]],"date-time":"2022-11-06T16:45:11Z","timestamp":1667753111000},"page":"299-310","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Association of Post-Vaccination Adverse Reactions After Influenza Vaccine with Mortality and Cardiopulmonary Outcomes in Patients with High-Risk Cardiovascular Disease: The INVESTED Trial"],"prefix":"10.1093","volume":"25","author":[{"given":"Alexander","family":"Peikert","sequence":"first","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KyungMann","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison , Madison, WI ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob A.","family":"Udell","sequence":"additional","affiliation":[{"name":"Peter Munk Cardiac Centre, University Health Network and Women's College Hospital, University of Toronto , Toronto, ONT ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Joseph","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]},{"name":"Department of Medicine , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay S.","family":"Desai","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Farkouh","sequence":"additional","affiliation":[{"name":"Peter Munk Cardiac Centre, University Health Network, University of Toronto , Toronto, ONT ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila M.","family":"Hegde","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian F.","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Michael","family":"Gaziano","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]},{"name":"Department of Medicine , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Keipp","family":"Talbot","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University , Nashville, TN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clyde","family":"Yancy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Northwestern University , Chicago, IL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inder","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis VA Health Care System , Minneapolis, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison , Madison, WI ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawton S.","family":"Cooper","sequence":"additional","affiliation":[{"name":"National Heart, Lung, and Blood Institute , Bethesda, MD ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orly","family":"Vardeny","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis VA Health Care System , Minneapolis, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,6]]},"reference":[{"key":"2026010913083473600_ejhf2716-bib-0001","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jchf.2018.10.011","article-title":"Effect of influenza on outcomes in patients with heart failure","volume":"7","author":"Panhwar","year":"2019","journal-title":"JACC Heart Fail"},{"key":"2026010913083473600_ejhf2716-bib-0002","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1056\/NEJMoa1702090","article-title":"Acute myocardial infarction after laboratory-confirmed influenza infection","volume":"378","author":"Kwong","year":"2018","journal-title":"N Engl J Med"},{"key":"2026010913083473600_ejhf2716-bib-0003","doi-asserted-by":"crossref","DOI":"10.7189\/jogh.09.020421","article-title":"Global mortality associated with seasonal influenza epidemics: new burden estimates and predictors from the GLaMOR Project","volume":"9","author":"Paget","year":"2019","journal-title":"J Glob Health"},{"key":"2026010913083473600_ejhf2716-bib-0004","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.amjcard.2020.05.045","article-title":"Influence of influenza infection on in-hospital acute myocardial infarction outcomes","volume":"130","author":"Tripathi","year":"2020","journal-title":"Am J Cardiol"},{"key":"2026010913083473600_ejhf2716-bib-0005","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1007\/s11606-021-07068-x","article-title":"Influenza vaccination and mortality among adults with heart failure in an integrated healthcare delivery system, 2009-2018","volume":"37","author":"Mefford","year":"2022","journal-title":"J Gen Intern Med"},{"key":"2026010913083473600_ejhf2716-bib-0006","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.amjcard.2020.05.019","article-title":"Influenza vaccination and outcome in heart failure","volume":"128","author":"Gotsman","year":"2020","journal-title":"Am J Cardiol"},{"key":"2026010913083473600_ejhf2716-bib-0007","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1001\/jama.2013.279206","article-title":"Association between influenza vaccination and cardiovascular outcomes in high-risk patients: a meta-analysis","volume":"310","author":"Udell","year":"2013","journal-title":"JAMA"},{"key":"2026010913083473600_ejhf2716-bib-0008","doi-asserted-by":"crossref","first-page":"e263","DOI":"10.1016\/j.jacc.2021.12.012","article-title":"2022 AHA\/ACC\/HFSA guideline for the management of heart failure: a report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"79","author":"Heidenreich","year":"2022","journal-title":"J Am Coll Cardiol"},{"key":"2026010913083473600_ejhf2716-bib-0009","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1093\/eurheartj\/ehw106","article-title":"2016 European guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts). 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