{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:25:30Z","timestamp":1790965530560,"version":"4.1.0"},"reference-count":15,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\n Background<\/jats:title>\n The primary chronic symptom of patients with heart failure with preserved ejection fraction (HFpEF) is severe exercise intolerance. The inability to adequately increase heart rate during exercise (chronotropic incompetence) is commonly present in HFpEF patients and contributes importantly to exercise intolerance in these patients. Since HFpEF patients often have cardiac comorbidities such as hypertension, coronary artery disease, and atrial fibrillation, beta-blockers are frequently prescribed for the treatment of these comorbidities. However, there is a concern that beta-blockers may worsen chronotropic incompetence by slowing heart rate in HFpEF patients and may further exacerbate their symptoms. There are several studies on the effects of beta-blocker withdrawal in HFpEF patients. We aim to perform the systematic review and meta-analysis of studies on the effects of beta-blocker withdrawal in HFpEF patients.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This meta-analysis will include randomized controlled trials and prospective cohort studies on the effect of beta-blocker withdrawal in HFpEF patients. Information of studies will be collected from PubMed, Web of Science, and Scopus. The primary outcome will be peak oxygen uptake (peak VO\n 2<\/jats:sub>\n ). The secondary outcome will be 6-minute walk distance. Other outcomes of interest will be health-related quality of life, plasma BNP levels, and cardiac structure and function.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n This systematic review and meta-analysis will evaluate whether beta-blocker withdrawal is beneficial for HFpEF patients, providing evidence regarding beta-blocker withdrawal in these patients.<\/jats:p>\n <\/jats:sec>\n \n Trial registration<\/jats:title>\n \n Systematic review registration:<\/jats:bold>\n INPLASY202370066<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0294347","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T13:37:42Z","timestamp":1700141862000},"page":"e0294347","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of beta-blocker withdrawal in patients with heart failure with preserved ejection fraction: A protocol for systematic review and meta-analysis"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9577-6586","authenticated-orcid":true,"given":"Hidekatsu","family":"Fukuta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Goto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kamiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"key":"pone.0294347.ref001","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1016\/S0735-1097(99)00118-7","article-title":"Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction","volume":"33","author":"RS Vasan","year":"1999","journal-title":"Journal of the American College of Cardiology"},{"key":"pone.0294347.ref002","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1056\/NEJMoa052256","article-title":"Trends in prevalence and outcome of heart failure with preserved ejection fraction","volume":"355","author":"TE Owan","year":"2006","journal-title":"N Engl J Med"},{"key":"pone.0294347.ref003","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1161\/CIRCRESAHA.119.313572","article-title":"Heart Failure With Preserved Ejection Fraction In Perspective","volume":"124","author":"MA Pfeffer","year":"2019","journal-title":"Circ Res"},{"key":"pone.0294347.ref004","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1161\/CIRCULATIONAHA.110.940577","article-title":"Chronotropic incompetence: causes, consequences, and management","volume":"123","author":"PH Brubaker","year":"2011","journal-title":"Circulation"},{"key":"pone.0294347.ref005","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nrcardio.2014.83","article-title":"The pathophysiology of heart failure with preserved ejection fraction","volume":"11","author":"BA Borlaug","year":"2014","journal-title":"Nat Rev Cardiol"},{"key":"pone.0294347.ref006","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1002\/ejhf.442","article-title":"Spectrum of epidemiological and clinical findings in patients with heart failure with preserved ejection fraction stratified by study design: a systematic review","volume":"18","author":"M Vaduganathan","year":"2016","journal-title":"Eur J Heart Fail"},{"key":"pone.0294347.ref007","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1093\/eurheartj\/ehx564","article-title":"Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials","volume":"39","author":"JGF Cleland","year":"2018","journal-title":"Eur Heart 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Functional Capacity in Heart Failure and Preserved Ejection Fraction","volume":"78","author":"P Palau","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"pone.0294347.ref011","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2046-4053-4-1","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement","volume":"4","author":"D Moher","year":"2015","journal-title":"Syst Rev"},{"key":"pone.0294347.ref012","doi-asserted-by":"crossref","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"JP Higgins","year":"2011","journal-title":"BMJ"},{"key":"pone.0294347.ref013","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.jclinepi.2010.09.011","article-title":"GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology","volume":"64","author":"GH 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