{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T07:14:24Z","timestamp":1778742864851,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T00:00:00Z","timestamp":1582070400000},"content-version":"vor","delay-in-days":0,"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":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex and multifactorial. Chronotropic incompetence (ChI) has emerged as a crucial pathophysiological mechanism. Beta\u2010blockers, drugs with negative chronotropic effects, are commonly used in HFpEF, although current evidence does not support its routine use in these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Hypothesis<\/jats:title><jats:p>We postulate beta\u2010blockers may have deleterious effects in HFpEF and ChI. This work aims to evaluate the short\u2010term effect of beta\u2010blockers withdrawal on functional capacity assessed by the maximal oxygen uptake (peakVO2) in patients with HFpEF and ChI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This is a prospective, crossover, randomized (1:1) and multicenter study. After randomization, the clinical and cardiac rhythm will be continuously registered for 30\u2009days. PeakVO2 is assessed by cardiopulmonary exercise testing (CPET) at 15 and 30\u2009days in both groups. Secondary endpoints include quality of life, cognitive, and safety assessment. Patients with stable HFpEF, functional class New York Heart Association (NYHA) II\u2010III, chronic treatment with beta\u2010blockers, and ChI will be enrolled. A sample size estimation [alfa: 0.05, power: 90%, a 20% loss rate, and delta change of mean peakVO2: +1.2 mL\/kg\/min (SD\u2009\u00b1\u20092.0)] of 52 patients is necessary to test our hypothesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients started enrolling in October 2018. As January 14th, 2020, 28 patients have been enrolled. It is projected to enroll the last patient at the end of July 2020.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Optimizing therapy that improves functional capacity remains an unmeet priority in HFpEF. Deprescribing beta\u2010blockers in patients with HFpEF and ChI seems a plausible intervention to improve functional capacity. This trial is an attempt towards precision medicine in this complex syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>: NCT03871803.<\/jats:p><\/jats:sec>","DOI":"10.1002\/clc.23345","type":"journal-article","created":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T14:16:47Z","timestamp":1582121807000},"page":"423-429","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Beta\u2010blockers withdrawal in patients with heart failure with preserved ejection fraction and chronotropic incompetence: Effect on functional capacity rationale and study design of a prospective, randomized, controlled trial (The Preserve\u2010HR trial)"],"prefix":"10.1002","volume":"43","author":[{"given":"Patricia","family":"Palau","sequence":"first","affiliation":[{"name":"FISABIO. Universitat Jaume I  Castell\u00f3n Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Seller","sequence":"additional","affiliation":[{"name":"Cardiology Department Hospital de Denia  Alicante Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7583-8818","authenticated-orcid":false,"given":"Eloy","family":"Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"FISABIO. Universitat Jaume I  Castell\u00f3n Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u00e9s","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Cardiology Department Hospital Cl\u00ednico Universitario de Santiago de Compostela, Santiago de Compostela  A Coru\u00f1a Spain"},{"name":"CIBERCV  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Mar\u00eda","family":"Ram\u00f3n","sequence":"additional","affiliation":[{"name":"CIBERCV  Madrid Spain"},{"name":"Cardiology Department Hospital Cl\u00ednico Universitario, INCLIVA. Universitat de Val\u00e8ncia  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Sastre","sequence":"additional","affiliation":[{"name":"CIBERCV  Madrid Spain"},{"name":"Cardiology Department Hospital Cl\u00ednico Universitario, INCLIVA. Universitat de Val\u00e8ncia  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"de la Espriella","sequence":"additional","affiliation":[{"name":"CIBERCV  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrique","family":"Santas","sequence":"additional","affiliation":[{"name":"CIBERCV  Madrid Spain"},{"name":"Cardiology Department Hospital Cl\u00ednico Universitario, INCLIVA. Universitat de Val\u00e8ncia  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8777-2588","authenticated-orcid":false,"given":"Gema","family":"Mi\u00f1ana","sequence":"additional","affiliation":[{"name":"CIBERCV  Madrid Spain"},{"name":"Cardiology Department Hospital Cl\u00ednico Universitario, INCLIVA. Universitat de Val\u00e8ncia  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco J.","family":"Chorro","sequence":"additional","affiliation":[{"name":"CIBERCV  Madrid Spain"},{"name":"Cardiology Department Hospital Cl\u00ednico Universitario, INCLIVA. Universitat de Val\u00e8ncia  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Ram\u00f3n","family":"Gonz\u00e1lez\u2010Juanatey","sequence":"additional","affiliation":[{"name":"Cardiology Department Hospital Cl\u00ednico Universitario de Santiago de Compostela, Santiago de Compostela  A Coru\u00f1a Spain"},{"name":"CIBERCV  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1672-7119","authenticated-orcid":false,"given":"Julio","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"CIBERCV  Madrid Spain"},{"name":"Cardiology Department Hospital Cl\u00ednico Universitario, INCLIVA. Universitat de Val\u00e8ncia  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,2,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfq121"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2014.11.106"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.recesp.2016.06.027"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11897-014-0223-7"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.632745"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008483-200603000-00007"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.03.077"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.12281"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.109.877720"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2015.06.038"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.09.029"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-017-9660-1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.03.610"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy626"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.16598"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx564"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.119.006213"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.592"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.940577"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.124.2.720"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehm037"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrtlng.2014.05.011"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(92)90986-6"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2011.02.001"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfr161"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.017119"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.979"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11897-012-0087-7"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.021884"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-13-1103"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.313572"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi115"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfs141"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2014.03.005"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2015.10.008"},{"key":"e_1_2_9_37_1","first-page":"CD012721","article-title":"Beta\u2010blockers and inhibitors of the renin\u2010angiotensin aldosterone system for chronic heart failure with preserved ejection fraction","volume":"6","author":"Martin N","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2017-311652"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2019.08.020"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1177\/1533317506295889"}],"container-title":["Clinical Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fclc.23345","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/clc.23345","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/clc.23345","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/clc.23345","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T02:06:19Z","timestamp":1693965979000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/clc.23345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,19]]},"references-count":39,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1002\/clc.23345"],"URL":"https:\/\/doi.org\/10.1002\/clc.23345","archive":["Portico"],"relation":{},"ISSN":["0160-9289","1932-8737"],"issn-type":[{"value":"0160-9289","type":"print"},{"value":"1932-8737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,19]]},"assertion":[{"value":"2019-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}