{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T04:15:02Z","timestamp":1777954502490,"version":"3.51.4"},"reference-count":37,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"unspecified","delay-in-days":123,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Netherlands CardioVascular Research Initiative","award":["2020B008"],"award-info":[{"award-number":["2020B008"]}]},{"DOI":"10.13039\/501100002996","name":"Dutch Heart Foundation","doi-asserted-by":"crossref","award":["2020T058"],"award-info":[{"award-number":["2020T058"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100018890","name":"Dutch Cardiovascular Alliance","doi-asserted-by":"publisher","award":["2020B004"],"award-info":[{"award-number":["2020B004"]}],"id":[{"id":"10.13039\/100018890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018890","name":"Dutch Cardiovascular Alliance","doi-asserted-by":"publisher","award":["2020B008 RECONNEXT"],"award-info":[{"award-number":["2020B008 RECONNEXT"]}],"id":[{"id":"10.13039\/100018890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Open Heart"],"accepted":{"date-parts":[[2026,4,13]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>\n                      The Heavy, Hypertensive, Atrial fibrillation, Pulmonary hypertension, Elder, Filling pressure (H\n                      <jats:sub>2<\/jats:sub>\n                      FPEF) score is a widely used diagnostic tool for heart failure with preserved ejection fraction (HFpEF). Angina symptoms are common in patients with HFpEF but are not included in the score. We aimed to determine whether incorporating angina into the H\n                      <jats:sub>2<\/jats:sub>\n                      FPEF score improves its diagnostic performance sex-specifically, given the well-known sex differences in both HFpEF and angina presentation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We included 515 individuals from the UHFO-DM cohort with suspected HFpEF. Participants underwent standardised symptom collection, including angina using WHO questionnaires, and expert-panel adjudication of HFpEF. Following evaluation of H\n                      <jats:sub>2<\/jats:sub>\n                      FPEF, we assessed the association of angina with HFpEF independent of H\n                      <jats:sub>2<\/jats:sub>\n                      FPEF using logistic regression. By adding angina to H\n                      <jats:sub>2<\/jats:sub>\n                      FPEF, we developed a modified algorithm and evaluated it by the area under the receiver operating characteristic curve (AUC), calibration, reclassification and decision curve analysis. All analyses were stratified by sex. We also included another 751 individuals with suspected HFpEF from a Combination cohort of UHFO-COPD (n=136), STRETCH (n=331) and TREE (n=284) for regression analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the UHFO-DM cohort, HFpEF prevalence was 24%. Overall H\n                      <jats:sub>2<\/jats:sub>\n                      FPEF discrimination (AUC) was 0.72, with 0.69 in women and 0.74 in men. Angina was independently associated with HFpEF in women (OR 3.96, 95%\u2009CI 1.72 to 9.11, p=0.001) but not in men (1.90, 0.88 to 4.10, 0.102). Adding one point for angina in a modified H\n                      <jats:sub>2<\/jats:sub>\n                      FPEF score in women improved AUC from 0.69 to 0.71 (DeLong p=0.030), increased sensitivity (0.53 to 0.60)\u2009and negative predictive value (0.80 to 0.82) and yielded a continuous net reclassification improvement of 0.449, with preserved calibration and higher net clinical benefit on decision curves. No performance gain was observed with the same modification in men. In the Combination cohort, angina was also independently associated with HFpEF only in women (women, 2.13, 1.14 to 3.97, 0.018; men, 0.85, 0.44 to 1.66, 0.638).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In women with suspected HFpEF, the presence of angina provides diagnostic information independent of H\n                      <jats:sub>2<\/jats:sub>\n                      FPEF to uncover HFpEF. A simple sex-specific modification of H\n                      <jats:sub>2<\/jats:sub>\n                      FPEF, adding one point for angina in women, may slightly improve discrimination and rule-out performance in women.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/openhrt-2026-004054","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T18:35:20Z","timestamp":1777919720000},"page":"e004054","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Incorporating angina into the H\n                    <sub>2<\/sub>\n                    FPEF score improves diagnostic performance for HFpEF in women"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5295-0361","authenticated-orcid":false,"given":"Kaiyong","family":"Qu","sequence":"first","affiliation":[{"name":"Experimental Cardiology, University Medical Centre Utrecht, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2360-913X","authenticated-orcid":false,"given":"N Charlotte","family":"Onland-Moret","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber","family":"de Vos","sequence":"additional","affiliation":[{"name":"Experimental Cardiology, University Medical Centre Utrecht, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1249-0767","authenticated-orcid":false,"given":"Anne Margje Lisa Naomi","family":"van Ommen","sequence":"additional","affiliation":[{"name":"Experimental Cardiology, University Medical Centre Utrecht, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne","family":"van Mourik","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelien E","family":"van Riet","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leandra","family":"Boonman - de Winter","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M L","family":"Handoko","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Amsterdam University Medical Centres, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maarten Jan","family":"Cramer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arco J","family":"Teske","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roxana","family":"Menken","sequence":"additional","affiliation":[{"name":"Cardiology Centers of the Netherlands, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frans","family":"Rutten","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hester M","family":"den Ruijter","sequence":"additional","affiliation":[{"name":"Experimental Cardiology, University Medical Centre Utrecht, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8999-9946","authenticated-orcid":false,"given":"Elisa","family":"Dal Canto","sequence":"additional","affiliation":[{"name":"Experimental Cardiology, University Medical Centre Utrecht, Utrecht, Netherlands"},{"name":"Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"2026050411351313000_13.1.e004054.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2017.65"},{"key":"2026050411351313000_13.1.e004054.2","doi-asserted-by":"crossref","DOI":"10.15420\/cfr.2023.05","article-title":"Global Public Health Burden of Heart Failure: An Updated Review","volume":"9","author":"Shahim","year":"2023","journal-title":"Card Fail Rev"},{"key":"2026050411351313000_13.1.e004054.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2024.07.001"},{"key":"2026050411351313000_13.1.e004054.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)02756-3"},{"key":"2026050411351313000_13.1.e004054.5","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1161\/CIRCULATIONAHA.120.053026","article-title":"Real-Time Cardiac Magnetic Resonance Imaging: A New Spin on the Evaluation of HFpEF","volume":"143","author":"Borlaug","year":"2021","journal-title":"Circulation"},{"key":"2026050411351313000_13.1.e004054.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2023.03.393"},{"key":"2026050411351313000_13.1.e004054.7","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz641"},{"key":"2026050411351313000_13.1.e004054.8","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.034646"},{"key":"2026050411351313000_13.1.e004054.9","doi-asserted-by":"crossref","DOI":"10.15420\/icr.2024.30","article-title":"Sex Differences in Heart Failure: A Step Forward","volume":"19","author":"Wijesinghe","year":"2025","journal-title":"Interv Cardiol"},{"key":"2026050411351313000_13.1.e004054.10","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.120.018574","article-title":"Sex Differences in Heart Failure With Preserved Ejection Fraction","volume":"10","author":"Sotomi","year":"2021","journal-title":"J Am Heart Assoc"},{"key":"2026050411351313000_13.1.e004054.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.09.039"},{"key":"2026050411351313000_13.1.e004054.12","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1001\/jamacardio.2021.1825","article-title":"Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction","volume":"6","author":"Rush","year":"2021","journal-title":"JAMA Cardiol"},{"key":"2026050411351313000_13.1.e004054.13","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.tcm.2016.08.002","article-title":"Sex differences in nonobstructive coronary artery disease: Recent insights and substantial knowledge gaps","volume":"27","author":"Paul","year":"2017","journal-title":"Trends Cardiovasc Med"},{"key":"2026050411351313000_13.1.e004054.14","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1177\/2047487318816774","article-title":"Opportunistic screening models for high-risk men and women to detect diastolic dysfunction and heart failure with preserved ejection fraction in the community","volume":"26","author":"Gohar","year":"2019","journal-title":"Eur J Prev Cardiol"},{"key":"2026050411351313000_13.1.e004054.15","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2579-0"},{"key":"2026050411351313000_13.1.e004054.16","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi291"},{"key":"2026050411351313000_13.1.e004054.17","doi-asserted-by":"publisher","DOI":"10.3122\/jabfm.2014.06.140045"},{"key":"2026050411351313000_13.1.e004054.18","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.110"},{"key":"2026050411351313000_13.1.e004054.19","doi-asserted-by":"publisher","DOI":"10.1053\/euhj.2001.2783"},{"key":"2026050411351313000_13.1.e004054.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejheart.2008.08.005"},{"key":"2026050411351313000_13.1.e004054.21","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfs105"},{"key":"2026050411351313000_13.1.e004054.22","first-page":"645","article-title":"The diagnosis of ischaemic heart pain and intermittent claudication in field surveys","volume":"27","author":"ROSE","year":"1962","journal-title":"Bull World Health Organ"},{"key":"2026050411351313000_13.1.e004054.23","doi-asserted-by":"publisher","DOI":"10.2307\/2531595"},{"key":"2026050411351313000_13.1.e004054.24","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1097\/EDE.0000000000000018","article-title":"Net reclassification indices for evaluating risk prediction instruments: a critical review","volume":"25","author":"Kerr","year":"2014","journal-title":"Epidemiology (Sunnyvale)"},{"key":"2026050411351313000_13.1.e004054.25","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu207"},{"key":"2026050411351313000_13.1.e004054.26","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s10741-023-10362-x","article-title":"The prevalence of coronary microvascular dysfunction (CMD) in heart failure with preserved ejection fraction (HFpEF): a systematic review and meta-analysis","volume":"29","author":"Lin","year":"2024","journal-title":"Heart Fail Rev"},{"key":"2026050411351313000_13.1.e004054.27","first-page":"473","article-title":"The parallel tales of microvascular angina and heart failure with preserved ejection fraction: a paradigm shift","volume":"38","author":"Crea","year":"2017","journal-title":"Eur Heart J"},{"key":"2026050411351313000_13.1.e004054.28","doi-asserted-by":"crossref","DOI":"10.1177\/17455057221140209","article-title":"Sex differences in heart failure with preserved ejection fraction: From traditional risk factors to sex-specific risk factors","volume":"18","author":"Kaur","year":"2022","journal-title":"Womens Health (Lond)"},{"key":"2026050411351313000_13.1.e004054.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.03.034"},{"key":"2026050411351313000_13.1.e004054.30","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.67"},{"key":"2026050411351313000_13.1.e004054.31","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.amjmed.2018.12.038","article-title":"Heart Failure With Preserved Ejection Fraction: Is Ischemia Due to Coronary Microvascular Dysfunction a Mechanistic Factor?","volume":"132","author":"Elgendy","year":"2019","journal-title":"Am J Med"},{"key":"2026050411351313000_13.1.e004054.32","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy531"},{"key":"2026050411351313000_13.1.e004054.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2016.07.301"},{"key":"2026050411351313000_13.1.e004054.34","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1002\/ejhf.2019","article-title":"The HFA-PEFF and H2 FPEF scores largely disagree in classifying patients with suspected heart failure with preserved ejection fraction","volume":"23","author":"Sanders-van Wijk","year":"2021","journal-title":"Eur J Heart Fail"},{"key":"2026050411351313000_13.1.e004054.35","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1161\/CIRCULATIONAHA.118.038594","article-title":"External Validation of the H2F-PEF Model in Diagnosing Patients With Heart Failure and Preserved Ejection Fraction","volume":"139","author":"Sepehrvand","year":"2019","journal-title":"Circulation"},{"key":"2026050411351313000_13.1.e004054.36","doi-asserted-by":"crossref","DOI":"10.1186\/s12916-022-02650-4","article-title":"Diastolic dysfunction and sex-specific progression to HFpEF: current gaps in knowledge and future directions","volume":"20","author":"van Ommen","year":"2022","journal-title":"BMC Med"},{"key":"2026050411351313000_13.1.e004054.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.11.065"}],"container-title":["Open Heart"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/openhrt-2026-004054","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T18:35:23Z","timestamp":1777919723000},"score":1,"resource":{"primary":{"URL":"https:\/\/openheart.bmj.com\/lookup\/doi\/10.1136\/openhrt-2026-004054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,5,4]]},"published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1136\/openhrt-2026-004054"],"URL":"https:\/\/doi.org\/10.1136\/openhrt-2026-004054","relation":{},"ISSN":["2053-3624"],"issn-type":[{"value":"2053-3624","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]}}}