{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T21:43:27Z","timestamp":1769118207701,"version":"3.49.0"},"reference-count":28,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,17]],"date-time":"2019-08-17T00:00:00Z","timestamp":1566000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002336","name":"Daiichi Sankyo Company","doi-asserted-by":"publisher","award":["FA714B4101"],"award-info":[{"award-number":["FA714B4101"]}],"id":[{"id":"10.13039\/501100002336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Aims. Two thirds of patients with heart failure and preserved ejection fraction (HFpEF) have an indication for oral anticoagulation (OAC) to prevent thromboembolic events. However, evidence regarding the safety of OAC in HFpEF is limited. Therefore, our aim was to describe bleeding events and to find predictors of bleeding in a large HFpEF cohort. Methods and Results. We recorded bleeding events in a prospective HFpEF cohort. Out of 328 patients (median age 71 years (interquartile range (IQR) 67\u201377)), 64.6% (n = 212) were treated with OAC. Of those, 65.1% (n = 138) received vitamin-K-antagonists (VKA) and 34.9% (n = 72) non-vitamin K oral anticoagulants (NOACs). During a median follow-up time of 42 (IQR 17\u201363) months, a total of 54 bleeding events occurred. Patients on OAC experienced more bleeding events (n = 49 (23.1%) versus n = 5 (4.3%), p &lt; 0.001). Major drivers of events were gastrointestinal (GI) bleeding (n = 18 (36.7%)]. HAS-BLED (Hypertension, Abnormal Renal\/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs\/Alcohol Concomitantly) score (hazard ratios (HR) of 2.15 (95% confidence interval (CI) 1.65\u20132.79, p &lt; 0.001)) was the strongest independent predictor for overall bleeding. In the subgroup of GI bleeding, mean right atrial pressure (mRAP: HR of 1.13 (95% CI 1.03\u20131.25, p = 0.013)) and HAS-BLED score (HR of 1.74 (95% CI 1.15\u20132.64, p = 0.009)] remained significantly associatiated with bleeding events after adjustment. mRAP provided additional prognostic value beyond the HAS-BLED score with an improvement from 0.63 to 0.71 (95% CI 0.58\u20130.84, p for comparison 0.032), by C-statistic. This additional prognostic value was confirmed by significant improvements in net reclassification index (61.3%, p = 0.019) and integrated discrimination improvement (3.4%, p = 0.015). Conclusion. OAC-treated HFpEF patients are at high risk of GI bleeding. High mRAP as an indicator of advanced stage of disease was predictive for GI bleeding events and provided additional risk stratification information beyond that obtained by HAS-BLED score.<\/jats:p>","DOI":"10.3390\/jcm8081240","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T06:10:14Z","timestamp":1566195014000},"page":"1240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Patients with Heart Failure and Preserved Ejection Fraction Are at Risk of Gastrointestinal Bleeding"],"prefix":"10.3390","volume":"8","author":[{"given":"Lore","family":"Schrutka","sequence":"first","affiliation":[{"name":"Division of Cardiology, Medical University of Vienna, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5169-8707","authenticated-orcid":false,"given":"Benjamin","family":"Seirer","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Medical University of Vienna, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franz","family":"Duca","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Medical University of Vienna, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Binder","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Medical University of Vienna, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9597-5745","authenticated-orcid":false,"given":"Daniel","family":"Dalos","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Medical University of Vienna, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7632-9879","authenticated-orcid":false,"given":"Andreas","family":"Kammerlander","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Medical University of Vienna, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Aschauer","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Medical University of Vienna, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenz","family":"Koller","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Medical University of Vienna, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Benazzo","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Medical University of Vienna, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asan","family":"Agibetov","sequence":"additional","affiliation":[{"name":"Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Gwechenberger","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Medical University of Vienna, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8284-2994","authenticated-orcid":false,"given":"Christian","family":"Hengstenberg","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Medical University of Vienna, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Mascherbauer","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Medical University of Vienna, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Bonderman","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Medical University of Vienna, A-1090 Vienna, Austria"},{"name":"Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1093\/eurheartj\/eht066","article-title":"Incidence and epidemiology of new onset heart failure with preserved vs. reduced ejection fraction in a community-based cohort: 11-year follow-up of PREVEND","volume":"34","author":"Brouwers","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.ijcard.2016.11.154","article-title":"Modes of death in patients with heart failure and preserved ejection fraction","volume":"228","author":"Aschauer","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jacc.2016.04.052","article-title":"Functional Status, Pulmonary Artery Pressure, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction","volume":"68","author":"Dalos","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1161\/CIRCIMAGING.113.000633","article-title":"Cardiac magnetic resonance postcontrast T1 time is associated with outcome in patients with heart failure and preserved ejection fraction","volume":"6","author":"Mascherbauer","year":"2013","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.ijcard.2015.10.220","article-title":"Atrial fibrillation and heart failure due to reduced versus preserved ejection fraction: A systematic review and meta-analysis of death and adverse outcomes","volume":"203","author":"Kotecha","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1093\/eurheartj\/ehw210","article-title":"2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS","volume":"37","author":"Kirchhof","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1056\/NEJMoa0905561","article-title":"Dabigatran versus warfarin in patients with atrial fibrillation","volume":"361","author":"Connolly","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1056\/NEJMoa1310907","article-title":"Edoxaban versus warfarin in patients with atrial fibrillation","volume":"369","author":"Giugliano","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1056\/NEJMoa1107039","article-title":"Apixaban versus warfarin in patients with atrial fibrillation","volume":"365","author":"Granger","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"857","DOI":"10.7326\/0003-4819-146-12-200706190-00007","article-title":"Meta-analysis: Antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation","volume":"146","author":"Hart","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJMoa1009638","article-title":"Rivaroxaban versus warfarin in nonvalvular atrial fibrillation","volume":"365","author":"Patel","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"297","DOI":"10.7326\/0003-4819-151-5-200909010-00003","article-title":"The net clinical benefit of warfarin anticoagulation in atrial fibrillation","volume":"151","author":"Singer","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1378\/chest.09-1584","article-title":"Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The euro heart survey on atrial fibrillation","volume":"137","author":"Lip","year":"2010","journal-title":"Chest"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1378\/chest.10-0134","article-title":"A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: The Euro Heart Survey","volume":"138","author":"Pisters","year":"2010","journal-title":"Chest"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1055\/s-0038-1675400","article-title":"Predicting Thromboembolic and Bleeding Event Risk in Patients with Non-Valvular Atrial Fibrillation: A Systematic Review","volume":"118","author":"Borre","year":"2018","journal-title":"Thromb. Haemost."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.ahj.2004.11.015","article-title":"Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: Observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study","volume":"149","author":"DiMarco","year":"2005","journal-title":"Am. Heart J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1093\/eurheartj\/ehr488","article-title":"Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: The Swedish Atrial Fibrillation cohort study","volume":"33","author":"Friberg","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_18","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). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"18","author":"Ponikowski","year":"2016","journal-title":"Eur. J. Heart Fail."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1016\/j.jacc.2013.05.019","article-title":"2013 ACCF\/AHA guideline for the management of heart failure: A report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines","volume":"62","author":"Yancy","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1093\/eurheartj\/ehy339","article-title":"Desormais I. 2018 ESC\/ESH Guidelines for the management of arterial hypertension","volume":"39","author":"Williams","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3035","DOI":"10.1093\/eurheartj\/eht108","article-title":"ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD)","volume":"34","author":"Ryden","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/j.1538-7836.2009.03678.x","article-title":"Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients","volume":"8","author":"Schulman","year":"2010","journal-title":"J. Thromb. Haemost."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/j.echo.2005.10.005","article-title":"Recommendations for chamber quantification: A report from the American Society of Echocardiography\u2019s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology","volume":"18","author":"Lang","year":"2005","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3350\/cmh.2016.0110","article-title":"Anticoagulation in cirrhosis: A new paradigm?","volume":"23","author":"Leonardi","year":"2017","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/S0140-6736(16)30506-2","article-title":"Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): A case-control study","volume":"388","author":"Chin","year":"2016","journal-title":"Lancet"},{"key":"ref_26","first-page":"701","article-title":"Heyde\u2019s syndrome: A review","volume":"13","author":"Pate","year":"2004","journal-title":"J. Heart Valve Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1016\/j.amjcard.2019.02.027","article-title":"Impact of Heart Failure Type on Thromboembolic and Bleeding Risk in Patients With Atrial Fibrillation on Oral Anticoagulation","volume":"123","author":"Mentias","year":"2019","journal-title":"Am. J. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.jacc.2008.11.051","article-title":"Pulmonary hypertension in heart failure with preserved ejection fraction: A community-based study","volume":"53","author":"Lam","year":"2009","journal-title":"J. Am. Coll. Cardiol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/8\/8\/1240\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:11:47Z","timestamp":1760188307000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/8\/8\/1240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,17]]},"references-count":28,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["jcm8081240"],"URL":"https:\/\/doi.org\/10.3390\/jcm8081240","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,17]]}}}