{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:02:40Z","timestamp":1791910960677,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000},"content-version":"am","delay-in-days":357,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T00:00:00Z","timestamp":1611014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["R21AG057879"],"award-info":[{"award-number":["R21AG057879"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>Prior studies failed to address the role of sex in modifying the pathophysiology and response to therapy in heart failure with preserved ejection fraction (HFpEF), potentially introducing bias into translational findings. We aimed to explore sex differences in outcomes and sought to identify the underlying mechanisms in a well\u2010established rat model of HFpEF.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Male rats with HFpEF exhibited worse survival compared with females and were at a higher risk for sudden death, attributable in part to QT prolongation, autonomic dysregulation and enhanced inflammation. These data might provide the basis for the development of sex\u2010specific interventions in HFpEF targeting these abnormalities.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Heart failure with preserved ejection fraction (HFpEF) accounts for 50% of heart failure, and sudden death is the leading cause of mortality. We aimed to explore sex differences in outcomes in rats with HFpEF and sought to identify the underlying mechanisms. Dahl salt\u2010sensitive rats of either sex were randomized into high\u2010salt diet (HS diet; 8% NaCl, <jats:italic>n<\/jats:italic>\u00a0=\u00a046, 50% female) or low\u2010salt diet (LS diet; 0.3% NaCl; <jats:italic>n<\/jats:italic>\u00a0=\u00a024, 50% female) at 7\u00a0weeks of age. After 6 and 10\u00a0weeks of LS or HS diets, the ECG, heart rate variability, cytokines and echocardiographic parameters were measured. The animals were monitored daily for development of HFpEF and survival. Over 6\u00a0weeks of HS diet, rats developed significant hypertension and signs of HFpEF. Compared with female HS diet\u2010fed rats, males exhibited more left ventricular dilatation, a longer QT interval, and worse autonomic tone, as assessed by heart rate variability and elevated inflammatory cytokines. Ten of 23 (46%) male rats died during follow\u2010up, compared with two of 23 (9%) female rats (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.01). There were four sudden deaths in males (with ventricular tachycardia documented in one rat), whereas the females died of heart failure. In conclusion, male rats with HFpEF exhibit worse survival compared with females and are at a higher risk for sudden death, attributable in part to QT prolongation, autonomic dysregulation and enhanced inflammation. These data might provide the basis for the development of sex\u2010specific interventions in HFpEF targeting these abnormalities.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep089163","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T06:14:16Z","timestamp":1610691256000},"page":"673-682","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Sex differences in the incidence and mode of death in rats with heart failure with preserved ejection fraction"],"prefix":"10.1113","volume":"106","author":[{"given":"Khaled","family":"Elkholey","sequence":"first","affiliation":[{"name":"University of Oklahoma Health Sciences Center  Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynsie","family":"Morris","sequence":"additional","affiliation":[{"name":"University of Oklahoma Health Sciences Center  Oklahoma City Oklahoma 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