{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T08:08:19Z","timestamp":1767514099875,"version":"build-2065373602"},"reference-count":26,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T00:00:00Z","timestamp":1740182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Heart failure with preserved ejection fraction (HFpEF) is a condition with limited large-scale data on the short- and long-term effects of SARS-CoV-2 infection. This study aimed to evaluate the prevalence of major adverse cardiac and cerebrovascular events (MACCEs) in HFpEF patients hospitalized with SARS-CoV-2 and identify sex-specific risk factors and predictors of MACCEs in this population. Methods: This retrospective study analyzed HFpEF patients hospitalized with SARS-CoV-2 from the 2020 National Inpatient Sample (NIS) using ICD-10 codes. Patients hospitalized with HFpEF and SARS-CoV-2 were categorized by age (18\u201344, 45\u201364, \u226565 years). Multivariate logistic regression was used to adjust for potential confounders, with the statistical significance set at a two-tailed p-value &lt; 0.05. Results: Among 109,750 HFpEF patients hospitalized with SARS-CoV-2, 31,960 (29.1%) experienced MACCEs. Males experienced a higher rate of MACCEs than females (31.1% vs. 27.5%, OR: 1.20, 95% CI: 1.12\u20131.28, p &lt; 0.001). Adjusted analysis revealed that elderly patients (\u226565 years, OR: 1.47, 95% CI: 1.33\u20131.62) compared with the 45\u201364 age group and males (OR: 1.20, 95% CI: 1.12\u20131.28, p &lt; 0.001) had a higher risk of MACCEs. Key predictors included prior coronary artery bypass grafting (CABG; OR: 1.15, 95% CI: 1.02\u20131.30), cancer (OR: 1.24, 95% CI: 1.08\u20131.42), and chronic kidney disease (OR: 1.15, 95% CI: 1.08\u20131.23). Subgroup analysis identified additional sex-specific risk factors. In males, hyperlipidemia, obesity, tobacco use disorder, prior stroke\/transient ischemic attack (TIA), prior venous thromboembolism (VTE), alcohol abuse, depression, and valvular disease were significant predictors of MACCEs. In females, hyperlipidemia, tobacco use disorder, prior stroke\/TIA, prior VTE, and depression were significant predictors. Conclusions: HFpEF patients hospitalized with SARS-CoV-2 have a high risk of MACCEs, with male sex, older age, prior CABG, cancer, and chronic kidney disease as key risk factors. This study provides the first large-scale analysis of sex-specific predictors of MACCEs in HFpEF patients hospitalized with SARS-CoV-2. These findings underscore the need for focused research and clinical gender-based strategies to mitigate cardiovascular risks in this unique and high-risk population.<\/jats:p>","DOI":"10.3390\/jcm14051469","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T05:36:47Z","timestamp":1740375407000},"page":"1469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sex-Specific Risk Factors and Predictors of Major Adverse Cardiac and Cerebrovascular Events in Heart Failure with Preserved Ejection Fraction with SARS-CoV-2 Infection: A Nationwide Analysis"],"prefix":"10.3390","volume":"14","author":[{"given":"Sai Prasanna","family":"Lekkala","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, UCHealth Parkview Medical Center, Pueblo, CO 81003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4298-6459","authenticated-orcid":false,"given":"Adil Sarvar","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Central Michigan University, Saginaw, MI 48859, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4560-7582","authenticated-orcid":false,"given":"Hafeezuddin","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Corewell Health Beaumont Royal Oak, Royal Oak, MI 48073, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meshal","family":"Al-Sulami","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jahangir","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Covenant Healthcare, Saginaw, MI 48706, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5315-6426","authenticated-orcid":false,"given":"Rupak","family":"Desai","sequence":"additional","affiliation":[{"name":"Independent Researcher, Atlanta, GA 30033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5963-090X","authenticated-orcid":false,"given":"Paritharsh","family":"Ghantasala","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Central Michigan University, Saginaw, MI 48859, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hemindermeet","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mercy St. Vincent Medical Center, Toledo, OH 43608, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed Sohail","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mercy St. Vincent Medical Center, Toledo, OH 43608, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Bianco","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,22]]},"reference":[{"key":"ref_1","first-page":"e895","article-title":"2022 AHA\/ACC\/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"145","author":"Heidenreich","year":"2022","journal-title":"Circulation"},{"key":"ref_2","unstructured":"(2023, August 31). Universal Definition and Classification of Heart Failure: A Step in the Right Direction from Failure to Function. Available online: https:\/\/www.acc.org\/Latest-in-Cardiology\/Articles\/2021\/07\/12\/12\/31\/http%3a%2f%2fwww.acc.org%2fLatest-in-Cardiology%2fArticles%2f2021%2f07%2f12%2f12%2f31%2fUniversal-Definition-and-Classification-of-Heart-Failure."},{"key":"ref_3","unstructured":"CDC (2023, August 31). Heart Failure | cdc.gov, Available online: https:\/\/www.cdc.gov\/heartdisease\/heart_failure.htm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e146","DOI":"10.1161\/CIR.0000000000000485","article-title":"Heart Disease and Stroke Statistics\u20142017 Update: A Report From the American Heart Association","volume":"135","author":"Benjamin","year":"2017","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Nasrullah, A., Gangu, K., Cannon, H.R., Khan, U.A., Shumway, N.B., Bobba, A., Sagheer, S., Chourasia, P., Shuja, H., and Avula, S.R. (2023). COVID-19 and Heart Failure with Preserved and Reduced Ejection Fraction Clinical Outcomes among Hospitalized Patients in the United States. Viruses, 15.","DOI":"10.3390\/v15030600"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100618","DOI":"10.1016\/j.cpcardiol.2020.100618","article-title":"COVID-19 and Multiorgan Response","volume":"45","author":"Zaim","year":"2020","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s11897-021-00509-y","article-title":"Myocardial Involvement in COVID-19: An Interaction Between Comorbidities and Heart Failure with Preserved Ejection Fraction. A Further Indication of the Role of Inflammation","volume":"18","author":"Zaccone","year":"2021","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_8","unstructured":"(2023, August 31). HCUP-US NIS Overview, Available online: https:\/\/hcup-us.ahrq.gov\/nisoverview.jsp."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.acvd.2021.04.003","article-title":"History of heart failure in patients with coronavirus disease 2019: Insights from a French registry","volume":"114","author":"Panagides","year":"2021","journal-title":"Arch. Cardiovasc. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1161\/CIRCULATIONAHA.118.034646","article-title":"A Simple, Evidence-Based Approach to Help Guide Diagnosis of Heart Failure With Preserved Ejection Fraction","volume":"138","author":"Reddy","year":"2018","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mansur, A.d.P., Del Carlo, C.H., Gon\u00e7alinho, G.H.F., Avakian, S.D., Ribeiro, L.C., Ianni, B.M., Fernandes, F., C\u00e9sar, L.A.M., Bocchi, E.A., and Pereira-Barretto, A.C. (2022). Sex Differences in Heart Failure Mortality with Preserved, Mildly Reduced and Reduced Ejection Fraction: A Retrospective, Single-Center, Large-Cohort Study. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph192316171"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jchf.2020.11.003","article-title":"Clinical Outcomes in Patients With Heart Failure Hospitalized With COVID-19","volume":"9","author":"Bhatt","year":"2021","journal-title":"JACC Heart Fail."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1016\/j.numecd.2020.07.031","article-title":"Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: Survival analysis and machine learning-based findings from the multicentre Italian CORIST Study","volume":"30","author":"Bonaccio","year":"2020","journal-title":"Nutr. Metab. Cardiovasc. Dis. NMCD"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e004052","DOI":"10.1161\/CIRCOUTCOMES.117.004052","article-title":"Neighborhood Deprivation Predicts Heart Failure Risk in a Low-Income Population of Blacks and Whites in the Southeastern United States","volume":"11","author":"Akwo","year":"2018","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.amepre.2020.04.003","article-title":"Disparities in the Population at Risk of Severe Illness From COVID-19 by Race\/Ethnicity and Income","volume":"59","author":"Raifman","year":"2020","journal-title":"Am. J. Prev. Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Gagliardi, I., Patella, G., Michael, A., Serra, R., Provenzano, M., and Andreucci, M. (2020). COVID-19 and the Kidney: From Epidemiology to Clinical Practice. J. Clin. Med., 9.","DOI":"10.3390\/jcm9082506"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.kint.2020.03.005","article-title":"Kidney disease is associated with in-hospital death of patients with COVID-19","volume":"97","author":"Cheng","year":"2020","journal-title":"Kidney Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4370","DOI":"10.1002\/ehf2.13760","article-title":"A year in heart failure: An update of recent findings","volume":"8","author":"Stretti","year":"2021","journal-title":"ESC Heart Fail."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3499","DOI":"10.2217\/fon-2021-0121","article-title":"Cancer and COVID-19: Analysis of patient outcomes","volume":"17","author":"Aboueshia","year":"2021","journal-title":"Future Oncol. Lond. Engl."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1111\/ans.17667","article-title":"Cardiac surgery on patients with COVID-19: A systematic review and meta-analysis","volume":"92","author":"Gupta","year":"2022","journal-title":"ANZ J. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dessie, Z.G., and Zewotir, T. (2021). Mortality-related risk factors of COVID-19: A systematic review and meta-analysis of 42 studies and 423,117 patients. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06536-3"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1002\/ejhf.3043","article-title":"Impact of COVID-19 in patients with heart failure with mildly reduced or preserved ejection fraction enrolled in the DELIVER trial","volume":"25","author":"Bhatt","year":"2023","journal-title":"Eur. J. Heart Fail."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jchf.2018.10.011","article-title":"Effect of Influenza on Outcomes in Patients With Heart Failure","volume":"7","author":"Panhwar","year":"2019","journal-title":"JACC Heart Fail."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/j.cardfail.2022.05.008","article-title":"Association of Reduced Hospitalizations and Mortality Rates Among COVID-19-Vaccinated Patients With Heart Failure","volume":"28","author":"Johnson","year":"2022","journal-title":"J. Card. Fail."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1016\/j.jacc.2021.02.017","article-title":"ACC Health Policy Statement on Cardiovascular Disease Considerations for COVID-19 Vaccine Prioritization: A Report of the American College of Cardiology Solution Set Oversight Committee","volume":"77","author":"Driggin","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1002\/ejhf.2356","article-title":"COVID-19 vaccination in patients with heart failure: A position paper of the Heart Failure Association of the European Society of Cardiology","volume":"23","author":"Rosano","year":"2021","journal-title":"Eur. J. Heart Fail."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/5\/1469\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:40:15Z","timestamp":1760028015000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/5\/1469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,22]]},"references-count":26,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["jcm14051469"],"URL":"https:\/\/doi.org\/10.3390\/jcm14051469","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2025,2,22]]}}}