{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:04:53Z","timestamp":1785405893027,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Erectile dysfunction and cardiovascular disease share common pathophysiological mechanisms, yet little is known about the postmortem cardiac profile of men with detectable sildenafil use. This study investigated whether postmortem sildenafil positivity is associated with acute or chronic cardiac pathological findings in men who died of ischemic heart disease. Methods: In a sample of 154 male decedents who died of ischemic heart disease, postmortem cardiac and toxicological findings in 77 sildenafil-positive cases were compared with those of age-matched controls. Heart weight z-scores were calculated based on 27,645 reference autopsies. Multivariable logistic regression analyses were performed to identify independent associations. Results: No significant differences were observed between groups regarding acute ischemic pathologies. However, chronic cardiac findings were more prevalent in the sildenafil-positive group, including coronary artery disease (96.1% vs. 85.7%; p = 0.025), congestive heart failure (40.3% vs. 24.7%; p = 0.039), prior coronary artery bypass grafting (24.7% vs. 11.7%; p = 0.037), increased heart weight (547.7 gr vs. 507.5 gr; p = 0.037) and z-score (+1.63 vs. 1.08; p = 0.040), and coronary calcification (88.3% vs. 74.0%; p = 0.023). After adjustment for cardiovascular comorbidities, only coronary calcification remained independently associated (adjusted OR: 2.586; 95% CI: 1.076\u20136.215; p = 0.034). Conclusions: Sildenafil-positive cases showed no excess of acute ischemic pathology. However, sildenafil-positive cases had a greater burden of chronic cardiac pathology, particularly coronary calcification. These findings are consistent with the proposed role of coronary artery calcification as a surrogate marker of erectile dysfunction and cardiovascular disease. They also underscore the importance of cardiovascular risk assessment in sildenafil users and support a cautious approach in individuals with poor cardiac reserve.<\/jats:p>","DOI":"10.3390\/diagnostics16152400","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:32:13Z","timestamp":1785403933000},"page":"2400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sildenafil Positivity and Chronic Cardiac Pathology in Men Who Died of Ischemic Heart Disease: An Age- and Sex-Matched Postmortem Case\u2013Control Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Alper","family":"\u00d6zk\u00f6k","sequence":"first","affiliation":[{"name":"Department of Forensic Medicine, Faculty of Medicine, Gazi University, 06500 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7385-4419","authenticated-orcid":false,"given":"\u00d6zden","family":"Se\u00e7kin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Faculty of Medicine, Gazi University, 06500 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8516-2209","authenticated-orcid":false,"given":"Bekir","family":"Din\u00e7er","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Faculty of Medicine, Samsun University, 55080 Samsun, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sait","family":"\u00d6zsoy","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Health Sciences University, 06018 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taner","family":"Akar","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Faculty of Medicine, Gazi University, 06500 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","first-page":"13","article-title":"Diagnosis of sudden cardiac death due to early myocardial ischemia: An ultrastructural and immunohistochemical study","volume":"62","author":"Benati","year":"2018","journal-title":"Eur. J. Histochem."},{"key":"ref_2","first-page":"e78560","article-title":"Unusual Cardiovascular Response to Sildenafil: Complete Heart Block in a Healthy Young Adult","volume":"17","author":"Choudhuri","year":"2025","journal-title":"Cureus"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S2213-2600(20)30356-8","article-title":"Efficacy and safety of sildenafil added to pirfenidone in patients with advanced idiopathic pulmonary fibrosis and risk of pulmonary hypertension: A double-blind, randomised, placebo-controlled, phase 2b trial","volume":"9","author":"Behr","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"124196","DOI":"10.1016\/j.jchromb.2024.124196","article-title":"Toxicologic analysis of 35 drugs in post mortem human blood samples with focus on antihypertensive and antiarrhythmic drugs","volume":"1242","author":"Bickel","year":"2024","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"111908","DOI":"10.1016\/j.forsciint.2023.111908","article-title":"Sudden death related to sexual activity: A multicenter study based on forensic autopsies (2010\u20132021)","volume":"354","author":"Lucena","year":"2024","journal-title":"Forensic Sci. Int."},{"key":"ref_6","unstructured":"(2026, March 18). Turkish Criminal Procedure Code, Article 87, T\u00fcrkiye. Available online: https:\/\/www.unodc.org\/cld\/uploads\/res\/document\/tur\/2005\/turkish_criminal_procedure_code_html\/2014_Criminal_Procedure_Code.pdf."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s004140050271","article-title":"Harmonisation of medico-legal autopsy rules","volume":"113","author":"Brinkmann","year":"1999","journal-title":"Int. J. Leg. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/s00428-017-2221-0","article-title":"Guidelines for autopsy investigation of sudden cardiac death: 2017 update from the Association for European Cardiovascular Pathology","volume":"471","author":"Basso","year":"2017","journal-title":"Virchows Arch."},{"key":"ref_9","unstructured":"Brown, J.C., Gerhardt, T.E., and Kwon, E. (2025, September 05). Risk Factors for Coronary Artery Disease, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK554410\/."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.forsciint.2015.04.036","article-title":"Postmortem heart weight modelled using piecewise linear regression in 27,645 medicolegal autopsy cases","volume":"252","author":"Wingren","year":"2015","journal-title":"Forensic Sci. Int."},{"key":"ref_11","unstructured":"Shahjehan, R.D., Sharma, S., and Bhutta, B.S. (2024). Coronary Artery Disease. Mistake-Based Learning in Cardiology: Avoiding Medical Errors, Elsevier. Available online: https:\/\/www.educate.elsevier.com\/book\/details\/9780323931571."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e55","DOI":"10.1212\/WNL.0000000000005740","article-title":"Incidence of cardiac fibrosis in SUDEP and control cases","volume":"91","author":"Devinsky","year":"2018","journal-title":"Neurology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.amjcard.2015.01.553","article-title":"The 50% coronary stenosis","volume":"115","author":"Rosenthal","year":"2015","journal-title":"Am. J. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1002\/ejhf.1406","article-title":"Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology","volume":"21","author":"Bauersachs","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"107391","DOI":"10.1016\/j.carpath.2021.107391","article-title":"Myocardial fibrosis: Morphologic patterns and role of imaging in diagnosis and prognostication","volume":"56","author":"Giordano","year":"2022","journal-title":"Cardiovasc. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R136","DOI":"10.1186\/cc11441","article-title":"Therapeutic and toxic blood concentrations of nearly 1000 drugs and other xenobiotics","volume":"16","author":"Schulz","year":"2012","journal-title":"Crit. Care"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1161\/CIR.0b013e3182447787","article-title":"Sexual activity and cardiovascular disease: A scientific statement from the American Heart Association","volume":"125","author":"Levine","year":"2012","journal-title":"Circulation"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0379-0738(02)00012-9","article-title":"Last performance with VIAGRA\u00ae: Post-mortem identification of sildenafil and its metabolites in biological specimens including hair sample","volume":"126","author":"Cirimele","year":"2002","journal-title":"Forensic Sci. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/sj.ijir.3900354","article-title":"Clinical safety of oral sildenafil citrate (VIAGRA) in the treatment of erectile dysfunction","volume":"10","author":"Morales","year":"1998","journal-title":"Int. J. Impot. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1161\/01.CIR.99.1.168","article-title":"Use of sildenafil (Viagra) in patients with cardiovascular disease","volume":"99","author":"Cheitlin","year":"1999","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Awad, A.K., Gad, E.R., Abdelgalil, M.S., Elsaeidy, A.S., Ahmed, O., and Elbadawy, M.A. (2023). Sildenafil for congenital heart diseases induced pulmonary hypertension, a meta-analysis of randomized controlled trials. BMC Pediatr., 23.","DOI":"10.1186\/s12887-023-04180-1"},{"key":"ref_22","unstructured":"U.S. Food and Drug Administration (2026, March 17). \n          Viagra (Sildenafil Citrate) Prescribing Information, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2007\/020895s027lbl.pdf."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1743-6109.2011.02537.x","article-title":"10-Year Analysis of Adverse Event Reports to the Food and Drug Administration for Phosphodiesterase Type-5 Inhibitors","volume":"9","author":"Lowe","year":"2012","journal-title":"J. Sex. Med."},{"key":"ref_24","first-page":"583","article-title":"Cardiovascular Safety of Phosphodiesterase Type 5 Inhibitors After Nearly 2 Decades on the Market, Sex","volume":"6","author":"Kloner","year":"2018","journal-title":"Med. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1093\/jsxmed\/qdad163","article-title":"Princeton IV consensus guidelines: PDE5 inhibitors and cardiac health","volume":"21","author":"Kloner","year":"2024","journal-title":"J. Sex. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kedia, G.T., \u00dcckert, S., Tsikas, D., Becker, A.J., Kuczyk, M.A., and Bannowsky, A. (2020). The use of vasoactive drugs in the treatment of male erectile dysfunction: Current concepts. J. Clin. Med., 9.","DOI":"10.3390\/jcm9092987"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1016\/j.jacc.2021.02.021","article-title":"Phosphodiesterase-5 Inhibitors and Survival in Men With Coronary Artery Disease","volume":"77","author":"Maas","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"107493","DOI":"10.1016\/j.pharmthera.2020.107493","article-title":"Pharmacology and perspectives in erectile dysfunction in man","volume":"208","author":"Mitidieri","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1159\/000499249","article-title":"Is the history of erectile dysfunction a reliable risk factor for new onset acute myocardial infarction? A systematic review and meta-analysis","volume":"14","author":"Adam","year":"2020","journal-title":"Curr. Urol."},{"key":"ref_30","first-page":"492","article-title":"Erectile Dysfunction as a Marker of Subclinical Biventricular Diastolic Dysfunction: A Prospective Echocardiographic Study","volume":"53","author":"Akan","year":"2025","journal-title":"Turk. Kardiyol. Dern. Ars."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"De Leonardis, F., Colalillo, G., Finazzi Agr\u00f2, E., Miano, R., Fuschi, A., and Asimakopoulos, A.D. (2022). Endothelial Dysfunction, Erectile Deficit and Cardiovascular Disease: An Overview of the Pathogenetic Links. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081848"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1093\/sxmrev\/qeaf014","article-title":"Understanding the erectile dysfunction\u2013cardiovascular disease connection: Clinical and pathophysiological insights","volume":"13","author":"An","year":"2025","journal-title":"Sex. Med. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/j.jacc.2005.06.068","article-title":"Subclinical coronary artery atherosclerosis in patients with erectile dysfunction","volume":"46","author":"Chiurlia","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/clc.22530","article-title":"Subclinical Vascular Disease and Subsequent Erectile Dysfunction: The Multiethnic Study of Atherosclerosis (MESA)","volume":"39","author":"Feldman","year":"2016","journal-title":"Clin. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e464","DOI":"10.1016\/j.juro.2010.02.700","article-title":"ERECTILE DYSFUNCTION IS AN INDEPENDENT RISK FACTOR FOR THE PRESENCE OF HIGH RISK CORONARY ARTERY CALCIFICATION","volume":"183","author":"Berookhim","year":"2010","journal-title":"J. Urol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1016\/j.nuclcard.2008.07.006","article-title":"Erectile dysfunction as a coronary artery disease risk equivalent","volume":"15","author":"Lee","year":"2008","journal-title":"J. Nucl. Cardiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.transproceed.2007.11.046","article-title":"Coronary Artery Calcifications in Hemodialysis Patients and Their Correlation With the Prevalence of Erectile Dysfunction","volume":"40","author":"Inci","year":"2008","journal-title":"Transplant. Proc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s11255-007-9293-8","article-title":"Erectile dysfunction may predict coronary artery disease: Relationship between coronary artery calcium scoring and erectile dysfunction severity","volume":"40","author":"Yaman","year":"2008","journal-title":"Int. Urol. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1159\/000351750","article-title":"Relationship between erectile dysfunction and silent coronary artery disease: Detection with multidetector computed tomography coronary angiography","volume":"92","author":"Umul","year":"2014","journal-title":"Urol. Int."},{"key":"ref_40","first-page":"e596","article-title":"2019 ACC\/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"140","author":"Arnett","year":"2019","journal-title":"Circulation"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1093\/eurheartj\/ehy217","article-title":"Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: The multi-ethnic study of atherosclerosis (MESA)","volume":"39","author":"Budoff","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.1161\/CIR.0000000000001168","article-title":"2023 AHA\/ACC\/ACCP\/ASPC\/NLA\/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association\/American College of Cardiology Joint Committee on Clinical Practice Guidelines","volume":"148","author":"Virani","year":"2023","journal-title":"Circulation"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/15\/2400\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:41:20Z","timestamp":1785404480000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/15\/2400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":42,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["diagnostics16152400"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16152400","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]}}}