{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:05:37Z","timestamp":1782950737464,"version":"3.54.5"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,24]],"date-time":"2022-04-24T00:00:00Z","timestamp":1650758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"KAKENHI","doi-asserted-by":"publisher","award":["18K15864, 21K16068"],"award-info":[{"award-number":["18K15864, 21K16068"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Most patients with Takotsubo Syndrome (TTS) are postmenopausal females. TTS in males is rare and gender differences have not been sufficiently investigated. Therefore, we investigated gender differences in TTS. TTS in males and females is often triggered by physical and emotional stress, respectively. Heart failure, a severe in-hospital complication, requires greater mechanical respiratory support in males. Fatal arrhythmias such as ventricular tachycardia and ventricular fibrillation and in-hospital mortality rates are higher in males. The white blood cell (WBC) count has been shown to be higher in males than in females with cardiovascular death compared with non-cardiovascular death. Therefore, the WBC count, a simple marker, may reflect severe TTS. Decreased estrogen levels, common in postmenopausal females, are a pathogenic mechanism of TTS. Females have a more significant increase in the extracellular matrix-receptor interaction than males. Moreover, the pathological findings after hematoxylin\u2013eosin staining were different in males and females. Males had more severe complications than females in the acute phase of TTS; thus, more careful observations and interventions are likely required. From these results, it can be considered that the mechanism of the onset of TTS may be different between males and females. Therefore, it is necessary to fully understand the gender differences in order to more effectively manage TTS.<\/jats:p>","DOI":"10.3390\/biology11050653","type":"journal-article","created":{"date-parts":[[2022,4,24]],"date-time":"2022-04-24T22:22:41Z","timestamp":1650838961000},"page":"653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Gender Differences in Takotsubo Syndrome"],"prefix":"10.3390","volume":"11","author":[{"given":"Tsutomu","family":"Murakami","sequence":"first","affiliation":[{"name":"Department of Cardiology, School of Medicine, Tokay University, Isehara 259-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2138-0084","authenticated-orcid":false,"given":"Tomoyoshi","family":"Komiyama","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, School of Medicine, Tokay University, Isehara 259-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, School of Medicine, Tokay University, Isehara 259-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5686-4324","authenticated-orcid":false,"given":"Yuji","family":"Ikari","sequence":"additional","affiliation":[{"name":"Department of Cardiology, School of Medicine, Tokay University, Isehara 259-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.ijcard.2015.03.162","article-title":"Mortality in takotsubo syndrome is similar to mortality in myocardial infarction\u2014a report from the SWEDEHEART registry","volume":"185","author":"Redfors","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Murakami, T., Yoshikawa, T., Maekawa, Y., Ueda, T., Isogai, T., Sakata, K., Nagao, K., Yamamoto, T., and Takayama, M. (2015). Gender Differences in Patients with Takotsubo Cardiomyopathy: Multi-Center Registry from Tokyo CCU Network. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136655"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/s00392-021-01857-4","article-title":"Ethnic comparison in takotsubo syndrome: Novel insights from the International Takotsubo Registry","volume":"111","author":"Imori","year":"2021","journal-title":"Clin. Res. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1056\/NEJMoa1406761","article-title":"Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy","volume":"373","author":"Templin","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.ijcard.2014.07.110","article-title":"Out-of-hospital versus in-hospital Takotsubo cardiomyopathy: Analysis of 3719 patients in the Diagnosis Procedure Combination database in Japan","volume":"176","author":"Isogai","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1136\/heartjnl-2016-309783","article-title":"Takotsubo syndrome: Aetiology, presentation and treatment","volume":"103","author":"Kato","year":"2017","journal-title":"Heart"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"50","DOI":"10.17987\/icfj.v5i0.239","article-title":"Recurrence of Takotsubo Cardiomyopathy","volume":"5","author":"Kato","year":"2016","journal-title":"Int. Cardiovasc. Forum J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.ijcard.2014.12.116","article-title":"Takotsubo cardiomyopathy, a new concept of cardiomyopathy: Clinical features and pathophysiology","volume":"182","author":"Yoshikawa","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1136\/heartjnl-2015-308712","article-title":"Early \u03b2-blocker use and in-hospital mortality in patients with Takotsubo cardiomyopathy","volume":"102","author":"Isogai","year":"2016","journal-title":"Heart"},{"key":"ref_10","first-page":"203","article-title":"Myocardial stunning due to simultaneous multivessel coronary spasms: A review of 5 cases","volume":"21","author":"Dote","year":"1990","journal-title":"J. Cardiol."},{"key":"ref_11","unstructured":"Kodama, K., Haze, K., and Hon, M. (1990). Takotsubo-type cardiomyopathy due to multivessel spasm. Clinical Aspect of Myocardial Injury: From Ischaemia to Heart Failure, Kagakuhyouronsya Co.,. (In Japanese)."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1016\/j.jacc.2010.11.029","article-title":"Why not just call it tako-tsubo cardiomyopathy: A discussion of nomenclature","volume":"57","author":"Sharkey","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1016\/j.jacc.2016.03.006","article-title":"Takotsubo Syndrome: Underdiagnosed, Underestimated, but Understood?","volume":"67","author":"Templin","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.31083\/j.rcm2204132","article-title":"Aneurysmal subarachnoid hemorrhage as a trigger for Takotsubo syndrome: A comprehensive review","volume":"22","author":"Wagner","year":"2021","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1093\/eurheartj\/ehy076","article-title":"International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology","volume":"39","author":"Ghadri","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1093\/eurheartj\/ehy077","article-title":"International Expert Consensus Document on Takotsubo Syndrome (Part II): Diagnostic Workup, Outcome, and Management","volume":"39","author":"Ghadri","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"257","DOI":"10.2169\/internalmedicine.51.6559","article-title":"Direct Comparison of Takotsubo Cardiomyopathy between Japan and USA: 3-year Follow-up Study","volume":"51","author":"Maekawa","year":"2012","journal-title":"Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1093\/eurheartj\/ehl032","article-title":"Apical ballooning syndrome or takotsubo cardiomyopathy: A systematic review","volume":"27","author":"Gianni","year":"2006","journal-title":"Eur. Heart J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1093\/qjmed\/hcg096","article-title":"The clinical features of takotsubo cardiomyopathy","volume":"96","author":"Akashi","year":"2003","journal-title":"QJM"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1161\/CIRCIMAGING.110.962845","article-title":"Mechanisms of acute mitral regurgitation in patients with takotsubo cardiomyopathy: An echocardiographic study","volume":"4","author":"Izumo","year":"2011","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1111\/echo.12949","article-title":"Determinants of Secondary Pulmonary Hypertension in Patients with Takotsubo Cardiomyopathy","volume":"32","author":"Izumo","year":"2015","journal-title":"Echocardiography"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1093\/ehjci\/jev145","article-title":"Impact of right ventricular involvement on the prognosis of takotsubo cardiomyopathy","volume":"17","author":"Kagiyama","year":"2016","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.jjcc.2013.09.003","article-title":"Characterization of predictors of in-hospital cardiac complications of takotsubo cardiomyopathy: Multi-center registry from Tokyo CCU Network","volume":"63","author":"Murakami","year":"2014","journal-title":"J. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ijcard.2017.02.090","article-title":"Physically triggered Takotsubo cardiomyopathy has a higher in-hospital mortality rate","volume":"235","author":"Sobue","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nrcardio.2015.39","article-title":"Epidemiology and pathophysiology of Takotsubo syndrome","volume":"12","author":"Akashi","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1097\/00005344-200312001-00024","article-title":"Estrogen attenuates the emotional stress-induced cardiac responses in the animal model of Tako-tsubo (Ampulla) cardiomyopathy","volume":"42","author":"Ueyama","year":"2003","journal-title":"J Cardiovasc. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1253\/circj.71.565","article-title":"Chronic estrogen supplementation following ovariectomy improves the emotional stress-induced cardiovascular responses by indirect action on the nervous system and by direct action on the heart","volume":"71","author":"Ueyama","year":"2007","journal-title":"Circ. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1186\/s13256-021-02856-9","article-title":"Examination of gender differences in patients with takotsubo syndrome according to left ventricular biopsy: Two case reports","volume":"15","author":"Murakami","year":"2021","journal-title":"J. Med. Case. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1159\/000430782","article-title":"Gender Differences and Predictors of Mortality in Takotsubo Cardiomyopathy: Analysis from the National Inpatient Sample 2009\u20132010 Database","volume":"132","author":"Krishnamoorthy","year":"2015","journal-title":"Cardiology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.ahj.2012.04.010","article-title":"In-hospital mortality among patients with takotsubo cardiomyopathy: A study of the National Inpatient Sample 2008 to 2009","volume":"164","author":"Brinjikji","year":"2012","journal-title":"Am. Heart J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.2169\/internalmedicine.6910-20","article-title":"Gender Differences in the Circadian and Seasonal Variations in Patients with Takotsubo Syndrome: A Multicenter Registry at Eight University Hospitals in East Japan","volume":"60","author":"Yoshizawa","year":"2021","journal-title":"Intern. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.ahj.2007.11.008","article-title":"Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): A mimic of acute myocardial infarction","volume":"155","author":"Prasad","year":"2008","journal-title":"Am. Heart J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1002\/ejhf.683","article-title":"A novel clinical score (InterTAK Diagnostic Score) to differentiate takotsubo syndrome from acute coronary syndrome: Results from the International Takotsubo Registry","volume":"19","author":"Ghadri","year":"2017","journal-title":"Eur. J. Heart Fail."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"416","DOI":"10.5603\/CJ.a2019.0086","article-title":"Evaluation of the InterTAK Diagnostic Score in differentiating Takotsubo syndrome from acute coronary syndrome. A single center experience","volume":"28","author":"Roik","year":"2021","journal-title":"Cardiol. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/ehf2.12603","article-title":"Takotsubo syndrome in heart failure and World Congress on Acute Heart Failure 2019: Highlights from the experts","volume":"7","author":"Keramida","year":"2020","journal-title":"ESC Heart Fail."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Laumer, F., Di Vece, D., Cammann, V.L., W\u00fcrdinger, M., Petkova, V., Sch\u00f6nberger, M., Sch\u00f6nberger, A., Mercier, J.C., Niederseer, D., and Seifert, B. (2022). Assessment of Artificial Intelligence in Echocardiography Diagnostics in Differentiating Takotsubo Syndrome From Myocardial Infarction. JAMA Cardiol., Online ahead of print.","DOI":"10.1001\/jamacardio.2022.0183"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wehbe, R.M., and Thomas, J.D. (2022). Validating Deep Learning to Distinguish Takotsubo Syndrome From Acute Myocardial Infarction-Beware of Shortcuts, Human Supervision Required. JAMA Cardiol., Online ahead of print.","DOI":"10.1001\/jamacardio.2022.0193"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Silverio, A., Parodi, G., Scudiero, F., Bossone, E., Di Maio, M., Vriz, O., Bellino, M., Zito, C., Provenza, G., and Radano, I. (2022). Beta-blockers are associated with better long-term survival in patients with Takotsubo syndrome. Heart, Online ahead of print.","DOI":"10.1136\/heartjnl-2021-320543"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Butt, J.H., Bang, L.E., R\u00f8rth, R., Schou, M., Kristensen, S.L., Yafasova, A., Havers-Borgersen, E., Vinding, N.E., Jessen, N., and Kragholm, K. (2022). Long-term Risk of Death and Hospitalization in Patients With Heart Failure and Takotsubo Syndrome: Insights From a Nationwide Cohort. J. Card. Fail., Online ahead of print.","DOI":"10.1016\/j.cardfail.2022.02.002"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1161\/CIRCULATIONAHA.121.055854","article-title":"Takotsubo Syndrome: Pathophysiology, Emerging Concepts, and Clinical Implications","volume":"145","author":"Singh","year":"2022","journal-title":"Circulation"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Gorini, A., Galli, F., Giuliani, M., Pierobon, A., Werba, J.P., Adriano, E.P., and Trabattoni, D. (2022). Psychological Characteristics of Patients with Takotsubo Syndrome and Patients with Acute Coronary Syndrome: An Explorative Study toward a Better Personalized Care. J. Pers. Med., 12.","DOI":"10.3390\/jpm12010038"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1002\/ejhf.1698","article-title":"Impact of aspirin on takotsubo syndrome: A propensity score-based analysis of the InterTAK Registry","volume":"22","author":"Gili","year":"2020","journal-title":"Eur. J. Heart Fail."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"111259","DOI":"10.1016\/j.biopha.2021.111259","article-title":"Persistent long-term platelet activation and endothelial perturbation in women with Takotsubo syndrome","volume":"136","author":"Amadio","year":"2021","journal-title":"Biomed. Pharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/clc.21986","article-title":"Clinical characteristics, sex hormones, and long-term follow-up in Swiss postmenopausal women presenting with Takotsubo cardiomyopathy","volume":"35","author":"Brenner","year":"2012","journal-title":"Clin. Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/2042-6410-3-25","article-title":"Sex-specific signaling through Toll-Like Receptors 2 and 4 contributes to survival outcome of Coxsackievirus B3 infection in C57Bl\/6 mice","volume":"3","author":"Roberts","year":"2012","journal-title":"Biol. Sex Differ."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Napp, L.C., Westenfeld, R., M\u00f8ller, J.E., Pappalardo, F., Ibrahim, K., Bonello, L., Wilkins, C., Pershad, A., Mannino, S.F., and Schreiber, T.L. (2021). Impella mechanical circulatory support for Takotsubo syndrome with shock: A retrospective multicenter analysis. Cardiovasc. Revasc. Med., Online ahead of print.","DOI":"10.1016\/j.carrev.2021.11.018"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Nakamori, T., Nakamura, M., and Imamura, T. (2022). Implication of percutaneous left ventricular assist device for Takotsubo syndrome. Cardiovasc. Revasc. Med., Online ahead of print.","DOI":"10.1016\/j.carrev.2022.03.020"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1253\/circrep.CR-19-0045","article-title":"Impact of Trigger on Outcome of Takotsubo Syndrome\u2015Multi-Center Registry From Tokyo Cardiovascular Care Unit Network","volume":"1","author":"Imori","year":"2019","journal-title":"Circ. Rep."},{"key":"ref_49","first-page":"33759445","article-title":"A review of the presentation and outcome of takotsubo cardiomyopathy in COVID-19","volume":"91","author":"John","year":"2021","journal-title":"Monaldi. Arch. Chest Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e001360","DOI":"10.1136\/openhrt-2020-001360","article-title":"Characteristics and outcome of patients with COVID-19 complicated by Takotsubo cardiomyopathy: Case series with literature review","volume":"7","author":"Hegde","year":"2020","journal-title":"Open Heart"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/11\/5\/653\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:59:47Z","timestamp":1760137187000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/11\/5\/653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,24]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["biology11050653"],"URL":"https:\/\/doi.org\/10.3390\/biology11050653","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,24]]}}}