In-hospital Takotsubo syndrome versus in-hospital acute myocardial infarction among patients admitted for non-cardiac diseases: a nationwide inpatient database study

  • Toshiaki IsogaiEmail author
  • Hiroki Matsui
  • Hiroyuki Tanaka
  • Kiyohide Fushimi
  • Hideo Yasunaga
Original Article


Takotsubo syndrome (TTS) and acute myocardial infarction (AMI) occasionally occur during hospitalization for non-cardiac diseases. However, no study has compared the clinical characteristics between in-hospital TTS and AMI. Using the Diagnosis Procedure Combination database in Japan between 2010 and 2014, we retrospectively identified eligible inpatients who were admitted for non-cardiac diseases and developed TTS (n = 230) or AMI (n = 611) as an early in-hospital complication diagnosed by coronary angiography within 7 days after admission. We examined factors associated with developing in-hospital TTS or AMI using multivariable logistic regression. We also compared 30-day and overall in-hospital mortality between patients with TTS and AMI using 1:1 propensity score matching. Despite similar age (72.7 ± 12.4 vs. 72.8 ± 10.4 years), patients with TTS were more often female (63.5 vs. 32.9%) and underweight (24.8 vs. 14.1%) and were more likely to have had impaired activities of daily living (ADL) and impaired consciousness than those with AMI. Multivariable logistic regression analysis showed that female sex [adjusted odds ratio: 4.16 (95% confidence interval: 2.73–6.34)], impaired ADL [2.33 (1.18–4.60)], chronic pulmonary disease [3.33 (1.49–7.44)], and pneumonia [3.00 (1.81–4.98)] were associated with developing TTS relative to AMI, while overweight status, aortic disease, cerebrovascular disease, peripheral arterial disease, and dyslipidemia were associated with developing AMI relative to TTS. Propensity score-matched analysis (189 pairs) showed that 30-day in-hospital mortality was not significantly different between patients with TTS and AMI (15.3 vs. 19.0%, p = 0.41), but overall in-hospital mortality was significantly lower in patients with TTS than in those with AMI (19.6 vs. 29.1%, p = 0.041). This study suggests that although in-hospital TTS and in-hospital AMI are similarly likely to occur in older patients, in-hospital TTS is more likely to occur in female patients with impaired ADL and/or respiratory disease and carries a similar 30-day mortality risk but a lower overall in-hospital mortality risk compared with in-hospital AMI. Our results indicate the importance of differentiating TTS from AMI in hospital settings.


Takotsubo syndrome Acute myocardial infarction In-hospital complication Non-cardiac disease Mortality 



This study was funded by Grants from the Ministry of Health, Labour and Welfare, Japan (Grant numbers: H30-Policy-Designated-004 and H29-ICT-General-004) and the Ministry of Education, Culture, Sports, Science and Technology, Japan (Grant number: 17H04141). The funders had no role in the execution of this study or the interpretation of the results.

Compliance with ethical standards

Human and animal rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Lyon AR, Bossone E, Schneider B, Sechtem U, Citro R, Underwood SR, Sheppard MN, Figtree GA, Parodi G, Akashi YJ, Ruschitzka F, Filippatos G, Mebazaa A, Omerovic E (2016) Current state of knowledge on Takotsubo syndrome: a Position Statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 18:8–27CrossRefGoogle Scholar
  2. 2.
    Akashi YJ, Nef HM, Lyon AR (2015) Epidemiology and pathophysiology of Takotsubo syndrome. Nat Rev Cardiol 12:387–397CrossRefGoogle Scholar
  3. 3.
    Redfors B, Shao Y, Lyon AR, Omerovic E (2014) Diagnostic criteria for takotsubo syndrome: a call for consensus. Int J Cardiol 176:274–276CrossRefGoogle Scholar
  4. 4.
    Parodi G, Citro R, Bellandi B, Provenza G, Marrani M, Bossone E, on behalf of the Tako-tsubo Italian Network (TIN) (2014) Revised clinical diagnostic criteria for Tako-tsubo syndrome: the Tako-tsubo Italian Network proposal. Int J Cardiol 172:282–283CrossRefGoogle Scholar
  5. 5.
    Nunez-Gil IJ, Almendro-Delia M, Andres M, Sionis A, Martin A, Bastante T, Cordoba-Soriano JG, Linares JA, Gonzalez Sucarrats S, Sanchez-Grande-Flecha A, Fabregat-Andres O, Perez B, Escudier-Villa JM, Martin-Reyes R, Perez-Castellanos A, Rueda Sobella F, Cambeiro C, Piqueras-Flores J, Vidal-Perez R, Bodi V, Garcia de la Villa B, Corbi-Pascua M, Biagioni C, Mejia-Renteria HD, Feltes G, Barrabes J, On behalf of RETAKO investigators (2016) Secondary forms of Takotsubo cardiomyopathy: a whole different prognosis. Eur Heart J Acute Cardiovasc Care 5:308–316CrossRefGoogle Scholar
  6. 6.
    Desai SK, Shinbane J, Das JR, Mirocha J, Dohad S (2015) Takotsubo cardiomyopathy: clinical characteristics and outcomes. Rev Cardiovasc Med 16:244–252Google Scholar
  7. 7.
    Murugiah K, Wang Y, Desai NR, Spatz ES, Nuti SV, Dreyer RP, Krumholz HM (2016) Trends in short- and long-term outcomes for Takotsubo cardiomyopathy among Medicare fee-for-service beneficiaries, 2007 to 2012. JACC Heart Fail 4:197–205CrossRefGoogle Scholar
  8. 8.
    Khera R, Light-McGroary K, Zahr F, Horwitz PA, Girotra S (2016) Trends in hospitalization for takotsubo cardiomyopathy in the United States. Am Heart J 172:53–63CrossRefGoogle Scholar
  9. 9.
    Isogai T, Yasunaga H, Matsui H, Tanaka H, Ueda T, Horiguchi H, Fushimi K (2014) Out-of-hospital versus in-hospital Takotsubo cardiomyopathy: analysis of 3719 patients in the Diagnosis Procedure Combination database in Japan. Int J Cardiol 176:413–417CrossRefGoogle Scholar
  10. 10.
    Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, Gencer B, Hasenfuss G, Kjeldsen K, Lancellotti P, Landmesser U, Mehilli J, Mukherjee D, Storey RF, Windecker S, ESC Scientific Document Group (2016) 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 37:267–315CrossRefGoogle Scholar
  11. 11.
    Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P, ESC Scientific Document Group (2018) 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 39:119–177CrossRefGoogle Scholar
  12. 12.
    O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, Woo YJ, Zhao DX, Anderson JL, Jacobs AK, Halperin JL, Albert NM, Brindis RG, Creager MA, DeMets D, Guyton RA, Hochman JS, Kovacs RJ, Kushner FG, Ohman EM, Stevenson WG, Yancy CW, American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines (2013) 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 127:e362–e425Google Scholar
  13. 13.
    Maynard C, Lowy E, Rumsfeld J, Sales AE, Sun H, Kopjar B, Fleming B, Jesse RL, Rusch R, Fihn SD (2006) The prevalence and outcomes of in-hospital acute myocardial infarction in the Department of Veterans Affairs Health System. Arch Intern Med 166:1410–1416CrossRefGoogle Scholar
  14. 14.
    Dai X, Bumgarner J, Spangler A, Meredith D, Smith SC, Stouffer GA (2013) Acute ST-elevation myocardial infarction in patients hospitalized for noncardiac conditions. J Am Heart Assoc 2:e000004CrossRefGoogle Scholar
  15. 15.
    Garberich RF, Traverse JH, Claussen MT, Rodriguez G, Poulose AK, Chavez IJ, Rutten-Ramos S, Hildebrandt DA, Henry TD (2014) ST-elevation myocardial infarction diagnosed after hospital admission. Circulation 129:1225–1232CrossRefGoogle Scholar
  16. 16.
    Tiulim J, Mak K, Shavelle DM (2018) ST segment elevation myocardial infarction in patients hospitalized for non-cardiac conditions. Cardiovasc Revasc Med 19:17–20CrossRefGoogle Scholar
  17. 17.
    Redfors B, Vedad R, Angeras O, Ramunddal T, Petursson P, Haraldsson I, Ali A, Dworeck C, Odenstedt J, Ioaness D, Libungan B, Shao Y, Albertsson P, Stone GW, Omerovic E (2015) Mortality in takotsubo syndrome is similar to mortality in myocardial infarction—a report from the SWEDEHEART registry. Int J Cardiol 185:282–289CrossRefGoogle Scholar
  18. 18.
    Stiermaier T, Moeller C, Oehler K, Desch S, Graf T, Eitel C, Vonthein R, Schuler G, Thiele H, Eitel I (2016) Long-term excess mortality in takotsubo cardiomyopathy: predictors, causes and clinical consequences. Eur J Heart Fail 18:650–656CrossRefGoogle Scholar
  19. 19.
    Isogai T, Matsui H, Tanaka H, Fushimi K, Yasunaga H (2016) Early β-blocker use and in-hospital mortality in patients with Takotsubo cardiomyopathy. Heart 102:1029–1035CrossRefGoogle Scholar
  20. 20.
    Isogai T, Yasunaga H, Matsui H, Tanaka H, Ueda T, Horiguchi H, Fushimi K (2015) Effect of weekend admission for acute myocardial infarction on in-hospital mortality: a retrospective cohort study. Int J Cardiol 179:315–320CrossRefGoogle Scholar
  21. 21.
    Hashimoto H, Ikegami N, Shibuya K, Izumida N, Noguchi H, Yasunaga H, Miyata H, Acuin JM, Reich MR (2011) Cost containment and quality of care in Japan: is there a trade-off? Lancet 378:1174–1182CrossRefGoogle Scholar
  22. 22.
    Mahoney FI, Barthel DW (1965) Functional evaluation: the Barthel Index. Md State Med J 14:61–65Google Scholar
  23. 23.
    Ono K, Wada K, Takahara T, Shirotani T (2007) Indications for computed tomography in patients with mild head injury. Neurol Med Chir 47:291–297CrossRefGoogle Scholar
  24. 24.
    Rubin DB, Schenker N (1991) Multiple imputation in health-care databases: an overview and some applications. Stat Med 10:585–598CrossRefGoogle Scholar
  25. 25.
    Isogai T, Matsui H, Tanaka H, Fushimi K, Yasunaga H (2018) Clinical characteristics of patients with Takotsubo syndrome diagnosed without coronary artery evaluation: a retrospective nationwide study. J Cardiol 71:268–276CrossRefGoogle Scholar
  26. 26.
    Misumida N, Ogunbayo GO, Kim SM, Abdel-Latif A, Ziada KM, Sorrell VL (2019) Clinical outcome of Takotsubo cardiomyopathy diagnosed with or without coronary angiography. Angiology 70:56–61CrossRefGoogle Scholar
  27. 27.
    Lee SR, Lee SE, Rhee TM, Park JJ, Cho H, Lee HY, Choi DJ, Oh BH (2017) Discrimination of stress (Takotsubo) cardiomyopathy from acute coronary syndrome with clinical risk factors and coronary evaluation in real-world clinical practice. Int J Cardiol 235:154–161CrossRefGoogle Scholar
  28. 28.
    Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, Cammann VL, Sarcon A, Geyer V, Neumann CA, Seifert B, Hellermann J, Schwyzer M, Eisenhardt K, Jenewein J, Franke J, Katus HA, Burgdorf C, Schunkert H, Moeller C, Thiele H, Bauersachs J, Tschöpe C, Schultheiss HP, Laney CA, Rajan L, Michels G, Pfister R, Ukena C, Böhm M, Erbel R, Cuneo A, Kuck KH, Jacobshagen C, Hasenfuss G, Karakas M, Koenig W, Rottbauer W, Said SM, Braun-Dullaeus RC, Cuculi F, Banning A, Fischer TA, Vasankari T, Airaksinen KE, Fijalkowski M, Rynkiewicz A, Pawlak M, Opolski G, Dworakowski R, MacCarthy P, Kaiser C, Osswald S, Galiuto L, Crea F, Dichtl W, Franz WM, Empen K, Felix SB, Delmas C, Lairez O, Erne P, Bax JJ, Ford I, Ruschitzka F, Prasad A, Lüscher TF (2015) Clinical features and outcomes of Takotsubo (stress) cardiomyopathy. N Engl J Med 373:929–938CrossRefGoogle Scholar
  29. 29.
    Isogai T, Yoshikawa T, Ueda T, Yamaguchi T, Imori Y, Maekawa Y, Sakata K, Murakami T, Mochizuki H, Arao K, Kimura A, Nagao K, Yamamoto T, Takayama M (2019) Apical Takotsubo syndrome versus anterior acute myocardial infarction: findings from the Tokyo Cardiovascular Care Unit network registry. Eur Heart J Acute Cardiovasc Care 8:86–95CrossRefGoogle Scholar
  30. 30.
    Aizawa K, Suzuki T (2013) Takotsubo cardiomyopathy: Japanese perspective. Heart Fail Clin 9(243–247):xGoogle Scholar
  31. 31.
    Nishida J, Kouzu H, Hashimoto A, Fujito T, Kawamukai M, Mochizuki A, Muranaka A, Kokubu N, Shimoshige S, Yuda S, Hase M, Tsuchihashi K, Miura T (2015) “Ballooning” patterns in Takotsubo cardiomyopathy reflect different clinical backgrounds and outcomes: a BOREAS-TCM study. Heart Vessels 30:789–797CrossRefGoogle Scholar
  32. 32.
    Corrales-Medina VF, Suh KN, Rose G, Chirinos JA, Doucette S, Cameron DW, Fergusson DA (2011) Cardiac complications in patients with community-acquired pneumonia: a systematic review and meta-analysis of observational studies. PLoS Med 8:e1001048CrossRefGoogle Scholar
  33. 33.
    Corrales-Medina VF, Musher DM, Wells GA, Chirinos JA, Chen L, Fine MJ (2012) Cardiac complications in patients with community-acquired pneumonia: incidence, timing, risk factors, and association with short-term mortality. Circulation 125:773–781CrossRefGoogle Scholar
  34. 34.
    Deshmukh A, Kumar G, Pant S, Rihal C, Murugiah K, Mehta JL (2012) Prevalence of Takotsubo cardiomyopathy in the United States. Am Heart J 164:66–71.e1CrossRefGoogle Scholar
  35. 35.
    Morris NA, Chatterjee A, Adejumo OL, Chen M, Merkler AE, Murthy SB, Kamel H (2019) The risk of Takotsubo cardiomyopathy in acute neurological disease. Neurocrit Care 30:171–176CrossRefGoogle Scholar
  36. 36.
    Zaghlol R, Kashyap K, Al-Shbool G, Basyal B, Desale S, Campia U, Barac A (2019) Usefulness of malignancy as a predictor of worse in-hospital outcomes in patients with Takotsubo cardiomyopathy. Am J Cardiol 123:995–1001CrossRefGoogle Scholar
  37. 37.
    Yassin AS, Adegbala O, Subahi A, Abubakar H, Akintoye E, Abdelrahamn M, Ahmed A, Agarwal A, Shokr M, Pahuja M, Elder M, Kaki A, Schreiber T, Mohamad T (2019) Clinical impact of advanced chronic kidney disease on outcomes and in-hospital complications of Takotsubo Syndrome (broken-heart-syndrome): propensity-matched national study. Int J Cardiol 277:16–19CrossRefGoogle Scholar
  38. 38.
    Desai R, Singh S, Baikpour M, Goyal H, Dhoble A, Deshmukh A, Kumar G, Sachdeva R (2018) Does obesity affect the outcomes in Takotsubo cardiomyopathy? Analysis of the Nationwide Inpatient Sample database 2010–2014. Clin Cardiol 41:1028–1034CrossRefGoogle Scholar
  39. 39.
    Vallabhajosyula S, Deshmukh AJ, Kashani K, Prasad A, Sakhuja A (2018) Tako-tsubo cardiomyopathy in severe sepsis: nationwide trends, predictors, and outcomes. J Am Heart Assoc 7:e009160Google Scholar
  40. 40.
    Desai R, Abbas SA, Goyal H, Durairaj A, Fong HK, Hung O, Sachdeva R, Barac A, Yusuf SW, Kumar G (2019) Frequency of takotsubo cardiomyopathy in adult patients receiving chemotherapy (from a 5-year nationwide inpatient study). Am J Cardiol 123:667–673CrossRefGoogle Scholar
  41. 41.
    Yamana H, Moriwaki M, Horiguchi H, Kodan M, Fushimi K, Yasunaga H (2017) Validity of diagnoses, procedures, and laboratory data in Japanese administrative data. J Epidemiol 27:476–482CrossRefGoogle Scholar
  42. 42.
    Yerasi C, Koifman E, Weissman G, Wang Z, Torguson R, Gai J, Lindsay J, Satler LF, Pichard AD, Waksman R, Ben-Dor I (2017) Impact of triggering event in outcomes of stress-induced (Takotsubo) cardiomyopathy. Eur Heart J Acute Cardiovasc Care 6:280–286CrossRefGoogle Scholar
  43. 43.
    Sobue Y, Watanabe E, Ichikawa T, Koshikawa M, Yamamoto M, Harada M, Ozaki Y (2017) Physically triggered Takotsubo cardiomyopathy has a higher in-hospital mortality rate. Int J Cardiol 235:87–93CrossRefGoogle Scholar

Copyright information

© Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Clinical Epidemiology and Health Economics, School of Public HealthThe University of TokyoTokyoJapan
  2. 2.Department of CardiologyTokyo Metropolitan Tama Medical CenterTokyoJapan
  3. 3.Department of Health Policy and Informatics, Graduate School of MedicineTokyo Medical and Dental UniversityTokyoJapan

Personalised recommendations