Antiplatelet therapy in Takotsubo cardiomyopathy: does it improve cardiovascular outcomes during index event?


Plasma catecholamines may play an important role in Takotsubo cardiomyopathy (TCM) pathophysiology. Patients with disproportionately high catecholamine responses to stressful events are prone to worse clinical outcomes. Catecholamines stimulate platelet activation and, therefore, may determine the clinical presentation and outcomes of TCM. We conducted a retrospective, descriptive study TCM patients admitted between 2003 and 2013 to Einstein Medical Center, Philadelphia, PA, USA and Danbury Hospital, Danbury, CT, USA. A total of 206 patients met Modified Mayo TCM criteria. Using a multiple logistic model, we tested whether aspirin, dual antiplatelet therapy (DAPT) aspirin + clopidogrel, beta blocker, statin, or ACE inhibitor use were independent predictors of major adverse cardiovascular events (MACE) during the index hospitalization. MACE was defined as in-hospital heart failure, in-hospital death, stroke or respiratory failure requiring mechanical ventilation. Incidence of in-hospital heart failure was 26.7 %, in-hospital death was 7.3 %, stroke was 7.3 % and MACE was 42.3 %. In a multiple logistic regression model (adjusted for gender, race, age, physical stressor, hypertension, diabetes, hyperlipidemia, smoking history, body mass index, initial left ventricular ejection fraction, single antiplatelet therapy, DAPT, beta blocker, statin, and ACE inhibitor) aspirin and DAPT at the time of hospitalization were independent predictors of a lower incidence of MACE during the index hospitalization (aspirin: OR 0.4, 95 % CI (0.16–0.9), P = 0.04; DAPT: OR 0.23; 95 % CI (0.1–0.55); P < 0.01. Physical stressor itself was also found to be an independent predictor of worse MACE: OR 5.1; 95 % CI (2.4–11.5); P < 0.01. In our study, aspirin and DAPT were independent predictors of a lower incidence of MACE during hospitalization for TCM. Prospective clinical trials are needed to confirm the findings of this study.

This is a preview of subscription content, access via your institution.


  1. 1.

    Clusters of ‘Broken Hearts’ May be Linked to Massive Natural Disasters Analysis of U.S. Takotsubo Cardiomyopathy cases shows pattern to cue emergency responders. American College of Cardiology available at

  2. 2.

    Gianni M, Dentali F, Grandi AM, Sumner G, Hiralal R, Lonn E (2006) Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review. Eur Heart J 27:1523–1529

    Article  PubMed  Google Scholar 

  3. 3.

    Kurowski V, Kaiser A, von Hof K, Killermann DP, Mayer B, Hartmann F, Schunkert H, Radke PW (2007) Apical and midventricular transient left ventricular dysfunction syndrome (tako-tsubo cardiomyopathy): frequency, mechanisms, and prognosis. Chest 132:809–816

    Article  PubMed  Google Scholar 

  4. 4.

    Nabi H, Hall M, Koskenvuo M, Singh-Manoux A, Oksanen T, Suominen S, Kivimaki M, Vahtera J (2010) Psychological and somatic symptoms of anxiety and risk of coronary heart disease: the health and social support prospective cohort study. Biol Psychiatry 67:378–385

    Article  PubMed  Google Scholar 

  5. 5.

    Lam NY, Rainer TH, Ng MH, Leung Y, Cocks RA (2002) Effect of stress hormones on the expression of fibrinogen-binding receptors in platelets. Resuscitation 55:277–283

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Pyo MK, Yun-Choi HS, Hong YJ (2003) Apparent heterogeneous responsiveness of human platelet rich plasma to catecholamines. Platelets 14:171–178

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    von Kanel R, Dimsdale JE (2000) Effects of sympathetic activation by adrenergic infusions on hemostasis in vivo. Eur J Haematol 65:357–369

    Article  Google Scholar 

  8. 8.

    Yun-Choi HS, Park KM, Pyo MK (2000) Epinephrine induced platelet aggregation in rat platelet-rich plasma. Thromb Res 100:511–518

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Tomoda F, Takata M, Kagitani S, Kinuno H, Yasumoto K, Tomita S, Inoue H (1999) Different platelet aggregability during mental stress in two stages of essential hypertension. Am J Hypertens 12:1063–1070

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Nunez-Gil IJ, Molina M, Bernardo E, Ibanez B, Ruiz-Mateos B, Garcia-Rubira JC, Vivas D, Feltes G, Luaces M, Alonso J, Zamorano J, Macaya C, Fernandez-Ortiz A (2012) Tako-tsubo syndrome and heart failure: long-term follow-up. Rev Esp Cardiol 65:996–1002

    Article  PubMed  Google Scholar 

  11. 11.

    Damås JK, Waehre T, Yndestad A, Otterdal K, Hognestad A, Solum NO, Gullestad L, Frøland SS, Aukrust P (2003) Interleukin-7-mediated inflammation in unstable angina: possible role of chemokines and platelets. Circulation 107:2670–2676

    Article  PubMed  Google Scholar 

  12. 12.

    Núñez-Gil IJ, Bernardo E, Feltes G, Escaned J, Mejía-Rentería HD, De Agustín JA, Vivas D, Nombela-Franco L, Jiménez-Quevedo P, Macaya C, Fernández-Ortiz A (2015) Platelet function in Takotsubo cardiomyopathy. J Thromb Thrombolysis 39(4):452–458

    Article  PubMed  Google Scholar 

  13. 13.

    Pirzer R, Elmas E, Haghi D, Lippert C, Kralev S, Lang S, Borggrefe M, Kälsch T (2012) Platelet and monocyte activity markers and mediators of inflammation in Takotsubo cardiomyopathy. Heart Vessels 27(2):186–192

    Article  PubMed  Google Scholar 

  14. 14.

    Finkel MS, Oddis CV, Jacob TD, Watkins SC, Hattler BG, Simmons RL (1992) Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 257:387–389

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Mitsuma W, Kodama M, Ito M, Kimura S, Tanaka K, Hoyano M, Hirono S, Aizawa Y (2010) Thromboembolism in Takotsubo cardiomyopathy. Int J Cardiol 139(1):98–100

    Article  PubMed  Google Scholar 

  16. 16.

    de Gregorio C, Grimaldi P, Lentini C (2010) Left ventricular thrombus formation and cardioembolic complications in patients with Takotsubo-like syndrome: a systematic review. Int J Cardiol 131(1):18–24

    Article  Google Scholar 

  17. 17.

    de Gregorio C (2010) Cardioembolic outcomes in stress-related cardiomyopathy complicated by ventricular thrombus: a systematic review of 26 clinical studies. Int J Cardiol 141:11–17

    Article  PubMed  Google Scholar 

  18. 18.

    Ouchi K, Nakamura F, Ikutomi M, Oshima T, Ishiwata J, Shinohara H, Kouzaki T, Amaki T (2015) Usefulness of contrast computed tomography to detect left ventricular apical thrombus associated with takotsubo cardiomyopathy. Heart Vessels. doi:10.1007/s00380-015-0637-5

    PubMed  Google Scholar 

  19. 19.

    Young ML, Stoehr J, Aguilar MI, Fortuin FD (2014) Takotsubo cardiomyopathy and stroke. Int J Cardiol 176(3):574–576

    Article  PubMed  Google Scholar 

  20. 20.

    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 (2014) “Ballooning” patterns in takotsubo cardiomyopathy reflect different clinical backgrounds and outcomes: a BOREAS-TCM study. Heart Vessels. doi:10.1007/s00380-014-0548-x

    PubMed  Google Scholar 

  21. 21.

    Núñez-Gil IJ, Almendro-Delia M, Andrés M, Sionis A, Martin A, Bastante T, Córdoba-Soriano JG, Linares JA, González Sucarrats S, Sánchez-Grande-Flecha A, Fabregat-Andrés O, Pérez B, Escudier-Villa JM, Martin-Reyes R, Pérez-Castellanos A, Rueda Sobella F, Cambeiro C, Piqueras-Flores J, Vidal-Perez R, Bodí V, García de la Villa B, Corbí-Pascua M, Biagioni C, Mejía-Rentería HD, Feltes G, Barrabés J (2015) Secondary forms of Takotsubo cardiomyopathy: a whole different prognosis. Eur Heart J Acute Cardiovasc Care. doi:10.1177/2048872615589512

    PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Andre Dias.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

In consideration of the Journal’s taking action in reviewing and editing our submission, the author undersigned hereby transfers, assigns, and otherwise conveys all copyright ownership to the Heart and Vessels in the event that such work is published in the Heart and Vessels. We wish to ensure you of our compliance with AMA ethical standards in the treatment of study participants. I warrant that the material contained in the manuscript represents original work, has not been published elsewhere, is not under concurrent consideration for publication elsewhere, and all authors have read and approved the manuscript.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Dias, A., Franco, E., Koshkelashvili, N. et al. Antiplatelet therapy in Takotsubo cardiomyopathy: does it improve cardiovascular outcomes during index event?. Heart Vessels 31, 1285–1290 (2016).

Download citation


  • Antiplatelets
  • Takotsubo cardiomyopathy
  • Cardiovascular outcomes