Clinical Research in Cardiology

, Volume 99, Issue 12, pp 771–780 | Cite as

Tako-Tsubo syndrome: dying of a broken heart?

  • Ch. Sinning
  • T. Keller
  • N. Abegunewardene
  • K.-F. Kreitner
  • T. Münzel
  • S. Blankenberg



The aim of the article is to review the etiology, pathology and epidemiology of a disease entity named Tako-Tsubo syndrome, receiving this name according to the picture obtained during ventriculography resembling a Japanese octopus trap. The Tako-Tsubo syndrome is a diagnosis encountered in patients with acute coronary syndrome and, therefore, is important to consider.


The literature search was performed in the MEDLINE database to identify the relevant topics. The references reported were used to complete the literature search.


The Tako-Tsubo syndrome is rising in incidence and makes up a relevant part of patients with acute coronary syndrome. The prevalence is described to be 0.6–2.5%. Especially, older women in the postmenopause with emotional stress are affected. The clinical changes and ECG alterations resemble the same characteristics like in acute coronary syndrome; however, the coronary arteries often show no impaired blood flow or only marginal changes. The reason for this syndrome is allocated to stress reactions with increased levels of stress hormones. As well, some patients develop contraction abnormalities like in Tako-Tsubo syndrome during intracranial bleeding, pheochromocytoma, seizures, infectious causes and sepsis, showing that not only emotional stress is responsible for the manifestation of this disease.


The prevalence of Tako-Tsubo syndrome is about 2%, therefore this syndrome has to be considered in patients with acute coronary syndrome. Despite the life-threatening complications during the acute phase, a complete regression of the contraction abnormality is often reported.


Tako-Tsubo syndrome Broken-heart syndrome Stress-cardiomyopathy Acute coronary syndrome 



We thank Dr. Tommaso Gori for his input.

Conflict of interest

None of the authors has any conflicts of interest to disclose.


  1. 1.
    Sato H, Tateishi H, Uchida T, Dote K, Ishihara M (1990) Tako-tsubo-like left ventricular dysfunction due to multivessel coronary spasm. In: Kodama K, Haze K, Hori M (eds) Clinical aspect of myocardial injury: from ischemia to heart failure. Kagakuhyoronsha Publishing Co., Tokyo, pp 56–64Google Scholar
  2. 2.
    Prasad A, Lerman A, Rihal CS (2008) Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J 155:408–417CrossRefPubMedGoogle Scholar
  3. 3.
    Akashi YJ, Goldstein DS, Barbaro G, Ueyama T (2008) Takotsubo cardiomyopathy: a new form of acute, reversible heart failure. Circulation 118:2754–2762CrossRefPubMedGoogle Scholar
  4. 4.
    Abe Y, Kondo M, Matsuoka R et al (2003) Assessment of clinical features in transient left ventricular apical ballooning. J Am Coll Cardiol 41:737–742CrossRefPubMedGoogle Scholar
  5. 5.
    Akashi YJ, Nakazawa K, Sakakibara M et al (2003) The clinical features of takotsubo cardiomyopathy. QJM 96:563–573CrossRefPubMedGoogle Scholar
  6. 6.
    Tsuchihashi K, Ueshima K, Uchida T et al (2001) Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina pectoris–myocardial infarction investigations in Japan. J Am Coll Cardiol 38:11–18CrossRefPubMedGoogle Scholar
  7. 7.
    Yoshida T, Hibino T, Kako N et al (2007) A pathophysiologic study of tako-tsubo cardiomyopathy with F-18 fluorodeoxyglucose positron emission tomography. Eur Heart J 28:2598–2604CrossRefPubMedGoogle Scholar
  8. 8.
    Botto F, Trivi M, Padilla LT (2008) Transient left midventricular ballooning without apical involvement. Int J Cardiol 127:e158–e159CrossRefPubMedGoogle Scholar
  9. 9.
    Bulut A, Rav-Acha M, Aydin O et al (2008) “Inverted Tako-Tsubo”: transient apical-sparing cardiomyopathy. Int J Cardiol 134(1):e35–e38CrossRefPubMedGoogle Scholar
  10. 10.
    Bybee KA, Kara T, Prasad A et al (2004) Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med 141:858–865PubMedGoogle Scholar
  11. 11.
    Desmet WJ, Adriaenssens BF, Dens JA (2003) Apical ballooning of the left ventricle: first series in white patients. Heart 89:1027–1031CrossRefPubMedGoogle Scholar
  12. 12.
    El Mahmoud R, Mansencal N, Pilliere R et al (2008) Prevalence and characteristics of left ventricular outflow tract obstruction in Tako-Tsubo syndrome. Am Heart J 156:543–548CrossRefPubMedGoogle Scholar
  13. 13.
    Facciorusso A, Vigna C, Amico C et al (2008) Prevalence of Tako-Tsubo syndrome among patients with suspicion of acute coronary syndrome referred to our centre. Int J Cardiol 134(2):255–259CrossRefPubMedGoogle Scholar
  14. 14.
    Hurst RT, Askew JW, Reuss CS et al (2006) Transient midventricular ballooning syndrome: a new variant. J Am Coll Cardiol 48:579–583CrossRefPubMedGoogle Scholar
  15. 15.
    Kurowski V, Kaiser A, von Hof K et al (2007) Apical and midventricular transient left ventricular dysfunction syndrome (tako-tsubo cardiomyopathy): frequency, mechanisms, and prognosis. Chest 132:809–816CrossRefPubMedGoogle Scholar
  16. 16.
    Mansencal N, El Mahmoud R, Pilliere R, Dubourg O (2008) Relationship between pattern of Tako-Tsubo cardiomyopathy and age: from midventricular to apical ballooning syndrome. Int J Cardiol 138(1):e18–e20CrossRefPubMedGoogle Scholar
  17. 17.
    Nef HM, Mollmann H, Hilpert P, Hamm C, Elsasser A (2008) Tako-Tsubo-cardiomyopathy. Dtsch Med Wochenschr 133:1629–1636 (quiz 1637–1640)CrossRefPubMedGoogle Scholar
  18. 18.
    Nef HM, Mollmann H, Hilpert P et al (2007) Sympathoadrenergic overstimulation in Tako-Tsubo cardiomyopathy triggered by physical and emotional stress. Int J Cardiol 130(2):266–268CrossRefPubMedGoogle Scholar
  19. 19.
    Nef HM, Mollmann H, Kostin S et al (2007) Tako-Tsubo cardiomyopathy: intraindividual structural analysis in the acute phase and after functional recovery. Eur Heart J 28:2456–2464CrossRefPubMedGoogle Scholar
  20. 20.
    Pilgrim TM, Wyss TR (2008) Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrome: a systematic review. Int J Cardiol 124:283–292CrossRefPubMedGoogle Scholar
  21. 21.
    Sharkey SW, Lesser JR, Zenovich AG et al (2005) Acute and reversible cardiomyopathy provoked by stress in women from the United States. Circulation 111:472–479CrossRefPubMedGoogle Scholar
  22. 22.
    Lauschke J, Maisch B (2009) Athlete’s heart or hypertrophic cardiomyopathy? Clin Res Cardiol 98:80–88CrossRefPubMedGoogle Scholar
  23. 23.
    Haghi D, Papavassiliu T, Heggemann F et al (2008) Incidence and clinical significance of left ventricular thrombus in tako-tsubo cardiomyopathy assessed with echocardiography. QJM 101:381–386CrossRefPubMedGoogle Scholar
  24. 24.
    Pilliere R, Mansencal N, Digne F et al (2006) Prevalence of tako-tsubo syndrome in a large urban agglomeration. Am J Cardiol 98:662–665CrossRefPubMedGoogle Scholar
  25. 25.
    Keller T, Zeller T, Peetz D et al (2009) Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med 361:868–877CrossRefPubMedGoogle Scholar
  26. 26.
    Maron BJ, Towbin JA, Thiene G et al (2006) Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 113:1807–1816CrossRefPubMedGoogle Scholar
  27. 27.
    Gaibazzi N, Ugo F, Vignali L et al (2008) Tako-Tsubo cardiomyopathy with coronary artery stenosis: a case-series challenging the original definition. Int J Cardiol 133(2):205–212CrossRefPubMedGoogle Scholar
  28. 28.
    Marti V, Carreras F, Pujadas S, De Rozas JM (2009) Transient left ventricular basal ballooning-”inverted” Tako-tsubo. Clin Cardiol 32:E20–E21CrossRefPubMedGoogle Scholar
  29. 29.
    Wittstein IS, Thiemann DR, Lima JA et al (2005) Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 352:539–548CrossRefPubMedGoogle Scholar
  30. 30.
    Sharkey SW, Windenburg DC, Lesser JR et al (2010) Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy. J Am Coll Cardiol 55:333–341CrossRefPubMedGoogle Scholar
  31. 31.
    Sharkey SW, Lesser JR, Menon M et al (2008) Spectrum and significance of electrocardiographic patterns, troponin levels, and thrombolysis in myocardial infarction frame count in patients with stress (tako-tsubo) cardiomyopathy and comparison to those in patients with ST-elevation anterior wall myocardial infarction. Am J Cardiol 101:1723–1728CrossRefPubMedGoogle Scholar
  32. 32.
    Madhavan M, Prasad A (2010) Proposed Mayo Clinic criteria for the diagnosis of Tako-Tsubo cardiomyopathy and long-term prognosis. Herz (Epub ahead of print)Google Scholar
  33. 33.
    de Souza F, Altenburg Odebrecht Curi Gismondi R, Henriques Cunha Neto S, de Mattos MA (2008) Tako-tsubo-like cardiomyopathy and extra-adrenal pheochromocytoma: case report and literature review. Clin Res Cardiol 97:397–401CrossRefPubMedGoogle Scholar
  34. 34.
    Akashi YJ, Nef HM, Mollmann H, Ueyama T (2010) Stress cardiomyopathy. Annu Rev Med 61:271–286CrossRefPubMedGoogle Scholar
  35. 35.
    Kurowski V, Radke PW, Schunkert H, Burgdorf C (2010) Patient care in the acute phase of stress induced cardiomyopathy (Tako-Tsubo cardiomyopathy) and thereafter? Herz (Epub ahead of print)Google Scholar
  36. 36.
    Akashi YJ, Musha H, Nakazawa K, Miyake F (2004) Plasma brain natriuretic peptide in takotsubo cardiomyopathy. QJM 97:599–607CrossRefPubMedGoogle Scholar
  37. 37.
    Nef HM, Mollmann H, Troidl C et al (2008) Tako-Tsubo cardiomyopathy: NT-proBNP as a reliable parameter of a favourable prognosis? Int J Cardiol 124:237–238CrossRefPubMedGoogle Scholar
  38. 38.
    Simon T, Becker R, Voss F et al (2008) Elevated B-type natriuretic peptide levels in patients with nonischemic cardiomyopathy predict occurrence of arrhythmic events. Clin Res Cardiol 97:306–309CrossRefPubMedGoogle Scholar
  39. 39.
    Potocki M, Breidthardt T, Reichlin T et al (2009) Midregional pro-adrenomedullin in addition to b-type natriuretic peptides in the risk stratification of patients with acute dyspnea: an observational study. Crit Care 13:R122CrossRefPubMedGoogle Scholar
  40. 40.
    Eitel I, Lucke C, Grothoff M et al (2010) Inflammation in takotsubo cardiomyopathy: insights from cardiovascular magnetic resonance imaging. Eur Radiol 20:422–431CrossRefPubMedGoogle Scholar
  41. 41.
    Gerbaud E, Montaudon M, Leroux L et al (2008) MRI for the diagnosis of left ventricular apical ballooning syndrome (LVABS). Eur Radiol 18:947–954CrossRefPubMedGoogle Scholar
  42. 42.
    Haghi D, Papavassiliu T, Hamm K et al (2007) Coronary artery disease in takotsubo cardiomyopathy. Circ J 71:1092–1094CrossRefPubMedGoogle Scholar
  43. 43.
    Meimoun P, Malaquin D, Benali T et al (2008) Transient impairment of coronary flow reserve in tako-tsubo cardiomyopathy is related to left ventricular systolic parameters. Eur J Echocardiogr 10(2):265–270CrossRefPubMedGoogle Scholar
  44. 44.
    Hombach V, Merkle N, Kestler HA et al (2008) Characterization of patients with acute chest pain using cardiac magnetic resonance imaging. Clin Res Cardiol 97(10):760–767CrossRefPubMedGoogle Scholar
  45. 45.
    Koeth O, Mark B, Kilkowski A et al (2008) Clinical, angiographic and cardiovascular magnetic resonance findings in consecutive patients with Takotsubo cardiomyopathy. Clin Res Cardiol 97:623–627CrossRefPubMedGoogle Scholar
  46. 46.
    Kanjanauthai S, Ananthasubramaniam K (2007) Integral role of cardiovascular magnetic resonance imaging in the diagnostic workup of suspected takotsubo cardiomyopathy: avoiding misdiagnosis. Cardiol J 14:592–594PubMedGoogle Scholar
  47. 47.
    Kurisu S, Inoue I, Kawagoe T et al (2003) Myocardial perfusion and fatty acid metabolism in patients with tako-tsubo-like left ventricular dysfunction. J Am Coll Cardiol 41:743–748CrossRefPubMedGoogle Scholar
  48. 48.
    Abdel-Aty H, Cocker M, Friedrich MG (2007) Myocardial edema is a feature of Tako-Tsubo cardiomyopathy and is related to the severity of systolic dysfunction: insights from T2-weighted cardiovascular magnetic resonance. Int J Cardiol 132(2):291–293CrossRefPubMedGoogle Scholar
  49. 49.
    Eitel I, Behrendt F, Schindler K et al (2008) Differential diagnosis of suspected apical ballooning syndrome using contrast-enhanced magnetic resonance imaging. Eur Heart J 29:2651–2659CrossRefPubMedGoogle Scholar
  50. 50.
    Eitel I, Schuler G, Thiele H (2009) Myocarditis mimicking Takotsubo cardiomyopathy or Takotsubo cardiomyopathy with secondary inflammation? Eur J Heart Fail 11:809 author reply 810)CrossRefPubMedGoogle Scholar
  51. 51.
    Rolf A, Nef HM, Mollmann H et al (2009) Immunohistological basis of the late gadolinium enhancement phenomenon in tako-tsubo cardiomyopathy. Eur Heart J 30:1635–1642CrossRefPubMedGoogle Scholar
  52. 52.
    Nef HM, Mollmann H, Troidl C et al (2009) Abnormalities in intracellular Ca2+ regulation contribute to the pathomechanism of Tako-Tsubo cardiomyopathy. Eur Heart J 30:2155–2164CrossRefPubMedGoogle Scholar
  53. 53.
    Bybee KA, Prasad A, Barsness GW et al (2004) Clinical characteristics and thrombolysis in myocardial infarction frame counts in women with transient left ventricular apical ballooning syndrome. Am J Cardiol 94:343–346CrossRefPubMedGoogle Scholar
  54. 54.
    Previtali M, Repetto A, Panigada S, Camporotondo R, Tavazzi L (2009) Left ventricular apical ballooning syndrome: prevalence, clinical characteristics and pathogenetic mechanisms in a European population. Int J Cardiol 134:91–96CrossRefPubMedGoogle Scholar
  55. 55.
    Elesber A, Lerman A, Bybee KA et al (2006) Myocardial perfusion in apical ballooning syndrome correlate of myocardial injury. Am Heart J 152:469 (e9-13)Google Scholar
  56. 56.
    Matsuoka K, Okubo S, Fujii E et al (2003) Evaluation of the arrhythmogenecity of stress-induced “Takotsubo cardiomyopathy” from the time course of the 12-lead surface electrocardiogram. Am J Cardiol 92:230–233CrossRefPubMedGoogle Scholar
  57. 57.
    Frankenstein L, Zugck C, Nelles M et al (2008) Primary ICD-therapy in patients with advanced heart failure: selection strategies and future trials. Clin Res Cardiol 97:594–600CrossRefPubMedGoogle Scholar
  58. 58.
    Haghi D, Athanasiadis A, Papavassiliu T et al (2006) Right ventricular involvement in Takotsubo cardiomyopathy. Eur Heart J 27:2433–2439CrossRefPubMedGoogle Scholar
  59. 59.
    Hitz MP, Bertram H, Koditz H et al (2008) Levosimendan for bridging in a pediatric patient with Alstrom syndrome awaiting heart-lung transplantation. Clin Res Cardiol 97:846–848CrossRefPubMedGoogle Scholar
  60. 60.
    Muller II, Klingel K, Nikolaev VO et al (2008) Immunoadsorption in a 40 year old man with dilated cardiomyopathy and underlying active myocarditis. Clin Res Cardiol 97:787–790CrossRefPubMedGoogle Scholar
  61. 61.
    Sadamatsu K, Tashiro H, Maehira N, Yamamoto K (2000) Coronary microvascular abnormality in the reversible systolic dysfunction observed after noncardiac disease. Jpn Circ J 64:789–792CrossRefPubMedGoogle Scholar
  62. 62.
    Ito K, Sugihara H, Kinoshita N, Azuma A, Matsubara H (2005) Assessment of Takotsubo cardiomyopathy (transient left ventricular apical ballooning) using 99mTc-tetrofosmin, 123I-BMIPP, 123I-MIBG and 99mTc-PYP myocardial SPECT. Ann Nucl Med 19:435–445CrossRefPubMedGoogle Scholar
  63. 63.
    Burgdorf C, Nef HM, Haghi D, Kurowski V, Radke PW (2010) Tako-tsubo (stress-induced) cardiomyopathy and cancer. Ann Intern Med 152:830–831PubMedGoogle Scholar
  64. 64.
    Kume T, Kawamoto T, Okura H et al (2008) Local release of catecholamines from the hearts of patients with tako-tsubo-like left ventricular dysfunction. Circ J 72:106–108CrossRefPubMedGoogle Scholar
  65. 65.
    Kurisu S, Inoue I, Kawagoe T et al (2007) Variant form of tako-tsubo cardiomyopathy. Int J Cardiol 119:e56–e58CrossRefPubMedGoogle Scholar
  66. 66.
    Hertting K, Krause K, Harle T et al (2006) Transient left ventricular apical ballooning in a community hospital in Germany. Int J Cardiol 112:282–288CrossRefPubMedGoogle Scholar
  67. 67.
    Inoue M, Shimizu M, Ino H et al (2005) Differentiation between patients with takotsubo cardiomyopathy and those with anterior acute myocardial infarction. Circ J 69:89–94CrossRefPubMedGoogle Scholar
  68. 68.
    Kurisu S, Sato H, Kawagoe T et al (2002) Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction. Am Heart J 143:448–455CrossRefPubMedGoogle Scholar
  69. 69.
    Sato M, Fujita S, Saito A et al (2006) Increased incidence of transient left ventricular apical ballooning (so-called ‘Takotsubo’ cardiomyopathy) after the mid-Niigata Prefecture earthquake. Circ J 70:947–953CrossRefPubMedGoogle Scholar
  70. 70.
    Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE (2008) Stress (Takotsubo) cardiomyopathy—a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 5:22–29CrossRefPubMedGoogle Scholar
  71. 71.
    Spinelli L, Trimarco V, Di Marino S et al (2010) L41Q polymorphism of the G protein coupled receptor kinase 5 is associated with left ventricular apical ballooning syndrome. Eur J Heart Fail 12:13–16CrossRefPubMedGoogle Scholar
  72. 72.
    Nef HM, Mollmann H, Troidl C et al (2008) Expression profiling of cardiac genes in Tako-Tsubo cardiomyopathy: insight into a new cardiac entity. J Mol Cell Cardiol 44:395–404CrossRefPubMedGoogle Scholar
  73. 73.
    Reuss CS, Lester SJ, Hurst RT et al (2007) Isolated left ventricular basal ballooning phenotype of transient cardiomyopathy in young women. Am J Cardiol 99:1451–1453CrossRefPubMedGoogle Scholar
  74. 74.
    Elesber AA, Prasad A, Lennon RJ et al (2007) Four-year recurrence rate and prognosis of the apical ballooning syndrome. J Am Coll Cardiol 50:448–452CrossRefPubMedGoogle Scholar
  75. 75.
    Parodi G, Del Pace S, Carrabba N et al (2007) Incidence, clinical findings, and outcome of women with left ventricular apical ballooning syndrome. Am J Cardiol 99:182–185CrossRefPubMedGoogle Scholar
  76. 76.
    Wedekind H, Moller K, Scholz KH (2006) Tako-tsubo cardiomyopathy. Incidence in patients with acute coronary syndrome. Herz 31:339–346CrossRefPubMedGoogle Scholar
  77. 77.
    Kume T, Akasaka T, Kawamoto T et al (2005) Assessment of coronary microcirculation in patients with takotsubo-like left ventricular dysfunction. Circ J 69:934–939CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Ch. Sinning
    • 1
  • T. Keller
    • 1
  • N. Abegunewardene
    • 1
  • K.-F. Kreitner
    • 2
  • T. Münzel
    • 1
  • S. Blankenberg
    • 1
  1. 1.Department of Internal Medicine IIUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
  2. 2.Department of Diagnostic and Interventional RadiologyUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany

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