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  • Review Article
  • Published:

Epidemiology and pathophysiology of Takotsubo syndrome

Nature Reviews Cardiology volume 12, pages 387–397 (2015)Cite this article

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This article has been updated

Key Points

  • Approximately 2% of patients who present to hospital with suspected acute coronary syndrome have Takotsubo syndrome, with a predominance in postmenopausal women

  • Mortality is higher than initially thought, and recurrence is seen in 1.2% of patients within 6 months and nearly 5% at 6 years, with no preventive therapy currently available

  • Systemic catecholamine surges can cause acute coronary and peripheral vasospasm followed by peripheral vasodilation; a common complication is cardiogenic shock, due at least in part to left ventricular systolic dysfunction

  • Biopsy samples taken during the acute phase of Takotsubo syndrome show morphological changes similar to those after catecholamine-induced cardiotoxic effects, supporting direct effects as well as vascular influences

  • The apical myocardium of the left ventricle has a high density of β-adrenoceptors and, therefore, is the region most sensitive to circulating catecholamines

  • During extreme stress, excessive epinephrine levels cause a switch from the Gsα stimulatory to the cardioprotective Giα cardioinhibitory secondary messenger pathway within cardiomyocytes, thereby acting as a positive inotrope

Abstract

Takotsubo syndrome is an acute cardiac syndrome first described in 1990 and characterized by transient left ventricular dysfunction affecting more than one coronary artery territory, often in a circumferential apical, mid-ventricular, or basal distribution. Several pathophysiological explanations have been proposed for this syndrome and its intriguing appearance, and awareness is growing that these explanations might not be mutually exclusive. The reversible apical myocardial dysfunction observed might result from more than one pathophysiological phenomenon. The pathophysiology of Takotsubo syndrome is complex and integrates neuroendocrine physiology, potentially involving the cognitive centres of the brain, and including the hypothalamic–pituitary–adrenal axis. Cardiovascular responses are caused by the sudden sympathetic activation and surge in concentrations of circulating catecholamines. The multiple morphological changes seen in the myocardium match those seen after catecholamine-induced cardiotoxicity. The acute prognosis and recurrence rate are now known to be worse than initially thought, and much still needs to be learned about the epidemiology and the underlying pathophysiology of this fascinating condition in order to improve diagnostic and treatment pathways.

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Figure 1: Histopathological features of Takotsubo syndrome.
Figure 2: Integrated pathophysiological model for acute apical dysfunction in Takotsubo syndrome.

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Change history

  • 08 June 2015

    In the version of this Review published online ahead of print, the details of the author contributions were missing. The author contributions are now included in the HTML and PDF versions of the article.

References

  1. Dote, K., Sato, H., Tateishi, H., Uchida, T. & Ishihara, M. Myocardial stunning due to simultaneous multivessel coronary spasms: a review of 5 cases [Japanese]. J. Cardiol. 21, 203–214 (1991).

    CAS  PubMed  Google Scholar 

  2. Chan, C. et al. Acute myocardial infarction and stress cardiomyopathy following the Christchurch earthquakes. PLoS ONE 8, e68504 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Maron, B. J. et al. 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, 1807–1816 (2006).

    Article  PubMed  Google Scholar 

  4. Elliott, P. et al. Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur. Heart J. 29, 270–276 (2008).

    Article  PubMed  Google Scholar 

  5. Deshmukh, A. et al. Prevalence of Takotsubo cardiomyopathy in the United States. Am. Heart J. 164, 66–71 (2012).

    Article  PubMed  Google Scholar 

  6. Prasad, A., Lerman, A. & Rihal, C. S. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am. Heart J. 155, 408–417 (2008).

    Article  PubMed  Google Scholar 

  7. Kurowski, V. et al. Apical and midventricular transient left ventricular dysfunction syndrome (tako-tsubo cardiomyopathy): frequency, mechanisms, and prognosis. Chest 132, 809–816 (2007).

    Article  PubMed  Google Scholar 

  8. Akashi, Y. J., Goldstein, D. S., Barbaro, G. & Ueyama, T. Takotsubo cardiomyopathy: a new form of acute, reversible heart failure. Circulation 118, 2754–2762 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Primetshofer, D., Agladze, R., Kratzer, H., Reisinger, J. & Siostrzonek, P. Tako-Tsubo syndrome: an important differential diagnosis in patients with acute chest pain. Wien. Klin. Wochenschr. 122, 37–44 (2010).

    Article  PubMed  Google Scholar 

  10. Patel, S. M., Chokka, R. G., Prasad, K. & Prasad, A. Distinctive clinical characteristics according to age and gender in apical ballooning syndrome (takotsubo/stress cardiomyopathy): an analysis focusing on men and young women. J. Card. Fail. 19, 306–310 (2013).

    Article  PubMed  Google Scholar 

  11. Murakami, T. et al. Characterization of predictors of in-hospital cardiac complications of takotsubo cardiomyopathy: multi-center registry from Tokyo CCU Network. J. Cardiol. 63, 269–273 (2014).

    Article  PubMed  Google Scholar 

  12. Isogai, T. et al. Out-of-hospital versus in-hospital Takotsubo cardiomyopathy: analysis of 3719 patients in the Diagnosis Procedure Combination database in Japan. Int. J. Cardiol. 176, 413–417 (2014).

    Article  PubMed  Google Scholar 

  13. Kawai, S., Kitabatake, A., Tomoike, H & Takotsubo Cardiomyopathy Group. Guidelines for diagnosis of takotsubo (ampulla) cardiomyopathy. Circ. J. 71, 990–992 (2007).

    Article  PubMed  Google Scholar 

  14. Omerovic, E. How to think about stress-induced cardiomyopathy?—Think “out of the box”! Scand. Cardiovasc. J. 45, 67–71 (2011).

    Article  PubMed  Google Scholar 

  15. Eitel, I. et al. Clinical characteristics and cardiovascular magnetic resonance findings in stress (takotsubo) cardiomyopathy. JAMA 306, 277–286 (2011).

    CAS  PubMed  Google Scholar 

  16. Parodi, G. et al. Revised clinical diagnostic criteria for Tako-tsubo syndrome: the Tako-tsubo Italian Network proposal. Int. J. Cardiol. 172, 282–283 (2014).

    Article  PubMed  Google Scholar 

  17. Akashi, Y. J., Nef, H. M., Mollmann, H. & Ueyama, T. Stress cardiomyopathy. Annu. Rev. Med. 61, 271–286 (2010).

    Article  CAS  PubMed  Google Scholar 

  18. Dib, C. et al. Clinical correlates and prognostic significance of electrocardiographic abnormalities in apical ballooning syndrome (Takotsubo/stress-induced cardiomyopathy). Am. Heart J. 157, 933–938 (2009).

    Article  PubMed  Google Scholar 

  19. Kosuge, M. et al. Simple and accurate electrocardiographic criteria to differentiate takotsubo cardiomyopathy from anterior acute myocardial infarction. J. Am. Coll. Cardiol. 55, 2514–2516 (2010).

    Article  PubMed  Google Scholar 

  20. Tamura, A. et al. A new electrocardiographic criterion to differentiate between Takotsubo cardiomyopathy and anterior wall ST-segment elevation acute myocardial infarction. Am. J. Cardiol. 108, 630–633 (2011).

    Article  PubMed  Google Scholar 

  21. Takashio, S. et al. Usefulness of SUM of ST-segment elevation on electrocardiograms (limb leads) for predicting in-hospital complications in patients with stress (takotsubo) cardiomyopathy. Am. J. Cardiol. 109, 1651–1656 (2012).

    Article  PubMed  Google Scholar 

  22. Kosuge, M. & Kimura, K. Electrocardiographic findings of takotsubo cardiomyopathy as compared with those of anterior acute myocardial infarction. J. Electrocardiol. 47, 684–689 (2014).

    Article  PubMed  Google Scholar 

  23. Johnson, N. P., Chavez, J. F., Mosley, W. J. 2nd, Flaherty, J. D. & Fox, J. M. Performance of electrocardiographic criteria to differentiate Takotsubo cardiomyopathy from acute anterior ST elevation myocardial infarction. Int. J. Cardiol. 164, 345–348 (2013).

    Article  PubMed  Google Scholar 

  24. Otalvaro, L., Zambrano, J. P. & Fishman, J. E. Takotsubo cardiomyopathy: utility of cardiac computed tomography angiography for acute diagnosis. J. Thorac. Imaging 26, W83–85 (2011).

    Article  PubMed  Google Scholar 

  25. Ogura, R. et al. Specific findings of the standard 12-lead ECG in patients with 'Takotsubo' cardiomyopathy: comparison with the findings of acute anterior myocardial infarction. Circ. J. 67, 687–690 (2003).

    Article  PubMed  Google Scholar 

  26. Kurisu, S. et al. Time course of electrocardiographic changes in patients with tako-tsubo syndrome: comparison with acute myocardial infarction with minimal enzymatic release. Circ. J. 68, 77–81 (2004).

    Article  PubMed  Google Scholar 

  27. Mitsuma, W. et al. Serial electrocardiographic findings in women with Takotsubo cardiomyopathy. Am. J. Cardiol. 100, 106–109 (2007).

    Article  PubMed  Google Scholar 

  28. Jabara, R. et al. Comparison of the clinical characteristics of apical and non-apical variants of “broken heart” (takotsubo) syndrome in the United States. J. Invasive Cardiol. 21, 216–222 (2009).

    PubMed  Google Scholar 

  29. Nishida, J. et al. “Ballooning” patterns in takotsubo cardiomyopathy reflect different clinical backgrounds and outcomes: a BOREAS-TCM study. Heart Vessels (in press).

  30. Ueyama, T. et al. Estrogen attenuates the emotional stress-induced cardiac responses in the animal model of Tako-tsubo (Ampulla) cardiomyopathy. J. Cardiovasc. Pharmacol. 42 (Suppl. 1), S117–119 (2003).

    Article  CAS  PubMed  Google Scholar 

  31. Ueyama, T. et al. 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. Circ. J. 71, 565–573 (2007).

    Article  CAS  PubMed  Google Scholar 

  32. Elesber, A. A. et al. Four-year recurrence rate and prognosis of the apical ballooning syndrome. J. Am. Coll. Cardiol. 50, 448–452 (2007).

    Article  PubMed  Google Scholar 

  33. Sharkey, S. W. et al. Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy. J. Am. Coll. Cardiol. 55, 333–341 (2010).

    Article  PubMed  Google Scholar 

  34. Schultz, T. et al. Stress-induced cardiomyopathy in Sweden: evidence for different ethnic predisposition and altered cardio-circulatory status. Cardiology 122, 180–186 (2012).

    Article  PubMed  Google Scholar 

  35. Song, B. G. et al. Clinical characteristics, ballooning pattern, and long-term prognosis of transient left ventricular ballooning syndrome. Heart Lung 39, 188–195 (2010).

    Article  PubMed  Google Scholar 

  36. Citro, R. et al. Differences in clinical features and in-hospital outcomes of older adults with tako-tsubo cardiomyopathy. J. Am. Geriatr. Soc. 60, 93–98 (2012).

    Article  PubMed  Google Scholar 

  37. Schneider, B. et al. Complications in the clinical course of tako-tsubo cardiomyopathy. Int. J. Cardiol. 176, 199–205 (2014).

    Article  PubMed  Google Scholar 

  38. Schneider, B. et al. Gender differences in the manifestation of tako-tsubo cardiomyopathy. Int. J. Cardiol. 166, 584–588 (2013).

    Article  PubMed  Google Scholar 

  39. Citro, R. et al. Echocardiographic correlates of acute heart failure, cardiogenic shock, and in-hospital mortality in tako-tsubo cardiomyopathy. JACC Cardiovasc. Imaging 7, 119–129 (2014).

    Article  PubMed  Google Scholar 

  40. Brinjikji, W., El-Sayed, A. M. & Salka, S. In-hospital mortality among patients with takotsubo cardiomyopathy: a study of the National Inpatient Sample 2008 to 2009. Am. Heart J. 164, 215–221 (2012).

    Article  PubMed  Google Scholar 

  41. Singh, K. et al. Meta-analysis of clinical correlates of acute mortality in takotsubo cardiomyopathy. Am. J. Cardiol. 113, 1420–1428 (2014).

    Article  PubMed  Google Scholar 

  42. Schneider, B., Athanasiadis, A. & Sechtem, U. Gender-related differences in takotsubo cardiomyopathy. Heart Fail. Clin. 9, 137–146 (2013).

    Article  PubMed  Google Scholar 

  43. Vriz, O. et al. Tako-tsubo cardiomyopathy: insights from a community hospital. J. Cardiovasc. Med. (Hagerstown) 14, 576–581 (2013).

    Article  Google Scholar 

  44. Lee, P. H. et al. Outcomes of patients with stress-induced cardiomyopathy diagnosed by echocardiography in a tertiary referral hospital. J. Am. Soc. Echocardiogr. 23, 766–771 (2010).

    Article  PubMed  Google Scholar 

  45. Previtali, M. et al. Clinical characteristics and outcome of left ventricular ballooning syndrome in a European population. Am. J. Cardiol. 107, 120–125 (2011).

    Article  PubMed  Google Scholar 

  46. Shimizu, M. et al. J wave and fragmented QRS formation during the hyperacute phase in Takotsubo cardiomyopathy. Circ. J. 78, 943–949 (2014).

    Article  PubMed  Google Scholar 

  47. Singh, K. et al. Systematic review and meta-analysis of incidence and correlates of recurrence of takotsubo cardiomyopathy. Int. J. Cardiol. 174, 696–701 (2014).

    Article  PubMed  Google Scholar 

  48. Santoro, F. et al. Lack of efficacy of drug therapy in preventing takotsubo cardiomyopathy recurrence: a meta-analysis. Clin. Cardiol. 37, 434–439 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Nef, H. M. et al. Tako-Tsubo cardiomyopathy: intraindividual structural analysis in the acute phase and after functional recovery. Eur. Heart J. 28, 2456–2464 (2007).

    Article  PubMed  Google Scholar 

  50. Szardien, S. et al. Molecular basis of disturbed extracellular matrix homeostasis in stress cardiomyopathy. Int. J. Cardiol. 168, 1685–1688 (2013).

    Article  PubMed  Google Scholar 

  51. Nef, H. M. et al. Activated cell survival cascade protects cardiomyocytes from cell death in Tako-Tsubo cardiomyopathy. Eur. J. Heart Fail. 11, 758–764 (2009).

    Article  CAS  PubMed  Google Scholar 

  52. Randhawa, M. S., Dhillon, A. S., Taylor, H. C., Sun, Z. & Desai, M. Y. Diagnostic utility of cardiac biomarkers in discriminating Takotsubo cardiomyopathy from acute myocardial infarction. J. Card. Fail. 20, 2–8 (2014).

    Article  PubMed  Google Scholar 

  53. Nef, H. M. et al. Expression profiling of cardiac genes in Tako-Tsubo cardiomyopathy: insight into a new cardiac entity. J. Mol. Cell. Cardiol. 44, 395–404 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Nef, J. M. et al. Abnormalities in intracellular Ca2+ regulation contribute to the pathomechanism of Tako-Tsubo cardiomyopathy. Eur. Heart. J. 30, 2155–2164 (2009).

    Article  CAS  PubMed  Google Scholar 

  55. Nef, H. M. et al. Reduced sarcoplasmic reticulum Ca2+-ATPase activity and dephosphorylated phospholamban contribute to contractile dysfunction in human hibernating myocardium. Mol. Cell. Biochem. 282, 53–63 (2006).

    Article  CAS  PubMed  Google Scholar 

  56. Nef, H. M., Mollmann, H., Akashi, Y. J. & Hamm, C. W. Mechanisms of stress (Takotsubo) cardiomyopathy. Nat. Rev. Cardiol. 7, 187–193 (2010).

    Article  PubMed  Google Scholar 

  57. Lyon, A. R., Rees, P. S., Prasad, S., Poole-Wilson, P. A. & Harding, S. E. Stress (Takotsubo) cardiomyopathy-a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat. Clin. Pract. Cardiovasc. Med. 5, 22–29 (2008).

    Article  CAS  PubMed  Google Scholar 

  58. Wittstein, I. S. et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N. Engl. J. Med. 352, 539–548 (2005).

    Article  CAS  PubMed  Google Scholar 

  59. Wilkinson, D. J. et al. Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress, and during panic attacks. Arch. Gen. Psychiatry 55, 511–520 (1998).

    Article  CAS  PubMed  Google Scholar 

  60. Jaguszewski, M. et al. A signature of circulating microRNAs differentiates takotsubo cardiomyopathy from acute myocardial infarction. Eur. Heart J. 35, 999–1006 (2014).

    Article  CAS  PubMed  Google Scholar 

  61. Baudry, A., Mouillet-Richard, S., Schneider, B., Launay, J. M. & Kellermann, O. miR-16 targets the serotonin transporter: a new facet for adaptive responses to antidepressants. Science 329, 1537–1541 (2010).

    Article  CAS  PubMed  Google Scholar 

  62. Bai, M. et al. Abnormal hippocampal BDNF and miR-16 expression is associated with depression-like behaviors induced by stress during early life. PLoS ONE 7, e46921 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Redfors, B. et al. Different catecholamines induce different patterns of takotsubo-like cardiac dysfunction in an apparently afterload dependent manner. Int. J. Cardiol. 174, 330–336 (2014).

    Article  PubMed  Google Scholar 

  64. Kurisu, S. et al. Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction. Am. Heart J. 143, 448–455 (2002).

    Article  PubMed  Google Scholar 

  65. Tsuchihashi, K. et al. 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, 11–18 (2001).

    Article  CAS  PubMed  Google Scholar 

  66. Patel, S. M., Lerman, A., Lennon, R. J. & Prasad, A. Impaired coronary microvascular reactivity in women with apical ballooning syndrome (Takotsubo/stress cardiomyopathy). Eur. Heart J. Acute Cardiovasc. Care 2, 147–152 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Pilgrim, T. M. & Wyss, T. R. Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrome: A systematic review. Int. J. Cardiol. 124, 283–292 (2008).

    Article  PubMed  Google Scholar 

  68. Angelini, P. Transient left ventricular apical ballooning: a unifying pathophysiologic theory at the edge of Prinzmetal angina. Catheter. Cardiovasc. Interv. 71, 342–352 (2008).

    Article  PubMed  Google Scholar 

  69. Abe, Y. et al. Assessment of clinical features in transient left ventricular apical ballooning. J. Am. Coll. Cardiol. 41, 737–742 (2003).

    Article  PubMed  Google Scholar 

  70. Stiermaier, T. et al. Frequency and significance of myocardial bridging and recurrent segment of the left anterior descending coronary artery in patients with takotsubo cardiomyopathy. Am. J. Cardiol. 114, 1204–1209 (2014).

    Article  PubMed  Google Scholar 

  71. Cocco, G. & Chu, D. Stress-induced cardiomyopathy: a review. Eur. J. Intern. Med. 18, 369–379 (2007).

    Article  CAS  PubMed  Google Scholar 

  72. Abraham, J. et al. Stress cardiomyopathy after intravenous administration of catecholamines and beta-receptor agonists. J. Am. Coll. Cardiol. 53, 1320–1325 (2009).

    Article  CAS  PubMed  Google Scholar 

  73. Shao, Y. et al. Novel rat model reveals important roles of beta-adrenoreceptors in stress-induced cardiomyopathy. Int. J. Cardiol. 168, 1943–1950 (2013).

    Article  PubMed  Google Scholar 

  74. Redfors, B. et al. Contrast echocardiography reveals apparently normal coronary perfusion in a rat model of stress-induced (Takotsubo) cardiomyopathy. Eur. Heart J. Cardiovasc. Imaging 15, 152–157 (2014).

    Article  PubMed  Google Scholar 

  75. Kawano, H., Okada, R. & Yano, K. Histological study on the distribution of autonomic nerves in the human heart. Heart Vessels 18, 32–39 (2003).

    Article  PubMed  Google Scholar 

  76. Mori, H. et al. Increased responsiveness of left ventricular apical myocardium to adrenergic stimuli. Cardiovasc. Res. 27, 192–198 (1993).

    Article  CAS  PubMed  Google Scholar 

  77. Brouri, F. et al. Blockade of beta 1- and desensitization of beta 2-adrenoceptors reduce isoprenaline-induced cardiac fibrosis. Eur. J. Pharmacol. 485, 227–234 (2004).

    Article  CAS  PubMed  Google Scholar 

  78. Paur, H. et al. High levels of circulating epinephrine trigger apical cardiodepression in a β2-adrenergic receptor/Gi-dependent manner: a new model of takotsubo cardiomyopathy. Circulation 126, 697–706 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Heubach, J. F., Ravens, U. & Kaumann, A. J. Epinephrine activates both Gs and Gi pathways, but norepinephrine activates only the Gs pathway through human β2-adrenoceptors overexpressed in mouse heart. Mol. Pharmacol. 65, 1313–1322 (2004).

    Article  CAS  PubMed  Google Scholar 

  80. Heubach, J. F., Blaschke, M., Harding, S. E., Ravens, U. & Kaumann, A. J. Cardiostimulant and cardiodepressant effects through overexpressed human beta2-adrenoceptors in murine heart: regional differences and functional role of beta1-adrenoceptors. Naunyn Schmiedebergs Arch. Pharmacol. 367, 380–390 (2003).

    Article  CAS  PubMed  Google Scholar 

  81. Chesley, A. et al. The beta(2)-adrenergic receptor delivers an antiapoptotic signal to cardiac myocytes through G(i)-dependent coupling to phosphatidylinositol 3′-kinase. Circ. Res. 87, 1172–1179 (2000).

    Article  CAS  PubMed  Google Scholar 

  82. Land, S. et al. Computational modelling of Takotsubo cardiomyopathy: effect of spatially varying beta-adrenergic stimulation in the rat left ventricle. Am. J. Physiol. Heart Circ. Physiol. (2014).

  83. Ieva, R. et al. Hyper-acute precipitating mechanism of Tako-Tsubo cardiomyopathy: in the beginning was basal hyperkinesis? Int. J. Cardiol. 167, e55–57 (2013).

    Article  PubMed  Google Scholar 

  84. Wright, P. T., Tranter, M. H., Morley-Smith, A. C. & Lyon, A. R. Pathophysiology of takotsubo syndrome: temporal phases of cardiovascular responses to extreme stress. Circ. J. 78, 1550–1558 (2014).

    Article  CAS  PubMed  Google Scholar 

  85. Sverrisdottir, Y. B., Schultz, T., Omerovic, E. & Elam, M. Sympathetic nerve activity in stress-induced cardiomyopathy. Clin. Auton. Res. 22, 259–264 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  86. Redfors, B., Shao, Y., Ali, A. & Omerovic, E. Are the different patterns of stress-induced (Takotsubo) cardiomyopathy explained by regional mechanical overload and demand: supply mismatch in selected ventricular regions? Med. Hypotheses 81, 954–960 (2013).

    Article  PubMed  Google Scholar 

  87. Spinelli, L. et al. L41Q polymorphism of the G protein coupled receptor kinase 5 is associated with left ventricular apical ballooning syndrome. Eur. J. Heart Fail. 12, 13–16 (2010).

    Article  CAS  PubMed  Google Scholar 

  88. Liggett, S. B. et al. A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure. Nat. Med. 14, 510–517 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Figtree, G. A. et al. No association of G-protein-coupled receptor kinase 5 or beta-adrenergic receptor polymorphisms with Takotsubo cardiomyopathy in a large Australian cohort. Eur. J. Heart Fail. 15, 730–733 (2013).

    Article  CAS  PubMed  Google Scholar 

  90. Kneale, B. J., Chowienczyk, P. J., Brett, S. E., Coltart, D. J. & Ritter, J. M. Gender differences in sensitivity to adrenergic agonists of forearm resistance vasculature. J. Am. Coll. Cardiol. 36, 1233–1238 (2000).

    Article  CAS  PubMed  Google Scholar 

  91. Patten, R. D. et al. 17beta-estradiol reduces cardiomyocyte apoptosis in vivo and in vitro via activation of phospho-inositide-3 kinase/Akt signaling. Circ. Res. 95, 692–699 (2004).

    Article  CAS  PubMed  Google Scholar 

  92. Ling, S., Komesaroff, P. & Sudhir, K. Cellular mechanisms underlying the cardiovascular actions of oestrogens. Clin. Sci. (Lond.) 111, 107–118 (2006).

    Article  CAS  Google Scholar 

  93. Kam, K. W., Qi, J. S., Chen, M. & Wong, T. M. Estrogen reduces cardiac injury and expression of beta1-adrenoceptor upon ischemic insult in the rat heart. J. Pharmacol. Exp. Ther. 309, 8–15 (2004).

    Article  CAS  PubMed  Google Scholar 

  94. Desmet, W. J., Adriaenssens, B. F. & Dens, J. A. Apical ballooning of the left ventricle: first series in white patients. Heart 89, 1027–1031 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Bybee, K. A. et al. Clinical characteristics and thrombolysis in myocardial infarction frame counts in women with transient left ventricular apical ballooning syndrome. Am. J. Cardiol. 94, 343–346 (2004).

    Article  PubMed  Google Scholar 

  96. Akashi, Y. J. et al. Reversible ventricular dysfunction takotsubo cardiomyopathy. Eur. J. Heart Fail. 7, 1171–1176 (2005).

    Article  PubMed  Google Scholar 

  97. Sharkey, S. W. et al. Acute and reversible cardiomyopathy provoked by stress in women from the United States. Circulation 111, 472–479 (2005).

    Article  PubMed  Google Scholar 

  98. Gianni, M. et al. Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review. Eur. Heart J. 27, 1523–1529 (2006).

    Article  PubMed  Google Scholar 

  99. Hertting, K. et al. Transient left ventricular apical ballooning in a community hospital in Germany. Int. J. Cardiol. 112, 282–288 (2006).

    Article  PubMed  Google Scholar 

  100. Spedicato, L. et al. Transient left ventricular apical ballooning syndrome: a 4-year experience. J. Cardiovasc. Med. (Hagerstown) 9, 916–921 (2008).

    Article  Google Scholar 

  101. El Mahmoud, R. et al. Prevalence and characteristics of left ventricular outflow tract obstruction in Tako-Tsubo syndrome. Am. Heart. J. 156, 543–548 (2008).

    Article  PubMed  Google Scholar 

  102. Previtali, M., Repetto, A., Panigada, S., Camporotondo, R. & Tavazzi, L. Left ventricular apical ballooning syndrome: prevalence, clinical characteristics and pathogenetic mechanisms in a European population. Int. J. Cardiol. 134, 91–96 (2009).

    Article  PubMed  Google Scholar 

  103. Eshtehardi, P. et al. Transient apical ballooning syndrome—clinical characteristics, ballooning pattern, and long-term follow-up in a Swiss population. Int. J. Cardiol. 135, 370–375 (2009).

    Article  PubMed  Google Scholar 

  104. Regnante, R. A. et al. Clinical characteristics and four-year outcomes of patients in the Rhode Island Takotsubo Cardiomyopathy Registry. Am. J. Cardiol. 103, 1015–1019 (2009).

    Article  PubMed  Google Scholar 

  105. Teh, A. W., New, G. & Cooke, J. A single-centre report on the characteristics of Tako-tsubo syndrome. Heart Lung Circ. 19, 63–70 (2010).

    Article  PubMed  Google Scholar 

  106. Parodi, G. et al. Natural history of tako-tsubo cardiomyopathy. Chest 139, 887–892 (2011).

    Article  PubMed  Google Scholar 

  107. Nunez-Gil, I. J. et al. Tako-tsubo syndrome and heart failure: long-term follow-up. Rev. Esp. Cardiol. (Engl. Ed.) 65, 996–1002 (2012).

    Article  Google Scholar 

  108. Brenner, R. et al. Clinical characteristics, sex hormones, and long-term follow-up in swiss postmenopausal women presenting with takotsubo cardiomyopathy. Clin. Cardiol. 35, 340–347 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Samardhi, H. et al. Takotsubo cardiomyopathy: an Australian single centre experience with medium term follow up. Intern. Med. J. 42, 35–42 (2012).

    Article  CAS  PubMed  Google Scholar 

  110. Bellandi, B. et al. Epidemiology of Tako-tsubo cardiomyopathy: the Tuscany Registry for Tako-tsubo Cardiomyopathy [Italian]. G. Ital. Cardiol. (Rome) 13, 59–66 (2012).

    Google Scholar 

  111. Cacciotti, L. et al. Observational study on Takotsubo-like cardiomyopathy: clinical features, diagnosis, prognosis and follow-up. BMJ Open 2, e001165 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  112. Sharma, V., Srinivasan, M., Sheehan, D. M. & Ionescu, A. Stress cardiomyopathy: case series and the review of literature. J. Emerg. Med. 45, e95–e98 (2013).

    Article  PubMed  Google Scholar 

  113. Pullara, A. et al. Takotsubo cardiomyopathy: real life management in the intensive coronary care unit. Minerva Med. 104, 537–544 (2013).

    CAS  PubMed  Google Scholar 

  114. Showkathali, R. & Ramoutar, A. Takotsubo cardiomyopathy and acute coronary syndrome—overlapping diagnoses will lead to confusion. Eur. J. Intern. Med. 25, e78 (2014).

    Article  PubMed  Google Scholar 

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Acknowledgements

Y.J.A. is supported by the Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Division of Cardiology, Department of Internal Medicine, St Marianna University School of Medicine, 2-16-1 Sugao Miyamae-ku, Kawasaki City, 216-8511, Kanagawa, Japan

    Yoshihiro J. Akashi

  2. Medizinische Klinik I, Kardiologie und Angiologie, Universitätsklinikum Gießen, Rudolf-Buchheim-Straße 8, 35392, Gießen, Germany

    Holger M. Nef

  3. NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and Imperial College, Sydney Street, London, SW3 6NP, UK

    Alexander R. Lyon

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  1. Yoshihiro J. Akashi
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  2. Holger M. Nef
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  3. Alexander R. Lyon
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Contributions

Y.J.A. researched data for the article. All authors substantially contributed to discussion of content, wrote, and reviewed and edited the manuscript before submission.

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Correspondence to Yoshihiro J. Akashi.

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Akashi, Y., Nef, H. & Lyon, A. Epidemiology and pathophysiology of Takotsubo syndrome. Nat Rev Cardiol 12, 387–397 (2015). https://doi.org/10.1038/nrcardio.2015.39

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