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J Res Med Sci. 2011 March; 16(3): 340–345.
PMCID: PMC3214344

Takotsubo cardiomyopathy or broken heart syndrome: A review article

Abstract

Stress-induced cardiomyopathy or Takotsubo cardiomyopathy is a recently increasing diagnosed disease showed by transient apical or mid left ventricular dilation and dysfunction. This sign is similar to acute myocardial infarction but without significant coronary artery stenosis and intra coronary clots. On the other hand there are important and essential differences in their management. Consequently, our physicians should know about its pathophysiology, diagnosis and treatment.

Keywords: Stress induced cardiomyopathy, Takotsubo cardiomyopathy, Broken heart syndrome, Apical ballooning syndrome, Ampulla cardiomyopathy

Transient left ventricular apical ballooning syndrome also called Takotsubo cardiomyopathy, Stress-induced cardiomyopathy (SICM), Broken heart syndrome and Ampulla cardiomyopathy. It was initially described in Japanese articles in 1990 and has since been diagnosed by transient LV apical hypokinesia without significant coronary artery stenosis in angiography or cardiomyopathy.1 The mid-ventricle and apex of the heart, when viewed by echocardiography or catheterization, has a spherical bottle with narrow neck in time of heart systole which resembles the old Japanese octopus trap called “Takotsubo” (Figure 1).2 Almost, patients are postmenopausal women with typical or atypical angina referred after an intensive emotional or surgical stressor such as serious environmental stimulations, suddenly loss of one loved him/her, complicated medical diseases, and noncardiac surgery with Electrocardiographic changes and elevation of cardiac biomarkers.3 Usually, coronary angiogram doesn’t show stenotic lesions. Transthoracic echocardiography or ventriculography manifest transient apical left ventricular dilation with compensa tory increased basal wall motion.4 The etiology is unknown; however, several pathologic reasons have been detected.5 Initially, left ventricular ejection fraction is low; afterwards it recovers within one month.6 SICM is a newly emerging clinical situation that is often under-diagnosed and mimic myocardial infarction with ST elevation, however high clinical suspicion can correctly recognize this transient cardiomyopathy. In order to recognize new aspects of this syndrome in the recent years that weren’t included in previous reviews, we searched ISI, PubMed, Cochrane and Scopus indexed papers and we found 214 articles that were directly related to our subject. Those were the database for collection and organization of the best and newly updated information for the present review.

Figure 1
traditional Japanese octopus trap

Epidemiology

SICM is diagnosed approximately in 1–2% of patients with history, signs and symptoms similar to acute myocardial infarction.7 Most patients with SICM are postmenopausal women. A systematic review of 14 studies by Gianni et al8 and Prasad et al1 showed 89% and 90% female predominance with age range of 58-77 and 58-75 years respectively.

Etiology

The etiology of the SICM has not been clearly recognized but Catecholamine induced myocardial stunning in patients face different kinds of stressors is established by serum catecholamine level elevation in more than the 70% of these patients.7 Strong evidences support this hypothesis. Myocardial scintillography with 123I-metaiodobenzylguanidine (MIBG) in these patients cleared a decreased uptake of radiotracer in several segments of left ventricle, emphasizing a severe adrenalin secretion produced by stress.9 The large interindividual differences in MIBG of patients with SICM may reflect variable responses to adrenergic stimulation; it may be justified by genetic inheritance at adrenalin synthesis, functions, storage, and elimination that may show an essential role in presentation of SICM in patients.10 Studies showed the higher density of beta-adrenergic receptors is located in apical heart, so the circulating catecholamine excessively influences this segment which results in apical negative cardiac myocyte inotropy.11 However, others suggest that the akinetic appearance of this region can be related to the high systolic apical circumferential wall stress.12

The reason of high prevalence in postmenopausal women is unknown but a hypothesis has proposed that reduced estrogens and their implications on microvascular system after menopause might be the main cause.1 Animal studies have shown estrogen attenuates immobility effects of stressors on the myocardium.13

Yoshida et al reported that endomyocardial biopsy shows “mixed cellular infiltrates (mononuclear lymphocytes and macrophages) with or without contraction band necrosis or interstitial fibrosis” in these patients,14 but did not report evidence of viral or bacterial myocarditis on biopsies or in serological studies.15

Kleinfeldt et al detected a mutation in gene of FMR1 (alleles with sizes between 40–55 triplet permutations) in the patients with SICM for the first time,16 also Kumar et al reported a familial apical ballooning in a mother and daughter which may explain why only a minority of postmenopausal women appear to be susceptible.17

Finally, subarachnoid hemorrhage,18 thyrotoxicosis,19 hypoglycemia,20 stroke,21 general anesthesia,22 dobutamine stress echocardiography,23 pheochromocytoma,24 Addison disease,25 after coronary intervention in a patient with anxiety,26 radiotherapy,27 and autoimmune polyendocrine syndrome type II28 may resemble the pattern of reversible left ventricular dysfunction of Takotsubo syndrome.

Recently, Mansencal et al has described the new form of takotsubo (apical-sparing variant) that is not rare and differs from the typical pattern of takotsubo in mean age (range: 30–32 year), so cardiologists should be aware and recognize this partial pattern.29

Precipitating events

The provocative events are typically severe emotional or physiological stressors. Emotional stressors were important precipitating events for stress-induced cardiomyopathy in case series report. For this reason, the name “Broken heart syndrome” was coined.8 Alternatively, physiological stressors can trigger an episode of apical ballooning syndrome, such as a severe medical illness, worsening of a chronic disease (e.g. heart failure), noncardiac surgical procedure,7 transplantation,30 brain death31 and seizure.32

Presentation

The most common symptoms are chest pain (two thirds of the patients) and dyspnea similar to those with acute myocardial infarction.8 Cardiogenic shock may present in patients with severe reduced left ventricular ejection fraction.33 In ECG, ST-segment elevation is absent in two thirds of patients with SICM.34 The ECG changes at presentation time do not correlate with the severity of ventricular dysfunction or prognosis.34 Bybee et al published that the most common ECG finding is QT prolongation33 and Torsades de pointes was reported in patients with SCIM and QT prolongation.35 Cardiac troponin are typically moderately elevated in SICM,7 also brain natriuretic peptide levels has elevated.36

Diagnosis

The principal criteria of SICM are: (1) acute emotional/physical stress before presentation with angina pectoris; (2) ischemic abnormalities on the ECG; (3) no significant epicardial coronary arteries stenosis or intracoronary thrombus on angiography37 (Figure (Figure2A2A & 2B); apical to mid ventricular ballooning with compensatory basal hyperkinesis on the left ventriculogram or echocardiogram (Figure 3); disproportionately low up to moderate plasma levels of cardiac biomarkers with respect to intensity of ventriclular dysfunction and (6) rapid improvement in left ventricular dysfunction and syndrome.38 Currently, Leurent et al suggest that cardiac Magnetic Resonance Imaging is a very useful tool in the diagnosis and management of SICM.39

Figure 2
Coronary angiogram [2A & 2B] in Takotsubo cardiomyopathy
Figure 3
Left ventriculogram in Takotsubo cardiomyopathy

Treatment

Management of patients with SICM is overall supportive and conservative. We should avoid the administration of thrombolytic agents.7 Left ventricular depression is treated with diuretics, beta blockers and angiotensin converting enzyme inhibitors. Additionally, beta blockers may block catecholamine excess which is the potential mechanism of SICM. Moreover, beta blockers have an essential role in reducing left ventricular outflow tract (LVOT) obstruction by decrease basal segment hypercontractility.7 Tamura et al believe that physicians should avoid administration of catecholamines for patients with SICM, LVOT obstruction and cardiogenic shock. Treatment with □-blockers, with careful observation for hemodynamic status, may be rationale in these patients.40 In 14 studies, totally 15 (2.5%) patients with left ventricular clot formation was reported over the last decade, therefore treatment with warfarin is recommended to prevent cardioembolic events.41

Prognosis

The prognosis for SICM is good without management and cardiac function recovers during less than 1 month;42,43 but, mortality rates are different from 0% to 8%.44,45 The left-sided heart failure is most common complication with or without pulmonary edema. Other complications are left ventricular mural clot, systemic or pulmonic embolic events, mitral valve regurgitation, ventricular arrhythmias, cardiogenic shock and maybe left ventricular wall rupture.7

Conclusion

SICM is an entity of acute heart failure that can mimic acute coronary syndrome and should be considered especially in patients with normal heart. We suggest that special emphasis be placed on awareness and diagnosis of the classical clinical features of SICM, such as old woman presenting with acute chest pain after stressful emotional or physical event. Furthermore, coronary angiography and ventriculography are needed to support SICM diagnosis. Short-term management is needed, however, early intensive care is necessary for patients with left-sided heart failure. Physicians should follow patients by echocardiography for assessment of left ventricular ejection fraction during outpatient periods46 and emphasize on possible complications of this disease and explain the possible causes lead to SICM for patients and their families.

Authors’ Contributions

AG analyzed the findings and writed the article draft. NS helped in writing the article draft, edited the article and finalysed it.

Footnotes

Conflict of Interests Authors have no conflict of interests.

References

1. Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J. 2008;155(3):408–17. [PubMed]
2. Tsuchihashi K, Ueshima K, Uchida T, Oh-mura N, Kimura K, Owa M, 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. 2001;38(1):11–8. [PubMed]
3. Sharkey SW, Lesser JR, Zenovich AG, Maron MS, Lindberg J, Longe TF, et al. Acute and reversible cardiomyopathy provoked by stress in women from the United States. Circulation. 2005;111(4):472–9. [PubMed]
4. Kurisu S, Sato H, Kawagoe T, Ishihara M, Shimatani Y, Nishioka K, et al. Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction. Am Heart J. 2002;143(3):448–55. [PubMed]
5. Akashi YJ, Nakazawa K, Sakakibara M, Miyake F, Koike H, Sasaka K. The clinical features of takotsubo cardiomyopathy. QJM. 2003;96(8):563–73. [PubMed]
6. Ako J, Sudhir K, Farouque HM, Honda Y, Fitzgerald PJ. Transient left ventricular dysfunction under severe stress: brain-heart relationship revisited. Am J Med. 2006;119(1):10–7. [PubMed]
7. Pilgrim TM, Wyss TR. Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrome: A systematic review. Int J Cardiol. 2008;124(3):283–92. [PubMed]
8. Gianni M, Dentali F, Grandi AM, Sumner G, Hiralal R, Lonn E. Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review. Eur Heart J. 2006;27(13):1523–9. [PubMed]
9. Soares-Filho GL, Felix RC, Azevedo JC, Mesquita CT, Mesquita ET, Valenca AM, et al. Broken heart or takotsubo syndrome: support for the neurohumoral hypothesis of stress cardiomyopathy. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(1):247–9. [PubMed]
10. Sharkey SW, Windenburg DC, Lesser JR, Maron MS, Hauser RG, Lesser JN, et al. Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy. J Am Coll Cardiol. 2010;55(4):333–41. [PubMed]
11. Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE. Stress (Takotsubo) cardiomyopathy--a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med. 2008;5(1):22–9. [PubMed]
12. Dandel M, Lehmkuhl H, Knosalla C, Hetzer R. Left ventricular wall motion abnormality and myocardial dysfunction in stress cardiomyopathy: new pathophysiological aspects suggested by echocardiography. Int J Cardiol. 2009;135(2):e40–3. [PubMed]
13. Ueyama T, Hano T, Kasamatsu K, Yamamoto K, Tsuruo Y, Nishio I. Estrogen attenuates the emotional stressinduced cardiac responses in the animal model of Tako-tsubo (Ampulla) cardiomyopathy. J Cardiovasc Pharmacol. 2003;42(Suppl 1):S117–9. [PubMed]
14. Yoshida T, Hibino T, Kako N, Murai S, Oguri M, Kato K, et al. A pathophysiologic study of tako-tsubo cardiomyopathy with F-18 fluorodeoxyglucose positron emission tomography. Eur Heart J. 2007;28(21):2598–604. [PubMed]
15. Teh AW, New G, Cooke J. A single-centre report on the characteristics of Tako-tsubo syndrome. Heart Lung Circ. 2010;19(2):63–70. [PubMed]
16. Kleinfeldt T, Schneider H, Akin I, Kische S, Gokmen TR, Nienaber CA, et al. Detection of FMR1-gene in Takotsubo cardiomyopathy: a new piece in the puzzle. Int J Cardiol. 2009;137(3):e81–3. [PubMed]
17. Kumar G, Holmes DR, Jr, Prasad A. “Familial” apical ballooning syndrome (Takotsubo cardiomyopathy) Int J Cardiol. 2010;144(3):444–5. [PubMed]
18. Otomo S, Sugita M, Shimoda O, Terasaki H. Two cases of transient left ventricular apical ballooning syndrome associated with subarachnoid hemorrhage. Anesth Analg. 2006;103(3):583–6. [PubMed]
19. Hutchings DC, Adlam D, Ferreira V, Karamitsos TD, Channon KM. Takotsubo cardiomyopathy in association with endogenous and exogenous thyrotoxicosis. QJM. 2010 [Epub ahead of print] [PubMed]
20. Ansari MJ, Prasad A, Pellikka PA, Klarich KW. Takotsubo cardiomyopathy caused by hypoglycemia A unique association with coronary arterial calcification. Int J Cardiol. 2011;147(2):e21–3. [PubMed]
21. Lee W, Profitis K, Barlis P, Van Gaal WJ. Stroke and Takotsubo cardiomyopathy: Is there more than just cause and effect? Int J Cardiol. 2009 [Epub ahead of print] [PubMed]
22. Gavish D, Rozenman Y, Hafner R, Bartov E, Ezri T. Takotsubo cardiomyopathy after general anesthesia for eye surgery. Anesthesiology. 2006;105(3):621–3. [PubMed]
23. Shah BN, Simpson IA, Rakhit DJ. Takotsubo (apical ballooning) syndrome in the recovery period following dobutamine stress echocardiography: a first report. Eur J Echocardiogr. 2011;12(1):E5. [PubMed]
24. Takizawa M, Kobayakawa N, Uozumi H, Yonemura S, Kodama T, Fukusima K, et al. A case of transient left ventricular ballooning with pheochromocytoma, supporting pathogenetic role of catecholamines in stress-induced cardiomyopathy or takotsubo cardiomyopathy. Int J Cardiol. 2007;114(1):e15–7. [PubMed]
25. Punnam SR, Gourineni N, Gupta V. Takotsubo cardiomyopathy in a patient with Addison disease. Int J Cardiol. 2010;144(2):e34–6. [PubMed]
26. Hussain J, Laufer N, Sorrof S, Pershad A. Takotsubo cardiomyopathy after coronary intervention developed during hospitalization. Ann Thorac Surg. 2009;88(6):e63–5. [PubMed]
27. Media S, Baiga W. Radiotherapy-induced Tako-tsubo Cardiomyopathy. Clin Oncol. 2009;21(4):361–2. [PubMed]
28. Lim T, Murakami H, Hayashi K, Watanabe H, Sasaki H, Muto H, et al. Takotsubo cardiomyopathy associated with autoimmune polyendocrine syndrome II. J Cardiol. 2009;53(2):306–10. [PubMed]
29. Mansencal N, El Mahmoud R, Pilliere R, Dubourg O. Relationship between pattern of Tako-Tsubo cardiomyopathy and age: from midventricular to apical ballooning syndrome. Int J Cardiol. 2010;138(1):e18–20. [PubMed]
30. Eagle SS, Thompson A, Fong PP, Pretorius M, Deegan RJ, Hairr JW, et al. Takotsubo cardiomyopathy and coronary vasospasm during orthotopic liver transplantation: separate entities or common mechanism? J Cardiothorac Vasc Anesth. 2010;24(4):629–32. [PubMed]
31. Berman M, Ali A, Ashley E, Freed D, Clarke K, Tsui S, et al. Is stress cardiomyopathy the underlying cause of ventricular dysfunction associated with brain death? J Heart Lung Transplant. 2010;29(9):957–65. [PubMed]
32. Le Ven F, Pennec PY, Timsit S, Blanc JJ. Takotsubo syndrome associated with seizures: an underestimated cause of sudden death in epilepsy? Int J Cardiol. 2011;146(3):475–9. [PubMed]
33. Bybee KA, Kara T, Prasad A, Lerman A, Barsness GB, Scott Wright R, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med. 2004;141(11):858–65. [PubMed]
34. Dib C, Asirvatham S, Elesber A, Rihal C, Friedman P, Prasad A. Clinical correlates and prognostic significance of electrocardiographic abnormalities in apical ballooning syndrome (Takotsubo/stress-induced cardiomyopathy) Am Heart J. 2009;157(5):933–8. [PubMed]
35. Denney SD, Lakkireddy DR, Khan IA. Long QT syndrome and torsade de pointes in transient left ventricular apical ballooning syndrome. Int J Cardiol. 2005;100(3):499–501. [PubMed]
36. Song BG, Park SJ, Noh HJ, Jo HC, Choi JO, Lee SC, et al. Clinical characteristics, and laboratory and echocardiographic findings in takotsubo cardiomyopathy presenting as cardiogenic shock. J Crit Care. 2010;25(2):329–35. [PubMed]
37. Novaro GM. Plaque rupture is not the cause of takotsubo cardiomyopathy. Med Hypotheses. 2011;76(2):305–6. [PubMed]
38. Cambronero F, Penafiel P, Moreno V, Nolte C, Valdes M. An atypical presentation of Tako-Tsubo cardiomyopathy. Int J Cardiol. 2010;138(3):e53–5. [PubMed]
39. Leurent G, Larralde A, Boulmier D, Fougerou C, Langella B, Ollivier R, et al. Cardiac MRI studies of transient left ventricular apical ballooning syndrome (takotsubo cardiomyopathy): a systematic review. Int J Cardiol. 2009;135(2):146–9. [PubMed]
40. Tamura A, Abe Y, Kadota J. The use of dopamine in Takotsubo cardiomyopathy. Int J Cardiol. 2010;145(1):132.
41. de Gregorio C, Grimaldi P, Lentini C. Left ventricular thrombus formation and cardioembolic complications in patients with Takotsubo-like syndrome: a systematic review. Int J Cardiol. 2008;131(1):18–24. [PubMed]
42. Lee PH, Song JK, Sun BJ, Choi HO, Seo JS, Na JO, et al. Outcomes of patients with stress-induced cardiomyopathy diagnosed by echocardiography in a tertiary referral hospital. J Am Soc Echocardiogr. 2010;23(7):766–71. [PubMed]
43. Silva C, Goncalves A, Almeida R, Dias P, Araujo V, Gavina C, et al. Transient left ventricular ballooning syndrome. Eur J Intern Med. 2009;20(5):454–6. [PubMed]
44. Le Ven F, Pennec PY, Timsit S, Blanc JJ. Takotsubo syndrome associated with seizures: an underestimated cause of sudden death in epilepsy? Int J Cardiol. 2011;146(3):475–9. [PubMed]
45. Movaheda MR, Donohueb D. Review: transient left ventricular apical ballooning, broken heart syndrome, ampulla cardiomyopathy, atypical apical ballooning, or Tako-Tsubo cardiomyopathy. Cardiovascular Revascularization Medicine. 2007;8(4):292–8. [PubMed]
46. Golabchi A, Sarrafzadegan N, Pormoghaddas M. A woman with Typical Chest Pain and Broken Heart. J Cardiovasc Thorac Res. 2011;2(4):31–4.

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