In order to bring you the best possible user experience, this site uses Javascript. If you are seeing this message, it is likely that the Javascript option in your browser is disabled. For optimal viewing of this site, please ensure that Javascript is enabled for your browser.
Did you know that your browser is out of date? To get the best experience using our website we recommend that you upgrade to a newer version. Learn more.

Differentiating Tako-tsubo cardiomyopathy from myocardial infarction.

An article from the e-journal of the ESC Council for Cardiology Practice

BNP/NT-proBNP elevation, ECG performance, echocardiography, and cardiovascular magnetic resonance, in parallel with cardiac catheterisation might all concur to exclude ischaemia and demonstrate extensive myocardial inflammation both of which are necessary for a diagnosis of Tako-tsubo cardiomyopathy.

Myocardial Disease


Tako-tsubo cardiomyopathy (TTC), also referred to as stress cardiomyopathy, apical ballooning syndrome or “broken heart syndrome” is an acute catecholamine-induced myocardial inflammation occurring mainly in aging women after severe stress. Acute development of segmental - usually periapical - left ventricular systolic dysfunction occurs almost exclusively, and is often precipitated by exposure to severe acute emotional stress. In a cohort study of 136 patients, 96% were female and about 90% were over 50 years of age. Clinically, it typically mimics acute myocardial infarction (MI), with acute onset of severe chest pain, dyspnoea, and ECG changes typical of MI - often with S-T segment elevation initially. Evaluation of left ventricular function by echocardiography usually reveals a periapical zone of akinesis or hypokinesis. Several investigations have shown that left ventricular (LV) wall motion may return to normal within a few weeks and symptoms may subside within a few days, yet severe complications such as LV free wall rupture, pulmonary oedema, heart failure, arrhythmias, dynamic LV outflow tract obstruction, hypotension and even death may occur (1-4). 

Exclusion of ischaemia and demonstration of extensive myocardial inflammation

There is evidence that clinical consequence of TTC is myocardial inflammation initiated by “pulse” exposure to catecholamines in susceptible myocardium. Available mechanistic data from a rat model suggest that the main effects of catecholamines are mediated by β2-aderenoceptor stimulation (5), and we have preliminary evidence to suggest that the coupling of such receptors with synthesis of nitric oxide may also be important (6). Associated with inflammatory activation and nitrosative stress there is probably also myocardial energetic impairment (7). Initial reports suggested that this was a relative rarity, and did not really delineate pathogenesis. Under such circumstances, it became effectively a diagnosis requiring exclusion of ischaemia (8). It is now clear that coronary disease may theoretically co-exist, and that diagnosis ultimately rests on the demonstration of extensive myocardial inflammation yet from a clinical point of view, differentiation from acute MI remains potentially difficult. In table 1, the therapeutic implications of differentiation with AMI/ischaemia are listed.

Table 1: Therapeutic implications of differentiation with AMI/ischaemia.

Common problemsAMI onlyTTC only
1. Hypotension/ Shock
(however, rare in Non-Q-wave AMI)
1. Re-infarction 1. Torsade de pointes
2. Risk of LV mural thrombosis (mainly in TTC) 2. Long-term systolic LV dysfunction 2. LV outflow track obstruction
3. Ongoing chest pain   3. Aggravation with catecholamine administration
    4. Aggravation with nitric oxyde donors

Mayo clinic 

The Mayo clinic requires the presence of all four criteria:

  1. Regional wall motion abnormalities (mid-LV and/or apical transient hypokinesis, akinesis, or dyskinesis);
  2. Absence of obstructive coronary artery disease or acute plaque rupture on angiography; 
  3. New ST-segment elevation and/or T-wave inversion; or modest serum cardiac troponin elevation; 
  4. Absence of pheochromocytoma or myocarditis (9). 

However, we note that these updated criteria (2008) do not mention:

  • Rationale for excluding patients with a history of pheochromocytoma (where an adrenal gland releases hormones that cause persistant or episodic high blood pressure) or myocarditis (10). Possible presence of incidental coronary disease of coronary artery disease is also not included. 
  • Selection bias from catherisation -  The condition has usually been recognised, particularly in the early series of cases, as a result of cardiac catheterisation in patients presenting with acute chest pain in which initial diagnosis was acute coronary syndrome. These reports largely related to patients presenting with initial S-T segment elevation on ECG, and therefore triaged to emergency cardiac catheterisation, however more recent studies indicate that only 40% of presentations include initial S-T segment elevation (11, 12). 
  • Single or multivessel coronary spasm as a possible underlying disorder - the distribution of hypokinesis rarely accords with the course of a single coronary artery. 

Very elderly, frail patients presenting with prolonged chest pain, especially without S-T elevation, may not undergo cardiac catheterisation, and therefore the diagnosis may easily be missed. All these reasons make it essential to establish consistent diagnostic criteria. 

General considerations

From study results not involving cardiac catheterisation which had thus far dominated, two differences with acute myocardial ischaemia/infarction have been put forward:

  • Limited release of markers of myocardial injury: Low levels of troponin (Tn) and creatine kinase (CK) are noted as indeed most patients have no long-term evidence of myocardial infarction on cardiovascular magnetic resonance (CMR) scanning. 
  • Myocardial stunning: No infarction combined with rapid improvement of regional LV wall motion suggest that it may represent a form of reversible chemical injury analogous to myocardial “stunning”. Indeed, a number of recent studies have revealed evidence of regional intracardiac inflammatory changes (from biopsy studies) (14) and oedema (from CMR studies) after acute attacks (15). 

How clinicians should differentiate it from Non-Q-wave acute myocardial infarction (NQAMI) 

1 - Clinical presentation 

Approached  according to the mode of presentation and duration of symptoms

  • Sudden emotional or physical stress: It is often triggered by sudden emotional or physical stress brought on by individually or communally stressful circumstances. The critical issue is that of the probability of precipitation by the stimuli concerned, which is unknown. 
  • Relationship with acute cerebral infarction: It is a well-recognised complication of both cerebral infarction and haemorrhage (16), but embolic cerebral infarction is also a potential complication (17). 
  • Stressors: Some patients bring up no stressors however, the majority experienced at least one recent severe stress event and 9 out of 10 were female (18). 
  • ACS symptoms: Clinical presentation usually mimics the symptoms of acute coronary syndrome with variable degrees of chest pain at rest in 50 to 60% of patients, and/or dyspnoea. 
  • Hypotension and shock are frequent early complications: the mechanism(s) responsible for haemodynamic impairment are probably combinations of impaired left ventricular contractility, together with inadequate tachycardic response and in some cases BNP-mediated vasodilatation (19).

2 - Bloodwork

The following tests do not enable a clear distinction between TTC and AMI patients.

  1. Cathecolamines - Laboratory findings are similar to those of acute coronary syndrome.  Compared to MI patients, a significant elevation of catecholamine levels on admission has been reported by Wittstein et al however, no significant difference in catecholamine levels with MI patients has been documented in other studies (20). This may be explained by the differences in time-course from time of the first symptom presentation, to the time that the actual blood sample is taken. 
  2. Elevated biomarkers - Cardiac biomarkers such as Tn, CK, and CK MB are slightly elevated in most cases (21). Substantial increases in BNP and NT-pro BNP have been found in several studies (22). 

3 - ECG changes

Individual changes in electrocardiogram vary, but may be similar to changes in MI patients with ST elevation, T-wave inversion, and pathological Q-waves (23). 

These test results are likely to appear in TTC patients and therefore are a useful method for identification:
  • Heterogeneous S-T and T wave changes - In a systemic review by Pilgrim & Wyss (21), ST segmental elevation was documented in more than 70% of patients, particularly in the precordial leads. However, in another study of 105 patients, only 34.2% had ST segmental elevation on ECG (11). Subsequently, T-wave inversion has been found to be very common. Furthermore, a prolonged QT interval has often been recognised (24) and torsades de pointes may occur as a result (25,26). Several attempts have been made to distinguish associated ECG changes from those of AMI patients with anterior infarction with S-T elevation due to left anterior descending (LAD) occlusion. In all, ST-segment elevation and progressive T-wave inversion on ECG are not reliable criteria to differentiate these conditions (27). Nevertheless, TTC tends to be associated with “anatomically heterogeneous” S-T and T wave changes, suggesting involvement of more than one area of coronary perfusion (Figure 1). 

Figure 1
: Typical pattern of QT prolongation and “multi-regional” T wave inversion in Takotsubo cardiomyopathy.

4 - Echocardiography

LV apical ballooning - Changes on echocardiography often show apical and/or midventricular akinesis/hypokinesis and basal hyperkinesis, distorting the shape of the LV, and showing “LV apical ballooning”. Approximately one third of patients also have apical right ventricular hypokinesis (28). The contractile dysfunction of the LV results in a lowered LVEF. Moderate to severe LV systolic/diastolic dysfunction is common but can be absent. Although the wall thickness in the akinetic segments may be reduced in the acute phase, the characteristics of these thinned regions have been reported to be different from the hyperechogenic fibrosis signals of a transmural MI. More importantly, the segmental rather than global wall motion abnormalities, which are not associated with any single coronary artery territory, could be used to distinguish it from AMI (29). Using a speckle tracking echocardiographic methods to quantitate regional LV systolic function, Mansencal et al. (30) reported that there were significant differences in strain, strain rate and systolic peak velocities between acute and chronic phases. Furthermore, in the acute phase, systolic dysfunction was circular with similar velocity among basal, mid ventricle, and apical segments and was different from that of patients with LAD coronary artery obstruction. 

5 - Cardiac catheterisation/coronary angiography 

Diagnosis is most commonly made by invasive coronary angiography and is rarely the initial diagnosis at hospital admission. In most cases, no significant coronary artery stenoses are found. Left ventriculography is a useful method to diagnose and classify forms, typically demonstrating the distinctive LV shape - similar to a Japanese octopus pot with a round bottom and a narrow neck. Approximately 30% of cases exhibit predominantly mid-ventricular hypokinesis, while there is also a rare basal or “inverted” form (31).
Regarding haemodynamics during the acute stages, these are common findings: 1) systemic hypotension or shock (19), 2) mild elevation of pulmonary capillary wedge pressure - although pulmonary oedema is rare (22). Occasionally, patients have haemodynamic evidence of intraventricular pressure gradients and/or severe mitral valve regurgitation. Due to the need for cardiac catheterisation (using the Mayo clinic criteria), the diagnostic process is subject to potential selection bias, as this investigation is more likely to be performed in patients with severe symptoms. 

6 - Cardiovascular magnetic resonance

Cardiovascular magnetic resonance (CMR) allows assessment of cardiac function and LV regional wall motion abnormalities with high resolution. Using T2-weighted CMR, periapical oedema is observed in most patients (32). However, careful T2 quantitation reveals oedema throughout the LV (15). Although delayed enhancement is not usually seen in patients with TTC on contrast-enhanced CMR, it has been reported in some cases (due to increase in extracellular matrix content, confirmed with collagen-1 staining) (32).The detection of marked plasma BNP/NT-proBNP elevation as well as a positive troponin T concentration in female patients with prior emotional or physical trauma and presence of ECG showing “multi-regional” changes and no ST segment elevation is suggestive of TTC. Assessments of regional LV wall motion using either echocardiography or coronary angiography followed by detection of myocardial oedema without infarction on CMR (with late gadolinium enhancement and T2-weighted imaging) are the steps which complete the diagnosis.


Therapeutics for TTC have not been firmly established yet they are to:

  1. Monitor for arrhythmias for at least 2 days
  2. Anti-coagulate with heparin to reduce risk of mural thrombosis
  3. Avoid administration of catecholamines. 
  4. Avoid organic nitrates since there is evidence that TTC may include nitrosative stress (33)
  5. Use ACE inhibitor therapy which may reduce the risk of recurrence (34) in the long-term according to a meta-analysis. 

However, therapeutics for 1) management of shock and 2) accelerating recovery of LV function are still awaiting clinical trial. 


TTC is a common differential diagnosis of AMI, irrespective of presence of S-T elevation. Differentiation is important because treatment is also different: while patients presenting with S-T elevation need to undergo cardiac catheterisation as the first diagnostic step, in practice this functions in parallel with clinical assessment, detection of elevated BNP/NT-proBNP levels, ECG performance and echocardiography as initial diagnostic tests and should be followed by the demonstration of extensive myocardial oedema on CMR. 


1. Takotsubo cardiomyopathy: a new form of acute, reversible heart failure.
Akashi YJ, Goldstein DS, Barbaro G, Ueyama T. Circulation. 2008;118(25):2754-62. Epub 2008/12/25.
2. Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy.
Sharkey SW, Windenburg DC, Lesser JR, Maron MS, Hauser RG, Lesser JN, et al. Journal of the American College of Cardiology. 2010;55(4):333-41.
3. Increased incidence of transient left ventricular apical ballooning (so-called 'Takotsubo' cardiomyopathy) after themid-Niigata Prefecture earthquake
Sato M, Fujita S, Saito A, Ikeda Y, Kitazawa H, Takahashi M, et al. Circulation journal : official journal of the Japanese Circulation Society. 2006;70(8):947-53. Epub 2006/07/26.
4. Neurohumoral features of myocardial stunning due to sudden emotional stress.
Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, et al.  N Engl J Med. 2005;352(6):539-48.
5. High levels of circulating epinephrine trigger apical cardiodepression in a beta2-adrenergic receptor/Gi-dependent manner: a new model of Takotsubo cardiomyopathy.
Paur H, Wright PT, Sikkel MB, Tranter MH, Mansfield C, O'Gara P, et al.  Circulation. 2012;126(6):697-706. Epub 2012/06/27.
6. Enhanced NO Signaling in Patients with Takotsubo Cardiomyopathy: Short-Term Pain, Long-Term Gain? 
Nguyen TH, Neil CJ, Sverdlov AL, Ngo DT, Chan WP, Heresztyn T, et al. Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy. 2013. Epub 2013/08/08.
7. Horowitz JD, Frenneaux MP. Tako-Tsubo cardiomyopathy : new insights into pathogenesis Braunwald's textbook of Cardiology. 2011.
8. Bybee KA, Kara T, Prasad A, Lerman A, Barsness GW, Wright RS, 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.
9. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction.
Prasad A, Lerman A, Rihal CS.  Am Heart J. 2008;155(3):408-17.
10. Why the current diagnostic criteria of Takotsubo syndrome are outmoded: a proposal for new criteria
Madias JE. International journal of cardiology. 2014;174(3):468-70. Epub 2014/05/14.
11. Clinical correlates and prognostic significance of electrocardiographic abnormalities in apical ballooning syndrome (Takotsubo/stress-induced cardiomyopathy). 
Dib C, Asirvatham S, Elesber A, Rihal C, Friedman P, Prasad A. Am Heart J. 2009;157(5):933-8.
12. Acute Heart Failure in Apical Ballooning Syndrome (TakoTsubo/Stress Cardiomyopathy) Clinical Correlates and Mayo Clinic Risk Score. Journal of the American College of Cardiology. 
Madhavan M, Rihal CS, Lerman A, Prasad A.  011;57(12):1400-1.
13. Proposed Mayo Clinic criteria for the diagnosis of Tako-Tsubo cardiomyopathy and long-term prognosis.
Madhavan M, Prasad A. Herz. 2010.
14.  Tako-Tsubo cardiomyopathy: intraindividual structural analysis in the acute phase and after functional recovery.
Nef HM, Mollmann H, Kostin S, Troidl C, Voss S, Weber M, et al. European heart journal. 2007;28(20):2456-64.
15. Slowly resolving global myocardial inflammation/oedema in Tako-Tsubo cardiomyopathy: evidence from T2-weighted cardiac MRI.
Neil C, Nguyen TH, Kucia A, Crouch B, Sverdlov A, Chirkov Y, et al.  Heart (British Cardiac Society). 2012;98(17):1278-84. Epub 2012/07/14.
16. Incidence and clinical characteristics of takotsubo cardiomyopathy post-aneurysmal subarachnoid hemorrhage. Abd TT, Hayek S, Cheng JW, Samuels OB, Wittstein IS, Lerakis S.  International journal of cardiology. 2014;176(3):1362-4. Epub 2014/08/16.
17. [Takotsubo cardiomyopathy and cerebral infarction]
Kato Y, Takeda H, Furuya D, Deguchi I, Tanahashi N. . Rinsho shinkeigaku = Clinical neurology. 2009;49(4):158-66. Epub 2009/05/26.
18. Acute stress cardiomyopathy.
Wittstein IS.  Curr Heart Fail Rep. 2008;5(2):61-8.
19. Dissociation between severity of takotsubo cardiomyopathy and presentation with shock or hypotension. 
Chong CR, Neil CJ, Nguyen TH, Stansborough J, Law GW, Singh K, et al. Clinical cardiology. 2013;36(7):401-6. Epub 2013/04/16.
20. Stress hormone and circulating biomarker profile of apical ballooning syndrome (Takotsubo cardiomyopathy): insights into the clinical significance of B-type natriuretic peptide and troponin levels.
Madhavan M, Borlaug BA, Lerman A, Rihal CS, Prasad A.  Heart (British Cardiac Society). 2009;95(17):1436-41.
21. Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrome: A systematic review.
International journal of cardiology. 
Pilgrim TM, Wyss TR. 2008;124(3):283-92.
22. N-terminal pro-brain natriuretic protein levels in takotsubo cardiomyopathy.
Nguyen TH, Neil CJ, Sverdlov AL, Mahadavan G, Chirkov YY, Kucia AM, et al. The American journal of cardiology. 2011;108(9):1316-21.
23. Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review. European heart journal. 
Gianni M, Dentali F, Grandi AM, Sumner G, Hiralal R, Lonn E. 2006;27(13):1523-9.
24. The vulnerable myocardium: long-QT syndrome in Tako-Tsubo cardiomyopathy.
Mahfoud F, Ukena C, Kindermann M, Mewis C, Bohm M.  Clin Res Cardiol. 2009;98(6):409-11.
25. Long QT syndrome and torsade de pointes in transient left ventricular apical ballooning syndrome.
Denney SD, Lakkireddy DR, Khan IA.  International journal of cardiology. 2005;100(3):499-501.
26. Acquired long QT syndrome from stress cardiomyopathy is associated with ventricular arrhythmias and torsades de pointes.
Madias C, Fitzgibbons TP, Alsheikh-Ali AA, Bouchard JL, Kalsmith B, Garlitski AC, et al.  Heart rhythm : the official journal of the Heart Rhythm Society. 2011;8(4):555-61. Epub 2010/12/15.
27. Electrocardiogram mimics of acute ST-segment elevation myocardial infarction: insights from cardiac magnetic resonance imaging in patients with tako-tsubo (stress) cardiomyopathy.
Sharkey SW.  J Electrocardiol. 2008;41(6):621-5.
28. Dissociation of Early Shock in Takotsubo Cardiomyopathy from either Right or Left Ventricular Systolic Dysfunction. Heart, lung & circulation.
Singh K, Neil CJ, Nguyen TH, Stansborough J, Chong CR, Dawson D, et al.  2014. Epub 2014/07/22.
29. Echocardiographic assessment of regional left ventricular wall motion abnormalities in patients with tako-tsubo cardiomyopathy: comparison with anterior myocardial infarction.
Citro R, Rigo F, Ciampi Q, D'Andrea A, Provenza G, Mirra M, et al.  European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology. 2011;12(7):542-9. Epub 2011/05/25.
30. Usefulness of two-dimensional speckle tracking echocardiography for assessment of Tako-Tsubo cardiomyopathy.
Mansencal N, Abbou N, Pilliere R, El Mahmoud R, Farcot JC, Dubourg O.  The American journal of cardiology. 2009;103(7):1020-4.
31. Transient midventricular ballooning syndrome: a new variant.
Hurst RT, Askew JW, Reuss CS, Lee RW, Sweeney JP, Fortuin FD, et al.  Journal of the American College of Cardiology. 2006;48(3):579-83. Epub 2006/08/01.
32. Immunohistological basis of the late gadolinium enhancement phenomenon in tako-tsubo cardiomyopathy. European heart journal. 
Rolf A, Nef HM, Mollmann H, Troidl C, Voss S, Conradi G, et al. 2009;30(13):1635-42.
33. Increased Myocardial Expression of Thioredoxin-Interacting Protein, and Evidence of Nitrosative Stress in a Rat Model of Tako-Tsubo Cardiomyopathy. 
Licari G, Singh K, Chong CR, Nguyen TH, Chapman M, Stafford I, et al. Abstract (AHA). 2013;2013; 128: A16386.
34. Systematic review and meta-analysis of incidence and correlates of recurrence of takotsubo cardiomyopathy. International journal of cardiology.
Singh K, Carson K, Usmani Z, Sawhney G, Shah R, Horowitz J.  2014. Epub 2014/05/09.

Notes to editor

Thanh H. Nguyen MD, M.Med.Sci, PhD 1,2
John D. Horowitz MBBS, B.Med.Sci (Hons), PhD, FRACP 1,2
1The Queen Elizabeth Hospital, Department of Cardiology 2. Basil Hetzel Institute, The University of Adelaide, Australia.

Authors’ disclosure: None declared.

Other ressources:

2008 and 2012 e-journal editions on the condition. 

Upcoming studies: Mayo clinics observations of TTC patient's personality profile, the University of Zurich's registry aiming to include 4,000 subjects and collection of biosamples to identify TTC specific biomarkers and mutations; a Tako tsubo and cancer Registry; a case control study of polymorphisms in the genes involved in the adrenergic pathway that would involve greater catecholamine sensitivity; a pilot study examining central nervous system and hormonal changes In Takotsubo cardiomyopathy, on examining endothelial function and another assessing cardiac sympathetic activity.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.