2004 The Mayo Criteria1
2007 Japanese Takotsubo Cardiomyopathy Group2
2008 The modified Mayo Criteria3
2012 Johns Hopkins criteria4
2013 Gothenburg Group5
2014 Takotsubo Italian Network6
2014 Madias-proposed criteria7
2015 European Society of Cardiology (Heart Failure Association)8
2018 International Takotsubo Diagnostic Criteria (InterTAK Diagnostic Criteria)9
There are now several publications that propose diagnostic criteria and diagnostic algorithms for Takotsubo syndrome (TTS) with subsequent modifications as knowledge about TTS has evolved. Some of these have been proposed by individual experts and institutional research groups. Others have been proposed by organisational working groups with international membership or panels of experts that include experts from around the world. Reassuringly, these proposed diagnostic criteria and algorithms differ mainly in format and the amount of detail included, and generally have the same (or similar) content, with some minor points of difference. The Mayo criteria (with the 2008 modifications) were used for several years. The most recent diagnostic criteria from the European Society of Cardiology and the InterTAK are shown below. They do not differ from each other in the core criteria but each has some added criteria. It is likely that these will continue to be revised as understanding of TTS evolves.
aAcute, reversible dysfunction of a single coronary territory has been reported.
bLeft bundle branch block may be permanent after Takotsubo syndrome, but should also alert clinicians to exclude other cardiomyopathies. T-wave changes and QTc prolongation may take many weeks to months to normalize after recovery of LV function.
cTroponin-negative cases have been reported, but are atypical.
dSmall apical infarcts have been reported. Bystander subendocardial infarcts have been reported, involving a small proportion of acutely dysfunctional myocardium. These infarcts are insufficient to explain the acute regional wall motion abnormality observed.
© 2015 Lyon et al. European Journal of Heart Failure © 2015 European Society of Cardiology
aWall motion abnormalities may remain for a prolonged period of time or documentation of recovery may not be possible. For example, death before evidence of recovery is captured.
bCardiac magnetic resonance imaging is recommended to exclude infectious myocarditis and diagnosis confirmation of takotsubo syndrome.
© Ghadri et al. 2018. Published by Oxford University Press on behalf of the European Society of Cardiology.
The ECG at TTS onset is like that of ACS in that it may show ST-segment elevation, T wave inversion, non-specific abnormalities, or no detectable abnormalities.
Key point Absence of ST-segment elevation or other ECG abnormalities at presentation does not rule out TTS.
Figure 1. ECG at 48 hours after onset of symptoms in Takotsubo syndrome in a 62-year-old female with apical ballooning
Image by Dr. Stephen Smith, http://hqmededecg.blogspot.com/2010/12/takostubo-stress-cardiomyopathy-with.html.
At a minimum, an ECG should be obtained at admission, 24 hours, and 48 hours following a suspected diagnosis of TTS, and with any change in the patient’s condition. In cases where there is QTc-interval prolongation, an ECG should be obtained daily during hospital admission or until the QTc-interval returns to normal.
Key point New and progressive T- wave inversion and QTc-prolongation in a patient who has a primary medical illness or in whom TTS not been diagnosed may indicate a need for further investigation.
Troponin and creatine kinase (CK)
Troponin values are almost always elevated in TTS but the rise in serum troponin or creatine kinase (CK) is disproportionately low relative to the extent of regional wall motion abnormality and cardiac dysfunction.8 Peak troponin and CK values are usually lower than those typically found in ACS. High admission troponin levels in TTS predict worse in-hospital outcome.14
B-type natriuretic peptide (BNP) and N-terminal prohormone of BNP (NT-proBNP)
Plasma levels of B-type natriuretic peptide (BNP) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are almost always elevated in TTS, often to extremely high levels. NT-proBNP/BNP increase significantly during the first 24 hours after the onset of symptoms with slow and incomplete resolution during the 3 months thereafter.15 NT-proBNP/BNP levels correlate more closely with the degree of ventricular wall motion abnormality and therefore may be more useful diagnostically than troponin in TTS.8 NT-proBNP is a valuable marker of myocardial deterioration and recovery. Low NT-proBNP at admission may reliably indicate a favourable prognosis8 while higher NT-proBNP/BNP levels are associated with adverse outcomes in TTS.16 It should be noted that angiotensin receptor-neprilysin inhibitor (ARNI) medications may falsely elevate BNP but does not affect NT-proBNP. A high BNP in patients taking ARNI medications does not necessarily mean a worse prognosis or outcome.
Key Point NT-proBNP are more useful diagnostic biomarkers than troponin, and it is recommended that they be measured in all suspected cases of TTS if the assay is available.
Coronary angiography is required to secure the diagnosis of TTS and exclude obstructive coronary artery disease as the cause of symptoms. Coronary angiography in TTS typically shows normal coronary arteries or mild to moderate coronary artery disease (CAD). Approximately 15% of patients with TTS will have significant CAD14 and biplane ventriculography in similar views is mandatory in these patients to detect perfusion-contraction mismatch.17,18
Venticulography in TTS will show regional wall motion abnormalities (hypokinesis, akinesis, or dyskinesis) in one of the following characteristic patterns:
Apical Takotsubo is the most commonly recognised form of TTS and accounts for around 80% of cases in the InterTAK Registry.14 Systolic apical ballooning of the left ventricle is present with depressed function of the mid and apical segments. Hyperkineses of the basal walls is often present. Around one-third of patients with the apical ballooning form of TS have a small zone of preserved contractility in the most distal portion of the apex. This has been described as the 'apical nipple sign'. which is described as the ‘apical nipple sign’.19
Mid-ventricular Takotsubo is restricted to the mid-ventriclular hypokinesis with relative sparing of the apex.
Basal (reverse or inverted Takotsubo) is associated with basal hypokinesis and sparing of the mid-ventricle and apex
Focal Takotsubo is characterised by dysfunction of an isolated segment (most commonly the anterolateral segment) of the LV. This is a relatively recently recognised form of Takotsubo and is likely under-recognised as a form of TTS.
Global Takotsubo is reportedly rare, but as with the focal type of Takotsubo, may be under-recognised as a form of TTS.
Four types of takotsubo (stress) cardiomyopathy — apical, midventricular, basal, and focal — are shown in videos of left ventricular angiography.
Sept 3, 2015.
Echocardiography plays a very important role in the assessment of heart function in TTS since it is easily available and has virtually no contraindications it is usually the first step in assessing pump function.
Transthoracic echocardiography (TTE) with colour and tissue Doppler should be the first non-invasive imaging technique to verify a suspected diagnosis of TTS. In addition to assessing LV morphology and function, TTE can identify anatomic variants, detect potential complications including left ventricular outflow obstruction (LVOTO), mitral regurgitation, right ventricular involvement, thrombus formation, and cardiac rupture. It is also used to monitor recovery.8
Accurate echocardiographic estimation of global left ventricular (LV) function can be subjective and for that reason, over the past few years, strain echocardiography has emerged as an important and accurate method of assessing LV function with the advantage of revealing myocardial dysfunction even before significant changes in ejection fraction have occurred.
This technique can be also used for monitoring recovery or early changes in LV function if new symptoms arise or recovery is taking longer than expected.
If available, cardiac magnetic resonance imaging (CMR) should be considered in all patients with suspected TTS in the acute phase (within 7 days). It is also useful to confirm recovery of ventricular function on follow-up.8
CMR is useful in distinguishing TTS from other diseases, acute myocardial infarction (MI) and myocarditis. During the acute phase of TTS, T2-weighted CMR shows oedema of the left ventricular (LV) myocardium as high signal intensity, with a diffuse or transmural distribution consistent with the wall motion abnormality. Typically, late gadolinium enhancement (LGE) is absent in TTS distinguishing it from MI. There is some controversy about whether minor LGE may be present during the acute phase of TTS but absent at follow up in some patients. Atypical cases with small areas of persistent apical transmural LGE have been reported.(Lyon) .
CMR is useful in assessment of regional wall motion abnormalities (RWMAs) in both the left and right ventricles and often provides more complete views of the right ventricle than echocardiography. TTS involves the right ventricle in up to one-third of patients..
Patients with extensive akinesia may benefit from CMR as CMR is superior to echocardiography in detecting apical LV thrombi.
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2Kawai, S., Kitabatake, A., Tomoike, H. and Takotsubo Cardiomyopathy Study Group, 2007. Guidelines for diagnosis of takotsubo (ampulla) cardiomyopathy. Circulation Journal, 71(6), pp.990-992. https://doi.org/10.1253/circj.71.990
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