Identifying takotsubo cardiomyopathy

Background

Takotsubo cardiomyopathy (TC) was initially described in 1991 in 22 female Japanese patients who all had undergone severe stress and was named on the basis of the aspect assumed by the left ventricle during systole akin to a fishing pot with a round bottom and a narrow neck that is used for trapping octopuses in Japan (1-5). It accounts for approximately 1% to 2% of patients. Nearly 90% of the patients with TC were women and more than 95% of them were above the age of 50 (3) however the syndrome has also been observed in women as young as in their twenties and occasionally, men. 
Since it was initially described, Takotsubo cardiomyopathy has been referred to in the literature as apical ballooning syndrome (ABS) or « broken heart syndrome » and is considered among the four existing stress cardiomyopathies along with acute left ventricular dysfunction associated with either 1) subarachnoid hemorrhage 2) pheochromocytoma and exogenous catecholamine administration or 3) the critically ill (6) although the most recent diagnostic criteria for TS no longer excludes patients who develop typical ballooning in the setting of subarachnoid hemorrhage.

Clinical presentation and pathophysiology

Chest pain is the most common presenting complaint among patients with takotsubo cardiomyopathy. The second most common presentation is dyspnoea and other less frequent clinical presentations include cardiogenic shock, syncope and cardiac arrest.(2,3,8) The onset of TC is preceded by a stressful event, either emotional - unexpected death of a relative, financial crisis, catastrophic medical diagnosis etc. or physical - exhausting work, trauma, exacerbation of a systemic disorder, etc. in around 65% of cases. In approximately 35% of cases no trigger can be identified.(3,8)
The impairment in left ventricular function seen in Takotsubo cardiomyopathy is transient, and typically recovers within 2 months of initial presentation. The underlying pathophysiology for Takotsubo cardiomyopathy remains unclear; however several mechanisms have been proposed including the following: multivessel epicardial spasm (9) acute microvascular spasm (10-11) catecholamine induced myocardial stunning (12) transient obstruction of the left ventricular outflow tract (14-15) or aborted myocardial infarction due to left anterior descending artery occlusion by a clot and spontaneous thrombus lysis. This could be the case in patients with long left anterior descending arteries that wrap around the apex and supply a large area of the inferior wall.(16)

Diagnosis and treatment

The updated diagnostic criteria from the Mayo Clinic, new compared to a previous article on the topic in Vol8 of the e-journal, are the following:

1. Transient hypokinesis, akinesis, or dyskinesis of the left ventricular midsegments with or without apical involvement; the regional wall motion abnormalities extend beyond a single epicardial vascular distribution; a stressful trigger is often, but not always present.
2. Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture. 
3. New electrocardiographic abnormalities (either ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin.
4. Absence of peochromocytoma or myocarditis. In both of the above circumstances, the diagnosis of ABS should be made with caution, and a clear stressful precipitating trigger must be sought.

To be noted, the release of the myocardial necrosis markers, troponin I or T and the MB fraction of CK are usually mildly raised in the majority of patients (3) as well as catecholamines, dihydroxyphenylalanine, epinephrine, norepinephrine (or adrenaline and noradrenaline in US English) and dopamine.

The most frequent electrocardiographic changes are ST-segment elevation, usually in the precordial leads and T wave inversion. Other ECG changes include QT prolongation and conduction disturbances.(3,8) It has been suggested that the absence of reciprocal changes and abnormal Q waves on the ECG may be helpful in differentiating between patients presenting with Takotsubo cardiomyopathy and those with anterior MI secondary to occlusion of the proximal left anterior descending artery.(17)
Echocardiography and left ventriculography will reveal marked left ventricular dysfunction dramatically improving within days or weeks. More specifically, the wall motion abnormalities extend beyond the distribution of any single coronary artery and include moderate to severe dysfunction of the mid-segment and the apical segment of the left ventricle with sparing and usually hyperkinesis of the basal segment.(3)
Cardiac magnetic resonance can demonstrate preserved myocardial viability, rule out myocardial infarction or myocarditis and evaluate the right ventricle as well in detail if its involvement is suspected.(18-19) 
Coronary angiography allows for early distinction from acute coronary syndrome by offering no evidence of significant coronary artery stenosis (more than 50%). (20) As the clinical, electrocardiographic and laboratory presentation of TC are similar, both entities are in general only distiguishable by coronary angiography.

However, there are no guidelines for the treatment of Takotsubo cardiomyopathy furthermore treatment is primarily empirical and needs to be individualised for each patient. Nevertheless, it should initially managed according to the guidelines for the diagnosis and treatment of acute coronary syndromes. Once the diagnosis of ABS is made, supportive care usually leads to spontaneous recovery.(8) Thus, management of TC is a two-step process: 

Step 1: Diagnosis must involve: 1) High index of suspicion 2) Quick but thorough medical history 3) ECG, Troponin and echocardiography 4) Coronary angiography 
Step 2: Supportive treatment will be 1) beta blockers for initial treatment (21) 2) ACE inhibitors or angiotensin II blockers because TC is associated with transient LV dysfunction.

Complications and prognosis

For haemodynamically unstable patients, echocardiography should rule out dynamic left ventricular outflow tract obstruction. If present, it should be cautiously treated with beta blockers aiming to reduce the contractility of the basal segment. Treatment with inotropes is contraindicated in this situation.
If low blood pressure is secondary to cardiogenic shock, treatment with inotropes and intra-aortic balloon counterpulsation is indicated.(8) Right ventricular involvement should also be ruled out in these cases.(19)
If there is suspicion of thrombus formation in the akinetic apex and irrespective of the heart rhythm, anticoagulation therapy should be given.(22) Duration of treatment should be at least 3 months as in patients with mural thrombi formation following a large anterior myocardial infarction.
Complication rates are close to 20% and include shock, thrombus formation, heart failure, cerebral vascular accident, ventricular tachycardia, left ventricular rupture and/or ventricular septal rupture.
Pulmonary oedema, cardiac arrhythmias and cardiogenic shock are life threatening complications to be treated according to relevant guidelines. Routine use of adenosine and endothelin antagonists is not justified at present but their role remains to be established in future trials. Long-term therapy with beta-blockers is encouraged by some centres aiming in this way to reduce the likelihood of  recurrence.(8) Here you may find a case-study demonstrating the importance of early diagnosis, or this case study for the importance of asessing LVOT obstruction during the early phase of Tako-Tsubo cardiomyopathy.

The prognosis of patients with takotsubo cardiomyopathy is generally favourable (8). In-hospital mortality is low, less than 2% and recurrence rate is around 10% (3). However, in a study by Lee et al mortality rate was significantly higher. It was found to be 16 % during hospitalisation. (23)age

Conclusion:

Takotsubo cardiomyopathy can be included among the differential diagnoses of patients who present to the emergency department with symptoms suggestive of acute coronary syndrome. Emergency department physicians should liaise with the interventional cardiologists to rule out acute coronary syndromes and initiate early and optimal supportive treatment.