Takotsubo cardiomyopathy

Definition

Takotsubo cardiomyopathy(TTC) also called stress cardiomyopathy, apical ballooning syndrome, or broken heart syndrome—is a condition in which left ventricular (LV) dilatation and acute transient systolic heart failure occur, typically following an emotional or physical stressor.

According to ESC it belongs to a group of unclassified cardiomyopathies.

Etiology and Pathophysiology

Either emotinonal or physical stress can trigger and then cause Takotsubo cardiomyopathy.

The most common emotional triggers are death of a loved one, conflicts in relationships or work, fear, anger, and anxiety. 

Because of  the correlation of TTC with stressful triggers and the onset of Takotsubo cardiomyopathy, it is suspected that the adrenergic system plays an important role in its pathophysiology.

More specifically, catecholamines as epinephrine and norepinephrine, which are highly released during stressful events, are thought to lead to apical ballooning due to their direct myocardial toxicity or to disruptions to the cardiac microvasculature.

This catecholamine influx  is thought to promote vasospasm of the epicardial vessels as well as the cardiac microvasculature. These vasospasms contribute to an increased cardiac workload, which is then followed by a mismatch of supply and demand which ultimately leads to postischemic myocardial stunning.

In approximately three quarters of the patients it occurs at the apex of the left ventricle, producing the classic appearance of Takotsubo cardiomyopathy.

In 10% - 20% of patients, mid ventricular ballooning occurs.

In rare cases there has been observed basal, biventricular, or focal ballooning.

Ventricular ballooning produces transient ST-segment elevation on ECG, increased levels of troponin and B-type natriuretic protein (BNP), and a reduced ejection fraction resulting in acute systolic heart failure.

Image 1 Types of Takotsubo CMP

Shimizu M, Kato Y, Matsukawa R, Masai H, Shima T, Miwa Y, Yamashita T, Okita Y. Recurrent severe mitral regurgitation due to left ventricular apical wall motion abnormality caused by coronary vasospastic angina: a case report. J Cardiol. 2006 Jan;47(1):31-7. PMID: 16475471.

Clinical manifestation

Takotsubo cardiomyopathy presents very similarly to AMI.

The most common symptoms include chest pain, dyspnea and dizziness. Patients also may develop generalized weakness and occasionally syncope.

Physical examination findings of patients with Takotsubo cardiomyopathy are consistent with acute systolic heart failure and commonly reveal crackles, tachycardia, hypotension, narrow pulse pressure, and jugular vein distension.

Patients also may have a systolic ejection murmur due to an obstruction of the left ventricular outflow tract and mitral regurgitation resulting from ventricular ballooning.

ECG manifestations of TC are:
- ST elevations
- T inversions
- No reciprocal ST depressions
- absence of Q waves
- QT interval prolongation

How to differentiate between STEMI ? ST elevations in TTC are most commonly in precordial leads, ST elevations in TTC are usually not present in V1, in contrast ST elevations are usually present in aVR.

Diagnostic approach

The InterTAK Diagnostic Score predicts the probability of the diagnosis of a Takotsubo cardiomyopathy event and differentiates patients from Acute coronary syndrome (Image 2).

https://www.takotsubo-registry.com/takotsubo-score.html

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Echocardiography findings

1. Assessment of LV wall motion and systolic function

In the majority of cases, TTC typically involve the apical and mid-ventricular segments (defined as apical ballooning) in contrast to the basal segments, which are often hyperkinetic.

1. LV myocardial dysfunction of Takotsubo CMP is characterized by symmetric WMAs which involve the mid-ventricular segments of the anterior, inferior, and lateral walls (segment 7–12 based on the ASE guideline) over the apical segment (segment 13–17 based on the ASE guideline). All these features  are supportive of  the hypothesis of diffuse ventricular dysfunction secondary to myocardial stunning underlying the pathogenesis of TTC. 
2. The assessment of LV ejection fraction (EF) is also important in the management of TTC because LVEF and WMA are closely associated with major adverse events.
3. Myocardial deformation imaging with the speckle tracking method evaluates symmetrical patterns of WMS and demonstrates transient circular impairments of longitudinal, circumferential and radial LV functions as well as LV twist mechanics deficiency.These techniques may help to differentiate TTC from anterior AMI.

Video 1 Apical form of Takotsubo cardiomyopathy, A4C view - akinesis of the apex with severe motion wall abnormalities with adjacent segments - ⅔ of antero-lateral, infero-lateral wall and septum. Notable hyperkinesis of the basal segments with severely reduced EF 20-25%. Septal bulge is not causing SAM in this patient. 

Video 2 Apical form of Takotsubo cardiomyopathy, A2C view - apical ballooning.

Video 3 Apical form of Takotsubo cardiomyopathy, adjusted PLAX view with apex viewed

Video 4 Apical form of Takotsubo cardiomyopathy, the same patient after 7 months

Video 5 Takotsubo cardiomyopathy, A4C view - extensive severe hypokinesis of the apical ½ of LV, supranormal kinetics of basal parts and EF 30-35%.

Video 6 Takotsubo cardiomyopathy after 3 months from onset, A4C view - the same patient, the LV shows no significant regional wall motion abnormality and the EF has risen to 55-60%.

Video 7 Takotsubo cardiomyopathy, SCG with left ventriculography - characteristic apical ballooning - hypokinesis of the apex, apical ½ of the septum and anterior wall, ⅓ of the posterior and inferior wall.  Hypercontractility of the basal segments produces EF of 40%.

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Image 3 Global longitudinal strain (GLS) measured in a patient with apical form of Takotsubo CMP - GLS 10%, notable akinesis of the apex.

Image 4 GLS performed 4 days after onset of symptoms (left) and 7 months later (right). The kinetics of the LV have improved significantly and the systolic function returned to almost normal parameters.

2. Left ventricular outflow tract obstruction (LVOTO)

LVOTO (defined as an intraventricular gradient ≥25 mmHg) which is in this case caused by mitral valve systolic anterior motion.

This complication can trigger myocardial stunning of the apical segments and hypercontraction of the basal LV myocardium

Image 5 Severe left ventricular outflow tract obstruction (peak pressure gradient of 155 mmHg)

3. Acute Mitral Regurgitation (MR)

Acute MR is one of the serious complications. The patients with significant MR have lower left ventricle EF and higher values of pulmonary artery pressure, which can sometimes lead to acute heart failure and even to cardiogenic shock. It is therefore key to early detect these conditions by using echocardiography to provide appropriate management.

Video 8 TTE with moderate to severe MiR and high gradient in LVOT in a patient with TTC

Video 9 TTE on discharge in a patient with TTC (mild MiR, no SAM and LVOT obstruction)

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4. Thrombus formation

Thrombus in the akinetic ventricular apex is observed in some patients with Takotsubo cardiomyopathy and it occasionally leads to stroke or arterial embolism.

Always remember to check the apex properly.

Management

Current treatment recommendations are based on clinical experience and expert opinions.

All patients should be administered anxiolytics, if stable beta blockers and ACE inhibitors.

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Treatment of patients with profound heart failure and LVOT obstruction is challenging - inotropes are inefficient or even detrimental in the presence of LVOTO.
Volume expansion is problematic in the presence of pulmonary edema, diuretics or nitrates can exacerbate LVOTO, and beta-blockers are unsuitable for their hypotensive and negative inotropic effect.  

In such cases, mechanical circulatory support (MCS) remains the only therapeutic option.
- The axial-flow LV pump Impella may be a better choice of MCS type, because, in contrast to ECMO, it does not impede the LV filling.
- The optimal timing of MCS is still unclear. Clinical experience suggests that in the absence of complications, the Impella device should be left in place longer, even if the patient remains stable.

Adequate fluid management to optimize LV filling is crucial to the treatment of TC with CS.  Our case demonstrates the importance of precision fluid therapy guided by invasive hemodynamic monitoring with a Swan-Ganz catheter. Measurement of invasive hemodynamics can also be useful while weaning from MCS.

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References

1. Izumo M, Akashi YJ. Role of echocardiography for takotsubo cardiomyopathy: clinical and prognostic implications. Cardiovasc Diagn Ther. 2018 Feb;8(1):90-100. doi: 10.21037/cdt.2017.07.03. PMID: 29541614; PMCID: PMC5835647.

2. Jelena-Rima Ghadri, Ilan Shor Wittstein, Abhiram Prasad, et al. International Expert Consensus Document on Takotsubo Syndrome (Part II): Diagnostic Workup, Outcome, and Management, European Heart Journal, Volume 39, Issue 22, 07 June 2018, Pages 2047–2062.

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