**4. Diagnostic modalities**

Traditionally, transthoracic echocardiography is one of the first non-invasive diagnostic tools utilized in patients with suspected Takotsubo syndrome. Transthoracic echocardiography depicts LV geometry, LV function and anatomic variants. In recent years, assessing global longitudinal strain (GLS) using speckle-tracking echocardiography, has become a sensitive marker for myocardial dysfunction with increasing prognostic utility (**Figure 1**). GLS is a simple parameter that expresses longitudinal shortening as a percentage (change in length as a proportion to baseline length) [7]. Not only does strain pattern help differentiate acute TTS from ACS, but it can help identify persistent LV dysfunction even after recovery of ejection fraction (EF) [9]. There is an increasing population of patients that have continued abnormal GLS even after complete LVEF recovery. The clinical implications of persistently abnormal GLS with association to recurrence of TTS has yet to be investigated.

Cardiac Magnetic Resonance (CMR) has become an increasingly utilized imaging tool in patients with TTS. Like echocardiography, CMR can visualize wall motion abnormalities and identify areas of LV dysfunction. More significantly, CMR can identify the presence of reversible (edema) and irreversible myocardial damage (scarring). CMR can also identify potential complications of TTS, such as LV outflow tract (LVOT) obstruction, valve disease, pericardial effusion, and LV thrombus. In TTS, the hallmark features of inflammatory injury and edema are visualized on CMR as signal hyperintensity in the T2- weighted sequences. Not only can the extent of edema

#### **Figure 1.**

*Global longitudinal strain plot on transthoracic echocardiography with 'evil eye' pattern seen in Takotsubo syndrome.*

be quantified with more diagnostic accuracy, CMR has the capability to identify potential areas of irreversibility. To assess for the presence/absence of scarring tissue, short and long axis acquisitions are performed after contrast injection using an inversion-recovery gradient echo sequence to help identify late gadolinium enhancement (LGE) (**Figure 2**). Though not common in TTS, LGE can identify areas of contraction-band necrosis often seen in endomyocardial biopsies in TTS patients [10].

Cardiac imaging advances not only assist in monitoring recovery and identifying persistent injury; they can also aid in elucidating pathogenesis of Takotsubo syndrome. Microcirculatory dysfunction as a pathologic mechanism of TTS has been previously underrecognized due to lack of imaging modalities. New studies involving single-photon emission computed tomography perfusion have shown a decrease in tracer uptake during the acute phase of TTS and a return to normal at follow-up, suggesting a role for coronary microvascular dysfunction as a trigger of myocardial ischemia in this condition. Additionally, perfusion CMR has corroborated disruptions in coronary microcirculation in the absence of obstructive epicardial disease in patients with TTS.

### **5. Treatment**

The treatment for Takotsubo syndrome is largely empiric and supportive. Angiotensin-converting enzyme inhibitors (ACE-i), angiotensin II receptor blockers (ARB), and/or beta-blockers are often utilized in stable patients. Beta-blockade initiated in the acute phase of TTS has been associated with a statistically significant higher long-term survival with a greater benefit seen in hypertensive patients or those who developed cardiogenic shock [11]. Neither beta-blockers nor ACE-i/ARB were shown to reduce the recurrence of TTS [12]. There exists a plethora of evidence regarding optimized medical treatment for patients with reduced LV function due to other etiologies. Again, few data exist regarding optimum regimen for patients with TTS.
