**9. Diagnosis**

#### **9.1. Laboratory investigations**

The measurement of cardiac enzymes such as serum troponin and creatinine kinase is essential to the diagnosis of the Takotsubo syndrome. Although, cardiac troponin levels are elevated in most patients with TTS, the rise in its levels is disproportionately low relative to the extent of regional wall-motion abnormality and cardiac dysfunction [24, 35]. In contrast, elevated values of cardiac natriuretic peptides, such as pro-BNP and NT-proBNP, serve as a better correlate for degree of ventricular wall dysfunction in the acute phase of TTS [36–38]. Normal values of NT-proBNP are extremely rare in Takotsubo syndrome, thus helping it serve as a valuable marker of myocardial deterioration and recovery.

Recent studies have suggested the potential of circulating microRNAs to differentiate between TTS and STEMI patients; however, conclusive research is needed to establish this as a routine diagnostic biomarker [39].

#### **9.2. Electrocardiography**

The acute phase of TTS is characterised by ECG abnormalities such as ST-segment elevation, ST-segment depression, new left bundle branch block, Q-waves, T-wave inversions and significant QT-interval prolongation developing 24–48 hours after onset. These changes are reflected in almost 95% of all patients diagnosed with the Takotsubo syndrome [40]. It is not uncommon for the QTc-interval to be prolonged more than 500 ms, predisposing the patient to torsades de pointes and ventricular fibrillation, see **Figure 1**.

#### **9.3. Echocardiography**

The initial assessment of LV morphology and function with the use of thoracic echocardiography is inherent to the diagnostic cascade of Takotsubo syndrome. Standard, colour and tissue Doppler techniques assist in the identification of anatomical variants, monitor recovery and help detect potential complications such as left ventricular outflow tract obstructions, RV involvement, mitral regurgitation and cardiac rupture [41–43].

The echocardiographic examination of patient in the acute phase of TTS shows a large area of poorly functioning myocardium extending beyond the territory of a single coronary artery.

**Figure 1.** Electrocardiogram of TTS patient with acquired long QT syndrome at admission.

The typical regional wall-motion abnormality is found in the apical to mid segments of the left ventricle, extending equally into the anterior, inferior and lateral walls. This 'circumferential pattern' is considered the hallmark of TTS. In certain cases, the use of a contrast agent for LV opacification eases assessment of the RWMA, while, myocardial deformation imaging with the speckle tracking method has been used to demonstrate a transient circular impairment of not only longitudinal LV function, but also circumferential and radial LV function [44–46].

#### **9.4. Cardiac magnetic resonance**

of NT-proBNP are extremely rare in Takotsubo syndrome, thus helping it serve as a valuable

Recent studies have suggested the potential of circulating microRNAs to differentiate between TTS and STEMI patients; however, conclusive research is needed to establish this as a routine

The acute phase of TTS is characterised by ECG abnormalities such as ST-segment elevation, ST-segment depression, new left bundle branch block, Q-waves, T-wave inversions and significant QT-interval prolongation developing 24–48 hours after onset. These changes are reflected in almost 95% of all patients diagnosed with the Takotsubo syndrome [40]. It is not uncommon for the QTc-interval to be prolonged more than 500 ms, predisposing the patient to torsades de

The initial assessment of LV morphology and function with the use of thoracic echocardiography is inherent to the diagnostic cascade of Takotsubo syndrome. Standard, colour and tissue Doppler techniques assist in the identification of anatomical variants, monitor recovery and help detect potential complications such as left ventricular outflow tract obstructions, RV

The echocardiographic examination of patient in the acute phase of TTS shows a large area of poorly functioning myocardium extending beyond the territory of a single coronary artery.

marker of myocardial deterioration and recovery.

pointes and ventricular fibrillation, see **Figure 1**.

involvement, mitral regurgitation and cardiac rupture [41–43].

**Figure 1.** Electrocardiogram of TTS patient with acquired long QT syndrome at admission.

diagnostic biomarker [39].

222 Interventional Cardiology

**9.2. Electrocardiography**

**9.3. Echocardiography**

The use of cardiac magnetic resonance imaging (CMR) has been advocated in the first 7 days (acute phase) to accurately assess both LV and RV regional function and demonstrate the typical patterns of RWMA, permitted by the full visualisation of the ventricles in the main long axes. Cardiac magnetic resonance imaging has a distinct advantage over standard transthoracic echocardiography in offering better views of the right ventricle and in detection of apical LV thrombi [47].

In CMR, tissue characterisation of acute myocardial changes occurring in the TTS patient shows a high signal intensity with a diffuse or transmural distribution, indicative of oedema of the hypokinetic LV myocardium. This oedema corresponds to the region of the wall-motion abnormality and is not restricted by the boundaries of a single coronary artery territory, unlike an acute myocardial infraction in which oedema is always coherent with a vascular distribution [42].

Late Gadolinium Enhancement (LGE) is typically absent in both the acute phase as well as follow-up, serving as an important criterion to distinguish between AMI and TTS. Recently, there has been some debate concerning the presence of minor LGE in the acute phase; however, this is dependent on the threshold of signal intensity used to define LGE presence [48, 49], see **Figure 2**.

**Figure 2.** Magnetic resonance tomogram of patient with biventricular TTS showing a left ventricular thrombus formation as a related complication to TTS.
