Left Ventricular Outflow Tract Obstruction
As a consequence of myocardial stunning of the apical segments and hypercontraction of the basal LV myocardium, a dynamic intraventricular pressure gradient due to mitral valve systolic anterior motion may develop in the acute phase. Significant LV outflow tract obstruction with gradients ranging from 20–140 mmHg have been observed in 10–25 % of patients, often accompanied by mitral regurgitation.28,53,56 A mid- ventricular or LVOTO gradient >25 mmHg is considered haemodynamically significant and ≥40 mmHg is a high-risk factor. Abnormal Q waves in the electrocardiogram, hypotension and cardiogenic shock are more frequent in these patients. Normally, the outflow tract obstruction resolves spontaneously over a few days.
Mitral Regurgitation
Acute mitral regurgitation is another potentially serious complication occurring in 14–25 % of patients.57,58 LV ejection fraction is lower and pulmonary artery pressure higher in cases with significant regurgitation and these patients present more frequently with acute heart failure or cardiogenic shock. Two independent mechanisms may cause acute mitral regurgitation: systolic anterior motion of the mitral valve in association with dynamic LV outflow tract obstruction and apical tethering of the subvalvular mitral valve apparatus.59 In most cases the mitral regurgitation improves with normalisation of LV function, which may be delayed compared with patients without acute mitral regurgitation.
Cardiogenic Shock
Cardiogenic shock, primarily due to acute LV dysfunction, may be aggravated by RV involvement, LV outflow tract obstruction or acute mitral regurgitation. Echocardiography plays an important role in determining the mechanism of cardiogenic shock in order to apply an appropriate therapy. The mortality of cardiogenic shock in Takotsubo syndrome is high (between 17–30 %).8,41,53,55,60
Arrhythmias
New onset of atrial fibrillation has been reported in 5–15 % of patients with Takotsubo syndrome.8,55,61,62 During the acute phase of Takotsubo syndrome, ventricular arrhythmias occur in 4–9 % of patients. Resuscitation as a result of cardiac arrest, which may be the initial presenting symptom, has been reported in 4–6 % of cases. Bradycardia due to atrioventricular block and asystole has been described in a limited number of patients (2–5 %).
Thrombus formation
Thrombus formation may be detected within the akinetic ventricular apex in 2–8 % of Takotsubo syndrome patients, occasionally resulting in stroke or arterial embolism.63
Pericardial Effusion
Acute pericarditis with recurrent chest pain, reappearance of ST-segment elevation and a small amount of pericardial effusion has been observed in some patients during the recovery phase of Takotsubo syndrome.64–66
Ventricular Wall rupture
Mechanical complications including rupture of the ventricular free wall or perforation of the interventricular septum are seen in less than 1 %.67,68
Mortality
Initial small case series have reported mortality rates varying from <1–12 %.17,69 In large studies and registries, in-hospital mortality is lower and has been observed in 2–5 % of the patients with Takotsubo syndrome, mainly caused by refractory cardiogenic shock or ventricular fibrillation.8,53 A recent meta-analysis evaluating 37 studies with 2,120 patients reported an in-hospital mortality of 4.5 %70 and this figure matches the 4.2 % in-hospital mortality reported in the large NIS- USA Takotsubo syndrome cohorts in 2008 to 2009.29,30
Recurrence
The reported incidence of recurrence varies between 3.5–22 % of cases from different series.13,16,41,55 If a patient has a recurrent episode of Takotsubo syndrome, they are once more at risk of complications. Prognosis should be individualised considering the likelihood of recurrence, triggering event and co-existing medical conditions. If an individual has a recurrent episode then long-term clinical follow up should be considered.
Long-term Prognosis
Data regarding long-term prognosis of patients with Takotsubo syndrome are limited, but initial reports from limited cohorts suggest prognosis may be similar to acute myocardial infarction, but driven by non-cardiovascular causes and higher than the healthy age- matched population.
Most patients settle rapidly following the acute episode and become asymptomatic. There is increasing evidence of physiological abnormalities persisting beyond the timeframe when resting contractile abnormalities have normalised macroscopically. There is also growing recognition of a subgroup of patients with persistent cardiac symptoms following the acute episode.71 These include angina, exertional breathlessness, palpitation and/or a tremulous anxiety state, reflecting heightened sympathetic tone. Although the coronary arteries are unobstructed and ventricular function has recovered macroscopically, it is helpful to document objective evidence of ongoing cardiac abnormalities to reassure the patient and to guide treatment. Twenty-four-hour Holter ECG monitors to assess for atrial arrhythmias or inappropriate sinus tachycardia (continuous or paroxysmal) and 24-hour ambulatory blood pressure monitors may be helpful for detecting transient and inappropriate hypertensive episodes. Persisting ECG changes and sometimes other evidence of autonomic disturbance can provide objective evidence and exclude non-cardiac explanations for ongoing symptoms.
Clinical Management
General Considerations
One of the most important criteria for the diagnosis of Takotsubo syndrome is eventual spontaneous restoration of normal cardiac function. The major objective of in-hospital treatment should be supportive care to sustain life and to minimise complications during recovery. In mild cases, either no treatment or a short course of limited medical therapy may be sufficient. In severe cases complicated by progressive circulatory failure and cardiogenic shock, the patient should be considered for early mechanical support as a ‘bridge-to-recovery’.