Ventricular Arrhythmias in Takotsubo Cardiomyopathy

Clinical Characteristics of Takotsubo Cardiomyopathy

The incidence of TC is estimated at 2% of patients initially suspected of an acute coronary syndrome, ^{, ,} but its diagnosis is increasing over time. TC patients are predominantly female, accounting for 80% to 100% of cases in different series. ^{, ,} The women are typically postmenopausal, with peak incidence in the seventh and eighth decades of life. Chest pain, similar to that experienced with angina, and dyspnea are the most common presenting symptoms. The symptoms and signs are similar to those seen in other acute cardiac conditions characterized by acute myocardial ischemia or heart failure and hence do not help in the differential diagnosis.

TC is characterized by decreased LV ejection fraction (LVEF) on presentation and, generally, recovery of normal systolic function occurs over days to weeks. The typical wall motion abnormality (hypokinesis to dyskinesis) involves the apical and midventricular segments, with the distribution extending beyond a single epicardial coronary distribution ( Fig. 93.1 ). Other patterns of regional wall motion abnormalities include the midventricular and reverse variants. Transient right ventricular (RV) systolic dysfunction may coexist in approximately 30% to 50% of patients and is associated with lower LVEF, greater likelihood of acute heart failure, and longer hospitalization. The RV apex is most frequently involved, and the regional wall motion abnormalities resolve over time. Acute heart failure occurs in approximately 40% of patients, and cardiogenic shock necessitating intraaortic balloon counterpulsation occurs in up to 10% to 20% of cases. ^, Other complications include dynamic LV outflow tract obstruction and acute mitral regurgitation because of transient valve dysfunction. Rare complications include thrombus formation in the ventricle and cardiac rupture. ^{, ,} The lack of a diagnostic test and the heterogeneity in clinical presentations necessitate the use of diagnostic criteria that encompass the broadest defining features of TC. The Mayo Clinic diagnostic criteria have been widely used and are based on an expert consensus.

Virtually all patients have elevated blood levels of cardiac troponin, and the great majority have an elevation of creatine kinase–MB fraction. The troponin T levels peak over the first 24 hours followed by a gradual fall, although the peak levels are significantly lower than those seen in ST segment elevation MI. TC patients usually have either normal coronary arteries or nonobstructive coronary artery disease; however, obstructive disease may coexist in a small proportion of patients. ^, Cardiac magnetic resonance imaging (MRI) is useful in differentiating TC from acute MI and myocarditis because, typically, the TC patients do not demonstrate delayed gadolinium enhancement. The vast majority of patients with TC have good prognosis. In-hospital mortality in older studies has been reported to be approximately 2%, ^, but more recent studies have found rates closer to 4%, similar to that of an acute MI. Among those who make a recovery and are discharged, long-term survival in an earlier cohort was reported to be similar to that for the age- and gender-matched population. In another study, increased mortality in the first year after the index event was noted; however, all the deaths were noncardiac (mostly because of cancer). More recently, it has been suggested that the mortality over 10 years is similar to those with acute coronary syndrome. Recurrence rates have been estimated at 1% to 2% per year. ^,

Electrocardiographic Changes

The ECG findings at presentation are often those associated with myocardial ischemia or an injury pattern. ST segment elevation occurs in approximately 30% to 50% of cases. Other findings include deep TWI, ST segment depression, anterior Q waves, bundle branch block, and minor nonspecific abnormalities; furthermore, in some patients the ECG may be normal. ^{, , , , ,}

The ECG changes are dynamic and are likely related to the magnitude of ventricular dysfunction and subsequent recovery. In the InterTAK Registry, ST segment elevation was present in 44%, T wave inversion in 41%, ST segment depression in 8%, and left bundle branch block in 5%. TC is associated with less ST segment elevation compared with anterior MI but with involvement of a greater number of leads and a greater frequency of involvement of limb leads.

Abnormal Q waves and reciprocal changes are less frequent and transient. Various ECG criteria have been proposed to differentiate ST segment elevation MI from TC, but none have sufficient accuracy to be used in clinical practice. ^,

In the subacute phase (days 2–3), if present, the ST segment elevation resolves. TWI is frequently observed and is more widespread and deeper compared with that in patients who sustain anterior MI. The TWI often progresses and deepens over time, with the negative peak usually occurring 2 to 3 days after admission. The TWI subsequently diminishes; however, in some patients, a second phase of TWI may develop that lasts for days to weeks, even after systolic function has recovered.

QT interval prolongation, which can be extreme, is also a common finding, and it follows a time course similar to that of the TWI, with a peak occurring at 2 to 3 days after admission. ^, The frequency ranges from 50% to as high as 100% in various case series. ^, The QT interval recovers over days in conjunction with resolution of the TWI. In patients with a biphasic pattern of TWI, the QT interval lengthens again but not to the extent seen during the subacute phase. The precise time course of QT interval recovery is not well defined, but repolarization changes can persist for weeks and beyond the period of wall motion recovery. ^, QT interval prolongation can lead to phase 2 reentry resulting in polymorphic ventricular tachycardia and may be a prognostic marker for sudden cardiac death.

Migliore et al. have proposed that myocardial edema, which occurs frequently in TC, may be the cause of the subacute ECG repolarization abnormalities. ^, They cite the following facts: (1) There is a parallel time course for the development and resolution of ventricular repolarization abnormalities and myocardial edema, (2) a correlation is present between the extent of ECG changes and the magnitude of edema, and (3) in some cases there is colocalization of the repolarization abnormalities on the ECG and regional distribution of myocardial edema.

The aforementioned ECG patterns described relate to the common apical ballooning variant of TC. Whether the same is true for other less frequently occurring variants is not clear, although some studies suggest that differences may exist.