We thank John Madias for his interest in our article about differences and similarities in electrocardiogram (ECG) between Takotsubo cardiomyopathy (TC) and acute coronary syndrome (ACS). He successfully focuses the attention on a couple of issues we would like to stress.

As already pointed out, widespread T-wave inversion and QTc prolongation represent risk factors for malignant ventricular arrhythmias, and TC has also been proposed as an acquired, although temporary, cause of long QT syndrome. Nonetheless, cumulative incidence of ventricular arrhythmias in our population was low, with 2 patients in the TC group and 1 patient in the ACS group (4% vs 2%; p = NS). One patient in each group presented with cardiac arrest due to ventricular fibrillation and was subsequently diagnosed with TC. Another patient developed a torsades de pointes episode 3 days after TC diagnosis. This is somewhat lower than the 8% in-hospital incidence already described in a similar population. It must be said, however, that this lower-than-expected incidence of ventricular arrhythmias could depend, at least in part, on the very high prevalence of preventive therapy with either β blockers or amiodarone in patients with TC (87% and 13%, respectively). Supporting this hypothesis, Madias et al reported a similar prevalence of β-blocker therapy (86%) in the subgroup of patients who did not experience ventricular arrhythmias.

The most interesting question raised by Prof. Madias is whether QRS amplitude could be used as a potential marker of TC. In his commentary, he writes that “A new ECG insight (transient attenuation of the QRS complexes) has just been reported, with some mechanistic association with myocardial oedema, a prominent pathologoanatomic correlate of TC.” Unfortunately, as intriguing as this hypothesis may be, there are still some gaps that need to be filled to demonstrate the utility of QRS amplitude as a preangiographic marker of TC. First, although there is robust evidence that myocardial edema detected by magnetic resonance is associated with transient systolic dysfunction in TC, its role as a cause of low-voltage ECG and amplitude attenuation has only been postulated. Second, ongoing pharmacologic therapies, namely, β blockers, angiotensin-converting enzyme inhibitors, and diuretics could act as potential confounders, modifying myocardial edema per se and other concomitant causes of low voltages such as peripheral edema and pulmonary congestion. Third, although low-voltage ECG has been described in at least 50% of patients with TC, and attenuation of electrocardiographic voltage in >70%, current prevalence of such abnormalities in patients with ACS has never been described, and we are verifying right now, as Prof. Madias suggested, eventual differences between TC and ACS in our patients. Only once all these issues have been dealt with, specific cutoffs for QRS amplitude and QRS attenuation should be calculated, and those markers validated in different ethnic groups according to the demonstrated variation in electrocardiographic presentation between Japanese and Caucasian patients. Until then, unfortunately, medical history and echocardiography remain the main weapons in our arsenal to raise clinical suspicion and coronary angiography the only tool to confirm TC diagnosis.