QTc interval in takotsubo cardiomyopathy: How the activation of insular cortex interacts

To the Editor: We read the interesting review article by Marafioti et al.,1 who reported on the association of prolonged QTc interval with takotsubo cardiomyopathy (Tc) in relation to right insular cortex (Ic) activity. Several points should be taken into account when interpreting the theory presented by Marafioti et al.1 First, in a dog model, adjusted QT interval at a high parasympathetic or low sympathetic tone was significantly longer than that at the low parasympathetic or high sympathetic tone.2 In Tc, ST-segment elevations were observed immediately after the onset. Thereafter, the T wave became progressively more negative with the QT interval prolonged.3 Although one possible mechanism underlying Tc was increased sympathetic nervous system (SNS) activity,4 the T-wave inversion and QT-interval prolongation were suggested to be observed in the phase of denervated SNS activity.5 Although Marafioti et al1 concluded that QTc prolongation in Tc was derived due to higher SNS activity, the point of time-course electrocardiography changes in relation to the autonomic nervous system was not taken into account. Second, recent studies have supported the notion that the cardiovascular system is regulated by a cortical network consisting of the Ic, anterior cingulate gyrus, and amygdala.6 In an earlier study,7 the right hemispheric inactivation induced an increase of high-frequency heart rate (HR) and blood pressure (BP), and the left hemispheric inactivation induced an increase in low-frequency HR and BP in patients with drug-refractory epilepsy. In addition, Oppenheimer et al8 identified a site of cardiac representation within the human Ic. Tachycardia or pressor effects were significantly more common after stimulation of the right Ic. The degree of tachycardia was significantly greater on stimulation of the right anterior than the right posterior Ic.8 Thus, the anterior portion of the right Ic might have a strong association with SNS activity. In the article by Marafioti et al.,1 although the relationship between right Ic and SNS was suggested, there was no description about the relationship between Ic and QTc interval in relation to anterior vs posterior Ic of the left hemisphere. Until now, there have been few reports assessing the Ic and QTc interval according to autonomic nervous system activity in Tc. The theory presented in the article by Marafioti et al1 would be much more important if the exact mechanism underlying that relationship were provided.