Reply to the letter by Ando et al.

Abstract

We would like to thank Ando and coworkers for their interesting comment [1] on our paper entitled «Takotsubo and Takotsubo-like syndrome: a common neurogenic myocardial stunning pathway»[2]. In our clinical experience, stress-induced cardiomyopathy detected by the specific scintigraphic signature associating severe 123I-MIBG and 18FDG defects contrasting with normal 99mTc-Tetrofosmin perfusion could be assessed in a large variety of clinical settings, including the classical stress-induced catecholamine stunning (Takotsubo syndrome), epinephrine treatment or overdosing, trauma, acute medical or surgical illness including shock, intracranial bleeding and pheochromocytoma [3,4]. Other groups share similar experience, emotional cause being evidenced in a minority of cases, whereas physical stress owing to acutemedical illness or surgical procedure now represents the vastmajority of triggers.Whatever the triggering eventmight be, recent analysis clearly depicted a common pathophysiological underlying mechanism [5,6]. In the outstanding paper published by Paur and coworkers, biased agonism of epinephrine for β [2] Adrenoreceptor (AR)-G(s) at low concentrations and for G(i) at high concentrations underpins the acute apical cardiodepression observed in Takotsubo cardiomyopathy, the apical–basal gradient in β [2] AR accounting for the differential regional responses. Although we recognize that some issues remain to be addressed such as the high prevalence of postmenopausal women, the spatial distribution of beta adrenergic receptors, the potential involvement of microvascular dysfunction, it is now thoroughly demonstrated that endogenous or exogenous epinephrine activation of β[2] Adrenoreceptor G(i) protein pathway represents the common underlying mechanism for catecholamine induced myocardial stunning. Activation of this pathway was found to be antiapoptotic and cardioprotective whereas its inhibition triggered cardiac death [6]. In this animal model, the inability of norepinephrine at equivalent or higher doses to initiate acute apical dysfunction excludes coronary vasospasm or β1AR-mediated signaling as a primary effector, in agreementwith clinical observations showing that the apical dysfunction in Takotsubo cardiomyopathy extends beyond the territory of a single coronary bed [6]. Therefore, we do not believe that the exclusion of pheochromocytoma or intracranial bleeding as suggested by thewidespread criteria is still pathophysiologically relevant. Because a common underlying pathophysiological pathway has been evidenced, we propose that the term «catecholamine induced myocardial stunning» could be used in the future to refer to stress cardiomyopathy.