Speculations on the pathophysiology of Takotsubo syndrome

Response to: Bathina J, Weiss S, Weintraub WS. Understanding the pathophysiology of apical ballooning syndrome: a step closer. Expert Rev Cardiovasc Ther 2015;13(1):5-8

I enjoyed very much reading the editorial by Bathina et al. [1], published in the January 2015 issue of Expert Review of Cardiovascular Therapy, in which the authors succeed succinctly and comprehensively in reviewing all the currently prevailing theories about the still elusive pathophysiology of Takotsubo syndrome (TTS). Thus, catecholamine-induced cardiotoxicity with all its plausible mediating mechanisms, via ‘stimulus trafficking’, microvascular dysfunction, left ventricular outflow tract obstruction (LVOTO), multivessel vasospasm, non-catecholamine mechanisms such as aborted myocardial infarction due to a plaque rupture with spontaneous recanalization, myocardial bridging and the possible genetic and hormonal links to TTS are briefly reviewed. The authors appropriately conclude that more work is needed to decipher this disease, and that the eventual elucidation of this puzzle will unravel a more complex multifactorial disease model than the one currently proposed.

I would like to bring to the attention of the authors the following issue, hoping to have their opinion on it: it is conceivable that TTS is a neuromechanical affliction caused by an autonomic adrenergic flare, resulting in intense basal hyperkinesis via local stimulation of the cardiomyocytes only adjacent to the cardiac nerve terminals [2], and not necessarily the circulating catecholamines, since cardiac autonomic innervation is more dense at the base than at the apex, with resultant apical, or apico-midventricular, akinesis initially, and then dyskinesis [3–6]. Such a mechanism could be at the root of ST-segment elevation, modest troponin release, microvascular dysfunction and myocardial edema [3–6]. Regarding the authors comment that ‘a large cohort published in 2008 showed that only 25% of the patients with TTS have LVOTO, which does not support this hypothesis completely, possibly lending to the conclusion that LVOTO obstruction is a consequence rather than a cause of TTS [7]’, it is possible that LVOTO, and many other particulars (e.g., levels of catecholamines) of TTS, may be much more prevalent at the inception of the illness, than later on (often 24–48 h), when the patients with TTS are assessed after their admission to the hospital. Animal models, and the early and frequent implementation of what is currently called ‘focused cardiac ultrasound’ by all members of caring team [8,9], may provide insights about what really happens early in the clinical course of TTS.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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