We are deluged by reports of the “rare” takotsubo syndrome (TTS) (as of November 15, 2012, there were 1,478 entries in PubMed using the search term “takotsubo” ), and while the reporting goes on, the pathophysiologic underpinning of the condition become muddier and muddier. The objective of this note is to gain the attention of clinicians who are destined to manage patients presenting with suspected TTS. Although the diagnosis of TTS is eventually made after a few hours to days of ambivalence in its differentiation from acute coronary syndromes (ACSs), we miss the opportunity to make a dent in our understanding of its pathophysiology, because of the varied and temporally haphazard application of our diagnostic techniques. We need to change our modus operandi.

Experience has shown that patients with TTS present with varying degrees (mild, moderate, severe) and types (hyperkinesia, hypokinesia, akinesia, dyskinesia) of transient regional wall contraction abnormalities (WCAs), with some patients showing different such abnormalities when experiencing recurrences of TTS. Also, it is conceivable that such WCAs are dynamic in the early course of TTS. Our imaging “snapshots,” implemented once or twice during hospitalization, cannot provide the full picture of what is taking place in these patients under our care. Certainly, invasive, risk-related, or expensive diagnostic procedures cannot be done more than once (or rarely twice). Coronary arteriography, contrast ventriculography, hemodynamic assessment, provocative testing for coronary vasospasm, evaluation for microcirculation impairment, nuclear myocardial perfusion and autonomic myocardial innervation imaging, cardiac magnetic resonance imaging, positron emission tomography, invasive electrophysiologic studies, and myocardial biopsies have provided all we currently know about TTS. However, we have reached an impasse in our quest to unravel the pathophysiology of TTS and its possible early dynamic evolution.

Where are we going from here? There are currently 5 “angles” that deserve our attention: (1) securing information about the time of onset of the illness (not necessarily its intensification, which led the patient to seek medical attention); (2) maintaining a high index of suspicion that we are dealing with TTS when evaluating a patient who has been exposed to any kind of stress, does not have risk factors for coronary artery disease, or is a postmenopausal woman; (3) implementing echocardiography immediately and repeatedly in the emergency department before and after coronary arteriography, daily during hospitalizations, and at follow-up (such repeat studies do not need to be complete or exhaustive, should focus on looking for WCAs of the left and right ventricles, and may be feasible with handheld devices); (4) measuring serum catecholamine values (particularly epinephrine) daily, starting in the emergency department, in view of recent information about the role of epinephrine in effecting left ventricular basal hyperkinesia and apical and medial hypokinesia, akinesia, or dyskinesia through preferential modulation of β ₂ -adrenergic receptor activation to stimulatory G protein–activated cardiostimulatory and G protein–activated cardioinhibitory pathways, in different myocardial territories ; and (5) implementing electrocardiography immediately and repeatedly in the emergency department, before and after coronary arteriography, daily during hospitalizations, as clinically warranted, and at follow-up, considering a recent insight that TTS results in transient attenuation of the electrocardiographic voltage (not seen in patients with ACSs) in the early phase of the illness, modulated by reversible myocardial edema as assessed by cardiac magnetic resonance imaging.