Tako Tsubo, where everything can be variable: or can it? The quest for solid grounds in a slippery entity

The recently described entity ‘Tako tsubo transient cardiomyopathy’ (TC) has gradually penetrated cardiologists' awareness, while coming to be recognized as allowing for an amazingly rich spectrum of varieties, as reviewed briefly by Hasdemir et al.1 On a rapid review, we can summarize the clinical features of such syndrome: Diagnostic tools include ECG, laboratory testing, and cardiac imaging: Current literature has generally failed to indicate a clear explanation for such amazing presentations: neither a clear pathophysiological mechanism nor a definite, ultimate cause, as yet. The frequent claim of the pivotal role of stress (hence, the new name of ‘stress-cardiomyopathy’) or of catecholamines, or microvascular dysfunction, besides the farfetched occurrence of transient coronary clots, has been proposed, but not substantiated by adequate demonstration. tako tsubo transient cardiomyopathy is most frequently seen in post-menopausal females, but not necessarily (some 10% occur in males and some 10% in pre-menopausal females); typically, it presents with a sudden onset, at the time of a stressful event, but it may also occur without any recognizable happening, in the life of the patient; it may present with subjective symptoms (more frequently dyspnoea, chest, or abdominal pain), but it may also occur without any symptoms or different symptoms at different times; it may severely compromise cardiac function, or not at all; some patient recover quickly and to normality (the majority), but some may be in shock, pulmonary oedema, or even die of it; it may occur only one time in the life of a patient (the typical event), or it may recur frequently, for some time-period. the ECG becomes altered consistently (it is the main clinical condition for its diagnosis), but sometimes it involves only T wave changes, sometimes segment (ST) elevation, sometimes ST depression, sometimes new Q waves; the left ventricular systolic function is constantly, but variably affected: initially and typically, the area of the main changes is the apical (with what has been named ‘ballooning’), but more recently many different patterns have been described (mid-ventricular, high-lateral, mid-inferior, basal, right ventricular). The present case would be the first case ever of global hypokinesia 1 ; cardiac enzymes elevation occurs frequently (not always!), but at very low levels (for the expected by the extent of ventricular dysfunction); myocardial perfusion imaging is typically abnormal only during the very early time (hours); coronary angiography shows consistently ‘normal epicardial’ vessels, if is performed after the first hour since onset; all testing modalities consistently indicate the return to normality, after the resolution of an episode: typically in a few days or weeks. Recently, our group at the Texas Heart Institute has first reported the experimental reproduction, in the Catheterization Laboratory, of the initial stages of TC by testing endothelial function by acetylcholine intracoronary infusion. 2 It seems that such testing in patient recovering from an episode of TC usually provokes intense, diffuse spasm of most coronary arteries, with subtotal stoppage of the flow—quite a rare occurrence outside this pathology. Simultaneously, echocardiographic monitoring indicated the appearance of apical dyskinesia; both events are totally and quickly reverted by intracoronary infusion of nitroglycerine. Additionally, in one patient with a history of spontaneous mid-ventricular variety of TC, acetylcholine induced the re-appearance of the same pattern of ventricular dysfunction, whereas all the coronary branches, with exception for the left anterior descending, showed severe diffuse spasm. While such observations need further confirmation in prospective, large multicenter trials, they seem to offer a clear and plausible common patho-physiological mechanism, in typical TC and its varieties. Endothelial dysfunction of the coronary bed (generalized or segmental) would appear to be the critical baseline abnormality in TC, whereas variable stimuli, such as emotional stress, anxiety, pains, and dobutamine infusion, would be the precipitating factors, more than the ultimate cause. It is possible to visualize a spectrum of TC forms, at this regards: from one form, in which baseline endothelial dysfunction is severe, and in which TC episodes occur recurrently, with minimal or not apparent stimuli, or, on the other side of the spectrum, episodes in which an overwhelmingly severe stressor could realize the condition for an isolated, single episode of TC. The case reported by Hasdemir et al.1 seems to be unique in different regards: We proposed that acetylcholine testing could be used as a method for establishing the definite nature of a given episode of transient left ventricular dysfunction (not all episode are necessarily TC, especially when unusual occurrences are involved during the event), but also to sub-classify TC episodes and patients (primary, severe endothelial dysfunction, vs. exposure to exogenous exceptional stressors) and their prognosis: the recurrence potential would be high, when the test can induce TC at low dosages, unlikely when the test is negative. We believe that prognosis and treatment can also be guided by such testing. the setting of an EPS routine study and treatment; the use of dobutamine/atropine infusion; the history of a prior episode of unexplained heart failure; the generalized pattern of transient left ventricular dysfunction; the (re-)occurrence of TC, in a premenopausal female.