The electrocardiographic paradox of tako-tsubo cardiomyopathy–comparison with acute ischemic syndromes and consideration of molecular biology and electrophysiology to understand the electrical-mechanical mismatching☆

From the electrocardiographic (ECG) point of view, the tako-tsubo cardiomyopathy (TTC) behaves like an acute subepicardial circumferential ischemic syndrome. The electrical manifestations are significantly different from those of acute transmural segmental ischemia, in which the ECG primarily expresses the electrophysiologic and metabolic changes occurring in the subepicardial layer. In comparison with transmural anterior ischemia and despite acute contraction impairment (circumferential middle and apical dyskinesis and basal hyperkinesis), in TTC there is typically only moderate ST elevation in the precordial leads.

This paradox can be understood by taking into consideration the molecular biology and basic electrophysiology. In the senescent female with hypoestrogenemia, the subepicardium is almost totally unprotected against “adrenergic storm.” In the fertile female, estrogen plays the pivotal role of protecting the myocardium at many levels of the metabolic cascade, such as in the regulation of the presynaptic release of adrenergic substances and by increasing the release of adenosine. There is consequental increase of the adenosine triphosphate (ATP)–sensitive K+ channels, thus regulating the inward flow of Ca2+ toward the sarcoplasmic reticulum. The ATP-sensitive K+ channels hyperpolarize the subepicardial cells during extremely aggressive situations such as ischemia and adrenergic storm. The hyperpolarization of the subepicardium is manifested in the ECG by tall, peaked T waves, indicating an increase of the repolarization gradient between the subendocardial and subepicardial layers. In the absence of estrogen, there are severe decreases in the concentration of adenosine and in the density of the ATP-sensitive K+ channels. The subepicardial myocytes cannot be hyperpolarized, and the adrenergic storm is manifested by moderate ST-T elevation. Furthermore, the very rapid appearance and disappearance of a Q wave are “against the rules.” This is a classical example of electrical stunning, that disappears before mechanical stunning in which contraction is typically recovered only after 1 week.