Plasma Epinephrine Level and its Causal Link to Takotsubo Syndrome Revisited: Critical Review with a Diverse Conclusion

Takotsubo syndrome (TS) is a recognized acute cardiac syndrome with a clinical presentation resembling that of an acute coronary syndrome (ACS). The defining feature of TS is the reversible left ventricular wall motion abnormality (LVWMA), which has a unique circumferential pattern resulting in a conspicuous ballooning of the left ventricle during systole, and extending beyond the coronary artery supply territory. The pathogenesis of TS is still elusive and several pathophysiological mechanisms have been proposed. A common portrayal of the syndrome in the literature is that the disease is characterized by massive surge of plasma catecholamines including epinephrine. Based on the assumption of massive plasma epinephrine elevation, some investigators hypothesized that the circulatory plasma epinephrine plays a pivotal role in the pathogenesis of TS. One typical such hypothesis is epinephrine induced switch in signal trafficking causing apical or mid-apical ballooning in TS. In-depth analysis of the literature reveals that no study with certainty has shown “massive” plasma epinephrine elevations in TS. Furthermore, the literature evidences challenging the epinephrine-induced switch in signal trafficking are substantial. In this review, sufficient data, indicating that the plasma epinephrine in TS is either normal or moderately elevated in all studies, are provided. Noteworthy, epinephrine may act as a trigger factor for TS-induction but there is no evidence for a direct causal link between epinephrine and TS.