Current hypotheses regarding the pathophysiology behind the takotsubo syndrome

- Five main hypotheses have been proposed regarding the pathophysiology of takotsubo.
- Excess regional wall tension links takotsubo to ischemic conditioning phenomena.
- Coronary vascular spasm and spontaneously dissolved thrombi imply causative perfusion defects.
- Local catecholamine release is contradicted by reports of systemically administered catecholamine inducing takotsubo.
- β2-adrenoreceptor/Gi-dependent cardiodepression is theoretically sophisticated but currently unsupported.
- The hypotheses are not mutually exclusive but in some ways complementary to each other.

Takotsubo syndrome is an increasingly recognized acute cardiac affliction which is characterized by severe regional left ventricular dysfunction that cannot be explained by one or more occlusive culprit lesions of a coronary artery. A preceding somatic and/or emotional stressor can be identified in a majority of these patients and older women are overrepresented among the afflicted.Catecholamine levels are elevated in patients with takotsubo and exogenous catecholamine administration may cause or exacerbate the condition. Hence, catecholamines appear implicated in the pathogenesis. However, beyond catecholamine the pathogenesis of the takotsubo syndrome is unclear. Five distinct hypotheses have been postulated which attempt to explain why specific regions within the left ventricle are affected in takotsubo.In this manuscript we critically review these hypotheses in light of the available data. We discuss how the different hypotheses may be complementary to each other and to which extent they are contradicting one another.