Friday, September 22, 2023
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Stress cardiomyopathy, also referred to as Takotsubo cardiomyopathy, is an increasingly recognized clinical syndrome characterized by acute reversible apical ventricular dysfunction. We hypothesize that stress cardiomyopathy is a form of myocardial stunning, but with different cellular mechanisms to those seen during transient episodes of ischemia secondary to coronary stenoses. In this syndrome, we believe that high levels of circulating epinephrine trigger a switch in intracellular signal trafficking in ventricular cardiomyocytes, from Gs protein to Gi protein signaling via the β2-adrenoceptor. Although this switch to β2-adrenoceptor–Gi protein signaling protects against the proapoptotic effects of intense activation of β1-adrenoceptors, it is also negatively inotropic. This effect is greatest at the apical myocardium, in which the β-adrenoceptor density is greatest. Our hypothesis has implications for the use of drugs or devices in the treatment of patients with stress cardiomyopathy.
In the 16 years since the first report by Satoh et al.,[1] the entity of stress cardiomyopathy (also termed Takotsubo cardiomyopathy, transient left ventricular apical ballooning syndrome, or ampulla-shaped cardiomyopathy) has been increasingly recognized. More than 300 articles on the topic have been published, the majority in the last 5 years. Despite this increased awareness, the pathophysiology of the condition remains unknown, and few reports have suggested a specific mechanism, beyond high catecholamine levels, as a trigger for the syndrome. Here, we review the clinical syndrome and suggest a novel pathophysiological explanation that focuses on the direct effects of high epinephrine levels on the ventricular myocardium. The syndrome represents a form of epinephrine-mediated acute myocardial stunning, with a predilection for the apical myocardium.
