Abstract
Takotsubo cardiomyopathy (TCM) is a transient myocardial stunning, typically showing apical ballooning. Although catecholamine toxicity, vasospasm, and disturbed microcirculation have been implicated, the precise pathophysiology of TCM is unknown. We present a two-step energy failure hypothesis which could explain the clinical course and pathogenesis. Sudden stress-induced increase in cardiac energy demand of normal subjects can be compensated for by additional supply of long chain fatty acids released from triglycerides stored in adipose tissues. Subjects at high risk for TCM cannot tolerate such stress-induced energy demand/supply imbalance, which triggers initial energy failure and induces myocytes’ stunning in vulnerable mid- and apical myocardial segments. Receptor-mediated uptake for energy substrates then declines due to impairment of contraction-dependent recruitment of responsible transporters (e.g. CD36). This in turn induces the second energy failure, which prolongs the myocardial stunning. Eventually, spontaneous or therapeutic improvements in the energetics awaken the heart.
