Energy Failure Hypothesis for Takotsubo Cardiomyopathy

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.

Serial changes of myocardial perfusion imaging in takotsubo and reverse takotsubo cardiomyopathy

“…Therefore, it has been considered that the pathophysiology of TTC is not a single etiology but a combination of several mechanisms in recent years. [27][28][29] However, there are only a few reports involving nuclear cardiology imaging for the variants of TTC 30,31 where the pathophysiology remains unclear. In this study, in the rTTC group, the decrease of the Tc-99m sestamibi uptake was observed in the area corresponding to the wall movement abnormalities in the acute phase as in the TTC group.…”

“…Single photon emission computed tomography (SPECT) was performed simultaneously in both groups in the respective acute and chronic phases. In the acute phase, SPECT was performed within a few days after admission (TTC: 3.0 [2.0-3.3] days vs rTTC: 3.0 [2.0-3.0] days, P = 0.72), and in the chronic phase, SPECT was performed approximately one month after admission (TTC: 33 [26][27][28][29][30][31][32][33][34][35][36][37] days vs rTTC: 35 days, P = 0.63).…”

Quantitative Lipidomic Analysis of Takotsubo Syndrome Patients' Serum

“…Long-chain fatty acid (LCFA) is the main sources of cardiomyocytes. TGs are hydrolyzed by adipose triglyceride lipase and released LCFAs which are oxidized in mitochondria to produce ATPs for cardiac energy ( 64 ). LCFAs are released on demand and delivered to the heart via the circulation and paracrine and used as energy substrates ( 64 ).…”

“…TGs are hydrolyzed by adipose triglyceride lipase and released LCFAs which are oxidized in mitochondria to produce ATPs for cardiac energy ( 64 ). LCFAs are released on demand and delivered to the heart via the circulation and paracrine and used as energy substrates ( 64 ). In normal circumstances, the stress-induced increase in cardiac energy demand can be compensated from hydrolyzing TGs.…”

“…In normal circumstances, the stress-induced increase in cardiac energy demand can be compensated from hydrolyzing TGs. In contrast, in TTS patients, excessive catecholamine-mediated myocardial segmental akinesia reduces lipid uptake and leads to lipid accumulation in the heart ( 9 , 14 , 64 ). Further studies are required to investigate the meaning of alterations in the composition of these individual lipid species.…”