Acute-phase Takotsubo syndrome was associated with a significantly higher percentage of cardiomyocytes showing positive membrane staining for GRK2 (28.0% vs 2.0%) compared to normal controls.
Observational (n=71)
Blinded evaluators
No
This study provides the first histologic evidence that alteration of β-adrenoceptor signaling, indicated by GRK2 and β-arrestin2 overexpression and membrane translocation, is involved in the development of acute-phase Takotsubo syndrome.
Absolute Event Rate: 28% vs 2%
p-value: p=<0.001
Accumulating evidence indicates alteration of the β-adrenoceptor (AR), such as desensitization and subtype switching of its coupling G protein, plays a role in the protection against catecholamine toxicity in heart failure. However, in human takotsubo syndrome (TTS), which is associated with a surge of circulating catecholamine in the acute phase, there is no histologic evidence of β-AR alteration. The purpose of this study was to investigate the involvement of alteration of β-AR signaling in the mechanism of TTS development. Left ventricular (LV) biopsied samples from 26 patients with TTS, 19 with normal LV function, and 26 with dilated cardiomyopathy (DCM) were studied. G protein-coupled receptor kinase 2 (GRK2) and β-arrestin2, which initiate the alteration of β-AR signaling, were more abundantly expressed in the myocardium in acute-phase TTS than in those of DCM and normal control as indicated by immunohistochemistry. The percentage of cardiomyocytes that showed positive membrane staining for GRK2 and β-arrestin2 was also significantly higher in acute-phase TTS. Sequential biopsies in the recovery-phase for two patients with TTS revealed that membrane expression of GRK2 and β-arrestin2 faded over time. This study provided the first histologic evidence of the involvement of alteration of β-ARs in the development of TTS.
Nakano et al. (2018) conducted an observational in Takotsubo syndrome (n=71). Acute-phase Takotsubo syndrome vs. Normal left ventricular function and dilated cardiomyopathy was evaluated on Percentage of cardiomyocytes with positive membrane staining for GRK2 (p=<0.001). Acute-phase Takotsubo syndrome was associated with a significantly higher percentage of cardiomyocytes showing positive membrane staining for GRK2 (28.0% vs 2.0%) compared to normal controls.