Abstract 17402: Pathological Findings of Takotsubo Cardiomyopathy Relating to Chatecholamine Toxicity: The Study Using Human Left Ventricular Endomyocardial Biopsy Specimens in the Acute Phase
Introduction: Takotsubo Cardiomyopathy (TTC) is characterized by transient hypokinesis of the left ventricular (LV) apex and mid-ventricular regions, and hyperkinesis of the LV base, without significant coronary artery stenosis. The precise pathogenic mechanism of TTC remains unknown. Earlier reports assumed that catecholamine excess is involved in the pathogenesis of TTC, from the elevation of plasma catecholamine concentration or by 123I-metaiodobenzylguanidine myocardial scintigraphy. However, there have been no pathological findings that directly support this scenario in human, so far. In this study, we investigated clinical and pathological features in TTC heart including expression of G-protein receptor kinase 2 (GRK2), which is a marker for acute desensitization of β-adrenergic receptors (β-ARs), and compared with those in non-TTC heart.
Methods and Results: The clinical and pathological features from 20 TTC patients (TTC group) and non-TTC patients (non-TTC group) were analyzed. In TTC patients, LV biopsy was performed at the acute phase. Non-TTC group of patients consisted of 14 patients with ventricular tachycardia or conduction disorder, who underwent LV biopsy to rule out primary myocardial diseases. Pathological data showed that the contraction band was more frequently observed in TTC than in non-TTC group (p=0.017) (Figure A), and the percentage of interstitial fibrosis area of TTC was higher than that of non-TTC group (12.1±7.7% vs 7.4±3.0%, p=0.036) (Figure B). Moreover, the percentage of GRK2 positive stained area in TTC was greater than in non-TTC group (49.0±17.8% vs 15.7±11.9%, p<0.001) (Figure C).
Conclusions: The present study demonstrates up-regulation of GRK2 for the first time in human TTC, and supports the involvement of catecholamine toxicity in the pathogenesis of TTC.
Author Disclosures: T. Nakano: None. K. Onoue: None. Y. Sakaguchi: None. K. Hatakeyama: None. D. Kamon: None. Y. Dote: None. Y. Nakada: None. A. Takitsume: None. H. Nakagawa: None. A. Seno: None. T. Ueda: None. T. Kumazawa: None. T. Nishida: None. T. Soeda: None. S. Okayama: None. Y. Takeda: None. M. Watanabe: None. H. Kawata: None. R. Kawakami: None. H. Okura: None. Y. Saito: Research Grant; Significant; Grants-in-Aid for Scientific Research (B), Health Labour Sciences Research Grant, Takeda Science Foundation Research Grant, Japan Heart Foundation Research Grant. Other Research Support; Modest; Genzyme Japan K.K., Nippon Boehringer Ingelheim Co ., Ltd., Chugai Pharmaceutical Co., Ltd., MSD Co., Ltd, Nihon Medi-Physics Co.,Ltd., Medtronic Japan Co., Ltd., Asahi Kasei Pharma Corporation. Other Research Support; Significant; Baxter Ltd., TEIJIN Pharma Ltd., KOWA Pharmaceutical Co., Ltd., Zeria Pharmaceutical Co., Ltd., Astellas Pharma Inc., Pfizer Japan Inc., Otsuka Pharmaceutical Co., Ltd, Sumitomo Dainippon Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Bayer Yakuhin, Ltd., Kyowa Hakko Kirin Co., Ltd., Ono Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Eisai Co., Ltd., Daiichi Sankyo Company Ltd., Shionogi & Co., Ltd.. Speakers Bureau; Modest; Daiichi Sankyo Company Ltd., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd.. Honoraria; Modest; Daiichi Sankyo Company Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd, KOWA Pharmaceutical Co., Ltd., Pfizer Japan Inc., Shionogi & Co., Ltd., Nippon Boehringer Ingelheim Co ., Ltd., Bayer Yakuhin, Ltd., TEIJIN Pharma Ltd., Mochida Pharmaceutical Co., Ltd., Astellas Pharma Inc., Nippon Shinyaku Co., Ltd., AstraZeneca K.K., Roche Diagnostics K.K., Ono Pharmaceutical Co., Ltd., MSD Co., Ltd. Consultant/Advisory Board; Modest; Ono Pharmaceutical Co., Ltd., Novartis Pharma K.K.. Other; Modest; Ono Pharmaceutical Co., Ltd., Novartis Pharma K.K, Pfizer Japan Inc.. Other; Significant; MSD Co., Ltd.
- © 2015 by American Heart Association, Inc.