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Abstract：
BACKGROUND: Stress cardiomyopathy, or Takotsubo syndrome (TTS), is an acute and reversible syndrome developing in strong association with psychological or physiological stressors. While a surge in the circulating catecholamine level is suspected as one of its pathophysiologies, the contribution of treatment with sympathomimetic drugs to the development of TTS remains uncertain.
METHODS: We conducted a disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database containing more than 500,000 patient cases recorded between April 2004 and March 2019, to detect TTS (\'stress cardiomyopathy\') as adverse event signals associated with adrenergic agonist drugs usage by calculating reporting odds ratio (ROR).
RESULTS: Among 306 TTS cases reported to JADER, we identified 58 TTS cases with exposure to adrenergic agonist drugs, predominantly of women (52/58, 89.7%) and those in the median age-decades of the 70s. After adjusting for age in decades and sex, most of the intravenous catecholamines showed significantly higher reporting (lower 95% ROR > 1) for TTS, including adrenaline, noradrenaline, dobutamine, dopamine, phenylephrine, and ephedrine. In addition, peroral midodrine, transdermal tulobuterol, inhaled salbutamol, and inhaled procaterol also showed significantly higher ROR for TTS. We also identified a small number of TTS cases with Parkinson\'s disease taking midodrine or droxidopa, but not receiving other adrenergic agonists.
CONCLUSIONS: The current pharmacovigilance study showed significantly higher RORs for TTS following the use of some of the adrenergic drugs, being mostly consistent with the TTS-related adrenergic drugs reported in earlier literature. A potential association of taking midodrine or droxidopa with the development of TTS was also suggested.
METHODS: We conducted a disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database containing more than 500,000 patient cases recorded between April 2004 and March 2019, to detect TTS (\'stress cardiomyopathy\') as adverse event signals associated with adrenergic agonist drugs usage by calculating reporting odds ratio (ROR).
RESULTS: Among 306 TTS cases reported to JADER, we identified 58 TTS cases with exposure to adrenergic agonist drugs, predominantly of women (52/58, 89.7%) and those in the median age-decades of the 70s. After adjusting for age in decades and sex, most of the intravenous catecholamines showed significantly higher reporting (lower 95% ROR > 1) for TTS, including adrenaline, noradrenaline, dobutamine, dopamine, phenylephrine, and ephedrine. In addition, peroral midodrine, transdermal tulobuterol, inhaled salbutamol, and inhaled procaterol also showed significantly higher ROR for TTS. We also identified a small number of TTS cases with Parkinson\'s disease taking midodrine or droxidopa, but not receiving other adrenergic agonists.
CONCLUSIONS: The current pharmacovigilance study showed significantly higher RORs for TTS following the use of some of the adrenergic drugs, being mostly consistent with the TTS-related adrenergic drugs reported in earlier literature. A potential association of taking midodrine or droxidopa with the development of TTS was also suggested.
摘要：
背景：应激性心肌病，或Takotsubo综合征（TTS），是一种与心理或生理应激源密切相关的急性和可逆综合征。虽然循环儿茶酚胺水平的升高被怀疑是其病理生理之一，拟交感神经药物治疗对TTS发展的贡献仍不确定.
方法：我们使用日本不良药物事件报告（JADER）数据库进行了不成比例的分析，该数据库包含2004年4月至2019年3月期间记录的超过500,000例患者病例，通过计算报告比值比（ROR）来检测TTS（“应激性心肌病”）作为与肾上腺素能激动剂药物使用相关的不良事件信号。
结果：在JADER报告的306例TTS病例中，我们确定了58例暴露于肾上腺素能激动剂药物的TTS病例，主要是女性（52/58，89.7％）和70年代的中位年龄。在调整了年龄和性别后，大多数静脉注射儿茶酚胺显示TTS的报告显著较高(低95%ROR>1)，包括肾上腺素,去甲肾上腺素,多巴酚丁胺,多巴胺,去氧肾上腺素,和麻黄碱.此外,经口米多君,经皮托布特罗，吸入沙丁胺醇，吸入丙卡特罗对TTS的ROR也显著升高。我们还确定了少数服用米多君或屈昔多巴的帕金森病TTS病例，但不接受其他肾上腺素能激动剂。
结论：目前的药物警戒研究显示，使用某些肾上腺素能药物后，TTS的ROR显著升高，与早期文献报道的TTS相关的肾上腺素能药物大多一致。还提出了服用米多君或屈昔多巴与TTS发展的潜在联系。
方法：我们使用日本不良药物事件报告（JADER）数据库进行了不成比例的分析，该数据库包含2004年4月至2019年3月期间记录的超过500,000例患者病例，通过计算报告比值比（ROR）来检测TTS（“应激性心肌病”）作为与肾上腺素能激动剂药物使用相关的不良事件信号。
结果：在JADER报告的306例TTS病例中，我们确定了58例暴露于肾上腺素能激动剂药物的TTS病例，主要是女性（52/58，89.7％）和70年代的中位年龄。在调整了年龄和性别后，大多数静脉注射儿茶酚胺显示TTS的报告显著较高(低95%ROR>1)，包括肾上腺素,去甲肾上腺素,多巴酚丁胺,多巴胺,去氧肾上腺素,和麻黄碱.此外,经口米多君,经皮托布特罗，吸入沙丁胺醇，吸入丙卡特罗对TTS的ROR也显著升高。我们还确定了少数服用米多君或屈昔多巴的帕金森病TTS病例，但不接受其他肾上腺素能激动剂。
结论：目前的药物警戒研究显示，使用某些肾上腺素能药物后，TTS的ROR显著升高，与早期文献报道的TTS相关的肾上腺素能药物大多一致。还提出了服用米多君或屈昔多巴与TTS发展的潜在联系。
