Cardiology Division, Massachusetts General Hospital and Harvard Medical School, MA, USA.
Cardiovascular Imaging Research Center, Boston, MA, USA.
Eur Heart J. 2021 May 14;42(19):1898-1908. doi: 10.1093/eurheartj/ehab029.
Activity in the amygdala, a brain centre involved in the perception of and response to stressors, associates with: (i) heightened sympathetic nervous system and inflammatory output and (ii) risk of cardiovascular disease. We hypothesized that the amygdalar activity (AmygA) ratio is heightened among individuals who develop Takotsubo syndrome (TTS), a heart failure syndrome often triggered by acute stress. We tested the hypotheses that (i) heightened AmygA precedes development of TTS and (ii) those with the highest AmygA develop the syndrome earliest.
Individuals (N=104, median age 67.5 years, 72% female, 86% with malignancy) who underwent clinical 18 F-FDG-PET/CT imaging were retrospectively identified: 41 who subsequently developed TTS and 63 matched controls (median follow-up 2.5 years after imaging). AmygA was measured using validated methods. Individuals with (vs. without) subsequent TTS had higher baseline AmygA (P=0.038) after adjusting for TTS risk factors. Further, AmygA associated with the risk for subsequent TTS after adjustment for risk factors [standardized hazard ratio (95% confidence interval): 1.643 (1.189, 2.270), P=0.003]. Among the subset of individuals who developed TTS, those with the highest AmygA (>mean + 1 SD) developed TTS ∼2 years earlier after imaging vs. those with lower AmygA (P=0.028).
Higher AmygA associates with an increased risk for TTS among a retrospective population with a high rate of malignancy. This heightened neurobiological activity is present years before the onset of TTS and may impact the timing of the syndrome. Accordingly, heightened stress-associated neural activity may represent a therapeutic target to reduce stress-related diseases, including TTS.
杏仁核是大脑中参与应激感知和反应的中心之一，其活动与以下两个方面相关：（i）交感神经系统和炎症反应增强；（ii）心血管疾病风险增加。我们假设，在发生 Takotsubo 综合征（TTS）的个体中，杏仁核活动（AmygA）比率会升高，Takotsubo 综合征是一种常由急性应激引发的心力衰竭综合征。我们检验了以下两个假设：（i）AmgyA 的升高先于 TTS 的发生；（ii）AmgyA 升高幅度最大的个体最早出现该综合征。
回顾性分析了接受临床 18 F-FDG-PET/CT 成像的个体（N=104，中位年龄 67.5 岁，72%为女性，86%患有恶性肿瘤）：41 例随后发生了 TTS，63 例匹配对照（中位随访时间为成像后 2.5 年）。使用经过验证的方法测量 AmgyA。在调整 TTS 风险因素后，患有（与未患有）随后 TTS 的个体的基线 AmgyA 更高（P=0.038）。此外，在调整风险因素后，AmgyA 与随后发生 TTS 的风险相关[标准化风险比（95%置信区间）：1.643（1.189，2.270），P=0.003]。在发生 TTS 的亚组个体中，AmgyA 最高（>平均值+1 个标准差）的个体在成像后约 2 年内发生 TTS，而 AmgyA 较低的个体（P=0.028）。
在恶性肿瘤发生率较高的回顾性人群中，较高的 AmgyA 与 TTS 风险增加相关。这种增强的神经生物学活性在 TTS 发作前多年就存在，可能会影响该综合征的发生时间。因此，应激相关神经活动的增强可能代表了减少应激相关疾病（包括 TTS）的治疗靶点。
