Chronotropic incompetence (CTI), the inability of the heart to increase its rate with increased activity, leads to exercise intolerance and predicts overall mortality. We previously reported that cardiac β-adrenergic receptor downregulation occurs in patients with CTI without heart failure (HF), indicating postsynaptic sympathetic nervous dysfunction. However, cardiac presynaptic sympathetic nervous system function in CTI is not fully understood. Notably, ¹¹C-hydroxyephedrine PET assesses cardiac presynaptic sympathetic nervous system function. Therefore, we investigated cardiac presynaptic sympathetic nervous system function using cardiac ¹¹C-hydroxyephedrine PET in patients with CTI without HF. Methods: We performed cardiac PET in 13 patients with CTI without HF and 9 age-matched healthy controls using ¹¹C-hydroxyephedrine (mean age, 75.1 ± 6.3 y; 59.1% male). The global hydroxyephedrine retention index was determined as myocardial tracer (¹¹C-hydroxyephedrine) activity between 30 and 40 min divided by the activity input integral. CTI was defined as failing to achieve 80% of the heart rate reserve during bicycle ergometer exercise testing. Results: The clinical characteristics, including echocardiographic parameters, did not significantly differ between patients with CTI and controls. Peak heart rate was significantly lower in patients with CTI than in controls (107.0 ± 8.2 vs. 138.4 ± 13.6 beats/min, P < 0.001). The global hydroxyephedrine retention index was significantly higher in patients with CTI than in controls (0.14 ± 0.04 vs. 0.10 ± 0.05 min⁻¹, P = 0.046). Conclusion: Hydroxyephedrine retention index was significantly higher in patients with CTI without HF than in controls. Our data suggested that impaired norepinephrine release in presynaptic sympathetic nerves contributes to the mechanism of CTI without HF.

变时性功能不全 （CTI），即心脏无法随着活动的增加而增加其速率，导致运动不耐受并预测总体死亡率。我们之前报道过，心脏 β-肾上腺素能受体下调发生在无心力衰竭 （HF） 的 CTI 患者中，表明突触后交感神经功能障碍。然而，CTI 中的心脏突触前交感神经系统功能尚不完全清楚。值得注意的是，¹¹C-羟基麻黄碱 PET 评估心脏突触前交感神经系统功能。因此，我们使用心脏 ¹¹C-羟基麻黄碱 PET 研究了无 HF 的 CTI 患者的心脏突触前交感神经系统功能。方法： 我们对 13 例无 HF 的 CTI 患者和 9 例年龄匹配的健康对照者进行了心脏 PET 使用 ¹¹C-羟基麻黄碱 （平均年龄 75.1 ± 6.3 岁;59.1% 男性）。整体羟基麻黄碱潴留指数确定为 30 至 40 分钟之间的心肌示踪剂 （¹¹C-羟基麻黄碱） 活性除以活性输入积分。CTI 被定义为在自行车测力计运动测试期间未能达到 80% 的心率储备。结果：CTI 患者和对照组之间的临床特征（包括超声心动图参数）无显著差异。CTI 患者的峰值心率显著低于对照组 （107.0 ± 8.2 vs. 138.4 ± 13.6 次/分钟，P < 0.001）。CTI 患者的总体羟基麻黄碱保留指数显著高于对照组 （0.14 ± 0.04 vs. 0.10 ± 0.05 ^min-1，P = 0.046）。 结论：无 HF 的 CTI 患者的羟基麻黄碱潴留指数显著高于对照组。我们的数据表明，突触前交感神经中去甲肾上腺素释放受损有助于无 HF 的 CTI 机制。