BACKGROUND A subset of patients with postural tachycardia syndrome (POTS) are thought to have a primary hyperadrenergic cause. We assessed clinical biomarkers to identify those that would benefit from sympatholytic therapy. METHODS We measured sympathetic function (supine muscle sympathetic nerve activity, upright plasma norepinephrine, and blood pressure responses to the Valsalva maneuver) in 28 patients with POTS (phenotyping cohort) to identify clinical biomarkers that are associated with responsiveness to the central sympatholytic guanfacine in a separate uncontrolled treatment cohort of 38 patients that had received guanfacine clinically for suspected hyperadrenergic POTS (HyperPOTS). RESULTS In the phenotyping cohort, an increase in diastolic blood pressure (DBP) >17 mm Hg during late phase 2 of the Valsalva maneuver identified patients with the highest quartile of resting muscle sympathetic nerve activity (HyperPOTS) with 71% sensitivity and 85% specificity. In the treatment cohort, patients with HyperPOTS, identified by this clinical biomarker, more often reported clinical improvement (85% versus 44% in nonhyperadrenergic; P=0.016), had better orthostatic tolerance (∆Orthostatic Hypotension Daily Activities Scale: -1.9±0.9 versus 0.1±0.5; P=0.032), and reported less chronic fatigue (∆PROMIS Fatigue Short Form 7a: -12.9±2.7 versus -2.2±2.2; P=0.005) in response to guanfacine. CONCLUSIONS These results are consistent with the concept that POTS is caused by a central sympathetic activation in a subset of patients, which can be identified clinically by an exaggerated DBP increase during phase 2 of the Valsalva maneuver and improved by central sympatholytic therapy. These results support further clinical trials to determine the safety and efficacy of guanfacine in patients with POTS enriched for the presence of this clinical biomarker.

中文翻译：

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高肾上腺素能体位性心动过速综合征：临床生物标志物和对胍法辛的反应。


背景 体位性心动过速综合征 （POTS） 患者亚群被认为具有原发性肾上腺素能过高原因。我们评估了临床生物标志物，以确定那些会从交感神经溶解治疗中受益的标志物。方法 我们测量了 28 例 POTS 患者的交感神经功能 （仰卧肌交感神经活动、直立血浆去甲肾上腺素和血压对 Valsalva 动作的反应） （表型队列），以确定与对中枢交感神经解药胍法辛的反应相关的临床生物标志物在另一个非对照治疗队列中，该队列包括 38 例临床接受胍法辛治疗疑似肾上腺素能过高的 POTS （HyperPOTS）。结果 在表型队列中，在 Valsalva 动作的第 2 阶段后期舒张压 （DBP） >17 mm Hg 增加确定了静息肌交感神经活动 （HyperPOTS） 最高四分位数的患者，敏感性为 71%，特异性为 85%。在治疗队列中，由该临床生物标志物识别的 HyperPOTS 患者更常报告临床改善（85% 对非肾上腺素能高下组为 44%;P=0.016），具有更好的直立耐受性 （∆直立性低血压日常活动量表：-1.9±0.9 对 0.1±0.5;P=0.032），并报告慢性疲劳较少 （∆PROMIS 疲劳简表 7a：-12.9±2.7 对 -2.2±2.2;P=0.005） 响应 guanfacine。结论这些结果与 POTS 是由一部分患者的中枢交感神经激活引起的概念一致，临床上可以通过 Valsalva 动作第 2 阶段 DBP 的夸大增加来识别，并通过中枢交感神经溶解治疗得到改善。 这些结果支持进一步的临床试验，以确定胍法辛在富含该临床生物标志物的 POTS 患者中的安全性和有效性。