Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■体位性心动过速综合征（POTS）患者的一部分被认为具有原发性高肾上腺素能原因。我们评估了临床生物标志物，以确定那些将受益于交感神经疗法的生物标志物。
■我们测量了交感神经功能（仰卧肌交感神经活动，直立血浆去甲肾上腺素，和对Valsalva动作的血压反应）在28例POTS患者（表型队列）中，以鉴定与对中枢交感神经溶解胍法辛的反应性相关的临床生物标志物在另一个不受控制的治疗队列中，38例患者因疑似高肾上腺素能POTS（HyperPOTS）而接受了胍法辛临床治疗。
■在表型队列中，在Valsalva动作的第2阶段后期,舒张压(DBP)升高>17mmHg,患者静息肌交感神经活动(HyperPOTS)的四分位数最高,敏感性为71%,特异性为85%.在治疗队列中，HyperPOTS患者，通过这种临床生物标志物鉴定，更经常报告的临床改善(85%对44%的非高肾上腺素；P=0.016)，具有更好的体位耐受性（Δ体位性低血压每日活动量表：-1.9±0.9对0.1±0.5；P=0.032），并报告了较少的慢性疲劳（ΔPROMIS疲劳简表7a：-12.9±2.7对-2.2±2.2；P=0.005）。
■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2期DBP的过度增加来确定，并通过中枢交感神经疗法得到改善。这些结果支持进一步的临床试验，以确定胍法辛在富含这种临床生物标志物的POTS患者中的安全性和有效性。
■我们测量了交感神经功能（仰卧肌交感神经活动，直立血浆去甲肾上腺素，和对Valsalva动作的血压反应）在28例POTS患者（表型队列）中，以鉴定与对中枢交感神经溶解胍法辛的反应性相关的临床生物标志物在另一个不受控制的治疗队列中，38例患者因疑似高肾上腺素能POTS（HyperPOTS）而接受了胍法辛临床治疗。
■在表型队列中，在Valsalva动作的第2阶段后期,舒张压(DBP)升高>17mmHg,患者静息肌交感神经活动(HyperPOTS)的四分位数最高,敏感性为71%,特异性为85%.在治疗队列中，HyperPOTS患者，通过这种临床生物标志物鉴定，更经常报告的临床改善(85%对44%的非高肾上腺素；P=0.016)，具有更好的体位耐受性（Δ体位性低血压每日活动量表：-1.9±0.9对0.1±0.5；P=0.032），并报告了较少的慢性疲劳（ΔPROMIS疲劳简表7a：-12.9±2.7对-2.2±2.2；P=0.005）。
■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2期DBP的过度增加来确定，并通过中枢交感神经疗法得到改善。这些结果支持进一步的临床试验，以确定胍法辛在富含这种临床生物标志物的POTS患者中的安全性和有效性。
