Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology (L.E.O., V.U., S.R., M.G., C.A.S., A.D., I.B.), Vanderbilt University Medical Center, Nashville, TN.
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN (J.J.A., J.K.S.-R., J.M.P.).
Hypertension. 2024 Nov;81(11):2237-2247. doi: 10.1161/HYPERTENSIONAHA.124.23035. Epub 2024 Aug 7.
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.
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).
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; =0.016), had better orthostatic tolerance (∆Orthostatic Hypotension Daily Activities Scale: -1.9±0.9 versus 0.1±0.5; =0.032), and reported less chronic fatigue (∆PROMIS Fatigue Short Form 7a: -12.9±2.7 versus -2.2±2.2; =0.005) in response to guanfacine.
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.
体位性心动过速综合征（POTS）的一部分患者被认为存在原发性高肾上腺素能病因。我们评估了临床生物标志物，以确定那些受益于交感神经抑制治疗的患者。
我们测量了 28 例 POTS 患者（表型队列）的交感神经功能（仰卧位肌肉交感神经活动、直立位血浆去甲肾上腺素、Valsalva 动作时血压反应），以确定与 38 例疑似高肾上腺素能 POTS（HyperPOTS）患者接受胍法辛临床治疗的单独未对照治疗队列中胍法辛中枢交感神经抑制反应相关的临床生物标志物。
在表型队列中，Valsalva 动作 2 期后期舒张压（DBP）升高>17mmHg 可识别出静息肌肉交感神经活动最高四分位的患者（HyperPOTS），具有 71%的敏感性和 85%的特异性。在治疗队列中，通过这种临床生物标志物识别出的 HyperPOTS 患者，更常报告临床改善（85%对非高肾上腺素能患者的 44%；=0.016），具有更好的直立耐量（∆Orthostatic Hypotension Daily Activities Scale：-1.9±0.9 对 0.1±0.5；=0.032），并且报告使用胍法辛后慢性疲劳（∆PROMIS Fatigue Short Form 7a：-12.9±2.7 对-2.2±2.2；=0.005）减轻。
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，通过 Valsalva 动作 2 期时 DBP 过度升高可以在临床上识别，并通过中枢交感神经抑制治疗得到改善。这些结果支持进一步的临床试验，以确定胍法辛在富含这种临床生物标志物的 POTS 患者中的安全性和疗效。
