Autonomic Determinants of POTS - Pilot 2

Postural tachycardia syndrome (POTS) is a relatively common condition affecting mostly otherwise healthy young women. These patients have high heart rate and disabling symptoms during standing. Quality of life may be poor. The sympathetic nerves in the autonomic nervous system help to maintain normal blood pressures and heart rates during activities of daily life. The purpose of this study is to determine the importance of sympathetic activation as a cause of orthostatic symptoms. The investigators will assess the effects of a blood pressure medication (Moxonidine) on the symptoms during standing. Moxonidine lowers sympathetic activity. The investigators believe patients with high resting sympathetic activity might benefit from Moxonidine. It might reduce high heart rate and improve symptoms during standing. This study should help clinicians and the growing population of patients with POTS gain a better understanding of this disorder and find more personalized treatment.

Patients with POTS experience symptoms and an increase in heart rate≥30 beats/min with standing in the absence of orthostatic hypotension. As a result of considerable functional impairment, individuals with POTS are often unable to attend school or work. There is agreement that POTS is a heterogeneous disorder with multiple overlapping pathophysiologies proposed to underlie the clinical phenotype of patients. It would be important to define the underlying pathophysiological mechanisms in an individual patient to design optimal therapy. Our overarching hypothesis is that there is a subset of POTS patients (psPOTS) with a central sympathetic activation as the primary pathophysiology. We have characterized these patients by an increase in muscle sympathetic nerve activity (MSNA, a reflection of central sympathetic outflow) even at rest. In this project, we will focus on the role of primary sympathetic activation in the pathogenesis of POTS. Direct neural recordings of sympathetic activity, central sympathetic inhibition and extensive autonomic phenotyping will enable us to identify and correct the primary pathophysiology to optimally benefit psPOTS patients. This is a mechanistic study, designed to assess the effects of 4 weeks of central sympatholysis with moxonidine on orthostatic tachycardia and symptoms (Specific Aim 1), hypovolemia (Specific Aim 2) and central and peripheral baroreflex properties (Specific Aim 3) in a randomized, crossover design with POTS patients having elevated resting sympathetic nerve activity.