autonomic determinants of pots - pilot 2

Conditions: Postural Tachycardia Syndrome

Summary: 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.

Eligibility criteria:
inclusion criteria: * meets criteria for postural tachycardia syndrome (pots) 1. a heart rate increase of ≥30 beats/min within 10 minutes of upright posture; 2. lack of orthostatic hypotension (blood pressure fall ≥ 20/10 mmhg within 3 minutes of standing); and 3. chronic symptoms during upright posture over at least 6 months, in the absence of any other acute cause. * in the follicular phase of the menstrual cycle (days 5-13 of a 28-day cycle) * pots with primary central sympathetic activation (pspots) as defined as having resting msna ≥ 25 bursts/min * able and willing to provide informed consent. exclusion criteria: * pregnancy, * smoker, * bmi\>30 kg/m2, * deconditioned status (if available vo2max\<80% of predicted) * unable to withdraw from medications known to affect autonomic function, blood pressure or blood volume * systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathies, and autoimmune neuropathies. * arteriosclerotic disease of carotid artery. history of neck surgery. * conditions associated with inflammatory processes, such as coronary artery disease, hypertension, smoking, hypercholesterolemia (or on statin therapy), rheumatoid arthritis, diabetes, * treatment with oral corticosteroids, current infections (e.g., urinary tract infection), or use of non-steroidal anti-inflammatory drugs. * other factors which in the investigator's opinion would prevent the subject from completing the protocol including clinically significant abnormalities in clinical, mental or laboratory testing.

Keywords: postural tachycardia syndrome hyperadrenergic moxonidine sympatholytic orthostatic symptoms pots