Autoimmune Basis for Postural Tachycardia Syndrome

The present study is designed to test the hypothesis that muscarinic autoantibody-mediated parasympathetic dysfunction contributes to the pathogenesis of POTS, and that parasympathetic (vagal) stimulation improves POTS symptoms, autoimmunity and inflammation.

Define and determine the prevalence, burden, and clinical significance of muscarinic autoantibodies in a well-phenotyped cohort of POTS patients with and without gastroparesis and a matched cohort of healthy control subjects.

Evaluate the impact of vagal stimulation on antibody suppression, inflammatory inhibition, and symptom improvement in POTS patients. Non-invasive transcutaneous stimulation of the auricular branch of the vagus nerve (tragus stimulation) will be used to increase parasympathetic activity.

Inclusion criteria

• 18-80 years old, female or male
• Either healthy control or individual with postural tachycardia syndrome (POTS) defined as heart rate increase >30 bpm from supine within 10 min of standing, in the absence of orthostatic hypotension (>20/10 mmHg fall in blood pressure), with chronic symptoms (>6 months), and in the absence of other acute cause of orthostatic tachycardia
• Able and willing to provide informed consent
• Understand and be able to comply with the study procedures and restrictions

Exclusion criteria

• Hypertension (>150 mmHg systolic and >100 mmHg diastolic) based on history or findings at screening
• Orthostatic hypotension (consistent drop in blood pressure >20/10 mmHg with 10 min of standing)
• Cardiovascular disease, such as myocardial infarction within 6 months
• History or presence of significant immunological or hematological disorders
• History of vagotomy
• Currently pregnant women or women planning on becoming pregnant ≤ 3 months
• Inability to comply with the protocol
• Patients with active implants (such as a cardiac pacemaker, or a cochlear implant)

Healthy control subjects will be healthy, non-smoking and on no chronic medications at the time of the study. Healthy control subjects will be group-matched to the POTS patients for age and gender.