Autoimmune Basis for Postural Tachycardia Syndrome

Postural tachycardia syndrome (POTS) is a debilitating disorder resulting from cardiovascular autonomic dysfunction, has many causes and is very difficult to treat effectively. The investigators have identified the presence of autoantibodies (immune proteins) directed against some receptors of the autonomic nervous system that can cause patient's symptoms on standing.

The present study is designed to test the hypothesis that patients with POTS harbor functional autoantibodies to adrenergic receptors that lead to an excessive tachycardia characteristic of POTS. For this purpose, this study will define the prevalence, burden, and the in vivo physiological significance of these adrenergic antibodies in a well-phenotyped and representative cohort of patients with POTS and a matched cohort of healthy control subjects, and will characterize the stability of these autoantibodies over time in affected POTS patients.

Inclusion criteria

• 18-50 years old
• Postural Tachycardia Syndrome: 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
• Female premenopausal subjects must utilize adequate birth control and willingness to undergo serum beta-hCG testing
• The subject must 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 stand)
• Pregnancy
• Cardiovascular disease, such as myocardial infarction within 6 months, angina pectoris, significant arrhythmia (sinus tachycardia is not excluded), deep vein thrombosis, pulmonary embolism
• History of serious neurologic disease
• History or presence of significant immunological or hematological disorders
• Clinically significant gastrointestinal impairment that could interfere with dietary compliance or drug absorption
• Impaired hepatic function (aspartate amino transaminase and/or alanine amino transaminase >1.5 x upper limit of normal range)
• Impaired renal function (serum creatinine >1.5 mg/dL)
• Hematocrit <28%
• Current or concurrent disease that could affect the absorption, action or disposition of the drug, or clinical or laboratory assessments.
• Any underlying or acute disease requiring regular medication that could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
• Inability to comply with the protocol

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. We will attempt to study female patients in the first half of their menstrual cycle to minimize cyclical variability.