Beta-3 Enhanced Autonomic Therapy for POTS

Participants will undergo 4 weeks of randomized treatment, with an optional 4-week extension, and a final safety follow-up visit 4 weeks after discontinuation (total participation up to 12 weeks). The investigators will perform skin sympathetic nerve activity (SKNA) recordings and assess self-reported symptom frequencies using the number of pushbutton events per day. The patients will also record symptoms in a daily diary. The investigators will assess quality of life (QOL) and overactive bladder (OAB) symptoms using validated questionnaires at baseline and after mirabegron treatment. The investigators will repeat the QOL questionnaires at 4 weeks and 8 weeks in those who choose to extend therapy.

Inclusion criteria

• Provision of a signed and dated informed consent form.
• Male or female, age ≥ 18 years old.
• Confirmed POTS diagnosis, which includes chronic (>3 months) orthostatic intolerance, an increase in heart rate (HR) of ≥30 beats per minute (bpm) without orthostatic hypotension (>20 mmHg drop of systolic BP) during orthostatic tests.

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

• Patients who are pacemaker-dependent because the pacing artifacts will complicate skin sympathetic nerve activity (SKNA) analysis.
• Clinically unstable (for example, acute myocardial infarction, decompensated heart failure, undergoing cancer chemotherapy, and other acute illnesses requiring hospitalization)
• Uncontrolled hypertension (systolic blood pressure ≥180 mm Hg or diastolic blood pressure ≥110 mm Hg, or both)18
• Active thyrotoxicosis
• Any experimental medication concomitantly or within 4 weeks of participation in the study
• Currently participating in a different clinical trial
• Severe renal impairment (CrCl < 30 ml/min)
• Hepatic disease (Child-Pugh Class C)
• Prisoners
• Pregnant
• Breastfeeding
• Cannot speak, write, or answer questions in English (Validated symptom questionnaires used in this study are available only in English.)
• Does not have the capacity to consent
• Patients who are known to be allergic to mirabegron or skin patch electrodes
• Patients taking codeine, oxycodone, thioridazine, flecainide, propafenone, and digoxin. (see explanation below)