Inclusion Criteria:

• Patients >18 years old with preexisting or newly confirmed diagnosis of POTS including:

• Presence of orthostatic symptoms for ≥3 months such as light-headedness, dizziness, nausea, head pressure, and/or dyspnea.

• Sustained increase in HR of ≥30 beats/minute or a sustained HR of ≥120 beats/minute withing 10 minutes of initiation of tilting during a tilt-table test or, if tilt-table testing is not available, a sustained increase in HR of ≥30 beats/minute or a sustained HR of ≥120 beats/minute withing 10 minutes of initiation of standing during an Active Stand Test, 3.

• Absence of orthostatic hypotension defined as a fall in systolic blood pressure of ≥20 mmHg and/or in diastolic blood pressure of ≥10 mmHg.

• Able to engage in exercise (without orthopedic or musculoskeletal limitations). Patients enrolled in this trial will be asked to maintain current medication regimens and not make additional adjustments for the duration of this trial. Although we appreciate that certain medications used for the treatment of POTS may influence multiple physiologic systems in various ways, we feel it is important, practical, and safe to study these patients under conditions of optimal care. Concurrent withdrawal of medications would likely result in moderate decompensation in a high proportion of patients. Accordingly, the impact of our intervention will be generalizable to POTS patients receiving standard optimized pharmacologic therapy, consistent with the general community. Informed consent will be obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.

Exclusion Criteria:

• History of chronic anemia.

• History of other chronic systemic diseases.

• Current smoking or pack year history >20 years.

• Individuals who are not able to engage in exercise (e.g. orthopaedic or musculoskeletal disorders/limitations)

• Unable or unwilling to provide informed consent.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 8/21/2025. Questions regarding updates should be directed to the study team contact.