Objective:

We characterized the clinical presentation of the neuropathic subtype of postural orthostatic tachycardia syndrome (POTS) and compared treatment response between neuropathic and non-neuropathic POTS patients. This information could guide selection of diagnostic testing and treatment options for patients with POTS.

Background:

Patients with POTS, an autonomic nervous system disorder including neuropathic, hyperadrenergic, and hypovolemic subtypes, commonly experience multi-year delays in diagnosis and repeat treatment failures. Limited prior studies suggest POTS subtypes respond differently to available medical therapies, but consensus guidelines for treatment selection by subtype do not yet exist. Further, testing to characterize neuropathic POTS can be expensive, time-consuming, and invasive.

Design/Methods:

We identified 382 patients with POTS meeting diagnostic criteria on the head-up tilt table test (HUTT). Patients scoring below 5% percentile for either an intraepidermal nerve fiber density skin biopsy or the quantitative sudomotor axon reflex test (QSART) were classified as neuropathic. Logistic regressions assessed for associations between clinical variables (HUTT parameters, prior diagnoses, neurologic examination findings, and questionnaires) and subsequent diagnosis of neuropathic POTS. Responses to nine treatments were compared between neuropathic and non-neuropathic patients using Cox proportional hazard and Kaplan-Meier estimator modeling. 

Results:

Patients with neuropathic POTS had a significantly reduced risk of treatment failure when treated with ivabradine (HR = 0.273, p = 0.028); median treatment duration in neuropathic patients was 26.7 months compared to 10.7 months in non-neuropathic patients. No significant difference was observed for other treatments. Of all clinical variables analyzed, only baseline heart rate associated significantly with neuropathic POTS (p = 0.021). Patients with abnormal findings in their neurological examination were less likely (p = 0.049) to have neuropathic POTS.

Conclusions:

Patients with neuropathic POTS may respond favorably to different treatment regimens than non-neuropathic patients, emphasizing the value of correctly characterizing each patient’s disease. Providers should consider testing for neuropathic POTS regardless of neurological exam findings.