Abstract

Background: COVID-19 vaccination may be associated with postural orthostatic tachycardia syndrome (POTS) incidence, but little is known of who is at risk, their autonomic state, or how they respond to therapy. Methods: This prospective cohort study analyzed clinical data of 10 POTS clinic patients with new-onset or worsening POTS after COVID-19 vaccination. We also compared heart rate variability (HRV, via spot and ambulatory electrocardiograms (ECGs)) and skin sympathetic nerve activation (SKNA) with 24 healthy controls. Results: Patient mean age was 41.5±7.9 years with equal gender balance. Ambulatory ECG showed no major arrhythmias. Mean standing norepinephrine level was 638.2±395.3 pg/mL, with 4 patients >600 pg/mL. All patients had conditions that could raise POTS risk: prior COVID-19 infection (N=4); hypermobile Ehlers-Danlos syndrome (N=6); mast cell activation syndrome (N=3 found pre-POTS, N=3 post-POTS); and autoimmune (N=7), cardiac (N=7), neurologic (N=6), or gastrointestinal conditions (4). HRV analysis indicated lower spot (36.09 ms±49.2) and ambulatory root mean square of successive differences (46.19 ms±24, p=0.042) vs control (72.49 ms±40.8). SKNA showed a reduced mean amplitude (0.97uV±0.052, p=0.011) vs control (1.2 uV±0.31) and burst amplitude (1.67 uV±0.16, p=0.018) vs control (4.3 uV±4.3). All patients received guideline-based POTS care. After 417.2±131.4 days of follow-up, 3 patients were on ivabradine, 2 on beta blockers, 2 on midodrine, 5 on antihistamines, 4 on mast cell stabilizers, and 1 on prednisone. All patients reported improvement, although 2 with COVID-19 reinfection and 1 with small fiber neuropathy did have relapses of POTS symptoms. Conclusion: POTS patients with post-vaccine onset or exacerbation had histories of potential predisposing conditions. These suggest a potential screening approach, though referral bias is possible. Elevated standing norepinephrine levels, decreased HRV, and decreased pRR50 support a sympathetic-dominant state. Though only 2/10 patients stayed on beta blockers, 8/10 did at least transiently use them. Reduced average SKNA and burst-to-mean amplitude ratio suggest the presence of peripheral autonomic neuropathy. Patients responded to standard POTS therapy.

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