Prospective Evaluation of Autonomic Dysfunction in Post-Acute Sequela of COVID-19

Abstract

Background: Patients with post-acute sequela of COVID-19 (PASC) often report symptoms of orthostatic intolerance and autonomic dysfunction. Numerous case reports link postural orthostatic tachycardia syndrome (POTS) to PASC. No prospective analysis has been performed.

Objectives: This study performed head-up tilt table (HUTT) testing in symptomatic patients with PASC to evaluate for orthostatic intolerance suggestive of autonomic dysfunction.

Methods: We performed a prospective, observational evaluation of patients with PASC complaining of poor exertional tolerance, tachycardia with minimal activity or positional change, and palpitations. Exclusion criteria included pregnancy, pre-PASC autonomic dysfunction or syncope, or another potential explanation of PASC symptoms. All subjects underwent HUTT.

Results: Twenty-four patients with the described PASC symptoms were included. HUTT was performed a mean of 5.8 ± 3.5 months after symptom onset. Twenty-three of the 24 had orthostatic intolerance on HUTT, with 4 demonstrating POTS, 15 provoked orthostatic intolerance (POI) after nitroglycerin, 3 neurocardiogenic syncope, and 1 orthostatic hypotension. Compared with those with POTS, patients with POI described significantly earlier improvement of symptoms.

Conclusions: This prospective evaluation of HUTT in patients with PASC revealed orthostatic intolerance on HUTT suggestive of autonomic dysfunction in nearly all subjects. Those with POI may be further along the path of clinical recovery than those demonstrating POTS.

Keywords: head-up tilt table (HUTT); neurocardiogenic syncope; orthostatic hypotension; orthostatic intolerance; postural orthostatic tachycardic syndrome (POTS).

Graphical abstract

Figure 1

Subject Responses to HUTT Testing Twenty-four consecutively enrolled patients underwent HUTT with 4 demonstrating POTS, 15 exhibiting POI, 3 with neurocardiogenic syncope, 1 demonstrating orthostatic hypotension, and 1 with a normal response. HUTT = head-up tilt table; POI = provoked orthostatic intolerance; POTS = postural orthostatic tachycardia syndrome.

Central Illustration

Examples of Head-Up Tilt Table Responses (A) Example of POTS response. On standing, classic PASC symptoms develop and heart rate increases >30 beats/min with minimal change in blood pressure. The heart rate normalizes and symptoms resolve with resumption of supine position. (B) Example of POI response. During the initial, nonpharmacological phase, no PASC symptoms are described and heart rate increases, although <30 beats/min. After administration of NTG, there is reproduction of classic PASC symptoms and heart rate increases >30 beats/min with minimal change in blood pressure. The heart rate normalizes and symptoms resolve with resumption of supine position. (C) Example of combination POI and neurocardiogenic syncope. POI response develops with sudden and significant fall in heart rate with loss of consciousness denoted by arrow labeled “syncope.” HUTT = head-up tilt table; NTG = sublingual nitroglycerin; PASC = post-acute sequela of COVID-19; POI = provoked orthostatic intolerance; POTS = postural orthostatic tachycardia syndrome.