Acetylcholinesterase Inhibition Improves Tachycardia in Postural Tachycardia Syndrome

BACKGROUND: Postural tachycardia syndrome (POTS) induces disabling chronic orthostatic intolerance notable for an excessive increase in heart rate that occurs on standing. Many current therapeutic strategies focus on sympatholysis, but the alternative strategy of enhancing cardiovagal tone has not been studied. The objective of this study was to test the hypothesis that acetylcholinesterase inhibitors will attenuate the tachycardia and improve symptom burden in patients with POTS. METHODS AND RESULTS: Seventeen patients with POTS underwent acute drug trials of pyridostigmine 30 mg orally and placebo, on separate mornings, in a randomized crossover design. Blood pressures, heart rate, and symptoms were assessed while patients were seated and after they had been standing for up to 10 minutes both before the study drug was given and at 2 and 4 hours after study drug. The heart rate was significantly lower at 2 hours after pyridostigmine than after placebo (100+/-16 versus 111+/-14 bpm, P=0.001). Pyridostigmine significantly decreased the standing heart rate from baseline (119+/-16 bpm) at 2 hours (104+/-16 bpm, P<0.001) and 4 hours (100+/-16 bpm, P<0.001) after administration. There was no significant change in blood pressure. The decrease in symptom burden within 4 hours after study drug was significantly greater with pyridostigmine than placebo (-10.4+/-14.0 AU versus 0.6+/-7.5 AU, P<0.025). CONCLUSIONS: Acute acetylcholinesterase inhibition significantly attenuated tachycardia in POTS. There was also an improvement in symptom burden with this promising therapy.