Background—Postural tachycardia syndrome (POTS) induces disabling chronic orthostatic intolerance with an excessive increase in heart rate on standing. -Blockade is an appealing treatment approach, but conflicting preliminary reports are conflicting. We tested the hypothesis that propranolol will attenuate the tachycardia and improve symptom burden in patients with POTS. In protocol 1, a low dose (20 mg) was compared with placebo, and the dose response was assessed in protocol 2.

Methods and Results—In protocol 1, patients with POTS (n=54) underwent acute drug trials of propranolol 20 mg orally and placebo, on separate mornings, in a randomized crossover design. Blood pressure, heart rate, and symptoms were assessed while the patients were seated and after standing for up to 10 minutes before and hourly after the study drug. Supine (P<0.001) and standing (P<0.001) heart rates were significantly lower after propranolol compared with placebo. The symptom burden improvement from baseline to 2 hours was greater with propranolol than placebo (median, -4.5 versus 0 arbitrary units; P=0.044). In protocol 2, 18 patients with POTS underwent similar trials of high-dose (80 mg) versus low-dose (20 mg) propranolol. Although the high dose elicited a greater decrease than the low dose in standing heart rate (P<0.001) and orthostatic tachycardia (P<0.001), the improvement in symptoms at 2 hours was greater with low-dose propranolol (-6 versus -2 arbitrary units; P=0.041).

Conclusions—Low-dose oral propranolol significantly attenuated tachycardia and improved symptoms in POTS. Higher-dose propranolol did not further improve, and may worsen, symptoms.