Propranolol decreases tachycardia and improves symptoms in the postural tachycardia syndrome: less is more

Abstract

Background: Postural tachycardia syndrome (POTS) induces disabling chronic orthostatic intolerance with an excessive increase in heart rate on standing. beta-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.

Conflict of interest statement

Conflicts of Interest

None

Figures

Figure 1. Seated, standing and orthostatic changes in heart rates and blood pressures before and after propranolol 20mg vs. placebo (Protocol #1)

Heart rate (HR) and systolic blood pressure (SBP) data are presented immediately before (pre), and hourly for 4 hours (4H) following study drug administration for the propranolol 20mg day (“Prop 20”; solid circles) and the placebo day (open squares). Peak HR after standing for a maximum of 10 minutes (Fig 1A), seated HR immediately before standing (Fig 1B) and the changes in HR from sit to stand (Fig 1C) are shown in the top 3 panels. Similarly, the data for standing SBP (Fig 1D), seated SBP (Fig 1E) and the changes in SBP from sit to stand (Fig 1F) are shown in the bottom 3 panels. The error bars represent the standard error of the mean. The ANOVA P values are presented for the overall effect of the study drug over time. bpm – beats per minute; mmHg – millimeters of mercury.

Figure 2. Seated, standing and orthostatic changes in heart rates and blood pressures before and after Low Dose (20mg) Propranolol vs. High Dose (80mg) Propranolol (Protocol #2)

Heart rate (HR) and systolic blood pressure (SBP) data are presented immediately before (pre), and hourly for 4 hours (4H) following study drug administration for the propranolol 20mg day (“Prop 20”; solid circles) and the propranolol 80mg day (“Prop 80”; open triangles). Peak HR after standing for a maximum of 10 minutes (Fig 1A), seated HR immediately before standing (Fig 1B) and the changes in HR from sit to stand (Fig 1C) are shown in the top 3 panels. Similarly, the data for standing SBP (Fig 1D), seated SBP (Fig 1E) and the changes in SBP from sit to stand (Fig 1F) are shown in the bottom 3 panels. The error bars represent the standard error of the mean. The ANOVA P values are presented for the overall effect of the study drug over time. bpm – beats per minute; mmHg – millimeters of mercury.

Figure 3. Change in symptoms with study medication

The changes in the total Vanderbilt POTS symptom score (in arbitrary units [au]) are presented from immediately before to 2 hours following study drug administration. Panel A shows the changes for Protocol #1, with data for the propranolol 20mg day (solid black) and the placebo day (black dots) for the 36 subjects that completed symptom reporting for both interventions. Panel B shows the changes for Protocol #2, with data for the propranolol 20mg day (solid black) and the propranolol 80mg (checkered) for the 18 subjects. A negative score reflects a reduction in symptom burden. The error bars represent standard error of the mean. The P value was generated using a Wilcoxon rank-sum test.

Figure 4. Changes in individual symptoms in Protocol #1

The changes in the 9 individual components of the Vanderbilt POTS symptom score (in arbitrary units [au]) are presented from immediately before to 2 hours following study drug administration for propranolol 20mg (solid black) and placebo (black dots). A negative number represents an improvement in symptoms.