Abstract 16180: Blockade of Norepinephrine Transporter Magnifies Tachycardia and Worsens Symptoms in Postural Tachycardia Syndrome
Background: The role of pharmacological norepinephrine transporter (NET) antagonists in the management POTS (heart rate [HR] increase >30 bpm on standing) is unsettled. NET inhibitors can promote increased peripheral sympathetic tone via decreased NE clearance. However, supratherapeutic doses of NET inhibitors can cause orthostatic tachycardia in healthy volunteers. Many physicians prescribe NET inhibitors for POTS in an effort to increase vascular resistance & blood pressure and improve symptoms. We prospectively tested the acute effects of atomoxetine, a potent NET inhibitor, on tachycardia and symptoms in POTS.
Methods: Patients with POTS (n=18;16 female,35±8 years) underwent a randomized single-blind crossover trial with oral atomoxetine 40 mg and placebo on separate mornings in a post-absorptive and drug-free state. Non-invasive HR and blood pressure (BP) were measured with the patient seated comfortably. At baseline, and hourly for 4h post-medication, the patients stood for up to 10 min, and their standing HR & BP were recorded. Symptoms were self-recorded q2hourly. Only complete datasets for each parameter were analyzed in the repeated measures general linear model. Data are presented as mean±SD.
Results: The standing HR increased from baseline (B) to 4h post drug for atomoxetine (B:108±18 bpm, 4h:116±14 bpm), but decreased for placebo (B:115±17 bpm, 4h:104±16 bpm; PDRUG=0.057; PINT<0.001). There was no difference in the standing systolic BP between atomoxetine (B:101±10 mmHg, 4h:108±11 mmHg) and placebo (B:101±9 mmHg, 4h:106±11 mmHg; PDRUG=0.181; PINT=0.590). Atomoxetine increased the symptom burden (B:16±11 bpm, 4h:18±16 bpm) while placebo did not (B:22±17 bpm, 4h:16±12 bpm; PINT=0.02).
Conclusions: Acute norepinephrine transporter inhibition with atomoxetine increases standing heart rate in POTS, without a significant increase in systolic blood pressure. Instead of improving symptom burden, it acutely worsened symptoms compared to placebo. These data suggest that drugs that block the norepinephrine transporter might be detrimental in the management of patients with POTS.
- Heart rate/Heart rate variability
- Arrhythmias, treatment of
- Autonomic nervous system
- Central nervous system
- © 2010 by American Heart Association, Inc.