Low-dose propranolol and exercise capacity in postural tachycardia syndrome

Abstract

Objective: To determine the effect of low-dose propranolol on maximal exercise capacity in patients with postural tachycardia syndrome (POTS). Methods:We compared the effect of placebo vs a single low dose of propranolol (20 mg) on peak oxygen consumption (VO 2 max), an established measure of exercise capacity, in 11 patients with POTS and 7 healthy subjects in a randomized, double-blind study. Subjects exercised on a semirecumbent bicycle, with increasing intervals of resistance to maximal effort.Results: Maximal exercise capacity was similar between groups following placebo. Low-dose propranolol improved VO 2 max in patients with POTS (24.5 6 0.7 placebo vs 27.6 6 1.0 mL/min/kg propranolol; p 5 0.024), but not healthy subjects. The increase in VO 2 max in POTS was associated with attenuated peak heart rate responses (142 6 8 propranolol vs 165 6 4 bpm placebo; p 5 0.005) and improved stroke volume (81 6 4 propranolol vs 67 6 3 mL placebo; p 5 0.013). In a separate cohort of POTS patients, neither high-dose propranolol (80 mg) nor metoprolol (100 mg) improved VO 2 max, despite similar lowering of heart rate.Conclusions: These findings suggest that nonselective b-blockade with propranolol, when used at the low doses frequently used for treatment of POTS, may provide a modest beneficial effect to improve heart rate control and exercise capacity. Classification of evidence:This study provides Class II evidence that a single low dose of propranolol (20 mg) as compared with placebo is useful in increasing maximum exercise capacity measured 1 hour after medication. Neurology â 2013;80:1927-1933 GLOSSARY BP 5 blood pressure; CI 5 confidence interval; CO 5 cardiac output; HF RRI 5 high-frequency R-R interval; HR 5 heat rate; LF RRI 5 low-frequency R-R interval; MAP 5 mean arterial pressure; POTS 5 postural tachycardia syndrome; SV 5 stroke volume; SVR 5 systemic vascular resistance; VO 2 max 5 peak oxygen consumption.Postural tachycardia syndrome (POTS) is a heterogeneous disorder characterized by sustained tachycardia ($30 bpm) upon standing, unrelated to medications or other medical conditions. 1 Although the underlying cause of POTS remains unclear, several mechanisms have been proposed, including sympathetic activation, hypovolemia, and, more recently, deconditioning.2-4 Indeed, endurance exercise training decreases standing heart rate (HR), restores blood volume, and improves orthostatic tolerance and associated symptoms in POTS. [5][6][7] Another frequently used treatment for POTS is nonselective b-adrenergic blockade with propranolol. 8,9 At low doses, propranolol reduces standing HR and improves orthostatic symptoms. 8,10,11 In contrast, higher doses can more effectively control tachycardia, but do not improve quality of life or orthostatic symptoms. 5,8 Because b-blockers impair exercise tolerance in healthy subjects, 12 this raises the concern that these drugs would counteract the beneficial effects of exercise training in POTS. We hypothesized, however, that by controlling tachycardia, b-blockers ...

Sympathetic activation is associated with increased IL-6, but not CRP in the absence of obesity: lessons from postural tachycardia syndrome and obesity

“…Taken together, our findings indicate the presence of a hyperadrenergic condition in lean females with POTS particularly while upright. This is in agreement with other studies (17,21,29,38,44), and our previous observations that POTS patients have an exaggerated decrease in BP induced by ganglionic blockade (30), and that the orthostatic tachycardia is responsive to ␤-blockade (4,46). We recognize that POTS is heterogeneous in presentation and pathophysiological mechanisms.…”

Postural Orthostatic Tachycardia Syndrome (POTS): Assess, Diagnose, and Evaluate for POTS Treatment (ADEPT)

“…Some studies cited the use of beta-blockers [6,12,13,14,30,45], which can control the palpitations, and fludrocortisone, for plasma volume expansion and possible sensitization of the peripheral adrenergic receptors to catecholamines [6,12,13], as treatments of choice. Interestingly, low-dose propranolol was found to be more effective for the treatment of POTS symptoms [45,46] than metoprolol and high-dose propranolol, which controlled the heart rate but unexpectedly worsened the POTS symptoms [46]. Because of the improvement in symptoms, low-dose propranolol was found to improve exercise capacity in patients with POTS [45].…”

“…Interestingly, low-dose propranolol was found to be more effective for the treatment of POTS symptoms [45,46] than metoprolol and high-dose propranolol, which controlled the heart rate but unexpectedly worsened the POTS symptoms [46]. Because of the improvement in symptoms, low-dose propranolol was found to improve exercise capacity in patients with POTS [45]. …”

“…The study by Mayuga et al [31] supported the hypothesis that POTS patients should resume the supine position with their legs elevated to alleviate their symptoms, since physical counter-maneuvers can offer quick recovery from symptoms. In addition, exercise retraining was found to be effective to improve functionality [6,12,45,48,49]. Finally, a number of studies included in the systematic review for chronic fatigue syndrome concluded that cognitive behavioral therapy reduces chronic fatigue severity, enhancing an overall sense of well-being [32].…”

Managing the patient with episodic sinus tachycardia and orthostatic intolerance

“…Although this mechanism is most often associated with IAST, hyperadrenergic POTS has been described. Recent studies have demonstrated increased exercise capacity in POTS with use of low-dose propranolol [36,37]. POTS and IAST patients may be highly sensitive to beta-blockers and develop many side effects; thus these agents should be initiated at a low dose and titrated slowly.…”