Postural tachycardia syndrome and inappropriate sinus tachycardia: role of autonomic modulation and sinus node automaticity

Abstract

Background: Inappropriate sinus tachycardia (IST) and postural tachycardia syndrome (POTS) are 2 disorders characterized by sinus tachycardia. It is debated whether the pathophysiology of IST and POTS results from abnormal autonomic regulation or abnormal sinus node function. We hypothesized that intrinsic heart rate (IHR) after autonomic blockade would be increased in patients with IST but not POTS.

Methods and results: We enrolled 48 POTS patients, 8 IST patients, and 17 healthy control (HC) subjects. Intravenous propranolol and atropine were given to block the sympathetic and parasympathetic limbs of the autonomic nervous system in order to determine the IHR. Patients with IST have a higher sympathetic contribution to heart rate when compared with POTS patients (31±13 bpm versus 12±7 bpm, P<0.001) and HC (8±4 bpm; P<0.001) and a trend to less parasympathetic contribution than POTS and HC (IST: 31±11 bpm versus POTS: 46±11 bpm versus HC: 48±11 bpm, ANOVA P=0.108). IHR was not significantly different between IST and either POTS or HC (IST: 111±11 bpm versus POTS: 108±11 bpm versus HC: 106±12 bpm, ANOVA P=0.237).

Conclusions: IST patients have more sympathetic tone when compared with either POTS or HC, but IST patients do not have abnormal sinus node automaticity. These data suggest that the treatment of IST and POTS should focus on sympatholysis, reserving sinus node modification for patients with continued debilitating symptoms after beta-blockade and possibly ivabradine.

Clinical trial registration url: http://clinicaltrials.gov/. Unique identifier: NCT00262470.

Keywords: autonomic nervous system; inappropriate sinus tachycardia; postural tachycardia syndrome; sinus node; sympathetic nervous system.

Figure 1.

Schematic diagram showing the study design. After a 10‐minute baseline to obtain resting heart rate (HR), subjects were given propranolol in 4 divided doses. This dose was enough to block the parasympathetic arm of the autonomic nervous system. After recording the post‐propranolol HR, atropine was given in 4 divided doses. The resultant HR is the intrinsic HR.

Figure 2.

Intrinsic heart rate (HR) data is presented after pharmacologic blockade with propranolol and atropine (A). Sympathetic contribution to HR was calculated as the drop in HR with IV propranolol (B), and the parasympathetic contribution to HR was calculated as the increase in HR with IV atropine (C). The error bars represent standard error of the mean. The adjusted ANOVA P values for age and BMI are presented as the overall difference and post‐hoc Bonferroni tests were used to adjust for multiple pair‐wise comparisons. ANOVA indicates analysis of variance; BMI, body mass index; HC, healthy control; IST, inappropriate sinus tachycardia; POTS, postural tachycardia syndrome; PSYM, parasympathetic; SYM, sympathetic.

Figure 3.

High frequency heart rate variability (RRI‐HF; A) and low frequency systolic blood pressure variability (SBP‐LF; B) are shown. Adjusted ANOVA P values are presented for overall difference and post‐hoc Bonferroni tests were used to adjust for multiple pair‐wise comparisons. ANOVA indicates analysis of variance; HC, healthy control; IST, inappropriate sinus tachycardia; POTS, postural tachycardia syndrome.

Figure 4.

Schematic cartoon of sinus tachycardia disorders spectrum. Postural tachycardia syndrome (POTS) patients have greater sympathetic tone (SNS) and less parasympathetic tone (PNS) than healthy subjects. Patients with inappropriate sinus tachycardia (IST) patients have even greater SNS tone and lower PNS tone compared to POTS patients.