Vagal and Sympathetic Function in Neuropathic Postural Tachycardia Syndrome

Abstract

The diagnosis of neuropathic postural tachycardia syndrome (POTS) requires research techniques not available clinically. We hypothesized that these patients will have impaired vagal and sympathetic cardiovascular control that can be characterized with clinical autonomic tests. We included 12 POTS patients with possible neuropathic subtype because of normal plasma norepinephrine and no increase in upright blood pressure. We compared them to 10 healthy subjects. We assessed hemodynamics, heart rate and blood pressure variability, baroreflex sensitivity, raw and integrated muscle sympathetic nerve activity, and blood volume. To understand the vagal/sympathetic control, we dissected the phase 2 of Valsalva maneuver (VM) into early (VM2e) and late (VM2l). POTS' upright heart rate increased 43±3 bpm. Patients had normal plasma volume but reduced red blood cell volume (1.29 L versus predicted normal values 1.58 L; P=0.02). Vagal indices of heart rate variability, HF_RRI (430±130 versus 1680±900; P=0.04), PNN50, and root mean squared of successive differences were lower in POTS. Patients showed a decrease in vagal baroreflex sensitivity (VM2e; P=0.04). In POTS, integrated muscle sympathetic nerve activity was lower at rest (12±1.5 versus 20±2 burst/min; P=0.004) and raw muscle sympathetic nerve activity spike analysis showed blunted responses during VM2e, despite a greater drop in systolic blood pressure (34±5 in POTS and 14±6 mm Hg in controls; P=0.01). This cohort of POTS patients enriched for possible neuropathic subtype had lower resting muscle sympathetic nerve activity, impaired vagal cardiac control, and exaggerated drop in blood pressure in response to VM and a delay in the sympathetic cardiovascular responsiveness during hypotensive challenge.

Keywords: Valsalva maneuver; baroreflex; blood pressure; heart rate; tachycardia.

Figure 1.

Representative response of heart rate, blood pressure, integrated muscle sympathetic nerve activity (iMSNA), instantaneous spike frequency and straining pressure to Valsalva Maneuver in a patient with neuropathic postural tachycardia syndrome (POTS) and healthy volunteer. Spike frequency was derived from wavelet denoised raw MSNA and is expressed as number of spikes per seconds.

Figure 2.

Averaged changes of systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) during early (VM2e) and late phase two (VM2l) of Valsalva in patients with postural tachycardia syndrome (POTS) and healthy controls (CON).

Figure 3.

Averaged sympathetic response during early (VM2e, left panels) and late phase 2 (VM2l, right panel) of the Valsalva maneuver in patients with postural tachycardia syndrome (POTS) and healthy controls (CON). Response are derived from integrated muscle sympathetic activity (iMSNA) and action potential detection on the. raw neurogram (mean and peak spike frequency, and total spike count).

Figure 4.

Spectral Characteristics of patients with postural tachycardia syndrome (POTS) and healthy controls (CON). RRI – R-R intervals. SBP – systolic blood pressure. LF – Low frequency power. HF- high frequency power. RMSSD – root of mean square of successive differences. PNN50 – percentage of normal heart beats with beat to beat differences less than 50 msec. BRS – baroreflex sensitivity by spectral analysis (Spectral BRS), or spontaneous sequence technique (Sequence BRS), or regression analysis of Valsalva response (Valsalva BRS).