Discordance between microneurographic and heart-rate spectral indices of sympathetic activity in pulmonary arterial hypertension
- Department of Medicine, University Health Network and Mount Sinai Hospital, and University of Toronto, Toronto, Ontario, Canada
- Dr J S Floras, Suite 1614, 600 University Avenue, Toronto, Ontario, Canada, M5G 1X5; john.floras{at}utoronto.ca
- Accepted 23 December 2008
- Published Online First 16 January 2009
Abstract
Objectives: To determine, in patients with pulmonary arterial hypertension (PAH), whether there is a relationship: (1) between sympathetic nerve firing rate and spectral indices of sympathetic neural heart rate modulation; and (2) between heart rate variability (HRV) and right atrial pressure, a stimulus to sinoatrial node stretch.
Design: Characterisation of patients and healthy controls.
Setting: Teaching hospital-based study.
Patients: 9 PAH patients without elevated pulmonary capillary wedge pressure and nine age-matched control subjects.
Interventions: Heart rate (HR) and muscle sympathetic nerve activity (MSNA) were recorded during 10 min of supine rest in both PAH patients studied after right heart catheterisation, and healthy volunteers. Coarse-graining spectral analysis determined HR spectral power.
Main outcome measures: (1) Low-frequency (PL) spectral component of HRV; (2) MSNA burst frequency; and in PAH patients: (3) right atrial pressure.
Results: MSNA burst frequency was higher in PAH patients (48 (24) and 29 (11) bursts/min, respectively; mean (SD); p = 0.05), whereas total power (p = 0.01), its fractal (p<0.01) and harmonic (p = 0.04) components, and PL (p = 0.01) were all reduced. PL related inversely to both MSNA burst frequency (r = −0.86, p = 0.005) and right atrial systolic pressure (r = −0.77, p = 0.04).
Conclusions: Thus, in PAH (as in patients with left ventricular systolic dysfunction) loss of PL relates inversely to gain in MSNA burst frequency. Diminished sympathetic neural heart rate modulation and increased right atrial stretch may combine to attenuate HRV, an adverse prognostic marker.
Footnotes
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Funding: This investigation was supported by the Heart & Stroke Foundation of Ontario (Grant in Aid #T4938; Career Investigator Award to JSF; Heart & Stroke Foundation of Ontario New Investigator Award to SM; Postdoctoral Research Fellowship Award to CLM), and the Canada Research Chairs Program (JSF).
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Competing interests: JSS has received honoraria from Actelion Pharmaceuticals and Encysive for Continuing Medical Education (CME) presentations. He has also received travel support for educational meetings and honoraria for advisory board meetings from Actelion Pharmaceuticals and GlaxoSmithKline (GSK). JTG has received funds from Actelion Pharmaceuticals for an investigator initiated trial, in addition to consultant and speakers honoraria from Actelion Pharmaceuticals, GSK, Encysive, United Therapeutics and Pfizer. Neither investigator participated directly in the acquisition or analysis of main outcome measures.
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Ethics approval: Ethics approval was provided by the University Health Network, Toronto Research Ethics Board.
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Patient consent: Obtained.
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This work was presented in part at the Experimental Biology 2007 Meeting (28 April to 2 May 2007, Washington, DC)
