Dissociation between microneurographic and heart rate variability estimates of sympathetic tone in normal subjects and patients with heart failure

Abstract

The concept that spectral analysis of heart rate variability (HRV) can estimate cardiac sympathetic nerve traffic in subjects with both normal and impaired left ventricular systolic function has not been validated against muscle sympathetic nerve activity (MSNA). We used coarse-graining spectral analysis to quantify the harmonic and non-harmonic, or fractal, components of HRV and to determine low-frequency (0.0-0.15 Hz; PL) and high-frequency (0.15-0.5Hz; PH) harmonic power. To test the hypothesis that MSNA and HRV representations of sympathetic nerve activity (PL and PL/PH) increase in parallel in heart failure, we recorded heart rate and MSNA during supine rest in 35 patients (age 52.4+/-2 years; mean+/-S. E.M.), with a mean left ventricular ejection fraction of 22+/-2%, and in 34 age-matched normal subjects. Power density was log10 transformed. Mean MSNA was 52.9+/-2.6 bursts/min in heart failure patients and 34.9+/-1.9 bursts/min in normal subjects (P<0.0001). In normal subjects, but not in heart failure patients, total power (PT) (r=-0.41; P=0.02) and fractal power (PF) (r=-0.36; P=0.04) were inversely related to age. In heart failure patients, total and fractal power were reduced (P<0.009 for both), and were inversely related to MSNA burst frequency (r=-0.55, P=0.001 and r=-0.60, P=0. 0003 respectively). In normal subjects, there was no relationship between MSNA and either PL or PH. In heart failure patients, as anticipated, PH was inversely related to MSNA (r=-0.41; P<0.02). However, PL was also inversely rather than directly related to MSNA (r=0.44 for 1/log10 PL; P<0.01). There was no relationship between other sympathetic (PL/PH) or parasympathetic (PH/PT) indices and MSNA in either heart failure patients or normal subjects. The lack of concordance between these direct and indirect estimates of sympathetic nervous system activity indicates that this component of HRV cannot be used for between-subject comparisons of central sympathetic nervous outflow. It is the absence of low-frequency power that relates most closely to sympathetic activation in heart failure.

Discordance between microneurographic and heart-rate spectral indices of sympathetic activity in pulmonary arterial hypertension

“…There was a significant decrease in absolute power in the low-frequency band of P HP and also in the P L /P H ratio. With the exception of the non-significant trend towards lower high-frequency power (possibly due to the number of PAH subjects studied), these alterations in HRV are remarkably similar to those reported previously for CHF 6. These observations suggest that the higher heart rates of these PAH subjects result primarily from augmented sympathetic, rather than diminished vagal, modulation of sinoatrial discharge.…”

“…Breathing patterns were recorded by a pneumobelt connected to a pressure transducer. Multiunit recordings of postganglionic MSNA were obtained with a unipolar tungsten electrode inserted selectively into a muscle-nerve fascicle of the right fibular nerve in accordance with previously described and published procedures 3 6. As with our previously published protocols, data were acquired simultaneously during 10 min of supine rest and spontaneous breathing 6…”

“…Signal output was inscribed by a Gould Viper recorder (Gould Instrument Systems, Madison, Wisconsin), sampled at a frequency of 200 Hz (with the exception of the electrocardiogram: 1000 Hz) and following conversion from analogue to digital format stored on a PC desktop for subsequent off-line analysis 3 6. Ensemble averages of 256 beat sequences were taken from a minimum time series of 400 to 500 beats.…”

“…To replicate our CHF protocol,6 pulse (R-R) intervals were analysed using coarse graining spectral analysis (CGSA),10 which first divided total spectral power (P T ) into its non-harmonic (1/f) or fractal (P F ) and its harmonic (P HP ) components, from which harmonic power integrated across the low-frequency (P L ) and high-frequency (P H ) ranges was calculated 6. P H normalised to total spectral power (P H /P T ) was derived to estimate parasympathetic heart-rate modulation 6 10. The ratio between P L and P H , a consensus estimate of sympathovagal balance,2 4 was also calculated.…”

“…Harmonic P H arises from vagal heart rate modulation, with respiration being its principal rhythmic stimulus, whereas P L is influenced primarily by sympathetic neural oscillations 2 4 – 10. However, in chronic heart failure (CHF), a condition characterised by increased central sympathetic outflow, total spectral power (P T ) and P L are markedly reduced,6 and there is an inverse rather than positive correlation between one of its manifestations, muscle sympathetic nerve activity (MSNA) and P L 6. Potential explanations for this loss of harmonic power include central attenuation of oscillations of efferent nerves modulating heart rate, reduced sinoatrial responsiveness to neurotransmitters, increased right atrial stretch and tachycardia-driven heart-rate invariance 6 11 12…”