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.

Short-Term Heart Rate Variability Strongly Predicts Sudden Cardiac Death in Chronic Heart Failure Patients

“…Both vagomimetic drugs 26 and ␤-blockers 27 improve autonomic balance in CHF patients. In the subset of patients in whom plasma catecholamines were assessed, peripheral noradrenaline was significantly higher in the presence of markedly reduced LF power, in agreement with the finding that markedly increased sympathetic discharge in CHF is correlated with reduced LF power, 22,23 thus providing the link with an increased risk for sudden death.…”

“…Reduced LF power during extreme sympathoexcitation might be due to (1) reduced responsiveness of the sinus node, 21 (2) loss of oscillatory behavior during overwhelming chronic sympathetic overactivity, 20 (3) a central abnormality in autonomic modulation, 22,23 or (4) the effect of an impaired baroreflex. 24 However, because variability in the LF band is also vagally mediated, a role for parasympathetic withdrawal (possibly due to low baroreflex sensitivity) cannot be excluded 25 ; the spectral patterns observed in advanced CHF patients are similar to those observed during progressive atropine blockade.…”

Arterial baroreflex function and cardiovascular variability: interactions and implications

“…In these patients, despite direct evidence of high levels of sympathetic activation (increased cardiac and total norepinephrine spillover and MSNA) (36,59), there is a blunting or absence of the LF component of R-R and SNA (83,116). The observed dissociation between sympathetic drive and LF power in the power spectra of cardiovascular variability implies that the traditional paradigm linking increased sympathetic drive to increased LF power in normal subjects cannot simply be extrapolated to include pathological conditions such as severe heart failure, where all homeostatic mechanisms are mobilized at close to maximum levels with little or no reserve to maintain variability.…”

To Pulse or Not to Pulse, Is That the Question?

“…1,[6][7][8] In contrast, in patients with chronic heart failure with reduced ejection fraction who have impaired exercise capacity, MSNA burst incidence commonly falls between 80 and 100 bursts per cardiac cycles. [7][8][9][10] Prior Heartmate II literature indicates that the circulatory stability achieved after ≥3 months is sufficient to improve cardiac sympathetic innervation and to establish a lower noradrenergic central set point.…”

“…In patients with chronic heart failure as a consequence of impaired systolic function, both this gating and the blood pressure-muscle sympathetic nerve activity (MSNA) relationship are preserved. [1][2][3] The evolution of mechanical left ventricular support from devices that generate a pulse wave to those that propel blood continuously thus raises a number of intriguing questions about the body's adaptation to this alien physiology: What effect does short-or long-term diminution or loss of arterial pulse pressure have on the neural regulation of the heart and circulation by the baroreceptor reflex? What impact do such changes have on endothelial biology, autoregulation of regional blood flow, and tissue or organ perfusion?…”