Neuroscience and heart-brain medicine: The year in review
ABSTRACT
Important recent publications in the area of neuroscience and heart-brain medicine center largely around three topics: (1) mechanisms of cardiac sympathetic denervation in Parkinson disease, (2) cytoplasmic monoamine metabolites as autotoxins, and (3) the validity of power spectral analysis of heart rate variability to indicate cardiac sympathetic tone. Findings by Orimo et al support a centripetal, retrograde pathogenetic process involving alpha-synuclein deposition and degeneration of cardiac noradrenergic neurons in Parkinson disease. Several studies suggest that processes increasing cytoplasmic monoamines lead to neuronal loss from auto-oxidation or enzymatic oxidation. Lack of correlation between commonly used indices from power spectral analysis of heart rate variability and cardiac norepinephrine spillover casts doubt on the validity of power spectral analysis to indicate cardiac sympathetic tone.
VALIDITY OF POWER SPECTRAL ANALYSIS OF HEART RATE VARIABILITY TO INDICATE CARDIAC SYMPATHETIC TONE
Power spectral analysis of heart rate variability is simple, relatively inexpensive, noninvasive, and widely used to indicate cardiac sympathetic “tone” or sympathovagal “balance.” Almost 2,000 studies to date have used this modality. Relatively increased cardiac sympathetic tone, reflected by low-frequency (LF) power or the ratio of LF power to high-frequency (HF) power, is an adverse prognostic sign in a variety of conditions. Nevertheless, the validity of LF power, or the LF:HF ratio, as an index of cardiac sympathetic tone remains unsettled.
In 2007 we assessed the validity of power spectral analysis rather directly, by taking advantage of our ability to delineate cardiac sympathetic innervation. We compared LF power in patients with cardiac sympathetic denervation, indicated by low myocardial levels of 6-[18F]fluorodopamine–derived radioactivity or low rates of norepinephrine entry into coronary sinus plasma (cardiac norepinephrine spillover), with values in patients with intact innervation. LF power was unrelated to myocardial 6-[18F]fluorodopamine–derived radioactivity or cardiac norepinephrine spillover, but it was related to baroreflex-cardiovagal gain. Patients with a low baroreflex-cardiovagal gain had low LF power, regardless of cardiac innervation. From these findings we concluded that LF power reflects baroreflex function, not cardiac sympathetic innervation.21
Recently Baumert et al also examined the relationship between indices from power spectral analysis of heart rate variability and cardiac norepinephrine spillover.22 They found, as we did, that none of the standard heart rate variability parameters was correlated with cardiac norepinephrine spillover (Figure 6). The same group reported a positive correlation between the heart rate–corrected QT interval and cardiac norepinephrine spillover.23 Among patients with major depression, the distribution of cardiac norepinephrine spillover seemed bimodal. Overall, cardiac norepinephrine spillover was not increased, although a subgroup had clearly increased spillover.
In congestive heart failure, baroreflex-cardiovagal gain tends to be low and cardiac sympathetic outflow markedly increased, yet the LF:HF ratio is not increased during supine rest.24,25 It therefore appears that power spectral analysis of heart rate variability may provide a measure of baroreflexive modulation of autonomic outflows to the heart but not a measure of those outflows themselves. The search continues for a valid, noninvasive means to assess cardiac sympathetic function.
