T his article discusses the clinical application and potentiality of a relatively new methodology, which in large part uses noninvasive recordings and appears to provide a quantitative evaluation of the sympathovagal interaction modulating cardiovascular function.As a result of this methodology, pathophysiological conditions of paramount importance, such as arterial hypertension, myocardial ischemia, sudden cardiac death, and heart failure, for which the promoting or aggravating role of neural factors is still largely unknown, might soon undergo a novel scrutiny with practical implications. Physiological BackgroundIn addition to cardiac cycle, two main rhythmic events affect the circulation: respiration and vasomotion. The respiratory activity has long been known to be accompanied by arterial pressure' and heart period fluctuations, whereas the finding of slow arterial pressure oscillations (also referred to as Mayer waves), having a period of approximately 10 seconds, has been more elusive.2-4 On the other hand, rhythmic discharges in phase with respiration have been described in the sympathetic5 and vagal6,7 outflows; similarly, a slower rhythm in phase with vasomotor waves has been found in the sympathetic8,9 and vagal10 efferent discharges.The neural regulation of circulatory function is mainly effected through the interplay of the sympathetic and vagal outflows. In most physiological conditions, the activation of either outflow is accompanied by the inhibition of the other. The sympathovagal balance is tonically and phasically modulated by the interaction of at least three major factors: central neural integration, peripheral inhibitory reflex mechanisms (with negative feedback characteristics), and peripheral excitatory reflex mechanisms (with positive feedback characteristics)"1-'3 (Figure 1).

The Task Force was established by the Board of the European Society of Cardiology and co-sponsored by the North American Society of Pacing and Electrophysiology. It was organised jointly by the Working Groups on Arrhythmias and on Computers of Cardiology of the European Society of Cardiology. After exchanges of written views on the subject, the main meeting of a

Following the publication of the Task Force document on heart rate variability (HRV) in 1996, a number of articles have been published to describe new HRV methodologies and their application in different physiological and clinical studies. This document presents a critical review of the new methods. A particular attention has been paid to methodologies that have not been reported in the 1996 standardization document but have been more recently tested in sufficiently sized populations. The following methods were considered: Long-range correlation and fractal analysis; Short-term complexity; Entropy and regularity; and Nonlinear dynamical systems and chaotic behaviour. For each of these methods, technical aspects, clinical achievements, and suggestions for clinical application were reviewed. While the novel approaches have contributed in the technical understanding of the signal character of HRV, their success in developing new clinical tools, such as those for the identification of high-risk patients, has been rather limited. Available results obtained in selected populations of patients by specialized laboratories are nevertheless of interest but new prospective studies are needed. The investigation of new parameters, descriptive of the complex regulation mechanisms of heart rate, has to be encouraged because not all information in the HRV signal is captured by traditional methods. The new technologies thus could provide after proper validation, additional physiological, and clinical meaning. Multidisciplinary dialogue and specialized courses in the combination of clinical cardiology and complex signal processing methods seem warranted for further advances in studies of cardiac oscillations and in the understanding normal and abnormal cardiac control processes.

SUMMARY The adaptive effects of physical training on cardiovascular control mechanisms were studied in 11 subjects with mild hypertension. In these subjects we assessed the gain of the heart periodsystolic arterial pressure relationship in the unfit and the fit state by using 1) an open loop approach, whereby the gain is expressed by the slope of the regression of heart period as a function of systolic arterial pressure, during a phenylephrine-induced pressure rise and 2) a closed loop approach with proper simplification, whereby the gain is expressed by the index a, obtained through simultaneous spectral analysis of the spontaneous variabilities of heart period and systolic arterial pressure. Both methods indicated that training significantly increased the gain of the relationship between heart period and systolk arterial pressure at rest and reduced arterial pressure and increased heart period significantly. This gam was drastically reduced during bicycle exercise both in the unfit and fit state. In a second group of normotensive (u = 7; systolic pressure, 133 ± 3 mm Hg) and hypertensive (n -1; systolic pressure, 180 ± 10 mm Hg) subjects undergoing 24 -hour diagnostic continuous ekctrocardiographic and high fidelity arterial pressure monitoring, the index a was significantly reduced in the hypertensive group at rest. Furthermore, when analyzed continuously over the entire 24-hour period, this index underwent minute-to-minute changes with lower values during the day and higher values during the night. We propose the index a as a quantitative indicator of the changes in the gain of baroreceptor mechanisms occurring with physical training in mild hypertension and during a 24-hour period in ambulatory subjects. This raises the possibility of recommending physical training as part of the nonpharmacological treatment of hypertension.1 -2 The mechanisms underlying the observed cardiovascular changes are not yet understood but are likely to be quite complex; they may include metabolic, cardiovascular, and neural factors in addition to changes in skeletal muscle fiber type. Our study explored the hypothesis that training induces new operating conditions in the neural regulatory mechanisms. We compared

An integrated approach to the complexity analysis of short heart period variability series (approximately 300 cardiac beats) is proposed and applied to healthy subjects during the sympathetic activation induced by head-up tilt and during the driving action produced by controlled respiration (10, 15, and 20 breaths/min, CR10, CR15, and CR20 respectively). The approach relies on: 1) the calculation of Shannon entropy (SE) of the distribution of patterns lasting three beats; 2) the calculation of a regularity index based on an entropy rate (i.e., the conditional entropy); 3) the classification of frequent deterministic patterns (FDPs) lasting three beats. A redundancy reduction criterion is proposed to group FDPs in four categories according to the number and type or of heart period changes: a) no variation (0V); b) one variation (1V); and c) two like variations (2LV); 4) two unlike variations (2UV). We found that: 1) the SE decreased during tilt due to the increased percentage of missing patterns; 2) the regularity index increased during tilt and CR10 as patterns followed each other according to a more repetitive scheme; and 3) during CR10, SE and regularity index were not redundant as the regularity index significantly decreased while SE remained unchanged. Concerning pattern analysis we found that: a) at rest mainly three classes (0V, 1V, and 2LV) were detected; b) 0V patterns were more likely during tilt; c) 1V and 2LV patterns were more frequent during CR10; and d) 2UV patterns were more likely during CR20. The proposed approach based on quantification of complexity allows a full characterization of heart period dynamics and the identification of experimental conditions known to differently perturb cardiovascular regulation.

In this study, we tested the hypothesis that the neural control of circulation in humans undergoes continuous but in part predictable changes throughout the day and night. Dynamic 24-hour recordings were obtained in two groups of ambulant subjects. In 18 hospitalized patients free to move, direct high-fidelity arterial pressures and electrocardiograms were recorded, and in an additional 28 nonhospitalized subjects, only electrocardiograms were obtained. Spectral analysis of systolic arterial pressure and of RR interval variabilities provided quantitative markers of sympathetic and vagal control of the sinus node and of sympathetic modulation of vasomotor tone. With this approach, the low-frequency (-0.1 Hz) component of RR interval and systolic arterial pressure variabilities is considered a marker primarily of sympathetic activity, whereas the high-frequency (-0.25 Hz) component of RR interval variability, related to respiration, seems to be a marker primarily of vagal activity. We observed a pronounced and consistent reduction in the markers of sympathetic activity and an increase in those of vagal activity during the night. In the invasive studies, while the subjects were still lying in bed after waking up, the markers of sympathetic activity rose rapidly and concomitantly with a simultaneous vagal withdrawal. Noninvasive studies confirmed the early morning rise of the markers of sympathetic activity and the circadian pattern of sympathovagal balance. These data indicate that the ominously increased rate of cardiovascular events in the morning hours may reflect the sudden rise of sympathetic activity and the reduction of vagal tone. (Circulation 1990;81:537-547

Despite several studies and models, much remains unclear about how the human basal ganglia operate. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for complicated Parkinson's disease, but how DBS acts also remains unknown. The clinical benefit of DBS at frequencies >100 Hz suggests the possible importance of neural rhythms operating at frequencies higher than the range normally considered for basal ganglia processing (<100 Hz). The electrodes implanted for DBS also offer the opportunity to record neural activity from the human basal ganglia. This study aimed to assess whether oscillations at frequencies >100 Hz operate in the human STN. While recording local field potentials from the STN of nine patients with Parkinson's disease through DBS electrodes, we found a dopamine- and movement-dependent 300-Hz rhythm. At rest, and in the absence of dopaminergic medication, in most cases (eight out of 11 nuclei) the 100-1000 Hz band showed no consistent rhythm. Levodopa administration elicited (or markedly increased) a 300-Hz rhythm at rest [(mean +/- SD) central frequency: 319 +/- 33 Hz; bandwidth: 72 +/- 21 Hz; power increase (after medication - before medication)/before medication: 1.30 +/- 1.25; n = 11, P = 0.00098]. The 300-Hz rhythm was also increased by apomorphine, but not by orphenadrine. The 300-Hz rhythm was modulated by voluntary movement. Before levodopa administration, movement-related power increase in the 300-Hz rhythm was variably present in different subjects, whereas after levodopa it became a robust phenomenon [before 0.014 +/- 0.014 arbitrary units (AU), after 0.178 +/- 0.339 AU; n = 8, P = 0.0078]. The dopamine-dependent 300-Hz rhythm probably reflects a bistable compound nuclear activity and supports high-resolution information processing in the basal ganglia circuit. An absent 300-Hz subthalamic rhythm could be a pathophysiological clue in Parkinson's disease. The 300-Hz rhythm also provides the rationale for an excitatory--and not only inhibitory--interpretation of DBS mechanism of action in humans.

Antepartum fetal monitoring based on the classical cardiotocography (CTG) is a noninvasive and simple tool for checking fetal status. Its introduction in the clinical routine limited the occurrence of fetal problems leading to a reduction of the precocious child mortality. Nevertheless, very poor indications on fetal pathologies can be inferred from the even automatic CTG analysis methods, which are actually employed. The feeling is that fetal heart rate (FHR) signals and uterine contractions carry much more information on fetal state than is usually extracted by classical analysis methods. In particular, FHR signal contains indications about the neural development of the fetus. However, the methods actually adopted for judging a CTG trace as "abnormal" give weak predictive indications about fetal dangers. We propose a new methodological approach for the CTG monitoring, based on a multiparametric FHR analysis, which includes spectral parameters from autoregressive models and nonlinear algorithms (approximate entropy). This preliminary study considers 14 normal fetuses, eight cases of gestational (maternal) diabetes, and 13 intrauterine growth retarded fetuses. A comparison with the traditional time domain analysis is also included. This paper shows that the proposed new parameters are able to separate normal from pathological fetuses. Results constitute the first step for realizing a new clinical classification system for the early diagnosis of most common fetal pathologies.