Eleonora Tobaldini

Heart rate variability explored in the frequency domain: a tool to investigate the link between heart and behavior.

The neural regulation of circulatory function is mainly effected through the interplay of the sympathetic and vagal outflows. This interaction can be explored by assessing cardiovascular rhythmicity with appropriate spectral methodologies. Spectral analysis of cardiovascular signal variability, and in particular of RR period (heart rate variability, HRV), is a widely used procedure to investigate autonomic cardiovascular control and/or target function impairment. The oscillatory pattern which characterizes the spectral profile of heart rate and arterial pressure short-term variability consists of two major components, at low (LF, 0.04-0.15Hz) and high (HF, synchronous with respiratory rate) frequency, respectively, related to vasomotor and respiratory activity. With this procedure the state of sympathovagal balance modulating sinus node pacemaker activity can be quantified in a variety of physiological and pathophysiological conditions. Changes in sympathovagal balance can be often detected in basal conditions, however a reduced responsiveness to an excitatory stimulus is the most common feature that characterizes numerous pathophysiological states. Moreover the attenuation of an oscillatory pattern or its impaired responsiveness to a given stimulus can also reflect an altered target function and thus can furnish interesting prognostic markers. The dynamic assessment of these autonomic changes may provide crucial diagnostic, therapeutic and prognostic information, not only in relation to cardiovascular, but also non-cardiovascular disease. As linear methodologies fail to provide significant information in conditions of extremely reduced variability (e.g. strenuous exercise, heart failure) and in presence of rapid and transients changes or coactivation of the two branches of autonomic nervous system, the development of new non-linear approaches seems to provide a new perspective in investigating neural control of cardiovascular system.

Temporal asymmetries of short-term heart period variability are linked to autonomic regulation

We exploit time reversibility analysis, checking the invariance of statistical features of a series after time reversal, to detect temporal asymmetries of short-term heart period variability series. Reversibility indexes were extracted from 22 healthy fetuses between 16th to 40th wk of gestation and from 17 healthy humans (aged 21 to 54, median=28) during graded head-up tilt with table inclination angles randomly selected inside the set {15, 30, 45, 60, 75, 90}. Irreversibility analysis showed that nonlinear dynamics observed in short-term heart period variability are mostly due to asymmetric patterns characterized by bradycardic runs shorter than tachycardic ones. These temporal asymmetries were 1) more likely over short temporal scales than over longer, dominant ones; 2) more frequent during the late period of pregnancy (from 25th to 40th week of gestation); 3) significantly present in healthy humans at rest in supine position; 4) more numerous during 75 and 90 degrees head-up tilt. Results suggest that asymmetric patterns observable in short-term heart period variability might be the result of a fully developed autonomic regulation and that an important shift of the sympathovagal balance toward sympathetic predominance (and vagal withdrawal) can increase their presence.

Heart rate variability in normal and pathological sleep

Sleep is a physiological process involving different biological systems, from molecular to organ level; its integrity is essential for maintaining health and homeostasis in human beings. Although in the past sleep has been considered a state of quiet, experimental and clinical evidences suggest a noteworthy activation of different biological systems during sleep. A key role is played by the autonomic nervous system (ANS), whose modulation regulates cardiovascular functions during sleep onset and different sleep stages. Therefore, an interest on the evaluation of autonomic cardiovascular control in health and disease is growing by means of linear and non-linear heart rate variability (HRV) analyses. The application of classical tools for ANS analysis, such as HRV during physiological sleep, showed that the rapid eye movement (REM) stage is characterized by a likely sympathetic predominance associated with a vagal withdrawal, while the opposite trend is observed during non-REM sleep. More recently, the use of non-linear tools, such as entropy-derived indices, have provided new insight on the cardiac autonomic regulation, revealing for instance changes in the cardiovascular complexity during REM sleep, supporting the hypothesis of a reduced capability of the cardiovascular system to deal with stress challenges. Interestingly, different HRV tools have been applied to characterize autonomic cardiac control in different pathological conditions, from neurological sleep disorders to sleep disordered breathing (SDB). In summary, linear and non-linear analysis of HRV are reliable approaches to assess changes of autonomic cardiac modulation during sleep both in health and diseases. The use of these tools could provide important information of clinical and prognostic relevance.

RT variability unrelated to heart period and respiration progressively increases during graded head-up tilt

Open-loop linear parametric models were exploited to describe ventricular repolarization duration (VRD) variability during graded head-up tilt. Surface ECG and thoracic movements were recorded in 15 healthy humans (age: 24-54 yr, median: 28 yr; 6 women and 9 men). Tilt table inclinations ranged from 15 to 90 degrees and were varied in steps of 15 degrees . All subjects underwent recordings at every step in random order. Heart period was assessed as the time difference between two consecutive R-wave peaks (RR) and the respiratory signal (R) as the sampling of the thoracic movement signal at the R-wave peaks. VRD was measured automatically as the temporal difference between the R-wave peak and T-wave apex (RT(a)) or T-wave end (RT(e)). The best model decomposed RT variability as due to RR changes (RR-related RT variability) to direct respiratory-related inputs (R-related RT variability) and to unknown rhythmical sources unrelated to RR changes and R (RR-R-unrelated RT variability). Using this model, RT(e) variability was found to be less predictable than RT(a) variability and composed of a smaller fraction of RR-related RT variability and a larger fraction of RR-R-unrelated RT variability. Predictability progressively decreased with tilt table angles, suggesting increased complexity of RT regulation. RT variance progressively increased with tilt table inclination. This increase was characterized by a gradual rise of the amount of RR-R-unrelated RT variability, whereas the amount of RR-related RT variability remained unchanged. These results suggest that the amount of RT variability, complexity of RT dynamics, and amount of RR-R-unrelated RT variability increase with the magnitude of the sympathetic drive directly related to tilt table inclination. We propose the utilization of the amount of RR-R-unrelated RT variability instead of overall RT variability as an indirect measure of autonomic regulation directed to ventricles.

Model-based assessment of baroreflex and cardiopulmonary couplings during graded head-up tilt

We propose a multivariate dynamical adjustment (MDA) modeling approach to assess the strength of baroreflex and cardiopulmonary couplings from spontaneous cardiovascular variabilities. Open loop MDA (OLMDA) and closed loop MDA (CLMDA) models were compared. The coupling strength was assessed during progressive sympathetic activation induced by graded head-up tilt. Both OLMDA and CLMDA models suggested that baroreflex coupling progressively increased with tilt table inclination. Only CLMDA model indicated that cardiopulmonary coupling due to the direct link from respiration to heart period gradually decreased with tilt table angles, while that due to the indirect link mediated by systolic arterial pressure progressively increased.

Short-term complexity of cardiac autonomic control during sleep: REM as a potential risk factor for cardiovascular system in aging.

INTRODUCTION Sleep is a complex phenomenon characterized by important modifications throughout life and by changes of autonomic cardiovascular control. Aging is associated with a reduction of the overall heart rate variability (HRV) and a decrease of complexity of autonomic cardiac regulation. The aim of our study was to evaluate the HRV complexity using two entropy-derived measures, Shannon Entropy (SE) and Corrected Conditional Entropy (CCE), during sleep in young and older subjects. METHODS A polysomnographic study was performed in 12 healthy young (21.1±0.8 years) and 12 healthy older subjects (64.9±1.9 years). After the sleep scoring, heart period time series were divided into wake (W), Stage 1-2 (S1-2), Stage 3-4 (S3-4) and REM. Two complexity indexes were assessed: SE(3) measuring the complexity of a distribution of 3-beat patterns (SE(3) is higher when all the patterns are identically distributed and it is lower when some patterns are more likely) and CCE(min) measuring the minimum amount of information that cannot be derived from the knowledge of previous values. RESULTS Across the different sleep stages, young subjects had similar RR interval, total variance, SE(3) and CCE(min). In the older group, SE(3) and CCE(min) were reduced during REM sleep compared to S1-2, S3-4 and W. Compared to young subjects, during W and sleep the older subjects showed a lower RR interval and reduced total variance as well as a significant reduction of SE(3) and CCE(min). This decrease of entropy measures was more evident during REM sleep. CONCLUSION Our study indicates that aging is characterized by a reduction of entropy indices of cardiovascular variability during wake/sleep cycle, more evident during REM sleep. We conclude that during aging REM sleep is associated with a simplification of cardiac control mechanisms that could lead to an impaired ability of the cardiovascular system to react to cardiovascular adverse events.

Short-term complexity indexes of heart period and systolic arterial pressure variabilities provide complementary information

It is unclear whether the complexity of the variability of the systolic arterial pressure (SAP) provides complementary information to that of the heart period (HP). The complexity of HP and SAP variabilities was assessed from short beat-to-beat recordings (i.e., 256 cardiac beats). The evaluation was made during a pharmacological protocol that induced vagal blockade with atropine or a sympathetic blockade (beta-adrenergic blockade with propranolol or central sympathetic blockade with clonidine) alone or in combination, during a graded head-up tilt, and in patients with Parkinsons disease (PD) without orthostatic hypotension undergoing orthostatic challenge. Complexity was quantified according to the mean square prediction error (MSPE) derived from univariate autoregressive (AR) and multivariate AR (MAR) models. We found that: 1) MSPE(MAR) did not provide additional information to that of MSPE(AR); 2) SAP variability was less complex than that of HP; 3) because HP complexity was reduced by either vagal blockade or vagal withdrawal induced by head-up tilt and was unaffected by beta-adrenergic blockade, HP was under vagal control; 4) because SAP complexity was increased by central sympathetic blockade and was unmodified by either vagal blockade or vagal withdrawal induced by head-up tilt, SAP was under sympathetic control; 5) SAP complexity was increased in patients with PD; and 6) during orthostatic challenge, the complexity of both HP and SAP variabilities in patients with PD remained high, thus indicating both vagal and sympathetic impairments. Complexity indexes derived from short HP and SAP beat-to-beat series provide complementary information and are helpful in detecting early autonomic dysfunction in patients with PD well before circulatory symptoms become noticeable.

Sleep, sleep deprivation, autonomic nervous system and cardiovascular diseases

HighlightsSleep deprivation (SD) can be due to lifestyle habits and sleep disorders.SD alters several mechanisms, i.e. autonomic nervous system, inflammation, endothelial dysfunction.SD are associated with increased risk of cardiovascular and metabolic diseases.An early diagnosis of sleep disorders is essential to prevent detrimental effects on health. ABSTRACT Sleep deprivation (SD) has become a relevant health problem in modern societies. We can be sleep deprived due to lifestyle habits or due to sleep disorders, such as insomnia, obstructive sleep apnea (OSA) and neurological disorders. One of the common element of sleep disorders is the condition of chronic SD, which has complex biological consequences. SD is capable of inducing different biological effects, such as neural autonomic control changes, increased oxidative stress, altered inflammatory and coagulatory responses and accelerated atherosclerosis. All these mechanisms links SD and cardiovascular and metabolic disorders. Epidemiological studies have shown that short sleep duration is associated with increased incidence of cardiovascular diseases, such as coronary artery disease, hypertension, arrhythmias, diabetes and obesity, after adjustment for socioeconomic and demographic risk factors and comorbidities. Thus, an early assessment of a condition of SD and its treatment is clinically relevant to prevent the harmful consequences of a very common condition in adult population.

Symbolic analysis detects alterations of cardiac autonomic modulation in congestive heart failure rats

Congestive heart failure (CHF) is associated with neurohumoral activation. Only very few studies have examined the progression of autonomic dysfunction in CHF in humans and scanty data are available in animal models of CHF. This study was performed to assess the changes in cardiac autonomic modulation during the progression of CHF in a rat model, using an innovative analysis of heart rate variability. Progression of cardiovascular autonomic dysfunction was assessed in a rat model of CHF induced by coronary artery ligation. Spectral and symbolic analyses were performed on heart period (approximated with pulse interval, PI) and systolic arterial pressure (SAP) signals, acquired ~2 and ~4 weeks after the surgical procedure. As CHF developed, symbolic analysis revealed a decrease of rhythmical physiological sympathetic modulation, as indicated by the reduction of the percentage of stable patterns. In addition, symbolic analysis revealed that runs of short-long-short and/or long-short-long PI values and high-low-high and/or low-high-low SAP values were more and more frequent as CHF progressed. On the contrary, spectral analysis of PI and SAP series was not able to detect any impairment of autonomic regulation. Indeed, low frequency and high frequency powers derived from both PI and SAP series were not significantly changed. These data indicate that the autonomic cardiovascular modulation is altered during the progression of CHF and that symbolic analysis seems to be more suitable than spectral analysis to describe alterations of heart period dynamics and of cardiovascular regulation in this animal model of CHF.

Frequency domain assessment of the coupling strength between ventricular repolarization duration and heart period during graded head-up tilt.

We test the hypothesis that the degree of correlation between ventricular repolarization duration (VRD) and heart period (HP) carries information on cardiac autonomic regulation. The degree of correlation was assessed in the frequency domain using squared coherence function during an experimental protocol known to gradually induce a shift of sympathovagal balance toward sympathetic predominance (ie, graded head-up tilt). We observed a progressive decrease of squared coherence with tilt table inclination, thus confirming the working hypothesis. The VRD-HP uncoupling occurs in the high-frequency band, centered on the respiratory rate, thus suggesting that vagal withdrawal is responsible for the VRD-HP uncoupling.