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Heart rate variability (HRV) reflects regulatory processes of the cardiovascular system and reveals fractal characteristics. In this paper we investigated standard HRV parameters and scaling characteristics in ten athletes before, during, and after a 2-week training camp to assess the effects of short-term overtraining on cardiovascular control. High-resolution ECGs were recorded over 30 min under resting conditions 1 week before the training camp, after 1 week of training in the camp, and after 3-4 days of recovery. Standard HRV analysis was performed according to Task Force recommendations. Scaling characteristics were assessed, applying detrended fluctuation analysis (DFA). Standard HRV analysis showed significant changes in meanNN and rmssd during the training camp. DFA revealed three distinct regions of scale-invariance and significant alterations during the training camp. In conclusion, HRV might be used to monitor the training state in athletes.

Objective: To assess the effects of abruptly intensified physical training on cardiovascular control. Design: Retrospective longitudinal study. Setting: Research laboratory. Participants: Ten healthy athletes (5 men and 5 women) from track and field as well as triathlon. Interventions: A 2-week training camp, including daily stepwise increasing cycling tests, running of 40 minutes, and additional cycling of 60 minutes. Main Outcome Measurements: Time and frequency domain parameters of resting heart rate and blood pressure variability (HRV and BPV) and baroreflex sensitivity (BRS), before, during, and after the training camp. Results: We found significantly reduced HRV during the training camp (mean beat-to-beat interval: 1042 [937 to 1194] ms vs. 933 [832 to 1103] ms vs. 1055 [947 to 1183] ms, P , 0.01; root-meansquare of beat-to-beat interval differences: 68 [52 to 95] ms vs. 52 [38 to 71] ms vs. 61 [48 to 78] ms, P , 0.05). Further, BRS was significantly reduced: 25.2 (20.4 to 40.4) ms/mmHg vs. 17.0 (12.9 to 25.7) ms/mmHg vs. 25.7 (18.8 to 29.1) ms/mmHg, P , 0.05. These effects disappeared at a large degree after 3 to 4 days of recovery. Conclusion: Abruptly intensified physical training results in an altered autonomic cardiovascular activity towards parasympathetic inhibition and sympathetic activation that can be monitored by means of HRVand BRS analyses and might provide useful markers to avoid the overtraining syndrome.

Sudden cardiac death (SCD) is a leading cause of mortality with an incidence of 3 million cases per year worldwide. Therapies for patients who have survived an SCD episode or have a high risk of developing lethal ventricular arrhythmia are well established and depend mainly on risk stratification. In this study we investigated the suitability of the non-linear measure compression entropy (HC) for improved risk prediction in cardiac patients. We recorded 24-h Holter ECG for 300 patients with congestive heart failure (CHF). During a mean follow-up period of 12 months, 32 patients died due to a cardiac event. HC depends on the compression parameters window length w and buffer length b, which were optimised by analysing a subgroup of patients. Compression entropies based on the beat-to-beat interval (BBI) were subsequently calculated and compared with standard heartrate variability parameters. Statistical analysis revealed significant differences between high- and low-risk CHF patients in standard HRV measures, as well as compression entropy based on the BBI (cardiac death, ps0.005; SCD, ps0.02). In conclusion, the implementation of non-linear compression entropy analysis in multivariate analysis seems to be useful for enhanced risk stratification of cardiac death, especially SCD, in ischaemic cardiomyopathy patients.

Background: Abnormal uterine perfusion is associated with the development of hypertensive pregnancy disorders. However, its impact on maternal autonomic cardiovascular control is poorly understood. The aim of our study was to investigate the adaptation of autonomic control during pregnancy with abnormal uterine perfusion with normal and pathologic outcome in comparison to normal pregnancies. based on blood pressure variability (BPV), baroreflex sensitivity (BRS), and heart rate variability (HRV) analyses. Methods: A total of 32 healthy pregnant women (CON, age 28 years, range 24 to 31 years); 16 women with abnormal uterine perfusion and normal outcome (AP-NO, age 29 years, range 28 to 33 years); and 19 women with abnormal uterine perfusion and pathologic outcome (AP-PO, age 26 years, range 25 to 30 years), were recruited for this longitudinal study. Beginning in the 20th week of pregnancy, the women were monitored every fourth week until delivery. For the analysis of BPV, BRS, and HRV, high-resolution ECG, and noninvasive continuous blood pressure (BP) recordings were taken simultaneously for 30 minutes. Results: CON showed pregnancy-induced adaptation of cardiovascular control; in the course of gestation BPV was increased while parameters of HRV and BRS were reduced. On the contrary, no changes during the second half of pregnancy could be observed in pregnancies with abnormal perfusion. Variability parameters were significantly altered in women with abnormal perfusion compared with CON, whereas these changes were more pronounced in AP-PO compared with AP-NO. Conclusions: Abnormal uterine perfusion, independently of the pregnancy outcome, has a significant impact on maternal cardiovascular control. Measures of BPV, BRS and HRV might be used for improved risk stratification.

Arterial blood pressure is modulated by several physiological regulatory processes. The analysis of beat-to-beat blood pressure dynamics provides information about cardiovascular control and patho-physiological conditions. In this paper we investigated the long-term correlations and fractal dimension of systolic blood pressure time series applying detrended fluctuation analysis (DFA) and Higuchi's algorithm (HFD). Thirty-minute blood pressure recordings in 25 patients with dilated cardiomyopathy (DCM) and 27 healthy controls (CON) were analyzed. The DFA and HFD revealed multifractal features in the blood pressure dynamics of CON as well as of DCM. At small scales, DFA and HFD of CON were significantly different from those of CON, reflecting patho-physiological changes. In conclusion, scaling analysis of blood pressure dynamics might lead to an enhanced assessment of autonomic cardiovascular control in patients with DCM.

Heart rate exhibits spontaneous fluctuations that are mainly modulated by control loops within the autonomic nervous system. Assessing the dynamics of heart rate fluctuations can provide valuable information about regulatory processes and patho-physiological behavior. In this paper heart rate fluctuations and its entropy are assessed using an algorithmic information theoretic concept applying a data compressor. First, the beat-to-beat fluctuations of heart rate are binary coded for decreases and increases, respectively. Subsequently, those symbol sequences are compressed using the LZ77 algorithm. The ratio of the length of the compressed sequences to the original length is used as an estimate of entropy. We investigated the compressibility of heart rate fluctuations in athletes before, during, and after a training camp. Heart rate time series were obtained from ECGs recorded over 30 minutes under supine resting conditions. We found a significant entropy reduction during the training camp, reflecting the effects of physical fatigue. In conclusion, the compression entropy seems to be a suitable approach to assess the complexity of heart rate fluctuations.

In the US, it is currently estimated that 3% of pregnant women have chronic hypertension, or more than 100,000 pregnant women each year. The aim of our study was to investigate the adaptation of autonomic control during pregnancy based on heart rate variability analysis and to determine whether chronic hypertension during pregnancy has an impact on this adaptation. Sixteen pregnant women with chronic hypertension (CH group; mean age, 30 years; range, 25-33 years) and 35 healthy pregnant women serving as controls (CON group; mean age, 28 years; range, 24-30 years) were recruited for this longitudinal study. Beginning at the 20th week of pregnancy, the women were monitored every 4th week until delivery. For the analysis of heart rate variability, Portapres signals (200 Hz) were recorded for 30 min under resting conditions. Women in the CH group had significantly elevated blood pressure compared to controls (CON, 111 mmHg [105-132]; CH, 140 mmHg [132-148]; p

BACKGROUND Neurovegetative and haemodynamic changes impact on the regulation pattern of blood pressure and heart rate in patients with heart failure. We studied these patterns and their interactions in patients with idiopathic dilated cardiomyopathy (IDC) and in healthy subjects (REF). METHODS We continually measured the heart rate and blood pressure (Portapres device) in twenty-five supine IDC patients (age: 51 +/- 13 y; left ventricular end-diastolic diameter 67 +/- 11 mm; ejection fraction 30 +/- 11%) and in twenty-seven REF (age: 50 +/- 11 y) Recording time was 30 minutes. The heart rate (HR) of each beat and the systolic blood pressure (SYS) of the subsequent beat were measured. Code numbers (symbols) were assigned to the beat-to-beat changes in HR and SYS (increase: 1; decrease: 0). The frequencies of the symbols sequences of three successive beats were counted. In this way we obtained a matrix consisting of eight (two to the power of three) HR and SYS combinations: 000, 100, 010, 001, 111, 110, 011 and 101. We then counted the frequencies of the different combinations of the symbol sequences in HR and SYS (2(3) x 2(3) = 64 combinations). The relative frequencies of symbol patterns appearing in HR, SYS and in the combined analysis of HR and SYS, were compared for IDC and REF using the T-test for independent samples. RESULTS Significant differences were seen between IDC and REF. The HR patterns 101 and 010 were more frequent in IDC than in REF patients (11.1 +/- 4.7 vs. 7.7 +/- 2.9%, p = 0.003, and 16.1 +/- 6.3 vs. 11.7 +/- 4.9%, p = 0.008). This finding was even more marked in the analysis of the SYS patterns 101 and 010 (11.0 +/- 7.4 vs. 8.2 +/- 2.9%, p < 0.001, and 11.6 +/- 7.4 vs. 5.4 +/- 2.7%, p < 0.001). Non-alternating patterns were more frequent in REF (e.g. 000HR & 111SYS: 4.6 +/- 3.3 vs. 2.9 +/- 2.4%, p = 0.03). CONCLUSIONS We demonstrated significant interaction of the regulation patterns of blood pressure and heart rate, as also their interactions in IDC. Opposed changes in HR and SYS mediated by the baroreflex, became superimposed by alternans phenomena in IDC. The pattern analysis of changes in HR and SYS detects these disturbances of neurovegetative short-term control.

The beat-to-beat variability of the diastolic blood pressure induces small variations in the afterload of the left ventricle. These variations influence myocardial contractility, and thus blood pressure amplitude. We assessed the interdependence of blood pressure and changes in the afterload. We continuously recorded blood pressure (duration 200 s, at rest) in 20 patients with dilated cardiomyopathy (ejection fraction 32 +/- 13%, left ventricular diameter 67 +/- 8 mm) and in 20 healthy volunteers. Interbeat intervals, diastolic pressures, systolic pressure amplitudes and mean slopes of systolic pressure amplitudes were measured. Correlation coefficients (r) were calculated to assess the interdependence of blood pressure amplitudes/mean systolic slopes and the preceding diastolic pressures/interbeat intervals, respectively. In healthy volunteers we found a strong interdependence between blood pressure amplitude and the preceding diastolic pressures (r = 0.62 +/- 0.21 and 0.47 +/- 0.22). Higher diastolic pressures were followed by higher blood pressure amplitudes, and by steeper slopes of the systolic peaks. In patients with dilated cardiomyopathy, such interdependence was significantly lower (r = 0.33 +/- 22 and r = 0.28 +/- 0.35), and in patients with severely reduced left ventricular function (ejection fraction < 32%) was only marginal (r = 0.23 +/- 0.27 and 0.21 +/- 0.44, respectively). The forces of the isovolumetric contraction necessary to initiate the ejection phase of the left ventricle depend on the afterload, i.e. on the diastolic pressure. The responses of amplitude and slope of the systolic blood pressure to small changes in the afterload make it possible to assess left ventricular contractility. The latter is impaired in dilated cardiomyopathy.

In heart failure patients with implantable cardioverter defibrillator (ICD) the risk of death from causes other than tachyarrhythmia is substantial. Benefit from ICD is determined by two competing risks: appropriate ICD shock or nonarrhythmic death. The goal of the study was to test predictors of competing outcomes.Patients with structural heart disease (N = 234, mean age 58.5 ± 15.1; 71% men, 80% whites, 61% ischemic cardiomyopathy) and primary (75%) or secondary prevention ICD underwent a 5-minute baseline near-field electrogram (NF EGM) recording. VV' alternans triplets were quantified as a percentage of three sinus VV' cycles sequences of "short-long-short" or "long-short-long" order. Appropriate ICD shock for fast ventricular tachycardia (FVT, cycle length ≤240 ms)/ventricular fibrillation (VF) and composite nonarrhythmic death (pump failure death or heart transplant) served as competing outcomes.Over a median follow-up of 2.4 years, 26 patients (4.6% per person-year of follow-up) developed FVT/VF with ICD shock, and 35 (6.3% per person-year of follow-up) had nonarrhythmic death. In competing risk analysis, after adjustment for demographics, left ventricular ejection fraction, New York Heart Association class, cardiomyopathy type, use of class I antiarrhythmics, and diabetes, increased percentage of VV' alternans triplets (69%) was associated with nonarrhythmic death (subhazard ratio [SHR] 2.09; 95% confidence interval [CI] 1.03-4.23; P = 0.041), rather than with FVT/VF (SHR 1.05; 95% CI 0.45-2.46; P = 0.901). Risk of nonarrhythmic death was especially high in diabetics with VV' alternans triplets in the highest quartile (SHR 3.46; 95% CI 1.41-8.50; P = 0.007).In ICD patients with structural heart disease sinus VV' alternans triplets on NF EGM is independently associated with nonarrhythmic death, rather than with FVT/VF.

Flow-mediated dilatation (FMD) is a tool widely used to measure arterial responsiveness to sheer stress. However, there is scant literature to show how the peripheral arterial response changes as the vascular system matures. One reason for this is that the feasibility of measuring FMD in younger children has not been established. The aim of the present study was to assess brachial artery function at rest and during the FMD response after 4 min ischaemia of the forearm in children aged 6–15 years. Time to reach maximum FMD (FMDmax) was found to be correlated with age (r = 0.4, P < 0.05), resting brachial artery diameter (r = 0.4, P < 0.05), height (r = 0.4, P < 0.05), body mass index (BMI; r = 0.45, P < 0.05), body surface area (r = 0.44, P < 0.05) and resting blood flow (r = 0.37, P < 0.05). However, there was no correlation between the traditional FMD response at 60 s or FMD maximal dilation and age, resting brachial artery diameter, height, weight, BMI, body surface area and resting blood flow. In conclusion, the time taken to reach the maximal dilation response is related to age, brachial artery luminal diameter and body habitus, but not the traditional measure of FMD response at 60 s or the maximal dilatation percentage. Refereed/Peer-reviewed

This contribution presents a novel warping method, two-dimensional signal warping (2DSW), for tracking beat-to-beat changes in time intervals from electrocardiograms. To evaluate the efficiency of 2DSW to capture subtle changes in the QT interval we apply 2DSW to the Physionet QT database. It is shown that 2DSW allows highly accurate tracking of QRS-onset and T-end, which renders the method useful for future clinical applications, in particular beat-to-beat variability analysis of ECG features.

Recently it could be demonstrated that systolic and diastolic blood pressure variability (BPV) as well as segmented Poincare plot analysis (SPPA) contribute to risk stratification in patients suffering from dilated cardiomyopathy (DCM). The aim of this study was to further improve the risk stratification applying multivariate technique including QT variability (QTV). 56 low risk and 13 high risk DCM patients were enrolled and significantly separated by nearly all methods except traditional heart rate variability analysis. The optimum set of indices included the diastolic BPV index DBP_Shannon and the index QTV_log achieving an area under the receiver operating characteristics curve (AUC) of 92%, sensitivity of 92.3% and specificity of 89.3%. Without BPV analysis the optimum multivariate approach including indices from SPPA and QTV achieved an AUC of 88.3%. Summarizing, we identified DCM patients with an increased risk of sudden cardiac death applying QTV analysis in a multivariate approach.

International audience; Microvascular perfusion is commonly used to study the peripheral cardiovascular system. Microvascular blood flow can be continuously and non-invasively monitored with laser speckle contrast imaging (LSCI) or with laser Doppler flowmetry (LDF). These two optical-based techniques give perfusion values in arbitrary units. Our goal is to better understand the perfusion time series given by each technique. For this purpose, we propose a nonlinear complexity analysis of LSCI and LDF time series recorded simultaneously in nine healthy subjects. This is performed through the computation of their multiscale compression entropy. The results obtained with LSCI time series computed from different regions of interest (ROI) sizes are examined. Our findings show that, for LSCI and LDF time series, compression entropy values are less than one for all of the scales analyzed. This suggests that, for all scales, there are repetitive structures within the data fluctuations. Moreover, at the largest scales studied, LDF signals seem to have structures that are different from those Entropy 2014, 16 5778 of Gaussian white noise. By opposition, this is not observed for LSCI time series computed from small ROI sizes.

STUDY OBJECTIVE To investigate respiratory cycle-related electroencephalographic changes (RCREC) in healthy children and in children with sleep disordered breathing (SDB) during scored event-free (SEF) breathing periods of sleep. DESIGN Interventional case-control repeated measurements design. SETTING Paediatric sleep laboratory in a hospital setting. PARTICIPANTS Forty children with SDB and 40 healthy, age- and sex-matched children. INTERVENTIONS Adenotonsillectomy in children with SDB and no intervention in controls. MEASUREMENTS AND RESULTS Overnight polysomnography; electroencephalography (EEG) power variations within SEF respiratory cycles in the overall and frequency band-specific EEG within stage 2 nonrapid eye movement (NREM) sleep, slow wave sleep (SWS), and rapid eye movement (REM) sleep. Within both groups there was a decrease in EEG power during inspiration compared to expiration across all sleep stages. Compared to controls, RCREC in children with SDB in the overall EEG were significantly higher during REM and frequency band specific RCRECs were higher in the theta band of stage 2 and REM sleep, alpha band of SWS and REM sleep, and sigma band of REM sleep. This between-group difference was not significant postadenotonsillectomy. CONCLUSION The presence of nonrandom respiratory cycle-related electroencephalographic changes (RCREC) in both healthy children and in children with sleep disordered breathing (SDB) during NREM and REM sleep has been demonstrated. The RCREC values were higher in children with SDB, predominantly in REM sleep and this difference reduced after adenotonsillectomy. CITATION Immanuel SA, Pamula Y, Kohler M, Martin J, Kennedy D, Saint DA, Baumert M. Respiratory cycle-related electroencephalographic changes during sleep in healthy children and in children with sleep disordered breathing.

This study sought to employ a novel approach based on joint symbolic dynamics (JSD) to study the influence of respiratory phase on baroreflex function. We recorded electrocardiograms (ECG), blood pressure and respiration in 10 (5 male/5 female) healthy experienced athletes. For our analysis, time series of R-R intervals and systolic blood pressure were extracted, and respiratory phases were obtained using the Hilbert transform. Based on the changes between successive values, each series was transformed into binary symbol vectors, and words of length `2' were formed. From parallel analysis of the symbolic dynamics in the three time series, the relationship between respiratory phases and baroreflex function was quantified. We analysed baroreflex patterns via different word combinations for specific respiratory phases and observed that baroreflex patterns occurred at similar frequency during expiration, inspiration and phase transitions (25.0±14.4% vs. 33.4±19.5%, expiration-inspiration: 25.0±12.6% and inspiration-expiration: 22.1±17.4%, respectively). From this study, it appears that JSD provides a novel and efficient technique for the combined analysis of interactions between respiration, heart rate and blood pressure.

Heart rate fluctuates beat by beat in a complex manner. The aim of this study was to develop a framework for entropy assessment of heart rate fluctuations on multiple time scales. We employed the Lempel-Ziv algorithm for lossless data compression to investigate the compressibility of RR interval time series on different time scales, using a coarse-graining procedure. We estimated the entropy of RR interval time series of 20 young and 20 old subjects and also investigated the compressibility of randomly shuffled surrogate RR time series. The original RR time series displayed significantly smaller compression entropy values than randomized RR interval data. The RR interval time series of older subjects showed significantly different entropy characteristics over multiple time scales than those of younger subjects. In conclusion, data compression may be useful approach for multiscale entropy assessment of heart rate variability.

Ageing has been associated with changes in cardiac electrophysiology that result in QT interval prolongation. The effect of age on rate-adaptation dynamics of the QT interval is less well understood. The aim of this study was to assess age-related changes in the temporal relationship between QT and RR interval variability. Resting ECG of 20 young and 20 elderly healthy subjects were analyzed. Beat-to-beat RR and QT interval time series were automatically extracted. Coupling between QT and RR was assessed by means of the QT variability index, coherence in the frequency domain, rate-corrected QT interval, cross-multiscale entropy, information based similarity index and joint symbolic dynamics. In addition to QT interval prolongation (433 ± 31 versus 405 ± 33 ms, p = 0.008), elderly subjects were characterized by a significantly increased QT variability index (-1.26 ± 0.28 versus -1.52 ± 0.22 ms, p < 0.0001), reduced coherence in high (0.11 ± 0.09 versus 0.29 ± 0.14 ms, p = 0.003), and low frequency bands (0.20 ± 0.16 versus 0.49 ± 0.15 ms, p < 0.0001), reduced information domain synchronization index (0.13 ± 0.07 versus 0.19 ± 0.05 ms, p = 0.001) as well as increased entropy and disparity in joint symbolic dynamics of QT and RR interval time series. In conclusion, ageing is associated with decoupling of QT variability from heart rate variability. Complexity analysis in addition to standard metrics may provide additional insight.

Objective: This study aims to investigate the impact of upper airway obstruction (UAO) in children by measuring thoracoabdominal asynchrony (TAA) during periods of sleep apnea/hypopnea and during scored-event-free (SEF) breathing periods. Conclusion: Upper airway obstruction in children is associated with increased TAA during SEF periods, indicative of continuous partial obstruction of the upper airway. Adenotonsillectomy decreased this effect significantly in non-REM sleep as evidenced by reduced asynchrony levels post-surgery. TAA assessment during sleep may therefore provide additional diagnostic information. Methods: Respiratory inductive plethysmographic signals were extracted from polysomnographic data, recorded before and after adenotonsillectomy in 40 children with UAO and 40 healthy, matched children at equivalent time points. Thoracoabdominal asynchrony was computed using a Hilbert transform-based phase difference estimation method in SEF periods during stage 2, stage 4 non-rapid eye movement (NREM), and rapid eye movement (REM) sleep and compared between the groups. Results: At baseline, in the UAO group, TAA during obstructions were significantly higher than TAA during SEF periods in both stage 2 and REM sleep. Compared to controls, children with UAO had a significantly higher TAA during SEF periods in stage 2, stage 4 sleep, and REM sleep. This between-group difference was not significant post adenotonsillectomy. UAO group showed a significant decrease in TAA compared to their baseline during SEF stage 2 and 4 NREM, but not in REM. Refereed/Peer-reviewed

The aim of this study was to enhance the ECG pre-processing modalities for beat-to-beat QT interval variability measurement based on template matching. The R-peak detection algorithm has been substituted and an efficient baseline removal algorithm has been implemented in existing computer software. To test performance we used simulated ECG data with fixed QT intervals featuring Gaussian noise, baseline wander and amplitude modulation and two alternative algorithms. We computed the standard deviation of beat-to-beat QT intervals as a marker of QT interval variability (QTV). Significantly a lower beat-to-beat QTV was found in the updated approach compared the original algorithm. In addition, the updated template matching computer software outperformed the previous version in discarding fewer beats. In conclusion, the updated ECG preprocessing algorithm is recommended for more accurate quantification of beat-to-beat QT interval variability.

Sleep disordered breathing (SDB) is characterized by repeated episodes of central or obstructive apneas, disturbing respiratory patterns. The purpose of this study is to quantify respiratory variability associated with apneic/hypopneic events by computing respiratory parameters and thoraco-abdominal asynchrony (TAA) over sleep periods preceding the occurrence of obstructive events in children with SDB. One minute artifact-free epochs of ribcage (RC) and abdominal (AB) signals were extracted from the respiratory inductive plethysmograph (RIP) channel of the PSG prior to the onset of each obstruction. Breath-by-breath values of TAA were computed using a Hilbert transform based technique that measures the phase shift between the RC and AB signals. In addition, the following parameters were computed breath-bybreath from the RC signal: inspiratory time (Ti), expiratory time (Te), total time (Ttot), and the inspiratory duty cycle (DC=Ti/Ttot). Standard deviation of the parameters (SD_TAA, SD_Ti, SD_Te, SD_Ttot, SD_DC) over each 1 min epoch were calculated and averaged over each subject with respect to sleep stage. For comparison, similar measures were computed from within quiet breathing periods of each subject. We found that breaths immediately before apnea/hypopneas were associated with a high degree of variability in respiratory timing and TAA. The proposed variability analysis of RIP signals may be useful for detecting acute epochs of respiratory instability in children with SDB. Refereed/Peer-reviewed

Study Objectives: To investigate the association between indices of sleep spindle activity and cognitive performance in a sample of healthy children. Conclusions: Basal sleep spindle activity is associated with different aspects of cognitive performance in children. To the extent that these associations in a pediatric population are different from what is known in adult sleep may play an important role in development. Design: Correlational. Intelligence (Stanford-Binet) and neurocognitive functioning (NEPSY) were assessed, with sleep variables being measured during overnight polysomnography. Interventions: N/A. Measurements and Results: Participants underwent a single night of overnight polysomnography after completing measures of intelligence and neurocognitive functioning. Sleep spindles were visually identified by an experienced sleep scoring technician and separated algorithmically into fast (> 13 Hz) and slow spindle (< 13 Hz) categories. The number of fast spindles was significantly correlated with narrative memory (rs = 0.38) and sensorimotor functioning (-0.43). Mean central frequency of spindles was also significantly correlated with sensorimotor functioning (-0.41), planning ability (-0.41), and working memory (-0.54). Participants: Twenty-seven healthy children (mean age 8.19 y; 14 female, 13 male). Setting: Hospital sleep laboratory. Refereed/Peer-reviewed

Assessment of breathing in polysomnographic studies is commonly performed by measuring ribcage and abdominal movements using respiratory inductive plethysmographic (RIP) effort sensors, in addition to nasal/oral airflow measurements. This paper aims to analyse RIP signals in healthy children for the degree of respiratory regularity across sleep stages. We quantified (a) respiratory waveform regularity by computing the percentage of low frequency energy (%LFE) using a wavelet-based approach and (b) associated thoraco-abdominal asynchrony (TAA) by computing the phase deviation between the ribcage and abdominal signals using a Hilbert transform approach, and examined the influence of sleep stages on these measures. Five minute segments of quiet breathing data during stage 2, 4 non-rapid eye movement (NREM) sleep and rapid-eye-movement (REM) sleep were extracted. The %LFE contained in the frequency range of 0.02 to 0.05 Hz was computed from the ribcage signal and TAA was calculated between corresponding ribcage and abdominal excursions. Sleep stage effects were significant for both measures with REM sleep exhibiting the greatest respiratory waveform irregularity and asynchrony compared to NREM sleep stages 2 and 4. Also TAA and %LFE were significantly correlated in REM sleep [r=0.625 p

Analysis of blood pressure waveform: a new method for the classification of hypertensive pregnancy disorders

Background— The pivot is critical to rotors postulated to maintain atrial fibrillation (AF). We reasoned that wavefronts circling the pivot should broaden the amplitude distribution of bipolar electrograms because of directional information encoded in these signals. We aimed to determine whether Shannon entropy (ShEn), a measure of signal amplitude distribution, could differentiate the pivot from surrounding peripheral regions and thereby assist clinical rotor mapping. Methods and Results— Bipolar electrogram recordings were studied in 4 systems: (1) computer simulations of rotors in a 2-dimensional atrial sheet; (2) isolated rat atria recorded with a multi-electrode array (n=12); (3) epicardial plaque recordings of induced AF in hypertensive sheep (n=11); and (4) persistent AF patients (n=10). In the model systems, rotation episodes were identified, and ShEn calculated as an index of amplitude distribution. In humans, ShEn distribution was analyzed at AF termination sites and with respect to complex fractionated electrogram mean. We analyzed rotation episodes in simulations (4 cycles) and animals (rats: 14 rotors, duration 80±81 cycles; sheep: 13 rotors, 4.2±1.5 cycles). The maximum ShEn bipole was consistently colocated with the pivot zone. ShEn was negatively associated with distance from the pivot zone in simulated spiral waves, rats, and sheep. ShEn was modestly inversely associated with complex fractionated electrogram; however, there was no relationship at the sites of highest ShEn. Conclusions— ShEn is a mechanistically based tool that may assist AF rotor mapping.

The aim of this study was to quantify cardiorespiratory interaction in patients with obstructive sleep apnea syndrome (OSAS) during night-time sleep using our recently proposed technique based on joint symbolic dynamics (JSD) and compare it with the synchrogram technique. We investigated overnight polysomnography data of 213 patients with OSAS. The R-R time series were extracted from electrocardiograms (ECG) and respiratory phases were obtained from abdominal displacement sensors using the Hilbert transform. For the JSD technique, both series were transformed into ternary symbol vectors based on the changes between two successive R-R intervals and the respective respiratory phases. Subsequently, words of length ‘3’ were formed and the correspondence between words of the two series was determined for each sleep stage to quantify cardio-respiratory interaction. To determine the effect of OSAS severity on cardiorespiratory interaction, the cohort was trichotomized based on the apnea-hypopnea index (AHI): AHI≤15, 15

Heart rate and respiration display fluctuations that are interlinked by central regulatory mechanisms of the autonomic nervous system (ANS). Joint assessment of respiratory time series along with heart rate variability (HRV) may therefore provide information on ANS dysfunction. The aim of this study was to investigate cardio-respiratory interaction in patients with Parkinson's disease (PD), a neurodegenerative disorder that is associated with progressive ANS dysfunction. Short-term ECG and respiration were recorded in 25 PD patients and 28 healthy controls during rest. To assess ANS dysfunction we analyzed joint symbolic dynamics of heart rate and respiration, cardio-respiratory synchrograms along with heart rate variability. Neither HRV nor cardio-respiratory synchrograms were significantly altered in PD patients. Symbolic analysis, however, identified a significant reduction in cardio-respiratory interactions in PD patients compared to healthy controls (16 ± 3.6 % vs. 20 ± 6.1 %; p= 0.02). In conclusion, joint symbolic analysis of cardio-respiratory dynamics provides a powerful tool to detect early signs of autonomic nervous system dysfunction in Parkinson's disease patients at an early stage of the disease.

We present a technique based on the Hilbert transform to quantify the thoraco-abdominal asynchrony (TAA) based on the phase shift between ribcage (RC) and abdomenal (AB) breathing signals acquired using respiratory inductive plethysmography (RIP). We employed this method to investigate RIP during overnight polysomnography (PSG) in 40 healthy children for analysis of their breathing patterns in various stages of sleep (ss 2, 3, 4 and REM) and in two common sleeping positions (supine and lateral). RIP signals free of respiratory or movement artifacts were segmented into 30 second epochs. Those epochs with maximum power in the quiet breathing frequency range and positional invariance throughout were included for further processing. TAA was calculated from corresponding RC and AB excursions. We found a statistically significant influence of sleep position on the level of TAA in all stages of non-REM sleep. In conclusion, the Hilbert transform provides a simple tool for the quantification of thoraco-abdominal asynchrony.

The aim of this paper was to study the effect of spontaneous arousals during night-time sleep on the interactions between R-R intervals and respiratory phases in healthy children. We collected overnight polysomnography data of 40 healthy children and investigated cardio-respiratory interaction before and after spontaneous arousals during stage 2 sleep using joint symbolic dynamics. The R-R time series were extracted from electrocardiograms (ECG) and respiratory phases were obtained from abdominal sensors using the Hilbert transform. Both the series were transformed into ternary symbol vectors based on the changes between two successive R-R intervals or respiratory phases, respectively. Subsequently, words of length 2 were formed and the correspondence between words of the two series was determined to quantify cardio-respiratory interaction for pre- and post-spontaneous arousal episodes. We observed a brief but significant shortening in R-R and respiratory intervals after arousal. There was also a significant short-term increase in cardio-respiratory interaction during the first 30-second post-arousal episode as compared to 30-second pre-arousal episode (7.5±3.4 vs. 5.2±3.7%, p

The aim of this study was to investigate beat-to-beat variations of spatial and temporal QRS and T loop morphology for identifying myocardial infarction (MI) patients. We investigated short-term 12-lead ECG recordings of 84 MI patients (22 female, mean age 63 ± 12 years and 62 male, mean age 56 ± 10 years) and 69 healthy control subjects (17 female, mean age 42 ± 18 years and 52 male, mean age 40 ± 13 years). To quantify spatial and temporal variations in QRS complex and T-wave morphology, we defined two descriptor parameters: point-to-point distance variability (DV) and mean loop length (MLL). These parameters were extracted from the reconstructed vector ECG, using singular value decomposition. The results showed that the beat-to-beat spatiotemporal point-to-point distance variability for QRS and T loops (DV QRS ; 0.13±0.04 vs. 0.10±0.04, p < 0.0001 and DV T ; 0.16±0.07 vs. 0.13±0.06, p < 0.05), were significantly higher in MI subjects compared to control subjects. In addition, the mean loop length of QRS and T loops were significantly higher in control subjects than MI (p < 0.001), respectively. In conclusion, the beat-to-beat spatiotemporal DV and MLL may be useful for characterizing conduction and repolarization characteristics in patients with MI.

Background Atrial premature contractions (APCs) are well described to precede the initiation of paroxysmal atrial fibrillation (pAF). However, whether APC characteristics alter with progression of the arrhythmia is unknown. Objective To determine the APC characteristics in terms of burden and relative coupling interval with progression of the AF disease process. Methods Fifty consecutive patients with pAF, 50 consecutive patients with persistent AF (perAF), and 25 age-matched controls underwent clinical review, transthoracic echocardiography, and ambulatory electrocardiogram monitoring. After excluding 29 patients who had AF for the entire recording (n = 24) or unreliable recordings (n = 5), we analyzed data from 49 patients with pAF, 24 patients with perAF, and 23 healthy controls. All normal morphology R-R intervals with a >25% decrease in R-R coupling compared with the previous R-R interval (coupling interval index) were deemed APCs (n = 95,873). Results The median APC burden was higher in patients with pAF (2 [1–22] APCs/h; P = .004) and perAF (3 [1–6] APCs/h; P = .04) than in controls (1 [0–1] APCs/h) but was not different ( P = .66) between the AF subgroups. Patients with pAF had a distinct increase in ectopy burden after 7 PM and elevation throughout the night ( P = .002) in comparison with a blunted and complementary temporal response in the perAF cohort ( P = .01). Patients with pAF demonstrated a greater proportion of shortly coupled APCs (29% [13–45]; P = .04) compared with persistent arrhythmia (17% [5–29]). Conclusions "Real-life" atrial trigger statistics of APC burden, timing, and diurnal rhythms track the transition from a trigger-based, autonomically sensitive paroxysmal arrhythmia to a more substrate-based persistent disease.

Objectives: Increased beat-to-beat variability in the QT interval has been associated with heart disease and mortality. The purpose of this study was to investigate the beat-to-beat spatial and temporal variations of ventricular depolarization and repolarization in vectorcardiogram (VCG) for characterising myocardial infarction (MI) patients. Methods: Standard 12-lead ECGs of 84 MI patients (22 f, 63612 yrs; 62 m, 56610 yrs) and 69 healthy subjects (17 f, 42618 yrs; 52 m, 40613 yrs) were investigated. To extract the beat-to-beat QT intervals, a template-matching algorithm and the singular value decomposition method have been applied to synthesise the ECG data to VCG. Spatial and temporal variations in the QRS complex and T-wave loops were studied by investigating several descriptors (point-to-point distance variability, mean loop length, T-wave morphology dispersion, percentage of loop area, total cosine R-to-T). Results: Point-to-point distance variability of QRS and T-loops (0.1360.04 vs. 0.1060.04, p, 0.0001 and 0.1660.07 vs. 0.1360.06, p, 0.05) were significantly larger in the MI group than in the control group. The average T-wave morphology dispersion was significantly higher in the MI group than in the control group (62u68u vs. 38u616u, p, 0.0001). Further, its beat-to-beat variability appeared significantly lower in the MI group than in the control group (12u65u vs. 15u66u, p, 0.005). Moreover, the average percentage of the T-loop area was found significantly lower in the MI group than the controls (46617 vs. 55615, p, 0.001). Finally, the average and beat-to-beat variability of total cosine R-to-T were not found statistically significant between both groups. Conclusions: Beat-to-beat assessment of VCG parameters may have diagnostic attributes that might help in identifying MI patients.

In this study we assessed the effect of body postural changes from the supine (Sup) to the upright (Up) position on the magnitude and phase of respiratory sinus arrhythmia (RSA) and the phase-locking between the heart rhythm and respiration. In eight healthy human subjects, electrocardiograms (ECG) and respiratory signals were recorded. The magnitude and phase of RSA were evaluated by selective averaging of R-R interval changes from multiple respiratory cycles over the respiratory phase. For the assessment of cardiorespiratory coordination, we analyzed the phase-locking between heart rate, computed from R-R intervals of ECG, and respiratory rate, computed from intervals of inspiratory onsets of respiration, using Hilbert transform. A significant decrease in the magnitude of RSA and percentage and duration of phase-locking between heart rate and respiratory rate was observed during Up as compared to Sup. Further, there was a significant increase in the phase of RSA during Up as compared to Sup. In conclusion, measures of RSA and interaction between cardiac and respiratory rhythms are affected by body posture in humans.

Pregnancy has impact on autonomic control. Since hypertensive pregnancy disorders are a major cause of maternal mortality we investigated the baroreflex sensitivity (BRS) in chronic hypertensive pregnant women (CH), normotensive pregnant (PRE) and non-pregnant (NPRE) women. In addition to the traditional 'sequence method' we used joint symbolic dynamics (JSD). BRS was significantly reduced in all pregnancies compared with NPRE (p < 0.00001) but there was no significant difference between CH and PRE. Contrary, the JSD measures revealed significant differences (p < 0.00001) in the heart rate and blood pressure interactions between PRE and CH. In conclusion, JSD measures uncovered a different gestation related adaptation of autonomic regulation in women with chronic.

Cardio-respiratory dynamics exhibit complex behaviour and underlying mechanisms responsible for their interaction have not been fully understood. The aim of this paper was to validate the approach for detection of cardio-respiratory interaction based on joint symbolic dynamics using two simulated non-linearly coupled systems, and to investigate the influence of age on the interaction between cardiac and respiratory cycles in healthy subjects. For symbolic analysis, the time series were transformed into ternary symbol vectors based on the changes between two successive time points of each series. Subsequently, words of length ‘3’ were formed and the correspondence between words of the two series was determined. The process was repeated using surrogate data to determine the effectiveness of the joint symbolic dynamics approach. Subsequently, the electrocardiograms (ECG) and respiratory signals of 20 young (age: 21–34 yrs) and 20 elderly (age: 68–85 yrs) healthy subjects were collected from Physionet, from which the R-R intervals and respiratory phases were extracted, respectively. Using the joint symbolic dynamics approach and an additional adaptive delay in the cardiac oscillator based on the maximization of the cross-correlation between the phases of respiration and the delayed R-R intervals, we found a significantly higher percentage of similarity in the symbolic dynamics of R-R intervals and respiratory phases in young subjects compared to elderly subjects (22.8±6.7 vs. 16.5±6.6 %, p

Hypertensive pregnancy disorders affect 6% to 8% of all pregnancies and can result in severe complications for the mother and the foetus of which pre-eclampsia (PE) has the worst perinatal outcome. Several studies suggested that the autonomic nervous system plays an important role in the process of developing hypertensive pregnancy disorders, especially PE. The aim of this retrospective study was to investigate whether women with PE could be differentiated from women with various other hypertensive pregnancy disorders, by employing an enhanced Poincare plot analysis (PPA), the segmented Poincare plot analysis (SPPA), to their beat-to-beat interval and blood pressure signals. Sixty-nine pregnant women with hypertensive disorders (29 PE, 40 with chronic or gestational hypertension) were included. The SPPA as well as the traditional PPA found significant differences between PE and other hypertensive disorders of diastolic blood pressure (p < 0.001 versus p < 0.001) but only the SPPA method revealed significant differences (p < 0.001) also of the systolic blood pressure. Further on, linear discrimination analysis demonstrated that indices derived from SPPA are more suitable for differentiation between chronic and gestational hypertension and PE than those from traditional PPA (area under the ROC curve 0.85 versus 0.69). Therefore this procedure could contribute to the differential diagnosis of hypertensive pregnancy disorders.

Pregnancy leads to physiological changes in various parameters of the cardiovascular system. The aim of this study was to investigate longitudinal changes in the structure and complexity of heart rate variability (HRV) and QT interval variability during the second half of normal gestation. We analysed 30-min high-resolution ECGs recorded monthly in 32 pregnant women, starting from the 20th week of gestation. Heart rate and QT variability were quantified using multiscale entropy (MSE) and detrended fluctuation analyses (DFA). DFA of HRV showed significantly higher scaling exponents towards the end of gestation (p

In this study we assessed the impact of movement on the interaction between the heart rhythm and respiration in rats while they were conscious and freely moving. In eight male adult Sprague-Dawley (SD, n=4) and Hooded Wistar (HW, n=4) rats, we recorded respiratory rate using whole-body plethysmography with a piezoelectric sensor attached to simultaneously monitor body movement. Heart rate was recorded using a radio-telemetry transmitter. For the assessment of cardiorespiratory coordination, we analysed the phase-locking between heart rate and respiration, estimating the instantaneous phases using Hilbert transform. For statistical analysis, the piezoelectric signal was dichotomized into low-intensity (LIm) and high-intensity (HIm) movement. The R-R intervals, respiratory intervals and cardiorespiratory coordination between LIm and HIm of each rat were assessed with Student's t-test. A significant decrease in the mean values for respiratory interval (0.34 ± 0.1 vs. 0.23 ± 0.1 s, p0.01 in HW rats) and R-R interval (0.19 ± 0.01 vs. 0.17 ± 0.01 s, p0.001 in SD rats) was observed during HIm. The phase-locking between the cardiac and respiratory signals also decreased significantly during HIm (overall coordination during LIm vs. HIm: 89.3 ± 3.3% vs. 8.7 ± 1.7%, p0.001). In conclusion the interaction between the cardiac and respiratory oscillators is affected by voluntary movements in rats.

The assessment of the autonomic cardiovascular regulation provides important diagnostic and prognostic information. The aim of this study was to investigate the alterations of this autonomic regulation in the progress of a normal pregnancy and in several pregnancy disorders associated with hypertension, especially pre-eclampsia, applying the method of Joint Symbolic Dynamics (JSD). The JSD reveals nonlinear interactions/ coupling between two time series.

Objective: The aim of this study was to test whether a new heart rate variability (HRV) complexity measure, the Point Correlation Dimension (PD2i), provides diagnostic information regarding early subclinical autonomic dysfunction in diabetes mellitus (DM). We tested the ability of PD2i to detect diabetic autonomic neuropathy (DAN) in asymptomatic young DM patients without overt neuropathy and compared them to age- and gender-matched controls. Methods: HRV in DM type 1 patients (n = 17, 10 female, 7 male) aged 12.9–31.5 years (duration of DM 12.4 ± 1.2 years) was compared to that in a control group of 17 healthy matched probands. The R–R intervals were measured over 1 h using a telemetric ECG system. Results: PD2i was able to detect ANS dysfunction with p = 0.0006, similar to the best discriminating MSE scale, with p = 0.0002. Discussion: The performance of PD2i to detect DAN in asymptomatic DM patients is similar to the best discriminative power of previously published complexity measures. Conclusions: The PD2i algorithm may prove to be an easy to perform and clinically useful tool for the early detection of autonomic neuropathy in DM type 1 patients, especially given its minimal data requirements.

Cardiac and respiratory rhythms reveal transient phases of phase-locking which were proposed to be an important aspect of cardiorespiratory interaction. The aim of this study was to quantify cardio-respiratory phase-locking in obstructive sleep apnea (OSA). We investigated overnight polysomnography data of 248 subjects with suspected OSA. Cardiorespiratory phase-coupling was computed from the R-R intervals of body surface ECG and respiratory rate, calculated from abdominal and thoracic sensors, using Hilbert transform. A significant reduction in phase-coupling was observed in patients with severe OSA compared to patients with no or mild OSA. Cardiorespiratory phase-coupling was also associated with sleep stages and was significantly reduced during rapid-eye-movement (REM) sleep compared to slow-wave (SW) sleep. There was, however, no effect of age and BMI on phase coupling. Our study suggests that the assessment of cardiorespiratory phase coupling may be used as an ECG based screening tool for determining the severity of OSA.

Objective: Upper airway obstruction (UAO) during childhood is associated with cardiovascular morbidity. The aim of this study was to investigate the cardio-respiratory response to cortical arousal during sleep in children with UAO. Methods: Standard paediatric overnight polysomnography (PSG) was conducted in 40 children with UAO (25 M, 7.5 ± 2.7 yrs) prior to and 6 months following adenotonsillectomy. For comparison a control group of 40 normal, sex and age matched children (21 M, 7.5 ± 2.6 yrs) underwent two PSGs without intervention at the same time points. Results: Heart rate and respiratory rate were measured during spontaneous and respiratory arousals in stage 2 and REM sleep 15 s prior to and 15 s immediately following cortical arousal onset. Cortical arousal was associated with a significant increase in heart and respiratory rate in both groups of children. UAO children, however, showed a significantly higher heart rate response in stage 2 sleep ( 17.5 ± 6.0 vs. 14.4 ± 4.8%; p < 0.05), a lower pre-arousal baseline respiratory rate (stage 2: 17.1 ± 1.4 vs. 18.2 ± 1.7 BPM; p < 0.01) and a prolonged increase in respiratory rate compared to control children. Cardiac and respiratory arousal responses were not significantly different from controls following adenotonsillectomy in the UAO children. Conclusions: UAO in children is associated with an altered cardiorespiratory response to spontaneous arousal from sleep, which may indicate early signs of autonomic dysfunction. Surgical treatment of UAO appears to reverse these outcomes. Refereed/Peer-reviewed

The maternal heart significantly adapts to the circulatory needs of pregnancy, but the effect of pregnancy on ventricular repolarization is poorly understood. The aim of this study was to quantify longitudinal changes in ventricular repolarization during pregnancy. Monthly electrocardiographs (ECGs) were recorded in 32 pregnant women with normal uterine perfusion and 32 pregnant women with abnormal perfusion, starting from the 20th week of gestation until 3 days postpartum. Ventricular repolarization was assessed through various QT interval variability and heart rate adaptation measures. The pregnancy outcomes of all women with normal perfusion were normal. Among pregnancies with abnormal uterine perfusion, 15 pregnancy outcomes were normal, but 17 pregnancies developed preeclampsia and/or small-for-gestational-age infants. In pregnancies with normal perfusion, the QT(c) interval was unaltered, but the QT interval-heart rate hysteresis lag was shorter and the QT interval-heart rate regression residual was higher compared with those of a control group of 10 healthy non-pregnant women. Pregnancies with abnormal uterine perfusion that developed pathological outcomes showed significantly smaller QT interval-heart rate regression residuals and a trend towards shorter QT(c) intervals compared with pregnant women with normal perfusion. In conclusion, pregnancy has a significant effect on ventricular repolarization. Pregnancies with abnormal uterine perfusion and subsequent pathological outcomes are paralleled by changes in ventricular repolarization that precede clinical symptoms.

Arousal from sleep is associated with transient and abrupt cardiorespiratory changes, and elevated arousals associated with sleep disorders may trigger adverse cardiovascular sequela. In this paper, we provide the first data in children on cardiorespiratory responses to cortical arousal. Heart rate and ventilatory responses to arousal from stage 2 and rapid eye movement (REM) sleep were investigated in 40 normal, healthy Caucasian children (age: 7.7 +/- 2.6 years; body mass index z-score: 0.30 +/- 0.8). All children underwent overnight polysomnography studies. Cortical arousals were scored according to standard criteria. Heart rate changes were assessed over 30 s, starting 15 s prior to cortical arousal onset. Breathing rates were quantified three breaths before and after arousal onset. Arousals from stage 2 as well as REM sleep resulted in an R-R interval shortening of about 15%, independent of age and gender. The R-R interval shortening initiated at least 3 s before the cortical arousal onset. The breathing interval immediately after cortical arousal onset was significantly shortened (P0.001). In conclusion, cortical arousals in children are associated with an increase in breathing rate and significant heart rate accelerations, which typically precede the cortical arousal onset.