Abstract: 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<0.0001). MSE analysis showed a significant decrease in sample entropy of HRV with progressing gestation on scales 1-4 (p<0.05). MSE analysis and DFA of QT interval time series revealed structures significantly different from those of HRV with no significant alteration during the second half of gestation. In conclusion, pregnancy is associated with increases in long-term correlations and regularity of HRV, but it does not affect QT variability. The structure of QT time series is significantly different from that of RR time series, despite its close physiological dependence.
Abstract: Sleep disordered breathing (SDB) in children is assessed by quantification of hypopnea and apnea events. Little is known, however, about respiratory timing and breath-to-breath variability during sleep. The aim of this study was to investigate respiratory parameters across sleep stages in children with SDB before and after treatment in comparison to normal children. Overnight polysomnography (PSG) was conducted in 40 children with SDB prior to and six months following adenotonsillectomy. For comparison, a control group of 40 normal, sex and age matched children underwent two PSGs at equivalent time points but without intervention. The following variables were measured breath by breath during obstruction free periods in stage 2 non-rapid-eye-movement (NREM), stage 4 NREM and rapid-eye-movement (REM) sleep: inspiratory time (Ti), expiratory time (Te), total time (Ttotal), inspiratory duty cycle (DC = Ti / Ttotal), respiratory frequency (fR), standard deviation of the parameters Ti, Te, fR and DC. Variability in waveform morphology was also computed using the residue of respiratory patterns. The severity of SDB was relatively mild in the study cohort (obstructive apnea hypopnea index: baseline: 5.1 ± 9.4 vs. 0.1 ± 0.2, p < 0.001; follow-up: 0.3±0.3 vs. 0.8 ± 1.0. p < 0.01). Compared to healthy controls, children with SDB showed significantly longer Ti and Te and a lower fR at baseline study. These differences were not significant after adenotonsillectomy. Sleep stages were associated with significant differences in all the respiratory measures in both groups of children. In conclusion, children with relatively mild SDB showed prolonged inspiration and expiration indicative of chronic narrowing of the upper airway. Treatment of SDB normalizes respiratory timing. Documentation of these parameters may aid in both understanding and management of children with SDB.
Abstract: To investigate whether grid-tag myocardial strain evaluation can characterise 'border-zone' peri-infarct region and identify patients at risk of ventricular arrhythmia as the peri-infarct myocardial zone may represent an important contributor to ventricular arrhythmia following ST-segment elevation myocardial infarction (STEMI).
Abstract: 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.
Abstract: Elevated beat-to-beat QT interval variability (QTV) has been associated with increased cardiovascular morbidity and mortality.The aim of this study was to investigate interlead differences in beat-to-beat QTV of 12-lead ECG and its relationship with the T wave amplitude.
Abstract: Time irreversibility is a characteristic feature of non-equilibrium, complex systems such as the cardiovascular control mediated by the autonomic nervous system (ANS). Time irreversibility analysis of heart rate variability (HRV) and blood pressure variability (BPV) represents a new approach to assess cardiovascular regulatory mechanisms. The aim of this paper was to assess the changes in HRV and BPV irreversibility during the active orthostatic test (a balance of ANS shifted towards sympathetic predominance) in 28 healthy young subjects. We used three different time irreversibility indices-Porta's, Guzik's and Ehler's indices (P%, G% and E, respectively) derived from data segments containing 1000 beat-to-beat intervals on four timescales. We observed an increase in the HRV and a decrease in the BPV irreversibility during standing compared to the supine position. The postural change in irreversibility was confirmed by surrogate data analysis. The differences were more evident in G% and E than P% and for higher scale factors. Statistical analysis showed a close relationship between G% and E. Contrary to this, the association between P% and G% and P% and E was not proven. We conclude that time irreversibility of beat-to-beat HRV and BPV is significantly altered during orthostasis, implicating involvement of the autonomous nervous system in its generation.
Abstract: Increased beat-to-beat variability in the QT interval (QTV) of ECG has been associated with increased risk for sudden cardiac death, but its measurement is technically challenging and currently not standardized. The aim of this study was to investigate the performance of commonly used beat-to-beat QT interval measurement algorithms. Three different methods (conventional, template stretching and template time shifting) were subjected to simulated data featuring typical ECG recording issues (broadband noise, baseline wander, amplitude modulation) and real short-term ECG of patients before and after infusion of sotalol, a QT interval prolonging drug. Among the three algorithms, the conventional algorithm was most susceptible to noise whereas the template time shifting algorithm showed superior overall performance on simulated and real ECG. None of the algorithms was able to detect increased beat-to-beat QT interval variability after sotalol infusion despite marked prolongation of the average QT interval. The QTV estimates of all three algorithms were inversely correlated with the amplitude of the T wave. In conclusion, template matching algorithms, in particular the time shifting algorithm, are recommended for beat-to-beat variability measurement of QT interval in body surface ECG. Recording noise, T wave amplitude and the beat-rejection strategy are important factors of QTV measurement and require further investigation.
Abstract: 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.
Abstract: Elevated QT interval variability is a predictor of malignant ventricular arrhythmia, but the underlying mechanisms are incompletely understood. A recent study in dogs with pacing-induced heart failure suggests that QT variability is linked to cardiac sympathetic nerve activity. The aim of this study was to determine whether increased cardiac sympathetic activity is associated with increased beat-to-beat QT interval variability in patients with essential hypertension. We recorded resting norepinephrine (NE) spillover into the coronary sinus and single-lead, short-term, high-resolution, body-surface ECG in 23 patients with essential hypertension and 9 normotensive control subjects. To assess beat-to-beat QT interval variability, we calculated the overall QT variability (QTVN) as well as the QT variability index (QTVi). Cardiac NE spillover (12.2 ± 6.5 vs. 20.7 ± 14.7, P = 0.03) and QTVi (-1.75 ± 0.36 vs. -1.42 ± 0.50, P = 0.05) were significantly increased in hypertensive patients compared with normotensive subjects. QTVN was significantly correlated with cardiac NE spillover (r(2) = 0.31, P = 0.001), with RR variability (r(2) = 0.20, P = 0.008), and with systolic blood pressure (r(2) = 0.16, P = 0.02). Linear regression analysis identified the former two as independent predictors of QTVN. In conclusion, elevated repolarization lability is directly associated with sympathetic cardiac activation in patients with essential hypertension.
Abstract: The aim of this study was to assess cardiac ventricular repolarization in patients with postural tachycardia syndrome (POTS) and further the possible link between ventricular repolarization and sympathetic nervous system activity.
Abstract: The aim of our study was to employ novel nonlinear synchronization approaches as a tool to detect baroreflex impairment in young patients with subclinical autonomic dysfunction in Type 1 diabetes mellitus (DM) and compare them to standard linear baroreflex sensitivity (BRS) methods. We recorded beat-to-beat pulse interval (PI) and systolic blood pressure (SBP) in 14 DM patients and 14 matched healthy controls. We computed the information domain synchronization index (IDSI), cross-multiscale entropy, joint symbolic dynamics, information-based similarity index (IBSI) in addition to time domain and spectral measures of BRS. This multi parametric analysis showed that baroreflex gain is well-preserved, but the time delay within the baroreflex loop is significantly increased in patients with DM. Further, the level of similarity between blood pressure and heart rate fluctuations was significantly reduced in DM. In conclusion, baroreflex function in young DM patients is changed. The quantification of nonlinear similarity and baroreflex delay in addition to baroreflex gain may provide an improved diagnostic tool for detection of subclinical autonomic dysfunction in DM.
Abstract: 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.
Abstract: Cardiac and respiratory rhythms are highly nonlinear and nonstationary. As a result traditional time-domain techniques are often inadequate to characterize their complex dynamics. In this article, we introduce a novel technique to investigate the interactions between R-R intervals and respiratory phases based on their joint symbolic dynamics. To evaluate the technique, electrocardiograms (ECG) and respiratory signals were recorded in 13 healthy subjects in different body postures during spontaneous and controlled breathing. Herein, the R-R time series were extracted from ECG and respiratory phases were obtained from abdomen impedance belts using the Hilbert transform. Both time series were transformed into ternary symbol vectors based on the changes between two successive R-R intervals or respiratory phases. Subsequently, words of different symbol lengths were formed and the correspondence between the two series of words was determined to quantify the interaction between cardiac and respiratory cycles. To validate our results, respiratory sinus arrhythmia (RSA) was further studied using the phase-averaged characterization of the RSA pattern. The percentage of similarity of the sequence of symbols, between the respective words of the two series determined by joint symbolic dynamics, was significantly reduced in the upright position compared to the supine position (26.4 ± 4.7 vs. 20.5 ± 5.4%, p < 0.01). Similarly, RSA was also reduced during upright posture, but the difference was less significant (0.11 ± 0.02 vs. 0.08 ± 0.01 s, p < 0.05). In conclusion, joint symbolic dynamics provides a new efficient technique for the analysis of cardiorespiratory interaction that is highly sensitive to the effects of orthostatic challenge.
Abstract: The aim of this paper was to study interactions between R-R intervals and respiratory phases in healthy children during night-time sleep using a novel technique based on joint symbolic dynamics. We investigated overnight polysomnography data of 40 healthy children. 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 for each sleep stage was determined to quantify cardio-respiratory interaction. We found a significantly higher percentage of similarity in the joint symbolic dynamics of R-R intervals and respiratory phases during slow-wave (SW) sleep compared to any other sleep stage. There was, however, no significant effect of age, gender or BMI on cardio-respiratory interaction. In conclusion, joint symbolic dynamics provides a novel efficient technique for the analysis of cardio-respiratory interaction.
Abstract: Cardiovascular control acts over multiple time scales, which introduces a significant amount of complexity to heart rate and blood pressure time series. Multiscale entropy (MSE) analysis has been developed to quantify the complexity of a time series over multiple time scales. In previous studies, MSE analyses identified impaired cardiovascular control and increased cardiovascular risk in various pathological conditions. Despite the increasing acceptance of the MSE technique in clinical research, information underpinning the involvement of the autonomic nervous system in the MSE of heart rate and blood pressure is lacking. The objective of this study is to investigate the effect of orthostatic challenge on the MSE of heart rate and blood pressure variability (HRV, BPV) and the correlation between MSE (complexity measures) and traditional linear (time and frequency domain) measures. MSE analysis of HRV and BPV was performed in 28 healthy young subjects on 1000 consecutive heart beats in the supine and standing positions. Sample entropy values were assessed on scales of 1-10. We found that MSE of heart rate and blood pressure signals is sensitive to changes in autonomic balance caused by postural change from the supine to the standing position. The effect of orthostatic challenge on heart rate and blood pressure complexity depended on the time scale under investigation. Entropy values did not correlate with the mean values of heart rate and blood pressure and showed only weak correlations with linear HRV and BPV measures. In conclusion, the MSE analysis of heart rate and blood pressure provides a sensitive tool to detect changes in autonomic balance as induced by postural change.
Abstract: The cardiorespiratory synchrogram, a graphical tool based on the stroboscopic technique, is an established method for evaluating phase-locking between cardiac and respiratory oscillators. In the original method, the phase of the respiratory oscillator is observed at the instants of time when the phase of the cardiac oscillator attains a certain value. In this article, we introduced an additional adaptive delay in the cardiac oscillator based on the maximisation of the cross-correlation or symbolic coupling traces between the phases of respiration and the delayed R-R intervals. We then investigated phase coordination in thirteen normal subjects (five males, eight females; age: 19-24 years) for different body postures. Cardiorespiratory coordination was observed to be significantly reduced in the upright position (supine vs. upright: 11.9 ± 5.1 vs. 6.9 ± 3.6, P < 0.05). Compared to the original algorithm we observed an increase in the detection of average cardiorespiratory coordination (supine original vs. delay: 11.9 vs. 18.9%), together with a decrease in standard deviation of the percentage of coordination in all the subjects, after introducing the heart rate delay (supine original vs. delay: 5.1 vs. 4.4%). In conclusion, the performance of the synchrogram technique was improved by including an adaptive delay in the cardiac oscillator.
Abstract: 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 (P < 0.001). 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.
Abstract: 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.
Abstract: Our aim was to assess the impact of motor activity and of arousing stimuli on respiratory rate in the awake rats. The study was performed in male adult Sprague-Dawley (SD, n=5) and Hooded Wistar (HW, n=5) rats instrumented for ECG telemetry. Respiratory rate was recorded using whole-body plethysmograph, with a piezoelectric sensor attached for the simultaneous assessment of motor activity. All motor activity was found to be associated with an immediate increase in respiratory rate that remained elevated for the whole duration of movement; this was reflected by: i) bimodal distribution of respiratory intervals (modes for slow peak: 336+/-19 and 532+/-80 ms for HW and SD, p<0.05; modes for fast peak 128+/-6 and 132+/-7 ms for HW and SD, NS); and ii) a tight correlation between total movement time and total time of tachypnoea, with an R(2) ranging 0.96-0.99 (n=10, p<0001). The extent of motor-related tachypnoea was significantly correlated with the intensity of associated movement. Mild alerting stimuli produced stereotyped tachypnoeic responses, without affecting heart rate: tapping the chamber raised respiratory rate from 117+/-7 to 430+/-15 cpm; sudden side move--from 134+/-13 to 487+/-16 cpm, and turning on lights--from 136+/-12 to 507+/-14 cpm (n=10; p<0.01 for all; no inter-strain differences). We conclude that: i) sniffing is an integral part of the generalized arousal response and does not depend on the modality of sensory stimuli; ii) tachypnoea is a sensitive index of arousal; and iii) respiratory rate is tightly correlated with motor activity.
Abstract: 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.
Abstract: 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, p < 0.01 in HW rats) and R-R interval (0.19 ± 0.01 vs. 0.17 ± 0.01 s, p < 0.001 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%, p < 0.001). In conclusion the interaction between the cardiac and respiratory oscillators is affected by voluntary movements in rats.
Abstract: 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.
Abstract: The purpose of this paper is to investigate the effect of orthostatic challenge on recurrence plot based complexity measures of heart rate and blood pressure variability (HRV and BPV). HRV and BPV complexities were assessed in 28 healthy subjects over 15 min in the supine and standing positions. The complexity of HRV and BPV was assessed based on recurrence quantification analysis. HRV complexity was reduced along with the HRV magnitude after changing from the supine to the standing position. In contrast, the BPV magnitude increased and BPV complexity decreased upon standing. Recurrence quantification analysis (RQA) of HRV and BPV is sensitive to orthostatic challenge and might therefore be suited to assess changes in autonomic neural outflow to the cardiovascular system.
Abstract: Methods from nonlinear dynamics (NLD) have shown new insights into heart rate (HR) variability changes under various physiological and pathological conditions, providing additional prognostic information and complementing traditional time- and frequency-domain analyses. In this review, some of the most prominent indices of nonlinear and fractal dynamics are summarized and their algorithmic implementations and applications in clinical trials are discussed. Several of those indices have been proven to be of diagnostic relevance or have contributed to risk stratification. In particular, techniques based on mono- and multifractal analyses and symbolic dynamics have been successfully applied to clinical studies. Further advances in HR variability analysis are expected through multidimensional and multivariate assessments. Today, the question is no longer about whether or not methods from NLD should be applied; however, it is relevant to ask which of the methods should be selected and under which basic and standardized conditions should they be applied.
Abstract: The aim of this study was to determine whether 5-HT2A receptors mediate cardiovascular and thermogenic responses to acute psychological stresses. For this purpose, adult male Wistar hooded rats instrumented for telemetric recordings of either electrocardiogram (ECG) (n=12) or arterial pressure (n=12) were subjected, on different days, to four 15-min episodes of social defeat. Prior to stress, animals received s.c. injection of the selective 5-HT2A receptor antagonist SR-46349B (trans-4-((3Z)3-[(2-dimethylaminoethyl)oxyimino]-3-(2-fluorophenyl)propen-1-yl)-phenol, hemifumarate) (at doses of 0.3, 1.0 and 3.0 mg/kg) or vehicle. The drug had no effect on basal heart rate or heart rate variability indexes, arterial pressure, and core body temperature. Social defeat elicited significant and substantial tachycardic (347+/-7 to 500+/-7 bpm), pressor (77+/-4 to 97+/-4 mm Hg) and hyperthermic (37.0+/-0.3 to 38.5+/-0.1 degrees C) responses. Blockade of 5-HT2A receptors, at all doses of the antagonist, completely prevented stress-induced hyperthermia. In contrast, stress-induced cardiovascular responses were not affected by the blockade (except small reduction of tachycardia by the highest dose of the drug). We conclude that in rats, 5-HT2A receptors mediate stress-induced hyperthermic responses, but are not involved in the genesis of stress-induced rises in heart rate or arterial pressure, and do not participate in cardiovascular control at rest.
Abstract: Sudden cardiac death appears to be more prevalent during the normal sleeping hours in obstructive sleep apnoea (OSA) patients compared with the general population as well as to cardiovascular disease patients. The reasons for this remain unclear, but there are three likely main contributors to nocturnal death in OSA patients; cardiac arrhythmias, stroke/ruptured cerebral aneurism and myocardial infarction. Particularly marked cardiovascular system activation with arousal may play a role in initiating sudden adverse cardiovascular events in OSA. The purpose of this study was to investigate cardiac RR, QT and PR interval changes in the electrocardiogram (ECG) associated with spontaneous and respiratory-related arousals in OSA patients. A detailed observational study of ECG records obtained during conventional diagnostic sleep study with no further interventions was carried out in 20 patients (12 males, age 42.8 +/- 2.1 years, body mass index 35.1 +/- 1.9 kg m(-2), and respiratory disturbance index 51.8 +/- 6.4 events/hour). RR and QT intervals showed significant shortening during arousals. RR interval shortening was found to be greater during respiratory arousals when compared to spontaneous arousals. PR interval showed a trend toward a greater prolongation during respiratory arousal. QT interval shortening was weakly correlated with arterial oxygen saturation levels preceding arousal. In conclusion, these data suggest that despite greater cardiac acceleration following respiratory versus spontaneous arousals from sleep, QT shortening and PR prolongation responses are similar independent of arousal type. These data support that arousals produce quite marked and differential cardiac conduction system activation in OSA and that the degree and pattern of activation may be partly influenced by the presence and severity of preceding respiratory events.
Abstract: Obesity is associated with autonomic nervous system dysfunction. The aim of the study was to evaluate baroreflex sensitivity, an indicator of autonomic nervous function, in 20 obese children and adolescents in comparison with 20 age- and sex-matched nonobese subjects. All subjects were examined in the supine position over a period of 50 min. Systolic blood pressure (SBP) and RR intervals were monitored continuously. Baroreflex sensitivity was assessed by cross-spectral analysis of SBP and RR interval oscillations (BRS index) and SBP and heart rate oscillations (BRSf index) within the low frequency range (0.04-0.15 Hz). Sensitivity was determined in 3 time intervals of 3 min each to evaluate changes during rest. The BRS index was significantly lower in obese children and adolescents than in the nonobese control group (p = 0.002). Significant changes in the BRS index over time (p = 0.004) were found only in nonobese subjects. In contrast, the BRSf index increased over time in both groups (p = 0.01), and no significant between-group difference was detected. In conclusion, obese children and adolescents show decreased resting baroreflex sensitivity with less variation compared with nonobese subjects. The BRS and BRSf indices appear to be only partially correlated.
Abstract: Changes in measures of heart rate variability (HRV) have been associated with an increased risk for sudden cardiac death. The mechanisms underlying this association are not known. The objective of this study was to assess the relationship between the amount of norepinephrine (NE) released from the cardiac sympathetic terminals and short-term HRV. The study comprised 8 healthy subjects, 12 patients with major depression, and 7 patients with panic disorder. Cardiac NE spillover was determined using direct coronary sinus blood sampling coupled with an NE isotope dilution methodology. Short-term HRV was quantified using detrended fluctuation analysis, symbolic dynamics, sample entropy, and standard time and frequency domain measures. Neither HRV nor cardiac NE spillover was significantly different between the analyzed groups. None of the standard HRV metrics was significantly correlated with cardiac NE spillover, but there was a moderate correlation between two complexity measures of HRV (symbolic dynamics) and cardiac NE spillover (patterns with 2 like variations, r = -0.37 and P = 0.05; and patterns with no variations: r = 0.34 and P = 0.06). In conclusion, there is no correlation between standard HRV measures and cardiac NE spillover in humans. Short-term complexity of heart rate is only moderately affected by sympathetic neural outflow. Therefore, the predictive value of most HRV measures for sudden cardiac death may predominantly result from their capacity to capture vagally mediated heart rate modulations.
Abstract: To determine OSA-related changes in variability of QT interval duration and in heart rate variability (HRV), and to evaluate the relationship of these parameters to disease severity.
Abstract: To better understand the central mechanisms that mediate increases in heart rate (HR) during psychological stress, we examined the effects of systemic and intramedullary (raphe region) administration of the serotonin-1A (5-HT(1A)) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) on cardiac changes elicited by restraint in hooded Wistar rats with preimplanted ECG telemetric transmitters. 8-OH-DPAT reduced basal HR from 356 +/- 12 to 284 +/- 12 beats/min, predominantly via a nonadrenergic, noncholinergic mechanism. Restraint stress caused tachycardia (an initial transient increase from 318 +/- 3 to 492 +/- 21 beats/min with a sustained component of 379 +/- 12 beats/min). beta-Adrenoreceptor blockade with atenolol suppressed the sustained component, whereas muscarinic blockade with methylscopolamine (50 microg/kg) abolished the initial transient increase, indicating that sympathetic activation and vagal withdrawal were responsible for the tachycardia. Systemic administration of 8-OH-DPAT (10, 30, and 100 microg/kg) attenuated stress-induced tachycardia in a dose-dependent manner, and this effect was suppressed by the 5-HT(1A) antagonist WAY-100635 (100 microg/kg). Given alone, the antagonist had no effect. Systemically injected 8-OH-DPAT (100 microg/kg) attenuated the sympathetically mediated sustained component (from +85 +/- 19 to +32 +/- 9 beats/min) and the vagally mediated transient (from +62 +/- 5 to +25 +/- 3 beats/min). Activation of 5-HT(1A) receptors in the medullary raphe by microinjection of 8-OH-DPAT mimicked the antitachycardic effect of the systemically administered drug but did not affect basal HR. We conclude that tachycardia induced by restraint stress is due to a sustained increase in cardiac sympathetic activity associated with a transient vagal withdrawal. Activation of central 5-HT(1A) receptors attenuates this tachycardia by suppressing autonomic effects. At least some of the relevant receptors are located in the medullary raphe-parapyramidal area.
Abstract: The aim of this study was to test whether new heart rate variability (HRV) complexity measures provide diagnostic information regarding early subclinical autonomic dysfunction in diabetes mellitus (DM).
Abstract: Suggestions were made that increased myocardial sympathetic activity is reflected by elevated QT variability (dynamic changes in QT interval duration). However, the relationship between QT variability and the amount of norepinephrine released from the cardiac sympathetic terminals is unknown. We thus attempted to assess this relationship. The study was performed in 17 subjects (12 with major depressive disorder and 5 with panic disorder). Cardiac norepinephrine spillover (measured by direct catheter technique coupled with norepinephrine isotope dilution methodology) was assessed before and 4 mo after treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants. The distribution of the cardiac norepinephrine spillover was bimodal, with the majority of patients having values of < or =10 ng/min. There was a positive correlation between cardiac norepinephrine spillover and corrected QT interval (r = 0.7, P = 0.03) but not with any of the QT variability measures. However, in a subgroup of five patients who had high levels of cardiac norepinephrine spillover (>20 ng/min) a tendency for a strong positive correlation with variance of QT intervals (r = 0.9, P = 0.08) was observed. There were significant correlations between the severity of depression and QT variability indexes normalized to the heart rate [QTVi and QT interval/R-R interval (QT/RR) coherence] and between the severity of anxiety and the QT/RR residual and regression coefficient, respectively. Treatment with SSRI antidepressants substantially reduced depression score but did not affect any of the QT variability indexes. We conclude that in depression/panic disorder patients with near-normal cardiac norepinephrine levels QT variability is not correlated with cardiac norepinephrine spillover and is not affected by treatment with SSRI.
Abstract: Multiscale entropy (MSE) analysis provides information about complexity on various time scales. The aim of this study was to test whether MSE is able to detect autonomic dysregulation in young patients with diabetes mellitus (DM). We analyzed heart rate (HR) oscillations, systolic (SBP) and diastolic blood pressure (DBP) signals in 14 patients with DM type 1 and 14 age- and sex-matched healthy controls. SampEn values (scales 1-10) and linear measures were computed. HR: among the linear measures of heart rate variability significant differences between groups were only found for RMSSD (p = 0.043). MSE was significantly reduced on scales 2 and 3 in DM (p = 0.023 and 0.010, respectively). SBP and DBP: no significant differences were detected with linear measures. In contrast, MSE analysis revealed significantly lower SampEn values in DM on scale 3 (p = 0.039 for SBP; p = 0.015 for DBP). No significant correlations were found between MSE and linear measures. In conclusion, MSE analysis of HR, SBP and DBP oscillations is able to detect subtle abnormalities in cardiovascular control in young patients with DM and is independent of standard linear measures.
Abstract: Ventricular tachycardia (VT) provokes sudden cardiac death (SCD), which is a major cause of mortality in developed countries. Implantable cardioverter-defibrillators (ICDs) are an efficient therapy for SCD prevention. In this study we analyze heart rate variability (HRV) in data stored by ICDs. In 29 patients exhibiting VT episodes, the last 1000 normal beat-to-beat intervals are analyzed and compared to an individually acquired control time series (CON). HRV analysis is performed with standard parameters of time and frequency domain as suggested by the HRV Task Force. For scaling analyses of heart rate time series, the fractal dimension is analysed, applying Higuchi's algorithm (HFD). Furthermore, detrended fluctuation analysis (DFA) is performed. None of the standard HRV parameters shows significant differences between CON and VT. Before the onset of VT, the scaling characteristics by means of HFD and DFA are significantly changed. In conclusion, scaling analysis reveals changes in autonomic heart rate modulation preceding VT.
Abstract: 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, p = 0.005; SCD, p = 0.02). 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.
Abstract: Scaling analysis of heart rate time series has emerged as a useful tool for the assessment of autonomic cardiac control. We investigate the heart rate time series of ten athletes (five males and five females), by applying detrended fluctuation analysis (DFA). High resolution ECGs are recorded under standardized resting conditions over 30 min and subsequently heart rate time series are extracted and artifacts filtered. We find three distinct regions of scale invariance, which correspond to the well-known VLF, LF and HF bands in the power spectra of heart rate variability. The scaling exponents alpha are alpha(HF): 1.15 [0.96-1.22], alpha(LF): 0.68 [0.57-0.84], alpha(VLF): 0.83[0.82-0.99], p < 10(-5)). In conclusion, DFA scaling exponents of heart rate time series should be fitted to the VLF, LF and HF ranges, respectively.
Abstract: Discrete hidden Markov models (HMMs) were applied to classify pregnancy disorders. The observation sequence was generated by transforming RR and systolic blood pressure time series using symbolic dynamics. Time series were recorded from 15 women with pregnancy-induced hypertension, 34 with preeclampsia and 41 controls beyond 30th gestational week. HMMs with five to ten hidden states were found to be sufficient to characterize different blood pressure variability, whereas significant classification in RR-based HMMs was found using fifteen hidden states. Pregnancy disorders preeclampsia and pregnancy induced hypertension revealed different patho-physiological autonomous regulation supposing different etiology of both disorders.
Abstract: Within 5 years of first diagnosis, nearly 60% of patients with heart failure (HF) suffer from cardiac death. Early diagnosis of HF and reliable risk prediction are still required. Therefore, the objective of this study was to develop a parameter set for enhanced risk stratification in HF patients. In 43 patients suffering from HF (NYHA class > or =II, ejection fraction <45%) and 10 healthy subjects (REF), heart rate and blood pressure variability (HRV and BPV), interactions between heart rate and blood pressure (joint symbolic dynamics, JSD) and blood pressure morphology (BPM) were analysed. BPV, BPM and JSD measures revealed high significance (p<0.0001) in discriminating REF and HF. A set of three parameters from BPV, JSD and BPM was developed for risk stratification (sensitivity 76.5%, specificity 84.2%, area under the receiver operating characteristic curve 81.4%) in patients with HF.
Abstract: 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.
Abstract: 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<0.001). An increased heart rate was found in both groups during the second half of pregnancy. Consequently, decreased heart rate variability was observed, but was more pronounced in the CON group. There was a shift in the frequency bands indicated by an elevation of the low-to-high frequency ratio (LF/HF) in both groups due to a decrease in HF, and thus a significant increase in LFn (LF power in normalized units). However, VLF (power of very low frequency range) increased exclusively in the CON pregnancies. Our data showed no significant difference in heart rate variability between the subjects of the CH and CON groups. Longitudinal variations were detectable in normal pregnancies and also, albeit to a lesser degree, in chronic hypertensive pregnant women. Thus, our data indicate that patients with long-term hypertension are still able to respond to the physiological changes occurring during pregnancy.
Abstract: Autonomic cardiovascular control involves complex interactions of heart rate and blood pressure. In patients with dilated cardiomyopathy (DCM), this control is impaired and parameters for its quantification might be of prognostic importance. In this paper, we introduce methods based on joint symbolic dynamics (JSD) for the enhanced analysis of heart rate and blood pressure interactions. To assess the coarse-grained dynamics beat-to-beat changes of heart rate and blood pressure are encoded in symbol strings. Subsequently, the distribution properties of short symbol sequences (words) as well as the scaling properties of the whole symbol string are assessed. The comparison of joint symbolic heart rate and blood pressure dynamics in DCM (n = 75) with those in healthy controls (n = 75) showed significant changes. Both, the distribution of words and the scaling properties indicate a loss in heart rate dynamics associated with blood pressure regulation in DCM. In conclusion, the analyses of short- and long-term JSDs provide insights into complex physiological heart rate and blood pressure interactions and furthermore reveal patho-physiological cardiovascular control in DCM.
Abstract: Assessing autonomic control provides information about patho-physiological imbalances. Measures of variability of the cardiac interbeat duration RR(n) and the variability of the breath duration T<inf>Tot</inf>(n) are sensitive to those changes. The interactions between RR(n) and T<inf>Tot</inf>(n) are complex and strongly non-linear. A study of joint symbolic dynamics is presented as a new short-term non-linear analysis method to investigate these interactions in patients on weaning trials. 78 patients from mechanical ventilation are studied: Group A (patients that failed to maintain spontaneous breathing and were reconnected) and Group B (patients with successful trials). Using the concept of joint symbolic dynamics, cardiac and respiratory changes were transformed into a word series, and the probability of occurrence of each word type was calculated and compared between both groups. Significant differences were found in 13 words, and the most significant p<inf>n</inf>(W<inf>c010, r010</inf>): 0.0041 ± 0.0036 (group A) against 0.0012 ± 0.0024 (group B), p-value = 0.00001. The number of seldom occurring word types (forbidden words) also presents significant differences fw<inf>cr</inf>: 6.9 ± 6.6 against 13.5 ± 5.3, p-value = 0.00004. Joint symbolic dynamics provides an efficient non-linear representation of cardiorespiratory interactions that offers simple physiological interpretations.
Abstract: Hypertensive pregnancy disorders are a leading cause of perinatal and maternal morbidity and mortality. Heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) are relevant predictors of cardiovascular risk in humans. The aim of the study was to evaluate whether HRV, BPV, and BRS differ between distinct hypertensive pregnancy disorders. Continuous heart rate and blood pressure recordings were performed in 80 healthy pregnant women as controls (CON), 19 with chronic hypertension (CH), 18 with pregnancy-induced hypertension (PIH), and 44 with pre-eclampsia (PE). The data were assessed by time and frequency domain analysis, nonlinear dynamics, and BRS. BPV is markedly altered in all three groups with hypertensive disorders compared to healthy pregnancies, whereby changes were most pronounced in PE patients. Interestingly, this increase in PE patients did not lead to elevated spontaneous baroreflex events, while BPV changes in both the other hypertensive groups were paralleled by alterations in baroreflex parameters. The HRV is unaltered in CH and PE but significantly impaired in PIH. We conclude that parameters of the HRV, BPV, and BRS differ between various hypertensive pregnancy disorders. Thus, distinct clinical manifestations of hypertension in pregnancy have different pathophysiological, regulatory, and compensatory mechanisms.
Abstract: Ventricular tachycardia (VT) provoking sudden cardiac death (SCD) are a major cause of mortality in the developed countries. The most efficient therapy for SCD prevention are implantable cardioverter defibrillators (ICD). In this study heart rate variability (HRV) measures were analyzed for short-term forecasting of VT in order to improve VT sensing and to enable a patient warning of forth-coming shocks.
Abstract: In order to evaluate blood pressure and heart rate variability as a potent diagnostic tool for different hypertensive pregnancy disorders we started a clinical trial recording these variables in early pregnancies predisposed for preeclampsia. During routine measurements one of the patients experienced a grand mal epileptic seizure. Since the parameters of both heart rate and blood pressure variability were sequentially altered immediately before the seizure, this case report provides an interesting insight into autonomic cardiovascular control in a developing convulsive fit and the pathophysiological generation of a grand mal seizure in pregnancy.
Abstract: Pregnancy induces important changes in the autonomic control. Measures of heart rate (HR) variability and systolic blood pressure (SP) variability are sensitive to those changes. The interactions between HR and SP are complex and strongly non-linear. Therefore they cannot be completely described by linear analysis techniques. A study of joint symbolic dynamics is presented as a new short-term non-linear analysis method to investigate the interactions between HR and SP. Continuous, non-invasive 30 min blood pressure recordings (Portapres) of 25 pregnant and 14 non-pregnant women were analysed. Time series of beat-to-beat HR and SP were extracted. Using the concept of joint symbolic dynamics, HR and SP changes were transformed into a bivariate symbol vector. Subsequently, this symbol vector was transformed into a word series (words consisting of three successive symbols), and the probability of occurrence of each word type was calculated and compared between both groups. Significant differences were found in five word types between pregnant and non-pregnant women: w0,4(0.021+/-0.011 against 0.008+/-0.006; p = 0.022), w4,6(0.020+/-0.010 against 0.007+/-0.003; p = 0.001), w3,2(0.004+/-0.003 against 0.007+/-0.003; p = 0.038), W6,5(0.009+/-0.007 against 0.023+/-0.008; p< 0.001) and w3,6(0.011+/-0.007 against 0.023+/-0.008; p = 0.001). Joint symbolic dynamics provides an efficient non-linear representation of HR and SP interactions that offers simple physiological interpretations.
Abstract: 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).
Abstract: Impaired myocardial performance is known to be associated with electrical and mechanical beat-to-beat alternans phenomena. The alternans in blood pressure and heart rate and their interdependency in idiopathic dilated cardiomyopathy (IDC) were studied. The arterial blood pressure and the electrocardiograph (ECG) were continuously recorded in 22 patients suffering from IDC (age 49 +/- 13 years, ejection fraction 0.33 +/- 0.13, left ventricular diameter of 67 +/- 8 mm) and in 21 healthy controls (age 52 +/- 15 years). The beat-to-beat variations of the interbeat intervals (IBI) and of the blood pressure amplitudes (AMP) were measured. An alternans beat was defined as a beat preceded and followed by beats that had higher or lower values in the respective modality. The percentages of singular and repetitive alternans patterns, and the interdependency of the alternans patterns in AMP and IBI were assessed. The study found significantly more singular and repetitive alternans patterns in the IDC group compared to the control group both in the analysis of AMP and IBI (singular alternans in IBI: 55 +/- 11 vs 47 +/- 7%, P < 0.01; singular alternans in AMP: 61 +/- 15 vs 45 +/- 6%, P < 0.01; triple alternans in IBI: 29 +/- 18 vs 16 +/- 9%, P < 0.01; triple alternans in AMP: 34 +/- 24 vs 12 +/- 7%, P < 0.01). The amplitudes of the AMP alternans patterns were higher in IDC compared to controls (9 +/- 7 vs 4 +/- 2% of AMP, P = 0.01) whereas they did not differ in IBI. The correlation analysis revealed a significant interdependency of the alternans pattern in IBI and AMP in 18 of 22 IDC patients and in 12 of 21 controls (r = 0.50 +/- 0.21 [IDC]; r = 0.26 +/- 0.05 [controls]). The slope of the linear regression (delta AMP vs delta IBI) was steeper in the IDC group compared to the control group (62 +/- 50 vs 20 +/- 22 mmHg/s, P < 0.01). The percentages of alternans patterns appearing in IBI and AMP were positively correlated to the left ventricular diameter (r = 0.70 in the IBI, and r = 0.30 in the AMP). The blood pressure amplitude and the heart rate did not differ between the two groups. Patients suffering from IDC have a higher prevalence, stability, amplitude, and interdependency of alternans patterns in IBI and AMP compared to the control group. The amount of alternans patterns indicates the stage of disease. The alternans analysis may have impact on the functional assessment of patients suffering from heart failure.
Abstract: 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.
Abstract: 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.
