Peter Van Leeuwen

Fetal heart rate variability and complexity in the course of pregnancy

Aim of this study was the examination of fetal heart rate variability and complexity measures during pregnancy using fetal magnetocardiography. We registered 80 fetal magnetocardiograms in 19 healthy fetuses between the 16th and 41st week of gestation. On the basis of beat to beat intervals, mean RR interval (mRR), its standard deviation (SD), root mean square of successive differences (RMSSD), as well as complexity variables such as dimension (ApD1), entropy (ApEn), Lyapunov exponent (ApML) and trajectory divergence rate (p) were calculated for each recording. Dependency of these variables on gestational age was evaluated with correlation analysis. All variables changed consistently over time. RMSSD showed the strongest dependency on gestational age, followed closely by ApEn, SD and p. ApD1 and mRR showed only weak dependency. We conclude that magnetocardiography is well suited to register fetal cardiac activity with sufficient accuracy to permit detailed analysis of various heart rate variables during the second and third trimester of pregnancy. The observed increases in heart rate variability and complexity of fetuses most likely reflect differing but overlapping aspects of fetal development. They may be linked to the maturation of the autonomic nervous system and could aid in the timely identification of pathological conditions.

Dependency of magnetocardiographically determined fetal cardiac time intervals on gestational age, gender and postnatal biometrics in healthy pregnancies

BackgroundMagnetocardiography enables the precise determination of fetal cardiac time intervals (CTI) as early as the second trimester of pregnancy. It has been shown that fetal CTI change in course of gestation. The aim of this work was to investigate the dependency of fetal CTI on gestational age, gender and postnatal biometric data in a substantial sample of subjects during normal pregnancy.MethodsA total of 230 fetal magnetocardiograms were obtained in 47 healthy fetuses between the 15th and 42nd week of gestation. In each recording, after subtraction of the maternal cardiac artifact and the identification of fetal beats, fetal PQRST courses were signal averaged. On the basis of therein detected wave onsets and ends, the following CTI were determined: P wave, PR interval, PQ interval, QRS complex, ST segment, T wave, QT and QTc interval. Using regression analysis, the dependency of the CTI were examined with respect to gestational age, gender and postnatal biometric data.ResultsAtrioventricular conduction and ventricular depolarization times could be determined dependably whereas the T wave was often difficult to detect. Linear and nonlinear regression analysis established strong dependency on age for the P wave and QRS complex (r2 = 0.67, p < 0.001 and r2 = 0.66, p < 0.001) as well as an identifiable trend for the PR and PQ intervals (r2 = 0.21, p < 0.001 and r2 = 0.13, p < 0.001). Gender differences were found only for the QRS complex from the 31st week onward (p < 0.05). The influence on the P wave or QRS complex of biometric data, collected in a subgroup in whom recordings were available within 1 week of birth, did not display statistical significance.ConclusionWe conclude that 1) from approximately the 18th week to term, fetal CTI which quantify depolarization times can be reliably determined using magnetocardiography, 2) the P wave and QRS complex duration show a high dependency on age which to a large part reflects fetal growth and 3) fetal gender plays a role in QRS complex duration in the third trimester. Fetal development is thus in part reflected in the CTI and may be useful in the identification of intrauterine growth retardation.

Is there evidence of fetal-maternal heart rate synchronization?

BackgroundThe prenatal condition offers a unique possibility of examining physiological interaction between individuals. Goal of this work was to look for evidence of coordination between fetal and maternal cardiac systems.Methods177 magnetocardiograms were recorded in 62 pregnancies (16th–42nd week of gestation). Fetal and maternal RR interval time series were constructed and the phases, i.e. the timing of the R peaks of one time series in relation to each RR interval of the other were determined. The distributions of these phases were examined and synchrograms were constructed for real and surrogate pairs of fetal and maternal data sets. Synchronization epochs were determined for defined n:m coupling ratios.ResultsDifferences between real and surrogate data could not be found with respect to number of synchronization epochs found (712 vs. 741), gestational age, subject, recording or n:m combination. There was however a preference for the occurrence of synchronization epochs in specific phases in real data not apparent in the surrogate for some n:m combinations.ConclusionThe results suggest that occasional coupling between fetal and maternal cardiac systems does occur.

The value of magnetocardiography in patients with and without relevant stenoses of the coronary arteries using an unshielded system.

Background: The diagnostic management of patients with chest pain remains a clinical challenge. Magnetocardiography (MCG) is a noninvasive method for the recording of cardiac electromagnetic signals at multiple sites above the chest cage. Contrary to electrocardiogram (ECG) the magnetic field is unaltered by surrounding tissues. The present study aimed to analyze the diagnostic value of an unshielded four‐channel MCG for the detection of coronary artery disease (CAD) in patients with chest pain.

Obstacle avoidance, visual detection performance, and eye-scanning behavior of glaucoma patients in a driving simulator: a preliminary study.

The objective of this study was to evaluate differences in driving performance, visual detection performance, and eye-scanning behavior between glaucoma patients and control participants without glaucoma. Glaucoma patients (n = 23) and control participants (n = 12) completed four 5-min driving sessions in a simulator. The participants were instructed to maintain the car in the right lane of a two-lane highway while their speed was automatically maintained at 100 km/h. Additional tasks per session were: Session 1: none, Session 2: verbalization of projected letters, Session 3: avoidance of static obstacles, and Session 4: combined letter verbalization and avoidance of static obstacles. Eye-scanning behavior was recorded with an eye-tracker. Results showed no statistically significant differences between patients and control participants for lane keeping, obstacle avoidance, and eye-scanning behavior. Steering activity, number of missed letters, and letter reaction time were significantly higher for glaucoma patients than for control participants. In conclusion, glaucoma patients were able to avoid objects and maintain a nominal lane keeping performance, but applied more steering input than control participants, and were more likely than control participants to miss peripherally projected stimuli. The eye-tracking results suggest that glaucoma patients did not use extra visual search to compensate for their visual field loss. Limitations of the study, such as small sample size, are discussed.

Spatial Distribution of Repolarization Times in Patients with Coronary Artery Disease

The potential clinical value of QT dispersion (QTd), a measure of the interlead range of QT interval duration in the surface 12‐lead ECG, remains ambiguous. The aim of the study was the temporal and spatial analysis of the QT interval in healthy subjects and in patients with coronary artery disease (CAD) using magnetocardiography (MCG) and surface ECG. Standard 12‐lead ECG and 37‐channel MCG were performed in 20 healthy subjects, 23 patients with CAD without prior myocardial infarction (MI), 31 MI patients and 11 MI patients with ventricular tachycardia (VT). QTd was increased in CAD without MI compared to normals (ECG 46.1 ± 6.0 vs 42.8 ± 5.0, P < 0.05 ; MCG 66.8 ± 20.3 vs 49.7 ± 10.8, P < 0.01 ) and in VT compared to MI (ECG 66.8 ± 16.5 vs 51.9 ± 16.6, P < 0.05 ; MCG 93.6 ± 29.6 vs 66.8 ± 20.8, P < 0.005 ). In MCG, spatial distribution of QT intervals in patient groups differed from those in healthy subjects in three ways: (1) greater dispersion, (2) greater local variability, and (3) a change in overall pattern. This was quantified on the basis of smoothness indexes (SI). Normalized SI was higher in CAD without MI compared to normals ( 3.8 ± 1.1 vs 2.7 ± 0.6, P < 0.001 ) and in VT compared to MI ( 6.4 ± 1.6 vs 4.2 ± 1.4, P < 0.0005 ). For the normal‐CAD comparison a sensitivity of 74% and a specificity of 80% was obtained, for MI‐VT, 100% and 77%, respectively. The results suggest that examining the spatial interlead variability in multichannel MCG may aid in the initial identification of CAD patients with unimpaired left ventricular function and the identification of post‐MI patients with augmented risk for VT. (PACE 2003; 26:1706–1714)

Heart rate variability in the individual fetus.

The change in fetal heart rate and its variability (HRV) during the course of gestation has been documented by numerous studies. The overall drop in heart rate and increase in fetal HRV is associated with fetal growth in general and with the increase in neural integration in particular. The increased complexity of the demands on the cardiovascular system leads to more variation in the temporal course of the heart rate. Most studies that document and interpret these changes are based on data acquired in groups of fetuses. The aim of this work was to investigate HRV within single fetuses. We acquired 213 5min fetal magnetocardiograms in 11 fetuses during the second and third trimesters (at least 10 data sets per fetus, median 17). From the magnetocardiograms we determined the fetal RR interval time series and calculated the standard deviation (SDNN), root mean square of successive differences (RMSSD), approximate entropy (ApEn) and temporal asymmetry (Irrev). For each subject and HRV measure, we performed regression analysis with respect to gestational age, alone and in combination with RR interval. The coefficient of determination R(2) was used to estimate goodness-of-fit. The coefficient of quartile dispersion (CQD) was used to compare the regression parameters for each HRV measure. Overall, the HRV measures increased with age and RR interval. The consistency of the HRV measures within the individual fetuses was greater than in the data pooled over all fetuses. The individual R(2) for the model including age and RR interval was best for ApEn (.79, .59-.94; median, 90% CI), followed by RMSSD (.71, .25-.88), SDNN (.55, .18-.90) and Irrev (.16, .01-.39). These values, except for Irrev, were higher than those calculated over all 213 data sets (R(2)=.65, .63, .35, .28, respectively). The slopes of the regressions of each individuals data were most consistent over all subjects for ApEn, followed by RMSSD and SDNN and Irrev. Interindividually, the time domain measures showed discrepancies and the within-fetus courses were more consistent than the course over all fetuses. On the other hand, the course of ApEn during gestation was not only very consistent within each fetus but also very similar between most of subjects. Complexity measures such as ApEn may thus more consistently reflect prenatal developmental factors influencing cardiovascular regulation.

Heart rate variability in the fetus: a comparison of measures

Abstract Background: In fetal surveillance, fetal heart rate changes are assessed using cardiotocography (CTG). Standard procedures used in the quantification of heart rate variability (HRV) are seldom applied as CTG does not deliver beat interval durations with the same accuracy as the electrocardiogram (ECG). Thus little is known about the interdependency of standard HRV measures prenatally. Materials and methods: Using fetal magnetocardiography (FMCG: the magnetic equivalent of the fetal ECG), we investigated standard HRV measures in a homogenous group of 20 healthy fetuses. Ten HRV measures were analyzed in 60 five-minute RR interval time series derived from FMCG acquisitions (16th–40th week of gestation). Results: Using regression analysis, we found a clear dependency on gestational age and mean RR interval for measures from the time and frequency domains as well as for a measure for complexity. Correlation analysis revealed a strong interdependency of the measures, in particular within the specific domains. An adequate description of fetal HRV may be achieved using the standard deviation from the time domain, the high frequency band (0.15–0.40 Hz) from the frequency domain and approximate entropy as a complexity measure. Conclusion: The results indicate that different characteristics of fetal HRV are embedded in the different domains.

Unexpected Course of Nonlinear Cardiac Interbeat Interval Dynamics during Childhood and Adolescence

The fluctuations of the cardiac interbeat series contain rich information because they reflect variations of other functions on different time scales (e.g., respiration or blood pressure control). Nonlinear measures such as complexity and fractal scaling properties derived from 24 h heart rate dynamics of healthy subjects vary from childhood to old age. In this study, the age-related variations during childhood and adolescence were addressed. In particular, the cardiac interbeat interval series was quantified with respect to complexity and fractal scaling properties. The R-R interval series of 409 healthy children and adolescents (age range: 1 to 22 years, 220 females) was analyzed with respect to complexity (Approximate Entropy, ApEn) and fractal scaling properties on three time scales: long-term (slope β of the power spectrum, log power vs. log frequency, in the frequency range 10−4 to 10−2 Hz) intermediate-term (DFA, detrended fluctuation analysis, α2) and short-term (DFA α1). Unexpectedly, during age 7 to 13 years β and ApEn were higher compared to the age <7 years and age >13 years (β: −1.06 vs. −1.21; ApEn: 0.88 vs. 0.74). Hence, the heart rate dynamics were closer to a 1/f power law and most complex between 7 and 13 years. However, DFA α1 and α2 increased with progressing age similar to measures reflecting linear properties. In conclusion, the course of long-term fractal scaling properties and complexity of heart rate dynamics during childhood and adolescence indicates that these measures reflect complex changes possibly linked to hormonal changes during pre-puberty and puberty.

Heart rate features in fetal behavioural states.

BACKGROUND AND AIM Fetal behavioural states have been defined on the basis of eye movements, body movements and heart rate patterns as presented by cardiotocography (CTG). The aim of this work was to determine whether behavioural states can be distinguished on the basis of heart rate features alone using high resolution beat-to-beat fetal magnetocardiography. STUDY DESIGN Five minute magnetocardiograms were recorded at a sampling rate of 1 kHz in 40 healthy fetuses (36th-41st week of gestation). In the reconstructed RR interval time series, 256-beat epochs corresponding to the behavioural states 1F, 2F and 4F were visually identified according to heart rate patterns as defined for CTG. These epochs were then quantified using mean RR interval, its standard deviation (SDNN), its root mean square of successive difference (RMSSD) and on the basis of symbolic dynamics of short 8 beat trains. RESULTS Pairwise comparison between the behavioural states showed that the values of each of these measures differed significantly between the states. Quadratic discriminant analysis further revealed that mean RR interval and SDNN sufficed to classify state with a correct classification of 92%. CONCLUSIONS The results suggest that measures that quantify overall aspects of heart rate can distinguish RR interval time series which were classified into different fetal behavioural states. The differences in short-term variability as quantified by RMSSD and symbolic dynamics may help reveal new aspects of these states.