Silke Lange

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.

A quantitative comparison of different methods to detect cardiorespiratory coordination during night-time sleep

BackgroundThe univariate approaches used to analyze heart rate variability have recently been extended by several bivariate approaches with respect to cardiorespiratory coordination. Some approaches are explicitly based on mathematical models which investigate the synchronization between weakly coupled complex systems. Others use an heuristic approach, i.e. characteristic features of both time series, to develop appropriate bivariate methods.ObjectiveIn this study six different methods used to analyze cardiorespiratory coordination have been quantitatively compared with respect to their performance (no. of sequences with cardiorespiratory coordination, no. of heart beats coordinated with respiration). Five of these approaches have been suggested in the recent literature whereas one method originates from older studies.ResultsThe methods were applied to the simultaneous recordings of an electrocardiogram and a respiratory trace of 20 healthy subjects during night-time sleep from 0:00 to 6:00. The best temporal resolution and the highest number of coordinated heart beats were obtained with the analysis of Phase Recurrences. Apart from the oldest method, all methods showed similar qualitative results although the quantities varied between the different approaches. In contrast, the oldest method detected considerably fewer coordinated heart beats since it only used part of the maximum amount of information available in each recording.ConclusionsThe method of Phase Recurrences should be the method of choice for the detection of cardiorespiratory coordination since it offers the best temporal resolution and the highest number of coordinated sequences and heart beats. Excluding the oldest method, the results of the heuristic approaches may also be interpreted in terms of the mathematical models.

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.

Reproducibility of two coronary calcium quantification algorithms in patients with different degrees of calcification

Purpose: To evaluate the reproducibility of coronary calcium quantification algorithms by electron beam CT (EBT) in patients with different amounts of calcified plaque using the conventional (Agatston) score and an area score and to demonstrate a potential application of these results for evaluation of follow-up scans. Methods: In 50 consecutive patients, the conventional calcium score (CCS = Agatston score) and the area score (AS) were summed for each artery and patient. Data were analyzed in four groups according to degrees of calcification: 0 (absent–minimal): CCS 0–9, I (mild): CCS 10–99, II (moderate): CCS 100–399, III (severe): CCS ≥ 400. We determined and compared the reproducibility for each algorithm within and among groups. Results: Median percent reproducibility improved with increasing amounts of calcified plaque for the CCS and the AS (p = 0.002 and p = 0.004, respectively). We demonstrate how these reproducibility values can be used to evaluate long-term follow-up studies. The reduction of median reproducibility per patient using the AS vs. the CCS was 32% (13 vs. 19%, respectively). On a vessel-by-vessel basis, the reduction of median reproducibility was 7% (24.3 vs. 22.6%, CCS vs. AS, p < 0.02), which was attributable to a 45% reduction in reproducibility in arteries with mild scores (46.1 vs. 25.5%, CCS vs. AS, p < 0.005). Conclusion: The AS has an improved reproducibility compared with the CCS, especially in patients with small amounts of coronary calcifications which may prove clinically useful. Different reproducibility values in different degrees of calcification can be used for an individual assessment of changes in amounts of coronary calcification.

Heart rate features in fetal behavioural states.

BACKGROUND AND AIMnFetal 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.nnnSTUDY DESIGNnFive 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.nnnRESULTSnPairwise 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%.nnnCONCLUSIONSnThe 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.

Gender-Related Changes in Magnetocardiographically Determined Fetal Cardiac Time Intervals in Intrauterine Growth Retardation

Prenatal growth deficiencies as well as gender have been associated with cardiovascular disease in later life. It is also known that the duration of fetal cardiac time intervals (CTI) are dependent on fetal development. The aim of this work was to examine the relationship between fetal CTI in healthy and intrauterine growth retardation (IUGR) fetuses, taking gender into account. A total of 269 magnetocardiograms (MCG) were obtained in 47 healthy and 27 IUGR pregnancies. In each signal-averaged MCG, durations of CTI were determined. Age- and heart rate–corrected values were compared between normal and IUGR fetuses separately with respect to gender. Overall, there was an association between atrial and ventricular conduction times and estimated fetal body weight. In female fetuses, IUGR was associated with shorter P WAVE, PQ segment, PR interval, and QRS complex and longer STT and QT intervals. For males, this was so only for P wave, QRS complex, and STT interval. The shortening of conduction times in IUGR may be explained by reduced cardiac muscle mass associated with lower body weight. On the other hand, the gender-specific differences, particularly in the IUGR fetuses may be due to hormonal factors.

Increase in regularity of fetal heart rate variability with age

Abstract It is generally assumed that fetal heart rate variability increases with gestation, reflecting prenatal development of the autonomic nervous system. We examined standard measures quantifying fetal heart rate variability, as well as a complexity measure, approximate entropy, in 66 fetal magnetocardiograms recorded from 22 healthy pregnant women between the 16th and 42nd week of gestation. In particular, regularity in the fetal RR interval time series was assessed on the basis of symbolic dynamics. The results showed that, beside an overall increase in fetal heart rate variability and complexity during pregnancy, there was also an increase in specific sets of binary patterns with low approximate entropy, i.e., a high degree of regularity. These sets were characterized by short epochs of heart rate acceleration and deceleration, and comparison with surrogate data confirmed that their random occurrence is rare. The results most likely reflect the influence of increasingly differentiated fetal behavioral states and transitions between them in association with fetal development.

Quantification of cardiac magnetic field orientation during ventricular de- and repolarization

We compared the stability and discriminatory power of different methods of determining cardiac magnetic field map (MFM) orientation within the context of coronary artery disease (CAD). In 27 healthy subjects and 24 CAD patients, multichannel magnetocardiograms were registered at rest. MFM orientation was determined during QT interval using: (a) locations of the positive and negative centres-of-gravity, (b) locations of the field extrema and (c) the direction of the maximum field gradient. Deviation from normal orientation quantified the ability of each approach to discriminate between healthy and CAD subjects. Although the course of orientation was similar for all methods, receiver operating characteristic analysis showed the best discrimination of CAD patients for the centre-of-gravity approach (area-under-the-curve = 86%), followed by the gradient (84%) and extrema (76%) methods. Consideration of methodological and discriminatory advantages with respect to noninvasive diagnosis of CAD suggests that the centres-of-gravity method is the most suited one.