Jan F. Kraemer

Modulations of Heart Rate, ECG, and Cardio-Respiratory Coupling Observed in Polysomnography

The cardiac component of cardio-respiratory polysomnography is covered by ECG and heart rate recordings. However, their evaluation is often underrepresented in summarizing reports. As complements to EEG, EOG, and EMG, these signals provide diagnostic information for autonomic nervous activity during sleep. This review presents major methodological developments in sleep research regarding heart rate, ECG, and cardio-respiratory couplings in a chronological (historical) sequence. It presents physiological and pathophysiological insights related to sleep medicine obtained by new technical developments. Recorded nocturnal ECG facilitates conventional heart rate variability (HRV) analysis, studies of cyclical variations of heart rate, and analysis of ECG waveform. In healthy adults, the autonomous nervous system is regulated in totally different ways during wakefulness, slow-wave sleep, and REM sleep. Analysis of beat-to-beat heart-rate variations with statistical methods enables us to estimate sleep stages based on the differences in autonomic nervous system regulation. Furthermore, up to some degree, it is possible to track transitions from wakefulness to sleep by analysis of heart-rate variations. ECG and heart rate analysis allow assessment of selected sleep disorders as well. Sleep disordered breathing can be detected reliably by studying cyclical variation of heart rate combined with respiration-modulated changes in ECG morphology (amplitude of R wave and T wave).

Cardio-Respiratory Coordination Increases during Sleep Apnea

Cardiovascular diseases are the main source of morbidity and mortality in the United States with costs of more than

Cardiovascular regulation in different sleep stages in the obstructive sleep apnea syndrome.

170 billion. Repetitive respiratory disorders during sleep are assumed to be a major cause of these diseases. Therefore, the understanding of the cardio-respiratory regulation during these events is of high public interest. One of the governing mechanisms is the mutual influence of the cardiac and respiratory oscillations on their respective onsets, the cardio-respiratory coordination (CRC). We analyze this mechanism based on nocturnal measurements of 27 males suffering from obstructive sleep apnea syndrome. Here we find, by using an advanced analysis technique, the coordigram, not only that the occurrence of CRC is significantly more frequent during respiratory sleep disturbances than in normal respiration (p-value<10−51) but also more frequent after these events (p-value<10−15). Especially, the latter finding contradicts the common assumption that spontaneous CRC can only be observed in epochs of relaxed conditions, while our newly discovered epochs of CRC after disturbances are characterized by high autonomic stress. Our findings on the connection between CRC and the appearance of sleep-disordered events require a substantial extension of the current understanding of obstructive sleep apneas and hypopneas.

Causality in physiological signals.

Abstract Heart rate and blood pressure variability analysis as well as baroreflex sensitivity have been proven to be powerful tools for the assessment of autonomic control in clinical practice. Their ability to detect systematic changes caused by different states, diseases and treatments shall be shown for sleep disorders. Therefore, we consider 18 normotensive and 10 hypertensive patients suffering from obstructive sleep apnea syndrome (OSAS) before and after a three-month continuous positive airway pressure (CPAP) therapy. Additionally, an age and sex matched control group of 10 healthy subjects is examined. Linear and nonlinear parameters of heart rate and blood pressure fluctuation as well as the baroreflex sensitivity are used to answer the question whether there are differences in cardiovascular regulation between the different sleep stages and groups. Moreover, the therapeutic effect of CPAP therapy in OSAS patients shall be investigated. Kruskal-Wallis tests between the sleep stages for each group show significant differences in the very low spectral component of heart rate (VLF/P: 0.0033–0.04 Hz, p<0.01) which indicates differences in metabolic activity during the night. Furthermore, the decrease of Shannon entropy of word distribution as a parameter of systolic blood pressure during non-REM sleep reflects the local dominance of the vagal system (p<0.05). The increased sympathetic activation of the patients leads to clear differences of cardiovascular regulation in different sleep stages between controls and patients. We found a significant reduction of baroreflex sensitivity in slow wave sleep in the OSAS patients (Mann-Whitney test, p<0.05) compared to controls, which disappeared after three months of CPAP therapy. Hence, our results demonstrate the ability of cardiovascular analyzes to separate between healthy and pathological regulation as well as between different severities of OSAS in this retrospective study.

On the difference of cardiorespiratory synchronisation and coordination

Health is one of the most important non-material assets and thus also has an enormous influence on material values, since treating and preventing diseases is expensive. The number one cause of death worldwide today originates in cardiovascular diseases. For these reasons the aim of understanding the functions and the interactions of the cardiovascular system is and has been a major research topic throughout various disciplines for more than a hundred years. The purpose of most of todays research is to get as much information as possible with the lowest possible effort and the least discomfort for the subject or patient, e.g. via non-invasive measurements. A family of tools whose importance has been growing during the last years is known under the headline of coupling measures. The rationale for this kind of analysis is to identify the structure of interactions in a system of multiple components. Important information lies for example in the coupling direction, the coupling strength, and occurring time lags. In this work, we will, after a brief general introduction covering the development of cardiovascular time series analysis, introduce, explain and review some of the most important coupling measures and classify them according to their origin and capabilities in the light of physiological analyses. We will begin with classical correlation measures, go via Granger-causality-based tools, entropy-based techniques (e.g. momentary information transfer), nonlinear prediction measures (e.g. mutual prediction) to symbolic dynamics (e.g. symbolic coupling traces). All these methods have contributed important insights into physiological interactions like cardiorespiratory coupling, neuro-cardio-coupling and many more. Furthermore, we will cover tools to detect and analyze synchronization and coordination (e.g. synchrogram and coordigram). As a last point we will address time dependent couplings as identified using a recent approach employing ensembles of time series. The scope of this review, as opposed to various other excellent reviews like (Hlaváčková-Schindler et al Phys. Rep. 441 1-46, Kramer et al 2004 Phys. Rev. E 70 1-10, Lombardi 2000 Circulation 101 8-10, Porta et al 2000 Am. J. Physiol.: Heart and Circulatory Physiol. 279 H2558-67, Schelter et al 2006 J. Neurosci. Methods 152 210-9), is to give a broader overview over existing coupling measures and where to look to find the most appropriate tool for a given situation. The review will comprise a test of one representative of the most important coupling measure groups using a simple toy model to illustrate some essential features of the tools. At the end we will summarise the performance of each measure and offer some advice on when to use which method.

Standard heart rate variability spectral analysis: does it purely assess cardiac autonomic function?

Cardiorespiratory phase synchronisation (CRS) is a type of cardiorespiratory coupling that manifests through a prediliction for heart beats to occur at specific points relative to the phase of the respiratory cycle. It has been under investigation for nearly 20 years, and while it seems to be mostly occurring in relaxed states such as deep sleep and anesthesia, no clear clinical implications have been established. Cardiorespiratory coordination (CRC) is a recent development in this field where the relationship between the respiratory onset and heart beat is analysed in the time domain and the possible relationship of each heart beat is considered for both the previous and the next respiratory onset. This ostensibly closely related effect must not only show relevant information content but also do so independent of CRS in order to be relevant for future studies. In this paper, we investigate CRC and its relation to CRS mainly using graphical and statistical methods on two exemplary datasets: measurements from a pregnant woman participating in a preeclampsia study and those from a man suffering from sleep apnea. We show fundamental differences between the results of both approaches and are able to show a formerly unknown dependency between the heart activity and respiratory rate, potentially indicating heartbeat-initiated inspiration. Despite their differences, methods developed for the quantification of CRS can be adapted to CRC. Completing the comparison is an investigation into the relationship between CRC and respiratory sinus arrhythmia. Similar to previous results for CRS, the two effects are found to be orthogonal, meaning that they can be observed independently or in conjunction.

Quantifying Effects of Pharmacological Blockers of Cardiac Autonomous Control Using Variability Parameters

In the 24-h ambulatory Holter electrocardiogram (ECG) recording of a 20-year-old woman, a non-sustained ventricular tachycardia (VT) was identified and a large amount, about 5000, ventricular premature complexes (VPCs) were detected. To ascertain the reason for the said VT and VPCs, a …

Increased cardiorespiratory coordination in preeclampsia

Objective: The aim of this study was to identify the most sensitive heart rate and blood pressure variability (HRV and BPV) parameters from a given set of well-known methods for the quantification of cardiovascular autonomic function after several autonomic blockades. Methods: Cardiovascular sympathetic and parasympathetic functions were studied in freely moving rats following peripheral muscarinic (methylatropine), β1-adrenergic (metoprolol), muscarinic + β1-adrenergic, α1-adrenergic (prazosin), and ganglionic (hexamethonium) blockades. Time domain, frequency domain and symbolic dynamics measures for each of HRV and BPV were classified through paired Wilcoxon test for all autonomic drugs separately. In order to select those variables that have a high relevance to, and stable influence on our target measurements (HRV, BPV) we used Fishers Method to combine the p-value of multiple tests. Results: This analysis led to the following best set of cardiovascular variability parameters: The mean normal beat-to-beat-interval/value (HRV/BPV: meanNN), the coefficient of variation (cvNN = standard deviation over meanNN) and the root mean square differences of successive (RMSSD) of the time domain analysis. In frequency domain analysis the very-low-frequency (VLF) component was selected. From symbolic dynamics Shannon entropy of the word distribution (FWSHANNON) as well as POLVAR3, the non-linear parameter to detect intermittently decreased variability, showed the best ability to discriminate between the different autonomic blockades. Conclusion: Throughout a complex comparative analysis of HRV and BPV measures altered by a set of autonomic drugs, we identified the most sensitive set of informative cardiovascular variability indexes able to pick up the modifications imposed by the autonomic challenges. These indexes may help to increase our understanding of cardiovascular sympathetic and parasympathetic functions in translational studies of experimental diseases.

Assessing cardiac autonomic function via heart rate variability analysis requires monitoring respiration.

Preeclampsia is one of the main sources of morbidity in pregnancy with a high mortality rate without a known ultimate cause. Using a corpus including 927 measurements of pregnant women with and without different hypertonic diseases at multiple stages of pregnancy, we utilised a new approach to analyse cardiorespiratory coordination. Since the recording quality of respiratory effort was limited due to a high signal to noise ratio, we applied an ECG derived respiration approach to create an ersatz respiratory signal. After applying the few available recordings with a sufficiently high quality of the respiratory signal to validate the substitute, coordigrams were calculated and quantified by utilising an epsilon method. We showed significant (p  <  0.05) differences in the coordination in a matched (BMI, age, gestational week) comparison of preeclamptic and healthy subjects. Hopefully future applications of and improvements on these methods are able to create a fast and convenient prediction methodology to reduce the impact of this disease as well as help in the determination of its underlying cause.

Is dynamic desaturation better than a static index to quantify the mortality risk in heart failure patients with Cheyne-Stokes respiration?

With great interest we have read the joint position statement about advances in heart rate variability (HRV) signal analysis presented by Dr Sassi et al. 1 They present a critical review of newly developed HRV methodologies developed after publication of the initial Task Force HRV overview2 and their applications in different physiological and clinical studies. These novel approaches improved the technical understanding of the HRV signal; however, their success in clinical applications, such as in the identification …