Eran Toledo

Does synchronization reflect a true interaction in the cardiorespiratory system

Cardiorespiratory synchronization, studied within the framework of phase synchronization, has recently raised interest as one of the interactions in the cardiorespiratory system. In this work, we present a quantitative approach to the analysis of this nonlinear phenomenon. Our primary aim is to determine whether synchronization between HR and respiration rate is a real phenomenon or a random one. First, we developed an algorithm, which detects epochs of synchronization automatically and objectively. The algorithm was applied to recordings of respiration and HR obtained from 13 normal subjects and 13 heart transplant patients. Surrogate data sets were constructed from the original recordings, specifically lacking the coupling between HR and respiration. The statistical properties of synchronization in the two data sets and in their surrogates were compared. Synchronization was observed in all groups: in normal subjects, in the heart transplant patients and in the surrogates. Interestingly, synchronization was less abundant in normal subjects than in the transplant patients, indicating that the unique physiological condition of the latter promote cardiorespiratory synchronization. The duration of synchronization epochs was significantly shorter in the surrogate data of both data sets, suggesting that at least some of the synchronization epochs are real. In view of those results, cardiorespiratory synchronization, although not a major feature of cardiorespiratory interaction, seems to be a real phenomenon rather than an artifact.

Individual time-dependent spectral boundaries for improved accuracy in time-frequency analysis of heart rate variability

Heart rate variability (HRV) is a major noninvasive technique for evaluating the autonomic nervous system (ANS). Use of time-frequency approach to analyze HRV allows investigating the ANS behavior from the power integrals, as a function of time, in both steady-state and non steady-state. Power integrals are examined mainly in the low-frequency and the high-frequency bands. Traditionally, constant boundaries are chosen to determine the frequency bands of interest. However, these ranges are individual, and can be strongly affected by physiologic conditions (body position, breathing frequency). In order to determine the dynamic boundaries of the frequency bands more accurately, especially during autonomic challenges, we developed an algorithm for the detection of individual time-dependent spectral boundaries (ITSB). The ITSB was tested on recordings from a series of standard autonomic maneuvers with rest periods between them, and the response to stand was compared to the known physiological response. A major advantage of the ITSB is the ability to reliably define the mid-frequency range, which provides the potential to investigate the physiologic importance of this range.

Parametric description of cardiac vagal control

Heart rate variability (HRV) indices that reflect the magnitude of respiratory sinus arrhythmia (RSA) are commonly applied as non-invasive measures of cardiac vagal control. Recently, however, serious doubts have been raised about the accuracy and validity of such assessments. To evaluate these methods, we derived a theoretical model for the dependence of mean heart rate and RSA on gradual vagal blockade by atropine, and compared its predictions to actual experimental results. The experiment involved the injection of nine consecutive intravenous bolus doses of atropine to eight young healthy male subjects. Seven-minute recordings of ECG and respiration were made for each atropine dose. The heart rate (HR) signal was derived from the ECG recording, and mean heart rate and the power of the high frequency peak of HRV (which measures the magnitude of RSA) were computed. The experimental data were fitted to the models equations, and optimal values were obtained for the models parameters. A tight agreement is observed between the theoretical fitted curves and the experimental data. The parameters that were computed from fitting the experimental data to the mean heart rate equation display a surprisingly small variance among the different subjects. The parameters that were computed from fitting the experimental data to the RSA equation, and the resulting shape of these fitted curves, explain many of the conflicting results previously published, and provide a new quantitative insight to cardiac vagal activity.

Very high frequency oscillations in the heart rate and blood pressure of heart transplant patients

The authors studied the recently reported very high frequency (VHF) peaks in the heart rate (HR) and blood pressure (BP) power spectra of heart transplant (HT) patients. These VHF peaks appear at frequencies much higher than the respiratory frequency, in addition to the typical low-frequency and high-frequency peaks. Twenty-five recordings obtained from 13 male HT patients (0.5–65 months following surgery) were compared with recordings from 14 normal male subjects. The ECG, continuous BP and respiration were recorded during 45 min of supine rest. Eight recordings from HT patients were excluded owing to arrhythmias. Spectral analysis was performed on all other recordings. VHF peaks were found in the spectra of both BP and HR in nine recordings obtained from six HT patients. In some cases, the power in the VHF peaks was markedly higher than that of the high-frequency peak. No VHF peaks were observed in eight recordings obtained from four HT patients or in recording from any of the normal subjects. No correlation was found between the incidence of VHF peaks and time after transplant. It was proved that the VHF peaks were not artifactual, and their significance within the framework of the theory of communication systems is discussed. The presence of those peaks was attributed to vagal denervation.

Detection of stress-induced myocardial ischemia from the depolarization phase of the cardiac cycle—a preliminary study

BACKGROUND Electrocardiogram (ECG)-based detection of ischemia is typically dependent on identifying changes in repolarization. Analysis of high-frequency QRS (HFQRS) components, related to the depolarization phase of the cardiac action potential, has been reported to better identify ischemia. Our aim was to test the hypothesis that HFQRS analysis is both more sensitive and specific than standard ECG for detecting exercise-induced ischemia in patients undergoing exercise myocardial perfusion imaging (MPI). METHODS Exercise MPI was performed in 133 consecutive patients (age, 63 +/- 12; 100 males) and used as the gold standard for ischemia. Patients with QRS duration more than 120 milliseconds (n = 20), technical problems (n = 8), or inconclusive MPI (n = 4) were excluded, leaving 101 patients for analysis. Conventional ECG was combined with high-resolution ECG acquisition that was digitized and analyzed using the HyperQ System (BSP, Tel Aviv, Israel). The relative HFQRS intensity change during exercise was used as an index of ischemia. RESULTS Of the 101 patients who were included in the analysis, 19 exhibited MPI ischemia. The HFQRS index of ischemia was found to be more sensitive (79% vs 41%; P < .05) and more specific (71% vs 57%; P < .05) than conventional ST analysis. CONCLUSIONS The HFQRS analysis was more sensitive and specific than conventional ECG interpretation in detecting exercise-induced ischemia and exhibited enhanced diagnostic performance in both women and men. Thus, it may aid in the noninvasive diagnosis of ischemic heart disease.

Cardiorespiratory synchronization: is it a real phenomenon?

Presents a quantitative approach to the analysis of cardiorespiratory synchronization, which is a newly discovered phenomenon. The primary aim of this study is to determine whether cardiorespiratory synchronization is a real phenomenon or a random one. The authors utilized the surrogate data analysis approach. A surrogate data set was constructed from recordings of ECG and respiration obtained from 14 healthy adults. The surrogate data lacks the coupling between the heart and respiration. The real and surrogate data were subjected to a quantification algorithm in order to determine the statistical properties of synchronization in the two data sets. Synchronization was found in both the real and surrogate data. However, synchronization was significantly less abundant in the surrogate data. In view of those results, cardiorespiratory synchronization seems to be a real phenomenon, yet it probably does not play a crucial role in cardiorespiratory interaction.

The use of a wavelet transform for the analysis of nonstationary heart rate variability signal during thrombolytic therapy as a marker of reperfusion

In this study, we used a special wavelet transform algorithm for the analysis of heart rate variability during thrombolytic therapy. The wavelet transform is suitable for time-frequency analysis in non-steady-state conditions and thus provides a time dependent estimation of autonomic activity. Myocardial infarction and reperfusion are known to affect autonomic activity. We examined the dynamics of heart rate fluctuations in concurrence with reperfusion. Clinical reperfusion was determined when a 50% decrease in ST elevations was recorded. We analyzed the heart rate signal obtained from 12 patients, 6 with anterior wall M1 and 6 with inferior wall M1. Mean heart rate and time dependent power spectral estimates of HR fluctuations at 0.1 Hz (LPF) and respiratory rate (HFP) were examined starting 25 min before reperfusion until 25 min after. Our results indicate that in concurrence with reperfusion an increase in the 0.1 Hz peak occurs in anterior wall M1 patients and a reduction of HR occurs in the inferior wall M1 patients.

A theoretical model for the dependency of heart rate on gradual vagal blockade by atropine

A mathematical model for the dependence of heart rate (HR) on atropine (AT) dose was devised, based on the IPFM (integral pulse frequency modulation) process as well as on other physiological and pharmacological assumptions. The model leads to two equations, which predict, as a function of AT dose, exact values for mean HR and for the power of HR fluctuations at respiratory frequency (HF/sub P/). ECG data from an experimental procedure was used to test the validity of our model. A remarkable agreement between theory and experiment was observed Moreover, the computed values of the pharmacodynamic parameters, which were defined by the model, displayed a surprisingly small variance among the different subjects. These findings suggest that these parameters might be a basis for a quantitative classification method for cardiovascular control, expressing specific heart or brain diseases.

Bispectrum and bicoherence for the investigation of very high frequency peaks in heart rate variability

Recently (2000), we reported the occurrence of very high frequency (VHF) peaks in the heart rate (HR) and blood pressure (BP) spectra in heart transplant (HT) patients. In this study, we apply the bicoherence function, which provides an estimate of correlation between three spectral peaks, thus allowing us to determine the relations between the VHF peaks and other peaks. A statistical approach was used to determine a threshold which discerns true bispectral peaks from spurious ones for any required level of significance. 25 recordings of HR, BP and respiration were obtained from 13 male HT patients. Extensive arrhythmias prevented spectral analysis in eight recordings. VHF peaks were found in the HR and BP in nine recordings. We found two types of VHF peaks: (1) harmonics of respiration, and (2) peaks totally uncorrelated with respiration. Four recordings exhibited type-1 peaks, one recording had only type-2 peaks and four recordings had both types. The nature of the VHF peaks remains to be resolved.

Ischemia monitoring by analysis of depolarization changes

Myocardial ischemia causes changes in the depolarization phase of the cardiac cycle, which can be quantified by analysis of high-frequency QRS components (HFQRS). We introduce a novel HFQRS analysis technology and evaluate its performance in monitoring transient ischemic episodes in patients hospitalized due to chest pain. Continuous monitoring by high-resolution 12-lead ECG was performed in 43 patients admitted to a chest pain unit, followed by cardiac imaging. Indices of HFQRS based on ischemia-specific morphological changes and conventional ST segment levels were extracted from signal-averaged ECG. HFQRS indices were positive for 5 of 10 patients that were diagnosed with coronary artery disease, while ST analysis was negative for all patients. The severity of the HFQRS indices was directly related to the likelihood of ischemic events. HFQRS is a promising technology for monitoring and early detection of acute coronary syndrome.