The Correlation Dimension of Heart Rate Variability Reflects Cardiac Autonomic Activity

Background: Linear methods of time series analysis such as summary statistics and frequency-domain parameters have been used to measure heart rate variability (HRV). More recently, nonlinear methods including the correlation dimension (CDim) have been used to evaluate HRV. The aim of this study was to examine the effect of autonomic perturbations on the CDim. Methods: The CDim was calculated from 2000 data points (RR intervals) collected over a relatively short period of time (20–40 min) in 12 healthy subjects aged between 20 and 40 years (mean 30 ± 2 years) during: (a) supine rest; (b) head up tilt (sympathetic activation, parasympathetic nervous system activity withdrawal); (c) intravenous infusion of atropine (parasympathetic nervous system activity withdrawal); and (d) following overnight administration of low dose transdermal scopolamine (parasympathetic nervous system augmentation. Results: The CDim was determined at rest (7.8 ± 0.3) and found to be significantly reduced during tilt (5.9 ± 0.4, P < 0.01) and atropine administration (4.2 ± 0.4, P < 0.01) and possibly increased by scopolamine (8.3 ± 0.5, NS). Conclusions: The changes following these interventions suggest that CDim can accurately measure cardiac autonomic nervous system activity.     

Interaction between Heart Rate and Heart Rate Variability

Heart rate variability (HRV) is significantly associated with average heart rate (HR), therefore, HRV actually provides information on two quantities, that is, on HR and its variability. It is difficult to conclude which of these two plays a principal role in the HRV clinical value, or in other words, what is the HR contribution to the clinical significance of HRV. Moreover, the association between HRV and HR is both a physiological phenomenon and a mathematical one. The physiological HRV dependence on HR is determined by the autonomic nervous system activity, but the mathematical one is caused by the nonlinear relationship between RR interval and HR. By employing modification methods of the HRV and HR relationship, it is possible to investigate the HR contribution to the HRV clinical value. Recent studies have shown that the removal of the HR impact on HRV makes HRV more predictive for noncardiac death, however, the enhancement of this impact causes HRV to be a better predictor of cardiovascular mortality. Thus, HR seems to constitute a cardiovascular factor of the HRV predictive ability. HR also influences the reproducibility of HRV, therefore, HR changes should be considered when one compares HRV measurements in a given patient. This review summarizes methodological aspects of investigations of the HRV and HR interaction as well as latest observations concerning its clinical utility. The issues discussed in this article should also refer to any other heart rate dynamics analysis which indices are significantly associated with HR.     

Effects of Menstrual Cycle on Cardiac Autonomic Innervation As Assessed By Heart Rate Variability

Objective: The aim of the study was to investigate the effects of menstrual cycle on cardiac autonomic function parameters in young healthy women by means of heart rate variability (HRV). Methods: Forty‐three nonobese regularly cycling women (age 29 ± 6, range 20–38) were enrolled. Recordings for HRV analysis were obtained during the two phases of the menstrual cycle when the estrogen and progesterone levels peaked (follicular phase 11 ± 1 days and luteal phase 21 ± 1 days from the start of bleeding). Power spectral analysis of HRV was performed to calculate the low frequency peak (LF, 0.04–0.15 Hz), high frequency peak (HF, 0.15–0.40 Hz), LF in normalized unit (LF nU), HF in normalized unit (HF nU), and LF/HF ratio during the two phases of menstrual cycle. Results: The heart rates, LF and HF, were similar in both phases (P > 0.05). A significant increase was noted in the LF NU in the luteal phase compared to follicular phase of the menstrual cycle (P = 0.014), whereas a tendency for increased HF NU was observed in the follicular phase (P = 0.053). Furthermore, LF/HF ratio was significantly higher in the luteal phase compared to follicular phase (2.1 ± 1.5 vs 1.6 ± 0.9, P = 0.002), suggesting increased sympathetic activity in the luteal phase. Conclusion: We concluded that regulation of autonomic tone is modified during menstrual cycle. The alteration in the balance of ovarian hormones might be responsible for these changes in the cardiac autonomic innervation. A.N.E. 2002;7(1):60–63     

Heart Rate Variability Assessment of the Effect of Physical Training on Autonomic Cardiac Control

Background: The effect of exercise interventions on autonomic nervous system (ANS) control of the heart by heart rate variability (HRV) is often investigated in just one position. It was hypothesized that results of exercise‐induced changes on ANS are dependent on body position and that it is possible to distinguish between exercise induced changes in vagal and sympathetic influence by taking measurements in different body positions. Methods: One hundred eighty‐three (male = 100, female = 83) healthy volunteers, between 18 and 22 years, participated in a prospective twelve week medium to high intensity exercise intervention study with a self‐control design. The influence of the exercise intervention was investigated on supine, rising, and standing as well as on the orthostatic response. Time domain, frequency domain and nonlinear (Poincaré) HRV analysis were performed. Results: The exercise intervention lead to a significant increase (P < 0.05) in vagal influence during supine, rising, and standing. Sympathetic control in the supine position was decreased and increased during rising and standing. In the initial orthostatic response to rising from the supine position, the exercise intervention lead to increased (P < 0.05) vagal withdrawal as well as increased sympathetic control. The orthostatic response measured as the difference between standing and supine indicated only an exercise induced increase in sympathetic control. Conclusions: Exercise‐induced changes in sympathetic and parasympathetic ANS control differ, depending on posture and period of measurement. Exercise induced changes in parasympathetic and sympathetic outflow, respectively, can be extracted from measurements from supine, through the orthostatic response, to standing, thereby detecting changes in ANS that are otherwise obscured.     

Heart Rate and Heart Rate Variability in Normal Young Adults

Heart Rate and Heart Rate Variability. Introduction: The relationships between heart rate (HR) and HR variability (HRV) are not simple. Because both depend on the autonomic nervous system (ANS), they are not independent variables. Technically, the quantification of HRV is influenced by the duration of the cardiac cycles. The complexity of these relationships does not justify ignoring HK when studying HRV, as frequently occurs. Methods and Results: Using spectral and nonspectral methods, the HR and various normalized and non-normalized indices of HRV were studied in 24-hour recordings of a homogeneous cohort of seventeen 20-year-old healthy males. The HR-HRV relationships were appraised by analyzing the same data in two different ways. The 24 mean hourly values provide consistent information on the circadian behavior of the indices, while the average 24-hour individual data show a wide spectrum of normality. Combined approaches allow assessment of the direct impact of RR interval on HRV evaluation. The correlations between HR and normalized indices of HRV arc weaker in 24-hour individual data than in pooled hourly data of the same individuals. These correlations are close to 1 in the latter case, which does not mean that measuring HRV is simply another method of evaluating HR, but that normal physiology supposes a harmonious behavior of the various indices. When considered individually without normalization, the specific indices of vagal modulation (high-frequency band of the spectrum, short-term HR oscillations of the nonspectral analysis) consistently increase at night and diminish during the day. However, the low-frequency power, which supposedly reflects sympathetic influences, also increases at night, whereas more logically the longer HR oscillations would predominate during the day. Moreover, the selective analysis of HR oscillations during HR acceleration or decrease indicates that their behavior differs accordingly. Conclusion: We recommend that closer attention be paid to the complex relationships between HR and HRV. The strong correlations found in healthy subjects may reflect either the physiological harmony of ANS functions or simple redundancy. Their tendency to deteriorate in diseased hearts suggests that redundancy is not the cause and that abnormalities of ANS functions are not demonstrated by HRV analysis alone.     

Physiological Background Underlying Short-Term Heart Rate Variability

A large number of papers has been published on heart rate variability (HRV) based on the assumption that the specific components of HRV provide specific information about cardiac parasympathetic or sympathetic efferent nerve activity. However, neural control of the cardiorespiratory system is very complex, and the physiological phenomenon underlying HRV in different conditions are far from being fully understood. This review summarizes, in the light of current literature, a series of studies focused on the mechanisms by which fluctuations in neural outflows are transferred into HRV. In the interpretation of HRV analyses, it should be taken into account that: (1) HRV seems to be strongly influenced by the parasympathetic nervous system at all the frequency components; (2) due to sympathovagal interactions, sympathetic outflow is able to reduce the variations generated by vagal modulation also in the high frequency band; and (3) the variations in heart rate reflect fluctuations in the neural activity rather than the mean level of sympathetic or parasympathetic neural activity. Thus, we should be cautious in interpreting a specific component of HRV as a specific marker of sympathetic or parasympathetic cardiac control. Furthermore, due to the complexity of the cardiorespiratory control system, the analysis of short-term HRV should be performed in well-controlled conditions, in which the behavior of the autonomic nervous system is well documented.     

心率变异性的研究及应用进展

心率变异性是评价自主神经功能最常用的无创方法,随着计算技术的发展越来越多测量心率变异性的新方法进入到实践之中。自主神经系统在不同系统疾病中的影响和作用,正由于这种无创评估方法的实用化而被逐渐认识。现仅就心率变异性方法学和应用领域方面的进展进行简要概述。     

Implication of Base Heart Rate in Autonomic Nervous Function,Blood Pressure and Health-Related QOL

Increased resting heart rate (HR) and increased sympathetic nervous activity are independent risk factors for cardiovascular disease. Recently, base heart rate (HRo: minimum stable HR during sleep) has been reported to relate to cardiac stroke volume and age. However, little is known about the relevance of HRo. The aim of our study was to evaluate how HRo is associated with HR variability (HRV), blood pressure and health-related quality of life (HRQOL) in healthy subjects. A total of 139 volunteers participated in this study that measured 24-hr HR, HRV, and blood pressure. HRo was estimated from the trendgram and the histogram of HR during the nighttime (sleep) period, and calculated as the 1% lowest value of its integral. HRQOL was assessed by Medical Outcome Study Short-Forum 36-Item Health Survey. Sympathetic nervous activity (ratio of low frequency to high frequency component: LF/HF) and parasympathetic nervous activity (high frequency component: HF) were calculated by ECG monitoring. HRo was positively correlated with 24-hr LF/HF and nighttime LF/HF. HRo was negatively correlated with 24-hr HF and nighttime HF. Moreover, HRo was positively correlated with the scores of social functioning and role-physical. Using multivariate analysis, HRo is related to LF/HF, body mass index, and the score of social functioning (HRQOL). HRo may be a useful indicator for assessing sympathetic nervous activity and HRQOL in normotensive healthy subjects.     

Autonomic Nervous System Function in Women with Irritable Bowel Syndrome

Autonomic nervous system (ANS) balance was assessed in women with and without irritable bowel syndrome (IBS) using laboratory tests of function (ie, expiratory/inspiratory ratio, Valsalva, posture changes, and cold pressor) and spectral and nonspectral measures of heart rate variability (HRV). Women with (N = 103) and without IBS (N = 49) were recruited, interviewed, then completed a laboratory assessment and wore a 24-hr Holter monitor Analysis using the entire sample showed little difference between IBS and control women and between subgroups with IBS on either laboratory measures or 24-hr HRV measures. However, analysis restricted to those women with severe IBS symptoms showed quite pronounced differences between two IBS subgroups on 24-hr HRV measures. Parasympathetic tone was significantly lower and ANS balance was significantly higher in the constipation-predominant compared to the diarrhea-predominant group. Subgroups of women with IBS do differ in ANS function as measured by 24-hr HRV; however, these differences are only apparent among women with severe symptoms. These findings point out the importance of considering symptom severity when interpreting studies of IBS.     

Automatic Filtering of R‐R Intervals for Heart Rate Variability Analysis

Background: In R‐R analysis for heart rate variability, rhythm modificatipns other than those related to autonomic nervous system activity must be avoided. We describe an algorithm that performs a correction based on the comparison of each interval with a normal standard. Methods: Starting with a given R‐R list, a parameter R between 0 and 1 is chosen, the normal R‐R range is defined as: (1‐R, 1+R]. The first interval then is divided by the mode of the entire R‐R list. If the resulting value lies within the normal range, then it could be accepted as normal. Subsequent intervals are divided by the last accepted one and the mean value of the accepted intervals. If either of these results is inside.the normal range, then the considered interval is accepted. The abnormal intervals are evaluated to find out if they are in the expected range, which is [T‐1, T+11, where T is a new parameter smaller than R. Not expected intervals are handled differently to be corrected and in a few cases are eliminated. Results: Two types of tests were carried out. One uses real recordings containing artifacts. The other test was carried out by means of a computer program that generates corrupted data. R value was set in 0.2 and T in 0.05. Comparisons between our filter and other automatic algorithms were done. Conclusions: Our filter is fast and strong enough to perform an accurate automatic correction.     

Heart Rate Variability: Measurement and Clinical Utility

Electrocardiographic RR intervals fluctuate cyclically, modulated by ventilation, baroreflexes, and other genetic and environmental factors that are mediated through the autonomic nervous system. Short term electrocardiographic recordings (5 to 15 minutes), made under controlled conditions, e.g., lying supine or standing or tilted upright can elucidate physiologic, pharmacologic, or pathologic changes in autonomic nervous system function. Long‐term, usually 24‐hour recordings, can be used to assess autonomic nervous responses during normal daily activities in health, disease, and in response to therapeutic interventions, e.g., exercise or drugs. RR interval variability is useful for assessing risk of cardiovascular death or arrhythmic events, especially when combined with other tests, e.g., left ventricular ejection fraction or ventricular arrhythmias.     

Frequency Ranges of Heart Rate Variability Related to Autonomic Nerve Activity in the Mouse

Mice have gained more and more attention in recent years and been widely used in transgenic experiments. Although the number of researches on the heart rate variability (HRV) of mice has been gradually increasing, a consensus on the frequency ranges of autonomic modulation has not been established. Therefore, the main purpose of this study was to find a HRV “prototype” for conscious mice in the state of being motionless and breathing regularly (called “genuinely resting”), and to determine the frequency ranges corresponding to the autonomic modulation. Further, whether these frequencies will change when the mice move freely was studied to evaluate the feasibility of the HRV spectrum as an index of the autonomic modulation of mice. The recording sites were specially arranged to simultaneously obtain the electrocardiography and electromyography data to be provided for the use of HRV analysis and motion monitoring, respectively. The states of being motionless and breathing regularly as judged from the electromyography results were selected as a genuine resting state of a conscious mouse. The frequencies related to autonomic modulation of HRV were determined by comparing the spectrum changes before and after blockades of the autonomic tone by different pharmaceutical agents in both the genuine resting state and freely moving states. Our results showed that the HRV of mice is not suitable for indexing sympathetic modulation; however, it is possible to use the spectral power in the frequency range between 0.1 and 1 Hz as an index of parasympathetic modulation.     

Significance of Autonomic Nervous System Activity in Functional Dyspepsia

The purpose of this study was to examine if patients with functional dyspepsia could be separated into meaningful groups based on their autonomic function. Subjects were divided into two groups, and symptoms, gastric myoelectrical activity, gastric emptying, and psychological factors were compared. Group 1 had less autonomic variability but more cardiac reactivity than group 2. Symptom reports did not differ between groups. Group 1 had higher neuroticism scores than group 2, while group 2 showed greater tachyarrhythmia in response to drinking water than group 1. The relatively low autonomic variability in group 1 is consistent with higher sympathetic activity and may be associated with the group's greater neuroticism. The relative lack of cardiac reactivity in group 2 is consistent with lack of autonomic flexibility and may be related to the tachyarrhythmia observed in that group. The results of this study suggest that autonomic function may play a significant role in functional dyspepsia.     

Autonomic Nervous System Modulation before the Onset of Sustained Atrioventricular Nodal Reentry Tachycardia

Introduction: Our study was designed to analyze dynamic changes in autonomic tone before the onset of typical sustained atrioventricular nodal reentry tachycardia (AVNRT) in a large group of patients without structural heart disease. Materials and Methods: Twenty‐four‐hour Holter tapes from 42 consecutive patients (27 men and 15 women; aged 30 ± 21 years) with several episodes of sustained typical AVNRT were analyzed. The diagnosis was validated by transesophageal electrophysiological study. The time‐domain calculated parameters were SDNN, SDANN, rMSSD, pNN50; the frequency‐domain parameters were low‐frequency power (LF, 0.04–0.15 Hz), high‐frequency power (HF, 0.15–0.40 Hz), very low‐frequency power (VLF, 0.008 to 0.04 Hz) and LF/HF. The mean values in the hour before the onset of sustained AVNRT were compared with the mean values of 2 hours before and 1 hour after the onset of sustained AVNRT. Results: The mean SDNN, rMSSD, pNN50, HF were significantly decreased during the hour preceding the onset of AVNRT, when compared to the mean values observed during the time periods selected. Instead, the LF values and LF/HF were increased before the onset of sustained AVNRT. No significant change in the VLF and atrial ectopic beats were observed. Conclusion: This study suggests that sustained typical AVNRT episodes are preceded by increase in adrenergic drive. Ann Noninvasive Electrocardiol 2010;15(1):49–55     

Circadian Variation of Heart Rate Variability in Postinfarction Patients With and Without Life-Threatening Ventricular Tachyarrhythmias

Circadian Variation of HRV. Introduction: Determination of heart rate variability (HRV) is widely used for noninvasive assessment of cardiac autonomic tone. A decreased HRV is associated with an increased mortality in patients surviving an acute myocardial infarction. There are, however, only sparse data about the circadian variation of different components of HRV that may be linked to the well-known circadian fluctuations in the occurrence of sudden death. In addition, the potential prognostic impact of circadian variations of HRV has not been examined. Methods and Results: The present study compared the circadian variation of HRV from 14 postinfarction patients who had survived at least one episode of out-of-hospital cardiac arrest (cardiac arrest group) with that of 14 age- and sex-matched patients without a history of malignant arrhythmias after their index infarct (control group). Several time- and frequency-domain measures of HRV were assessed from 24-hour Holter recordings. Circadian variations of high- (HF), low- (LF), and total-frequency (TF) components were determined by calculating for each parameter the hourly difference from the day's mean. The average of these differences was calculated for every hour as well as for predefined day and night periods. There was no significant difference between the two groups with regard to HRV indices that predominantly reflect vagal tone, such as SDNN (78 ± 25 vs 96 ± 24 msec), pNN50 (2.7%± 4.6% vs 4.9%± 4.2%), or HF (6.3 ± 3.0 vs 7.8 ± 3.2 msec; cardiac arrest vs control group). There was also no significant difference in the circadian variation of LF or TF between the two groups during daytime and nighttime. However, a significant difference in circadian variation of HF was found during daytime (0.02 ± 0.5 vs -0.6 ± 0.5 msec; P = 0.006) and nighttime (0.19 ± 0.64 vs 1.5 ± 0.75 msec; P = 0.0002). In cardiac arrest survivors, there was no difference in the mean deviation of HF between the day-and the nighttime periods. Conclusions: These results show an almost complete abolition in circadian variation of parasympathetic tone in postinfarction patients surviving an episode of out-of-hospital cardiac arrest, whereas circadian variation of sympathetic tone is comparable to that of postinfarction patients without arrhythmic episodes. These findings indicate that determination of diurnal variation of HRV may add to the prognostic value of HRV with respect to identifying patients at high risk of sudden death.     

Heart Rate Variability in Obstructive Sleep Apnea: A Prospective Study and Frequency Domain Analysis

Background: Cyclic variation of the heart rate is observed during apneic spells in obstructive sleep apnea (OSA). We hypothesized that autonomic changes would affect frequency‐domain measures of heart rate variability (HRV). Methods: We studied 20 patients (15 men, 5 women, mean age 47.2 ± 12.2 years) with suspected OSA undergoing overnight polysomnography, and five patients (4 men, 1 woman, mean age 49.2 ± 8.6 years) with recently diagnosed sleep apnea undergoing polysomnography while wearing continuous positive airway pressure (CPAP). Holter monitors were applied during sleep studies and data were analyzed in 5‐minute blocks over the course of the night. Using spectral analysis, low frequency (LF) and high frequency (HF) powers were calculated for each interval. Overall mean and standard deviation (SD) for LF power, HF power, and the LF:HF ratio were recorded for each patient. Comparisons were made between patients with severe OSA (apnea hypopnea index (AHI) > 30, n = 8 ), moderate OSA (AHI 1–30, n = 5 ), without OSA (AHI < 10, n = 7 ), and patients wearing CPAP (n = 5 ). Results: Assessment of overnight LF or HF power revealed no significant difference between the four groups. The LF:HF ratio, which represents sympathovagal balance, was higher among those with moderate disease compared to normals and those with severe OSA (both P = 0.037 ). The standard deviation of the LF:HF ratio was higher among those with moderate disease compared to normals (P = 0.0064) and those with severe OSA (P = 0.0006) . OSA patients receiving CPAP behaved like patients with moderate OSA, with increased SD of the LF:HF ratio. Conclusions: The observed changes in the LF:HF ratio and its SD suggest an increased sympathetic tone and discordance in sympathovagal activity in moderate OSA, which is blunted in severe OSA. CPAP may restore autonomic defects, characteristic of severe OSA, to moderate levels.     

Evaluation of Effects of Intra aortic Balloon Counterpulsation on Autonomic Nervous System Functions by Heart Rate Variability Analysis

Background: In patients with acute myocardial infarction (AMI), intraaortic balloon counterpulsation (IABC) may improve cardiac performance, decrease the incidence of recurrent ischemia, and improve survival. Although there have been several reports concerning circulatory maintenance with the IABC, response of the autonomic nervous system to these hemodynamic changes is not clear. Heart rate variability (HRV) analysis has been extensively used to evaluate autonomic modulation of sinus node and to identify patients at risk for an increased cardiac mortality. In this study, we evaluated effects of the IABC on autonomic nervous system functions by HRV analysis. Methods: The study group was composed of 32 consecutive patients (13 female, 19 male aged 61.8 ± 8.8 years) undergoing IABC. Transthoracic echocardiography and 1‐hour Holter recordings for HRV analysis in each IAB pumping mode were obtained. Results: The IABC improved left ventricular diastolic and systolic functions as well as caused an increase in SDNN1, PNN50(1), RMSSD1, and HF1 and a decrease in LF1, LF/HF1, mean heart rate, and the number of ventricular extrasystoles. The improvements in HRV parameters were correlated with some hemodynamic changes such as the increase in MAP and CO during counterpulsation. The only independent factors affecting in‐hospital mortality were the change in LF/HF1 ratio (ΔLF/HF1) and the change in the number of ventricular extrasystole (ΔVES). The decrease in LF/HF1 ≥4.9 decreased the mortality by 1.7‐folds (RR = 0.6, P = 0.04, 95% CI: 0.1–2.3). The decrease in VES ≥27/15 minutes resulted in mortality reduction by 16‐folds (RR = 0.06, P = 0.02, 95% CI: 0.01–0.4). Conclusions: As a result, the IABC, especially in 1:1 support, causes an increase in HRV, decrease in sympathetic overactivity, and improvement in sympathovagal balance besides the favorable hemodynamic changes, and these electrophysiologic changes may explain the role of the IABC in the treatment of ventricular arrhythmias.