Intraindividual Reproducibility of Heart Rate Variability

Heart rate variability was determined from three consecutive Holter recordings performed on days 1, 7, and 28 in 17 normal subjects, in 13 patients with angiographically normal coronary arteries, and in 9 patients with remote myocardial infarctions. Group data of several time and frequency domain measures of heart rate variability were highly reproducible (correlation coefficients 0.629–0.894). However, some individuals exhibited considerably larger day-to-day variations in heart rate variability. Single heart rate indices differed by up to 50% between two Holter recordings. Such potential differences must be considered when repeated heart rate variability determinations are used to assess changes in neurocardiac reflex regulation or effects of therapeutic interventions.     

Changes in Heart Rate, Heart Rate Variability, and Heart Rate Turbulence during Evolving Reperfused Myocardial Infarction

Depressed cardiac parasympathetic activity is associated with electrical instability and adverse outcomes after myocardial infarction (MI). Heart rate turbulence (HRT), reflecting reflex vagal activity, and heart rate variability (HRV), reflecting tonic autonomic variations are both reduced in the subacute phase of MI. However, the evolution of these components of cardiac autonomic control between subacute and chronic phase of MI has not been defined. We prospectively studied 100 consecutive patients with a recent first MI with ST-segment elevation, who underwent successful direct percutaneous coronary interventions. Beta-adrenergic blockers and angiotensin-converting enzyme (ACE) inhibitors were administered according to the state-of-the-art medical practice guidelines. HRT and HRV were measured from 24-hour ambulatory electrocardiographic recordings 10 days and 12 months after the index MI. There was no significant difference in mean RR interval between the subacute and chronic phase of MI (875 ± 145 versus 859 ± 122 ms). Indices of HRV increased significantly during the observation period (SDNN: from 88.8 ± 26.8 to 116.0 ± 35.7 ms, P < 0.001; SDNNi: from 37.9 ± 15.9 to 46.0 ± 16.3 ms, P < 0.001; SDANN: from 79.6 ± 34.7 to 105.6 ± 35.4 ms, P < 0.001). In contrast, there were no significant changes in indices of HRT (turbulence onset: from −0.008 ± 0.022 to −0.012 ± 0.025%; turbulence slope: from 7.78 ± 5.9 to 8.06 ± 6.8 ms/beat). In contrast to reflex autonomic activity, there was a significant recovery of tonic autonomic activity within 12 months after MI. These different patterns of recovery of reflex versus tonic cardiac autonomic control after MI need to be considered when risk stratifying post-MI patients.     

Variable Effects of Physical Training of Heart Rate Variability, Heart Rate Recovery, and Heart Rate Turbulence in Chronic Heart Failure

Background: Heart rate variability (HRV), heart rate turbulence (HRT), and heart rate recovery (HRR), indices that reflect autonomic nervous system (ANS) activity, are outcome predictors in patients with chronic heart failure (CHF). It is not clear, however, whether they reflect the same components of ANS activity. No study has examined the effects of physical training (PT) training on HRV, HRT, and HRR in CHF.
Study Objective: To examine the responses of HRV, HRT, and HRR to a PT program in patients presenting with CHF.
Methods: In 41 patients (mean age = 58.7 ± 10.2 years) in New York Heart Association CHF functional classes II or III, and with a left ventricular ejection fraction <40%, HRV, HRT, and HRR were measured before and after 8 weeks of PT.
Results: The training was clinically effective in all patients. Before versus after PT, standard deviation of all normal RR intervals increased from 107 ± 30 to 114 ± 32 ms (P = 0.047), high frequency increased from 210 ± 227 to 414 ± 586 ms²/Hz (P = 0.02), and the low/high frequency ratio decreased from 1.8 ± 1.55 to 1.1 ± 1.2 (P = 0.002). HRT and HRR did not change significantly after PT.
Conclusions: In patients with CHF, the positive effects of PT were limited to HRV indices, which reflect parasympathetic activity, without significantly changing HRR and HRT. These observations indicate that different mechanisms modulate HRV, HRR, and HRT, which provide complementary information regarding ANS activity. The 8-week PT program failed to completely normalize ANS function.     

Heart Rate Turbulence in Chagas Disease

RIBEIRO, A.L.P., et al. : Heart Rate Turbulence in Chagas Disease. Heart rate turbulence (HRT) quantifies the biphasic response of the sinus node to ventricular premature complexes (VPCs) and is a powerful electrocardiogram related risk predictor. VPCs are frequent in Chagas disease, a potentially lethal illness, and can hamper the analysis by conventional methods of autonomic heart control. The aim of the study was to examine HRT in patients with Chagas disease. Chagas disease patients and healthy controls (group   0, n = 11   ) without other diseases were submitted to a standardized protocol, including electrocardiogram, echocardiography, and 24-hour Holter monitoring. Chagas disease patients were divided according to their left ventricular systolic function: normal (group   1, n = 103   ) and reduced ejection fraction (group   2, n = 23   ). Two HRT indices, turbulence onset (TO) and turbulence slope (TS), were calculated and compared among groups after adjustment for covariates like the prevalence of VPCs and the mean heart rate. Chagas disease patients had significantly altered TO (group 1: −0.0186, group 2: −0.0126) and TS (group 1: 10.844, group 2: 7.870) values in comparison with controls (TO − 0.0256, TS 19.829);   P < 0.001   for both comparisons. In conclusion, HRT data may be useful in the electrocardiographic analysis of autonomic heart control in Chagas disease. Its prognostic value remains to be determined. (PACE 2003; 26[Pt. II]:406–410)     

Reproducibility of Time and Frequency Domain Analysis of Heart Rate Variability in Patients with Chronic Stable Angina

Before heart rate variability (HRV) can be used to investigate the effects of drugs or other clinical interventions in chronic stable angina, it is important to establish the stability and reproducibility of HRV indices over time. HRV analysis was performed on two consecutive 24-hour ambulatory ECG recordings in 19 patients with chronic stable angina. Time-domain analysis included average heart rate, variance, SDNN, SDANN5, ASDNN5, and PNN50. The power spectral analysis was computed using fast Fourier transformation for the total power (0.003 and 0.40 Hz), low frequency (0.04–0.15 Hz), and high frequency (0.15–0.40 Hz) bands. No statistically significant differences in the time or frequency domains were found between the two ambulatory ECG recordings. HRV indices in the time and frequency domains are consistent and reproducible in patients with chronic stable angina. Thus, cardiac autonomic tone can be evaluated using HRV analyses, and any significant changes that occur after medical therapy or other clinical interventions can be ascribed to the intervention rather than the lability of cardiac autonomic tone.     

Epicardial Mapping: Ventricular Epicardial Activation is Unaffected by Heart Position

Epicardial ventricular mapping was performed in five dogs during sinus rhythm with a sock array containing 41 bipolar electrodes. Maps were generated with a computer-assisted mapping system when the heart was in situ and when the heart was lifted by 44 degrees out of the chest. Times of earliest and latest epicardial activation in these two states did not differ. Despite a different frontal plane QRS axis, location of earliest activation was not affected by lifting the heart. In two of the five animals, the site of latest epicardial activation was minimally different from the heart in situ, but the general pattern of epicardial activation was unchanged. Therefore, the change in frontal plane QRS axis with lifting the heart was due to a change in heart position rather than a general change of heart activation.     

24-Hour Heart Rate Variability in Patients with Vasovagal Syncope

Since alterations in the autonomic nervous system are thought to play a major role in the pathogenesis of vasovagal syncope, we characterized the chronic autonomic profile of 44 patients with syncope and 20 healthy subjects by means of heart rate variability using 24-hour Holter recordings (time- and frequency-domain indexes), and evaluated whether the different types of responses to tilting (vasodepressive versus cardioinhibitory) could be associated with different cardiac autonomic patterns. Twenty-three patients exhibited a positive response to tilting, which was vasodepressive in 11 patients and cardioinhibitory in 12 patients. All vasodepressive patients had a standard deviation of the averages of NN (SDANN) intervals in all 5-minute segments lower than 100 ms. Patients with vasodepressive syncope also had significantly lower values of RMSSD (the 24-hour square root of the mean of the sum of the squares of differences between adjacent normal RR intervals) than those with cardioinhibitory response, and lacked the day-night rhythm of the low frequency/high frequency ratio. However, only SDANN values correctly identified patients with vasodepressive response to tilting. We conclude that (1) the population of patients with vasovagal syncope is heterogeneous, (2) patients with vasodepressive syncope have a peculiar chronic autonomic profile as assessed by 24-hour heart rate variability analysis, and (3) the evaluation of the autonomic profile in 24-hour Holter recordings could be of value in the diagnosis of patients with syncope.     

Changes in Heart Rate Variability with Age

Depressed heart rate variability (HRV) after a myocardial infarction is associated with increased mortality. This is thought to be due to reduced parasympathetic activity and heightened sympathetic activity. Aging is associated with depressed HRV, but little is known of the affect of aging on parasympathetic activity. This study examined 56 healthy subjects (age range 40–102 years; 39 women). None had a history of heart disease or were on medication that would affect cardiac function. All had normal resting ECGs, normal heart size on chest X ray, and normal electrolytes. In all subjects, 24-hour Holter recordings were performed and used to measure HRV. In particular, the study examined the affect of age on HRV triangular index, which gives an estimate of overall HRV, and on RMSSD (square root of the mean squared differences of successive normal-to-normal RR intervals), which gives an estimate of short-term components of HRV and is thought to reflect the overall extent of vagal modulations of heart rates. Both these parameters were compared in patients younger and older than 70 years. Each recording lasted at least 17 hours; the majority of recordings were longer than 20 hours. There was a significant decrease in HRV triangular index with age (r =?0.4, P < 0.05) and no significant change in RMSSD with age(r =?0.08, P = NS). There was a significant difference in HRV index in those > 70 years compared with those < 70 years (38.0 ± 9.3 vs 31.0 ± 11, respectively, P <0.02). There was no significant difference in RMSSD between the two age groups (26.7 ± 8.2 ms vs 28.4 ± 11.3 ms, respectively, P = NS). Thus, the study concludes that aging reduces the global measure of HRV and may reflect reduced responsiveness of autonomic activity to external environmental stimuli with age. However, the time-domain short-term components of HRV are not affected by age and, therefore, the fast and presumably vagal modulations of heart rate appear to be maintained.     

Heart Rate Variability in Isolated Rabbit Hearts

The presence of heart rate variability (HRV) in patients with cardiac denervation after heart transplantation raised our interest in HRV of isolated, denervated hearts. Hearts from seven adult white ELCO rabbits were transferred to a perfusion apparatus. All hearts were perfused in the working mode and in the Langendorff mode for 20 minutes each. HRV was analyzed in the frequency domain. A computer simulated test ECG at a constant rate of 2 Hz was used for error estimation of the system. In the isolated, denervated heart, HRV was of random, broadband fluctuations, different from the well-characterized oscillations at specific frequencies in intact animals. Mean NN was 423 ± 51 ms in the Langendorff mode, 406 ± 33 ms in the working heart mode, and 500 ms in the test ECG. Total power was 663 ± 207 ms², 817 ± 318 ms², and 3.7 ms², respectively. There was no significant difference in any measure of HRV between Langendorff and working heart modes. The data provide evidence for the presence of HRV in isolated, denervated rabbit hearts. Left atrial and ventricular filling, i.e., the working heart mode, did not alter HRV, indicating that left atrial or ventricular stretch did not influence the sinus nodal discharge rate.     

Analysis of Heart Rate Variability Five Minutes Before the Onset of Paroxysmal Atrial Fibrillation

BACKGROUND: Various experimental and clinical observations suggest changes in sympathetic and vagal neural regulatory mechanisms play a critical role in altering cardiac electrical properties and favor the occurrence of arrhythmic events. There is limited information about the influences of the autonomic tone on the development of episodes of paroxysmal atrial fibrillation in patients with no evidence of organic heart disease. The aim of this study was to investigate changes in sympatho-vagal balance 5 minutes before the onset of atrial fibrillation. METHODS: We evaluated 28 patients with no history of heart disease who were not undergoing pharmacological treatment and who had at least one episode of paroxysmal atrial fibrillation recorded during an 24-hour ECG Holter monitoring. We analyzed values of frequency domain heart rate variability parameters 5 minutes before the onset of atrial fibrillation (prefa period) compared to an equivalent period at least 1 hour after from atrial fibrillation (random period). RESULTS: Thirty-six episodes of atrial fibrillation were recorded and our results showed we had two types of episodes. Eighteen were classified as Type A, in which we had an increase of low frequency (LF) (79.15 +/- 10.76 in comparison with 62.64 +/- 19.55) (P = 0.004) and a decrease of high frequency (HF) (20.82 +/- 10.74 in comparison with 37.64 +/- 20.20) (P = 0.004) consistent with an increase of sympathetic tone; and 18 were classified as Type B in which there was a decrease of LF (62.82 +/- 15.38 in comparison with 85.97 +/- 8.48) (P < 0.001), and an increase of HF (36.79 +/- 14.72 compared with 14.01 +/- 8.48) (P < 0.001), consistent with an increase of parasympathetic tone. CONCLUSION: We observed abrupt changes in sympathovagal balance in the last 5 minutes preceding an episode of atrial fibrillation. This can be related to a double behavior in the neurogenic drive: in Type A episodes there is an increase of the LF spectrum, LF:HF ratio, and a decrease of the HF spectrum consistent with an increase of neurogenic sympathetic drive; in Type B episodes there is a reduction of the LF spectrum, LF/HF ratio, and an increase of HF spectrum consistent with an enhancement of the neurogenic parasympathetic drive. In some patients, we found that the two mechanisms operate during different hours of the day and that sometimes there is an increase of sympathetic tone, and in the same instances an increase of parasympathetic tone. Heart-rate variability measures fluctuation in autonomic inputs to the heart rather than the mean level of autonomic impulse; autonomic imbalance is probably more important than the vagal or sympathetic drive alone.     

病毒性心肌炎的室性心律失常与窦性心率震荡的关系及药物干预研究

目的:探讨病毒性心肌炎患者24小时动态心电图(DCG)中室性心律失常与心率震荡(HRT)的关系。方法:56例临床诊断室性心律失常患者分为病毒性心肌炎组(A组)和无器质性病变者组(B组),均行DCG监测,计算心率震荡的初始值(TO)、斜率(TS)。A组患者口服美托洛尔(25mg/次,每天二次)1月后复查24hDCG。结果:A组TO、TS分别较B两明显升高和降低,且A组口服美托洛尔1月后明显改善。结论:自主神经调节功能受损是病毒性心肌炎发生室性心律失常的重要原因,HRT可作为病毒性心肌炎判断预后的重要指标,口服美托洛尔可改善HRT。     

抑郁患者的心率变异性分析

目的:对抑郁患者的心率变异性进行分析,评价自主神经张力的改变。方法:选择24例抑郁患者及正常对照组23例,进行HRV分析。结果:抑郁组SDANN、SDNN及rMSSD明显低于对照组,且SDANN均<100ms,LF/HF昼夜节律性变化消失。结论:抑郁患者交感神经张力明显增加,并引起交感神经和副交感神经平衡失常。     

Heart Rate Variability in Patients with Familial Amyloid Polyneuropathy

The purpose of this study was to evaluate heart rate variability (HRV) in patients with familial amyloid polyneuropathy (FAP) using the time- and frequency-domain analysis. The study population consisted of 19 patients with FAP, and 19 age and sex matched normal volunteers. The 24-hour Holter recordings of all subjects in sinus rhythm and off medication were analyzed. Five time-domain indices of HRV were computed. The frequency component of HRV was calculated by fast Fourier transform analysis of the RR intervals. The power spectrum of the low frequency (LF) between 0.04–0.15 Hz and high frequency (HF) between 0.15–0.40 Hz and the LF/HF ratio was calculated. Global measures of HRV including the standard deviation of the mean of RR intervals (SDNN) and the standard deviation of 5-minute mean RR intervals (SDANN) were decreased in patients with FAP. Specific vagal influences on HRV including the proportion of RR intervals more than 50 milliseconds different (pNN50) and the HF power on spectral analysis were less in patients with FAP. LF power and LF/HF ratio were more decreased in patients with FAP at the advanced stage than at the early stage. In conclusion, HRV was significantly decreased in patients with FAP at the early stage, and sympathetic activity was more decreased in patients at the advanced stage. These findings suggest that the decrease of the HRV is an indicator of this disease and the power spectral analysis of the HRV is beneficial in assessing the severity of the autonomic dysfunction.     

Effects of a Selective Al-Adenosine Receptor Agonist on Heart Rate and Heart Rate Variability During Permanent Atrial Fibrillation

Background: Mean heart rate and irregularity of the rate, i.e., heart rate variability (HRV), are two aspects of heart rate during atrial fibrillation (AF). An important goal of AF therapy is to control mean heart rate during exercise; the determinants of HRV during AF remain poorly known although its prognostic value has been established. Objectives: To investigate the effects of a stable, long-acting, selective A1-adenosine receptor agonist, SDZ WAG994, on heart rate during exercise and on HRV. Methods: In a multicenter, double-blind, randomized, placebo-controlled, parallel group study, patients with permanent AF performed a symptom-limited exercise test and underwent 24-hour ECG monitoring on day 1 during treatment with placebo, and on day 2 during treatment with either placebo or 2 mg SDZWAG994 orally. Changes in mean heart rate during exercise and changes in HRV indices between day 1 and day 2 were compared between the two groups. Results: Thirty-two patients (64 ± 8 years; 81% male; 25% in NYHA Class II; 38% with no structural heart disease) were included in the study. During active treatments, heart rate remained unchanged at rest and increased significantly during exercise. A significant daytime increase in short-term HRV indices (DpNN50 = 4.5% P = 0.01; DrMSSD = 6% P = 0.03; DSDNN Index = 6% P = 0.02) occurred during active treatment. Conclusions: Selective A1-adenosine receptor agonism with SDZ/WAG994 limits the increase in mean heart rate during exercise in patients with AF. In addition, this agonist selectively increases short-term HRV indices, suggesting that pNN50, rMSSD, and SDNN reflect vagal influences during AF.     

Prognostic Value of Heart Rate Variability in Patients Awaiting Cardiac Transplantation

Time and frequency domain parameters of heart rate variability (HRV) were determined in patients with severe end stage heart failure awaiting cardiac transplantation (HTX). These parameters were then correlated with mortality to investigate the performance of HRV in discriminating between groups with high and low risk of death. The standard deviation of five consecutive RR intervals (SDANN) was found to be the parameter with the greatest sensitivity (90%) and specificity (91%). Patients with SDANN values of < 55 msec had a twenty-fold increased risk of death (90% confidence limits: 4–118, P < 0.001). The results furthermore suggest that measurements of HRV are superior to other prognostic markers such as left ventricular ejection fraction, pulmonary artery wedge pressure, cardiac index, and serum sodium levels. We conclude that HRV is a powerful, noninvasive tool to assess the risk of death in candidates for HTX. HRV measurements can therefore be used as a supplement to other markers of risk to determine the optimal therapeutic strategy in patients with severe congestive heart failure.     

Heart Rate Variability After Cardiac Transplantation in Humans

The reappearance of cardiac innervation after cardiac transplantation remains a matter of debate. We evaluated the ability of heart rate variability (HRV) analysis to detect the extent and time course of functional cardiac allograft reinnervation. Time- and frequency-domain analysis of heart rate was performed on Holter recordings of 120 heart transplant and four heart-lung transplant recipients. A high frequency (HF) component was clearly distinguished on visual inspection of power spectral density in 42 patients. In eight patients an HF component of normal magnitude was detected. The other 34 patients in this group, including all four heart-lung transplants, presented with a very small HF component. The other 82 patients showed a flat spectrum. The group with an HF component of normal amplitude was significantly different, compared to the other groups, for all HRV parameters. Serial plotting of HRV parameters of the patients with an HF component of normal amplitude against time posttransplant, revealed, from 12 months onwards, a progressive increase of parameters denoting HF variability. In five heart transplant patients with acute allograft rejection, the use of HRV analysis for rejection monitoring was unsuccessful. These results suggest that, inasmuch as the HF component of HRV is caused by parasympathetic cardiac innervation, the HF component of normal amplitude, observed in only a minority of cardiac transplant recipients (6%), is a marker for parasympathetic reinnervation. The evolution over time of this HF component is compatible with a biological phenomenon as gradual parasympathetic reinnervation of the sinus node.     

Heart Rate Variability in Emergency Department Patients with Sepsis

OBJECTIVE: To test the hypothesis that heart rate variability (HRV) can provide an early indication of illness severity among patients presenting to the emergency department (ED) with sepsis. METHODS: The authors enrolled a convenience sample of 15 ED patients meeting the American College of Chest Physicians/Society of Critical Care Medicine criteria for sepsis. Each patient had continuous Holter monitoring performed in the ED. Acute Physiology and Chronic Health II (APACHE II) and Sequential Organ Failure (SOFA) scores were calculated for the day of presentation. Holter tapes obtained in the ED were analyzed off-line to calculate HRV variables for the 5-minute segment with the least artifact and non-sinus beats. These variables were correlated with APACHE II and SOFA scores. RESULTS: LFnu (normalized low-frequency power), an assessment of the relative sympathetic contribution to overall HRV, was correlated with increased illness severity as calculated using APACHE II (r = -0.67, r(2) = 0.43) and SOFA (r = -0.80, r(2) = 0.64) scores. LF/HF ratio (low-frequency/high-frequency ratio), a measure of sympathovagal balance, was correlated with the SOFA score [r = -0.54 (95% CI = -0.83 to -0.01), r(2) = 0.29]. All five patients who required critical care monitoring or ventilatory support or who died during the first 5 days of their hospitalization had LFnu values below 0.5 and LF/HF ratios less than 1.0. None of the patients with measurements greater than these threshold values died or required these interventions during the five days following admission. CONCLUSIONS: A single variable, LFnu, which reflects sympathetic modulation of heart rate, accounted for 40-60% of the variance in illness severity scores among patients presenting to the ED with sepsis. HRV, as reflected in LFnu and the LF/HF ratio and measured with a single brief (5-minute) period of monitoring while in the ED, may provide the emergency physician with a readily available, noninvasive, early marker of illness severity. The threshold effect of LFnu and LF/HF in the prediction of early clinical deterioration was an unexpected finding and should be regarded as hypothesis-generating, pending further study.     

Exploratory Study of Heart Rate Variability and Sleep among Emergency Medical Services Shift Workers

Objectives: To characterize the continuity and duration of sleep, and to measure nocturnal cardiac autonomic balance via heart rate variability (HRV) in a group of emergency medical technicians (EMTs) on and off duty. Methods: Fourteen EMTs completed an online, daily sleep log that recorded total sleep duration, bedtime, rise time, and the number of alarms that caused awakening. HRV was captured using a physiological status monitor (PSM) affixed to a chest strap during sleep. Results: For the 7-day trial, each of the 14 EMTs logged three work days (WDs) and four non-work days (NWDs). They reported sleeping significantly fewer hours per night on WDs (6.4 ± 2.1) than on NWDs (7.9 ± 0.5; P < 0.05), and experienced more sleep disruptions on WDs (4.4 ± 2.8) than on NWDs (1.3 ± 2.2; P < 0.001) as measured by the number of alarms. Global and vagal indices of HRV during sleep were significantly reduced during WDs (Standard Deviation of Normal R-R Intervals (SDNN) = 43.4 ± 2.0 ms and High Frequency (HF) = 24.3 ± 1.2 ms²) when compared to NWDs (SDNN = 61.1 ± 1.0 ms and HF = 42.7 ± 1.5 ms²; P < 0.001). Conclusion: EMTs who worked 24-hour shifts had shorter, more fragmented sleep associated with greater cumulative exposure to increased sympathetic and decreased parasympathetic activity as measured via sleep HRV. These changes in cardiac autonomic tone constitute one plausible pathway through which sleep deprivation may increase risk for cardiovascular disease.