Twenty-four-hour heart rate variability to assess autonomic function in Parkinson's disease

OBJECTIVES: To evaluate the autonomic dysfunction in Parkinson's disease patients by means of a 24-h heart rate variability (HRV) method. MATERIAL AND METHODS: Thirteen patients with a diagnosis of Parkinson's disease were compared with 13 age-matched healthy persons (control group). The 13 patients had a mean age of 70.5 years, and mean disease duration of 10.9 years. The autonomic function was evaluated by HRV analysis using a continuous 24-h ECG. The parameters of SDNN (standard deviation of the normal-to-normal intervals between adjacent QRS complexes), of LF (power in low frequency) and of HF (power in high frequency) were studied during the following 3 periods: 24 h, night and day. RESULTS: The data show a statistically significant difference between groups for SDNN and LF in all the periods, while for HF parameters the difference is statistically significant only in the night period. CONCLUSION: The use of the 24-h HRV method can provide more accurate and reproducible data than other conventional cardiovascular tests.     

Heart rate variability and autonomic function tests in HIV positive individuals in India

Supine heart rate variability (HRV) and autonomic tests were carried to determine whether autonomic activity was affected in HIV positive patients. The pressor response following handgrip and cold pressor test was blunted in HIV+ patients, and the degree of dysfunction correlated with CD4 cell counts. The extent of autonomic impairment was mild and subclinical.     

癫

目的探讨癫     

癫癎患者发作间期心血管自主神经功能与心率变异性

目的　探讨癫　患者发作间期心血管自主神经功能与心率变异性（ＨＲＶ）的变化。方法　５１例癫　患者根据标准心血管自主神经功能试验结果分为阳性（ＡＮＦＴ＋）组及阴性（ＡＮＦＴ－）组,与正常对照组３６例对比,进行ＨＲＶ分析。结果　癫　患者发作间期心血管自主神经功能异常率为４５．１％,且病程越长异常率越高。癫　患者在ＨＲＶ时域分析及非线性定量分析指标上均较对照组降低,且以　ＡＮＦＴ＋组患者最明显。ＨＲＶ直方图、散点图亦有特征性改变,以ＡＮＦＴ＋组患者最为显著。结论　癫　患者发作间期心血管自主神经功能存在紊乱现象,这种现象可能与癫　患者的猝死发生有关,ＨＲＶ是测定这一变化的敏感方法。     

Standardized tests of heart rate variability: normal ranges obtained from 309 healthy humans, and effects of age, gender, and heart rate

The authors undertook this study to determine the effects of age, gender, and heart rate (HR) on the results of cardiac autonomic function tests for measuring heart rate variability (HRV) in a large sample of healthy subjects (n=309). Conventional tests (deep breathing, maximum/minimum 30∶15 ratio), and a standardized 5-minute resting study, including spectral analysis of HR, were used. The main findings included (1) the indices of all tests, except for the ratio of the low- (LF) to high-frequency (HF) spectral power (LF/HF ratio) and HR itself, are inversely related to age in both sexes; (2) the 5-minute spectral bands (except for the LF/HF ratio), the variation coefficient, expiratory-inspiratory ratio during deep breathing, and the maximum/minimum 30∶15 ratio are independent of HR; (3) women up to the age of 55 years have a higher resting HR compared with men; (4) young and middleaged women show a significantly lower LF power and LF/HF ratio compared with age-matched men, whereas no significant gender differences are observed in the absolute HF power. The authors computed age- and gender-dependent normal values for each of the HRV indices studied here and discuss the clinical consequences arising from gender differences in HRV.     

Relationship between heart rate variability and endothelial function in healthy subjects

In various diseased states reduced cardiac vagal activity is accompanied by impaired endothelial function. Evidence from animal studies indicates interaction between the two systems, but such data from human studies is limited. The aim of this study was to test the hypothesis that cardiac vagal activity and endothelial function are related in healthy individuals. 46 young males were studied. From 10 minute long ECG recordings mean RR-interval and time and frequency domain vagal heart rate variability indices (RMSSD; pNN50 and HF, respectively) were determined. Heart rate variability indices were used to define cardiac vagal activity. Endothelial function was assessed by measuring brachial artery flow mediated dilation. Hyperemic, diastolic shear rate was used to normalize flow mediated dilation. All three vagal heart rate variability indices correlated significantly and positively with flow mediated dilation across subjects, with r values within the range of 0.43-0.52, p<0.01 for all relations. After adjusting for potential confounders, vagal heart rate variability indices remained significantly associated with normalized flow mediated dilation. RR-interval was related to most heart rate variability indices, but was not related to flow mediated dilation. Our data demonstrate that vagal heart rate variability indices are related to flow mediated dilation across healthy male subjects. The results cannot serve as evidence of a causal relationship, but are of interest and render for further investigation into underlying mechanisms.     

Spectral analysis of heart rate in diabetic autonomic neuropathy. A comparison with standard tests of autonomic function

Power spectral analysis of the heart rate was compared with standard tests of autonomic function performed on 15 insulin-dependent diabetic patients with symptoms of autonomic dysfunction. The high-frequency power, low-frequency power, and total power of the heart rate power spectrum measured in the supine position--possible measures of parasympathetic nervous system function--were significant predictors of the expiratory-inspiratory ratio, the beat-to-beat heart rate difference on deep respiration, the standard deviation of the resting heart rate, the 30:15 ratio, and the Valsalva ratio. The change in low-frequency power on moving from the supine to upright position, a possible measure of sympathetic nervous system function, was a modest predictor of the systolic and diastolic blood pressure fall in response to postural change, but a poor predictor of the blood pressure response to isometric exercise and a cold stimulus. This study supports the role of heart rate power spectral analysis as a clinical test of autonomic function in patients with known or suspected autonomic failure.     

Abnormal heart rate variability reflecting autonomic dysfunction in brainstem infarction

Objectives Brainstem infarctions frequently cause disturbances of cardiovascular and other autonomic functions, but the pathophysiologic mechanisms of these prognostically unfavourable complications are not well-known.
Material & methods In order to evaluate the effects of ischemic brainstem infarction on autonomic cardiac regulation, we analyzed the power spectrum of heart rate variability in 15 consecutive patients with brainstem infarction and in 15 age- and sex-matched healthy control subjects. The components of the power spectrum which reflect quantitatively both sympathetic and parasympathetic cardiovascular regulatory functions were measured from 24-hour electrocardiogram in the acute phase and at 1 month and 6 months after the infarction.
Results All the measured components of heart rate variability, i.e. total power (p < 0.01), very-low-frequency power (p < 0.001), low-frequency power (p < 0.01), and high-frequency power (p < 0.05), were significantly lower in the patients with medullary brainstem infarction than in the control subjects in the acute phase of the infarction. By 6 months, these abnormalities had been reversed. On the contrary, heart rate variability in pontine brainstem infarct patients did not differ significantly from that in the control subjects.
Conclusions These results suggest that brainstem infarction located in the medulla oblongata causes cardiovascular autonomic dysregulation manifesting as impaired heart rate variability. Medullary brainstem infarction seems to cause both sympathetic and parasympathetic dysfunction, which may contribute to the occurrence of cardiac complications in stroke.     

A comparison of cardiovascular reflex tests and spectral analysis of heart rate variability in healthy subjects

Determination of whether results of cardiovascular reflex tests and spectral analysis of heart rate variability are age dependent and whether there is correlation between results of both, cardiovascular reflex tests (the Valsalva manoeuvre, deep breathing test, handgrip test, cold face stimulus test, orthostatic test) and spectral analysis of heart rate variability were performed on 83 healthy volunteers of both genders, aged 21 to 70 years. We found that results of all heart rate based tests and results of spectral analysis decreased with aging, while results of blood pressure based tests did not. Parasympathetic activity predominated in younger subjects, while in older subjects sympathetic activity was dominant. Valsalva, deep breathing, and orthostatic ratios correlated with integrals of amplitude spectra in the standing posture and deep breathing and cold face stimulus ratios with integrals of amplitude spectra in the supine posture, whereas blood pressure changes during handgrip and orthostatic test did not correlate with integrals of the amplitude spectra. These findings suggest that tests based on heart rate may be more sensitive than tests based on blood pressure changes. This study supports the use of spectral analysis as an additional clinical test of autonomic nervous system function and stresses the importance of age in the evaluation of the results of autonomic nervous system function testing.     

Clinical significance of the resting heart rate in the assessment of autonomic function by cardiovascular reflex tests

The effect of the resting heart rate on heart rate responses in standard cardiovascular autonomic function tests was studied in a sample of 845 subjects. The responses, which were calculated using instantaneous heart rate changes and R—R interval ratios, were divided into quantiles according to their absolute values. The effect of resting heart rate on each cardiovascular index was studied by linear regression analysis, first in the whole group and then in the group with responses belonging to the lowest quantile. As regards the whole group, eight out of ten indices diminished significantly with increasing resting heart rate. However, no response-attenuating effect of increasing resting heart rate could be found among the responses in the lowest quantile. Since particularly low heart rate responses in cardiovascular reflex testing are of clinical importance when autonomic neuropathy is diagnosed, it can be concluded that the usefulness of standard cardiovascular reflex test based on heart rate changes is not limited by the level of the resting heart rate.     

Evaluation of autonomic nervous system function with spectral analysis of heart rate variability in a case of tetanus

The autonomic nervous system is affected in a wide variety of neurological disorders. Its dysfunction may play an important role in the clinical course and may result in serious complications, such as cardiac arrest. We report a case of tetanus who presented with severe autonomic nervous system dysfunction which was detected by spectral analysis of heart rate variability monitored over 24 h. This is a semi-quantitative method for evaluation of the status of the autonomic nervous system. In the present case, the analysis revealed profoundly decreased activity of both sympathetic and parasympathetic nervous system modulation of cardiac rhythm. The parasympathetic nervous system activity was more severely impaired than that of the sympathetic nervous system. The relative predominance of the sympathetic nervous system in the present case may have resulted in unopposed sympathetic nervous system hyperactivity manifested in this patient by tachycardia and excessive sweating. We further infer that the documented diminished buffering capacity of the autonomic nervous system may have lead to a sudden cardiac arrest in our case. Thus, spectral analysis of heart rate variability is a non-invasive and sensitive method for evaluating the status of the autonomic nervous system of critically ill patients in the hospital setting.     

Threat-induced autonomic dysregulation in panic disorder evidenced by heart rate variability measures

Objective

The objective was to compare autonomic response to threatening stimuli between patients with panic disorder (PD) and healthy volunteers by using 5-min recordings of heart rate variability (HRV).

Methods

Twenty-seven patients with PD and 20 healthy controls were recruited. The first 5-min measurement of HRV was conducted at resting state. HRV measurement during threatening stimuli was conducted while participants were viewing 15 threatening pictures. Spectral analyses measures included high-frequency (HF; 0.15–0.4 HZ) component, low-frequency (LF; 0.04–0.15 Hz) component and LF/HF ratio.

Results

There was no significant HRV difference between the two groups at the resting state. During threatening stimuli, the PD group had significantly higher LF power and LF/HF ratio and significantly lower HF power than the healthy controls (for all, P< .01). A two-way analysis of variance was employed to determine the effect of group (patient and control) and condition (threatening and resting) on all three HRV measures. The analysis showed a significant main effect of group (F= 12.21; P< .01), condition (F= 14.21; P< .001) and interaction effect between group and condition (F= 4.83; P< .05) on LF/HF ratio.

Conclusions

The findings from the present study suggest that patients with PD exhibit a sympathetic predominance when faced with threatening stimuli compared with normal control subjects.     

Spectral analysis of heart rate variability in the assessment of autonomic diabetic neuropathy

We studied heart rate variability in 49 uncomplicated diabetics (27 with insulin therapy; 22 with oral hypoglycemic agents) and in 40 age-matched controls. An automatic autoregressive algorithm was used to compute the power spectral density (PSD) of beat by beat RR variability derived from the surface ECG. The PSD contains two major components (a low frequency approximately 0.1 Hz (LF) and a high frequency, respiratory linked, approximately 0.25 Hz (HF] that provide, respectively, quantitative markers of sympathetic and vagal modulatory activities and of their balance. As compared to controls, in diabetics, besides a reduced RR variance at rest (2722 +/- 300 and 1436 +/- 241 ms2, respectively), we observed during passive tilt an altered response of spectral indices of sympathetic activation and vagal withdrawal, suggestive of a complex modification in the neural control activities. In addition, we compared this approach to the commonly used clinical tests score, and observed that the latter provides overall results similar to those obtained with spectral changes induced by tilt (r = 0.42; P less than 0.01). Of potential clinical importance is that the data obtained with spectral analysis appear more thoroughly quantifiable and do not require the active collaboration of the patients.     

Effects of drugs on the autonomic control of short-term heart rate variability

The autonomic nervous system links the brain and the heart. Efferent links in the neural control of the heart consist of sympathetic and parasympathetic (vagal) fibers innervating the sinus node. Because sympathetic and vagal firing alter spontaneous sinus node depolarization, cardiac rate and rhythm convey information about autonomic influences on the heart. The easy availability of ECG rendered possible the assessment of sinus rhythm as an index of autonomic outflow. The frequency-domain approach uses non-invasive recordings and appears to provide a quantitative evaluation of the autonomic modulation of cardiovascular function. Spectral profiles resulting from vagal or sympathetic blockades at the cardiac (or vascular) level might be used as references to unravel the mechanism of action of the drug under examination. A more comprehensive assessment will be obtained if spectral analysis is used as a complement to existing techniques applied for describing the neurohumoral status of patients (microneurographic recordings, norepinephrine spillover). This review also reports some pitfalls encountered in variability studies.     

Correlation between indexes of autonomic maneuvers and heart rate variability in hemodialysis patients

Purpose

The autonomic maneuvers are simple methods to evaluate autonomic balance, but the association between autonomic maneuvers and heart rate variability (HRV) in hemodialysis patients remains unknown. This study aimed to evaluate the correlation between HRV and respiratory sinus arrhythmia (RSA) and Valsalva maneuver (VM) indexes in hemodialysis patients and to compare two methods for RSA indexes acquisitions.

Methods

Forty-eight volunteers on hemodialysis (66.7 % men) were evaluated by VM, RSA, and 24 h Holter monitoring. At the VM, the Valsalva index (VI) was the variable considered. In the RSA, the ratio and difference between the RR intervals of inspiratory and expiratory phase (E:I and E–I, respectively) were considered by traditional form (average of respiratory cycles) and independent respiratory cycles (E:Iindep and E–Iindep). The HRV indexes evaluated were standard deviation of all normal RR intervals (SDNN), standard deviation of sequential 5-min RR interval means (SDANN), root mean square of the successive differences (rMSSD) and percentage of adjacent RR intervals with difference of duration greater than 50 ms (pNN50).

Results

The SDNN, SDANN showed significant correlation with all classic indexes of RSA (E:I: r = 0.62, 0.55, respectively, E–I: r = 0.64, 0.57, respectively), E:Iindep (r = 0.59, 0.54, respectively), E–Iindep (r = 0.47, 0.43, respectively) and VI (r = 0.42, 0.34, respectively). Significant correlation of rMSSD with E:I (r = 0.37), E–I (r = 0.41) and E:Iindep (r = 0.34) was also observed. There was no association of any variable with pNN50. Have been show high values for all variables of independent cycles method (p < 0.05).

Conclusion

The autonomic maneuvers, especially RSA, are useful methods to evaluate cardiac autonomic function in hemodialysis patients. The acquisition of the RSA index by independent cycles should not be used in this population.

     

Blood pressure and heart rate variability in autonomic disorders: a critical review

Spectral analysis (SA) of blood pressure (BP) and heart rate (HR) fluctuations has been proposed as a unique approach to obtain a deeper insight into cardiovascular regulatory mechanisms in health and disease. A number of studies performed over the last 15 years have shown that autonomic influences are involved in the modulation of fast BP and HR fluctuations (with a period<1 min), particularly at frequencies between 0.2 and 0.4 Hz [high frequency (HF) region or respiratory frequency] and around 0.1 Hz [mid frequency (MF) region]. In patients with secondary or primary autonomic dysfunction, SA of BP and HR signals recorded at rest or during orthostatic challenge in a laboratory environment have shown the occurrence of a reduction in the power of MF and/or HF, BP and HR components. Such a reduction is associated or may even precede the clinical manifestation of autonomic neuropathy. However, the above results collected in standardized laboratory conditions cannot reflect the features of neural cardiovascular control during daily life in ambulant individuals with autonomic failure. To investigate this issue, SA techniques have been applied to 24 h beat-to-beat intra-arterial and non-invasive finger BP recordings obtained in elderly subjects and in pure autonomic failure patients, respectively. In these conditions, HR powers displayed a reduction over a wide range of frequencies (from 0.5 to below 0.01 Hz). Conversely, BP powers underwent a complex rearrangement characterized by a reduction in the power around 0.1 Hz and by an increase in the powers at the respiratory frequency and at frequencies below 0.01 Hz. Dynamic quantification of the sensitivity of the baroreceptor-heart rate reflex by combined analysis of systolic BP and pulse interval (i.e. the interval between consecutive systolic peaks) powers around 0.1 Hz (alpha technique) has shown that in elderly subjects, and even more so in pure autonomic failure patients, baroreflex sensitivity is markedly reduced over the 24 h, and is no longer characterized by its physiological day-night modulation. In conclusion, although in some instances SA of cardiovascular signals may fail to fully reflect the features of autonomic cardiovascular control, the evidence discussed clearly demonstrates that this approach represents a promising tool for a dynamic assessment of the early impairment of neural circulatory control in autonomic failure. This is particularly the case when these analyses are performed on 24 h continuous BP and HR recordings in ambulant subjects.     

Impaired heart rate variability as a marker of cardiovascular autonomic dysfunction in multiple sclerosis

Multiple sclerosis (MS) can cause alterations in autonomic cardiovascular functions. We aimed to investigate the correlation of disease activity and disability with heart rate variability (HRV) of cardiovascular autonomic dysfunction (CAD) demonstrated by 24-h Holter monitorization. Thirty-four patients with clinically active relapsing-remitting MS, age 33.8 +/- 7.6 years, were studied. Twenty healthy volunteers served as controls. The time domain long-term HRV parameters were recorded by a digicorder recorder calculated by ambulatory electrocardiograms. Variabilities in time domain were lower in the MS patients: SDNN (standard deviation of all R-R intervals, p = 0,019), SDANN (standard deviation of the averages of R-R intervals in all 5-minute segments of the entire recordings, p = 0,040), RMSSD (the square root of the mean of the sum of the squares of differences between adjacent R-R intervals, p = 0,026), HRVM (mean of the SDNN in all the 5-minute intervals, p = 0,029), HRVSD (standard deviation of the SDNN in all the 5-minute, p = 0,043). These results suggest that MS causes CAD manifesting as long-term HRV abnormalities. This illness seems to cause a dysfunction in parasympathetic cardiovascular tone. Depressed HRV parameters are independent from the clinicalfindings, but the illness progression partially seems to provoke a decrease in such parameters.     

Cardiovascular autonomic function tests to provide normative data from a healthy older population

We aimed to derive normative data for cardiovascular autonomic function tests (AFT) in an older population using new measures. The AFT were performed in 48 healthy control subjects. The average heart rate (HR) response to deep breathing (DB) (HR_DB), Valsalva ratio (VR), magnitude of the HR and blood pressure (BP) response of different phases of the Valsalva maneuver, BP recovery times (PRT 100 and PRT 50) and HR and BP changes on head-up tilting were calculated. The mean age (±standard deviation) of study participants was 58 ± 14.5 years (range 20–82 years), of whom 29 (60%) were men. The systolic blood pressure (SBP) early phase 2 amplitude showed an inverse relationship with age (p = 0.03). There was a trend for progressive attenuation of SBP late phase 2 amplitude with age (p = 0.09). The systolic BP recovery time was not affected by age, gender or body mass index. We concluded that age has a significant effect on most AFT variables. Age and gender did not influence the systolic BP recovery time; hence, systolic BP recovery time could be useful in the evaluation of adrenergic failure.     

The effect of varenicline on heart rate variability in healthy smokers and nonsmokers

Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist. In this study, we assessed the effects of varenicline on heart rate variability (HRV). Thirty subjects were included in the randomized, double-blind, placebo-controlled, crossover study. Varenicline or placebo was administered in two different testing sessions. Time domain parameters and power spectral analysis of HRV were assessed in the supine position and during handgrip exercise before and after the participants were given placebo or varenicline. Fifteen healthy non-smokers (NS) and fifteen healthy smokers (S) were included in the study. There were no statistically significant differences among any of the time domain parameters obtained before and after placebo administration or between the S and NS groups with respect to varenicline administration. In frequency domain analyses, normalized HF (high-frequency) powers were significantly higher in the S group than in the NS group (before placebo, NS:6.57±3.58 vs. S:13.85±7.50, p=0.002, after placebo, NS:6.33±3.89 vs. S:10.82±4.88, p=0.007). After varenicline administration, the normalized HF power was significantly higher (NS:6.65±4.34 vs. S:11.06±4.52, p=0.01), and the ratio of LF (low-frequency) to HF was significantly lower (NS:8.44±5.89 vs. S:4.97±4.60, p=0.02) in the S group than in the NS group. Administration of a single dose of varenicline significantly increased the LF/HF ratio (5.83±2.69 vs. 8.44±5.89) in the NS group, but in the S group, there were no significant differences related to any of the time or frequency domain parameters. We concluded that a single dose of varenicline does not affect HRV in healthy smokers but that it may alter HRV when administered at a therapeutic dose to healthy non-smokers during mild sympathetic stimulation.     

Enhancement of heart rate variability by cholinergic stimulation with pyridostigmine in healthy subjects

The purpose of this study was to determine the effect of the oral administration of pyridostigmine bromide on indices of heart rate variability (HRV) in healthy young volunteers. Seventeen healthy participants (11 men, 6 women; aged 27 +/- 8 y) submitted to a randomized, crossover, double-blind protocol, in which they received 30 mg pyridostigmine bromide (PYR) or placebo orally at 8-hour intervals for 24 hours, on two separate days. Venous blood samples were collected 2 and 24 hours after the first dose for determination of serum cholinesterase activity. Holter tapes were recorded during the 24-hour period and analyzed using a semiautomatic technique to evaluate time- and frequency-domain indices of HRV and to build three-dimensional return maps for later quantification. Symptoms were mild and occurred similarly during administration of PYR and placebo (p = 0.140). Serum cholinesterase activity was reduced by 15% at 2 hours (p = 0.013) and by 14% at 24 hours (p = 0.010) after the first dose of PYR, but not after administration of placebo. Pyridostigmine administration caused a significant increase in the mean 24-hour R-R interval (placebo: 814 +/- 20 msec; PYR: 844 +/- 18 msec; p = 0.003) and in time-domain indices of HRV, such as the standard deviation of all R-R intervals (SDNN; placebo: 151 +/- 9 msec; PYR: 164 +/- 9 msec; p = 0.017), and the percentage of pairs of adjacent R-R intervals differing by more than 50 msec (pNN50; placebo: 12.8 +/- 1.8%; PYR: 13.9 +/- 1.5%; p = 0.029). Pyridostigmine had no significant effect on frequency-domain indices of HRV, but resulted in significant increase in P2, a parasympathetic index derived from the three-dimensional return map (placebo: 93 +/- 13 msec; PYR: 98 +/- 13 ms; p = 0.029). In conclusion, low-dose pyridostigmine reduced mean heart rate and increased HRV during a 24-hour period in healthy young subjects.