Repeatability of heart rate variability measures

Due to the sparse data on the repeatability of short and ultra-short term heart rate variability (HRV) measures, we measured the repeatability of common HRV measures derived from 10-second, 2-minute, and 6-minute recordings in 63 healthy men and women, aged 45-64, in Chapel Hill, North Carolina. Three 10-second and 2 six-minute heart rate recordings were obtained during each of 2 visits, separated by 1 to 2 weeks. We partitioned the measurement error into components and computed intraclass correlation coefficients using nested, random effects models. Repeatability improved with the length of recording: intraclass correlation coefficients were greater than 0.7 for 6-minute measures and 2-minute time domain measures and greater than 0.5 for 2-minute frequency domain measures. Repeatability of measures from 10-second records was lower, but improved considerably when the mean from 2 or 3 records was used. Correlations between the same measures from different length recordings were quite high. Our findings support the use of records of at least 5 minutes in length in epidemiological studies, in accordance with previous guidelines. Researchers using 10-second records should consider taking the mean of several recordings, when possible, or using statistical methods to correct for measurement error.     

Nitric oxide enhances the inotropic response to β-adrenergic stimulation in the isolated guinea-pig heart

Nitric oxide (NO) exerts several effects on myocardial contraction, including enhancement of relaxation and diastolic function, modulation of β-adrenergic inotropic responses, and inotropic effects in the absence of agonist pre-stimulation. Different effects have been observed in different species and preparations, and it is unclear whether they are species- or preparation-specific, or whether they represent a range of responses that can manifest in most mammalian species. We therefore examined the effects of NO on the inotropic response to β-adrenergic stimulation in the isolated guinea-pig heart, a species in which we have previously shown that NO enhances basal left ventricular (LV) relaxation and modulates the Frank-Starling response. Isolated ejecting hearts were perfused with Krebs buffer at constant paced heart rate (1 μM indomethacin, 37°C, constant loading conditions), and high fidelity LV pressure was monitored by an apical 2F Millar catheter. All hearts were initially treated with dobutamine (0.1 μM) and then, once the peak inotropic and chronotropic response had been established, with either (a) no further treatment (n=6), (b) the NO donor sodium nitroprusside (1 μM, n=6; 10 μM, n=6), or (c) the specific agonist for NO release, substance P (0.1 μM, n=6). Dobutamine (0.1 μM) produced a rapid positive inotropic and chronotropic response, associated with a fall in LV end-diastolic pressure (LVEDP) and a rise in coronary flow. The positive inotropic effect of dobutamine declined over 20–28 minutes, while the chronotropic response persisted over this period. Low dose sodium nitroprusside (1 μM) delayed the decline in the inotropic response to dobutamine and exaggerated the fall in LVEDP. Similar effects were observed with substance P (0.1 μM). In contrast, a higher dose of sodium nitroprusside (10 μM) did not alter the response to dobutamine. These data indicate that “low dose” NO augments the inotropic response to β-adrenergic stimulation in the isolated ejecting guinea-pig heart, in addition to its previously reported effects on basal LV relaxation in the same preparation. Received: 3 September 1997, Returned for revision: 30 September 1997, Revision received: 16 December 1997, Accepted: 19 January 1998     

慢性阻塞性肺部疾病的心率变异性分析

为探讨慢性阻塞性肺部疾病与心率变异性的关系,对２４例慢性阻塞性肺部疾病和２４例对照组进行心率变异性分析,并观察其与第ｌｓ用力呼气量的相关性。结果显示：慢性阻塞性肺部疾病患者的ＳＤＮＮ、ＳＤＡＮＮ、ＳＤＮＮＩｎｄｅｘ、ｒＭＳＳＤ、ＰＮＮ５０均明显低于对照组（Ｐ〈０．００５）,且第ｌｓ用力呼气量与上述时域指标呈高度正相关（ｒ＝０．６１～０．８９,Ｐ〈０．０１）。提示心率变异时域指标反映慢性阻塞性肺部疾     

Aging,heart rate variability and patterns of autonomic regulation of the heart

ObjectivesTo evaluate the effects of aging, gender and body mass index on the heart rate variability (HRV), and to compare the patterns of global autonomic regulation (GAR) and parasympathetic outflow (PO) throughout the aging process.Design, setting and participants: cross-sectionalLarge sample of community-based adults and elderly people. Individuals aged from 40 to 100 years, functionally independent and with satisfactory cognitive function defined as the self-capacity to interact with an interviewer (N = 1743).Material and methodsThe study enrolled individuals of both genders, stratified into five age-groups. We did adjustments for hypertension, dyslipidemia and non-insulin-dependent diabetes, as well as the body mass index (BMI). All groups undertook long-term electrocardiograms and five time-domain HRV parameters were measured, three (SDNN, SDANN, SDNN-index) reflecting the GAR and two (rMSSD and pNN50) the PO.ResultsSDNN, SDANN and SDNN-index decreased linearly with age and BMI, and women had lower values than men (p < 0.001). There was a U-shaped pattern of rMSSD and pNN50, with the nadir between 60 and 69 years for both genders, and women had higher values than men (p < 0.001). The lowest levels of all HRV variables were found in diabetics (p < 0.001). There was no influence of hypertension or dyslipidemia.ConclusionsThe GAR decreased linearly with the age in both genders. It is comparatively lower in women, diabetics and overweight individuals. The PO presented the U-shape in both genders with the nadir at the 7th decade. It was also comparatively lower in men and diabetics. Hypertension and dyslipidemia imparted no significant influence.     

Low frequency spectral component of heart rate variability and myocardial beta-adrenoceptor density after acute myocardial infarction

Objective The low frequency spectral component (LF; 0.04–0.15 Hz) of heart rate variability (HRV) is considered to be an index of sympathetic modulation of sinus node activity under physiological conditions, although the relationship is less clearly defined in non-physiological conditions. Several cardiovascular diseases are characterized by an absent or blunted 24-h pattern of the LF spectral component. The aim of the present study was to investigate the relationship between chronically increased neural sympathetic efferent drive to the heart, quantified in terms of downregulation of myocardial β-receptors, and the 24-h power of the LF spectral component in patients after acute myocardial infarction. Methods In 24 patients, HRV was analyzed for a 24-h period, one month after an uncomplicated Q wave myocardial infarction. The following time domain measures and spectral components were calculated: mean RR, SDNN, SDANN, RMSSD, SDNN index, pNN50, and very low frequency (VLF), low frequency (LF) and high frequency (HF) spectral components. The density of β-adrenoceptors was measured in vivo by positron emission tomography (PET) with ¹¹C-CGP-12177. Results Post-AMI patients had normal plasma levels of adrenaline and noradrenaline (respectively 1.48 ± 0.18 and 0.28 ± 0.03 IU/L) but reduced myocardial β-adrenoceptor density (6.86 ± 0.24 pmol/g). Patients had similar heart rates but lower values of SDNN and SDANN compared with control subjects. The absolute and normalized power of the spectral components were similar in the two groups, but the usual day-night oscillation was blunted in patients. Moreover, the day-night change in the power of the LF spectral component was positively related (r = 0.51; p < 0.001) to the myocardial β-adrenoceptor density. Conclusions The loss of the day-night oscillation of the LF spectral component appears to be a significant marker of sustained sympathetic over-activity in post-AMI patients. Received: 6 June 2001, Returned for revision: 26 June 2001, Revision received: 8 August 2001, Accepted: 28 August 2001     

Different methods of heart rate variability analysis reveal different correlations of heart rate variability spectrum with average heart rate

Heart rate variability (HRV) spectrum can be calculated from the R-R or the sequence of instantaneous heart rates (IHRs). Because these signals are reciprocal, their use in the determination of the correlation of HRV with average HR may yield opposite results. AIM: The aim of this study is to reveal how HRV parameters correlate with HR depending on the kind of signal used and whether the normalization procedure or use of corrected signals affect the correlations. METHODS: Electrocardiographic recordings (512 beats) of 55 patients were considered in the analysis. RR and IHRs were calculated. Both signals were divided by their average values yielding the corrected RR and IHR. Heart rate variability spectra were estimated from these 4 kinds of signals. Total power (TP), low frequency (LF) and high frequency (HF) components, LF/HF ratio, and normalized values (ie, nLF, nHF) were calculated. RESULTS: Total power and LF estimated from RR correlated negatively with HR, but those calculated from IHR revealed a trend toward a positive correlation (respective correlation coefficients significantly differed, P < .01). The sign of correlation between HF and HR was the same regardless of the type of signal applied. The application of corrected signals made the results almost identical despite different signal origins (RR or IHR). The correlations of LF/HF, nLF, and nHF with HR were similar in all cases. CONCLUSIONS: The type of signal determines the sign of correlation among TP, LF, and HR. The parameters obtained from corrected signals, normalized quantities, and LF/HF reveal a consistent relationship with HR.     

室性心律失常患者的心率变异性分析

为研究自主神经系统活动在室性心律失常发生中的作用,分析３５例正常人（对照组）、３４例无器质性心脏病室性心律失常者（无心脏病组）及３５例器质性心脏病室性心律失常者（心脏病组）的心率变异性。结果显示（１）与对照组比较,无心脏病组ＳＤＮＮ、ＰＮＮ５０、ＲＭＳＳＤ、ＨＲＶＴＩ显著降低（Ｐ〈０．０５～０．０１）,ＳＤＡＮＮ、ＳＤＮＮＩｎｄｅｘ无显著差异（Ｐ〉０．０５）;而心脏病组各项指标均非常显著降低（Ｐ〈     

Interleukin-6 levels are inversely correlated with heart rate variability in patients with decompensated heart failure

INTRODUCTION: Increased local and systemic elaboration of cytokines have an important role in the pathogenesis of congestive heart failure (CHF) through diverse mechanisms. Because cytokines are known to act at the neuronal level in both the peripheral and central nervous system, we sought to determine whether increased cytokine levels are associated with the autonomic dysfunction that characterizes CHF. METHODS AND RESULTS: We studied 64 patients admitted for decompensated CHF (mean age 59+/-12 years). Autonomic function was assessed using time- and frequency-domain heart rate variability (HRV) measures, obtained from 24-hour Holter recordings. In addition, norepinephrine, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured in all patients. TNF-alpha levels did not correlate with any of the HRV measures. IL-6 inversely correlated with the time-domain parameters of standard deviation of RR intervals (SDNN) (r = -0.36, P = 0.004) and standard deviation of all 5-minute mean RR intervals (SDANN) (r = -0.39, P = 0.001), and with the frequency-domain parameters of total power (TP) (r = -0.37, P = 0.003) and ultralow-frequency (ULF) power (r = -0.43, P = 0.001). No correlation was found between IL-6 and indices of parasympathetic modulation. Using multiple linear regression models, adjusting for clinical variables and drug therapies, the strong inverse relationship between IL-6 and SDNN (P = 0.006), SDANN (P = 0.001), TP (P = 0.04), and ULF power (P = 0.0007) persisted. CONCLUSION: Reduction of long-term HRV indices is associated with increased levels of IL-6 in patients with decompensated heart failure. The ability of long-term HRV parameters to better reflect activation of diverse hormonal systems may explain their greater prognostic power for risk stratification in patients with CHF.     

Determinants of heart rate variability in heart transplanted subjects during physical exercise

Respiratory sinus arrhythmia has been described in heart transplantedsubjects. In order to investigate the mecha nisms involved inthe generation of this condition in the transplanted heart andits evolution after surgery, graded exercise was performed (0–75W in 25 W steps) on a cycle ergometer by 41 subjects (mean age44 years) who had undergone heart transplantation 28 months(range 3–60) earlier and by six age matched-control subjects.R-R interval, respiratory signal, O₂ consumption (VO₂ and CO₂production (VCO were measured. Respiratory sinus arrhythmiawas assessed by the autoregressive power spectrum of the R-Rinterval and respiration. All subjects reached the anaerobicthreshold (heart transplants: 60% at 50 W, 40% at 75W Controls:150 W). In control subjects, the respiratory sinus arrhythmiawas higher than in heart transplanted subjects (5·80± 0·30 vs 1·45 ± 0·16 lnms²) and it decreased significantly (4·66 ± 0·30In ms² P<0·05) during exercise, despite the increasein breathing rate and depth. When the group of heart transplantedsubjects was considered as a whole, respiratory sinus arrhythmiawas found to be present in all conditions. It significantlyincreased at 25 W (from 1·45 ± 0·16 to2·00 ± 0·17 In ms² P<0·01), thensignificantly fell below baseline during recovery (to 0·97± 0·23 In ms P<0·01). Multiple regressionanalysis showed that a linear combination of heart rate (inversecorrelation) and VO² (direct correlation) together with monthshaving passed since transplantation surgery, could explain theobserved changes in heart rate during exercise (multiple regression:r=0·658, P<0·0001). In five long-term transplantedsubjects, non respiratory-related low frequency (0·1Hz) waves were present on the R-R spectrum, but respiratorysinus arrhythmia is also present in the recently transplantedheart and depends on the opposing effects of ventilation andheart rate. In a few cases, sympathetic modulation (re-innervation)could not be excluded. (Eur Heart J 1996; 17: 462–471)     

No Evidence of Cardiac Autonomic Involvement in Ankylosing Spondylitis, as Assessed by Heart Rate Variability

The aim of this study was to investigate the involvement of autonomic nervous system (ANS) function by using power spectral analysis of heart rate variability (HRV) method in patients with ankylosing spondylitis (AS). The study included 94 AS patients all fulfilling the New York criteria for AS, and 49 healthy volunteers. Recordings for HRV were obtained with a PC-based high-resolution electrocardiographic system and analysed using power spectral analysis. The peak around 0.04–0.15 Hz was defined as low-frequency peak (LF) and the other, around 0.15–0.40 Hz, was defined as high-frequency peak (HF), representing mostly the sympathetic and the parasympathetic components of the ANS, respectively. The following variables were calculated and compared between groups: the LF in absolute and normalised units (LF nU); the HF in absolute and normalised units (HF nU); and LF/HF ratio. The AS group included 47 male and 47 female subjects with a mean age of 33 ± 11 years (range 16–64). In the control group there were 23 male and 26 female healthy subjects (mean age 33 ± 8; range 19–60). None of the patients or control subjects had any cardiac or neurological symptoms. Both groups were similar with respect to age and sex characteristics (p >0.05). The HRV analysis indicated that the peaks of LF, LF nU, HF, HF nU and LF/HF ratio were similar in both groups. Groups also did not differ with respect to heart rate at the time of examination. Our data demonstrated no evidence of ANS involvement as assessed by HRV analysis in AS patients. Received: 19 July 2000 / Accepted: 25 October 2000     

健康儿童心率变异性长程时域指标的

目的探讨健康儿童心率变异性(HRV)长程时域指标的特点。方法对266例健康儿童HRV24小时长程时域指标（SCL、SDNN、SDNNindex、SDANN、RMSSD、三角指数）进行不同年龄、性别及与成人正常参考值间进行分析比较。结果①儿童不同性别组间HRV差异无显著性;②儿童不同年龄组间虽心动周期（或心率）存在差异,但HRV差异无显著性;③儿童组与成人正常参考值中SDNN、SDANN、RMSSD存在有差异显著性,RMSSD在儿童中明显高于成人组。结论SDANN、SDNNindex是反映交感神经功能的敏感指标,而RMSSD更能反映迷走神经功能,可见儿童的自主神经功能较成人活跃,而随着年龄的增长即自主神经功能的减退,尤其是迷走神经的紧张性抑制功能明显减退。     

Heart rate variability as a predictor of mortality in patients with AA and AL amyloidosis.

AIMS: Patients with AA and AL amyloidosis have a limited life-expectancy. The aim of this study was to investigate whether heart rate variability can predict mortality in these patients. METHODS AND RESULTS: Twenty-two recently diagnosed patients with AA and 23 patients with AL amyloidosis were included. Fifteen patients (5 AA, 10 AL) died within 1 year. Twenty-four hour Holter recording was performed to quantify the mean of all normal to normal RR-intervals (mean NN) and the standard deviation of all normal to normal RR-intervals (SDNN). The SDNN predicted 1-year mortality in the total group of patients with amyloidosis. The median SDNN was 73 ms. In patients with an SDNN < or =73 ms, the risk of dying within 1 year was found to have increased 3.5-fold (P=0.0036; 95% CI 1.1-11.0). An SDNN < or =50 ms, a predictor of mortality in other patient groups, increased the risk of dying within 1 year 22-fold (P=0.0001; 95% CI 5.4-90.4). In contrast to patients with AA amyloidosis, in the subgroup analysis of patients with AL amyloidosis the SDNN remained a predictive parameter (SDNN < or =50 ms: risk ratio 11.5, 95% CI 2.4-56.2, P=0.0025). CONCLUSION: The SDNN is a strong predictor of short-term mortality in patients with AL amyloidosis.     

心率和心率变异性用于评定颈部手法刺激对自主神经系统的影响

目的应用心率和心率变异性分析,评定颈部手法刺激对自主神经系统的影响。方法选择正常青年男性志愿者,对受试者进行颈部手法刺激,刺激前和刺激后各记录5min动态心电图,以心率和心率变异性作为观测指标,判断颈部手法刺激对自主神经系统的影响。结果对30名正常青年男性志愿者观察发现,颈部手法刺激后,心率显著降低(RR间期延长);时域分析中SDNN有显著性增加,频域分析中VLF和总功力谱有显著性增加。结论心率和心率变异性是一项评定颈部手法刺激对自主神经系统效应的有用指标。     

The inotropic response of the isolated,perfused, working rat heart to norepinephrine is attenuated by inhibition of nitric oxide

Experiments on isolated, perfused, working left ventricular (LV) hearts of 66 female Wistar rats were done to examine whether nitric oxide (NO) influences the effects of norepinephrine (NE) on coronary flow as well as on contraction and relaxation. Functional parameters were monitored before and after application of NE at a concentration of 3 × 10⁻⁸ M in the absence and presence of the nitric oxide synthase (NOS) inhibitor L-nitro-arginine (L-NA) at a concentration of 1 × 10⁻⁴ M and of the spontaneous NO donor sodium (Z)-1-(N,N-diethylamino) diazen-1-ium-1,2-diolat (DEA/NO) at a concentration of 1 × 10⁻⁷ M. In control experiments, heart rate was varied by electrical stimulation between 200 and 400 beats/min. Within this range of heart rates, coronary flow and cardiac output remained constant, while stroke volume, LV peak pressure and LV dP/dt_max decreased with increasing heart rate. NE increased coronary flow from 7.6 ± 0.4 to 9.8 ± 0.7 ml/min and induced the well-known positive chronotropic and inotropic effects. DEA/NO increased coronary flow; however, the inotropic and lusitropic parameters were not affected. Simultaneous infusion of NE with DEA/NO further increased coronary flow from 9.8 ± 0.7 to 12.1 ± 0.8 ml/min without a significant effect on any other functional parameter. When NOS was inhibited by L-NA, the positive inotropic effect of NE was attenuated. Cardiac output, however, was increased, while coronary flow did not change significantly. Under these conditions, NE increased dP/dt_max by 65.5 ± 5.8% (from 2999 ± 97 to 4929 ± 230 mmHg/s) compared with an increase by 92.8 ± 6.7% (from 3770 ± 82 to 7234 ± 211 mmHg/s) under control conditions. Application of DEA/NO reversed the attenuated inotropic response, but relaxation remained partially impaired. Thus, the presence of NO seems to be necessary for the inotropic effect of NE to become manifest. Received: 9 February 2001, Returned for 1. revision: 22 February 2001, 1. Revision received: 25 May 2001, Returned for 2. revision: 12 June 2001, 2. Revision received: 20 July 2001, Returned for 3. revision: 2 August 2001, Accepted: 20 August 2001     

Analysis of nonlinear heart rate dynamics in cardiac arrhythmias

Summary Analysis of heart rate dynamics by methods based on nonlinear dynamics has opened a new approach for studying the abnormalities in heart rate behavior as a predictor of cardiac arrhythmias. Recent studies have shown that the new nonlinear measures, particularly fractal analysis methods of heart rate dynamics, perform better than traditional analysis methods as a predictor of sudden cardiac death in post-infarction populations. Altered short-term fractal properties of heart rate dynamics have also been shown to precede the onset of ventricular tachyarrhythmias. Reduced approximate entropy, a measure of complexity of heart rate variability has been observed to precede the spontaneous onset of atrial fibrillation. These findings support the notion that some nonlinear methods, such as fractal and complexity measures, give important new information for the prediction of the onset of cardiac arrhythmias.?   This article provides a review of our current knowledge of the usefulness of newer dynamic measures of heart rate fluctuation both in risk stratification and as predictors of spontaneous onset of cardiac arrhythmias. Received: 3 April 2000/Accepted: 15 May 2000     

冠心病心肌缺血发作前后心脏自主神经功能的变化

为了解冠心病慢性心肌缺缺血发生前后心脏自主神经变化情况，采用频域法对比分析３０例冠心病和６０例正常对照组和心率变异性变化，及冠心病心肌缺血前后心率变异的变化。结果冠心病组全频和主频面积显著降低，低频面积明显增高，低频／高频比值极显著增高；心肌缺血发作前低频，低频／高频显著增高，而高频降低。     

Changes in heart rate variability during concentration meditation

This study aims at investigating changes in heart rate variability (HRV) measured during meditation. The statistical and spectral measures of HRV from the RR intervals were analyzed. Results indicate that meditation may have different effects on health depending on frequency of the resonant peak that each meditator can achieve. The possible effects may concern resetting baroreflex sensitivity, increasing the parasympathetic tone, and improving efficiency of gas exchange in the lung.     

支气管哮喘患者心率变异性的观察

目的 观察支气管哮喘患者心率变异性,以了解其自主神经功能的变化。方法 对69例年轻男性急性发作期支气管哮喘患者（哮喘组,轻度、中度和重度各23例）和23名健康对照者（对照组）作前瞻性对照研究,记录支气管哮喘患者和健康对照者的24h动态心电图,作时域和频域分析。结果 反映迷走神经张力的高频（HF）和相邻心搏的R－R间期之差＞50ms的心搏数（NN50）计数占总R－R间期的百分比（pNN50）,支气管哮喘患者与对照组比较,差异有显著性（P＜0.01）;而主要反映交感神经张力的低频（LF）、每5min正常R－R间期标准差的平均值（SDANN）,支气管哮喘患者与健康对照组比较,差异也有显著性（P＜0.01）,且重度支气管哮喘患者的变化更为显著。结论 支气哮喘患者在非急性发作期可能存在自主神经功能的障碍。     

Improvements in heart rate variability with exercise therapy

Heart rate variability (HRV) is a noninvasive, practical and reproducible measure of autonomic nervous system function. A heart rate that is variable and responsive to demands is believed to bestow a survival advantage, whereas reduced HRV may be associated with poorer cardiovascular health and outcomes. In recent years, many researchers have investigated the prognostic implications of HRV in a variety of clinical populations. Evidence suggests that reduced HRV has prognostic significance for individuals with myocardial infarction, chronic heart failure, unstable angina and diabetes mellitus. Interventions to increase HRV, such as exercise therapy, have also been examined. The findings of the present review suggest that exercise therapy may improve HRV in myocardial infarction, chronic heart failure and revascularization patients by increasing vagal tone and decreasing sympathetic activity. One hypothesis is that a shift toward greater vagal modulation may positively affect the prognosis of these individuals. While the underlying mechanisms by which exercise training improves vagal modulation are speculative at present, angiotensin II and nitric oxide may be potential mediators.