Autonomic response to cardiac dysfunction in chronic heart failure: a risk predictor based on autonomic information flow

Background: Chronic heart failure (CHF) is associated with a complex dysfunction of cardiac, cardiovascular, autonomic, and other mechanisms. Autonomic information flow (AIF) characteristics calculated from heart rate patterns were recently found as promising predictors of outcome in several cardiovascular diseases.
Aim: To assess the prognostic value of AIF indices in CHF patients.
Methods: We analyzed 24-hour Holter recordings from 200 consecutive CHF patients in sinus rhythm and computed AIF over the shortest possible interval of an interbeat series, namely over one heart beat interval (BDnn), and over longer intervals (12.5–166.7 seconds, PDmVLF), which reflect slower heart rate modulations. End-point for survival analysis over three years (Cox model) was total cardiac death. A prognostic model was built (backward elimination) considering known clinical and functional risk factors, and the ability of AIF indices to add prognostic information to this model assessed.
Results: Out of candidate predictors, New York Heart Association class, left ventricular ejection fraction, peak VO_2, and systolic pressure were selected as the variables with the highest joint predictive value. When entered into this model, both BDnn and PDmVLF added prognostic information (HR (95%CI): 1.76 (1.00–3.09), P = 0.05, 1.73 (1.05–2.85), P = 0.031 respectively). High risk was associated with reduced fast AIF and increased slower AIF.
Conclusion: In CHF patients, AIF indices provide prognostic information independent of known risk factors.     

Derangement of heart rate variability during a catastrophic earthquake: a possible mechanism for increased heart attacks

At 1:47 AM on September 21, 1999, the middle part of Taiwan was struck by a major earthquake measuring 7.3 on the Richter scale. It has been shown that the mental stress caused by an earthquake could lead to a short- or long-term increase in frequency of cardiac death probably through activation of the sympathetic nervous system. The aim of this study was to investigate the effects of emotional stress on the autonomic system during an actual earthquake. Fifteen patients receiving a 24-hour Holter ECG study starting from 10+/-4 hours before the onset of the earthquake were included for the analysis of time- and frequency-domains of heart rate variability (HRV) at several time periods. A 24-hour Holter study recorded 2-6 months before the earthquake in 30 age- and sex-matched subjects served as the control group. Heart rate and the low frequency (LF) to high frequency (HF) ratio increased significantly after the earthquake and were attributed mainly to the withdrawal of the high frequency component (parasympathetic activity) of HRV. Sympathetic activation was blunted in elderly subjects > 60 years old. The concomitant ST-T depression observed in the Holter study correlated with a higher increment of LF as compared to HF components. The changes observed in HRV recovered completely 40 minutes following the earthquake. The derangement of HRV results from the withdrawal of the parasympathetic component and the arousal of sympathetic activity by the stressful earthquake. However, this autonomic derangement returned towards normal 40 minutes following the earthquake.     

冠心病患者心率变异性分析

目的了解冠心病（CHD）患者的心率变异性（HRV）特点,探讨CHD患者自主神经变化的临床意义。方法测定93例CHD患者和49例健康对照者24h心率变异性的时域指标,并进行比较分析。结果CHD组24hHRV指标水平明显低于健康对照组（P〈0．01）,差异有统计学意义。结论CHD患者HRV降低提示心血管自主神经系统功能受损害。     

Day-to-day variability of cardiac autonomic regulation parameters in normal subjects

Summary. We examined the reproducibility of day-to-day variability in cardiovascular autonomic nervous function parameters (classical clinical tests and domain analysis of heart rate variability) in four healthy men during a period of 1 working week. The results did not show any significant difference in any of the parameters over the five repeated measurements. The maximum-minimum difference as percentage of the mean was under 15% for expiration to inspiration (E/I) ratio, Valsalva ratio, tachycardia ratio, 30/15 ratio, acceleration index and brake index; about 45% for baroreflex sensitivity for systolic and diastolic blood pressure and for root mean square difference (RMSSD) of successive R-R intervals; about 65–85% for low and high frequency bands, total power and medium to high frequency ratio; and about 125% for medium frequency band. The intraclass correlation coefficient (ICC) values showed that the agreement for classical autonomic parameters (except for brake index) was good. ICC for RMSSD, baroreflex sensitivity for systolic blood pressure and the spectral estimates of heart rate variation were less good. Coefficient of variation (CV) was 4% for E/I ratio, 2% for 30/15 ratio, 6% for Valsalva, 3% for tachycardia ratio, 4% for acceleration index and 5% for brake index. CV for baroreflex sensitivity and for RMSSD was about 20%. It is concluded that the variation in baroreflex sensitivity is clearly larger than in the classical autonomic nervous function parameters. One-minute fixed pace breathing period seems to be too short to allow reproducible measurement of RMSSD and the spectral parameters of heart rate variation. Learning effect could be excluded.     

康复运动对冠心病患者心脏自主神经功能的影响

摘要 目的：探讨有氧运动对冠心病患者心脏自主神经功能的影响。 方法：18例女性冠心病患者（实验组）,14例女性非冠心病患者（对照组）为本研究的受试者,在康复程序前、后,对她们进行了运动前（安静时）和运动后的心率变异性（HRV）指标的测定,其中包括极低频功率（VLF）、低频功率（LF）、高频功率（HF）、总功率（TP）和低高频比值（LF/HF）。 结果：①与对照组相比,实验组康复程序前安静时VLF、LF、HF和TP均显著降低,而LF/HF显著增高（P＜0.01）,运动后也有相似的趋势。②与康复程序前相比,12周心脏康复程序后,实验组安静时VLF、LF、HF和TP均有显著增高,LF/HF有所降低（P＜0.01和P＜0.05）;运动后HF显著增高,LF/HF显著降低（P＜0.05）。③与安静时相比,康复程序前实验组递增负荷运动后心率变异性指标均无显著性改变;康复程序后实验组递增负荷运动后VLF、LF、TP和LF/HF均有显著降低（P＜0.01和P＜0.05）;对照组递增负荷运动后VLF、LF、HF和TP均有显著降低（P＜0.01和P＜0.05）,LF/HF有显著增高（P＜0.01）。 结论：12周运动心脏康复程序不仅可以提高冠心病患者安静时自主神经的调节功能,而且对改善一次急性运动后自主神经的均衡性也有积极作用。     

吸烟对老年男性冠心病患者自主神经功能康复的影响

目的:探索吸烟对老年冠心病患者自主神经功能康复的影响。方法:33例男性冠心病患者,根据吸烟情况分为吸烟组、不吸烟组,为了能针对吸烟对冠心病患者自主神经功能影响进行定量的分析,本研究又进一步根据吸烟的数量将吸烟组分为轻度亚组(≤20支/日)和重度亚组(20支/日)[1]。在心脏康复程序前后对他们进行了运动前(安静时)和递增负荷运动实验后(运动后)的心率变异性(HRV)指标以及辅助指标的测定,其中包括低频功率(LF)、高频功率(HF)、低高频功率比值(LF/HF)、总功率(TP)、心肌缺血(ST段)和心率收缩压双乘积(RPP)。结果:1康复程序前安静时两组患者间的LF、HF、LF/HF、TP、ST段、RPP未显示出显著性差异;2康复程序前运动后两组患者LF、LF/HF、RPP有升高的趋势,HF、TP、ST段有降低的趋势;3康复程序后安静时,与康复前相比两组患者HF和TP有显著性增高(P0.05,P0.01),但吸烟组HF、TP的改善程度小于不吸烟组,二者间有显著性差异(P0.05),吸烟组的重度亚组HF、TP的改善小于轻度亚组,亚组间有显著性差异(P0.05);4康复程序后运动后,与康复前相比两组患者HF有显著性增高(P0.05,P0.01),ST段降低显著减少(P0.05),LF/HF、RPP有显著性下降(P0.05,P0.01),吸烟组HF、RPP的改善程度小于不吸烟组,二者间有显著性差异(P0.05),吸烟组的亚组间HF有显著性差异(P0.05)。结论:12周运动心脏康复能提高冠心病患者自主神经的调节功能,但是吸烟将降低心脏自主神经功能的恢复效果。     

Autonomic dysfunction in HIV patients on antiretroviral therapy: studies of heart rate variability

BACKGROUND: The presence of autonomic dysfunction in HIV patients is largely unknown. Early studies found autonomic dysfunction in patients with AIDS. Introduction of highly active antiretroviral combination therapy (ART) has dramatically changed the course of the disease and improved prognosis and decreased morbidity. At present it is not known whether introduction of ART also has decreased autonomic dysfunction. AIM: To evaluate whether autonomic dysfunction is present in an ART-treated HIV population. METHODS: HIV patients receiving ART for at least 3 years (n = 16) and an age-matched control group of healthy volunteers (n = 12) were included. All were non-smokers, non-diabetic and had never received medication for dyslipidaemia or hypertension. Following a 10 min resting period a 5 min ECG recording was performed. Heart rate variability (HRV) analysis was performed in accordance with current guidelines and data reported as median (interquartile range). RESULTS: The resting heart rate was higher in HIV patients compared with controls [69 (62-74) versus 57 (52-60); P<0.001]. Total HRV measured as standard deviation of normal-to-normal (SONN) was lower in the HIV group compared with the controls [36 (25-55) versus 74 (57-84) ms; P<0.01] as was parasympathetic activity measured as square root of the mean squared difference of successive normal-to-normal intervals (RMSSD) [22 (9-30) versus 35 (24-62) ms; P<0.05]. Low frequency power was lower in the HIV group compared with the control group [294 (161-602) versus 946 (711-1668) ms(2); P<0.01]. High frequency power as well as systolic and diastolic blood pressure did not differ between the groups. CONCLUSIONS: The HIV patients in ART have increased resting heart rate and decreased short-term heart rate variability indicating parasympathetic dysfunction.     

Heart rate recovery: a practical clinical indicator of abnormal cardiac autonomic function

The autonomic nervous system (ANS) and cardiovascular function are intricately and closely related. One of the most frequently used diagnostic and prognostic tools for evaluating cardiovascular function is the exercise stress test. Exercise is associated with increased sympathetic and decreased parasympathetic activity and the period of recovery after maximum exercise is characterized by a combination of sympathetic withdrawal and parasympathetic reactivation, which are the two main arms of the ANS. Heart rate recovery after graded exercise is one of the commonly used techniques that reflects autonomic activity and predicts cardiovascular events and mortality, not only in cardiovascular system disorders, but also in various systemic disorders. In this article, the definition, applications and protocols of heart rate recovery and its value in various diseases, in addition to exercise physiology, the ANS and their relationship, will be discussed.     

Chronotropic incompetence response to exercise in congestive heart failure,relationship with the cardiac autonomic status

In chronic congestive heart failure (CHF), attenuated heart rate response to exercise, a manifestation of chronotropic incompetence (CI), contributes to limiting exercise capacity. The present study was thus conducted to evaluate the respective role of chronic attenuation of cardiac vagal tone associated with depressed baroreflex sensitivity or affected cardiac sympathetic responsiveness in CHF patients with CI. Spontaneous cardiac baroreflex sensitivity (BRS) assessed by sequence method and spectral‐ and time‐domain analysis of heart rate variability (HRV) were analysed in 21 chronic CHF patients. All patients performed a symptom‐limited exercise test with measurement of gas exchange. Chronic incompetence which was defined as failure to achieve ≥80% of the heart rate reserve (%HRR) given by (HR_peak – HR_rest)/(predictive maximal heart rate – HR_rest) was observed in 14 (66%) patients. There was no significant difference in age, heart rate, peak oxygen uptake or left ventricular ejection fraction between the patients with and without CI. Although there was no significant difference in BRS, low frequency power of HRV in normalized units (LFnu) and SDNN were significantly lower in CI patients. Percentage of HRR correlated significantly with LFnu on 15 min (r=0·64, P<0·005) and, with LFnu on 24 h (r=0·52, P<0·01), SDNN (r=0·48, P=0·03) and SDANN (r=0·48, P=0·03), but not BRS (r=0·04, P=NS). Autonomic nervous system derangement is a complex process in CHF. The role of basal depressed cardiac sympathetic tone seems to contribute more closely than depressed baroreflex sensitivity to the impaired heart rate response to exercise frequently observed in CHF patients.     

Taichiquan acutely increases heart rate variability

A group of 15 elderly men and 14 young male students of physical education made twice a series of Taichiquan (TCQ) practices. Their electrocardiograms were recorded on tape-recorder and heart rates and heart rate variability (HRV) were calculated from digitized data. Here we report the results of recordings in supine positions before and after the first and second series of TCQ. Intervals between heart beats (RRIs) and their standard deviation (SDNN) increased in older men from recordings before the exercise to postexercise. In young subjects the SDNN and total variance (TV) of RRIs increased. HRV increases immediately after TCQ-exercise in young and old male healthy subjects. Whether these practices have permanent effects and effects in patients need controlled and prospective studies.     

Heart Rate Variability: Its Association with Hemodynamic Function of the Left Ventricle in Patients with Coronary Heart Disease

Patients with heart failure secondary to coronary heart disease (CHD) are characterized by an imbalance of the autonomic nervous system, which can be assessed by analysis of the heart rate variability (HRV). However it is still unclear whether all patients with CHD reveal suppression of HRV and if it is related to hemodynamic function and contractile disturbances of the left ventricle. To answer these questions data from 105 consecutive patients were analyzed and compared with 17 healthy subjects. All study participants underwent 24-hour ambulatory ECG recordings with calculation of HRV parameters and angiographic examination after collection of clinical data and other noninvasive evaluations. Time- (SDRR, SDANN, SD, pNN50) and frequency- (LF, HF) domain parameters of HRV were assessed. All ventriculographic and hemodynamic measurements were used in the analysis. Highly significant correlations were found between all HRV parameters, and left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (P < 0.001). Patients with LVEF < 40% were characterized by significantly lower values of HRV and impairment or lack (LVEF < 20%) of diurnal variation of frequency-domain measurements of HRV. Patients with segmental akinesis or dyskinesis also had lower values of HRV. The group with dyskinesis was characterized by significantly lower diurnal rhythms of LF and HF, independent of LVEF.     

Effect of diabetes mellitus on heart rate variability in patients with congestive heart failure

This study sought to determine if the severity of autonomic perturbations in patients with heart failure are affected by the presence of diabetes. Decreased HRV is frequent in diabetic patients free of clinically apparent heart disease and has been invoked as a risk factor for sudden cardiac death. However, reduced HRV is also commonly present in patients with left ventricular dysfunction. The effect of diabetes on autonomic dysfunction in this setting is not known. Holter ECGs from 69 diabetic patients and 85 nondiabetic control subjects with heart failure were analyzed. The severity of autonomic dysfunction was assessed using 24-hour time- and frequency-domain HRV analysis. Prognostically important time- and frequency-domain HRV measures (SDNN, SDANN5, total power, and ultra-low frequency power) were not different between the two groups. Time- and frequency-domain parameters modulated by parasympathetic tone (pNN50, RMSSD, and HF power) were depressed to a similar degree in the diabetic and the nondiabetic groups. The low frequency power was significantly lower in diabetic patients (5.8 +/- 0.7 vs 5.3 +/- 1.0, P = 0.02). The ratio of low to high frequency power was substantially lower in the diabetic group (2.2 +/- 0.2 vs 1.4 +/- 0.2, P < 0.0001). These differences were more apparent in insulin-treated diabetics. In the presence of heart failure, HRV parameters that are most predictive of adverse outcome are similar in diabetic and nondiabetic patients. Furthermore, during increased sympathetic stimulation in the setting of heart failure, diabetes does not worsen parasympathetic withdrawal but may mitigate sympathetic activation.     

12周运动康复对冠心病患者心脏变时性功能和心率恢复值的影响

目的:探讨12周运动康复对冠心病患者心脏变时性功能和心率恢复值(HRR1)的影响。方法:对30例男性冠心病患者进行递增负荷运动试验,根据实验结果将其分为两组,变时性功能正常组(G1,n=19,HRR%≥0.8);变时性功能不全组(G2,n=11,HRR%0.8),并测定受试者运动前、运动中和运动后心率(HR)、摄氧量(VO2)、ST段下降数值和血压。12周运动康复后再次进行递增负荷运动实验,对患者的运动能力和上述指标进行测定分析。结果:与康复程序前相比,12周康复程序后,G1和G2组的VO2peak、HRR1均有显著增加(G1,8%,P0.01;G2,4%,P0.05)、(G1,18.6±3.3—23.8±4.5,P0.01;G2,12.8±4.2—13.7±3.5,P0.05),而G1比G2提高的更加明显。ST段降低显著改善(G1,-0.7±0.5—-0.2±0.5,P0.05;G2,-0.9±0.5—-0.3±0.6,P0.05)。HRR%有显著增加(G1,84.2±2.5—88.9±6.1,P0.05;G2,60.2±8.3—75.8±3.8,P0.05)。结论:12周运动康复可以改善冠心病患者(包括变时性功能正常者和变时性功能不全者)的运动能力,提高冠心病患者运动时自主神经的调节功能,上述积极作用对变时性功能正常者的体现则更为明显。     

Diabetic cardiovascular autonomic neuropathy: clinical implications

Diabetic cardiovascular autonomic neuropathy (DCAN), the impairment of the autonomic balance of the cardiovascular system in the setting of diabetes mellitus (DM), is frequently observed in both Type 1 and 2 DM, has detrimental effects on the quality of life and portends increased mortality. Clinical manifestations include: resting heart rate disorders, exercise intolerance, intraoperative cardiovascular lability, orthostatic alterations in heart rate and blood pressure, QT-interval prolongation, abnormal diurnal and nocturnal blood pressure variation, silent myocardial ischemia and diabetic cardiomyopathy. Clinical tests for autonomic nervous system evaluation, heart rate variability analysis, autonomic innervation imaging techniques, microneurography and baroreflex analysis are the main diagnostic tools for DCAN detection. Aldose reductase inhibitors and antioxidants may be helpful in DCAN therapy, but a regular, more generalized and multifactorial approach should be adopted with inclusion of lifestyle modifications, strict glycemic control and treatment of concomitant traditional cardiovascular risk factors, in order to achieve the best therapeutic results. In the present review, the authors provide aspects of DCAN pathophysiology, clinical presentation, diagnosis and an algorithm regarding the evaluation and management of DCAN in DM patients.     

Parasympathetic dysfunction in hypertrophic cardiomyopathy assessed by heart rate variability: comparison between short-term and 24-h measurements

In this study, we evaluate cardiac autonomic function in hypertrophic cardiomyopathy (HCM) by assessing heart rate variability (HRV), comparing a short-term laboratory method with an ambulatory (24-h) method, in patients with and without beta-blockade. Reduced HRV is a risk factor for adverse events in some cardiac diseases, but is not a proven risk indicator in HCM. Analysis of HRV has been based on either short- or long-term electrocardiographic recordings and previous studies in HCM have shown conflicting results. There is no consensus on which method to prefer, and we evaluate, for the first time, both short- and long-term analyses in patients with HCM. Long- and short-term HRV analyses were performed in 43 patients with HCM. They were divided in two groups, 22 patients on beta-blockade and 21 non-treated patients. As controls, 121 healthy subjects were used. Young patients without beta-blockade showed a reduction in HRV parameters reflecting parasympathetic function, both in the short- and long-term registrations, which was attenuated by beta-blockade. Parasympathetic autonomic regulation was found to be impaired in young patients with HCM. This may be of clinical relevance as abnormal autonomic function might be a substrate for malignant dysrhythmias. The impairment was attenuated by beta-blockade, which might indicate a clinically useful effect. We also show that short- and long-term methods yield similar results, suggesting that a short-term registration might be sufficient to assess HRV in patients with HCM.     

Reproducibility of abnormal heart rate variability indices: the case of hypertensive sleep apnoea syndrome

Before heart rate variability can be used as an investigational tool in the clinical setting, its reproducibility must be known. We studied heart rate variability four times during 44 weeks in 15 hypertensive patients with sleep apnoea syndrome. Time and frequency domain analytical approaches were used during the spontaneous and controlled breathing tests, orthostatic manoeuvre and the cold pressor test. Alterations in resting heart rate were taken into account using the coefficient of component variance. In general, the response of heart rate variability was abnormal and variability was reduced in the hypertensive patients with sleep apnoea syndrome compared with reference data. Time domain measures of heart rate variability demonstrated generally better reproducibility over four recordings than frequency domain measures in these hypertensive patients with sleep apnoea syndrome. On the other hand, the reproducibility of frequency domain measures depended on the specific conditions: during orthostatic manoeuvre and cold pressor test the best reproducibility was found using normalized units. In the reference data set, there were no significant differences between the two heart rate variability recordings during any of the autonomic nervous function tests. In this follow-up study we found that simple procedures such as the controlled breathing test show good reproducibility. More complex tests such as the orthostatic manoeuvre require special attention in order to obtain acceptable reproducibility of heart rate variability measurements. Quantitatively minor changes in the variability indices when the overall variability is reduced exert major effects on the results. Therefore we suggest that reproducibility data obtained in healthy volunteers are not valid for the interpretation of data in patients with damaged cardiovascular autonomic control.     

Effects of one-lung ventilation on cardiac autonomic nervous activity as evaluated by power spectral analysis of heart rate variability

The purpose of this prospective study was to evaluate the effects ofone-lung ventilation on the activity of the cardiac autonomic nervous system.Ten adult patients who underwent thoracotomy were endotracheally intubatedwith a double-lumen tube under general anesthesia using isoflurane. Afterinduction of anesthesia, a continuous, 256-sec electrocardiogram (ECG) wasobtained during bilateral lung ventilation (control) followed by recordingsduring one-lung ventilation of each side. Using the R–R intervaltachograms obtained for the 256-sec ECGs, low frequency (LF: 0.04–0.15Hz) and high frequency (HF: 0.15–0.40 Hz) bands of the spectral densityof the heart rate variability and the HF/LF ratio were analyzed using the fastFourier transform algorithm. Log(HF), which indicates parasympatheticactivity, increased during one-lung ventilation on each side, but did notdiffer between ventilated sides. Log(LF), which represents sympathetic andparasympathetic activity, increased similarly to log(HF) on both sides.Log(HF/LF), the balance of the sympathetic and parasympathetic activity, didnot change during one-lung ventilation. We suggest that one-lung ventilationalone does not substantially affect the cardiac autonomic nervous system.     

On- and off-responses of heart rate to exercise - relations to heart rate variability

During physical exercise, heart rate (HR) increases by parasympathetic withdrawal and increase of sympathetic activity to the heart. HR variability (HRV) in time and frequency domains provides information about autonomic control of the cardiovascular system. Non-linear analysis using the Poincaré plot method is able to reveal supplementary information about cardiac autonomic control. The aim of this study was to determine the association between HRV parameters, the initial increase of HR at the onset of exercise (on-response) and HR decrease in the recovery phase after acute exercise (off-response). HR was continuously monitored in 17 healthy male subjects (mean age: 20.3 +/- 0.2 (SEM) years) at rest (25 min supine; 5 min standing), during exercise (8 min of step test at 70% of maximal power output) and in the recovery phase (30 min supine). HRV analysis in time and frequency domains and evaluation of the Poincaré plot measures (length, widths) were performed on selected segments of HR time series. HR on- and off-responses were quantified using an exponential curve fitting technique. The time constants T(on) and T(off), representing the rate of on- and off-responses to exercise, were computed. Postexercise HRV indices and time constant of on-response - T(on) - to exercise were negatively correlated. From preexercise HRV indices, only Poincaré plot parameters were correlated with T(on). No correlation between HRV indices and parameters of off-response was found. In conclusion, preexercise HRV parameters are not closely correlated with the rate of cardioacceleration at the onset of exercise and cannot predict the rate of HR recovery. On the other hand, postexercise HRV parameters are related to the rate of initial adjustment of HR to exercise referring to the importance of rapid HR on-response for a faster recovery after exercise.