Standard Deviation Of All Normal RR Intervals Research Articles

Mental stress inhibits pain perception and heart rate variability but not a nociceptive withdrawal reflex.

Do distraction from- or attention to sural nerve stimulation affect pain, heart rate variability, and a spinal withdrawal reflex? In 26 male volunteers, electrical stimulation at the distal cutaneous receptive field of the sural nerve elicited pain and a nociceptive withdrawal reflex. Intensity of pain was rated on a numeric rating scale. Electromyographic reflex responses were measured from biceps femoris muscle. Cardiac autonomic function was estimated by heart rate variability measures and was expressed in the time domain as mean of RR-intervals for normal heart beats (mean-RR) and standard deviation of all normal RR-intervals (SD-NN) and, in the frequency domain, where pure vagal activity was assessed by high frequency power (0.15-0.4 Hz). Low frequency power (0.04-0.15 Hz) reflects both parasympathetic and sympathetic control. Effect parameters were recorded before and during random distraction and attention. Distraction from sural nerve stimulation was induced by a mental arithmetic test, paced auditory serial addition task (PASAT), while attention was induced by concentrating on painful foot stimulation. Paced auditory serial addition task decreased mean-RR and SD-NN, frequency domain parameters, as well as pain (P<0.001). In contrast, PASAT did not change the spinal withdrawal reflex. Attention did not affect any effect parameter. Distraction by PASAT altered autonomic activity and inhibited pain but failed to affect withdrawal reflex responses, while attention had no effect on either parameter. Psychological distraction and attention may have different effects on noxious evoked pain perception and autonomic activity. Pain relief during PASAT probably involves supraspinal mechanisms.

Lower heart rate variability is associated with the development of coronary heart disease in individuals with diabetes: the atherosclerosis risk in communities (ARIC) study.

The objective of this study was to test prospectively in a population sample whether individuals with impaired heart rate variability (HRV) are at increased risk of developing coronary heart disease (CHD) and of non-CHD mortality and to test whether this relationship is more pronounced among individuals with diabetes. We examined the association between HRV and incident CHD and non-CHD mortality in a cohort of 11,654 men and women aged 45-64 years at intake, from the biracial, population-based Atherosclerosis Risk in Communities Study. Supine, resting, 2-min beat-to-beat heart rate data were collected at the baseline examination. High frequency (HF; 0.15-0.40 Hz) and low frequency (LF; 0.04-0.15 Hz) spectral powers, LF/HF ratio, normalized HF and LF, the standard deviation of all normal R-R intervals (SDNN), and the mean of the sum of the squared differences between adjacent normal R-R intervals (MSSD) were used as the conventional indexes of HRV to measure cardiac autonomic control. From this cohort, 635 cases of incident CHD (including 346 cases of incident myocardial infarction [MI] and 82 cases of fatal CHD), and 623 non-CHD deaths were identified and validated after an average of 8 years of follow-up. Among individuals with diabetes, the multivariable adjusted proportional hazards ratios (95% CI) were 2.03 (1.28-3.23), 1.60 (1.12-2.27), 1.50 (0.65-3.42), and 1.27 (0.84-1.91) for incident MI, incident CHD, fatal CHD, and non-CHD deaths, respectively, comparing the lowest quartile to the upper most three quartiles of HF. A similar pattern of associations was found for LF, SDNN, and MSSD. By contrast, there was no consistent pattern of associations among individuals without diabetes. At the population level, a lower HRV (reflective of impaired cardiac autonomic control) is statistically significantly related to the development of CHD among individuals with diabetes, independent of markers of the duration/severity of the glucose metabolism impairment. These data suggest a contribution of an impaired cardiac autonomic control to the risk of CHD among individuals with diabetes.

Prognostic Value of Heart Rate Variability Analysis in Patients with Carcinoid Syndrome

Background/Aims: Recently, a decrease in heart rate variability measures was found in patients with carcinoid syndrome suffering from carcinoid heart disease compared to those without cardiac involvement of carcinoid syndrome. The prognostic relevance of this finding, however, was not clear. Patients and Methods: Therefore, 35 patients with carcinoid syndrome (21 men, age 56 ± 11 years), all of them suffering from metastatic carcinoid tumors, were followed prospectively at our institution. Digital 24-hour Holter monitoring, echocardiography, and serum serotonin and urine 5-hydroxyindole acetic acid (5-HIAA) samplings were performed in all study patients at baseline. Indices of time domain heart rate variability obtained from Holter recordings included the standard deviation of all normal RR intervals (SDNN) representing overall variability, the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD), and the percentage of the number of pairs of adjacent normal RR intervals differing by >50 ms (pNN50), both indices reflecting predominantly vagal influences on heart rate. Results: During a mean follow-up of 18 ± 7 months, 15 of 35 patients with carcinoid syndrome (43%) died. Patients with cardiac manifestation of the carcinoid syndrome showed a tendency towards an increased mortality in comparison to patients without cardiac involvement (p = 0.09). Patients with the combination of decreased heart rate variability (SDNN <100 ms) and presence of carcinoid heart disease had a significant worse prognosis (p = 0.04) compared to patients without carcinoid heart disease and preserved heart rate variability (SDNN ≧100 ms). Conclusions: The presence of carcinoid heart disease in combination with decreased heart rate variability is associated with the most adverse prognosis in the setting of carcinoid syndrome.

Decreased autonomic nervous system activity as assessed by heart rate variability in patients with chronic tetraplegia

Wang Y-H, Huang T-S, Lin J-L, Hwang J-J, Chan H-L, Lai J-S, Tseng Y-Z. Decreased autonomic nervous system activity as assessed by heart rate variability in patients with chronic tetraplegia. Arch Phys Med Rehabil 2000;81:1181-4. Objectives: To assess the alterations of autonomic nervous functions and sympathovagal balance of the subjects with spinal cord injuries (SCIs) in different levels by heart rate variability analysis. Design: Prospective, observational study. Setting: All participants were recruited from the outpatient clinic from National Taiwan University Hospital, which is a tertiary referral center. Participants: Thirty-one patients with traumatic chronic complete SCI (more than 6 months): 14 with paraplegia (Group A), and 17 with tetraplegia (Group B). Main Outcome Measures: Heart rate variability assessed by 24-hour Holter monitoring. Results: Two patients in Group A and 1 in Group B were excluded from final data analysis because of poor recording data. Two time domain variables, the standard deviation (SD) of all normal RR intervals (SDNN) and the mean of the SDs of all normal RR intervals for all 5-minute intervals (SDNNi), over 24 hours were decreased in Group B. All time domain variables, SDNN, SDNNi, root mean square of the successive normal RR interval difference (rMSSD), and the percentage of RR intervals differing >50msec from the preceding one (pNN50), were decreased during the nighttime recordings (all p <.05) in Group B. The very-low-frequency, low-frequency (LF), and high-frequency (HF) components of the power spectrum of the RR intervals were also decreased in Group B (p <.05), irrespective of the daytime and nighttime recordings. The LF-to-HF ratio did not differ significantly in these two groups, indicating the maintained sympathovagal balance in the chronic SCI patients. Conclusion: These findings suggested that the autonomic nervous system activity was depressed in the patients with chronic tetraplegia, but the autonomic nervous system still maintained homeostasis. © 2000 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Correlation between cardiac autonomic activity and compromise of left ventricular function in dilated cardiomyopathy

In recent years, evaluation of cardiac autonomic activity by means of heart rate variability (HRV) determination and baroreflex sensitivity (BRS) testing has become readily available. The results of the ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) study showed that both diminished HRV and baro-reflex sensitivity are associated with poor outcome in patients after myocardial infarction. In contrast to patients with coronary disease little information is available concerning cardiac autonomic activity in idiopathic dilated cardiomyopathy (IDC). Therefore, HRV and BRS were assessed in 160 patients with IDC and preserved sinus rhythm in order to investigate the relationship between HRV, BRS, and left ventricular ejection fraction. Time domain indices of HRV were computed from 24-hour digital Holter recordings. BRS testing was performed using the noninvasive phenylephrine method. Mean standard deviation of all normal RR intervals (SDNN) of the whole study population was 112 +/- 46 ms. A well preserved HRV (SDNN > 105 ms) was found in 74 patients (46%), a moderately decreased HRV (SDNN 70-105 ms) in 59 patients (37%), and a severely decreased HRV (SDNN < 70 ms) in 27 patients (17%). Mean BRS was 7.5 +/- 5.0 ms/mm Hg. A well preserved BRS (> 6 ms/mm Hg) was present in 78 patients (57%), a moderately decreased BRS (3-6 ms/mm Hg) was present in 38 patients (28%), and a severely decreased BRS (< 3 ms/mm Hg) in 21 patients (15%). There was only a weak correlation between SDNN and BRS (r = 0.19; p < 0.05). A weak correlation was found for SDNN and left ventricular ejection fraction (r = 0.29; p < 0.05). There was no significant correlation between BRS and left ventricular ejection fraction (r = 0.14). In summary, there was only a weak correlation between the HRV, BRS, and left ventricular ejection fraction in patients with IDC suggesting that these 3 variables may be independent predictors of sudden death in IDC. The relative prognostic value of these variables and other potential risk predictors including the presence of arrhythmias on Holter, microvolt T wave alternans, QTc dispersion, and signal-averaged ECG is currently under investigation in a large prospective observational study (Marburg Cardiomyopathy Study (MACAS)) during 5-year follow-up at our institution.

Cardiac autonomic tone and its relation to nonsustained ventricular tachyarrhythmias in idiopathic dilated cardiomyopathy.

In contrast to postinfarct patients, little is known about cardiac autonomic tone and its relation to spontaneous ventricular tachyarrhythmias in idiopathic dilated cardiomyopathy (IDC). Both heart rate variability (HRV) and baroreflex sensitivity (BRS) are indices of autonomic innervation of the heart. The aim of the present study was to determine the relation between cardiac autonomic tone assessed by HRV and BRS and spontaneous nonsustained ventricular tachycardia (NSVT) on Holter in a large patient population with IDC. 24-h digital Holter recordings including HRV analysis and BRS testing were prospectively performed in 137 patients with IDC and preserved sinus rhythm. Mean age was 48 +/- 12 years, and mean left ventricular (LV) ejection fraction was 32 +/- 9%. The HRV analysis on Holter included the mean RR interval (RRm), the standard deviation of all normal RR intervals (SDNN), the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD), and the proportion of adjacent normal RR intervals differing more than 50 ms (pNN50). Testing for BRS was performed noninvasively using the phenylephrine method. Of 137 study patients, 42 (31%) had spontaneous NSVT on 24-h Holter. Compared with patients without NSVT, patients with NSVT on Holter had a higher New York Heart Association (NYHA) functional class (NYHA III: 40 vs. 18%, p < 0.01), a lower ejection fraction (29 +/- 9 vs. 34 +/- 9%, p = 0.01), and an increased LV end-diastolic diameter (69 +/- 8 mm vs. 66 +/- 7 mm, p = 0.03). The HRV variables rMSSD, pNN50, RRm, and BRS did not differ significantly between patients with and without spontaneous NSVT. Only SDNN on Holter was slightly lower in patients with versus without NSVT (106 +/- 45 vs. 121 +/- 46 ms, p = 0.08). Patients with IDC and spontaneous NSVT on Holter are characterized by a higher NYHA functional class, a lower LV ejection fraction, an increased LV end-diastolic diameter, and a tendency toward a lower SDNN value compared with patients without NSVT. The remaining measures of HRV including rMSSD and pNN50 reflecting primarily tonic vagal activity, as well as BRS reflecting predominantly reflex vagal activity, were similar in patients with and without NSVT. The prognostic significance of these findings in patients with IDC is currently under investigation in the Marburg Cardiomyopathy Study (MACAS) at our institution.

Prospective evaluation of effect of carvedilol therapy on heart rate variability in patients with dilated cardiomyopathy

The aim of the present study was to assess the effects of carvedilol therapy in addition to conventional heart failure therapy on heart rate variability (HRV) and on left ventricular function in 14 patients with mild to moderate heart failure due to idiopathic dilated cardiomyopathy (IDC). After a 3- to 4-week titration period, carvedilol was titrated up to 50mg daily, or the highest dose tolerated (at least 25mg daily). Maintenance treatment was then continued for 8 weeks. Digital 24-hour Holter recordings were obtained at baseline and after 8 weeks of carvedilol therapy. HRV for the entire 24-hour period was computed in the time domain using the Oxford Medilog Excel 2 analysis system. Measures of HRV included the mean of all coupling intervals between normal beats (RRm), the standard deviation of all normal RR intervals (SDNN), the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD), and the proportion of adjacent normal RR intervals differing >50 ms (pNN50). Additional treatment with carvedilol induced a significant increase in HRV: SDNN increased from 77+/-21 ms to 110+/-22 ms (p=0.001), rMSSD from 19+/-7 ms to 26+/-7 ms (p=0.02), and mean pNN50-value increased from 1.7+/-1.3% to 5.5+/-4.5% (p<0.01) under therapy with carvedilol. Mean heart rate on carvedilol calculated over 24 hours was 13 beats less than at baseline (75 bpm versus 88 bpm, p<0.01). After 2 months of additional treatment with carvedilol, both hemodynamic and clinical parameters improved: left ventricular ejection fraction increased from 24+/-7% to 30+/-10% (p<0.05), and New York Heart Association class decreased from 2.5+/-0.8 to 1.8+/-0.7 (p<0.05). In summary, eight weeks of additional carvedilol therapy induced a significant increase in HRV parameters related to parasympathetic activity in patients with IDC. Whether increased vagal tone may contribute to the protective effect of carvedilol has to be evaluated by further studies.

Heart rate variability in obesity and the effect of weight loss

To investigate the effects of obesity and weight loss on cardiovascular autonomic function, we examined 28 obese patients referred for weight-reducing gastroplasty, 24 obese patients who received dietary recommendations, and 28 lean subjects. Body weight, blood pressure, and 24-hour urinary norepinephrine excretion were measured, and time and frequency domain indexes of heart rate variability (HRV) were obtained from 24-hour Holter recordings. A measure of long-term HRV, the SD of all normal RR intervals (SDANN), was used as an index of sympathetic activity and the high-frequency (HF) component of the frequency domain, reflecting short-term HRV, as an estimate of vagal activity. All 3 study groups were investigated at baseline, and the 2 obese groups were reexamined at 1-year follow-up. Obese patients had higher blood pressure, higher urinary norepinephrine excretion, and attenuated SDANN and HF values than lean subjects (p <0.01). Obese patients treated with surgery had a mean weight loss of 32 kg (28%), whereas the obese group treated with dietary recommendations remained weight stable (p <0.001). At follow-up the weight-loss group displayed decreases in blood pressure and norepinephrine excretion and showed increments in SDANN and HF values. These changes were significantly greater than those observed in the obese control group (p <0.05). Our findings suggest that obese patients have increased sympathetic activity and a withdrawal of vagal activity and that these autonomic disturbances improve after weight loss.

Multiple metabolic syndrome is associated with lower heart rate variability. The Atherosclerosis Risk in Communities Study.

To test at the population level whether people with multiple metabolic syndrome (MMS) disorders have reduced cardiac autonomic activity (CAA). We examined the association between the level of CAA and MMS disorders, at the degree of clustering and the segregate combination levels, using a random sample of 2,359 men and women aged 45-64 years from the biracial, population-based Atherosclerosis Risk in Communities (ARIC) Study. Supine resting 2-min beat-to-beat heart rate data were collected. High-frequency (HF) (0.15-0.35 Hz) and low-frequency (LF) (0.025-0.15 Hz) spectral powers, the ratio of LF to HF, and the SD of all normal R-R intervals (SDNN) were used as the conventional indices of heart rate variability (HRV) to measure CAA. The MMS disorders included hypertension, type 2 diabetes, and dyslipidemia. HRV indices were significantly lower in individuals with MMS disorders. The multivariable adjusted mean HF was 0.85 (beat/min)2 in subjects with all three MMS disorders, in contrast to 1.31 (beat/min)2 in subjects without any MMS disorder. At the segregated combination level, the multivariable adjusted means +/- SEM of HF were 1.34 +/- 0.05, 1.16 +/- 0.05, 1.01 +/- 0.17, and 1.34 +/- 0.05 (beat/min)2, respectively, for subjects without any MMS disorder, with hypertension only, with diabetes only, and with dyslipidemia only, and the means +/- SEM of HF were 0.93 +/- 0.04, 0.70 +/- 0.15, and 1.20 +/- 0.05 (beat/min)2, respectively, for subjects with diabetes and hypertension, diabetes and dyslipidemia, and hypertension and dyslipidemia. An increase in fasting insulin of 1 SD was associated with 88% higher odds of having a lower HF. The pattern of associations was similar for LF and SDNN. These findings suggest that MMS disorders adversely affect cardiac autonomic control and a reduced cardiac autonomic control may contribute to the increased risk of subsequent cardiovascular events in individuals who exhibit MMS disorders.

Sympathetic inhibition with clonidine improves autonomic balance in congestive heart failure

In this double-blind, placebo-controlled crossover study, we examined the effect of transdermal clonidine (given for 5 days) on autonomic control in 14 patients with mild to moderate congestive heart failure by heart rate variability analysis. Compared with placebo, clonidine increased the 24-h mean R-R interval from 718±110 to 811±117 ms ( P<0.01), increased the S.D. of all normal RR intervals (SDNN) from 60.8±18.5 to 80.9±21.4 ms ( P<0.01), the S.D. of the average RR intervals for all 5-min segments (SDANN) from 54.7±15.2 to 70.5±18.4 ms ( P<0.01) and the mean of the S.D.s of all RR intervals for all 5-min segments (SDNN index) from 29.2±8.3 to 36.5±8.1 ms ( P<0.01). The root mean square successive differences (r-MSSD) and the percent of differences between adjacent RR intervals >50 ms (pNN50) were also increased from 18.3±6.7 to 23.1±7.0 ms ( P<0.01) and from 2.1±1.9 to 4.5±3.0% ( P<0.01). In addition, total power, low frequency power and high frequency power were increased from 641±322 to 898±403 ms 2/Hz ( P<0.01), from 149±97 to 216±133 ms 2/Hz ( P<0.01) and from 52.8±27.1 to 93.2±41.3 ms 2/Hz ( P<0.01), respectively. The plasma norepinephrine level was decreased significantly from 0.52±0.18 to 0.24±0.09 ng/ml ( P<0.01) after clonidine therapy. Changes in heart rate variability measures after clonidine administration were positively related to changes in plasma norepinephrine level. These results indicate that suppressing the sympathetic nervous system by clonidine improves autonomic balance in patients with congestive heart failure. But whether such restoration of the autonomic control has a beneficial effect on the long-term management of these patients still needs further investigation.

Association of cardiac automatic function and the development of hypertension: The ARIC study

To relate cardiac autonomic function measured by heart rate variability (HRV) with prevalent and incident hypertension at the population level, the authors examined a stratified random sample of 2,061 examinees from the biracial Atherosclerosis Risk in Communities (ARIC) cohort. Baseline, supine, resting beat-to-beat heart rate data were collected. High frequency (HF, 0.15 to 0.35 Hz), low frequency (LF, 0.025 to 0.15 Hz) spectral powers, and LF/HF ratio, estimated from spectral analysis, and standard deviation of all normal RR intervals (SDNN), calculated from time domain analysis, were used as the conventional indices of cardiac autonomic function. From this sample, 650 prevalent hypertensives were identified. Of those normotensive at baseline (n = 1,338), 64 participants developed hypertension during 3 years of follow-up. In the cross-sectional analysis, the adjusted geometric means of HF were 1.26, 1.20, and 1.00 (beat/min)2 for normotensives, untreated hypertensives, and treated hypertensives, respectively; means of LF were 3.24, 3.26, and 2.58; means of LF/HF ratio were 2.57, 2.70, and 2.56; and means of SDNN were 39, 34, and 35 (ms) respectively. In the prospective analysis, a statistically significant, graded inverse association between baseline HF and the risk of incident hypertension was observed: the adjusted incident odds ratios (95% CI) were 1.00, 1.46 (0.61, 3.46), 1.50 (0.65, 3.50) and 2.44 (1.15, 5.20) from the highest to the lowest quartile of HF. No clear pattern of association was observed for LF. Significant trends of association for LF/HF and SDNN and incident hypertension were also found. These results suggest that cardiac autonomic function is associated with prevalent hypertension, and that reduced vagal function and the imbalance of sympatho-vagal function are associated with the risk of developing hypertension.

Heart period variability in patients with variant angina

To clarify how cardiac autonomic control is affected in variant angina, we analyzed heart period variability in 35 patients with variant angina and in 19 control subjects. Patients with variant angina were divided into 1 — vessel (group S, n = 17) and multivessel spasm groups (group M, n = 18) according to the site(s) of ST elevation on the electrocardiogram during attacks. The 24-hour Holter electrocardiogram recorded 6 ± 3 days after the treatment with calcium antagonist was analyzed to avoid the possible influence of spontaneous attacks. In 5 group M patients, the electrocardiogram recorded 1 month after the treatment was also analyzed. There was no difference in the number of spontaneous attacks between groups S and M. The standard deviation of all normal RR intervals (SDNN) and the percentage of differences between adjacent normal RR intervals > 50 (pNN50) in variant angina were slightly but significantly lower than those in controls. There were no differences in other indexes between variant angina and controls. When the data were analyzed separately in groups S and M, averaged RR intervals (MN), SDNN, pNN50, high-frequency power, and low-frequency power in group M were significantly lower than those in group S and controls, and the ratio of low- to high-frequency power in group M was significantly higher than that in group S and controls. There was no difference in any index between group S and controls. All abnormal indexes in group M recovered to levels similar to those in controls 1 month after the treatment. In conclusion, depressed cardiac vagal control and sympathetic-dominant sympathovagal interaction were present in patients with variant angina, especially in those with multivessel spasm.

Short- and long-term assessment of heart rate variability for risk stratification after acute myocardial infarction

Depressed heart rate variability (HRV) has been shown to be a powerful and independent risk factor in patients following acute myocardial infarction (AMI). A detailed comparison of the predictive values between short- and long-term HRV has not been made. The predictive value of short-term HRV for 1-year total cardiac mortality was studied in 700 consecutive patients after AMI. All patients underwent 24-hour Holler monitoring before discharge from the hospital (5 to 8 days after AMI) and were followed up for 1 year. Short-term HRV was computed as the standard deviation of all normal RR intervals (SDNN) from a 5-minute stationary period selected from 24-hour Holter electrocardiographic recordings. Long-term HRV was computed as an HRV index over the entire 24 hours. There was a significant but relatively poor correlation between SDNN and HRV index (r = 0.51, p < 0.001). The positive predictive accuracy of SDNN for 1-year mortality (13% to 18%) was lower than the HRV index (17% to 43%) over a range of sensitivity of 25% to 75%. Assessment of HRV index in ≥35% of the patients preselected by the lowest SDNN was able to achieve predictive power similar to that of HRV index assessed in all the patients. These data suggest that lower predischarge short-term HRV is associated with increased 1-year total cardiac mortality in patients after AMI. Analysis of long-term HRV for postinfarction risk stratification can safely be limited to patients preselected by depressed short-term HRV measures.

Effects of enalapril on heart rate variability in patients with congestive heart failure

Congestive heart failure (CHF) is characterized by sympathetic activation and parasympathetic withdrawal, and the magnitude of sympathoneural activation is associated with adverse outcome. Angiotensin-converring enzyme inhibitor therapy has been shown to reduce mortality and improve prognosis in patients with CHF, but whether this therapy improves cardiac autonomic control is not well known. This double-blind, placebo-controlled, crossover study examines the effects of enalapril on autonomic control in 12 patients with mild to moderate CHF by heart rate variability analysis. Compared with placebo, enalapril increased the SD of all normal RR intervals (SDNN) from 39 ± 13 to 48 ± 15 ms (p < 0.01), the SD of the average RR intervals for all 5-minute segments from 33 ± 12 to 42 ± 15 ms (p < 0.01), and the mean of the SDs of all RR intervals for all 5-minute segments (SDNN index) from 19 ± 5 to 23 ± 6 ms (p < 0.01). The root-mean-square successive differences and the percent differences between adjacent RR intervals >50 ms were also increased from 17 ± 8 to 21 ± 8 ms (p < 0.01) and from 1.1 ± 2.1 to 2.8 ± 2.9% (p < 0.05). In addition, total, low-frequency, and high-frequency power were increased from 560 ± 349 to 786 ± 504 ms 2/Hz (p < 0.01), from 125 ± 107 to 179 ± 135 ms 2/Hz (p < 0.01), and from 46 ± 32 to 94 ± 78 ms 2/Hz (p < 0.01), respectively. The plasma angiotensin II level was decreased significantly from 131 ± 66 to 47 ± 18 pg/ml (p < 0.01). Changes in heart rate variability measures after enalapril therapy were positively related to changes in plasma angiotensin II level. These results indicate that enalapril therapy attenuates the autonomic imbalance associated with a poor prognosis in patients with CHF, which is related to the inhibition of the initially activated renin-angiotensin system.