Influence of age on ambulatory electrocardiogram-derived heart rate variability

OBJECTIVE: To evaluate the quantitative change in heart rate variability with age by using 24 h Holter ambulatory monitoring of electrocardiogram and to set the lower limit of heart rate variability depending on age. PARTICIPANTS: Eighty healthy subjects without any medication (male to female ratio 40:40, 45.6 +/- 14.1 years of age, range 16 to 68 years). METHODS: Holter monitoring was performed, and frequency and time domain heart rate variability was obtained. RESULTS: A significant inverse relationship was found between age and heart rate variability, especially in the frequency domain, and, in the time domain analysis, in the root mean square of the difference in the RR intervals of sinus rhythm (NN) between successive beats and in the portion of NN cycles greater than 50 ms apart. Except for the standard deviation of the mean of RR intervals taken every 5 mins and averaged over 24 h and the ratio of low frequency high frequency power spectra, all parameters decreased to a certain age and did not change thereafter, and the rate of decrease differed among the parameters of heart rate variability. Because age had a strong influence on heart rate variability, the lower limit of heart rate variability for a certain age was determined by using the polynomial curve fitting of the moving average minus 2 SD of 10 consecutive subjects. By using these equations, it could be determined whether heart rate variability was normal or abnormal depending on age.     

Higher heart rate variability of smokers after acute myocardial infarction

Although cigarette smoking is known to be a strong risk factor for the development of coronary artery disease, several large clinical studies have demonstrated that current smokers had a favorable prognosis compared to nonsmokers after myocardial infarction. This study sought to evaluate the effect of smoking status on heart rate variability after onset of acute myocardial infarction. We studied 52 patients (34 smokers, 18 nonsmokers) with a first myocardial infarction within 24 h of onset. We recorded 24-h ambulatory ECG to calculate very low frequency power (VLF), low frequency power (LF) and high frequency power (HF) 14 days after onset. Although smokers had a tendency to be younger than nonsmokers (mean age 57 versus 62, P = 0.0812), clinical characteristics were not statistically different between smokers and nonsmokers. After adjustment for age, left ventricular ejection fraction, history of diabetes, acute revascularization and use of beta-blockers, VLF (P = 0.0183) of smokers 14 days after onset was significantly higher than for nonsmokers. In conclusion, although smoking reduces heart rate variability in the general population, higher heart rate variability was observed in smokers than nonsmokers after acute myocardial infarction under the condition of smoking cessation.     

Prognostic significance of blood pressure and heart rate variabilities: the Ohasama study

To investigate the association between cardiovascular mortality and short-term variabilities in blood pressure and heart rate, we performed a long-term prospective study of ambulatory blood pressure monitoring in Ohasama, Japan, starting in 1987. We obtained ambulatory blood pressure and heart rate in 1542 subjects >/=40 years of age. Blood pressure and heart rate variabilities were estimated as a standard deviation measured every 30 minutes by ambulatory monitoring. There were 67 cardiovascular deaths during the follow-up period (mean=8.5 years). The Cox proportional hazards model, adjusted for possible confounding factors, demonstrated a significant increase in cardiovascular mortality, with an increase in daytime systolic ambulatory blood pressure variability. A similar trend was observed in daytime diastolic and nighttime ambulatory blood pressures. Cardiovascular mortality rate increased linearly, with a decrease in daytime heart rate variability. Subjects in whom the daytime systolic ambulatory blood pressure variability was larger than third quintile and the daytime heart rate variability was lower than the mean-SD were at extremely high risk of cardiovascular mortality. The blood pressure and heart rate variabilities obtained every 30 minutes by ambulatory blood pressure monitoring were independent predictors for cardiovascular mortality in the general population.     

Relation of mean heart rate and heart rate variability in patients with left ventricular dysfunction.

The new finding was that mean heart rate and heart rate variability were more closely coupled in patients with more advanced LV dysfunction. Mean heart rate explained a larger portion of variance in heart rate variability in patients in the lowest LVEF quartile than in those in the highest one. These results support our hypothesis that sympathetic activation in patients with more severe LV dysfunction results in closer correlation between heart rate and heart rate variability. Generally, the correlation between mean heart rate and heart rate variability is weak because heart rate and heart rate variability represent different modalities of cardiovascular regulation. Mean heart rate is normally determined by the interactions of both the sympathetic and parasympathetic nervous systems, whereas modulation of these activities, with different gains, determines the magnitude of heart rate variability. This results in great complexity in control of the heart by the autonomic nervous system. However, heart rate is likely to be more dominantly regulated by the sympathetic nervous system because of vagal withdrawal in patients with more severe LV dysfunction. The effect of sympathetic cardiac modulation has been shown to be more sluggish than that of the parasympathetic nervous system in beat-to-beat regulation of heart rate. This may result in more blunted heart rate variability concomitantly with elevated mean heart rate. Thus, variation in heart rate variability in any given mean heart rate is likely to be lower than in patients with more preserved LV function, and hence with more complex cardiac autonomic regulation with involvement of the parasympathetic nervous system. Indeed, even the slopes of regression lines between mean heart rate and heart rate variability were similar in the first and fourth LVEF quartile; the intercept of the regression line was significantly higher in the fourth quartile than in the first one. This further supports our hypothesis.     

Normal ranges for the variability in heart rate in young infants while sleeping

OBJECTIVE: Measurements of the variability in heart rate are increasingly used as markers of cardiac autonomic activity. We sought to establish the development this variability in healthy young infants while sleeping. PATIENTS: We carried out polygraphic studies with electrocardiographic recording in 587 healthy infants aged from 5 to 26 weeks. METHODS: We determined several variables over a period of 400 minutes sleeping: mean RR interval, 5 time-domain (SDNN, SDNNi, SDANNi, RMSSD, and pNN50) and 5 frequency-domain indexes (spectral power over 3 regions of interest, total power and low-to-high frequency ratio). Frequency-domain indexes were also assessed separately for the periods of quiet sleep and those of rapid eye movement sleep. RESULTS: Our data showed a significant correlation between the indexes of heart rate variability and the mean RR interval, the breathing rate, and the corrected age of the infants. We also demonstrated the importance of the maturation of the sleeping patterns. CONCLUSION: These data in a large cohort of healthy infants confirm a progressive maturation of the autonomic nervous system during sleep, and may be used to examine the influence of physiological and pathophysiological factors on autonomic control during polygraphic studies.     

Effect of mibefradil on heart rate variability in patients with chronic heart failure

BACKGROUND: Mibefradil was recently withdrawn from the market because of an unfavorable clinical profile in patients with chronic heart failure. Although drug interactions appear to play a role, other mechanisms such as proarrhythmia and autonomic deterioration could also be relevant. Chronic heart failure is accompanied by autonomic impairment and analysis of heart rate variability can be used to examine autonomic modulation of heart rate. METHODS: We studied 18 heart failure patients (age 63.2+/-10.1 years (mean+/-S.D. ), ejection fraction 0.21+/-0.07) treated with mibefradil or placebo, who participated in the MACH-I (Mortality Assessment in Chronic Heart failure) trial in our center, and compared them with 18 healthy matched controls. Heart rate variability analysis was performed at baseline and after 7 months of treatment. RESULTS: At baseline, heart rate variability parameters were impaired in patients with heart failure compared to healthy controls (P<0.05). After 7 months of treatment a reduction in (24-h) heart rate was observed (P=0.02, versus placebo). Apart from the effect on mean NN, no significant differences were observed for the remaining heart rate variability parameters. CONCLUSIONS: Mibefradil does not impair autonomic balance and in fact reduces heart rate in patients with heart failure. These findings suggest that autonomic activation did not contribute to the adverse effects of mibefradil.     

Reduced heart rate variability following repair of tetralogy of Fallot

OBJECTIVE: To examine autonomic function as assessed by heart rate variability in patients 10 or more years after repair of tetralogy of Fallot, and to relate this to cardiac structure, function, and electrocardiographic indices. METHODS: Heart rate variability was measured by standard time domain techniques on a 24 hour Holter ECG in 28 patients, aged 12 to 34 years (mean 19.5), who had undergone repair of tetralogy of Fallot at least 10 years previously. Echocardiography was performed to assess left ventricular size and function, right ventricular size and pressure, and any proximal pulmonary arterial stenosis. Right ventricular function was evaluated by radionuclide scan. QRS duration, QT interval, and QT dispersion were measured on a standard 12 lead ECG. Measurements of heart rate variability were compared with values from 28 age matched healthy controls (mean age 19.9 years). Interrelations between variables were assessed using Pearson correlation coefficients and stepwise regression analysis. RESULTS: Heart rate variability was reduced, compared with values for age matched normal controls, in 12 of the 28 patients. Reduced heart rate variability was associated with increased age, increased right ventricular size and pressure, and widening of the QRS complex. CONCLUSIONS: Reduced heart rate variability is a feature following repair of tetralogy of Fallot. It is associated with increasing age, impaired right ventricular haemodynamics, and widening of the QRS complex. Under these circumstances, reduced heart rate variability may be a marker for deteriorating right ventricular function. Increased QRS duration has been identified as a risk factor for sudden death following repair of tetralogy of Fallot, and impaired cardiac autonomic control may be one of the mechanisms involved.     

Effect of physiologic and pharmacologic adrenergic stimulation on heart rate variability

Objectives. The aim of this study was to evaluate and compare the effects of physiologic and pharmacologic sympathetic stimulation on time and frequency domain indexes of heart rate variability.Background. Measurements of heart rate variability have been used as indexes of sympathetic tone. To date, the effects of circulating catecholamines on heart rate variability have not been evaluated.Methods. Fourteen normal subjects (eight men, six women, mean (± SD) age 28.5 ± 48 years) were evaluated. Five-minute electrocardiographic recordings were obtained in triplicate after physiologic and pharmacologic sympathetic stimulation: during upright tilt, after maximal exercise, during epinephrine and isoproterenol infusions at 50 ng/kg body weight per min, during beta-adrenergic blockade and during combined beta-adrenergic and parasympathetic blockade.Results. Beta-adrenergic stimulation resulted in a significant decrease in time domain measures of heart rate variability. The frequency domain indexes showed variable responses, depending on the individual stimulus. Tilt caused an increase in low frequency power and in the ratio of low to high frequency power. These changes were not necessarily observed with other conditions of beta-adrenergic stimulation. Double blockade suppressed baseline heart rate variability, but beta-adrenergic blockade had no significant effect. Time domain measures of heart rate variability demonstrated excellent reproducibility over the three recordings, but the frequency domain variables demonstrated fair to excellent reproducibility.Conclusions. These findings suggest that different modes of beta-adrenergic stimulation may result in divergent heart rate variability responses. Thus, current heart rate variability techniques cannot be used as general indexes of “sympthetic” tone. Studies utilizing heart rate variability to quantify sympathetic tone need to consider this.     

Prognostic value of heart rate turbulence and heart rate variability in children with dilated cardiomyopathy

The aim of our study is to evaluate the prognostic value of heart rate turbulence and heart rate variability in children with dilated cardiomyopathy (DCM). Twenty-five children with DCM and 24 age- and sex-matched healthy children who were admitted between January 2002 and September 2004, enrolled in this prospective study at our hospital. After the echocardiographic examination, three-channel 24-ambulatory ECG recordings were obtained in all patients with DCM and in the control group. Time domain heart rate variability parameters were obtained in both groups. Heart rate turbulence was measured in DCM patients, but we could not calculate heart rate turbulence in the control group since no ventricular ventricular premature complexes (PVC) were found in the 24-hour ECG monitoring in the control group. The mean follow-up period of the DCM group was 13.4 months (3-26 months). Five patients died (20%) during the follow-up period. Triangle index, turbulence slope (TS), age and availability of nonsustained ventricular tachycardia (VT) on 24-hour ECG monitoring were prognostic factors according to the correlation analyses. Only triangle index was detected as an independent risk factor among the prognostic factors according to the logistic regression analyses. This study assessed the prognostic value of heart rate turbulence and heart rate variability in children with dilated cardiomyopathy. Further studies are needed to investigate the prognostic value of heart rate turbulence.     

Reduced heart rate variability in hypertension: associations with lifestyle factors and plasma renin activity

Limited information exists on the relations between heart rate variability, hypertension, lifestyle factors and renin-angiotensin-aldosterone system. A total of 191 newly diagnosed yet untreated hypertensive men and women, 35-54 years of age, were compared with an age- and gender-stratified random population sample of 105 normotensive men and women to find out independent determinants of heart rate variability. Heart rate variability was computed from 5-min ECG time series using the standard deviation of normal-to-normal RR intervals (SDNN), the square root of the mean of squared differences between adjacent normal RR intervals (RMSSD) and the fast Fourier transform spectral analysis. All absolute measures of heart rate variability were reduced in hypertension (P<0.001 for each, ANOVA). In multivariate regression analyses, reduced heart rate variability was independently associated with higher heart rate (P<0.001 for all absolute measures of heart rate variability), higher age (P=0.001 for SDNN, total and LF powers; P<0.001 for RMSSD and HF power) and higher mean arterial pressure (P<0.05 for total power, P<0.01 for the other absolute measures) but not with sodium and alcohol intakes, body mass index and smoking. Increased plasma renin activity (PRA) was an independent attributor of reduced HF power (P<0.05) and reduced RMSSD (P<0.01). Increased blood pressure and heart rate are associated with decreased heart rate variability without any direct effects on heart rate variability of lifestyle factors. High PRA is an independent determinant of diminished modulation of vagal activity.     

Reduced low-frequency heart rate variability relates to greater intimal-medial thickness of the carotid wall in two samples

INTRODUCTION: We investigated the relationship between heart rate variability and preclinical carotid intima-media thickening, a putative index of atherosclerosis. METHODS: A sample of 350 men and women (mean age 56.8 years) selected for the presence or absence of untreated hypertension was assessed for heart rate variability at rest and separately for carotid intima-media thickness using duplex ultrasonography (Pittsburgh study). Findings from this sample were cross-validated in a subsample of 68 men drawn from the Kuopio Ischemic Heart Disease Risk Factor trial and selected for the presence or absence of angina. RESULTS: In both samples, regression analyses, controlling for known risk factors, showed a significant negative relationship between mean carotid intima-media thickness and low-frequency (0.05-0.15 Hz) heart rate variability, but not high-frequency variability. DISCUSSION: The mechanism underlying this relationship remains unclear. The absence of difference in high-frequency variation questions any interpretation in terms of vagal function; the difference in low-frequency variation may implicate vessel wall characteristics or decreased sympathetic nervous system influence. CONCLUSION: Decreased amplitude of low-frequency heart rate variability seems associated with a preclinical atherosclerotic index.     

Relationship between heart rate turbulence and heart rate, heart rate variability, and number of ventricular premature beats in coronary patients

INTRODUCTION: Heart rate variability (HRV) illustrates regulation of the heart by the autonomic nervous system whereas heart rate turbulence (HRT) is believed to reflect baroreflex sensitivity. The aim of this study was to determine the association between HRT and HRV parameters and the relationship between HRT parameters and heart rate and number of ventricular premature beats (VPBs) used to calculate HRT parameters. METHODS AND RESULTS: In 146 patients (117 males and 29 females; mean age 62 years) with coronary artery disease, a 24-hour ECG Holter monitoring was performed to calculate mean heart rate (RR interval), number of VPBs, time- and frequency-domain HRV parameters and two HRT parameters: turbulence onset (TO) and turbulence slope (TS). Univariate and multivariate regression analyses were performed to evaluate the association between tested parameters. Significant correlation between TS and mean RR interval was observed (r = 0.42; p < 0.001), while no association for TO vs. RR interval was found. TS values were significantly higher in patients with less than 10 VPBs/24 hours than in patients with more frequent VPBs. Significant associations between HRT and HRV parameters were found with TS showing stronger correlation with HRV parameters than TO (r value ranging from 0.35 to 0.62 for TS vs. -0.16 to -0.38 for TO). CONCLUSION: HRT parameters correlate strongly with HRV parameters indicating that HRT should be considered as a reflection of both baroreceptors response and overall autonomic tone. Heart rate dependence of turbulence slope indicates the need to adjust this parameter for heart rate.     

Circadian variation of heart rate variability

STUDY OBJECTIVE--The aim of the study was to examine the circadian variation in heart rate variability and to test the hypothesis that the variation is due to vagal influence. DESIGN--Human subjects, some with vagal neuropathy, underwent ambulatory 24 h electrocardiographic monitoring, the recordings being played back through an analyser which identified and timed successive pulse (R-R) intervals. Heart rate variability was measured for each 30 min period over 24 h as the standard deviation of the successive differences between R-R intervals, which filtered out low frequency components of heart rate variability that were not autonomic in origin. Modelled curves of heart rate variability were compared using analysis of variance. SUBJECTS--The subjects were aged between 33 and 65 years and were matched in three groups for age and sex. There were 11 healthy controls, 12 insulin dependent diabetics and seven alcoholics with vagal neuropathy. RESULTS--A significant circadian variation in heart rate variability was present, characterised by a rise during sleep. Mean heart rate variation was significantly reduced in groups with vagal neuropathy, although the amplitude of the cycle and time of peak variability was not significantly different. The circadian variation was sustained regardless of the degree of vagal neuropathy. CONCLUSIONS--The cycle of heart rate variability is not dependent on vagal interaction. It may be due to fluctuations in sympathetic activity affecting beat to beat variability.     

The chronic effect of rilmenidine on heart rate variability in patients with mild hypertension

The purpose of this study was to evaluate the chronic effect of rilmenidine on time domain indexes of heart rate variability in patients with mild hypertension. Twenty patients (12 males, eight females; mean age, 47 yr; age range, 38-55 yr), with untreated and newly diagnosed mild hypertension were studied. There was no evidence of diseases other than hypertension. All patients received 1 mg of rilmenidine once daily. If the diastolic blood pressure was still greater than 90 mm Hg after 4 weeks of active treatment, the dose was increased to 2 mg once daily. Twenty-four hour ambulatory electrocardiograms were recorded before, and 4 and 12 weeks after the start of therapy. Time domain parameters of heart rate variability were calculated. Rilmenidine therapy determined a marked decrease in blood pressure. At 4 weeks, rilmenidine induced a significant reduction in systolic and diastolic blood pressure and a further reduction was observed after 12 weeks. At 4 and 12 weeks, time domain parameters of heart rate variability and heart rate were not significantly different in the data obtained before therapy. In conclusion, this study demonstrated that the administration of rilmenidine to patients with mild essential hypertension induced significant reductions in blood pressure, without any significant changes in time domain parameters of heart rate variability.     

Heart rate variability and heart rate in healthy volunteers. Is the female autonomic nervous system cardioprotective?

Aims Heart rate variability has been proposed as an indicator ofcardiovascular health. Since women have a lower cardiovascularrisk, we hypothesized that there are gender differences in autonomicmodulation. Methods and Results In 276 healthy subjects (135 women, 141 men) between 18 and71 years of age, 24h heart rate and heart rate variability weredetermined. All heart rate variability parameters, except forpNN50 and high frequency power, were higher in men. After adjustmentfor heart rate, we obtained gender differences for: the standarddeviation (P=0·049), the standard deviation of the 5minaverage (P=0·047), low frequency power (absolute values,P=0·002;normalized units,P<0·001) and ratio low frequency/highfrequency (P<0·001). There were no significant genderdifferences in heart rate variability parameters denoting vagalmodulation. Gender differences were confined to age categoriesof less than 40 years of age. The majority of heart rate variabilityparameters decreased with age. Only in men, was a higher bodymass index associated with a higher heart rate and with lowerheart rate variability parameters (P<0·001). Conclusion Cardiac autonomic modulation as determined by heart rate variability,is significantly lower in healthy women compared to healthymen. We hypothesize that this apparently paradoxical findingmay be explained by lower sympathetic activity (low frequencypower) in women. This may provide protection against arrhythmiasand against the development of coronary heart disease.     

Serial assessment of variability in heart rate in children with the Fontan circulation

Autonomic nervous control of the heart can be studied by analysing variability in heart rate. Although earlier studies have shown reduced variability in patients with the Fontan circulation, we are not aware of any previous study examining longitudinal changes in such children. We have examined 13 patients who had undergone total cavopulmonary connection, and 37 healthy controls matched for age and gender. The examinations included complete echocardiography, and 24-hour ambulatory electrocardiogram for analysis of the parameters for variability in heart rate. After the Fontan procedure, three follow-up examinations were performed at a mean of 4.4 years, 5.6 and 7.2 years. Reduced variability was found in those with the Fontan circulation. A significant difference was found between patients and their controls with respect to high-frequency power at the second, p equal to 0.05, and third, p equal to 0.03, examination. The ratio of low-to-high-frequency components progressively increased in those with the Fontan circulation, a phenomenon that led to a significant difference, p equal to 0.03, at the third examination. Our study shows that, in patients with the Fontan circulation, routine ambulatory electrocardiographic monitoring including analysis of variability in heart rate, detects over time a progressive sympatovagal imbalance.     

Clinical, hemodynamic and sympathetic neural correlates of heart rate variability in congestive heart failure.

Heart rate (HR) variability has long been recognized as a sign of cardiac health. In the presence of heart disease, HR variability decreases, an observation that has been associated with poor prognosis in a number of recent studies. HR variability is particularly altered in congestive heart failure (CHF), a condition associated with a number of typical functional hemodynamic and neurohumoral alterations. The relation of measurements of HR variability to these abnormalities in patients with heart failure has not been carefully examined. Twenty-three patients (19 men, 4 women, mean age 49 years) with New York Heart Association class II to IV CHF were studied prospectively without cardiac medications; radionuclide ventriculography, right-sided heart catheterization, peroneal microneurography, plasma norepinephrine and 24- to 48-hour ambulatory electrocardiography were performed. Average RR interval and its standard deviation, and HR power spectrum (0 to 0.5, 0.05 to 0.15 and 0.2 to 0.5 Hz) were derived from the ambulatory electrocardiographic recordings and compared with left ventricular ejection fraction, thermodilution cardiac output, pulmonary arterial wedge pressure, New York Heart Association class, age, muscle sympathetic nerve activity (peroneal nerve) and norepinephrine level by linear regression. None of the measures of HR variability were significantly related to age, left ventricular ejection fraction, cardiac output or functional classification, whereas the 0.05 to 0.15 and 0.20 to 0.50 Hz components were weakly but significantly related to cardiac output (r = 0.49 and 0.42, p = 0.02 and 0.045, respectively). In contrast, a generally stronger and negative relation was demonstrated between spectral and nonspectral measurements of HR variability, and indicators of sympathoexcitation, muscle sympathetic nerve activity and plasma norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Marked abnormalities in heart rate variability are associated with progressive deterioration of renal function in type I diabetic patients with overt nephropathy

BACKGROUND: Cardiac autonomic neuropathy is a common complication of long-standing, type 1 diabetes and is associated with increased morbidity and mortality. Impaired heart rate variability is a sensitive and reproducible marker of cardiac autonomic neuropathy. We sought to examine the relationship between cardiac autonomic neuropathy as assessed by heart rate variability and overt nephropathy, with emphasis on the progression of renal dysfunction over 1 year. METHOD: Baseline and 12 month clinical and biochemical characteristics, as well as autonomic function tests, were analyzed in 23, type 1 diabetic patients (mean age 37+/-10 years, 65% males), who were prospectively enrolled as a part of a multi-center investigation. In addition, ambulatory, 24-h, 3-channel electrocardiograms were recorded, and heart rate variability indices were assessed in the time and frequency domains over the same period. RESULTS: All heart rate variability indices were markedly decreased in our study population. On univariate analysis, heart rate variability was associated with creatinine clearance, and to a lesser extent, mean 24-h blood pressures and cholesterol. On multivariate analysis, only heart rate variability was a significant and independent predictor of abnormalities in creatinine clearance. Severe reduction in heart rate variability at baseline was also significantly associated with the further deterioration in renal function at 1 year. CONCLUSION: Heart rate variability is significantly reduced in long-standing, type 1 diabetics with proteinuria or overt nephropathy. Marked abnormalities in heart rate variability are significantly associated with and predictive of progressive renal deterioration at 1 year. These findings may have implications for aggressive medical intervention to improve prognosis and survival in this population.     

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 > or =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.     

Effect of beta-blockade on heart rate variability in decompensated heart failure

BACKGROUND: One of the putative mechanisms for the salutary effects of beta-blockers in patients with congestive heart failure is their ability to improve autonomic dysfunction. However, patients with profound neurohumoral abnormalities derive little survival benefit from beta-blockers. The purpose of the current study was to evaluate the effect of beta-blockers on heart rate variability in decompensated heart failure. METHODS: Time and frequency domain heart rate variability indices were obtained from 24-h Holter recordings and compared to assess the role of beta-blockade in 199 patients (mean age 60+/-14 years [range 21 to 87]) with decompensated heart failure (New York Heart Association functional class III [66%] and IV [34%]). RESULTS: All heart rate variability indices were markedly suppressed but were substantially higher in patients who were on beta-blockers. Time domain measures of parasympathetic cardiac activity, the percentage of RR intervals with >50 ms variation (4.9+/-0.6 vs. 7.7+/-1.2%, P=0.006) and the square root of mean squared differences of successive RR intervals (22.7+/-2.0 vs. 31.6+/-4.1 ms, P=0.004), were higher in the beta-blocker group. Spectral analysis revealed that the total power and the ultra low frequency power were significantly higher in patients on beta-blockers (82% and 59%, respectively). The high frequency power, a spectral index of parasympathetic modulation, was 41% higher in the beta-blocker group (121+/-25 vs. 171+/-27 ms(2), P=0.02). Multiple linear regression, adjusted for clinical parameters and drug therapies, revealed a strong positive relationship between beta-blockade and higher values of time and frequency domain measures. The mean number of ventricular tachycardia episodes were significantly lower in patients on beta-blocker therapy (3.6+/-1.5 vs. 19.0+/-5.3, P=0.04). CONCLUSIONS: beta-blockers improve the impaired cardiac autonomic regulation during high sympathetic stress of decompensated heart failure.