Standard Deviation Of RR Intervals Research Articles

Depressed Heart Rate Variability as an Independent Predictor of Death in Chronic Congestive Heart Failure Secondary to Ischemic or Idiopathic Dilated Cardiomyopathy

After acute myocardial infarction, depressed heart rate variability (HRV) has been proven to be a powerful independent predictor of a poor outcome. Although patients with chronic congestive heart failure (CHF) have also markedly impaired HRV, the prognostic value of HRV analysis in these patients remains unknown. The aim of this study was to investigate whether HRV parameters could predict survival in 102 consecutive patients with moderate to severe CHF (90 men, mean age 58 years, New York Heart Association [NYHA] class II to IV, CHF due to idiopathic dilated cardiomyopathy in 24 patients and ischemic heart disease in 78 patients, ejection fraction [EF], 26%; peak oxygen consumption, 16.9 ml/kg/min) after exclusion of patients in atrial fibrilation with diabetes or with chronic renal failure. In the prognostic analysis (Cox proportional-hazards model, Kaplan-Meier survival analysis), the following factors were investigated: age, CHF etiology, NYHA class, EF, peak oxygen consumption, presence of ventricular tachycardia on Holter monitoring, and HRV measures derived from 24-hour electrocardiography monitoring, calculated in the time (standard deviation of all normal RR intervals [SDNN], standard deviation of 5-minute RR intervals [SDANN], mean of all 5-minute standard deviations of RR intervals [SD], root-mean-square of difference of successive RR intervals [rMSSD], and percentage of adjacent RR intervals >50 ms different [pNN50]) and frequency domain (total power [TP], power within low-frequency band [LF], and power within high-frequency band [HF]). During follow-up of 584 ± 405 days (365 days in all who survived), 19 patients (19%) died (mean time to death: 307 ± 315 days, range 3 to 989). Cox's univariate analysis identified the following factors to be predictors of death: NYHA (p = 0.003), peak oxygen consumption (p = 0.01), EF (p = 0.02), ventricular tachycardia on Holter monitoring (p = 0.05), and among HRV measures: SDNN (p = 0.004), SDANN (p = 0.003), SD (p = 0.02), and LF (p = 0.003). In multivariate analysis, HRV parameters (SDNN, SDANN, LF) were found to predict survival independently of NYHA functional class, EF, peak oxygen consumption, and ventricular tachycardia on Holter monitoring. The Kaplan-Meier survival curves revealed SDNN <100 ms to be a useful risk factor; 1-year survival in patients with SDNN <100 ms was 78% when compared with 95% in those with SDNN >100 ms (p = 0.008). The coexistence of SDNN <100 ms and a peak oxygen consumption <14 ml/kg/min allowed identification of a group of 18 patients with a particularly poor prognosis (1-year survival 63% vs 94% in the remaining patients, p <0.001). We conclude that depressed HRV on 24-hour ambulatory electrocardiography monitoring is an independent risk factor for a poor prognosis in patients with CHF. Whether analysis of HRV could be recommended in the risk stratification for better management of patients with CHF needs further investigation.In 102 consecutive patients with stable chronic congestive heart failure and sinus rhythm, several heart rate variability measures derived from 24-hour electrocardiographic recording were significant prognostic risk markers, independent of clinical variables (New York Heart Association class, peak oxygen consumption, left ventricular ejection fraction). The coexistence of the standard deviation of all normal RR intervals <100 ms and peak oxygen consumption <14 ml/kg/min had the worst prognosis, and it is concluded that heart rate variability analysis is useful for noninvasive heart transplant assessment.

Abnormal heart rate variability as a manifestation of autonomic dysfunction in hemispheric brain infarction.

Abnormal heart rate variability is related to prognostically unfavorable ventricular arrhythmias and sudden arrhythmic death in coronary artery disease. Short-term electrocardiographic (ECG) recordings have shown similar abnormalities of heart rate variability in patients with acute stroke. However, there is no information regarding the clinical significance of these abnormalities and of heart rate variability in long-term ECG recordings in stroke. In this prospective study, we analyzed the time domain and frequency domain measures of heart rate variability from 24-hour ECG recordings in 31 consecutive patients with hemispheric brain infarction in the acute phase and at 1 and 6 months after the infarction and in 31 age- and sex-matched healthy control subjects. All the measured components of heart rate variability, ie, standard deviation of RR intervals (P < .001), total power (P < .0001), very-low-frequency power (P < .0001), low-frequency power (P < .001), and high-frequency power (P < .05), were significantly lower than those of the control subjects in both the acute phase and 1 and 6 months later. Impaired heart rate variability correlated with the severity of neurological deficits and disability. In five patients with increased intracranial pressure due to large brain infarction, no relevant spectral components were found. Hemispheric brain infarction seems to cause significant long-lasting damage to the cardiovascular autonomic regulatory system manifested as abnormalities of heart rate variability. Distorted heart rate variability in the acute phase of stroke may be prognostically unfavorable.

Value of Heart Rate Variability Parameters for Prediction of Serious Arrhythmic Events in Patients with Malignant Ventricular Arrhythmias

Heart rate variability (HRV) assesses the electrical stability of the heart and can identify patients at risk of sudden cardiac death (SCD). The value of 10 HRV parameters from 24 hour ECG (in both time and frequency domain) to predict serious arrhythmic events (SAE) in a group of 56 patients with ventricular tachycardia and/or ventricular fibrillation of different etiologies not due to acute myocardial infarction was explored. Eighteen patients had low left ventricular ejection fractions (LVEF). During follow-up (6-46 months, mean = 24) 8 SCD and 12 recurrences of malignant ventricular arrhythmias or ICD discharges were recorded. Proportional hazard analysis (Cox model) for SAE revealed that the mean of all 5 minute standard deviation of RR intervals (SD) and the amplitude of low frequency spectrum (L) were independent risk factors of SAE (P < 0.05). The best models were: SD+EF and L+EF where predictive values were high (sensitivity approximately 60%, specificity over 95%, positive predictive value over 90% and negative predictive value approximately 80%). Event-free survival curves revealed a significantly shorter survival in patients with EF < 40%: 47% vs. 92%, SD < 43 ms; 56% vs. 92% and L < 16 ms; 56% vs. 89% (all P < 0.001) after 2 years. The subgroup with low EF and SD < 43 ms revealed a significantly shortened survival (27% vs 83% at 2 years, P < 0.01). Some HRV parameters, SD from the time and L from the frequency domain, were predictive of a fatal outcome in VT/VF patients. Combined SD+EF and L+EF values are powerful predictors of serious arrhythmic events.

Abnormalities in Beat to Beat Complexity of Heart Rate Dynamics in Patients With a Previous Myocardial Infarction

Objectives. The purpose of this research was to study possible abnormalities in the beat to beat complexity of heart rate dynamics in patients with a previous myocardial infarction.Background. Analysis of approximate entropy of time series data provides information on the complexity of both deterministic and random processes. It has been proposed that regularity or loss of complexity of RR interval dynamics may be related to pathologic states, but this hypothesis has not been well tested in cardiovascular disorders.Methods. Approximate entropy and conventional time and frequency domain measures of RR interval variability were compared between 40 healthy subjects with no evidence of heart disease and 40 patients with coronary artery disease and a previous Q wave myocardial infarction. The groups were matched with respect to age, and cardiac medication was discontinued in the patients with coronary artery disease before the 24-h electrocardiographic recordings.Results. Approximate entropy was significantly higher in the postinfarction patients (1.21 ± 0.18 [mean ± SD]) than in the healthy subjects (1.05 ± 0.11, p < 0.001), whereas the standard deviation of RR intervals (63 ± 19 vs. 86 ± 23 ms, p < 0.001) and the very low, low and high frequency spectral components were lower (p < 0.01, p < 0.001, p < 0.05, respectively). Approximate entropy was not related to the time domain or the spectral components of heart rate variability and was more commonly abnormal in postinfarction patients (62.5%) than any linear measure (from 20% to 42.5%) when the 90% percentile of the values obtained for healthy subjects was defined as the normal range for each measure.Conclusions. Despite reduced linear measures of heart rate variability, the unpredictability or randomness of beat to beat heart rate dynamics is increased in patients with a previous myocardial infarction. Complexity analysis of RR interval dynamics may provide useful information on abnormalities in heart rate behavior that are not easily detected by the commonly used moment statistics.

Relationship Between Heart Rate Variability and Cardiovascular Risk Factors in Middle‐Aged Males

Background: Abnormal autonomic control of heart rate is associated with an inreased risk of cardiovascular morbidity and mortality. There are few population‐based reports on the interindividual variation and determinants of cardiac control in healthy middle‐aged males.Methods: Autonomic modulation of heart rate was studied in 172 randomly selected middle‐aged males (mean age 50 ± 6 years) by measuring the heart rate variability (HRV), which was related to life style data, personality type, blood pressure, lipid analyses, results of the 2‐hour glucose tolerance test and left ventricular function.Results: Large interindividual variation was observed in the standard deviation of RR intervals (mean 59 ± 20 ms; coefficient of variation (CV) 34%) compared to variation of the average heart rate (mean 76 ± 11 beats/min, CV 14%). When analyzed as normalized units, marked interindividual variation was observed in the low (CV 16%) and high frequency component (CV 37%). The total power of HRV had significant indirect univariate correlations with age, blood pressure, body mass index, 2‐hour blood glucose level, fasting and 2‐hour serum insulin levels, triglyceride level, and a direct correlation with left ventricular fractional shortening. In a multiple regression analysis, the total power of HRV was best predicted by age (β=−0.27, P = 0.0002), followed by the fractional shortening (β= 0.25, P = 0.0004), systolic blood pressure (/3 =−0.2 1, P = 0.005) and 2‐hour insulin level (β=−0. 9, P = 0.01).Conclusions: Overall HRV has a wide interindividual variation and is related to several cardiovascular risk factors, perhaps contributing to the observed association between low HRV and cardiovascular mortality. Normalized units of HRV reflecting sympathovagal balance are unrelated to age, life style, or cardiovascular risk factors.

Heart rate variations during sleep in preadolescents.

Heart rate variations during sleep have been documented for infant and adult populations, but not for children and adolescents. To provide normative data for the preadolescent age group, this investigation used a combination of time-domain measures and nonlinear procedures (Poincare plots) to describe heart rate variations during two consecutive nights of undisturbed baseline sleep in 14 normal 8- to 10-year-old males. Heart rate variables, based on all-night analyses of computer-determined beat-to-beat (RR) intervals, were related to sleep stage and sleep cycle measures within and across nights. Time-domain summary statistics revealed a tendency for higher mean heart rates in rapid eye movement (REM) compared to slow-wave (SW) and stage 2 sleep, but the differences were not significant. Heart rate variability, as measured by average RR interval standard deviation, was greatest in stage 2 and least in SW sleep, but it did not vary significantly across sleep stages. Analyses of heart rate variables across the initial four sleep cycles showed a significant heart rate decrease (quadratic trend) and a significant increase (linear trend) for heart rate variability. All effects replicated across nights. Poincare plots revealed wide-ranging individual differences, generally characterized by greater dispersion at longer RR intervals and a remarkable night-to-night consistency in whole-night as well as stage-specific patterns. The sleep-stage plots uniformly indicated reduced overall range and variability in SW relative to REM and stage 2 and a general equivalence of stage 2 and REM patterns. The results indicate several features of sleep-related heart rate variations in preadolescents that differ from those in adults. The differences can be attributed to developmental variations in autonomic cardiac control and are consistent with increased parasympathetic influences reported to occur at this time.

Evidence for time-dependent autonomic cardiac reinnervation in children subsequent to transplantation of the heart

AbstractAutonomic denervation has been assumed to persist after orthotopic heart transplantation. Analyzing spontaneous and induced variations of heart rate, the status of autonomic cardiac innervation was investigated in six children 19–37 months after cardiac transplantation. The age at the time of transplantation varied from three weeks to 15.4 years. Heart rate variability was assessed on 24-hour Holter recordings by calculating time-domain indices (standard deviation of all RR intervals; standard deviation of the mean RR intervals from successive five-minute periods; mean of the standard deviations of RR intervals from successive five-minute periods; proportion of adjacent RR intervals &gt; 50 msec different; square root of mean square successive differences in RR intervals) and frequency-domain variables (low frequency power, high frequency power and total spectrum power). Sinus node recovery time, sinoatrial conduction time and post-pacing cycle lengths were examined at different rates of endocardial atrial pacing. After the first year subsequent to transplantation, standard deviation of the mean RR intervals reached the normal range in four patients, whereas the other time-domain variables became normal in two patients. Both patients displayed normal or near-normal power spectrums of heart rate with normal day-to-night variations. For the remaining patients, spectrums of heart rate failed to show the main frequency peaks. Only the patient with normal variability in heart rate exhibited a decrease in corrected sinus node recovery time at higher stimulation rates, shortening of the first recovery cycle below the pre-pacing level, and a rapid decline of the accelerated post-pacing heart rate as described in innervated hearts. These results suggest the evolution of time-dependent efferent autonomic reinnervation after cardiac transplantation in children.

Heart rate variability and head-up tilt testing in patients with syncope of undetermined etiology.

Indices of heart rate variability are non-invasive indicators of neural control of the heart. To investigate the significance of changes in heart rate variability in neurally mediated syncope, we performed head-up tilt testing in 45 patients with syncope of undetermined etiology. Seventeen patients showed a negative response and 28 showed a positive response; 18 had a vasodepressor response (systolic blood pressure dropped > or = 50% without a decrease in heart rate) and 10 had a vasovagal response (systolic blood pressure dropped > or = 50% with a decrease in heart rate of > or = 30%). The mean RR-interval, the standard deviation of normal sinus RR-intervals (standard deviation of RR-interval) and power spectra were measured in consecutive 2 min periods throughout the study. Power spectra consisted of low frequency (0.04-0.15 Hz), high frequency (0.15-0.40 Hz) and total spectra (0.01-1.0 Hz). Both high frequency spectra and the low/high frequency spectra ratio significantly changed with head-up tilt testing regardless of the response. However, high frequency, low frequency and total spectra increased in relation to symptoms. These changes were most profound in the high frequency spectra of subjects with a vasovagal response. Since high frequency spectra reflect parasympathetic tone, a profound change in the high frequency spectra implies that parasympathetic activities play a significant role in patients with a vasovagal response. The assessment of heart rate variability during head-up tilt testing can provide new insight into the pathogenesis of syncope of undetermined etiology.

Alterations of sympathovagal balance in patients with hypertrophic and dilated cardiomyopathies assessed by spectral analysis of RR interval variability.

Spectral analysis of RR interval variability was performed in 35 ambulatory patients with early hypertrophic cardiomyopathy (HCMa, NYHA class I), 21 hospitalized patients with advanced hypertrophic cardiomyopathy (HCMh, NYHA class II or III), and 18 hospitalized patients with dilated cardiomyopathy (DCMh, NYHA class I, II or III). Twenty-nine ambulatory subjects (COTa) and 20 hospitalized volunteers (COTh) served as normal controls. The RR interval standard deviation (SD), the high-frequency power (HF: 0.15-0.40 Hz) corrected by the mean RR interval (CCVHF) and the normalized unit of the HF power (NUHF) served as markers of vagal modulation. Low-frequency power (LF: 0.04-0.15 Hz) corrected by the mean RR interval (CCVLF) and the normalized unit of LF power (NULF) were markers of sympathetic modulation. The LF/HF ratio was an index of sympathovagal balance. There was no significant difference in the SD, CCVHF, NUHF, CCVLF, NULF or the LF/HF ratio between the HCMa and COTa groups. At night, the SD was lower in the HCMh group relative to the COTh group (P < 0.01). The HCMh group demonstrated lower CCVHF and NUHF values (P < 0.01), higher NULF values (P < 0.01) and higher LF/HF ratios (P < 0.05) at night relative to the COTh group. Two patients who later died suddenly in the HCMh group had markedly reduced CCVHF values (0.2-0.8%) relative to the survivors in the group (mean +/- SD in the morning, afternoon and night, 1.07 +/- 0.43%).(ABSTRACT TRUNCATED AT 250 WORDS)

Do increases in markers of vagal activity imply protection from sudden death? The case of scopolamine.

Low-dose scopolamine increases heart rate variability (HRV) in patients with a prior myocardial infarction (MI). This observation, combined with the evidence that elevated cardiac vagal activity during acute myocardial ischemia is antifibrillatory, has generated the hypothesis that scopolamine might be protective after MI. We tested low-dose scopolamine in a clinically relevant experimental preparation for sudden death in which other vagomimetic interventions are effective. Nineteen mongrel dogs that survived an anterior MI were used in the study. Occurrence or lack of ventricular fibrillation (VF) due to acute myocardial ischemia during submaximal exercise identified dogs at high and low risk for sudden death. Dose-response curves performed in 12 dogs at high (n = 6) and low (n = 6) risk showed that scopolamine at 3 micrograms/kg exerts the greatest effect on HRV. A second group of 7 high-risk dogs were exposed to an exercise-and-ischemia test after treatment with scopolamine (3 micrograms/kg i.v.). Scopolamine increased the standard deviation of RR intervals by 41%, increased the high-frequency band of spectral analysis by 48%, and decreased resting heart rate by 14%. Despite the increase in markers of vagal activity, VF recurred during the exercise-and-ischemia test in 6 dogs (86%). The significant increase in HRV induced by acute scopolamine did not result in a decreased risk for VF due to acute myocardial ischemia in association with sympathetic activation. Caution must be applied when extrapolating the potential antifibrillatory activity of an intervention from its influence on autonomic markers.

The effect of nadolol on heart rate and the standard deviation of the RR intervals

The aim of this study was to evaluate the effect of nadolol in modifying the standard deviation of RR intervals (SDRR) and the coefficient of variance (CV) in 47 patients characterized by symptomatic, frequent (> 30 h-1) and reproducible premature ventricular contractions (PVCs). Sixteen patients had suffered a previous myocardial infarction (Group 1), 22 had various non-ischaemic cardiac diseases (Group 2) and nine had no heart disease (Group 3). All patients underwent two 24 h Holter recordings during the washout period, and a third Holter recording was taken 5 days after the administration of nadolol (80 mg.day-1). The RR cycle length (RR), SDRR and CV were evaluated for each 24 h period, as well as for six daytime (1000-1600h) and six night-time hours (0000-0600h). In all three groups, nadolol was highly effective in lengthening RR. However, the effect on SDRR was different in the three groups; 24-h SDRR tended to be reduced in all three groups (but the reduction was significant only in Group 1) due to a certain RR homogeneity. On the other hand, daytime SDRR tended to increase (but the increase was significant only in Group 3). CV is concomitantly affected by heart rate and SDRR, therefore it may be more sensitive in evaluating the effect of beta-blockers. The reduction in CV post-nadolol means that the bradycardia-induced effect is associated with an inadequate increase, or even a reduction in SDRR, whereas the absence of any CV changes (found only in Group 3) is the result of a concomitant increase in both RR cycle length and SDRR.(ABSTRACT TRUNCATED AT 250 WORDS)

749-2 Autonomic Imbalance in Patients with Inappropriate Sinus Tachycardia

Mechanisms responsible for inappropriate sinus tachycardia (IST) may include an intrinsic defect in the sinus node, autonomic imbalances, or both. To disclose the existence of spontaneous autonomic abnormalities, we analyzed heart rate variability (HRV) in 24-hour ECG recordings in 6 ambulatory adult pts with IST (defined as 24-hr average heart rate ≥ 95 bpm) and in 6 ageand sex-matched normal controls. All subjects were free of heart disease, diabetes, and autonomic disfunction. Mean average HR was 98 ± 2.6 bpm in pts with IST and 69.6 ± 7 bpm in controls. Percent of difference between adjacent RR intervals greater than 50 msec (pNN50) was 2.63 in pts and 23.9 in controls (p &lt; 0.001). Standard deviation of RR intervals (SDNN), root mean square of successive differences (RMSSD), and standard deviation of 5-minute RR intervals (SDANN)forthe 24 hour period were significantly lower in pts than in controls for both day- and night-times (table). SDNN RMSSD SDANN Day Night Day Night Day Night Patients 47.59 51.22 19.04 23.4 62.3 30.7 Controls 98.1 97.78 41.9 58.55 50.55 29.9 P value &lt; 0.001 &lt; 0.001 &lt; 0.001 &lt; 0.001 &lt; 0.001 0.01 Hourly variation for RMSDDs is plotted in the figure. Low and high frequency (freq) power were estimated at 10-min intervals throughout the 24 hour-period. Average Ln of low freq power was 10.26 in pts with IST and 11.27 in controls (p = 0.09). Average Ln of high freq power was 9.81 in pts and 11.31 in controls (p = 0.002). 1) HRV is markedly decreased in pts with IST; 2) This seems to be related to an abnormally low parasympathetic tone; 3) The long-term prognosis of pts with IST deserves further investigation.

Relation between heart rate variability and spontaneous and induced ventricular arrhythmias in patients with coronary artery disease

Objectives. The aim of this study was to determine the relation between autonomic control of heart rate and the spontaneous occurrence and inducibility of ventricular arrhythmias in patients with coronary artery disease.Background. Low heart rate variability increases the risk of arrhythmic events. It is not known whether impaired autonomic heart rate control reflects alterations in functional factors that contribute to the initiation of spontaneous arrhythmias or whether it is the consequence of an anatomic substrate for reentrant tachyarrhythmias.Methods. Fifty-four patients with coronary artery disease with a history of sustained ventricular tachycardia (n = 25) or cardiac arrest (n = 29) were studied by 24-h ambulatory electrocardiographic recording and by programmed electrical stimulation. Heart rate variability was compared among the patients with and without spontaneous ventricular arrhythmias and with and without inducibility of sustained ventricular tachyarrhythmias.Results. Eight patients had a total of 21 episodes of sustained ventricular tachycardia on Holter recordings. Standard deviation of RR intervals and low frequency and very low frequency components of heart rate variability were significantly blunted in patients with sustained ventricular tachycardias compared with those without repetitive ventricular ectopic activity (p < 0.05, p < 0.01 and p < 0.05, respectively). However, no significant alterations were observed in heart rate variability before the onset of 21 episodes of sustained ventricular tachycardia. Heart rate variability did not differ between the patients with or without nonsustained episodes of ventricular tachycardia. In patients with frequent ventricular ectopic activity, low frequency and very low frequency power components were significantly blunted compared with those with infrequent ventricular ectopic activity (p < 0.01 and p < 0.001, respectively). Heart rate variability did not differ significantly between the patients with and without inducible sustained ventricular tachyarrhythmias.Conclusions. Impaired very low and low frequency oscillation of heart rate reflects susceptibility to the spontaneous occurrence of ventricular arrhythmias but may not reflect the instantaneous triggers for life-threatening arrhythmias or a specific marker of the arrhythmic substrate for ventricular tachyarrhythmias.

Late potentials and heart rate variability in heart muscle disease.

To elucidate the incidence and clinical significance of ventricular late potentials (LP) and reduced heart rate variability (HRV) in primary and secondary heart muscle disease, 157 patients with dilated cardiomyopathy (DCM, n = 19), chronic myocarditis (MC, n = 50), hypertrophic cardiomyopathy (HCM, n = 27) and systemic hypertension (HT, n = 61) were studied. LP measured by the signal averaging technique were found in 24% of the total study group--47% of the patients with DCM, 28% with MC, 29% with HCM and 10% with HT. Complex ventricular arrhythmias were detected during Holter monitoring in 56% of patients with DCM, in 41% with MC, in 21% with HT and in 16% with HCM. An electrophysiological study was performed in a total of 75 patients. Non-sustained or sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) were inducible during programmed ventricular stimulation in 32% of patients with MC, in 30% with HT, in 20% with DCM and in 17% with HCM. The total duration of the signal-averaged, filtered QRS complex was the only independent predictive factor for severe arrhythmic events and sudden cardiac death. HRV measured in 39 patients were most reduced in patients with DCM (RR interval standard deviation (HRV-SD) 39 +/- 23 ms), followed by 44 +/- 16 ms in patients with HCM, 45 +/- 28 ms in patients with HCM and 67 +/- 51 ms in patients with HT. A significant reduction in the HRV-SD below 30 ms was recorded in 24% of patients measured.(ABSTRACT TRUNCATED AT 250 WORDS)

353 HEART RATE VARIABILITY AND SUDDEN INFANT DEATH SYNDROME

We studied 465 newborns enrolled in a previous prospective electrocardiographic study to evaluate the predictive value of QT interval for SIDS. We analyzed the ECGs recorded with babies alert on the 4th day of life and after 2, 4, 6 and 12 months. For each ECG, the HRV was calculated using the first standard deviation of RR intervals (ms) measured for 2 minutes. Besides, the HRV values were correlated with QTc values in order to asses a possible relationship between the 2 variables. Data are reported in table:Our data seems to confirm a delayed maturation or impaired fuctioning of the autonomic nervous system in the first months of life, reflecting a direct correlation with QT prolongation.

Effect of Beta-blockade on heart rate variability in patients with coronary artery disease

Objectives. This study assessed the effects of beta-blockade on heart rate variability in patients with coronary artery disease and determined whether the effects of metoprolol in a controlledrelease formulation and atenolol differ with regard to electrocardiographic measures of cardiac autonomic control.Background. Low heart rate variability is common in coronary artery disease and is associated with increased mortality. Beta-adrenergic blocking drugs may increase heart rate variability in healthy subjects, but there is limited knowledge of whether they are able to modify heart rate variability in patients with uncomplicated coronary artery disease.Methods. In a randomly allocated, double-blind crossover study with three 2-week treatment periods, 200 mg of controlledrelease metoprolol once a day, 100 mg of atenolol once a day or placebo once a day were administered in 18 male patients with stable coronary artery disease. The 24-h heart rate variability was measured in both the time and frequency domains.Results. Beta-blokade induced a significant increase in heart rate variability, but no significant differences were found between atenolol and metoprolol. The average 24-h high frequency power increased by 64% after atenolol and by 62% after metoprolol. The root-mean-square successive difference of normal RR intervals increased by 79% after atenolol and by 62% after metoprolol, and the standard deviations of RR intervals increased by 20% and 16%, respectively. Beta-blockade had no significant effects on the amplitude of the circadian rhythm of heart rate variability, although both metoprolol and atenolol blunted the abrupt decrease of high frequency power after arousal.Conclusions. Beta-blockade by metoprolol and atenolol enhance the heart rate variability in patients with coronary artery disease. This may contribute to the protective effects of betablockade in ischemic heart disease.

Letters to the editor

Summary: To evaluate heart rate variability (expressed as the standard deviation of RR intervals) within 5 years of follow-up, we studied 20 patients (14 males, 6 females, mean age 44 f I2 years) who underwent orthotopic heart transplantation. Six measurements were taken: one in the first 3 weeks after transplantation, and the others once annually, for 5 years. Twenty healthy subjects (mean age 44 f 7 years) constituted the control group. Heart rate variability increased significantly inthefirst3yearsoffollow-up(7.2f 1 vs. 11.1 f4,p<0.001; 1 I. 1 f 4 vs. 15.2 k 4, p<O.OI; 15.2 k 4 vs. 18.9 k 5, p< 0.05); in the following years this trend slackened and values did not reach a statistically significant difference ( 18.9 f 5 vs. 2 1.4 f 5; 2 1.4 f 5 vs. 22.5 k 5). The mean standard deviation was invariably greater in the control group (63.6 f 12). These findings show that sinus rhythm variability in the denervated heart progressively increased over 5 years of follow-up. The absence of presynaptic uptake, which is responsible for adrenergic hypersensitivity to circulating catecholamines and intrinsic cardiac reflexes, does not appear to cause this phenomenon, since these mechanisms are not able to evolve in time after cardiac transplantation. Therefore, an enhanced beta-adrenergic receptors density or affinity to circulating catecholamines or a limited sympathetic reinnervation may be the more probable underlying mechanism.

Heart rate variability in patients with orthotopic heart transplantation: Long‐term follow‐up

To evaluate heart rate variability (expressed as the standard deviation of RR intervals) within 5 years of follow-up, we studied 20 patients (14 males, 6 females, mean age 44 +/- 12 years) who underwent orthotopic heart transplantation. Six measurements were taken: one in the first 3 weeks after transplantation, and the others once annually, for 5 years. Twenty healthy subjects (mean age 44 +/- 7 years) constituted the control group. Heart rate variability increased significantly in the first 3 years of follow-up (7.2 +/- 1 vs. 11.1 +/- 4, p < 0.001; 11.1 +/- 4 vs. 15.2 +/- 4, p < 0.01; 15.2 +/- 4 vs. 18.9 +/- 5, p < 0.05); in the following years this trend slackened and values did not reach a statistically significant difference (18.9 +/- 5 vs. 21.4 +/- 5; 21.4 +/- 5 vs. 22.5 +/- 5). The mean standard deviation was invariably greater in the control group (63.6 +/- 12). These findings show that sinus rhythm variability in the denervated heart progressively increased over 5 years of follow-up. The absence of presynaptic uptake, which is responsible for adrenergic hypersensitivity to circulating catecholamines and intrinsic cardiac reflexes, does not appear to cause this phenomenon, since these mechanisms are not able to evolve in time after cardiac transplantation. Therefore, an enhanced beta-adrenergic receptors density or affinity to circulating catecholamines or a limited sympathetic reinnervation may be the more probable underlying mechanism.

Circadian rhythm of heart rate variability in survivors of cardiac arrest

Reduced heart rate (HR) variability is associated with increased risk of cardiac arrest in patients with coronary artery disease. In this study, the power spectral components of HR variability and their circadian pattern in 22 survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction were compared with those of 22 control patients matched with respect to age, sex, previous myocardial infarction, ejection fraction and number of diseased coronary arteries. Survivors of cardiac arrest had significantly lower 24-hour average standard deviation of RR intervals than control patients (29 ± 10 vs 51 ±15 ms, p < 0.001), and the 24-hour mean high frequency spectral area was also lower in survivors of cardiac arrest than in control patients (13 ± 7 ms 2 × 10 vs 28 ± 14 ms 2 × 10, p < 0.01). In a single cosinor analysis, a significant circadian rhythm of HR variability was observed in both groups with the acrophase of standard deviation of RR intervals and high-frequency spectral area occurring between 3 and 6 A.M. which was followed by an abrupt decrease in HR variability after arousal. The amplitude of the circadian rhythm of HR variability did not differ between the groups. Thus, HR variability is reduced in survivors of cardiac arrest but its circadian rhythm is maintained so that a very low HR variability is observed in the morning after awakening, corresponding to the time period at which the incidence of sudden cardiac death is highest.

Correlation dimension of heartbeat intervals is reduced in conscious pigs by myocardial ischemia.

A reduced standard deviation of RR intervals (SDRR) predicts increased mortality in groups of survivors of myocardial infarction. Like SDRR, the correlation dimension (D2) describes variation within a sampled time series, but uniquely it reveals 1) the epoch's geometric structure and 2) the degrees of freedom of the generator. These unique features may be more sensitive predictors of mortality than SDRR. We developed a new algorithm for estimating D2 (i.e., the "point-D2"), tested it with known data, and found that it had greater accuracy for finite data than other published algorithms. Analysis of RR intervals from eight conscious pigs undergoing acute occlusion of the left anterior descending coronary artery revealed a drop in the point-D2 from a control mean and standard deviation of 2.50 +/- 0.81 to 1.58 +/- 0.64 during the first minute of ischemia (p less than 0.01) and to 1.07 +/- 0.18 during the last minute preceding ventricular fibrillation (p less than 0.01). Partial occlusions (50-90% reduction of coronary blood flow) evoked point-D2 reductions only 25-30% of control (p less than 0.01). The point-D2 means were correlated between pigs with the magnitude of the respiratory sinus arrhythmia (p less than 0.01), but during ischemia this correlation was replaced by one between the standard deviation of the point-D2s and SDRRs. Because the simultaneous reduction in the mean point-D2 and its standard deviation to 1.07 +/- 0.18 occurred in every case, was unique to the few minutes preceding ventricular fibrillation, and never reached these low values during other conditions in which it was reduced, we conclude that the point-D2 may be an accurate prospective predictor of mortality within the individual subject.