Comparison of spontaneous vs. metronome-guided breathing on assessment of vagal modulation using RR variability.

R-R interval variability (RR variability) is increasingly being used as an index of autonomic activity. High-frequency (HF) power reflects vagal modulation of the sinus node. Since vagal modulation occurs at the respiratory frequency, some investigators have suggested that HF power cannot be interpreted unless the breathing rate is controlled. We hypothesized that HF power during spontaneous breathing would not differ significantly from HF power during metronome-guided breathing. We measured HF power during spontaneous breathing in 20 healthy subjects and 19 patients with heart disease. Each subject's spontaneous breathing rate was determined, and the calculation of HF power was repeated with a metronome set to his or her average spontaneous breathing rate. There was no significant difference between the logarithm of HF power measured during spontaneous and metronome-guided breathing [4.88 +/- 0.29 vs. 5.29 +/- 0.30 ln(ms(2)), P = 0.32] in the group as a whole and when patients and healthy subjects were examined separately. We did observe a small (9.9%) decrease in HF power with increasing metronome-guided breathing rates (from 9 to 20 breaths/min). These data indicate that HF power during spontaneous and metronome-guided breathing differs at most by very small amounts. This variability is several logarithmic units less than the wide discrepancies observed between healthy subjects and cardiac patients with a heterogeneous group of cardiovascular disorders. In addition, HF power is relatively constant across the range of typical breathing rates. These data indicate that there is no need to control breathing rate to interpret HF power when RR variability (and specifically HF power) is used to identify high-risk cardiac patients.

Mechanisms of death in the CABG Patch trial: a randomized trial of implantable cardiac defibrillator prophylaxis in patients at high risk of death after coronary artery bypass graft surgery.

BACKGROUND: The CABG Patch trial compared prophylactic implantable cardiac-defibrillator (ICD) implantation with no antiarrhythmic therapy in coronary bypass surgery patients who had a left ventricular ejection fraction <0.36 and an abnormal signal-averaged ECG. There were 102 deaths among the 446 ICD group patients and 96 deaths among the 454 control group patients, a hazard ratio of 1.07 (P=0.63). The mechanisms of death were classified, and hypotheses were tested about the effects of ICD therapy on arrhythmic and nonarrhythmic cardiac deaths in the CABG Patch Trial and the Multicenter Automatic Defibrillator Implantation Trial (MADIT). METHODS AND RESULTS: The 198 deaths in the trial were reviewed by an independent Events Committee and classified by the method of Hinkle and Thaler. Only 54 deaths (27%) occurred out of hospital; 145 deaths (73%) were witnessed. Seventy-nine (82%) of the 96 deaths in the control group and 76 (75%) of the 102 deaths in the ICD group were due to cardiac causes. Cumulative arrhythmic mortality at 42 months was 6.9% in the control group and 4.0% in the ICD group (P=0. 057). Cumulative nonarrhythmic cardiac mortality at 42 months was 12. 4% in the control group and 13.0% in the ICD group (P=0.275). Death due to pump failure was significantly associated with death >1 hour from the onset of symptoms, dyspnea within 7 days of death, and overt heart failure within 7 days of death. CONCLUSIONS: In the CABG Patch Trial, ICD therapy reduced arrhythmic death 45% without significant effect on nonarrhythmic deaths. Because 71% of the deaths were nonarrhythmic, total mortality was not significantly reduced.

R-R variability detects increases in vagal modulation with phenylephrine infusion.

High-frequency power, measured from power spectral analysis of R-R variability, reflects vagal modulation of the sinus node. Unexpectedly, a recent study reported a decrease in high-frequency power during the infusion of phenylephrine despite a prolongation of R-R intervals, indicating an increase in vagal activity. To better define the limitations of high-frequency power to quantify vagal modulation, we measured high-frequency power during the infusion of phenylephrine (0.4, 0.8, and 1.2 micrograms.kg-1.min-1) into 10 normal subjects. We found increasing doses of phenylephrine produced progressive increases in systolic blood pressure from 118 +/- 4 to 129 +/- 5 mmHg (P < 0.005), R-R intervals from 881 +/- 44 to 1,274 +/- 69 ms (P < 0.0001), and the logarithm of high-frequency power from 5.83 +/- 0.22 to 7.73 +/- 0.24 ln(ms2) (P < 0.0001). The conclusion was high-frequency power increases with increasing doses of phenylephrine. These data strongly support the ability of high-frequency power to detect an increase in vagal modulation during baroreceptor activation from an increase in systolic blood pressure with the infusion of phenylephrine.

Baseline characteristics of patients in the coronary artery bypass graft (CABG) Patch Trial.

BACKGROUND: Patients with left ventricular dysfunction who undergo coronary artery bypass graft (CABG) surgery frequently have late sudden cardiac death. The CABG Patch Trial is a prospective, randomized, multicenter clinical trial that randomized patients at high risk at the completion of CABG surgery to implantation of an epicardial implantable cardioverter defibrillator (ICD) or to no antiarrhythmic treatment. The trial was designed to determine whether prophylactic implantation of an ICD at the time of CABG surgery would result in a lower total mortality in long-term follow-up. METHODS: Patients undergoing CABG surgery were eligible for the trial if they were younger than 80 years, had a left ventricular ejection fraction less than 0.36, and had an abnormal signal averaged electrocardiogram. Patients with a history of sustained ventricular tachycardia or ventricular fibrillation were excluded from the trial. All patients were scheduled to undergo follow-up at 3-month intervals until 42 months after surgery. RESULTS: Randomization of patients in the trial ended in February 1996. During the recruitment period 71,855 patients were screened, 1,422 were eligible, 1,055 were enrolled (signed consent forms), and 900 patients (76% of eligible patients) were randomized. The mean age of the 446 patients in the ICD group was 64 years versus 63 years for the 454 patients in the control group. A total of 87% of the participants in the ICD group were men versus 82% in the control group (p = NS). Most of the patients had a history of hypertension (55%), smoking (78%), and hypercholesterolemia (54%). Half of the patients had clinical heart failure, and the mean ejection fraction for both patient groups was 0.27 +/- 0.06. No difference was seen in the history of myocardial infarction (83%), congestive heart failure (50%), or atrial (11%) or ventricular (17%) arrhythmias between the two groups. Major clinical characteristics (age, sex, number of previous infarctions, incidence of heart failure, and mean left ventricular ejection fraction) were almost identical to those found in another ICD primary prevention trial, the Multicenter Automatic Defibrillator Implantation Trial (MADIT). CONCLUSIONS: A high risk sample of patients was enrolled in The CABG Patch Trial, as shown by examination of their baseline characteristics.

Long-term carvedilol therapy increases parasympathetic nervous system activity in chronic congestive heart failure.

To determine the effect of beta blockade on parasympathetic nervous system activity, we assessed RR variability during 24-hour Holter monitoring in 10 patients with congestive heart failure before and after 3 to 4 months of treatment with the beta blocker carvedilol. High-frequency power increased from 26 to 64 ms2, root-mean-square of successive differences in RR interval increased from 14.3 to 23.7 ms2, and percentage of absolute differences >50 ms between successive normal RR intervals increased from 0.8% to 4.7%, all p <0.01, indicating a substantial increase in parasympathetic modulation of RR intervals.

Physical fitness as a determinant of vagal modulation.

The association between increasing age and decreasing vagal modulation is well known. However, the importance of fitness as a determinant of the decline in vagal modulation with age is not established. To test the hypothesis that decreasing vagal modulation is largely a function of declining fitness rather than increasing age, we studied a sample of healthy volunteers with a wide range of fitness levels, but a narrow age range. We assessed fitness by measuring the maximal oxygen uptake (VO2max) achieved during incremental bicycle exercise. Vagal modulation was assessed by calculating high frequency power (0.15-0.40 Hz) of the RR variability power spectrum from 24-h ECG recordings. We studied 37 healthy volunteers who were 22-44 yr old. In our sample, VO2max ranged from 25 to 70 mL.min-1.kg-1 (mean of 45 +/- 13). Age was not significantly related to high frequency power, but VO2max was highly correlated with high frequency power (r = 0.74, P = 0.0001), indicating that physical fitness is strongly associated with vagal modulation. Thus, the decline in vagal modulation often attributed to increasing age may, instead, be the result of a decline in fitness.

Power law behavior of RR-interval variability in healthy middle-aged persons, patients with recent acute myocardial infarction, and patients with heart transplants.

BACKGROUND: The purposes of the present study were (1) to establish normal values for the regression of log(power) on log(frequency) for, RR-interval fluctuations in healthy middle-aged persons, (2) to determine the effects of myocardial infarction on the regression of log(power) on log(frequency), (3) to determine the effect of cardiac denervation on the regression of log(power) on log(frequency), and (4) to assess the ability of power law regression parameters to predict death after myocardial infarction. METHODS AND RESULTS: We studied three groups: (1) 715 patients with recent myocardial infarction; (2) 274 healthy persons age and sex matched to the infarct sample; and (3) 19 patients with heart transplants. Twenty-four-hour RR-interval power spectra were computed using fast Fourier transforms and log(power) was regressed on log(frequency) between 10(-4) and 10(-2) Hz. There was a power law relation between log(power) and log(frequency). That is, the function described a descending straight line that had a slope of approximately -1 in healthy subjects. For the myocardial infarction group, the regression line for log(power) on log(frequency) was shifted downward and had a steeper negative slope (-1.15). The transplant (denervated) group showed a larger downward shift in the regression line and a much steeper negative slope (-2.08). The correlation between traditional power spectral bands and slope was weak, and that with log(power) at 10(-4) Hz was only moderate. Slope and log(power) at 10(-4) Hz were used to predict mortality and were compared with the predictive value of traditional power spectral bands. Slope and log(power) at 10(-4) Hz were excellent predictors of all-cause mortality or arrhythmic death. To optimize the prediction of death, we calculated a log(power) intercept that was uncorrelated with the slope of the power law regression line. We found that the combination of slope and zero-correlation log(power) was an outstanding predictor, with a relative risk of > 10, and was better than any combination of the traditional power spectral bands. The combination of slope and log(power) at 10(-4) Hz also was an excellent predictor of death after myocardial infarction. CONCLUSIONS: Myocardial infarction or denervation of the heart causes a steeper slope and decreased height of the power law regression relation between log(power) and log(frequency) of RR-interval fluctuations. Individually and, especially, combined, the power law regression parameters are excellent predictors of death of any cause or arrhythmic death and predict these outcomes better than the traditional power spectral bands.

Vagal modulation of RR intervals during head-up tilt and the infusion of isoproterenol.

The objective of this study was to characterize the autonomic effects of 2 interventions, head-up tilt and isoproterenol infusion, which alter autonomic balance by different mechanisms but produce the same RR intervals. We compared the effect of head-up tilt with the effect of isoproterenol on autonomic balance as measured by power spectral analysis of RR variability. Fifteen normal subjects had baseline measurements and then underwent head-up tilt. After return to baseline supine values, isoproterenol was infused at a rate of 1 microgram/min (low-dose isoproterenol), which was then increased to 2.1 +/- 0.5 microgram/min (high-dose isoproterenol). All subjects underwent a second tilt during high-dose isoproterenol, and 9 subjects completed this second tilt study. During the experiment, normal RR intervals were recorded and 5-minute segments were used to calculate power spectra. High-frequency (HF) power (0.15 to 0.40 Hz) was used as a measure of vagal activity. The effects of head-up tilt were compared with the effects of low-dose isoproterenol. Despite nearly identical mean RR intervals (784 ms with tilt vs 792 ms with low-dose isoproterenol, p = NS), there was significantly (p < 0.05) less HF power during head-up tilt in the drug-free state (172 ms2) than during low-dose isoproterenol in the supine position (307 ms2). A second head-up tilt was performed during the infusion of high-dose isoproterenol. During high-dose isoproterenol, tilt caused a decrease in RR intervals (from 573 to 491 ms; p < 0.01) and a decrease in HF power (from 68 to 28 ms2; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

RR variability in healthy, middle-aged persons compared with patients with chronic coronary heart disease or recent acute myocardial infarction.

BACKGROUND: The purpose of this investigation was to establish normal values of RR variability for middle-aged persons and compare them with values found in patients early and late after myocardial infarction. We hypothesized that presence or absence of coronary heart disease, age, and sex (in this order of importance) are all correlated with RR variability. METHODS AND RESULTS: To determine normal values for RR variability in middle-aged persons, we recruited a sample of 274 healthy persons 40 to 69 years old. To determine the effect of acute myocardial infarction RR variability, we compared measurements of RR variability made 2 weeks after myocardial infarction (n = 684) with measurements made on age- and sex-matched middle-aged subjects with no history of cardiovascular disease (n = 274). To determine the extent of recovery of RR variability after myocardial infarction, we compared measurements of RR variability made in the group of healthy middle-aged persons with measurements made in 278 patients studied 1 year after myocardial infarction. We performed power spectral analyses on continuous 24-hour ECG recordings to quantify total power, ultralow-frequency (ULF) power, very-low-frequency (VLF) power, low-frequency (LF) power, high-frequency (HF) power, and the ratio of LF to HF (LF/HF) power. Time-domain measures also were calculated. All measures of RR variability were significantly and substantially lower in patients with chronic or subacute coronary heart disease than in healthy subjects. The difference from normal values was much greater 2 weeks after myocardial infarction than 1 year after infarction, but the fractional distribution of total power into its four component bands was similar for the three groups. In healthy subjects, ULF power did not change significantly with age; VLF, LF, and HF power decreased significantly as age increased. Patients with chronic coronary heart disease showed little relation between power spectral measures of RR variability and age. Patients with a recent myocardial infarction showed a strong inverse relation between VLF, LF, and HF power and age and a weak inverse relation between ULF power and age. ULF power best separates the healthy group from either of the two coronary heart disease groups. Differences in RR variability between men and women were small and inconsistent among the three groups. CONCLUSIONS: All measures of RR variability were significantly and substantially higher in healthy subjects than in patients with chronic or subacute coronary heart disease. The difference between healthy middle-aged persons and those with coronary heart disease was much greater 2 weeks after myocardial infarction than 1 year after infarction, but the fractional distribution of total power into its four component bands was similar for the healthy group and the two coronary heart disease groups. Values of RR variability previously reported to predict death in patients with known chronic coronary heart disease are rarely (approximately 1%) found in healthy middle-aged individuals. Thus, when measures of RR variability are used to screen groups of middle-aged persons to identify individuals who have substantial risk of coronary deaths or arrhythmic events, misclassification of healthy middle-aged persons should be rare.

Brief interval heart period variability by different methods of analysis correlates highly with 24 h analyses in normals.

Heart period variability (HPV) measured from 24 h ECG recordings predicts mortality following myocardial infarction and may be a measure of cardiovascular health in the general population. Since epidemiologic evaluation of healthy people will require alternatives less intensive than 24 h recording, we investigated the relationship between HPV derived from 24 h and 5 min recordings, using two approaches for obtaining RR intervals. Template-matching (TM) algorithms were applied to 24 h ECG recordings from 41 normal subjects (mean age 35.7 +/- 13 years). Five min of ECG data during this 24 h period also were collected by an on-line microcomputer-based system for peak detection (PD) analysis. Intraclass correlations comparing the TM and PD approaches on the 5 min period were .80 or greater for all measures of HPV. Pearson correlation coefficients between the 5 min (TM) estimates and 24 h data and 5 min (PD) estimates and 24 h data exceeded .60 and .55, respectively, for all but one variable, with all p values < .05. Thus, in healthy adults, TM and PD approaches to HPV estimation from short segments of ECG data are highly consistent and the correlations between HPV obtained from brief intervals and 24 h measures were substantial, suggesting that assessment of HPV as a screening measure of cardiac autonomic control in healthy adults may be feasible.

Effect of mental stress throughout the day on cardiac autonomic control.

Although many laboratory studies have demonstrated changes in cardiac autonomic control during psychological stress, few have attempted to demonstrate this effect in ambulatory subjects. To address this issue, 24-h electrocardiographic recordings of 33 healthy subjects were analyzed for RR interval and heart period variability (HPV) responses associated with periodic diary entries measuring physical position, negative effect, and time of day. A total of 362 diary entries were made during the 24-h sessions, each in response to a device which signaled on an average of once per hour. HPV was analyzed in the frequency domain, yielding estimates of spectral power in low (LF) and high (HF) frequency bands, as well as the LF/HF ratio. Because of the high correlations of the measures of negative affect (alpha = 0.91), they were combined to create a single index of stress. Multivariate analysis was used to assess the effect of individual subject differences, physical position, and stress on RR interval and HPV. Results revealed significant effects of individual differences, stress, and physical position on RR interval, with increases in stress associated with decreases in RR interval as expected. HF power was significantly lower and the LF/HF ratio significantly higher in the standing compared with the sitting position. Psychological stress was significantly associated with an increase in the LF/HF ratio, suggesting increases in the relative predominance of sympathetic nervous system activity during stressful periods of the day. Overall, these findings suggest that in ambulatory normal subjects, cardiac autonomic control varies throughout the day as a function of self-reported stress.

Predicting mortality after myocardial infarction from the response of RR variability to antiarrhythmic drug therapy.

OBJECTIVES: This study was designed to test the hypothesis that antiarrhythmic drugs that decrease RR variability will predict all-cause mortality during follow-up after myocardial infarction. BACKGROUND: RR variability, a noninvasive indicator of autonomic nervous system activity, predicts death after acute myocardial infarction independently of other risk predictors and changes substantially in response to some drugs. A previous study in patients with chronic heart disease and frequent ventricular premature complexes reported that flecainide decreased vagal modulation of RR intervals but amiodarone did not. The investigators of that study speculated that changes in RR variability during antiarrhythmic drug therapy predict an increased mortality rate during long-term drug treatment. To explore this hypothesis further, we compared the effects of encainide and flecainide, which increase long-term mortality substantially, on RR variability with the effects of placebo and moricizine, which have no significant effect on mortality during long-term treatment of unsustained ventricular arrhythmias after myocardial infarction. METHODS: The 24-h power spectral density was computed from the baseline electrocardiographic recordings and drug evaluation tapes, and six frequency domain measures of RR variability were calculated: ultra-low frequency (< 0.0033 Hz), very low frequency (0.0033 to < 0.04 Hz), low frequency (0.04 to < 0.15 Hz) and high frequency power (0.15 to < 0.40 Hz), plus total power (< 0.40 Hz) and the ratio of low to high frequency power. Changes in power spectral measures were related to drug treatment and to mortality. RESULTS: In the placebo group, values for RR interval and RR variability increased because of recovery from the effects of acute myocardial infarction. Contrasting placebo treatment with all three active antiarrhythmic drug treatments taken together showed that of all the measures of RR variability, only NN50, pNN50 and low frequency power changed significantly during drug treatment (Bonferroni adjusted p value < 0.025); these variables all decreased during drug therapy. Contrasting encainide and flecainide with moricizine, we found that the encainide and flecainide groups taken together showed a larger decrease in dLF than moricizine, but the difference was of borderline significance (Bonferroni adjusted p value < 0.08). Survival was significantly worse in the groups treated with encainide and flecainide than in the groups treated with placebo or moricizine (relative risk > 2.0, adjusted p < 0.05). The antiarrhythmic drug-induced change in measures of RR variability was not a significant predictor of all-cause mortality during a year of follow-up after myocardial infarction. CONCLUSIONS: Encainide, flecainide and moricizine all caused a decrease in RR variability in patients studied approximately 1 month after acute myocardial infarction. Encainide and flecainide caused a significant increase in mortality rates; placebo and moricizine did not. Baseline measurements of RR variability also predicted all-cause mortality after myocardial infarction. The decrease in RR variability produced by the three antiarrhythmic drugs did not predict mortality during follow-up.

The ability of several short-term measures of RR variability to predict mortality after myocardial infarction.

BACKGROUND: We studied 715 patients 2 weeks after myocardial infarction to test the hypothesis that short-term power spectral measures of RR variability (calculated from 2 to 15 minutes of normal RR interval data) will predict all-cause mortality or arrhythmic death. METHODS AND RESULTS: We performed power spectral analyses on the entire 24-hour RR interval time series. To compare with the 24-hour analyses, we selected short segments of ECG recordings from two time periods for analysis: 8 AM to 4 PM and midnight to 5 AM. The former corresponds to the time interval during which short-term measures of RR variability would most likely be obtained. The latter, during sleep, represent a period of increased vagal tone, which may simulate the conditions that exist when patients have a signal-averaged ECG recorded, ie, lying quietly in the laboratory. Four frequency domain measures were calculated from spectral analysis of heart period data over a 24-hour interval. We computed the 24-hour power spectral density and calculated the power within three frequency bands: (1) 0.0033 to < 0.04 Hz, very low frequency power, (2) 0.04 to < 0.15 Hz, low frequency power, and (3) 0.15 to 0.40 Hz, high frequency power. In addition, we calculated the ratio of low to high frequency power. These measures were calculated for 15-, 10-, 5-, and 2-minute segments during the day and at night. Mean power spectral values from short periods during the day and night were similar to 24-hour values, and the correlations between short segment values and 24-hour values were strong (many correlations were > or = 0.75). Using the optimal cutpoints determined previously for the 24-hour power spectral values, we compared the survival experience of patients with low values for RR variability in short segments of ECG recordings to those with high values. We found that power spectral measures of RR variability were excellent predictors of all-cause, cardiac, and arrhythmic mortality and sudden death. Patients with low values were 2 to 4 times as likely to die over an average follow-up of 31 months as were patients with high values. The power spectral measures of RR variability did not predict arrhythmic or sudden deaths substantially better than all-cause mortality. CONCLUSIONS: Power spectral measures of RR variability calculated from short (2 to 15 minutes) ECG recordings are remarkably similar to those calculated over 24 hours. The power spectral measures of RR variability are excellent predictors of all-cause mortality and sudden cardiac death.

Effects of digoxin and enalapril on heart period variability and response to head-up tilt in normal subjects.

To test the effects of digitalis and angiotensin-converting enzyme inhibition on the RR interval variability in an electrocardiogram, 20 normal subjects were given digoxin 0.25 mg, enalapril 10 mg, and placebo twice daily in a randomized, double-blind, crossover study. Continuous 24-hour electrocardiographic recordings obtained on day 5 of each treatment were analyzed and several time domain and power spectral measures of heart period variability were calculated. Digoxin markedly increased (up to 51%) indexes of vagal modulation of heart period without changing mean RR interval. Enalapril did not change any measure of heart period variability despite a modest hypotensive effect. To determine the effect of each treatment on the response to orthostatic stress, 10 subjects also underwent 15 minutes of 60 degrees head-up tilt; power spectra were calculated for 15 minutes at 0 degree and at 60 degrees of tilt. Neither active treatment affected the response to head-up tilt.

Frequency domain measures of heart period variability to assess risk late after myocardial infarction.

OBJECTIVES: To determine whether spectral measures of heart period (RR) variability predict death when measured late after infarction, we studied patients in the Cardiac Arrhythmia Pilot Study (CAPS) who survived for 1 year and had a 24-h electrocardiographic (ECG) recording made after the CAPS drug was washed out. BACKGROUND: Four components of the heart period power spectrum--ultra low frequency (< 0.0033 Hz), very low frequency (0.0033 to < 0.04 Hz), low frequency (0.04 to < 0.15 Hz) and high frequency power (0.15 to < 0.40 Hz)--plus total power (1.157 x 10(-5) to < 0.40 Hz) and the ratio of low to high frequency power predict mortality when measured < 30 days after myocardial infarction. However, these variables increase to steady state values by 3 months after infarction and the prognostic significance of recovery values is unknown. METHODS: The 24-h power spectral density was computed from ECG recordings made 1 year after infarction using fast Fourier transforms and the six measures listed were calculated. The values were dichotomized at cut points that maximized the association with mortality. RESULTS: Each measure of RR variability had a strong and significant univariate association with mortality; the relative risks for these variables ranged from 2.5 to 5.6. After adjustment for age, New York Heart Association functional class, rales in the coronary care unit, left ventricular ejection fraction and ventricular arrhythmias, some measures of heart period variability still had a strong and significant independent association with all-cause mortality. CONCLUSIONS: Spectral measures of heart period variability, measured late after infarction, predict death.

Comparison of 24-hour parasympathetic activity in endurance-trained and untrained young men.

OBJECTIVES: This study compares 24-h parasympathetic activity in aerobically trained and untrained healthy young men. BACKGROUND: Higher values of parasympathetic nervous system activity are associated with a low mortality rate in patients after myocardial infarction, but it remains uncertain what therapeutic interventions can be used to increase parasympathetic activity. Although it is thought that exercise training can increase parasympathetic activity, studies have reported conflicting results, perhaps because this variable was measured for only brief intervals and usually inferred from changes in reflex responses induced by pharmacologic blockade. METHODS: Parasympathetic activity was assessed noninvasively from 24-h ECG recordings by calculating high frequency (0.15 to 0.40 Hz) beat to beat heart period variability in eight endurance-trained men (maximal oxygen consumption greater than or equal to 55 ml/kg per min) and eight age-matched (mean = 29 yr) untrained men (maximal oxygen consumption less than or equal to 40 ml/kg per min). The data were analyzed separately for sleeping hours when parasympathetic activity is dominant and also for waking hours. RESULTS: The geometric mean of high frequency power was greater in the trained than in the untrained men during the day (852 vs. 177 ms2, p less than 0.005), during the night (1,874 vs. 427 ms2, p less than 0.005) and over the entire 24 h (1,165 vs. 276 ms2, p less than 0.001). CONCLUSIONS: Parasympathetic activity is substantially greater in trained than in untrained men, and this effect is present during both waking and sleeping hours. These data suggest that exercise training may increase parasympathetic activity over the entire day and may therefore prove to be a useful adjunct or alternative to drug therapy in lessening the derangements of autonomic balance found in many cardiovascular diseases.

Correlations among time and frequency domain measures of heart period variability two weeks after acute myocardial infarction.

Seven hundred fifteen participants from a multicenter natural history study of acute myocardial infarction were studied (1) to determine the correlations among time and frequency domain measures of heart period variability, (2) to determine the correlations between the measures of heart period variability and previously established post-infarction risk predictors, and (3) to determine the predictive value of time domain measures of heart period variability for death during follow-up after acute myocardial infarction. Twenty-four hour electrocardiographic recordings obtained 11 +/- 3 days after acute myocardial infarction were analyzed and 11 measures of heart period variability were computed. Each of 4 bands in the heart period power spectrum had 1 or 2 corresponding variables in the time domain that correlated with it so strongly (r greater than or equal to 0.90) that the variables were essentially equivalent: ultra low frequency power with SDNN* and SDANN index,* very low frequency power and low-frequency power with SDNN index,* and high-frequency power with r-MSSD* and pNN50.* As expected from theoretical considerations, SDNN and the square root of total power were almost perfectly correlated. Correlations between the time and frequency domain measures of heart period variability and previously identified postinfarction risk predictors, e.g., left ventricular ejection fraction and ventricular arrhythmias, are remarkably weak. Time domain measures of heart period variability, especially those that measure ultra low or low-frequency power, are strongly and independently associated with death during follow-up. * Defined in Table II.

Stability over time of heart period variability in patients with previous myocardial infarction and ventricular arrhythmias. The CAPS and ESVEM investigators.

To determine the reproducibility of frequency domain measures of heart period variability in patients with previous myocardial infarction, 2 random samples of 40 patients each (1 from the Cardiac Arrhythmia Pilot Study [CAPS] [unsustained ventricular arrhythmias], and 1 from the Electrophysiologic Studies Versus Electrocardiographic Monitoring [ESVEM] [sustained ventricular arrhythmias] trial) were studied. For each patient, two 24-hour continuous electrocardiographic recordings were analyzed, and the average normal RR interval, total power and 4 components of total power were calculated. Group means and standard deviations for each sample were virtually identical for the pairs of 24-hour recordings. Furthermore, measurements for individual patients were stable from day to day, as measured by the intraclass correlation coefficients and the standard errors of measurement. Reproducibility of heart period variability measurements is excellent in patients with previous myocardial infarction and ventricular arrhythmias, and is comparable to the high stability previously found in a small group of normal subjects. The stability of measures of heart period variability facilitates distinguishing real changes due to progression or regression of cardiac disease or to drug effects from apparent changes due to random variation.

Frequency domain measures of heart period variability and mortality after myocardial infarction.

BACKGROUND: We studied 715 patients 2 weeks after myocardial infarction to establish the associations between six frequency domain measures of heart period variability (HPV) and mortality during 4 years of follow-up. METHODS AND RESULTS: Each measure of HPV had a significant and at least moderately strong univariate association with all-cause mortality, cardiac death, and arrhythmic death. Power in the lower-frequency bands--ultra low frequency (ULF) and very low frequency (VLF) power--had stronger associations with all three mortality end points than power in the higher-frequency bands--low frequency (LF) and high frequency (HF) power. The 24-hour total power also had a significant and strong association with all three mortality end points. VLF power was the only variable that was more strongly associated with arrhythmic death than with cardiac death or all-cause mortality. In multivariate Cox regression models using a step-up approach to evaluate the independent associations between frequency domain measures of heart period variability and death of all causes, ULF power was selected first (i.e., was the single component with the strongest association). Adding VLF or LF power to the Cox regression model significantly improved the prediction of outcome. With both ULF and VLF power in the Cox regression model, the addition of the other two components, LF and HF power, singly or together, did not significantly improve the prediction of all-cause mortality. We explored the relation between the heart period variability measures and all-cause mortality, cardiac death, and arrhythmic death before and after adjusting for five previously established postinfarction risk predictors: age, New York Heart Association functional class, rales in the coronary care unit, left ventricular ejection fraction, and ventricular arrhythmias detected in a 24-hour Holter ECG recording. CONCLUSIONS: After adjustment for the five risk predictors, the association between mortality and total, ULF, and VLF power remained significant and strong, whereas LF and HF power were only moderately strongly associated with mortality. The tendency for VLF power to be more strongly associated with arrhythmic death than with all-cause or cardiac death was still evident after adjusting for the five covariates. Adding measures of HPV to previously known predictors of risk after myocardial infarction identifies small subgroups with a 2.5-year mortality risk of approximately 50%.