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J T Bigger

Publications and source records attributed to J T Bigger.

At least 19 recordsLinked to original sources
PubMed1996

Patency of infarct-related artery. Effect of restoration of anterograde flow on vagal reflexes. ATRAMI (Automatic Tone and Reflexes After Myocardial Infarction) Investigators.

BACKGROUND: In post-myocardial infarction (MI) patients, the restoration of anterograde flow in the infarct-related artery (IRA) significantly improves survival. Limitation of infarct size and increased electrical stability of the myocardium are likely operating mechanisms for this beneficial effect. We tested the hypothesis that patency of the IRA may enhance vagal reflexes, a factor known to affect electrical stability of the infarcted myocardium. METHODS AND RESULTS: Analysis of angiographic data was performed in 359 of 1284 post-MI patients enrolled in a multicenter prospective study within 8 weeks after the index MI. All the patients underwent baroreflex sensitivity (BRS) assessment by the phenylephrine method. The BRS of the entire population averaged 8.2+/-5.5 ms/mm Hg and was significantly related to age but not to ejection fraction (EF). One-, two-, and three-vessel disease was present in 138, 96, and 99 patients, respectively, while no coronary stenosis was observed in 26. IRA patency was documented in 234 patients (65%), while in the remaining 125 (35%), the artery remained occluded. Patients with occluded IRAs had more extensive coronary disease (2 to 3 vessels, 71% versus 46%, P<.01) and more depressed left ventricular (LV) function (LVEF, 48+/-13% versus 53+/-12%, P<.001). Patency of the IRA was associated with higher BRS values (BRS, 8.9+/-5.8 versus 7.1+/-4.7 ms/mm Hg, P<.005) and with a lower incidence (9% versus 18% P<.02) of markedly depressed BRS (<3 ms/mm Hg), a condition suggested by preliminary studies to be associated with an increased risk of post-MI mortality. The association between IRA patency and BRS was more evident in anterior than in inferior MI. Multivariate regression analysis showed that age of the patient and patency of the IRA were the major independent determinants of BRS, while LVEF was weakly related to BRS and only when analyzed as a categorized variable. CONCLUSIONS: The presence of an open IRA is associated with higher baroreflex sensitivity, and this effect is largely independent of limitation of infarct size by IRA patency. These data offer new insights into the mechanisms by which coronary artery patency may affect cardiac electrical stability and survival.

Adult↗
PubMed1996

Clinical trial enrollers vs. nonenrollers: the Cardiac Arrhythmia Suppression Trial (CAST) Recruitment and Enrollment Assessment in Clinical Trials (REACT) project.

The Recruitment and Enrollment Assessment in Clinical Trials (REACT) was a National Heart, Lung, and Blood Institute (NHLBI)-sponsored substudy to the Cardiac Arrhythmia Suppression Trial (CAST). Two-hundred-sixty (260) patients who enrolled in CAST and 140 partially or fully eligible patients who did not enroll were compared across several parameters, including demographic variables, disease severity, psychosocial functioning, health beliefs, recruitment experience, and understanding of informed consent procedures used in CAST. Significant predictors of enrollment included several demographic variables (e.g., being male, not having medical insurance), episodes of ventricular tachycardia, and health beliefs (e.g., extra beats are harmful, a higher degree of general health concern). Enrollment was higher for those who read and understood the informed consent and those who were initially recruited after hospital discharge, particularly nondepressed patients. In the multivariate model, the key variables that emerged were the patient's reading of the informed consent form and the patient's lack of medical insurance. These results suggest that (1) the clinical trial staff's interaction with the patient and the time when recruitment is initiated contribute significantly to the decision to enroll; and (2) it may be a greater challenge to motivate patients to enroll in future clinical trials if health care reform improves access to medical insurance coverage. Some of the significant variables are modifiable, suggesting interventions that may increase enrollment rates in future trials.

Aged↗
PubMed1996

Heart rate reactivity and heart period variability throughout the first year after heart transplantation.

Heart rate reactivity to mental stress is substantially blunted early after heart transplantation, suggesting that the loss of neural modulation limits the cardiovascular response to mental stress. We tested whether reactivity to mental stress recovers during the first year after heart transplantation. Hemodynamic and respiratory responses to mental arithmetic challenge were studied in 20 heart transplant recipients 3, 6, and 12 months after surgery. A normal comparison group was studied at equivalent intervals. Heart rate reactivity to mental arithmetic was significantly reduced in the cardiac transplant group compared to the normal subjects. This effect persisted up to 1 year after transplantation. Heart period variability in the heart transplant recipients was minimal in all three test sessions. The findings suggest that no functional reinnervation or other compensatory adaptation occurs up to 1 year after heart transplantation.

Female↗
PubMed1995

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)

Adult↗
PubMed1995

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.

Age Factors↗
PubMed1995

Association between ease of suppression of ventricular arrhythmia and survival.

BACKGROUND: We tested the hypothesis that patients whose ventricular arrhythmias are easy to suppress have a lower rate of arrhythmic death, defined as arrhythmic death and nonfatal cardiac arrest, the primary end point in the Cardiac Arrhythmia Suppression Trials (CAST-I and CAST-II), than patients whose ventricular arrhythmias are hard to suppress. In addition, we evaluated the association between ease of suppression of ventricular arrhythmias and mortality of all causes. METHODS AND RESULTS: CAST-I investigated the effect on arrhythmic death of ventricular premature depolarization (VPD) suppression achieved by three drugs, encainide, flecainide, and moricizine, at two different dose levels; CAST-II investigated the same effect, using moricizine alone at three dose levels. If suppression was achieved, patients were randomized to the effective active drug or corresponding placebo. To examine the independence of easily suppressed ventricular arrhythmias as a predictor of arrhythmic death, we adjusted statistically for other variables that were related both to ease of suppression and arrhythmic death. Patients with ventricular arrhythmias (n = 1778) that were easy to suppress had fewer arrhythmic deaths during follow-up than those with ventricular arrhythmias that were hard to suppress (n = 1173) (relative risk, .59; P = .003). Patients whose VPDs were easily suppressed were older and had a lower frequency of prior history of heart failure and myocardial infarction. They also had a higher incidence of anterior myocardial infarction, VPD frequency, and average ejection fraction. After adjusting for these variables, we found that easily suppressed ventricular arrhythmias were still significant predictors of arrhythmic death (relative risk, .66; P = .013). CONCLUSIONS: This study shows that the ease of VPD suppression identifies a subgroup of postmyocardial infarction patients who have low risk of arrhythmic death.

Aged↗
PubMed1995

Computer-assisted mapping of infarcted and viable regions of gross cardiac sections following experimental myocardial infarction.

We have developed a computer-assisted method that creates digital maps of the viable and infarcted regions of tetrazolium-stained gross cardiac sections. Here we describe and test the method, using a canine occlusion-reperfusion infarction model. Quantitative image analysis showed that the method accurately recorded differences between infarcted and viable regions at a spatial resolution of 5-20 pixels per mm2. Microscopic analysis of tissue samples taken from the sections showed that the maps were accurate. In 15 of 15 cases the histology of the samples matched that predicted by the maps. A comparison of infarct area measurements derived from the maps showed that the method was reproducible. The average intraoperator standard deviation was +/- 8% of a slice's infarcted area and the average interoperator standard deviation was +/- 20%. We conclude that the method creates accurate, detailed, and reproducible maps of the infarcted and viable regions of tetrazolium-stained cardiac sections.

Animals↗
PubMed1995

Effect of long-term digoxin therapy on autonomic function in patients with chronic heart failure.

OBJECTIVES: This study was conducted to determine the effect of long-term digoxin therapy on autonomic function in patients with mild to moderate chronic heart failure. BACKGROUND: Chronic heart failure is characterized by increased sympathetic activity and decreased parasympathetic activity. Intravenous digitalis has been found to reduce sympathetic activity immediately in these patients, but whether short-term neurohormonal effects are sustained during long-term oral therapy has not been assessed. METHODS: We determined sympathetic activity in 26 patients with heart failure by measuring plasma norepinephrine levels and parasympathetic activity from variables of heart period variability derived from 24-h ambulatory electrocardiographic Holter recordings obtained before and after 4 to 8 weeks of digoxin therapy. RESULTS: After digoxin therapy, plasma norepinephrine decreased significantly from a mean +/- SEM of 552 +/- 80 to 390 +/- 37 ng/ml. In addition, the RR interval increased significantly from 719 +/- 19 to 771 +/- 20 ms. High frequency power increased from 84 +/- 24 to 212 +/- 72 ms2, and the root mean square of successive differences in RR interval increased from 20.3 +/- 1.8 to 27.0 +/- 3.4 ms, indicating a substantial increase in parasympathetic activity. Low frequency power, an index of baroreflex activity, was also significantly increased (239 +/- 80 to 483 +/- 144 ms2) by digoxin therapy. CONCLUSIONS: These results indicate 1) that long-term therapy with digoxin acts to ameliorate the autonomic dysfunction of patients with heart failure, and 2) that the short-term neurohormonal effects of digoxin are sustained during prolonged treatment with the drug.

Autonomic Nervous System↗
PubMed1995

Temporal stability of heart period variability during a resting baseline and in response to psychological challenge.

Central to the psychophysiologic reactivity hypothesis of the etiology of coronary artery disease is the assumption that reactivity is an individual characteristic that is stable over time. Although heart rate (HR) and blood pressure reactivity appear to meet this criterion, temporal stability of cardiac autonomic control as measured by analysis of heart period variability (HPV) has not been assessed. In this study, we tested the stability of HPV, measured in both the time and frequency domain, during a quiet, resting baseline and in response to 5-min mental arithmetic and reaction time tasks, in 20 normal subjects measured in three testing sessions during a 9-month period. Stability, assessed by the intraclass correlation coefficient (ICC), was excellent for resting baseline measures of HR and HPV, with ICCs of 0.68-0.86. However, HR and HPV reactivity to either arithmetic or reaction time tasks generally was less stable, with ICCs of 0.17-0.73, in contrast to results of previous studies demonstrating long-term stability of HR responses to psychological challenge. Stability of aggregated reactivity scores was only slightly improved. Whether for individual tasks or aggregated measures, reactivity of total and low-frequency measures of HPV was moderately stable but stability of high-frequency HPV reactivity was poor.

Adult↗
PubMed1994

Beta-blocker therapy in the Cardiac Arrhythmia Suppression Trial. CAST Investigators.

The Cardiac Arrhythmia Suppression Trial (CAST) showed antiarrhythmic drug suppression of asymptomatic or mildly symptomatic ventricular arrhythmias in survivors of myocardial infarction to be harmful. This study retrospectively searched the CAST results for evidence of mortality and morbidity reduction in patients receiving optional beta-blocker therapy. All enrolled (n = 2,611) and suppressed main study (n = 1,735) CAST patients with an ejection fraction of < or = 40% were examined using univariate analysis, Kaplan-Meier curves, and a Cox proportional-hazards multivariate analysis with respect to optional beta-blocker therapy prescribed at baseline. CAST patients receiving beta-blocker therapy had significantly enhanced survival at 30 days, and at 1 and 2 years of follow-up against all-cause and arrhythmic death or nonfatal cardiac arrest. Multivariate analysis showed beta-blocker therapy to be independently associated with a one-third reduction in arrhythmic death or cardiac arrest (p = 0.036). In CAST patients with a history of congestive heart failure, beta-blocker therapy was independently associated with longer time to occurrence of new or worsened congestive heart failure (p = 0.015). This study supports the secondary preventive benefit of beta-blocker therapy in high-risk post-myocardial infarction patients, and calls attention to the possible preventive benefit of beta-blocker therapy against proarrhythmic events experienced in the CAST.

Adrenergic beta-Antagonists↗
PubMed1994

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.

Anti-Arrhythmia Agents↗
PubMed1994

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.

Adult↗
PubMed1994

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.

Adult↗
PubMed1994

Cardiac denervation and cardiovascular reactivity to psychological stress.

OBJECTIVE: This study investigated the mechanisms responsible for increases in heart rate and blood pressure during psychological stress, which are incompletely understood. Since cardiac transplant patients have denervated hearts, they provide a unique model for isolating central versus peripheral influences on the cardiovascular response to stress. METHODS: The authors compared the responses to two laboratory stressors of 20 ambulatory heart transplant recipients and two groups of normal subjects, one whose ages were matched to the ages of the transplant patients (mean = 46 years) and one whose ages were matched to the ages of the heart donors (mean = 27 years). The three groups of subjects performed mental arithmetic and reaction time tasks. RESULTS: Heart rate increase during the mental arithmetic task was significantly attenuated in the transplant recipients. During stress, stroke volume increased in the transplant recipients but decreased in both groups of comparison subjects. The difference in age between the heart recipients and donors did not account for the difference in reactivity between the heart transplant patients and the normal subjects. CONCLUSIONS: Direct neural stimulation of the heart is more important than peripherally circulating factors in producing tachycardia during psychological stress. Cardiac but not vascular responses to psychological stress are altered by cardiac denervation.

Adult↗
PubMed1993

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.

Adult↗