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Biomedical subjects

R E Kleiger

Publications and source records attributed to R E Kleiger.

At least 37 records · Page 2Linked to original sources

Pulmonary artery aneurysm: review and case report.

Aneurysms involving the main pulmonary artery and its branches are rare. Clinical experience is limited and current knowledge is mainly derived from autopsy findings. This case report describes a patient with a pulmonary artery aneurysm associated with a previous, partially corrected stenotic pulmonary valve. The patient presented with symptoms suggestive of aneurysm dissection three decades after commissurotomy. The diagnostic approach and therapeutic intervention are emphasized with a review of the literature.

Aneurysm↗

Stability of index of heart rate variability in patients with congestive heart failure.

Stability of indexes of heart rate variability (HRV) has not been established for patients with congestive heart failure (CHF). We therefore measured Holter-derived HRV indexes in 17 stable patients with class II or III CHF (mean age 52 +/- 9 yr; 5 men and 12 women) on two occasions 2 weeks apart. Stability was determined via paired t tests and intraclass correlation coefficients (ICCs). ICCs for time domain indexes of HRV were > or = 0.86 for 24 hours, > or = 0.73 for daytime, and > or = 0.72 for nighttime indexes reflecting longer-term variability. After log transformation, ICCs for the short-term 24-hour measures PNN50 (percentage of N-N intervals > 50 msec different from preceding interval) and RMSSD (the root mean square of successive differences) were 0.85 and 0.67. ICCs for frequency domain indexes of HRV were 0.86 to 0.91. We compared HRV indexes, serum norepinephrine (NE) levels, and respiratory sinus arrhythmia induced by paced breathing, also considered measures of autonomic tone. NE correlated weakly with average R-R interval, and all indexes of HRV reflecting longer-term variation (r = -0.32 to r = -0.50). ICC was 0.78 for NE. Respiratory sinus arrhythmia was highly repeatable (ICC = 0.70) but did not correlate significantly with NE or any measure of HRV. We conclude that time and frequency domain indexes of HRV are stable over time in CHF patients without intervening events.

Adult↗

Limited usefulness of exercise testing and thallium scintigraphy in evaluation of ambulatory patients several months after recovery from an acute coronary event: implications for management of stable coronary heart disease. Multicenter Myocardial Ischemia Research Group.

OBJECTIVES: This study evaluated the value of noninvasive testing to predict cardiac events in patients with stable coronary disease after hospital admission (and risk stratification) for an acute coronary event. BACKGROUND: Exercise testing with thallium perfusion imaging identifies patients with obstructive coronary artery disease and has been used to stratify patients after myocardial infarction. Its usefulness for predicting cardiac events in patients with stable coronary disease after recovery from an acute coronary event was explored. METHODS: Nine hundred thirty-six patients were enrolled 1 to 6 months after hospital admission for a coronary event. Patients underwent exercise treadmill testing with planar thallium-201 scintigraphy and were followed up for an average of 23 months (range 6 to 43). End points were 1) unstable angina requiring hospital admission, nonfatal myocardial infarction or cardiac death; 2) nonfatal infarction or cardiac death; or 3) cardiac death alone. RESULTS: Twelve patients died of cardiac causes (1.2%); 32 had a nonfatal myocardial infarction (3.4%); and 79 patients (8.4%) developed unstable angina in the first year. Exercise testing improved proportional hazards models constructed from clinical variables for all three end points (p < 0.05). The perfusion scan further improved models for the end points (nonfatal infarction or cardiac death and cardiac death alone, p < 0.05). However, the exercise test with or without thallium added little to the overall prediction of primary events (area under the receiver operating curve increased from 0.649 to 0.663), and only 2% to 13% of patients with abnormal results either had a nonfatal infarction or died. CONCLUSIONS: Thallium-201 scintigraphy and exercise testing variables identify patients at risk for subsequent cardiac events. However, the poor predictive performance of these tests in this group of patients with stable coronary disease severely limits their usefulness. These results suggest a limited role for exercise and thallium testing in predicting cardiac events in patients with known coronary disease.

Coronary Disease↗

Heart rate variability: a measure of cardiac autonomic tone.

Analysis of HRV based on routine 24-hour Holter recordings provides a sensitive, noninvasive measurement of autonomic input to the heart. HRV can be measured in the time or frequency domain. Each frequency domain variable correlates at least r = 0.85 with a time domain variable. Thus time domain measures can be used as surrogates for frequency domain measures which may simplify future studies. Abnormalities of autonomic input to the heart, which are indicated by decreased indices of HRV, are associated with increased susceptibility to ventricular arrhythmias. Decreased indices of HRV are also associated with CHF, diabetes, and alcoholic cardiomyopathy. Decreased indices of HRV are an independent risk factor for mortality post MI and in patients with advanced CHF. Medications can also affect HRV, and that effect may become an important clinical consideration, especially in high-risk patients.

Autonomic Nervous System↗

Alterations in temporal patterns of heart rate variability after coronary artery bypass graft surgery.

BACKGROUND: Preliminary studies have indicated that autonomic nervous system dysfunction may be present in patients after cardiac surgery. The purpose of this study was to evaluate cardiac autonomic nervous system function, as assessed by analysis of heart rate variability (HRV), in adult patients undergoing uncomplicated coronary artery bypass graft surgery. METHODS: Longitudinal changes in HRV were determined perioperatively by continuous electrocardiographic monitoring in 40 adult patients undergoing elective coronary artery bypass graft surgery and were compared with HRV in two groups of control subjects: 15 patients undergoing nonthoracic major vascular surgery and 19 healthy volunteers. Exclusion criteria were diabetes, renal failure, recent or perioperative myocardial infarction, or use of inotropic drugs. HRV data during electrocardiographically documented episodes of myocardial ischemia were omitted. RESULTS: There were no differences in any measurement of preoperative HRV between groups during the day, but HRV was greater at night (12:00 AM to 5:00 AM) in volunteers than in patients in either surgical group. In the hour after induction of anesthesia (before cardiopulmonary bypass), the components of HRV were decreased compared with those in the preoperative daytime but were similar in the two surgical groups. After surgery, HRV in the group undergoing nonthoracic vascular surgery remained at about the same level as that observed after induction of anesthesia, whereas in the group undergoing coronary artery bypass graft surgery, HRV was further reduced and was approximately 40-50% less than that in the vascular surgery group (P < 0.05). In the coronary artery bypass group, the reduction in HRV compared with the preoperative daytime measurements persisted on postoperative day 5. CONCLUSIONS: HRV is reduced after uncomplicated coronary artery bypass graft surgery. Although we cannot exclude the effects of uncontrolled variables in this reduction of postoperative HRV, the observed changes in HRV did not appear to result from general anesthesia, perioperative stress responses, and other factors associated with the early postoperative period. These data are consistent with the supposition that cardiac autonomic nervous system function is impaired after cardiac surgery.

Autonomic Nervous System↗

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↗

Long-term prognostic significance of ST segment depression during acute myocardial infarction. The Multicenter Diltiazem Postinfarction Trial Research Group.

OBJECTIVES: The purpose of this study was to evaluate the long-term prognostic value of ST segment depression on the electrocardiogram (ECG) in patients with acute myocardial infarction. BACKGROUND: The prognostic importance of ST segment depression on the ECG has been studied in small groups of patients with infarction, but larger numbers are needed. METHODS: Coronary care unit ECGs of 1,234 patients who survived the coronary care unit with acute Q wave (n = 896) or non-Q wave (n = 338) myocardial infarction were analyzed for the presence of ST segment depression. Patients were followed up for up to 4 years. RESULTS: ST segment depression was present in 607 patients. Those with ST segment depression had a 1-year mortality rate of 10.3% compared with a rate of 5.6% for those without ST segment depression (p = 0.002). This effect was seen in both the Q wave and non-Q wave subgroups. Of the 437 patients with anterior ST segment elevation, those with ST segment depression in other regions had a 13.6% 1-year mortality rate compared with a rate of 6.9% for those with no ST segment depression (p = 0.0005). Of the 514 patients with inferior ST segment elevation, those with ST segment depression in other leads had an 11.0% 1-year mortality rate compared with a 1.8% rate for those with no ST segment depression (p = 0.0001). The Cox proportional hazards model showed that ST segment depression was an independent predictor of mortality over the follow-up period. CONCLUSIONS: ST segment depression on the admitting ECG in patients with acute myocardial infarction is a predictor of increased mortality in the year after infarction.

Adult↗

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.

Electrocardiography, Ambulatory↗

The relationship between 1-year mortality and infarct location in patients with non-Q wave myocardial infarction.

The association between 1-year mortality and infarct location was evaluated in 544 patients with acute non-Q wave myocardial infarction. Infarcts were anterior (alone or including other locations) in 51.1% (n = 278) of cases, localizable but not anterior 29.6% (n = 161) of the time, and nonlocalizable in 19.3% (n = 105) of patients. One-year actuarial mortality (73 deaths) was 16.9% in the anterior group, 13.3% in the nonanterior group, and 6.8% in nonlocalizable patients (p = 0.037). Anterior and localizable nonanterior mortality were similar (p = 0.367). However, there were differences when mixed location infarcts were excluded. Mortality in the inferior infarction only group (2.8%, n = 36) was less than in the lateral infarction only group (16.8%, n = 79, p = 0.041) and almost significantly less than in the anterior only group (15.1%, n = 62, p = 0.064). The positive prognosis in the inferior infarction only group may be associated with the low rate of ST depression among these patients compared with those with other infarct locations (p less than 0.0001). Mortality among localizable infarcts (15.5%) was greater than among those that were nonlocalizable (6.8%, p = 0.021). Despite the low overall risk of the nonlocalizable infarcts, 41.9% (n = 44) of these patients developed at least one important risk factor while in hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

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%.

Aged↗

Time domain measurements of heart rate variability.

Assessment of HRV through time domain variables is a simple and practical method of assessing autonomic function. In this capacity its utility has been demonstrated in normal subjects and in diverse cardiac and noncardiac pathologic states. It can be used to assess the effects of drugs and other interventions, including exercise and psychological and physical stress on cardiac autonomic tone. Importantly, decreased HRV is almost uniformly associated with adverse outcome. The prognostic information appears to incorporate both alterations in autonomic tone and longer term components and is best assessed using ambulatory ECG recordings. Defining the clinical applicability and physiologic mechanisms of changes in HRV remain active areas of research.

Electrocardiography, Ambulatory↗

Stability over time of variables measuring heart rate variability in normal subjects.

Both time and frequency domain measures of heart rate (HR) variability have been used to assess autonomic tone in a variety of clinical conditions. Few studies in normal subjects have been performed to determine the stability of HR variability over time, or the correlation between and within time and frequency domain measures of HR variability. Fourteen normal subjects aged 20 to 55 years were studied with baseline and placebo 24-hour ambulatory electrocardiograms performed 3 to 65 days apart to assess the reproducibility of the following time domain measures of cycle length variability: the standard deviation of all normal cycle intervals; mean normal cycle interval; mean day normal cycle interval; night/day difference in mean normal cycle interval; root-mean-square successive cycle interval difference; percentage of differences between adjacent normal cycle length intervals that are greater than 50 ms computed over the entire 24-hour electrocardiographic recording (proportion of adjacent intervals greater than 50 ms); and the frequency domain measures of high (0.15 to 40 Hz), low (0.003 to 0.15) and total (0.003 to 0.40) power. The mean and standard deviations of these measures were virtually identical between placebo and baseline measurements and within the studied time range. Variables strongly dependent on vagal tone (high-frequency, low-frequency and total power, root-mean-square successive difference, and percentage of differences between adjacent normal cycle intervals greater than 50 ms computed over the entire 24-hour electrocardiographic recording) were highly correlated (r greater than 0.8). It is concluded that measures of HR variability are stable over short periods of time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Electrocardiographic subset analysis of diltiazem administration on long-term outcome after acute myocardial infarction. The Multicenter Diltiazem Post-Infarction Trial Research Group.

The effect of diltiazem on long-term outcome after acute myocardial infarction (AMI) was assessed in 2,377 patients enrolled in the Multicenter Diltiazem Post-Infarction Trial and subsequently followed for 25 +/- 8 months. The study population included 855 patients (36%) with at least 1 prior AMI before the index infarction and 1,522 patients (64%) with a first AMI, of whom 409 (27%) had a first non-Q-wave AMI, 664 (44%) a first inferior Q-wave AMI, and 449 (30%) a first anterior Q-wave AMI. This post hoc analysis revealed that, among patients with first non-Q-wave and first inferior Q-wave AMI, there were fewer cardiac events during follow-up in the diltiazem than in the placebo group, and that the reverse was true for patients with first anterior Q-wave AMI or prior infarction. The diltiazem:placebo Cox hazard ratio (95% confidence limits) for the trial primary end point (cardiac death or nonfatal reinfarction, whichever occurred first) was: first non-Q-wave AMI-0.48 (0.26, 0.89); first inferior Q-wave AMI-0.66 (0.40, 1.09); first anterior Q-wave AMI-0.82 (0.51, 1.31); and prior AMI-1.11 (0.85, 1.44). Use of cardiac death alone as an end point gave an even more sharply focused treatment difference: first non-Q-wave AMI-0.46 (0.18, 1.21); first inferior Q-wave AMI-0.53 (0.27, 1.06); first anterior Q-wave AMI-1.28 (0.68, 2.40); prior infarction-1.26 (0.90, 1.77). Further analysis revealed that these differences in the effect of diltiazem in large part reflected the different status of the 4 electrocardiographically defined subsets in terms of left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Diltiazem↗

Effect of atenolol and diltiazem on heart period variability in normal persons.

Several time and frequency domain measures of heart period variability are reduced 1 to 2 weeks after myocardial infarction, and a reduced standard deviation of normal RR intervals over a 24 h period (SDNN) is associated with increased mortality. The predictive accuracy of heart period variability may be reduced by drugs used to treat patients after myocardial infarction. Accordingly, a randomized, three period, placebo-controlled, crossover (Latin square) design was used to determine the effect of atenolol and diltiazem on time and frequency measures of heart period variability calculated from 24 h continuous electrocardiographic recordings during treatment with atenolol, diltiazem and placebo in 18 normal volunteers. During atenolol treatment, the 24 h average normal RR (NN) interval increased 24% (p less than 0.001). The three measures of tonic vagal activity were significantly increased (p less than 0.001) during atenolol treatment: percent of successive normal RR intervals greater than 50 ms = 69%, root mean square successive difference of normal RR intervals = 61% and high frequency power in the heart period power spectrum = 84%. Low frequency power also increased 45% (p less than 0.01), indicating that this variable also is an indicator of tonic vagal activity over 24 h. Diltiazem had no significant effect on the 24 h average NN interval or on any measure of heart period variability. The decreased mortality rate after myocardial infarction associated with beta-adrenergic blocker but not calcium channel blocker therapy may be attributed in part to an increase in vagal tone caused by beta-blockers.

Adult↗

Effect of diltiazem on cardiac rate and rhythm after myocardial infarction. Multicenter Diltiazem Postinfarction Trial Investigators.

The a priori hypothesis that diltiazem would reduce the frequency and repetitiveness of ventricular arrhythmias was tested 3 months after myocardial infarction in patients participating in the Multicenter Diltiazem Postinfarction Trial. After 3 months of follow-up, 1,546 of the 2,466 patients enrolled had a 24-hour continuous electrocardiographic recording that contained greater than or equal to 12 hours of analyzable data. They were similar to the patients who survived 3 months but chose not to have a 24-hour electrocardiographic recording (i.e., they were representative of the entire group that survived 3 months). After 3 months of follow-up, there were no significant differences between the diltiazem and placebo groups in the prevalence of atrioventricular block, the frequency of atrial arrhythmias or the frequency or repetitiveness of ventricular arrhythmias. Heart rate was significantly lower (67 +/- 12 vs 71 +/- 12 beats/min) and there was a significantly greater proportion of patients with sinus pauses greater than or equal to 2 seconds in duration in the diltiazem group (6%) than in the placebo group (3%). Comparison with placebo revealed no evidence either for an anti- or proarrhythmic effect of diltiazem. There was no reduction in sudden or arrhythmic death attributable to diltiazem treatment; the fraction of total deaths that were arrhythmic by the Hinkle classification was 41% in the placebo group and 42% in the diltiazem group. It may be that the lack of effect of diltiazem on ventricular arrhythmias is partially responsible for its lack of effect on mortality after myocardial infarction.

Adult↗

The independence of cycle length variability and exercise testing on predicting mortality of patients surviving acute myocardial infarction. The Multicenter Postinfarction Research Group.

Cycle length variability (CLV), defined as the standard deviation of normal cycle length intervals, has been found to be a powerful predictor of subsequent mortality in a population of 808 survivors of acute myocardial infarction. Decreased CLV is associated with a significant increase in mortality. CLV remained an independent predictor of outcome even after adjusting for left ventricular ejection fraction, clinical risk factors, heart rate and ventricular arrhythmias. In the same population of survivors of acute myocardial infarction, the results of exercise testing also strongly predicted outcome, with those failing to take the test having the worst survival, and those completing the low-level stress test taken before discharge having the best prognosis. The hypothesis that the status of stress test (completed; did not complete; failed to take) and CLV were measuring the same factor related to mortality was tested. Although the distribution of CLV was shifted to higher CLV in patients who completed the test and to lower CLV in those who failed to take the test, both predictors of mortality remained independent predictors of long-term mortality (average of 31 months of follow-up) after controlling for each other. Moreover, subgroups with an approximate 15-fold difference in mortality were defined using both variables (CLV less than 50 ms, did not take test had a 54% mortality; CLV greater than 100 ms, completed the test had a mortality of 3.5%). CLV is a measure of autonomic tone; it is not strongly related to exercise ability and using the results of both stress testing and CLV results in the identification of subgroups of postinfarction patients with markedly disparate risks of mortality.

Blood Pressure↗