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Biomedical subjects

B R Chaitman

Publications and source records attributed to B R Chaitman.

At least 55 records · Page 3Linked to original sources

Myocardial infarction and cardiac mortality in the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial.

BACKGROUND: Cardiac mortality and myocardial infarction (MI) rates are used to evaluate the efficacy of coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). We compared 5-year cardiac mortality and MI rates in 1829 patients with multivessel disease randomized to CABG or PTCA. METHODS AND RESULTS: The 5-year cardiac mortality rate was 8.0% in patients assigned to PTCA compared with 4.9% in those assigned to CABG (relative risk [RR] of 1.55 with a 95% confidence interval [CI] of 1.07 to 2.23; P=.022). In a subgroup of 1476 nondiabetic patients, there were no significant differences between treatment groups in cardiac mortality either overall (4.6% versus 4.2%; RR= 1.04, 95% CI, 0.65 to 1.66; P=.908) or in subgroups based on symptoms, left ventricular function, number of diseased vessels, or stenotic proximal left anterior descending artery. The two treatment groups had similar event rates for the combined end point of cardiac death or MI. The RR for cardiac mortality in 264 patients who sustained an MI compared with those who did not was 5.9 (P<.001). MIs were more common after CABG during index hospitalization (P=.004), but in the PTCA group, they were more common after discharge (P<.001). CONCLUSIONS: The Bypass Angioplasty Revascularization Investigation (BARI) trial indicates 5-year cardiac mortality in patients with multivessel disease was significantly greater after initial treatment with PTCA than with CABG. The difference was manifest in diabetic patients on drug therapy. There were no significant differences overall for the composite end point of cardiac mortality or MI between treatment groups or for cardiac mortality in nondiabetic patients regardless of symptoms, left ventricular function, number of diseased vessels, or stenotic proximal left anterior descending artery.

Angioplasty, Balloon, Coronary↗

Long-term cardiopulmonary exercise performance after heart transplantation.

Functional capacity is an important outcome variable for heart transplantation, but there are few data that examine the temporal relation and duration of improvement in cardiopulmonary exercise performance after cardiac transplantation. Cardiopulmonary exercise performance was measured in 140 patients who underwent 426 treadmill exercise tests up to 9 years after cardiac transplantation. Univariate and multivariate analyses were used to predict postoperative improvement in functional capacity. Peak oxygen consumption (VO2) significantly improved from 14.2 +/- 3.7 ml/min/kg before to 21.4 +/- 5.6 ml/min/kg at a mean of 11.2 +/- 3.0 months after the transplant procedure (p < 0.001). When peak aerobic capacity was compared with a normal population, peak VO2 was < 50% of predicted in only 9 patients (12%), from 50% to 70% in 34 patients (44%), from 70% to 90% of predicted in 24 patients (31%); 10 patients (13%) were able to achieve > 90% of peak predicted VO2. The improvement seen at 6 months did not significantly change over 9 years of follow-up. Significant preoperative univariate predictors of.1-year postoperative improvement in peak VO2 were preoperative peak VO2 (p = 0.004), age (p < 0.001), ischemic cardiomyopathy (p = 0.007), and preoperative left ventricular ejection fraction (p < 0.001). Peak VO2 at 1 year in patients able to perform the test was not significantly influenced by acute rejection episodes, donor body surface area, or donor/recipient size ratio. In conclusion, exercise capacity is significantly improved within 6 months after cardiac transplantation, and maintained as long as 9 years after procedure. The magnitude of postoperative improvement is inversely related to preoperative peak VO2 and age.

Adult↗

Circadian variation in the onset of unstable angina and non-Q-wave acute myocardial infarction (the TIMI III Registry and TIMI IIIB).

Circadian variation has been demonstrated in several types of acute cardiovascular disease, including acute myocardial infarction (AMI), sudden cardiac death, silent ambulatory ischemia, and thrombotic stroke. In contrast, no diurnal variation was observed in 1 study of non-Q-wave AMI, and limited data are available for unstable angina. To assess whether circadian variation is present in unstable angina and non-Q-wave AMI, we examined the time of onset of ischemic pain in 7,731 patients who were prospectively identified in the Thrombolysis in Myocardial Ischemia (TIMI) III Registry, 3,318 of whom were enrolled in the prospective study, and in 1,473 patients enrolled in the TIMI IIIB trial. A circadian variation in the onset of pain was observed, with an increase in the number of patients experiencing the onset of pain in the morning hours between 6 A.M. and 12 noon (p <0.001). This circadian variation was observed both in patients with unstable angina and in those with evolving non-Q-wave AMI. A similar circadian pattern was observed in all subgroups tested. These findings were confirmed in the TIMI IIIB trial and complement previous studies suggesting that circadian variation exists in the onset of the full spectrum of myocardial ischemic syndromes.

Aged↗

Long-term survival of African Americans in the Coronary Artery Surgery Study (CASS).

OBJECTIVES: This study sought to determine the long-term (> 15 years) outcome of a clinically well characterized cohort of African Americans with known or suspected coronary artery disease (CAD). BACKGROUND: The mortality rate from CAD is higher in African Americans than in whites. An earlier analysis of data from the Coronary Artery Surgery Study (CASS) registry suggested that African American and white patients treated surgically had equal 5-year survival rates. METHODS: Survival data from the CASS registry were analyzed to determine whether 1) African American race is an independent predictor of mortality; and 2) initial therapy is predictive of mortality among African American patients. RESULTS: Overall, 60% of white and 52% of African American patients survived 16 years (p < 0.00001). Multivariate Cox models confirmed that African American race was independently associated with higher mortality in both the medical group (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.11 to 1.63) and the surgical group (HR 1.63, 95% CI 1.19 to 2.23). Initial therapy was not predictive of survival among African American patients (p = 0.81). However, smoking status significantly influenced survival: African Americans who did not smoke experienced significantly improved survival (60% vs. 48% for smokers), which equaled survival for white nonsmokers (61%, p = NS). CONCLUSIONS: In contrast to results from shorter term studies, African Americans experienced higher overall mortality rates than whites over the long term, regardless of the type of initial treatment. Survival among nonsmoking African Americans at 16 years equaled survival among nonsmoking whites.

Adult↗

Human fatty acid ethyl ester synthase-III gene: genomic organization, nucleotide sequencing and chromosomal localization.

The complete gene for human fatty acid ethyl ester Synthase-III (FAEES-III) was isolated from a human genomic lambda phage library for functional and structural determination. The gene spans approximately 3.3 kb which includes 791 base pairs of the 5' and 124 base pairs of the 3' flanking regions. The gene is comprised of seven exons and is interrupted by six introns. Several transcription regulatory sequences were identified in the promoter region. Primer extension experiments demonstrated the existence of two possible transcription initiation sites at nucleotide -29 and 32 position, 5' to the start of the translation. In addition to a TATA box at position-29 relative to the transcription initiation site and two Spl GGGCGG recognition sequences at nucleotide positions -42 to -37 and -50 to -45, the promoter contains a sequence motif matching the transcription activating factor AP-1. We also found an A + T rich region between nucleotide -505 and -390 which contained twenty-two AAAAT tandem repeats. The gene for FAEES-III was localized to human chromosome 11 by hybridizing the genomic fragment Xh01 to Chinese hamster/human somatic cell hybrid panels. These data extend our knowledge of non-oxidative alcohol metabolism and permit linkage analyses between this pathway and alcohol-related phenotypes.

Acyltransferases↗

Using automated analysis of the resting twelve-lead ECG to identify patients at risk of developing transient myocardial ischaemia--an application of an adaptive logic network.

The aim of this study was to introduce an adaptive logic network computing method for detecting patients who were likely to show transient ischaemic episodes during ambulatory Holter monitoring, using parameters from a previously recorded standard twelve-lead resting electrocardiogram (ECG). In the present study, the adaptive logic network computing method is compared with other commonly used classification methods, such as backpropagation network and discriminant analysis techniques. Of 1367 study subjects aged 65 and above, 733 were women and 634 were men. Ambulatory Holter recordings were made to detect episodic ischaemia in study patients. Those subjects showing ischaemic episodes were classified as 'ischaemic' patients, and the remaining subjects were 'non-ischaemic'. Accuracy was 67% using the adaptive logic network computing method, 56% using the backpropagation network computing method, and 65% using statistical discriminant analysis. We concluded that the adaptive logic network technique offers a slightly higher accuracy and shows several potential advantages for automated detection of ischaemia in resting electrocardiograms.

Adult↗

Moderate alcohol feeding attenuates postinjury vascular cell proliferation in rabbit angioplasty model.

Our studies in the cholesterol-fed rabbit model indicate that moderate alcohol consumption reduces the risk of restenosis by preventing low-density lipoprotein (LDL) oxidation. Eighteen hypercholesterolemic rabbits underwent arterial injury by Fogerty balloon endothelial denudation of iliac arteries. Two weeks later, balloon angioplasty of atherogenic or atherosclerotic arterial segments was performed. Nine rabbits (control) received water ad lib, whereas nine rabbits (moderate alcohol treated) received an average of 2.5 ml alcohol per 500 ml water daily, from the day of feeding hypercholesterolemic diet until they were killed, 10 weeks later. There was a 26% increase in lumen size of the moderate alcohol-treated group compared with the control group. The percentage neointima formation (NI) values of the moderate alcohol-treated and control groups were 77 +/- 2.1 and 61 +/- 1.9, respectively (p < 0.001). The lumen/neointima (L/NI) ratio of the moderate alcohol-treated group was 0.71 +/- 0.07 compared with the control group, 0.33 +/- 0.04 (p < 0.001). The number of foam cells in the moderate alcohol-treated group was threefold less than the control group [i.e., 1.4 +/- 0.4 and 3.9 +/- 0.8, respectively (p = 0.005)]. The arterial lesion malondialdehyde (MDA) values of the control and the moderate alcohol-treated groups were 13.6 +/- 2.8 and 4.4 +/- 0.5 (p = 0.004), respectively. By radioimmunoassay, the moderate alcohol-treated group had less macrophage chemotactic protein-1 (MCP-1; 3,277 cpm/microg protein) and platelet-derived growth factor (PDGF; 2,261 cpm/microg protein) compared with the controls (MCP-1, 4,529 cpm/microg protein; PDGF, 3,583 cpm/microg protein). Thus we conclude that low concentrations of alcohol reduce neointimal formation, and the extent of lipid oxidation, the number of foam cells in the neointimal area and may decrease the expression of MCP-1 and PDGF by reducing LDL oxidation in an animal model of postangioplasty restenosis.

Angioplasty, Balloon↗

Ischemic cerebral infarction after rt-PA and heparin therapy for acute myocardial infarction. The TIMI-II pilot and randomized clinical trial combined experience.

BACKGROUND AND PURPOSE: Ischemic cerebral infarction (CI) is a serious complication of acute myocardial infarction (MI). Little information exists on CI after thrombolytic therapy for MI. METHODS: Of 3924 MI patients treated with recombinant tissue plasminogen activator (rt-PA) and heparin, 29 (0.7%) developed CI after treatment. All CI patients had detailed neurological evaluations, and 27 (93%) had CT scans centrally reviewed. RESULTS: Age range was 40 to 74 years (mean, 60 years); 25 patients (86%) were men, and 22 (76%) were white. The electrocardiographic location of MI was anterior in 22 (76%) and nonanterior in 7 (24%). Five CIs occurred within 6 hours, 4 between 6 to 24 hours, 8 during the remainder of the first week, 10 during the second week, and 2 others distributed over the 4 weeks after study entry. Six of 29 CIs did not involve the cerebral cortex; 9 patients (31%) had multiple CIs. Of 28 CIs thought to be embolic in origin, 17 showed strong evidence for at least one cardiac abnormality (mural clot, wall-motion abnormality, aneurysm, or atrial fibrillation) known to be associated more specifically with embolism than MI. Eight of 27 CIs (30%) with CT scans had hemorrhagic transformation of varying degrees; 5 were symptomatic. CONCLUSIONS: The time of occurrence and sites of CI after rt-PA and heparin therapy for acute MI are similar to those reported during the prethrombolytic era.

Adult↗

Asymptomatic Cardiac Ischemia Pilot (ACIP) Study. Relationship between exercise-induced and ambulatory ischemia in patients with stable coronary disease.

BACKGROUND: We investigated whether the presence and frequency of asymptomatic ischemic episodes recorded during ambulatory ECG (AECG) monitoring could be predicted on the basis of clinical characteristics or exercise treadmill test (ETT) performance in patients with stable coronary disease and whether the estimate of ischemia severity was similar between the AECG and ETT. METHODS AND RESULTS: Patients screened for the Asymptomatic Cardiac Ischemia Pilot (ACIP) study were selected for the current analysis if data were available from 48-hour AECG monitoring as well as from an ETT during which the patient developed > or = 1-mm ST-segment depression. Exercise ECG data were available for 143 of the 910 patients without ischemic episodes and for 659 of the 910 patients with ischemic episodes during AECG monitoring. Angina was more frequent among patients with ambulatory ischemic episodes than among patients without such ischemia (P < .001). Patients with AECG ischemia had a consistently more marked ischemic response on the ETT than patients without AECG ischemia; patients likely to have AECG ischemia could be predicted on the basis of ETT performance characteristics. However, the correlation coefficients between the severity of ischemia estimated by ETT and by AECG were small. CONCLUSIONS: There are significant relations between ischemia detected by AECG monitoring and by ETT, but the relations are limited, indicating that the two tests are not redundant to characterize coronary patients. A larger study investigating the prognostic significance of the ischemia identified by each modality, with follow-up for clinical events, will be necessary to determine the most appropriate methods to evaluate patients with stable coronary disease.

Coronary Disease↗

Diabetics with coronary disease have a prevalence of asymptomatic ischemia during exercise treadmill testing and ambulatory ischemia monitoring similar to that of nondiabetic patients. An ACIP database study. ACIP Investigators. Asymptomatic Cardiac Ischemia Pilot Investigators.

BACKGROUND: There are conflicting data as to whether diabetics have a higher prevalence of asymptomatic ST-segment depression during exercise treadmill testing (ETT) and ambulatory ECG (AECG) monitoring. This study was conducted to determine whether diabetic patients with coronary disease enrolled in the Asymptomatic Cardiac Ischemia Pilot (ACIP) have more episodes of asymptomatic ischemia during ETT and 48-hour AECG monitoring than nondiabetic patients and to compare differences in angiographic variables and the magnitude of ischemia as measured by standard ETT and AECG criteria. METHODS AND RESULTS: Angiographic variables and the prevalence and magnitude of ischemia during the qualifying ETT and 48-hour AECG were compared by the presence and absence of diabetes mellitus in 558 randomized ACIP patients. Seventy-seven patients had a history of diabetes and were taking oral hypoglycemics or insulin (diabetic group); 481 patients did not meet these criteria (nondiabetic group). Multivessel disease (87% versus 74%, P = .01) was more frequent in the diabetic group. The percentages of patients without angina during the ETT were similar in the diabetic and nondiabetic groups (36% and 39%, respectively). Time to onset of > or = 1-mm ST-segment depression and time to onset of angina were similar in both groups. The percentages of patients with only asymptomatic ST-segment depression during the 48-hour AECG were similar in the diabetic and nondiabetic groups (94% versus 88%, respectively). However, total ischemic time per 24 hours (15.0 +/- 21.4 versus 23.6 +/- 31.1 minutes, P = .02), ischemic time per episode (6.3 +/- 4.6 versus 9.0 +/- 8.7 minutes, P < .01), and the maximum depth of ST-segment depression tended to be less in the diabetic group. CONCLUSIONS: Patients enrolled in ACIP were selected on the basis of an abnormal ETT and 48-hour AECG and ability to undergo coronary revascularization. When patients with diabetes mellitus were compared with those without diabetes, there was a similar prevalence of asymptomatic ischemia during ETT and 48-hour AECG monitoring. Despite more extensive and diffuse coronary disease, diabetic ACIP patients tended to have less measurable ischemia during the 48-hour AECG.

Aged↗

Correlation of poststenotic hyperemic coronary flow velocity and pressure with abnormal stress myocardial perfusion imaging in coronary artery disease.

The functional significance of coronary stenoses is frequently determined by adjunctive noninvasive myocardial perfusion imaging. Poststenotic coronary flow velocity and pressure can be measured directly during routine cardiac catheterization. The aim of this study was to correlate poststenotic (distal) flow velocity and pressure with stress perfusion imaging in patients. Quantitative angiography, basal and hyperemic transstenotic coronary flow velocities, and pressure gradients were measured in 50 patients within 1 week of exercise (n = 29) or of pharmacologic (n = 21) stress perfusion imaging. Twenty-two of 25 patients (88%) with reversible perfusion abnormalities had diminished distal coronary flow velocity reserves (CFVR) of < or = 2.0 x baseline, whereas 22 of 25 (88%) with normal perfusion imaging studies had a normal distal CFVR of > 2.0 (p = 0.000 1). Thirteen of 25 patients (52%) with reversible perfusion abnormalities had transstenotic gradients > or = 20 mm Hg, whereas 20 of 25 (80%) with normal perfusion studies had gradients <20 mm Hg (p = 0.01). Quantitative angiography did not differentiate patients with normal versus abnormal myocardial perfusion imaging. Distal CFVR was correlated more significantly with myocardial perfusion imaging results (kappa = 0.76) than with pressure gradients (kappa = 0.32). Exercise and pharmacologic stress myocardial perfusion imaging abnormalities reflect diminished post-stenotic coronary flow to a greater degree than transstenotic pressure gradients.

Adult↗

Purification and characterization of human heart fatty acid ethyl ester synthase/carboxylesterase.

Fatty acid ethyl ester synthase metabolizes ethanol non-oxidatively in those extrahepatic organs most commonly damaged by alcohol abuse. This study was designed to purify human myocardial fatty acid ethyl ester synthase (FAEES)/carboxylesterase from human heart. The enzyme was purified to homogeneity after chromatography over DEAE-cellulose, Sephadex G-100 and hydroxylapatite. The homogenous enzyme, 62 kDa, has both synthase and carboxylesterase activities. The N-terminal amino acid sequence of the first 17 residues of the purified enzymes were 88% homologous to that of the carboxylesterase from rat liver and adipose tissue. Antibody was raised against pure synthase/carboxylesterase cross-reacted with human cytosolic and microsomal fractions. With a constant oleic acid concentration of 0.25 mM, a calculated apparent Km and Vmax for ethanol were 0.30 M and 3700 nmol/mg protein/h., respectively. With constant ethanol concentrations of 1.2 M, the activity increased with the concentration of oleic acid to 0.17 mM, plateau to 0.25 mM. Because synthase/carboxylesterase esterifies free fatty acids with ethanol to produce its esters with potentially toxic effects, it may now be feasible to establish a link between alcohol consumption and end-organ damage.

Acyltransferases↗

Prognostic value of cardiopulmonary exercise testing using percent achieved of predicted peak oxygen uptake for patients with ischemic and dilated cardiomyopathy.

OBJECTIVES: We tested the hypothesis that percent achieved of predicted peak oxygen uptake (predicted VO2max) improves the prognostic accuracy of identifying high risk ambulatory patients with congestive heart failure considered for heart transplantation compared with absolute peak oxygen uptake (VO2max) in 181 patients with ischemic or dilated cardiomyopathy. BACKGROUND: Peak oxygen uptake during exercise has been shown to be a useful prognostic measurement to risk stratify patients with heart failure. The prognostic value of percent predicted VO2max has not been assessed in these patients. METHODS: We retrospectively studied 181 ambulatory patients referred to the Saint Louis University Heart Failure Unit. Clinical, hemodynamic (137 patients) and coronary angiographic (145 patients) data were recorded, and all patients underwent symptom-limited cardiopulmonary exercise. RESULTS: During a mean follow-up period of 12 +/- 6 months, 26 patients died, and 18 were listed as Status 1 priority for heart transplantation. The actuarial 1- and 2-year survival of the 89 patients who achieved < or = 50% predicted VO2max was 74% and 43%, respectively, compared with 98% and 90% in the 92 who achieved > 50% predicted VO2max (p = 0.001). Multivariable analysis selected < or = 50% predicted VO2max as the most significant predictor of cardiac death (p = 0.007) and cardiac death or Status 1 priority (p = 0.0005). CONCLUSIONS: Percent achieved of predicted VO2max provides important information that can be used to risk stratify ambulatory patients with heart failure with ischemic or dilated etiology that exceeds that provided by measurement of VO2max alone. Patients who achieve > 50% predicted VO2max have an excellent short-term prognosis when treated medically, and heart transplantation can be safely deferred.

Cardiomyopathy, Dilated↗