Biomedical subjects
Publications and source records attributed to E D Foster.
Although the toxic effects of lead on the central nervous system have been well described, the blood concentration at which lead begins to exert adverse effects remains the focus of debate. A meta-analysis of occupational studies was conducted evaluating the association between neurobehavioural testing results and moderate blood lead concentrations.
OBJECTIVES: To show the effect of clinical, angio and demographic traits on late survival of Coronary Artery Surgery Study (CASS) patients following coronary artery bypass grafting (CABG) and introduce Hazard Function analysis to CASS survival data. METHODS: Patients were reached by mail survey with 94% response. By National Death Index, vital status was obtained in 99.7% (n = 8221) with a mean follow up of 15 years. Cox proportional hazard and Blackstone Hazard Function regressions were used to assess effects of preoperative traits. RESULTS: Ninety percent of patients were alive at 5, 74% at 10 and 56% at 15 years. Of those age 65 and age 75 at operation, 74% and 59% were living at 10 years and 54% and 33% at 15 years (now age 90), survival exceeding the matched U.S. population. Hazard Function falls rapidly after CABG to 9 to 12 months, then rises, doubling by 15 years. Young patients, below age 35, had lower late survival. The time-segmented Cox model (divided at time suggested by the Hazard Function) identified traits showing predictive power early, throughout and late. Female sex, small body surface, ischemic symptoms and emergency status affected survival early. Heavier weight, infarct(s), diuretics, diabetes, smoking, left main and LAD stenosis and use of vein grafts only increased hazard late only. CONCLUSIONS: There are still lessons from the CASS database. CABG in the elderly is supported by the survival pattern of our patients age 75 at operation. Time-segmented Cox analysis and Hazard Function analysis separate baseline variables into those that predict early mortality and those that predict long survival.
OBJECTIVE: Patients with lower extremity arterial disease (LEAD) are at an increased risk of having coronary artery disease (CAD). Diabetics are at especially high risk for having LEAD with concomitant CAD. This study was undertaken (1) to define the clinical and arteriographic features associated with CAD among diabetics and nondiabetics with LEAD and (2) to determine the long-term survival and predictors of mortality of diabetics and nondiabetics with LEAD and CAD. RESEARCH DESIGN AND METHODS: Two hundred sixty-three diabetics and 1137 nondiabetics from the Coronary Artery Surgery Study who had evidence of LEAD, who were 50 years and older, and who had arteriographically proven CAD were monitored for a mean of 12.8 years. RESULTS: Among all the subjects with LEAD there was a high prevalence of current and past smoking, history of previous myocardial infarction, systemic hypertension, congestive heart failure, high degrees of angina pectoris and unstable angina pectoris, and use of beta-blockers. On arteriographic evaluation a high prevalence of three-vessel epicardial coronary disease and involvement of multiple coronary segments with > or =50% diameter narrowing was found. Multivariate analysis showed the number of coronary segments with >50% occlusion, the presence of cerebrovascular disease, the use of digitalis, and elevated systolic blood pressure were independently associated with diabetes. On follow-up diabetics had a significantly higher mortality rate (mostly cardiac) than nondiabetics: median survival, 8.1 years and 12.7 years, respectively. At 15 years the mortality rates were 77.1% and 62.0%, respectively. On multivariate analysis, age, number of coronary occlusions, number of significantly narrowed epicardial arteries, diminished myocardial contractility, hypertension, and smoking were significant predictors of mortality in the total group and in each subgroup. Coronary artery bypass grafting surgery was protective. The presence of diabetes was an independent risk factor for mortality. CONCLUSIONS: The presence of LEAD is associated with multivessel epicardial and multiple coronary segment occlusion. On long-term follow-up there is a high mortality rate. In patients with LEAD and diabetes, CAD is especially severe and prognosis is poor.
BACKGROUND: The influence of prior coronary artery bypass surgery (CABG) versus medical therapy for reducing the risk of postoperative cardiac complications after noncardiac surgery continues to be debated. To further clarify this controversy we studied 24,959 participants in the Coronary Artery Surgery Study (CASS) database with suspected coronary disease by identifying those who required noncardiac surgery during more than 10 years of follow-up. METHODS AND RESULTS: CASS registry enrollees were either treated with CABG or medical therapy after initial entry. During follow-up, patients who required noncardiac operations were evaluated for hospital death or out-of-hospital death within 30 days of noncardiac surgery and nonfatal postoperative myocardial infarction (MI). At a mean follow-up of 4.1 years, 3368 patients underwent noncardiac surgery, with abdominal (36%), urologic (21%), orthopedic (15%), and vascular being most common. Abdominal, vascular, thoracic, and head and neck surgery each had a combined MI/death rate among patients with nonrevascularized coronary disease >4%. Among 1961 patients undergoing higher-risk surgery, prior CABG was associated with fewer postoperative deaths (1.7% versus 3.3%, P=.03) and MIs (0.8% versus 2.7%, P=.002) compared with medically managed coronary disease. Contrariwise, 1297 patients undergoing urologic, orthopedic, breast, and skin operations had mortality of <1% regardless of prior coronary treatment. Prior CABG was most protective in patients with advanced angina and/or multivessel coronary artery disease. CONCLUSIONS: In patients with known coronary artery disease, noncardiac surgeries involving the thorax, abdomen, vasculature, and head and neck are associated with the highest cardiac risk, which is reduced among patients with prior CABG.
OBJECTIVE: Patients who have diabetes and lower-extremity arterial disease (LEAD) are at an increased risk of dying from coronary artery disease (CAD). This study was undertaken to: 1) define the clinical and arteriographic factors associated with LEAD among diabetic patients; 2) determine the long-term survival and predictors of mortality of diabetic patients with LEAD, compared to those without LEAD; and 3) determine if the presence of LEAD is an independent risk factor for mortality among diabetic patients with CAD. RESEARCH DESIGN AND METHODS: A total of 263 diabetic patients from the Coronary Artery Surgery Study (CASS) registry with LEAD, who were > or = 50 years of age, and who had arteriographically proven CAD, were identified and followed for a mean of 12.8 years. A total of 1,349 comparably aged diabetic patients from the CASS registry with CAD and no evidence of LEAD were followed for an equivalent period of time. RESULTS: Compared with diabetic patients without LEAD, diabetic patients with LEAD were characterized by the presence of cerebrovascular disease, a high rate of current smoking, elevated systolic blood pressure, high grades of angina pectoris, and digitalis use. Severity of epicardial CAD and extent of CAD were not independent predictors of the presence of LEAD. On follow-up, diabetic patients with LEAD had significantly higher mortality (mostly cardiovascular) than diabetic patients without LEAD, with a median survival of 8.1 and 10.9 years, respectively. On multivariate analysis, age, the number of significantly narrowed coronary arteries, and the presence of left ventricular dysfunction predicted mortality in both subsets of diabetic patients. Among all the diabetic patients with CAD, the presence of LEAD was an independent risk factor for mortality. CONCLUSIONS: Diabetic patients with LEAD have a higher mortality rate (mostly cardiovascular) than diabetic patients without LEAD, despite no apparent anatomic differences in the severity and extent of CAD. This suggests that factors associated with the presence of LEAD, other than the anatomy of the coronary circulation, may play a role in determining survival among diabetic patients with LEAD and CAD.
BACKGROUND: Among patients with combined coronary artery and peripheral vascular disease, long-term benefits of surgical therapy compared with medical therapy for coronary artery disease are unknown. METHODS AND RESULTS: Using prospectively collected data from the Coronary Artery Surgery Study registry, we performed a retrospective cohort analysis of 1834 patients (mean age, 56 years; 20% women) with both coronary artery and peripheral vascular disease and evaluated their long-term outcomes. Of these patients, 986 received (nonrandomly) coronary artery bypass graft surgery, and 848 were treated medically. Perioperative mortality was 4.2% (2.9% in the absence of peripheral vascular disease; P = .02). In a mean follow-up period of 10.4 years, 1100 deaths occurred (80% due to cardiovascular causes). For the surgical group, 4-, 8-, 12-, and 16-year estimated probabilities of survival were 88%, 72%, 55%, and 41%, respectively, and 73%, 57%, 44%, and 34%, respectively, for the medical group (P < .0001). Multivariate analysis demonstrated that type of therapy was independently associated with survival (P = .0001; chi 2 = 15.34). Subgroup analysis suggested that benefits of surgical treatment on survival were limited to patients with three-vessel coronary artery disease and were inversely related to ejection fraction. Survival free of death or myocardial infarction was also significantly better among the surgical group. Type of therapy was significantly associated with occurrence of late events (P = .01; chi 2 = 6.55). Subgroup analysis again demonstrated that beneficial effects of surgery were limited to patients with three-vessel coronary artery disease and were inversely related to ejection fraction. CONCLUSIONS: Surgical treatment provides long-term benefit for certain subgroups of patients with combined coronary artery and peripheral arterial vascular disease.
OBJECTIVES: Respiratory quotient, the ratio of CO2 production to oxygen consumption (VO2), is principally affected by the fuel source used for aerobic metabolism. Since the respiratory quotient, VO2, and CO2 production cannot be directly measured easily, indirect calorimetry is commonly used to determine the value of these variables at the airway level (i.e., airway respiratory quotient, airway VO2, and airway CO2 production). However, under nonsteady-state conditions, a variety of phenomena can alter the relationship between true metabolic activity and measurements determined by indirect calorimetry. During exercise, for example, airway respiratory quotient increases as anaerobic threshold is reached because of the disproportionate increase in airway CO2 production that results from the CO2 liberated through the buffering of excess hydrogen ions by bicarbonate. We hypothesized that hemorrhage and reinfusion might change airway respiratory quotient in a consistent manner as shock is produced and reversed. DESIGN: Prospective laboratory study. SETTING: University animal laboratory. SUBJECTS: Eight pigs (25 +/- 2 [SD] kg), anesthetized with fentanyl and relaxed with pancuronium bromide, and mechanically ventilated on room air. INTERVENTIONS: The animals were sequentially hemorrhaged and then autotransfused while metabolic and hemodynamic measurements were obtained, using continuous indirect calorimetry and continuous applications of the Fick principle. Hemoglobin, arterial lactate concentration, and blood gases for calibration were measured serially. Analysis of variance was used to compare various periods in time. MEASUREMENTS AND MAIN RESULTS: Between baseline and peak hemorrhage, and between peak hemorrhage and postreinfusion, all of the following variables changed significantly (p < .05): airway VO2 (baseline 6.4 +/- 0.9 mL/min/kg, peak hemorrhage 3.9 +/- 0.6 mL/min/kg, postreinfusion 7.0 +/- 1.4 mL/min/kg); airway CO2 production (baseline 5.5 +/- 0.9 mL/min/kg, peak hemorrhage 4.5 +/- 0.9 mL/min/kg, postreinfusion 6.0 +/- 1.4 mL/min/kg); airway respiratory quotient (baseline 0.87 +/- 0.07, peak hemorrhage 1.16 +/- 0.07, postreinfusion 0.87 +/- 0.05); lactate concentration (baseline 2.4 +/- 1.2 mmol/L, peak hemorrhage 6.7 +/- 1.9 mmol/L, postreinfusion 5.1 +/- 2.0 mmol/L); and delta PCO2 (venous PCO2-PaCO2) (baseline 4.5 +/- 3.6 torr [0.6 +/- 0.5 kPa], peak hemorrhage 12.1 +/- 5.3 torr [1.6 +/- 0.7 kPa], postreinfusion 2.7 +/- 2.7 torr [0.4 +/- 0.4 kPa]). CONCLUSIONS: Airway respiratory quotient increases in hemorrhagic shock and decreases again as shock is reversed during reinfusion. This phenomenon appears related to the buffering of excess of hydrogen ion during hemorrhagic shock.
A cohort of 317 diabetic patients, aged > or = 65 years, with angiographically proven coronary artery disease, was analyzed and followed for a mean of 12.8 years. Compared with 1,843 age-matched nondiabetic patients, diabetic patients were more likely to (1) have a higher number of coronary occlusions, (2) not be current smokers, (3) have higher systolic but lower diastolic blood pressures, (4) have evidence of peripheral vascular disease, and (5) be women. They did not differ significantly with respect to total cholesterol, family history of coronary artery disease, history of hypertension, or left ventricular hypertrophy. In the total elderly cohort, diabetes was found to be an independent predictor of mortality, conferring a 57.0% increased risk of death. Survival analysis showed that diabetic subjects consistently had higher mortality than nondiabetics. However, the relative survival benefit of coronary artery bypass graft surgery versus medical therapy was comparable in diabetic and nondiabetic patients. Surgical therapy conferred a reduction in mortality of 44%.
OBJECTIVES: The purpose of this study was to determine the importance of peripheral arterial disease in predicting long-term survival in patients with clinically evident coronary artery disease. BACKGROUND: Patients in the Coronary Artery Surgery Study (CASS) Registry were followed up for > 10 years. METHODS: Survival in 2,296 patients with peripheral arterial disease was compared with that of 13,953 patients without peripheral arterial disease using Kaplan-Meier survival curves. All patients had known stable coronary artery disease. Clinical, electrocardiographic (ECG), chest X-ray film and catheterization variables of the two groups were compared using the chi-square statistic or the two-sample t test. The independent effect of peripheral arterial disease (as well as other variables) on mortality was determined utilizing a Cox proportional hazards model. RESULTS: Patients with peripheral vascular disease were more likely to have hypertension, diabetes, family history of coronary artery disease, previous angina or myocardial infarction, previous coronary bypass surgery or to have smoked. They also had a higher incidence of congestive heart failure, ECG abnormality and modestly increased frequency of three-vessel disease. Independent correlates of long-term mortality for the entire cohort included age, smoking, diabetes, number of diseased coronary vessels, left ventricular function, hypertension, pulmonary disease, anginal class, previous myocardial infarction and peripheral vascular disease (all p < 0.001). At any point in time, patients with peripheral vascular disease had a 25% greater likelihood of mortality than patients without peripheral vascular disease (multivariate chi-square 25.83, hazard ratio 1.25, 95% confidence interval 1.15 to 1.36, p < 0.001). CONCLUSIONS: Peripheral vascular disease is a strong, independent predictor of long-term mortality in patients with stable coronary artery disease. Aggressive attempts at secondary disease prevention are warranted in this high risk group.
OBJECTIVES: The Coronary Artery Surgery Study (CASS) required participants to undergo follow-up angiography at 5 years to identify clinical and angiographic features associated with progression of coronary artery disease. BACKGROUND: The CASS randomized 780 patients at 11 participating clinical centers between an initial strategy of medical therapy versus bypass surgery. Five clinical sites accomplished follow-up angiography in > 50% of their randomized subjects within a 42- to 66-month period after the entry arteriogram (n = 314). METHODS: Qualified clinical site angiographers, using side by side film review, evaluated an average of 13 segments/patient on both arteriograms for initial stenosis severity, morphologic features, lesion location and occurrence of disease progression or occlusion. Progression was defined as further definite narrowing by > or = 15% and occlusion as lesion progression to > or = 98%. Lesions were subcategorized as to whether they were univariate and had or had not been treated with bypass surgery. Multivariate logistic regression analyses were performed. RESULTS: For nonbypassed segments, right coronary artery and left anterior descending artery proximal and midlocations were associated with disease progression. For stenosis-containing segments, the initial severity, a non-left anterior descending artery location and increased treadmill duration predicted progression. Segment occlusion was associated with initial lesion severity, right coronary artery location and subsequent interval myocardial infarction. There were few predictors of progression or occlusion in bypassed arteries, other than initial lesion severity. CONCLUSIONS: Univariate and multivariate associations with lesion progression and occlusion included diabetes, lesion location, elevated cholesterol level, interval infarction and lesion morphology. These angiographic results, collected in a prospective trial, are consistent with known risk factors.
An imaging study is needed that can detect sternal wound infections and distinguish between superficial and deep sternal wound infection when a clinical diagnosis is uncertain and a decision regarding surgical intervention must be made. We retrospectively reviewed the 99mTc-leukocyte scans of 29 patients referred to rule out sternal wound infection. The presence or absence of deep or superficial sternal wound infection was determined by microbiology and long-term follow-up. Images obtained 4 and 20 hr after injection were reviewed by two nuclear physicians who were blinded to the clinical history. Findings were categorized as normal or abnormal. Abnormal images were further defined as having intense uptake at 4 and 20 hr, increasing uptake between 4 and 20 hr, or other patterns such as focal cold regions, irregular uptake at 4 and 20 hr or increasing uptake between 4 and 20 hr were 100% sensitive and 89% specific for the detection of deep sternal wound infection. The images were also useful for determining the extent of infection. Superficial sternal wound infection could not be reliably detected. The results indicate that 99mTc-leukocyte imaging is useful for the diagnosis of deep sternal wound infection.
The Coronary Artery Surgery Study (CASS) includes 780 patients with mild or moderate stable angina pectoris or asymptomatic survivors of a myocardial infarction who were randomized to either medical or surgical therapy and 1,319 patients who were eligible for randomization but were not randomized (randomizable patients). There were no substantial aggregate differences observed in any of the survival comparisons after 10 years of follow-up study between the randomized and randomizable patients assigned to the medical (79% versus 80%) or surgical (82% versus 81%) groups or in patient subgroups stratified according to coronary artery disease extent and left ventricular ejection fraction. Cox regression analyses were done with independent variables known to be predictors of survival, including surgical versus medical therapy and randomized versus randomizable group, to test the null hypothesis of a mortality difference between medical versus surgical assignment according to group assignment (randomized versus randomizable). In no case did the initial group category enter as a significant predictor of survival. The results in the randomizable group reinforce those in the randomized group with respect to the medical versus surgical comparison. Two subgroups are identified with a significant surgical advantage: 1) patients with proximal left anterior descending coronary artery stenosis greater than or equal to 70% and an ejection fraction less than 0.50, and 2) patients with three vessel coronary artery disease and an ejection fraction less than 0.50. In both groups, coronary bypass surgery had a statistically significant beneficial effect on survival (p less than 0.05). After a decade of follow-up, the CASS randomizable patients confirm conclusions reached on the basis of the CASS randomized trial.
Plasma fibronectin, also called cold-insoluble globulin, is a cryoprecipitable glycoprotein with both opsonic and adhesive activities. It binds to collagen, actin, and heparin and can form soluble as well as cryoprecipitable complexes in the cold. Fibronectin augments particulate phagocytosis by the reticuloendothelial system and can influence lung vascular permeability. Plasma fibronectin deficiency is temporally associated with respiratory failure in septic surgical, trauma, and burn patients. We measured plasma fibronectin and albumin levels in nine adults undergoing elective cardiopulmonary bypass to determine whether dilution alone could account for the changes in plasma fibronectin. Plasma fibronectin concentration decreased 17% with the surgical trauma of opening of the chest and placement of the vascular cannulas. On heparinization and initiation of cardiopulmonary bypass, plasma fibronectin fell an additional 48% (P less than 0.001), whereas albumin concentration (corrected for albumin in the pump prime) fell only 25% (P less than 0.001), emphasizing that dilution was not the only mechanism contributing to the decline in plasma fibronectin. Fibronectin levels began to increase after discontinuation of cardiopulmonary bypass and in association with diuresis, but unexpectedly they remained subnormal until 4 days postoperation. Thus the decline in fibronectin concentration with cardiopulmonary bypass may be due to dilution as well as opsonic consumption and possible complexing with heparin in the cold.
The risks of homologous blood transfusion are well documented and recently increased with the emergence of acquired immunodeficiency syndrome. Preoperative autologous donation has been suggested to reduce these risks. This is a report concerning 104 consecutive adult autologous donors (group 1) who had an elective cardiac operation. A similar group of 111 patients operated on during the same period but without autologous blood donation was used for comparison (group 2). Both groups contained similar numbers of patients with coronary artery disease, valvular disease, and mixed lesions, and both had several patients with atrial septal defects. Group 2 patients (mean age, 67.8 years) were significantly older than group 1 patients (mean age, 58.9 years) (p less than 0.05). The mean donation in group 1 was 4.1 units, but 12 (11.5%) had to discontinue donations. Increasing angina in 10 (12.2%) of the 82 patients with coronary artery disease was the most common complication, and necessitated hospitalization in two instances. In 77 (75.5%) of the 102 group 1 patients who had operation and 23 (21%) of the 110 group 2 patients, no homologous blood products were required. Group 1 patients used significantly less homologous fresh frozen plasma (0.1 unit versus 0.97 unit; p less than 0.005) and packed red blood cells (0.6 unit versus 2.1 units; p less than 0.001) than group 2 patients. Group 1 patients received 3.3 and 3.1 units of autologous packed cells and plasma, respectively. No complications of autologous transfusion were seen. Predonation of autologous blood is an effective, safe method of reducing homologous blood requirements in elective cardiac operations, but it does carry some risk, especially in patients with coronary artery disease.
The internal mammary artery is the premier conduit for initial and repeat coronary artery bypass grafting and should be used as either a pedicled or free graft whenever possible. Saphenous veins from the greater and lesser systems are distinctly second choices but can serve satisfactorily as aortocoronary grafts for many years. When neither the internal mammary arteries nor the saphenous veins are available, the cardiac surgeon today must choose from a wide variety of alternative conduits that have been used periodically over the past two decades for coronary artery bypass grafting.
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A simple technique for replacing a valve prosthesis within a composite aortic root graft is described. This method allows isolated valve replacement without removing the Dacron tube graft or altering the original coronary artery repair.