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Biomedical subjects

L J Shaw

Publications and source records attributed to L J Shaw.

At least 19 recordsLinked to original sources
PubMed1999

The noninvasive prediction of cardiac mortality in men and women with known or suspected coronary artery disease. Economics of Noninvasive Diagnosis (END) Study Group.

PURPOSE: The association between myocardial perfusion imaging defects and cardiac mortality in women is undefined. We examined whether myocardial perfusion imaging predicted cardiac mortality in men and women and compared this with other variables influencing prognosis. SUBJECTS AND METHODS: Six academic institutions with high-volume nuclear cardiology laboratories consecutively studied 5,009 men aged 62 +/- 12 years (mean ISD) and 3,402 women aged 66 +/- 11 years with symptomatic known or suspected coronary artery disease undergoing exercise (n = 7,486) or pharmacologic stress (n = 925) myocardial perfusion imaging. A pretest clinical risk index was calculated from age, history of myocardial infarction, diabetes, hypertension, and hypercholesterolemia. Myocardial perfusion images were analyzed for stress-induced defects or any defect in the territories of the three major coronary arteries. RESULTS: Stress-induced perfusion defects were seen in 39% of men and 25% of women (P = 0.0001). Extensive stress-induced or fixed defects (>2 vascular territories) were less common in women than men (10% vs 19%, and 4% vs 18%, both P = 0.0001). During a mean of 2.4 +/- 1.5 years of follow-up, 143 patients died of cardiac causes. The clinical risk index and number of territories with perfusion defects were associated with cardiac mortality in women and men. In women undergoing exercise myocardial perfusion imaging, the number of abnormal territories remained the strongest correlate of mortality after adjustment for exercise variables. CONCLUSIONS: The results of myocardial perfusion imaging are important, independent predictors of survival in both women and men.

Aged↗
PubMed1999

The economic consequences of available diagnostic and prognostic strategies for the evaluation of stable angina patients: an observational assessment of the value of precatheterization ischemia. Economics of Noninvasive Diagnosis (END) Multicenter Study Group.

OBJECTIVES: The study aim was to determine observational differences in costs of care by the coronary disease diagnostic test modality. BACKGROUND: A number of diagnostic strategies are available with few data to compare the cost implications of the initial test choice. METHODS: We prospectively enrolled 11,372 consecutive stable angina patients who were referred for stress myocardial perfusion tomography or cardiac catheterization. Stress imaging patients were matched by their pretest clinical risk of coronary disease to a series of patients referred to cardiac catheterization. Composite 3-year costs of care were compared for two patients management strategies: 1) direct cardiac catheterization (aggressive) and 2) initial stress myocardial perfusion tomography and selective catheterization of high risk patients (conservative). Analysis of variance techniques were used to compare costs, adjusting for treatment propensity and pretest risk. RESULTS: Observational comparisons of aggressive as compared with conservative testing strategies reveal that costs of care were higher for direct cardiac catheterization in all clinical risk subsets (range: $2,878 to $4,579), as compared with stress myocardial perfusion imaging plus selective catheterization (range: $2,387 to $3,010, p < 0.0001). Coronary revascularization rates were higher for low, intermediate and high risk direct catheterization patients as compared with the initial stress perfusion imaging cohort (13% to 50%, p < 0.0001); cardiac death or myocardial infarction rates were similar (p > 0.20). CONCLUSIONS: Observational assessments reveal that stable chest pain patients who undergo a more aggressive diagnostic strategy have higher diagnostic costs and greater rates of intervention and follow-up costs. Cost differences may reflect a diminished necessity for resource consumption for patients with normal test results.

Angina Pectoris↗
PubMed1999

Using an outcomes-based approach to identify candidates for risk stratification after exercise treadmill testing.

OBJECTIVE: To develop a hierarchical approach to cardiac risk stratification after treadmill testing. PATIENTS: Clinical and treadmill test data were used to identify a patient population that may be candidates for further risk stratification with stress tomographic myocardial perfusion imaging. A prospective series of 3, 620 medically treated patients (42% female, mean age 63 years) with a 2.5% mortality was identified (follow-up 2.5 +/- SD 1.5 years). MEASUREMENTS AND MAIN RESULTS: A Cox proportional hazards model was used to estimate a patient's likelihood of cardiac death. Kaplan-Meier survival curves were used to estimate time to cardiac death by nuclear test results. Annual rates of cardiac death were 0. 4% (n = 921), 1% (n = 2,498), and 1% (n = 201) for patients with low, intermediate, and high Duke treadmill scores (DTS). For patients with an intermediate DTS, multivariate estimators of cardiac death included the number of ischemic vascular territories (relative risk per defect 1.4, p =.01), the number of infarcted vascular territories (relative risk per defect 2.4, p =.00001), and the DTS (relative risk per unit 0.97, p =.00001), following adjustment for a patient's pretest risk of coronary disease. For patients with an intermediate DTS, the presence of no, one or two, and three vascular territories with defects was associated with annual rates of cardiac death of 0.5%, 1.4%, and 2.5%, respectively (p <.0001). Kaplan-Meier survival curves exhibited a statistically worsening survival for patients with defects by 1 year after treadmill exercise. CONCLUSIONS: For symptomatic patients with an intermediate treadmill test score, the exercise myocardial perfusion scan may be used to stratify their risk of cardiac death over 3 years of follow-up. Patient management may be efficiently guided by further outcome assessment, with an exercise nuclear scan for patients whose treadmill test score is intermediate.

Aged↗
PubMed1998

Value of exercise treadmill testing in women.

OBJECTIVES: We sought to determine the ability of a treadmill score to provide accurate diagnostic and prognostic risk estimates in women. BACKGROUND: Treadmill testing has been reported to have a lower accuracy for diagnosis of chest pain in women. The diagnostic and prognostic value of the Duke Treadmill Score (DTS) in women is unknown. METHODS: We determined the diagnostic and prognostic value of the DTS in 976 women and 2,249 men who underwent both treadmill testing and cardiac catheterization in a single institution from 1984 to 1994. RESULTS: Women and men differed significantly in DTS (1.6 vs. -0.3, p < 0.0001), disease prevalence (32% vs. 72% significant coronary artery disease [CAD], p < 0.001), and 2-year mortality (1.9% vs. 4.9%, p < 0.0001). The DTS provided information beyond clinical predictors of both coronary disease and survival in women and men. Although overall women had better survival, the DTS performed equally well in stratifying both genders into prognostic categories. The DTS actually performed better in women than in men for excluding disease, with fewer low risk women having any significant coronary disease (> or = 1 vessel with > or =75% stenosis) (20% vs. 47%, p < 0.001), or severe disease (3-vessel disease or > or =75% left main stenosis) (3.5% vs. 11.4%, p < 0.001). CONCLUSIONS: By combining several aspects of treadmill testing, the DTS effectively stratifies women into diagnostic and prognostic risk categories.

Coronary Disease↗
PubMed1998

Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups.

BACKGROUND: Exercise testing is useful in the assessment of symptomatic patients for diagnosis of significant or extensive coronary disease and to predict their future risk of cardiac events. The Duke treadmill score (DTS) is a composite index that was designed to provide survival estimates based on results from the exercise test, including ST-segment depression, chest pain, and exercise duration. However, its usefulness for providing diagnostic estimates has yet to be determined. METHODS AND RESULTS: A logistic regression model was used to predict significant (>/=75% stenosis) and severe (3-vessel or left main) coronary artery disease, and a Cox regression analysis was used to predict cardiac survival. After adjustment for baseline clinical risk, the DTS was effectively diagnostic for significant (P<0.0001) and severe (P<0.0001) coronary artery disease. For low-risk patients (score >/=+5), 60% had no coronary stenosis >/=75% and 16% had single-vessel >/=75% stenosis. By comparison, 74% of high-risk patients (score <-11) had 3-vessel or left main coronary disease. Five-year mortality was 3%, 10%, and 35% for low-, moderate-, and high-risk DTS groups (P<0.0001). CONCLUSIONS: The composite DTS provides accurate diagnostic and prognostic information for the evaluation of symptomatic patients evaluated for clinically suspected ischemic heart disease.

Adult↗
PubMed1998

Use of an intravenous contrast agent (Optison) to enhance echocardiography: efficacy and cost implications. Optison Multicenter Study Group.

OBJECTIVE: To compare the overall diagnostic costs associated with non-contrast and contrast echocardiography. STUDY DESIGN: Phase III clinical trial. PATIENTS AND METHODS: In a secondary analysis of data from a phase III clinical trial of the intravenous contrast agent Optison, we compared the costs associated with obtaining a diagnosis in 203 patients who underwent non-contrast and contrast echocardiography. Costs for the initial test and any follow-up tests were derived from adjusted Medicare charges and a transition-1 microcost accounting system. RESULTS: Diagnostic yield from echocardiograms was 87% with the use of Optison (3 mL) and 49% when no contrast agent was used (P < 0.001). Because technically inadequate echocardiograms were more common in the non-contrast group, follow-up testing was recommended for 42% of patients in this group compared with 12% of those who had undergone a contrast-enhanced echocardiogram (P < 0.001). Although use of Optison increased the initial diagnostic cost by $125, overall costs were 17% lower when Optison was used (P < 0.0001). Use of Optison also resulted in a 17% to 70% decrease in confirmatory transesophageal echocardiography, catheterization, and nuclear studies. Optison improved diagnostic accuracy by 2.7-fold in patients with an initial non-diagnostic echocardiogram, resulting in a substantial cost savings of $269 per patient.

Cardiomyopathies↗
PubMed1998

TNF-alpha and 9-cis-retinoic acid synergistically induce ICAM-1 expression: evidence for interaction of retinoid receptors with NF-kappa B.

TNF-alpha and 9-cis-retinoic acid (9-cis-R) synergistically enhance ICAM-1 protein expression in immortalized human aortic endothelial cells (HAECTs). At a TNF-alpha concentration of 0.1 ng/ml, 1 microM 9-cis-R enhanced ICAM-1 protein expression 4-fold. Treatment with 1 microM 9-cis-R alone caused no induction of ICAM-1 expression. Functional analysis of human ICAM-1 promoter-luciferase constructs revealed that the synergism was attributable to transcriptional regulation. Expression of a luciferase reporter vector containing a 311-bp fragment of the ICAM-1 promoter (-252 to + 59 bp relative to the transcriptional start site) was increased 2.9- and 4.9-fold by treatment with 9-cis-R and TNF-alpha, respectively, while cotreatment with 9-cis-R and TNF-alpha induced expression to 19.9-fold. Mutation studies revealed that RARE and NF-kappa B sites located respectively at -226 and -188 bp relative to the transcription start site are essential for the synergistic control of promoter activity. Mutation of either the RARE or the NF-kappa B site eliminated the synergistic enhancement of promoter activity. Moreover, mutation of the RARE abrogated promoter activity induced by treatment with TNF-alpha alone and mutation of the NF-kappa B site eliminated promoter activity induced by treatment with 9-cis-R alone. We conclude that retinoid receptors and NF-kappa B act in concert at the promoter level to facilitate ICAM-1 expression in endothelial cells.

Alitretinoin↗
PubMed1998

Incremental prognostic value of myocardial perfusion single photon emission computed tomography for the prediction of cardiac death: differential stratification for risk of cardiac death and myocardial infarction.

BACKGROUND: The incremental prognostic value of stress single photon emission computed tomography (SPECT) for the prediction of cardiac death as an individual end point and the implications for risk stratification are undefined. METHODS AND RESULTS: We identified 5183 consecutive patients who underwent stress/rest SPECT and were followed up for the occurrence of cardiac death or myocardial infarction. Over a mean follow up of 642+/-226 days, 119 cardiac deaths and 158 myocardial infarctions occurred (3.0% cardiac death rate, 2.3% myocardial infarction rate). Patients with normal scans were at low risk (< or =0.5%/y), and rates of both outcomes increased significantly with worsening scan abnormalities. Patients who underwent exercise stress and had mildly abnormal scans had low rates of cardiac death but higher rates of myocardial infarction (0.7%/y versus 2.6%/y; P<.05). After adjustment for prescan information, scan results provided incremental prognostic value toward the prediction of cardiac death. The identification of patients at intermediate risk of nonfatal myocardial infarction and low risk for cardiac death by SPECT may result in significant cost savings when applied to a clinical testing strategy. CONCLUSIONS: Myocardial perfusion SPECT yields incremental prognostic information toward the identification of cardiac death. Patients with mildly abnormal scans after exercise stress are at low risk for cardiac death but intermediate risk for nonfatal myocardial infarction and thus may benefit from a noninvasive strategy and may not require invasive management.

Adenosine↗
PubMed1998

Influence of race on the prediction of cardiac events with stress technetium-99m sestamibi tomographic imaging in patients with stable angina pectoris.

The prognostic value of myocardial perfusion imaging in African-Americans is unknown. This study compared the prediction of cardiac events of stress technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) imaging in symptomatic Caucasian and African-American patients. Prospectively collected stress Tc-99m sestamibi tomographic imaging data from 4 medical centers, with follow-up information in 1,086 Caucasian and African-American patients, were analyzed in a core statistical laboratory. Primary events of cardiac death and nonfatal myocardial infarction and secondary events of all-cause mortality were analyzed using Kaplan-Meier survival analysis and Cox proportional-hazards multivariable model. Normal images in both African-Americans and Caucasians were associated with a low-annual cardiac event rate, whereas abnormal images were significantly associated with a higher cardiac event rate. The highest predictor of cardiac events was multivessel abnormality in both races. Use of this technique could identify patients at high risk and potentially reduce the high-cardiac event rate in African-Americans by utilizing appropriate therapies.

Aged↗
PubMed1998

Comparative prognostic value of automatic quantitative analysis versus semiquantitative visual analysis of exercise myocardial perfusion single-photon emission computed tomography.

OBJECTIVES: The purpose of this study was to determine the prognostic value of automatic quantitative analysis in exercise dual-isotope myocardial perfusion single-photon emission computed tomography (SPECT) and to compare the prognostic value of quantitative analysis to semiquantitative visual SPECT analysis. BACKGROUND: Extent, severity and reversibility of exercise myocardial perfusion defects have been shown to correlate with prognosis. However, most studies examining the prognostic value of SPECT in chronic coronary artery disease (CAD) have been based on visual analysis by experts. METHODS: We studied 1,043 consecutive patients with known or suspected CAD who underwent rest Tl-201/exercise Tc-99m sestamibi dual-isotope myocardial perfusion SPECT and were followed up for at least 1 year (mean 20.0+/-3.7 months). After censoring 59 patients with early coronary artery bypass grafting or percutaneous transluminal coronary angioplasty, <60 days after nuclear testing, the final population consisted of 984 patients (36% women, mean age 63+/-12 years). RESULTS: During the follow-up period, 28 hard events (14 cardiac deaths, 14 nonfatal myocardial infarctions) occurred. Patients with higher defect extent (>10%), severity (>150) and reversibility (>5%) by quantitative SPECT defect analysis, as well as those with an abnormal scan (>2 abnormal segments, summed stress score >4 and summed difference score >2) by semiquantitative visual SPECT analysis, had a significantly higher hard event rate compared to patients with a normal scan (p < 0.001). With both visual and quantitative analyses, hard event rates of approximately 1% with normal scans and 5% with abnormal scans (p > 0.05) were observed over the 20-month follow-up period. A Cox proportional hazards regression model showed that chi-square increased similarly with the addition of quantitative defect extent and visual summed stress score variables after considering both clinical and exercise variables (improvement chi-square = 11 for both, p < 0.0007). There were no significant differences in the areas under receiver operating characteristic curves between quantitative and visual analysis (p > 0.70). Linear regression analysis also indicated that quantitative assessments correlated well with visual semiquantitative assessments. CONCLUSIONS: The findings of this study indicate that automatic quantitative analysis of exercise stress myocardial perfusion SPECT is similar to semiquantitative expert visual analysis for prognostic stratification. These findings may be of particular clinical importance in laboratories with less experienced visual interpreters.

Aged↗
PubMed1998

Prognosis by measurements of left ventricular function during exercise. Duke Noninvasive Research Working Group.

UNLABELLED: This study was performed to determine whether gated equilibrium radionuclide angiogram measurements of left ventricular function during rest and exercise add independent information to clinical and catheterization data in predicting cardiac death. METHODS AND RESULTS: The study population consisted of 863 consecutive patients undergoing exercise gated equilibrium radionuclide angiography within 90 days of cardiac catheterization with data prospectively entered into the Duke Cardiovascular Database. All patients were symptomatic, medically treated, with significant coronary artery disease and had undergone follow-up for < or = 6 yr. A univariable and multivariable Cox regression analysis was utilized to evaluate the independent power in predicting 147 (17.0%) cardiac deaths. This risk-adjusted analysis revealed that only rest and exercise ejection fraction as well as maximum workload contained independent prognostic information; the nuclear variables contributed 63% of the total information within the model. A multivariable model including exercise ejection fraction and clinical history variables provided slightly more prognostic information than the combination of cardiac catheterization and clinical data. CONCLUSION: Multigated equilibrium radionuclide angiography is a key predictor of cardiac death when compared to clinical and cardiac catheterization data in patients with symptomatic, medically treated coronary artery disease. Thus, long-term outcome for patients may be determined by utilizing this noninvasive tool even when clinical and cardiac catheterization data are also available.

Cardiac Catheterization↗
PubMed1997

Cost effectiveness of inpatient initiation of antiarrhythmic therapy for supraventricular tachycardias.

This study assessed the cost effectiveness of inpatient antiarrhythmic therapy initiation for supraventricular tachycardias using a metaanalysis of proarrhythmic risk and a decision analysis that compared inpatient to outpatient therapy initiation. A MEDLINE search of trials of antiarrhythmic therapy for supraventricular tachycardias was performed, and episodes of cardiac arrest, sudden or unexplained death, syncope, and sustained or unstable ventricular arrhythmias were recorded. A weighted average event rate, by sample size, was calculated and applied to a clinical decision model of therapy initiation in which patients were either hospitalized for 72 hours or treated as outpatients. Fifty-seven drug trials involving 2,822 patients met study criteria. Based on a 72-hour weighted average event rate of 0.63% (95% confidence interval, 0.2% to 1.2%), inpatient therapy initiation cost $19,231 per year of life saved for a 60-year-old patient with a normal life expectancy. Hospitalization remained cost effective when event rates and life expectancies were varied to model hypothetical clinical scenarios. For example, cost-effectiveness ratios for a 40-year-old without structural heart disease and a 60-year-old with structural heart disease were $37,510 and $33,310, respectively, per year of life saved. Thus, a 72-hour hospitalization for antiarrhythmic therapy initiation is cost effective for most patients with supraventricular tachycardias.

Anti-Arrhythmia Agents↗
PubMed1997

Usefulness of serial radionuclide angiography in predicting cardiac death after coronary artery bypass grafting and comparison with clinical and cardiac catheterization data.

This investigation assesses the prognostic value of radionuclide measurements of cardiac function in patients undergoing coronary artery bypass grafting (CABG). Radionuclide angiograms during exercise and at rest were obtained in 182 patients before (< or = 30 days), early (< or = 3 months), and late (< or = 3 years) after CABG. Cox proportional hazard regression analysis was used to identify independent predictors of 44 cardiac deaths that occurred a median 12 years after bypass. Although the exercise ejection fractions before and early after CABG were significantly related to subsequent cardiac death (chi-square = 10.84, p = 0.001, and chi-square = 7.4, p = 0.006, respectively), the late postoperative exercise ejection fraction was the strongest predictor (chi-square = 13.9, p = 0.0002), contributing above and beyond clinical and catheterization data. These data document the validity of the exercise ejection fraction as an important predictor of cardiac death after CABG and suggest the potential clinical application of serial measurements of the exercise ejection fraction as an important noninvasive adjunct to postoperative evaluation of these patients.

Cardiac Catheterization↗
PubMed1997

Risk stratification after myocardial infarction.

PURPOSE: To review the literature on risk stratification after acute myocardial infarction in the reperfusion era and to propose an algorithm for early and continual risk assessment. DATA SOURCES: A MEDLINE search of the English-language literature on humans was done using the terms myocardial infarction, prospective studies, and prognosis. This search was supplemented by narrowed searches for subheadings (such as cardiogenic shock, thrombolytic therapy, and stress testing) and surveys of references cited in review articles and book chapters. STUDY SELECTION: Literature on prognosis and myocardial infarction published from 1981 to 1996 was considered. From the literature on stress testing methods, studies that enrolled patients before 1980, enrolled patients for indications other than myocardial infarction, tested patients more than 6 weeks after infarction, were missing outcome data, or had inadequate follow-up were excluded. DATA EXTRACTION: Because too few randomized trials were available to allow the cross-comparison of risk-stratification methods, the available observational data were synthesized and supplemented with clinical judgments to produce recommendations. DATA SYNTHESIS: Risk stratification must begin when acute myocardial infarction is diagnosed. High-risk patients (such as those with cardiogenic shock) and candidates for reperfusion therapy must be identified quickly if ideal emergency care is to be given. At specific points during hospitalization, specialized tests may be useful if they add incremental information to the results of clinical evaluations. High-risk patients who have complications after infarction or significant left ventricular dysfunction probably benefit from early angiography; patients without these conditions are at low risk for recurrent events and should have noninvasive stress testing for further risk stratification. CONCLUSIONS: Physicians should continually reappraise risk throughout hospitalization to optimize both patient outcomes and cost containment.

Algorithms↗
PubMed1997

Impact of contrast echocardiography on diagnostic algorithms: pharmacoeconomic implications.

The major goal of medicine in the era of managed care is to control escalating costs and to attain a high level of quality health care. Capitation has limited access to expensive and unnecessary testing, placing an emphasis on the prudent use of available technology. A vast armamentarium of available diagnostic screening tests are available within cardiology. Routine two-dimensional (2-D) echocardiography is a high-quality, low-cost test that provides enhanced portability and real-time test interpretation over other noninvasive test modalities. The echocardiogram may cost up to 50% less than competitive nuclear single-photon emission computed tomography (SPECT) imaging. However, on average 10% of routine and 33% of stress echocardiograms are suboptimal (disproportionately affecting obese patients and those with lung disease). Myocardial contrast echocardiography has been shown to provide enhanced endocardial border delineation and left ventricular opacification, to enhance Doppler signal, and to provide information on myocardial perfusion. In several recent phase II and III studies, the use of a contrast agent has been shown to improve the diagnostic accuracy of echocardiography substantially. Improvements in the diagnostic capabilities of echocardiography have been shown to (1) impact upon downstream repetitive testing in patients with an initially nondiagnostic echocardiogram, (2) potentially increase laboratory throughput, and (3) reduce the rate of false-positive and negative tests as a result of improved image quality. As clinical and cost-effectiveness parallel one another, the use of myocardial contrast echocardiography in selected patient cohorts will result in improved diagnostic accuracy and a cost-effective pattern of care.

Albumins↗
PubMed1997

Cost implications of selective preoperative risk screening in the care of candidates for peripheral vascular operations.

The preoperative identification that patients are at high risk for adverse postoperative outcomes is the first step toward preventing costly in-hospital complications. The economic implications of noninvasive screening strategies in the care of patients undergoing peripheral vascular operations must be clarified. A decision model was developed from the peer-reviewed literature on patients undergoing preoperative screening by means of dipyridamole myocardial perfusion imaging, dobutamine echocardiography, or cardiac catheterization before vascular operations (n = 23 studies). Routine versus selective screening strategies were compared for patients with an intermediate likelihood of having coronary artery disease on the basis of clinical history of coronary disease or typical symptoms. Median costs (1994 US dollars) of preoperative screening strategies were derived with two microcosting approaches: adjusted Medicare charges (top-down approach) and a bottom-up approach with Duke University Center direct cost estimate data. In-hospital cost was 11% higher for preoperative screening by means of routine cardiac catheterization ($27,760) than for routine pharmacologic stress imaging ($24,826, P = 0.001). The total cost of a do-nothing strategy, that is, no preoperative testing, was 5.9% less than that of routine preoperative pharmacologic stress imaging and 15.9% lower than that of cardiac catheterization (P = 0.001). Selective screening among patients with a history of coronary disease or typical angina resulted in further reduction of the cost of care to a level comparable with that of a do-nothing strategy (52.5% reduction in cost with pharmacologic stress imaging, P > 0.20). Use of noninvasive testing for preoperative risk stratification was cost effective for patients 60 to 80 years of age. Cost per life saved ranged from $33,338 to $21,790. However, coronary revascularization after an abnormal noninvasive test was cost effective only for patients older than 70 years. In this economic decision model, substantial cost savings were predicted when selective noninvasive stress imaging was added to preoperative screening for patients about to undergo vascular operations. With a selective screening approach, the economic impact of initial diagnostic testing may be minimized without compromising patient outcomes.

Decision Trees↗