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Publications and source records attributed to L J Shaw.
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Effective allocation of medical resources in stable chest pain patients requires the accurate diagnosis of coronary artery disease and the stratification of future cardiac risk. We studied the relative predictive value for cardiac death of 3 commonly applied noninvasive strategies, clinical assessment, stress electrocardiography, and myocardial perfusion tomography, in a large, multicenter population of stable angina patients. The multicenter observational series comprised 7 community and academic medical centers and 8,411 stable chest pain patients. All patients underwent pretest clinical screening followed by stress (exercise 84% or pharmacologic 16%) electrocardiography and myocardial perfusion tomography. Risk-adjusted multivariable Cox proportional hazards models were developed to predict cardiac death. Kaplan-Meier rates of time to cardiac catheterization were also computed. Cardiac mortality was 3% during the 2.5 +/- 1.5 years of follow-up. The number of infarcted vascular territories and pretest clinical risk factors were strong predictors of cardiac mortality, whereas the number of ischemic vascular territories gained increasing importance when determining post-test resource use requirements (i.e., the decision to perform cardiac catheterization). Exertional ST-segment depression in a population with a high frequency of electrocardiographic abnormalities at rest was not a significant differentiator of cardiac death risk. Stable chest pain patients are accurately identified as being at high risk for near-term cardiac events by both physicians' screening clinical evaluation and by the results of stress myocardial perfusion imaging. Disease management strategies for stable chest pain patients aimed at risk reduction should incorporate knowledge of relevant end points in treatment and guideline development.
Recent updates in the field of echocardiography have resulted in improvements in image quality, especially in those patients whose ultrasonographic (ultrasound) evaluation was previously suboptimal. Intravenous contrast agents are now available in the United States and Europe for the indication of left ventricular opacification and enhanced endocardial border delineation. The use of contrast enables acquisition of ultrasound images of improved quality. The technique is especially useful in obese patients and those with lung disease. Patients in these categories comprise approximately 10% to 20% of routine echocardiographic examinations. Stress echocardiography examinations can be even more challenging, as the image acquisition time factor is critically important for accurate detection of coronary disease. Improvements in image quality with intravenous contrast agents can facilitate image acquisition and enhance delineation of regional wall motion abnormalities at the peak level of exercise. Recent phase III clinical trial data on the use of Optison and several other agents (currently under evaluation) have revealed that for approximately half of patients, image quality substantively improves, which enables the examination to be salvaged and/or increases diagnostic accuracy. For the "difficult-to-image" patient, this added information results in (1) enhanced laboratory efficiency, (2) a reduction in downstream testing, and (3) possible improvements in patient outcome. In addition, substantial research efforts are underway to use ultrasound contrast agents for assessment of myocardial perfusion. The detection of myocardial perfusion during echocardiographic examinations will permit the simultaneous assessment of global and regional myocardial structure, function, and perfusion-all of the indicators necessary to enable the optimal noninvasive assessment of coronary artery disease. Despite the added benefit in improved efficacy of testing, few data exist regarding the long-term effectiveness of these agents. Currently under evaluation are the clinical and economic outcome implications of intravenous contrast agent use for daily clinical decision making in a variety of patient subsets. Until these data are known, this document offers a preliminary synthesis of available evidence on the value of intravenous contrast agents for use in rest and stress echocardiography. At present, it is the position of this guideline committee that intravenous contrast agents demonstrate substantial value in the difficult-to-image patient with comorbid conditions limiting an ultrasound evaluation of the heart. For such patients, the use of intravenous contrast agents should be encouraged as a means to provide added diagnostic information and to streamline early detection and treatment of underlying cardiac pathophysiology. As with all new technology, this document will require updates and revisions as additional data become available.
The effectiveness of a procedure is increasingly guided by the evaluation of patient outcomes. Outcomes data is used to develop clinical pathways of care and to define appropriate resource-use levels without sacrificing quality of care. Integration of the economic implications of medical services into an outcome-based guideline allows for the development of disease-management strategies. In cardiovascular medicine, risk reduction is associated with high cost due to the "pay-back" of new technologies and therapies. A major challenge is to define a balance between "high tech" care and cost. This paper devises an outpatient evidence-based guideline using clinical and economic outcomes data for the diagnosis of coronary disease.
The aim of this study was to investigate the relation between reversible thallium single-photon emission computed tomography (SPECT) myocardial perfusion defects at 1-year after revascularization and quantitative indexes in Emory Angioplasty versus Surgery Trial (EAST) and outcomes 3 years after revascularization in 336 patients. EAST was a randomized controlled trial assessing cardiac outcomes for angioplasty versus bypass surgery for patients with multivessel coronary artery disease. During this prospective trial, a substudy included the evaluation of the prognostic value of reversible defects on quantitative thallium SPECT. At 1-year after revascularization, 336 patients underwent SPECT thallium-201 stress myocardial perfusion and 3-hour delayed imaging. Subsequent events, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery, myocardial infarction, and death, were recorded at 3 years. A stress-induced reversible thallium-201 defect was defined using a quantitative index of a reversibility score >30% and severity score >500. Reversible defects were observed more frequently in the percutaneous transluminal coronary angioplasty than in the coronary artery bypass graft surgery treatment groups (46% vs 27%, p <0.001). A total of 123 patients had stress-induced, reversible thallium defects and more events than patients with other perfusion results (freedom from all events was 81.3% vs 94% [p <0.001], and freedom from myocardial infarction and death 88.3% vs 95.5% [p = 0.031]). Quantitative thallium SPECT at 1 year after revascularization risk stratifies patients as to their likelihood of major cardiac outcomes.
BACKGROUND: Because of its brief hemodynamic effects and minor effect on determinants of myocardial oxygen demand, vasodilator stress myocardial perfusion imaging (MPI) can be applied very early after acute myocardial infarction (AMI) for risk stratification, allowing management decisions to be made earlier and thus potentially shortening hospitalization stays, reducing costs, and preventing early cardiac events. This multicenter randomized trial compared the prognostic value of early dipyridamole MPI and standard predischarge submaximal exercise MPI in patients who presented with AMI. METHODS AND RESULTS: Patients who presented with their first AMI (n=451) were randomized in a 3:1 ratio to undergo either both an early (day 2 to 4) dipyridamole (99m)Tc-sestamibi MPI study and a predischarge (day 6 to 12) submaximal exercise (99m)Tc-sestamibi MPI study or only the predischarge study. Multivariate predictors of in-hospital cardiac events included nuclear imaging summed stress and summed reversibility scores and peak creatine kinase. For postdischarge cardiac events, multivariate predictors in patients undergoing dipyridamole MPI included only the summed stress, reversibility, and rest imaging scores and anterior MI. For a given summed stress score, the interaction of reversibility score further improved the predictive value. Dipyridamole MPI showed better risk stratification than submaximal exercise MPI. CONCLUSIONS: Dipyridamole MPI very early after MI predicts early and late cardiac events, with superior prognostic value compared with submaximal exercise imaging. The extent and severity of the stress defect and reversibility of the defect were the most important predictors of cardiac death and recurrent MI. This technique can allow management decisions to be made earlier with regard to AMI patients and could have important economic impact if applied widely.
This review suggests that the field of nuclear cardiology is alive, well, and thriving, providing relevant information that aids in everyday clinical decision making for nuclear medicine and referring physicians alike. Despite the competition from other modalities, the clinically appropriate applications of nuclear cardiology techniques are likely to increase. The foundation of this optimism is based on the vast amount of data documenting cost-effective clinical applications for diagnosis, risk stratification, and assessing therapy in both chronic and acute coronary artery disease (CAD), the powerful objective quantitative analysis of perfusion and function provided by the technique, and the increasing general availability of the approach.
BACKGROUND: Previous studies have shown that myocardial perfusion single photon emission computed tomography (SPECT) provides incremental prognostic information in the general population, but the prognostic efficacy of nuclear testing in patients with diabetes mellitus is unclear. METHODS: We conducted a study with 1271 consecutively registered patients with diabetes and 5862 patients without diabetes with known or suspected coronary artery disease undergoing rest thallium 201/stress technetium 99m sestamibi dual-isotope myocardial perfusion SPECT with exercise or adenosine pharmacologic testing. Patients were followed up for at least 1 year. The successful follow-up rate was 92.4% for patients with diabetes and 94.0% for subjects without diabetes. The mean follow-up period was 23.7 +/- 7.7 months for the former group and 21.5 +/- 6.1 months for the latter. RESULTS: Over the follow-up period, patients with diabetes had significantly higher rates of hard events (cardiac death or nonfatal myocardial infarction) (4.3% per year versus 2.3% per year, P <.001) and higher total event rates (hard events and late revascularization) (9.0% per year versus 5.3% per year, P <. 001) compared with rates among patients without diabetes. Cox proportional hazards analysis revealed that nuclear testing added incremental value over clinical and historical variables among patients with diabetes (global chi(2) increased 46% for the exercise group [n = 619] and 88% for the adenosine group [n = 461]; both P <. 001). The event rates rose significantly as a function of summed stress score and summed difference score among both patients with diabetes and patients without diabetes (P <.001). The patients with diabetes with normal scans had relatively low hard event rates (1% to 2% per year), those with mildly abnormal scans had intermediate hard event rates (3% to 4% per year), and those with moderately to severely abnormal scans had relatively high hard event rates (>7% per year). CONCLUSIONS: The results of this study indicated that exercise and adenosine stress myocardial perfusion SPECT are valuable for risk stratification and management of patients with diabetes.
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.
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.
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.
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The dramatic transformations taking place in the healthcare environment have created a new paradigm for healthcare and pose far-reaching changes for cardiovascular care. This 2-part paper reviews these changes and discusses the major implications for cardiovascular specialists, based on literature reviews and summaries of legislative initiatives. The new healthcare paradigm focuses on a continuum of care, wellness maintenance and promotion, accountability for the healthcare of defined populations, and provider differentiation based on ability to add 'value' to the patient's healthcare outcome. This paradigm will become 'standard operating procedure' in the cardiovascular market. As a result, major areas of change in the cardiovascular environment include: continuing growth of managed care arrangements, expanding physician and other payment reforms, growing influence of state and private payer initiatives, expanding role of 'centers of excellence,' continuing surplus of physicians, growth in pharmaceuticals and new technologies, and extension of evidence-based guidelines. Practice guidelines, in particular, will become an integral part of medical practice and will represent the standards against which medical practice will be measured. Given the prominent position of cardiovascular disease in healthcare, cardiovascular specialists will remain in the forefront of these developments.
This paper, the second in a series of 2, reviews major developments and trends in the current healthcare arena that will affect cardiovascular disease (CVD) treatment over the next 10 years. The paper also discusses the implications and future outlook for cardiovascular services in a managed care environment.
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.
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.
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.
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.