Biomedical subjects
Publications and source records attributed to Leslee J Shaw.
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Noninvasive cardiac imaging has undergone a recent resurgence with the development of new approaches for imaging coronary atherosclerosis. Non-contrast computed tomography (CT) for imaging the extent of coronary artery calcification (CAC) and contrast CT for noninvasive coronary angiography (CTA) are developments with a growing evidence base regarding risk assessment and the diagnosis of obstructive coronary disease. This review discusses the role of CAC for risk assessment of asymptomatic individuals and for the use of coronary CTA in symptomatic patients. By comparison, gated myocardial perfusion scintigraphy (MPS) is a well-established noninvasive imaging modality that is a core element in evaluation of patients with stable chest pain syndromes. Stress MPS is the most commonly used stress imaging technique for patients with suspected or known coronary disease. In contrast to the nascent evidence noted with coronary CTA, MPS has a robust evidence base, including the support of numerous clinical guidelines. We highlight the current evidence supporting the diagnostic accuracy and risk stratification data for MPS for symptomatic patients with known or suspected coronary artery disease. It is likely that assessing the extent of atherosclerosis using CAC or coronary CTA will become an increasing part of mainstream cardiovascular imaging practices. In some patients, further ischemia testing with MPS will be required. Similarly, in some patients referred for MPS, anatomic definition of atherosclerosis using CAC by CT may be appropriate. Thus, this review also provides a synopsis of the available literature on imaging that integrates both CT and MPS in combined strategies for the assessment of atherosclerotic and obstructive coronary disease burden. We also propose possible risk-based strategies through which imaging might be used to identifying candidates for more intensive prevention and risk factor modification strategies as well as those who would benefit from referral to coronary angiography and revascularization.
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OBJECTIVES: The purpose of this study was to determine the relative benefit of intensive medical therapy compared with coronary revascularization for suppressing scintigraphic ischemia. BACKGROUND: Although medical therapies can reduce myocardial ischemia and improve patient survival after acute myocardial infarction, the relative benefit of medical therapy versus coronary revascularization for reducing ischemia is unknown. METHODS: A prospective randomized trial in 205 stable survivors of acute myocardial infarction was made to define the relative efficacy of an intensive medical therapy strategy versus coronary revascularization for suppressing scintigraphic ischemia as assessed by serial gated adenosine Tc-99m sestamibi myocardial perfusion tomography. All patients at baseline had large total (> or =20%) and ischemic (> or =10%) adenosine-induced left ventricular perfusion defects and an ejection fraction > or =35%. Imaging was performed during 1 to 10 days of hospital admission and repeated in an identical fashion after optimization of therapy. Patients randomized to either strategy had similar baseline demographic and scintigraphic characteristics. RESULTS: Both intensive medical therapy and coronary revascularization induced significant but comparable reductions in total (-16.2 +/- 10% vs. -17.8 +/- 12%; p = NS) and ischemic (-15 +/- 9% vs. -16.2 +/- 9%; p = NS) perfusion defect sizes. Likewise, a similar percentage of patients randomized to medical therapy versus coronary revascularization had suppression of adenosine-induced ischemia (80% vs. 81%; p = NS). CONCLUSIONS: Sequential adenosine sestamibi myocardial perfusion tomography can effectively monitor changes in scintigraphic ischemia after anti-ischemic medical or coronary revascularization therapy. A strategy of intensive medical therapy is comparable to coronary revascularization for suppressing ischemia in stable patients after acute infarction who have preserved LV function.
OBJECTIVES: The purpose of this study was to determine whether gated adenosine Tc-99m sestamibi single-photon emission computed tomography (ADSPECT) could accurately define risk and thereby guide therapeutic decision making in stable survivors of acute myocardial infarction (AMI). BACKGROUND: Controversy continues as to the role of noninvasive stress imaging in stratifying risk early after AMI. METHODS: The INSPIRE (Adenosine Sestamibi Post-Infarction Evaluation) trial is a prospective multicenter trial which enrolled 728 clinically stable survivors of AMI who had gated ADSPECT within 10 days of hospital admission and subsequent 1-year follow-up. Event rates were assessed within prospectively defined INSPIRE risk groups based on the adenosine-induced left ventricular perfusion defect size, extent of ischemia, and ejection fraction. RESULTS: Total cardiac events/death and reinfarction significantly increased within each INSPIRE risk group from low (5.4%, 1.8%), to intermediate (14%, 9.2%), to high (18.6%, 11.6%) (p < 0.01). Event rates at 1 year were lowest in patients with the smallest perfusion defects but progressively increased when defect size exceeded 20% (p < 0.0001). The perfusion results significantly improved risk stratification beyond that provided by clinical and ejection fraction variables. The low-risk INSPIRE group, comprising one-third of all enrolled patients, had a shorter hospital stay with lower associated costs compared with the higher-risk groups (p < 0.001). CONCLUSIONS: Gated ADSPECT performed early after AMI can accurately identify a sizeable low-risk group who have a <2% death and reinfarction rate at 1 year. Identifying these low-risk patients for early hospital discharge may improve utilization of health care resources at considerable cost savings.
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AIMS: Technological advances in cardiac imaging have led to dramatic increases in test utilization and consumption of a growing proportion of cardiovascular healthcare costs. The opportunity costs of strategies favouring exercise echocardiography or SPECT imaging have been incompletely evaluated. METHODS AND RESULTS: We examined prognosis and cost-effectiveness of exercise echocardiography (n = 4884) vs. SPECT (n = 4637) imaging in stable, intermediate risk, chest pain patients. Ischaemia extent was defined as the number of vascular territories with echocardiographic wall motion or SPECT perfusion abnormalities. Cox proportional hazard models were employed to assess time to cardiac death or myocardial infarction (MI). Total cardiovascular costs were summed (discounted and inflation-corrected) throughout follow-up. A cost-effectiveness ratio < Dollars 50,000 per life year saved (LYS) was considered favourable for economic efficiency. The risk-adjusted 3-year death or MI rates classified by extent of ischaemia were similar, ranging from 2.3 to 8.0% for echocardiography and from 3.5 to 11.0% for SPECT (model chi2 = 216; P < 0.0001; interaction P = 0.24). Cost-effectiveness ratios for echocardiography were < Dollars 20,000/LYS when the annual risk of death or MI was < 2%. However, when yearly cardiac event rate were > 2%, cost-effectiveness ratios for echocardiography vs. SPECT were in the range of Dollars 66,686-Dollars 419,522/LYS. For patients with established coronary disease (i.e. > or = 2% annual event risk), SPECT ischaemia was associated with earlier and greater utilization of coronary revascularization (P < 0.0001) resulting in an incremental cost-effectiveness ratio of Dollars 32,381/LYS. CONCLUSION: Health care policies aimed at allocating limited resources can be effectively guided by applying clinical and economic outcomes evidence. A strategy aimed at cost-effective testing would support using echocardiography in low-risk patients with suspected coronary disease, whereas those higher risk patients benefit from referral to SPECT imaging.
BACKGROUND: Coronary angiography is one of the most frequently performed procedures in women; however, nonobstructive (ie, < 50% stenosis) coronary artery disease (CAD) is frequently reported. Few data exist regarding the type and intensity of resource consumption in women with chest pain after coronary angiography. METHODS AND RESULTS: A total of 883 women referred for coronary angiography were prospectively enrolled in the National Institutes of Health--National Heart, Lung, and Blood Institute--sponsored Women's Ischemia Syndrome Evaluation (WISE). Cardiovascular prognosis and cost data were collected. Direct (hospitalizations, office visits, procedures, and drug utilization) and indirect (out-of-pocket, lost productivity, and travel) costs were estimated through 5 years of follow-up. Among 883 women, 62%, 17%, 11%, and 10% had nonobstructive and 1-vessel, 2-vessel, and 3-vessel CAD, respectively. Five-year cardiovascular death or myocardial infarction rates ranged from 4% to 38% for women with nonobstructive to 3-vessel CAD (P < 0.0001). Five-year rates of hospitalization for chest pain occurred in 20% of women with nonobstructive CAD, increasing to 38% to 55% for women with 1-vessel to 3-vessel CAD (P < 0.0001). The volume of repeat catheterizations or angina hospitalizations was 1.8-fold higher in women with nonobstructive versus 1-vessel CAD after 1 year of follow-up (P < 0.0001). Drug treatment was highest for those with nonobstructive or 1-vessel CAD (P < 0.0001). The proportion of costs for anti-ischemic therapy was higher for women with nonobstructive CAD (15% versus 12% for 1-vessel to 3-vessel CAD; P = 0.001). For women with nonobstructive CAD, average lifetime cost estimates were $767,288 (95% CI, $708,480 to $826,097) and ranged from $1,001,493 to $1,051,302 for women with 1-vessel to 3-vessel CAD (P = 0.0003). CONCLUSIONS: Symptom-driven care is costly even for women with nonobstructive CAD. Our lifetime estimates for costs of cardiovascular care identify a significant subset of women who are unaccounted for within current estimates of the economic burden of coronary heart disease.
PURPOSE: Non-invasive evaluation of coronary artery disease (CAD) in patients with left bundle branch block (LBBB) has limitations inherent to different tests, and the relative merits of these tests are unclear. This meta-analysis assessed the accuracy of the frequently used non-invasive techniques, including exercise electrocardiography (ECG), myocardial perfusion imaging (MPI) and stress echocardiography (SE), for detection of CAD and prediction of cardiac events in patients with LBBB. METHODS: A review was conducted of all reports on detection of CAD and prediction of cardiac events in patients with LBBB (published between January 1970 and December 2004), and revealed 55 diagnostic and nine prognostic reports with sufficient details to calculate test accuracy. Weighted (by sample size) sensitivity and specificity were calculated. Summary relative risk ratios (95% confidence intervals) were calculated. RESULTS: Overall sensitivity was higher for exercise ECG and (quantitatively analysed) MPI than for SE (83.4% and 88.5% versus 74.6% respectively, p<0.0001). SE had a higher specificity (88.7%) than MPI (41.2%) and exercise ECG (60.1%) (p<0.0001). Based on analysis of eight reports, the relative risk of cardiac death or myocardial infarction in patients with an abnormal SE and MPI was elevated more than sevenfold, but it did not differ by imaging modality (p=0.9). CONCLUSION: Meta-analysis of non-invasive CAD assessment in LBBB patients revealed that exercise ECG and MPI had the highest sensitivity, while SE had the highest specificity. The prognostic accuracy of MPI and SE appeared similar.
Screening for early-stage asymptomatic cancers (eg, cancers of breast and colon) to prevent late-stage malignancies has been widely accepted. However, although atherosclerotic cardiovascular disease (eg, heart attack and stroke) accounts for more death and disability than all cancers combined, there are no national screening guidelines for asymptomatic (subclinical) atherosclerosis, and there is no government- or healthcare-sponsored reimbursement for atherosclerosis screening. Part I and Part II of this consensus statement elaborated on new discoveries in the field of atherosclerosis that led to the concept of the "vulnerable patient." These landmark discoveries, along with new diagnostic and therapeutic options, have set the stage for the next step: translation of this knowledge into a new practice of preventive cardiology. The identification and treatment of the vulnerable patient are the focuses of this consensus statement. In this report, the Screening for Heart Attack Prevention and Education (SHAPE) Task Force presents a new practice guideline for cardiovascular screening in the asymptomatic at-risk population. In summary, the SHAPE Guideline calls for noninvasive screening of all asymptomatic men 45-75 years of age and asymptomatic women 55-75 years of age (except those defined as very low risk) to detect and treat those with subclinical atherosclerosis. A variety of screening tests are available, and the cost-effectiveness of their use in a comprehensive strategy must be validated. Some of these screening tests, such as measurement of coronary artery calcification by computed tomography scanning and carotid artery intima-media thickness and plaque by ultrasonography, have been available longer than others and are capable of providing direct evidence for the presence and extent of atherosclerosis. Both of these imaging methods provide prognostic information of proven value regarding the future risk of heart attack and stroke. Careful and responsible implementation of these tests as part of a comprehensive risk assessment and reduction approach is warranted and outlined by this report. Other tests for the detection of atherosclerosis and abnormal arterial structure and function, such as magnetic resonance imaging of the great arteries, studies of small and large artery stiffness, and assessment of systemic endothelial dysfunction, are emerging and must be further validated. The screening results (severity of subclinical arterial disease) combined with risk factor assessment are used for risk stratification to identify the vulnerable patient and initiate appropriate therapy. The higher the risk, the more vulnerable an individual is to a near-term adverse event. Because <10% of the population who test positive for atherosclerosis will experience a near-term event, additional risk stratification based on reliable markers of disease activity is needed and is expected to further focus the search for the vulnerable patient in the future. All individuals with asymptomatic atherosclerosis should be counseled and treated to prevent progression to overt clinical disease. The aggressiveness of the treatment should be proportional to the level of risk. Individuals with no evidence of subclinical disease may be reassured of the low risk of a future near-term event, yet encouraged to adhere to a healthy lifestyle and maintain appropriate risk factor levels. Early heart attack care education is urged for all individuals with a positive test for atherosclerosis. The SHAPE Task Force reinforces existing guidelines for the screening and treatment of risk factors in younger populations. Cardiovascular healthcare professionals and policymakers are urged to adopt the SHAPE proposal and its attendant cost-effectiveness as a new strategy to contain the epidemic of atherosclerotic cardiovascular disease and the rising cost of therapies associated with this epidemic.
AIMS: Women with chest pain but without obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular (CV) events, but half continue to experience debilitating chest pain over many years. This study compared CV outcomes in women with persistent chest pain (PChP) vs. those without PChP. METHODS AND RESULTS: We studied 673 Women's Ischaemia Syndrome Evaluation (WISE) participants with chest pain undergoing coronary angiography for suspected myocardial ischaemia and at least 1 year of follow-up. PChP was defined as self-reported continuing chest pain after 1 year. Events occurring after that year were recorded for a median of 5.2 years. We compared CV event rates for women with and without PChP in subgroups with and without obstructive CAD. The median age was 58 years, 20% were racial minorities, 45% had PChP, 39% had obstructive CAD. Among women without CAD, those with PChP had more than twice the rate of composite CV events (P = 0.03), that included non-fatal myocardial infarctions (P = 0.11), strokes (P = 0.03), congestive heart failure (P = 0.38), and CV deaths (P = 0.73), compared with those without PChP. In women with CAD, there was no difference in composite CV events in those with and without PChP (P = 0.72). CONCLUSION: Among women undergoing coronary angiography for suspected myocardial ischaemia, PChP in women with no obstructive CAD predicted adverse CV outcomes. Such women might benefit from additional evaluation and aggressive risk factor modification therapy.
The metabolic syndrome represents a constellation of risk factors caused by insulin resistance, dyslipidemia, hypertension, and obesity, resulting in elevated coronary disease risk. From a multicenter prospective registry of 7,849 patients, the relation among the metabolic syndrome, diabetes, and risk stratification with stress technetium-99m tetrofosmin single photon-emission computed tomography (SPECT) was evaluated. The percentage of stress myocardial defects was calculated as < or = 5%, 5.1% to 10%, 10.1% to 15%, and > 15%. A Cox proportional-hazards model was used to estimate cardiovascular death or myocardial infarction (n = 752). Of 7,849 patients, 42% had the metabolic syndrome. Patients with the metabolic syndrome had an 84% 2-year event-free survival rate, lower than patients with normal metabolic status (p <0.0001). In patients with the metabolic syndrome, the percentage of moderate to severely abnormal SPECT findings ranged from 11% to 44% for those with 3 to 5 risk factors for the metabolic syndrome. There was an additive relation between the number of risk factors for the metabolic syndrome and the extent and severity of abnormalities in SPECT findings (p <0.0001). Patients with 5 risk factors for the metabolic syndrome were at the greatest risk, with hazard ratios from 7.8- to 14.1-fold for mild to severely abnormal SPECT findings. For diabetic patients requiring combined oral and insulin therapy, relative risk ratios increased from 15 to 21.4 for patients with > 5% to > 15% stress myocardial perfusion defects. In conclusion, cardiovascular prognosis is affected by the degree of metabolic dysfunction, and stress-induced reductions in myocardial perfusion provide an accurate means for near-term risk stratification.
OBJECTIVES: The purpose of this study was to assess the relationship between body mass index (BMI) and the prognostic value of myocardial perfusion single-photon emission computed tomography (MPS). BACKGROUND: The prognostic value of MPS in the obese has not been evaluated. METHODS: We studied 4,720 patients with and 10,019 patients without known coronary artery disease (CAD) who underwent rest Tl-201/stress Tc-99m sestamibi MPS, including 5,233 gated MPS studies and followed up (mean 2.7 to 3.2 years). Patients were categorized as normal weight (BMI 18.5 to 24.9 kg/m2), overweight (BMI 25.0 to 29.9 kg/m2), or obese (BMI > or =30.0 kg/m2). RESULTS: Unadjusted annual rates of cardiac death (CD) rose versus stress MPS abnormalities in all weight groups (p < 0.001). Obese or overweight patients with or without known CAD who had normal MPS were at low CD risk (<1%/year), similar to normal weight patients. In CAD, obese and overweight patients with abnormal MPS had lower rates of CD compared with normal weight patients (p < 0.01). In patients with low ejection fraction (EF) by gated MPS, those with normal weight had highest CD rate (p = 0.001). Multivariable models revealed that BMI was not a predictor of CD in suspected CAD patients (hazard ratio [HR] 0.99; 95% confidence interval [CI] 0.95 to 1.02) but was an independent inverse predictor of CD in known CAD patients (HR 0.95; 95% CI 0.92 to 0.98), especially in women, adenosine stress, low EF, or abnormal perfusion. CONCLUSIONS: Normal MPS was associated with low risk of CD in patients of all weight categories. In patients with known CAD undergoing MPS, obese and overweight patients were at lower risk of CD over three years than normal weight patients.
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AIMS: To determine the prevalence and clinical predictors of subclinical atherosclerosis and myocardial ischaemia in uncomplicated type 2 diabetes and assess their relationship to short-term outcome. METHODS AND RESULTS: Established risk factors and coronary artery calcium (CAC) scores were prospectively measured in 510 asymptomatic type 2 diabetic subjects (mean age 53+/-8 years, 61% males) without prior cardiovascular disease. Myocardial perfusion scintigraphy (MPS) was performed in all subjects with CAC > 100 Agatston units (AU) (n=127), and a random sample of the remaining patients with CAC < or = 100 AU (n=53). Significant CAC (> 10 AU) was found in 46.3%. Twenty events occurred (two coronary deaths, nine non-fatal myocardial infarctions, three acute coronary syndromes, three non-haemorrhagic strokes, and three late revascularisations) during a median follow-up of 2.2 years (25th-75th percentile = 1.9-2.5 years). The age, systolic blood pressure, the duration of diabetes, United Kingdom Prospective Diabetes Study risk score, CAC score, and extent of myocardial perfusion abnormality were significant predictors of time to cardiovascular events in a univariable Cox proportional hazard model. No cardiac events or perfusion abnormalities occurred in subjects with CAC < or = 10 AU up until 2 years of follow-up. CAC and MPS findings were synergistic for the prediction of short-term cardiovascular events. CONCLUSION: Subclinical atherosclerosis, measured by CAC imaging, is superior to the established cardiovascular risk factors for predicting silent myocardial ischaemia and short-term outcome. Further studies evaluating the impact of CAC imaging on clinical outcomes and its cost effectiveness are warranted.
Coronary heart disease is the leading cause of death and disability in the U.S., but recent advances have not led to declines in case fatality rates for women. The current review highlights gender-specific issues in ischemic heart disease (IHD) presentation, evaluation, and outcomes with a special focus on the results derived from the National Institutes of Health-National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. In the second part of this review, we will assess new evidence on gender-based differences in vascular wall or metabolic alterations, atherosclerotic plaque deposition, and functional expression on worsening outcomes of women. Additionally, innovative cardiovascular imaging techniques will be discussed. Finally, we identify critical areas of further inquiry needed to advance this new gender-specific IHD understanding into improved outcomes for women.
Despite a dramatic decline in mortality over the past three decades, coronary heart disease is the leading cause of death and disability in the U.S. Importantly, recent advances in the field of cardiovascular medicine have not led to significant declines in case fatality rates for women when compared to the dramatic declines realized for men. The current review highlights gender-specific issues in ischemic heart disease presentation, evaluation, and outcomes with a special focus on the results published from the National Institutes of Health-National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. We will present recent evidence on traditional and novel risk markers (e.g., high sensitivity C-reactive protein) as well as gender-specific differences in symptoms and diagnostic approaches. An overview of currently available diagnostic test evidence (including exercise electrocardiography and stress echocardiography and single-photon emission computed tomographic imaging) in symptomatic women will be presented as well as data using innovative imaging techniques such as magnetic resonance subendocardial perfusion, and spectroscopic imaging will also be discussed.
OBJECTIVES: We evaluated whether the relationship between hypertension, other cardiac risk factors, and coronary artery disease (CAD) is modulated by menopausal status and/or age. BACKGROUND: The relative contribution of age versus menopausal status in the development of CAD in women remains unclear. METHODS: We compared systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and traditional cardiac risk factors for CAD in premenopausal (n = 123) and postmenopausal (n = 482) women undergoing coronary angiography for suspected ischemia. To assess the relative contribution of age versus menopausal status, we fit a hypertension-menopausal status interaction term and adjusted for age. RESULTS: There were similar relationships with regard to traditional coronary risk factors and angiographic CAD in premenopausal versus postmenopausal women, with few exceptions. Twenty percent of premenopausal women had angiographic CAD versus 31% of postmenopausal women (p = 0.02). Premenopausal women had lower mean (standard deviation) SBP (132 [25] vs. 139 [20] mm Hg; p < 0.0001) and lower PP (54 [18] vs. 62 [18] mm Hg; p < 0.0001) compared to postmenopausal women; however, multivariable analyses revealed that SBP was a risk factor for CAD in premenopausal (p = 0.002) but not postmenopausal women (p = 0.13), and regression slopes were significantly different (p = 0.04). This interaction effect remained after age adjustment, suggesting independent risk contribution from both age and menopausal status. A similar slope difference was observed for PP (p = 0.03) but not for DBP. CONCLUSIONS: Among women undergoing angiography for suspected ischemia, elevated SBP and PP are potent risk factors in premenopausal women. The results suggest that identification of hypertension in premenopausal women dictates additional CAD risk factor assessment and management.