Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.     

Comparative localization of myocardial ischemia by exercise electrocardiography and myocardial perfusion SPECT

BACKGROUND: Prior angiographic study has shown that the patterns of ST-segment depression during exercise do not provide localizing information of the responsible coronary lesion. However, little is known regarding the ability of exercise-induced ST-segment displacement to localize myocardial perfusion defects. METHODS AND RESULTS: We studied 552 consecutive patients without prior myocardial infarction who had reversible perfusion defect in one vascular territory on rest 201Tl/exercise 99mTc-labeled sestamibi dual-isotope myocardial perfusion single photon emission computed tomography (SPECT) and ischemic ST depression or elevation during exercise. Of these, 192 patients had angiographically documented coronary artery disease (CAD). Two hundred thirty-two patients had maximal ST depression in anterior leads, 247 patients had maximal ST depression in inferior leads, and 45 patients had similar maximal ST depression in both anterior and inferior leads. Twenty-eight (5%) patients had ST elevation with absent Q waves. In patients with maximal ST depression in anterior leads, perfusion defects were found in the territory of the left anterior descending coronary artery (LAD) in 30%, in the territory of the right coronary artery (RCA) in 52%, and in the territory of the left circumflex coronary artery (LCX) in 18%. In patients with maximal ST depression in inferior leads, perfusion defects were found in RCA territory in 44%, in the LAD territory in 42%, and in the LCX territory in 14%. Compared with exercise ST depression, the less common finding of ST elevation did provide accurate localization of perfusion defects. When ST elevation was greatest in the anterior leads, 96% of patients had LAD territory defects. When ST elevation was most prominent in the inferior leads, 100% patients had RCA territory defects. Data of coronary angiograms demonstrated that myocardial perfusion SPECT correctly identified the most stenotic coronary disease for LAD (94%), LCX (72%), and RCA (75%). CONCLUSIONS: The findings of this study indicate that the site of maximal ST-segment depression does not identify the localization of myocardial perfusion defects. However, the less common finding of exercise-induced ST-segment elevation does predict localization of myocardial ischemia.     

Relationship between stress-induced myocardial ischemia and atherosclerosis measured by coronary calcium tomography

OBJECTIVES: We assessed the relationship between stress-induced myocardial ischemia on myocardial perfusion single-photon emission computed tomography (MPS) and magnitude of coronary artery calcification (CAC) by X-ray tomography in patients undergoing both tests. BACKGROUND: There has been little evaluation regarding the relationship between CAC and inducible ischemia or parameters that might modify this relationship. METHODS: A total of 1,195 patients without known coronary disease, 51% asymptomatic, underwent stress MPS and CAC tomography within 7.2 +/- 44.8 days. The frequency of ischemia by MPS was compared to the magnitude of CAC abnormality. RESULTS: Among 76 patients with ischemic MPS, the CAC scores were >0 in 95%, >or=100 in 88%, and >or=400 in 68%. Of 1,119 normal MPS patients, CAC scores were >0, >or=100, and >or=400 in 78%, 56%, and 31%, respectively. The frequency of ischemic MPS was <2% with CAC scores <100 and increased progressively with CAC >or=100 (p for trend <0.0001). Patients with symptoms with CAC scores >or=400 had increased likelihood of MPS ischemia versus those without symptoms (p = 0.025). Absolute rather than percentile CAC score was the most potent predictor of MPS ischemia by multivariable analysis. Importantly, 56% of patients with normal MPS had CAC scores >or=100. CONCLUSIONS: Ischemic MPS is associated with a high likelihood of subclinical atherosclerosis by CAC, but is rarely seen for CAC scores <100. In most patients, low CAC scores appear to obviate the need for subsequent noninvasive testing. Normal MPS patients, however, frequently have extensive atherosclerosis by CAC criteria. These findings imply a potential role for applying CAC screening after MPS among patients manifesting normal MPS.     

Clinical outcomes after both coronary calcium scanning and exercise myocardial perfusion scintigraphy.

OBJECTIVES: The purpose of this work was to assess the prognosis in patients undergoing both coronary artery calcium (CAC) scanning and exercise myocardial perfusion scintigraphy (MPS). BACKGROUND: Whereas the prognostic effectiveness of MPS is well established, recent studies indicate that quantification of CAC also predicts cardiac outcomes. However, prognostic information is not yet available upon which to guide the management of patients who have had both tests. METHODS: We assessed the frequency of cardiac death and myocardial infarction over a mean follow-up of 32 +/- 16 months in 1,153 patients undergoing both CAC scanning and MPS. Results were compared with those from a referent cohort of 9,308 patients who had earlier undergone MPS only. RESULTS: The frequency of myocardial ischemia rose with increasing CAC scores (p < 0.001), but ischemia was present in only 64 patients. Among the 1,089 nonischemic patients, of which only 3 (0.3%) underwent early revascularization, the annualized cardiac event rate was <1% in all CAC subgroups, including those with CAC scores >1,000. Kaplan-Meier analysis revealed similarly low cardiac event rates among nonischemic patients with CAC scores >1,000 and nonischemic patients with Bayesian coronary artery disease likelihood > or =85%. Late myocardial revascularization rates were also similar in these 2 groups. CONCLUSIONS: Among patients with nonischemic MPS studies, high CAC scores do not confer an increased risk for cardiac events. Thus, although patients with high CAC scores may be considered for intensive medical therapy to prevent future coronary artery disease events, a normal MPS study in such patients suggests no need for more aggressive interventions.     

Concordance of coronary artery calcium estimates between MDCT and electron beam tomography

OBJECTIVE: The objective of our study was to compare MDCT with electron beam tomography (EBT) for the quantification of coronary artery calcification (CAC). MATERIALS AND METHODS: Sixty-eight patients underwent both MDCT and EBT within 2 months for the quantification of CAC. The images were scored in a blinded fashion and independently by two observers with a minimum of 7 days between the interpretations of images obtained from one scanner type to the other. RESULTS: Presence versus absence of CAC was discordant by EBT versus MDCT in 6% (n = 4) of the cases by observer 1, with one of these cases also discordant by observer 2. All cases except one (aortic calcium misidentified as CAC) were among those with a mean Agatston score of less than 5 present on EBT but absent on MDCT. EBT and MDCT scores correlated well (r = 0.98-0.99). The relative median variability between EBT and MDCT for the Agatston score was 24% for observer 1 and 27% for observer 2 and was 18% and 14%, respectively, for volume score (average for both observers: 27% for Agatston score and 16% for volume score). Scores were higher for EBT than MDCT in approximately half of the cases, with little systematic difference between the two (median EBT-MDCT difference: Agatston score, -0.55; volume score, 3.4 mm3). The absolute median difference averaged for the two observers was 28.75 for the Agatston score and 15.4 mm3 for the volume score. CONCLUSION: Differences in CAC measurements using EBT and MDCT are similar to interscan differences in CAC measurements previously reported for EBT or for other MDCT scanners individually.