Gary V. Heller

Cardiac Outcomes After Screening for Asymptomatic Coronary Artery Disease in Patients With Type 2 Diabetes: The DIAD Study: A Randomized Controlled Trial

CONTEXT Coronary artery disease (CAD) is the major cause of mortality and morbidity in patients with type 2 diabetes. But the utility of screening patients with type 2 diabetes for asymptomatic CAD is controversial. OBJECTIVE To assess whether routine screening for CAD identifies patients with type 2 diabetes as being at high cardiac risk and whether it affects their cardiac outcomes. DESIGN, SETTING, AND PATIENTS The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study is a randomized controlled trial in which 1123 participants with type 2 diabetes and no symptoms of CAD were randomly assigned to be screened with adenosine-stress radionuclide myocardial perfusion imaging (MPI) or not to be screened. Participants were recruited from diabetes clinics and practices and prospectively followed up from August 2000 to September 2007. MAIN OUTCOME MEASURE Cardiac death or nonfatal myocardial infarction (MI). RESULTS The cumulative cardiac event rate was 2.9% over a mean (SD) follow-up of 4.8 (0.9) years for an average of 0.6% per year. Seven nonfatal MIs and 8 cardiac deaths (2.7%) occurred among the screened group and 10 nonfatal MIs and 7 cardiac deaths (3.0%) among the not-screened group (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.44-1.88; P = .73). Of those in the screened group, 409 participants with normal results and 50 with small MPI defects had lower event rates than the 33 with moderate or large MPI defects; 0.4% per year vs 2.4% per year (HR, 6.3; 95% CI, 1.9-20.1; P = .001). Nevertheless, the positive predictive value of having moderate or large MPI defects was only 12%. The overall rate of coronary revascularization was low in both groups: 31 (5.5%) in the screened group and 44 (7.8%) in the unscreened group (HR, 0.71; 95% CI, 0.45-1.1; P = .14). During the course of study there was a significant and equivalent increase in primary medical prevention in both groups. CONCLUSION In this contemporary study population of patients with diabetes, the cardiac event rates were low and were not significantly reduced by MPI screening for myocardial ischemia over 4.8 years. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00769275.

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

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:

Clinical value of acute rest technetium-99m tetrofosmin tomographic myocardial perfusion imaging in patients with acute chest pain and nondiagnostic electrocardiograms

2,878 to

Comparative Effectiveness of Exercise Electrocardiography With or Without Myocardial Perfusion Single Photon Emission Computed Tomography in Women With Suspected Coronary Artery Disease Results From the What Is the Optimal Method for Ischemia Evaluation in Women (WOMEN) Trial

4,579), as compared with stress myocardial perfusion imaging plus selective catheterization (range:

Safety of dipyridamole testing in 73,806 patients: The Multicenter Dipyridamole Safety Study

2,387 to

Patient management after noninvasive cardiac imaging: Results from SPARC (Study of myocardial perfusion and coronary anatomy imaging roles in coronary artery disease)

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.

The noninvasive prediction of cardiac mortality in men and women with known or suspected coronary artery disease

OBJECTIVES We sought to evaluate the clinical use and cost-analysis of acute rest technetium-99m (Tc-99m) tetrofosmin single-photon emission computed tomographic (SPECT) myocardial perfusion imaging in patients with chest pain and a normal electrocardiogram (ECG). BACKGROUND Current approaches used in emergency departments (EDs) for treating patients presenting with chest pain and a nondiagnostic ECG result in poor resource utilization. METHODS Three hundred fifty-seven patients presenting to six centers with symptoms suggestive of myocardial ischemia and a nondiagnostic ECG underwent Tc-99m tetrofosmin SPECT during or within 6 h of symptoms. Follow-up evaluation was performed during the hospital period and 30 days after discharge. All entry ECGs, SPECT images and cardiac events were reviewed in blinded manner and were not available to the admitting physicians. RESULTS By consensus interpretation, 204 images (57%) were normal, and 153 were abnormal (43%). Of 20 patients (6%) with an acute myocardial infarction (MI) during the hospital period, 18 had abnormal images (sensitivity 90%), whereas only 2 had normal images (negative predictive value 99%). Multiple logistic regression analysis demonstrated abnormal SPECT imaging to be the best predictor of MI and significantly better than clinical data. Using a normal SPECT image as a criterion not to admit patients would result in a 57% reduction in hospital admissions, with a mean cost savings per patient of

Functional assessment with electrocardiographic gated single-photon emission computed tomography improves the ability of technetium-99m sestamibi myocardial perfusion imaging to predict myocardial viability in patients undergoing revascularization.

4,258. CONCLUSIONS Abnormal rest Tc-99m tetrofosmin SPECT imaging accurately predicts acute MI in patients with symptoms and a nondiagnostic ECG, whereas a normal study is associated with a very low cardiac event rate. The use of acute rest SPECT imaging in the ED can substantially and safely reduce the number of unnecessary hospital admissions.

Independent prognostic value of intravenous dipyridamole with technetium-99m sestamibi tomographic imaging in predicting cardiac events and cardiac-related hospital admissions

Background— There is a paucity of randomized trials regarding diagnostic testing in women with suspected coronary artery disease (CAD). It remains unclear whether the addition of myocardial perfusion imaging (MPI) to the standard ECG exercise treadmill test (ETT) provides incremental information to improve clinical decision making in women with suspected CAD. Methods and Results— We randomized symptomatic women with suspected CAD, an interpretable ECG, and ≥5 metabolic equivalents on the Duke Activity Status Index to 1 of 2 diagnostic strategies: ETT or exercise MPI. The primary end point was 2-year incidence of major adverse cardiac events, defined as CAD death or hospitalization for an acute coronary syndrome or heart failure. A total of 824 women were randomized to ETT or exercise MPI. For women randomized to ETT, ECG results were normal in 64%, indeterminate in 16%, and abnormal in 20%. By comparison, the exercise MPI results were normal in 91%, mildly abnormal in 3%, and moderate to severely abnormal in 6%. At 2 years, there was no difference in major adverse cardiac events (98.0% for ETT and 97.7% for MPI; P=0.59). Compared with ETT, index testing costs were higher for exercise MPI (P<0.001), whereas downstream procedural costs were slightly lower (P=0.0008). Overall, the cumulative diagnostic cost savings was 48% for ETT compared with exercise MPI (P<0.001). Conclusions— In low-risk, exercising women, a diagnostic strategy that uses ETT versus exercise MPI yields similar 2-year posttest outcomes while providing significant diagnostic cost savings. The ETT with selective follow-up testing should be considered as the initial diagnostic strategy in symptomatic women with suspected CAD. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT00282711.

Diagnostic accuracy of cardiac positron emission tomography versus single photon emission computed tomography for coronary artery disease: a bivariate meta-analysis.

BackgroundDipyridamole imaging is widely used as an alternative to exercise testing to identify and risk stratify patients with coronary artery disease. Safety data on intravenous dipyridamole stress testing has been derived largely from individual institutional data.Methods and ResultsData were collected retrospectively by 85 coinvestigators from 73,806 patients who underwent intravenous dipyridamole stress imaging in 59 hospitals and 19 countries to determine the incidence of major adverse reactions during testing. The dose of dipyridamole infused was 0.56 mg/kg in 64,740 patients, 0.74 mg/kg in 6551 patients, and 0.84 mg/kg in 2515 patients. Combined major adverse events among the entire 73,806 patients included seven cardiac deaths (0.95 per 10,000), 13 nonfatal myocardial infarctions (1.76 per 10,000), six nonfatal sustained ventricular arrhythmias (0.81 per 10,000) ((ventricular tachycardia in two and ventricular fibrillation in four), nine transient cerebral ischemic attacks (1.22 per 10,000), (with speech or motor deficit), one stroke, and nine severe bronchospasms (1.22 per 10,000) (one intubation and eight near intubations). In addition to the safety data, detailed demographic, peripheral hemodynamic, side effect, and concomitant drug data were examined in a subgroup of 3751 patients. End points from subsets of patients were compared with those of the group as a whole. Multivariate analysis revealed that dipyridamole-induced chest pain was more common in patients less than 70 years old (p = 0.0017), those with a history of coronary revascularization (p = 0.002), or patients taking aspirin (p = 0.0001). Minor noncardiac side effects were less frequent among the elderly (p = 0.0053) and more frequent in women (p = 0.0001) and patients taking maintenance aspirin (p = 0.0034). When a patient was judged on the basis of the adequacy of hemodynamic response to be a dipyridamole “nonresponder” (< 10 mm Hg drop in systolic blood pressure and 10 beats/min increase in heart rate), the only significant predictor was angiotensin-converting enzyme inhibitor intake (p = 0.0025). Inferoposterior hypoperfusion was significantly more frequent in patients with dipyridamole-induced hypotension: 57% (44/77) (p < 0.0001) of those who had hypotension and 89% (8/9) (p = 0.0076) who had severe symptomatic bradyarrhythmias displayed inferoposterior defects on thallium scanning. Caffeine levels were determined in 391 consecutive patients: levels greater than 5 mg/L were observed in only eight patients (2%), suggesting that methylxanthine levels sufficients to alter the hemodynamic response to dipyridamole resulting in suboptimal hyperemic stress are unlikely when patients take nothing by mouth after midnight.ConclusionThe risk of serious dipyridamole-induced side effects is very low and is comparable to that reported for exercise testing in a similar patient population.