Initial Invasive or Conservative Strategy for Stable Coronary Disease.

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Temporal Trends of Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging in Patients With Coronary Artery Disease: A 22-Year Experience From a Tertiary Academic Medical Center.

BACKGROUND: There has been a gradual decline in the prevalence of abnormal stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging studies among patients without history of coronary artery disease (CAD). The trends of SPECT studies among patients with known CAD have not been evaluated previously. METHODS AND RESULTS: We assessed the Mayo Clinic nuclear cardiology database for all stress SPECT tests performed between January 1991 and December 2012 in patients with history of CAD defined as having previous myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting. The study cohort was divided into 5 time periods: 1991 to 1995, 1996 to 2000, 2001 to 2005, 2006 to 2010, and 2011 to 2012. There were 19 373 patients with a history of CAD who underwent SPECT between 1991 and 2012 (mean age, 66.2±10.9 years; 75.4% men). Annual utilization of SPECT in these patients increased from an average of 495 tests per year in 1991 to 1995 to 1425 in 2003 and then decreased to 552 tests in 2012 without evidence for substitution with other stress modalities. Asymptomatic patients initially increased until 2006 and then decreased. Patients with typical angina decreased, whereas patients with dyspnea and atypical angina increased. High-risk SPECT tests significantly decreased, and the percentage of low-risk SPECT tests increased despite decreased SPECT utilization between 2003 and 2012. Almost 80% of all tests performed in 2012 had a low-risk summed stress score compared with 29% in 1991 (P<0.001). CONCLUSIONS: In Mayo Clinic, Rochester, annual SPECT utilization in patients with previous CAD increased between 1992 and 2003, but then decreased after 2003. High-risk SPECT tests declined, whereas low-risk tests increased markedly. Our results suggest that among patients with a history of CAD, SPECT was being increasingly utilized in patients with milder CAD. This trend parallels reduced utilization of other stress modalities, coronary angiography, reduced smoking, and greater utilization of optimal medical therapy for prevention and treatment of CAD.

Population-based study of the use of cardiac stress imaging and referral for coronary angiography and repeated revascularization after coronary artery bypass graft surgery.

OBJECTIVE: To assess stress single-photon emission computed tomography (SPECT) and stress echocardiography use after coronary artery bypass grafting (CABG) and their effect on referral for coronary angiography and revascularization. PATIENTS AND METHODS: The referral, timing, and results of stress imaging after CABG; referral for coronary angiography and revascularization; and all-cause mortality were assessed in this longitudinal, population-based, retrospective study of 1138 Olmsted County, Minnesota, patients undergoing CABG between January 1, 1993, and December 31, 2003. RESULTS: A total of 570 patients (50.1%) underwent a stress imaging study (341 SPECT and 229 echocardiography) during the study period. Of the 1138 patients, 372 (32.7%) were referred for coronary angiography, and 144 of those patients (12.7%) underwent repeated revascularization (132 percutaneous revascularization and 12 CABG). The median interval between CABG and the index stress imaging study was 3.0 years (25th-75th percentile, 1.2-5.7 years). The results of 75.7% (258 of 341) of the stress SPECT studies and 70.7% (162 of 229) of the stress echocardiograms were abnormal. Seventy-six of 570 patients (13.3%) referred for stress imaging underwent coronary angiography within 180 days after the stress test. Repeated coronary revascularization was performed in 25 patients (4.4%) who underwent a stress imaging study within the preceding 180 days. The 5- and 10-year survival rates in the entire study cohort (83.5% and 65.1%, respectively) were not significantly different than predicted for the age- and sex-matched Minnesota population. CONCLUSION: Half of this community-based population of patients with CABG underwent stress SPECT or echocardiography during median follow-up of 8.9 years. Despite that approximately 75% of the results of stress imaging studies were abnormal, subsequent referral for coronary angiography within 180 days was low (13.3%), and the yield for repeated revascularization was very low (4.4%).

Application of appropriateness criteria to stress single photon emission computed tomography sestamibi studies: a comparison of the 2009 revised appropriateness criteria to the 2005 original criteria.

BACKGROUND: The 2005 appropriate use criteria (AUC) for stress single-photon emission computed tomographic myocardial perfusion imaging (SPECT MPI) were revised in 2009 to reflect changes in published evidence, clinical practice and experience with application of the 2005 AUC. The purpose of this study was to compare the 2009 AUC for SPECT MPI with the original 2005 criteria. METHODS: Using the Mayo Rochester Nuclear Cardiology Laboratory database, we retrospectively examined 281 patients who underwent stress SPECT MPI at Mayo Clinic Rochester between May 1, 2005, and May 15, 2005, using the revised 2009 AUC and compared these findings to our previously published results in this same cohort using the 2005 AUC. RESULTS: Compared to the 2005 AUC, the 2009 AUC resulted in a highly significant overall change (P < .001) in the classification of appropriateness. The 2009 AUC eliminated unclassified patients, reduced appropriate studies (59.8% vs 63.7%, P = .02), increased studies of uncertain appropriateness (16.0% vs 10.7%, P = .01), and increased inappropriate studies (24.2% vs 14.6%, P < .001). CONCLUSIONS: In this cohort of patients undergoing SPECT MPI, compared to our previous study using the original 2005 AUC, the 2009 AUC had a significant impact on the classification of appropriateness. The 2009 AUC eliminated unclassified patients, increased inappropriate studies and increased studies of uncertain appropriateness.

The timing and impact of follow-up studies after normal stress single-photon emission computed tomography sestamibi studies.

BACKGROUND: The purpose of this study was to determine the prevalence and timing of routine follow-up single-photon emission computed tomography (SPECT) studies after a normal stress SPECT scan compared with the patient's warranty period (ie, time to 1% risk of death or myocardial infarction). METHODS AND RESULTS: We identified patients at Mayo Clinic Rochester who had normal stress SPECT scans in 2002. Of 2354 patients without prior coronary artery disease, 309 (13%) had routine follow-up scans. The time to routine follow-up was a median of 2.1 years (25th percentile, 1.2 years; 75th percentile, 3.6 years). This interval was a median of 45% of the warranty period. Of the 309 patients, only 9 (3%) underwent subsequent coronary angiography, without revascularization. Of 656 patients with prior coronary artery disease, 171 (26%) had routine follow-up scans. The time to routine follow-up was a median of 1.6 years (25th percentile, 1.0 years; 75th percentile, 2.7 years). This interval was a median of 164% of the warranty period. Of the 171 patients, only 7 (4%) underwent coronary angiography, without revascularization. CONCLUSIONS: In patients without prior coronary artery disease, routine follow-up SPECT scans are performed infrequently but well before the end of the patient's warranty period. Routine follow-up scans are performed more commonly in patients with prior coronary artery disease but generally after the end of the warranty period. Routine follow-up SPECT scans have minimal impact on referral to catheterization or revascularization.

Temporal trends in compliance with appropriateness criteria for stress single-photon emission computed tomography sestamibi studies in an academic medical center.

BACKGROUND: The purpose of this study was to apply published appropriateness criteria for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in a single academic medical center to determine if the percentage of inappropriate studies was changing over time. In a previous study, we applied the American College of Cardiology Foundation/American Society of Nuclear Cardiology (ASNC) appropriateness criteria for stress SPECT MPI and reported that 14% of stress SPECT studies were performed for inappropriate reasons. METHODS: Using similar methodology, we retrospectively examined 284 patients who underwent stress SPECT MPI in October 2006 and compared the findings to the previous cohort of 284 patients who underwent stress SPECT MPI in May 2005. RESULTS: The indications for testing in the 2 cohorts were very similar. The overall level of agreement in characterizing categories of appropriateness between 2 experienced cardiovascular nurse abstractors was good (kappa = 0.68), which represented an improvement from our previous study (kappa = 0.56). There was a significant change between May 2005 and October 2006 in the overall classification of categories for appropriateness (P = .024 by chi(2) statistic). There were modest, but insignificant, increases in the number of patients who were unclassified (15% in the current study vs 11% previously), appropriate (66% vs 64%), and uncertain (12% vs 11%). Only 7% of the studies in the current study were inappropriate, which represented a significant (P = .004) decrease from the 14% reported in the 2005 cohort. CONCLUSIONS: In the absence of any specific intervention, there was a significant change in the overall classification of SPECT appropriateness in an academic medical center over 17 months. The only significant difference in individual categories was a decrease in inappropriate studies. Additional measurements over time will be required to determine if this trend is sustainable or generalizable.

Abnormal electron beam computed tomography results: the value of repeating myocardial perfusion single-photon emission computed tomography in the ongoing assessment of coronary artery disease.

OBJECTIVE: To determine whether asymptomatic patients with atherosclerosis, indicated by the presence of coronary artery calcium on electron beam computed tomography, are at enough risk for progression of disease to justify a repeated stress single-photon emission computed tomography (SPECT) examination after an initial normal to low-risk perfusion study. PATIENTS AND METHODS: We retrospectively identified patients who had abnormal results on electron beam computed tomography (coronary artery calcium score > 0) and normal to low-risk results on SPECT (defined as a summed stress score of 0-3) within a 3-month period from January 1, 1995, to October 31, 2002. Of the 504 identified patients, 285 remained after exclusion criteria were applied. Of the 285 patients, 69 (mean +/- SD age, 58.2 +/- 7.6 years; 91% male) underwent at least 1 repeated myocardial perfusion SPECT imaging study within 4 years of their initial assessment as normal or at low risk without recurrence of symptoms. The value of repeated SPECT imaging was assessed by detection of a substantial change in the repeated SPECT study and by documentation of a clinical event (death, nonfatal myocardial infarction, or revascularization). Follow-up was 100% complete at a mean of 4.3 +/- 1.6 years. RESULTS: Only 4 patients (6%) had a substantial progression in their SPECT risk category; substantial changes on the SPECT scans occurred only in patients with a coronary artery calcium score greater than 100. Three patients underwent revascularization, yielding a 5-year rate for survival free of revascularization of 94% (95% confidence interval, 88%-100%). No deaths or nonfatal myocardial infarctions were reported. CONCLUSION: The principal findings of this study indicate that asymptomatic patients with initial normal or low-risk results from stress SPECT performed because of abnormal coronary artery calcium scores who remain asymptomatic are at low risk of death, myocardial infarction, or coronary revascularization. Three patients underwent revascularization by percutaneous coronary intervention despite the absence of symptoms. A substantial change in SPECT results (defined as progression from normal or low-risk summed stress score to intermediate- or high-risk summed stress score) affected 6% of patients and was not associated with any adverse hard events (nonfatal myocardial infarction or death).

Relationship and prognostic value of coronary artery calcification by electron beam computed tomography to stress-induced ischemia by single photon emission computed tomography.

BACKGROUND: Stress single photon emission computed tomography (SPECT) is commonly performed in patients with abnormal electron beam computed tomography (EBCT) to define risk stratification, but the published prognostic data for patients undergoing both SPECT and EBCT are limited. The objective of the study was to examine the association and prognostic value between EBCT, coronary artery calcium score (CACS), and stress SPECT imaging. METHODS: We identified 835 patients (age 54.8 +/- 10.0 years, 77% male) who underwent EBCT and stress SPECT within a 3-month period. Coronary artery calcium score was categorized as normal (0), minimal (1-10), mild (11-100), moderate (101-400), and severe (>400). Single photon emission computed tomography summed stress score (SSS) was categorized as normal, low risk, intermediate risk, and high risk per Cedar Sinai criteria. Average follow-up was 4.8 +/- 3.2 years. End points were all-cause death, death/myocardial infarction (MI), and death/MI/late revascularization. RESULTS: The correlation of CACS to SSS was weak but statistically significant (r = +0.19, P < .001). The percentage of high-risk SSS increased with higher CACS scores; 4% of patients with normal EBCT and 18% with severe CACS had high-risk SSS. Coronary artery calcium score (chi2 = 11.4, P < .001), diabetes mellitus (chi2 = 4.6, P = .031), and chest pain class (chi2 = 8.7, P = .003) were independently associated with high-risk SPECT. The SSS (chi2 = 6.9, P = .009) and CACS (chi2 = 7.8, P = .005) were independently associated with mortality, as well as with both secondary end points of death/MI and death/MI/late revascularization. Only CACS predicted mortality in the 408 asymptomatic patients (chi2 = 5.2, P = .02), but these patients had an annual mortality of only 0.4% over the next 5 years. CONCLUSIONS: In selected patients undergoing both EBCT and SPECT, CACS is weakly correlated with SPECT SSS, likely reflecting the different information provided by EBCT and SPECT. Coronary artery calcium score is independently associated with high-risk SPECT after adjustment for clinical variables. Coronary artery calcium score and SSS are complementary for the prediction of mortality in symptomatic patients. Only CACS predicted mortality in the asymptomatic patients, but they had a low annual mortality.

Screening asymptomatic diabetic patients for coronary artery disease: why not?

Given the elevated risk of cardiovascular events and the higher prevalence of silent coronary artery disease (CAD) in diabetic versus non-diabetic patients, screening asymptomatic diabetic patients for CAD is an appealing concept. However, many factors argue against implementing a broad-based screening program at the present time. Foremost is the lack of any published data demonstrating that a prospectively applied screening program improves outcome in asymptomatic diabetic patients. The true prevalence of CAD, and in particular prognostically important CAD, in this population is uncertain. Consensus documents recommend more aggressive treatment of hypertension and hyperlipidemia solely on the basis of diabetes status, without differentiation based on the presence or absence of identifiable CAD. There is no evidence that use of anti-ischemic medication can alter the natural history of CAD in these patients. Retrospectively performed studies using stress single-photon emission computed tomography (SPECT) imaging have reported that approximately 50% and 20% of patients have abnormal and high-risk images, respectively. However, the only prospectively designed study, the DIAD (Detection of Ischemia in Asymptomatic Diabetics) study, reported a much lower percentage of abnormal SPECT images (16%) and images with a very large (>/=10% of the left ventricle) defect (1%). The financial implications of screening all asymptomatic diabetic patients determined to be at intermediate and high risk by clinical scoring systems is enormous. Clearly more data are needed to address this issue. Future studies should consider possible methods to enrich the patient subset that might benefit from screening and should include carefully performed cost-effective analyses.

Improved survival in asymptomatic diabetic patients with high-risk SPECT imaging treated with coronary artery bypass grafting.

BACKGROUND: The Bypass Angioplasty Revascularization Investigation trial demonstrated that symptomatic diabetics with multivessel coronary artery disease had a survival advantage with initial coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI). No published study has examined different treatments and outcome in asymptomatic diabetics. METHODS AND RESULTS: This study group consisted of 826 asymptomatic diabetics (age 62+/-12 years; 76% men) without known coronary artery disease who had abnormal myocardial perfusion during stress single photon emission computed tomography (SPECT). SPECT images were classified as low-, intermediate-, and high-risk. Early revascularization (CABG or PCI < or =4 months after SPECT) was performed in 76 patients. Survival (follow-up, 5.3+/-3.3 years) was compared in patients treated with CABG, PCI, or medical therapy. Revascularization (CABG or PCI) was performed in 54 of 261 patients with high-risk scans and was independently associated with improved survival (chi2=4.55; P=0.03 after multivariate adjustment). Subset analysis demonstrated that the survival advantage was confined to patients treated with CABG (n=39), with a 5-year survival CABG at 85%, PCI at 72%, and medical therapy at 67% (P=0.02 for 3 groups). Although CABG was associated with better survival, mortality remained high (3% per year). There was no survival advantage by treatment for patients with less-severe SPECT abnormalities. CONCLUSIONS: These nonrandomized data suggest that CABG improves survival in asymptomatic diabetic patients with high-risk SPECT, although revascularization was performed infrequently in these patients. These results parallel those of the Bypass Angioplasty Revascularization Investigation trial in symptomatic diabetic patients.

The prognostic value of pharmacologic stress myocardial perfusion imaging in patients with permanent pacemakers.

BACKGROUND: The aim of this study is to assess the prognostic value of pharmacologic stress (adenosine or dipyridamole) myocardial perfusion imaging in patients with permanent electronic ventricular pacemakers. METHODS AND RESULTS: Between October 1986 and December 1995, 93 patients with pacemakers underwent pharmacologic stress testing with myocardial perfusion single photon emission computed tomography imaging. Follow-up information on 91 patients (98%) was obtained. Mean follow-up was 5.6 +/- 2.4 years. Previously published clinical and image variables were analyzed for their prognostic significance with regard to cardiac death, cardiac death/nonfatal myocardial infarction, and cardiac death/nonfatal myocardial infarction/late revascularization. The presence of a high-risk scan was a significant predictor of subsequent cardiac death by both univariate (chi 2 = 9.4, P < .001) and multivariate analysis (chi 2 = 6.5, P = .01) after adjustment for clinical score. Clinical score was not a significant predictor of cardiac death. CONCLUSION: This study demonstrates that pharmacologic stress myocardial perfusion imaging provides significant prognostic information in patients with permanent pacemakers. In this population, pharmacologic stress myocardial perfusion imaging can differentiate patients at high risk of a subsequent cardiac event from those at low risk. These results support the American College of Cardiology/American Heart Association guideline recommendations for pharmacologic stress perfusion imaging in patients with permanent pacemakers.

Identifying high-risk asymptomatic diabetic patients who are candidates for screening stress single-photon emission computed tomography imaging.

OBJECTIVES: The purpose of this study was to identify which asymptomatic diabetic patients are candidates for screening single-photon emission computed tomography (SPECT) imaging and to examine angiographic findings and mortality in patients according to SPECT imaging categories. BACKGROUND: Previously we reported a high percentage of abnormal and high-risk SPECT imaging scans in asymptomatic diabetic patients. METHODS: We examined the associations between several clinical and laboratory variables and a high-risk stress SPECT imaging scan in 1,427 asymptomatic diabetic patients without known coronary artery disease (CAD). Results of coronary angiography and long-term outcome were also analyzed. RESULTS: An abnormal stress SPECT imaging scan was present in 826 patients (58%) and a high-risk scan in 261 patients (18%). Multivariate analysis demonstrated that seven variables were independently associated with a high-risk scan (model chi-square=107, p <0.0001). The two most important variables were electrocardiogram (ECG) Q waves (adjusted chi-square=38.3, p <0.001) and peripheral arterial disease (PAD) (adjusted chi-square=13.9, p <0.001). Coronary angiography was performed in 127 (49%) high-risk SPECT imaging patients, 61% of whom had angiographic high-risk CAD. Annual mortality rates for patient subsets categorized by SPECT imaging scans were high-risk 5.9%, intermediate-risk 5.0%, and low-risk 3.6% (p <0.001 for differences between groups). CONCLUSIONS: High-risk findings on stress SPECT imaging were present in 18% of asymptomatic diabetic patients without known CAD. Patients with high-risk scans had a high prevalence of severe CAD and a high annual mortality rate. ECG Q waves and/or evidence of PAD identified the most suitable candidates for screening.

Prognostic significance of ischemic electrocardiographic changes during vasodilator stress testing in patients with normal SPECT images.

BACKGROUND: Patients with ischemic electrocardiographic (ECG) findings during exercise stress testing but normal perfusion images generally have a low risk of cardiac death or myocardial infarction (<1% per year). During vasodilator stress testing, however, the prognostic significance of the combination of normal perfusion images and ischemic ECG changes is unknown. METHODS AND RESULTS: Among 5526 patients who underwent vasodilator stress single photon emission computed tomography (SPECT), 49 (0.9%) had normal images but ischemic ECG changes. A unique feature of this population was that 43 (88%) were women with a mean age of 67 +/- 10 years. Ischemic ECG changes occurred at a mean heart rate of 101 +/- 15 beats per minute and persisted for 6.8 +/- 4.7 minutes after termination of drug infusion. During follow-up of 28 +/- 20 months, cardiac death occurred in 2 patients and nonfatal myocardial infarction in 4 patients. The rate of cardiac death or nonfatal myocardial infarction was 4% at 1 year, 10% at 2 years, and 14% at 3 years. Of the 12 patients who underwent coronary angiography or autopsy during follow-up, 11 had multivessel coronary artery disease, indicating that these patients likely had false-negative SPECT image results. Eight patients required coronary revascularization. CONCLUSIONS: The finding of ischemic ECG changes with normal SPECT images during vasodilator infusion is uncommon, occurs primarily in older women, and is associated with a higher subsequent cardiac event rate than is customarily associated with normal images.

Use of a simple clinical score to predict prognosis of patients with normal or mildly abnormal resting electrocardiographic findings undergoing evaluation for coronary artery disease.

OBJECTIVE: To determine whether a simple clinical score, which was shown previously to predict the likelihood of severe coronary artery disease (CAD) in patients referred for coronary angiography, could predict prognosis in a separate cohort of patients with normal or mildly abnormal findings on their resting electrocardiogram (ECG) who were undergoing noninvasive evaluation for possible CAD. PATIENTS AND METHODS: The study group included 2255 symptomatic patients with normal (n=1466) or mildly abnormal (nonspecific ST-T-wave abnormalities; n=789) findings on their resting ECG who were referred for exercise thallium testing between 1989 and 1991. Follow-up was 94% complete at a mean +/- SD duration of 6.9+/-1.5 years. The clinical score, which ranged from 0 (lowest risk) to 10 (highest risk), was calculated by awarding 1 point each for male sex, history of myocardial infarction, typical angina, diabetes mellitus, insulin use, and each decade of age older than 40 years. RESULTS: In each ECG group, the clinical score was a significant predictor of cardiac death, nonfatal myocardial infarction, or late revascularization, considered individually or combined, unadjusted or with adjustment for age. Most patients had a score lower than 5; these patients had an excellent 5-year cardiac survival rate (99.7% for the normal ECG findings group and 98.8% for the ST-T-wave abnormalities group). The small subset of patients with a score higher than 5 had a much lower 5-year survival rate (923% for the 8% of patients with normal ECG findings and 86.6% for the 14% of patients with ST-T-wave abnormalities). For patients with a score of 5, the 5-year survival rate was 97.7% for the normal ECG findings group and 95.9% for the ST-T-wave abnormalities group. CONCLUSION: In symptomatic patients with known or suspected CAD and normal or mildly abnormal resting ECG findings, this simple, easily computed clinical score is a useful and valid tool to help determine prognosis.

Effects of adjustment for referral bias on the sensitivity and specificity of single photon emission computed tomography for the diagnosis of coronary artery disease.

PURPOSE: Referral bias, in which the result of a diagnostic test affects the subsequent referral for a more definitive test, influences the accuracy of noninvasive tests for coronary artery disease. This study evaluates the effect of referral bias on the apparent accuracy of single photon emission computed tomography (SPECT). METHODS: Over a 10-year period, 14,273 patients without known coronary artery disease underwent stress SPECT. Coronary angiography was performed within 3 months after the stress test in 1853 patients (13%). The apparent sensitivity, specificity, and likelihood ratios of SPECT were determined in these patients, and then adjusted for referral bias using two different formulas. RESULTS: The overwhelming majority (95%) of patients who underwent angiography had abnormal SPECT images. Apparent values for test indices were a sensitivity of 98%, a specificity of 13%, a likelihood ratio for a positive test of 1.1, and a likelihood ratio for a negative test of 0.15. Test indices adjusted for referral bias (using the two methods) were a sensitivity of 65% or 67%, a specificity of 67% or 75%, a likelihood ratio for a positive test of 2.0 or 2.7, and a likelihood ratio for a negative test of 0.44 or 0.52. CONCLUSION: Referral bias has a marked effect on the apparent accuracy of stress SPECT for the diagnosis of coronary disease. Adjustment for referral bias yields estimates for sensitivity and specificity and likelihood ratios that better reflect the accuracy of the technique.