Comparison of fully automated computer analysis and visual scoring for detection of coronary artery disease from myocardial perfusion SPECT in a large population.

UNLABELLED: We compared the performance of fully automated quantification of attenuation-corrected (AC) and noncorrected (NC) myocardial perfusion SPECT (MPS) with the corresponding performance of experienced readers for detection of coronary artery disease (CAD). METHODS: Rest-stress (99m)Tc-sestamibi MPS studies (n = 995; 650 consecutive cases with coronary angiography and 345 with likelihood of CAD < 5%) were obtained by MPS with AC. The total perfusion deficit (TPD) for AC and NC data was compared with the visual summed stress and rest scores of 2 experienced readers. Visual reads were performed in 4 consecutive steps with the following information progressively revealed: NC data, AC + NC data, computer results, and all clinical information. RESULTS: The diagnostic accuracy of TPD for detection of CAD was similar to both readers (NC: 82% vs. 84%; AC: 86% vs. 85%-87%; P = not significant) with the exception of the second reader when clinical information was used (89%, P < 0.05). The receiver-operating-characteristic area under the curve (ROC AUC) for TPD was significantly better than visual reads for NC (0.91 vs. 0.87 and 0.89, P < 0.01) and AC (0.92 vs. 0.90, P < 0.01), and it was comparable to visual reads incorporating all clinical information. The per-vessel accuracy of TPD was superior to one reader for NC (81% vs. 77%, P < 0.05) and AC (83% vs. 78%, P < 0.05) and equivalent to the second reader (NC, 79%; and AC, 81%). The per-vessel ROC AUC for NC (0.83) and AC (0.84) for TPD was better than that for the first reader (0.78-0.80, P < 0.01) and comparable to that of the second reader (0.82-0.84, P = not significant) for all steps. CONCLUSION: For detection of ≥70% stenoses based on angiographic criteria, a fully automated computer analysis of NC and AC MPS data is equivalent for per-patient and can be superior for per-vessel analysis, when compared with expert analysis.

Combined quantitative analysis of attenuation corrected and non-corrected myocardial perfusion SPECT: Method development and clinical validation.

BACKGROUND: Attenuation corrected myocardial perfusion SPECT (AC-MPS) has been demonstrated to improve the specificity of detecting coronary artery disease (CAD) by visual analysis which utilizes both non-corrected (NC) and AC data. However, the combined automated quantification of NC and AC-MPS has not been previously described. We aimed to develop a combined quantitative analysis from AC and NC data to improve the accuracy of automated detection of CAD from AC-MPS. METHODS: Stress total perfusion deficit (TPD) values were generated by standard analysis for NC (NC-TPD), AC (AC-TPD) and by combined NC-AC analysis (NA-TPD), in which the hypoperfusion severity in each polar map location was defined as the average of AC and NC severity computed by comparison with separate AC and NC normal limits. Ischemic TPD was also calculated as the difference between stress TPD and rest TPD for each measure. Stress/rest Tc-99m sestamibi MPS studies in 650 patients with correlating coronary angiography and in 345 patients with a low-likelihood (LLk) of CAD were used to assess diagnostic performance of combined NC-AC analysis. RESULTS: NA-TPD had a higher receiver-operator-characteristic area under the curve (ROC-AUC) (0.87) than NC-TPD (0.85; P < .01) or AC-TPD (0.85; P < .01) for detection of stenosis >or=70% in angiographic group. It also had higher specificity (75%) vs NC-TPD (65%; P < .0001), or AC-TPD (70%; P = .016). In LLk group, the normalcy rate of NA-TPD (95%) was higher than for NC-TPD (90%; P < .01) and similar to AC-TPD (94%; P = NS). NA-TPD had higher ROC-AUC than that for 17-segment expert visual scoring of stress scans in angiographic group (0.84; P = .01), comparable accuracy (81%) and similar normalcy rates (95% vs 97%; P = NS). Ischemic TPD by combined NC-AC analysis had higher ROC-AUC than that for any ischemic measure. Similar to stress NA-TPD, it also obtained the similar performance results as compared with ischemic TPD based on NC or AC and higher sensitivity (89% vs 85%; P = .0295) as compared with ischemic visual score in angiographic group. CONCLUSION: Combined NC-AC MPS quantification using either stress or ischemic TPD shows significant improvements for ROC-AUC and specificity of MPS in the detection of CAD compared with standard NC-MPS or AC-MPS and comparable performance to expert visual scoring. This technique may lead to an enhancement in a fully automated quantification for the perfusion analysis by AC-MPS.

Improved quantification and normal limits for myocardial perfusion stress-rest change.

UNLABELLED: We aimed to improve the quantification of myocardial perfusion stress-rest changes in myocardial perfusion SPECT (MPS) studies for the optimal automatic detection of ischemia and coronary artery disease (CAD). METHODS: Rest-stress (99m)Tc MPS studies (997 cases; 651 consecutive cases with correlating angiography and 346 cases with less than 5% likelihood (low likelihood [LLK]) of CAD) were analyzed. Normal limits for stress-rest changes were derived from additional LLK patients (40 women, 40 men). We computed the global stress-rest change (C-SR) by integrating direct stress-rest changes for each polar map pixel. Additionally, stress-rest change and total perfusion deficit (TPD) at stress were combined in 1 variable (C-TPD) for the optimal detection of CAD. RESULTS: The area under the receiver-operating-characteristic curve (AUC) for C-SR (0.92) was larger than that for stress TPD-rest TPD (0.88) for the identification of stenosis of 70% or more (P < 0.0001). AUC (0.94) and sensitivity (90%) for C-TPD were higher than those for stress TPD (0.91 and 83%, respectively) (P < 0.0001), whereas specificity remained the same (81%). CONCLUSION: C-SR and C-TPD provide higher diagnostic performance than difference between stress and rest TPD or stress hypoperfusion analysis.

Quantification of 3D regional myocardial wall thickening from gated magnetic resonance images.

PURPOSE: To develop 3D quantitative measures of regional myocardial wall motion and thickening using cardiac magnetic resonance imaging (MRI) and to validate them by comparison to standard visual scoring assessment. MATERIALS AND METHODS: In all, 53 consecutive subjects with short-axis slices and mid-ventricular 2-chamber/4-chamber views were analyzed. After correction for breath-hold-related misregistration, 3D myocardial boundaries were fitted to images and edited by an imaging cardiologist. Myocardial thickness was quantified at end-diastole and end-systole by computing the 3D distances using Laplace's equation. 3D thickening was represented using the standard 17-segment polar coordinates. 3D thickening was compared with 3D wall motion and with expert visual scores (6-point visual scoring of wall motion and wall thickening; 0 = normal; 5 = greatest abnormality) assigned by imaging cardiologists. RESULTS: Correlation between ejection fraction and thickening measurements was (r = 0.84; P < 0.001) compared to correlation between ejection fraction and motion measurements (r = 0.86; P < 0.001). Good negative correlation between summed visual scores and global wall thickening and motion measurements were also obtained (r(thick) = -0.79; r(motion) = -0.74). Additionally, overall good correlation between individual segmental visual scores with thickening/wall motion (r(thick) = -0.69; r(motion) = -0.65) was observed (P < 0.0001). CONCLUSION: 3D quantitative regional thickening and wall motion measures obtained from MRI correlate strongly with expert clinical scoring.

Automated quality control for segmentation of myocardial perfusion SPECT.

UNLABELLED: Left ventricular (LV) segmentation, including accurate assignment of LV contours, is essential for the quantitative assessment of myocardial perfusion SPECT (MPS). Two major types of segmentation failures are observed in clinical practices: incorrect LV shape determination and incorrect valve-plane (VP) positioning. We have developed a technique to automatically detect these failures for both nongated and gated studies. METHODS: A standard Cedars-Sinai perfusion SPECT (quantitative perfusion SPECT [QPS]) algorithm was applied to derive LV contours in 318 consecutive (99m)Tc-sestamibi rest/stress MPS studies consisting of stress/rest scans with or without attenuation correction and gated stress/rest images (1,903 scans total). Two numeric parameters, shape quality control (SQC) and valve-plane quality control, were derived to categorize the respective contour segmentation failures. The results were compared with the visual classification of automatic contour adequacy by 3 experienced observers. RESULTS: The overall success of automatic LV segmentation in the 1,903 scans ranged from 66% on nongated images (incorrect shape, 8%; incorrect VP, 26%) to 87% on gated images (incorrect shape, 3%; incorrect VP, 10%). The overall interobserver agreement for visual classification of automatic LV segmentation was 61% for nongated scans and 80% for gated images; the agreement between gray-scale and color-scale display for these scans was 86% and 91%, respectively. To improve the reliability of visual evaluation as a reference, the cases with intra- and interobserver discrepancies were excluded, and the remaining 1,277 datasets were considered (101 with incorrect LV shape and 102 with incorrect VP position). For the SQC, the receiver-operating-characteristic area under the curve (ROC-AUC) was 1.0 +/- 0.00 for the overall dataset, with an optimal sensitivity of 100% and a specificity of 98%. The ROC-AUC was 1.0 in all specific datasets. The algorithm was also able to detect the VP position errors: VP overshooting with ROC-AUC, 0.91 +/- 0.01; sensitivity, 100%; and specificity, 70%; and VP undershooting with ROC-AUC, 0.96 +/- 0.01; sensitivity, 100%; and specificity, 70%. CONCLUSION: A new automated method for quality control of LV MPS contours has been developed and shows high accuracy for the detection of failures in LV segmentation with a variety of acquisition protocols. This technique may lead to an improvement in the objective, automated quantitative analysis of MPS.

Quantitative assessment of myocardial perfusion abnormality on SPECT myocardial perfusion imaging is more reproducible than expert visual analysis.

BACKGROUND: Current guidelines of Food and Drug Administration for the evaluation of SPECT myocardial perfusion imaging (MPI) in clinical trials recommend independent visual interpretation by multiple experts. Few studies have addressed whether quantitative SPECT MPI assessment would be more reproducible for this application. METHODS AND RESULTS: We studied 31 patients (age 68 +/- 13, 25 male) with abnormal stress MPI who underwent repeat exercise (n = 11) or adenosine (n = 20) MPI within 9-22 months (mean 14.9 +/- 3.8 months) and had no interval revascularization or myocardial infarction and no change in symptoms, stress type, rest or stress ECG, or clinical response to stress on the second study. Visual interpretation per FDA Guidance used 17-segment, 5-point scoring by two independent expert readers with overread of discordance by a third expert, and percent myocardium abnormal was derived from normalized summed scores. The quantitative magnitude of perfusion abnormality was assessed by the total perfusion deficit (TPD), expressing stress, rest, and ischemic perfusion abnormality. High linear correlations were observed between visual and quantitative size of stress, rest, and ischemic defects (R = 0.94, 0.92, 0.84). Correlations of two tests were higher by quantitative than by visual methods for stress (R = 0.97 vs R = 0.91, P = 0.03) and rest defects (R = 0.94 vs R = 0.82, P = 0.03), respectively, and statistically similar for ischemic defects (R = 0.84 vs R = 0.70, P = ns). CONCLUSIONS: In stable patients having serial SPECT MPI, quantification is more reproducible than visual for magnitude of perfusion abnormality, suggesting its superiority for use in randomized clinical trials and monitoring the effects of therapy in an individual patient.

Underestimation of extent of ischemia by gated SPECT myocardial perfusion imaging in patients with left main coronary artery disease.

BACKGROUND: There have been limited data regarding the value of gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for the detection of left main coronary artery disease (CAD). METHODS AND RESULTS: We studied 101 patients with angiographic left main CAD (> or = 50% stenosis) and no prior myocardial infarction or coronary revascularization who underwent gated exercise or adenosine stress technetium 99m sestamibi SPECT MPI. By perfusion assessment alone, high-risk disease with moderate to severe defects (> 10% myocardium at stress) was identified in only 56% of patients visually and 59% quantitatively. Absence of significant perfusion defect (> or = 5% myocardium) was seen in 13% of patients visually and 15% quantitatively. However, by combining visual perfusion data and nonperfusion variables, especially transient ischemic dilation, 83% of patients were identified as high risk. CONCLUSIONS: The findings of this study demonstrate that assessment of perfusion data alone by visual or quantitative SPECT MPI analysis underestimates the magnitude of left main CAD. The combination of perfusion and nonperfusion abnormalities on gated MPI identifies high risk in most patients with left main CAD.

Simplified normal limits and automated quantitative assessment for attenuation-corrected myocardial perfusion SPECT.

BACKGROUND: We aimed to compare normal limits and the detection of coronary artery disease (CAD) with attenuation-corrected (AC) and non-attenuation-corrected (NC) myocardial perfusion single photon emission computed tomography (MPS) by use of a recently improved automated quantification technique. METHODS AND RESULTS: We acquired 415 rest/stress technetium 99m MPS studies on a Vertex dual-detector camera with a gadolinium 153 line source (Vantage Pro). Gender-specific NC, AC, and gender-combined AC normal limits were created from rest/stress images of 50 women and 50 men with a low likelihood of CAD (< 5%) and a median body mass index (BMI) of 30 kg/m2 in each gender group. BMI-specific normal limits (< 30 kg/m2 and > or = 30 kg/m2) were also compared. Total perfusion deficit and 17-segment summed scores in 174 patients were compared with angiography, and normalcy rates were established from 141 studies of low-likelihood patients. There were no differences between low-BMI and high-BMI normal limits for AC or NC studies. Male and female normal limits differed in 12 of 17 segments for NC stress studies and in 3 of 17 segments for AC stress studies (P < .01). The sensitivity, specificity, and normalcy rates for stenoses with 70% narrowing or greater were 89%, 73%, and 91%, respectively, for NC studies and 87%, 80%, and 95%, respectively, for AC studies (P = not significant). CONCLUSION: Automated detection of CAD by AC and NC MPS demonstrated similar sensitivity, specificity, and normalcy rates. Some gender differences were noted for AC normal limits.

Left ventricular shape index assessed by gated stress myocardial perfusion SPECT: initial description of a new variable.

BACKGROUND: Ventricular remodeling is predictive of congestive heart failure (CHF). We aimed to automatically quantify a new myocardial shape variable on gated myocardial perfusion single photon emission computed tomography (SPECT) (MPS) and to evaluate the association of this new SPECT parameter with the risk of hospitalization for CHF. METHODS AND RESULTS: A computer algorithm was used to measure the 3-dimensional (3D) left ventricular (LV) shape index (LVSI), derived as the ratio of maximum 3D short- and long-axis LV dimensions, for end systole and end diastole. LVSI normal limits were obtained from stress technetium 99m sestamibi MPS images of 186 patients (60% of whom were men) (control subjects) with a low likelihood of CAD (< 5%). These limits were tested in a consecutive series of 93 inpatients (85% of whom were men) having MPS less than 1 week after hospitalization, of whom 25 were hospitalized for CHF exacerbation. Variables associated with CHF hospitalization were tested by receiver operating characteristic curve and multivariate logistic regression analyses. LVSI repeatability was assessed in 52 patients with ischemic cardiomyopathy who had sequential stress MPS within 60 days after the initial MPS without clinical events in the interval between MPS studies. Control subjects had lower end-systolic and end-diastolic LVSIs compared with patients with CHF and those without CHF (P < .001). Receiver operating characteristic curve areas for the prediction of hospitalization as a result of CHF were similar for LV ejection fraction and end-systolic LVSI. End-systolic and end-diastolic LVSIs were independent predictors of CHF hospitalization by multivariate analysis; however, end-systolic LVSI had the greatest added value among all tested variables. Repeatability was excellent for both end-systolic LVSI (R2 = 0.85, P < .0001) and end-diastolic LVSI (R2 = 0.82, P < .001). CONCLUSION: LVSI is a promising new 3D variable derived automatically from gated MPS providing highly repeatable ventricular shape assessment. Preliminary findings suggest that LVSI might have clinical implications in patients with CHF.

Diagnostic accuracy of gated Tc-99m sestamibi stress myocardial perfusion SPECT with combined supine and prone acquisitions to detect coronary artery disease in obese and nonobese patients.

BACKGROUND: The diagnostic value of gated myocardial perfusion single-photon emission computed tomography (MPS) with combined supine and prone acquisitions to detect coronary artery disease (CAD) in obese and nonobese patients has not been defined. METHODS AND RESULTS: We studied 1511 patients without prior myocardial infarction or coronary revascularization who either had coronary angiography within 3 months of MPS (n = 785) or had a low pretest likelihood of CAD (n = 726). All patients underwent rest thallium 201/gated exercise or adenosine stress technetium 99m sestamibi MPS in both the supine and prone positions. According to body mass index (BMI), patients were categorized as normal weight (BMI of 18.5-24.9 kg/m2), overweight (BMI of 25.0-29.9 kg/m2), or obese (BMI > or = 30.0 kg/m2). There were no significant differences in stress, fixed, or ischemic defects among patients in different weight categories. The sensitivity of MPS was 85%, 86%, and 89% for detecting patients with 50% or greater coronary stenosis and 89%, 91%, and 92% for detecting those with 70% or greater coronary stenosis in the normal-weight, overweight, and obese groups, respectively. Normalcy rates were nearly identical among the 3 weight groups (99%, 98%, and 99%, respectively). Multivariate logistic regression analysis further confirmed that BMI was a nonsignificant predictor for the detection of CAD. In a subset of 290 patients, automated quantitative MPS analysis confirmed that combined supine and prone MPS increased specificity (86%) in identifying CAD, without a significant reduction in sensitivity (83% for > or = 50% stenosis and 88% for > or = 70% stenosis). CONCLUSION: The findings of this study suggest that MPS performed with gating and combined supine and prone acquisitions without attenuation correction had a similar diagnostic accuracy for the detection of CAD in normal-weight, overweight, and obese patients.

Integration of automatically measured transient ischemic dilation ratio into interpretation of adenosine stress myocardial perfusion SPECT for detection of severe and extensive CAD.

UNLABELLED: The aim of our study was to derive and to validate the normal threshold for an automatically measured left ventricular transient ischemic dilation (TID) ratio in patients referred for adenosine stress myocardial perfusion SPECT (MPS) and to assess the value of integrating TID in detecting severe and extensive coronary artery disease (CAD). METHODS: Normal limits for the TID ratio were derived using dual-isotope MPS data from 38 patients with a low (<5%) likelihood of CAD. Criteria for abnormality were calculated on the basis of data from 179 consecutive patients who had undergone coronary angiography less than 3 mo after index adenosine MPS: 41 patients (23%) had severe and extensive CAD (> or =90% stenosis) in the proximal left anterior descending artery or in 2 or more coronary arteries, 64 (36%) had no significant CAD (<70% stenosis), and 74 (41%) had mild or moderate CAD. The criteria were then prospectively validated in a cohort of 177 patients, of whom 41 patients (23%) had severe and extensive CAD, 55 (31%) had no significant CAD, and 81 (46%) had mild or moderate CAD. RESULTS: By analysis of receiver-operating-characteristic curves, the best threshold for adenosine TID ratio abnormality was the mean adenosine TID ratio in the low-CAD-likelihood patients + 2 SDs (TID ratio > 1.36). Abnormal TID ratio using this threshold demonstrated high sensitivity and specificity for severe and extensive CAD (71% and 86%, respectively), and similar sensitivity and specificity were observed in the prospective validation group (73% and 88%, respectively). In the combined pilot and validation groups, the absence of both abnormal TID ratio and abnormal perfusion was highly specific for the absence of severe and extensive CAD; only one (1.3%) of 79 patients with severe and extensive CAD had neither of these abnormal findings on adenosine MPS. In patients with both abnormal TID ratio and abnormal perfusion, 55 of 84 (65%) had severe and extensive CAD. When patients had one but not both of these findings, 26 of 193 (13%) had severe and extensive CAD. CONCLUSION: The automatically measured TID ratio is a useful clinical marker that is sensitive and highly specific for identification of severe and extensive CAD in patients undergoing adenosine MPS. Integration of abnormal TID ratio into the dual-isotope MPS image interpretation algorithm improves the identification of severe and extensive CAD in adenosine MPS.

Prognostic implications of atrial fibrillation in patients undergoing myocardial perfusion single-photon emission computed tomography.

OBJECTIVES: The aim of this research was to determine whether presence of atrial fibrillation (AF) provides incremental prognostic information relative to myocardial perfusion single-photon emission computed tomography (MPS) with respect to risk of cardiac death (CD). BACKGROUND: The prognostic significance of AF in patients undergoing MPS is not known. METHODS: A total of 16,048 consecutive patients undergoing MPS were followed-up for a mean of 2.21 +/- 1.15 years for the development of CD. Of those, 384 patients (2.4%) had AF. Cox proportional hazards method was used to compare clinical and perfusion data for the prediction of CD in patients with and without AF. RESULTS: Atrial fibrillation was a significant predictor of CD in patients with normal (1.6% per year vs. 0.4% per year in non-AF patients), mildly abnormal (6.3% per year vs. 1.2% per year), and severely abnormal MPS (6.4% per year vs. 3.7% per year) (p < 0.001 for all). By multivariable analysis, AF patients had worse survival (p = 0.001) even after adjustment for the variables most predictive of CD: age, diabetes, shortness of breath, use of vasodilator stress, rest heart rate, and the nuclear variables. In the 4,239 patients with left ventricular ejection fraction evaluated by gated MPS, AF demonstrated incremental prognostic value not only over clinical and nuclear variables, but also over left ventricular ejection in predicting CD (p = 0.014). CONCLUSIONS: The presence of AF independently increases the risk of cardiac events over perfusion and function variables in patients undergoing MPS. Patients with AF have a high risk of CD, even when MPS is only mildly abnormal. Whether patients with AF and mildly abnormal MPS constitute a group more deserving of early referral to cardiac catheterization is a question warranting further study.

Prognostic validation of a 17-segment score derived from a 20-segment score for myocardial perfusion SPECT interpretation.

BACKGROUND: Recently, a 17-segment model of the left ventricle has been recommended as an optimally weighted approach for interpreting myocardial perfusion single photon emission computed tomography (SPECT). Methods to convert databases from previous 20- to new 17-segment data and criteria for abnormality for the 17-segment scores are needed. METHODS AND RESULTS: Initially, for derivation of the conversion algorithm, 65 patients were studied (algorithm population) (pilot group, n = 28; validation group, n = 37). Three conversion algorithms were derived: algorithm 1, which used mid, distal, and apical scores; algorithm 2, which used distal and apical scores alone; and algorithm 3, which used maximal scores of the distal septal, lateral, and apical segments in the 20-segment model for 3 corresponding segments of the 17-segment model. The prognosis population comprised 16,020 consecutive patients (mean age, 65 +/- 12 years; 41% women) who had exercise or vasodilator stress technetium 99m sestamibi myocardial perfusion SPECT and were followed up for 2.1 +/- 0.8 years. In this population, 17-segment scores were derived from 20-segment scores by use of algorithm 2, which demonstrated the best agreement with expert 17-segment reading in the algorithm population. The prognostic value of the 20- and 17-segment scores was compared by converting the respective summed scores into percent myocardium abnormal. Conversion algorithm 2 was found to be highly concordant with expert visual analysis by the 17-segment model (r = 0.982; kappa = 0.866) in the algorithm population. In the prognosis population, 456 cardiac deaths occurred during follow-up. When the conversion algorithm was applied, extent and severity of perfusion defects were nearly identical by 20- and derived 17-segment scores. The receiver operating characteristic curve areas by 20- and 17-segment perfusion scores were identical for predicting cardiac death (both 0.77 +/- 0.02, P = not significant). The optimal prognostic cutoff value for either 20- or derived 17-segment models was confirmed to be 5% myocardium abnormal, corresponding to a summed stress score greater than 3. Of note, the 17-segment model demonstrated a trend toward fewer mildly abnormal scans and more normal and severely abnormal scans. CONCLUSION: An algorithm for conversion of 20-segment perfusion scores to 17-segment scores has been developed that is highly concordant with expert visual analysis by the 17-segment model and provides nearly identical prognostic information. This conversion model may provide a mechanism for comparison of studies analyzed by the 17-segment system with previous studies analyzed by the 20-segment approach.

Transient ischemic dilation ratio of the left ventricle is a significant predictor of future cardiac events in patients with otherwise normal myocardial perfusion SPECT.

OBJECTIVES: This study evaluated the prognostic value of transient ischemic dilation (TID) of the left ventricle (LV) in patients with normal stress myocardial perfusion single photon emission computed tomography (MPS). BACKGROUND: The prognostic value of TID in patients with an otherwise normal MPS has not been defined. METHODS: We identified 1,560 patients who had normal stress MPS (436 vasodilator and 1,124 exercise stress), and no rest LV enlargement (Population 1) and followed up for 2.30 +/- 0.67 years for hard events (HE) (cardiac death or myocardial infarction) and soft events (SE) (revascularization). Prediction of first HE or SE (total events [TE]) was evaluated by multivariable Cox analysis, which was also applied to a broader group of 2,037 patients (including patients with minimal defects (Population 2). RESULTS: In Population 1, there were 13 HE, 36 SE, and 42 TE. Patients in the highest TID quartile (TID > or =1.21) had a higher TE rate than others, regardless of stress type. By multivariable analysis, highest TID quartile was predictive of TE (p = 0.008). Other independent predictors of TE were age, typical angina, and diabetes. In Population 2, TID was also predictive of TE. CONCLUSIONS: An entirely normal stress MPS study does not always imply an excellent prognosis. In patients with otherwise normal MPS, TID is an independent and incremental prognostic marker of TE even after significant clinical variables--age, typical angina, and diabetes--are accounted for. When TID is present, caution in making low-risk prognostic statements may be warranted, especially in patients with typical angina, the elderly, and diabetics. Our findings also appear to apply to the broader population of "normal" MPS, which included patients with minimal perfusion defects.