Prognostic implications of myocardial perfusion single-photon emission computed tomography in the elderly.

BACKGROUND: The goal of this study was to assess the clinical value of stress myocardial perfusion scintigraphy (MPS) in elderly patients (> or =75 years of age). METHODS AND RESULTS: We followed up 5200 elderly patients (41% exercise) after dual-isotope MPS over 2.8+/-1.7 years (362 cardiac deaths [CDs], 7.0%, 2.6%/y) and a subset with extended follow-up (684 patients for 6.2+/-2.9 years; 320 all-cause deaths). Survival modeling of CD revealed that both MPS-measured ischemia and fixed defect added incrementally to pre-MPS data in both adenosine and exercise stress patients. Modeling a subset with gated MPS (n=2472) revealed that ejection fraction and perfusion data added incrementally to each other, further enhancing risk stratification. Unadjusted, annualized post-normal MPS CD rate was 1.3% but <1% in patients with normal rest ECG, exercise stress, or age of 75 to 84 years and was 2.3% to 3.7% in patients > or =85 years of age or undergoing pharmacological stress. However, compared with age-matched US population CD rates (75 to 84 years of age, 1.5%; > or =85 years, 4.8%), normal MPS CD rates were approximately one-third lower than the baseline risk of US individuals (both P<0.05). Modeling of all-cause death in 684 patients with extended follow-up revealed that after risk adjustment, an interaction between early treatment and ischemia was present; increasing ischemia was associated with increasing survival with early revascularization, whereas in the setting of little or no ischemia, medical therapy had improved outcomes. CONCLUSIONS: Stress MPS effectively stratifies CD risk in elderly patients and may identify optimal post-MPS therapy. CD rates after normal MPS are low in all subsets in relative terms compared with the age-matched US population.

Threshold, incidence, and predictors of prognostically high-risk silent ischemia in asymptomatic patients without prior diagnosis of coronary artery disease.

BACKGROUND: Little is known about incidence, threshold, and predictors of prognostically relevant silent ischemia (SI). The aim was to study these three aspects of silent coronary artery disease (CAD). METHODS: In total, 3,664 consecutive asymptomatic patients without prior diagnosis of CAD undergoing myocardial perfusion SPECT (MPS) were evaluated and followed-up > or = 1 year for Events (HE): cardiac death or myocardial infarction. MPS was interpreted using a 20 segment model to define summed stress, rest, and difference scores (the extent of % myocardium ischemic was derived). Prognostic high-risk ischemia was defined as ischemia consistent with a HE rate > or = 3%. RESULTS: Overall, > or = 7.5% myocardium ischemic was consistent with high risk. Twenty-one and six percent of patients had ischemia and high-risk ischemia, respectively. Patients with high-risk ischemia had a worse prognosis than patients with less SI, HE rate of 3.1 and 0.4%, respectively, (P = .0001). Sex, age, diabetes, hypertension, abnormal resting ECG, angina, peak heart rate, blood pressure during treadmill testing, ST-depression, and Duke treadmill score were independent predictors of relevant SI. CONCLUSIONS: In total, > or = 7.5% myocardium ischemic revealed to be consistent with high risk. Six percent of patients had evidence of high-risk SI. Diagnostic scores are provided to most likely identify patients with high-risk SI.

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.

Comparative use of radionuclide stress testing, coronary artery calcium scanning, and noninvasive coronary angiography for diagnostic and prognostic cardiac assessment.

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.

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.

Combined supine and prone quantitative myocardial perfusion SPECT: method development and clinical validation in patients with no known coronary artery disease.

UNLABELLED: Acquisition in the prone position has been demonstrated to improve the specificity of visually analyzed myocardial perfusion SPECT (MPS) for detecting coronary artery disease (CAD). However, the diagnostic value of prone imaging alone or combined acquisition has not been previously described using quantitative analysis. METHODS: A total of 649 patients referred for MPS comprised the study population. Separate supine and prone normal limits were derived from 40 males and 40 females with a low likelihood (LLk) of CAD using a 3 average-deviation cutoff for all pixels on the polar map. These limits were applied to the test population of 369 consecutive patients (65% males; age, 65 +/- 13 y; 49% exercise stress) without known CAD who had diagnostic coronary angiography within 3 mo of MPS. Total perfusion deficit (TPD), defined as a product of defect extent and severity scores, was obtained for supine (S-TPD), prone (P-TPD), and combined supine-prone datasets (C-TPD). The angiographic group was randomly divided into 2 groups for deriving and validating optimal diagnostic cutoffs. Normalcy rates were validated in 2 additional groups of consecutive LLk patients: unselected patients (n = 100) and patients with body mass index >30 (n = 100). RESULTS: C-TPD had a larger area under the receiver-operating-characteristic (ROC) curve than S-TPD or P-TPD for identification of stenosis >or=70% (0.86, 0.88, and 0.90 for S-TPD, P-TPD, and C-TPD, respectively; P < 0.05). In the validation group, sensitivity for P-TPD was lower than for S- or C-TPD (P < 0.05). C-TPD yielded higher specificity than S-TPD and a trend toward higher specificity than P-TPD (65%, 83%, and 86% for S-, P-, and C-TPD, respectively, P < 0.001; vs. S-TPD and P = 0.06 vs. P-TPD). Normalcy rates for C-TPD were higher than for S-TPD in obese LLk patients (78% vs. 95%, P < 0.001). CONCLUSION: Combined supine-prone quantification significantly improves the area under the ROC curve and specificity of MPS in the identification of obstructive CAD compared with quantification of supine MPS alone.

Roles of nuclear cardiology, cardiac computed tomography, and cardiac magnetic resonance: Noninvasive risk stratification and a conceptual framework for the selection of noninvasive imaging tests in patients with known or suspected coronary artery disease.

This review deals with noninvasive imaging for risk stratification and with a conceptual approach to the selection of noninvasive tests in patients with suspected or known chronic coronary artery disease (CAD). Already widely acknowledged with SPECT, there is an increasing body of literature data demonstrating that CT coronary calcium assessment is also of prognostic value. The amount of coronary atherosclerosis, as can be extrapolated from CT coronary calcium score, has been shown to be highly predictive of cardiac events. The principal difference between myocardial perfusion SPECT (MPS) and CT coronary calcium for prognostic application appears to be that the former is an excellent tool for assessing short-term risk, thus effectively guiding decisions regarding revascularization. In contrast, the atherosclerosis imaging methods are likely to provide greater long-term risk assessment and, thus, are more useful in determination of the need for aggressive medical prevention measures. Although the more recent development of CT coronary angiography is promising for diagnosis, there has been no information to date regarding the prognostic value of the CT angiographic data. Similarly, cardiac MRI has not yet been adequately studied for its prognostic content. The selection of the most appropriate test for a given patient depends on the specific question being asked. In patients with a very low likelihood of CAD, no imaging test may be required. In screening the remaining asymptomatic patients, atherosclerosis imaging may be beneficial. In symptomatic patients, MPS, CT coronary angiography, and cardiac MRI play important roles. We consider it likely that, with an increased emphasis on prevention and a concomitant aging of the population, many forms of noninvasive cardiac imaging will continue to grow, with nuclear cardiology continuing to grow.

Roles of nuclear cardiology, cardiac computed tomography, and cardiac magnetic resonance: assessment of patients with suspected coronary artery disease.

Noninvasive cardiac imaging is now central to the diagnosis and management of patients with known or suspected chronic coronary artery disease (CAD). Although rest echocardiography has become the most common of the techniques, nuclear cardiology and more recently cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) play important roles in this regard. This review examines the current applications and interactions of noninvasive cardiac imaging approaches for the assessment of patients with suspected CAD. In addition to considering the strengths and weaknesses of each technique, this review attempts to provide a guide to the selection of a test (or tests) that is based on the question being asked and the ability of each test to answer this question. In patients with suspected CAD, the pretest likelihood of disease, a clinical assessment, becomes the most important determinant of the initial test. If the likelihood is very low, no testing is needed. However, if the likelihood is low, recent data suggest that assessment of early atherosclerosis is likely to be the most useful and cost-effective test. In patients who have an intermediate likelihood of CAD, nuclear cardiology with myocardial perfusion SPECT (MPS) becomes highly valuable; however, coronary CT angiography (CTA), with fast 16-slice or greater scanners, may emerge as the initial test of choice. MPS would then be used if the CTA is inconclusive or if there is a need to assess the functional significance of a stenosis defined by CTA. Coronary CTA, however, is not yet widely available and is limited in patients with dense coronary calcification. In older patients with a high likelihood of CAD, MPS may be the initial test of choice, since a high proportion of these patients have too much coronary calcium to allow accurate assessment of the presence of coronary stenoses. PET/CT or SPECT/CT could emerge as important modalities combining the advantages of each modality. While CMR has great promise as a radiation-free and contrast-free "one-stop" shop, it currently lags behind CTA for noninvasive coronary angiography. Nonetheless, CMR clearly has the potential for this application and has already emerged as a highly effective method for assessing ventricular function, myocardial mass, and myocardial viability, and there is increasing use of this approach for clinical rest and stress perfusion measurements. CMR is particularly valuable in distinguishing ischemic from nonischemic cardiomyopathy. While CT and CMR are likely to grow considerably in diagnostic evaluation over the next several years, MPS and PET will continue to be very valuable techniques for this purpose.

Prognostic value of poststress left ventricular volume and ejection fraction by gated myocardial perfusion SPECT in women and men: gender-related differences in normal limits and outcomes.

BACKGROUND: Whether there are gender differences in the prognostic application of gated myocardial perfusion single photon emission computed tomography (SPECT) has not been assessed. METHODS AND RESULTS: Gender-specific normal limits of poststress volume and ejection fraction (EF) were obtained in 597 women and 824 men with a low likelihood of coronary artery disease and normal perfusion and were applied in a prognostic evaluation of 6713 patients (2735 women and 3978 men). Patients underwent rest thallium-201/stress technetium-99m sestamibi gated myocardial perfusion SPECT and were followed up for 35 +/- 14 months. The upper limit of the end-systolic volume (ESV) index was 27 mL/m2 in women and 39 mL/m2 in men, and the upper limit of the end-diastolic volume index was 60 mL/m2 in women and 75 mL/m2 in men. The lower limit of the EF was 51% in women and 43% in men. Gated SPECT variables provided incremental prognostic information in both genders. Women with severe ischemia and an EF lower than 51% or an ESV index greater than 27 mL/m2 were at very high risk of cardiac death or myocardial infarction (3-year event rates of 39.8% and 35.1%, respectively), whereas women with severe ischemia but an EF of 51% or greater or an ESV index of 27 mL/m2 or less were at intermediate or high risk (3-year event rates of 10.8% and 15.2%, respectively). CONCLUSION: Poststress EF and ESV index by gated myocardial perfusion SPECT provide comparable incremental prognostic information over perfusion in women and men. After separate criteria for abnormal EF and ESV index in women are used, the combination of severe ischemia and abnormal EF or ESV index identifies women at very high risk of cardiac events.

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.

Computer-aided detection and evaluation of lipid-rich plaque on noncontrast cardiac CT.

OBJECTIVE: Noncontrast electron beam CT (EBCT) and MDCT are established for the assessment of calcified plaque, but not lipid-rich plaque. We developed software to identify lipid-rich plaque with noncontrast electron beam tomography (EBT) and MDCT. MATERIALS AND METHODS: A computer algorithm was developed to automatically find contiguous lipid-rich lesions with voxel intensities below a calculated patient-specific lipid threshold. Lipid density and lipid inhomogeneity in Hounsfield units were calculated in the proximal left coronaries of three populations: 34 low-risk patients (low-risk group < 6% Framingham risk score, no calcium), 31 high-risk patients (high-risk group > 20% Framingham risk score, no calcium), and 37 patients with calcified plaque (calcium group). RESULTS: The mean lipid density was -19.6 +/- 3.0 (SD) H in the low-risk group, -25.3 +/- 8.2 H in the high-risk group, and -34.3 +/- 13.0 H in the calcium group (p < 0.05). The mean lipid inhomogeneity was 17.7 +/- 3.6 H in the low-risk group, 21.5 +/- 5.5 H in the high-risk group, and 29.0 +/- 7.6 H in the calcium group (p < 0.05). The mean interscan variability in lipid density and lipid inhomogeneity were 2.0 +/- 3.3 H and 2.1 +/- 3.6 H, respectively. In five patients, the locations of lipid-rich plaque correlated well with available intravascular sonography findings. CONCLUSION: Our method may be able to identify lipid-rich plaque on noncontrast cardiac CT.

Metabolic syndrome and diabetes are associated with an increased likelihood of inducible myocardial ischemia among patients with subclinical atherosclerosis.

OBJECTIVE: Coronary artery calcification (CAC) is associated with cardiac events and the likelihood of inducible myocardial ischemia. Because metabolic syndrome contributes to atherosclerosis, we assessed whether it also influences the relationship between CAC levels and myocardial ischemia. RESEARCH DESIGN AND METHODS: We evaluated 1,043 patients without known coronary artery disease (CAD) who underwent stress myocardial perfusion scintigraphy (MPS) and computed tomography. Metabolic syndrome was defined by modified National Cholesterol Education Program criteria. Metabolic abnormalities were present in 313 patients (30%), including 140 with diabetes (with or without metabolic syndrome) and 173 who had metabolic syndrome without diabetes. RESULTS: Although CAC scores <100 identified a low likelihood ( approximately 2%) of ischemia, the presence (versus absence) of metabolic abnormalities (metabolic syndrome or diabetes) was a predictor of more frequent ischemia among patients with CAC scores of 100-399 (13.0 vs. 3.6%, P < 0.02) and CAC scores >/=400 (23.4 vs. 13.6%, P = 0.03). Similar trends were observed when patients with metabolic syndrome and diabetes were considered separately. Multiple logistic regression revealed the odds of MPS ischemia to be 4.3-fold greater per SD of log CAC (P < 0.001) and 2.0-fold greater in the presence of metabolic abnormalities (P < 0.01). CONCLUSIONS: Among patients with CAC scores >/=100, metabolic abnormalities, and even metabolic syndrome in the absence of diabetes predicted a higher likelihood of inducible ischemia. These findings suggest the need for assessment of metabolic status when interpreting the results of CAC imaging among patients undergoing such testing because of suspected CAD.

Is there a referral bias against catheterization of patients with reduced left ventricular ejection fraction? Influence of ejection fraction and inducible ischemia on post-single-photon emission computed tomography management of patients without a history of coronary artery disease.

OBJECTIVES: The objective of this work was to define the relationship between left ventricular perfusion/ function measures and referral rates to catheterization and revascularization early after stress gated myocardial perfusion single-photon emission computed tomography (MPS). BACKGROUND: Although revascularization yields the greatest survival benefit in patients with low ejection fraction (EF) and extensive coronary artery disease, referral patterns to catheterization and revascularization after noninvasive testing are not well defined. METHODS: We identified 3,369 patients without previous myocardial infarction or revascularization who underwent exercise or adenosine stress MPS and who were followed-up (97% complete) for occurrence of early (<60 days) post-single-photon emission computed tomography (SPECT) revascularization. Multivariable logistic regression modeling was used to determine the association of various patient characteristics and test results with performance of catheterization and revascularization as separate end points. RESULTS: In the first 60 days after stress MPS, 445 catheterizations (13.2%) and 254 revascularizations (7.5%) occurred, including 140 coronary artery bypass graft surgeries (4.1%) and 114 percutaneous coronary interventions (3.4%). Both post-stress gated EF and percent of the myocardium ischemic by stress MPS were independent predictors of revascularization. Logistic regression revealed that the likelihood of catheterization increased with both increasing ischemia and decreasing EF (c-index = 0.94, chi-square = 590). Predicted referral rates to catheterization increased with decreasing EF except in patients with severe ischemia (>15% of myocardium), where rates decreased with decreasing EF. Similar modeling of revascularization (c-index = 0.94, chi-square = 329) revealed that the likelihood of revascularization increased with increasing ischemia but, in general, decreased with decreasing EF. CONCLUSIONS: Although post-SPECT referral to both catheterization and revascularization is driven by ischemia, EF has the opposite effect on these two outcomes. Further studies evaluating the appropriateness of these referral patterns are warranted.

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.

Adenosine myocardial perfusion single-photon emission computed tomography in women compared with men. Impact of diabetes mellitus on incremental prognostic value and effect on patient management.

OBJECTIVES: This study was designed to assess the incremental prognostic value of adenosine stress myocardial perfusion single-photon emission computed tomography (MPS) in women versus men, and to explore the prognostic impact of diabetes mellitus. BACKGROUND: Limited data are available regarding the incremental value of adenosine stress MPS for the prediction of cardiac death in women versus men and the impact of diabetes mellitus on post-adenosine MPS outcomes. Of 6,173 consecutive patients who underwent rest thallium-201/adenosine technetium-99m sestamibi MPS, 254 (4.1%) were lost to follow-up, and 586 with early revascularization < or = 60 days after MPS were censored, leaving 2,656 women and 2,677 men. RESULTS: Women had significantly smaller adenosine stress, rest, and reversible defects than men. During 27.0 +/- 8.8 month follow-up, cardiac death rates were lower in women than men (2.0%/year vs. 2.7%/year, respectively, p < 0.05). Before and after risk adjustment, cardiac death risk increased significantly in both men and women as a function of MPS results. Multivariable models revealed that MPS results provided incremental prognostic value over pre-scan data for the prediction of cardiac death in both genders. Also, while comparative unadjusted rates of early (< or =60 days post-test) coronary angiography (17% vs. 23%) and revascularization (8% vs. 12%) were significantly lower in women (p < 0.05), after adjusting for MPS, these rates were similar in men and women. Importantly, diabetic women had a significantly greater risk of cardiac death compared with other patients. Also, after risk adjustment, patients with insulin-dependent diabetes mellitus (IDDM) had higher risk of cardiac death for any MPS result than patients with non-insulin-dependent diabetes mellitus. CONCLUSION: The findings suggest that adenosine MPS has comparable incremental value for prediction of cardiac death in women and men and that MPS is appropriately influencing subsequent invasive management decisions in both genders. Diabetic women and patients with IDDM appear to have greater risk of cardiac death than other patients for any MPS result.

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.

Automatic quantification of myocardial perfusion stress-rest change: a new measure of ischemia.

UNLABELLED: In myocardial perfusion SPECT (MPS), ischemia is typically quantified as the difference between stress and rest defect sizes obtained by separate comparisons with stress and rest normal limits. Such an approach is not optimal because images are not compared directly with each other and a complex set of stress and rest normal limits is required. METHODS: We developed a fully automatic technique to quantify stress-rest change. We applied it to 204 patients whose SPECT images were acquired using a same-day dual-isotope (99m)Tc/(201)Tl protocol and on whom coronary angiography had been performed. A 10-parameter registration of rest and stress images was performed by an iterative search of best translational, rotational, scaling, and optimal stress-rest count normalization parameters. Identical stress-rest 3-dimensional left ventricle (LV) contours were automatically derived from stress images. Integrated deficit counts (normalized rest-stress) within the LV volume were derived from registered image pairs. A global measure of ischemia (ISCH) was calculated as the ratio of the total deficit stress LV counts to the total rest LV counts. RESULTS: Registration and derivation of quantitative measures were fully automatic. The average processing time was <40 s on a 2-GHz processor. When compared for prediction of stenosis, the area under the receiver operating characteristic curve (0.88 +/- 0.03) was significantly better for ISCH than that obtained by existing quantitative approaches, which use reference databases (0.80-0.82 +/- 0.03). The normalized stress-rest change could be visualized and localized directly on raw patient images using overlay display. CONCLUSION: Automatic stress-rest MPS image registration allows a direct estimation of ischemia from SPECT that does not require comparisons with normal limits.

Prognostic implications of combined prone and supine acquisitions in patients with equivocal or abnormal supine myocardial perfusion SPECT.

UNLABELLED: Although acquisition of (99m)Tc-sestamibi myocardial perfusion SPECT (MPS) with the patient in the prone position is commonly used to minimize attenuation artifacts, the impact of combined prone and supine imaging on the prognostic evaluation of coronary artery disease (CAD) has not been determined. The prognostic implications of MPS obtained in both prone and supine positions in patients with perfusion defects on supine MPS were evaluated. METHODS: We studied 3,834 patients who were monitored for 24.2 +/- 6.0 mo after rest (201)Tl/stress (99m)Tc-sestamibi MPS acquired during 1994-1995, when prone acquisition was performed only in patients with inferior wall perfusion defects that might represent attenuation or motion artifact. RESULTS: During follow-up, there were 132 hard events (cardiac death or myocardial infarction) and 375 total events (hard events or late myocardial revascularization). Overall, patients who underwent prone and supine acquisitions had similar characteristics to those who underwent supine-only imaging, with the exception of being more commonly male. In multivariable analysis, there were similar independent predictors for hard events and total events; the type of acquisition (prone and supine or supine-only) was not a significant predictor of either of these outcome events. After risk adjustment, the predicted event rates were nearly identical for patients undergoing prone and supine compared with supine-only studies. Both observed and predicted hard event rates of patients with normal prone and supine versus supine-only imaging were very low (observed, 0.7%/y and 0.5%/y, respectively; predicted, 1.5% over 24 mo for both). There was no reduction in the higher rates of events associated with abnormal scan results with the combination of prone and supine imaging. CONCLUSION: Patients with inferior wall defects on supine MPS that are not present on prone MPS have a low risk of subsequent cardiac events, similar to that of patients with normal supine-only studies.

"Motion-frozen" display and quantification of myocardial perfusion.

UNLABELLED: Gated myocadial perfusion SPECT (MPS) incorporates functional and perfusion information of the left ventricle (LV). To improve the image quality and accuracy of gated MPS we propose to eliminate the influence of cardiac LV motion in the display and quantification by a novel "motion-frozen" (MF) technique. METHODS: Three-dimensional LV contours were identified on images of the individual time phases. Three-dimensional phase-to-phase motion vectors were derived by sampling of the epi- and endocardial surfaces. A nonlinear image warping (thin-plate spline) was applied to warp all image phases to fit the end-diastolic (ED) phase. Warped images were created to provide the LV image in the ED phase but containing counts from an arbitrary number of time intervals. MF quantification has been performed using the same phase-to-phase motion vectors. MF normal perfusion limits were created from (99m)Tc sestamibi gated MPS studies of 40 females and 40 males with low likelihood (<5%) of coronary artery disease. All MF processing was completely automated. In the initial evaluation, we assessed the display quality and quantification of stress images using MF processing in 51 consecutive patients with 16-frame electrocardiographic gating and available coronary angiography. RESULTS: The display quality was significantly better for MF images as assessed visually. The MF images had the appearance of ED frames but were less noisy and of higher resolution than the summed images. MF images had higher maximum count values in the LV (116% +/- 6%) and higher contrast (12.5 +/- 7.7 vs. 9.5 +/- 3.2) than the corresponding summed images. The area under the receiver operator characteristic curve for prediction of stenoses > or = 70% by the MF method was 0.92 +/- 0.04 versus 0.89 +/- 0.04 by standard quantification (P = not significant). The computation time for automated MF quantification and warping was <25 s for each case. CONCLUSION: We have developed a novel technique for display and quantification of gated myocardial perfusion images, which retrospectively eliminates blur due to cardiac motion. Such processing of gated MPS appears to improve the effective resolution of images. Initial evaluation indicates that it may improve the accuracy of gated MPS in detection of coronary artery disease.

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.