Quantitative upright-supine high-speed SPECT myocardial perfusion imaging for detection of coronary artery disease: correlation with invasive coronary angiography.

UNLABELLED: A recently developed camera system for high-speed SPECT (HS-SPECT) myocardial perfusion imaging shows excellent correlation with conventional SPECT. Our goal was to test the diagnostic accuracy of an automated quantification of combined upright and supine myocardial SPECT for detection of coronary artery disease (CAD) (≥ 70% luminal diameter stenosis or, in left main coronary artery, ≥ 50% luminal diameter stenosis) in comparison to invasive coronary angiography (ICA). METHODS: We studied 142 patients undergoing upright and supine HS-SPECT, including 56 consecutive patients (63% men; mean age ± SD, 64 ± 13 y; 45% exercise stress) without known CAD who underwent diagnostic ICA within 6 mo of HS-SPECT and 86 consecutive patients with a low likelihood of CAD. Reference limits for upright and supine HS-SPECT were created from studies of patients with a low likelihood of CAD. Automated software adopted from supine-prone analysis was used to quantify the severity and extent of perfusion abnormality and was expressed as total perfusion deficit (TPD). TPD was obtained for upright (U-TPD), supine (S-TPD), and combined upright-supine acquisitions (C-TPD). Stress U-TPD ≥ 5%, S-TPD ≥ 5%, and C-TPD ≥ 3% myocardium were considered abnormal for per-patient analysis, and U-TPD, S-TPD, and C-TPD ≥ 2% in each coronary artery territory were considered abnormal for per-vessel analysis. RESULTS: On a per-patient basis, the sensitivity was 91%, 88%, and 94% for U-TPD, S-TPD, and C-TPD, respectively, and specificity was 59%, 73%, and 86% for U-TPD, S-TPD, and C-TPD, respectively. C-TPD had a larger area under the receiver-operating-characteristic curve than U-TPD or S-TPD for identification of stenosis ≥ 70% (0.94 vs. 0.88 and 0.89, P < 0.05 and not significant, respectively). On a per-vessel basis, the sensitivity was 67%, 66%, and 69% for U-TPD, S-TPD, and C-TPD, respectively, and specificity was 91%, 94%, and 97% for U-TPD, S-TPD, and C-TPD, respectively (P = 0.02 for specificity U-TPD vs. C-TPD). CONCLUSION: In this first comparison of HS-SPECT with ICA, new automated quantification of combined upright and supine HS-SPECT shows high diagnostic accuracy for detecting clinically significant CAD, with findings comparable to those reported using conventional SPECT.

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.

Are shades of gray prognostically useful in reporting myocardial perfusion single-photon emission computed tomography?

BACKGROUND: We have advocated the use of a 5-category "normal," "probably normal," "equivocal," "probably abnormal," and "definitely abnormal" approach to final interpretation of myocardial perfusion single-photon emission computed tomography (SPECT). The prognostic value of expressing levels of certainty compared with a dichotomous normal/abnormal classification or categories for summed stress scores is unclear. METHODS AND RESULTS: Myocardial perfusion SPECT (MPS) was visually assessed using a standard semiquantitative approach, yielding summed scores that were used for preliminary interpretation using 5 levels of certainty. The interpreter was permitted to then shift the level of certainty in the final interpretation by 1 degree, based on nonperfusion MPS variables and available clinical information. To examine the prognostic value of expressing levels of clinical certainty, we evaluated 20 740 unique consecutive patients who underwent rest Tl-201/stress Tc-99m sestamibi MPS (34.3% vasodilator stress), of whom 845 (4.4%) were lost to follow-up and 1695 were excluded from prognostic analysis due to an early revascularization (<60 days after MPS). The remaining 18 200 patients (59.1% men; age, 65+/-13 years) were followed up for cardiac death for a mean of 2.7+/-1.7 years. During the follow-up, a total of 591 cardiac death events occurred. By univariable analysis, there were substantial differences in the distribution of follow-up cardiac death by the category of clinical MPS certainty. The clinical certainty was found to be an independent multivariable predictor of cardiac death in the study population and better identified patients at increased risk of cardiac death than the approaches based solely on the standard categories of summed perfusion scores or based solely on categories of segmental perfusion scores. CONCLUSIONS: The use of multicategory reporting of MPS results incorporating nonperfusion MPS results and clinical information enhances risk stratification compared with both a dichotomous normal/abnormal approach or approaches based solely on segmental categories of perfusion scores. Whether this enhanced risk stratification based on the clinical certainty of the MPS interpretation leads to a more effective therapeutic regimen, tailored to the individual patient's need, requires further prospective evaluation.

Stress thallium-201/rest technetium-99m sequential dual isotope high-speed myocardial perfusion imaging.

OBJECTIVES: Our purpose was to describe a novel, rapid stress thallium-201 (Tl-201)/rest technetium-99m (Tc-99m) agent myocardial perfusion imaging (MPI) protocol (Tl/Tc) with a high-speed MPI scanner and to compare this protocol with a standard rest/stress Tc-99m agent protocol (Tc/Tc) with respect to image quality and radiation dosimetry. BACKGROUND: Recent advances in gamma camera technology have provided opportunity for improved SPECT MPI protocols. A rapid Tl/Tc protocol that could improve image information while maintaining a low radiation burden for the patient would be desirable. METHODS: We compared high-speed SPECT MPI studies in 374 consecutive patients undergoing exercise or pharmacologic Tl/Tc protocol to those of 262 patients undergoing rest/stress Tc/Tc protocol. RESULTS: Tl/Tc imaging was accomplished in <20 min. Overall image quality was good to excellent in 96% and 98% of patients with the Tl/Tc and the Tc/Tc protocols, respectively (p = ns). Beginning rest imaging within 2 min after rest injection with the Tl/Tc protocol did not result in reduced confidence in image interpretation. Early rest Tc images of the Tl/Tc protocol showed less extracardiac activity than was observed on standard rest imaging used in the Tc/Tc protocol (84% vs. 61%), respectively (p < 0.01). The normalcy rate was high in both groups (100% vs. 92%). Radiation burden was similar between the Tl/Tc and Tc/Tc protocols. CONCLUSIONS: A rapid stress Tl-201/rest Tc-99m protocol for use with high-speed SPECT MPI has image quality and radiation dosimetry similar to those observed with a conventional rest/stress Tc-99m protocol. The Tl/Tc protocol offers promise as an efficient and relatively low radiation dose method, in which the superior qualities of Tl-201 for stress imaging and of the Tc-99m agents for rest imaging can be preserved. The findings also suggest that with rapid imaging rest MPI immediately after Tc-99m agent injection may be superior to standard delayed image initiation.

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.

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.

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.

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.

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.

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.

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.

Impact of body mass index on cardiac mortality in patients with known or suspected coronary artery disease undergoing myocardial perfusion single-photon emission computed tomography.

OBJECTIVES: The purpose of this study was to assess the relationship between body mass index (BMI) and the prognostic value of myocardial perfusion single-photon emission computed tomography (MPS). BACKGROUND: The prognostic value of MPS in the obese has not been evaluated. METHODS: We studied 4,720 patients with and 10,019 patients without known coronary artery disease (CAD) who underwent rest Tl-201/stress Tc-99m sestamibi MPS, including 5,233 gated MPS studies and followed up (mean 2.7 to 3.2 years). Patients were categorized as normal weight (BMI 18.5 to 24.9 kg/m2), overweight (BMI 25.0 to 29.9 kg/m2), or obese (BMI > or =30.0 kg/m2). RESULTS: Unadjusted annual rates of cardiac death (CD) rose versus stress MPS abnormalities in all weight groups (p < 0.001). Obese or overweight patients with or without known CAD who had normal MPS were at low CD risk (<1%/year), similar to normal weight patients. In CAD, obese and overweight patients with abnormal MPS had lower rates of CD compared with normal weight patients (p < 0.01). In patients with low ejection fraction (EF) by gated MPS, those with normal weight had highest CD rate (p = 0.001). Multivariable models revealed that BMI was not a predictor of CD in suspected CAD patients (hazard ratio [HR] 0.99; 95% confidence interval [CI] 0.95 to 1.02) but was an independent inverse predictor of CD in known CAD patients (HR 0.95; 95% CI 0.92 to 0.98), especially in women, adenosine stress, low EF, or abnormal perfusion. CONCLUSIONS: Normal MPS was associated with low risk of CD in patients of all weight categories. In patients with known CAD undergoing MPS, obese and overweight patients were at lower risk of CD over three years than normal weight patients.

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.

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: 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 myocardial perfusion SPECT versus exercise electrocardiography in patients with ST-segment depression on resting electrocardiography.

BACKGROUND: The value of exercise-induced ST-segment depression for the prognostic evaluation of patients with 1 mm of ST depression or greater on the resting electrocardiogram is controversial. METHODS AND RESULTS: Patients who underwent exercise myocardial perfusion single photon emission computed tomography (MPS) and had resting ST depression of 1 mm or greater with a nondiagnostic exercise electrocardiographic response (n = 1122) were followed up for 3.4 +/- 2.3 years. Those with paced rhythm, pre-excitation, left bundle branch block, or myocardial revascularization within the first 60 days after MPS were excluded. Additional exercise-induced ST-segment depression was considered significant if > or = 2 mm MPS was scored semiquantitatively by use of a 20-segment model of the left ventricle; the percentage of myocardium involved with stress defects (% myo) was derived by normalizing to the maximal possible score of 80. Hard events were defined as nonfatal myocardial infarction or cardiac death. A Cox analysis was used to determine independent predictors of hard events among clinical, exercise, and nuclear variables. Hard event rates increased as a function of % myo for either patients with exercise-induced ST depression (1.4%/y for normal MPS vs 4.1%/y for % myo >10%, P < .03) or those without it (0.7%/y for normal MPS vs 3.0%/y for % myo >10%, P = .0001). Age, diabetes mellitus, shortness of breath as the presenting symptom, and % myo were independent predictors of hard events. Exercise-induced ST depression was predictive of hard events only when it was 3 mm or greater. The presence and extent of perfusion defects, reflected in the % myo, had incremental prognostic value over clinical variables and also over all degrees of exercise-induced ST depression. CONCLUSIONS: Although MPS effectively risk-stratifies patients with resting ST depression of 1 mm or greater, the prognostic value of exercise-induced ST depression is limited in these patients, with a small added risk when severe (> or = 3 mm).

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

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

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.

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.