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Background: The role of single photon emission computed tomography myocardial perfusion imaging (SPECT MPI) in cardiac evaluation of the very elderly patients is unclear. We investigated the clinical value of SPECT MPI in very elderly patients (≥80 years) with suspected coronary artery disease (CAD) as well as in comparison to younger patients.Methods and Results: A retrospective analysis of prospectively collected data from 8,864 patients [1,093 patients ≥80 years (very elderly), 3,369 patients 65-79 years (elderly), and 4,402 patients 50-64 years (middle-aged)] with suspected CAD who underwent exercise and/or pharmacologic stress testing with SPECT MPI between 1996 and 2005 was performed. Clinical and SPECT MPI characteristics, cardiac event rates, early (≤60 days) cardiac catheterization and revascularization rates of very elderly patients were compared to that of younger patients. Mean follow-up for cardiac events (cardiac death or non-fatal myocardial infarction) was 1.9 ± 0.9 years. Very elderly patients with moderate to severely abnormal SSS had a significantly higher annualized cardiac event rate than those with mildly abnormal or normal study (9.6% vs 3.4% and 2.5% respectively, P < .001). Across all categories of SSS, very elderly patients had a significantly higher cardiac event rate as compared to younger patients (P < .001). Early cardiac catheterization and revascularization referrals in very elderly patients increased as a function of severity of ischemia on SPECT MPI (P < .001), although these referral rates were significantly lower in very elderly patients with mild to moderate and severe ischemia as compared to younger patients (P < .05).Conclusions: In very elderly patients (≥80 years) with suspected CAD, SPECT MPI has prognostic and incremental value in the noninvasive cardiovascular assessment for risk stratification and may influence medical decisions. [ABSTRACT FROM AUTHOR]

Although stress gated technetium-99m single-photon emission computed tomographic (SPECT) myocardial perfusion imaging (MPI) is useful in differentiating ischemic from nonischemic cardiomyopathy, its prognostic usefulness in this patient population is not well understood. Consecutive unique patients with suspected coronary artery disease who, for clinical indications, underwent technetium-99m rest and stress MPI demonstrating ejection fractions ≤40% by gated SPECT imaging were retrospectively identified. In addition to prescan variables, previously defined cutoffs for gated SPECT parameters using visual and standard 17-segment semiquantitative scoring were applied and related to the occurrence of cardiac death up to 5 years after MPI. Of the 475 patients fulfilling criteria for study inclusion, follow-up was complete in 444 (93%) over 3.7 ± 1.6 years. Of 393 patients without subsequent early (≤60 days) coronary revascularization, cardiac death occurred in 64 (16%). The summed stress score, an MPI measure of the extent and severity of coronary artery disease that also accounts for the ischemic burden, was the gated SPECT parameter most related to cardiac death with Kaplan-Meier 5-year cardiac death-free survival of 85.6% and 67.3% in patients with summed stress scores ≤8 and >8, respectively (p <0.001). In multivariate Cox regression analysis, a summed stress score >8 independently contributed to cardiac death (adjusted hazard ratio 2.20, 95% confidence interval 1.34 to 3.61), and its addition to the model significantly increased the global chi-square value over prescan variables (from 32.46 to 41.67, p = 0.002). In conclusion, stress MPI data from gated technetium-99m SPECT scans are useful for the prediction of cardiac death in patients with moderate to severe left ventricular systolic dysfunction in whom there is suspicion of underlying coronary artery disease. [ABSTRACT FROM AUTHOR]

Although the combined assessment of perfusion and function using rest electrocardiographic (ECG)-gated technetium-99m (Tc-99m) sestamibi single-photon emission computed tomographic (SPECT) imaging has been shown to improve sensitivity and accuracy over perfusion alone in the prediction of myocardial viability, no data are available comparing this technique with rest-redistribution thallium-201. Thirty patients with coronary artery disease and left ventricular dysfunction (ejection fraction < or = 40%) underwent rest-redistribution thallium-201 and rest ECG-gated Tc-99m sestamibi SPECT imaging before revascularization and rest ECG-gated Tc-99m sestamibi SPECT imaging at 1 or 6 weeks after revascularization. All thallium-201 and Tc-99m sestamibi images were interpreted by a consensus agreement of 3 experienced readers without knowledge of patient identity or time of imaging with Tc-99m sestamibi (before or after revascularization) using a 17-segment model. Concordance between techniques for the prediction of viability was 89% (kappa 0.556 +/- 0.109). With rest-redistribution thallium-201, sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy were 95%, 59%, 88%, 78%, and 86%, respectively. With rest ECG-gated Tc-99m sestamibi SPECT imaging, sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy were 96%, 55%, 87%, 80%, and 86%, respectively (p = NS vs rest-redistribution thallium-201). Although both techniques are comparable for detecting viable myocardium, rest ECG-gated Tc-99m sestamibi SPECT imaging allows direct assessment of both myocardial perfusion and ventricular function, which may be clinically useful in patients who require assessment of myocardial viability. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether exercise technetium-99m sestamibi gated single-photon emission computed tomography (SPECT) accurately distinguishes between patients with ischemic cardiomyopathy and patients with nonischemic left ventricular systolic dysfunction. Noninvasive tests have previously failed to accurately separate patients with ischemic cardiomyopathy from those with nonischemic cardiomyopathy. Technetium-99m gated SPECT imaging offers advantages that have the potential to overcome the limitations of previous studies. Thirty-seven adults with a left ventricular ejection fraction < or = 35%, including 24 patients with nonischemic cardiomyopathy and 13 patients with ischemic cardiomyopathy, were prospectively evaluated using symptom-limited metabolic exercise treadmill testing with technetium-99m sestamibi gated SPECT imaging. Interpretation of myocardial perfusion and regional wall motion was performed, using a 17-segment model. Summed stress, rest, and reversibility perfusion defect scores were determined, and the variance of segmental wall motion scores was computed. Summed stress, rest, and reversibility perfusion defect scores were significantly lower in nonischemic cardiomyopathy patients, compared with those with ischemic cardiomyopathy (summed stress defect score: 6.9 +/- 3.8 vs 32.9 +/- 7.7, respectively, p <0.001). Variability in segmental wall motion was also significantly lower in patients with nonischemic cardiomyopathy compared with those with ischemic cardiomyopathy (variance: 0.3 +/- 0.3 vs 1.2 +/- 0.8, respectively, p <0.001). Thus, assessment of myocardial perfusion and regional ventricular function with exercise technetium-99m sestamibi gated SPECT imaging can reliably distinguish between patients with ischemic cardiomyopathy and patients with nonischemic dilated cardiomyopathy. [ABSTRACT FROM AUTHOR]

This study evaluates the use of electrocardiographic (ECG) gated single-photon emission computed tomographic (SPECT) myocardial perfusion imaging for the prediction of viability in patients undergoing revascularization, who have coronary disease and left ventricular dysfunction. Fifty patients underwent technectium-99m (Tc-99m) sestamibi ECG gated SPECT imaging preoperatively at rest and 1 week after revascularization, whereas 36 (72%) also underwent imaging 6 weeks after revascularization. Images were interpreted by the consensus of 3 experienced readers without knowledge of patient identity or time of imaging (pre- or postrevascularization) for perfusion and wall motion using a 17-segment model. Results of perfusion alone were compared with perfusion and wall motion combined. One hundred five coronary artery territories were revascularized, 96 of which were viable and 9 nonviable. Perfusion alone predicted 87 to be viable and 18 nonviable (sensitivity 86%, specificity 55%, positive predictive value 95%, negative predictive value 28%, and overall accuracy 85%). Perfusion and wall motion combined identified 95 territories to be viable (sensitivity 95%; p <0.025; specificity 55%, positive predictive value 96%, negative predictive value 50%, and overall accuracy 91%; p <0.05). Thus, Tc-99m sestamibi ECG gated SPECT myocardial perfusion imaging at rest allows assessment of both perfusion and wall motion, which significantly improves the sensitivity and overall accuracy for determination of viability in comparison with perfusion alone. [ABSTRACT FROM AUTHOR]

Background: The use of myocardial perfusion imaging (MPI) in the management of coronary artery disease (CAD) is well established. Although prior studies have shown disparities in the use of invasive angiography in patients with acute MI, data on factors affecting referral to angiography post-MPI are lacking. We sought to evaluate the primary determinants of referral to invasive angiography post-MPI and specifically assess the role of non-traditional non-clinical factors such as race/ethnicity, socioeconomic factors, insurance status, and marital status., Methods: All patients without known CAD who underwent stress SPECT MPI over 15 years were reviewed and the performance of coronary angiography within 90 days of their MPI was recorded. Multiple factors were analyzed for an association with referral to angiography, including exercise and MPI results, baseline demographics, traditional cardiac risk factors, and non-traditional factors such as ethnicity, insurance, marital and socioeconomic status. In a secondary analysis, these factors were assessed with regard to abnormal MPI results., Results: Out of 27,895 total patients, 2,150 (7.7%) underwent invasive coronary angiography. On multivariate analysis, inpatient location, positive ECG response, and abnormal MPI results were the strongest predictors of angiography. Non-traditional factors such as race/ethnicity and insurance status had a significant association with referral to angiography with Caucasians (OR 1.42, 95% CI 1.18-1.71, P < .0001) and those with private insurance (OR 1.35, 95% CI 1.13-1.62, P = .001) or Medicare (OR 1.30, 95% CI 1.08-1.56, P = .006) having higher rates of angiography despite controlling for traditional risk factors and test results., Conclusion: Our study results indicate that non-traditional factors such as race/ethnicity and insurance status influence patient management decisions and impact the performance of downstream cardiac invasive testing after stress MPI. Higher rates of angiography in Caucasians, privately insured and Medicare patients were seen despite controlling for traditional risk factors and abnormal test results. Further research is needed to better understand these disparities, especially in the current healthcare environment., (© 2020. American Society of Nuclear Cardiology.)

Background: Although the diagnostic accuracy and prognostic utility of vasodilator stress MPI have been well established in the non-acute setting, the efficacy of all of the vasodilator stressors in risk stratifying post-MI patients as well as the evaluation of cardiac troponin elevation of unclear etiology is not established. Accordingly, the aim of the present study was to investigate the prognostic efficacy of vasodilator stress MPI in the setting of elevated cardiac troponin to accurately risk stratify these higher-risk patients., Methods: All patients from two tertiary centers, from 1/1/2010 through 12/31/2012, with elevated cardiac biomarkers within < 7 days and undergoing stress SPECT MPI testing were studied. Results of stress MPI were scored using a 17-segment model based on semiquantitative scoring as normal or abnormal (mild, moderate, or severe) using a total perfusion defect (TPD) of 0%, 1-10%, 10-20%, and > 20%. Mortality data through the year 2014 were obtained from the National Death Index, and survival analyses were performed. The primary endpoint was all-cause mortality with the secondary endpoint being cardiac mortality., Results: A total of 503 patients were followed for an average of 33.6 ± 16.2 months, with a mean age of 69.3 years; 53.7% male; and a majority (88.7%) of them undergoing vasodilator stress. A significant increase in all-cause mortality was seen based on the severity of TPD results for all vasodilators (P < .0001) and regadenoson (P < .0001). Similar prognostic ability was seen for all-cause mortality. This association was maintained even after adjustment for cardiac risk factors, previous coronary disease, and troponin quartiles. MPI results (stress TPD and LVEF) added to traditional cardiac risk factors, and troponin values resulted in a significant incremental increase in the ability to predict all-cause and cardiac mortality, and stress TPD remained independently predictive for both all-cause and cardiac mortality in a multivariate model., Conclusion: Vasodilator stress (including regadenoson) MPI effectively risk stratifies patients with recently elevated cardiac biomarkers, with the increasing risk of mortality with the increasing severity of perfusion defects. It provides incremental prognostic value, in addition to clinical factors and degree of troponin elevation.

Background: Several publications and guidelines designate diabetes mellitus (DM) as a coronary artery disease (CAD) risk equivalent. The aim of this investigation was to examine DM cardiac risk equivalence from the perspective of stress SPECT myocardial perfusion imaging (MPI)., Methods and Results: We examined cardiovascular outcomes (cardiac death or nonfatal MI) of 17,499 patients referred for stress SPECT-MPI. Patients were stratified into four categories: non-DM without CAD, non-DM with CAD, DM without CAD, and DM with CAD, and normal or abnormal perfusion. Cardiac events occurred in 872 (5%), with event-free survival best among non-DM without CAD, worst in DM with CAD, and intermediate in DM without CAD, and non-DM with CAD. After multivariate adjustment, risk remained comparable between DM without CAD and non-DM with CAD [AHR 1.0 (95% CI 0.84-1.28), P =0.74]. Annualized event rates for normal subjects were 1.4% and 1.6% for non-DM with CAD and DM without CAD, respectively (P = 0.48) and 3.5% (P = 0.95) for both abnormal groups. After multivariate adjustment, outcomes were comparable within normal [AHR 1.4 (95% CI 0.98-1.96) P = 0.06] and abnormal [AHR 1.1 (95% CI 0.83-1.50) P = 0.49] MPI., Conclusions: Diabetic patients without CAD have comparable risk of cardiovascular events as non-diabetic patients with CAD after stratification by MPI results. These findings support diabetes as a CAD equivalent and suggest that MPI provides additional prognostic information in such patients.

Background: Stress-only Tc-99m SPECT MPI saves time and reduces radiation exposure while a normal study has a benign prognosis. However, no guidelines exist as to which patients should undergo stress-first MPI. The purpose of this study was to validate a previously published pre-test prediction scoring model and refine the stress-first triage process further if possible., Methods: We retrospectively reviewed all patients who underwent an attenuation-corrected Tc-99m SPECT MPI over a 39-month period. Based on 17-segment model semi-quantitative scoring, a successful stress-first MPI was defined as a summed stress attenuation-corrected score ≤ 1. Based on results from multivariate analysis, the previously published prediction score (comprised eight clinical and demographic variables) was compared to triage based on coronary artery disease (CAD) status alone and with the addition of other highly associated variables. Logistic regression and Chi-squared analyses were used to determine the magnitude of variable effect and to compare model results., Results: A total of 2,277 patients were included, and the prediction score successfully stratified patients into low-risk (91.1% successful stress-first), intermediate-risk (79.4%), and high-risk (50.7%) groups. Comparing the use of the prediction score to the use of a history of CAD as the only triage factor, 69.0% of patients would be accurately triaged using the prediction score with a cutoff of 7 (maximized sensitivity and specificity), while 78.6% were correctly triaged with CAD status alone (P < .0001). The addition of variables highly associated with a successful stress-first protocol (congestive heart failure [OR 3.4] and an abnormal resting ECG [OR 2.1]) to CAD status further enhanced triage accuracy to 81% (P < .0001)., Conclusions: While the previously described prediction score effectively identifies patients who can successfully undergo stress-first MPI, it is cumbersome. Triaging based solely on CAD status and with the addition of other key variables is practical and provides improved predictive accuracy for successful stress-first MPI. Utilizing this simplified pre-test scoring model may allow for wider adoption of stress-first imaging protocols which have clear advantages over traditional rest-stress protocols.

Background: Increasing numbers of patients are undergoing transcatheter aortic valve replacement, which often involves assessment of coronary artery disease ischemic burden. The safety and diagnostic accuracy of vasodilator stress agents in patients with severe aortic stenosis (AS) undergoing SPECT myocardial perfusion imaging (MPI) has not been established., Methods: Patients with severe AS (valve area <1 cm 2 ) on echocardiography who underwent vasodilator stress SPECT MPI at two centers were identified. Patients with aortic valve intervention prior to MPI or who underwent concurrent exercise during stress testing were excluded. AS patients were matched to controls without AS based on age, gender, BMI, ejection fraction, and stress agent. Symptoms, serious adverse events, hemodynamic response, and correlation to invasive angiography were assessed., Results: A total of 95 cases were identified with 45% undergoing regadenoson, 31% dipyridamole, and 24% adenosine stress. A significant change in systolic blood pressure (BP), cases vs controls, was observed with adenosine [-17.9 ± 20.1 vs -2.6 ± 24.9 P = .03)], with a trend toward significance with regadenoson [-16.8 ± 20.3 vs -9.4 ± 17.9 (P = .08)] and dipyridamole [-17.8 ± 20.6 vs -9.0 ± 12.1 (P = .05)]. The change in heart rate was significantly different only for adenosine [5.3 ± 16.8 vs 14.2 ± 10.8 (P = .04)]. Overall, 45% of cases vs 24% of controls (P = .004) had a >20 mmHg decrease in systolic BP. Age, BMI, and resting systolic BP were related to a >20 mmHg decrease in systolic BP on univariate analysis, although only higher resting systolic BP was a predictor on multivariate analysis. In 33 patients who underwent angiography, the sensitivity, specificity, and diagnostic accuracy of vasodilator stress MPI was 77%, 69%, and 73%, respectively. No serious adverse events occurred in the severe AS patients., Conclusion: Severe AS patients are more likely to have a hemodynamically significant decrease in systolic BP with vasodilator stress. There were no serious adverse events in this severe AS cohort with good diagnostic performance of MPI compared to angiography.

Background: A stress-first myocardial perfusion imaging (MPI) protocol saves time, is cost effective, and decreases radiation exposure. A limitation of this protocol is the requirement for physician review of the stress images to determine the need for rest images. This hurdle could be eliminated if an experienced technologist and/or automated computer quantification could make this determination., Methods: Images from consecutive patients who were undergoing a stress-first MPI with attenuation correction at two tertiary care medical centers were prospectively reviewed independently by a technologist and cardiologist blinded to clinical and stress test data. Their decision on the need for rest imaging along with automated computer quantification of perfusion results was compared with the clinical reference standard of an assessment of perfusion images by a board-certified nuclear cardiologist that included clinical and stress test data., Results: A total of 250 patients (mean age 61 years and 55% female) who underwent a stress-first MPI were studied. According to the clinical reference standard, 42 (16.8%) and 208 (83.2%) stress-first images were interpreted as "needing" and "not needing" rest images, respectively. The technologists correctly classified 229 (91.6%) stress-first images as either "needing" (n = 28) or "not needing" (n = 201) rest images. Their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 66.7%, 96.6%, 80.0%, and 93.5%, respectively. An automated stress TPD score ≥1.2 was associated with optimal sensitivity and specificity and correctly classified 179 (71.6%) stress-first images as either "needing" (n = 31) or "not needing" (n = 148) rest images. Its sensitivity, specificity, PPV, and NPV were 73.8%, 71.2%, 34.1%, and 93.1%, respectively. In a model whereby the computer or technologist could correct for the other's incorrect classification, 242 (96.8%) stress-first images were correctly classified. The composite sensitivity, specificity, PPV, and NPV were 83.3%, 99.5%, 97.2%, and 96.7%, respectively., Conclusion: Technologists and automated quantification software had a high degree of agreement with the clinical reference standard for determining the need for rest images in a stress-first imaging protocol. Utilizing an experienced technologist and automated systems to screen stress-first images could expand the use of stress-first MPI to sites where the cardiologist is not immediately available for interpretation.

Background: While adenosine and dipyridamole as myocardial perfusion imaging (MPI) stress agents have literature supporting their safety in the setting of myocardial infarction (MI), regadenoson does not. Studying a high risk cohort of patients with elevated cardiac biomarkers may shed light on potential safety issues of these agents which might also affect lower risk cohorts., Methods: All patients who had undergone a clinically indicated stress MPI study at two academic centers from 1/1/2010 through 12/31/2012 with elevated troponin ≤7 days prior to testing were included. The primary endpoint was a composite of death, non-fatal MI, congestive heart failure (CHF), stroke, ventricular arrhythmias, atrial fibrillation/flutter, or atrioventricular block requiring intervention within 24 h of testing., Results: Of the 703 stress MPI studies that met inclusion criteria, 360 (51.2%), 199 (28.3%), 74 (10.5%), 9 (1.3%), and 61 (8.7%) underwent regadenoson, dipyridamole, adenosine, dobutamine, and exercise stress, respectively. The primary endpoint occurred in 11 (1.6%) patients with an incidence of 1.4% (n = 5), 1.0% (n = 2), 1.4% (n = 1), 11.1% (n = 1), and 3.3% (n = 2) following regadenoson, dipyridamole, adenosine, dobutamine, and exercise stress, respectively (P = 0.137). The adverse events included non-fatal MI in 7 (1.0%) patients, death in 1 (0.1%) patient, CHF in 1 (0.1%) patient, ventricular arrhythmia in 1 (0.1%) patient, and atrial arrhythmia in 1 (0.1%) patient., Conclusion: In the setting of elevated troponin, serious complications associated with either exercise or vasodilator stress testing appear to be relatively rare with no increased risk attributable to a particular vasodilator agent.

Introduction: Temporal trends of myocardial perfusion imaging (MPI) among diabetics and non-diabetics and the influence of gender and prior coronary artery disease (CAD) status has not been previously investigated., Materials and Methods: Consecutive patients who underwent clinically indicated stress-MPI over a 17-year period (1996 through 2012) were studied. Data were collected prospectively as a part of the ongoing clinical databases. Study patients were divided into 4 temporal subgroups (1996 to 2000, 2001 to 2004, 2005 to 2008 and 2009 to 2012) to compare the trends of cardiac risk factors and the frequency of abnormal and ischemic MPI., Results: Of 78,344 total stress MPI studies, 30.2% were in diabetics. The frequency of abnormal MPI studies, while substantially higher in diabetics, significantly declined over time both in diabetics (53.6% in 1996 to 39.8% in 2012) and non-diabetics (37% in 1996 to 27.4% in 2012), despite an increase in the cardiac risk factor profile. Furthermore, among patients with no known CAD, the temporal prevalence of abnormal MPI was highest in diabetic men (57.5% in 1996 to 31.9% in 2012), lowest in non-diabetic women (18.8% in 1996 to 11% in 2012), and both intermediate and comparable in non-diabetic men and diabetic women (36.4% and 35.7% in 1996 and 20.7% and 17.5% in 2012, respectively)., Conclusions: Despite a temporal reduction in the prevalence of abnormal studies from 1996 through 2012, stress MPI continues to play an important clinical role, particularly in diabetics, men and patients with known-CAD., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Recent literature suggests that the frequency of abnormal SPECT myocardial perfusion imaging (MPI) has decreased over the past two decades despite an increase in the prevalence of many cardiac risk factors. This study examined the trends in the prevalence of obstructive coronary artery disease (CAD) by abnormal and ischemic MPI and invasive angiography., Methods: We analyzed all patients who underwent stress MPI or invasive angiography at two academic centers between January 1996 and December 2012, for their demographic data and study results., Results: A total of 108,654 MPI studies were performed. Over time, the percentage of patients with hypertension, hyperlipidemia, diabetes, and a history of smoking increased. There was a decline in the prevalence of abnormal MPI studies in all patients as well as in those with and without known CAD (from 47.2%, 71.8%, and 31.4% in 1996 to 33.9%, 64.8%, and 18.8% in 2012, respectively, all P < .0001). Similarly, there was a decline in the prevalence of ischemic MPI studies in all patients as well as in those with and without known CAD. A total of 142,924 invasive angiograms were performed. There was a decline in the prevalence of one-vessel and multi-vessel coronary disease (from 29.1% and 53.6% in 1996 to 22.4% and 35.9% in 2012, respectively, all P < .0001)., Conclusions: There has been a temporal decline in the prevalence of abnormal and ischemic MPI studies as well as the frequency and extent of obstructive CAD on angiography. However, this decline was not to the same extent as previously reported, and the overall 34% abnormal MPI rate, with 19% in patients with no known CAD and 65% in patients with known CAD, remains a clinically relevant percentage of patients tested.

Background: In patients with functional limitations, the use of adjunctive exercise with vasodilator stress has advantages over vasodilator stress alone in single photon emission computed tomography myocardial perfusion imaging (MPI) for technical reasons and with regards to more effective cardiac risk stratification. Whether patients who undergo vasodilator with adjunctive exercise stress MPI possess clinical characteristics and cardiac risk that differs from those who undergo standard exercise or vasodilator stress MPI is unknown., Methods: Prospectively collected data on 19,367 consecutive patients referred for stress MPI to a tertiary care center (9,331 [48%] underwent exercise-only, 3,793 [20%] underwent vasodilator plus exercise, and 6,243 [32%] underwent vasodilator-only) were analyzed. Perfusion data were scored using the ASNC 17-segment with a summed stress score (SSS) < 4 = normal, 4-8 = mildly abnormal, and > 8 = moderate to severely abnormal. Patients were followed a mean of 1.96 ± 0.95 years. Demographics, clinical characteristics, and the occurrence of major adverse cardiac events (cardiac death or nonfatal myocardial infarction) were compared between the three stress modality groups., Results: Comparison of demographics and clinical characteristics revealed significant differences in gender, age, cardiac risk factors, and stress MPI between the three stress modality groups (P < .001). In follow-up, cardiac event-free survival of patients in the vasodilator plus exercise stress group was significantly higher than those in the vasodilator-only group but lower than those in the exercise-only group (P < .001). Annualized cardiac event rates of patients in the vasodilator plus exercise stress group were significantly lower than those in the vasodilator-only group for all three categories of the SSS (P < .001). After multivariable adjustment, with exercise-only as reference category, vasodilator plus exercise and vasodilator-only stress emerged as independent predictors (more likely occurrence) of cardiac death, while vasodilator-only stress emerged as an independent predictor (more likely occurrence) of cardiac death or nonfatal myocardial infarction. With vasodilator-only as the reference category, exercise-only and vasodilator plus exercise stress emerged as independent predictors (less likely occurrence) of cardiac death as well as of cardiac death or nonfatal myocardial infarction., Conclusions: Patients undergoing vasodilator plus exercise stress MPI possess clinical characteristics and cardiac risk that differs significantly from those undergoing either standard exercise or vasodilator stress MPI and places them in a lower risk category compared to vasodilator stress alone.

Purpose: Hospitalization in patients with systolic heart failure is associated with morbidity, mortality, and cost. Myocardial sympathetic innervation, imaged by (123)I-meta-iodobenzylguanidine ((123)I-mIBG), has been associated with cardiac events in a recent multicenter study. The present analysis explored the relationship between (123)I-mIBG imaging findings and hospitalization., Methods: Source documents from the ADMIRE-HF trial were reviewed to identify hospitalization events in patients with systolic heart failure following cardiac neuronal imaging using (123)I-mIBG. Time to hospitalization was analyzed with the Kaplan-Meier method and compared to the mIBG heart-to-mediastinum (H/M) ratio using multiple-failure Cox regression., Results: During 1.4 years of median follow-up, 362 end-point hospitalizations occurred in 207 of 961 subjects, 79 % of whom had H/M ratio <1.6. Among subjects hospitalized for any cause, 88 % had H/M ratio <1.6 and subjects with H/M ratio <1.6 experienced hospitalization earlier than subjects with higher H/M ratios (log-rank p = 0.003). After adjusting for elevated brain natriuretic peptide (BNP) and time since heart failure diagnosis, a low mIBG H/M ratio was associated with cardiac-related hospitalization (HR 1.48, 95 % CI 1.05 - 2.0; p = 0.02)., Conclusion: The mIBG H/M ratio may risk-stratify patients with heart failure for cardiac-related hospitalization, especially when used in conjunction with BNP. Further studies are warranted to examine these relationships.

Background: Although line source attenuation correction (AC) in SPECT MPI studies improves diagnostic accuracy, its prognostic value is less understood., Methods: Consecutive patients (n = 6,513) who underwent rest/stress AC ECG-gated SPECT MPI were followed for cardiac death or non-fatal myocardial infarction (MI). A 17-segment model and AC summed stress score (SSS) were used to classify images., Results: Of the 6,513 patients, cardiac death or non-fatal MI occurred in 267 (4.1%), over 2.0 ± 1.4 years. The AC-SSS in patients with a cardiac event (5.6 ± 7.8) was significantly higher than in those without (1.9 ± 4.6, P < .001). The annualized cardiac event rate in patients with an AC-SSS 1-3 (3.6%) was significantly higher than in those with an AC-SSS = 0 (1.1%, P < .001) but similar to that in those with an AC-SSS 4-8 (2.9%, P = .4). Accordingly, patients were classified to AC-SSS = 0, 1-8, and >8 with annualized cardiac event rates of 1.1%, 3.2%, and 8.5%, respectively (P < .0001). In multivariate analysis, an AC-SSS 1-8 and >8 emerged as independent predictors of cardiac events (P < .02 and P < .0001, respectively)., Conclusion: Rest/stress ECG-gated SPECT MPI with line source AC provides highly effective and incremental risk stratification for future cardiac events.

Background: Ambulatory patients with uncertain functional capacity may benefit from combined exercise and vasodilator stress protocols for myocardial perfusion imaging (MPI). The safety and MPI image quality with regadenoson administered during symptom-limited exercise have not been prospectively evaluated., Methods and Results: A total of 140 patients (mean age 61 years, 48% female) referred for exercise with vasodilator stress MPI were randomized 2:1 to a strategy of exercise with regadenoson-as-necessary (Ex-Reg, n = 96) or dipyridamole with exercise (Dip-Ex, n = 44) after Duke Activity Status Index (DASI) scoring (median score 28 vs 24, P = .09). Ex-Reg subjects commenced treadmill exercise and regadenoson was administered only if the subject was unable to reach standard endpoints. Dip-Ex subjects received dipyridamole prior to symptom-limited exercise. Hemodynamics were recorded throughout. Subjects completed symptom questionnaires and MPI image quality was assessed by blinded read. Ex-Reg subjects were more likely to achieve ≥85% age-predicted maximum heart rate than Dip-Ex subjects (57% vs 32%, P < .01). Only 50% of subjects meeting inclusion criteria and randomized to Ex-Reg required regadenoson and none had symptomatic hemodynamic changes. Severe side effects or adverse events occurred in 16% of Ex-Reg and 24% of Dip-Ex subjects (P = .12). MPI image quality was "good" or "excellent" in 88% of Ex-Reg subjects and 86% of Dip-Ex subjects (P = .33)., Conclusion: A strategy of exercise with regadenoson-as-needed for MPI offers similar safety and side effect profile with similar image quality compared to dipyridamole with exercise, with reduced pharmaceutical use.

Background: In selected patients, stress-only SPECT imaging has been proposed as an alternative to rest-stress SPECT imaging to improve laboratory efficiency and reduce radiation exposure. The impact of attenuation correction (AC) upon interpretation, post-test patient management and cardiac risk stratification in relation to stress-only imaging is not well understood., Objectives: The purpose of this study was to determine the clinical value for laboratory throughput and predicting outcomes of normal and abnormal stress-only SPECT imaging with AC in a consecutive series of clinically referred patients., Methods: A retrospective analysis of 1,383 consecutive patients who were scheduled for stress-only SPECT imaging for symptom assessment of suspected myocardial ischemia was performed. All images had been interpreted and categorized using the standard 17-segment model without AC followed by AC. Follow-up data for 2.1 ± 1.3 years after SPECT imaging for the occurrence of cardiac events (non-fatal MI, cardiac death, and cardiac revascularization) previously collected by routine methods were reviewed., Results: Non-AC SPECT image interpretation revealed that 58% (802/1383) of patients had abnormal stress images. AC image interpretation of the abnormal non-AC images re-classified 83% (666/802) of these as normal. Among patients with abnormal stress images after AC (136/1383), 63% (86/136) returned for additional rest scans, while the remaining 37% (50/136) were clinically managed without further rest images. The incidence of cardiac death or non-fatal MI was very low in patients with normal stress-only scans (0.7%)., Conclusion: A strategy of stress-only imaging with AC in symptomatic patients is an efficient method which appropriately identifies at risk and low-risk patients yielding a low percentage requiring rest imaging. Clinical decisions can be made based on abnormal stress-only imaging without further rest imaging if clinically appropriate.

Background: Significance of electrocardiographic (ECG) changes during vasodilator stress myocardial perfusion imaging (MPI) is controversial. We examined the diagnostic and prognostic significance of ECG changes during vasodilator single photon emission computerized tomography (SPECT) MPI., Methods: We studied consecutive patients who underwent vasodilator SPECT MPI from 1995 to 2009. Patients with baseline ECG abnormalities, previous history of coronary artery bypass graft surgery or myocardial infarction (MI) were excluded. Significant coronary artery disease (CAD) was defined as >70% stenosis of any vessel or ≥50% stenosis of left main. Mean follow-up was 2.4 ± 1.5 years for cardiac events (cardiac death and non-fatal MI)., Results: Of patients in the diagnostic cohort, ST depression was associated with increased incidence of CAD with abnormal (P = .020 and P <.001) but not in those with normal perfusion (P = .342). Of 3,566 patients with follow-up in the prognostic cohort, including 130 (5.0%) with ST depression and normal perfusion, the presence of ST depression ≥1 mm did not affect the outcomes in any summed stress score category., Conclusions: ST depression ≥1 mm during vasodilator SPECT MPI is associated with CAD in patients with abnormal perfusion, but provides no additional risk stratification beyond concomitant perfusion imaging, including those with normal studies.

Background: Stress electrocardiogram(ECG)-gated single photon emission computed tomography (SPECT) imaging is highly effective in risk stratification of diabetic patients for adverse cardiac events. While patients with diabetes are predisposed to a more aggressive progression of vascular disease, the impact of its duration and type of therapy on risk stratification are unknown., Methods: From the Hartford Hospital Nuclear Cardiology clinical database, 886 diabetic patients who underwent exercise or pharmacologic stress ECG-gated SPECT were identified, with complete follow-up regarding the occurrence of adverse cardiac events and information regarding the duration of diabetes and the type of therapy (insulin vs oral medication only) at the time of testing. Images were interpreted using the American College of Cardiology/ASNC standard 17-segment scoring model., Results: Of the 886 diabetic patients, 98 (11%) suffered cardiac death or non-fatal myocardial infarction during follow-up (2.5 ± 1.6 years). A receiver operator characteristics curve demonstrated that diabetes ≥10 years in duration provided the maximal sum of sensitivity and specificity for the prediction of adverse cardiac outcomes. Multivariate analysis identified the following as independent predictors of adverse outcome: Post-stress ejection fraction (EF) <40% (P = .001), age (P = .004), insulin therapy (P = .031), diabetes duration >10 years (P = .038), summed stress score (SSS) >8 (P = .046). For patients with an SSS >8, diabetes duration and type of therapy significantly enhanced risk stratification. Similar findings emerged for patients with a post-stress EF <40%., Conclusion: For diabetic patients undergoing stress ECG-gated SPECT myocardial perfusion imaging, disease duration and type of therapy provide independent and incremental prognostic information. Integration of these variables with this cardiovascular imaging technology significantly enhances cardiac risk stratification.

Introduction: The prognostic value of a blunted heart rate response (BHR) during ECG-gated vasodilator stress SPECT MPI in relation to ventricular function on long-term cardiovascular events is not well established. We performed this study to evaluate the incremental prognostic value of BHR during pharmacological stress SPECT MPI., Methods: Consecutive patients who underwent dipyridamole stress Tc-99m sestamibi ECG-gated SPECT MPI (without exercise) were identified. The ratio of peak stress heart rate to baseline was noted. If the ratio was <1.20, it was considered blunted (BHR). The images were interpreted using the standard ASNC 17 segment model. Patients were followed up for a mean time period of 2.3 +/- 1.5 years., Results: Sixty-four percent (2,890/4,484) of patients demonstrated BHR during dipyridamole stress testing. Cardiac death, the primary end point, occurred in 6.8% of patients. Patients with BHR had a significantly lower cardiac death-free survival as compared to NO BHR group in total population (83% vs 94%; P < .001) as well as in subgroup with normal ejection fraction (89% vs 96%; P < .001). BHR was an independent predictor of cardiac death after adjusting for multiple clinical, perfusion, and function-related gated SPECT variables., Conclusion: Blunted heart rate response during vasodilator stress SPECT MPI is an important prognostic marker for cardiac death.

Background: The field of nuclear cardiology is limited by image quality and length of procedure. The use of depth-dependent resolution recovery algorithms in conjunction with iterative reconstruction holds promise to improve image quality and reduce acquisition time. This study compared the Astonish algorithm employing depth-dependent resolution recovery and iterative reconstruction to filtered backprojection (FBP) using both full-time (FTA) and half-time (HTA) data. Attenuation correction including scatter correction in conjunction with the Astonish algorithm was also evaluated., Methods: We studied 187 consecutive patients (132 with cardiac catheterization and 55 with low likelihood for CAD) from three nuclear cardiology laboratories who had previously undergone clinically indicated rest/stress Tc-99m sestamibi or tetrofosmin SPECT. Acquisition followed ASNC guidelines (64 projections, 20-25 seconds). Processing of the full-time data sets included FBP and Astonish (FTA). A total of 32 projection data sets were created by stripping the full-time data sets and processing with Astonish (HTA). Attenuation correction was applied to both full-time and half-time Astonish-processed images (FTA-AC and HTA-AC, respectively). A consensus interpretation of three blinded readers was performed for image quality, interpretative certainty, and diagnostic accuracy, as well as severity and reversibility of perfusion and functional parameters., Results: Full-time and half-time Astonish processing resulted in a significant improvement in image quality in comparison with FBP. Stress and rest perfusion image quality (excellent or good) were 85%/80% (FBP), 98%/95% (FTA), and 95%/92% (HTA), respectively (p < 0.001). Interpretative certainty and diagnostic accuracy were similar with FBP, FTA, and HTA. Left ventricular functional data were not different despite a slight reduction in half-time gated image quality. Application of attenuation correction resulted in similar image quality and improved normalcy (FTA vs. FTA-AC: 76% vs. 95%; HTA vs. HTA-AC: 76% vs. 100%) and specificity (FTA vs. FTA-AC: 62% vs. 78%; HTA vs. HTA-AC: 63% vs. 84%) (p < 0.01 for all comparisons)., Conclusion: Astonish processing, which incorporates depth-dependent resolution recovery, improves image quality without sacrificing interpretative certainty or diagnostic accuracy. Application of simultaneously acquired attenuation correction, which includes scatter correction, to full-time and half-time images processed with this method, improves specificity and normalcy while maintaining high image quality.

Background: Despite growing recognition of attenuation correction (AC) utilizing an external radiation source, prognostic studies using AC are lacking., Methods: Consecutive patients (n = 419) who underwent stress Tc-99m sestamibi SPECT imaging with AC but without ECG-gating, due to arrhythmia, were followed for cardiac death or non-fatal myocardial infarction (MI). A 17-segment model and the summed stress score (SSS) were used to classify both the non-AC and AC images., Results: The 419 patients had a mean age of 71.5 +/- 11.7 years and most (70.6%) underwent pharmacologic stress. In follow-up, 35 (8.4%) patients suffered an adverse cardiac event. Patients with AC-SSS 1-3 and AC-SSS 4-8 had similar cardiac event rates (11.4% vs 10.5%, P = NS). Accordingly, AC-SSS cutoffs of 0, 1-8, and >8 were selected to classify perfusion as normal, mildly abnormal, and moderately to severely abnormal with annualized event rates of 2.1%, 10.8%, and 18.7%, respectively (P < .001). In multivariable analysis, AC-SSS >8 was the most powerful predictor of cardiac events followed by AC-SSS 1-8, history of CAD, age >75 and pharmacologic stress., Conclusions: AC provides powerful risk stratification when added to clinical variables in patients undergoing stress Tc-99m sestamibi SPECT imaging without ECG-gating. Moreover, smaller/less severe defects on AC data are more significant than if the same defects were seen on non-AC data.

Background: Although attenuation correction (AC) has been successfully applied to large field of view (LFOV) cameras, applicability to small field of view (SFOV) cameras is a concern due to truncation. This study compared perfusion images between a LFOV and SFOV camera with truncation compensation, using the same AC solution., Methods and Results: Seventy-eight clinically referred patients underwent rest-stress single-photon emission computed tomography (SPECT) using both a SFOV and LFOV camera in a randomized sequence. Blinded images were interpreted by a consensus of three experienced readers. The percentage of normal images for SFOV and LFOV was significantly higher with than without AC (72% vs 44% and 72% vs 49%, both P < .001). Interpretive agreement between cameras was better with than without AC (kappa = 0.736 to 0.847 vs 0.545 to 0.774). Correlation for the summed stress score was higher with than without AC (r (2) = 0.892 vs 0.851, both P < 0.001) while Bland Altman analysis demonstrated narrower limits with than without AC (4.0 to -4.3 vs 5.9 to -5.6)., Conclusion: Attenuation correction using truncation compensation with a SFOV camera yields similar results to a LFOV camera. The higher interpretive agreement between cameras after attenuation correction suggests that such images are preferable to non-attenuation-corrected images.

Background: Whether left ventricular ejection fraction (EF) obtained by gated rubidium 82 positron emission tomography (PET) myocardial imaging can identify patients at risk for future cardiac events is unclear., Methods and Results: Consecutive patients with known or suspected coronary artery disease who underwent dipyridamole stress gated Rb-82 PET imaging were evaluated. Scoring of perfusion was accomplished by use of a 17-segment model. EF was automatically generated. Patients were stratified based on summed stress scores (SSSs) (0-3, 4-8, or >8) and stress EF (>50%, 40%-49%, or <40%). All-cause mortality was determined by use of the Social Security Death Index. Of 1,441 patients, 132 (9.2%) died during mean follow-up of 2.7 +/- 0.8 years. Annualized mortality rates across SSS groups were 2.4% for SSS of 0 to 3, 4.1% for SSS of 4 to 8, and 6.9% for SSS greater than 8 (P < .001). Similarly, annualized mortality rates were 2.4%, 6.2%, and 9.2% for the group with EF greater than 50%, group with EF of 40% to 49%, and group with EF lower than 40%, respectively (P < .001). On multivariate analysis, the addition of EF to clinical and perfusion variables significantly increased the global chi(2) (73.3 to 107.7, P < .001). Integration of EF with SSS significantly enhanced risk stratification., Conclusion: EF assessed by stress gated Rb-82 PET imaging provides independent and incremental prognostic information and, hence, should be routinely incorporated in risk assessment.

Background: Combining vasodilator and exercise stress reduces noncardiac side effects, improves image quality, and enhances the detection of ischemia, compared with suboptimal exercise or vasodilator stress alone. However, prognostic data with combined protocols are limited., Methods and Results: Consecutive patients (n = 2064) who underwent symptom-limited exercise and dipyridamole stress with gated single-photon emission computed tomography (SPECT) imaging, without early revascularization, were studied. Subsequent cardiac death or nonfatal myocardial infarction was related to exercise and gated SPECT variables. Cox proportional hazards regression modeling was performed to identify predictors of adverse outcome. Annualized event rates in patients with normal and abnormal images were 0.96% and 2.71%, respectively (P < .001). With abnormal imaging, annualized event rates were 0.86% and 3.13% in patients with average to high and fair or poor functional capacity, respectively (P = .019). Abnormal imaging, a severely reduced post-stress ejection fraction, transient ischemic dilation, and fair or poor functional capacity emerged as predictors of adverse outcome. Accordingly, patients were stratified into low-risk, intermediate-risk, and high-risk cohorts with annualized event rates of 0.94%, 2.24%, and 8.19%, respectively (P < .001 in any two-way comparison)., Conclusions: A protocol that combines symptom-limited exercise and dipyridamole stress with gated SPECT imaging provides highly effective risk stratification for adverse outcomes.

Background: The global left-ventricular (LV) ejection fraction (EF) is a powerful predictor of cardiac death (CD). There are limited data on the prognostic value of regional LV function. We examined the role of visually assessed regional wall motion in risk stratification for future cardiac events., Methods and Results: A prospectively gathered database of 10,336 patients who underwent technetium (Tc)-99m sestamibi-gated single-photon emission computed tomography (SPECT) was analyzed. The summed stress score (SSS) and summed wall-motion score (SWMS) were calculated using a standard 17-segment model. The post-stress EF was generated using QGS software. The follow-up was 90.2% complete over 28.6 +/- 16 months. Patients with early (or=5) was an independent predictor of cardiac death (odds ratio = 1.78, 95% confidence interval = 1.11 to 2.85, P = .016). Among patients with an EF >or=45%, abnormal wall motion was the only gated SPECT variable that independently predicted cardiac death (odds ratio = 1.69, 95% confidence interval = 1.06 to 2.7, P = .028). In patients with an EF >or=45% and reversible perfusion defects, abnormal wall motion predicted an intermediate (2.2%/year) risk for CD, and a high (4.2%/year) risk for the combined endpoint of cardiac death and nonfatal MI., Conclusions: Regional LV function data from gated SPECT provide important prognostic information, and may identify a subgroup of patients with preserved EF and ischemia who are at significant risk for future cardiac events.

Objectives: The purpose of this research was to evaluate the significance of heart rate response to dobutamine and the assessment of left ventricular (LV) function during risk stratification of patients undergoing dobutamine stress myocardial perfusion imaging (DSMPI)., Background: Dobutamine stress myocardial perfusion imaging has been shown to effectively risk stratify highly selected patients. However, based on perfusion alone, patients with normal and abnormal tests have twice the risk as comparable patients with exercise testing. The added value of assessment of LV function and the heart rate response to dobutamine in risk stratification of these patients is unknown., Methods: Follow-up information (cardiac death or non-fatal myocardial infarction) was obtained on 1,367 consecutive patients who underwent DSMPI due to inability to perform adequate exercise and contraindications to vasodilators. Perfusion images were interpreted using a 17-segment model. Abnormal perfusion and function were defined as: summed stress score > or =4 and ejection fraction <50%, respectively., Results: Annualized event rates (AERs) were related to the extent/severity of perfusion defects and worsening LV function. A three-risk category model was constructed from combined assessment of perfusion and function, with AERs of 2.4% (both normal), 5.8% (discordant), and 11.3% (both abnormal); p < 0.001. Stress electrocardiogram (ECG) data added incremental value to myocardial perfusion alone but not to combined assessment of perfusion and function. Importantly, inability to achieve 85% of mean predicted heart rate was associated with worse outcomes and was an independent predictor of cardiac events. For patients in whom perfusion, function, and stress ECG response were normal, inability to achieve target heart rate was associated with significantly higher AER (1.5% vs. 3.4%, respectively, p = 0.021)., Conclusions: In highly selected patients undergoing DSMPI, assessment of perfusion and function is effective in risk stratification. The stress ECG and heart rate response to dobutamine have prognostic value and should be incorporated into image interpretation so as to maximize risk stratification.

The noninvasive differentiation between ischemic and nonischemic cardiomyopathy is frequently difficult. We examined the clinical value of stress electrocardiographic gated (ECG-gated) single-photon emission computed tomography (SPECT) to identify ischemic cardiomyopathy and detect coronary artery disease (CAD) in 164 patients without known CAD, ejection fraction < or =40% by ECG-gated SPECT, and subsequent coronary angiography. Summed stress, rest, and difference scores were measured from the SPECT studies, and regional wall motion variance was calculated from the ECG-gated images. Sensitivity and 95% confidence intervals for the diagnosis of ischemic cardiomyopathy and for detection of any CAD (>50% diameter stenosis) were estimated using previously defined cutoffs for summed stress score and regional wall motion variance. For the diagnosis of ischemic cardiomyopathy, sensitivity of stress SPECT (summed stress score >8) was 87% (95% confidence interval [CI] 78 to 95), with a specificity of 63% (95% CI 60 to 82). The addition of wall motion information (summed stress score >8 or regional wall motion variance >0.114) increased sensitivity to 88% (95% CI 80 to 96) and decreased specificity to 45% (95% CI 35 to 55). If reversibility was also taken into account (summed stress score >8, regional wall motion variance >0.114, or summed difference score >0), sensitivity further increased to 94% (95% CI 88 to 100) and specificity decreased to 32% (95% CI 23 to 41). For detection of any CAD, the combined approach using stress perfusion, reversibility, and region of wall motion had a sensitivity of 94% (95% CI 89 to 99) and a specificity of 45% (95% CI 35 to 57). Therefore, ECG-gated SPECT is very sensitive for detection of ischemic cardiomyopathy and CAD among patients with moderate to severe systolic dysfunction.

Background: The ability of stress radionuclide myocardial perfusion imaging to predict adverse cardiac events is well accepted. As left ventricular systolic function has also been shown to be an important prognostic indicator, the objective of this study was to determine whether electrocardiography (ECG)-gated single photon emission computed tomography (SPECT) functional data add additional power., Methods and Results: In this study 3207 patients who underwent stress myocardial perfusion imaging with ECG gating, without early (

Objectives: The goal of this study was to examine the effect of acute beta-blockade on dipyridamole Tc-99m sestamibi myocardial perfusion imaging (DMPI)., Background: Studies suggest that antianginal drugs may reduce the presence and severity of myocardial perfusion defects with dipyridamole stress. However, there are no data regarding specific drugs., Methods: Patients with catheterization-proven coronary artery disease (CAD) were enrolled in this prospective, double-blind, placebo-controlled study and randomly assigned to DMPI after placebo, low-dose metoprolol (up to 10 mg), and high-dose metoprolol (up to 20 mg). Patients underwent one Tc-99m sestamibi study at rest on a separate day. The interval between DMPI studies was

Objectives: This study was designed to determine how long nuclear myocardial perfusion imaging (MPI) remains abnormal following transient myocardial ischemia., Background: Acute rest MPI identifies myocardial ischemia with a high sensitivity when the radionuclide is injected during chest pain. However, the sensitivity of this technique is uncertain when the radionuclide is injected following the resolution of symptoms., Methods: Forty patients undergoing successful coronary angioplasty were randomized into four equal groups. Tc-99m sestamibi was injected intravenously during the last balloon inflation (acute MPI) in 30 patients and then reinjected 1, 2, or 3 h later (delayed MPI). In a fourth group, the radiopharmaceutical was injected at 15 min following balloon deflation (delayed MPI). A final injection was performed at 24 to 48 h (late MPI) in 37 patients (93%)., Results: A perfusion defect was detected in all 30 acute MPI studies; in 7/10 patients (70%) injected at 15 min; in 11/30 patients (37%) injected at 1, 2, or 3 h; and in 7/37 patients (19%) injected at 24 to 48 h. Perfusion scores were 13.0 +/- 9.2 on acute MPI, 5.1 +/- 2.8 at 15 min (p < 0.001 vs. acute MPI); 2.6 +/- 3.0 at 1, 2, and 3 h (p < 0.001 vs. acute MPI); and 1.3 +/- 2.4 at 24 to 48 h (p < 0.001 vs. acute MPI; p < 0.03 vs. delayed MPI)., Conclusions: Myocardial perfusion imaging may remain abnormal for several hours following transient myocardial ischemia even when normal flow is restored in the epicardial coronary artery.

Background: Stress electrocardiography (ECG)-gated single photon emission computed tomography (SPECT) for assessment of left ventricular perfusion and function improves the confidence of interpretation and enhances specificity for detection of coronary artery disease. The reproducibility of visual interpretation of ECG-gated SPECT images and the significance of training and experience have not been reported previously in a large series of consecutive patients. We evaluated both intraobserver and interobserver agreement of interpretation of ECG-gated SPECT images among 3 cardiology trainees and 3 experienced nuclear cardiologists from 3 institutions., Methods and Results: Three nuclear cardiologists and 3 cardiology trainees who had fulfilled American College of Cardiology/American Society of Nuclear Cardiology Core Cardiology Training Symposium (ACC/ASNC COCATS) guidelines for level II training in nuclear cardiology independently evaluated 106 consecutive technetium 99m sestamibi SPECT images with ECG gating of either the stress or rest images. All cases were interpreted blindly, twice in random sequence, without clinical data. We assessed intraobserver and interobserver agreement for myocardial perfusion, left ventricular regional and global systolic function, and overall clinical impression, by means of percent agreement and Cohen's kappa statistic. Intraobserver agreement was good (82%-92%, kappa = 0.54-0.84) for assessment of myocardial perfusion, systolic function, and overall impression. Interobserver agreement was also good, ranging from 65% to 90% (kappa = 0.32-0.76), with better agreement found for assessment of function (77%-85%, kappa = 0.52-0.7) than for perfusion (65%-80%, kappa = 0.32-0.6). For all measures, there were no significant differences in reproducibility between nuclear cardiologists and cardiology trainees., Conclusions: Interpretation of ECG-gated SPECT images has high reproducibility and agreement among both nuclear cardiologists and cardiology trainees.

Background: Studies on the effect of estrogen on atherosclerotic coronary artery disease (CAD) risk in women have produced conflicting results. Similar confusion, but fewer data, exists on the effect of testosterone on CAD risk in men., Methods: We used 99mTc sestamibi single-photon emission computed tomography (SPECT) myocardial perfusion imaging to examine the acute effect of intravenous testosterone in 32 men (mean age, 69.1 +/- 6.4 years) with provocable myocardial ischemia on standard medical therapy. Patients performed 3 exercise (n = 18) or adenosine (n = 16) stress tests during the infusion of placebo or 2 doses of testosterone designed to increase testosterone 2 or 6 times baseline., Results: Serum testosterone increased 137 +/- 58% and 488 +/- 113%, and estradiol levels increased 27 +/- 46% and 76 +/- 57%, (P <.001 for all) during the 2 testosterone infusions. There were no differences among the placebo or testosterone groups in peak heart rate, systolic blood pressure, maximal rate pressure product, perfusion imaging scores, or the onset of ST-segment depression., Conclusions: Acute testosterone infusion has neither a beneficial nor a deleterious effect on the onset and magnitude of stress-induced myocardial ischemia in men with stable CAD.

Study Objective: To determine the effect of metoprolol on dobutamine stress testing with technetium-99m sestamibi single-photon emission computed tomography imaging and ST-segment monitoring, and to assess the impact of intravenous glucagon on metoprolol's effects., Design: Randomized, double-blind, placebo-controlled trial., Setting: Community hospital., Patients: Twenty-two patients with known reversible perfusion defects., Intervention: Patients underwent dobutamine stress tests per standard protocol. Before dobutamine was begun, no therapy was given during the first visit, and patients were randomized on subsequent visits to receive metoprolol or metoprolol plus glucagon 1 mg. Metoprolol was dosed to achieve a resting predobutamine heart rate below 65 beats/minute or a total intravenous dose of 20 mg., Measurements and Main Results: Metoprolol reduced maximum heart rate 31%, summed stress scores 29%, and summed difference scores 43% versus control. Metoprolol plus glucagon also reduced the maximum heart rate 29% versus control. Summed stress and summed difference scores were not significantly reduced, although they were 18% and 30% lower, respectively, than control. No significant differences were found in any parameter between metoprolol and metoprolol-glucagon., Conclusion: During dobutamine stress testing, metoprolol attenuates or eliminates evidence of myocardial ischemia. Glucagon 1 mg, although somewhat effective, does not correct this effect to the extent that it can be administered clinically.

Previous studies have demonstrated that intravenous testosterone can dilate coronary arteries and increase exercise treadmill time, but the electrocardiographic and hemodynamic effects are unknown. This trial determined the hemodynamic and electrocardiographic effects of dosing intravenous testosterone to achieve a physiologic and a superphysiologic serum testosterone concentration. Twenty men (70.6 +/- 6.2 years) had individualized testosterone bolus and continuous infusions designed to increase the serum testosterone concentration by two (physiologic) and six times baseline (superphysiologic). The men were studied on three occasions when they were randomly allocated to received a placebo, physiologic testosterone regimen, or superphysiologic testosterone regimen. Blood pressures and 12-lead electrocardiograms (ECGs) were taken preinfusion and 28 minutes after initiating the infusion on each visit. The blood pressure (systolic and diastolic) and ECG variables (PR, QRS, QT, QTc, and RR intervals) preinfusion and during the infusion were compared, and the delta changes in the variables were compared between groups. The physiologic testosterone regimen increased the serum testosterone concentration by 2.39 +/- 0.48 times the preinfusion concentration, while the superphysiologic regimen increased it by 6.22 +/- 0.99 times. No significant changes occurred in the blood pressure or ECG variables in any group versus preinfusion values or between the three groups. Exogenously administered intravenous testosterone does not significantly affect the blood pressure or ECG variables when given to achieve physiologic or superphysiologic concentrations.

Limited exercise combined with dipyridamole increases myocardial perfusion defect severity compared with dipyridamole alone. The impact of limited exercise combined with adenosine on myocardial perfusion defect severity is unknown. This study compares myocardial perfusion defect severity with adenosine alone and adenosine combined with limited exercise. Thirty-two patients with coronary artery disease underwent on separate days and in randomized order technetium-99m sestamibi (25 to 30 mCi) single-photon emission computed tomographic imaging at rest, after adenosine (140 microg/kg/min x 6 minutes), and after adenosine (140 microg/kg/min x 4 minutes) during 6 minutes of modified Bruce treadmill exercise (adenosine-exercise). Radiopharmaceutical was injected at 3 and 5 minutes during adenosine and adenosine-exercise, respectively. Images were interpreted by a consensus agreement of 3 nuclear cardiologists without knowledge of patient identity, stress protocol, or clinical data using a 17-segment model and 5-point scoring system. A summed stress score (SSS), summed rest score (SRS), and summed difference (SSS-SRS) score (SDS) were calculated for each image. Peak stress heart rate and rate-pressure product were higher for adenosine-exercise than adenosine (102 +/- 19 vs 81 +/- 11 beats/min and 13,972 +/- 4,265 vs 10,623 +/- 2,131, respectively; both p <0.001). Sensitivity for detection of > or = 50% coronary stenosis was 75% and 72% for adenosine-exercise and adenosine, respectively (p = NS). There were no differences in SSS and SDS between adenosine-exercise and adenosine (8.2 +/- 5.9 vs 8.1 +/- 6.3 and 4.9 +/- 4.1 vs 5.2 +/- 4.6, respectively; both p = NS). Thus, in patients with coronary artery disease, limited treadmill exercise combined with adenosine does not increase myocardial perfusion defect severity compared with standard adenosine technetium-99m sestamibi single-photon emission computed tomographic myocardial perfusion imaging.

Purpose: The purpose of this study was to compare defect extent and severity and myocardial uptake with exercise and pharmacologic stress with technetium-99m (Tc-99m) tetrofosmin tomographic myocardial perfusion imaging., Background: Detection of stress-induced myocardial perfusion defects depends on both a disparity in blood flow between normal and stenotic vessels and the extraction fraction and linearity of myocardial uptake of the tracer. There are limited clinical data for exercise or pharmacologic stress with Tc-99m tetrofosmin tomographic myocardial perfusion imaging., Methods: Thirty-one patients with coronary artery disease and 7 with a < 5% likelihood of coronary artery disease underwent on separate days Tc-99m tetrofosmin single-photon emission computed tomographic imaging at rest and after exercise, dipyridamole, adenosine, and dobutamine stress. Images were interpreted by a blinded consensus of 3 experienced readers with a 17-segment model and 5-point scoring system., Results: Compared with exercise, the summed stress score was smaller with dipyridamole (P < .01), and the reversibility score was smaller with both dipyridamole (P < .01) and dobutamine (P < .05), whereas the number of abnormal and reversible segments was less with both dipyridamole (P < .01 and P < .001, respectively) and dobutamine (both P < .05). No significant differences were found in the summed stress or reversibility scores and the number of abnormal or reversible segments between exercise and adenosine., Conclusions: Compared with exercise, defect extent, severity, and reversibility are less with dipyridamole and dobutamine with Tc-99m tetrofosmin single photon emission computed tomographic imaging.

Background: Observer variability has been shown with interpretation of planar thallium-201 images. The interpretive reproducibility of technetium-99m sestamibi tomographic imaging is unknown. This study evaluated the interpretive reproducibility of interpretable Tc-99m sestamibi tomographic images among nuclear cardiologists with a wide range of training and experience., Methods: Three experienced readers (EX) and 3 less-experienced readers (LEX) interpreted 138 exercise and rest Tc-99m sestamibi tomographic images (101 were abnormal in patients with coronary artery disease [CAD], 37 were normal in patients with <5% likelihood of CAD) twice in random sequence without clinical data. Images of good to excellent quality were randomly selected from a database at 2 nuclear cardiology laboratories. Intraobserver and interobserver agreement for global, left anterior descending (LAD) territory, non-LAD first (normal/abnormal) and second (normal/fixed/reversible) order, and defect extent (normal/single-vessel CAD/multi-vessel CAD) were assessed with percent agreement and Cohen's kappa (kappa) statistic., Results: With regard to intraobserver agreement, first and second order ranged from 87% to 94% and 80% to 90% for global, 82% to 96% and 78% to 95% for LAD, and 88% to 91% and 80% to 90% for non-LAD, respectively. Defect extent ranged from 75% to 90%. There were no differences between EX and LEX for global and non-LAD first and second order, LAD first order, and defect extent. LAD second order was 93% for EX compared with 88% (P = .015) for LEX. With regard to interobserver agreement, first and second order ranged from 73% to 89% and 64% to 85% for global, 73% to 93% and 69% to 91% for LAD, and 76% to 88% and 68% to 84% for non-LAD, respectively. Defect extent ranged from 61% to 82%. Global first and second order ranged from 85% to 87% and 78% to 82% for EX compared with 73% to 84% and 64% to 79% for LEX. LAD first and second order ranged from 89% to 91% and 88% to 89% for EX compared with 73% to 91% and 69% to 70% for LEX. Non-LAD first and second order ranged from 82% to 86% and 76% to 77% for EX compared with 76% to 86% and 68% to 81% for LEX. Defect extent ranged from 69% to 75% for EX compared with 59% to 77% for LEX., Conclusions: There is moderate to excellent interpretive reproducibility with stress Tc-99m sestamibi SPECT imaging among nuclear cardiologists with a wide range of training and experience.

Unlabelled: Iodine-123-labeled idophenylpentadecanoic acid (IPPA) metabolic imaging has been shown to be clinically useful for the identification of myocardial viability in patients with coronary artery disease and left ventricular dysfunction. Imaging is usually performed under fasting conditions since nonfasting conditions may affect myocardial uptake of 123I-IPPA. The purpose of this study was to examine the impact of dietary condition on 123I-IPPA metabolic imaging., Methods: Forty patients with stable coronary artery disease underwent, in randomized order and on separate days, 123I-IPPA SPECT myocardial imaging under fasting and nonfasting conditions. Patients were injected with 123I-IPPA (4-5 mCi) at rest with imaging performed at 4 (initial) and 30 (delay) min. For each image (initial and delay images), 10 segments were analyzed by three experienced observers without knowledge of patient identity or dietary condition using a 5-point grading system (O = no uptake to 4 = normal uptake). A summed global score was obtained for each image by adding the scores for all 10 segments. Image quality was assessed using a 3-point grading system., Results: Visual agreement for normal and abnormal segments between fasting and nonfasting conditions was 82% (kappa = 0.63). There were no significant differences in the summed global scores for both conditions. Image quality was equivalent for both conditions in 65% of cases and superior under the nonfasting condition in 25% of cases., Conclusion: Image quality as well as the presence, location and severity of defects are similar under fasting and nonfasting conditions with 123I-IPPA. Therefore, fasting is not necessary before 123I-IPPA SPECT imaging for the assessment of myocardial viability.

Estradiol USP was extemporaneously compounded for intravenous administration. Eight postmenopausal women were randomized to receive one of four estradiol dosages. Serum estradiol concentrations were determined at frequent intervals after single bolus dosing. The concentration-time profile was stripped and fit, and pharmacokinetic values were generated. Approximate dosage proportionality was seen with area under the curve, the terminal half-life was 27.45+/-5.65 minutes, and volume of distribution was very low (0.082+/-0.015 L/kg). Estradiol was well tolerated by all study participants.