Pericardial complications and postcardiac injury syndrome after cardiovascular implantable electronic device placement : A meta-analysis and systematic review.

BACKGROUND: Postcardiac injury syndrome (PCIS) is an emerging condition including pericarditis with or without pericardial effusion after an injury to cardiac tissue. Data are lacking on its incidence and clinical predictors after cardiovascular implantable electronic device (CIED) placement. We therefore performed this meta-analysis to determine the incidence of PCIS. METHODS: Medline, Embase, and Cochrane CENTRAL databases were searched according to PRISMA guidelines from February 2007 to February 2017 for studies evaluating pericardial complications subsequent to CIED implantation. Primary outcome was the total number of cases of pericarditis, pericardial effusion, and cardiac tamponade documented. RESULTS: Of 2931 references, 22 articles (enrolling 188,944 patients) were included. Pooled estimates from random-effects analysis showed an overall incidence of 5.82 per 1000 patients (95% confidence interval [CI], 4.33-8.17) at 30 days, and 1.60 per 1000 (95% CI: 0.13-3.07) at 1 year. Advanced age and prior coronary artery bypass graft (CABG) surgery were associated with increased rates of pericardial complications. CONCLUSION: Our analysis revealed that CIED implantations are associated with a low incidence (0.6%) of pericardial complications at 30 days. Patients with advanced age and prior CABG are high-risk patients for pericardial complications.

Impact of ischemia and scar on therapeutic benefit of myocardial revascularization.

The question of how to optimally manage coronary artery disease (CAD) has been a challenge for the cardiology community. The results of early, large randomized clinical trials (RCTs) comparing strategies of medical therapy alone versus revascularization plus medical therapy in patients with stable CAD suggested a survival advantage for a revascularization strategy in the setting of more advanced, higher-risk CAD (left main, three-vessel CAD), but a superiority of medical therapy in patients with more limited, relatively lower-risk CAD (one vessel, limited two-vessel CAD). The results of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) and Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trials redefined the management of CAD, supporting the concept that the impact of aggressively applied modern "medical therapy" on patient survival and patient-reported outcomes is not further improved by the addition of percutaneous intervention. On the other hand, RCTs incorporating fractional flow reserve have shown that this physiologic metric can help identify which patients will benefit from a revascularization strategy. This paradigm has been extended to the use of myocardial perfusion imaging-identified ischemia to determine which patients may have enhanced survival with early revascularization versus medical therapy. Although data from a series of observational studies suggest that inducible ischemia on myocardial perfusion scintigraphy can identify revascularization candidates, several studies, including substudies from major RCTs, do not support this idea. Until RCTs comparing revascularization with medical therapy strategies are performed, many questions remain open. The correct thresholds for treatment, the metric to guide treatment, and how revascularization should be performed are as yet undefined.

Long-term outcome of patients with intermediate-risk exercise electrocardiograms who do not have myocardial perfusion defects on radionuclide imaging.

BACKGROUND: The appropriate management of patients with intermediate-risk Duke treadmill scores is not established. The purpose of this study was to determine the long-term risk of subsequent cardiovascular events in patients with an intermediate-risk treadmill score who do not have myocardial perfusion defects on radionuclide imaging. METHODS AND RESULTS: The existing databases of the nuclear cardiology laboratories of 4 academic institutions were searched retrospectively. A total of 4649 patients were identified who had intermediate-risk Duke treadmill scores (-10 to 4), normal or near-normal exercise single photon-emission computed tomographic myocardial perfusion images using either thallium-201 or technetium-99m sestamibi, and no previous coronary revascularization. Follow-up was 95% complete. Cardiovascular survival was 99.8% at 1 year, 99.0% at 5 years, and 98.5% at 7 years. Cardiac survival free of myocardial infarction was similarly high at 96.6% at 7 years. Cardiac survival free of myocardial infarction or revascularization was 87.1% at 7 years. Near-normal scans and cardiac enlargement were independent predictors of time to cardiac death. Seven-year cardiac survival was still high at 97.0% in the 357 patients with near-normal scans and normal cardiac size and somewhat lower, at 89.0%, in the 167 patients with cardiac enlargement. CONCLUSIONS: Patients with an intermediate-risk treadmill score but with normal or near-normal exercise myocardial perfusion images and normal cardiac sizes are at low risk for subsequent cardiac death and can be safely managed medically until their symptoms warrant revascularization. The appropriate management of patients with cardiac enlargement will remain a matter of clinical judgment.

Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease.

BACKGROUND: Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS: Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS: The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

Gender-related differences in clinical management after exercise nuclear testing.

OBJECTIVES: This study sought to determine the rate of referral to cardiac catheterization in men and women early after nuclear testing as a function of the magnitude of myocardial ischemia by radionuclide perfusion imaging. BACKGROUND: Although many previous studies have suggested that gender-related differences are present in the clinical management of coronary artery disease, the presence of such a difference with respect to referral to catheterization after noninvasive testing is disputed. METHODS: We examined 3,211 consecutive patients (1,074 women, 2,137 men) who underwent exercise dual-isotope single-photon emission computed tomography and had follow-up evaluation performed at least 1 year after nuclear testing (mean [+/- SD] follow-up 19 +/- 5 months) for "hard" events (cardiac death and myocardial infarction) and referral to cardiac catheterization or revascularization within 60 days of nuclear testing. Multiple logistic regression analysis was performed to determine the best predictors of referral to catheterization as well as to examine whether gender itself added further information to this model. RESULTS: Although men were referred to catheterization more frequently than women (10.6% vs 7.1%, p < 0.001) early after exercise nuclear testing, there were no differences in the rate of referral to catheterization or revascularization after stratification by the amount of abnormally perfused myocardium detected by the nuclear scan. Both men and women with normal scan results were infrequently referred to subsequent catheterization. In the setting of severe ischemia, women were referred to catheterization more frequently than men. This higher rate appears to be clinically appropriate because women with severely abnormal scan results had a significantly higher event rate than men (17.5% vs. 6.3%, p < 0.0001). This greater risk in women than in men appeared to be underappreciated because the increased rate of hard events in women with severely abnormal scan results was out of proportion to the smaller increase in their rate of referral to cardiac catheterization. Although gender added information to the multivariate model most predictive of referral to catheterization models when nuclear variables were not included, when nuclear variables were considered, the addition of gender added no further significant information. This finding suggests that adjusting for differences in perfusion scan abnormalities by the use of nuclear testing eliminated the apparent gender-related referral bias. CONCLUSIONS: After controlling for differences in perfusion scan abnormalities, no gender-related referral bias to catheterization was present. In the setting of severe ischemia, women had a greater rate referral to catheterization than men. As a function of risk, both men and women were appropriately referred to catheterization at a low rate when the scan result was normal. However, because women with severe perfusion abnormalities had a greater rate of cardiac death and myocardial infarction then men, women in this high risk subgroup were underreferred to catheterization relative to men. This finding points to the need to better identify women at high cardiac risk.

Incremental value of prognostic testing in patients with known or suspected ischemic heart disease: a basis for optimal utilization of exercise technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography.

OBJECTIVES: This study assessed the incremental prognostic implications of normal and equivocal exercise technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) and sought to determine its incremental prognostic value, impact on patient management and cost implications. BACKGROUND: The prognostic implications of Tc-99m sestamibi SPECT are not well defined, and risk stratification using this test has not been explored. METHODS: We studied 1,702 patients referred for exercise Tc-99m sestamibi SPECT who were followed up for a mean (+/- SD) of 20 +/- 5 months. Patients with previous percutaneous transluminal coronary angioplasty or coronary artery bypass surgery were excluded. The SPECT studies were assessed using semiquantitative visual analysis. Cardiac death and myocardial infarction were considered "hard" events, and coronary angioplasty and bypass surgery > 60 days after testing were considered "soft" events. RESULTS: Of the 1,702 patients studied, 1,131 had normal or equivocal scan results. A total of 10 events occurred in this group (1 cardiac death and 1 myocardial infarction [0.2% hard events]; 4 coronary angioplasty and 4 bypass surgery procedures [0.7% soft events]). The rates of hard events and referral to catheterization after SPECT were similarly low in patients with a low (< 0.15), intermediate (0.15 to 0.85) and high (> 0.85) post-exercise treadmill test (ETT) likelihood of coronary artery disease. With respect to scan type, patients with normal, probably normal or equivocal scan results had similarly low hard event rates. In the 571 patients with abnormal scan results, there were 43 hard events (7.5%) and 42 soft events (7.4%) (p < 0.001 vs. 1,131 patients with normal scan results for both). When the complete spectrum of scan responses was considered, SPECT provided incremental prognostic value in all patient subgroups analyzed. However, the nuclear scan was cost-effective only in patients with interpretable exercise ECG responses and an intermediate to high post-ETT likelihood of coronary artery disease and in those with uninterpretable exercise ECG responses and an intermediate to high pre-ETT likelihood of coronary artery disease. CONCLUSIONS: Normal or equivocal exercise Tc-99m sestamibi study results are associated with a benign prognosis, even in patients with a high likelihood of coronary artery disease. Although incremental prognostic value is added by nuclear testing in all patient subgroups, a testing strategy incorporating nuclear testing proved to be cost-effective only in the groups with an intermediate to high likelihood of coronary artery disease before scanning.

Impact of myocardial perfusion single-photon emission computed tomography on referral to catheterization of the very elderly. Is there evidence of gender-related referral bias?

OBJECTIVES: This study sought to assess the impact of myocardial perfusion studies on subsequent management in the very elderly with respect to referral to catheterization or revascularization. BACKGROUND: The very elderly are a rapidly growing segment of the U.S. population, and myocardial perfusion studies are frequently performed in this patient subset for evaluation of coronary artery disease. METHODS: The study utilized 1,006 consecutive patients > or = 80 years old (511 men, 495 women) who underwent stress myocardial perfusion single-photon emission computed tomography (SPECT) using pharmacologic stress (n = 605) or treadmill exercise (n = 401). Referral to catheterization or revascularization within 60 days of the nuclear scan was correlated with clinical and nuclear variables. RESULTS: Catheterization and revascularization were performed in 119 and 77 patients, respectively. Stratification of referral rates showed a low rate in normal and mildly abnormal scan categories and significantly higher rates in patients with severely abnormal scan results irrespective of the presenting symptoms or pretest likelihood of coronary artery disease. Multiple logistic regression analysis of clinical and nuclear variables revealed that extent and severity of reversibility by SPECT and the final scan result were the two most powerful predictors of referral to catheterization and revascularization in men and women (catheterization: chi-square 65 and 78; revascularization: chi-square 37 and 68, respectively). Overall, referral rates to catheterization and revascularization were similar in men and women (catheterization: 13% vs. 11%; revascularization: 8% vs. 8%, respectively). However, women with severely abnormal scan results were more frequently referred to catheterization (28% vs. 18%, p < 0.03) and revascularization (21% vs. 12%, p < 0.01) than men. CONCLUSIONS: In patients > or = 80 years old, myocardial perfusion SPECT had a significant impact on patient management. The apparent discrepancy in referral rates for interventional management in men and women is unexplained but may be appropriate in light of our previous observations that women with severely abnormal scan results are at increased risk for hard cardiac events than are men with severely abnormal scan results.

Comparative prognostic value of automatic quantitative analysis versus semiquantitative visual analysis of exercise myocardial perfusion single-photon emission computed tomography.

OBJECTIVES: The purpose of this study was to determine the prognostic value of automatic quantitative analysis in exercise dual-isotope myocardial perfusion single-photon emission computed tomography (SPECT) and to compare the prognostic value of quantitative analysis to semiquantitative visual SPECT analysis. BACKGROUND: Extent, severity and reversibility of exercise myocardial perfusion defects have been shown to correlate with prognosis. However, most studies examining the prognostic value of SPECT in chronic coronary artery disease (CAD) have been based on visual analysis by experts. METHODS: We studied 1,043 consecutive patients with known or suspected CAD who underwent rest Tl-201/exercise Tc-99m sestamibi dual-isotope myocardial perfusion SPECT and were followed up for at least 1 year (mean 20.0+/-3.7 months). After censoring 59 patients with early coronary artery bypass grafting or percutaneous transluminal coronary angioplasty, <60 days after nuclear testing, the final population consisted of 984 patients (36% women, mean age 63+/-12 years). RESULTS: During the follow-up period, 28 hard events (14 cardiac deaths, 14 nonfatal myocardial infarctions) occurred. Patients with higher defect extent (>10%), severity (>150) and reversibility (>5%) by quantitative SPECT defect analysis, as well as those with an abnormal scan (>2 abnormal segments, summed stress score >4 and summed difference score >2) by semiquantitative visual SPECT analysis, had a significantly higher hard event rate compared to patients with a normal scan (p < 0.001). With both visual and quantitative analyses, hard event rates of approximately 1% with normal scans and 5% with abnormal scans (p > 0.05) were observed over the 20-month follow-up period. A Cox proportional hazards regression model showed that chi-square increased similarly with the addition of quantitative defect extent and visual summed stress score variables after considering both clinical and exercise variables (improvement chi-square = 11 for both, p < 0.0007). There were no significant differences in the areas under receiver operating characteristic curves between quantitative and visual analysis (p > 0.70). Linear regression analysis also indicated that quantitative assessments correlated well with visual semiquantitative assessments. CONCLUSIONS: The findings of this study indicate that automatic quantitative analysis of exercise stress myocardial perfusion SPECT is similar to semiquantitative expert visual analysis for prognostic stratification. These findings may be of particular clinical importance in laboratories with less experienced visual interpreters.

Effective risk stratification using exercise myocardial perfusion SPECT in women: gender-related differences in prognostic nuclear testing.

OBJECTIVES: This study was designed to evaluate the incremental prognostic value over clinical and exercise variables of rest thallium-201/exercise technetium-99m sestamibi single-photon emission computed tomography (SPECT) in women compared with men and to determine whether this test can be used to effectively risk stratify patients of both genders. BACKGROUND: To minimize the previously described gender-related bias in the evaluation of coronary artery disease in women, there is a need to identify a noninvasive testing strategy that is able to accurately and effectively risk stratify women. METHODS: We identified 4,136 consecutive patients (2,742 men, 1,394 women) who underwent dual-isotope SPECT. The incremental value of nuclear testing was determined using both a stepwise Cox proportional hazards model and Kaplan-Meier survival analysis. Receiver operating characteristic curve analysis was performed to determine test discrimination for high risk patients in men and women. RESULTS: The patient population was followed up for 20 +/- 5 months for events (cardiac death or nonfatal myocardial infarction). During this time, 63 myocardial infarctions and 32 cardiac deaths occurred in the men, and 31 myocardial infarctions and 14 cardiac deaths occurred in the women. Nuclear testing significantly stratified both men and women irrespective of their rest electrocardiogram. Cox proportional hazards analysis revealed that nuclear testing added incremental prognostic value in both men and women after inclusion of the most predictive clinical exercise variables (overall chi-square 89 in men vs. 120 in women, p < 0.005). Kaplan-Meier survival analysis demonstrated that nuclear testing further stratified men and women with both intermediate to high and low prescan likelihoods of coronary artery disease (p < 0.005 for all). Receiver operating characteristic curve analysis demonstrated superior discrimination for the nuclear scan results in identifying high risk women than men (area under the curve: 0.84 +/- 0.03 vs 0.71 +/- 0.03 in men, p < 0005). The odds ratio comparing event rates in patients with women than in men, suggesting superior stratification using nuclear testing in women. CONCLUSIONS: Dual-isotope myocardial perfusion imaging yields incremental prognostic value in both men and women. This modality identifies low risk women and men equally well but relatively high risk women more accurately than relatively high risk men and, thus, is able to stratify women more effectively than men.

Identification of severe and extensive coronary artery disease by automatic measurement of transient ischemic dilation of the left ventricle in dual-isotope myocardial perfusion SPECT.

OBJECTIVES: This study sought to assess whether a transient ischemic dilation ratio, determined from automatically derived stress and rest left ventricular volumes during stress technetium-99m (Tc-99m) sestamibi/rest thallium-201 dual-isotope myocardial perfusion single-photon emission computed tomography (SPECT), is useful for the identification of patients with severe and extensive coronary artery disease. BACKGROUND: Transient ischemic dilation of the left ventricle on stress/redistribution thallium-201 scintigraphy has been shown to be a clinically useful marker of severe and extensive coronary artery disease. However, in practice, its assessment is highly subjective. This study automatically assessed the transient ischemic dilation ratio on the basis of a previously described algorithm to estimate three-dimensional ventricular boundaries. METHODS: Normal limits for the transient ischemic dilation ratio were developed using data from 54 patients with a low likelihood (< 5%) of coronary artery disease, and criteria for abnormality were developed based on data from 97 who under-went catheterization, of whom 34 had severe and extensive coronary artery disease, defined as > or = 90% stenosis in the proximal left anterior descending coronary artery or in two or more coronary arteries, and 63 had no coronary artery disease (15 patients) or mild to moderate coronary artery disease (48 patients). The criteria were then tested in a validation cohort of 77 additional patients who underwent catheterization, of whom 36 had severe and extensive coronary artery disease. The quantitative results of the dilation ratio were compared with the visual results of the dilation ratio and perfusion defect analysis. RESULTS: For normal limits, receiver operating characteristic curve analysis showed that abnormal transient ischemic dilation ratio values corresponded to left ventricular endocardial volume ratios > 1.22 (mean +/- 2 SD). Transient ischemic dilation assessment using these criteria for abnormality showed high sensitivity (24 [71%] of 34) and very high specificity (60 [95%] of 63) for severe and extensive coronary artery disease. When the analysis was applied to the prospective catheterization group, similar sensitivity and specificity for severe and extensive coronary artery disease were observed (77% and 92%, respectively). Significant agreement (p = 0.0001) was found between the degree of transient ischemic dilation and the Tc-99m sestamibi defect extent, the latter assessed by semiquantitative visual analysis (summed stress score). CONCLUSIONS: The automatic measurement of transient ischemic dilation in dual-isotope myocardial perfusion SPECT is a clinically useful marker that is sensitive and highly specific for detection of severe and extensive coronary artery disease.

The economic consequences of available diagnostic and prognostic strategies for the evaluation of stable angina patients: an observational assessment of the value of precatheterization ischemia. Economics of Noninvasive Diagnosis (END) Multicenter Study Group.

OBJECTIVES: The study aim was to determine observational differences in costs of care by the coronary disease diagnostic test modality. BACKGROUND: A number of diagnostic strategies are available with few data to compare the cost implications of the initial test choice. METHODS: We prospectively enrolled 11,372 consecutive stable angina patients who were referred for stress myocardial perfusion tomography or cardiac catheterization. Stress imaging patients were matched by their pretest clinical risk of coronary disease to a series of patients referred to cardiac catheterization. Composite 3-year costs of care were compared for two patients management strategies: 1) direct cardiac catheterization (aggressive) and 2) initial stress myocardial perfusion tomography and selective catheterization of high risk patients (conservative). Analysis of variance techniques were used to compare costs, adjusting for treatment propensity and pretest risk. RESULTS: Observational comparisons of aggressive as compared with conservative testing strategies reveal that costs of care were higher for direct cardiac catheterization in all clinical risk subsets (range: $2,878 to $4,579), as compared with stress myocardial perfusion imaging plus selective catheterization (range: $2,387 to $3,010, p < 0.0001). Coronary revascularization rates were higher for low, intermediate and high risk direct catheterization patients as compared with the initial stress perfusion imaging cohort (13% to 50%, p < 0.0001); cardiac death or myocardial infarction rates were similar (p > 0.20). CONCLUSIONS: Observational assessments reveal that stable chest pain patients who undergo a more aggressive diagnostic strategy have higher diagnostic costs and greater rates of intervention and follow-up costs. Cost differences may reflect a diminished necessity for resource consumption for patients with normal test results.

The noninvasive prediction of cardiac mortality in men and women with known or suspected coronary artery disease. Economics of Noninvasive Diagnosis (END) Study Group.

PURPOSE: The association between myocardial perfusion imaging defects and cardiac mortality in women is undefined. We examined whether myocardial perfusion imaging predicted cardiac mortality in men and women and compared this with other variables influencing prognosis. SUBJECTS AND METHODS: Six academic institutions with high-volume nuclear cardiology laboratories consecutively studied 5,009 men aged 62 +/- 12 years (mean ISD) and 3,402 women aged 66 +/- 11 years with symptomatic known or suspected coronary artery disease undergoing exercise (n = 7,486) or pharmacologic stress (n = 925) myocardial perfusion imaging. A pretest clinical risk index was calculated from age, history of myocardial infarction, diabetes, hypertension, and hypercholesterolemia. Myocardial perfusion images were analyzed for stress-induced defects or any defect in the territories of the three major coronary arteries. RESULTS: Stress-induced perfusion defects were seen in 39% of men and 25% of women (P = 0.0001). Extensive stress-induced or fixed defects (>2 vascular territories) were less common in women than men (10% vs 19%, and 4% vs 18%, both P = 0.0001). During a mean of 2.4 +/- 1.5 years of follow-up, 143 patients died of cardiac causes. The clinical risk index and number of territories with perfusion defects were associated with cardiac mortality in women and men. In women undergoing exercise myocardial perfusion imaging, the number of abnormal territories remained the strongest correlate of mortality after adjustment for exercise variables. CONCLUSIONS: The results of myocardial perfusion imaging are important, independent predictors of survival in both women and men.

Automatic reorientation of three-dimensional, transaxial myocardial perfusion SPECT images.

UNLABELLED: We developed a completely automatic technique to reorient transaxial images into short-axis (oblique) myocardial perfusion SPECT images. METHODS: The algorithm starts by isolating (segmenting) the left ventricle (LV) myocardium using a combination of iterative clusterification and rule-based location/size/shape criteria. The three-dimensional, mid-myocardial LV surface is initially estimated as the locus of the trilinearly interpolated maxima for the count profiles originating from the center of mass of the segmented LV. The final mid-myocardial surface is obtained by iteratively applying this process, incorporating additional constraints of shape and texture and using the nonsegmented, nonthresholded transaxial image to obtain information on hypoperfused areas of the myocardium. It is then fitted to an ellipsoid, of which the major axis is assumed to represent the long axis of the LV, and the three-dimensional image volume is resliced perpendicularly to it. RESULTS: The algorithm was retrospectively applied to 400 dual-isotope studies (200 rest 201TI, 200 stress 99mTc-sestamibi) from 200 consecutive patients. Segmentation was successful in 394/400 (98.5%) of the patients. The reproducibility of computer-based reorientation was perfect and significantly better than either intraobserver or interobserver reproducibility. CONCLUSION: Automatic reorientation offers the potential for consistently faster and more accurate image processing and analysis and is an important step towards totally operator-less management of myocardial perfusion SPECT data.

Evidence-based risk assessment in noninvasive imaging.

UNLABELLED: Assessment of important clinical and economic outcomes has become central to the evaluation of patient care. Outcome research is deeply rooted in epidemiology, including the use of multivariable, risk-adjusted regression analysis. In our current health care environment, these methods are increasingly being used to assess the quality of care and to profile physicians and laboratories. Nuclear medicine physicians therefore need to better understand outcome methodologies in order to evaluate patient outcomes, develop guidelines, and decide on patient management. METHODS: This review describes the methods of assessing the diagnostic and prognostic value of nuclear medicine techniques and, briefly, the methodologic limitations of sample size, frequency and type of events, and follow-up periods and the incremental value of imaging. Also described are logistic regression and Cox proportional hazards modeling. Models for risk assessment are designed to identify whether patients require conservative (i.e., low-risk) or aggressive (i.e., high-risk) treatment. Treatment selection is currently based on risk assessment and the formation of an integrated, empiric risk stratification algorithm of care. This review also includes the methods of assessing economic effectiveness and quality-of-life issues for patients examined with nuclear medicine techniques. CONCLUSION: In this era of constrained resources, low-cost outpatient-based care may be of increasing importance. High-quality evidence of the clinical and economic outcome of nuclear imaging is essential for helping health care providers and payers assess its value.

Does the presence and site of myocardial ischemia on perfusion scintigraphy predict the occurrence and site of future myocardial infarction in patients with stable coronary artery disease?

In 47 patients who had undergone myocardial scintigraphy, reversible perfusion abnormality was detected in only 28 segments (60%) that were the site of future acute myocardial infarction.

Identification of severe or extensive coronary artery disease in women by adenosine technetium-99m sestamibi SPECT.

To assess the ability of adenosine technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography (SPECT) to identify high-risk women with severe or extensive coronary artery disease (CAD), we studied 130 consecutive women who underwent adenosine sestamibi myocardial perfusion SPECT and catheterization within 2 months. Severe (> or = 50% stenosis of left main coronary artery, > or = 90% stenosis in the proximal left anterior descending or in > or = 2 coronary arteries) or extensive (> or = 70% stenosis in 3 vessels) CAD was present in 54 patients, whereas 76 had no CAD or mild to moderate CAD. Semiquantitative visual SPECT analysis used 20 segments and a 5-point scoring system (0 = normal, 4 = absent uptake). Among the clinical, hemodynamic and nuclear variables analyzed, univariate predictors of severe or extensive CAD included a higher prescan likelihood of CAD, history of myocardial infarction, a higher heart rate at rest, a lower increase in heart rate during adenosine infusion, a higher summed stress score, summed reversibility score, and multivessel scan abnormality. Multivariate logistic analysis of the most predictive clinical (prescan likelihood of CAD), hemodynamic (increase in heart rate during adenosine infusion), and scan variables (summed stress score) revealed summed stress score (chi-square = 32; p <0.0001) and prescan likelihood of CAD (chi-square = 6.4; p <0.05) as the only independent predictors of severe or extensive CAD. Based on these logistic models, we determined the probability for the presence of severe or extensive CAD in patients with low, intermediate, and high prescan likelihood of CAD across the range of values of a summed stress score. This revealed that there were incremental increases in the probability for severe or extensive CAD both as a function of prescan likelihood of CAD and summed stress score. A severely abnormal scan (summed stress score > 8) during adenosine technetium-99m sestamibi myocardial perfusion SPECT had a high sensitivity of 91% and a moderately high specificity of 70% for identifying high-risk women with severe or extensive CAD. These results coupled with the previously defined prognostic significance of these findings suggest this test to be a useful diagnostic tool for the evaluation of CAD in women.

Risk stratification in coronary artery disease: implications for stabilization and prevention.

Noninvasive nuclear imaging techniques, including dual-isotope myocardial perfusion single-photon emission computed tomography (SPECT), have been employed in the development of strategies for diagnosis and risk stratification of patients with suspected or known coronary artery disease. These risk-stratification strategies are based on studies in which known outcome has been linked to diagnostic and prognostic information provided by myocardial perfusion SPECT. This article describes a validated dual-isotope exercise protocol for assessment of perfusion and function and reviews the evidence on which a cost-effective risk management strategy is based.

Incremental prognostic value of adenosine stress myocardial perfusion single-photon emission computed tomography and impact on subsequent management in patients with or suspected of having myocardial ischemia.

We examined 1,159 consecutive patients who underwent adenosine stress dual isotope single-photon emission computed tomography (SPECT) and had follow-up performed at a mean of 27.5 +/- 9.1 months (94% complete) for hard events (cardiac death and myocardial infarction) and referral to cardiac catheterization after nuclear testing. During follow-up, 120 hard events occurred (11.0% hard event rate; 72 cardiac deaths [6.7% cardiac death rate] and 57 myocardial infarctions [5.3% myocardial infarction rate]). Cox proportional hazards analysis revealed that nuclear testing added incremental value after adjusting for clinical and historical variables (global chi-square increased 13 to 98 for cardiac death as the end point, global chi-square increased 19 to 105 for hard events as the end point; p <0.0001 for both). Kaplan-Meier analysis demonstrated that after clinical risk stratification of the patient population, the results of nuclear testing were further able to significantly stratify both low- and intermediate- to high-risk patients. Patients with both normal and mildly abnormal scans were at low risk of cardiac death (<1% cardiac death per year of follow-up) and the risk of events increased significantly with worsening scan result. Multivariable analysis revealed that the only predictor of referral to catheterization was the extent and severity of reversible defect present on the scan. Referral rates to early catheterization were very low in patients with normal scans and increased significantly as a function of worsening scan results. In patients who underwent myocardial perfusion SPECT using adenosine stress, the results of nuclear testing yielded incremental prognostic information and clinically relevant risk stratification. Referring physicians predominantly utilized nuclear information when referring patients to catheterization after nuclear testing and do so at rates comparable with those after exercise SPECT despite the higher risk of events in patients undergoing pharmacologic stress.

Incremental prognostic value of adenosine myocardial perfusion single-photon emission computed tomography in women with suspected coronary artery disease.

Adenosine myocardial perfusion single-photon emission computed tomography (SPECT) is now increasingly used for risk stratification of patients with known or suspected coronary artery disease. However, the incremental prognostic value of this test over clinical and historical information in a large series of women has not been examined. Thus, we studied 923 consecutive women who underwent adenosine technetium (Tc)-99m sestamibi myocardial perfusion SPECT and were followed-up for a mean period of 26+/-8 months. During the follow-up period, 77 hard events (46 cardiac deaths and 31 nonfatal myocardial infarctions) occurred. The results of the perfusion scan significantly risk stratified the population; patients with normal scans had a low rate of nonfatal myocardial infarction and cardiac death (< 1%/year of follow up). Patients with mildly abnormal scans had low cardiac death rates (0.9%/year of follow up); these rates increased as a function of scan abnormality (4.1% and 7.5% mortality per year of follow up in moderate and severely abnormal scans). Cox proportional hazards analysis demonstrated that after adjusting for prior myocardial infarction and diabetes mellitus (the most predictive individual clinical variables [global chi-square=22.5, p <0.001]), as well as heart rate at rest (the most predictive physiologic variable [chi-square=3.8; p=0.05]), the most predictive nuclear variable (summed stress score [chi-square=48.5; p <0.0001]) added significant incremental prognostic information (global chi-square increased from 22.5 to 56.2 [p <0.0001]). In conclusion, adenosine myocardial perfusion SPECT added significant incremental prognostic information to clinical and physiologic variables in women. Normal scans were associated with an excellent prognosis. In contrast, patients with moderately to severely abnormal scans were at a higher risk for future cardiac events.

Noninvasive strategies for the estimation of cardiac risk in stable chest pain patients. The Economics of Noninvasive Diagnosis (END) Study Group.

Effective allocation of medical resources in stable chest pain patients requires the accurate diagnosis of coronary artery disease and the stratification of future cardiac risk. We studied the relative predictive value for cardiac death of 3 commonly applied noninvasive strategies, clinical assessment, stress electrocardiography, and myocardial perfusion tomography, in a large, multicenter population of stable angina patients. The multicenter observational series comprised 7 community and academic medical centers and 8,411 stable chest pain patients. All patients underwent pretest clinical screening followed by stress (exercise 84% or pharmacologic 16%) electrocardiography and myocardial perfusion tomography. Risk-adjusted multivariable Cox proportional hazards models were developed to predict cardiac death. Kaplan-Meier rates of time to cardiac catheterization were also computed. Cardiac mortality was 3% during the 2.5 +/- 1.5 years of follow-up. The number of infarcted vascular territories and pretest clinical risk factors were strong predictors of cardiac mortality, whereas the number of ischemic vascular territories gained increasing importance when determining post-test resource use requirements (i.e., the decision to perform cardiac catheterization). Exertional ST-segment depression in a population with a high frequency of electrocardiographic abnormalities at rest was not a significant differentiator of cardiac death risk. Stable chest pain patients are accurately identified as being at high risk for near-term cardiac events by both physicians' screening clinical evaluation and by the results of stress myocardial perfusion imaging. Disease management strategies for stable chest pain patients aimed at risk reduction should incorporate knowledge of relevant end points in treatment and guideline development.