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Objectives: The aim of this study was to assess the performance of beta-methyl-p-[123I]-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) to detect acute coronary syndromes (ACS) in emergency department patients with chest pain., Background: Emergency department diagnosis of chest pain is problematic, often requiring prolonged observation and stress testing. BMIPP SPECT detects abnormalities in fatty acid metabolism resulting from myocardial ischemia, even many hours after symptom cessation., Methods: Emergency department patients with suspected ACS were enrolled at 50 centers. Patients received 5 mCi BMIPP within 30 h of symptom cessation. BMIPP SPECT images were interpreted semiquantitatively by 3 blinded readers. Initial clinical diagnosis was based on symptoms, initial electrocardiograms, and troponin, whereas the final diagnosis was based on all available data (including angiography and stress SPECT) but not BMIPP SPECT. Final diagnoses were adjudicated by a blinded committee as ACS, intermediate likelihood of ACS, or negative for ACS., Results: A total of 507 patients were studied and efficacy was evaluated in 448 patients with sufficient data. The sensitivity of BMIPP by 3 blinded readers for a final diagnosis of ACS and intermediate likelihood of ACS was 71% (95% confidence interval [CI]: 64% to 79%), 74% (95% CI: 68% to 81%), and 69% (95% CI: 62% to 77%); the corresponding specificity of BMIPP was 67% (95% CI: 61% to 73%), 54% (95% CI: 48% to 60%), and 70% (95% CI: 64% to 76%). Compared with the initial diagnosis alone, BMIPP+initial diagnosis increased sensitivity from 43% to 81% (p<0.001), negative predictive value from 62% to 83% (p<0.001), and positive predictive value from 41% to 58% (p<0.001), whereas specificity was unchanged (61% to 62%, p=NS)., Conclusions: The addition of BMIPP data to the initially available clinical information adds incremental value toward the early diagnosis of an ACS, potentially allowing determination of the presence or absence of ACS to be made earlier in the evaluation process. (Safety and Efficacy Iodofiltic Acid I 123 in the Treatment of Acute Coronary Syndrome [Zeus-ACS]; NCT00514501)., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to determine whether single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is an effective method of risk stratification for sudden cardiac death (SCD) in patients with coronary artery disease (CAD) and left ventricular ejection fraction (LVEF)>35%., Background: Most victims of SCD have an LVEF>35%., Methods: The study population included 4,865 patients with CAD and LVEF>35% who underwent gated SPECT MPI. We used Cox proportional hazard modeling to examine the relationship between patient characteristics and SCD., Results: The median age of the population was 63 years (25th, 75th percentile: 54, 71 years), and the median LVEF was 56% (25th, 75th percentile: 50%, 64%). The median follow-up for all patients was 6.5 years (25th, 75th percentile: 3.6, 9.3 years). During follow-up, there were 161 SCDs (3.3%). After multivariable adjustment, LVEF, the Charlson index, hypertension, smoking, antiarrhythmic drug therapy, and the summed stress score (SSS) were associated with SCD (all p<0.05). For each 3-U increase in the SSS, the hazard ratio for SCD was 1.13 (95% confidence interval: 1.04 to 1.23). The addition of perfusion data to the clinical history and LVEF was associated with increased discrimination for SCD events (c-index 0.728). Risk stratification with a derived SPECT nomogram did not result in statistically significant net reclassification improvement (p=0.26) or integrated discrimination improvement (p=0.38)., Conclusions: Among patients with CAD and LVEF>35%, the extent of stress MPI perfusion defects is associated with an increased risk of SCD. Future large prospective studies should address the role of perfusion imaging in the identification of high-risk patients with LVEF>35% who might benefit from ICD implantation., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Vasodilator stress myocardial perfusion imaging (MPI) accounts for up to 50% of all stress MPI studies performed in the U.S. In 2008, the Food and Drug Administration approved regadenoson for stress testing in conjunction with MPI. Regadenoson, unlike adenosine, is a selective A(2A) agonist that is given as an intravenous bolus at a fixed dose, with less undesirable side effects including atrioventricular block and bronchospasm. Unlike adenosine, regadenoson could be used in patients with mild-to-moderate reactive airway disease. This review will summarize the pre-clinical and clinical data on regadenoson, as they specifically relate to its use as a vasodilator stress agent, currently the only approved selective A(2A) agonist.

Chronic kidney disease (CKD) affects approximately 13% of the U.S. population and is associated with increased risk of cardiovascular complications. Once renal replacement therapy became available, it became apparent that the mode of death of patients with advanced CKD was more likely than not related to cardiovascular compromise. Further observation revealed that such compromise was related to myocardial disease (related to hypertension, stiff vessels, coronary heart disease, or uremic toxins). Early on, the excess of cardiovascular events was attributed to accelerated atherosclerosis, inadequate control of blood pressure, lipids, or inflammatory cytokines, or perhaps poor glycemia control. In more recent times, outcome research has given us further information that relates even lesser degrees of renal compromise to an excess of cardiovascular events in the general population and in those with already present atherosclerotic disease. As renal function deteriorates, certain physiologic changes occur (perhaps due to hemodynamic, inflammatory, or metabolic changes) that decrease oxygen-carrying capacity of the blood by virtue of anemia, make blood vessels stiffer by altering collagen or through medial calcinosis, raise the blood pressure, increase shearing stresses, or alter the constituents of atherosclerotic plaque or the balance of thrombogenesis and thrombolysis. At further levels of renal dysfunction, tangible metabolic perturbations are recognized as requiring specific therapy to reduce complications (such as for anemia and hyperparathyroidism), although outcome research to support some of our current guidelines is sorely lacking. Understanding the process by which renal dysfunction alters the prognosis of cardiac disease might lead to further methods of treatment. This review will outline the relationship of CKD to coronary heart disease with respect to the current understanding of the traditional and nontraditional risk factors, the role of various imaging modalities, and the impact of coronary revascularization on outcome.

Antianginal and lipid-lowering medications may modify the results of stress myocardial perfusion imaging. Several studies have shown the beneficial potential of these agents in suppressing myocardial ischemia in patients with known coronary artery disease. The effects of nitrates, calcium-channel blockers, beta-blockers, and statins on myocardial perfusion imaging are likely attributable to changes in myocardial blood flow and myocardial oxygen supply-demand ratio. This comprehensive review examines relevant experimental and clinical published data. Technical issues in image interpretation specific to myocardial perfusion imaging and implications of use of cardiac medications to results of myocardial perfusion imaging are discussed.

Cardiovascular imaging has enjoyed both rapid technological advances and sustained growth, yet less attention has been focused on quality than in other areas of cardiovascular medicine. To address this deficit, representatives from cardiovascular imaging societies, private payers, government agencies, the medical imaging industry, and experts in quality measurement met, and this report provides an overview of the discussions. A consensus definition of quality in imaging and a convergence of opinion on quality measures across imaging modalities was achieved and are intended to be the start of a process culminating in the development, dissemination, and adoption of quality measures for all cardiovascular imaging modalities.

Objectives: The purpose of this research was to study the effect of one cup of coffee taken 1 h before adenosine stress on the results of myocardial perfusion imaging., Background: Caffeine is believed to attenuate the coronary hyperemic response to adenosine by competitive blockade of the A2a receptor. Caffeine is commonly withheld before adenosine single-photon emission computed tomography (SPECT) perfusion imaging so as not to mask ischemia detection., Methods: We studied the effect of one 8-oz cup of coffee taken 1 h before adenosine stress in patients who had demonstrable reversible defects on adenosine SPECT perfusion imaging performed while off caffeine., Results: There were 22 men and 8 women, age 64 +/- 9 years. The blood level of caffeine 1 h after intake was 3.1 +/- 1.6 mg/l. There were two patients with ST-segment depression before and one after caffeine intake (p = NS). The summed stress score (SSS) based on 17 segments (scale of 0 to 3, 3 being normal) was 44 +/- 5 before and 45 +/- 5 after caffeine (p = NS). The summed difference score was 3.8 +/- 1.9 before and. 3.9 +/- 2.3 after caffeine (p = NS), reflecting that around 50% of the perfusion abnormality was reversible before and after caffeine. Using polar maps, the perfusion abnormality was 12 +/- 10% at baseline and 12 +/- 10% after caffeine (p = NS) in agreement with SSS. The left ventricular ejection fraction by gated SPECT was 50 +/- 13% at baseline and 51 +/- 13 % after caffeine (p = NS)., Conclusions: A cup of coffee does not mask the presence or severity of reversible defects induced by adenosine SPECT imaging.

Objectives: Regadenoson, a selective A2A adenosine receptor agonist, was evaluated for tolerability and effectiveness as a pharmacological stress agent for detecting reversible myocardial hypoperfusion when combined with single-photon emission computed tomography (SPECT)., Background: Adenosine and dipyridamole are nonselective adenosine agonists currently used as pharmacologic stressors. Despite proven safety, these agents often cause undesirable side effects and require a continuous infusion., Methods: This Phase II, multicenter, open-label trial was conducted in 36 patients who had demonstrated ischemia on a 6-min adenosine SPECT imaging study within the previous 2 to 46 days. Patients received regadenoson as a rapid intravenous bolus dose of 400 microg (n = 18) or 500 microg (n = 18). The radiopharmaceutical was then delivered within one minute. The SPECT images were acquired in a standard manner and uniformly processed at a central laboratory. Regadenoson and adenosine studies were presented in random order and interpreted blindly with a 17-segment model by three observers. Additionally, quantitative analysis was performed with 4D-MSPECT software (University of Michigan, Ann Arbor, Michigan)., Results: Overall agreement for the presence of reversible hypoperfusion was 86%. The 400-mug dose was better tolerated. Overall, regadenoson was well-tolerated; side effects (e.g., chest discomfort, flushing, dyspnea) were generally mild in severity and self-limiting. High-grade atrioventricular block and bronchospasm were not observed., Conclusions: Regadenoson is well-tolerated and seems as effective as adenosine for detecting and quantifying the extent of hypoperfusion observed with SPECT perfusion imaging. Phase III clinical trials are now underway, given the promise of regadenoson's reduced side effects and simplicity of bolus administration.

Under the auspices of the American College of Cardiology Foundation (ACCF) and the American Society of Nuclear Cardiology (ASNC), an appropriateness review was conducted for radionuclide cardiovascular imaging (RNI), specifically gated single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI). The review assessed the risks and benefits of the imaging test for several indications or clinical scenarios and scored them based on a scale of 1 to 9, where the upper range (7 to 9) implies that the test is generally acceptable and is a reasonable approach, and the lower range (1 to 3) implies that the test is generally not acceptable and is not a reasonable approach. The mid range (4 to 6) implies that the test may be generally acceptable and may be a reasonable approach for the indication. The indications for this review were primarily drawn from existing clinical practice guidelines and modified based on discussion by the ACCF Appropriateness Criteria Working Group and the Technical Panel members who rated the indications. The method for this review was based on the RAND/UCLA approach for evaluating appropriateness, which blends scientific evidence and practice experience. A modified Delphi technique was used to obtain first- and second-round ratings of 52 clinical indications. The ratings were done by a Technical Panel with diverse membership, including nuclear cardiologists, referring physicians (including an echocardiographer), health services researchers, and a payer (chief medical officer). These results are expected to have a significant impact on physician decision making and performance, reimbursement policy, and future research directions. Periodic assessment and updating of criteria will be undertaken as needed.

Objectives: The primary objective of this study was to determine whether intracoronary administration of the adenoviral gene for fibroblast growth factor (Ad5FGF-4) can improve myocardial perfusion compared with placebo., Background: Animal studies and observational clinical studies have shown improvement in perfusion of the ischemic myocardium using genes encoding angiogenic growth factors; however, randomized, double-blind data in humans are lacking., Methods: We performed a randomized, double-blind, placebo-controlled trial of intracoronary injection of 10(10) adenoviral particles containing a gene encoding fibroblast growth factor (Ad5FGF-4) to determine the effect on myocardial perfusion. Fifty-two patients with stable angina and reversible ischemia comprising >9% of the left ventricle on adenosine single-photon emission computed tomography (SPECT) imaging were randomized to gene therapy (n = 35) or placebo (n = 17). Clinical follow-up was performed, and 51 (98%) patients underwent a second adenosine SPECT scan after 8 weeks., Results: Overall (n = 52), the mean total perfusion defect size at baseline was 32.4% of the left ventricle, with 20% reversible ischemia and 12.5% scar. At eight weeks, Ad5FGF-4 injection resulted in a significant reduction of ischemic defect size (4.2% absolute, 21% relative; p < 0.001) and placebo-treated patients had no improvement (p = 0.32). Although the change in reversible perfusion defect size between Ad5FGF-4 and placebo was not significant (4.2% vs. 1.6%, p = 0.14), when a single outlier was excluded a significant difference was observed (4.2% vs. 0.8%, p < 0.05). Ad5FGF-4 was well tolerated and did not result in any permanent adverse sequelae., Conclusions: Intracoronary injection of Ad5FGF-4 showed an encouraging trend for improved myocardial perfusion; however, further studies of therapeutic angiogenesis with Ad5FGF-4 will be necessary.

Objectives: We evaluated a novel protocol of dual-isotope, gated single-photon emission computed tomographic (SPECT) imaging combined with low and high dose dobutamine as a single test for the characterization of various types of altered myocardial dysfunction., Background: Myocardial perfusion tomography and echocardiography have been used separately for the assessment of myocardial viability. However, it is possible to assess perfusion, function and contractile reserve using gated SPECT imaging., Methods: We studied 54 patients with ischemic cardiomyopathy using rest and 4 h redistribution thallium-201 imaging and dobutamine technetium-99m sestamibi SPECT imaging. The sestamibi images were acquired 1 h after infusion of the maximal tolerated dose of dobutamine and again during infusion of dobutamine at a low dose to estimate contractile reserve. Myocardial segments were defined as hibernating, stunned, remodeled or scarred., Results: Severe regional dysfunction was present in 584 (54%) of 1,080 segments. Based on the combination of function and perfusion characteristics in these 584 segments, 24% (n = 140) were labeled as hibernating; 23% (n = 136) as stunned; 30% (n = 177) as remodeled; and 22% (n = 131) as scarred. Contractile reserve, represented by improvement in wall motion/thickening by low dose dobutamine, was observed in 83% of stunned, 59% of hibernating, 35% of remodeled and 13% of scarred myocardial segments (p<0.05)., Conclusions: It is possible with this new imaging technique to characterize dysfunctional myocardium as stunned, hibernating, remodeled and nonviable. These subtypes often coexist in the same patient.

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.

Objectives: This review summarizes the results of single-photon emission computed tomographic (SPECT) technetium-99m (Tc-99m) tracer imaging in patients with stable symptoms, patients with acute coronary syndromes, patients undergoing major non-cardiac surgery and patients with chest pain in the emergency department., Background: Previous studies have examined the prognostic value of stress thallium imaging in several subsets of patients with ischemic heart disease. At present, >50% of myocardial perfusion studies are performed with technetium-labeled tracers in the United States. Furthermore, there is a shift from diagnostic to the prognostic utility of stress testing. There are important differences between technetium-labeled tracers and thallium-201. It is therefore important to review the prognostic value of technetium-labeled tracers., Methods: We analyzed published reports in English on risk assessment using Tc-99m perfusion tracers. Results. The largest experience is in patients with stable symptoms, comprising >12,000 patients in 14 studies. In these patients, normal stress SPECT sestamibi images were associated with an average annual hard event rate of 0.6% (death or nonfatal myocardial infarction [MI]). In contrast, patients with abnormal images had a 12-fold higher event rate (7.4% annually). Both fixed and reversible defects are prognostically important, and quantitative analysis shows increased risk in relation to the severity of the abnormality. These results are similar to those obtained with thallium-201., Conclusions: Patients with stable chest pain syndromes and normal stress SPECT sestamibi images have a very low risk of death or nonfatal MI. It is highly unlikely that coronary revascularization can improve survival in such patients. Patients with abnormal images have an intermediate to high risk for future cardiac events, depending on the degree of the abnormality. Further prospective studies comparing aggressive medical therapy with coronary revascularization in these patients are warranted.

Objectives: The purposes of this study were to examine the effects of dipyridamole infusion on hemodynamic variables and to compare these changes with myocardial perfusion., Background: Dipyridamole stress testing with myocardial perfusion imaging is widely used in the assessment of patients with known or suspected coronary artery disease (CAD). Few studies, however, have correlated the hemodynamic effects of dipyridamole using invasive monitoring with perfusion patterns in patients with chest pain syndromes., Methods: Hemodynamic measurements were made in the cardiac catheterization laboratory with a Swan-Ganz thermodilution catheter before, during and after infusion of dipyridamole (142 microg/kg body weight per min for 4 min). Technetium-99m sestamibi was injected 3 min after the completion of the infusion., Results: There were 20 patients with and 6 without CAD, as demonstrated by angiography. Compared with baseline values, dipyridamole resulted in an increase in pulmonary capillary wedge pressure (54 +/- 78% vs. 32 +/- 26%, p = NS), cardiac index (36 +/- 21% vs. 40 +/- 18%, p = NS) and stroke volume index (16 +/- 18% vs. 40 +/- 18%, p = NS) and a decrease in systemic vascular resistance (22 +/- 13% vs. 24 +/- 11%, p = NS), aortic pressure (2 +/- 9% vs. 0 +/- 6%, p = NS) and pulmonary vascular resistance (19 +/- 25% vs. 11 +/- 32%, p = NS) in patients with and without CAD. The peak effect of dipyridamole on heart rate, systemic vascular resistance and pulmonary capillary wedge pressure was evident at 3 min after infusion in 70% of patients. Aminophylline, given to 20 patients, improved hemodynamic variables within 2 min. The single-photon emission computed tomographic sestamibi images were normal in the 6 patients without and abnormal in the 18 patients with CAD., Conclusions: Dipyridamole-induced coronary hyperemia produces mild hemodynamic changes in patients with and without CAD; these changes are at or near peak effect at 3 min after infusion and are rapidly reversed by aminophylline.