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Objectives . Theophylline has been shown to delay the onset of myocardial ischemia and to prolong exercise duration. The present study was done to evaluate the mechanisms and actions of intravenous theophylline on the onset of ischemia and exercise duration. Background . The ischemic threshold may be altered by the differential coronary vasodilation induced by endogenous adenosine. Theophylline is a competitive receptor antagonist of adenosine and may have a potential as an anti-ischemic medication. Methods . A double-blind, placebo-controlled crossover trial using an infusion of intravenous theophylline (8.0 ± 2.0 mg/liter) or placebo before exercise in 12 patients was done. Oxygen uptake, heart rate, blood pressure and heart rate-blood pressure product were determined at the onset of ≥0.1-mV ST segment depression and angina pectoris, as well as at peak exercise. The extent of myocardial ischemia was evaluated by electrocardio graphic criteria and quantitation of thallium-201 images at peak exercise. Results . When compared with placebo, theophylline significantly delayed time to the onset of exercise-induced ischemia. Ischemia occurred at a higher heart rate-blood pressure product and oxygen uptake. Exercise duration was prolonged but was not associated with greater ischemia, as determined by oxygen uptake, ST segment depression, angina pectoris and size of thallium-201 defect. Conclusions . It is concluded that theophylline favorably alters myocardial ischemia not only by delaying its onset but also by enabling it to occur at a higher threshold without causing deleterious effects during exercise. The mechanism for the increased ischemic threshold may be through the inhibition of adenosine and the coronary steal phenomenon.

To compare exercise tolerance testing (ETT) with gated single photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI) risk stratification in women with an intermediate to high CAD pretest risk and known estrogen status (ES).SPECT-MPI is an effective test for risk stratifying patients with stable angina. However in women, the current guidelines recommend the exercise tolerance testing (ETT) as first line test. Further, the relationship of stress imaging to ES, an independent risk indicator for CAD, is unknown.2,194 women with an intermediate to high CAD pre-test risk were referred for a clinically indicated ETT with gated SPECT-MPI. Duke treadmill scores (DTS) and summed stress score (SSS) were calculated. SSS were classified as normal (SSS 3), mildly abnormal (SSS 4-8), or moderate-severely abnormal (SSS 8). The ES was assessed as premenopausal, postmenopausal on hormone replacement therapy (HRT) as ES+ while postmenopausal not on HRT were ES-. An annualized cardiac event rate of a composite of cardiac death, unstable angina (UA) leading to hospitalization, non-fatal myocardial infarction, or late coronary revascularization was calculated for all the groups.The annualized cardiac event rate was 1.3% PPY, 2.1% PPY, and 3.2% PPY for low, intermediate, and high risk DTS (P = .2). Patients with intermediate DTS and mildly abnormal or moderate-severely abnormal gated SPECT-MPI had a significantly higher cardiac event rates (5.3% PPY and 10.8% PPY, respectively) than those with a normal gated SPECT-MPI (1.2%, PPY, P = .01). This was also demonstrated on further Cox-regression analysis. Risk stratification of SPECT-MPI over DTS was independent of ES.Gated SPECT-MPI provides risk stratification beyond standard exercise stress testing for women with suspected coronary artery disease, especially in patients with intermediate DTS and is independent of ES.

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. 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

Context Coronary artery disease (CAD) is the major cause of mortality and morbidity in patients with type 2 diabetes. But the utility of screening patients with type 2 diabetes for asymptomatic CAD is controversial. Objective To assess whether routine screening for CAD identifies patients with type 2 diabetes as being at high cardiac risk and whether it affects their cardiac outcomes. Design, Setting, and Patients The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study is a randomized controlled trial in which 1123 participants with type 2 diabetes and no symptoms of CAD were randomly assigned to be screened with adenosine-stress radionuclide myocardial perfusion imaging (MPI) or not to be screened. Participants were recruited from diabetes clinics and practices and prospectively followed up from August 2000 to September 2007. Main Outcome Measure Cardiac death or nonfatal myocardial infarction (MI). Results The cumulative cardiac event rate was 2.9% over a mean (SD) follow-up of 4.8 (0.9) years for an average of 0.6% per year. Seven nonfatal MIs and 8 cardiac deaths (2.7%) occurred among the screened group and 10 nonfatal MIs and 7 cardiac deaths (3.0%) among the not-screened group (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.44-1.88; P = .73). Of those in the screened group, 409 participants with normal results and 50 with small MPI defects had lower event rates than the 33 with moderate or large MPI defects; 0.4% per year vs 2.4% per year (HR, 6.3; 95% CI, 1.9-20.1; P = .001). Nevertheless, the positive predictive value of having moderate or large MPI defects was only 12%. The overall rate of coronary revascularization was low in both groups: 31 (5.5%) in the screened group and 44 (7.8%) in the unscreened group (HR, 0.71; 95% CI, 0.45-1.1; P = .14). During the course of study there was a significant and equivalent increase in primary medical prevention in both groups. Conclusion In this contemporary study population of patients with diabetes, the cardiac event rates were low and were not significantly reduced by MPI screening for myocardial ischemia over 4.8 years. Trial Registration clinicaltrials.gov Identifier: NCT00769275

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.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.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.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% (p0.001), negative predictive value from 62% to 83% (p0.001), and positive predictive value from 41% to 58% (p0.001), whereas specificity was unchanged (61% to 62%, p=NS).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).

Cardiovascular imaging has gained an important role in the evaluation of patients with either known or suspected coronary artery disease. The choices have expanded, imaging procedures have improved. Currently, testing procedures include echocardiography, magnetic resonance imaging, cardiac CTA, cardiac catheterization, and nuclear myocardial perfusion imaging with either single photon emission computed tomography (SPECT) or positron emission tomography (PET). Each of these imaging modalities has its strengths and weaknesses. However, SPECT myocardial perfusion imaging has emerged as a reliable and widely available tool for physicians to use in the assessment of their patient for the exclusion or presence and severity of CAD. Recently, cardiac PET has emerged as an alternative to SPECT imaging. Cardiac positron emission tomography (PET) imaging has gained considerable support and use in the field of cardiovascular imaging over the past several years. For example, delivery of the most accessible PET tracer, Rubidium-82 (RB-82) has quadrupled; the use of myocardial viability studies has increased, and the value of cardiac PET perfusion imaging is now being recognized. This recent increase in activity and interest has been spearheaded by several factors, such as availability of the camera technology, advances in cardiac PET acquisition and perfusion procedures, improved display procedures and software, as well as literature supporting the diagnostic and prognostic accuracy of PET perfusion imaging. This review will highlight cardiac PET as presented in a recent symposium with regards to differences between SPECT imaging and PET, literature supporting cardiac PET for both diagnostic accuracy and risk stratification, and features of cardiac PET/CT that differentiate it from SPECT. The review includes recent literature advances.

It is generally accepted that angina pectoris and, presumably, myocardial ischemia occur at a fixed heart rate-systolic blood pressure product in a given patient. This concept of a fixed threshold has recently been challenged. To evaluate the effects of varying exercise intensity on the ischemic threshold, 33 patients with coronary artery disease and provokable myocardial ischemia, documented by thallium-201 myocardial perfusion imaging, underwent two exercise tests 2 to 7 days apart. A symptom-limited incremental treadmill exercise test was followed by a 20 min submaximal treadmill test at an intensity approximating 70% of the peak heart rate attained during the incremental test. During the incremental exercise test, angina pectoris developed in 16 patients and 17 patients were asymptomatic. At least 0.1 mV of ST segment depression developed in all subjects during the incremental exercise test at a mean exercise duration of 5.3 ± 2.6 min, a rate-pressure product of 19,130 ± 5,735 and oxygen uptake of 19.6 ± 7.0 ml/kg per min. During the submaximal exercise test, 28 (85%) of the 33 patients had significant ST segment depression. Of these patients, 24 (86%) were asymptomatic, including 10 patients who had previously reported anginal symptoms during the incremental test. The average time to onset of 0.1 mV ST segment depression during the submaximal test was 8.1 ± 4.5 min. These changes occurred at a rate-pressure product of 15,250 ± 3,705 and an oxygen uptake of 14.3 ± 5.9 ml/kg per min, and were significantly (p These results demonstrate that myocardial ischemia, whether or not accompanied by angina pectoris, can occur at a lower rate-pressure product and oxygen uptake during submaximal, steady state exercise compared with symptom-limited incremental exercise. It may be concluded that the ischemic threshold varies under different exercise conditions.

To determine the prevalence of septal defects in a generalized referral population, the records of 93 consecutive patients with complete left bundle branch block (BBB) who underwent symptom-limited treadmill exercise testing with thallium-201 myocardial imaging over a 3-year period were reviewed. Segmental analysis of the planar thallium-201 images was performed in a blinded fashion with agreement by consensus. Computerized quantitative analysis of the images also was independently performed, and was correlated with the visual interpretations. Forty-seven patients (51%) had normal images, and 46 (49%) had defects of greater than or equal to 2 segments. In the abnormal studies, only 13 patients (14% of the total population) had septal defects, while a much higher number of patients, 33 (39%), had inferior or apical defects, or both. Coronary angiography was performed in 6 patients with septal defects: Significant narrowing of the left anterior descending coronary artery was found in 4 patients, a narrowed right coronary artery was found in 1, and normal coronary arteries were seen in the other patient. In conclusion, whereas previous studies have suggested a high percentage of false-positive septal defects in patients with left BBB, this study demonstrates a low prevalence (14%) of septal defects in a large population of unselected patients presenting for exercise thallium-201 imaging. Therefore, exercise thallium-201 imaging remains a useful procedure for evaluating patients with complete left BBB.

On behalf of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Investigators, we wish to thank Drs Joshi, Tarantini, and colleagues for their letters to the editor regarding our article.1 Many excellent comments were made that serve to clarify the COURAGE nuclear substudy. It is important to note that this study was devised to compare treatment effectiveness using nuclear quantification of ischemia as a surrogate outcome. The design of the substudy was based on the prognostic findings from observational registries of tens of thousands of patients undergoing stress myocardial perfusion single photon emission computed tomography (SPECT).2–4 Importantly, no published data were available previously to suggest that significant relative risk reduction would be seen in patients with ischemia reduction. Therefore, this study was not powered to examine differences in prognosis but was designed to determine whether percutaneous coronary intervention (PCI) resulted in a greater reduction of objective ischemia than did optimal medical therapy alone, extending prior, small series that found serial changes in …

Despite growing recognition of attenuation correction (AC) utilizing an external radiation source, prognostic studies using AC are lacking.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.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, and8 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-SSS8 was the most powerful predictor of cardiac events followed by AC-SSS 1-8, history of CAD, age75 and pharmacologic stress.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.

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. 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. 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

The accreditation of laboratories performing noninvasive cardiac procedures is now routinely available and often required by insurance companies. In this article, the history of the accreditation for cardiac procedures is reviewed, the process explained, and the number of accredited laboratories listed. Decision pathways are listed, and common reasons for a laboratory being delayed in approval are described specific for the various modalities. Some of the common compliments and concerns received by the Intersocietal Accreditation Commission are described.

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. 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

Background— Extent and severity of myocardial ischemia are determinants of risk for patients with coronary artery disease, and ischemia reduction is an important therapeutic goal. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) nuclear substudy compared the effectiveness of percutaneous coronary intervention (PCI) for ischemia reduction added to optimal medical therapy (OMT) with the use of myocardial perfusion single photon emission computed tomography (MPS). Methods and Results— Of the 2287 COURAGE patients, 314 were enrolled in this substudy of serial rest/stress MPS performed before treatment and 6 to 18 months (mean=374±50 days) after randomization using paired exercise (n=84) or vasodilator stress (n=230). A blinded core laboratory analyzed quantitative MPS measures of percent ischemic myocardium. Moderate to severe ischemia encumbered ≥10% myocardium. The primary end point was ≥5% reduction in ischemic myocardium at follow-up. Treatment groups had similar baseline characteristics. At follow-up, the reduction in ischemic myocardium was greater with PCI+OMT (−2.7%; 95% confidence interval, −1.7%, −3.8%) than with OMT (−0.5%; 95% confidence interval, −1.6%, 0.6%; P P =0.0004), especially patients with moderate to severe pretreatment ischemia (78% versus 52%; P =0.007). Patients with ischemia reduction had lower unadjusted risk for death or myocardial infarction ( P =0.037 [risk-adjusted P =0.26]), particularly if baseline ischemia was moderate to severe ( P =0.001 [risk-adjusted P =0.08]). Death or myocardial infarction rates ranged from 0% to 39% for patients with no residual ischemia to ≥10% residual ischemia on follow-up MPS ( P =0.002 [risk-adjusted P =0.09]). Conclusions— In COURAGE patients who underwent serial MPS, adding PCI to OMT resulted in greater reduction in ischemia compared with OMT alone. Our findings suggest a treatment target of ≥5% ischemia reduction with OMT with or without coronary revascularization.

Coronary artery disease remains the leading cause of morbidity and mortality in women. The optimal non-invasive test for evaluation of ischemic heart disease in women is unknown. Although current guidelines support the choice of the exercise tolerance test (ETT) as a first line test for women with a normal baseline ECG and adequate exercise capabilities, supportive data for this recommendation are controversial. The what is the optimal method for ischemia evaluation in women? (WOMEN) study was designed to determine the optimal non-invasive strategy for CAD risk detection of intermediate and high risk women presenting with chest pain or equivalent symptoms suggestive of ischemic heart disease. The study will prospectively compare the 2-year event rates in women capable of performing exercise treadmill testing or Tc-99 m tetrofosmin SPECT myocardial perfusion imaging (MPI). The study will enroll women presenting for the evaluation of chest pain or anginal equivalent symptoms who are capable of performing >5 METs of exercise while at intermediate-high pretest risk for ischemic heart disease who will be randomized to either ETT testing alone or with Tc-99 m tetrofosmin SPECT MPI. The null hypothesis for this project is that the exercise ECG has the same negative predictive value for risk detection as gated myocardial perfusion SPECT in women. The primary aim is to compare 2-year cardiac event rates in women randomized to SPECT MPI to those randomized to ETT. The WOMEN study seeks to provide objective information for guidelines for the evaluation of symptomatic women with an intermediate-high likelihood for CAD.

OBJECTIVE—The purpose of this study was to assess whether the prevalence of inducible myocardial ischemia increases over time in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—Participants enrolled in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study underwent repeat adenosine-stress myocardial perfusion imaging 3 years after initial evaluation. Patients with intervening cardiac events or revascularization and those who were unable or unwilling to repeat stress imaging were excluded. RESULTS—Of the initial 522 DIAD patients, 358 had repeat stress imaging (DIAD-2), of whom 71 (20%) had ischemia at enrollment (DIAD-1). Of 287 patients with normal DIAD-1 studies, 259 (90%) remained normal in DIAD-2, whereas 28 (10%) developed new ischemia in DIAD-2. Of the 71 patients with abnormal DIAD-1 studies, 56 (79%) demonstrated resolution of ischemia, whereas 15 (21%) remained abnormal. During this 3-year interval, medical treatment was intensified, with more patients using statins, aspirin, and ACE inhibitors than at baseline. Patients with resolution of ischemia had significantly greater increases in these medications than patients who developed new ischemia (P = 0.04). CONCLUSIONS—Thus, the majority of asymptomatic patients with type 2 diabetes demonstrated resolution of ischemia upon repeat stress imaging after 3 years. This resolution was associated with more intensive treatment of cardiovascular risk factors.

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 (≤60 days) revascularization were censored, leaving 8,767 for analysis. A multivariate analysis demonstrated that abnormal wall motion (SWMS ≥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≥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≥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. Conclusion 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.

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.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).A protocol that combines symptom-limited exercise and dipyridamole stress with gated SPECT imaging provides highly effective risk stratification for adverse outcomes.

Objective: The primary aim of this secondary analysis was to determine whether cardiac autonomic neuropathy independently predicted adverse cardiac outcomes in asymptomatic individuals with type 2 diabetes. Additional aims include the determination of the correlation of standard autonomic testing measures and power spectral analysis of heart rate variability, and the association of diabetes-related and cardiac risk factors with cardiac autonomic neuropathy measures. Methods: Cardiac autonomic neuropathy was assessed at the study entry into the Detection of Ischemia in Asymptomatic Diabetics study, using autonomic heart rate and blood pressure testing, and power spectral analysis of heart rate variability. All participants were prospectively followed for the composite clinical outcome of cardiac death, acute coronary syndromes, heart failure, or coronary revascularization. Results: Over 5 years of follow-up, 94 of 1119 (8.4%) subjects developed symptomatic cardiac disease. In unadjusted bivariate analyses, abnormalities in several cardiac autonomic neuropathy tests, including lower Valsalva and Standing Heart Rate Ratios, higher resting Heart Rate, greater systolic blood pressure decrease on standing, and lower low-frequency power, were predictive of symptomatic disease. Independent predictors of poor cardiac outcome were a lower Valsalva Heart Rate Ratio, non-Black ethnicity, longer diabetes duration, higher glycated hemoglobin (HbA1c), insulin use, reported numbness in the extremities, higher pulse pressure, family history of coronary artery disease, and higher waist-to-hip ratio. Clinical factors independently associated with a lower Valsalva Heart Rate Ratio were insulin use, clinical proteinuria, higher pulse pressure, use of angiotensin-converting enzyme inhibitor and non-Black ethnicity. Conclusion: Cardiac autonomic neuropathy predicted adverse cardiac outcomes in asymptomatic type 2 diabetes without known cardiac disease. Clinical variables may help to identify patients who might have cardiac autonomic neuropathy and warrant consideration for autonomic testing.

In summary, a thorough QA program involves all aspects of image acquisition, processing, and interpretation and is essential to the high-quality practice of nuclear cardiology.

Aims Technological advances in cardiac imaging have led to dramatic increases in test utilization and consumption of a growing proportion of cardiovascular healthcare costs. The opportunity costs of strategies favouring exercise echocardiography or SPECT imaging have been incompletely evaluated. Methods and results We examined prognosis and cost-effectiveness of exercise echocardiography (n ¼ 4884) vs. SPECT (n ¼ 4637) imaging in stable, intermediate risk, chest pain patients. Ischaemia extent was defined as the number of vascular territories with echocardiographic wall motion or SPECT perfusion abnormalities. Cox proportional hazard models were employed to assess time to cardiac death or myocardial infarction (MI). Total cardiovascular costs were summed (discounted and inflation-corrected) throughout follow-up. A cost-effectiveness ratio ,$50 000 per life year saved (LYS) was considered favourable for economic efficiency. The risk-adjusted 3-year death or MI rates classified by extent of ischaemia were similar, ranging from 2.3 to 8.0% for echocardiography and from 3.5 to 11.0% for SPECT (model x 2 ¼ 216; P , 0.0001; interaction P ¼ 0.24). Cost-effectiveness ratios for echocardiography were ,$20 000/LYS when the annual risk of death or MI was ,2%. However, when yearly cardiac event rate were .2%, cost-effectiveness ratios for echocardiography vs. SPECT were in the range of $66 686–$419 522/LYS. For patients with established coronary disease (i.e. � 2% annual event risk), SPECT ischaemia was associated with earlier and greater utilization of coronary revascularization (P , 0.0001) resulting in an incremental cost-effectiveness ratio of $32 381/LYS. Conclusion Health care policies aimed at allocating limited resources can be effectively guided by applying clinical and economic outcomes evidence. A strategy aimed at cost-effective testing would support using echocardiography in low-risk patients with suspected coronary disease, whereas those higher risk patients benefit from referral to SPECT imaging.

PURPOSE OF REVIEW The role of myocardial perfusion imaging in the diagnosis of coronary artery disease in various patient populations has been expanding. Recent literature from March 2004 to February 2005 has advanced the concept of attenuation correction and electrocardiographic gating in improving the diagnosis of coronary artery disease. RECENT DEVELOPMENTS The American Heart Association encourages the use of electrocardiographic-gated single photon emission computerized tomography in women. Asymptomatic diabetic patients may benefit from screening with myocardial perfusion imaging. Dobutamine stress perfusion imaging is an important diagnostic tool in elderly patients who are unable to exercise. In patients with chest pain, acute imaging may decrease unnecessary admissions. Vasodilator stress imaging has high sensitivity and specificity in patients with left bundle branch block. Patients undergoing endovascular stent grafting may benefit from risk stratification with vasodilator myocardial perfusion imaging. The American Society of Nuclear Cardiology and the Society of Nuclear Medicine have recognized the role of attenuation correction in increasing the diagnostic accuracy of myocardial perfusion imaging. Multiple studies emphasize the importance of electrocardiographic gating in myocardial perfusion imaging. SUMMARY Recent developments have resulted in an important statement by the American Heart Association that assigns a larger role for myocardial perfusion imaging in the diagnosis of coronary artery disease in women. The role of myocardial perfusion imaging is also expanding in various other patient populations. The literature has validated the concept of attenuation correction for the accurate assessment of attenuation artifacts as well as electrocardiographic gating in enhancing the diagnosis and risk stratification for coronary artery disease.

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).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.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 scoreor =4 and ejection fraction50%, respectively.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); p0.001. 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).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.

Although pharmacologic stress myocardial perfusion imaging (MPI) and exercise stress MPI have comparable diagnostic accuracy, their comparative value for risk stratification of patients with known or suspected coronary disease is not known. The data of 14,918 patients were combined from 24 studies evaluating prognosis in patients undergoing either pharmacologic stress or exercise stress MPI. Studies were included if a 2 x 2 table for hard cardiac events (cardiac death and myocardial infarction [MI]) could be constructed from the data available. Excluded were studies performed for post-MI, post-revascularization, or preoperative risk stratification. A weighted t test was used to compare the cardiac events, and a random effects model was used to calculate summary odds ratios. Summary odds ratios for hard cardiac events were similar for pharmacologic stress and exercise stress MPI. Summary receiver operating characteristic curves also showed no difference in discriminatory power between the stressors. The cardiac event rates were significantly higher with normal and abnormal test results with pharmacologic stress MPI than with exercise stress MPI (1.78% vs 0.65% [P < .001] for normal results and 9.98% vs 4.3% [P < .001] for abnormal results). Subgroup analysis revealed that both cardiac death and nonfatal MI were significantly higher with pharmacologic stress MPI. Patients undergoing pharmacologic stress MPI had a significantly higher prevalence of poor prognostic factors, and meta-regression revealed that exercise capacity was the single most important predictor of cardiac events. This meta-analysis shows that exercise stress MPI and pharmacologic stress MPI are comparable in their ability to risk-stratify patients. However, patients undergoing pharmacologic stress studies are at a higher risk for subsequent cardiac events. This is true even for those with normal perfusion imaging results.

To assess the prevalence and clinical predictors of silent myocardial ischemia in asymptomatic patients with type 2 diabetes and to test the effectiveness of current American Diabetes Association screening guidelines.In the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study, 1,123 patients with type 2 diabetes, aged 50-75 years, with no known or suspected coronary artery disease, were randomly assigned to either stress testing and 5-year clinical follow-up or to follow-up only. The prevalence of ischemia in 522 patients randomized to stress testing was assessed by adenosine technetium-99m sestamibi single-photon emission-computed tomography myocardial perfusion imaging.A total of 113 patients (22%) had silent ischemia, including 83 with regional myocardial perfusion abnormalities and 30 with normal perfusion but other abnormalities (i.e., adenosine-induced ST-segment depression, ventricular dilation, or rest ventricular dysfunction). Moderate or large perfusion defects were present in 33 patients. The strongest predictors for abnormal tests were abnormal Valsalva (odds ratio [OR] 5.6), male sex (2.5), and diabetes duration (5.2). Other traditional cardiac risk factors or inflammatory and prothrombotic markers were not predictive. Ischemic adenosine-induced ST-segment depression with normal perfusion (n = 21) was associated with women (OR 3.4). Selecting only patients who met American Diabetes Association guidelines would have failed to identify 41% of patients with silent ischemia.Silent myocardial ischemia occurs in greater than one in five asymptomatic patients with type 2 diabetes. Traditional and emerging cardiac risk factors were not associated with abnormal stress tests, although cardiac autonomic dysfunction was a strong predictor of ischemia.

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.In this study 3207 patients who underwent stress myocardial perfusion imaging with ECG gating, without early (/=60 days) revascularization, were studied. Subsequent nonfatal myocardial infarction and cardiac death were related to perfusion and ECG-gated SPECT ventricular function parameters. Cox proportional hazards regression analysis was used to evaluate the independent predictive value of these parameters, as well as their added utility over clinical and ECG parameters. Patients with abnormal perfusion images had an annual event rate of 5.1% compared with 1.6% for patients with normal images (P.001). An abnormal gated SPECT wall motion score was associated with an annual event rate of 6.1% compared with 1.6% for a normal score (P.001), and an abnormal left ventricular ejection fraction was associated with an event rate of 7.4% compared with 1.8% for normal patients (P.001). Abnormal ECG-gated SPECT results worsened outcome in both patients with normal perfusion images and those with abnormal perfusion images. Cardiac death was predicted by the number of territories with a perfusion defect and an abnormal ejection fraction, whereas myocardial infarction was predicted by the number of territories with a perfusion defect but not by ejection fraction.Ventricular function data from ECG-gated SPECT add important prognostic value to data obtained from perfusion imaging alone in predicting adverse cardiac events.

Background— Dipyridamole and adenosine cause frequent side effects as a result of nonspecific adenosine receptor stimulation. Selective agonism of the adenosine A 2A receptor should result in a similar degree of coronary vasodilation (and thus similar perfusion images) with fewer side effects. Methods and Results— In a multicenter, randomized, single-blind, 2-arm crossover trial, 240 patients underwent 2 single photon emission computed tomographic (SPECT) imaging studies in random order, first after pharmacological stress with adenosine and a second study with the selective adenosine A 2A receptor agonist binodenoson, using 1 of 4 dosing regimens. Safety, tolerability, and SPECT image concordance between the 2 agents were examined. Exact categorical agreement in the extent and severity of reversible perfusion defects ranged from 79% to 87%, with kappa values from 0.69 to 0.85, indicating very good to excellent agreement between binodenoson and adenosine. The risk of any safety event/side effect was significantly lower with any dose of binodenoson than with adenosine ( P ≤0.01) because of a dose-related reduction in subjective side effects, as objective events were infrequent. There was a reduction in the severity of chest pain, dyspnea, and flushing in all binodenoson doses compared with adenosine ( P Conclusions— The selective adenosine A 2A receptor agonist binodenoson results in an extent and severity of reversible perfusion defects on SPECT imaging similar to nonselective adenosine receptor stimulation, accompanied by a dose-related reduction in the incidence and severity of side effects.

Coronary artery revascularization and medical intervention have become powerful therapies in the management of ischemic heart disease. Although coronary angiography forms the basis for much of our existing therapies for patients with known coronary artery disease (CAD), its cost and invasive nature preclude its routine and frequent use in the evaluation of all patients. Furthermore, angiography provides predominantly anatomic assessments and does not standardly assess the physiologic significance of an individual coronary stenosis. Nuclear stress imaging, with its ability to provide information about the physiologic significance of stenoses and risk stratification of CAD patients, is ideally suited to provide supplementary information to assess patients after intervention.1–3

Given the limitations of low enrollments, this study suggests that a change of 130% for B-type natiuretic peptide (BNP) and 90% for N-terminal (NT)-proBNP are necessary before results of serially collected data can be considered statistically different. This study also shows that there are important differences in the performance of BNP versus NT-proBNP in monitoring patients with congestive heart failure that need to be further explored.

Failure to achieve an adequate heart rate limits the sensitivity of exercise myocardial perfusion imaging (MPI) for the detection of coronary artery disease. In addition, it is often not possible to discontinue medications that may blunt the heart rate response to exercise, because of conditions such as hypertension or angina. However, if pharmacologic stress testing is performed, the ability to assess functional capacity is lost. Accordingly, we developed a protocol that incorporates adenosine stress with symptom-limited exercise.As part of a multicenter study, 35 patients were enrolled prospectively and underwent both exercise MPI and exercise MPI with a 4-minute adenosine infusion on a separate day. Technetium 99m sestamibi was injected at or near peak exercise (exercise only) and at 2 minutes into the adenosine infusion (combined exercise and adenosine). The perfusion images were interpreted in a blinded fashion. The combined adenosine and exercise protocol was well tolerated. The summed stress scores and summed difference scores were greater in the exercise-plus-adenosine group than in the exercise-only group (10.0 vs 8.5, P =.02, and 4.9 vs 3.3, P =.002, respectively). Exercise time was slightly but significantly less with the exercise-plus-adenosine protocol (8 minutes 46 seconds vs 8 minutes 11 seconds, P =.027).A protocol combining 4 minutes of adenosine infusion with symptom-limited exercise was safe and well tolerated. Furthermore, this protocol resulted in a greater amount of myocardial ischemia detected on MPI while allowing for the assessment of functional capacity. A combined exercise and adenosine protocol may be a useful test for patients undergoing MPI who are unlikely to achieve an adequate chronotropic response.

Pharmacologic stress testing with myocardial perfusion imaging has enabled patients who cannot complete adequate exercise to undergo diagnostic and prognostic evaluation for coronary artery disease. Pharmacologic stress agents belong to two groups: vasodilators (such as adenosine and dipyridamole), and inotropes (such as dobutamine). All have similar sensitivity (89%-91%) and specificity (78%-86%) for the diagnosis of coronary disease. For risk stratification, the risk of future cardiac events is related to the extent and severity of perfusion abnormalities. Pharmacologic stress testing permits risk stratification as early as 1 to 4 days following an acute myocardial infarction, and is superior to exercise stress testing in this regard. Similarly, it identifies patients at high risk for perioperative cardiac events prior to noncardiac surgery. This review summarizes the current evidence available regarding the diagnostic and prognostic use of pharmacologic stress testing.

ContextObservational studies of acute myocardial perfusion imaging in emergency department (ED) patients with chest pain have suggested high sensitivity and negative predictive value for acute cardiac ischemia, but use of this method has not been prospectively tested.ObjectiveTo assess whether incorporating acute resting perfusion imaging into an ED evaluation strategy for patients with suspected acute ischemia but no initial electrocardiogram (ECG) changes diagnostic of acute ischemia improves clinical decision making for initial ED triage.Design, Setting, and PatientsProspective, randomized controlled trial conducted at 7 academic medical centers and community hospitals between July 1997 and May 1999 among 2475 adult ED patients with chest pain or other symptoms suggestive of acute cardiac ischemia and with normal or nondiagnostic initial ECG results.InterventionPatients were randomly assigned to receive either the usual ED evaluation strategy (n = 1260) or the usual strategy supplemented with results from acute resting myocardial perfusion imaging using single-photon emission computed tomography with injection of 20 to 30 mCi of Tc-99m sestamibi (n = 1215), interpreted in real time by local staff physicians and with results provided to the ED physician for incorporation into clinical decision making.Main Outcome MeasureAppropriateness of triage decision either to admit to hospital/observation or to discharge directly home from the ED.ResultsAmong patients with acute cardiac ischemia (ie, acute myocardial infarction [MI] or unstable angina; n = 329), there were no differences in ED triage decisions between those receiving standard evaluation and those whose evaluation was supplemented by a sestamibi scan. Among patients with acute MI (n = 56), 97% vs 96% were hospitalized (relative risk [RR], 1.00; 95% confidence interval [CI], 0.89-1.12), and among those with unstable angina (n = 273), 83% vs 81% were hospitalized (RR, 0.98; 95% CI, 0.87-1.10). However, among patients without acute cardiac ischemia (n = 2146), hospitalization was 52% with usual care vs 42% with sestamibi imaging (RR, 0.84; 95% CI, 0.77-0.92).ConclusionsSestamibi perfusion imaging improves ED triage decision making for patients with symptoms suggestive of acute cardiac ischemia without obvious abnormalities on initial ECG. In this study, unnecessary hospitalizations were reduced among patients without acute ischemia, without reducing appropriate admission for patients with acute ischemia.

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

In their recently published paper, Monaco et al. ([1][1]) examined the efficacy of 2 different strategies for pre-operative risk stratification in patients requiring vascular surgery. The selective strategy used noninvasive testing for ischemia followed by angiography in patients identified as