Planar Thallium-201 Research Articles

Abstract 18459: CT-guided Planar Imaging for the Assessment of Right Ventricular Myocardial Perfusion: a Novel, Noninvasive Monitoring Tool for Patients With Pulmonary Hypertension

Introduction: In patients with pulmonary hypertension (PH), right ventricular (RV) dysfunction as a consequence of increased RV pressure may result in RV enlargement and hypertrophy, which also increases the RV myocardial perfusion. Hypothesis: We assessed the hypothesis that RV myocardial perfusion detected by planar thallium-201 (201Tl) imaging is useful for quantitative evaluation for RV dysfunction in PH patients. Method: The study groups included 16 PH patients with chronic thromboembolic pulmonary hypertension (CTEPH) and 24 healthy controls. All subjects underwent myocardial perfusion SPECT/CT. Cardiac CT was used to obtain the optimal angle to differentiate the RV from the left ventricle (LV). Forty minutes after intravenously administration of 111 MBq of 201Tl, planar acquisition from the optimal angle was performed. In the planar image, we measured the total counts of 201Tl in the RV and LV. The relative count of the RV to LV (HR/HL) was calculated as RV myocardial perfusion indicator for this study. Mean pulmonary artery pressure (mPAP) by cardiac catheterization was obtained in all PH patients to estimate the severity. Results: HR/HL was significantly elevated in the PH group compared with control (0.57 ± 0.13 vs. 0.36 ± 0.07, p <0.01). In the PH group, average mPAP was 42.2 ± 8.84mmHg, which was significantly correlated with HR/HL (r=0.70, p<0.01). In 7 patients with CTEPH who underwent pulmonary endarterectomy (PEA), HR/HL significantly decreased after PEA (from 0.57±0.16 to 0.42±0.07, p<0.05). The decrease of HR/HL was significantly associated with the decrease of mPAP after PEA (r=0.78, p<0.05). Conclusion: Relative RV accumulation in CT-guided 201Tl planar imaging by SPECT/CT was associated with the severity of PH in CTEPH patients and decreased after surgical treatment of CTEPH in parallel with the reduction of mPAP. This method may represent a novel, noninvasive monitoring tool for PH patients.

Cost analysis favours SPECT over PET and CTA for evaluation of coronary artery disease: the SPARC study.

There are many ways to perform noninvasive testing in patients with coronary artery disease (CAD), including myocardial perfusion imaging with single-photon emission computed tomography (SPECT), positron-emission tomography (PET), and coronary computed tomography angiography (CTA). Results from series of patients evaluated with single modalities have already been published by many researchers [1–3], but there are few head-to-head comparisons of the outcomes of alternative test strategies [4, 5]. Consequently, the comparative effectiveness of different noninvasive cardiac testing strategies has been difficult to assess. The recently published SPARC registry (Study of Myocardial Perfusion and Coronary Anatomy Imaging Roles in Coronary Artery Disease) in JACC by the group of DiCarli et al. (Stanford, CA, USA) was a multicentre study designed to collect standardised clinical data on patients undergoing CTA, PET, or SPECT [6]. The primary purpose of the SPARC study was to evaluate the economic outcomes of using CTA, PET, or SPECT to evaluate patients with suspected CAD. The authors used an observational registry of 1703 patients: 590 patients underwent CTA, 548 patients had PET and 565 patients SPECT for diagnosis of suspected CAD. Patients were followed for 2 years; documented resource use, medical costs for CAD, and clinical outcomes were assessed. The main findings were that costs were significantly lower for SPECT compared with CTA or PET in the evaluation of suspected CAD. SPECT was economically attractive compared with PET, whereas CTA was associated with higher costs and no significant difference in mortality compared with SPECT. More specifically, the authors observed that patients who underwent coronary CTA and PET experienced higher rates of subsequent invasive coronary arteriography (16 % and 15 %, respectively) as compared with patients who underwent SPECT (7 %). The mean total radiation was significantly higher for CTA (15.1 mSV) compared with SPECT (11.7 mSV), both for the initial tests (13 mSV vs. 11 mSV) and for follow-up tests and procedures (2.1 mSV vs. 0.7 mSV). Exposure from follow-up tests and procedures was higher after PET (2.0 mSV) than after SPECT (0.6 mSV). The findings in favour of SPECT are in line with a decision model by Garber and Solomon [7], who compared exercise treadmill testing, stress echocardiography, planar thallium imaging, SPECT, and PET imaging with a strategy of immediate invasive angiography. They found SPECT to be much more cost-effective than PET for noninvasive diagnosis, and SPECT to be a better option than immediate invasive coronary angiography. In terms of outcomes, Shaw et al. [1] found that patients who underwent initial SPECT with selective cardiac catheterisation had lower costs than patients who underwent routine coronary angiography (END study). In the EMPIRE study by Underwood et al. [2] it was demonstrated that strategies using myocardial perfusion imaging were cheaper and equally effective when compared with strategies that did not use myocardial perfusion imaging, both for the cost of diagnosis and for overall 2-year management costs; the 2-year patient outcome was the same. Sharples et al. [8] randomised 898 patients to SPECT, stress echocardiography, magnetic resonance imaging (MRI), or direct invasive coronary angiography, and found SPECT to be as useful as immediate invasive angiography with similar costs. A limitation of the SPARC study is the fact that MRI was not included in the comparative strategies. In addition, as the study started in 2006, in recent years many technological revolutions have taken place for all imaging modalities indicating that studies such as SPARC should be repeated and extended every 5–10 years [9]. Analysis of the current SPARC registry at least suggests that SPECT is the noninvasive imaging procedure of choice to evaluate patients with suspected CAD in terms of subsequent medical costs. SPECT offered the lowest costs over 2 years of follow-up among patients with suspected CAD. The significantly higher costs among patients undergoing CTA or PET were primarily due to higher rates of subsequent invasive cardiac procedures, because there was little difference in initial costs of testing. To conclude, the use of SPECT myocardial perfusion imaging was associated with lower costs over 2 years of follow-up than the use of CTA or PET, primarily because of fewer subsequent invasive procedures. Consequently, SPECT imaging seems to be the preferred imaging strategy in patients with suspected CAD. The value of SPECT imaging has been underscored by several recent reports [10–13]. However, larger and more definitive studies, such as the ongoing PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial (NCT01174550), are needed to assess the value and cost effectiveness of the various noninvasive imaging strategies.

The ninth annual Mario S. Verani memorial lecture: Testing our tests: The evidence bar is rising. Regulatory considerations in the development of cardiac imaging agents

It is indeed an enormous honor and a privilege to have been invited to present the ninth annual Mario S. Verani memorial lecture. It has been almost 10 years since Mario left us, and it is likely that many here with us today at the American Society of Nuclear Cardiology Annual meeting are not very aware of the major contributions he made to our field. As one of the purposes of this annual lectureship is to honor that body of work, and carry on its legacy, I thought it would be fitting to start with a reminiscence of the mark he made on the field of Nuclear Cardiology. In the contemporary era, many of us are very highly specialized in our clinical and investigative work, even within a subspecialty such as Nuclear Cardiology. In contrast, because Dr. Verani was among those at the forefront of the field of Nuclear Cardiology at its inception, his research touched on an amazingly broad swath of cardiovascular disease, and how the imaging techniques in this nascent modality could potentially benefit our patients. He was interested not only in the development of the techniques themselves, but also in how the imaging modalities within the field could illuminate pathophysiology in a manner that could not have been done before. I learned many lessons from his work. In the area of the ability of perfusion imaging to detect angiographic coronary artery disease (CAD), his were among the first papers to critically evaluate this new technique, examining the performance of planar thallium-201 scintigrams to detect CAD in native vessels, and also the role of this modality in assessing disease in coronary bypass grafts. He published the seminal paper on the role of pharmacologic stress testing with adenosine to detect CAD in patients who were unable to exercise, in 1990. Ten years later, he continued to advance the field of pharmacologic stress testing with very early work on more selective agonism of adenosine A2a receptors to cause coronary arteriolar vasodilatation, recognizing that other adenosine receptor subtypes were predominantly responsible for the common side effects seen during adenosine testing. This work led to continuing development of this class of agents, culminating in the recent approval of regadenoson. As noted above, one of the features of his work that I most admire was how he used these new imaging techniques to study pathophysiology in a way that could not have been done noninvasively before they were developed. In a 1981 paper, he reported on the effect of exercise training on left ventricular function and stress myocardial perfusion, in a tour de force study for the time, using rest and exercise radionuclide angiography and exercise thallium-201 scintigraphy, as well as cardiopulmonary exercise testing, before and after 12 weeks of exercise training. This type of work was well ahead of its time. In the area of assessment of myocardial viability, his work also had important impact. His 1996 paper on the validation of Tc99m-sestamibi for viability involved intraoperative myocardial biopsies of patients with ischemic cardiomyopathy undergoing heart transplantation who had been injected with the tracer on the way in to the operating room. The analysis correlated the histologic findings in the explanted heart with quantitative analysis of tracer uptake from slices of the explanted heart that had been imaged on a gamma camera. The results of this very clever study design validated the use of Tc99m-sestamibi for this purpose, at a time when many were skeptical of that use. Even prior to the approval of the Tc99m-based agents that had minimal redistribution, Dr. Verani took advantage of that property and published a paper that had enormous subsequent impact, on the use of Tc99mhexakis 2-MIBI (now known as sestamibi) for the From the The Division of Cardiology and the CardioVascular Center, Tufts Medical Center, Boston, MA. Reprint requests: James E. Udelson, MD, The Division of Cardiology and the CardioVascular Center, Tufts Medical Center, Box 70, 800 Washington St., Boston, MA 02111; JUdelson@tuftsmedicalcenter. org. J Nucl Cardiol 2011;18:547–60. 1071-3581/$34.00 Copyright 2011 American Society of Nuclear Cardiology. doi:10.1007/s12350-011-9404-x

Digital pulse processing and electronic noise analysis for improving energy resolutions in planar TlBr detectors

Digital pulse processing and electronic noise analysis are proposed for improving energy resolution in planar thallium bromide (TlBr) detectors. An energy resolution of 5.8% FWHM at 662 keV was obtained from a 0.5 mm thick planar TlBr detector at room temperature using a digitizer with a sampling rate of 100 MS/s and 8 bit resolution. The electronic noise in the detector–preamplifier system was measured as a function of pulse shaping time in order to investigate the optimum shaping time for the detector. The depth of interaction (DOI) in TlBr detectors for incident gamma-rays was determined by taking the ratio of pulse heights for fast-shaped to slow-shaped signals. FWHM energy resolution of the detector was improved from 5.8% to 4.2% by implementing depth correction and by using the obtained optimum shaping time.

Advances in quantitative perfusion SPECT imaging

Quantitative software for myocardial perfusion single photon emission computed tomography (SPECT) has advanced significantly over the last 25 years. The strength and availability of quantitative tools for perfusion SPECT have in many ways provided a competitive advantage to nuclear cardiology compared with other higher-resolution noninvasive imaging modalities for the detection of coronary artery disease. The purpose of this report is to review the advances in quantitative diagnostic software for cardiac SPECT over the past 25 years. The time period ending with the 1980s (“the past”) saw the origins of nuclear cardiology with the development of planar thallium 201 imaging and perfusion SPECT imaging without electrocardiographic gating. The period from 1990 to the present saw the development of gated SPECT imaging providing both perfusion and functional information and attenuation correction SPECT with improved perfusion information. The report concludes with a look into the future, where hybrid multimodality imaging systems may provide a comprehensive noninvasive evaluation with previously unmatched accuracy in a single imaging session.

Perioperative and long-term prognostic value of dipyridamole Tc-99m sestamibi myocardial tomography in patients evaluated for elective vascular surgery

Background Patients with peripheral vascular disease are at increased risk for perioperative and long-term cardiac morbidity and mortality. Substantial data exist supporting the use of preoperative clinical risk stratification and planar thallium myocardial scintigraphy. Only limited data are available assessing the role of technetium-99m (Tc-99m) single photon emission computed tomography (SPECT) for preoperative evaluation in this population. Methods and results In our study 153 patients who underwent peripheral vascular surgery were followed up for up to 4 years after preoperative dipyridamole Tc-99m sestamibi SPECT to determine clinical and SPECT predictors of perioperative and long-term adverse cardiac events by multivariate analysis. There were no statistically significant clinical or SPECT predictors of perioperative risk, although no perioperative events occurred in patients with normal scans. Abnormality in the left anterior descending (LAD) territory (risk ratio = 3.1; 95% confidence interval, 1.4-7.1) was the only statistically significant univariate predictor of long-term death or myocardial infarction. Only abnormality in the LAD territory appeared to improve model fit beyond clinical risk (risk ratio = 2.9; 95% confidence interval, 1.2-7.3; P = .02). Conclusions Patients with normal preoperative scans have a low risk of perioperative cardiac events and may safely undergo peripheral vascular surgery without further coronary intervention. However, scan abnormality in the LAD distribution confers poor long-term prognosis, suggesting that patients with this finding before peripheral vascular surgery should receive aggressive medical therapy and possibly invasive intervention to improve long-term survival.

Validation of an algorithm for predicting cardiac events in renal transplant candidates

A 2-tiered noninvasive cardiac risk stratification algorithm was first evaluated in a test population with planar thallium myocardial perfusion imaging and subsequently in a validation population using single-photon emission computed tomographic (SPECT) thallium myocardial perfusion imaging. This study examines if SPECT imaging was as predictive of cardiac death as planar imaging and also if SPECT imaging predicted nonfatal cardiac events in the patient population. Renal transplant candidates were evaluated using a 2-tiered noninvasive cardiac risk stratification algorithm. The first tier of risk assessment utilized 5 variables: age >50 years, insulin-dependent diabetes mellitus, abnormal electrocardiogram, and a history of either angina or congestive heart failure. Patients without risk factors were considered low risk and underwent no further cardiac evaluation. Patients with ≥1 risk factor were considered high risk and underwent a second tier of risk assessment with planar (n = 95) or SPECT (n = 112) imaging. In the test population, 13 of 16 cardiac deaths (81%) occurred in high-risk patients with abnormal planar studies. In the validation group, all cardiac deaths (5 of 60) and nonfatal cardiac events (13 of 60) occurred in high-risk patients with abnormal SPECT studies. SPECT imaging was at least as predictive as planar imaging and also predicted nonfatal as well as fatal cardiac events. Pretransplant risk stratification by clinical variables identified low-risk patients who may not require further cardiac evaluation and high-risk patients with normal SPECT imaging who may not require angiography.

Incidence and significance of ischemic ST-segment depression occurring solely during recovery after exercise testing

Although ischemic ST-segment depression (ST↓) during exercise testing is an accepted finding suggesting the presence of coronary artery disease (CAD), the significance of ST↓ that appears solely during the recovery period is less well defined. There have been only a few studies1–5 addressing this issue. Only 1 study correlated ST↓ in recovery with scintigraphic incidence of ischemia, and that study used planar thallium-201 (Tl-201) imaging.3 Tl-201 imaging usually begins as soon as possible after exercise testing, making it difficult to perform careful postexercise electrocardiographic (ECG) monitoring. Technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) is superior to Tl-201 in this regard because Tc-99m sestamibi does not rapidly redistribute. This yields ample time for poststress ECG monitoring before acquiring postexercise images. Therefore, the purpose of this study was to comprehensively investigate this uncommon ECG response of recovery ST↓ using ECG-gated SPECT Tc-99m sestamibi imaging for determining the incidence of ischemic exercise test responses.

Pharmacological stress testing

Pharmacological stress in conjunction with radionuclide myocardial perfusion imaging has become a widely used noninvasive method of assessing patients with known or suspected coronary artery disease. In the United States, over one third of perfusion imaging studies are performed with pharmacological stress. Pharmacological stress agents fall into two categories: coronary vasodilating agents such as dipyridamole and adenosine, and cardiac positive inotropic agents such as dobutamine and arbutamine. For both, in the presence of coronary artery disease (CAD), perfusion image abnormalities result from heterogeneity of coronary blood flow reserve. Vasodilating agents work directly on the coronary vessels to increase blood flow, whereas inotropic agents work indirectly by increasing myocardial work load, which then leads to an increase in coronary blood flow. Both classes of agents have high accuracies for diagnosing coronary artery disease, and they have excellent safety records with acceptably low occurrences of side effects. For dipyridamole planar thallium imaging, pooled analysis yields a sensitivity of 85% and a specificity of 87% for diagnosis of coronary disease, but there is a large variation in reported values depending on various factors, such as the extent of postcatheterization referral bias, the type of imaging (planar versus single photon emission computed tomography [SPECT]), the types of patients being studied (single versus multivessel disease, men versus women), and the imaging agent used (thallium versus one of the technetium-based agents). Diagnostic accuracies for adenosine are similar to those of dipyridamole, with reported overall sensitivities ranging from 83% to 97%, and specificities ranging from 38% to 94%. For dobutamine, pooled analyses yield a sensitivity of 82% and a specificity of 75%. There is some concern that dobutamine may interfere with uptake of technetium-99m sestamibi, lowering the sensitivity for detection of disease, and thus the vasdodilating agents are generally preferred. Pharmacological stress testing has high clinical use for risk stratifying patients with known or suspected CAD, in patients after myocardial infarction, and in patients needing noncardiac surgery. Vasodilating agents are particularly advantageous in assessing post-myocardial infarction patients, allowing testing as soon as 2 days after the event. Like patients undergoing exercise stress testing, patients with normal perfusion images by pharmacological stress have a <1% annual incidence of cardiac events. The likelihood of an event increases with the extent and severity of perfusion abnormalities. However, it is important to consider clinical variables when using perfusion imaging for risk stratification, particularly in the presurgery patients. As with exercise testing, adjunct markers such as ST segment depression during testing, lung uptake of radiotracer (if thallium is used), and ventricular cavity dilatation add additional prognostic information to that available from the perfusion images alone. The aim of current research is to find better agents that are easier to use and that have fewer side effects. MRE-0470 is an experimental vasodilating agent that is more receptor selective than adenosine and promises a lower incidence of hypotension. Arbutamine more closely simulates exercise than dobutamine, and it can be administered by a closed-loop computerized delivery device. Work is also underway to look at novel uses of pharmacological stress agents, such as acquiring gated SPECT images during dobutamine infusion to enhance detection of myocardial viability. With increasing use of noninvasive testing in elderly patients and in patients with comorbidities that preclude adequate exercise, pharmacological stress testing has become an indispensable tool for radionuclide myocardial perfusion imaging studies. A good understanding of pharmacological stress testing is essential for performing high-quality nuclear cardiology

Cost-effectiveness of alternative test strategies for the diagnosis of coronary artery disease.

The appropriate roles for several diagnostic tests for coronary disease are uncertain. To evaluate the cost-effectiveness of alternative approaches to diagnosis of coronary disease. Meta-analysis of the accuracy of alternative diagnostic tests plus decision analysis to assess the health outcomes and costs of alternative diagnostic strategies for patients at intermediate pretest risk for coronary disease. Studies of test accuracy that met inclusion criteria; published information on treatment effectiveness and disease prevalence. Men and women 45, 55, and 65 years of age with a 25% to 75% pretest risk for coronary disease. 30 years. Societal. Diagnostic strategies were initial angiography and initial testing with one of five noninvasive tests--exercise treadmill testing, planar thallium imaging, single-photon emission computed tomography (SPECT), stress echocardiography, and positron emission tomography (PET)--followed by coronary angiography if noninvasive test results were positive. Testing was followed by observation, medical treatment, or revascularization. Life-years, quality-adjusted life-years (QALYs), costs, and costs per QALY. Life expectancy varied little with the initial diagnostic test; for a 55-year-old man, the best-performing test increased life expectancy by 7 more days than the worst-performing test. More sensitive tests increased QALYs more. Echocardiography improved health outcomes and reduced costs relative to stress testing and planar thallium imaging. The incremental cost-effectiveness ratio was $75,000/QALY for SPECT relative to echocardiography and was greater than $640,000 for PET relative to SPECT. Compared with SPECT, immediate angiography had an incremental cost-effectiveness ratio of $94,000/QALY. Qualitative findings varied little with age, sex, pretest probability of disease, or the test indeterminancy rate. Results varied most with sensitivity to severe coronary disease. Echocardiography, SPECT, and immediate angiography are cost-effective alternatives to PET and other diagnostic approaches. Test selection should reflect local variation in test accuracy.

Interpretive reproducibility of stress Tc-99m sestamibi tomographic myocardial perfusion imaging

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

Ischemia detection in women: The diagnostic value of exercise QRS duration changes

Aim: To compare the diagnostic accuracy of exercise electrocardiographic (ECG) ST-T changes and QRS duration changes as a means of ischemia detection in a female population. Methods and Results: A total of 101 women from a pool of 318 referred for ECG stress testing underwent standard testing using ST-T criteria with the additional measurement of QRS duration before and at peak exercise using a new computerized optic scanner for precise QRS duration measurement. The diagnostic accuracy of the test was determined using planar thallium stress testing as a “gold standard”. For the overall population, the sensitivity of ST-T criteria was 47% with a specificity of 58%. The sensitivity of QRS duration changes was 91% with a specificity of 89%. For Group 1 (age 27–50) the sensitivity of the ST-T criteria was 40% with a specificity of 58%. The sensitivity of the QRS duration changes was 80% with a specificity of 83%. For Group 2 (age 51–83), the sensitivity of the ST-T criteria was 43% with a specificity of 56%. The sensitivity of the QRS duration changes was 94% with a specificity of 90%. Conclusion: In our female population exercise, QRS duration changes using our computerized method were better markers of ischemia than standard ST-T criteria.

Lung uptake of thallium-201: a marker of defect reversibility?

High lung uptake of thallium-201 at stress is reported to be associated with a large number of perfusion defects and poor prognosis. This study was performed to assess whether the reversibility of stress perfusion defects was related to lung uptake. Gated planar thallium scans at stress and at redistribution from 102 consecutive patients with essentially normal left ventricular ejection fraction (using gated blood pool ventriculography) were graded in terms of defect size. Lung and myocardial uptake of thallium were quantitated by region of interest methods relative to the given activity in a previously validated method. There was no significant correlation (non-parametric) between lung uptake and degree of redistribution (). There was a weak but positive correlation between lung uptake and defect size (). Both exercise time and double product showed a negative correlation with lung uptake (e.g. for double product, ). In conclusion, contrary to our expectation, lung uptake is not related to the degree of redistribution. High lung uptake seems to reflect poor cardiovascular reserve.

Predictive Value of Planar 1 8F-Fluorodeoxyglucose Imaging for Cardiac Events in Patients After Acute Myocardial Infarction

This long-term study examines the predictive value of planar myocardial 18F-fluorodeoxyglucose (FDG) imaging for cardiac events after acute myocardial infarction (AMI). From December 1989 to April 1991, 59 consecutive patients with AMI had undergone planar rest thallium-201 (Tl-201)/FDG imaging for viability assessment; 53 (42 men) were included in this study. Mean follow-up was 47 ± 15 months. Cardiac events were defined as cardiac-related death, reinfarction, late revascularization, and unstable angina pectoris. A mismatch pattern was defined as a FDG uptake exceeding Tl-201 uptake by ≥20%. A concordant reduction in flow and metabolism was defined as a match. In the mismatch group (n = 39) were 19 events versus 1 event in the match group (n = 14) (p <0.009). In the mismatch group were 5 cardiac deaths, 3 reinfarctions, 7 late revascularizations, and 4 patients had unstable angina pectoris. There was 1 cardiac death in the match group. The event-free rate estimated using Kaplan Meier curves for patients with and without a mismatch was significantly different (p = 0.018). The relative risk for patients with a mismatch for developing a future cardiac event was estimated at 7.8 versus patients with a match. Thus, planar myocardial FDG imaging shortly after AMI has important prognostic significance for prediction of future cardiac events. Patients with a mismatch shortly after AMI have a high risk for future cardiac events on medical therapy.

Design and Baseline Characteristics of the Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) Trial

Objectives. The Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) trial was designed to compare outcomes of patients with a non–Q wave myocardial infarction (NQMI) who were randomized prospectively to an early “invasive” strategy versus an early “conservative” strategy. The primary objective was to compare early and late outcomes between the two strategies using a combined trial end point (all-cause mortality or nonfatal infarction) during at least 1 year of follow-up.Background. Because of the widely held view that survivors of NQMI are at high risk for subsequent cardiac events, management of these patients has become more aggressive during the last decade. There is a paucity of data from controlled trials to support such an approach, however.Methods. Appropriate patients with a new NQMI were randomized to an early “invasive” strategy (routine coronary angiography followed by myocardial revascularization, if feasible) versus an early “conservative” strategy (noninvasive, predischarge stress testing with planar thallium scintigraphy and radionuclide ventriculography), where the use of coronary angiography and myocardial revascularization was guided by the development of ischemia (clinical course or results of noninvasive tests, or both).Results. A total of 920 patients were randomized (mean follow-up 23 months, range 12 to 44). The mean patient age was 61 ± 10 years; 97% were male; 38% had ST segment depression at study entry; 30% had an anterior NQMI; 54% were hypertensive; 26% had diabetes requiring insulin; 43% were current smokers; 43% had a previous acute myocardial infarction; and 45% had antecedent angina within 3 weeks of the index NQMI.Conclusions. Baseline characteristics were compatible with a moderate to high risk group of patients with an NQMI.

Course of impaired left ventricular function after acute myocardial infarction predicted with planar thallium-201 chloride and F18-fluorodeoxyglucose imaging

Planar rest myocardial thallium-201 chloride ( 201T1)/F18-fluorodeoxyglucose (FDG) imaging has been shown to distinguish between viable and non-viable tissue. Twenty-five patients (60 ± 9 years) with acute myocardial infarction were studied using this technique within 6 ± 2 days (T1) after infarction and again after 42 ± 4 days (T6). Serial assessment of wall motion with 2D-echocardiography was performed to determine the predictive value of radionuclide indices for the course of impaired regional left ventricular function. No revascularization procedure was performed. Segmental 201T1 and FDG uptake was evaluated using circumferential profiles. Echocardiographic wall motion was scored as normal, hypokinetic or akinetic. Myocardial segments were considered non-viable if a match between 201T1 and FDG uptake was present, which is a concordant reduction in 201T1 and FDG uptake (Group A). Myocardial segments were considered viable if: a mismatch was present between 201T1 and FDG uptake which was defined as a segmental FDG uptake exceeding 201T1 uptake by >- 20% in a segment with reduced 201T1 uptake (Group B); a normal FDG uptake (>- 75%) was present without a mismatch pattern in a segment with reduced 201T1 uptake ( 201T1 < 75% of peak activity) (Group C); a normal 201T1 uptake was present in the area of wall motion abnormality (Group D). Corresponding scintigraphic images obtained at T1 and T6 were compared. Results: 51 segments were normokinetic, 37 were hypokinetic and 26 were akinetic at T1. Of the 63 segments with wall motion abnormalities at T1, 18 regions showed a match (FDG- 201T1 < 20%) (Group A). Regional function improved in only one (6%) of these segments. In 19 regions a mismatch was present (FDG- 201T1 >- 20%) (Group B) of which three (16%) showed spontaneous improvement in function ( P = NS vs. matched segments), although recovery varied considerably among patients. Regional function in two segments deteriorated. In 14 regions with reduced 201T1 uptake, FDG uptake was normal (Group C) of which five (36%) were improved after 6 weeks ( p < 0.05 vs. Match; p = NS vs. mismatched segments). Of the 12 segments with normal 201T1 uptake (Group D), seven (58%) showed improvement in function, whereas five (42%) did not show improvement ( p < 0.05 vs. Match). In addition, all scintigraphically selected viable segments were grouped (Group B+C+D) and compared with the non-viable segments (Group A). The predictive value of a positive viability test for spontaneous functional improvement was 33%. The predictive value of a negative viability test for lack of functional improvement was 94%. Conclusions: absence of residual FDG uptake shortly after infarction is associated with irreversible injury, while preservation of metabolic activity identifies segments with variable outcome. Wall motion alone is not a good indicator for the presence of viable tissue. Planar 201T1/FDG imaging allows early identification of viable but jeopardized tissue and may help select patients who will benefit from aggressive therapy to salvage endangered myocardium.

Identification of Viable Myocardium by Nitrate Echocardiography After Myocardial Infarction: Comparison with Planar Thallium Reinjection Scintigraphy

The aim of this study was to validate a new diagnostic tool, nitrate echocardiography (NE), for the identification of viable noncontracting myocardium in patients with a history of prior myocardial infarction (MI). Nitroglycerin (NTG) may be useful for this purpose for its peculiar pharmacodynamic action and may represent an option other than dobutamine echocardiography for the detection of hibernating segments in the presence of severely reduced coronary reserve. Twenty selected patients (pts) with an old MI were studied with NE and planar thallium scintigraphy with reinjection. NE was performed by administering i.v. NTG starting at 0.4 mcg/kg/minute with equal increments every five minutes up to 2 mcg/kg/minute or to early interruption of the test (decrease of systolic blood pressure > or = 20% or improvement of previously akinetic segments). Left ventricular wall motion was analyzed by dividing the left ventricle (LV) into 16 segments, and a wall motion score index (WMSI) was calculated. Thallium images were obtained at peak exercise, at four hours, and after reinjection. Myocardial viability was defined as an improvement in thallium uptake after reinjection in fixed defects. Basal echo demonstrated 74 akinetic segments; of these 21 (28%, 11 pts) showed improved contractility during NTG infusion at a mean dose of 0.87 +/-0.33 mcg/kg/minute. WMSI decreased from 1.69 +/- 0.29 to 1.46 +/- 0.31 (P = .001). The only hemodynamic response was a drop in systolic blood pressure (136 mmHg to 124; P = .02). Thallium studies showed 29 segments with a four-hour reversible defect and 79 segments with a four-hour fixed defect; of the latter, 14 regions demonstrated improvement in tracer uptake after reinjection (17.7%; 10 pts). Nine pts had a positive echo and thallium study, while 8 showed no improvement either during NE or after thallium reinjection. Two pts had a false-positive nitrate echocardiogram. Therefore, according to an echo/thallium study match, sensitivity, specificity, and accuracy are 90%, 80%, 85%, respectively. NE is a reliable and low-cost method for the detection of viable noncontracting myocardium in selected patients with CAD but needs further validation for widespread application.

Is planar thallium-201/fluorine-18 fluorodeoxyglucose imaging a reasonable clinical alternative to positron emission tomographic myocardial viability scanning?

This comparative study was performed to determine whether a conventional planar gamma camera optimised for 511-keV imaging can reliably assess myocardial viability using the fluorine-18 fluorodeoxyglucose (FDG) metabolic tracer previously developed for positron emission tomography (PET). Twenty-seven patients with severe ischaemic cardiomyopathy (mean left ventricular ejection fraction: 20% +/- 9%) having clinically indicated nitrogen-13 ammonia/FDG PET myocardial viability studies consented to resting, four-view, planar myocardial thallium-201 perfusion and FDG metabolism imaging. The resultant PET and planar perfusion/metabolism images (PPI) were independently assessed for FDG defect size and perfusion/metabolism mismatch, using a four-point scale, in each of four vascular regions: apex, circumflex, left anterior and posterior descending coronary artery territories. Of 108 regions, 106 were evaluable (two not assessed by PET). There was complete agreement in 70% of coronary vascular territories, giving an unweighted kappa score of 0.56. Moreover, in 94% of segments agreement was within one grade. Interestingly, six of the seven differences of more than one grade occurred in the circumflex coronary territory, which was also the only region for which planar positron imaging underestimated FDG defect size. Three of four moderate areas of perfusion/metabolism mismatch seen with PET were also seen on PPI. PPI showed three small regions of mismatch not seen on PET, whilst the reverse occurred with one other small region of mismatch. Thus, for this PET protocol, PPI provides very similar information on the extent of regional FDG uptake and occurrence of mismatch.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative studies of monoclonal antibody targeting to disialoganglioside GD2 in human brain tumors.

Iodine-131 3F8, a murine IgG3 monoclonal antibody that targets to GD2-bearing tumors, was administered intravenously to 12 patients with brain tumors. Six patients received 2 mCi (0.74 Bq) of 131I-3F8, five patients 10 mCi (3.7 Bq)/1.73 m2 of 131I-3F8, and one patient 2.6 mCi (0.96 Bq) of 124I-3F8, with no side-effects. Nine of 11 malignant gliomas and the single metastatic melanoma showed antibody localization, with the best tumor delineation on single-photon emission tomography (SPET) following 10 mCi (3.7 Bq)/1.73 m2 dose. No nonspecific uptake in the normal craniospinal axis was detected. There was no difference in the pharmacokinetics of low-dose versus the higher-dose antibody groups; plasma and total-body half-lives were 18 h and 49 h, respectively. Surgical sampling and time-activity curves based on quantitative imaging showed peak uptake in high-grade glioma at 39 h, with a half-life of 62 h. Tumor uptake at time of surgery averaged 3.5 x 10(-3) %ID/g and peak activity by the conjugate view method averaged 9.2 x 10(-3) %ID/g (3.5-17.8). Mean radiation absorption dose was 3.9 rad per mCi injected (range 0.7-9.6) or 10.5 cGy/Bq (range 1.9-26). There was agreement on positive sites when immunoscintigraphy was compared with technetium-99m glucoheptonate/diethylene triamine penta-acetic acid planar imaging, thallium-201 SPET, and fluorine-18 fluorodeoxyglucose positron emission tomography. Taken together, these data suggest that quantitative estimates of antibody targeting to intracranial tumors can be made using the modified conjugate view method.

Clinical value of immediate thallium-201 reinjection imaging for the detection of ischaemic heart disease.

Immediate reinjection of thallium-201 after acquisition of the stress images followed by imaging 60 min later has been proposed as a novel time-saving and patient-convenient approach for the evaluation of myocardial ischaemia and viability. The objective of this study was to establish the clinical value of thallium-201 stress immediate reinjection imaging in the evaluation of patients with suspected and known coronary artery disease. Quantitative planar thallium-201 stress immediate reinjection imaging was performed in 138 patients with undiagnosed chest pain, of whom 114 underwent cardiac catheterization and 24 had a < 5% likelihood for coronary artery disease; 56 patients had previously suffered a myocardial infarction. Sensitivities and accuracies were determined for coronary artery disease, reversible myocardial ischaemia, and myocardial viability. Of the 138 patients studied for coronary artery disease, thallium stress scintigraphy identified 85 of 93 patients with angiographically proven coronary artery lesions (overall sensitivity 91%). The normalcy rate in the low-likelihood patients was 88% (21 of 24 patients) and the overall diagnostic accuracy was 83%. In the 56 patients who had suffered a previous myocardial infarction, and in whom the suitability for reversible ischaemia was sought, the overall patient-related sensitivity and accuracy were 93% and 92% respectively. In the 56 patients with a previous myocardial infarction a total of 168 vessel regions were studied to detect viability. Of the 142 normal or hypokinetic regions, 127 regions were scintigraphically identified as viable (sensitivity 89%). The thallium stress immediate reinjection imaging protocol is an appropriate clinical approach in patients with undiagnosed chest pain. The combined identification of stress-induced ischaemia and viability by thallium stress immediate reinjection imaging provides adequate algorithms allowing optimal management and risk assessment in the individual cardiac patient.