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The Council of the Canadian Cardiovascular Society commissioned working groups to examine issues of access to, and wait times for, various aspects of cardiovascular care. The present article summarizes the deliberations on targets for medically acceptable wait times for access to cardiovascular specialist evaluation and on the performance of noninvasive testing needed to complete this evaluation. Three categories of referral indications were identified: those requiring hospitalization due to substantial ongoing risk of mortality and morbidity; those requiring an expedited early review in an ambulatory setting; and, finally, a larger category in which delays of two to six weeks can be justified. The proposed wait time targets will provide guidance on the timeliness of care to busy clinicians charged with the care of patients with cardiovascular disease, help policy makers appreciate the clinical challenges in providing access to high quality care, and highlight the critical need for a thoughtful review of cardiology human resource requirements. Wait time implementation suggestions are also included, such as the innovative use of disease management and special need clinics. The times proposed assume that available clinical practice guidelines are followed for clinical coronary syndrome management and for treatment of associated conditions such as hypertension, diabetes, renal disease, smoking cessation and lipid disorders. Although media attention tends to focus on wait times for higher profile surgical procedures and high technology imaging, it is likely that patients face the greatest wait-related risk at the earlier phases of care, before the disease has been adequately characterized.

Cardiovascular nuclear medicine uses agents labelled with radioisotopes that can be imaged with cameras (single-photon emission tomography [SPECT] or positron emission tomography [PET]) capable of detecting gamma photons to show physiological parameters such as myocardial perfusion, myocardial viability or ventricular function. There is a growing body of literature providing guidelines for the appropriate use of these techniques, but there are little data regarding the appropriate timeframe during which the procedures should be accessed. An expert working group composed of cardiologists and nuclear medicine specialists conducted an Internet search to identify current wait times and recommendations for wait times for a number of cardiac diagnostic tools and procedures, including cardiac catheterization and angioplasty, bypass grafting and vascular surgery. These data were used to estimate appropriate wait times for cardiovascular nuclear medicine procedures. The estimated times were compared with current wait times in each province. Wait time benchmarks were developed for the following: myocardial perfusion with either exercise or pharmacological stress and SPECT or PET imaging; myocardial viability assessment with either fluorodeoxyglucose SPECT or PET imaging, or thallium-201 SPECT imaging; and radionuclide angiography. Emergent, urgent and nonurgent indications were defined for each clinical examination. In each case, appropriate wait time benchmarks were defined as within 24 h for emergent indications, within three days for urgent indications and within 14 days for nonurgent indications. Substantial variability was noted from province to province with respect to access for these procedures. For myocardial perfusion imaging, mean emergent/urgent wait times varied from four to 24 days, and mean nonurgent wait times varied from 15 to 158 days. Only Ontario provided limited access to viability assessment, with fluorodeoxyglucose available in one centre. Mean emergent/urgent wait times for access to viability assessment with thallium-201 SPECT imaging varied from three to eight days, with the exception of Newfoundland, where an emergent/urgent assessment was not available; mean nonurgent wait times varied from seven to 85 days. Finally, for radionuclide angiography, mean emergent/urgent wait times varied from two to 20 days, and nonurgent wait times varied from eight to 36 days. Again, Newfoundland centres were unable to provide emergent/urgent access. The publication of these data and proposed wait times as national targets is a step toward the validation of these recommendations through consultation with clinicians caring for cardiac patients across Canada.

Background: Recent data suggest an early outcome benefit with reduction in cholesterol using statin therapy in patients with coronary artery disease (CAD). This may be caused by effects of low-density lipoprotein cholesterol (LDL-C) reduction on endothelial function and vascular reactivity in the coronary bed. The aim of this randomized placebo-controlled study was to examine the early effects of important reductions in LDL-C on myocardial perfusion and peripheral endothelial function., Methods and Results: Seventy-two patients with CAD and LDL-C between 3.0 and 5.9 mmol/L (116-228 mg/dL) were randomized to receive simvastatin 20 mg daily, pravastatin 40 mg daily, or placebo for 8 weeks. At baseline, 2 weeks, and 8 weeks, patients underwent dynamic positron emission tomography perfusion imaging to quantify the retention of rubidium-82 as a measure of myocardial flow at rest and after dipyridamole stress. Patients also underwent brachial artery ultrasound to measure endothelium-dependent flow-mediated vasodilatation. At 2 and 8 weeks, the simvastatin and pravastatin groups showed a significant reduction (P < .001) in LDL-C compared with placebo. At 8 weeks, simvastatin led to an improvement in flow-mediated vasodilatation compared with placebo (6.86% +/- 4.4% vs 3.44% +/- 4.0%, P < .05), whereas pravastatin was not significantly different than placebo (5.62% +/- 4.1% vs 3.44% +/- 4.0%, P = NS). Despite this improvement in peripheral endothelial function with simvastatin, there were no significant differences observed in global stress flow and coronary flow reserve at 8 weeks with either drug., Conclusions: Short-term LDL reduction with simvastatin therapy improves peripheral endothelial function in patients with stable CAD, although an early effect on coronary vascular reactivity could not be demonstrated.

The incidence of cardiovascular disease is increasing with the aging population. This has stimulated a need for innovative means to evaluate and develop therapeutic strategies intended to improve patient care. Positron emission tomography (PET) imaging is an advanced nuclear imaging technology. The advantage of PET over other non-invasive imaging modalities is its ability to accurately measure tissue concentrations of specific radiolabeled compounds. These radioligands can be used as molecular probes to quantify physiological processes and the effects of therapy. Molecular imaging with PET has been applied to evaluate new and established drugs and therapies, as well as their effects on physiological parameters. New radiolabeled receptor ligands will also allow in vivo pharmacokinetic studies following drug treatment, yielding insights into drug delivery, optimal drug occupancy, and mechanism of action at the receptor level. These exciting tissue pharmacokinetic data could revolutionize evaluation of drug therapies in cardiovascular diseases. In addition, serial evaluations of these processes are now possible in both animals and humans permitting sensitive means to evaluate disease progression and therapies. New tools for imaging such as PET/CT and small animal PET broaden the potential of PET in drug evaluation. This review will describe the accuracy of PET as a non-invasive modality to quantify various parameters, and the application of PET in evaluating new and established therapies. This paper will also review the application of receptor ligand imaging and the principles of using surrogate physiological end-points in early drug development and evaluation.

A (82)Rb infusion system is described with two important features for imaging with 3D positron emission tomography. First, a generator bypass line is added to flush the patient infusion line at the end of an elution. Second, feedback control is implemented to permit 'slow-bolus' constant-activity elutions. A model for the activity eluted from a (82)Sr/(82)Rb generator based on a volume-activity empirical relationship, is used as the basis for performing simulations to demonstrate the efficacy of varying the flow rate through the generator to achieve desired eluted (82)Rb activity rate profiles. A (82)Rb infusion system was constructed to verify the accuracy of the simulations. The system can deliver accurate constant-activity elutions from 10% to 70% of the total generator activity.

A rubidium-82 (/sup 82/Rb) elution system is described for use with clinical positron emission tomography. The system is self-calibrating with 1.4% repeatability, independent of generator activity and elution flow rate. Saline flow is switched between a /sup 82/Sr//sup 82/Rb generator and a bypass line to achieve a constant activity elution of /sup 82/Rb. In the present study, pulse width modulation (PWM) of a solenoid valve is compared to simple threshold control as a means to simulate a proportional valve. A predictive-corrective control algorithm is developed which produces a constant activity elution within the constraints of long feedback delay and short elution time. Accurate constant-activity elutions of 10-70% of the total generator activity were demonstrated using the threshold comparison control. The adaptive-corrective control of the PWM valve provided a substantial improvement in precision of the steady-state output.

Patients with severe ventricular dysfunction and coronary disease have high morbidity and mortality. They may benefit from revascularization but have significant perioperative morbidity and mortality. Positron emission tomography (PET) imaging with F-18-fluorodeoxyglucose (FDG) can detect viable myocardium that may recover from revascularization in such patients. It is unclear whether use of FDG PET in this population improves outcome or is cost-effective. The principal aim of this study is to determine whether FDG PET-guided therapy improves clinical outcome compared to standard care. Secondary objectives are to determine whether FDG PET-guided therapy improves left ventricular (LV) function, improves quality of life, and provides a cost benefit versus standard care. Included in this multicenter randomized controlled trial are patients with coronary artery disease and severe LV dysfunction who are referred for revascularization, heart failure, or cardiac transplantation or in whom FDG PET is potentially useful. Consenting subjects will be randomized to therapy directed by FDG PET or standard care. The primary outcome is the composite cardiovascular endpoint of cardiac death, myocardial infarction, transplantation, or rehospitalization for unstable angina or heart failure. Secondary outcomes include health-related quality of life, costs, mortality, cardiovascular events, and LV function. Assuming two-sided alpha=0.05, power=80%, a sample size of 206 patients per group is required to detect a 15% absolute difference in the primary outcome between PET-directed therapy compared to standard care. Analyses will be conducted on an intention-to-treat basis. To our knowledge, this is the first large trial to evaluate whether FDG PET-directed therapy is effective and provides a cost benefit in patients with severe LV dysfunction. If so, thousands of such patients can be risk-stratified to select who is likely to benefit from revascularization.

Unlabelled: In patients with non-insulin-dependent diabetes mellitus (NIDDM), FDG PET imaging is often problematic because of poor uptake of FDG. Different protocols have been used; however, these have not been directly compared in patients with NIDDM who have both coronary artery disease (CAD) and severe left ventricular (LV) dysfunction, for which defining viability is most relevant. The aim of this study was to better define the optimal means of FDG PET imaging, assessed by image quality and myocardial glucose utilization rate (rMGU), among 3 imaging protocols in patients with NIDDM, CAD, and severe LV dysfunction., Methods: Ten patients with NIDDM, CAD, and severe LV dysfunction (mean ejection fraction, 29.8% +/- 7.1%) underwent dynamic FDG PET scanning using 3 different protocols: the standard protocol, consisting of oral glucose loading or a supplemental insulin bolus based on fasting glucose; the niacin protocol, consisting of pretreatment with niacin to lower free fatty acids; and the insulin clamp protocol, consisting of hyperinsulinemic euglycemic clamp. Image quality was satisfactory with at least 1 approach in 8 patients, who formed the primary analysis group., Results: Myocardium-to-blood-pool ratios were significantly higher with the insulin clamp (standard, 1.7 +/- 1.2; niacin, 1.6 +/- 1.0; insulin clamp, 3.4 +/- 2.5 [P < 0.05 vs. standard and niacin]). Values for rMGU were higher with the insulin clamp (standard, 0.11 +/- 0.07 micromol/g/min; niacin, 0.12 +/- 0.11 micromol/g/min; insulin clamping, 0.22 +/- 0.12 micromol/g/min [P = 0.004 vs. standard and 0.07 vs. niacin])., Conclusion: The hyperinsulinemic euglycemic clamp yielded the highest FDG PET image quality and the highest rMGU in a comparison with the standard and niacin protocols in this difficult group of patients with NIDDM, CAD, and severe LV dysfunction. The hyperinsulinemic euglycemic clamp may be the preferred method for FDG PET viability imaging in this population. Larger clinical trials are needed to assess whether accuracy is greater with this approach.

Objectives: We sought to directly compare primary stenting with accelerated tissue plasminogen activator (t-PA) in patients presenting with acute ST-elevation myocardial infarction (AMI)., Background: Thrombolysis remains the standard therapy for AMI. However, at some institutions primary angioplasty is favored. Randomized trials have shown that primary angioplasty is equal or superior to thrombolysis, while recent studies demonstrate that stent implantation improves the results of primary angioplasty., Methods: Patients presenting with AMI were randomly assigned to primary stenting (n = 62) or accelerated t-PA (n = 61). The primary end point was the composite of death, reinfarction, stroke or repeat target vessel revascularization (TVR) for ischemia at six months., Results: The primary end point was significantly reduced in the stent group compared with the accelerated t-PA group, 24.2% versus 55.7% (p < 0.001). The event rates for other outcomes in the stent group versus the t-PA group were as follows: mortality: 4.8% versus 3.3% (p = 1.00); reinfarction: 6.5% versus 16.4% (p = 0.096); stroke: 1.6% versus 4.9% (p = 0.36); recurrent unstable ischemia: 9.7% versus 26.2% (p = 0.03) and repeat TVR for ischemia: 14.5% versus 49.2% (p < 0.001). The median length of the initial hospitalization was four days in the stent group and seven days in the t-PA group (p < 0.001)., Conclusions: Compared with accelerated t-PA, primary stenting reduces death, reinfarction, stroke or repeat TVR for ischemia. In centers where facilities and experienced interventionists are available, primary stenting offers an attractive alternative to thrombolysis.

Unlabelled: Serial changes in myocardial perfusion may represent an important marker of disease progression or regression or the effects of therapy for patients with coronary artery disease (CAD). Quantitative methods have not been developed for the assessment of serial changes in perfusion. The objective of this study was to use receiver operator characteristic (ROC) analysis to determine the sensitivity and specificity of direct paired comparisons (DPCs) to detect changes in absolute myocardial perfusion measured with 82Rb PET., Methods: Repeated dynamic 82Rb PET scans were obtained on 8 dogs at rest and during hyperemia induced with dobutamine (n = 4) or atrial pacing (n = 4). Radiolabeled microspheres were used to verify perfusion changes. Polar maps of absolute 82Rb retention and associated SD were estimated from the dynamic images. Paired comparisons were then performed using a t test on each of the 532 polar map sectors. Rest-rest and stress-stress differences were used to assess specificity and reproducibility, and stress-rest differences were used to assess sensitivity., Results: 82Rb retention differences of 20% over baseline were detected with 85%-90% sensitivity and specificity, using the optimal DPC probability value and image smoothness. The average 82Rb retention differences correlated well with microspheres (r = 0.74; P = 0.001). Reproducibility of the mean retention values was 4.7% +/- 2.1%. As reproducibility varies, the DPC probability value can be adjusted to maintain specificity. These ROC results are directly applicable to other image modalities that produce measurements with similar SEs (3.7% +/- 0.9%)., Conclusion: The developed method of DPCs is sensitive and specific for the detection of changes in absolute myocardial perfusion measured with 82Rb PET.

Background: Revascularization of occluded coronary arteries after myocardial infarction (MI) may restore flow to viable myocardium and improve ventricular function. The aim of this pilot study was to determine the potential utility of thallium-201 viability imaging for the prediction of recovery of regional ventricular function in patients undergoing revascularization of total or subtotal occlusion of infarct-related arteries (TIMI 0-2 flow) during the convalescent period after MI., Methods: Twenty-three patients were identified < 6 weeks after MI and underwent Tl-201 viability imaging (rest imaging, n = 16; stress/reinjection imaging, n = 7) and radionuclide angiography. Patients were revascularized with percutaneous transluminal coronary artery in 10, stent in 10, and bypass in 3. Follow-up radionuclide angiography at 3 months was used to assess recovery of regional wall motion., Results: Among 41 abnormal wall motion segments in the infarct territories, the sensitivity, specificity, and accuracy for Tl-201 imaging in the prediction of recovery of regional function were 89% (25/28), 54% (7/13), and 78% (32/41), respectively. When 8 segments supplied by vessels with restenosis to >70% were excluded, specificity improved to 70%. Wall motion scores improved in those with adequate revascularization (1.6+/-1.4 vs 2.7+/-1.6; P < .001) but not in those with restenosis or occlusion (1.8+/-1.0 vs 2.0+/-1.6; P = NS)., Conclusions: In patients with an occluded artery after MI, Tl-201 viability imaging can detect recoverable myocardium with reasonable accuracy and may help select which patients will most benefit from revascularization.

Background: The implication of an arrhythmogenic role for infarction-induced disruption of regional myocardial sympathetic nerve activity has led to a search for noninvasive methods to study regional sympathetic nerve activity in patients after infarction., Methods and Results: By using positron emission tomography, we measured the time course of myocardial hypoperfusion with [13N]-ammonia retention and sympathetic innervation with [18F]-6-fluorodopamine within the infarct zone in 10 patients at 2 weeks, 3 months, and 6 months after a first-onset Q-wave myocardial infarction. The time course for reestablishment of global cardiac autonomic function was also determined by measuring the power spectrum of heart rate variability with an autoregressive technique. The average infarct defect size as determined by the fractional uptake of [13N]-ammonia was 17.22% +/- 5.95% of the left ventricular myocardium. The fractional uptake of [18F]-fluorodopamine in the infarct zone was similar, at 15.83% +/- 4.45% (not significant). There was a significant increase (14% to 15%; P <.05) in myocardial blood flow and [18F]-fluorodopamine uptake to the infarct zone between 2 weeks and 3 months, with no further change between 3 months and 6 months. However, the average rate of loss (t1/ 2 hour) of [18F]- fluorodopamine continued to decrease between 2 weeks and 6 months. This paralleled a continuing fall in the low-frequency to high-frequency autospectral power ratio throughout the 6 months after infarction., Conclusions: This study demonstrates a modest increase in myocardial blood flow and evidence for sympathetic reinnervation to the infarct zone between 2 weeks and 3 months after acute myocardial infarction. Despite a flow-dependent effect on the uptake of [18F]-fluorodopamine by 3 months, there is a suggestion that restoration of sympathetic activity within the infarct zone continues between 3 months and 6 months after acute myocardial infarction.

Background: The identification of high-risk patients who require early revascularization has become increasingly important with the present emphasis on reducing health care resources. This is particularly relevant to health care systems with prolonged waiting times for interventions. Myocardial viability imaging with the use of fluorine 18-fluorodeoxyglucose (FDG) PET may help to identify high-risk patients with severe left ventricular dysfunction. The aim of this study was to evaluate the consequences of prolonged waiting time on cardiac outcomes in patients with left ventricular dysfunction directed to revascularization based on FDG PET imaging., Methods and Results: Forty-six patients with coronary disease and an ejection fraction of < or = 35% were considered candidates for revascularization based on FDG PET viability imaging. Thirty-five of 46 patients were subsequently accepted for revascularization. Patients were divided into 2 groups based on the median waiting time after PET: an early group (< 35 days; n = 18) and a late group (> or = 35 days; n = 17). Preoperative mortality rates were significantly increased in the late group (4 of 17 [24%] versus 0 of 18 in the early group; P < 0.05). In postoperative follow-up (17 +/- 7 months), cardiac events occurred in 2 of 18 (11%) and 1 of 13 (7.8%) patients in the early and late groups, respectively. Left ventricular ejection fraction increased after early revascularization (24 +/- 7% to 29 +/- 8%, P < 0.001, baseline versus 3 months) but not in the late group (27 +/- 5% to 28 +/- 6%, P = NS)., Conclusions: Preoperative FDG PET can be used to identify a high-risk group of patients who may benefit from early revascularization. A long waiting time for revascularization is associated with a high mortality rate and suggests that early revascularization is desirable after the identification of hibernating viable myocardium.

Objectives: This study sought to assess the late clinical and angiographic outcomes of patients who received stents within the first week of acute myocardial infarction (AMI)., Background: Recent studies have demonstrated that stenting of the infarct-related artery is a useful adjunct to balloon angioplasty in patients with AMI. However, there are limited data on the late clinical and angiographic outcomes of these patients., Methods: Between January 1994 and September 1995, 32 patients at our institution underwent stenting of the infarct-related artery within 1 week of AMI: 13 within 14 hours (evolving group) and 19 between days 2 and 7 (recent AMI group). Late clinical follow-up was obtained on all survivors. Quantitative angiographic measurements were recorded on the stented segments before stenting, immediately after stenting, and on the follow-up angiograms., Results: At 13.1+/-6.4 months from the time of stenting, three patients died and three required repeat angioplasty, but no patient had reinfarction or required bypass surgery. At follow-up 26 (81%) of 32 patients remained free of major cardiac events; of these, 24 (92%) were free of angina. Repeat angiography performed at 10.8+/-7.5 months in 26 (87%) of 30 discharged patients showed that all infarct-related arteries were patent and the restenosis rate was low: 22% in the 13 patients with evolving AMI (<14 hours) and 12% in the 19 patients with recent AMI (days 2 through 7)., Conclusion: In this study stenting of the infarct-related artery in patients with evolving and recent AMI was associated with a favorable late clinical outcome. Patency of the infarct-related artery was well maintained, and the restenosis rate was low.

Objectives: Regional myocardial blood flow (MBF) and flow reserve measurements using nitrogen-13 (N-13) ammonia positron emission tomography (PET) were compared with quantitative coronary angiography to determine their utility in the detection of significant coronary artery disease (CAD)., Background: Dynamic PET protocols using N-13 ammonia allow regional quantification of MBF and flow reserve. To establish the diagnostic performance of this method, the sensitivity and specificity must be known for varying decision thresholds., Methods: MBF and flow reserve for three coronary territories were determined in 20 normal subjects and 31 patients with angiographically documented CAD by means of dynamic PET and a three-compartment model for N-13 ammonia kinetics. Ten normal subjects defined the normal mean and SD of MBF and flow reserve, and 10 normal subjects were compared with patients. PET flow obtained in the territory with the most severe stenosis in each patient was correlated with the angiographic assessment of the stenosis (severity > or = 50%, > or = 70%, > or = 90%). Receiver operating characteristic (ROC) curve analysis was performed for 1.5, 2.0, 2.5, 3.0 and 4.0 SD of flow abnormalities., Results: MBF and flow reserve values from the normal subjects and from territories with documented stenoses > or = 50% were significantly different (p < 0.05). A significant difference was found between normal subjects and angiographically normal territories of patients with CAD. High diagnostic accuracy and sensitivity, with moderately high specificity, were demonstrated for detection of all stenoses., Conclusions: Quantification of myocardial perfusion using dynamic PET and N-13 ammonia provides a high performance level for the detection and localization of CAD. The specificity of dynamic PET was excellent in patients with a low likelihood of CAD, whereas an abnormal flow reserve in angiographically normal territories was postulated to represent early functional abnormalities of vascular reactivity.

The effect of F-18-fluorodeoxyglucose positron emission tomography imaging on decision making in the selection of patients with impaired ventricular function for revascularization was determined in 87 patients. In 57% of patients, positron emission tomography data influenced management decisions, indicating an important effect of myocardial viability determination on difficult therapy decisions in these patients.

Objectives: The hypothesis of this study was that evaluation of myocardial flow and metabolism using nitrogen-13 (N-13) ammonia kinetic modeling with dynamic positron emission tomographic (PET) imaging could identify regions of myocardial scar and viable myocardium as defined by fluorine-18 fluorodeoxyglucose (F-18 FDG) PET., Background: Uptake of most perfusion tracers depends on both perfusion and metabolic retention in tissue. This characteristic has limited their ability to differentiate myocardial scar from viable tissue. The kinetic modeling of N-13 ammonia permits quantification of blood flow and separation of the metabolic component of its uptake, which may permit differentiation of scar from viable tissue., Methods: Sixteen patients, > 3 months after myocardial infarction, underwent dynamic N-13 ammonia and F-18 FDG PET imaging. Regions of reduced and normal perfusion were defined on static N-13 ammonia images. Patients were classified into two groups (group I [ischemic viable], n = 6; group II [scar], n = 10) on the basis of percent of maximal F-18 FDG uptake in hypoperfused segments. Nitrogen-13 ammonia kinetic modeling was applied to dynamic PET data, and rate constants were determined. Flow was defined by K1; volume of distribution (VD = K1/k2) of N-13 ammonia was used as an indirect indication of metabolic retention., Results: Fluorine-18 FDG uptake was reduced in patients with scar compared with normal patients with ischemic viable zones (ischemic viable 93 +/- 27% [mean +/- SD]; scar 37 +/- 16%, p < or = 0.01). Using N-13 ammonia kinetic modeling, flow and VD were reduced in the hypoperfused regions of patients with scar (ischemic viable flow: 0.65 +/- 0.20 ml/min per g, scar: 0.36 +/- 0.16 ml/min per g, p < or = 0.01; VD: 3.9 +/- 1.3 and 2.0 +/- 1.07 ml/g, respectively, p < or = 0.01). For detection of viable myocardium in these patients, the sensitivity and specificity were 100% and 80% for N-13 ammonia PET flow > 0.45 ml/min per g; 100% and 70% for VD > 2.0 ml/g; and 100% and 90% for both flow > 0.45 ml/min per g and VD > 2.0 ml/g, respectively. The positive and negative predictive values for the latter approach were 86% and 100%, respectively., Conclusions: In this cohort, patients having regions with flow < or = 0.45 ml/min per g or VD < or = 2.0 ml/g had scar. Viable myocardium had both flow > 0.45 ml/min per g and VD > 2.0 ml/g. Nitrogen-13 ammonia kinetic modeling permits determination of blood flow and metabolic integrity in patients with previous myocardial infarction and can help differentiate between scar and ischemic but viable myocardium.

Positron emission tomography (PET) represents an advanced form of nuclear imaging technology. The use of positron emitting isotopes, such as C-11, O-15, N-13, and F-18 permit radiolabelling of naturally occurring compounds in the body or close analogues. This, combined with technical advantages of PET imaging, allow quantification of physiological processes in humans. PET has become established as the most accurate noninvasive means for the diagnosis of coronary artery disease using myocardial perfusion radiotracers, which include rubidium-82, N-13-amonia, and O-15-water. These approaches have also been applied for long term evaluation of the effects of therapy and for the quantification of myocardial bloodflow. Radiolabelling of metabolic substrates, including C-11 palmitate, C-11 acetate and F-18 flurodeoxyglucose (FDG) have permitted evaluation of myocardial metabolism. F-18 FDG PET imaging has been established as the best means for defining viable myocardium in patients with reduced ventricular function being considered for revascularization. FDG PET can also identify patients being considered for cardiac transplant, who may be candidates for revascularization. In this review, other applications for metabolic, autonomic nervous system and receptor imaging are also discussed. The availability of cardiac PET in Canada is currently limited. However, with the reducing costs of capital and more cost effectiveness data, PET may become more widely available. Cardiac PET imaging is established as a tremendous diagnostic tool for defining viable myocardium, assessment of perfusion and long term evaluation of therapy without invasive procedures. PET is also a vital research tool capable of evaluating flow, metabolism, myocardial receptors, autonomic nervous system and potentially radiolabelled drugs. Cardiac PET imaging will continue to provide important insight, expanding our understanding and treatment of patients with cardiovascular disease.

Data on the feasibility, safety, and clinical outcome of intracoronary stenting in acute myocardial infarction (AMI) are limited. This study examined the immediate angiographic results and the early and late outcomes in 32 patients who had stenting during AMI. Coronary angiograms recorded at the time of stenting were reviewed with quantitative measurements obtained on the "target" coronary lesion before and after stenting. Immediate angiographic success was achieved in 30 patients (94%). The minimal luminal diameter increased from 0.36 +/- 0.37 to 2.58 +/- 0.41 mm (p<0.0001). Two patients died in the hospital. Of the remainder, none had reinfarction or required bypass surgery, whereas 2 required repeat coronary angioplasty for recurrent ischemia. Although thrombus at the infarct-related coronary lesion was initially detected in 41% of the patients, its presence was not associated with adverse procedural outcome. Only 1 patient had persistent thrombus after stenting, which resolved with intracoronary urokinase. At a mean follow-up of 6.1 +/- 4.1 months, there was 1 additional cardiac death, and no patient had AMI or required repeat coronary angioplasty or bypass; among the 29 survivors, 86% were free of angina. Thus, intracoronary stenting of the infarct-related artery in the setting of AMI is associated with excellent immediate angiographic success and a favorable clinical outcome, and remains an option even in the presence of thrombus.

Arrhythmias are common problems following Mustard's operation for D-transposition of the great arteries. A 19-year-old male is presented who was diagnosed at birth with D-transposition of the great arteries and a right aortic arch and underwent a Mustard procedure at 12 months of age. He developed sinus node dysfunction and atrial flutter unresponsive to antiarrhythmic drugs and dual chamber pacing. Following complete heart block with radiofrequency catheter ablation of the atrioventricular junction, the patient's heart was paced in VVIR mode. Ventricular function improved after the ablation and persisted in two years' follow-up.

Objectives: The aim of this study was to evaluate patients with coronary artery disease to 1) determine the relation between flow reserve measured by nitrogen-13 (N-13) ammonia kinetic modeling and stenosis severity assessed by quantitative angiography, and 2) examine whether flow reserve is impaired in regions supplied by vessels without significant angiographic disease., Background: With the advent of new therapeutic approaches for coronary disease, an accurate noninvasive approach for absolute quantification of flow and flow reserve is needed to evaluate functional severity and extent of atherosclerosis. Nitrogen-13 ammonia kinetic modeling may permit such evaluation., Methods: Twenty-seven subjects were classified into three groups: group 1 = 5 young volunteers: group 2 = 7 middle-aged volunteers; and group 3 = 15 patients with coronary artery disease. Dynamic N-13 ammonia positron emission tomographic imaging was performed at rest and during adenosine infusion. A three-compartment model was fit to regional N-13 ammonia kinetic data to determine myocardial flow. Group 3 patients underwent quantitative coronary angiography., Results: The regional blood flow results in patients with coronary disease were classified into four subgroups: no significant detectable disease and mild (50% to 69.9% area stenosis), moderate (70% to 94.9% area stenosis) or severe (95% to 100% area stenosis) coronary disease. Flow reserve was 2.95 +/- 0.65; 2.09 +/- 0.47; 2.02 +/- 0.51; 1.3 +/- 0.32, respectively (p < or = 0.01 except mild vs. moderate). Flow reserve was correlated with percent area stenosis (r = -0.56) and minimal lumen diameter (r = 0.75). In volunteers (groups 1 and 2), flow reserves were greater than in segments without detectable disease in group 3 patients (4.10 +/- 0.71 and 3.79 +/- 0.42, respectively, vs. 2.88 +/- 0.56, p < or = 0.02)., Conclusions: The functional severity of coronary disease measured by N-13 ammonia positron emission tomography varied for a given stenosis but was significantly related to angiographic severity. Among patients with coronary disease, myocardial regions without significant angiographic stenoses displayed reduced flow reserve than did regions in control subjects, indicating that vascular reactivity was more diffusely impaired in group 3 than was suggested by angiography. Noninvasive quantification of myocardial flow reserve using dynamic N-13 ammonia positron emission tomography yields important functional data that permit definition of the extent of disease even when disease is not apparent by angiography.

Objectives: This study was performed to test the hypothesis that regional variation in ventricular function in patients with nonischemic dilated cardiomyopathy is related to regional variation in oxidative metabolism., Background: Heterogeneity in regional left ventricular function has long been noted in patients with nonischemic dilated cardiomyopathy. Regional variation in wall stress has been proposed as the pathophysiologic mechanism. By correlating regional function with oxidative metabolism, one can test the hypothesis that heterogeneity in wall stress is responsible for heterogeneity in function. We hypothesized that preserved function as a result of more favorable loading conditions would be associated with regional oxidative metabolism that is equal to or lower than that in other regions., Methods: Fifteen patients with nonischemic dilated cardiomyopathy (mean [+/- SD] ejection fraction 20.7 +/- 4.0%) were studied. Regional ventricular function was determined using short-axis chordal shortening on two-dimensional echocardiography. Regional oxidative metabolism was assessed by carbon-11 acetate clearance kinetics on dynamic positron emission tomography. An eight-segment model of the left ventricle was used. Segmental function and oxidative metabolism were defined as increased if they varied at least 1 SD from the respective mean value for that patient., Results: Thirteen (87%) of 15 patients exhibited segments with increased function. In 7 (54%) of 13 patients, regional function was increased in the proximal lateral wall. Multivariate linear regression analysis showed a direct relation between regional function and oxidative metabolism (p = 0.02). The average concordance between increased function and increased oxidative metabolism among patients was 0.87 +/- 0.11 (95% confidence interval 0.70 to 1.00)., Conclusions: Patients with nonischemic dilated cardiomyopathy display heterogeneity in regional ventricular function. Relative preservation is observed most frequently in the proximal lateral wall. Relative preservation of function is associated with higher regional oxidative metabolism, suggesting that mechanisms other than or in addition to local loading conditions may be responsible for heterogeneity in function.

The application of 11C acetate kinetics determined by positron emission tomography (PET) imaging has been proposed as a noninvasive means to measure myocardial oxygen consumption in order to determine myocardial efficiency. Such an approach considers the balance of the effect of ventricular performance and myocardial oxygen consumption (MVO2), which may be important in the assessment of heart failure but is not usually evaluated by current methods. In this paper, the authors review their previously published series of studies, in which the aim was to: first, apply the 11C acetate PET approach in patients with dilated cardiomyopathy in order to determine myocardial oxidative metabolism and estimate myocardial efficiency; second, verify a correlation between 11C acetate kinetics and directly measured MVO2; and third, evaluate the effects of dobutamine and nitroprusside on MVO2 and efficiency in dilated cardiomyopathy. In these previous studies, 13 patients with severe dilated cardiomyopathy were studied, via echocardiography, hemodynamic and PET studies, at baseline and during drug infusion. Seven patients were given dobutamine and six were given nitroprusside. A two-compartment kinetic model approach was applied to 11C time activity curves obtained from dynamic 11C acetate PET imaging to determine the clearance rate constant, k2. Myocardial efficiency was estimated from a work metabolic index, defined as (stroke work index multiplied by heart rate) divided by k2. The k2 significantly increased with dobutamine (P < or = 0.05), consistent with increased MVO2, and tended to decrease with nitroprusside. The work metabolic index derived from hemodynamic parameters increased significantly with both drug regimens (P < or = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Unlike nonselective coronary vasodilators, nitroglycerin (GTN) is said to exert its primary vasodilatory effect on epicardial conductance vessels. Thus, in experimental models of coronary occlusion GTN appears to preferentially direct blood flow to poststenotic zones of ischemia. This phenomenon has, to date, not been tested in humans. Using positron emission tomography we examined the effect of transdermal GTN on global and regional myocardial perfusion in patients with angiographically proven coronary artery disease., Methods and Results: Myocardial perfusion with [13N]ammonia was estimated from dynamic time-activity curves at baseline and 3 hours following application of either a 0.4 mg/h GTN skin patch (n = 10) or a placebo patch (n = 10) in a double-blind parallel design. From resliced cross-sectional images, regional flow, expressed as [13N]ammonia retention, was estimated from 216 myocardial sectors. Ischemia was defined as a significant reduction (> 2 SDs from average counts/pixel in maximally perfused zones) in [13N]ammonia retention within 10 contiguous myocardial sectors coupled with an increase or no change in counts derived from [18F]fluorodeoxyglucose. There was no change in global myocardial blood flow as expressed by [13N]ammonia retention following either placebo (0.61 +/- 0.14 to 0.62 +/- 0.12 min-1) or GTN (0.75 +/- 0.22 to 0.74 +/- 0.19 min-1). Conversely, there was a significant increase in the proportion of blood flow to the ischemic zones with GTN (73.9 +/- 12.6% to 94.9 +/- 17.8%; P < .05). No change in the distribution of blood flow to either ischemic or nonischemic zones was observed with placebo. A slight but insignificant decrease in [13N]ammonia retention in nonischemic zones was observed with GTN (1.01 +/- 0.31 to 0.93 +/- 0.26 min-1)., Conclusions: This study suggests that under resting conditions topical GTN alters myocardial perfusion by preferentially increasing flow to areas of reduced perfusion with little or no change in global myocardial perfusion in patients whose angina is responsive to GTN.

Unlabelled: One of the unique aspects of PET is its ability to noninvasively quantify metabolic processes. Metabolic rate parameters are estimated by fitting the time-activity curves from regions of interest (ROIs) placed on dynamic PET images with a kinetic model. In many cases it is possible to couple these datasets with common parameters, such as the time delay between arrival of tracer in the ROIs and the sampling site., Methods: Data from eight ROIs placed about images of the myocardium were coupled by the parameters describing the metabolite concentration in the blood. The method was evaluated by comparing estimates of k2 made using the coupled region method and the standard process of fitting data from each region separately. In addition, comparisons were made between estimates of k2 and measured myocardial oxygen consumption., Results: Very little change in mean values of k2 was obtained. The variances, however, were reduced by an average of 37%, compared to the standard method, when the common parameters were not constrained. When the values of the common metabolite parameters were constrained to values previously measured, the average variance in estimates of k2 was reduced by 30%., Conclusion: We have demonstrated that the use of this technique can significantly increase the precision of estimates of myocardial oxygen consumption utilizing 11C-acetate PET images. More precise estimates of such quantities can facilitate detection of small regional and/or temporal physiological changes measured with PET. Furthermore, this method can be utilized whenever it is known a priori that one or more kinetic model parameters has the same value for every set of ROI data.

Myocardial fatty acid metabolism may be impaired in adriamycin cardiomyopathy. In order to determine the extent of fatty acid metabolism alterations, we measured steady state [14C]palmitate oxidation and the incorporation of [14C]palmitate into the neutral lipid pool in a rat model of adriamycin cardiomyopathy. Isolated hearts from control rats and rats treated with adriamycin were perfused with 1.2 mmol/l of [14C]palmitate for 30 min to achieve steady state oxidation measured as [14C]O2 production; then perfused with 1.2 nmol/l of unlabelled palmitate. Hearts were killed early (0-5 min) or late (10-30 min) after the [14C]palmitate perfusion, to determine incorporation into the neutral lipid pool, and neutral lipid utilization. In the control group steady state oxidation was reached in 10 min ([14C]O2 production = 580 +/- 61 nmol/min/g dry wt) of perfusion. In the adriamycin treated group, mean CO2 production was significantly reduced at 10 min (329 +/- 44 nmol/min/g dry wt, P < 0.01 v control). At 30 min, [14C]O2 production in the treated group was not significantly different than controls (521 +/- 65 nmol/min/g dry wt v 617 +/- 36 nmol/min/g dry wt, P = N.S.). The incorporation of [14C]palmitate into the neutral lipid pool measured in the early subgroup was significantly reduced for adriamycin treated hearts v controls (7.2 +/- 0.6 v 12.0 +/- 1.4 mumol/g dry wt respectively, P < 0.01). In the control group 14C labelled neutral lipid reduced with time to 8.4 +/- 1.1 mumol/g dry wt (P < 0.05) in the late group. The adriamycin group demonstrated no significant change between early and late measurements. In conclusion, in adriamycin cardiomyopathy: (1) there is significant delay in achieving steady state palmitate oxidation, although the steady state rate is near normal; (2) palmitate incorporation into the neutral lipid pool is reduced; (3) neutral lipid pool utilization may also be reduced. These data suggest impaired uptake of palmitate into the cell in adriamycin cardiomyopathy, with a relatively maintained capacity for oxidative metabolism.

Objectives: The purpose of this study was to determine the relative value of single-photon emission computed tomographic (SPECT) imaging at rest using technetium-99m methoxyisobutyl isonitrile (technetium-99m sestamibi) with positron emission tomography for detection of viable myocardium., Background: Recent studies comparing positron emission tomography and thallium-201 reinjection with rest technetium-99m sestamibi imaging have suggested that the latter technique underestimates myocardial viability., Methods: Twenty patients with a previous myocardial infarction underwent rest technetium-99m sestamibi imaging and positron emission tomography using fluorine (F)-18 deoxyglucose and nitrogen (N)-13 ammonia. In each patient, circumferential profile analysis was used to determine technetium-99m sestamibi, F-18 deoxyglucose and N-13 ammonia activity (expressed as percent of peak activity) in nine cardiac segments and in the perfusion defect defined by the area having technetium-99m sestamibi activity < 60%. Technetium-99m sestamibi defects were graded as moderate (50% to 59% of peak activity) and severe (< 50% of peak activity). Estimates of perfusion defect size were compared between technetium-99m sestamibi and N-13 ammonia., Results: Sixteen (53%) of 30 segments with moderate defects and 16 (47%) of 34 segments with severe defects had > or = 60% F-18 deoxyglucose activity considered indicative of viability. Fluorine-18 deoxyglucose evidence of viability was still present in 50% of segments with technetium-99m sestamibi activity < 40%. There was no significant difference in the mean (+/- SD) technetium-99m sestamibi activity in segments with viable (40 +/- 7%) and nonviable segments (49 +/- 7%, p = 0.84). Of the 18 patients who had adequate F-18 deoxyglucose studies, the area of the technetium-99m sestamibi defect was viable in 5 (28%). In 16 patients (80%), perfusion defect size determined by technetium-99m sestamibi exceeded that measured by N-13 ammonia. The difference in defect size between technetium-99m sestamibi and N-13 ammonia was significantly greater in patients with viable (21 +/- 9%) versus nonviable segments (7 +/- 9%, p = 0.007)., Conclusions: Moderate and severe rest technetium-99m sestamibi defects frequently have metabolic evidence of viability. Technetium-99m sestamibi SPECT yields larger perfusion defects than does N-13 ammonia positron emission tomography when the same threshold values are used.

Objectives: The aim of this study was to use positron emission tomography (PET)-derived carbon (C)-11 acetate kinetics to determine the effects of dobutamine on oxidative metabolism and its effects on myocardial efficiency in a group of patients with dilated cardiomyopathy., Background: Dobutamine is known to improve myocardial function but may do so at the expense of myocardial oxygen consumption, which could be a potential deleterious effect. Carbon-11 acetate kinetics correlate with myocardial oxygen consumption as shown in animal models. Combining these scintigraphic measurements of oxygen consumption with estimates of cardiac work results in a work-metabolic index, which reflects cardiac efficiency., Methods: Eight patients with nonischemic dilated cardiomyopathy underwent dynamic PET imaging, echocardiography and hemodynamic measurements. Seven of these patients were also studied while receiving dobutamine. Direct measurements of myocardial oxygen consumption using coronary sinus catheterization were obtained with eight of the PET studies to validate C-11 acetate in patients with cardiomyopathy., Results: The mean (+/- SD) C-11 clearance rate significantly increased with dobutamine from 0.105 +/- 0.027 to 0.155 +/- 0.023 min-1 (p = 0.001). Directly measured myocardial oxygen consumption had a linear relation to the mean C-11 clearance rate (r = 0.8, p = 0.018). Dobutamine was noted to significantly reduce systemic vascular resistance as well as the severity of mitral regurgitation. The work-metabolic index determined using hemodynamic variables and PET data increased from 2 +/- 0.7 x 10(4) to 2.6 +/- 0.6 x 10(4) (p = 0.04). Efficiency, estimated by employing the oxygen consumption to k2 relation, also increased from 13 +/- 4.5% to 16.9 +/- 6.4% (p = 0.04)., Conclusions: Despite an increase in myocardial oxygen consumption, dobutamine led to an increase in work-metabolic index in patients with dilated nonischemic cardiomyopathy. Dobutamine reduced systemic vascular resistance and mitral regurgitation, suggesting that in this group of patients, it had important vasodilatory action in addition to its inotropic effects. The use of the C-11 acetate PET for determining myocardial oxygen consumption and estimating efficiency could potentially complement existing clinical measures of ventricular performance and may allow improved and objective evaluation of therapy in patients with heart failure.

Positron emission tomography (PET), in combination with myocardial blood flow tracers, allows highly accurate diagnosis of coronary artery disease using visual data interpretation. To increase the objectivity of data analysis and to reduce interobserver variability, we developed an automated analysis method for the three-dimensional definition of myocardial activity, which includes true volumetric data extraction and mathematical constraints of activity sampling to the expected shape of the left ventricle. Data are displayed in a standardized polar map or three-dimensional format for comparison with a normal database. The first clinical evaluation of this method in 52 patients using receiver operating characteristics (ROC) curve analysis demonstrated high diagnostic accuracy for detection as well as localization of coronary artery stenosis in predefined vascular territories. The interobserver and intraobserver agreement for localization of disease was excellent, with correlation coefficients varying from 0.85 to 0.99 for individual vascular territories. Thus, this automated quantitative analysis program provides highly accurate and reproducible evaluation of cardiac PET flow studies. Definite determination of its diagnostic accuracy requires a prospective multicenter trial in a larger patient population employing the criteria for abnormality established in this initial clinical evaluation.

In combination with PET, the tracer 13N-ammonia can be employed for the noninvasive quantification of myocardial perfusion at rest and after pharmacological stress. The purpose of this study was to develop an analysis method for the quantification of regional myocardial blood flow in the clinical setting. The algorithm includes correction for patient motion, an automated definition of multiple regions and display of absolute flows in polar map format. The effects of partial volume and blood to tissue cross-contamination were accounted for by optimizing the radial position of regions to meet fundamental assumptions of the kinetic model. In order to correct for motion artifacts, the myocardial displacement was manually determined based on edge-enhanced images. The obtained results exhibit the capability of the presented algorithm to noninvasively assess regional myocardial perfusion in the clinical environment.

Positron emission tomography has been shown to provide quantitative estimates of myocardial blood flow using 13N-ammonia and 15O-water. In a validation study, myocardial blood flow was noninvasively determined in 11 open-chest anesthetized dogs using dynamic positron emission tomography. The radiopharmaceuticals 13N-ammonia and 15O-water were intravenously administered and measurements were carried out at rest and following pharmacological vasodilation to assess blood flow over a range from 53 to 580 ml/100 g/min. Quantification of blood flow based on tracer kinetic modeling of 13N-ammonia data correlated closely with myocardial blood flow determined by microspheres (y = 0.944 x +7.22, r = 0.986) and with the 15O-water injection technique y = 1.054 x -15.8 (r = 0.99). The use of 13N-ammonia with positron emission tomography enables the accurate quantification of myocardial blood flow. Using this technique, uncomplicated study protocols simplify the measurement procedures while providing excellent qualitative and quantitative information.

Objectives: The aim of this study was to compare the myocardial retention of technetium-99m (Tc-99m) sestamibi and thallium-201 over a wide range of blood flow at different time points after tracer injection., Background: Technetium-99m sestamibi has been proposed as a new perfusion tracer with better physical characteristics than those of thallium-201 for scintigraphic imaging. However, no studies have simultaneously compared the ability of both tracers to assess myocardial blood flow during pharmacologic vasodilation., Methods: The myocardial retention of Tc-99m sestamibi and thallium-201 were compared over a wide range of blood flow induced by regional coronary occlusion and dipyridamole infusion in an open chest dog model. Myocardial retention of both tracers was determined by in vitro tissue counting at 2, 5, and 20 min after tracer injection and was correlated with microsphere-determined blood flow., Results: Thallium-201 demonstrated greater absolute tissue retention than did Tc-99m sestamibi. At 2 min after tracer injection, there was an almost linear relation between the retention of both tracers and myocardial blood flow over a wide flow range. However, this relation was not maintained over time. At 20 min after injection, the retention of both tracers underestimated myocardial blood flow at higher flow rates. At 2, 5 and 20 min after injection, increments of relative tracer retention between the different levels of flow were always greater for thallium-201 than for Tc-99m sestamibi., Conclusions: Thallium-201 displays more suitable physiologic characteristics as a flow tracer and may allow better differentiation of myocardial regions with different levels of coronary flow reserve. For both tracers, early cardiac imaging may minimize underestimation of blood flow at higher flow rates.

Objectives: The aim of this study was to define the temporal changes in the relationship between technetium-99m teboroxime tissue retention and myocardial blood flow in a canine model., Background: Technetium-99m teboroxime is a new neutral lipophilic myocardial perfusion agent. It is known to be highly extracted by the myocardium but to have a rapid clearance rate., Methods: A wide range of myocardial blood flow was induced in each experiment by regional coronary occlusion and dipyridamole infusion. Myocardial retention of technetium-99m teboroxime was determined by in vitro tissue counting at 1, 2 or 5 min after injection of the tracer. Tracer retention was correlated with microsphere-determined blood flow and the data were fitted to nonlinear functions., Results: Correlation coefficients for these functions were 0.92, 0.95 and 0.95 at 1, 2, and 5 min, respectively. At 1 min after injection, the relationship of technetium-99m teboroxime retention to blood flow was linear over a wide flow range, becoming nonlinear at flow rates greater than 4.5 ml/min per g. After 5 min the retention-flow relationship was linear only to 2.5 ml/min per g, above which little change in retention was noted. Normalized myocardial retention, expressed as a percent of the retention at 1 ml/min per g, was also calculated. At flow rates of 1, 2, 3, 4 and 5 ml/min per g, normalized retention was 100, 169, 228, 277 and 317% at 1 min and 100, 171, 217, 239 and 237% at 5 min after injection., Conclusions: At 1 min after injection, the relationship of technetium-99m teboroxime myocardial retention to blood flow is well maintained over a wide range of flow. However, after only 5 min, tracer retention underestimates flow changes at moderate and high flow rates. Thus, rapid acquisition protocols are necessary to fully exploit the potential of this promising new tracer in the evaluation of myocardial perfusion.

Copper-62-labeled pyruvaldehyde bis(N-4-methylthiosemicarbazone) copper(II) (PTSM) is a generator-produced myocardial perfusion tracer. Animal studies have shown high myocardial tissue extraction and prolonged retention. The aim of this study was to define myocardial kinetics of 62Cu-PTSM and to determine its suitability for evaluating myocardial perfusion at rest and during pharmacological vasodilation in human subjects. In six healthy volunteers, 62Cu-PTSM was administered at baseline and during a 6-min adenosine infusion (140 micrograms/kg/min). Dynamic PET imaging with high temporal resolution was performed over 20 min. Good image quality was observed at rest and following adenosine. Myocardial kinetics demonstrated prolonged tissue retention with a clearance half-life of 105 +/- 49 min at rest and 101 +/- 65 min following adenosine (p = ns). Copper-62-PTSM tissue retention was quantified and showed only a 1.97-fold increase from rest to adenosine studies. This suggests attenuation of tracer retention at high flow rates. Copper-62-PTSM represents a promising new radiopharmaceutical for the evaluation of myocardial perfusion in the human heart.

Positron-emission tomography is an advanced imaging technology that can be used for the noninvasive evaluation of myocardial blood flow, determination of myocardial metabolism, and the assessment of myocardial tissue viability. 82Rb and 13N-ammonia represent the most commonly used tracers for qualitative evaluation of regional myocardial perfusion. In combination with pharmacologic vasodilation, these agents provide accurate detection of coronary artery disease. Comparative studies using single-photon emission CT with 201Tl have shown 82Rb positron-emission tomography to be superior in terms of diagnostic accuracy. The use of tracer kinetic modeling with the radiopharmaceuticals 15O-water or 13N-ammonia has allowed accurate quantification of myocardial blood flow and determination of regional coronary flow reserve using dynamic positron-emission tomography imaging. The labeling of metabolic substrates such as 11C-palmitate, 11C-acetate, and 18F-fluorodeoxyglucose has proven to be useful in evaluating cardiac metabolism. The use of fluorodeoxyglucose uptake as a marker of exogenous myocardial glucose utilization allows the differentiation of ischemic but viable tissue from myocardial scar. The relationship of 11C-acetate turnover to oxidative metabolism and myocardial oxygen consumption may have important future applications for evaluating the efficiency of energy conversion of the heart into external work. Such a parameter could be used to evaluate the condition of patients with impaired left ventricular performance and to assess their response to therapy. Positron-emission tomography offers a useful research and clinical tool for the noninvasive evaluation of many aspects of cardiac disease. With the development of quantitative techniques, the clinical importance of positron-emission tomography is expected to further increase in the future.