Myocardial perfusion imaging after coronary revascularization: a clinical appraisal

Revascularization procedures, including percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), are performed in many patients with coronary artery disease. Despite the effectiveness of these procedures, different follow-up strategies need to be considered for the management of patients after revascularization. Stress myocardial perfusion single-photon emission computed tomography (MPS) is a suitable imaging method for the evaluation of patients who have undergone PCI or CABG, and it has been used in the follow-up of such patients. Radionuclide imaging is included in the follow-up strategies after PCI and CABG in patients with symptoms, but guidelines warn against routine testing of all asymptomatic patients after revascularization. After PCI, in the absence of symptoms, radionuclide imaging is recommended and indicated as appropriate after incomplete or suboptimal revascularization and in specific asymptomatic patient subsets. On the other hand, the value of MPS late after CABG in risk stratification has been demonstrated even in the absence of symptoms. Thus, given the adverse outcome associated with silent ischaemia, it can be speculated that all patients regardless of clinical status should undergo stress testing late after revascularization. Larger prospective studies are needed to assess whether stress MPS will have an impact on the outcome in asymptomatic patients after revascularization.     

Myocardial perfusion and coronary microcirculation: From pathophysiology to clinical application

In the past 2 decades, enough evidence has been produced by different centers and by means of different methodologies to demonstrate the existence of coronary microvascular abnormalities in various cardiovascular diseases. Unfortunately, because of the technical difficulties in exploring coronary microcirculation, studies currently available on this subject are limited to relatively small groups of patients, preventing a definitive conclusion on the clinical relevance of peculiar microvascular alterations in each disease in terms of prevalence, incidence, and prognosis. Despite this limitation, available information strongly calls for caution in the binary attribution of perfusion abnormalities to coronary stenosis or, by exclusion, to technical artifacts. In this respect, it is now clear that perfusion defects secondary to microcirculatory dysfunction are frequent and indistinguishable from the defects commonly observed in ischemic heart disease, relative to regionality, extension, and severity. With regard to the physiopathology of microvascular disorders, it should be considered that the models of coronary pathology in “healthy” animals, developed in the last half century, are largely inadequate for the reproduction of human pathology, in light of new acquisitions in the field of vascular and molecular biology. It appears evident that the classical model of coronary circulation suffers from oversimplification and that the regional increase in microvascular resistance observed in patients cannot simply be attributed to extrinsic factors such as hemodynamics or ventricular hypertrophy. Understanding the nature and significance of functional and structural intrinsic factors as they relate to human coronary pathology requires a greater research effort, primarily in clinical models.     

Myocardial perfusion imaging in the elderly: a review

Coronary artery disease is a major cause of morbidity and mortality in the elderly population. As a result of ageing of the population and better medical, interventional and surgical treatment of patients with coronary artery disease, more and more elderly patients are referred to the cardiology department for diagnostic work-up. Stress testing, in combination with myocardial perfusion imaging, is routinely used in elderly patients, a population in which the diagnosis of significant coronary artery disease is often challenging because of atypical symptomatology. Since the introduction of technetium-99m ligands for myocardial perfusion imaging, it is possible to perform electrocardiogram-gated perfusion imaging. This not only improves the specificity of the test for coronary artery disease detection, but also enables the simultaneous assessment of left ventricular functional parameters. This article briefly overviews the possible stress modalities, diagnostic accuracy and prognostic value of myocardial perfusion imaging in elderly patients.     

Myocardial perfusion scintigraphy: the evidence

This review summarises the evidence for the role of myocardial perfusion scintigraphy (MPS) in patients with known or suspected coronary artery disease. It is the product of a consensus conference organised by the British Cardiac Society, the British Nuclear Cardiology Society and the British Nuclear Medicine Society and is endorsed by the Royal College of Physicians of London and the Royal College of Radiologists. It was used to inform the UK National Institute of Clinical Excellence in their appraisal of MPS in patients with chest pain and myocardial infarction. MPS is a well-established, non-invasive imaging technique with a large body of evidence to support its effectiveness in the diagnosis and management of angina and myocardial infarction. It is more accurate than the exercise ECG in detecting myocardial ischaemia and it is the single most powerful technique for predicting future coronary events. The high diagnostic accuracy of MPS allows reliable risk stratification and guides the selection of patients for further interventions, such as revascularisation. This in turn allows more appropriate utilisation of resources, with the potential for both improved clinical outcomes and greater cost-effectiveness. Evidence from modelling and observational studies supports the enhanced cost-effectiveness associated with MPS use. In patients presenting with stable or acute chest pain, strategies of investigation involving MPS are more cost-effective than those not using the technique. MPS also has particular advantages over alternative techniques in the management of a number of patient subgroups, including women, the elderly and those with diabetes, and its use will have a favourable impact on cost-effectiveness in these groups. MPS is already an integral part of many clinical guidelines for the investigation and management of angina and myocardial infarction. However, the technique is underutilised in the UK, as judged by the inappropriately long waiting times and by comparison with the numbers of revascularisations and coronary angiograms performed. Furthermore, MPS activity levels in this country fall far short of those in comparable European countries, with about half as many scans being undertaken per year. Currently, the number of MPS studies performed annually in the UK is 1,200/million population/year. We estimate the real need to be 4,000/million/year. The current average waiting time is 20 weeks and we recommend that clinically appropriate upper limits of waiting time are 6 weeks for routine studies and 1 week for urgent studies.Abbreviations Acc Diagnostic accuracy - ACS Acute coronary syndromes - BCS British Cardiac Society - BNCS British Nuclear Cardiology Society - BNMS British Nuclear Medicine Society - CABG Coronary artery bypass grafting - CHD Coronary heart disease - CT Computed X-ray tomography - LBBB Left bundle branch block - MI Myocardial infarction - MIBI Technetium-99m 2-methoxy-isobutyl-isonitrile - MPS Myocardial perfusion scintigraphy - NSF National Service Framework for Cardiovascular Disease - NSTEMI Non-ST segment elevation myocardial infarction - PCI Percutaneous coronary intervention - Q Quantitative analysis - QALY Quality-adjusted life-year - RCP Royal College of Physicians of London - RCR Royal College of Radiologists - Sens Sensitivity - Spec Specificity - SPET Single-photon emission tomography - STEMI ST segment elevation myocardial infarction - Tetro or tetrofosmin Technetium-99m 1,2-bis[bis(2-ethoxyethyl) phosphino] ethane - 201Tl or thallium Thallium-201 thallous chloride - UA Unstable angina - V Visual analysis     

Myocardial kinetics of radiolabeled perfusion agents: Basis for perfusion imaging

The myocardial deposition of radiolabeled perfusion agents permits the noninvasive assessment of regional coronary blood flow. The design of imaging protocols and the optimal interpretation of clinical perfusion studies are based on an understanding of the kinetics of blood-tissue exchange for these compounds. Thallium 201 and the technetium 99m-labeled compounds sestamibi, teboroxime, and tetrofosmin show differing myocardial extraction and retention. This review focuses on studies that used cell culture, isolated heart, and intact animal models that form the basis of our current understanding of the myocardial kinetics of these imaging agents.     

Myocardial visualization on a perfusion lung scan

Myocardial activity was noted on a lung scan performed following the i.v. administration of Tc-99m macroaggregated albumin. The patient had primary pulmonary hypertension with a right-to-left shunt through a functionally patent foramen ovale.     

User interface paradigms for patient-specific surgical planning: lessons learned over a decade of research.

This paper covers work in virtual reality-based, patient-specific surgical planning over the past decade. It aims to comprehensively examine the user interface paradigms and system designs during that period of time and to objectively analyze their effectiveness for the task. The goal is to provide useful feedback on these interface and implementation paradigms to aid other researchers in this field. First, specialized systems for specific clinical use were produced with a limited set of visualization tools. Later, through collaboration with NASA, an immersive virtual environment was created to produce high-fidelity images for surgical simulation, but it underestimated the importance of collaboration. The next system, a networked, distributed virtual environment, provided immersion and collaboration, but the immersive paradigm was found to be of a disadvantage and the uniqueness of the framework unwieldy. A virtual model, workbench-style display was then created using a commercial package, but limitations of each were soon apparent. Finally, a specialized display, with an integrated visualization and simulation system is described and evaluated. Lessons learned include: surgical planning is an abstract process unlike surgical simulation; collaboration is important, as is stereo visualization; and that high-resolution preoperative images from standard viewpoints are desirable, but interaction is truly the key to planning.     

Myocardial perfusion imaging agents: SPECT and PET

The advent of myocardial perfusion imaging 30 years ago was a major landmark, which heralded the emergence of the field of nuclear cardiology into clinical practice. Over the years, the different tracers cited in this review have been used with SPECT or PET imaging technologies for the noninvasive evaluation of regional myocardial blood flow, which has enhanced our ability to diagnose CAD, assess prognosis, detect viable myocardium, and evaluate the efficacy of therapies aimed at improving myocardial blood flow. In the future, new SPECT perfusion agents should be developed and validated in the experimental laboratory for feasibility in the clinical setting. Hopefully, such new radiolabeled perfusion agents will have a high first-pass extraction, will be more linear with flow increases in the hyperemic range, and will be labeled with Tc-99m. The clearance rates from the myocardium after initial uptake should be slow enough, as with Tl-201, to acquire high-quality poststress gated SPECT images. Ideally, such perfusion agents should also be extracted intracellularly with quantitative uptake reflecting the degree of viability (eg, as with Tl-201). Absolute quantitation of myocardial blood flow in milliliters per minute per gram by use of SPECT technology would be highly desirable, particularly to increase the detection rate of multivessel disease in which flow reserve is uniformly diminished. This is often categorized as balanced ischemia. Absolute quantitation is a major strength of PET perfusion tracers, as is the ability to accurately correct for attenuation, thereby providing high sensitivity and specificity for CAD detection. The roll-off or plateau in myocardial uptake with hyperemia is also seen with the PET perfusion tracers such as N-13 ammonia and Rb-82. Despite the advent of molecular imaging and the introduction of new imaging agents by which to noninvasively evaluate biologic processes such as apoptosis and angiogenesis in vivo, myocardial perfusion imaging will remain the mainstay of nuclear cardiology in the near future. Continued research and development for this imaging technique are warranted for the reasons cited in this review.     

Myocardial perfusion visualized with SPECT: three-dimensional representation

A recently developed computer program for three-dimensional (3D) reconstruction of SPECT images has been employed to study myocardial perfusion in coronaropathic patients using MIBI-99mTc or 201Tl chloride. By subtracting after-stress from at-rest 3D reconstructed images, even small ischemic lesions could be located in the myocardium, with good morphological definition. The general characteristics of the method and some clinical results are here presented.     

Human reporter genes: potential use in clinical studies

The clinical application of positron-emission-tomography-based reporter gene imaging will expand over the next several years. The translation of reporter gene imaging technology into clinical applications is the focus of this review, with emphasis on the development and use of human reporter genes. Human reporter genes will play an increasingly more important role in this development, and it is likely that one or more reporter systems (human gene and complimentary radiopharmaceutical) will take leading roles. Three classes of human reporter genes are discussed and compared: receptors, transporters and enzymes. Examples of highly expressed cell membrane receptors include specific membrane somatostatin receptors (hSSTrs). The transporter group includes the sodium iodide symporter (hNIS) and the norepinephrine transporter (hNET). The endogenous enzyme classification includes human mitochondrial thymidine kinase 2 (hTK2). In addition, we also discuss the nonhuman dopamine 2 receptor and two viral reporter genes, the wild-type herpes simplex virus 1 thymidine kinase (HSV1-tk) gene and the HSV1-tk mutant (HSV1-sr39tk). Initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: (a) gene therapy and (b) adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adenoviral-based, retroviral-based and lenteviral-based gene therapies, oncolytic bacterial and viral therapies, and adoptive cell-based therapies. Translational applications of noninvasive in vivo reporter gene imaging are likely to include: (a) quantitative monitoring of gene therapy vectors for targeting and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; (b) monitoring of cell trafficking, targeting, replication and activation in adoptive T-cell and stem/progenitor cell therapies; (c) and assessments of endogenous molecular events using different inducible reporter gene imaging systems.     

盐酸去甲乌药碱负荷心肌灌注显像在冠心病诊断中的价值

目的 评价盐酸去甲乌药碱负荷MPI在冠心病诊断中的有效性、安全性及诊断价值.方法 68例拟诊冠心病患者分别行盐酸去甲乌药碱注射液和安慰剂注射液的负荷MPI.以CAG结果为“金标准”,计算MPI诊断冠心病的效能.采用SPSS 16.0软件进行统计学处理,率的比较采用x2检验,2组间均值比较采用t检验.结果 盐酸去甲乌药碱负荷MPI诊断冠心病的灵敏度、特异性、准确性、阳性预测值和阴性预测值分别为65.52％(19/29)、84.85％(28/33)、75.81％(47/62)、79.17％(19/24)和73.68％(28/38),其诊断冠心病的灵敏度高于安慰剂负荷MPI(21.43％,6/28;x2=11.246,P=0.001).盐酸去甲乌药碱负荷MPI诊断单支、双支、三支冠状动脉病变的灵敏度分别为52.94％(9/17)、6/8和4/5,对直径狭窄≥50％且＜75％组和≥75％组冠状动脉诊断的灵敏度分别为43.33％(13/30)和72.22％(13/18),两者比较差异无统计学意义(x2=3.782,P＞0.05).盐酸去甲乌药碱负荷过程中发生胸闷、胸痛、心慌、头晕等不良反应的比例为40.32％(25/62),反应均为一过性.结论 盐酸去甲乌药碱负荷MPI能安全、有效地诊断冠心病,作为负荷药物安全性高,不良反应少,有望成为新型负荷药物.     

The use of perfusion imaging in acute myocardial infarction: Applications for clinical trials and clinical care

The use of perfusion imaging in the acute phase of myocardial infarction has been facilitated by the introduction of technetium 99m-labeled sestamibi (^99mTc-sestamibi). Because of minimal redistribution, myocardium at risk can be quantified without delaying reperfusion therapy. The use of perfusion imaging with ^99mTc-sestamibi has been extensively validated in a series of important animal studies in contrast to other methods used to assess outcome from acute myocardial infarction. This has important implications regarding the assessment of reperfusion therapy. With an accurate means to define myocardium at risk, myocardial salvage can be measured for specific therapies or patient subsets. Such measures also have clinical utility for the care of individual patients. Infarct size measures with ^99mTc-sestamibi are accurate and predictive of subsequent left ventricular remodeling as well as prognosis. The identification of jeopardized myocardium in patients with nondiagnostic electrocardiograms and the noninvasive prospective measurement of collateral blood flow before reperfusion therapy are two new areas where perfusion imaging has special clinical use. Because of the ability of perfusion imaging with ^99mTc-sestamibi to measure most of the variables known to determine infarct size, comparative clinical trials can be accomplished by using relatively small sample sizes. This has important implications regarding the assessment of new therapies for acute myocardial infarction.     

Myocardial perfusion imaging in Denmark: activity from 1997 to 2001 and current practice

A questionnaire was sent to all departments of nuclear medicine in Denmark (n=20) asking for details of myocardial perfusion imaging (MPI), including the number of patients examined each year from 1997 to 2001 and the current clinical and technical practice. All (100%) departments replied, and the survey thus covers all MPI performed in Denmark during the period in question. The number of MPI studies (examined patients) was 2,531 in 1997 (0.47 MPI/1,000/year) and 4,961 (0.93 MPI/1,000/year) in 2001, which is a doubling in activity in 5 years. Nineteen (95%) of the Danish departments performed MPI in 2001, and 14 (74%) of these reported that activity had increased over the past 5 years. MPI activity was unevenly distributed between hospitals and regions. In 2001, the university hospitals in the central Copenhagen region (capital) accounted for the highest MPI activity (2.00/1,000/year), while the non-university hospitals in general had the lowest activity rate (0.73/1,000/year). The most pronounced increment found in the period was observed in the university hospitals outside Copenhagen, where activity increased by 300% from 0.44/1,000/year in 1997 to 1.33/1,000/year in 2001. All departments providing MPI used tomographic acquisition technique and all departments used technetium tracers. The more sophisticated techniques of MPI - gated acquisition, attenuation correction and iterative reconstruction - were used in 74%, 32% and 42% of departments, respectively. The stress mode in perfusion studies was dipyridamole/adenosine in 76%, exercise in 18% and dobutamine in 6%. Despite these encouraging figures, MPI activity for 2001 remained well below what is recommended by other national and international societies. The anticipated further increase in nuclear cardiology is encouraging, but the nuclear medicine community needs to address the issues that prevent it from keeping up with demand. In general, the restricted camera time and the limited number of trained personnel explain the excessive waiting lists in Denmark.     

Myocardial perfusion scintigraphy: patients' perception of benefit and risk

BACKGROUND AND AIM: Myocardial perfusion scintigraphy is a useful and safe investigation, which has now received approval by the National Institute of Clinical Excellence (NICE). However, there are common unpleasant side-effects to the drugs used and there is a risk from radiation. This study was performed to assess patients' perceptions of the benefits and risks of myocardial perfusion scintigraphy, and to determine whether the cardiac stress component influenced these perceptions. METHODS: Ninety patients attending our institution for thallium-201 myocardial perfusion study over a period of 2 months were interviewed with regard to their perception of the benefits of the study. Patients were interviewed prior to and following the stress study. RESULTS: On average, patients thought they had a good (three in four) chance of benefiting from myocardial perfusion imaging. Sixty per cent of patients were unaware that they were going to be exposed to ionizing radiation and over 80% were unaware of the side-effects. Two-thirds of the patients said they would undergo the test even if there was only a one in ten chance of benefiting. The majority of patients were uninfluenced by the stress component of the study. CONCLUSIONS: Many patients lack a knowledge of the risks of myocardial perfusion scintigraphy. Most patients would undergo myocardial perfusion studies even if they had a poor chance of benefit.