European Heart Journal Advance Access originally published online on January 17, 2008
European Heart Journal 2008 29(4):557-563; doi:10.1093/eurheartj/ehm607
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Clinical value, cost-effectiveness, and safety of myocardial perfusion scintigraphy: a position statement
1 Cardiology Department, S. Maugeri Foundation, IRCCS, Scientific Institute of Veruno, V. Revislate 13, 28010 Veruno, NO, Italy
2 Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
3 Division of Nuclear Medicine, John Hopkins University School of Medicine, Baltimore, MD, USA
4 Department of Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
5 Department of Nuclear Medicine, Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
6 National Heart and Lung Institute, Imperial College London, London, UK
Received 15 August 2007; revised 15 November 2007; accepted 6 December 2007; online publish-ahead-of-print 17 January 2008.
* Corresponding author. Tel: +39 0322884711, Fax: +39 0322884269, Email: claudio.marcassa{at}fsm.it
See page 531 for the editorial comment on this article (doi:10.1093/eurheartj/ehm544)
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Abstract |
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Top
Abstract
IntroductionMortality rates due to coronary artery disease (CAD) have declined in recent years as result of improved prevention, diagnosis, and management. Nonetheless, CAD remains the leading cause of death worldwide with most casualties expected to occur in developing nations. Myocardial perfusion scintigraphy (MPS) provides a highly cost-effective tool for the early detection of obstructive CAD in symptomatic individuals and contributes substantially to stratification of patients according to their risk of cardiac death or nonfatal myocardial infarction. MPS also provides valuable information that assists clinical decision-making with regard to medical treatment and intervention. A large body of evidence supports the current applications of MPS, which has become integral to several guidelines for clinical practice.
Key Words: Coronary artery disease • Cost-effectiveness • Myocardial perfusion scintigraphy • Radionuclide • Scintigraphy
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Introduction |
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Referral of patients for myocardial perfusion scintigraphy (MPS) has increased in all European countries over the last 20 years, but with variations both between and within countries. Substantial evidence supports the accuracy and cost-effectiveness of MPS for the diagnosis of coronary artery disease (CAD). This position statement aims to summarize the current state-of-the art of MPS and its clinical value alongside other diagnostic modalities for the evaluation of patients with suspected or known CAD. Instead of creating another set of guidelines, the leading European Nuclear Cardiology bodies [European Council of Nuclear Cardiology (ECNC), ESC Working Group 5 (Nuclear Cardiology and Cardiac CT), and European Association of Nuclear Medicine Cardiovascular Committee] have decided to provide a review with special emphasis on existing current clinical and procedural guidelines and recommendations (Table 1), to assist in the appropriate clinical use of MPS.1,2
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Diagnostic value of myocardial perfusion scintigraphy in stable coronary artery disease |
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There is consensus across national and international guidelines in favour of MPS as a non-invasive diagnostic tool for the detection of obstructive CAD in patients with intermediate pre-test probability of disease.3–5 A recent meta-analysis of large studies, including thallium-201 and the technetium-99m-labelled tracers sestamibi and tetrofosmin and either exercise or pharmacological stress tests, reported an average sensitivity of 87% and a specificity of 73% for the detection of angiographically significant CAD.6 These values are consistent and independent of sub-populations selected (i.e. women, obese, and diabetic patients). However, in the last 10 years, a decline in the apparent specificity of MPS has been observed because of a post-test referral bias. The normalcy rate (the percentage of patients with below 5% likelihood of disease with a normal MPS) corrects for referral bias, and it is estimated at 91% (weighted mean).6
ECG-gated acquisition of MPS is now routine practice. In addition to information on left ventricular (LV) function, ECG-gating assists with the discrimination of true perfusion abnormality from artefact, particularly in case of inferior wall defects in men or anterior wall attenuation in women, with a significant reduction in the false positive rate.7,8 Moreover, the availability of ECG-gated images reduces the number of borderline ‘normal’ or ‘abnormal’ interpretations, thus increasing the accuracy up to 90%.9 Attenuation and scatter compensation also assists the detection of artefacts, further increasing the accuracy of MPS.10
Although MPS is effective in stratifying patients with intermediate likelihood of CAD according to their risk of cardiac events, its role as a primary diagnostic tool remains undefined, in particular with regard to women. The European Society of Cardiology (ESC) recognizes the superior diagnostic accuracy of MPS in women, and recommend its use as an alternative to exercise ECG provided that adequate resources and expertise are available.3 In contrast, the American College of Cardiology (ACC) and the American Heart Association (AHA) support the exercise ECG as the initial test but recommends stress imaging in subgroups including women with diabetes and those in whom a poor exercise performance is anticipated.4,11 As a secondary test, MPS is indicated in patients with non-diagnostic or unexpected exercise ECG results, i.e. patients with a low or high pre-test likelihood of CAD and an abnormal or normal exercise ECG, respectively.4 Because MPS adds prognostic information to exercise ECG results, both European and American guidelines recommend its use in patients with an intermediate risk Duke treadmill score.3,4
In patients with known CAD and prior coronary revascularization, all guidelines give MPS a class I indication as the initial test in patients presenting with continuing or recurrent chest pain.3–5 The usefulness of MPS in this population relies on its ability to define the site and severity of ischaemia, an important consideration for further management that cannot be assessed accurately by the exercise ECG. MPS also provides information on the probability of subsequent cardiac events and hence the need for intervention. The site and extent of inducible perfusion abnormalities on MPS reflects the anatomical distribution of a haemodynamically significant coronary stenosis. Therefore, the ESC and the ACC/AHA favour the use of MPS before coronary revascularization to estimate the severity of disease and identify the target lesion(s).3,4 This application is particularly relevant to the management of patients with angiographically moderate coronary stenoses and in those with lesions of uncertain functional significance. In addition, the ACC/AHA recognizes the effectiveness of selective MPS for risk stratification after percutaneous coronary intervention or coronary artery bypass grafting, particularly in patients with incomplete revascularization, proximal left anterior descending disease, diabetes, or other high-risk factors.12,13
The accuracy of MPS has been compared with that of stress echocardiography, generally showing MPS to have higher sensitivity and equivalent specificity (Figure 1).
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Prognostic value of myocardial perfusion scintigraphy in stable coronary artery disease |
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The value of MPS in assessing prognosis in patients with stable CAD has been established in large cohorts of patients with a variety of underlying risk profiles and pathologies. The following conclusions can be made.
- (i) Normal MPS in patients with intermediate to high likelihood of CAD predicts a very low event rate (
1%/year), leading to a negative predictive value 
99%.14,15
- (ii) Abnormal MPS in patients with intermediate to high likelihood of CAD increases the annualized event rate by a factor of 7, and the risk of events is related to the severity of perfusion abnormalities (from 3% annual death or myocardial infarction with mild to moderate perfusion defects up to 7% in patients with severe perfusion abnormalities).14–16
- (iii) In patients with a number of risk factors (diabetes, dyslipidaemia, hypertension) low event rates extend for at least 2 years and reassessment may be warranted thereafter.17
- (iv) Functional data from ECG-gated MPS are additional prognostic indicators with LV ejection fraction after stress
45% or end-systolic volume 70 mL indicating an adverse outcome even in the presence of mild inducible perfusion abnormalities.18
- (v) ECG-gated MPS provides additional prognostic information even when the clinical history, exercise ECG and coronary angiography are available. This has been shown in the general population, following an acute coronary syndrome and after revascularization.18
- (vi) Markers of LV dysfunction are more efficient in the prediction of death, whereas markers of ischaemia are better predictors of ischaemic events such as recurrent chest pain and non-fatal infarction.15
- (ii) Abnormal MPS in patients with intermediate to high likelihood of CAD increases the annualized event rate by a factor of 7, and the risk of events is related to the severity of perfusion abnormalities (from 3% annual death or myocardial infarction with mild to moderate perfusion defects up to 7% in patients with severe perfusion abnormalities).14–16
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Myocardial perfusion scintigraphy after acute coronary syndromes |
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Because of its ability to identify low-risk individuals among those presenting with acute chest pain and non-diagnostic ECG, acute resting MPS has received a class II indication for excluding acute infarction and ischaemia in this setting.19–21 Current guidelines also recommend MPS after an episode of unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI) for risk stratification, especially in patients with a low to intermediate likelihood of cardiac events according to traditional markers of risk. As in the stable setting, MPS should be performed selectively in patients unable to exercise adequately, in those with an inconclusive exercise ECG and in women.21
Before routine reperfusion therapy, MPS was more accurate than the exercise ECG for the prediction of cardiac events following an acute ST-segment elevation myocardial infarction (STEMI). Now that reperfusion is common practice, the reduced cardiac death and re-infarction rate might reduce the predictive value of MPS. However, recent studies have shown that both infarct size and the magnitude of inducible ischaemia are associated with an increased risk of adverse events after STEMI.22 Moreover, with the use of vasodilator stress agents, MPS can be performed safely 24–72 h after an uncomplicated STEMI allowing early risk assessment.23 Therefore, MPS is currently recommended in patients after STEMI who might have received thrombolytic therapy but who have not yet undergone coronary angiography to determine the extent of ischaemic myocardium before possible revascularization.5,24,25 For the same purpose, MPS should be used in patients with preserved LV function who have an uninterpretable ECG.24
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Myocardial perfusion scintigraphy before non-cardiac surgery |
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MPS has received a class I indication for risk stratification of patients undergoing elective non-cardiac surgery.26 Stress imaging is particularly effective in patients with intermediate clinical predictors of cardiac risk and either a reduced exercise tolerance [<4 metabolic equivalents (METs)] or a high surgical risk (Table 1). MPS with pharmacological stress is also effective in determining risk in patients with poor exercise capacity undergoing high-risk surgery regardless of clinical predictors.26 Information derived from MPS should be used not only for surgical risk stratification but also for the subsequent cardiac management of patients after the non-cardiac surgery.
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Myocardial perfusion scintigraphy for the assessment of viable and hibernating myocardium |
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A number of studies have demonstrated the role of MPS in the assessment of patients with CAD and LV dysfunction. Extensive dysfunctional but viable myocardium is associated with poor prognosis, which can be reversed by appropriate intervention. American guidelines incorporate non-invasive imaging for the assessment of viability and hibernation in the initial evaluation of heart failure patients with known CAD without angina (class IIa).27
Non-invasive imaging is also recommended for the detection of obstructive CAD in patients with symptomatic LV dysfunction. This indication is given a class IIb status by the American guidelines.27 The recently published European guidelines for the diagnosis and treatment of chronic heart failure have not commented on the role of viability assessment in patients with LV dysfunction28 although the subject has been reviewed by the ESC and recommendations made.29
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Cost-effectiveness of myocardial perfusion scintigraphy |
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Cost-effectiveness analysis combines the diagnostic accuracy of a particular test and the costs incurred in a test-led strategy.30 MPS is cost-effective in several settings because it is an outpatient investigation of moderate cost, high diagnostic accuracy and low risk.31–33
Stable angina in intermediate likelihood of coronary artery disease
Several economic models have shown that, in patients with stable angina and intermediate pre-test probability of CAD, MPS is more cost effective than the exercise ECG and X-ray coronary angiography. An MPS-led management strategy results in 23–41% cost-savings compared with direct referral to coronary angiography.15,34–36 Although upfront costs are higher with MPS than conventional exercise ECG, MPS is more cost effective because of its better diagnostic performance. Marwick et al.37 showed that a normal exercise ECG does not prevent additional diagnostic testing and causes an unexpected increase in the use of coronary angiography, whereas a normal MPS is a strong deterrent of additional investigations.38 In patients with known CAD, MPS may lead to significant savings by limiting costly therapeutic procedures to patients with high-risk scans who have the most to gain from intervention. The greatest cost-effectiveness of MPS is in women, resulting in a significant reduction in the number of normal coronary angiograms and an increase in the detection of patients with multivessel disease (from 23 to 42%).32,36–39
Acute coronary syndromes
The role of MPS as a gatekeeper to hospital admission for acute chest pain is well documented.40,41 MPS has a high negative predictive accuracy for ruling out acute coronary syndromes and future cardiac events (99 and 97%, respectively) in patients presenting to the emergency room with acute chest pain, non-diagnostic ECG and negative cardiac enzymes.42 In general, only one-third of patients with acute chest pain will have an underlying cardiac cause, and several studies have demonstrated that MPS can reduce costs by avoiding unnecessary admissions without compromising patient outcome.41 MPS results do influence triage decisions and lower the threshold for early discharge of patients with low-risk scans.43 Moreover, an MPS-guided chest pain work-up decreases the rates of hospitalization and ensuing admission diagnosis of ‘myocardial infarction excluded’.44,45 Recent studies suggest that MPS may be particularly cost-effective in special subgroups including patients with diabetes.46
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Safety |
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Radiation exposure
MPS exposes patients to ionizing radiation. The level of exposure varies depending upon the tracer used and the protocol employed. In general, the risk from radiation exposure must be balanced by the clinical benefit and the impact test results may have on patient outcome. The harmful effects of radiation exposure are related to the absorbed energy, with an additional lifetime risk of 0.04%/Sv of fatal cancer in young or middle-aged patients. In elderly patients, the risk is lower because of the delay between exposure and adverse event. The recently published EANM/ESC procedural guidelines for MPS recommend a total activity of 1600–2000 MBq for a 1-day MPS study with a technetium-99m-labelled tracer with corresponding effective doses in the region of 12 and 20 mSv.1,47 Activities between 600 and 900 MBq per scan per day are recommended for a 2-day imaging study with the same tracers, which corresponds to effective doses between 4.5 and 9 mSv. A stress-redistribution thallium-201 MPS protocol is associated with effective doses in the region of 12.9 and 19.5 mSv for 74–111 MBq of thallium-201 with an additional dose of 6.5 mSv (37 MBq) if stress-reinjection thallium-201 imaging is performed.1,47 Therefore, radiation exposure from a 1-day stress/rest MPS study with 1600 MBq (12 mSv) of technetium-99m-tetrofosmin is higher than that from a conventional X-ray coronary angiogram (2–6 mSv)48,49 but comparable to that from multi-detector CT coronary angiography (6–15 mSv).50,51 However, MPS is non-invasive and provides the functional effect of an atherosclerotic lesion.
Complications from stress tests
The complication rate of dynamic exercise (death, infarction, or sustained ventricular tachycardia) is 1.2 per 10 000 tests.52,53 The complication rate of pharmacological stress with dypiridamole or adenosine is comparable.54 Interestingly, the complication rate is low even shortly after an uncomplicated acute infarction (<3 days).23 A higher complication rate is reported using dobutamine (one severe adverse reaction every 335 tests in a meta-analysis of 26 438 patients).55
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Conclusions |
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MPS has proven a safe and highly cost-effective strategy for the early detection of obstructive CAD in symptomatic individuals. It is powerful to stratify patients according to their risk of cardiac death or nonfatal myocardial infarction and assists clinical decision-making with regard to medical treatment and intervention. A large body of evidence supports the current application of MPS, and radionuclide imaging guidelines have been established by multiple societies. Also, MPS is successfully integrated in several guidelines for clinical practice in cardiology. Further, formal integration of this diagnostic and prognostic tool into the clinical practice and training of general cardiology is encouraged.
Conflict of interest: none declared.
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