INDICATION OVERVIEW

Ischemia results from the inadequate supply of blood to an organ or tissue caused by blockage of the blood vessels to the area. Within the heart, this blockage is most often due to coronary atherosclerosis-related stenosis (narrowings). Myocardial ischemia (lack of blood flow to the heart) is the most common cause of symptoms of coronary heart disease — also referred to as coronary artery disease (CAD).¹ Prolonged or significant ischemic conditions in the heart may result in a myocardial infarction (MI) — that is, a heart attack — or sudden death. MIs contribute to heart failure. Therefore, diagnosis of CAD prior to a heart attack or other event is important. Symptoms of myocardial ischemia may include chest pain, shortness of breath, nausea and vomiting, palpitations, and sweating. In some cases, myocardial ischemia is not associated with any symptoms (silent ischemia).

In addition to clinical symptoms and laboratory testing, cardiac imaging is often used in patients suspected to have CAD. Imaging can assist not only in detecting ischemia and diagnosing CAD, but also in stratifying patients according to their risk of having an ischemic event — low, intermediate, or high. Risk stratification can assist physicians in planning patient management. Imaging in patients with known CAD is also performed to assess the extent of damage to the myocardium, or heart tissue. Patients with viable myocardium may benefit from revascularization,² a treatment that involves restoring the flow of blood to damaged areas of the myocardium.

Population: Patients with suspected CAD (for diagnosis and immediate treatment) or patients with known CAD undergoing risk stratification and subsequent treatment planning.

Intervention: Stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) with technetium-99m (^99mTc)

During cardiac nuclear imaging, the relative amount of the radioisotope that collects in the cardiac muscle is reflective of the areas of reduced blood flow and therefore areas of ischemia.³ This information can be used to help inform disease management and to determine risk for short- or long-term future cardiac events.³ The basic principle of radionuclide MPI is to administer a tracer labelled with a radioisotope (often thallium-201 [²⁰¹TI] or technetium-99m [^99mTc] sestamibi or tetrafosmin) intravenously and image blood flow to the heart muscle (myocardial perfusion), both at rest and under stress conditions. Stress is induced by either exercise or a pharmaceutical agent (e.g., dobutamine, dipyridamole, or adenosine), which increases coronary blood flow to the myocardium.⁴ Viable myocardial cells take up the radionuclide tracer in proportion to blood flow.^4,5 Through sequential image acquisition, the gamma camera works with a computer to evaluate perfusion of the cardiac muscle.⁶

Comparators: For this report, the following diagnostic tests are considered as alternatives to MPI using ^99mTc:

• Computed tomography (CT) angiography (CTA): In a CT scan, a rotating X-ray device moves around the patient and takes detailed multiple images of organs and body parts⁷ and reconstructs them into a three-dimensional (3-D) image. This series of X-rays images are often referred to as “slices,” and are taken from varying angles in order to reconstruct a 3-D image of the heart’s anatomy. A contrast agent is administered intravenously before images are taken, to better visualize the body part being examined;⁷ a sedative may also be administered if the patient is uncomfortable.⁸
• Stress echocardiogram (Echo, ECG; also called stress test): During stress Echo, adhesive electrodes are placed onto the bare chest of the patient and a sonographer takes several ultrasound (U/S) images of the heart while the patient is at rest. Blood pressure and Echo recordings are also measured at rest. The exercise-induced phase involves the patient engaging in physical activity (e.g., walking or running on the treadmill, pedalling a stationary bike) and the recording of blood pressure. In some cases when exercise is not an option for the patient, a pharmacological stressor may be used to simulate the stress of exercise. Following the stress phase, the patient is instructed to lie down again, and U/S images of the heart are taken a second time, as are blood pressure and Echo measurements.⁹
• Stress MPI using ²⁰¹Tl: The procedure for ²⁰¹Tl-SPECT is the same as ^99mTc-SPECT, except the isotope ²⁰¹Tl is used in place of ^99mTc.
• Stress magnetic resonance imaging (MRI): A cardiac MRI uses magnets and a computer to reproduce images of the organs and tissues while the heart is beating.¹⁰ As with other cardiac imaging approaches, patients are assessed under rest and stress conditions. During an MRI examination, a patient is required to lie down on a table that glides into the scanner’s cavity. The patient is required to lie still for the duration of the examination, which ranges from 15 minutes to over an hour.¹¹
• Stress positron emission tomography (PET): PET perfusion studies use radiopharmaceuticals (Rubidium-82 chloride, ¹⁵O-labelled water, and ¹³N-labelled ammonia [¹³NH₃]) to visualize how well blood flows to the heart. The radiopharmaceutical is administered intravenously while the patient lies under the camera. Images are then taken for 10 to 20 minutes. To induce stress-related symptoms, a drug (e.g., dobutamine, dipyridamole, or adenosine) is administered. The patient lies still again for 10 to 20 minutes while additional images are taken. A second drug (aminophylline) is given at the end of the test to reverse the effects of the pharmacological stressor. The total duration of the test is approximately one hour.¹²

It is recognized that treadmill alone may be sufficient to diagnose ischemia, in some cases. For the purpose of this report, however, we have assumed that the need for imaging has been predetermined. Treadmill testing, therefore, is not included as a comparator in this report.

Outcomes: Eleven outcomes (referred to as criteria) are considered in this report:

• Criterion 1: Size of the affected population
• Criterion 2 : Timeliness and urgency of test results in planning patient management
• Criterion 3: Impact of not performing a diagnostic imaging test on mortality related to the underlying condition
• Criterion 4: Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition
• Criterion 5: Relative impact on health disparities
• Criterion 6: Relative acceptability of the test to patients
• Criterion 7: Relative diagnostic accuracy of the test
• Criterion 8: Relative risks associated with the test
• Criterion 9: Relative availability of personnel with expertise and experience required for the test
• Criterion 10: Accessibility of alternative tests (equipment and wait times)
• Criterion 11: Relative cost of the test.

Definitions of the criteria are in Appendix 1.

METHODS

The literature search was performed by an information specialist using a peer-reviewed search strategy.

Published literature was identified by searching the following bibliographic databases: MEDLINE with In-Process records & daily updates via Ovid; The Cochrane Library (2011, Issue 3) via Wiley; and PubMed. The search strategy consisted of both controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. The main search concepts were radionuclide imaging and myocardial ischemia.

Methodological filters were applied to limit retrieval to health technology assessments (HTA), systematic reviews (SR), meta-analyses (MA), and diagnostic accuracy studies (primary studies of randomized and non-randomized design). Where possible, retrieval was limited to the human population. The search was also limited to the English language. No date limits were applied for the systematic review search. The primary studies search was limited to the human population and to documents published between January 1, 2006 and March 29, 2011. Regular alerts were established to update the search until October 2011. Detailed search strategies are located in Appendix 2.

Grey literature (literature that is not commercially published) was identified by searching relevant sections of the CADTH Grey Matters checklist. Google was used to search for additional web-based materials. The searches were supplemented by reviewing the bibliographies of key papers. See Appendix 2 for more information on the grey literature search strategy.

Targeted searches were done as required for the criteria, using the aforementioned databases and Internet search engines. When no literature was identified that addressed specific criteria, experts were consulted.

SEARCH RESULTS

The literature search identified 131 health technology assessments/systematic reviews/meta-analyses and 1,107 primary studies. Forty-one of the 131 health technology assessments/systematic reviews/meta-analyses (HTA/SR/MA) articles identified underwent full-text screening. These included a series of seven reports published in 2010 from the Ontario Ministry of Health and Long-Term Care Medical Advisory Secretariat (MAS)^13–19 to assist the Ministry in providing an evidentiary platform for the effectiveness and cost-effectiveness of non-invasive cardiac imaging technologies. These reports were reviewed and summarized, as each consisted of a meta-analysis of research from over the past six to seven years (2004 to 2009).

One-hundred and thirty-eight of the 1,107 primary studies identified in the search underwent full-text screening. A total of 17 studies related to the criterion of diagnostic accuracy were included in the final report.^20–36 For the detection of ischemia, primary studies were excluded if they were published before the search date for the MAS reports (i.e., eligible for inclusion in the MAS report), with the exception of: primary studies comparing ^99mTc-based imaging to PET imaging, as this was not an eligible comparison in the MAS reports; if sensitivity and specificity outcomes were not reported; if the purpose of the study was to evaluate the accuracy of SPECT using ^99mTc alone and in combination with another imaging modality (e.g., ^99mTc-SPECT versus ^99mTc-SPECT/CT), if both ^99mTc-SPECT and ²⁰¹TI-SPECT were used in a study and separate analyses for the isotopes were not provided; or, if the primary study was already evaluated in one of the five MAS reports. For the evaluation of myocardial viability, inclusion was limited to studies in which ^99mTc-based imaging was compared directly with another cardiac imaging modality. Studies that were included in the MAS reports on myocardial viability on MRI and PET were not assessed separately in the current report.

SUMMARY TABLE

Table 1. Summary of Criterion Evidence (PDF, 242K)

CRITERION 3: Impact of not performing a diagnostic imaging test on mortality related to the underlying condition (link to definition)

A report published by the Public Health Agency of Canada states that ischemic heart disease was responsible for 39,311 deaths (17.3% of all deaths) in 2004.³⁷ The rate of death is higher in men than in women and increases with age.

The Myoview Prognosis Registry provides data on 7,849 outpatients (from five tertiary medical centres in the United States) evaluated by stress MPI for suspected, or known, CAD.⁵⁹ A 2008 publication, based on data from this registry, investigated the relationship between cardiovascular outcomes and the extent and severity of ischemia, as well as perfusion defects on the resting MPI.⁵⁹ In two years of follow-up, 274 deaths were reported (3.5% of the study population) including 29 fatal MIs, 72 sudden cardiac deaths, 14 heart failures, and 16 fatal cerebrovascular accidents.⁵⁹ Although the study population was stratified by per cent ischemic myocardium (73% of the study cohort had 0% ischemic myocardium, 11% had 1% to 4.9% ischemic myocardium, 9% had 5% to 9.9% ischemic myocardium, and 7% had > 10% ischemic myocardium), the mortality rates for these subgroups were not reported.⁵⁹ It was noted that rest and ischemic defects on MPI were highly significant (P < 0.0001) estimators of the combined end point of CAD-related events (including fatal MI, non-fatal MI, and sickle-cell disease) according to univariate Cox models.⁵⁹ An earlier publication, based on this registry, reported that the annualized cardiac death rate among patients with a normal perfusion scan is less than one per cent.⁶⁰

A 2003 publication by Hachamovitch et al.⁶¹ compared the survival benefit associated with revascularization versus medical therapy. The final study population included 10,627 patients who underwent exercise or adenosine stress myocardial perfusion scintigraphy between 1991 and March 1997.⁶¹ The majority (n = 9,956) were prescribed medical therapy, while 671 patients underwent early revascularization.⁶¹ Patients were followed for an average of 1.9 years with cardiac death as the sole end point.⁶¹ The rate of cardiac death among revascularized patients was 2.8% versus 1.3% among the medical therapy group; however, the baseline characteristics of the two groups were found to differ significantly.⁶¹ Propensity scores were calculated, using logistic regression, in order to adjust for the lack of randomization.⁶¹ A Cox proportional hazards model was used to predict mortality rates in patients treated with revascularization versus medical therapy.⁶¹ The model predicted that patient mortality rates among those treated medically would increase significantly as a function of per cent myocardium ischemic, but that increased per cent myocardium ischemic would not be associated with an increase in mortality among revascularized patients (Table 2). This study highlights the importance of detecting and quantifying ischemia.

Table 2

Predicted Mortality Rates in Non-diabetic Patients Treated with Revascularization Versus Medical Therapy Based on Cox Proportional Hazards Model.

Overall, limited information was available to directly inform this criterion. Patients with intermediate pre-test likelihood of disease are most likely to benefit from a diagnostic and prognostic perspective, but high pre-test likelihood patients will also benefit from a prognostic perspective (Medical Isotopes and Imaging Modalities Advisory Committee [MIIMAC] expert opinion).

Return to Summary Table.

CRITERION 7: Relative diagnostic accuracy of the test (link to definition)

The literature search for health technology assessments (HTA)/systematic reviews/meta-analyses identified 131 studies, five of which are included in the current report.^15–19 These HTAs evaluated the use of non-invasive cardiac imaging technologies including stress Echo (with and without contrast agent),^13,14 MRI,¹⁵ CT,¹⁶ and SPECT¹⁷ for the diagnosis of CAD.

The literature search for primary studies identified 1,107 titles. When limited by date (so that only those studies published following the end of the search period of the corresponding HTA were included), 138 underwent full-text screening, and nine non-randomized studies were included in the final report.^20–28 No randomized controlled trials that met inclusion criteria were identified.

A summary of two position statements not meeting inclusion criteria — one a joint position statement published in 2007 by the Canadian Cardiovascular Society (CCS), Canadian Association of Radiologists, Canadian Association of Nuclear Medicine, Canadian Cardiovascular Society, and the Canadian Society of Cardiovascular Magnetic Resonance on the use of PET, MRI, and CT in the diagnosis of ischemic heart disease,⁶⁵ and a second released jointly in 2011 by the European Association of Nuclear Medicine, the European Society of Cardiac Radiology, and the European Council of Nuclear Cardiology on the use of hybrid cardiac imaging with SPECT or PET combined with CT (SPECT/CT, PET/CT) to image anatomical and physiologic cardiac abnormalities in a single setting⁶⁶ — is provided in Appendix 3 as background information. The Canadian position statement⁶⁵ was based on a systematic review of the literature relating to PET, MRI, and CT; however, it did not assess ^99mTc-SPECT. The European consensus statement discussed SPECT/CT hybrid technology.

Health technology assessments

In July 2009, MAS of the Ontario Ministry of Health and Long-Term Care began an evidence-based review of the literature surrounding cardiac imaging modalities. Systematic reviews, meta-analyses, randomized controlled trials, prospective observational trials, and retrospective analyses with a sample size of 20 or more patients were included; non-systematic reviews, case reports, grey literature, and abstracts were excluded. The interventions of interest were cardiac MRI, SPECT (using ^99mTc or ²⁰¹Tl), 64-slice computed tomographic coronary angiography (CTCA), stress echocardiography, and stress echocardiography with contrast. The comparator was coronary angiography (CA). The outcomes of interest were accuracy, adverse events, and costs. The use of imaging for risk stratification purposes was not considered as part of the reports. A summary of the findings of the MAS reports on the use of non-invasive cardiac imaging technologies for the diagnosis of coronary artery disease^13–17 can be found in Appendix 4.

^99mTc-SPECT MPI versus coronary angiography

A review of the literature was completed to assess the diagnostic accuracy of SPECT, in comparison to CA, for the diagnosis of CAD.¹⁷ From the search period of January 1, 2004 to August 22, 2009, a total of 86 studies (10,870 patients) were analyzed by MAS.¹⁷ For the purpose of this report, the results for ^99mTc-SPECT and ²⁰¹TI-SPECT are reported separately.¹⁷ A total of 39 (n = 3,488) studies looked exclusively at ^99mTc-SPECT in comparison with CA.¹⁷ The pooled sensitivity and specificity of ^99mTc-SPECT, relative to CA, in the diagnosis of CAD were 88% and 70%, respectively.¹⁷ It is not clear from the report whether the included studies considered recent technological advances in SPECT with attenuation correction.

The diagnostic accuracies of the five imaging modalities were calculated against the reference standard of coronary angiography; therefore, the evidence relating to each of the modalities is presented in this report.

CTCA versus CA

A review of the literature to assess the diagnostic accuracy of 64-slice CTCA, compared with CA, in the diagnosis of CAD in stable symptomatic patients was completed.¹⁶ From the search period of January 1, 2004 to July 20, 2009, a total of eight studies (1,513 patients) were included in the review.¹⁶ The pooled sensitivity and specificity of CTCA, relative to CA, in the diagnosis of CAD, were 97.7% and 78.8%, respectively.¹⁶ In February 2010, results of the Ontario Multidetector Coronary Angiography Study (OMCAS) were made available.¹⁶ This non-randomized double-blinded study (n=169) evaluated CTCA versus CA in the diagnosis of CAD and found the sensitivity of CTCA versus CA to be 81.2% and the specificity to be 95.8%.¹⁶ When the OMCAS results were added to the MAS meta-analysis, the specificity of CTCA was greater (81.5%), while the sensitivity dropped to 96.1%.¹⁶

²⁰¹TI-SPECT MPI versus CA

A total of 24 studies (n = 3,338) included in the MAS SPECT review evaluated ²⁰¹TI-SPECT in comparison with CA.¹⁷ The pooled sensitivity and specificity of ²⁰¹TI-SPECT, relative to CA, in the diagnosis of CAD were 84% and 71%, respectively.¹⁷

Stress Echo (with and without contrast) versus CA

A review of the literature was completed to assess the diagnostic accuracy of stress Echo, in comparison with CA, for the diagnosis of CAD.¹⁴ From the search period of January 1, 2004 to August 22, 2009, 127 studies (13,035 patients) were included in the review.¹⁴ The available evidence was pooled and the overall results indicated a sensitivity of 80% and a specificity of 84%.¹⁴ These estimates may not be generalizable outside of the setting of a strong research laboratory as stress Echo has been associated with low reproducibility (MIIMAC expert opinion).

A second report published by MAS evaluated contrast Echo, in comparison with CA, for the diagnosis of CAD.¹³ In patients with suspected CAD, in only (11 studies), the pooled sensitivity and specificity were 87%, and 86%, respectively.¹³ Twelve studies evaluated the diagnostic accuracy of contrast Echo in patients with suspected or known CAD — six based on myocardial perfusion analysis (MPA) and six based on wall motion analysis (WMA).¹³ When results from the MPA studies were pooled, the sensitivity was 88% and the specificity was 65%.¹³ The pooled WMA results indicated a sensitivity of 69% and a specificity of 79%.¹³

Stress MRI versus CA

A review of the literature was completed to assess the diagnostic accuracy of stress MRI, compared with CA, in the diagnosis of CAD.¹⁵ From the search period of January 1, 2005 to October 9, 2008, one meta-analysis and 11 primary studies were found.¹⁵ The studies from the meta-analysis were pooled with the new literature for a total of 37 studies using MPA and WMA imaging.¹⁵ The pooled results for diagnostic accuracy including MPA produced a sensitivity of 91% and a specificity of 79%.¹⁵ Regarding the WMA, the pooled sensitivity and specificity were 81% and 85%.¹⁵

Primary studies

The MAS report reviewed the available literature for the diagnostic accuracy of SPECT in comparison with CA for the diagnosis of CAD (January 1, 2004 to August 22, 2009). A search for studies published after August 2009 identified five studies on the relative diagnostic accuracy of ^99mTc-SPECT, as it pertains to the diagnosis of ischemia.^{20–22,27,28} In addition, four studies^23–26 reported the diagnostic accuracy of one or more comparators in the diagnosis of ischemia, using ^99mTc–SPECT as the gold standard.

^99mTc-SPECT/CTA versus CA

A recent study by Kong et al. (2011)²⁰ compared the diagnostic accuracy of ^99mTc sestamibi SPECT/CTA 3-D fusion with that of invasive CA.²⁰ One-hundred and four patients (mean age: 63.6 years) with typical or atypical angina symptoms were included in this retrospective analysis.²⁰ SPECT/CTA, in comparison with CA, yielded a sensitivity of 100% and a specificity of 80.8%.²⁰ The positive predictive value and the negative predictive value of the test were 94% and 100%, respectively.²⁰ The authors stated that the results of this study support the use of SPECT/CTA for the diagnosis of CAD.²⁰

Also in 2011, Weustink et al.²¹ compared the diagnostic accuracy of bicycle testing/ CTCA (also referred to as CTA) and ^99mTc-sestamibi SPECT/CTCA in the diagnosis of CAD, using invasive CA as the gold standard.²¹ Three-hundred and seventy-six symptomatic patients (mean age: 60.4) participated in the study.²¹ A comparison between bicycle testing and SPECT was not made. In patients who underwent SPECT (n = 61), the sensitivity of SPECT (89%) was found to be statistically significantly less than that of CTCA (98%) (P= 0.021). CTCA was more specific than SPECT (82% compared to 77%), but this difference was not statistically significant (P = 1.0).²¹ The authors concluded that the results of this study demonstrate a high diagnostic performance for CT and SPECT.²¹

^99mTc –SPECT and stress Echo versus CA

In 2010, Lu et al.²² evaluated the diagnostic accuracy of SPECT (^99mTc sestamibi), stress Echo (dipyridamole and dobutamine), and CA for the detection of CAD in a population of 76 female hypertensive patients (mean age: 60 years) with no previous MI or history of CAD.²² CA was used as the reference standard.²² The results of this prospective study are provided in Table 3. The authors suggested that, based on these results, dobutamine Echo should be used as a first-line diagnostic in women with suspected CAD, due to its high diagnostic value.²²

Table 3

Relative Diagnostic Accuracy of SPECT and Echo for the Diagnosis of CAD in Female Hypertensive Patients.

CTCA versus ^99mTc –SPECT

A 2010 study by Cheng et al.²³ compared the relative diagnostic accuracy of dual-source CTCA (DS-CTCA) to gated SPECT (^99mTc tetrofosmin). A total of 55 patients had clinical symptoms of CAD (e.g., chest pain, shortness of breath), were asymptomatic but had risk factors, or had known CAD.²³ The mean age of the population was 60.7 years and the majority of the patients were male (58%).²³ All patients underwent both ^99mTc –SPECT and DS-CTCA.²³ A diagnosis of CAD was noted on the DS-CTCA if stenosis was a minimum of 50%, and was compared with SPECT at rest and during stress.²³ Compared to SPECT at rest, the sensitivity, specificity, and accuracy of DS-CTCA were 100%, 78%, and 83.6%.²³ Compared to SPECT using stress conditions, the sensitivity, specificity, and accuracy of DS-CTCA were 83.3%, 90.3%, and 87.3%.²³ However, when rest/stress-SPECT was used as the reference standard, the sensitivity of DS-CTCA to detect high-grade stenosis (a minimum of 50%) was 59% and the specificity was 89%. There was a lack of correlation between DS-CTCA and SPECT findings. The authors concluded that DS-CTCA may provide additional information regarding perfusion defects first identified by ^99mTc-SPECT.

A 2009 study by Bauer et al.²⁴ was conducted to determine the correlation between the diagnostic accuracy of 64-slice multidetector computed tomography (MDCT, referred to as CT) readings of calcification in comparison with ischemia detected by ^99mTc-SPECT with ^99mTc tetrofosmin.²⁴ Seventy-two patients with known (n = 23) or suspected (n = 49) CAD underwent CT angiography and stress-rest SPECT.²⁴ Stenosis was classified as insignificant (< 50%), significant (≥ 50%), or severe (≥ 70%) based on CT imaging.²⁴ SPECT images were reviewed for the presence of reversible and fixed perfusion defects.²⁴ Patient-based and vessel-based results were presented.²⁴ When the diagnostic outcomes were evaluated at the patient level for any perfusion defect on SPECT and ≥ 50% stenosis on CT, the sensitivity and specificity were 46% and 83%.²⁴ When the diagnostic outcomes were evaluated at the patient level for any perfusion defect on SPECT and ≥ 70% stenosis on CT, the sensitivity and specificity were 38% and 98%, respectively.²⁴ When the data was evaluated for reversible perfusion defects on SPECT compared with ≥50% stenosis on CT, the sensitivity and specificity were 33% and 83%, respectively.²⁴ The comparison between ≥ 70% stenosis on CT and the presence of reversible perfusion defects on SPECT provided a sensitivity estimate of 25% and specificity estimate of 98%.²⁴ The authors concluded that the degree of stenosis as determined by CT was not a reliable predictor of ischemia at stress-rest SPECT in this heterogeneous, clinically-representative patient group.²⁴

The performance of dual source dual energy computed tomography (DECT) for the integrative imaging of the coronary arteries was evaluated by Ruzsics et al.²⁵ in 2009. A total of 36 patients with known (n = 9) or suspected (n = 27) CAD were evaluated for a diagnosis of CAD with stenosis ≥ 50%.²⁵ DECT and ^99mTc-SPECT with tetrofosmin were performed in all patients and the images were compared for perfusion defects (fixed and reversible).²⁵ When the diagnostic outcomes were evaluated at the patient level for any perfusion defect on SPECT and ≥ 50% stenosis on CT, the sensitivity and specificity were 97% and 67% (as in Table 6).²⁵ When the data were evaluated for reversible perfusion defects on SPECT compared with ≥ 50% stenosis on CT, the sensitivity and specificity were 100% and 67%.²⁵ Data evaluated for fixed perfusion defects on SPECT compared with ≥ 50% stenosis on CT provided a sensitivity estimate of 94% and a specificity estimate of 67%.²⁵ The authors noted that, although their findings for DECT compared with SPECT were favourable, the study was limited by the small sample size and a higher prevalence of CAD than would be found in the general population.²⁵

Table 6

Diagnostic Imaging Equipment in Canada.

Stress Echo versus ^99mTc –SPECT

Abdelmoneim et al.²⁶ evaluated the diagnostic accuracy of stress Echo, compared with SPECT (^99mTc sestamibi). Patients (n = 88) with known or suspected CAD underwent both stress Echo (adenosine) with contrast and SPECT.²⁶ The images for both tests were interpreted and compared.²⁶ Coronary deficiencies in Echo were interpreted by wall motion analysis (WMA) or real-time perfusion using myocardial contrast echocardiography (MCE) techniques.²⁶ In total, 88 patients were included in the final analysis of MCE and 73 patients for final analysis of WMA.²⁶ In comparison with SPECT, the sensitivity and specificity of stress Echo were determined to be 88% and 85%.²⁶ The authors concluded that adenosine MCE in real time is effective in the detection of myocardial defects.²⁶

^99mTc-SPECT versus PET

Husmann et al.²⁷ compared the diagnostic accuracy of MPI with PET or SPECT in two comparable patient cohorts with known or suspected CAD, using coronary angiography as the gold standard. The SPECT group consisted of 80 patients (15 female, 65 male; mean age 60 ± 9 years) and the ¹³NH₃-PET group consisted of 70 patients (14 female, 56 male; mean age 57 ± 10 years). The SPECT group included patients who received either ²⁰¹Tl chloride or ^99mTc sestamibi. Coronary angiography findings did not significantly differ between groups. All patients underwent a one-day stress/rest protocol. PET and SPECT images were transferred to external workstations and evaluated by two independent observers blinded to results of the angiography. In the detection of CAD, the overall sensitivity of SPECT was 85% compared with 96% for PET. For the SPECT group, the overall sensitivity and specificity for localization of stensosis was 77% and 84%, respectively. Comparatively, in the PET group, the sensitivity was 97% and the specificity 84%. For the detection of ischemia, the specificity was 74% for SPECT and 91% for PET. Husmann et al. concluded that MPI with ¹³NH₃-PET is more sensitive in the detection and localization of coronary stenosis, and more specific in the detection of ischemia than MPI using SPECT with either ^99mTc or ²⁰¹Tl. The Husmann et al. study was included in this report despite the fact that the authors did not provide separate analyses for ^99mTc and ²⁰¹Tl. It is possible that the sensitivity and specificity of ^99mTc is lower or higher than the pooled value. This study was included based on the limited available information for comparing ^99mTc-based imaging to PET; however, the limitations of the study should be noted.

Bateman et al. (2006)²⁸ compared the diagnostic accuracy of ^99mTc sestamibi SPECT and ⁸²Rb-PET for MPI of patients matched by gender, body mass index, and presence and extent of coronary disease.²⁸ Included patients were identified retrospectively from an electronic nuclear cardiology database and were categorized as having a low likelihood for CAD (n = 27) or had coronary angiography within 60 days (n = 27). Four experienced nuclear medicine cardiologists blinded to patients’ clinical information interpreted scans obtained from 112 ^99mTc-SPECT and 112 ⁸²Rb-PET Echo-gated rest/pharmacologic stress studies. By consensus, the quality of the perfusion images were deemed superior with PET (78% and 79% for rest and stress scans, respectively) than SPECT (62% and 62%; both P > 0.05). Interpretive certainty was also rated higher with PET versus SPECT scans (96% versus 81%, P = 0.001). Diagnostic accuracy was better for PET over SPECT — for patients with a stenosis severity of 70% by angiography, the sensitivity was 82% for SPECT and 87% for PET (P = 0.41) and the specificity was 73% for SPECT versus 93% for PET (P = 0.02), resulting in a significant improvement in overall accuracy by PET (89% versus 79%, P = 0.03). For patients with 50% stenosis, the respective comparative accuracy was 71% for SPECT versus 87% for PET (P = 0.003). Bateman and colleagues conclude that for this patient population, a major benefit of PET over SPECT is higher diagnostic accuracy.

Return to Summary Table.

CRITERION 8: Relative risks associated with the test (link to definition)

Non–radiation-related risks

Cardiac Stress Tests

The main risks of non-invasive preoperative assessment relate to the stress component of the tests:

• With exercise stress testing, there is a small risk of the patient sustaining an MI if they have significant coronary artery disease.⁴²
• With dipyridamole stress testing, there are multiple potential side effects, including headache, exacerbated asthma, and heart attack (risk of this event is low).⁴²
• With adenosine stress testing, side effects similar to dipyridamole may be experienced. Symptoms of chest pain or pressure may also occur, but these side effects go away quickly once the adenosine administration stops.⁴²
• With dobutamine stress testing, some patients may experience light-headedness and nausea. There is a theoretical risk of inducing a fast and abnormal cardiac rhythm (i.e., atrial fibrillation, ventricular tachycardia, ventricular fibrillation); however, this is unlikely with the doses of dobutamine used. A slight risk of MI exists.⁴²

The overall risk of sustaining a heart attack from a stress test is estimated to be about 2 to 4 in 10,000.⁴²

Stress SPECT

Apart from risks associated with stress testing, a review of undesirable events with radiopharmaceuticals reported anaphylactic reactions and erythema multiforme (i.e., a type of skin reaction) with sestamibi, although these reactions may be rare.⁴³

CTCA

Some patients may experience an allergic reaction to the contrast agent (if required), which may worsen with repeated exposure.⁶⁷ In addition, patients may experience mild side effects such as nausea, vomiting, or hives from the contrast agent. A 2009 retrospective review of all intravascular doses of low-osmolar iodinated and gadolinium (Gd) contrast materials administered at the Mayo Clinic between 2002 and 2006 (456,930 doses) found that 0.15% of patients given CT contrast material experienced side effects, most of which were mild. A serious side effect was experienced by 0.005% of patients.⁶⁸ CT is contraindicated in patients with elevated heart rate, hypercalcemia, and impaired renal function. Patients must be able to take rate-lowering medications. Although rarely used in cardiac imaging, Gd is contraindicated in patients with renal failure or end-stage renal disease, as they are at risk of nephrogenic systemic fibrosis. According to the American College of Radiology Manual on Contrast Media,⁴⁴ the frequency of severe, life-threatening reactions with Gd are extremely rare (0.001% to 0.01%). Moderate reactions resembling an allergic response (i.e., rash, hives, urticaria) are also very unusual and range in frequency from 0.004% to 0.7%.⁴⁴

Stress Echo

Apart from risks associated with stress testing, three relatively large studies — with sample sizes of 42,408 patients (2009),⁶⁹ 26,774 patients (2009),⁷⁰ and 5069 patients (2008)⁷¹ — compared cardiac outcomes (non-fatal MI or death) between patients who underwent contrast-enhanced Echo with patients who had an Echo without contrast. All three studies concluded that the risk of an adverse event is low and is no different than for patients who received no contrast. No additional risks associated with Echo were identifed.

Stress MRI

Apart from risks associated with stress testing, MRI is contraindicated in patients with metallic implants including pacemakers.⁷² MRI is often used in conjunction with the contrast agent Gd. Some patients may experience an allergic reaction to the contrast agent (if required), which may worsen with repeated exposure.⁶⁷ Side effects of Gd include headaches, nausea, and metallic taste. Gd is contraindicated in patients with renal failure or end-stage renal disease, as they are at risk of nephrogenic systemic fibrosis. According to the American College of Radiology Manual on Contrast Media,⁴⁴ the frequency of severe, life-threatening reactions with Gd are extremely rare (0.001% to 0.01%). Moderate reactions resembling an allergic response (i.e., rash, hives, urticaria) are also very unusual and range in frequency from 0.004% to 0.7%.⁴⁴

Stress PET

The Pharmacopeia Committee of the Society of Nuclear Medicine conducted a four-year prospective evaluation of adverse reactions to PET and reported no adverse reactions among the 33,925 scans conducted in 22 participating PET centres in the United States.⁴⁵ The risks associated with stress testing would apply for cardiac imaging using PET.

Radiation-related Risks

Among the modalities to diagnose ischemia, SPECT MPI, CTCA, and stress PET expose the patient to ionizing radiation. The average effective dose of radiation delivered with each of these procedures can be found in Table 4.

Table 4

Effective Doses of Radiation.

Return to Summary Table.

CRITERION 9: Relative availability of personnel with expertise and experience required for the test (link to definition)

The personnel required for the performance of the imaging tests to detect ischemia are presented by imaging modality. A summary of the availability of personnel required to detect ischemia, by SPECT or any of the alternative imaging modalities, is provided in Table 5.

Table 5

Medical Imaging Professionals in Canada, 2007.

^99mTc-labelled radiotracer SPECT MPI

In Canada, physicians involved in the performance, supervision, and interpretation of cardiac nuclear imaging (specifically MPI using ^99mTc-labelled radiotracer) should be nuclear medicine physicians with particular expertise in nuclear cardiology (nuclear cardiologists). Cardiologists also provide much of the nuclear cardiology services. According to the Canadian Medical Association (CMA), there are 1,149 practising cardiologists in Canada (CMA, 2011).

Nuclear medicine technologists are required to conduct MPI. Technologists must be certified by the Canadian Association of Medical Radiation Technologists (CAMRT) or an equivalent. A stress technologist or dedicated physician should be on hand to monitor any procedures involving stress testing.

All alternative imaging modalities

In Canada, physicians involved in the performance, supervision, and interpretation of diagnostic CT scans, MRI, and ultrasound should be diagnostic radiologists⁵⁵ and must have a Fellowship or Certification in Diagnostic Radiology with the Royal College of Physicians and Surgeons of Canada and/or the Collège des médecins du Québec. Foreign-trained radiologists also are qualified if they are certified by a recognized certifying body and hold a valid provincial license.⁷³ According to the CMA, there are 1,149 practicing cardiologists in Canada (CMA, 2011).

Medical radiation technologists (MRTs) must be certified by the CAMRT, or an equivalent licensing body. A stress technologist or dedicated physician should be on hand to monitor any procedures involving stress testing.

Service engineers are needed for system installation, calibration, and preventive maintenance of the imaging equipment at regularly scheduled intervals. The service engineer's qualification will be ensured by the corporation responsible for service and the manufacturer of the equipment used at the site.

Qualified medical physicists (on site or contracted-part time) should be available for the installation, testing, and ongoing quality control of CT scanners, MR scanners, and nuclear medicine equipment.⁷³

CTCA

CTCA is a CT-based test. Cardiologists provide much of the CTCA service. According to the CMA, there are 1,149 practicing cardiologists in Canada (CMA, 2011).

For the performance of CT scan, medical radiation technologists who are certified by the CAMRT, or an equivalent licensing body recognized by the CAMRT, are required. The training of technologists specifically engaged in CT should meet with the applicable and valid national and provincial specialty qualifications.

Stress Echo

Echo is a U/S based test. Cardiologists provide much of the Echo service. A 2002 report by the CCS reported that 43% of cardiologists do Echo. According to the CMA, there are 1,149 practicing cardiologists in Canada (CMA, 2011). It is assumed that less than 500 of them do Echo.

Sonographers (or ultrasonographers) should be graduates of an accredited school of sonography or have obtained certification by the Canadian Association of Registered Diagnostic Ultrasound Professionals. They should be members of their national or provincial professional organization. Sonography specialties include general sonography, vascular sonography, and cardiac sonography.⁵⁵ In Quebec, sonographers and medical radiation technologists are grouped together; in the rest of Canada, sonographers are considered a distinct professional group.⁵⁵ A stress technologist or dedicated physician should be on hand to monitor any procedures involving stress testing.

Stress MRI

Medical technologists must have CAMRT certification in magnetic resonance or be certified by an equivalent licensing body recognized by CAMRT. A stress technologist or dedicated physician should be on hand to monitor any procedures involving stress testing.

Stress PET

In Canada, physicians involved in stress PET scanning should be nuclear medicine physicians, nuclear cardiologists, or cardiologists with training and expertise in nuclear imaging. In Canada, physicians who perform PET imaging studies must be certified by either the Royal College of Physicians and Surgeons of Canada or le Collège des médecins du Quebec.

Technologists must be certified by CAMRT or an equivalent licensing body. A stress technologist or dedicated physician should be on hand to monitor any procedures involving stress testing.

Return to Summary Table.

CRITERION 11: Relative cost of the test (link to definition)

Fee codes from the Ontario Schedule of Benefits were used to estimate the relative costs of SPECT MPI and its alternatives. Technical fees are intended to cover costs incurred by the hospital (i.e., radiopharmaceutical costs, medical/surgical supplies, and non-physician salaries). Maintenance fees are not billed to OHIP — estimates here were provided by St. Michael’s Hospital in Toronto. Certain procedures (i.e., PET scan, CT scan, MRI scan) are paid for, in part, out of the hospital’s global budget; these estimates were provided by The Ottawa Hospital. It is understood that the relative costs of imaging will vary from one institution to the next.

According to our estimates (Table 7), the cost of MPI with ^99mTc-based radioisotopes is $964.53. The cost of MPI with ²⁰¹TI or with PET is assumed to be greater than imaging with ^99mTc-based radioisotopes. Stress MRI is minimally less costly than MPI with ^99mTc. CTCA and stress Echo are moderately less costly.

Table 7

Cost Estimates Based on the Ontario Schedule of Benefits for Physician Services Under the Health Insurance Act (September 2011).

Return to Summary Table.

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APPENDICES