INDICATION OVERVIEW

Sudden cardiac arrest (SCA) is defined as an abrupt loss of consciousness and unexpected death (sudden cardiac death [SCD]) due to cardiac causes which occurs within one hour of symptom onset.¹ SCA is caused by ventricular arrhythmias, which are very rapid heartbeats that can lead to chaotic electrical heart activity resulting in death.² Eighty percent of SCA is attributed to ventricular tachycardia (VT) and ventricular fibrillation (VF).¹ Patients at risk for SCA may receive implantable cardioverter-defibrillators (ICDs). Individuals at the greatest risk for cardiac death are those with left ventricular (LV) dysfunctions. Nuclear imaging helps in determining cardiac blood flow, severity of disease, and therefore the likelihood for SCD from ischemia, which would benefit from revascularization (see ischemia section). Nuclear tests also evaluate LV function, which assists in determining if the patient is likely to benefit from an ICD.³

Population: Patients at risk for SCD who may benefit from an ICD.

Evidence from randomized clinical trials that confirmed the efficacy of ICD for primary and secondary prevention of SCD identified the populations who benefit from ICD. The benefits are restricted to those individuals with severe LV dysfunction as measured by ejection fraction (EF). The Canadian Cardiovascular Society (CCS) has published the following recommendations regarding the implantation of ICDs:^4,5

• Referral for ICD therapy should be considered for patients with ischemic heart disease with or without mild to moderate heart failure symptoms and an LV ejection fraction of ≤ 30%, measured at least one month after myocardial infarction (MI) and at least three months following the coronary revascularization procedure.
• An ICD may be considered in patients with non-ischemic cardiomyopathy present for at least nine months, New York Heart Association (NYHA) functional class II to III heart failure, and an LV ejection fraction of ≤ to 30% or an LV ejection fraction of 31% to 35%.
• An ICD may be considered in patients with ischemic heart disease, previous myocardial infarction, LV dysfunction (LV ejection fraction 31% to 35%) measured at least one month after myocardial infarction and three months after coronary revascularization and with inducible ventricular fibrillation/sustained ventricular fibrillation/sustained ventricular tachycardia at electrophysiology study or without an electrophysiology study.
• An ICD should not be implanted in patients with poor life expectancy due to non-cardiac disease or NYHA class IV heart failure who are not expected to improve with further therapy and who are not candidates for cardiac transplantation.

Intervention: Radionuclide angiography (RNA) cardiac blood pooling imaging using ^99mTechnetium (^99mTc)-labelled radiotracer or gated single-photon emission computed tomography (SPECT) using ^99mTc-labelled radiotracer.

Synonyms for RNA include radionuclide ventriculography, radionuclide cine angiography, gated blood pool, multiple gated acquisition scan, and equilibrium radionuclide angiography. The term RNA will be used throughout this report.

To perform RNA, red blood cells are labelled with ^99mTc. Radioactivity is measured with a gamma camera suitably positioned over the patient’s chest as the radioactive blood flows through the large vessels and heart. The number of counts recorded at any time is proportional to the amount of blood radioactivity and these counts are proportional to the LV volume.

The two methods used for measurement are first-pass and equilibrium RNA. First-pass RNA measures the radioactivity of only a few beats (usually six to 10) whereas equilibrium RNA accumulates data over a five- to 10-minute period. LV counts at end diastole and at end systole or throughout the cardiac cycle are measured by constructing an LV region of interest (ROI). The measured LV counts within these LV ROIs are corrected for background scatter (BkCorr). The left ventricular ejection fraction (LVEF) = ([BkCorr end-diastolic counts – BkCorr end systolic counts]/BkCorr end-diastolic counts) × 100.⁶

Comparators: For this report, the following diagnostic tests are considered as alternatives to RNA or ^99mTc-labelled radiotracer red blood cell SPECT:

• Echocardiography (Echo)
• Magnetic resonance imaging (MRI).

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 and 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 implantable cardioverter-defibrillators.

Methodological filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, and non-randomized studies, including diagnostic accuracy studies. The search was limited to English language documents. No date limits were applied for the systematic reviews search. For primary studies, the retrieval was limited to documents published between January 1, 2006 and March 23, 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 addressing specific criteria, experts were consulted.

SEARCH RESULTS

There were 40 potential clinical articles identified through the meta-analysis/systematic review/health technology assessment (MA/SR/HTA) filtered search and nine were subjected to full-text review. One systematic review and meta-analysis (2002)⁷ is included in this report.

There were 345 potential articles identified through searching the primary diagnostic accuracy literature, of which 22 were subjected to full-text screening. Four primary studies, comparing RNA to its comparators, were identified in the primary literature search.^8–11 Three of the studies^8–10 evaluated RNA versus Echo and the fourth, also published in 2010,¹¹compared RNA imaging with MRI in the determination of LVEF.

SUMMARY TABLE

Table 1. Summary of Criterion Evidence (PDF, 198K)

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

Systematic reviews and meta-analyses

One systematic review and meta-analysis (2002)⁷ was identified in this report’s metaanalysis/ systematic review/health technology assessment (MA/SR/HTA).

^99mTc-SPECT compared with MRI

Ioannidis et al. (2002)⁷ performed a meta-analysis of all available data comparing electrocardiography(ECG)-gated SPECT with cardiac MRI in terms of the accurate assessment of LV and end-diastolic volumes, end-systolic volume, and EF. Data were eligible regardless of whether they referred to healthy subjects, patients with suspected or proven disease, and regardless of whether the SPECT images were captured at rest or after stress. All technical parameters and algorithms used for LV volumes and EF calculations were included. Only the ^99mTc data were pooled in the analysis.

Nine studies were included in the analysis (164 subjects who had both a ^99mTc-SPECT and MRI scan). Study populations included: known or suspected coronary artery disease (n = 5), post-MI (n = 1), post-coronary artery bypass grafting (n = 1), normal EF (n = 1), EF < 40% (n = 1), mixed (SPECT referrals, n = 1). All studies used rest acquisitions. Seven studies reported that test interpretation was blinded to the results of the other test. Sensitivity and specificity were calculated for each study and pooled using simple pooling techniques. In cases of significant heterogeneity, random effects analysis was used (Table 2).

Table 2

Diagnostic Accuracy Characteristics for EF Measurements of ^99mTc-SPECT Using MRI as the Gold Standard.

Primary Studies

Four primary studies comparing RNA to its comparators were identified in the primary literature search.^8–11 Three of the studies^8–10 evaluated RNA versus Echo and the fourth, also published in 2010,¹¹ compared RNA imaging to MRI in the determination of LVEF.

^99mTc-RNA versus Echo

An important Canadian study by Lane et al. (2010)⁸ examined the usefulness of current screening techniques using Echo to identify patients who should receive a primary prophylactic ICD. Two-hundred and forty-one patients, seen for consideration for a primary prophylactic defibrillator and referred for both Echo and RNA, were included in the analysis.⁸ The screening Echo used semi-quantitative or quantitative methods to measure the LVEF.⁸ In Table 3 and 3A, Echo grade 3 refers to LVEF of 20% to 39%, and Echo grade 4 refers to LVEF of < 20%.⁸ The study authors concluded that Echo and RNA are not equivalent modalities for measuring LVEF.⁸

Table 3

Semi-quantitative Echo Diagnostic Criteria for Screening LVEF.

Table 3A

Quantitative Echo for Screening LVEF.

Müller et al. (2010)⁹ compared LVEF measures between RNA and three-dimensional (3-D) Echo. Consecutive patients sent to their facility with an LVEF < 35% measured visually by twodimensional Echo underwent a full-volume 3-D Echo and an RNA one week later. All images were interpreted blindly. Fifty patients were enrolled: 58% with ischemic heart disease, and 42% with dilated cardiomyopathy. Only 38 patients (76%) had Echo images of sufficient quality for evaluation. The study authors concluded that RNA and 3-D Echo are not interchangeable for LVEF measures in patients with severely depressed systolic function.

Table 4LVEF measures for 3-D Echo and RNA

View in own window

	Mean LVEF (SD)		Mean Difference (SD) (Echo — RNA)	Agreement (95% limits)
	RNA	3-D Echo
All patients (n = 50)	0.27 (0.09)	0.20 (0.07)*	−0.07 (0.09)	−0.24 to 0.10
Only good quality images (n = 38)	0.27 (0.08)	0.21 (0.07)*	−0.05 (0.07)	−0.20 to 0.09

3-D = three-dimensional; Echo = echocardiography; LVEF = left ventricular ejection fraction; RNA = angiography; SD = standard deviation

*

=statistically significantly smaller values, p<0.001

In a 2010 publication by Hutyra et al., a cohort (n = 70) of ischemic cardiomyopathy patients underwent both Echo (monoplane and two-dimensional) and ^99mTc sestamibi-labelled SPECT scans to measure LVEF.¹⁰ SPECT scans were followed by Echo one hour later. ^99mTc-SPECT EFs were obtained using software. Single-measured Echo parameters were triplanar, biplanar, and monoplanar, and images were interpreted blindly. Patients with ischemic cardiomyopathy indicated for cardiosurgical revascularization based on coronarography were evaluated. All patients were New York Heart Association (NYHA) I-III and 65% had verified LV systolic dysfunction defined by LVEF < 50%. As indicated in Table 5, ^99mTc-SPECT and Echo LVEF measurements were significantly correlated, with the best agreement seen with triplanar Echo.

Table 5

Diagnostic Parameters of Echo and SPECT.

The study authors concluded that, for a one-time measurement, two-dimensional Echo using the triplanar analysis is interchangeable with ^99mTc-SPECT.

^99mTc-RNA versus MRI

Harel et al.¹¹ evaluated the use of a radionuclide-gated blood pool SPECT algorithm and cardiac MRI, with a study population of 55 patients. The mean delay between the two imaging tests was 12 ± 10 days. The mean LVEF estimates estimated by the different imaging modalities and algorithms are provided in Table 6. LVEFs calculated with planar, MHI_space, and QBS_space methods were correlated with LVEF values obtained by cardiac MRI. Count-based algorithms provided increased correlation. The authors concluded that RNA provided good estimates of LVEF when compared to cardiac MRI as the gold standard.

Table 6

Left Ventricular Ejection Fraction (LVEF) Estimates.

Return to Summary Table.

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

Non–radiation-related Risks

RNA

No information was identified regarding non–radiation-related risks for patients.

Echo

Three relatively large studies — with sample sizes of 42,408 patients (2009),²² 26,774 patients (2009),²³ and 5069 patients (2008)²⁴ — 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 that of patients who received no contrast. No additional risks associated with Echo were identified.

MRI

MRI is contraindicated in patients with metallic implants including pacemakers.²⁵ MRI is often used in conjunction with the contrast agent gadolinium (Gd). Some patients may experience an allergic reaction to the contrast agent (if required), which may worsen with repeated exposure.¹⁶ 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,¹⁷ 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%.¹⁷

Radiation-related Risks

Among the modalities to assess chemotherapy-induced cardiotoxicity, RNA is the only one to expose the patient to ionizing radiation. The average effective dose of radiation delivered with each of these procedures can be found in Table 7.

Table 7

Effective Radiation Doses for Various Imaging Tests.

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 make decisions regarding ICD implantation are presented by imaging modality. A summary of the availability of personnel required for ICD decision-making, by RNA or any of the alternative imaging modalities, is provided in Table 8.

Table 8

Medical Imaging Professionals in Canada, 2006.

RNA

In Canada, physicians involved in the performance, supervision, and interpretation of cardiac nuclear imaging (specifically RNA using ^99mTc-labelled radiotracer) should be nuclear medicine physicians with particular expertise in nuclear cardiology. In some jurisdictions, 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 RNA scans. Technologists must be certified by the Canadian Association of Medical Radiation Technologists (CAMRT) or an equivalent licensing body.

All alternative imaging modalities

In Canada, physicians involved in the performance, supervision, and interpretation of diagnostic CT scans, MRI, and ultrasound should be diagnostic radiologists¹⁹ 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 are also qualified if they are certified by a recognized certifying body and hold a valid provincial licence.²⁹ According to the CMA, there are 1,149 practising cardiologists in Canada (CMA, 2011).

Medical radiation technologists must be certified by CAMRT or an equivalent licensing body.

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, MRI scanners, and nuclear medicine equipment.²⁹

Echo

Echocardiography is an ultrasound-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 practising 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 (CARDUP). They should be members of their national or provincial professional organization. Sonography specialties include general sonography, vascular sonography, and cardiac sonography.¹⁹ In Quebec, sonographers and medical radiation technologists are grouped together; in the rest of Canada, sonographers are considered a distinct professional group.¹⁹

MRI

Medical technologists must have CAMRT certification in magnetic resonance imaging or be certified by an equivalent licensing body recognized by CAMRT.

Return to Summary Table.

CRITERION 10: Accessibility of alternative tests (equipment and wait times (link to definition)

There are notable variations in the availability of medical imaging technologies across Canada. Table 9 provides an overview of the availability of equipment required to make decisions regarding ICD implantation. Data for nuclear medicine cameras (including SPECT) are current to January 1, 2007. The number of MRI and SPECT/CT scanners is current to January 1, 2010. Data were not available for Echo.

Table 9

Diagnostic Imaging Equipment in Canada.

RNA

Nuclear medicine facilities with gamma cameras are required for SPECT imaging. Three jurisdictions — the Yukon, the Northwest Territories, and Nunavut — do not have any nuclear medicine equipment.¹⁹

Echo

No information was found to identify how many Echo machines are available in Canada.

MRI

No MRI scanners are available in the Yukon, Northwest Territories, or Nunavut.³⁰ According to the Canadian Institute for Health Information’s National Survey of Selected Medical Imaging Equipment database, the average number of hours of operation per week for MRI scanners in 2006–2007 ranged from 40 hours in PEI to 99 hours in Ontario, with a national average of 71 hours.¹⁹ In 2010, the average wait time for MRI in Canada was 9.8 weeks.²⁰

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 RNA 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 10), the cost of RNA with ^99mTc-based radioisotopes is $330.40. Echo is a minimally less costly alternative, whereas MRI is moderately more costly than RNA with ^99mTc-based radioisotopes.

Table 10

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

Return to Summary Table.

REFERENCES

1.

Buxton M, Caine N, Chase D, Connelly D, Grace A, Jackson C, et al. A review of the evidence on the effects and costs of implantable cardioverter defibrillator therapy in different patient groups, and modelling of cost-effectiveness and cost-utility for these groups in a UK context. Health Technol Assess [Internet] 2006;10(27):iii–iv. ix–xi, 1–164. [cited 2011 Apr 14]; Available from: http://www​.hta.ac.uk/execsumm/summ1027​.htm. [PubMed: 16904046]

2.

Primary Prevention ICD/CRT Task Force report & recommendations: prepared for the Ministry of Health and Long-Term Care [Internet]. Toronto: Ontario Ministry of Health and Long-Term Care; Dec, 2004. [cited 2011 Apr 14]. Available from: http://www​.health.gov​.on.ca/english/public​/pub/ministry_reports​/primary_prevent/primary​_prevent_icd_120104.pdf.

3.

Ganz LI. UpToDate [Internet]. Version 19.1. Waltham (MA): UpToDate, Inc.; Oct 12, 2009. [cited 2011 Jul 7]. Role of implantable cardioverter-defibrillators for the primary prevention of sudden cardiac death after myocardial infarction. c2005 - . Available from: http://www​.uptodate.com Subscription required.

4.

Tang AS, Ross H, Simpson CS, Mitchell LB, Dorian P, Goeree R, et al. Canadian Cardiovascular Society/Canadian Heart Rhythm Society position paper on implantable cardioverter defibrillator use in Canada. Can J Cardiol. 2005;21 Suppl A:11A–18A. [PubMed: 15953939]

5.

Howlett JG, McKelvie RS, Arnold JM, Costigan J, Dorian P, Ducharme A, et al. Canadian Cardiovascular Society Consensus Conference guidelines on heart failure, update 2009: diagnosis and management of right-sided heart failure, myocarditis, device therapy and recent important clinical trials. Can J Cardiol [Internet] 2009 Feb;25(2):85–105. [cited 2011 Sep 20]; Available from: http://www​.ncbi.nlm.nih​.gov/pmc/articles/PMC2691911. [PMC free article: PMC2691911] [PubMed: 19214293]

6.

Corbett JR, Akinboboye OO, Bacharach SL, Borer JS, Botvinick EH, DePuey EG, et al. Equilibrium radionuclide angiocardiography. J Nucl Cardiol. . 2006 Nov;13(6):e56–e79. [PubMed: 17174797]

7.

Ioannidis JP, Trikalinos TA, Danias PG. Electrocardiogram-gated single-photon emission computed tomography versus cardiac magnetic resonance imaging for the assessment of left ventricular volumes and ejection fraction: a meta-analysis. J Am Coll Cardiol. 2002;39(12):2059–2068. [PubMed: 12084609]

8.

Lane C, Dorian P, Ghosh N, Radina M, O'Donnell S, Thorpe K, et al. Limitations in the current screening practice of assessing left ventricular ejection fraction for a primary prophylactic implantable defibrillator in southern Ontario. Can J Cardiol [Internet] . 2010 Mar;26(3):e118–e124. [cited 2011 Aug 3]; Available from: http://www​.ncbi.nlm.nih​.gov/pmc/articles/PMC2851474. [PMC free article: PMC2851474] [PubMed: 20352140]

9.

Muller H, Frangos C, Fleury E, Righetti A, Lerch R, Burri H. Measurement of left ventricular ejection fraction by real time 3D echocardiography in patients with severe systolic dysfunction: comparison with radionuclide angiography. Echocardiography. 2010 Jan;27(1):58–63. [PubMed: 19765068]

10.

Hutyra M, Skala T, Kaminek M, Zapletalova J. Comparison of left ventricular volumes and ejection fraction assessment by two-dimensional echocardiography compared with gated myocardial SPECT in patients with ischemic cardiomyopathy. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010 Mar;154(1):47–54. [PubMed: 20445711]

11.

Harel F, Finnerty V, Gregoire J, Thibault B, Marcotte F, Ugolini P, et al. Gated blood-pool SPECT versus cardiac magnetic resonance imaging for the assessment of left ventricular volumes and ejection fraction. J Nucl Cardiol. 2010 Jun;17(3):427–434. [PubMed: 20151236]

12.

Wait Time Alliance. It's about time! Achieving benchmarks and best practices in wait time management: final report [Internet]. Ottawa: Canadian Society of Nuclear Medicine; Aug, 2005. [cited 2011 Apr 14]. Available from: http://www​.csnm-scmn​.ca/PDF/Its_about_time-e.pdf.

13.

Neubauer S. The failing heart--an engine out of fuel. N Engl J Med. 2007 Mar 15;356(11):1140–1151. [PubMed: 17360992]

14.

Murphy KJ, Brunberg JA. Adult claustrophobia, anxiety and sedation in MRI. Magn Reson Imaging. 1997;15(1):51–54. [PubMed: 9084025]

15.

MacKenzie R, Sims C, Owens RG, Dixon AK. Patients' perceptions of magnetic resonance imaging. Clin Radiol. 1995;50(3):137–143. [PubMed: 7889700]

16.

Siddiqi NH. Medscape reference [Internet]. New York: WebMD; Apr 20, 2011. [cited 2011 Oct 5]. Contrast medium reactions. c1994 - . Available from: http://emedicine​.medscape​.com/article/422855-overview.

17.

ACR Committee on Drugs and Contrast Media. ACR manual on contrast media [Internet]. Version 7. Reston (VA): American College of Radiology; 2010. [cited 2011 Oct 5]. Available from: http://www​.acr.org/SecondaryMainMenuCategories​/quality_safety​/contrast_manual/FullManual.aspx.

18.

Danias PG, Heller GV. UpToDate [Internet]. Version 19.1. Waltham (MA): UpToDate; Nov 24, 2009. [cited 2011 Jul 8]. Noninvasive methods for measurement of left ventricular systolic function. c2005 - . Available from: http://www​.uptodate.com Subscription required.

19.

Canadian Institute for Health Information. Medical imaging in Canada 2007 [Internet]. Ottawa: The Institute; 2008. [cited 2011 Apr 12]. p. 199. Available from: http://secure​.cihi.ca​/cihiweb/products/MIT_2007_e.pdf.

20.

Barua B, Rovere M, Skinner BJ. Waiting your turn: wait times for health care in Canada [Internet]. 20th ed. Vancouver (BC): Fraser Institute; Dec, 2010. [cited 2011 Apr 15]. p. 90. (Studies in health care policy). Available from: http://www​.fraserinstitute​.org/uploadedFiles​/fraser-ca/Content​/research-news/research​/publications/waiting-your-turn-2010.pdf.

21.

Schron EB, Exner DV, Yao Q, Jenkins LS, Steinberg JS, Cook JR, et al. Quality of life in the antiarrhythmics versus implantable defibrillators trial: impact of therapy and influence of adverse symptoms and defibrillator shocks. Circulation. 2002 Feb 5;105(5):589–594. [PubMed: 11827924]

22.

Dolan MS, Gala SS, Dodla S, Abdelmoneim SS, Xie F, Cloutier D, et al. Safety and efficacy of commercially available ultrasound contrast agents for rest and stress echocardiography a multicenter experience. J Am Coll Cardiol. 2009 Jan 6;53(1):32–38. [PubMed: 19118722]

23.

Abdelmoneim SS, Bernier M, Scott CG, Dhoble A, Ness SA, Hagen ME, et al. Safety of contrast agent use during stress echocardiography: a 4-year experience from a single-center cohort study of 26,774 patients. JACC Cardiovasc Imaging. 2009 Sep;2(9):1048–1056. [PubMed: 19761981]

24.

Shaikh K, Chang SM, Peterson L, Rosendahl-Garcia K, Quinones MA, Nagueh SF, et al. Safety of contrast administration for endocardial enhancement during stress echocardiography compared with noncontrast stress. Am J Cardiol. 2008 Dec 1;102(11):1444–1450. [PubMed: 19026293]

25.

College of Physicians and Surgeons of Ontario. Independent health facilities: clinical practice parameters and facility standards; magnetic resonance imaging [Internet]. 2nd ed. Toronto: The College; 2009. [cited 2011 Jun 13; revised 2010 Apr]. Available from: http://www​.cpso.on.ca​/uploadedFiles/policies​/guidelines/facilties/MagneticRI.pdf.

26.

Canadian Nuclear Safety Commission. Radioactive release data from Canadian nuclear power plants 1999–2008 [Internet]. Ottawa: CNSC; Sep, 2009. [cited 2011 Sep 13]. Report No.: INFO- 0210/Rev. 13. Available from: http:​//nuclearsafety​.gc.ca/pubs_catalogue​/uploads/INFO0210_R13_e.pdf.

27.

Grasty RL, LaMarre JR. The annual effective dose from natural sources of ionising radiation in Canada. Radiat Prot Dosimetry. 2004;108(3):215–226. [PubMed: 15031443]

28.

Mettler FA, Huda W, Yoshizumi TT, Mahesh M. Effective doses in radiology and diagnostic nuclear medicine: a catalog. Radiology [Internet] 2008 Jul;248(1):254–263. [cited 2011 Jun 13]; Available from: http://radiology​.rsna​.org/content/248/1/254.long. [PubMed: 18566177]

29.

Royal College of Physicians and Surgeons of Canada. Objectives of training in nuclear medicine [Internet]. Ottawa: The College; 2009. [cited 2011 Jun 13]. Available from: http://rcpsc​.medical​.org/residency/certification​/objectives/nucmed_e.pdf.

30.

Canadian Institute for Health Information (CIHI). Selected medical imaging equipment in Canada [Internet]. Ottawa: The Institute; Jan 1, 2010. [cited 2011 Jun 29]. Report No.: MI5. Available from: http://apps​.cihi.ca/MicroStrategy​/asp/Main​.aspx?server=torapprd30​.cihi.ca&project​=Quick+Stats&uid​=pce_pub_en&pwd​=&evt​=2048001&visualizationMode​=0&documentID​=50A7B0D5472B6AE40A9AE7AA062D42EC Source: National Survey of Selected Medical Imaging Equipment, CIHI, 2010.

31.

Ontario Ministry of Health and Long-Term Care. Schedule of benefits for physician services under the Health Insurance Act: effective September 1, 2011 [Internet]. Toronto: OMHLTC; 2011. [cited 2011 Oct 5]. Available from: http://www​.health.gov​.on.ca/english/providers​/program/ohip/sob​/physserv/physserv_mn.html.

APPENDICES