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NON-INVASIVE CARDIAC DIAGNOSTIC TESTS IN ONTARIO: TEMPORAL TRENDS IN UTILIZATION AND
ASSOCIATION WITH OBSTRUCTIVE CORONARY ARTERY DISEASE
by
IDAN ROIFMAN
A thesis submitted in conformity with the requirements for the degree of Master of Science (Clinical Epidemiology)
Institute of Health Policy, Management and Evaluation University of Toronto
NON-INVASIVE CARDIAC DIAGNOSTIC TESTS IN ONTARIO: TEMPORAL TRENDS IN UTILIZATION AND
ASSOCIATION WITH OBSTRUCTIVE CORONARY ARTERY DISEASE
Idan Roifman
Master of Science
Institute of Health Policy, Management and Evaluation University of Toronto
2016
Abstract
Contemporary temporal trends in utilization of graded exercise stress test (GXT), myocardial
perfusion scanning (MPI), stress echocardiography (stress echo), and cardiac computed
tomography angiography (CCTA) are unknown. The optimal initial testing strategy to evaluate
stable coronary artery disease (CAD) is also unknown. We conducted a repeated cross sectional
study of the adult population of Ontario in order to assess the temporal trends in utilization of these
modalities and a retrospective inception cohort study in order to compare the relationship between
differing initial testing strategies and the presence of obstructive CAD on downstream
angiography. Our results indicate stable utilization patterns for GXT and MPI. We had insufficient
data to make definitive conclusions regarding the temporal trends for CCTA and stress echo. An
initial diagnostic strategy consisting of CCTA, MPI or stress echo was not significantly different
than an initial strategy with a GXT in detecting obstructive CAD on downstream angiography.
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Acknowledgments
I would like to thank my committee members: Jack Tu, Harindra Wijeysundera, Peter Austin and
Graham Wright for their help and support in all facets of my thesis. I would like to thank the
Heart and Stroke/Richard Lewar Centre of Excellence and the Queen Elizabeth 2 Graduate
Scholarship in Science and Technology for their direct funding support. Further, this project was
also supported by the Institute for Circulatory and Respiratory Health/Canadian Institutes of
Health Research (CIHR) Team Grant to the Cardiovascular Health in Ambulatory Care Research
Team (CANHEART) TCA 118349 (Dr. Tu). I would like to thank Reza Rezai, Jiming Fang and
Laura Maclagan for their help in navigating the world of UNIX, SAS and the ICES databases.
Lastly, I want to thank my wife Jacoba and children Orly and Ben for their endless support.
Without it, pursuing this degree would be impossible.
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Table of Contents
Abstract .......................................................................................................................................... ii Acknowledgments ......................................................................................................................... iii Table of Contents .......................................................................................................................... iv
List of Tables .................................................................................................................................. vi List of Figures ............................................................................................................................. viii List of Appendices ......................................................................................................................... ix
Chapter 1: Background ................................................................................................................. 1 1.1 Coronary artery disease – incidence, prevalence and mortality ................................... 1 1.2 Non-invasive cardiac diagnostic tests .............................................................................. 2 1.3 Temporal trends in the utilization of non-invasive cardiac diagnostic tests ................ 5 1.4 Clinical efficacy and effectiveness of MPI, CCTA, and stress echo .............................. 7 1.5 Real world results on angiography; yield of obstructive CAD ...................................... 8 1.6 Preferred initial cardiac non-invasive diagnostic test for evaluation of stable CAD .. 8 1.7 Gaps in current knowledge ............................................................................................... 9 1.8 Importance ....................................................................................................................... 10 1.9 Objectives ......................................................................................................................... 12 1.10 Hypotheses ....................................................................................................................... 12
Chapter 2: Temporal trends of cardiac non-invasive diagnostic tests in Ontario, 2008-2013 ........................................................................................................................................................ 13
2.3 Results .............................................................................................................................. 16 2.3.1 Temporal trends of CCTA in Ontario; 2011-2013 ............................................................ 16 2.3.2 Temporal trends of GXT in Ontario; 2008-2013 .............................................................. 17 2.3.3 Temporal trends of MPI in Ontario; 2008-2013 ............................................................... 18 2.3.4 Temporal trends of stress echocardiography in Ontario; 2011-2013 ................................ 19 2.3.5 Head-to-head comparison of MPIs, CCTAs, GXTs and stress echos performed in Ontario,
2011-2013 ...................................................................................................................... 20 2.3.6 Temporal change in age-and-sex standardized rates of MPI, CCTA, GXT and stress
2.4.1 Temporal trends in the utilization of cardiac non-invasive diagnostic tests...................... 22 2.4.2 Self-referral ....................................................................................................................... 22 2.4.3 Comparison of our results with previous work ................................................................. 23 2.4.4 Limitations ........................................................................................................................ 25
Chapter 3: The relationship between an initial diagnostic evaluation with GXT, CCTA, MPI or stress echo and downstream yield of obstructive CAD in the evaluation of patients for stable CAD .............................................................................................................................. 27
3.2 Methods ............................................................................................................................ 28 3.2.1 Design ............................................................................................................................... 28 3.2.2 Derivation of the cohort .................................................................................................... 28 3.2.3 Data sources ...................................................................................................................... 29 3.2.4 Objective 1: Downstream invasive angiography and subsequent non-invasive tests ....... 31 3.2.5 Objective 2: Assessment of obstructive CAD in those patients who underwent invasive
angiography for the assessment of stable angina ........................................................... 32 3.3 Results .............................................................................................................................. 35
3.3.1 Objective 1: Downstream invasive angiography and subsequent non-invasive tests ....... 35 3.3.1.1 Cohort creation .......................................................................................................................... 35 3.3.1.2 Baseline characteristics of the cohort ........................................................................................ 35 3.3.1.3 Angiography within 6 months of the index cardiac non-invasive diagnostic test ...................... 35 3.3.1.4 Subsequent cardiac non-invasive tests ....................................................................................... 36
3.3.2 Objective 2: Assessment of obstructive CAD in those patients who underwent invasive angiography for stable angina ........................................................................................ 37
3.3.2.1 Cohort creation .......................................................................................................................... 37 3.3.2.2 Characteristics of patients undergoing angiography for the evaluation of stable angina ......... 37 3.3.2.3 Yield of Obstructive CAD .......................................................................................................... 37 3.3.2.4 Yield of obstructive CAD after removing patients who had a subsequent non-invasive cardiac
diagnostic test ............................................................................................................................ 38 3.4 Discussion ......................................................................................................................... 38
4.2.1 Trends in Utilization.......................................................................................................... 46 4.2.2 Relationship of initial non-invasive diagnostic testing with downstream obstructive CAD
on invasive angiography in patients being assessed for stable angina ........................... 48 4.3 Future work ..................................................................................................................... 49 4.4 Conclusions ...................................................................................................................... 51
Table 2: Characteristics of patients receiving and physicians performing coronary
computed tomography angiography in Ontario, 2011-2013
2011 2012 2013 Total p-value N 2,777 5,427 7,013 15,217 Age in years (mean ± standard deviation) 59.5 ± 12.5 59.7 ± 12.9 60.3 ± 12.9 60.0 ± 12.8 0.003 Female sex (%) 1,192
(42.9%) 2,294
(42.3%) 3,007 (42.9%) 6,493 (42.7%) 0.759 Top 3 performing specialties
Diagnostic Radiology 2,434 (87.6%)
4,634 (85.4%)
5,520 (79.5%) 12,588 (83.1%)
<0.0001
Cardiology 322 (11.6%)
661 (12.2%)
968 (13.9%) 1,951 (12.9%)
Nuclear Medicine 10 (0.4%) 7 (0.1%) 298 (4.3%) 315 (2.1%) Top 3 referring specialties
Figure 8: Multivariable model displaying the odds ratios and 95% confidence intervals of the
yield of obstructive CAD amongst the different index cardiac non-invasive diagnostic tests in
patients who underwent invasive angiography for the assessment of stable angina - after
removing patients who had a subsequent non-invasive test (GXT is the reference test)
* adjusted for age, sex, presence of diabetes mellitus, dyslipidemia, hypertension, income
quintile, resting ECG abnormalities, Charlson co-morbidity index score, serum creatinine,
smoking history, CCS class angina symptom scale, COPD and PVD
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References
1. Ergin A, Muntner P, Sherwin R, He J. Secular trends in cardiovascular disease mortality, incidence, and case fatality rates in adults in the united states. The American journal of medicine. 2004;117:219-227
2. Arciero TJ, Jacobsen SJ, Reeder GS, Frye RL, Weston SA, Killian JM, Roger Vr V. Temporal trends in the incidence of coronary disease. The American journal of medicine. 2004;117:228-233
3. Cheng Y, Chen KJ, Wang CJ, Chan SH, Chang WC, Chen JH. Secular trends in coronary heart disease mortality, hospitalization rates, and major cardiovascular risk factors in taiwan, 1971-2001. International journal of cardiology. 2005;100:47-52
4. McGovern PG, Pankow JS, Shahar E, Doliszny KM, Folsom AR, Blackburn H, Luepker RV. Recent trends in acute coronary heart disease--mortality, morbidity, medical care, and risk factors. The minnesota heart survey investigators. The New England journal of medicine. 1996;334:884-890
5. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Stafford R, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J. Executive summary: Heart disease and stroke statistics--2010 update: A report from the american heart association. Circulation. 2010;121:948-954
6. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: A systematic analysis for the global burden of disease study 2013. Lancet. 2015
7. World health organization website; http://www.Who.Int/mediacentre/factsheets/fs317/en/.
july 11, 2015. 8. Conference board of canada. The canadian heart health strategy: Risk factors and future
cost implications report. 2010 9. Shiralkar S, Rennie A, Snow M, Galland RB, Lewis MH, Gower-Thomas K. Doctors'
knowledge of radiation exposure: Questionnaire study. BMJ. 2003;327:371-372 10. Razavi R, Hill DL, Keevil SF, Miquel ME, Muthurangu V, Hegde S, Rhode K, Barnett M, van
Vaals J, Hawkes DJ, Baker E. Cardiac catheterisation guided by mri in children and adults with congenital heart disease. Lancet. 2003;362:1877-1882
11. Muthurangu V, Razavi RS. The value of magnetic resonance guided cardiac catheterisation. Heart. 2005;91:995-996
12. Ripley DP, Brown JM, Everett CC, Bijsterveld P, Walker S, Sculpher M, McCann GP, Berry C, Plein S, Greenwood JP. Rationale and design of the clinical evaluation of magnetic resonance imaging in coronary heart disease 2 trial (ce-marc 2): A prospective, multicenter, randomized trial of diagnostic strategies in suspected coronary heart disease. American heart journal. 2015;169:17-24 e11
13. Patel MR, Peterson ED, Dai D, Brennan JM, Redberg RF, Anderson HV, Brindis RG, Douglas PS. Low diagnostic yield of elective coronary angiography. The New England journal of medicine. 2010;362:886-895
14. Libby B, Mann, Zipes. Braunwald's heart disease: A textbook for cardiovascular medicine. Saunders Elsevier; 2008.
15. Bruce RA, Lovejoy FW, Jr., et al. Normal respiratory and circulatory pathways of adaptation in exercise. The Journal of clinical investigation. 1949;28:1423-1430
16. Ajlan AM, Heilbron BG, Leipsic J. Coronary computed tomography angiography for stable angina: Past, present, and future. The Canadian journal of cardiology. 2013;29:266-274
17. Fuster W, Harrington. Hurst's: The heart. 13th edition. Mcgraw-hill companies. 2011 18. Dowsley T, Al-Mallah M, Ananthasubramaniam K, Dwivedi G, McArdle B, Chow BJ. The
role of noninvasive imaging in coronary artery disease detection, prognosis, and clinical decision making. The Canadian journal of cardiology. 2013;29:285-296
19. Small GR, Wells RG, Schindler T, Chow BJ, Ruddy TD. Advances in cardiac spect and pet imaging: Overcoming the challenges to reduce radiation exposure and improve accuracy. The Canadian journal of cardiology. 2013;29:275-284
20. Chow BJ, Larose E, Bilodeau S, Ellins ML, Galiwango P, Kass M, Sheth T, Jassal DS, Kirkpatrick ID, Mancini GB, Mayo J, Abraham A, White J. The 'what, when, where, who and how?' Of cardiac computed tomography in 2009: Guidelines for the clinician. The Canadian journal of cardiology. 2009;25:135-139
21. Alter DA, Stukel TA, Newman A. Proliferation of cardiac technology in canada: A challenge to the sustainability of medicare. Circulation. 2006;113:380-387
22. Ministry of health and long term care of ontario; non-invasive cardiac imaging technologies for the diagnosis of coronary artery disease. Ontario Health Technology Assessment Series. 2010;10
23. Blecker S, Bhatia RS, You JJ, Lee DS, Alter DA, Wang JT, Wong HJ, Tu JV. Temporal trends in the utilization of echocardiography in ontario, 2001 to 2009. JACC. Cardiovascular imaging. 2013;6:515-522
24. Lucas FL, DeLorenzo MA, Siewers AE, Wennberg DE. Temporal trends in the utilization of diagnostic testing and treatments for cardiovascular disease in the united states, 1993-2001. Circulation. 2006;113:374-379
25. Andrus BW, Welch HG. Medicare services provided by cardiologists in the united states: 1999-2008. Circulation. Cardiovascular quality and outcomes. 2012;5:31-36
26. Hung MC, Chang PW, Hsieh WA, Hwang JJ. Myocardial perfusion scintigraphy in taiwan from 2005 to 2009. Nuclear medicine communications. 2012;33:733-738
27. Levin DC, Parker L, Intenzo CM, Rao VM. Recent reimbursement changes and their effect on hospital and private office use of myocardial perfusion imaging. Journal of the American College of Radiology : JACR. 2013;10:198-201
28. McNulty EJ, Hung YY, Almers LM, Go AS, Yeh RW. Population trends from 2000-2011 in nuclear myocardial perfusion imaging use. Jama. 2014;311:1248-1249
29. Duszak R, Jr., Optican RJ, Brin KP, Woodard PK. Cardiac ct and coronary cta: Early medicare claims analysis of national and regional utilization and coverage. Journal of the American College of Radiology : JACR. 2011;8:549-555
76
30. Douglas PS, Taylor A, Bild D, Bonow R, Greenland P, Lauer M, Peacock F, Udelson J. Outcomes research in cardiovascular imaging: Report of a workshop sponsored by the national heart, lung, and blood institute. Circulation. Cardiovascular imaging. 2009;2:339-348
31. Douglas PS, Taylor A, Bild D, Bonow R, Greenland P, Lauer M, Peacock F, Udelson J. Outcomes research in cardiovascular imaging: Report of a workshop sponsored by the national heart, lung, and blood institute. JACC. Cardiovascular imaging. 2009;2:897-907
32. Douglas PS, Taylor A, Bild D, Bonow R, Greenland P, Lauer M, Peacock F, Udelson J. Outcomes research in cardiovascular imaging: Report of a workshop sponsored by the national heart, lung, and blood institute. Journal of cardiovascular computed tomography. 2009;3:212-223
33. Douglas PS, Taylor A, Bild D, Bonow R, Greenland P, Lauer M, Peacock F, Udelson J. Outcomes research in cardiovascular imaging: Report of a workshop sponsored by the national heart, lung, and blood institute. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography. 2009;22:766-773
34. Gibbons RJ, Balady GJ, Bricker JT, Chaitman BR, Fletcher GF, Froelicher VF, Mark DB, McCallister BD, Mooss AN, O'Reilly MG, Winters WL, Jr., Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Russell RO, Smith SC, Jr. Acc/aha 2002 guideline update for exercise testing: Summary article: A report of the american college of cardiology/american heart association task force on practice guidelines (committee to update the 1997 exercise testing guidelines). Circulation. 2002;106:1883-1892
35. Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, Pepine CJ, Schaeffer JW, Smith EE, 3rd, Steward DE, Theroux P, Gibbons RJ, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Smith SC, Jr. Acc/aha guideline update for the management of patients with unstable angina and non-st-segment elevation myocardial infarction--2002: Summary article: A report of the american college of cardiology/american heart association task force on practice guidelines (committee on the management of patients with unstable angina). Circulation. 2002;106:1893-1900
36. Froelicher VF, Lehmann KG, Thomas R, Goldman S, Morrison D, Edson R, Lavori P, Myers J, Dennis C, Shabetai R, Do D, Froning J. The electrocardiographic exercise test in a population with reduced workup bias: Diagnostic performance, computerized interpretation, and multivariable prediction. Veterans affairs cooperative study in health services #016 (quexta) study group. Quantitative exercise testing and angiography. Annals of internal medicine. 1998;128:965-974
37. Klocke FJ, Baird MG, Lorell BH, Bateman TM, Messer JV, Berman DS, O'Gara PT, Carabello BA, Russell RO, Jr., Cerqueira MD, St John Sutton MG, DeMaria AN, Udelson JE, Kennedy JW, Verani MS, Williams KA, Antman EM, Smith SC, Jr., Alpert JS, Gregoratos G, Anderson JL, Hiratzka LF, Faxon DP, Hunt SA, Fuster V, Jacobs AK, Gibbons RJ, Russell RO. Acc/aha/asnc guidelines for the clinical use of cardiac radionuclide imaging--executive summary: A report of the american college of cardiology/american heart association task force on practice guidelines (acc/aha/asnc committee to revise the
77
1995 guidelines for the clinical use of cardiac radionuclide imaging). Journal of the American College of Cardiology. 2003;42:1318-1333
38. Klocke FJ, Baird MG, Lorell BH, Bateman TM, Messer JV, Berman DS, O'Gara PT, Carabello BA, Russell RO, Jr., Cerqueira MD, St John Sutton MG, DeMaria AN, Udelson JE, Kennedy JW, Verani MS, Williams KA, Antman EM, Smith SC, Jr., Alpert JS, Gregoratos G, Anderson JL, Hiratzka LF, Faxon DP, Hunt SA, Fuster V, Jacobs AK, Gibbons RJ, Russell RO. Acc/aha/asnc guidelines for the clinical use of cardiac radionuclide imaging--executive summary: A report of the american college of cardiology/american heart association task force on practice guidelines (acc/aha/asnc committee to revise the 1995 guidelines for the clinical use of cardiac radionuclide imaging). Circulation. 2003;108:1404-1418
39. Pellikka PA. Stress echocardiography for the diagnosis of coronary artery disease: Progress towards quantification. Current opinion in cardiology. 2005;20:395-398
40. Armstrong WF, Zoghbi WA. Stress echocardiography: Current methodology and clinical applications. Journal of the American College of Cardiology. 2005;45:1739-1747
41. Garcia MJ, Lessick J, Hoffmann MH. Accuracy of 16-row multidetector computed tomography for the assessment of coronary artery stenosis. Jama. 2006;296:403-411
42. Leschka S, Alkadhi H, Plass A, Desbiolles L, Grunenfelder J, Marincek B, Wildermuth S. Accuracy of msct coronary angiography with 64-slice technology: First experience. European heart journal. 2005;26:1482-1487
43. Raff GL, Gallagher MJ, O'Neill WW, Goldstein JA. Diagnostic accuracy of noninvasive coronary angiography using 64-slice spiral computed tomography. Journal of the American College of Cardiology. 2005;46:552-557
44. Leber AW, Knez A, von Ziegler F, Becker A, Nikolaou K, Paul S, Wintersperger B, Reiser M, Becker CR, Steinbeck G, Boekstegers P. Quantification of obstructive and nonobstructive coronary lesions by 64-slice computed tomography: A comparative study with quantitative coronary angiography and intravascular ultrasound. Journal of the American College of Cardiology. 2005;46:147-154
45. Mollet NR, Cademartiri F, van Mieghem CA, Runza G, McFadden EP, Baks T, Serruys PW, Krestin GP, de Feyter PJ. High-resolution spiral computed tomography coronary angiography in patients referred for diagnostic conventional coronary angiography. Circulation. 2005;112:2318-2323
46. Ropers D, Rixe J, Anders K, Kuttner A, Baum U, Bautz W, Daniel WG, Achenbach S. Usefulness of multidetector row spiral computed tomography with 64- x 0.6-mm collimation and 330-ms rotation for the noninvasive detection of significant coronary artery stenoses. The American journal of cardiology. 2006;97:343-348
47. Memisoglu E, Ropers D, Hobikoglu G, Tepe MS, Labovitz AJ. Usefulness of electron beam computed tomography for diagnosis of an anomalous origin of a coronary artery from the opposite sinus. The American journal of cardiology. 2005;96:1452-1455
48. Chow BJ, Abraham A, Wells GA, Chen L, Ruddy TD, Yam Y, Govas N, Galbraith PD, Dennie C, Beanlands RS. Diagnostic accuracy and impact of computed tomographic coronary angiography on utilization of invasive coronary angiography. Circulation. Cardiovascular imaging. 2009;2:16-23
78
49. Douglas PS, Hoffmann U, Patel MR, Mark DB, Al-Khalidi HR, Cavanaugh B, Cole J, Dolor RJ, Fordyce CB, Huang M, Khan MA, Kosinski AS, Krucoff MW, Malhotra V, Picard MH, Udelson JE, Velazquez EJ, Yow E, Cooper LS, Lee KL. Outcomes of anatomical versus functional testing for coronary artery disease. The New England journal of medicine. 2015;372:1291-1300
50. Demir OM, Bashir A, Marshall K, Douglas M, Wasan B, Plein S, Alfakih K. Comparison of clinical efficacy and cost of a cardiac imaging strategy versus a traditional exercise test strategy for the investigation of patients with suspected stable coronary artery disease. The American journal of cardiology. 2015;115:1631-1635
51. Buechel RR, Kaufmann BA, Tobler D, Wild D, Zellweger MJ. Non-invasive nuclear myocardial perfusion imaging improves the diagnostic yield of invasive coronary angiography. European heart journal cardiovascular Imaging. 2015;16:842-847
52. Guidelines for coronary angiography. A report of the american college of cardiology/american heart association task force on assessment of diagnostic and therapeutic cardiovascular procedures (subcommittee on coronary angiography). Journal of the American College of Cardiology. 1987;10:935-950
53. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: A systematic analysis for the global burden of disease study 2013. Lancet. 2015;385:117-171
54. de Bono D. Investigation and management of stable angina: Revised guidelines 1998. Joint working party of the british cardiac society and royal college of physicians of london. Heart. 1999;81:546-555
55. Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, Douglas PS, Foody JM, Gerber TC, Hinderliter AL, King SB, 3rd, Kligfield PD, Krumholz HM, Kwong RY, Lim MJ, Linderbaum JA, Mack MJ, Munger MA, Prager RL, Sabik JF, Shaw LJ, Sikkema JD, Smith CR, Jr., Smith SC, Jr., Spertus JA, Williams SV, Anderson JL. 2012 accf/aha/acp/aats/pcna/scai/sts guideline for the diagnosis and management of patients with stable ischemic heart disease: A report of the american college of cardiology foundation/american heart association task force on practice guidelines, and the american college of physicians, american association for thoracic surgery, preventive cardiovascular nurses association, society for cardiovascular angiography and interventions, and society of thoracic surgeons. Circulation. 2012;126:e354-471
56. Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, Bugiardini R, Crea F, Cuisset T, Di Mario C, Ferreira JR, Gersh BJ, Gitt AK, Hulot JS, Marx N, Opie LH, Pfisterer M, Prescott E, Ruschitzka F, Sabate M, Senior R, Taggart DP, van der Wall EE, Vrints CJ, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Knuuti J, Valgimigli M, Bueno H, Claeys MJ, Donner-Banzhoff N, Erol C, Frank H, Funck-Brentano C, Gaemperli O, Gonzalez-Juanatey JR, Hamilos M, Hasdai D, Husted S, James SK, Kervinen K, Kolh P, Kristensen SD, Lancellotti P, Maggioni AP, Piepoli MF, Pries AR, Romeo F, Ryden L, Simoons ML, Sirnes PA, Steg PG, Timmis A, Wijns W, Windecker S, Yildirir A, Zamorano JL. 2013 esc guidelines on the management of stable coronary artery disease: The task force on the
79
management of stable coronary artery disease of the european society of cardiology. European heart journal. 2013;34:2949-3003
57. Kolh P, Windecker S, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Juni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Sousa Uva M, Achenbach S, Pepper J, Anyanwu A, Badimon L, Bauersachs J, Baumbach A, Beygui F, Bonaros N, De Carlo M, Deaton C, Dobrev D, Dunning J, Eeckhout E, Gielen S, Hasdai D, Kirchhof P, Luckraz H, Mahrholdt H, Montalescot G, Paparella D, Rastan AJ, Sanmartin M, Sergeant P, Silber S, Tamargo J, ten Berg J, Thiele H, van Geuns RJ, Wagner HO, Wassmann S, Wendler O, Zamorano JL. 2014 esc/eacts guidelines on myocardial revascularization: The task force on myocardial revascularization of the european society of cardiology (esc) and the european association for cardio-thoracic surgery (eacts). Developed with the special contribution of the european association of percutaneous cardiovascular interventions (eapci). European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2014;46:517-592
58. Beller GA. Tests that may be overused or misused in cardiology: The choosing wisely campaign. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2012;19:401-403
59. Bhatia RS, Pendrith C, Ross H. Cardiac testing in an asymptomatic 42-year-old man. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2015;187:747-749
60. Baron RJ, Wolfson D. Advancing medical professionalism and the choosing wisely campaign. JAMA internal medicine. 2015;175:464-465
61. Anderson JL, Heidenreich PA, Barnett PG, Creager MA, Fonarow GC, Gibbons RJ, Halperin JL, Hlatky MA, Jacobs AK, Mark DB, Masoudi FA, Peterson ED, Shaw LJ. Acc/aha statement on cost/value methodology in clinical practice guidelines and performance measures: A report of the american college of cardiology/american heart association task force on performance measures and task force on practice guidelines. Circulation. 2014;129:2329-2345
62. Anderson JL, Heidenreich PA, Barnett PG, Creager MA, Fonarow GC, Gibbons RJ, Halperin JL, Hlatky MA, Jacobs AK, Mark DB, Masoudi FA, Peterson ED, Shaw LJ. Acc/aha statement on cost/value methodology in clinical practice guidelines and performance measures: A report of the american college of cardiology/american heart association task force on performance measures and task force on practice guidelines. Journal of the American College of Cardiology. 2014;63:2304-2322
63. Kickback and physician self-referral. Office of inspector general: Us department of health and human services. 2015;2015
64. Gazelle GS, Halpern EF, Ryan HS, Tramontano AC. Utilization of diagnostic medical imaging: Comparison of radiologist referral versus same-specialty referral. Radiology. 2007;245:517-522
80
65. Levin DC, Rao VM. Turf wars in radiology: The overutilization of imaging resulting from self-referral. Journal of the American College of Radiology : JACR. 2004;1:169-172
66. Learning what works: Infrastructure required for comparative effectiveness research: Workshop summary. 2011
67. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, 3rd, Moy CS, Mussolino ME, Neumar RW, Nichol G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner MB. Heart disease and stroke statistics--2014 update: A report from the american heart association. Circulation. 2014;129:e28-e292
68. Wyman RM, Safian RD, Portway V, Skillman JJ, McKay RG, Baim DS. Current complications of diagnostic and therapeutic cardiac catheterization. Journal of the American College of Cardiology. 1988;12:1400-1406
69. Iglehart JK. Health insurers and medical-imaging policy--a work in progress. The New England journal of medicine. 2009;360:1030-1037
70. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB. Executive summary: Heart disease and stroke statistics--2013 update: A report from the american heart association. Circulation. 2013;127:143-152
71. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB. Heart disease and stroke statistics--2013 update: A report from the american heart association. Circulation. 2013;127:e6-e245
72. Roifman I, Rezai MR, Wijeysundera HC, Chow BJ, Wright GA, Tu JV. Utilization of cardiac computed tomography angiography and outpatient invasive coronary angiography in ontario, canada. Journal of cardiovascular computed tomography. 2015
73. Alter DA, Franklin B, Ko DT, Austin PC, Lee DS, Oh PI, Stukel TA, Tu JV. Socioeconomic status, functional recovery, and long-term mortality among patients surviving acute myocardial infarction. PLoS One. 2013;8:e65130
74. Joseph KS, Fahey J. Validation of perinatal data in the discharge abstract database of the canadian institute for health information. Chronic diseases in Canada. 2009;29:96-100
75. Juurlink D PC, Croxford R, Chong A, Austin P, Tu J et al. Canadian institute for health information discharge abstract database: A validation study. 2006
76. Tu K, Gong Y, Austin PC, Jaakimanian L, Tu JV. An overview of the types of physicians treating acute cardiac conditions in canada. The Canadian journal of cardiology. 2004;20:282-291
81
77. Mark J. Anson FJF, Frank J. Jones. The handbook of traditional and alternative investment vehicles. Hoboken, New Jersey: John Wiley and Sons, Inc.; 2011.
78. Ontario ministry of health and long term care; april 1, 2011, changes to the schedule of benefits for physician services (schedule) and to the out-of-country prior approval program. 2011
79. Ontario ministry of health and long term care; bulletin 4540 - 2008 physician services agreement – changes effective september 1, 2011 - chart 4. 2011
80. Levin DC, Parker L, Intenzo CM, Sunshine JH. Recent rapid increase in utilization of radionuclide myocardial perfusion imaging and related procedures: 1996-1998 practice patterns. Radiology. 2002;222:144-148
81. Maitino AJ, Levin DC, Parker L, Rao VM, Sunshine JH. Practice patterns of radiologists and nonradiologists in utilization of noninvasive diagnostic imaging among the medicare population 1993-1999. Radiology. 2003;228:795-801
82. Maitino AJ, Levin DC, Parker L, Rao VM, Sunshine JH. Nationwide trends in rates of utilization of noninvasive diagnostic imaging among the medicare population between 1993 and 1999. Radiology. 2003;227:113-117
83. Hillman AL, Pauly MV, Kerstein JJ. How do financial incentives affect physicians' clinical decisions and the financial performance of health maintenance organizations? The New England journal of medicine. 1989;321:86-92
84. Hillman AL. Financial incentives for physicians in hmos. Is there a conflict of interest? The New England journal of medicine. 1987;317:1743-1748
85. Hillman BJ, Joseph CA, Mabry MR, Sunshine JH, Kennedy SD, Noether M. Frequency and costs of diagnostic imaging in office practice--a comparison of self-referring and radiologist-referring physicians. The New England journal of medicine. 1990;323:1604-1608
86. Hillman AL, Eisenberg JM, Pauly MV, Bloom BS, Glick H, Kinosian B, Schwartz JS. Avoiding bias in the conduct and reporting of cost-effectiveness research sponsored by pharmaceutical companies. The New England journal of medicine. 1991;324:1362-1365
87. Ontario ministry of health and long-term care. Schedule of benefits for physician services under the health insurance act. 2014
88. You JJ, Venkatesh V, Laupacis A. Better access to outpatient magnetic resonance imaging in ontario - but for whom? Open medicine : a peer-reviewed, independent, open-access journal. 2009;3:e22-25
89. Demeter S, Reed M, Lix L, MacWilliam L, Leslie WD. Socioeconomic status and the utilization of diagnostic imaging in an urban setting. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2005;173:1173-1177
90. Alter DA, Iron K, Austin PC, Naylor CD. Socioeconomic status, service patterns, and perceptions of care among survivors of acute myocardial infarction in canada. Jama. 2004;291:1100-1107
91. Alter DA, Naylor CD, Austin P, Tu JV. Effects of socioeconomic status on access to invasive cardiac procedures and on mortality after acute myocardial infarction. The New England journal of medicine. 1999;341:1359-1367
92. Statistics canada, income statistics division, catalogue no. 13c0015: Annual income estimates for census families and individuals: Individual data-user's guide
82
. 2013 93. Finkelstein MM. Ecologic proxies for household income: How well do they work for the
analysis of health and health care utilization? Can J Public Health. 2004;95:90-9494. Mustard CA, Derksen S, Berthelot JM, Wolfson M. Assessing ecologic proxies for
household income: A comparison of household and neighbourhood level incomemeasures in the study of population health status. Health Place. 1999;5:157-171
95. Dedic A, Rossi A, Ten Kate GJ, Neefjes LA, Galema TW, Moelker A, van Domburg RT,Schultz CJ, Mollet NR, de Feyter PJ, Nieman K. First-line evaluation of coronary arterydisease with coronary calcium scanning or exercise electrocardiography. Internationaljournal of cardiology. 2013;163:190-195
96. Patel MR, Dai D, Hernandez AF, Douglas PS, Messenger J, Garratt KN, Maddox TM,Peterson ED, Roe MT. Prevalence and predictors of nonobstructive coronary arterydisease identified with coronary angiography in contemporary clinical practice.American heart journal. 2014;167:846-852 e842
97. Tu JV, Chu A, Donovan LR, Ko DT, Booth GL, Tu K, Maclagan LC, Guo H, Austin PC, HoggW, Kapral MK, Wijeysundera HC, Atzema CL, Gershon AS, Alter DA, Lee DS, JackeviciusCA, Bhatia RS, Udell JA, Rezai MR, Stukel TA. The cardiovascular health in ambulatorycare research team (canheart): Using big data to measure and improve cardiovascularhealth and healthcare services. Circulation. Cardiovascular quality and outcomes.2015;8:204-212
98. Maclagan LC, Park J, Sanmartin C, Mathur KR, Roth D, Manuel DG, Gershon A, Booth GL,Bhatia S, Atzema CL, Tu JV. The canheart health index: A tool for monitoring thecardiovascular health of the canadian population. CMAJ : Canadian Medical Associationjournal = journal de l'Association medicale canadienne. 2014;186:180-187
99. Austin PC, Daly PA, Tu JV. A multicenter study of the coding accuracy of hospitaldischarge administrative data for patients admitted to cardiac care units in ontario.American heart journal. 2002;144:290-296
100. Lee DS, Stitt A, Wang X, Yu JS, Gurevich Y, Kingsbury KJ, Austin PC, Tu JV. Administrative hospitalization database validation of cardiac procedure codes. Med Care. 2013;51:e22-26
101. Kokotailo RA, Hill MD. Coding of stroke and stroke risk factors using international classification of diseases, revisions 9 and 10. Stroke. 2005;36:1776-1781
102. Tu JV, Donovan LR, Lee DS, Wang JT, Austin PC, Alter DA, Ko DT. Effectiveness of public report cards for improving the quality of cardiac care: The effect study: A randomized trial. Jama. 2009;302:2330-2337
103. Tu K, Campbell NR, Chen ZL, Cauch-Dudek KJ, McAlister FA. Accuracy of administrative databases in identifying patients with hypertension. Open medicine : a peer-reviewed, independent, open-access journal. 2007;1:e18-26
104. Hux JE, Ivis F, Flintoft V, Bica A. Diabetes in ontario: Determination of prevalence and incidence using a validated administrative data algorithm. Diabetes care. 2002;25:512-516
105. Tu JV, Bowen J, Chiu M, Ko DT, Austin PC, He Y, Hopkins R, Tarride JE, Blackhouse G, Lazzam C, Cohen EA, Goeree R. Effectiveness and safety of drug-eluting stents in ontario. The New England journal of medicine. 2007;357:1393-1402
83
106. Wijeysundera HC, Stukel TA, Chong A, Natarajan MK, Alter DA. Impact of clinical urgency, physician supply and procedural capacity on regional variations in wait times for coronary angiography. BMC Health Serv Res. 2010;10:5
107. Ko DT, Guo H, Wijeysundera HC, Natarajan MK, Nagpal AD, Feindel CM, Kingsbury K, Cohen EA, Tu JV. Assessing the association of appropriateness of coronary revascularization and clinical outcomes for patients with stable coronary artery disease. Journal of the American College of Cardiology. 2012;60:1876-1884
108. Wijeysundera HC, Trubiani G, Abrahamyan L, Mitsakakis N, Witteman W, Paulden M, van der Velde G, Kingsbury K, Krahn M. Specialized multi-disciplinary heart failure clinics in ontario, canada: An environmental scan. BMC Health Serv Res. 2012;12:236
109. Tu JV, Ko DT, Guo H, Richards JA, Walton N, Natarajan MK, Wijeysundera HC, So D, Latter DA, Feindel CM, Kingsbury K, Cohen EA. Determinants of variations in coronary revascularization practices. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2012;184:179-186
110. Schwalm JD, Wijeysundera HC, Tu JV, Guo H, Kingsbury KJ, Natarajan MK. Influence of coronary anatomy and syntax score on the variations in revascularization strategies for patients with multivessel disease. The Canadian journal of cardiology. 2014;30:1155-1161
111. Rosengren A, Hawken S, Ounpuu S, Sliwa K, Zubaid M, Almahmeed WA, Blackett KN, Sitthi-amorn C, Sato H, Yusuf S. Association of psychosocial risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the interheart study): Case-control study. Lancet. 2004;364:953-962
112. Steyn K, Sliwa K, Hawken S, Commerford P, Onen C, Damasceno A, Ounpuu S, Yusuf S. Risk factors associated with myocardial infarction in africa: The interheart africa study. Circulation. 2005;112:3554-3561
113. Teo KK, Ounpuu S, Hawken S, Pandey MR, Valentin V, Hunt D, Diaz R, Rashed W, Freeman R, Jiang L, Zhang X, Yusuf S. Tobacco use and risk of myocardial infarction in 52 countries in the interheart study: A case-control study. Lancet. 2006;368:647-658
114. Lanas F, Avezum A, Bautista LE, Diaz R, Luna M, Islam S, Yusuf S. Risk factors for acute myocardial infarction in latin america: The interheart latin american study. Circulation. 2007;115:1067-1074
115. Anand SS, Islam S, Rosengren A, Franzosi MG, Steyn K, Yusufali AH, Keltai M, Diaz R, Rangarajan S, Yusuf S. Risk factors for myocardial infarction in women and men: Insights from the interheart study. European heart journal. 2008;29:932-940
116. Teo KK, Liu L, Chow CK, Wang X, Islam S, Jiang L, Sanderson JE, Rangarajan S, Yusuf S. Potentially modifiable risk factors associated with myocardial infarction in china: The interheart china study. Heart. 2009;95:1857-1864
117. Guo J, Li W, Wang Y, Chen T, Teo K, Liu LS, Yusuf S. Influence of socioeconomic status on acute myocardial infarction in the chinese population: The interheart china study. Chin Med J (Engl). 2012;125:4214-4220
118. Hemann BA, Bimson WF, Taylor AJ. The framingham risk score: An appraisal of its benefits and limitations. Am Heart Hosp J. 2007;5:91-96
119. Kraus JF, Borhani NO, Franti CE. Socioeconomic status, ethnicity, and risk of coronary heart disease. Am J Epidemiol. 1980;111:407-414
84
120. Ko DT, Tu JV, Austin PC, Wijeysundera HC, Samadashvili Z, Guo H, Cantor WJ, Hannan EL. Prevalence and extent of obstructive coronary artery disease among patients undergoing elective coronary catheterization in new york state and ontario. Jama. 2013;310:163-169
121. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the interheart study): Case-control study. Lancet. 2004;364:937-952
122. Gibbons RJ, Balady GJ, Beasley JW, Bricker JT, Duvernoy WF, Froelicher VF, Mark DB, Marwick TH, McCallister BD, Thompson PD, Winters WL, Jr., Yanowitz FG, Ritchie JL, Cheitlin MD, Eagle KA, Gardner TJ, Garson A, Jr., Lewis RP, O'Rourke RA, Ryan TJ. Acc/aha guidelines for exercise testing: Executive summary. A report of the american college of cardiology/american heart association task force on practice guidelines (committee on exercise testing). Circulation. 1997;96:345-354
123. Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, Douglas PS, Foody JM, Gerber TC, Hinderliter AL, King SB, 3rd, Kligfield PD, Krumholz HM, Kwong RY, Lim MJ, Linderbaum JA, Mack MJ, Munger MA, Prager RL, Sabik JF, Shaw LJ, Sikkema JD, Smith CR, Jr., Smith SC, Jr., Spertus JA, Williams SV. 2012 accf/aha/acp/aats/pcna/scai/sts guideline for the diagnosis and management of patients with stable ischemic heart disease: Executive summary: A report of the american college of cardiology foundation/american heart association task force on practice guidelines, and the american college of physicians, american association for thoracic surgery, preventive cardiovascular nurses association, society for cardiovascular angiography and interventions, and society of thoracic surgeons. Circulation. 2012;126:3097-3137
124. Shaw LJ, Berman DS. Functional versus anatomic imaging in patients with suspected coronary artery disease. Cardiology clinics. 2009;27:597-604
125. Shaw LJ, Tandon S, Rosen S, Mieres JH. Evaluation of suspected ischemic heart disease in symptomatic women. The Canadian journal of cardiology. 2014;30:729-737
126. Shaw LJ, Bugiardini R, Merz CN. Women and ischemic heart disease: Evolving knowledge. Journal of the American College of Cardiology. 2009;54:1561-1575
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Appendices
Appendix 1: Search strategy for identifying published literature examining the temporal
trends in the utilization of cardiac non-invasive diagnostic tests
We systematically searched for articles via a MEDLINE search between the years 1966-2015. A
combination of the following keywords used were:
1. For CCTA: “coronary computed tomography angiography” OR “coronary CTA” OR “CCTA”
OR “CTA” OR “coronary CT” OR “cardiac CT” AND “temporal trends” OR “resource
utilization” OR “utilization”.
2. For MPI: “MPI” OR “myocardial perfusion scan” OR “SPECT” AND “temporal trends” OR
“resource utilization” OR “utilization”.
3. For GXT: “GXT” OR “graded exercise stress test” OR “exercise stress test” AND “temporal
trends” OR “resource utilization” OR “utilization”.
4. For stress echo: “stress echo” OR “stress echocardiogram” AND “temporal trends” OR “resource
utilization” OR “utilization”.
These searches produced a total of 370 English language articles. Out of these, 8 papers were found
to have pertinent information on the temporal utilization trends of CCTA, stress echo, GXT and/or
MPI. Further, the references of all pertinent papers were scanned and we were able to identify
another relevant non-MEDLINE listed publication.
86
Appendix 2: Search strategy for identifying published literature assessing the results on
angiography (normal, obstructive, non-obstructive) relative to an upstream cardiac non-
invasive diagnostic test
We systematically searched for articles via a MEDLINE search between the years 1966-2015. A
combination of the following keywords used were:
1. “Yield of obstructive coronary artery disease” OR “Yield of obstructive CAD”
2. For CCTA: “coronary computed tomography angiography” OR “coronary CTA” OR “CCTA”
OR “CTA” OR “coronary CT” OR “cardiac CT” AND “downstream obstructive CAD” OR
“downstream obstructive coronary artery disease” OR “downstream normal angiography” OR
“downstream normal angiogram” OR “downstream non-obstructive CAD”
3. For stress echo: “stress echo” OR “stress echocardiogram” AND “downstream obstructive
CAD” OR “downstream obstructive coronary artery disease” OR “downstream normal
angiography” OR “downstream normal angiogram” OR “downstream non-obstructive CAD”
4. For MPI: “MPI” OR “myocardial perfusion scan” OR “SPECT” AND “downstream
obstructive CAD” OR “downstream obstructive coronary artery disease” OR “downstream
normal angiography” OR “downstream normal angiogram” OR “downstream non-obstructive
CAD”
5. For GXT: “GXT” OR “graded exercise stress test” OR “exercise stress test” AND
“downstream obstructive CAD” OR “downstream obstructive coronary artery disease” OR
“downstream normal angiography” OR “downstream normal angiogram” OR “downstream
non-obstructive CAD”
87
These searches yielded a total of 41 studies, 4 of which discussed downstream normal angiography,
obstructive CAD, non-obstructive CAD or yield of obstructive CAD for any of the cardiac non-