Annick C. Weustink, MD; Nico R. Mollet, MD, PhD; Lisan A. Neefjes, MD; W. Bob Meijboom, MD; Tjebbe W. Galema, MD; Carlos A. van Mieghem, MD, PhD; Stamatis Kyrzopoulous, MD; Rick Neoh Eu, MD; Koen Nieman, MD, PhD; Filippo Cademartiri, MD, PhD; Robert-Jan van Geuns, MD, PhD; Eric Boersma, MSc, PhD; Gabriel P. Krestin, MD, PhD; Pim J. de Feyter, MD, PhD
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M09-0625.
Reproducible Research Statement:Study protocol and statistical code: Available from Dr. de Feyter (firstname.lastname@example.org). Data set: Not available.
Requests for Single Reprints: Pim J. de Feyter, MD, PhD, Erasmus University Medical Center, Department of Cardiology, Thoraxcenter, Box 2040, 3000 CA Rotterdam, the Netherlands; e-mail, email@example.com.
Current Author Addresses: Drs. Weustink, Mollet, Neefjes, and Krestin: Department of Radiology, Erasmus University Medical Center, Box 2040, 3000 CA Rotterdam, the Netherlands.
Drs. Meijboom, Nieman, van Geuns, and de Feyter: Erasmus University Medical Center, Department of Cardiology, Thoraxcenter, Box 2040, 3000 CA Rotterdam, the Netherlands.
Drs. Galema and Boersma: Erasmus University Medical Center, Department of Cardiology, 's Gravendijkwal 230, 3015 CE Rotterdam, the Netherlands.
Dr. van Mieghem: Interventional Cardiology, Cardiac Imaging, and Intensive Care Medicine, Room 1024, OLV Hospital Aalst, Cardiovascular Center, Moorselbaan 164, 9300 Aalst, Belgium.
Dr. Kyrzopoulous: 356 Syngrou Avenue, 17674 Kallithea, Athens, Greece.
Dr. Eu: Room 41, Gleneagles Medical Centre, 1 Jalan Pangkor, 10050 Georgetown, Penang, Malaysia.
Dr. Cademartiri: Dipartimento ad Attività Integrate di Radiologia e Diagnostica per Immagine, c/o Piastra Tecnica, Piano 0, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43126 Parma, Italy.
Author Contributions: Conception and design: A.C. Weustink, N.R. Mollet, W.B. Meijboom, T.W. Galema, F. Cademartiri, R.J. van Geuns, G.P. Krestin, P.J. de Feyter.
Analysis and interpretation of the data: A.C. Weustink, N.R. Mollet, L.A. Neefjes, W.B. Meijboom, T.W. Galema, C.A. van Mieghem, S. Kyrzopoulous, R.N. Eu, K. Nieman, F. Cademartiri, E. Boersma, P.J. de Feyter.
Drafting of the article: A.C. Weustink, N.R. Mollet, W.B. Meijboom, F. Cademartiri, P.J. de Feyter.
Critical revision of the article for important intellectual content: A.C. Weustink, N.R. Mollet, L.A. Neefjes, W.B. Meijboom, C.A. van Mieghem, K. Nieman, F. Cademartiri, E. Boersma, G.P. Krestin, P.J. de Feyter.
Final approval of the article: A.C. Weustink, N.R. Mollet, W.B. Meijboom, C.A. van Mieghem, K. Nieman, F. Cademartiri, R.J. van Geuns, G.P. Krestin, P.J. de Feyter.
Provision of study materials or patients: A.C. Weustink, N.R. Mollet, W.B. Meijboom, C.A. van Mieghem, F. Cademartiri, R.J. van Geuns.
Statistical expertise: K. Nieman, W.B. Meijboom, E. Boersma.
Administrative, technical, or logistic support: A.C. Weustink, N.R. Mollet, W.B. Meijboom, K. Nieman, F. Cademartiri, G.P. Krestin.
Collection and assembly of data: A.C. Weustink, N.R. Mollet, L.A. Neefjes, W.B. Meijboom, T.W. Galema, C.A. van Mieghem, S. Kyrzopoulous, F. Cademartiri, R.J. van Geuns, P.J. deFeyter.
Weustink A., Mollet N., Neefjes L., Meijboom W., Galema T., van Mieghem C., Kyrzopoulous S., Eu R., Nieman K., Cademartiri F., van Geuns R., Boersma E., Krestin G., de Feyter P.; Diagnostic Accuracy and Clinical Utility of Noninvasive Testing for Coronary Artery Disease. Ann Intern Med. 2010;152:630-639. doi: 10.7326/0003-4819-152-10-201005180-00003
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Published: Ann Intern Med. 2010;152(10):630-639.
Computed tomography coronary angiography (CTCA) has become a popular noninvasive test for diagnosing coronary artery disease.
To compare the accuracy and clinical utility of stress testing and CTCA for identifying patients who require invasive coronary angiography (ICA).
University medical center in Rotterdam, the Netherlands.
517 patients referred by their treating physicians for evaluation of chest symptoms by using stress testing or ICA.
Stress testing and CTCA in all patients.
Diagnostic accuracy of stress testing and CTCA compared with ICA; pretest probabilities of disease by Duke clinical score; and clinical utility of noninvasive testing, defined as a pretest or posttest probability that suggests how to proceed with testing (no further testing if â‰¤5%, proceed with ICA if between 5% and 90%, and refer directly for ICA if â‰¥90%).
Stress testing was not as accurate as CTCA; CTCA sensitivity approached 100%. In patients with a low (<20%) pretest probability of disease, negative stress test or CTCA results suggested no need for ICA. In patients with an intermediate (20% to 80%) pretest probability, a positive CTCA result suggested need to proceed with ICA (posttest probability, 93% [95% CI, 92% to 93%]) and a negative result suggested no need for further testing (posttest probability, 1% [CI, 1% to 1%]). Physicians could proceed directly with ICA in patients with a high (>80%) pretest probability (91% [CI, 90% to 92%]).
Referral and verification bias might have influenced findings. Stress testing provides functional information that may add value to that from anatomical (CTCA or ICA) imaging.
Computed tomography coronary angiography seems most valuable in patients with intermediate pretest probability of disease, because the test can distinguish which of these patients need invasive angiography. These findings need to be confirmed before CTCA can be routinely recommended for these patients.
Cardiology and Radiology Division. Hospital Universitario Central de Asturias. Oviedo Spain
May 20, 2010
Proper indications in computed tomography coronary angiography
We have read with great interest the excellent article recently published in your journal by Weustink et al in which they compare the accuracy and clinical utility of stress testing and computed tomography coronary angiography (CTCA) for identifying patients who require invasive coronary angiography (ICA).
It reflects the importance of the pretest probability in the selection of patients who are candidates for CTCA (1). Proper and careful patient selection is extremely important when we ask for a CTCA. Those patients with a high suspicion of coronary artery disease (CAD) are not good candidates for non invasive angiography as they will probably require percutaneous coronary intervention; and what is more, in high risk patients, calcium score can be too high to make a proper diagnosis. Anyway, we just have to follow the current practice guidelines. This way, exercise testing is recommended as the first-line diagnosis tool in patients with suspicion of CAD . In fact, it is class I recommendation both in the European and the American guidelines about the management of stable angina pectoris (2,3). Moreover, in symptomatic patients, the current European and American guidelines for the use of CTCA establish and appropriate indication of this technique in those cases with uninterpretable or equivocal stress test, ECG uninterpretable or unable to exercise and intermediate pre-test probability (4,5).
Of course, it is well-known the higher diagnostic sensitivity and specificity of the CTCA, when comparing with conventional exercise testing but we must realize that CTCA is not only more expensive, and we must not forget health care, but also, and more important, it implies radiation and contrast exposure. So in our opinion, in the management of patients with suspected CAD, we must follow the proper indications and the recommendations of the current practice guidelines. CTCA has a high negative predictive value which makes it specially useful to rule out the presence of CAD in patients with intermediate pretest likelihood with uninterpretable or unable to stress test. As a result, CTCA is a very useful tool for cardiologist if it is used properly in the adequate and selected patients.
1.- Weustink AC, Mollet NR, Neefjes LA, Meijboom WB, Galema TW, Van Mieghem CA, Kyrzopoulous S, Eu RN, Nieman K, Cademartiri F, Van Geuns RJ, Boersma E, Krestin GP, de Feyter PJ. Diagnostic accuracy and clinical utility of noninvasive testing for coronary artery disease. Ann Intern Med. 2010 May 18;152(10):630-9.
2. Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F, Daly C, De Backer G, Hjemdahl P, Lopez-Sendon J, Marco J, Morais J, Pepper J, Sechtem U, Simoons M, Thygesen K, Priori SG, Blanc JJ, Budaj A, Camm J, Dean V, Deckers J, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo J, Zamorano JL; Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology; ESC Committee for Practice Guidelines (CPG).Eur Heart J. 2006 Jun;27(11):1341- 81.
3- Fraker TD Jr, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS, Ferguson TB Jr, Fihn SD, Fraker TD Jr, Gardin JM, O'Rourke RA, Williams SV, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura R, Page RL, Riegel B, Tarkington LG, Yancy CW.2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina.Circulation.2007 Dec 4; 116(23):2762-72.
4.- Schroeder S, Achenbach S, Bengel F, Burgstahler C, Cademartiri F, de Feyter P, George R, Kaufmann P, Kopp AF, Knuuti J, Ropers D, Schuijf J, Tops LF, Bax JJ; Working Group Nuclear Cardiology and Cardiac CT; European Society of Cardiology; European Council of Nuclear Cardiology. Cardiac computed tomography: indications, applications, limitations, and training requirements: report of a Writing Group deployed by the Working Group Nuclear Cardiology and Cardiac CT of the European Society of Cardiology and the European Council of Nuclear Cardiology. Eur Heart J. 2008 Feb; 29(4):531-56.
5.- Hendel RC, Patel MR, Kramer CM, Poon M, Hendel RC, Carr JC, Gerstad NA, Gillam LD, Hodgson JM, Kim RJ, Kramer CM, Lesser JR, Martin ET, Messer JV, Redberg RF, Rubin GD, Rumsfeld JS, Taylor AJ, Weigold WG, Woodard PK, Brindis RG, Hendel RC, Douglas PS, Peterson ED, Wolk MJ, Allen JM, Patel MR. ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 appropriateness criteria for cardiac computed tomography and cardiac magnetic resonance imaging: a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group, American College of Radiology, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, American Society of Nuclear Cardiology, North American Society for Cardiac Imaging, Society for Cardiovascular Angiography and Interventions, and Society of Interventional Radiology. J Am Coll Cardiol. 2006 Oct 3; 48(7):1475-97.
Ali Salavati MD MPH Salavati MD MPH
Zentralklinik Bad Berka
June 1, 2010
Should We Use Noninvasive Tests Prior To Elective Coronary Angiography?
To the editor: Recently two papers considering the role of non- invasive tests in obstructive coronary artery disease have been published. The earlier was published by Patel et. al.(1) in appreciated 'New England Journal of Medicine' and the other one in your influential journal by Weustink et al (2),but their conclusions regarding the utility of non- invasive tests in the management of coronary artery disease contradicted each other. While the former casts doubt on the value of noninvasive tests, the latter concludes that computed tomography coronary angiography (CTCA) could be applied reliably as a first-line test in diagnostic work- up of patients with intermediate pretest probability. We think this conflict can be explained based on different nature of these studies. Patel et al used data of Cardiology National Cardiovascular Data Registry (NCDR) of 663 hospitals, which provide great facts about contemporary clinical practice; however, several factors including legal and economic considerations, may influence the accuracy of national registry data as a research source.(3)As they also mentioned, in contrast to current guideline recommendation(4),noninvasive-tests paradoxically used more often in patients with high Framingham risk score than in patients with low and intermediate risk score. Therefore, it is not surprising why the statistical model was not able to show the benefits of noninvasive tests. In contrast, Weustink et al stratified their cohort based on the pretest probability of CAD and as anticipated, neither CTCA nor stress test was beneficial to high risk patients; nevertheless, CTCA was reliable enough to determine whether intermediate probability group needs ICA or not. Moreover, NCDR includes a broad range of tests with different diagnostic performance not only among these modalities(5), but also among different generations of them(6). Although, the exact proportion of patients who underwent different kinds of noninvasive tests was not clear in their study, moderate diagnostic accuracy of exercise-ECG and nuclear stress perfusion was shown previously and it was suggested they might not reliably distinguish patients who need invasive coronary angiography (ICA) (5). In contrast, several studies regarding multidetector computed tomography coronary angiography ,which was classified as noninvasive test in Patel et al study, showed its clinical effectiveness (6-8) and cost-effectiveness (8), at least, as a reliable gatekeeper for low and intermediate-risk individuals. Weustink et al assessed the clinical value of stress test and CTCA separately and showed that these tests could not be regarded collectively as 'noninvasive tests'. Although the study by Weustink et al is a single center trial with potential referral and verification biases, it was conducted prospectively with special attention to all details and its results seem more concordant with available evidence. Thus, we think if huge data of NCDR were also stratified base on different types of noninvasive tests, it would show not only remarkable advantages of CTCA versus other noninvasive tests but also dramatic drop would be observed in total number of patients who underwent unnecessary ICA in CTCA stratum. Hypothetically, it would show significant outcome, if chronological developments of each technology were also incorporated into statistical models.
1. Patel MR, Peterson ED, Dai D, et al. Low diagnostic yield of elective coronary angiography. N Engl J Med;362:886-95.
2. Weustink AC, Mollet NR, Neefjes LA, et al. Diagnostic accuracy and clinical utility of noninvasive testing for coronary artery disease. Ann Intern Med;152:630-9.
3. Kardooni S, Haut ER, Chang DC, et al. Hazards of benchmarking complications with the National Trauma Data Bank: numerators in search of denominators. J Trauma 2008;64:273-7; discussion 7-9.
4. Fraker TD, Jr., Fihn SD, Gibbons RJ, et al. 2007 chronic angina focused update of the ACC/AHA 2002 guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 guidelines for the management of patients with chronic stable angina. J Am Coll Cardiol 2007;50:2264-74.
5. Fox K, Garcia MA, Ardissino D, et al. Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J 2006;27:1341-81.
6. Vanhoenacker PK, Heijenbrok-Kal MH, Van Heste R, et al. Diagnostic performance of multidetector CT angiography for assessment of coronary artery disease: meta-analysis. Radiology 2007;244:419-28.
7. Budoff MJ, Dowe D, Jollis JG, et al. Diagnostic performance of 64- multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol 2008;52:1724-32.
8. Mowatt G, Cummins E, Waugh N, et al. Systematic review of the clinical effectiveness and costeffectiveness of 64-slice or higher computed tomography angiography as an alternative to invasive coronary angiography in the investigation of coronary artery disease. Health Technol Assess 2008;12:iiiiv, ix-143.
Ali Salavati MD MPH
Zentralklinik Bad Berka , Germany
June 15, 2010
Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging or Computed Tomography Coronary Angiography?
Weustink et al(1) showed higher accuracy of computed tomography coronary angiography (CTCA) in comparison with stress testing in their excellent study. They suggested performing stress testing as a first-line diagnostic study in patients with low pretest probability. However, they did not clarify which kind of stress testing should be used; in their study, stress testing comprised exercise ECG and pharmacologic single photon emission computed tomography (SPECT), based on the current guidelines. Although they did not state the proportion of patients in each pretest probability cluster who underwent different types of stress testing, exercise ECG was non-conclusive in 118 patients (23% of all cases). Thus, were the data extrapolated to daily practice, approximately 23% of patients with suspected coronary artery disease (CAD) would undergo pharmacologic SPECT.
According to the report by the National Council on Radiation Protection and Measurements, the per capita effective radiation dose of the U.S. population from all sources increased by 72% in the past 30 years, mostly due to 5.7-fold increase in the average radiation dose of medical imaging (2). Approximately 22% of the radiation exposure associated with medical imaging comes from 9 million myocardial perfusion imaging (MPI) performed each year in the U.S. (3). Considering the fact that the number of MPIs has increased by more than 6% per year between 1993 and 2001, it is appropriate to rethink whether it is being used properly (4). This growth rate was greater than any other cardiac diagnostic and therapeutic procedures, with no justification for their use based on disease rates, or newly published definitive randomized trials (4).
Moreover, according to several meta-analyses (5-8), sensitivity (75% to 88%) and specificity (48% to 77%) of MPI are not satisfactory to discriminate patients who need further investigation from others. Even in high-risk obstructive CAD subsets including patients with isolated left main disease or in combination with additional coronary involvement, left main equivalent (proximal left anterior descending and proximal circumflex disease) and triple vessel disease, it is neither sensitive (75%) nor specific (48%) (8). Ironically, MPI is the single most applied non- invasive test in the management of CAD and it is predicted to keep first place, at least in the next decade(9).
There is evidence that, in many situations better structural and/or functional tests are available. For example, stress echocardiography, as a functional test, has been shown to have similar or even higher diagnostic accuracy in comparison with MPI (5, 6, 8). As Weustink et al also stated, several systematic reviews and multicenter studies confirmed the near perfect diagnostic accuracy of 64-slice or higher computed tomography angiography in the assessment of CAD with similar or even lower radiation than SPECT-MPI, using appropriate dose reduction protocols (10). Therefore, it seems reasonable to perform CTCA or stress echocardiography instead of pharmacologic SPECT in patients with low pretest probability when they have inadequate exercise capacity, contraindications to ECG stress testing or equivocal exercise ECG test. However, as structural stenosis not always correlates with the functional state, MPI will still play its unique role to provide objective evidence of ischemia and prognostic information in patients who need revascularization.
1.Weustink AC, Mollet NR, Neefjes LA, et al. Diagnostic accuracy and clinical utility of noninvasive testing for coronary artery disease. Ann Intern Med;152(10):630-9.
2.NCRP Publications. Report No.160,Ionizing Radiation Exposure of the Population of the United States (2009). http://www.ncrppublications.org/Reports/160.Accessed June 1, 2010.
3.Fazel R, Krumholz HM, Wang Y, et al. Exposure to low-dose ionizing radiation from medical imaging procedures. N Engl J Med. 2009;361(9):849- 57.
4.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(3):374-9.
5.Fleischmann KE, Hunink MG, Kuntz KM, Douglas PS. Exercise echocardiography or exercise SPECT imaging? A meta-analysis of diagnostic test performance. JAMA. 1998;280(10):913-20.
6.Garber AM, Solomon NA. Cost-effectiveness of alternative test strategies for the diagnosis of coronary artery disease. Ann Intern Med. 1999;130(9):719-28.
7.Heijenbrok-Kal MH, Fleischmann KE, Hunink MG. Stress echocardiography, stress single-photon-emission computed tomography and electron beam computed tomography for the assessment of coronary artery disease: a meta-analysis of diagnostic performance. Am Heart J. 2007;154(3):415-23.
8.Mahajan N, Polavaram L, Vankayala H, et al. Diagnostic accuracy of myocardial perfusion imaging and stress echocardiography for the diagnosis of left main and triple vessel coronary artery disease: a comparative meta -analysis. Heart;96(12):956-66.
9.Gershlick AH, de Belder M, Chambers J, et al. Role of non-invasive imaging in the management of coronary artery disease: an assessment of likely change over the next 10 years. A report from the British Cardiovascular Society Working Group. Heart. 2007;93(4):423-31.
10.Einstein AJ, Moser KW, Thompson RC, Cerqueira MD, Henzlova MJ. Radiation dose to patients from cardiac diagnostic imaging. Circulation. 2007;116(11):1290-305.
Annick C. Weustink
November 22, 2010
The increase of radiation exposure associated with medical imaging is of concern and where possible should be avoided. In symptomatic patients with a low pretest probability a negative ECG stress test outcome, just as a negative CT scan, is associated with a very low post test probability of CAD and further downstream testing is not warranted. We prefer to use, as an initial test, ECG stress testing because it is widely available, inexpensive and avoids radiation exposure. If however an ECG stress test is positive in these patients with a low pretest probability than the likelihood of a false positive test outcome is rather high. In some patients, depending on the severity of symptoms and occurrence of ST segment depression during minimal or moderate exercise a second functional test may be justified. This may, depending on the local availability and experience, be either stress echocardiography or preferably pharmacological SPECT with its acknowledged prognostic information and providing of objective evidence of ischemia that is required for revascularization treatment.
A.C. Weustink P.J. de Feyter
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