Computed Tomographic Angiography

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The Centers for Medicare and Medicaid Services (CMS) has decided to make no change to section 220.1 of the National Coverage Determination Manual titled “Computed Tomography” (Pub. 100-3, 220.1). We have decided that no national coverage determination on the use of cardiac computed tomography angiography for coronary artery disease is appropriate at this time and that coverage should be determined by local contractors through the local coverage determination process or case-by-case adjudication.

Decision Memo: To: Administrative File: CAG 00385N Computer Tomographic Angiography From: Steve E. Phurrough, MD, MPA Director, Coverage and Analysis Group Marcel E. Salive, MD, MPH Director, Division of Medical and Surgical Services JoAnna Baldwin, MS Lead Analyst Joseph Chin, MD, MS Medical Officer Subject: Coverage Decision Memorandum for Cardiac Computed Tomographic Angiography for the Diagnosis of Coronary Artery Disease Date: March 12, 2008 I. Decision The Centers for Medicare and Medicaid Services (CMS) has decided to make no change to section 220.1 of the National Coverage Determination Manual titled “Computed Tomography” (Pub. 100-3, 220.1). We have decided that no national coverage determination on the use of cardiac computed tomography angiography for coronary artery disease is appropriate at this time and that coverage should be determined by local contractors through the local coverage determination process or case-by-case adjudication. II. Background Computed tomographic angiography (CTA) is a general phrase used to describe noninvasive imaging of the arteries with various types of computed tomography (CT) machines, such as multislice CT (MSCT), multidetector CT (MDCT), and dual source CT (DSCT). The use of CTA has increased over the years due to advances in the technology and rapid diffusion of the machines outside the hospital settings. The initial single slice CT machines produced poor quality images. In the late 1990’s, 4 slice CT machines were introduced, with 16 slice and 64 slice CT machines following shortly afterwards. Image quality and performance reportedly increased with each model. However, questions remain on the indications for use. A particular focus has been the use of CTA for evaluation of the coronary arteries in patients with chest pain. Proponents have claimed that cardiac or coronary CTA may reduce the need for invasive coronary angiography for certain patients. Critics have pointed out the lack of evidence on outcomes and the limitations to the technology including uninterpretable/unassessable segments and the health risks from the considerable radiation exposure. Although there are other uses of CTA, this decision focuses only on the use of CTA for the evaluation of the coronary arteries in patients with symptomatic coronary artery disease (e.g., chest pain). Imaging performed on patients without chest pain (asymptomatic patients) would be considered screening and is not an available benefit in the Medicare program. Chest pain (angina pectoris) can be classified as “typical angina, atypical angina and noncardiac chest pain” (Snow, 2004 – Appendix A). Angina is defined “as a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arm” (Snow, 2004). Unstable angina is defined as “angina that presents in 1 of 3 principal ways: rest angina, severe new-onset angina, or increasing angina” (Snow, 2004). Given the prevalence and incidence of CAD in the US, angina has been well studied and evidence-based guidelines are available for unstable and stable angina. The ACC/AHA guidelines on unstable angina (Gibbons, 2007) and chronic stable angina (Gibbons, 2002) are such examples and are well recognized and accepted. Although these guidelines do not directly incorporate coronary CTA, the treatment algorithms provide clues on possible scenarios where CTA may be considered. For unstable angina, patients who are at high or intermediate short term risk of death (Appendix A) are almost always treated as inpatients in the hospital setting. These patients typically undergo cardiac catheterization and invasive coronary angiography so the role of CTA is very limited (Anderson, 2007). However, “low-risk patients with unstable angina have a short-term risk not substantially different from those with stable angina” and “their evaluation can be accomplished safely and expeditiously in an outpatient setting” (Gibbons, 2002). Risk in patients with unstable angina may be estimated using validated methods such as the TIMI risk score (Antman, 2000) as noted in the ACC/AHA guidelines (Appendix A). For chronic stable angina, the ACC/AHA and ACP have developed guidelines with treatment algorithms that may also help guide the consideration for use of imaging such as coronary CTA (Gibbons, 2002). Specifically, for patients with chronic stable angina and an intermediate probability of CAD, imaging may be considered when the exercise test does not suggest high risk and there is inadequate information on diagnosis (Appendix A). The guidelines provide a narrow window for the use of imaging. The current recommended approach for risk determination in patients with stable chest pain is based upon the results of exercise testing. The pretest probability of CAD may be determined by several validated methods (Appendix A) such as published models by Diamond and Forrester (1979), Mark (1987) and Pryor (1993). Appropriateness criteria have also been published (Hendel, 2006). While these were based on consensus, the criteria may provide additional information on specific uses of CTA, especially for those indications which were considered inappropriate. Most studies, as noted in the Blue Cross Blue Shield technology assessments, have not specifically evaluated long term health outcomes but have looked at diagnostic test characteristics and test performance compared to invasive angiography. The question of how coronary CTA may fit into the current recommended clinical pathways needs to be addressed by research and clinical experts. In addition, there are a number of aspects or dimensions of imaging quality, as noted by Douglas and colleagues (Douglas et al., 2006), that are relevant and applicable to coronary CTA. Many of these aspects are implicit in the process of imaging but being such may be areas that deserve some explicit focus to ensure that quality is maintained and not forgotten in everyday practice. III. History of Medicare Coverage Medicare has an NCD, last revised in 1985, that discusses general uses of CT. The policy does not specifically address the use of CTA technology or CT for the diagnosis of CAD as such an indication was not in clinical practice at the time the policy was last updated. Therefore, CTA has never been addressed through national policy and in the absence of national policy that addresses CTA, coverage is at the discretion of local Medicare contractors. The majority of local contractors have similar local coverage determination policies (LCDs) on CTA. Medicare is a defined benefit program (§ 1812 (Scope of Part A); § 1832 (Scope of Part B) § 1861(s) (Definition of Medical and Other Health Services)). An item or service must fall within a benefit category as a prerequisite to Medicare coverage. CTA may be eligible for coverage under the Social Security Act section 1861(s)(3). IV. Timeline of Recent Activities Date Action June 13, 2007 CMS opens National Coverage Analysis for CTA. July 13, 2007 Initial 30-day public comment period ends. December 13, 2007 CMS posts proposed decision. A second 30-day public comment period begins. January 12, 2008 The second 30-day public comment period ends. V. FDA Status Currently, CT imaging systems and post-processing software go through the 510(k) process at the FDA to obtain clearance for commercial distribution. To obtain 510(k) clearance, the sponsor must demonstrate that the device is substantially equivalent to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). Below are examples of two CT related devices (one CT scanner and one software system) cleared by the FDA through the 510(k) process. The indications for use were copied from the FDA’s 510(k) online database at http://www.fda.gov/cdrh/pdf7/K071806.pdf and http://www.fda.gov/cdrh/pdf6/K062386.pdf respectively. Device Name: ECLOS Computed Tomography X-ray System Clearance Dated: August 28, 2007 The ECLOS Computed Tomography system is an x-ray imaging device that produces cross-sectional images of the body at different angles. The system reconstructs, processes, displays, and stores the collected images. The device output can provide an aid to diagnosis when used by a qualified physician and is intended for general purpose CT applications. Device Name: QAngio CT Clearance Dated: October 5, 2006 QAngio CT software solution has been developed for the objective and reproducible analysis of vessels in CTA images. It enables the quantitative analysis of CT angiograms based on automated segmentation. More specifically, QAngio CT can be used to quantify a number of lesion characteristics. QAngio CT is intended for use as an auxiliary tool in assessing CTA studies in clinical practice and in clinical trials. The analysis results obtained with QAngio CT are to be interpreted by cardiologists and radiologists. VI. General Methodological Principles When making national coverage decisions, CMS evaluates relevant clinical evidence to determine whether or not the evidence is of sufficient quality to support a finding that an item or service falling within a benefit category is reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member. The critical appraisal of the evidence enables us to determine to what degree we are confident that: 1) the specific assessment questions can be answered conclusively; and 2) the intervention will improve health outcomes for patients. An improved health outcome is one of several considerations in determining whether an item or service is reasonable and necessary. A detailed account of the methodological principles of study design that the agency utilizes to assess the relevant literature on a therapeutic or diagnostic item or service for specific conditions can be found in Appendix B. In general, features or clinical studies that improve quality and decrease bias include the selection of a clinically relevant cohort, the consistent use of a single good reference standard, and the blinding of readers of the index test, and reference test results. Public comments sometimes cite the published clinical evidence and give CMS useful information. Public comments that give information on unpublished evidence such as the results of individual practitioners or patients are less rigorous and therefore less useful for making a coverage determination. Public comments that contain personal health information will not be made available to the public. CMS uses the initial public comments to inform its proposed decision. CMS responds in detail to the public comments on a proposed decision when issuing the final decision memorandum. VII. Evidence A. Introduction In this coverage analysis, we considered coronary CTA studies and evidence that were published after the BCBS TEC assessments (published in 2005 and 2006), since the indications are similar. We considered the evidence in the hierarchical framework of Fryback and Thornbury (1991) where Level 2 addresses diagnostic accuracy, sensitivity, and specificity of the test; Level 3 focuses on whether the information produces change in the physician's diagnostic thinking; Level 4 concerns the effect on the patient management plan and Level 5 measures the effect of the diagnostic information on patient outcomes. Most studies have focused on test characteristics and have not considered health outcomes, such as mortality, morbidity or reduction of invasive angiography. We believe that health outcomes are more important than test characteristics. In evaluating diagnostic tests, Mol and colleagues (2003) reported: “Whether or not patients are better off from undergoing a diagnostic test will depend on how test information is used to guide subsequent decisions on starting, stopping, or modifying treatment. Consequently, the practical value of a diagnostic test can only be assessed by taking into account subsequent health outcomes.” When a proven, well established association or pathway is available, intermediate health outcomes may also be considered. For example, if a particular diagnostic test result can be shown to change patient management and other evidence has demonstrated that those patient management changes improve health outcomes, then those separate sources of evidence may be sufficient to demonstrate positive health outcomes from the diagnostic test. 1. Literature Search CMS searched PubMed from 2005 to present. General keywords included computed tomographic angiography, CTA and coronary. Initially, we searched for studies that presented original data, examined health outcomes and were published in peer-reviewed English language journals. Since only one study met these criteria, the search was expanded to included technology assessments, meta-analysis, reviews, and studies that reported only test characteristics compared to invasive coronary angiography. Abstracts were excluded. B. Discussion of evidence reviewed 1. Evidence Questions Is the evidence sufficient to conclude that cardiac CTA has the ability to diagnose or exclude coronary artery disease as well as invasive coronary angiography? Is the evidence sufficient to conclude that cardiac CTA reduces the need for invasive coronary angiography? Is the evidence sufficient to conclude that the use of cardiac CTA improves health outcomes for patients with acute chest pain who present in the emergency room or other settings? 2. External technology assessments DHHS Agency for Healthcare Research and Quality. Non-Invasive Imaging for Coronary Artery Disease. AHRQ 2006; available at: http://www.cms.hhs.gov/Medicare/Coverage/DeterminationProcess/downloads/id34TA.pdf [PDF, 251KB]. In 2006, the Agency for Healthcare Research and Quality commissioned a technology assessment on non-invasive imaging for CAD that was performed by Matchar and colleagues at the Duke Evidence-based Practice Center. For CTA, the authors of the assessment noted: “We identified 29 studies using 16-array or greater multi-detector computed tomography (MDCT) assessing coronary CTA for evaluation of native coronary arteries stenosis, and 13 MRA studies evaluating native coronary artery stenosis using more recent MRI imaging sequences. These studies were generally small, performed at single centers, and often did not include information that would serve to provide confident assessments of the key questions. In particular, we did not identify any studies evaluating the clinical impact of diagnostic strategies including NITs [non-invasive imaging tests] of coronary anatomy compared with strategies that did not include these techniques. The populations studied tended to be relatively young (<65 years of age), and limited results subgrouped by age were available.” They concluded: “At present, there is limited evidence regarding test performance of NITs for identifying, quantifying, or otherwise characterizing coronary artery stenoses. The available evidence provides preliminary data on the ability of coronary MRA (1.5 T) and coronary CTA using at least 16-array MDCT technology to detect obstructive coronary artery lesion in the proximal to mid coronary arteries. The evidence regarding detection of coronary lesions in branch vessels or distal coronary arteries remains unclear and may well improve as the technology improves. Studies conducted to date primarily fall into the “proof of concept” category with study patients having a high pre-test probability of CAD. Patients providing suboptimal images were often excluded from calculations of test accuracy. Future work will need to examine these tests in larger, less selected populations representing the clinical settings in which they are actually expected to be used. The effect of biases in selection of study patients and in the publication of accuracy results for these tests was not assessed in this preliminary analysis.” Blue Cross Blue Shield Technology Evaluation Center. Contrast-enhanced cardiac computed tomographic angiography in the diagnosis of coronary artery stenosis or for evaluation of acute chest pain. TEC Assessment Program, Volume 20, No. 4, May 2005. In 2005, the BCBS TEC published a technology assessment “to evaluate the clinical effectiveness of contrast-enhanced cardiac computed tomographic angiography, hereafter referred to as CTA, for coronary artery evaluation.” Study inclusion criteria were (quoted as follows): Used contrast-enhanced EBCT with slice thickness no greater than 1.5 mm or contrast- enhanced MDCT with at least 16 rows Applied an appropriate reference standard such as conventional coronary angiography or clinical reference standard Reported sensitivity and/or specificity of CTA or sufficient data to generate a 2 × 2 contingency table Included only human subjects Published in English as a full-length, peer-reviewed journal article Twenty-one studies (16 on MDCT, 6 on EBCT; 1016 total patients) were included in the assessment. The TEC reported:” The evidence is insufficient to determine whether the use of CTA improves net health outcome or whether it is as beneficial as any established alternatives.” The TEC criteria and results were as follows: 1. The technology must have final approval from the appropriate governmental bodies. (Met) 2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes. (Not met) 3. The technology must improve the net health outcome. (Not met) 4. The technology must be as beneficial as any established alternatives. (Not met) 5. The improvement must be attainable outside the investigational settings. (Not met) They concluded that: “the use of contrast-enhanced cardiac CT angiography for screening or diagnostic evaluation of the coronary arteries does not meet the TEC criteria.” Blue Cross Blue Shield Technology Evaluation Center. Contrast-enhanced cardiac computed tomographic angiography in the diagnosis of coronary artery stenosis or for evaluation of acute chest pain. TEC Assessment Program, Volume 21, No. 5, August 2006. In 2006, the BCBS TEC published an update of their 2005 assessment of CTA. The objective was “to determine the usefulness of CTA as a substitute for coronary angiography for two indications: 1) in the diagnosis of coronary artery stenosis, and 2) in the evaluation of acute chest pain in the emergency room (ER).” The TEC report focused on “studies examining 64-row CTA, which provides better resolution than the previous generation of 16-row machines.” For CTA as a substitute for invasive angiography, study inclusion criteria were (quoted as follows): Used contrast-enhanced EBCT with slice thickness no greater than 1.5 mm or contrast- enhanced MDCT with at least 32 rows Applied the reference standard of invasive angiography to all patients Reported sensitivity and/or specificity of CTA or sufficient data to generate a 2×2 contingency table Included only human subjects Published in English as a full-length, peer-reviewed journal article For CTA in the ER; “prospective studies were selected in which patients meeting specific chest pain and clinical criteria for evaluation with CTA were chosen to have the test.” Seven studies (480 patients) were evaluated for CT diagnostic accuracy, and 2 studies (100 patients) for CTA in the ER. The TEC reported: “The available evidence is inadequate to determine whether CTA improves the net health outcome or is as beneficial as established alternatives for diagnosis of coronary artery stenosis or for evaluation of acute chest pain in the ER.” The TEC criteria and results were as follows: 1. The technology must have final approval from the appropriate governmental bodies. (Met) 2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes. (Not met) 3. The technology must improve the net health outcome. (Not met) 4. The technology must be as beneficial as any established alternatives. (Not met) 5. The improvement must be attainable outside the investigational settings. (Not met) They concluded: “CTA as a substitute for coronary angiography in the diagnosis of coronary artery stenosis does not meet the TEC criteria. CTA in the evaluation of acute chest pain in the emergency room also does not meet the TEC criteria.” 3. Internal technology assessments Meta-Analyses Hamon M, Biondi-Zoccai G, Malagutti P, et al. Diagnostic performance of multislice spiral computed tomography of coronary arteries as compared with conventional invasive coronary angiography. A meta-analysis. J Am Coll Cardiol 2006;48:1896 –1910. In 2006, Hamon and colleagues reported the results of a meta-analysis “to define the current role of multislice spiral computed tomography (MSCT) for the diagnosis of coronary artery disease (CAD) using a meta-analytic process.” The authors included 29 studies (2024 patients), published from 2002 to 2006, that evaluated the coronary arteries using both CTA (at least 16 slice) and conventional coronary angiography. Study inclusion criteria were: “1) it used MSCT as a diagnostic test for obstructive CAD, with >50% diameter stenosis selected as the cut-off criterion for significant CAD, using conventional invasive angiography as the reference standard; 2) it used the newest generation of MSCT ( ≥16 slices); and 3) it reported cases in absolute numbers of true positive (TP), false positive (FP), true negative (TN), and false negative (FN) results or presented sufficiently detailed data for deriving these figures.” Exclusion criteria were studies performed: “1) only in patients after coronary artery bypass graft surgery; 2) after percutaneous coronary intervention for long-term stent patency assessment; 3) in a subset of patients with prior heart transplant; or 4) with fewer than 30 enrolled patients.” Patient symptomatology was not specified. A random-effects model was used for the analysis. The authors noted a considerable percentage of uninterpretable segments that were excluded from the analysis by the study investigators. Pooled sensitivity, specificity, positive and negative predictive values per-segment were 81%, 93%, 67.8% and 96.5%, respectively, and per patient were 96%, 74%, 83% and 94%, respectively. The authors concluded: “Multislice spiral computed tomography has shortcomings difficult to overcome in daily practice and, at the more clinically relevant per-patient analysis, continues to have moderate specificity in patients with high prevalence of CAD. Studies evaluating the diagnostic performance of the newest generation of MSCT, including patients with low to moderate CAD prevalence, will be critical in establishing the clinical role of this emerging technology as an alternative to CA.” Schuijf JD, Bax JJ, Shaw LJ, et al. Meta-analysis of comparative diagnostic performance of magnetic resonance imaging and multislice computed tomography for noninvasive coronary angiography. Am Heart J 2006;151:404- 11. In 2006, Schuijf and colleagues reported the results of a meta-analysis “to clarify the current accuracy of both modalities in the detection of significant coronary artery lesions (compared to conventional angiography as the gold standard).” The authors included 24 studies (1300 patients), published from 2001 to 2005, that compared MSCT (4 to 16 slice) to invasive coronary angiography in patients with known or suspected CAD. Reports with insufficient data to calculate sensitivity and specificity were excluded. Meta-analysis model was not specified. Summary odds ratios were calculated using the “Comprehensive Meta Analysis” program. The authors reported pooled test parameters as follows: sensitivity 85%, specificity 95%, PPV 76% and NPV 97%. They concluded: “Meta-analysis of the available studies with MRI and MSCT for noninvasive coronary angiography indicates that MSCT has currently a significantly higher accuracy to detect or exclude significant coronary artery disease.” Sun Z, Jiang W. Diagnostic value of multislice computed tomography angiography in coronary artery disease: A meta-analysis. European Journal of Radiology 2006;60:279–286. In 2006, Sun and Jiang reported the results of a meta-analysis to determine “the diagnostic value of multislice CT (MSCT) angiography in the detection of coronary artery disease (CAD) when compared to conventional coronary angiography.” The authors included 47 studies (3149 patients), published from 2001 to 2006, that studied at least 4 slice CT. Study inclusion criteria were: “(a) patients undergoing both MSCT angiography and coronary angiography examinations; (b) studies included at least 10 patients; (c) assessment or comparison of MSCT angiography with coronary angiography was focused on the visualization of coronary arteries and detection or exclusion of coronary artery stenosis; (d) diagnostic value of MSCT angiography was addressed when compared to coronary angiography in terms of sensitivity, specificity, either segments-, vessels- or patients-based assessment.” Exclusion criteria, study types, patient symptomatology and setting were not specified. Model for analysis was not specified. The authors reported pooled sensitivities and specificities for 4, 16 and 64 slice CT in the detection of CAD (76%, 93%; 82%, 95%; 92%, 94%; respectively). They concluded that: “MSCT angiography has potential diagnostic accuracy in the detection of CAD. Diagnostic performance of MSCT angiography has been significantly improved with the latest 64-slice CT, with resultant high qualitative and quantitative diagnostic accuracy. 16-slice CT was limited in spatial resolution which makes it difficult to perform quantitative assessment of coronary artery stenoses.” Systematic Reviews Janne d’Othee B, Siebert U, Cury R, et al. A systematic review on diagnostic accuracy of CT-based detection of significant coronary artery disease. European Journal of Radiology 2007, in Press. In 2007, Janne d’Othee and colleagues reported the results of a systematic review to estimate sensitivity and specificity of various imaging modalities. Studies were included if they “used contrast-enhanced CT as a diagnostic test, evaluated native coronary arteries, used catheter-based coronary angiography (CCA) as a reference standard independently of CT findings, reported raw data (i.e., numbers that allowed recalculation of 2×2 contingency tables), and were published in peer reviewed journals.” Coronary artery bypass graft and coronary stent studies were excluded. Catheter based coronary angiography was the reference standard. Forty-one studies (2515 patients) were analyzed. A random effects model was used to calculate summary estimates. The authors reported: “Analysis of all coronary segments yielded a sensitivity of 95% (80%, 89%, 86%, 98% for electron beam CT, 4/8-slice, 16-slice and 64-slice MDCT, respectively) for a specificity of 85% (77%, 84%, 95%, 91%).” They noted: “In conclusion, recent advances in CT technology have resulted in an increase in the proportion of coronary segments assessable by CT and in improved diagnostic accuracy from EBCT to 4/8, 16, and 64-slice MDCT. The latter improvement is best demonstrated by the all-segment analysis. With current 64 slice scanners, diagnostic accuracy of CE-CCT is high on a per segment basis. Per patient however, this accuracy may be lower in patients with multi-vessel disease, which may limit the clinical utility of CT in populations at high risk for CAD. The utility of CT in patients with intermediate risk for CAD remains to be established.” Stein PD, Beemath A, Kayali F, et al. Multidetector computed tomography for the diagnosis of coronary artery disease: a systematic review. American Journal of Medicine 2006;119: 203-216. In 2006, Stein and colleagues reported the results of a meta-analysis “to determine the sensitivity and specificity of contrast-enhanced multidetector computed tomography (CT) for the detection of coronary artery disease.” The authors included 33 studies (1606 patients), published from 2001 to 2005, that compared MSCT (4 to 16 slice and 1 study on 64 slice) with invasive coronary angiography. Studies were included if they reported type of machines, data on sensitivity and specificity and patient selection criteria. Abstracts, in vitro studies, series with ≤ 10 patients were among those excluded. Meta-analysis model was not specified. Average sensitivity and specificity were calculated from pooled data. The authors reported: “Average sensitivity for patient-based detection of significant (>50% or ≥50%) stenosis was 61 of 64 (95%) with 4-slice CT, 276 of 292 (95%) with 16-slice CT, and 47 of 47 (100%) with 64-slice CT. Average specificity was 84% for 4-slice CT, 84% for 16-slice CT, and 100% for 64-slice CT.” They concluded: “Multidetector CT has the potential to be used as a screening test in appropriate patients. Contrast-enhanced 16-slice CT seems to be reasonably sensitive and specific for the detection of significant coronary artery disease but has shortcomings. Preliminary data with 64-slice CT suggest that it is more sensitive and specific.” 16 Slice MSCT Garcia MJ, Lessick J, Hoffmann MHK, CATSCAN investigators. Accuracy of 16-Row Multidetector Computed Tomography for the Assessment of Coronary Artery Stenosis. JAMA 2006;296:403-411. In 2006, Garcia and colleagues reported the results of a case series of 238 patients “to determine the diagnostic accuracy of 16-row MDCT for the detection of obstructive coronary disease.” Included patients were between 30 and 70 years of age who were referred for clinically indicated nonemergency coronary angiography, for evaluation of chest pain, and for intermediate or high probability of disease. Exclusion criteria included prior bypass surgery, arrhythmias, pacemakers/defibrillators, renal insufficiency and contrast allergy. MDCT was performed using 16 row scanners and was done prior to invasive angiography. Invasive angiography was the reference standard. Of the 238 patients, 187 underwent 16 row MDCT with contrast and β blocker drugs. Forty-five percent of patients were classified as intermediate probability for CAD and 55% as high probability, according to the ACC/AHA guidelines (Gibbons et al., 2002). Invasive angiography was the reference standard. Mean age was 60 years. Men comprised 68% of the study population. Of the 1629 segments, 29% were uninterpretable. The authors reported: After censoring all nonevaluable segments as positive, the sensitivity for detecting more than 50% luminal stenoses was 89%; specificity, 65%; positive predictive value, 13%; and negative predictive value, 99%. In a patient-based analysis, the sensitivity for detecting patients with at least 1 positive segment was 98%; specificity, 54%; positive predictive value, 50%; and negative predictive value, 99%.” The authors concluded: “The results of this study indicate that MDCT coronary angiography performed with 16-row scanners is limited by a high number of nonevaluable cases and a high false-positive rate. Thus, its routine implementation in clinical practice is not justified. Nevertheless, given its high sensitivity and negative predictive value, 16-row MDCT may be useful in excluding coronary disease in selected patients in whom a false-positive or inconclusive stress test result is suspected.” There was no follow-up on health outcomes. Hoffmann MHK, Shi H, Schmitz BL, et al. Noninvasive coronary angiography with multislice computed tomography. JAMA 2005;293:2471-2478. In 2005, Hoffmann and colleagues reported the results of a case series of 103 patients “to assess the accuracy and robustness of MSCT vs the criterion standard of invasive coronary angiography for detection of obstructive coronary artery disease.” All patients had suspected CAD, were in sinus rhythm, were able to hold their breath for 25 seconds, and had been referred for invasive coronary angiography prior to inclusion in the study. Exclusion criteria included prior revascularization, renal insufficiency and contrast allergy. Scans were performed using a 16 detector MSCT with contrast and β blocker drugs. Pretest probability for CAD was assessed according to ACC/AHA guidelines (Gibbons et al., 2002). Invasive coronary angiography was the reference standard. Mean age was 62 years. Men comprised 69% of the study population. For CAD, 2% were determined to have low probability; 63% at intermediate probability; and d 35% at high probability. The authors reported: “Compared with invasive coronary angiography for detection of significant lesions (>50% stenosis), segment-based sensitivity, specificity, and positive and negative predictive values of MSCT were 95%, 98%, 87%, and 99%, respectively.” These estimates excluded 27% of the study patients who had “only partial coronary tree coverage available.” Of the 1384 segments, 88 (6.4%) were uninterpretable. Sensitivity, specificity, and positive and negative predictive values per patient were 97%, 87%, 90%, 95%, respectively. The authors concluded: “Multislice computed tomography provides high accuracy for noninvasive detection of suspected obstructive coronary artery disease. This promising technology has potential to complement diagnostic invasive coronary angiography in routine clinical care.” There was no follow-up on health outcomes. Kuettner A, Beck T, Drosch T, et al. Diagnostic accuracy of noninvasive coronary imaging using 16-detector slice spiral computed tomography with 188 ms temporal resolution. J Am Coll Cardiol 2005;45:123–127 . In 2005, Kuettner and colleagues reported the results of a case series of 72 patients “to evaluate the diagnostic accuracy of 16-multi-detector spiral computed tomography (MDCT) with 188 ms temporal resolution.” All patients were scheduled for invasive angiography and also underwent MDCT imaging. Exclusion criteria include arrhythmias, renal insufficiency and contrast allergy. Scans were performed using 16 detector MDCT with contrast and β blocker drugs. Pretest probability was not specified. Invasive angiography was the reference standard. Mean age was 64 years. Men comprised 63% of the study population. The authors reported: “Sensitivity, specificity, and positive and negative predictive values for the whole study group were as follows: 82%, 98%, 87%, and 97%, respectively. The correct clinical diagnosis of presence or absence of significant CAD was obtained in 65 of 72 (90%) patients.” Of the 936 segments, 62 (6.6%) were uninterpretable. Per patient estimates were not reported. The authors noted: “In conclusion, noninvasive MDCT imaging is becoming more and more accurate. However, further improvements of spatial and temporal resolution are still required to challenge diagnostic invasive coronary angiography.” There was no follow-up on health outcomes. Mollet NR, Cademartiri1 F, Mieghem CV, et al. Adjunctive value of CT coronary angiography in the diagnostic work-up of patients with typical angina pectoris. European Heart Journal 2007;28:1872–1878. In 2007, Mollet and colleagues reported the results of a consecutive series of 62 patients “to determine the adjunctive value of CT coronary angiography (CTCA) in the diagnostic work-up of patients with typical angina pectoris.” Patients included had typical angina, sinus heart rhythm and were able to hold their breaths for at least 20 seconds. Exclusion criteria included arrhythmias, renal insufficiency and contrast allergy. Scans were performed using 16 slice CT with contrast and β blocker drugs. Pre-test probability was high (81%). Invasive angiography was the reference standard. Mean age was 59 years. Men comprised 73% of the study population. The authors reported sensitivity, specificity, PPV, NPV of 100%, 87%, 96%, 100%, respectively, per patient. They concluded: “Non-invasive CTCA is a potentially useful tool, in the diagnostic work-up of patients with typical angina pectoris, both to detect and to exclude significant CAD.” They also noted: “We have studied a relatively small number of patients who are at high risk of having significant CAD and excluded a significant number of patients because of logistic inability to perform CTCA before the conventional angiogram.” Health outcomes were not reported. 64 Slice MSCT Meijboom WB, Mollet NR, Van Mieghem CA, et al. 64-slice computed tomography coronary angiography in patients with non-ST elevation acute coronary syndrome. Heart 2007 (online);doi:10.1136/hrt.2006.112771. In 2007, Meijboom and colleagues reported the results of a non-consecutive case series of 104 patients to study “the diagnostic performance of 64-slice CT coronary angiography in patients with non-ST elevation acute coronary syndrome.” Patients presented with either unstable angina or non-ST elevation myocardial infarction. Exclusion criteria included atrial fibrillation, renal insufficiency and contrast allergy. Scans were performed using 64 slice CT with contrast and β blocker drugs. Pre-test probability was either high (68%) or low with positive or inconclusive exercise tests or high suspicion of CAD (32%). Invasive angiography was the reference standard. Mean age was about 59 years. Men comprised 72% of the study population. The authors reported sensitivity, specificity, PPV, NPV of 100%, 75%%, 96%, 100%, respectively, per patient. Of the 1525 segments evaluated, 243 (15.9%) were not visualized and excluded. They concluded: “64-slice CT angiography has a high sensitivity to detect significant coronary stenoses and is reliable to exclude the presence of significant coronary artery disease in patients who present with a non-ST elevation acute coronary syndrome. The role of CT coronary angiography in these patients, particular in the lower risk group, needs to be further evaluated.” Health outcomes were not reported. Francone M, Napoli A, Carbone I, et al. Noninvasive imaging of the coronary arteries using a 64-row multidetector CT scanner: initial clinical experience and radiation dose concerns. Radiol med 2007;112:31–46 . In 2007, Francone and colleagues reported the results of a case series of 114 patients to evaluate 64 detector CT. Of the 114 patients, 23 patients had MDCT to evaluate the coronary arteries for typical or atypical chest pain, 37 for evaluation of stent patency, 40 for patency of bypass grafts, 3 for inconclusive myocardial perfusion scintigraphy, and 11 for inconclusive stress echocardiography. Exclusion criteria included arrhythmia, kidney failure and contrast allergy. Scans were performed using 64 detector MDCT with contrast and β blocker drugs. Pretest probability was not reported. No reference standard was specified. Mean age was 63 years. Findings were not separately presented for the group of patients with chest pain. Test parameters and assessable segments were not reported. The authors concluded: “In our initial clinical experience, the use of 64-MDCT has provided very promising results. Although the technique needs to be validated with systematic comparisons with clinical, laboratory and coronarographic data, the latest generation of 64-MDCT scanners offers new possibilities for clinical management of patients with coronary artery disease. The increase in spatial and temporal resolution translates into improved diagnostic image quality with respect to previous generations of multidetector devices. Thus, 64-MDCT is a noninvasive technique capable of identifying patients requiring interventional or surgical procedures such as selective coronarography with primary angioplasty or stent placement, or surgical revascularisation with bypass grafts. The use of suitable systems for the automatic control of radiation exposure seems nonetheless indispensable in order to limit patient dose, which given the current state of affairs is the main limitation to the clinical use of the technique.” Ehara M, Surmely J, Kawai M, et al. Diagnostic accuracy of 64-slice computed tomography for detecting angiographically significant coronary artery stenosis in an unselected consecutive patient population. Circ J 2006;70:564–571 . In 2006, Ehara and colleagues reported the results of a case series of 69 patients “to investigate the accuracy of 64-slice MSCT (64 MSCT) in daily practice, without any patient selection.” Nineteen patients with suspected CAD, 50 patients with proven CAD were enrolled. Exclusion criteria included arrhythmias, renal insufficiency and contrast allergy. Scans were performed using a 64 slice MSCT machine with contrast and β blocker drugs as needed. Pretest probability was not specified. Reference standard was invasive angiography. Mean age was 67 years. Men comprised 75% of the study population. The authors reported: “Compared with ICAG (invasive coronary angiography) the sensitivity of CTA to diagnose significant stenosis was 90%, specificity 94%, positive predictive value (PPV) 89% and negative predictive value (NPV) 95%. With regard to 58 stented lesions, the sensitivity, specificity, PPV and NPV were 93%, 96%, 87% and 98%, respectively. On the patient-based analysis, the sensitivity, specificity, PPV and NPV of CTA to detect CAD were 98%, 86%, 98% and 86%, respectively.” Of the 966 segments, 82 (8%) were uninterpretable. The authors concluded: “Sixty-four-MSCT has a high accuracy for the detection of significant CAD in an unselected patient population and therefore can be considered as a valuable noninvasive technique.” No health outcomes were reported. Ropers D, Rixe J, Anders K, et al. 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. Am J Cardiol 2006;97:343–348. In 2006, Ropers and colleagues reported the results of a case series of 84 patients to analyze “the accuracy of 64-slice MDCT coronary angiography for the detection of significant coronary artery stenoses compared with quantitative coronary angiography.” All patients enrolled in the study had been referred for invasive angiography due to suspected CAD. Exclusion criteria included acute coronary syndromes, arrhythmias, and contrast allergy. Scans were performed using 64 slice MDCT with contrast and β blocker drugs. Pretest probability was not specified. Invasive angiography was the reference standard. Mean age was 58 years. Men comprised 62% of the study population. The authors reported: “After exclusion of unevaluable coronary segments (4%), multidetector computed tomography demonstrated a sensitivity of 93%, a specificity of 97%, and a negative predictive value of 100% in a per-segment analysis. In a per-artery analysis, 15 of 336 arteries (4%) were unevaluable. Sensitivity and specificity in evaluable arteries were 95% and 93%, respectively. In a per-patient analysis (81 of 84 patients included), sensitivity and specificity were 96% and 91%, respectively.” Other Nonspecified CTA Budoff MJ, Gopal A, Gul KM, et al. Prevalence of obstructive coronary artery disease in an outpatient cardiac CT angiography environment. International Journal of Cardiology 2007; In Press. In 2007, Budoff and colleagues reported the results of a descriptive study of 493 patients “to determine the prevalence of significant obstructive disease and non-diagnostic studies using coronary computed tomographic angiography (CTA) in an outpatient environment, to establish if CTA could help avoid unnecessary diagnostic cardiac catheterizations.” All patients that received CTA “over one year with an indication that could warrant a cardiac catheterization to establish the presence or absence of coronary artery disease (CAD).” Exclusion criteria included prior myocardial infarction, revascularization and congenital heart diseases. “Referred patients generally had an intermediate pre-test probability of obstructive disease (20–80%).” Specific pretest probabilities were not noted. Scans were performed using an electron beam scanner with unspecified detectors. Reference standard was not used for all patients. Mean age was 58 years. Men comprised 68% of the population. The authors reported: "Of the 493 index cases evaluated, 157 (32%) cases were reported to be normal, 204 patients were classified as having nonobstructive disease (41%), 93 patients were defined to have obstructive CAD (19%), and 39 cases were inconclusive (8%).” Sensitivity, specificity and predictive values were not reported. In this study, there was no comparison test. There was no follow-up on health outcomes and patients who received invasive angiography subsequently. Dual Source CT Heuschmid M, Burgstahler C, Reimann A, et al. Usefulness of noninvasive cardiac imaging using dual-source computed tomography in an unselected population with high prevalence of coronary artery disease. Am J Cardiol 2007;100:587–592. In 2007, Heuschmid and colleagues reported the results of a case series of 51 patients “to evaluate the diagnostic accuracy of new DSCT in unselected patients with a high prevalence of CAD, irregular heart rate, and extensive calcific deposits.” All patients were scheduled for invasive angiography due to CAD. Exclusion criteria were unstable angina, renal insufficiency, allergy to contrast. Scans were performed using DSCT with contrast. Pretest probability was not specified. Invasive angiography was the reference standard. Mean age was 64 years. Men comprised 73% of the study population. The authors reported: Based on a coronary segment model, sensitivity was 96%, specificity 87%, positive predictive value 61%, and negative predictive value 99% for the detection of significant lesions (>50% diameter stenosis).” Of the 632 segments that were not stented, 117 (18.5%) were uninterpretable. They concluded: “our initial data indicate that DSCT allows a high accuracy to exclude relevant coronary stenosis in unselected patients with a high prevalence of CAD and a relevant number with heart rhythm irregularities. However, overestimation of stenosis, especially in cases of calcifications, is still a limitation.” There was no follow-up on health outcomes. Weustink AC, Meijboom WB, Moller NR, et al. Reliable high-speed coronary computed tomography in symptomatic patients. J Am Coll Cardiol 2007;50:786–794. In 2007, Weustink and colleagues reported the results of a case series of 100 patients with chest pain “to prospectively evaluate the diagnostic performance of the high-speed dual-source computed tomography scanner (DSCT), with an increased temporal resolution (83 ms), for the detection of significant coronary lesions (≥50% lumen diameter reduction) in a clinically wide range of patients.” All patients were symptomatic with “atypical angina, typical angina, and unstable coronary artery disease (unstable angina or non–ST segment elevation myocardial infarction) scheduled for conventional coronary angiography (CCA).” Patients with arrhythmias, past percutaneous coronary intervention, or bypass surgery, and allergy to contrast were excluded. Scans were performed using DSCT with contrast with nitroglycerin medication. Pretest probability was not specified. Invasive angiography was the reference standard. Mean age was 61 years. Men comprised 79% of the study population. The authors reported: “Sensitivity, specificity, and positive and negative predictive values of DSCT coronary angiography for the detection of significant lesions on a segment-by-segment analysis were 95% (95% confidence interval [CI] 90 to 97), 95% (95% CI 93 to 96), 75% (95% CI 69 to 80), 99% (95% CI 98 to 99), respectively, and on a patient-based analysis 99% (95% CI 92 to 100), 87% (95% CI 65 to 97), 96% (95% CI 89 to 99), and 95% (95% CI 74 to 100), respectively.” Image quality was poor in 14% of the coronary segments. They concluded: “Dual source computed tomography scanner coronary angiography demonstrated a high diagnostic accuracy for the detection or exclusion of significant stenoses in patients with various heart rates without exclusion of unevaluable segments. These results indicate that the technique may now be tested in a cohort with a low-to-intermediate pretest probability of coronary artery disease or in patients with nonanginal chest pain to establish the role of DSCT coronary angiography in the management of patients with suspected coronary artery disease.” Scheffel H, Alkadhi H, Plass A, et al. Accuracy of dual-source CT coronary angiography: first experience in a high pre-test probability population without heart rate control. Eur Radiol 2006;16:2739–2747. In 2006, Scheffel and colleagues reported the results of a case series of 30 patients “to assess the diagnostic accuracy of dual source computed tomography (DSCT) for evaluation of coronary artery disease (CAD) in a population with extensive coronary calcifications without heart rate control.” Thirty patients who had invasive coronary angiography were included in the study. DSCT was performed within 30 days of catheterization. Exclusion criteria included previous stent or bypass surgery, renal insufficiency and contrast allergy. Scans were performed using DSCT with contrast and nitrate drugs. Based on a clinical score developed by Morise and colleagues (Morise et al., 1997), all patients were determined to have high pre-test probability of CAD. Invasive coronary angiography was the reference standard. Mean age was 63 years. Men comprised 80% of the study population. The authors reported: “Overall sensitivity, specificity, positive and negative predictive value for evaluating CAD were 96.4, 97.5, 85.7, and 99.4%, respectively.” Of the 420 coronary segments, 6 (1.4%) were uninterpretable. They concluded: “First experience indicates that DSCT coronary angiography provides high diagnostic accuracy for assessment of CAD in a high pre-test probability population with extensive coronary calcifications and without heart rate control. Further