Coronary CT Angiography: Are We There Yet?
Abstract & Commentary
By Andrew J. Boyle, MBBS, PhD, Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco Dr. Boyle reports no financial relationships relevant to this field of study.
Sources: Miller JM, et al. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med. 2008;359: 2324-2836; Budoff MJ, 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;52:1724-1732.
Invasive coronary angiography (ICA) is the gold standard for assessment of epicardial coronary artery disease. There is much interest in non-invasive alternatives to ICA to assess coronary arteries in order to eliminate the complications associated with arterial access and catheter manipulation during ICA. The 64-row computed tomography (CT) has vastly improved spatial resolution compared to previous generations of CT scanners, making coronary angiography feasible. Previous smaller, single-center studies had suggested that 64-row coronary CT angiography (CCTA) had similar diagnostic ability to ICA in evaluating epicardial coronary artery stenoses. Two recent studies compared CCTA to ICA in the same patients being evaluated for chest pain, and reached conflicting conclusions.
Miller et al performed a multicenter study at nine hospitals in seven countries (three in the United States and one each in Germany, Japan, Brazil, Canada, Singapore, and the Netherlands). They enrolled patients older than age 40 with symptoms suggestive of coronary artery disease, who were referred for ICA. Their exclusion criteria were a coronary Agatston calcium score > 600, a history of cardiac surgery, allergy to iodinated contrast dye or contrast-induced nephropathy, multiple myeloma, organ transplantation, elevated serum creatinine level (> 1.5 mg/dL), atrial fibrillation, class III or IV heart failure, aortic stenosis, percutaneous coronary intervention within the past six months, intolerance to beta blockers, or a body-mass index (BMI) of more than 40. The patients underwent CCTA using a median dose of 76 mL of iopamidol, after sublingual nitroglycerin and beta blocker if the heart rate was above 70/min. They then underwent ICA a mean of 10 hours post CCTA. ICA was performed in standard fashion, and was analyzed using quantitative coronary angiography (QCA) in a core lab.
Miller et al present data on both a patient-based and a vessel-based analysis. They included 291 patients (74% male) with a mean age of 59 years. Fifty-six percent of patients had at least one coronary artery stenosis > 50% by QCA. The area under the curve of the receiver operating characteristic (ROC) curve was 0.93. The CCTA had sensitivity and specificity of 85% and 90%, respectively, for detecting coronary artery stenoses > 50%. The corresponding positive and negative predictive values were 91% and 83%, respectively. Quantitative and visual estimation of severity of lesions on CCTA yielded similar values. Vessel-based analysis also showed similar results, with no difference seen in the sensitivity and specificity between different vessels. They concluded that coronary 64-row multi-detector CT angiography is accurate in identifying coronary stenoses and characterizing disease severity in symptomatic patients who have coronary calcium scores of 600 or less. However, multi-detector CT angiography cannot be used as a simple replacement for conventional coronary angiography, given its negative predictive value of 83% and positive predictive value of 91% in this population of patients.
Budoff et al performed a multicenter study in 16 US sites, performing CCTA in patients referred for ICA for symptoms suggestive of ischemia. They enrolled patients older than 18 years of age and did not exclude anyone based on coronary artery calcium score or BMI. Their exclusion criteria were: known allergy to iodinated contrast, creatinine > 1.7 mg/dL, irregular cardiac rhythm, resting heart rate > 100/min, resting systolic blood pressure < 100 mmHg, contraindication to beta blockers, calcium-channel blockers, or nitroglycerin, pregnancy, or known history of CAD (prior myocardial infarction, percutaneous coronary intervention or coronary artery bypass surgery). The patients underwent CCTA using 80 mL of iodixanol after sublingual nitroglycerin and a beta blocker if the heart rate was above 65/min. They then underwent ICA a mean of 5.9 days post CCTA; ICA was performed in standard fashion and was analyzed using QCA.
In a similar fashion to the previous study, Budoff et al present data on both a patient-based and a vessel-based analysis. Results are reported for 230 patients (59% male) with a mean age of 57 years. Twenty-five percent were found to have at least one coronary artery stenosis > 50% by QCA. The area under the curve of the ROC was 0.96. The CCTA had sensitivity and specificity of 95% and 83%, respectively, for detecting coronary artery stenoses > 50%. The corresponding positive and negative predictive values were 64% and 99%, respectively. Quantitative and visual estimation of severity of lesions on CCTA yielded similar values. Vessel-based analysis also showed similar results, with no difference seen in the sensitivity and specificity between different vessels. They also repeated the analyses using a cut-off of 70% stenosis on ICA, and found similar sensitivity and specificity; the negative predictive value was still 99%. Furthermore, they compared the results of patients with coronary calcium scores above and below 400 Agatston units, finding similar sensitivity but reduced specificity in patients with elevated coronary calcium scores. In addition, they compared patients with BMI above and below 30, and found no significant difference in sensitivity or specificity. They conclude that CCTA demonstrates high accuracy for detection of obstructive coronary artery stenosis in patients with chest pain, but without known coronary artery disease, and that the high negative predictive value (99%) establishes CCTA as an effective non-invasive method to rule out obstructive coronary artery stenosis.
These two studies were rigorously performed, prospective, multicenter studies that demonstrate the new generation of 64-detector CT scanners is able to demonstrate coronary stenoses accurately in the majority of cases. They have very similar trial designs, and provide important data on the utility of CCTA in patients referred for coronary angiography. They are both prospective, multicenter studies that performed CCTA and invasive coronary angiography in the same patients, strengthening the results, because each patient is their own control group, and the test studied (CCTA) is referenced to a gold standard test. The cohorts were of similar size and age, with Miller et al's group having a higher proportion of males and Budoff et al's group having higher BMI and higher coronary calcium scores. The area under the ROC curves was similar in the two studies in assessing the presence of 50% stenoses on a patient-based analysis. Why then, were the conclusions discordant? Clinicians want to use CCTA to exclude obstructive CAD, and do not want to miss a lesion that could be responsible for the patient's symptoms, or could lead to myocardial infarction. Therefore, the negative predictive value of the test is paramount. The major difference between groups is the prevalence of coronary artery stenoses. In Miller et al's study, 56% had coronary stenoses, compared to 25% in Budoff et al's study. It is unlikely that this biased away from Miller et al's study, and we are left with no clear explanation for the differing negative predictive values between these two studies. A negative predictive value of 99% may be acceptable for a new test, but 83% clearly is not.
It is important to note that both studies were performed in symptomatic patients and, therefore, the results cannot be extrapolated to screening asymptomatic individuals. The difference between the negative predictive values in these studies leaves some doubt as to the role of CCTA in assessing patients with chest pain.