Author + information
- Steven E. Nissen, MD⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Steven E. Nissen, Cleveland Clinic Foundation, Cardiovascular Medicine, 9500 Euclid Avenue, Desk F-15, Cleveland, Ohio 44195-0001
In this issue of the Journal, Arbab-Zadeh et al. (1) report on the influence of calcification and the pre-test likelihood of disease on the diagnostic accuracy of coronary computed tomography angiography (CTA) in a small multicenter study (CORE-64 [Coronary Artery Evaluation Using 64-Row Multidetector Computed Tomography Angiography]). Their report provides valuable insights into the importance of coronary calcification as an unresolved limitation of CTA. The original CORE-64 report pre-specified exclusion of patients with a calcium score >600 Agatston units, a criterion that eliminated 89 of 405 patients (22%) from the analysis (2). In the current paper (1), the authors have appropriately included such patients, documenting an important limitation in the diagnostic accuracy of CTA when applied in an unselected population. For patients with Agatston score >600, the performance of CTA was unfavorable. Regardless of pre-test likelihood of disease, the negative predictive value was 0.50 for quantitative assessment of CAD and 0.63 for visual assessment.
The current study also demonstrates that lesser degrees of coronary calcification can impair the diagnostic accuracy of coronary CTA. Among patients with any calcification score >0, the negative predictive value of CTA in patients with a high pre-test probability of disease ranged from approximately 50% to 60%. Similar deterioration in performance was observed for patients with coronary calcification and an intermediate probability of disease, particularly if the Agatston score exceeded 100. The careful analysis provided by the current study will be valuable to practitioners considering how to optimally apply coronary CTA in routine clinical practice. These findings suggest that CTA, using current technology, probably should not be used for diagnostic purposes in patients with substantial coronary calcification.
Understanding the exclusion criteria in any imaging study is critical to interpretation of the findings. The original CORE-64 study report, like several similar studies, was designed to evaluate coronary CTA under reasonably ideal conditions. The list of exclusion criteria included prior cardiac surgery, creatinine levels >1.5 mg/dl, atrial fibrillation, class III or IV heart failure, coronary intervention within the past 6 months, intolerance to beta-blockers, and a body mass index >40 kg/m2. It is useful to consider the profile of patients undergoing catheterization for suspected coronary disease in the United States. The median body mass index of patients undergoing catheterization in recent studies exceeds 30 kg/m2, with substantial numbers exceeding 40 kg/m2. The prevalence of atrial fibrillation in the U.S. population is substantial and increases with age, reaching nearly 10% by 80 years of age (3). Approximately 11% of American over the age of 60 years have a creatinine level ≥1.6 mg/dl (4). The prevalence of chronic obstructive pulmonary disease is also high among patients undergoing catheterization, suggesting that intolerance to beta-blockers will result in exclusion of additional patients.
For ethical reasons, the CORE-64 study population only included patients for whom cardiac catheterization was deemed clinically indicated. Ninety-eight patients (26%) actually had known coronary disease. Such patients represent a high-risk subset of those seeking medical care for chest pain of suspected cardiac origin, which likely explains the relatively high prevalence of coronary calcification. The symptoms exhibited by these patients were sufficient to warrant the risk and expense of cardiac catheterization. In this population, we must consider whether the results of CTA would allow deferral of coronary angiography. In the current analysis (1), the negative predictive value of coronary CTA for patients with known CAD was approximately 0.50. In the group with an intermediate probability of disease, the sensitivity and specificity were more acceptable, with false positive and false negative rates in the 10% to 15% range. Therefore, as documented in the current study (1), error rates remain too high to recommend use of CTA as an alternative to cardiac catheterization or imaging stress tests in patients with a high probability of CAD.
In determining when to use coronary CTA in clinical practice, we must also consider the potential harm produced by coronary CTA imaging as currently practiced. The doses of radiation are substantial, although gradually falling at sophisticated centers with technical improvements in study methods. The median radiation dose in a large multicenter study of CTA was 12 mSv, equivalent to 600 chest radiographs (5). The CORE-64 study authors report slightly higher doses, ranging from 12 to 15 mSv, with a top limit of 20 mSv. By comparison, most studies of conventional diagnostic coronary angiography report a dose range from 2 to 6 mSv. Accordingly, the radiation dosage from CTA is equivalent to 3 to 7 diagnostic catheterizations. The likely effect of such doses has been debated, but it is generally accepted that there is no safe dosage of radiation and that exposure to current dose levels will predictably increase rates of malignancy. Many patients will likely receive numerous CTA studies and other radiographic and nuclear imaging procedures for cardiac and noncardiac indications. Accordingly, the patient care benefits of any imaging procedure that exposes patients to ionizing radiation must clearly exceed the hazards.
In addition to the problem of coronary calcification demonstrated by the current study, it must also be recognized that the presence of a coronary stenosis per se does not accurately determine the physiological consequences of such lesions. The presence or absence of a 50% stenosis in the coronary arteries does not define whether revascularization is appropriate or inappropriate. Symptoms and the presence of reversible ischemia are the pivotal factors determining the appropriateness of coronary interventions. Accordingly, in the assessment of patients with an intermediate probability of CAD, coronary CTA remains less useful than imaging stress tests. For such patients, we are less interested in the presence of stenosis than evidence documenting whether obstructions are ischemia-producing. Accordingly, an abnormal CTA may require another imaging procedure in many patients to determine the physiologic impact of observed stenoses.
In future studies, what proof of benefit should we demand of CTA? To justify widespread usage, the technique must be shown to improve relevant patient outcomes, including survival, improve the accuracy of diagnoses, or substantially reduce health care costs. None of these benefits has yet been demonstrated convincingly for coronary CTA. Nonetheless, CT coronary imaging continues to grow in utilization, often fueled by weekend “training” courses designed to achieve certification for participants. Some practitioners have purchased devices to enable in-office imaging of patients, a situation that creates incentives for over-use. Unfortunately, for some patients, an abnormal CT scan rather than symptoms or evidence of ischemia, are the primary driver for invasive procedures, including coronary interventions.
A case recently reported in the Archives of Internal Medicine poignantly illustrates the risks of decision making overly influenced by the presence of a stenosis in the presence of coronary calcification (6). We describe a 52-year-old nurse with atypical chest pain and a low pre-test probability of disease, who underwent CTA to “reassure” her. The presence of a difficult to visualize calcified left anterior descending artery lesion led to cardiac catheterization, which resulted in a catastrophic dissection of the left main coronary artery, eventually leading to heart transplantation. This case dramatically highlights the importance of understanding how coronary calcification limits the accuracy of CTA.
The current study reported by Arbab-Zadeh et al. (1) helps us understand what must be expected in subsequent studies examining the clinical utility of CTA. Future studies must evaluate important clinical outcomes, not just the extent of stenoses, in a wide spectrum of patients not selected because they represent ideal candidates for CTA. Pending such evaluation, coronary imaging using CTA should be used sparingly, with full recognition of the radiation burdens and risks of misdiagnosis.
The author has reported he has no relationships relevant to the contents of this paper to disclose.
↵⁎ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
- American College of Cardiology Foundation
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