The results of our analysis suggest that the sensitivity (98%) and specificity (85%) of CCTA for significant coronary artery stenosis appear to be relatively high. These findings compare favorably with accuracy estimates for other non-invasive strategies for CAD detection. Findings from recent series examining the diagnostic accuracy of SPECT, for example, suggest somewhat lower sensitivity (85–90%) than CCTA and comparable specificity (80–90%).71,72
However, as noted previously with published multicenter studies,20–22
diagnostic accuracy can vary widely based on patient selection criteria, evaluation methodology, and even type of CT scanner used. For example, the diagnostic accuracy results of the multi-center ACCURACY study, with entry criteria designed to reflect typical clinical practice, were similar to those in our review;20
however, findings from a Dutch multicenter evaluation, which employed an “intent-to-diagnose” method similar to our own to reflect clinical decision-making,22
showed comparable sensitivity but lower specificity.
Evidence on CCTA’s impact on clinical decision-making and patient outcomes is very limited. While there are preliminary data suggesting that use of CCTA for triage purposes in the emergency department has the potential to speed discharge and reduce costs in a large number of low-to-intermediate risk patients with negative CCTA findings, we found no studies that measured the potential for CCTA to alter decision-making and reduce unnecessary testing in the outpatient setting through explicit comparisons to other diagnostic strategies.
Our estimate of CCTA’s sensitivity is comparable to pooled estimates from other systematic reviews,12,76–79
however, pooled specificity is somewhat lower in comparison. For example, one review of 18 studies yielded summary estimates of 99% (95% Bayesian credible interval: 97%, 99%) and 89% (83%, 94%) for sensitivity and specificity.12
In another review, an analysis of individual random-effects models for sensitivity and specificity in 13 studies reporting patient-based results yielded estimates of 97.5% (95% CI: 96%, 99%) and 91% (87.5%, 94%) respectively.76
Explicit comparisons of these findings to our results are problematic given differences in study methodology and sample. However, our analysis is based on the largest number of studies reported to date, including 3 recent reports of multi-center studies. Differences may therefore simply be a function of greater variability in study design and patient populations in our sample relative to the other reviews. In addition, a larger number of studies will also reflect greater variability in the interpretation of what constitutes “significant” stenosis, leading to a greater heterogeneity in the false-positive rate (and accordingly, specificity). Indeed, as described previously, the 3 multi-center evaluations produced specificity estimates of 91%, 83%, and 64%;20–22
in addition to differences in study protocol and entry criteria, the number of centers involved and interpretations provided may also have contributed to this variation.
There are a number of important questions that the current evidence is unable to address. For one, the lack of data on long-term outcomes with CCTA makes it difficult to ascribe value to its ability to reduce the rate of false-positive and false-negative findings relative to other strategies. Without these data, it is not possible to know whether and when patients with false-negative findings will re-present with symptoms and be diagnosed correctly, and whether they will suffer any health consequences in the intervening period. It is also impossible to know the degree to which heightened clinical attention given to patients with false-positive CCTA tests might provide a net health benefit given that CAD will develop over time in many healthy individuals.
It is important to note that the data on long-term outcomes related to radiation exposure and extra-coronary “incidental” findings are so limited that they were not considered here, although they remain key considerations in clinical and policy decisions. Another critical but unstudied issue is whether widespread adoption of CCTA would result in a shift in the number or type of patients sent for diagnostic intervention. For example, availability of CCTA may lead to increased diagnostic testing of patients at very low risk of significant CAD.73
If this occurs, the relative balance of true-positive and false-positive results may shift, which may in turn increase the number of unnecessary tests and alter perceptions of the net health benefit of CCTA.
Because of CCTA’s visual precision, “mild” levels of stenosis (i.e., 20–70%) can be detected; the benefits of aggressive management of this level of CAD are unknown. While not a focus of this systematic review, several studies have attempted to examine CCTA’s ability to diagnose functional cardiac deficits, using SPECT or another functional test as a reference.2,74,75
While negative predictive value for these abnormalities was similar to that reported in the ICA-reference studies, positive predictive value only ranged between 50–60%, which is indicative of overestimation of clinically significant obstruction by CCTA. Some have posited that, with increasingly precise technology, the ability to use CCTA to study blood flow and perfusion deficits will be heightened; evidence has not yet accumulated to evaluate this hypothesis.
The state of current evidence on CCTA and the unanswered questions described above make CCTA’s role in the diagnostic armamentarium unclear. For patients who require data on cardiac function, SPECT or other testing followed by ICA is the likely pathway. For those who otherwise exhibit characteristics associated with high risk of CAD, immediate ICA without non-invasive testing would be in order.7
For patients at lower CAD risk, the high sensitivity of CCTA makes it a valuable test for excluding CAD as a cause of chest pain. It remains to be seen, however, whether this capability truly represents an advance over clinical judgment and basic stress testing, particularly in very low-risk individuals.
Our review is subject to some important limitations. For one, while efforts were undertaken to reduce publication bias and duplicative research, certain aspects of our search strategy (e.g., exclusion of non-English-language articles) may be subject to residual levels of such bias. In addition, while results from multi-center studies are included, the majority of findings were from small, single-center evaluations from major research centers, restricting the generalizability of our findings to the full spectrum of patients likely to receive this test as well as to conditions of typical community practice. Finally, as noted previously, the “intent-to-diagnose” paradigm employed for our primary analysis, which assumed all non-diagnostic findings on CCTA would be shown to be false-positives upon further testing, may have underestimated CCTA’s true diagnostic accuracy. However, we feel that exclusion of non-diagnostic results from analysis -- the approach taken by many of the studies in our sample -- provides an unwarranted boost to estimates of diagnostic accuracy. Our findings are therefore presented using both approaches so that the reader can visualize the interval in which CCTA’s true specificity most likely resides.
Despite these limitations, we believe our study represents an important summary of the existing literature, highlighting how limited the current evidence is on the overall impact of CCTA on clinical decision-making and patient outcomes. Further research is needed that captures important outcomes and allows a direct comparison of contemporaneous groups of patients evaluated with and without CCTA. In addition, the remaining uncertainties regarding broader use of CCTA and its impact on the clinical care of patients with mild-to-moderate stenoses will require ongoing evaluation of this technology in multiple patient populations.