Discussion
This study reports on the clinical use of latest-generation CTCA in the real world and is unique in several ways. Most importantly, we provided a complete patient analysis without arbitrary exclusion of coronary artery segments deemed too small to have impact on clinical management. Second, recognising the fact that in clinical practice ICA remains essential to guide patient management, also in patients with rather atypical symptoms, we were able to assess diagnostic accuracy in patients with a low-to-intermediate pretest likelihood in whom it was deemed necessary on clinical grounds and not for study purposes to perform ICA after CTCA. Third, we provide clinical data on patients with an elevated CACS, who according to good clinical practice did not undergo a contrast scan.
The major findings of this study are the following:
With regard to clinical management, CTCA in general showed good performance to replicate the therapeutic recommendations as formulated after ICA for the large majority of patients.
As expected, prevalence of significant CAD in small-vessel segments is rather low. The need for treatment with antianginal drugs or revascularisation in this clinical scenario is below 5%.
The overall diagnostic performance of dual-source CTCA, without exclusion of small coronary artery segments, showed following metrics: 90% sensitivity, 40% specificity, 53% PPV, 84% NPV.
Patients with CACS ≥1000 showed a high prevalence of significant CAD on ICA. The majority of these patients needed revascularisation.
CTCA and patient management
The patients selected to undergo CTCA do fit the recommendations of clinical guidelines. For the majority of the 5438 patients, a CTCA without additional ICA was sufficient to guide subsequent clinical management. The patients who are the subject of this report and in whom ICA was required to direct further management, fitted the criterium of ‘intermediate pretest probability’, more precisely 26%, and had a disease prevalence of 43%.
As opposed to the somewhat artificial boundaries of the research environment, assessment of the true clinical performance of CTCA in day-to-day clinical practice, necessitates the inclusion of small vessel segments. A small vessel diameter together with extensive vessel calcifications are the two main predictors of diagnostic inaccuracy on CTCA.15 Recently published major clinical studies systematically excluded vessels with a diameter smaller than 1.5 or 2 mm.4 5 16 Severely calcified vessels make it impossible to assess the degree of coronary stenosis and most experts would agree on a certain threshold level of calcium above which it is advisable not to proceed with a contrast scan.3 16 In our study, we used an CACS ≥1000 as exclusion criterion. Within these boundaries of vessel calcification, we performed an ‘intention-to-diagnose’ analysis, allowing to formulate clinical management on a true patient level. In the clinical situation where an ICA is deemed necessary, the management plan is fundamentally based on these findings. The setup of our study makes it therefore feasible to make a head-to-head comparison of CTCA with ICA and sort out clinical precision of CTCA using the ICA-based strategy as gold standard.
It is important to realise that in patients who qualify for a ‘CTCA-first’ strategy, the need for subsequent use of ICA and/or revascularisation mounts up to 34% and even 50%, in expert centres.16 17 It is therefore reassuring that in our study CTCA correctly identified the majority of patients who end up with medical therapy and/or revascularisation.
Small vessel disease
Pathology reports and subsequently studies using ICA have demonstrated that CAD most frequently involves the proximal portions of the major epicardial vessels.18–20 When the burden of atherosclerosis increases, it also starts to affect the distal segments but always to a lesser extent as compared with the proximal parts of the coronary tree.21
This ‘proximal-to-distal’ distribution of CAD was also obvious in our study: significant CAD affecting the large-vessel and small-vessel segments occurred in, respectively, 40% and 16% of the population.
In view of the higher spatial resolution, disease in small vessel segments will be better visualised using ICA. Indeed, diagnostic performance of CTCA in our study was substantially lower when focusing on these small vessel segments and is in accordance with the results of previous reports on this subject.15 22
The systematic exclusion of vessel segments with a diameter below 1.5 or 2 mm, easily mounts up to at least 10% of the coronary tree.16 This ‘pruning of the framework’ which is eventually used for further study involves two consequences: (1) overestimation of the ‘real-world’ diagnostic accuracy and (2) the possibility of overlooking clinically relevant findings as they would affect further patient management. In our study, significant disease in small vessel segments occurred in 16% of the population and was often combined with disease in large segments. The prevalence of significant CAD limited to the small vasculature was very low but not negligible and occurred in 3.5% of the patients. When translated to disease with clinical impact, this would affect less than 1% (6 out of 29 patients needed antianginal therapy and/or revascularisation) of the population. From a statistical standpoint this would be a negligible number. From an individual’s standpoint who is seeking medical advice, the uncovering and appropriate treatment of small vessel disease could make a significant difference in well-being.
Patients with a high calcium score
The utilisation of a CACS threshold before deciding to administer contrast remains controversial.23 24 We are in favour of using such a threshold, in our study a CACS ≥1000, for two reasons.
First, CTCA remains most useful for excluding the presence of CAD in patients with a low-to-intermediate pretest probability of having significant CAD, or in other words being a reliable non-invasive alternative to ICA for patients with atypical chest pain in whom the prevalence of significant CAD is low. Patients with a high CACS, typically above 400, define a category in whom the prevalence of significant CAD on ICA is high, irrespective of the patient pretest likelihood.25 For this reason, in the multicentre Spiral
Computed Tomography Angiography Using 64 Detectors (CORE64) trial, patients with a CACS above 600 were excluded from the main analysis.16 This specific patient group demonstrated a prevalence of significant CAD of 89% on ICA.26 In these circumstances, that is, high likelihood of significant CAD, the chances of missing out significant disease becomes as high as 37%.26
Second, in the presence of significant CAD or high likelihood of this condition, the point of interest becomes not the stenosis per se, but whether the stenosis is producing ischemia and revascularisation would become necessary. To resolve the issue of ischemia, it has become clear that ICA in combination with functional assessment using fractional flow reserve would be the preferred strategy, or as an alternative the addition of another noninvasive functional test.27 28
Limitations
To determine the clinical impact of CTCA, we relied on the therapeutic recommendation of the treating physician, which was driven by the findings on ICA. We subsequently assessed whether the CTCA report withheld the diagnosis of significant CAD or not and used this as a proximate to identify patients in whom revascularisation and/or antianginal drug therapy would be necessary. Ideally, a prespecified management plan, initially based on the findings of CTCA and subsequently compared with the recommendations after performance of ICA, would have been analysed in a prospective way.
However, it should be stressed that CTCA essentially should be used as gatekeeper and not as a substitute for ICA.1 The knowledge that the majority of patients in whom medical treatment or revascularisation appeared to be necessary were identified on the index CT scan, is an add-on comforting idea.
The a priori exclusion of coronary segments smaller than 1.5 or 2 mm is common practice in most CTCA studies and could contribute to the perception that small vessel pathology represents an entity of minor clinical importance as compared with the larger and proximally located coronary arteries, which are almost exclusively targeted for CABG or PCI. As is obvious from this study, small vessel disease targeted for medical therapy and/or revascularisation is relatively infrequent but not absent. In addition, we should not forget that chest pain in the absence of obstructive CAD, so-called microvascular angina, frequently finds its origin in the coronary microcirculation, which actually cannot be visualised through any in vivo imaging technique in humans.29 Microvascular angina is by no means infrequent in clinical practice and needs for its definitive diagnosis advanced functional testing such as positron emission tomography or invasively obtained coronary physiology parameters.30