Author + information
- William Wijns, MD, PhD⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. William Wijns, Cardiovascular Centre, OLV Hospital, Moorselbaan 164, 9300 Aalst, Belgium
Coronary anatomy or function? We need both!
Over the last decade, we have witnessed significant changes in the understanding, treatment, and outcomes of stable and acute forms of coronary artery disease to the point that conventional diagnostic and treatment paradigms are being challenged.
Facts and evidence driving this change are mainly 3-fold:
1. Coronary anatomy used to be accessible only through invasive catheterization. As a consequence, patients with suspected or probable coronary artery disease would undergo noninvasive evaluation for diagnostic and prognostic stratification purposes first. With the emergence of multidetector computed tomography (CT), it has become possible to access coronary anatomy noninvasively, and the gatekeeper function of stepwise functional noninvasive testing has lost grounds continuously (1). Today, coronary anatomy is known in many low-risk patients or even in asymptomatic subjects, mostly prompted by high-risk profile for developing the disease.
2. As a direct consequence of the above, chances were that the simple documentation of the presence of plaque was deemed sufficient to trigger coronary stenting or bypass, irrespective of symptomatic status, functional and prognostic significance of the stenoses, or any form of functional evaluation. The inappropriateness of such behavior has now been demonstrated beyond any doubt (2). Financial constraints in the present economic environment will no longer allow its persistence.
3. In low-risk patients, revascularization does not offer prognostic benefit beyond best medical therapy. In high-risk patients, revascularization is most effective when there is objective evidence of reversible ischemia downstream the stenoses, even though all may be technically amenable to stent implantation or bypass. Accordingly, for the first time in 2010, European Practice Guidelines have recommended that documentation of ischemia should be available in addition to the presence of severe coronary lesions to justify revascularization procedures (3). Thus, in tomorrow's world, the combined integrated evaluation of coronary anatomy and function will reign supreme. If possible at all, the ideal method or technique shall be noninvasive, widely accessible, and radiation-free.
Extracting functional data from routine coronary CT
The fact that the diagnostic accuracy of coronary CT is in need of improvement is well accepted: stenosis severity is typically overestimated; coronary calcifications, when extensive, prevent proper evaluation of the underlying residual luminal size; and many intermediate stenoses are being called obstructive, when they are not by functional standards (4). In other words, false-positive outcomes contribute to degrading the specificity and positive predictive value metrics, as well as the positive likelihood ratio.
In this issue of iJACC Yoon et al. (5) are comparing 2 fascinating approaches that have the potential to address the clinical demands on combined evaluation of coronary anatomy and function, both being based on post-hoc computer analysis of clinically obtainable coronary CT examinations using 64-multidetector row scanners. The gradient of intraluminal radiological attenuation across stenoses was shown to correlate linearly with angiographic stenosis severity (6). On the other hand, computational fluid dynamics applied to volumetric CT images allow to derive pressure and flow estimates needed to calculate fractional flow reserve (FFRCT), potentially a noninvasive surrogate (7) for invasively measured FFR using pressure wires and chemically-induced hyperhemia (2). It is important to stress that both approaches can be computed from typically-acquired CT examinations, without the need of additional image acquisition, hence radiation, or administration of extra contrast or medication. In a nutshell, findings were that transluminal attenuation gradient (TAG) did not correlate well with the invasively measured reference FFR. As a result, sensitivity, positive and negative predictive values, as well as positive likelihood ratio are nondiagnostic. The authors speculate that TAG might need to be measured during hyperhemic stress in order to improve its correlation with FFR.
FFRCT, on the other hand, reported near ideal diagnostic performance: sensitivity 81%, specificity 94%, positive predictive value 90%, negative predictive value 89%, positive likelihood ratio 13.5, and negative likelihood ratio 0.2 (5). Results were especially good in the absence of severe calcifications (<70% of the plaque volume >130 HU).
It should be remembered that these outstanding results stem from a retrospective analysis of a single-center Seoul subset of the DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) database (7) from which 82 vessels with 32 ischemic stenoses (invasive FFR <0.80) underwent additional TAG analysis.
These outstanding results could not be reproduced in the recently reported prospective, multicenter, international DeFACTO study (8). DeFACTO examined 408 vessels in 252 patients (37.1% with abnormal invasive FFR). Use of noninvasive FFR plus CT resulted in improved accuracy versus CT alone to diagnose hemodynamically significant disease on a per-patient level. However, specificity (54%, 95% confidence intervals of the estimate at 46% to 83%) and positive predictive value (67%, 95% confidence intervals of the estimate at 60% to 74%) were nondiagnostic. Unfortunately, the authors did not report per vessel analysis, except that the false-positive rate can be calculated at 23.6%, meaning that 96 of 407 vessels had FFRCT ≤0.80 while invasive reference FFR was above 0.80.
Of note, in the presently reported study by Yoon et al. (5), an internally consistent “optimal cut-off” for invasive FFR was set at ≤0.77 versus above, yielding the outstanding diagnostic performance, as reported. When the FFR cut-off was set at the generally accepted 0.80 threshold, the issue with false-positive FFRCT became apparent again since the specificity degrades from 94% to 84%, the positive predictive value from 90% to 78%, and the positive likelihood ratio from 13.54 to 5.66 (per vessel analysis).
How appealing both approaches may appear since they are available from clinically-acquired coronary CT, one has to admit that both TAG analyses and current versions of FFRCT computation analysis need to be further optimized before they can be tested in clinical diagnostic strategies, let alone implemented in practice.
Combining coronary CT with CT stress myocardial perfusion imaging
Several approaches, such as hybrid imaging combining coronary CT for anatomy and stress-rest nuclear imaging for perfusion by single-photon or positron emission tomography, have been described and evaluated. However, these approaches are adding up the complexity, cost, and radiation burden of both technologies. In theory, a single imaging device that could provide both anatomical and functional assessment in one go would be preferable. Ko et al. (9), from Australia, are reporting in this issue of iJACC another innovative way to achieve integrated anatomic and functional evaluation by combining coronary imaging and myocardial perfusion imaging during adenosine stress with use of the same 320-multidetector row CT machine.
Feasibility of the approach has been reported previously by the same and other authors, but this study is unique in 2 aspects: perfusion was evaluated both qualitatively and quantitatively (by measuring the ratio of contrast attenuation between endocardium and epicardium); secondly, 3-vessel FFR was obtained during catheterization in 77 of 120 vessels (in 40 patients). The additional use of both qualitative and quantitative CT perfusion assessment with CT angiography significantly improved the specificity and overall accuracy of CT angiography. Sensitivity, specificity, and positive and negative predictive value were 95%, 78%, 68%, and 97%, respectively, for CT angiography only, versus 87%, 95%, 89%, and 94% for combined anatomical and functional CT evaluation. Thus, in the authors' single-center experience, this combined approach successfully reduced the false-positive rates, when analyzed per vessel and per patient. In the absence of a ≥50% stenosis on CT, the majority of vessels had normal CT perfusion (98%) and nonsignificant FFR (97%).
Of note, the proposed approach requires 2 separate CT examinations. Mean radiation dose for rest CTA was 4.7 ± 3.2 mSv, for the stress perfusion scan 4.5 ± 1.8 mSv, and for the entire CT protocol 9.2 ± 3.5 mSv. Such level of radiation exposure will only be acceptable when it can be demonstrated that other procedures involving radiation, such as nuclear imaging or coronary angiography, can be avoided because they are no longer required.
Summary and (near) future developments
The world of cardiac imaging is proposing to the clinician an ever increasing spectrum of options and tools, with the disadvantage that patients are presently submitted to multiple, sequential, time-consuming, and costly diagnostic procedures and tests, sometimes with contradicting results. The concept of obtaining combined anatomic and functional tri-dimensional noninvasive imaging of the coronary circulation and myocardial perfusion in a single session is particularly appealing. When available and properly validated, such “one-stop shop” approach has the potential to become the central decision-making element in the future diagnostic and therapeutic strategy for patients with coronary artery disease.
The new evidence provided by both articles (5,9) in this issue of iJACC represents a significant step forward.
If indeed the diagnostic accuracy of FFRCT can be improved, routine coronary CT enriched with this functional information should be tested as a first choice approach in the context of novel diagnostic strategies, with the potential of improved risk stratification and more appropriate use of invasive resources.
In the meanwhile, integrated evaluation of anatomy and function by CT seems very appealing, in spite of the high radiation burden. The present outstanding results (9) need to be confirmed in larger, multicenter studies. Here again, new disruptive diagnostic strategies based on this technology will have to be tested prospectively, firstly against invasive FFR as an adequate, per-vessel gold standard.
Exciting times are ahead of us: it is likely that diagnostic and treatment paradigms will continue to evolve in a disruptive manner, with the potential of improved outcomes when revascularization procedures will more precisely target stenoses that are responsible for myocardial ischemia. Stay tuned: the case is not closed … .
Dr. Wijns has received an institutional research grant from HeartFlow, Inc., and is a co-investigator for the DeFACTO trial.
↵⁎ Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
- American College of Cardiology Foundation
- Topol E.J.,
- Ellis S.G.,
- Cosgrove D.M.,
- et al.
- Wijns W.,
- Kolh P.,
- Danchin N.,
- et al.
- Sarno G.,
- Decraemer I.,
- Vanhoenacker P.K.,
- et al.
- Yoon Y.E.,
- Choi J.-H.,
- Kim J.-H.,
- et al.
- Koo B.K.,
- Erglis A.,
- Doh J.H.,
- et al.
- Ko B.S.,
- Cameron J.D.,
- Leung M.,
- et al.