Improved Precision of Initial Chest Pain Evaluation With Fractional Flow Reserve Computed Tomography

F ollowing publication of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) trial, there has been a noticeable increase in the use of fractional flow reserve (FFR) in the cardiac catheterization laboratories across the country. The FAME study provided evidence in support of FFR-guided revascularization. This was a welcome change as opposed to trusting the gold standard visual estimation of invasive angiography. In the FAME trial, invasive FFR led to a reduction in the number of stents deployed, and this reduction in stent numbers was associated with a significant decrease in the primary end point of repeat revascularization, myocardial infarction, and death. While use of invasive FFR is appealing, especially in patients presenting directly to invasive coronary angiography, a vast majority of patients with stable chest pain undergo noninvasive assessment for risk stratification before invasive coronary angiography. Low diagnostic yield of invasive angiography in general practice calls for better noninvasive risk stratification. Noninvasive fractional flow reserve computed tomography (FFRCT) is a recent advancement that could further impact the landscape of diagnostic evaluation of chest pain. Using a computational fluid dynamics model, it is now possible to estimate the FFR of all major coronary vessels noninvasively, by analyzing a single set of coronary computed tomographic angiography (CTA) images, without administration of adenosine. This expands CTA use from pure anatomic evaluation of atherosclerotic plaque to functional assessment of stenosis, with less need for additional stress testing. Several studies have shown how FFRCT analysis improves specificity of intermediate stenosis detected by CTA, even in patients with increased calcium burden. For FFRCT to have the greatest impact, we need to consider coronary CTA as the first test for evaluation of chest pain. Several studies have focused on the performance of CTA as the first test for chest pain evaluation. The largest study on this subject was the PROMISE (The Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial. It was designed to compare anatomic testing with CTA to functional testing in patients without prior history of coronary artery disease. The study included 10 003 outpatients with chest discomfort at moderate risk for coronary artery disease. Because of concerns for complications with invasive angiography, the prespecified combined primary end point was not only death, myocardial infarction, and unstable angina, but also major complications with invasive procedures such as anaphylaxis, bleeding, stroke, and renal failure. Use of CTA as first test compared with stress testing was associated with a larger number of invasive angiograms (12.2% versus 8.1%) and more revascularization procedures (6.2% versus 3.2%, P<0.001). Despite a noticeable increase in percutaneous or surgical revascularization within the CTA arm, there were significantly fewer deaths or myocardial infarctions during the first 12 months among patients randomized to CTA (hazard ratio, 0.66; 95% confidence interval, 0.44–1.00; P=0.049). Over a median follow-up of 25 months, there was no difference in the incidence of the primary end point between patients randomized to CTA or functional testing (3.3% versus 3.0%, hazard ratio 1.04 with 95% confidence interval, 0.83– 1.29, P=0.75). The main reason for not reaching a prespecified end point was increased frequency of unstable angina within the CTA arm, but there was no significant increase in complications with invasive angiography. The reason for increased unstable angina is most likely because of the fundamental difference between CTA and stress testing, where CTA is likelier to report intermediate obstructive coronary artery disease. Patients undergoing CTA might therefore be less likely to ignore worsening symptoms, whereas patients with a negative stress test might feel as if they were “cleared” and avoid reporting more symptoms. The PROMISE trial did not account for crossover and was not powered to assess the effect of invasive angiography. Other The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the University of Iowa Hospital and Clinics, Iowa City, IA. Correspondence to: Gardar Sigurdsson, MD, University of Iowa Hospital and Clinics, 200 Hawkins Dr, Iowa City, IA 52242. E-mail: gardar-sigurdsson@ uiowa.edu J Am Heart Assoc. 2017;6:e006835. DOI: 10.1161/JAHA.117.006835. a 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.