The recommendations of FFR-CT are premature
The CCTA field recognizes that CCTA (and ICA) cannot confidently rule-in functionally significant CAD and now advocates fractional flow reserve (FFR)-CT to determine functional significance of what is anatomically described as “obstructive CAD” (50–90% stenosis) and extending further to a 40% narrowing. A stress CMR may be more cost-effective than FFR-CT or PET in sequential testing. While, CCTA may be the best test to exclude anatomically significant CAD, PET and CMR can effectively rule-in and rule-out functionally significant CAD.
The 2021 AHA/ACC Chest Pain Guidelines have 4 recommendations for FFR-CT in acute and chronic stable chest pain syndromes and FFR-CT was broadly described as an instrument for assessing likelihood of ischemia with established robustness for decision-making in lesions of 40–90% detected on CTA. FFR-CT was displayed in numerous flow charts to represent equivalent class 2a recommendations compared to any other functional imaging modality.
However, the diagnostic and prognostic utilities of FFR-CT are not as robustly evidenced as any of the stress imaging modalities (stress CMR, SPECT, PET, and stress echocardiography). FFR-CT does not improve the sensitivity of CT, and only modestly improves the specificity of identifying flow-limiting obstructive coronary artery lesions when compared with invasive FFR and functional testing [
5‐
8]. FFR-CT has only limited diagnostic accuracy in detecting hemodynamically significant CAD in the intermediate range of coronary stenosis of 0.6–0.85 where management decisions are most needed [
7]. Studies evaluating FFR-CT have shown inferior incremental diagnostic and prognostic value in comparison to functional testing [
7,
9]. Additionally, the recent FORECAST (Fractional Flow Reserve Derived From Computed Tomography Coronary Angiography in the Assessment and Management of Stable Chest Pain) trial of over 1400 patients, while referral to invasive angiography was lower, the use of FFR-CT did not demonstrate any benefits in terms of healthcare costs, cardiovascular outcomes, or quality of life compared to CT-alone [
10]. Similarly, the recent RAPID-CT (Rapid Assessment of Potential Ischaemic Heart Disease with CTCA) trial [
11] included 1748 patients with intermediate risk with suspected or a provisional diagnosis of acute coronary syndrome randomised to Early CCTA and standard of care compared with standard of care only. The study demonstrated that early CCTA did not alter overall coronary therapeutic interventions or one-year clinical outcomes.
Furthermore, there are practical implications regarding FFR-CT. FFR-CT is only feasible in a subset of CCTA cases that are relatively artifact-free and remains highly limited in patients with prior coronary artery stenting, extensive calcification, severe valvular heart disease, sequential luminal lesions or prior coronary artery bypass graft surgery. FFR-CT is currently only available by a single company (HEARTFlow, Redwood City, California, USA). The CPT Category III code used to reimburse FFR-CT is reserved for emerging technologies. Finally, FFR-CT costs 3-times as much as a standard CCTA.
The ischemia imaging modalities were inappropriately compared as a group against anatomical CCTA
The 2021 AHA/ACC Chest Pain Guidelines put all stress imaging modalities in the same “functional imaging” group for the purpose of comparison against CCTA, as shown in many flow charts and tables. This approach has little clinical basis but also misses critical attributes of different ischemia tests that may be relevant in the management of a vastly diverse patient spectrum. In the contemporary era, there is clear randomised trial evidence for the use of stress CMR in reducing unnecessary ICA referral or coronary revascularization rates, and thus improving patient care, health outcomes and healthcare resource utilization [
12,
13].
The largest randomized trial to date, PROMISE (PROspective Multicenter Imaging Study for Evaluation of chest pain), prospectively evaluated the utility of an anatomic (CCTA) testing approach in comparison with functional testing (stress imaging and treadmill ECG testing) amongst 193 North American centers in over 10,000 patients [
14]. After a median of 2-years follow-up, no differences in adverse cardiac outcomes were observed, while the anatomic approach led to higher downstream utilization of both ICA and coronary revascularization.
The SCOT-HEART (Scottish COmputed Tomography of the HEART) trial conducted within the United Kingdom failed to meet its original primary endpoint, but did observe a late reduction in non-fatal myhocardial infarction (MI) [
15]. However, it was a trial of serial testing in one arm (standard care using ETT plus CCTA) versus standard of care (ETT only). This form of layered testing might be expected to produce better outcomes, especially as exercise tolerance testing (ETT) without imaging is well recognized for lower sensitivity and specificity than stress imaging tests. In addition, participants in the SCOT-Heart trial were not systematically treated with optimal medical therapy for primary prevention, a standard of care that has been part of modern cardiology practice for many years.
Definitions of obstructive CAD, anatomically significant CAD, and functionally significant CAD
The 2021 AHA/ACC Chest Pain Guidelines do not have clear definitions of “Obstructive CAD”, “Anatomically Significant CAD”, and “Functionally Significant CAD”. These three definitions overlap with each other and contribute to miscommunication among healthcare providers and confuse patients. In general, the 2021 AHA/ACC Chest Pain Guidelines do not systematically differentiate anatomic CAD and functional CAD. This may contribute to an overestimation of the utility of CCTA compared with stress imaging modalities.
“Obstructive CAD” has been used to describe a 50% or greater coronary artery diameter stenosis by quantitative coronary angiography (QCA) and is now widely used to describe CCTA findings. However, the majority of 50–70% stenoses are not severe enough to impair coronary flow reserve [
16].
Invasive FFR has been shown in several multi-center trials to provide better outcomes than management by stenosis severity [
17‐
19]. Thus, “functionally significant CAD” represents the subset of coronary artery stenoses that impair flow during vasodilation or increased coronary flow demand. Stress imaging tests are inherently designed to detect abnormal flow reserve detected during exercise or pharmacological stress. We believe the cardiology community should work to clarifying terminology and avoid using words like “obstructive” that suggest a physiological importance to an anatomic stenosis that may or may not impair coronary flow reserve.
Women’s health
The 2021 AHA/ACC Chest Pain Guidelines briefly mention women-specific considerations in text but do not make any formal recommendations that recognize appropriateness or level of evidence. CCTA, SPECT, and PET directly deliver radiation to the breasts. Now that zero ionizing radiation methodologies like CMR can perform as well as CCTA and PET, and are superior to stress echocardiography and SPECT, CMR seems the logical choice for stress perfusion imaging in women if local equipment and expertise is available.