LCD L38613: Non-Invasive Fractional Flow Reserve (FFR) for Ischemic Heart Disease

FDA-approved FFRct technology may be considered reasonable and necessary in the management of patients with:

a. Intermediate-risk* patients with acute or stable chest pain, with no known history coronary artery stenosis and with finding of 40-90% in proximal or middle coronary artery on CCTA 1 OR

b. Intermediate risk* patients with acute chest pain and known non-obstructive ( 1 OR

c. Stable non-obstructive coronary artery disease ( 1

AND

Not in conjunction with stress testing* (unless CCTA was not sufficient quality for FFRCT, and an alternative study is needed)

*Intermediate and high-risk and stress test as defined in the 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain 1

**Persistent symptoms are unacceptable ischemia-related symptoms despite maximally tolerated medical therapy.

FFRct is not considered reasonable in the following clinical circumstances:

• Prior placement of prosthetic valves

• Prior placement of grafts in coronary bypass surgery

• Suspicion of acute coronary syndrome (where MI or unstable angina have not been ruled out)

• Intracoronary metallic stent

• Status post-heart transplantation

• Recent MI (30 days or less)

• Prior pacemaker or defibrillator lead placement

• Newly diagnosed systolic heart failure, with no prior left heart catherization

• Left main coronary artery disease with Intermediated Coronary Stenosis (lumen reduction less than or equal to 40%)

• Non-obstructing stenosis (

This service should be performed in patients with stable coronary symptoms. It should not be performed until after the base study (CCTA) has been completed and interpreted. If higher grade stenoses (i.e. greater than 90%) are present, this study is not medically necessary, as the patient should proceed to catheterization. Similarly, low-grade stenoses (less than 40%) do not require additional confirmatory data. This should be performed as an alternative to stress testing.

Background

The concept of invasive fractional flow reserve as a diagnostic tool was introduced in the early 1990’s. The FAME and FAME-II trials supported an FFR-wire guided revascularization strategy as opposed to purely angiographically guided revascularization. 2 The National Cardiovascular Data Registry demonstrated a low diagnostic yield from traditional exercise stress testing when the patient progressed to invasive coronary angiography. Fractional flow reserve is considered the gold standard for assessing the hemodynamic significance of intermediate coronary stenosis by measuring the pressure difference across a coronary artery stenosis. 3 Intracoronary catheter pressure measurement before and after the stenosis are compared, and FFR of 0.80 correlates with a 20% pressure drop after the stenosis. This measurement can help determine if the vessel narrowing is limiting blood flow and assess the need for revascularization or stenting. Clinical studies have demonstrated that invasive FFR reduces unnecessary stenting procedures and associated risk. 2,4 The use of invasive FFR is supported by the Society of Cardiac Angiography and Interventions (SCAI) and American College of Cardiology (ACC). 4,5

Noninvasive fractional flow reserve is an alternative modality to gain this information without the need for invasive intracoronary instrumentation in patients with known or suspected coronary artery disease (CAD). FFRct is a fractional flow reserve derived from computed tomography that relies on computer-assisted processing of coronary computed tomographic angiography (CCTA) images to estimate coronary blood flow changes related to coronary artery stenoses. Based on physical theories of fluid dynamic modeling, FFRct is a post-processing software for analyzing previously acquired digital imaging from CCTA. Limitations include that the technology is dependent on the image quality of the CCTA, the images must be sent out for post-processing; therefore, real time results are not feasible, and how to apply FFRct results to clinical practice is still in development. Emerging technologies include virtual FFR (vFFR), where the measurements are based on a 3-D image of coronary vessels created by the software using x-ray angiographic imaging. Angio-derived FFR is calculated at the time of coronary angiogram.

Persistent CAD symptoms are unacceptable ischemia-related symptoms that persist despite optimal medical therapy. Optimal medical therapy is defined by the ISCHEMIA trial protocol 6 as unacceptable ischemia-related symptoms despite maximally tolerated medical therapy. This includes at least two anti-anginal drugs from different drug classes added to beta-blocker therapy and titrated to maximally tolerated doses before medical therapy is considered to have failed. 6

The analysis of coronary artery disease by NON-INVASIVE CORONARY computed tomographic analysis has been limited by low specificity. The addition of computer derived flow analysis of the CTA data has added the potential for a NON-INVASIVE test that yields both anatomic and functional data. This emerging technology aims to reduce the need for invasive cardiac procedures and associated risks.

The DeFACTO study (Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography) compared the first iteration of FFRct technology against invasive angiography and FFR in patients with suspected or known CAD, but did not achieve the pre-specified target accuracy. 3 Another study, DISCOVER-FLOW, demonstrated an accuracy of 84.6%. 7 A second iteration of the FFRct algorithm was tested against invasive angiography with FFR in 254 patients with suspected CAD in the NXT (Analysis of Coronary Blood Flow Using CT Angiography- Next Steps) trial. This study reported a diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 81%, 86%, 79%, 65% and 83% respectively. 8 In this trial, 484 vessels in 254 patients and found that FFRct significantly improved the per patient specificity and PPV (32 to 84% and 40 to 65%, respectively) and the per vessel specificity and PPV (60 to 86% and 33 to 67%, respectively) compared to CTA. However, this does not translate into benefit compared to CTA alone for identifying patients whose invasive FFR will warrant intervention, and 35% of the abnormal results were false positives. 9 A sub analysis of the NXT study evaluated 206 participants and reported no cardiac death or myocardial infarctions in participants with normal FFRct at a median follow-up of 4.7 years. The authors concluded that an FRRct value of 0.8 or less is a predictor of long term outcomes driven by planned and unplanned revascularization and is superior to clinically significant stenosis on coronary CCTA. 10

The PROMISE study demonstrated that patients with an FFRct less than or equal to 0.80 were significantly more likely to have coronary revascularization and to meet the composite endpoint of major adverse cardiac events or revascularization than those with FFRct greater than 0.80. 9 The study also showed that reserving invasive coronary angiography for patients with FFRct less than or equal to 0.80 could reduce the rate of performing invasive coronary angiography by 28%. The initial trial did include a CCTA strategy, which did not improve outcomes after two years of follow-up. The study, a retrospective, observational, cohort study, also highlighted the dependence of FFRct on the quality of the CCTA images being post-processed, with one-third of the images submitted for review of insufficient quality. 11

The FFRct RIPCORD study involved 200 patients and compared the management of patients by cardiologists with and without the addition of FFRct data to the baseline CTA data. The additional FFRct data changed the management plan for 72 patients (36%) based on lesion severity assessment. With inclusion of changes in the PCI target vessel, patient management was altered in 44% of patients. 12