Coverage Indications, Limitations, and/or Medical Necessity
Coverage Guidance, Limitations, and Reasonable and Necessary Criteria
Noninvasive Fractional Flow Reserve (FFRCT)
Noninvasive fractional flow reserve deduced from computed tomography (FFRCT) involves computer-assisted processing of coronary computed tomography angiography (CCTA) images to estimate changes in blood pressure inside coronary arteries that have partial blockages, with the goal of determining how severely the blockages impede blood flow to the heart. FFRCT is a post-processing software for the clinical quantitative and qualitative analysis of previously acquired computed tomography (CT) Digital Imaging and Communications in Medicine (DICOM) data for clinically stable symptomatic patients with coronary artery disease (CAD). FFRCT analysis is intended to support the functional evaluation of CAD. The results of this analysis are provided to support qualified clinicians to aid in the evaluation and assessment of coronary arteries.
FDA-approved non-invasive calculated coronary fractional flow reserve (FFRCT) technology derived from cCTA may be reasonable and necessary to guide qualified-provider decisions about the use of invasive coronary angiography (ICA) in clinically stable symptomatic patients with CAD of unknown functional significance AND the following appropriate CCTA criteria:
- Left main disease with intermediate coronary stenosis (lumen diameter reduction 30-70%) OR
- Proximal left anterior descending coronary artery (LAD) disease with intermediate coronary stenosis OR
- Proximal left dominant circumflex disease with intermediate coronary stenosis* OR
- Two- or three-vessel disease with intermediate coronary stenosis in at least 2 vessels OR
- Single vessel disease (not proximal LAD or proximal left dominant circumflex artery ) with >50% stenosis AND insufficient response to optimal medical therapy (OMT)
*NOTE: Proximal left dominant circumflex disease with intermediate – severe coronary stenosis is considered equivalent to two-vessel disease. Therefore this lesion in combination with any other main coronary artery would be equivalent to triple vessel disease1
FFRCT testing is not reasonable and therefore not covered for patients with the following conditions:
- Severe obesity (BMI >35 kg/m2)
- Bare metal intracoronary stent
- Prosthetic valves
- Heart rate or arrhythmia > 65 beats/min at the time of image acquisition
- Allergy or intolerance to iodinated contrast material
- Extensive coronary calcification by plain film or high calcium scores with prior Agatston score > 1000
- Renal insufficiency (i.e. estimated glomerular filtration rate < 60mL/min/1.73m2)
- Uncooperative patient
- Patient unable to sustain breath-hold for 5-10 seconds
- Heart transplantation
- Recent prior myocardial infarction within 30 days
- Suspicion for acute coronary syndrome (where acute myocardial infarction or unstable angina have not been ruled out)
- Severe aortic stenosis
- Known severe 3-vessel disease (> 50% stenosis is all 3 major vessels)
- Post coronary artery bypass surgery, evaluation of venous grafts
Credentialing and Accreditation Standards
Optimal outcomes of FFRCT procedures depend on the knowledge, skill and experience of the provider. Services will be considered medically reasonable and necessary only if performed by appropriately trained providers. Consequently, the provider performing the procedure must be capable of demonstrating documented training and experience according to the following standards2:
- For the technical component, the recommended level of competence is fulfilled with the image acquisition is obtained under all of the following conditions:
- The service is performed by a radiology technologist who is credentialed by the American Registry of Radiologic Technologists or equivalent, adequately trained in cardiac CT, including adequate knowledge of the ALARA principle (“As Low As Reasonably Achievable”) and meets state licensure requirements.
- Supervising physician with advanced knowledge in cardiovascular CT and ALARA principle. Certification of advanced expertise in cardiac CT is preferred, e.g. Diplomat of the Certification Board of Cardiovascular CT (CBCCT), holder of the ACR Certificate of Proficiency in Cardiac CT, or American Board of Radiology ABR/ABMS Focused Practice Recognition in Cardiac CT (FP-CCT).
- At least one accredited cCTA reader (or equivalent experience of >150 cardiac CTs) – may be SCCT Level 1+ or accredited through other organizations/fellowship
- If intravenous beta blockers or nitrates are to be given prior to a CT coronary angiogram, the test must be under the direct supervision of a certified registered nurse and physician who are available to respond to medical emergencies and it is strongly recommended that the certified registered nurse and physician be ACLS certified.
- When contrast studies are performed, the physician must provide direct supervision and the radiologic technologist or registered nurse administering the contrast must have appropriate training on the use and administration of contrast media
- Image data storage should be in the Digital Imaging and Communications in Medicine (DICOM) standard format. A picture archiving and communication system (PACS) or equivalent CT image data archiving system is required to allow storage and retrieval of the entire diagnostic image data set.
- For the professional component, a recommended level of competence is fulfilled when the interpretation is performed by a physician meeting the following requirements:
- The interpreting physician(s) shall have adequate training as described in competency statements issued by medical specialty societies e.g. the ACC/AHA Clinical Competence Statement on Cardiac Imaging with Computed Tomography and Magnetic Resonance or the ACR Practice Guideline for the Performance and Interpretation of Cardiac Computed Tomography.
- Physicians interpreting FFRCT analysis shall have the FFRCT manufacturer training with certification specific to the FDA-approved FFRCT technology.
Summary of Evidence
Ischemic heart disease is a significant public health problem with an estimated greater than 1 in 3 adults in the United States with some form of cardiovascular disease, including ≥40 million estimated to be ≥ 60 years of age.3 Stable ischemic heart disease (SIHD) is diagnosed by symptoms (e.g. chest pain or ‘ischemic equivalents’ such as shortness of breath (dyspnea), neck/jaw or arm pain, palpitations, dizziness, syncope/near syncope) that are reproducible primarily with exertion and are not progressing in severity. The diagnostic approach for patients with symptoms that suggest SIHD, is to determine whether such symptoms represent the initial clinical recognition of chronic stable angina, a correlate of supply/demand mismatch precipitated by a change in activity or concurrent illness (e.g. anemia or infection).4 Invasive coronary angiography (ICA) is frequently unnecessary in patients with suspected stable ischemic heart disease (SIHD), as evidenced by low diagnostic yields for significant obstructive CAD. For example, from a sample of over 132,000 ICAs, Patel et al. found 48.8% of elective ICAs performed in patients with what was thought to be stable angina did not detect obstructive CAD (left main stenosis ≥50% or ≥70% in a major epicardial or branch >2.0 mm in diameter).5 Moreover, for the large majority of patients with SIHD, revascularization offers no survival advantage over medical therapy.1 Noninvasive cCTA is very sensitive in detecting obstructive CAD, but is limited in its positive predictive value.6 cCTA also does not assess the functional significance of visualized lesions, and often leads to further evaluation with either stress testing or invasive angiography, or both.7
Determination of Functionally Significant CAD Using Vessel Anatomy and FFRCT
Although it is recognized that individual coronary anatomy is highly variable, the anatomic construct for CAD is based on the presence or absence of flow-limiting obstructions in the coronary arteries categorized by the number of vessels involved (1-, 2-, and 3-vessel, and/or left main CAD) as well as the amount of myocardium at risk.1
Although imperfect, the commonly used classification of 1-, 2-, and 3-vessel disease and left main disease remains widely used in clinical practice.1 The coronary artery anatomy derived from cCTA can now be augmented with information derived from the physiologic testing of stenosis with FFRCT technology.8,9 The COURAGE investigators, along with outcome data from other trials involving more than 5,000 patients, confirmed that PCI (percutaneous coronary intervention) can be safely deferred with use of optimal medical therapy (OMT) in patients with stable coronary artery disease, even in those with multi-vessel involvement and inducible ischemia.10-13 The accepted standards for coronary revascularization in patients with SIHD are outlined in collaborative, multi-society guidelines that define appropriate use criteria for coronary revascularization in patients with SIHD.1,4 These management recommendations are determined by the number of vessels, vessel type, location of stenosis, and intensity of medical therapy.1 When applied to the decision-making for revascularization, FFRCT proves useful in providing information to characterize vessel disease when PCI is a consideration, as opposed to when optimal medical therapy is recommended. For example, PCI is not recommended, and in fact, may induce harm in patients with single-vessel disease involving the right coronary artery, even with a hemodynamically significant lesion, if they are not first provided OMT.1 As a result, FFRCT analysis would not contribute to medical-decision making for this clinical scenario. Alternatively, FFRCT may be useful in re-categorization of multi-vessel disease identified by cCTA. If the cCtA suggests 2 intermediate-severe stenosis (lumen diameter reduction of 50-90%), but FFR testing indicates that only one is hemodynamically significant, the clinical management then should be considered based on AUC guidelines for the group with 1-vessel CAD.1,10
Selective FFRCT Guides Determination for Invasive Coronary Angiography
There is evidence, provided by 2 prospective and 2 retrospective cohort studies, that compares health outcomes observed during 90-day to 1-year follow-up for strategies using cCTA particularly in combination with selective FFR-CT with strategies using ICA or other noninvasive imaging tests.
The PLATFORM trial was a prospective, longitudinal, comparative-effectiveness study designed to assess the impact of using FFRCT on stable patients with suspected CAD and referred for ICA.14,15 The primary endpoint (rate of ICA showing non-obstructive disease within 90 days) included a control cohort of 187 consecutive patients referred for ICA (“usual care”) and 193 patients referred instead to cCTA and FFRCT. Exclusion criteria included suspicion of acute coronary syndrome, prior CABG, prior PCI, and contraindications for cCTA which included body mass index (BMI) > 35 kg/m2 (supplemental data online). Using information obtained from the FFRCT analysis, clinicians were able to cancel 61% of planned ICAs leading to an 83% reduction in the primary endpoint of ICAs showing no obstructive disease. One-year outcomes reported that FFRCT was safe to use with zero adverse events for those patients with canceled ICA. It is important to note that this study examined a strategy of using FFRCT to guide management among patients eligible to undergo cCTA testing. 88% of cCTAs performed were of sufficient quality to assess FFRCT consistent with the fact that FFRCT may not be technically feasible in all patients.14
The PROMISE FFRCT study further supports use of FFRCT for guiding referral to ICA.16 This retrospective, observational, cohort study examined whether FFRCT accurately predicts coronary revascularization and adverse events. Using FFRCT to selectively refer patients to ICA improved catheterization lab efficiency by showing a reduction in patients referred to ICA by 28% and an increase in the rate of ICA leading to revascularization by 24%. A positive FFRCT value was significantly better than cCTA at predicting whether a patient had an adverse event or underwent revascularization. In a ‘real world’ patient population and study design resulting in sites not receiving specific FFRCT training and feedback (including standard administration of nitroglycerin and appropriate image reconstruction), the image quality requirements for FFRCT were much more significant. One-third (33%) of the cCTAs sent to the FFRCT core laboratory were inadequate for FFRCT analysis. It is also notable that the BMI of participants of the initial PROMISE cCTA study, the population from which this FFRCT population was derived, reported to the mean BMI to be 30.5 ± 6.1kg/m2.7
The ADVANCE registry (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) included 5,083 patients with symptoms suggestive of angina from 38 centers in Europe, North America, and Japan.17 FFRCT provided information to physicians that resulted in a change in the management plans in two-thirds of patients (66.9%), compared to the management plan after cCTA. The prospective international multi-center study also demonstrated that for patients with CAD by cCTA and a negative FFRCT (>0.80), medical management was safe. There were zero adverse events at 90 days for the 1592 patients in this group. This contrasts with 19 adverse events (10 death, 4 myocardial infarction (MI), and 5 hospitalization and urgent revascularization) in patients with positive FFRCT (≤0.80) (MACE hazard ratio 19.75, p<0.001). The investigators concluded that FFRCT can identify patients in need of invasive assessment. Among patients whose post-FFRCT management plan was revascularization and who underwent ICA, 72.6% were re-vascularized. FFRCT effectively differentiated patients who needed further invasive assessment from those who could be managed with medical therapy. A total of 190 subjects did not have their CCTA examinations submitted for FFRCT analysis at the site discretion: 111 because the invasive treatment decision was made due to the severity of the stenosis; 61 owing to minimal CAD; 9 because of multiple coronary stents; 2 because of CCTA exams not acquired in a fashion acceptable for FFRCT analysis.17 BMI characteristics were not reported, however, the US population studied made up less than 23% of the international registry that included patients from Canada, Europe, and Japan and it is not clear from the data if the mean BMI across sites significantly varied (supplemental data).
2-Year FFRCT Data Demonstrate Positive Health Outcomes
Norgaard et al (NXT Trial) reported 2-year outcomes from a single-center, observational study that included 3,674 consecutive patients with stable chest pain. Participants had a median age of 60 ± 9 years and a BMI of 26 ± 4 kg/m2 and were followed for a median of 24 months (range of 8-41 months) after evaluated with CTA and selective FFRCT.18 The results demonstrate the ability of physicians to use the FFRCT service to differentiate patients in need of PCI or CABG from those who could be managed with OMT alone. Patients with intermediate stenosis (30-70%) by cCTA who had a negative FFRCT (>0.80) had 2-year outcomes equivalent to patients with no to minimal stenosis (0-30%) by cCTA. The composite endpoint (all-cause death, MI, hospitalization for unstable angina, and unplanned coronary revascularization) was 3.9% for the intermediate stenosis/ FFRCT negative group versus 2.8% for no to minimal stenosis by cCTA group (p=0.58). Additionally, patients with a positive FFRCT (≤0.80) who underwent invasive assessment had fewer MIs than those with a positive FFRCT who were managed medically (1.3% versus 8.0%, p<0.001). This study demonstrated the safety of using FFRCT information to select the best treatment for patients.
Positive Health Outcomes Demonstrated in Medicare Population
Lastly, clinical evidence evaluating 254 Medicare-eligible subjects in a sub-analysis for the NXT study found that FFRCT has a high diagnostic performance compared to invasively measured FFR, identifying patients with hemodynamically significant obstructions with high sensitivity (85%) and specificity (79%) in subjects ≥ 65 years old with stenoses in the intermediate range (30-70%).19 Over 90% of patients in the analysis had the intermediate range stenoses. The data also established that myocardial ischemia is unlikely in patients with FFRCT > 0.80 (negative predictive value (NPV) of 93%) again supporting the role of cCTA with FFRCT as a reliable gatekeeper to ICA and revascularization. Other notable characteristics of the study population include mean BMI of 26 ± 3 kg/m2, normal LVEF of 62% ± 7, and normal renal function. Patient with acute coronary syndrome, previous coronary intervention or bypass surgery, or BMI > 35 kg/m2 were excluded. Additionally, 12% (44) cCTA subjects were excluded due to cCTA image artifacts. Stringent protocols for cCTA acquisition and analysis were also notable with laboratories following quality standards as defined in the SCCT guidelines.2 This included oral and/or intravenous beta-blockers to achieve to target a heart rate of < 60 beats/min and sublingual nitrates to ensure coronary vasodilation.
Analysis of Evidence
(Rationale for Determination)
Level of evidence – Good (I-IIb, with risks of bias)
Strength of recommendation - Good
The available evidence provides support that use of cCTA with selective FFRCT is likely to reduce the use of ICA in individuals with SIHD who are unlikely to benefit from revascularization by demonstrating the absence of functionally significant obstructive CAD. Also, the benefits are likely to outweigh potential harms given that rates of revascularization for functionally significant obstructive CAD appear to be similar and cardiac-related adverse events do not appear to be increased following a cCTA with selective FFRCT strategy. Furthermore, the evidence on the diagnostic performance, shows higher specificity of FFRCT and better negative likelihood ratio as compared with cCTA alone. Lastly, cCTA combined with a selective FFRCT strategy will more likely than not lead to changes in management that would be expected to improve health outcomes, particularly by limiting unnecessary ICA testing. The evidence is sufficient to determine that the technology results in meaningful improvements in the net health outcome.