Description/Background 
History of FFR: Fractional Flow Reserve (FFR) is the ratio of baseline coronary flow to coronary flow during maximal hyperemia. Its use in the cardiac catheterization laboratory has successfully demonstrated utility in the quantitation of intracoronary flow dynamics secondary to lesional and microvasculature conditions. This technology has proven helpful in evaluating individual patients, with respect to prognostication of coronary artery disease and with decisions regarding the appropriateness of coronary revascularization. (A caveat is discussed in the Additional Information.)

Adaptation to CCTA: Fractional Flow Reserve using Coronary Computed Tomography Angiography (FFR-CT) is a new technology that seeks to provide an estimation of FFR by non-invasive methodology. Following assessment of quality CCTA images, in the appropriate subsets of patients with coronary stenoses, the technology makes mathematical assumptions to simulate maximal hyperemia, and calculates an estimation of FFR (fractional flow reserve) for those coronary vessels with lesions, based upon the principles of fluid mechanics inherent to the Navier-Stokes Theorem. 

Effort to reduce unnecessary ICA: Since conventional FFR measurement has been performed in conjunction with invasive coronary arteriography (ICA), FFR-CT has been developed with the intention of noninvasively adding hemodynamic information to the anatomic findings on CCTA, with the purpose of safely reducing the frequency of unnecessary ICA procedures (defined as all ICA lesions < 50%). Such a reduction in ICA by FFR-CT has been suggested, but not rigorously proven, by the clinical trials to date. (A caveat is discussed in the Additional Information.) 

Current Methodology: The analysis requires a CCTA with at least a 64-slice capability and good-quality images. At present, the process involves transmitting the CCTA data to an off-site location, where a digital model of coronary anatomy is constructed, and using the CCTA data, FFR is calculated using the above described computational fluid dynamics. In this fashion, a report of estimated FFR for the vessels in question is generated, with the intention of reporting coronary hemodynamic information to the requesting clinician.

Policy 
The purpose of FFR-CT is to determine if an invasive cardiac catheterization (ICA) can be avoided. All requirements for MEDICALLY NECESSITY below must be met:

1. The patient was selected for evaluation with coronary computed tomography angiography (CCTA) as a non-invasive test for significant coronary artery disease:
   • Is stable, and
   • Has a pre-test probability of significant, ischemia-producing coronary artery disease between 20% and 50% (low to moderate probability) based on a reliable calculator prior to the CCTA, and
   • The CCTA result demonstrates lesions ≥ 50% OR
2. The patient was selected for evaluation with CCTA as a non-invasive test for significant coronary artery disease:
   • Is stable, and
   • Has a pre-test probability of significant, ischemia-producing coronary artery disease between 51% and 80% (moderate to high moderate probability based on a reliable calculator prior to CCTA, and
   • The  CCTA result demonstrates lesions between 30% and 50% 
3. None of the following clinical scenarios apply since FFR-CT has not been adequately validated due to inapplicability of computational dynamics, artifacts, and/or clinical circumstances; These indications will be considered NOT MEDICALLY NECESSARY:
   • Suspicion of, or current presentation of, an acute coronary syndrome, unless the patient has unstable angina, myocardial infarction was excluded, and ICA would not be recommended if FFR-CT were negative
   • Known ischemic coronary artery disease that has not been revascularized, and there has been no change in patient status or in the CCTA images
   • Recent myocardial infarction within 30 days
   • Prior coronary artery bypass graft surgery
   • Patients who require emergent or urgent ICA or have any evidence of ongoing or active clinical instability, including acute chest pain (sudden onset), cardiogenic shock, unstable blood pressure with systolic blood pressure <90 mmHg, severe congestive heart failure (New York Heart Association [NYHA] III or IV) or acute pulmonary edema
   • Complex congenital heart disease or VSD with Qp/Qs > 1.4
   • BMI > 35
   • Metallic stents in the coronary system
   • Coronary vessels with extensive or heavy calcification
   • Coronary lesions needing evaluation in which vessel diameter < 1.8 mm
   • Cardiac Implanted Electrical Devices (CIEDs)
   • Prosthetic Heart Valves
   • Severe wall motion abnormality on CCTA results
   • Severe myocardial hypertrophy
   • High risk indicators on stress test
   • ICA within the past 90 days
   • Marginal quality of the submitted imaging data, due to motion, blooming, misalignment, arrhythmia, etc.

Rationale: 
FFR-CT Results:
Quantitative estimation of coronary lesional hemodynamic severity using FFR-CT may enable deferral of invasive coronary arteriography when values are above 0.80.

A decision to follow through with coronary revascularization should not be based upon FFR-CT. Thus, justification for percutaneous coronary intervention should usually require additional invasive FFR or other corroborative non-invasive or angiographic data. FFR-CT data to date provides no evidence showing outcomes comparable to outcomes based upon invasive FFR determinations. By virtue of the assumption of maximal hyperemia, the microvasculature’s true behavior is not actually measured by FFR-CT. This is important, since a coronary lesional intervention will not improve flow if the microvasculature will not allow further increase in flow.

Because of the lack of long-term outcomes data and flaws in the design of multiple trials, and given the controversy evidenced by numerous editorials in peer-reviewed journals, there is a lack of formal guidelines from professional societies at this time. Based upon findings in the PLATFORM trial, patients who are evaluated initially by CCTA with contingent FFR-CT, could be perceived as actually having a higher rate of unnecessary ICA. This has necessitated numerous considerations based upon multiple published trials and meta-analyses in formulating this de novo guideline.

Calculations of pre- and post-test probability:
Prior to each non-invasive test, there is a pretest probability of finding significant coronary artery disease. The result of a non-invasive test yields a post-test probability, which then becomes the pretest probability for a subsequent non-invasive test. This is helpful when a patient who had a prior stress test is being considered for FFR-CT.

1. 1. University of Washington pretest and post-test probability table (preferred), to determine a pretest probability for patients undergoing FFR-CT subsequent to a prior non-invasive test. The University of Washington Calculator for Pre- and Post-test Probability can be found at this address:  http://faculty.washington.edu/dtlinker/CAD.html 
   2. Updated Diamond Forrester Pretest Probability Table, based upon symptoms prior to initial non-invasive testing:

The source of the tables above can be found at https://doi.org/10.1093/eurheartj/ehr015.

1. 3.  European Society of Cardiology CAD Consortium Pretest Probability, based upon clinical information (CAC optional) prior to non-invasive testing for coronary artery disease. The ESC CAD Consortium Pretest Probability Calculator can be found at this address: https://www.qxmd.com/calculate/calculator_287/pre-test-probability-of-cad-cad-consortium

Abbreviations:
CCTA = Coronary Computerized Tomographic Angiography
CIED = Cardiac Implanted Electrical Devices
ESC = European Society of Cardiology
FFR = Fractional Flow Reserve
ICA = Invasive Coronary Arteriography
MACE = Major Adverse Coronary Events
NPV = Negative Predictive Value

References: 

1. A Arbab-Zadeh, JM Miller, CE Rochitte, et al. Diagnostic Accuracy of Computed Tomography Coronary Angiography According to Pre-Test Probability of Coronary Artery Disease and Severity of Coronary Arterial Calcification: The CorE-64 International, Multicenter Study. https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=22261160. doi: 10.1016/j.jacc.2011.06.079
2. BL Norgaard, J Hjort, S Gaur, et al. Clinical Use of Coronary CTA–Derived FFR for Decision-Making in Stable CAD. JACC Cardiovascular Imaging, Vol 10, No5, 2017, p 5451-550. https://www.ncbi.nlm.nih.gov/pubmed/27085447
3. BL Nørgaard, J Leipsic, S Gaur, et al. Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). J Am Coll Cardiol. Apr 1 2014; 63(12):1145-1155. PMID 24486266. https://doi.org/10.1161/JAHA.117.005587
4. BL Nørgaard, S Gaur, J Leipsic, et al. Influence of coronary calcification on the diagnostic performance of CT angiography derived FFR in coronary artery disease: a substudy of the NXT Trial. JACC Cardiovasc Imaging. Sep 2015; 8(9):1045-1055. http://ac.els-cdn.com/S1936878X15004209/1-s2.0-S1936878X15004209-main.pdf?_tid=1f36befc-8e9f-11e7-96c4-00000aab0f02&acdnat=1504220153_7781c1008bf3f875aeef2f85b0c5e65d
5. CA Taylor, TA Fonte, JK Min. Computational fluid dynamics applied to cardiac computed tomography for noninvasive quantification of fractional flow reserve: scientific basis. J Am Coll Cardiol. Jun 4 2013; 61(22):2233- 2241. doi: 10.1016/j.jacc.2012.11.083
6. D Newby, M Williams, A Hunter, (SCOT-Heart Investigators) et al. CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial. The Lancet Volume 385, No. 9985, p2383–2391, 13 June 2015. DOI: http://dx.doi.org/10.1016/S0140-6736(15)60291-4
7. De Bruyne B, Fearon WF, Pijls NH. et al. Fractional flow reserve-guided PCI for stable coronary artery disease. N Engl J Med. Sep 25 2014; 371(13):1208-1217. DOI: 10.1056/NEJMoa1408758
8. DT Linker. Decision-Support Tool to Calculate Pre- and Post-Test Probabilities of Coronary Artery Disease with Cardiac Functional Tests. http://faculty.washington.edu/dtlinker/CAD.html
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12. JK Min, J Leipsic, MJ Pencina, et al. Diagnostic Accuracy of Fractional Flow Reserve From Anatomic CT Angiography. JAMA. Sep 26 2012; 308(12):1237-1245. http://jamanetwork.com/journals/jama/fullarticle/1352969
13. JK. Min. Look Backwards But Live Forwards JACC Cardiovasc Imaging. 2017 May;10(5):551-553. doi: 10.1016/j.jcmg.2015.12.014
14. M Dewey, M Rief, P Martus, et al. Evaluation of computed tomography in patients with atypical angina or chest pain clinically referred for invasive coronary angiography: randomised controlled trial. BMJ 2016; 355 doi: https://doi.org/10.1136/bmj.i5441
15. MA Hlatky, DeBruyne, G Pontone, et al. Quality-of-Life and Economic Outcomes of Assessing Fractional Flow Reserve with Computed Tomography Angiography: PLATFORM J Am Coll Cardiol. 2015 Dec 1;66(21):2315-23. doi: 10.1016/j.jacc.2015.09.051. Epub 2015 Oct 14.
16. MR Patel, JH Calhoon, GJ Dehmer, et al. ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 Appropriate Use Criteria for coronary revascularization in patients with stable ischemic heart disease: a report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society of Thoracic Surgeons. J Am Coll Cardiol. May 02 2017; 69(17):2212-2241. DOI: 10.1016/j.jacc.2017.02.001
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19. National Institute for Health and Care Excellence. HeartFlow FFRCT for estimating fractional flow reserve from coronary CT angiography https://www.nice.org.uk/guidance/mtg32
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21. PS Douglas, B DeBruyne, G Pontone, et al. 1-Year Outcomes of FFRCT-Guided Care in Patients with Suspected Coronary Disease: The PLATFORM Study. J Am Coll Cardiol. 2016 Aug 2;68(5):435-45. doi: 10.1016/j.jacc.2016.05.057
22. PS Douglas, G Pontone, MA Hlatky, et al. Clinical outcomes of fractional flow reserve by computed tomographic angiography-guided diagnostic strategies vs. usual card in patients with suspected coronary artery disease: the prospective longitudinal trial of FFR (CT): outcome and resource impacts study. Eur Heart J. 2015 Dec 14;36(47):3359-67. doi: 10.1093/eurheartj/ehv444. Epub 2015 Sep 1. Supplemental reference: https://clinicaltrials.gov/ct2/show/NCT01943903
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25. S Gaur, CA Taylor, JM Jensen, et al. FFR Derived From Coronary CT Angiography in Nonculprit Lesions of Patients With Recent ST-segment elevation myocardial infarction. JACC VOL. 10, NO. 4, 2017 p 424-433 DOI: 10.1016/j.jcmg.2016.05.019.
26. S Gaur, HG Bezerra, JF Lassen, et al. Fractional flow reserve derived from coronary CT angiography: variation of repeated analyses. J Cardiovasc Comput Tomogr. Jul-Aug 2014; 8(4):307-314. PMID 25151923 DOI: 10.1016/j.jcct.2014.07.002
27. S Packard, RP. Karlsberg. Integrating FFRCT into Routine Clinical Practice: A Solid PLATFORM or Slippery Slope? J Am Coll Cardiol. 2016 Aug 2;68(5):446-9. doi: 10.1016/j.jacc.2016.05.056. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378152/
28. SD Fihn, JM Gardin, J Abrams, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. Dec 18 2012; 60(24):e44-e164. DOI: 10.1016/j.jacc.2012.07.013
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31. Van Nunen LX, Zimmermann FM, Tonino PA. et al. Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial. Lancet. Nov 7 2015; 386(10006):1853-1860. DOI: http://dx.doi.org/10.1016/S0140-6736(15)00057-4

Coding Section 

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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