Coronary Computed Tomography Angiography with Selective Noninvasive Fractional Flow Reserve

POLICY NUMBER

A.6.01.59

DESCRIPTION

Invasive coronary angiography (ICA) is clinically useful in stable ischemic heart disease when there is coronary artery obstruction that may benefit from revascularization. However, many individuals currently undergoing ICA will not benefit from revascularization. Therefore, if there are noninvasive alternatives to guide decisions about the use of ICA to spare individuals from unnecessary ICA, there is potential to improve health outcomes. Using noninvasive measurement of fractional flow reserve (FFR) as part of a noninvasive imaging strategy may be beneficial to avoid the need for ICA.

Stable Ischemic Heart Disease

Coronary artery disease (CAD) is a significant cause of morbidity and mortality. Various epidemiologic risk factors have been well studied. Evaluation of obstructive CAD involves quantifying arterial stenoses to determine whether significant narrowing is present. Lesions with stenosis more than 50% to 70% in diameter accompanied by symptoms are generally considered significant. It has been suggested that coronary computed tomography angiography (CCTA) or other noninvasive functional cardiac testing may help rule out CAD and avoid invasive coronary angiography (ICA) in patients with a low clinical likelihood of significant CAD. However, ICA is frequently unnecessary in patients with suspected stable ischemic heart disease, as evidenced by low diagnostic yields for significant obstructive CAD. Patel and colleagues found that from a sample of over 132,000 ICAs, 48.8% of elective ICAs performed in patients with stable angina did not detect obstructive CAD (left main stenosis ≥50% or ≥70% in a major epicardial or branch >2.0 mm in diameter). Invasive coronary angiography is clinically useful when patients with stable angina have failed optimal medical therapy and may benefit from revascularization. A noninvasive imaging test performed before ICA as a gatekeeper, which can distinguish candidates who may benefit from early revascularization (eg, patients with unprotected left main stenosis ≥50% or hemodynamically significant disease) from those unlikely to benefit, could avoid unnecessary invasive procedures and their potential adverse consequences. Moreover, for the large majority of patients with stable ischemic heart disease, revascularization offers no survival advantage over medical therapy; few might benefit from ICA if they have not first failed optimal medical therapy.

Clinical Risk Prediction for Stable Ischemic Heart Disease

A 2012 collaborative medical association guideline for the diagnosis and management of patients with stable heart disease lists several class I recommendations on the use of noninvasive testing in patients with suspected stable ischemic heart disease. A class I recommendation indicates that a test should be performed. In general, patients with at least intermediate risk (10% to 90% risk by standard risk prediction instruments) are recommended to have some type of test, the choice depending on the interpretability of the electrocardiogram, the capacity to exercise, and the presence of comorbidity. In 2023, an updated collaborative medical association guideline for patients with chronic coronary disease was published to provide an update to and consolidate new evidence since the 2012 guideline for the diagnosis and management of patients with stable heart disease and the corresponding 2014 focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease. A class 1 recommendation states that "in patients with chronic coronary disease, it is recommended that risk stratification incorporate all available information, including noninvasive, invasive, or both cardiovascular diagnostic testing results or use validated risk scores to classify patients as low (<1%), intermediate (1%-3%), or high (>3%) yearly risk for cardiovascular death or nonfatal myocardial infarction." The text further states that noninvasive test results alone are insufficient to adequately risk stratify patients with chronic coronary disease, and the additional information improves risk prediction.

Clinical prediction scores or models have been developed to help estimate the pretest probability of CAD in individuals with stable chest pain. Diamond and Forrester (1979) developed the original version of a commonly cited clinical prediction model based on age, sex, and type of pain symptoms. Versteylen and colleagues (2011) published a comparison of clinical prediction results for the Diamond and Forrester (1979) model, the Framingham risk score, the PROCAM risk score, and the SCORE risk estimation model. Min and colleagues published another model, and in 2016 a CAD consortium developed an online calculator.

Gatekeepers to Invasive Coronary Angiography

Imposing an effective noninvasive gatekeeper strategy with one or more tests before planned ICA to avoid unnecessary procedures is compelling. The most important characteristic of a gatekeeper test is its ability to accurately identify and exclude clinically insignificant disease where revascularization would offer no potential benefit. From a diagnostic perspective, an optimal strategy would result in few false-negative tests while avoiding an excessive false-positive rate—it would provide a low post-test probability of significant disease. Such a test would then have a small and precise negative likelihood ratio and high negative predictive value. An effective gatekeeper would decrease the rate of ICA while increasing the diagnostic yield (defined by the presence of obstructive CAD on ICA). At the same time, there should be no increase in major adverse cardiac events. A clinically useful strategy would satisfy these diagnostic performance characteristics and impact the outcomes of interest. Various tests have been proposed as potentially appropriate for a gatekeeper function before planned ICA, including CCTA, magnetic resonance imaging, single-photon emission computed tomography, positron emission tomography, and stress echocardiography. More recently, adding noninvasive measurement of fractional flow reserve (FFR) using CCTA has been suggested, combining functional and anatomic information.

Fractional Flow Reserve

Invasively measured fractional flow reserve evaluates the severity of ischemia caused by coronary artery obstructions and can predict when revascularization may be beneficial. Fractional flow reserve has not been used as a diagnostic test for ischemic heart disease, but as a test to evaluate the degree of ischemia caused by stenosis.

Invasive fractional flow reserve is rarely used in the U.S. to guide percutaneous coronary intervention (PCI). Pothineni and colleagues (2016), using the National Inpatient Sample, reported that 201,705 PCIs were performed in 2012, but just 21,365 fractional flow reserve procedures. Assuming the intention of fractional flow reserve is to guide PCI, it would represent just 4.3% of PCI procedures. Whether noninvasively obtained fractional flow reserve will influence decisions concerning ICA, over and above anatomic considerations, is therefore important to establish empirically.

Randomized controlled trials and observational studies have demonstrated that fractional flow reserve-guided revascularization can improve cardiovascular outcomes, reduce revascularizations, and decrease costs. For example, the Fractional Flow Reserve versus Angiography for Multivessel Evaluation trial randomized 1,005 patients with multivessel disease and planned PCI. At 1 year, compared with PCI guided by angiography alone, fractional flow reserve-guided PCI reduced the number of stents placed by approximately 30%, followed by lower rates (13.2% vs 18.3%) of major adverse cardiac events (myocardial infarction, death, repeat revascularization) and at a lower cost. The clinical benefit persisted through two years, although by five years, event rates were similar between groups.

European guidelines (2013) for stable CAD have recommended that fractional flow reserve be used "to identify hemodynamically relevant coronary lesion(s) when evidence of ischaemia is not available" (class Ia), and "[r]evascularization of stenoses with fractional flow reserve <0.80 is recommended for patients with angina symptoms or a positive stress test." A 2019 European guideline on chronic coronary syndromes recommends to "consider revascularization on top of medical therapy" in patients without evidence of ischaemia but with fractional flow reserve ≤0.80. Other guidelines (2014) have recommended using "fractional flow reserve to identify haemodynamically relevant coronary lesion(s) in stable patients when evidence of ischaemia is not available" (class Ia recommendation). The U.S. guidelines (2012) have stated that a fractional flow reserve of 0.80 or less provides level Ia evidence for revascularization for "significant stenoses amenable to revascularization and unacceptable angina despite guideline directed medical therapy." A 2023 U.S guideline for patients with chronic coronary disease notes the following for patients with fractional flow reserve of 0.80 or less: "consideration of revascularization, antianginal therapy as per guidelines." Also, the importance of fractional flow reserve in decision making appears prominently in the 2017 appropriate use criteria for coronary revascularization in patients with stable ischemic heart disease.

Measuring fractional flow reserve during ICA can be accomplished by passing a pressure-sensing guidewire across a stenosis. Coronary hyperemia (increased blood flow) is then induced and pressure distal and proximal to the stenosis is used to calculate flow across it. Fractional flow reserve is the ratio of flow in the presence of a stenosis to flow in its absence. Fractional flow reserve levels less than 0.75 to 0.80 are considered to represent significant ischemia while those 0.94 to 1.0 are considered normal. Measurement is valid in the presence of serial stenoses, is unaffected by collateral blood flow, and reproducibility is high. Potential complications include adverse events related to catheter use such as vessel wall damage (dissection); the time required to obtain fractional flow reserve during a typical ICA is less than 10 minutes.

Fractional flow reserve using CCTA requires at least 64-slice CCTA and cannot be calculated when images lack sufficient quality (11% to 13% in recent studies), eg, in obese individuals (eg, body mass index, >35 kg/m²). The presence of dense arterial calcification or an intracoronary stent can produce significant beam-hardening artifacts and may preclude satisfactory imaging. The presence of an uncontrolled rapid heart rate or arrhythmia hinders the ability to obtain diagnostically satisfactory images. Evaluation of the distal coronary arteries is generally more difficult than the visualization of the proximal and mid-segment coronary arteries due to greater cardiac motion and the smaller caliber of coronary vessels in distal locations.

Noninvasive Fractional Flow Reserve Measurement

Fractional flow reserve can be modeled noninvasively using images obtained during CCTA (HeartFlow software termed FFR_CT; Siemens cFFR). The process involves constructing a digital model of coronary anatomy and calculating fractional flow reserve across the entire vascular tree using computational fluid dynamics. Fractional flow reserve using CCTA can also be used for "virtual stenting" to simulate how stent placement would be predicted to improve vessel flow.

Only HeartFlow FFR_CT software has been cleared by the U.S. Food and Drug Administration (FDA). Imaging analyses require uploading data to a cloud for analysis, taking as little as 5 hours to complete. Other prototype software developed by Siemens is workstation-based with onsite analyses.

In November 2014, FFR_CT simulation software (HeartFlow) was cleared for marketing by the FDA through the de novo 510(k) process (class II, special controls; FDA product code: PJA). In January 2016, the FFR_CT v2.0 device was cleared through a subsequent 510(k) process.

HeartFlow FFR_CT post-processing software is cleared:

"for the clinical quantitative and qualitative analysis of previously acquired Computed Tomography [CT] DICOM [Digital Imaging and Communications in Medicine] data for clinically stable symptomatic patients with coronary artery disease. It provides fractional flow reserve using coronary computed tomography angiography, a mathematically derived quantity, computed from simulated pressure, velocity and blood flow information obtained from a 3D computer model generated from static coronary CT images. Fractional flow reserve using coronary computed tomography angiography analysis is intended to support the functional evaluation of coronary artery disease. The results of this analysis [FFR_CT] are provided to support qualified clinicians to aid in the evaluation and assessment of coronary arteries. The results of HeartFlow fractional flow reserve using coronary computed tomography angiography are intended to be used by qualified clinicians in conjunction with the patient's clinical history, symptoms, and other diagnostic tests, as well as the clinician's professional judgment."

In April 2022, DeepVessel® FFR software (Keya Medical) received FDA approval through the 510(k) process.

DeepVessel FFR software is cleared:

"for the clinical quantitative and qualitative analysis of previously acquired Computed Tomography [CT] DICOM data for clinically stable symptomatic patients with coronary artery disease. It provides DVFFR (a CT-derived FFR measurement) computed from static coronary CTA images using deep learning neural networks that encode imaging, structural, and functional characteristics of coronary arteries through learning. DEEPVESSEL FFR analysis is intended to support the functional evaluation of coronary artery disease. The results of the analysis are provided to support qualified clinicians to aid in the evaluation and assessment of coronary arteries. DEEPVESSEL FFR results are intended to be used by qualified clinicians in conjunction with the patient’s clinical history, symptoms, and other diagnostic tests, as well as the clinician’s professional judgment."

Related medical policy - 

• Cardiac Computed Tomographic Angiography (CCTA)

POLICY

The use of noninvasive fractional flow reserve following a positive coronary computed tomography angiography may be considered medically necessary to guide decisions about the use of invasive coronary angiography in individuals with stable chest pain at intermediate risk of coronary artery disease (ie, suspected or presumed stable ischemic heart disease).

The use of noninvasive fractional flow reserve not meeting the criteria outlined above is considered investigational.

POLICY EXCEPTIONS

Federal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Fractional flow reserve using coronary computed tomography angiography requires at least 64-slice coronary computed tomography angiography and cannot be calculated when images lack sufficient quality (11% to 13% in recent studies; eg, in obese individuals [body mass index, >35 kg/m²]). The presence of dense arterial calcification or an intracoronary stent can produce significant beam-hardening artifacts and may preclude satisfactory imaging. The presence of an uncontrolled rapid heart rate or arrhythmia hinders the ability to obtain diagnostically satisfactory images. Evaluation of the distal coronary arteries is generally more difficult than visualization of the proximal and mid-segment coronary arteries due to greater cardiac motion and the smaller caliber of coronary vessels in distal locations.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B. appropriate with regard to standards of good medical practice; and

C. not solely for the convenience of the Member, his or her Provider; and

D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

11/21/2019: Approved by Medical Policy Advisory Committee.

06/19/2020: Policy description updated. Policy statements unchanged.

08/02/2021: Policy description updated regarding software cleared by the FDA. Policy statements unchanged. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity."

06/20/2022: Policy description revised regarding clinical risk prediction studies. Policy statement updated to change "patients" to "individuals."

09/30/2022: Code Reference section updated to add new ICD-10 diagnosis codes I25.112 and I25.752, effective 10/01/2022.

07/14/2023: Policy description updated regarding software cleared by the FDA. Policy statements unchanged.

09/29/2023: Code Reference section updated to revise the code description for ICD-10 diagnosis code I25.112, effective 10/01/2023.

12/21/2023: Code Reference section updated to add new 2024 CPT code 75580, effective 01/01/2024.

06/13/2024: Policy description updated regarding clinical risk prediction for stable ischemic heart disease. Policy statements unchanged.

08/12/2025: Policy description updated regarding fractional flow reserve. Policy statements unchanged. Code Reference section updated to remove deleted CPT codes 0501T, 0502T, 0503T, and 0504T.

SOURCE(S)

Blue Cross Blue Shield Association policy # 6.01.59

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Medically Necessary Codes

CPT copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.