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Clinical Evidence Summary
Cardiologists use a number of noninvasive diagnostic tests including exercise treadmill, stress
echocardiography, and nuclear SPECT in order to determine which patients have coronary artery disease
and who may benefit from revascularization. However Patel et al. (2014) found that despite widespread use of
these tools, 58.4% of patients sent to invasive coronary angiography (ICA) did not have significant CAD. In fact,
Chinnaiyan et al. found that stress test results were not predictive of which patients had significant CAD and
provided no predictive value beyond traditional cardiovascular risk factors such as high blood pressure or a
history of smoking.
In a recent study performed by Vavalle et al. researchers found that only 48% (7,564 of 15,766) of patients had
obstructive disease at the time of ICA. Furthermore, patients with positive stress test results were less likely to
undergo revascularization (35.2%) than patients with negative results (47.9%) or no stress test at all (40.3%).
These studies underscore the need for a better noninvasive test that more accurately determines who may
benefit from invasive evaluation.
Fractional Flow Reserve (FFR), measured during ICA, serves as the gold standard for identifying vessel-specific
ischemia and is used to identify patients who may benefit from coronary revascularization. The FAME study
(Tonino et al.) randomized patients with multivessel CAD to angiography-guided Percutaneous Coronary
Intervention (PCI) or FFR-guided PCI. The FFR-guided group, in which stents were placed only when a
stenosis was associated with FFR < 0.80, had a significantly lower rate of adverse clinical events. In the FAME
II study (De Bruyne et al.), patients in whom at least one stenosis was functionally significant (FFR < 0.80) were
randomized to FFR-guided PCI or best available medical therapy. Patients in the FFR-guided group had a
significantly lower rate of adverse clinical events.
Data from the prospective IRIS-FFR registry performed by Ahn et al. confirmed the superior outcomes of FFR-
guided care in 5,846 patients. The authors report that for lesions with a low FFR, the risk of an adverse cardiac
event was much lower if the lesion was revascularized. Conversely, for lesions with a high FFR, the data strongly
supports medical treatment as a reasonable and safe treatment strategy. A recent meta-analysis performed
by Nagaraja et al. showed that the availability of FFR data changed the management strategy in 22-48% of
patients compared to an angiography-guided strategy. These studies demonstrate the ability for FFR to guide
treatment safely and effectively for patients with stable CAD.
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Scientific Basis
Taylor et al. have described the scientific basis for the noninvasive FFRCT analysis, explaining how recent
advances in computational fluid dynamics and image-based modeling underlie the ability to calculate
FFR values mathematically. When these methods are applied to standard coronary CT angiograms (cCTA),
the result is a color-coded 3 dimensional map of FFRCT values at every point in the coronary arterial tree.
Visualization of FFRCT values in patient-specific anatomy enables physicians to identify ischemia-producing
coronary lesions.
Validation of FFRCT
HeartFlow FFRCT has been evaluated in three multicenter prospective clinical trials that directly compared FFRCT
values with invasively measured FFR values in over 600 patients at major medical centers worldwide. Clinical
data from the landmark NXT study (Nørgaard et al. 2014) utilized the most current version, and showed that the
HeartFlow FFRCT Analysis had a greater ability to determine whether significant CAD is present and whether a
coronary stenosis is obstructing blood flow, i.e. low FFR, as compared to cCTA alone. The HeartFlow Analysis
had higher diagnostic accuracy (86%) than cCTA (65%) and ICA showed only 71% accuracy in the study.
When compared with other noninvasive testing methods, FFRCT demonstrated significantly higher diagnostic
accuracy (Nørgaard et al. 2015).
Clinical Use of the HeartFlow Analysis
The HeartFlow FFRCT Analysis has been shown to significantly affect treatment decisions for patients with
suspected CAD. In the FFRCT RIPCORD study, Curzen et al. reported that treatment decisions based on cCTA
changed in 44% of patients when FFRCT data were made available.
The prospective controlled clinical utility and cost effectiveness PLATFORM trial (Douglas et al. 2015) showed
that in patients scheduled for ICA the addition of FFRCT data was associated with cancellation of the invasive
procedure in 61% of patients. In addition, the proportion of patients who underwent ICA only to find no
obstructive CAD dropped from 73% in the usual care group to 12% in the group guided by a pathway
incorporating cCTA and FFRCT. Importantly, there were no adverse events during 1 year of follow-up in the 117
patients whose ICA was cancelled based on FFRCT findings (Douglas et al. 2016). By reducing the number of
unnecessary invasive procedures performed, Benton et al. argue that FFRCT has the ability to lower health care
expenditures and become the true gatekeeper to ICA.
suspected coronary artery disease: the prospective longitudinal trial of FFRCT : outcome and resource impacts study. Douglas, P.S. et al. (2015).
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Health Economics
There is also evidence that the HeartFlow Analysis can reduce costs associated with diagnosing and treating CAD.
One year follow-up of the PLATFORM study performed by Douglas et al. found that for patients with a planned ICA,
evaluation via a pathway incorporating cCTA and FFRCT led to significantly lower costs of care compared with standard
treatment ($8,127 vs. $12,145, a reduction of 33%). When the $1500 cost of FFRCT was included, total savings to the
healthcare system was 26%. In addition, evaluation via a pathway incorporating cCTA and FFRCT was associated with
improved Quality of Life compared with a strategy of evaluation with ICA or other noninvasive tests (Hlatky et al. 2015).
An earlier health economic analysis performed by Hlatky et al. (2013) found that incorporating FFRCT into patient
management could lead to 30% lower costs and a 12% reduction in the rate of death and heart attack over a period of
one year. Rajani et al. and Kimura et al. published similar findings using UK and Japanese health economic
models respectively.
Real World Experience with the FFRCT Analysis
Nørgaard et al. (2016) recently shared their experience using cCTA and FFRCT as the initial diagnostic modality to
evaluate patients with new onset chest pain and no known CAD. In this population with a low to intermediate pre-test
likelihood of disease, FFRCT was ordered for 189 patients (15.1%) who had one or two intermediate coronary stenoses
(lumen narrowing 30% to 70%) found by cCTA. Conclusive FFRCT results were obtained in 98% of patients and 123
patients (65%) had their ICA deferred based on the results. The authors report no adverse clinical events for these
patients through a median follow-up period of 12 months. In a follow-up report (2017) the authors report that switching
from MPI to FFRCT to evaluate patients with intermediate stenoses led to a reduction in patients who needed a second
noninvasive test, a reduction in ICA utilization, a decrease in the rate of finding no obstructive CAD at ICA, and an
increase in the number of ICAs performed with functional information available.
Jensen et al. examined the impact of adopting a diagnostic strategy composed of cCTA with selective FFRCT testing for
all symptomatic patients with suspected CAD (N = 774). This replaced an earlier strategy that used frontline cCTA for
patients with a low-intermediate risk of CAD and referred patients with high risk directly to ICA. Of the 181 patients with
a high risk of CAD, use of cCTA and FFRCT led to cancellation of 75% (115/153) of planned ICAs. In the 593 patients with
a low-intermediate risk of CAD, cCTA with selective FFRCT safely kept 91% of patients out of the cath lab. The authors
reported four adverse events, none of which occurred in a patient who had an ICA cancelled based on FFRCT results.
For more information, contact:
HeartFlow, Inc.
Heather Brown
1400 Seaport Blvd, Bldg B
Senior Vice President,
Redwood City, CA 94063
Market Access and Reimbursement
ph: +1.650.241.1221
ph: +1.650.241.4873
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