Trial Outcomes & Findings for Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care (NCT NCT02499679)

Last Updated: 2025-07-30

Results Overview

The reclassification rate of management plans was assessed by the blinded independent review committee and local physician teams separately. These evaluations are meant to assess the potential impact of FFRCT on downstream testing and clinical decision making but were not be used to determine actual patient care. This endpoint is aimed at determining the incremental value of FFRCT over coronary CTA alone in the management of stable angina. FFRCT is non-invasive method to determine FFR which computes the hemodynamic significance of CAD (FFRCT) from subject-specific cCTA data using computational fluid dynamics under rest and simulated maximal coronary hyperemic conditions (Taylor 2013).

Recruitment status

COMPLETED

Target enrollment

4737 participants

Primary outcome timeframe

at 90 days

Results posted on

2025-07-30

Participant Flow

All clinically stable, symptomatic patients diagnosed with CAD by coronary CTA that meet the following eligibility criteria are candidates for enrollment in the ADVANCE Registry: age \>18 years, ability to provide informed consent, and meet eligibility criteria for FFRCT based on CAD, with an anatomical stenosis \>25%, diagnosed on coronary CTA.

The ADVANCE Registry screened a total of 5,083 patients, and 4,893 of them had coronary CTA submitted for FFRCT analysis. Of these submitted, 4,737 (96.80%) were of sufficient image quality for FFRCT analysis.

Participant milestones

Participant milestones
Measure	All Patients Diagnosed With CAD by cCTA+FFRCT All clinically stable, symptomatic patients diagnosed with CAD by coronary computed tomography angiography (cCTA) and FFRCT (Fractional Flow Reserve derived from coronary computed tomography angiography).
Overall Study STARTED	4737
Overall Study COMPLETED	4737
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

There was no significant difference between subject group demographics or risk factors for those receiving CCTA alone vs. CCTA plus FFRCT. Information represented in this table is for all subjects with FFRCT results.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Patients Diagnosed With CAD by cCTA n=4737 Participants All clinically stable, symptomatic patients diagnosed with CAD by coronary computed tomography angiography (cCTA), that meet eligibility criteria, and are able and willing to participate are candidates for the ADVANCE Registry. Those patients that meet all inclusion/exclusion criteria and who sign the ethics committee (EC)/institutional review board (IRB) approved informed consent will be enrolled in the registry. Obstructive CAD will be defined as luminal diameter stenosis \>50% by invasive angiography visual assessment or non-invasive cCTA, or invasively measured FFR of ≤0.80. cCTA is defined as coronary computed tomographic angiography. FFR (Fractional Flow Reserve) is defined as the ratio of the mean distal intracoronary arterial pressure, (Pd) to the mean arterial pressure (Pa) under conditions of adenosine induced maximal hyperemia.
Age, Continuous	66.1 years STANDARD_DEVIATION 10.3 • n=4737 Participants • There was no significant difference between subject group demographics or risk factors for those receiving CCTA alone vs. CCTA plus FFRCT. Information represented in this table is for all subjects with FFRCT results.
Sex: Female, Male Female	1603 Participants n=4737 Participants • There was no significant difference between subject group demographics or risk factors for those receiving CCTA alone vs. CCTA plus FFRCT. Information represented in this table is for all subjects with FFRCT results.
Sex: Female, Male Male	3134 Participants n=4737 Participants • There was no significant difference between subject group demographics or risk factors for those receiving CCTA alone vs. CCTA plus FFRCT. Information represented in this table is for all subjects with FFRCT results.
Hypertension	3045 Participants n=4737 Participants
Diabetus mellitus	1136 Participants n=4737 Participants
Hyperlipidemia	2957 Participants n=4737 Participants
Smoking Current smoking	797 Participants n=4737 Participants
Smoking Former smoker	1615 Participants n=4737 Participants
Smoking Never smoked	1973 Participants n=4737 Participants
Smoking Unknown	352 Participants n=4737 Participants
Angina status Atypical	1727 Participants n=4737 Participants • There was no significant difference between subject group demographics or risk factors for those receiving CCTA alone vs. CCTA plus FFRCT. Information represented in this table is for all subjects with FFRCT results.
Angina status Typical	1025 Participants n=4737 Participants • There was no significant difference between subject group demographics or risk factors for those receiving CCTA alone vs. CCTA plus FFRCT. Information represented in this table is for all subjects with FFRCT results.
Angina status Non-cardiac pain	297 Participants n=4737 Participants • There was no significant difference between subject group demographics or risk factors for those receiving CCTA alone vs. CCTA plus FFRCT. Information represented in this table is for all subjects with FFRCT results.
Angina status Dyspnea	472 Participants n=4737 Participants • There was no significant difference between subject group demographics or risk factors for those receiving CCTA alone vs. CCTA plus FFRCT. Information represented in this table is for all subjects with FFRCT results.
Angina status None	1164 Participants n=4737 Participants • There was no significant difference between subject group demographics or risk factors for those receiving CCTA alone vs. CCTA plus FFRCT. Information represented in this table is for all subjects with FFRCT results.
Angina status Unknown	52 Participants n=4737 Participants • There was no significant difference between subject group demographics or risk factors for those receiving CCTA alone vs. CCTA plus FFRCT. Information represented in this table is for all subjects with FFRCT results.

PRIMARY outcome

Timeframe: at 90 days

Population: The primary endpoint of reclassification between core lab CCTA alone and CCTA plus FFRCT-based management.

Outcome measures

Outcome measures
Measure	Reclassification Rate by Core Lab n=4737 Participants For each enrolled patient, the endpoint review committee used data from coronary CTA and FFRCT, along with the clinical data such as medical history and demographics to determine the management plan using the following criteria: (a) optimal medical therapy, (b) percutaneous coronary intervention, (c) coronary artery bypass graft surgery, or (d) more information required. The management plan recommended by the committee was compared with the therapy that the patient received, as determined by his or her local team of physicians.	ICA Patients With FFRCT ≤0.80 Patients undergoing ICA procedure and FFRCT result showing Obstructive CAD.	Site-determined Post-FFRCT Treatment Plan - Further Diagnostics All clinically stable, symptomatic patients diagnosed with CAD by coronary computed tomography angiography (cCTA) and FFRCT.
Percentage of Participants With Reclassification of CAD Management, Assessed as the Therapeutic Recommendations Made Based on Review of Coronary CTA Alone Versus CTA + FFRCT, When Available, by a Central Integration Core Laboratory.	66.9 percentage of participants Interval 64.8 to 67.6	—	—

SECONDARY outcome

Timeframe: at 90 days

Population: All participants who were enrolled in the study and received cCTA and FFRCT analysis.

Coronary computed tomography angiography-derived fractional flow reserve resulted in revision of the clinical management plan as determined by the site investigators.

Outcome measures

Outcome measures
Measure	Reclassification Rate by Core Lab n=4737 Participants For each enrolled patient, the endpoint review committee used data from coronary CTA and FFRCT, along with the clinical data such as medical history and demographics to determine the management plan using the following criteria: (a) optimal medical therapy, (b) percutaneous coronary intervention, (c) coronary artery bypass graft surgery, or (d) more information required. The management plan recommended by the committee was compared with the therapy that the patient received, as determined by his or her local team of physicians.	ICA Patients With FFRCT ≤0.80 Patients undergoing ICA procedure and FFRCT result showing Obstructive CAD.	Site-determined Post-FFRCT Treatment Plan - Further Diagnostics All clinically stable, symptomatic patients diagnosed with CAD by coronary computed tomography angiography (cCTA) and FFRCT.
Percentage of Participants With Reclassification Between Investigator Management Plan Based on cCTA Alone Compared to Actual Clinical Management	63.5 percentage of participants Interval 62.0 to 65.0	—	—

SECONDARY outcome

Timeframe: At 90 days

Population: The rate of anatomically defined 'non-obstructive' disease at ICA (no stenosis defined as \>50% at ICA)

Invasive catheterization without obstructive disease was measured by either site read coronary angiogram showing no stenosis of ≥ 50% or no invasively-measured FFR ≤ 0.80 in a segment distal to a stenosis.

Outcome measures

Outcome measures
Measure	Reclassification Rate by Core Lab n=281 Participants For each enrolled patient, the endpoint review committee used data from coronary CTA and FFRCT, along with the clinical data such as medical history and demographics to determine the management plan using the following criteria: (a) optimal medical therapy, (b) percutaneous coronary intervention, (c) coronary artery bypass graft surgery, or (d) more information required. The management plan recommended by the committee was compared with the therapy that the patient received, as determined by his or her local team of physicians.	ICA Patients With FFRCT ≤0.80 n=694 Participants Patients undergoing ICA procedure and FFRCT result showing Obstructive CAD.	Site-determined Post-FFRCT Treatment Plan - Further Diagnostics All clinically stable, symptomatic patients diagnosed with CAD by coronary computed tomography angiography (cCTA) and FFRCT.
Percentage of Participants With Invasive Catheterization Without Obstructive Disease	43.8 percentage of participants	14.4 percentage of participants	—

SECONDARY outcome

Timeframe: 90 days

Population: MACE: Major adverse cardiac event (MI, Death, Hospitalization for ASC and urgent revascularization).

MACE is defined as the composite rate of all cause death, non-fatal myocardial infarction (MI) and unplanned hospitalization for acute coronary syndrome (ACS) leading to urgent revascularization.

Outcome measures

Outcome measures
Measure	Reclassification Rate by Core Lab n=1592 Participants For each enrolled patient, the endpoint review committee used data from coronary CTA and FFRCT, along with the clinical data such as medical history and demographics to determine the management plan using the following criteria: (a) optimal medical therapy, (b) percutaneous coronary intervention, (c) coronary artery bypass graft surgery, or (d) more information required. The management plan recommended by the committee was compared with the therapy that the patient received, as determined by his or her local team of physicians.	ICA Patients With FFRCT ≤0.80 n=3145 Participants Patients undergoing ICA procedure and FFRCT result showing Obstructive CAD.	Site-determined Post-FFRCT Treatment Plan - Further Diagnostics All clinically stable, symptomatic patients diagnosed with CAD by coronary computed tomography angiography (cCTA) and FFRCT.
Percentage of Major Adverse Coronary Events (MACE) at 90 Days	0 Participants	19 Participants	—

SECONDARY outcome

Timeframe: 90 days

Population: MI - myocardial infarction ACS - acute coronary syndrome

Individual components of MACE defined as all cause death, non-fatal MI, unplanned hospitalization for ACS leading to urgent revascularization

Outcome measures

Outcome measures
Measure	Reclassification Rate by Core Lab n=1592 Participants For each enrolled patient, the endpoint review committee used data from coronary CTA and FFRCT, along with the clinical data such as medical history and demographics to determine the management plan using the following criteria: (a) optimal medical therapy, (b) percutaneous coronary intervention, (c) coronary artery bypass graft surgery, or (d) more information required. The management plan recommended by the committee was compared with the therapy that the patient received, as determined by his or her local team of physicians.	ICA Patients With FFRCT ≤0.80 n=3145 Participants Patients undergoing ICA procedure and FFRCT result showing Obstructive CAD.	Site-determined Post-FFRCT Treatment Plan - Further Diagnostics All clinically stable, symptomatic patients diagnosed with CAD by coronary computed tomography angiography (cCTA) and FFRCT.
Percentage of Individual Components of MACE at 90 Days MI	0 Participants	4 Participants	—
Percentage of Individual Components of MACE at 90 Days Urgent unplanned hospitazation for ACS and urgent revascularization.	0 Participants	5 Participants	—
Percentage of Individual Components of MACE at 90 Days Death	0 Participants	10 Participants	—

SECONDARY outcome

Timeframe: Baseline

Population: All patients referred for clinical consecutive coronary CT angiography who had FFRCT analysis performed

Cumulative radiation exposure calculated in non-invasive coronary diagnostic tests: cCTA effective radiation dose. Effective radiation dose measured as the product of dose-length product times for conversion coefficient for the chest (K = 0.026 mSv/mGy·cm).

Outcome measures

Outcome measures
Measure	Reclassification Rate by Core Lab n=2778 Participants For each enrolled patient, the endpoint review committee used data from coronary CTA and FFRCT, along with the clinical data such as medical history and demographics to determine the management plan using the following criteria: (a) optimal medical therapy, (b) percutaneous coronary intervention, (c) coronary artery bypass graft surgery, or (d) more information required. The management plan recommended by the committee was compared with the therapy that the patient received, as determined by his or her local team of physicians.	ICA Patients With FFRCT ≤0.80 Patients undergoing ICA procedure and FFRCT result showing Obstructive CAD.	Site-determined Post-FFRCT Treatment Plan - Further Diagnostics All clinically stable, symptomatic patients diagnosed with CAD by coronary computed tomography angiography (cCTA) and FFRCT.
Cumulative Radiation Exposure From cCTA MilliSievert (mSv)	10.0 mSv Standard Deviation 9.1	—	—

SECONDARY outcome

Timeframe: 90 days

Population: All stable patients who undergo cCTA and are diagnosed with CAD.

Resource utilization composite defined as the composite of invasive diagnostic and therapeutic coronary procedures and noninvasive cardiac testing. Site treating physician recommended clinical management strategies following coronary computed tomography angiography-derived fractional flow reserve.

Outcome measures

Outcome measures
Measure	Reclassification Rate by Core Lab n=1418 Participants For each enrolled patient, the endpoint review committee used data from coronary CTA and FFRCT, along with the clinical data such as medical history and demographics to determine the management plan using the following criteria: (a) optimal medical therapy, (b) percutaneous coronary intervention, (c) coronary artery bypass graft surgery, or (d) more information required. The management plan recommended by the committee was compared with the therapy that the patient received, as determined by his or her local team of physicians.	ICA Patients With FFRCT ≤0.80 n=2679 Participants Patients undergoing ICA procedure and FFRCT result showing Obstructive CAD.	Site-determined Post-FFRCT Treatment Plan - Further Diagnostics n=121 Participants All clinically stable, symptomatic patients diagnosed with CAD by coronary computed tomography angiography (cCTA) and FFRCT.
Resource Utilization at 90 Days. Site-determined Post FFRCT Treatment Plan Medical Therapy	504 Participants	2545 Participants	92 Participants
Resource Utilization at 90 Days. Site-determined Post FFRCT Treatment Plan PCI	799 Participants	115 Participants	25 Participants
Resource Utilization at 90 Days. Site-determined Post FFRCT Treatment Plan CABG	115 Participants	19 Participants	4 Participants

SECONDARY outcome

Timeframe: 1 year

Population: MACE: Major adverse cardiac event (MI, Death, Hospitalization for ASC and urgent revascularization).

MACE is defined as the composite rate of all cause death, non-fatal myocardial infarction (MI) and unplanned hospitalization for acute coronary syndrome (ACS) leading to urgent revascularization.

Outcome measures

Outcome measures
Measure	Reclassification Rate by Core Lab n=1592 Participants For each enrolled patient, the endpoint review committee used data from coronary CTA and FFRCT, along with the clinical data such as medical history and demographics to determine the management plan using the following criteria: (a) optimal medical therapy, (b) percutaneous coronary intervention, (c) coronary artery bypass graft surgery, or (d) more information required. The management plan recommended by the committee was compared with the therapy that the patient received, as determined by his or her local team of physicians.	ICA Patients With FFRCT ≤0.80 n=3145 Participants Patients undergoing ICA procedure and FFRCT result showing Obstructive CAD.	Site-determined Post-FFRCT Treatment Plan - Further Diagnostics All clinically stable, symptomatic patients diagnosed with CAD by coronary computed tomography angiography (cCTA) and FFRCT.
Percentage of Major Adverse Coronary Events (MACE) at 1 Year	12 Participants	43 Participants	—

SECONDARY outcome

Timeframe: 1 year

Population: MI - myocardial infarction ACS - acute coronary syndrome

Individual components of MACE defined as all cause death, non-fatal MI, unplanned hospitalization for ACS leading to urgent revascularization

Outcome measures

Outcome measures
Measure	Reclassification Rate by Core Lab n=12 Participants For each enrolled patient, the endpoint review committee used data from coronary CTA and FFRCT, along with the clinical data such as medical history and demographics to determine the management plan using the following criteria: (a) optimal medical therapy, (b) percutaneous coronary intervention, (c) coronary artery bypass graft surgery, or (d) more information required. The management plan recommended by the committee was compared with the therapy that the patient received, as determined by his or her local team of physicians.	ICA Patients With FFRCT ≤0.80 n=43 Participants Patients undergoing ICA procedure and FFRCT result showing Obstructive CAD.	Site-determined Post-FFRCT Treatment Plan - Further Diagnostics All clinically stable, symptomatic patients diagnosed with CAD by coronary computed tomography angiography (cCTA) and FFRCT.
Percentage of Individual Components of MACE at 1 Year Death	7 Participants	28 Participants	—
Percentage of Individual Components of MACE at 1 Year MI	3 Participants	9 Participants	—
Percentage of Individual Components of MACE at 1 Year ACS leading to unplanned hospitalization and revascularization	2 Participants	6 Participants	—

Adverse Events

Patients Receiving cCTA and FFRCT >0.80

Serious events: 12 serious events

Other events: 80 other events

Deaths: 7 deaths

Patients Receiving cCTA and FFRCT≤0.80

Serious events: 43 serious events

Other events: 1036 other events

Deaths: 28 deaths

Serious adverse events

Serious adverse events
Measure	Patients Receiving cCTA and FFRCT >0.80 n=1591 participants at risk；n=4737 participants at risk All clinically stable, symptomatic patients diagnosed with CAD by coronary computed tomography angiography (cCTA) and received FFRCT analysis results.	Patients Receiving cCTA and FFRCT≤0.80 n=3137 participants at risk；n=4737 participants at risk All clinically stable, symptomatic patients diagnosed with CAD by coronary computed tomography angiography (cCTA) and received FFRCT analysis results.
Cardiac disorders Death (any cause)	0.15% 7/4737 • Number of events 35 • Clinical Events at 1 year Note: this study involved prospective data collection to validate in a blinded manner a non-invasive test and further patient management therefore adverse event information is reported based only on the standard of care index procedure.	0.59% 28/4737 • Number of events 35 • Clinical Events at 1 year Note: this study involved prospective data collection to validate in a blinded manner a non-invasive test and further patient management therefore adverse event information is reported based only on the standard of care index procedure.
Cardiac disorders MI	0.06% 3/4737 • Number of events 12 • Clinical Events at 1 year Note: this study involved prospective data collection to validate in a blinded manner a non-invasive test and further patient management therefore adverse event information is reported based only on the standard of care index procedure.	0.19% 9/4737 • Number of events 12 • Clinical Events at 1 year Note: this study involved prospective data collection to validate in a blinded manner a non-invasive test and further patient management therefore adverse event information is reported based only on the standard of care index procedure.
Cardiac disorders ACS leading to urgent hospitalization and revascularization	0.04% 2/4737 • Number of events 8 • Clinical Events at 1 year Note: this study involved prospective data collection to validate in a blinded manner a non-invasive test and further patient management therefore adverse event information is reported based only on the standard of care index procedure.	0.13% 6/4737 • Number of events 8 • Clinical Events at 1 year Note: this study involved prospective data collection to validate in a blinded manner a non-invasive test and further patient management therefore adverse event information is reported based only on the standard of care index procedure.

Other adverse events

Other adverse events
Measure	Patients Receiving cCTA and FFRCT >0.80 n=1591 participants at risk；n=4737 participants at risk All clinically stable, symptomatic patients diagnosed with CAD by coronary computed tomography angiography (cCTA) and received FFRCT analysis results.	Patients Receiving cCTA and FFRCT≤0.80 n=3137 participants at risk；n=4737 participants at risk All clinically stable, symptomatic patients diagnosed with CAD by coronary computed tomography angiography (cCTA) and received FFRCT analysis results.
Cardiac disorders Revascularization	5.0% 80/1591 • Number of events 80 • Clinical Events at 1 year Note: this study involved prospective data collection to validate in a blinded manner a non-invasive test and further patient management therefore adverse event information is reported based only on the standard of care index procedure.	33.0% 1036/3137 • Number of events 1036 • Clinical Events at 1 year Note: this study involved prospective data collection to validate in a blinded manner a non-invasive test and further patient management therefore adverse event information is reported based only on the standard of care index procedure.

Additional Information

Sarah Mullen

HeartFlow

Phone: 650-241-1221

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60