Coronary Artery Disease
Conditions
Brief summary
The objective of the HeartFlow ADVANCE Registry is to evaluate utility, clinical outcomes and resource utilization of FFRCT-guided evaluation in clinically stable, symptomatic patients with coronary artery disease (CAD) in order to further inform patients, health care providers, and other stakeholders about which technologies are most effective and efficient in the diagnosis and management of CAD.
Detailed description
REGISTRY OBJECTIVE The objective of the HeartFlow ADVANCE Registry is to evaluate utility, clinical outcomes and resource utilization of FFRCT-guided evaluation in clinically stable, symptomatic patients with CAD in order to further inform patients, health care providers, and other stakeholders about which technologies are most effective and efficient in the diagnosis and management of CAD. SPECIFIC OBJECTIVES: 1. To determine if the availability of FFRCT, in addition to coronary anatomy from the cCTA, will lead to a significant change in the coronary management plan. 2. To assess the real world outcomes of utilizing FFRCT to guide invasive management and/or medical treatment. 3. To assess resource utilization, following standard practice for diagnostic and treatment pathways incorporating FFRCT as the preferred CAD diagnostic test. 4. To provide society including patients, health care providers, and other stakeholders with information about which diagnostic technologies are most effective and efficient in managing patients with CAD.
Interventions
None listed
Sponsors
HeartFlow, Inc.
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provide written informed consent 2. Clinically stable, symptomatic patients who undergo cCTA and are diagnosed with CAD and meet eligibility criteria for FFRCT.
Exclusion criteria
1. cCTA showing no CAD 2. Uninterpretable cCTA by site assessment, in which severe artifacts prevent angiographic evaluation 3. Any active, serious, life-threatening disease with a life expectancy of less than 1 year 4. Inability to comply with follow-up requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | at 90 days | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Invasive Catheterization Without Obstructive Disease | At 90 days | 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. |
| Percentage of Major Adverse Coronary Events (MACE) at 90 Days | 90 days | 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. |
| Percentage of Individual Components of MACE at 90 Days | 90 days | Individual components of MACE defined as all cause death, non-fatal MI, unplanned hospitalization for ACS leading to urgent revascularization |
| Percentage of Participants With Reclassification Between Investigator Management Plan Based on cCTA Alone Compared to Actual Clinical Management | at 90 days | Coronary computed tomography angiography-derived fractional flow reserve resulted in revision of the clinical management plan as determined by the site investigators. |
| Resource Utilization at 90 Days. Site-determined Post FFRCT Treatment Plan | 90 days | 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. |
| Percentage of Major Adverse Coronary Events (MACE) at 1 Year | 1 year | 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. |
| Percentage of Individual Components of MACE at 1 Year | 1 year | Individual components of MACE defined as all cause death, non-fatal MI, unplanned hospitalization for ACS leading to urgent revascularization |
| Cumulative Radiation Exposure From cCTA MilliSievert (mSv) | Baseline | 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). |
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Patients Diagnosed With CAD by cCTA 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. | 4,737 |
| Total | 4,737 |
Baseline characteristics
| Characteristic | Patients Diagnosed With CAD by cCTA | — |
|---|---|---|
| Age, Continuous | 66.1 years STANDARD_DEVIATION 10.3 | — |
| Angina status Atypical | 1727 Participants | — |
| Angina status Dyspnea | 472 Participants | — |
| Angina status Non-cardiac pain | 297 Participants | — |
| Angina status None | 1164 Participants | — |
| Angina status Typical | 1025 Participants | — |
| Angina status Unknown | 52 Participants | — |
| Diabetus mellitus | 1136 Participants | — |
| Hyperlipidemia | 2957 Participants | — |
| Hypertension | 3045 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 1603 Participants | — |
| Sex: Female, Male Male | 3134 Participants | — |
| Smoking Current smoking | 797 Participants | — |
| Smoking Former smoker | 1615 Participants | — |
| Smoking Never smoked | 1973 Participants | — |
| Smoking Unknown | 352 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 4,737 | 28 / 4,737 |
| other Total, other adverse events | 80 / 1,591 | 1,036 / 3,137 |
| serious Total, serious adverse events | 12 / 4,737 | 43 / 4,737 |
Outcome results
Primary
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.
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).
Time frame: at 90 days
Population: The primary endpoint of reclassification between core lab CCTA alone and CCTA plus FFRCT-based management.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reclassification Rate by Core Lab | 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 |
Secondary
Cumulative Radiation Exposure From cCTA MilliSievert (mSv)
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).
Time frame: Baseline
Population: All patients referred for clinical consecutive coronary CT angiography who had FFRCT analysis performed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reclassification Rate by Core Lab | Cumulative Radiation Exposure From cCTA MilliSievert (mSv) | 10.0 mSv | Standard Deviation 9.1 |
Secondary
Percentage of Individual Components of MACE at 1 Year
Individual components of MACE defined as all cause death, non-fatal MI, unplanned hospitalization for ACS leading to urgent revascularization
Time frame: 1 year
Population: MI - myocardial infarction ACS - acute coronary syndrome
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reclassification Rate by Core Lab | Percentage of Individual Components of MACE at 1 Year | Death | 7 Participants |
| Reclassification Rate by Core Lab | Percentage of Individual Components of MACE at 1 Year | MI | 3 Participants |
| Reclassification Rate by Core Lab | Percentage of Individual Components of MACE at 1 Year | ACS leading to unplanned hospitalization and revascularization | 2 Participants |
| ICA Patients With FFRCT ≤0.80 | Percentage of Individual Components of MACE at 1 Year | Death | 28 Participants |
| ICA Patients With FFRCT ≤0.80 | Percentage of Individual Components of MACE at 1 Year | MI | 9 Participants |
| ICA Patients With FFRCT ≤0.80 | Percentage of Individual Components of MACE at 1 Year | ACS leading to unplanned hospitalization and revascularization | 6 Participants |
Secondary
Percentage of Individual Components of MACE at 90 Days
Individual components of MACE defined as all cause death, non-fatal MI, unplanned hospitalization for ACS leading to urgent revascularization
Time frame: 90 days
Population: MI - myocardial infarction ACS - acute coronary syndrome
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reclassification Rate by Core Lab | Percentage of Individual Components of MACE at 90 Days | MI | 0 Participants |
| Reclassification Rate by Core Lab | Percentage of Individual Components of MACE at 90 Days | Urgent unplanned hospitazation for ACS and urgent revascularization. | 0 Participants |
| Reclassification Rate by Core Lab | Percentage of Individual Components of MACE at 90 Days | Death | 0 Participants |
| ICA Patients With FFRCT ≤0.80 | Percentage of Individual Components of MACE at 90 Days | MI | 4 Participants |
| ICA Patients With FFRCT ≤0.80 | Percentage of Individual Components of MACE at 90 Days | Urgent unplanned hospitazation for ACS and urgent revascularization. | 5 Participants |
| ICA Patients With FFRCT ≤0.80 | Percentage of Individual Components of MACE at 90 Days | Death | 10 Participants |
Secondary
Percentage of Major Adverse Coronary Events (MACE) at 1 Year
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.
Time frame: 1 year
Population: MACE: Major adverse cardiac event (MI, Death, Hospitalization for ASC and urgent revascularization).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reclassification Rate by Core Lab | Percentage of Major Adverse Coronary Events (MACE) at 1 Year | 12 Participants |
| ICA Patients With FFRCT ≤0.80 | Percentage of Major Adverse Coronary Events (MACE) at 1 Year | 43 Participants |
Secondary
Percentage of Major Adverse Coronary Events (MACE) at 90 Days
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.
Time frame: 90 days
Population: MACE: Major adverse cardiac event (MI, Death, Hospitalization for ASC and urgent revascularization).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reclassification Rate by Core Lab | Percentage of Major Adverse Coronary Events (MACE) at 90 Days | 0 Participants |
| ICA Patients With FFRCT ≤0.80 | Percentage of Major Adverse Coronary Events (MACE) at 90 Days | 19 Participants |
Secondary
Percentage of Participants With Invasive Catheterization Without Obstructive Disease
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.
Time frame: At 90 days
Population: The rate of anatomically defined 'non-obstructive' disease at ICA (no stenosis defined as \>50% at ICA)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reclassification Rate by Core Lab | Percentage of Participants With Invasive Catheterization Without Obstructive Disease | 43.8 percentage of participants |
| ICA Patients With FFRCT ≤0.80 | Percentage of Participants With Invasive Catheterization Without Obstructive Disease | 14.4 percentage of participants |
Secondary
Percentage of Participants With Reclassification Between Investigator Management Plan Based on cCTA Alone Compared to Actual Clinical Management
Coronary computed tomography angiography-derived fractional flow reserve resulted in revision of the clinical management plan as determined by the site investigators.
Time frame: at 90 days
Population: All participants who were enrolled in the study and received cCTA and FFRCT analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reclassification Rate by Core Lab | Percentage of Participants With Reclassification Between Investigator Management Plan Based on cCTA Alone Compared to Actual Clinical Management | 63.5 percentage of participants |
Secondary
Resource Utilization at 90 Days. Site-determined Post FFRCT Treatment Plan
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.
Time frame: 90 days
Population: All stable patients who undergo cCTA and are diagnosed with CAD.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reclassification Rate by Core Lab | Resource Utilization at 90 Days. Site-determined Post FFRCT Treatment Plan | CABG | 115 Participants |
| Reclassification Rate by Core Lab | Resource Utilization at 90 Days. Site-determined Post FFRCT Treatment Plan | PCI | 799 Participants |
| Reclassification Rate by Core Lab | Resource Utilization at 90 Days. Site-determined Post FFRCT Treatment Plan | Medical Therapy | 504 Participants |
| ICA Patients With FFRCT ≤0.80 | Resource Utilization at 90 Days. Site-determined Post FFRCT Treatment Plan | CABG | 19 Participants |
| ICA Patients With FFRCT ≤0.80 | Resource Utilization at 90 Days. Site-determined Post FFRCT Treatment Plan | Medical Therapy | 2545 Participants |
| ICA Patients With FFRCT ≤0.80 | Resource Utilization at 90 Days. Site-determined Post FFRCT Treatment Plan | PCI | 115 Participants |
| Site-determined Post-FFRCT Treatment Plan - Further Diagnostics | Resource Utilization at 90 Days. Site-determined Post FFRCT Treatment Plan | CABG | 4 Participants |
| Site-determined Post-FFRCT Treatment Plan - Further Diagnostics | Resource Utilization at 90 Days. Site-determined Post FFRCT Treatment Plan | PCI | 25 Participants |
| Site-determined Post-FFRCT Treatment Plan - Further Diagnostics | Resource Utilization at 90 Days. Site-determined Post FFRCT Treatment Plan | Medical Therapy | 92 Participants |