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| Name | Class |
|---|---|
| Case Western Reserve University | OTHER |
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To determine the diagnostic performance of FFRCT by coronary computed tomographic angiography (cCTA), as compared to cCTA alone, for non-invasive determination of the presence of a hemodynamically significant coronary lesion, using direct measurement of fractional flow reserve (FFR) during cardiac catheterization as a reference standard.
Recently, coronary Computed Tomography Angiography (cCTA) of 64-detector rows or greater has emerged as a novel non-invasive imaging modality that is capable of providing high-resolution images of coronary artery lesions (Budoff 2008; Miller 2008; Meijboom 2008). While cCTA demonstrates good diagnostic performance for detection and exclusion of anatomic coronary artery stenoses, numerous prior studies have revealed an unreliable relationship between detection of obstructive anatomic coronary artery stenoses by cCTA and hemodynamically (HD)-significant coronary artery disease (CAD), identified by myocardial perfusion SPECT or fractional flow reserve (FFR) (Di Carli 2007; Klauss 2007; Rispler 2007; van Werkhoven 2009). Individual subjects may have HD-significant CAD despite cCTA assessment demonstrating angiographically mild (<50%) maximal stenosis (Schuijf 2006). These findings emphasize the need for additional measures beyond anatomic stenosis severity for the detection and exclusion of HD-significant CAD.
Measurement of FFR during invasive cardiac catheterization represents the "gold standard" for assessment of the hemodynamic significance of coronary artery lesions (Kern 2010). Anatomic coronary artery stenosis assessment by quantitative coronary angiography (QCA) also correlates very poorly with FFR Melikian 2010). This was highlighted by the results of the FAME study in which FFR-guided coronary revascularization improved healthcare and economic outcomes compared to the conventional angiographically guided strategy (Pijls 2010; Tonino 2009; Tonino 2010).
The major disadvantage of FFR is that it has to be measured invasively. HeartFlow, Inc. ('HeartFlow') has recently developed a 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. Preliminary results in subjects suggest that FFRCT accurately predicts the hemodynamic significance of coronary lesions when compared to directly-measured FFR during invasive cardiac catheterization (Koo 2011).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard of care: FFR, ICA, cCTA, FFRct | Other | (ICA) Invasive coronary angiography with (FFR) fractional flow reserve measurement in standard of care environment, and cCTA (computed coronary tomography angiography) and FFRct Analysis (fractional flow reserve computed tomography) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ICA (Invasive Coronary Angiography) | Procedure | Per the protocol, patients will have an Invasive Coronary Angiography. |
|
| Measure | Description | Time Frame |
|---|---|---|
| AUC of FFRct Versus Coronary CTA for Demonstration of Ischemia (≤0.80) on a Per-patient Basis | The primary statistical measure will be the area under the receiver operating characteristic curve (AUC of ROC) of a patient-based model to detect hemodynamically significant obstruction. ROC graphs the change in sensitivity as the cut-point for positive/negative diagnosis moves from its lower to upper limit. FFR is used as the reference standard to determine the presence or absence of hemodynamic obstruction. For FFR, hemodynamically-significant obstruction of a coronary artery is defined as an FFR≤0.80 in any major epicardial coronary artery segment with diameter ≥2.0 mm during adenosine-mediated hyperemia. For cCTA, hemodynamically-significant obstruction of a coronary artery is defined as a stenosis >50% . FFRCT will be calculated for each patient as the minimum FFRCT in any coronary artery segment . cCTA stenosis will be calculated for each patient as the highest cCTA stenosis category for any vessel all measurements will take place only in segments with diameter ≥2.0 mm. | 1 day; Outcome measures were comparing FFRct to FFR. Incident time for FFR was dependent on the length of time on the cath procedure. FFRct was done remotely at HeartFlow's processing center in Redwood City with a turnaround time of 24 hours from CT scan. |
| Measure | Description | Time Frame |
|---|---|---|
| AUC of FFRct Versus Coronary CTA for Demonstration of Ischemia (≤0.80) on a Per-vessel Basis | 1 day | |
| Per-Patient Analysis: Diagnostic Performance of FFRct, Coronary CTA, and ICA | 1 day; Outcome measures were comparing FFRct to FFR. Incident time for FFR was dependent on the length of time on the cath procedure. FFRct was done remotely at HeartFlow's processing center in Redwood City with a turnaround time of 24 hours from CT scan. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bjarne Norgaard, MD | Aarhus University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aarhus University Hospital | Aarhus | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31184558 | Derived | Ihdayhid AR, Norgaard BL, Gaur S, Leipsic J, Nerlekar N, Osawa K, Miyoshi T, Jensen JM, Kimura T, Shiomi H, Erglis A, Jegere S, Oldroyd KG, Botker HE, Seneviratne SK, Achenbach S, Ko BS. Prognostic Value and Risk Continuum of Noninvasive Fractional Flow Reserve Derived from Coronary CT Angiography. Radiology. 2019 Aug;292(2):343-351. doi: 10.1148/radiol.2019182264. Epub 2019 Jun 11. | |
| 29866619 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Standard of Care: FFR and ICA | Single arm Measured FFR: Fractional Flow Reserve |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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prospective, multicenter study to evaluate the diagnostic performance of cCTA plus FFRCT employing ≥64-detector row CT scanners for the detection and exclusion of significant obstructive CAD, as defined by invasively-measured FFR, the reference standard
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No Masking
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| FFR (Fractional Flow Reserve) | Procedure | Per the protocol, patients will have a Fractional Flow Reserve procedure. |
|
| cCTA (coronary computed tomography angiography) | Procedure | Per the protocol, patients will have a coronary computed tomography angiography. |
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| FFRct Analysis (Fractional Flow Reserve Computed Tomography) | Other | Per the protocol, patients will have a fractional flow reserve computed tomography. |
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| Per Vessel Diagnostic Performance of FFRct, Coronary CTA, and ICA | 1 day; Outcome measures were comparing FFRct to FFR. Incident time for FFR was dependent on the length of time on the cath procedure. FFRct was done remotely at HeartFlow's processing center in Redwood City with a turnaround time of 24 hours from CT scan. |
| Derived |
| Ovrehus KA, Gaur S, Leipsic J, Jensen JM, Dey D, Botker HE, Ahmadi A, Achenbach S, Ko B, Norgaard BL. CT-based total vessel plaque analyses improves prediction of hemodynamic significance lesions as assessed by fractional flow reserve in patients with stable angina pectoris. J Cardiovasc Comput Tomogr. 2018 Jul-Aug;12(4):344-349. doi: 10.1016/j.jcct.2018.04.008. Epub 2018 May 8. |
| 26444662 | Derived | Ko BS, Wong DT, Norgaard BL, Leong DP, Cameron JD, Gaur S, Marwan M, Achenbach S, Kuribayashi S, Kimura T, Meredith IT, Seneviratne SK. Diagnostic Performance of Transluminal Attenuation Gradient and Noninvasive Fractional Flow Reserve Derived from 320-Detector Row CT Angiography to Diagnose Hemodynamically Significant Coronary Stenosis: An NXT Substudy. Radiology. 2016 Apr;279(1):75-83. doi: 10.1148/radiol.2015150383. Epub 2015 Oct 6. |
| 24486266 | Derived | Norgaard BL, Leipsic J, Gaur S, Seneviratne S, Ko BS, Ito H, Jensen JM, Mauri L, De Bruyne B, Bezerra H, Osawa K, Marwan M, Naber C, Erglis A, Park SJ, Christiansen EH, Kaltoft A, Lassen JF, Botker HE, Achenbach S; NXT Trial Study Group. 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. 2014 Apr 1;63(12):1145-1155. doi: 10.1016/j.jacc.2013.11.043. Epub 2014 Jan 30. |
| 24268114 | Derived | Gaur S, Achenbach S, Leipsic J, Mauri L, Bezerra HG, Jensen JM, Botker HE, Lassen JF, Norgaard BL. Rationale and design of the HeartFlowNXT (HeartFlow analysis of coronary blood flow using CT angiography: NeXt sTeps) study. J Cardiovasc Comput Tomogr. 2013 Sep-Oct;7(5):279-88. doi: 10.1016/j.jcct.2013.09.003. Epub 2013 Oct 1. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Standard of Care: FFR and ICA | Single arm Measured FFR (Fractional Flow Reserve) and ICA (Invasive Coronary Angiography) |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Diabetes | Number | participants |
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| Hypertension | Number | participants |
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| Hyperlipidemia | Number | participants |
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| Current smoker | Number | participants |
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| Previous myocardial infarction | Number | participants |
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| Body Mass Index, kg/m^2 | Mean | Standard Deviation | kg/m^2 |
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| Creatinine, mg/dl | Mean | Standard Deviation | mg/dl |
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| Left ventricular ejection fraction, % | Mean | Standard Deviation | percent |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | AUC of FFRct Versus Coronary CTA for Demonstration of Ischemia (≤0.80) on a Per-vessel Basis | 22 of the 276 enrolled subjects were excluded by the FFR/QCA Core Lab, leaving an ITD population of 254 subjects. 3 additional subjects were excluded from the ITD analysis due to missing cCTA 30%-90% stenosis by coronary CTA. | Posted | Number | 95% Confidence Interval | probability | 1 day | Vessels | Vessels |
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| Primary | AUC of FFRct Versus Coronary CTA for Demonstration of Ischemia (≤0.80) on a Per-patient Basis | The primary statistical measure will be the area under the receiver operating characteristic curve (AUC of ROC) of a patient-based model to detect hemodynamically significant obstruction. ROC graphs the change in sensitivity as the cut-point for positive/negative diagnosis moves from its lower to upper limit. FFR is used as the reference standard to determine the presence or absence of hemodynamic obstruction. For FFR, hemodynamically-significant obstruction of a coronary artery is defined as an FFR≤0.80 in any major epicardial coronary artery segment with diameter ≥2.0 mm during adenosine-mediated hyperemia. For cCTA, hemodynamically-significant obstruction of a coronary artery is defined as a stenosis >50% . FFRCT will be calculated for each patient as the minimum FFRCT in any coronary artery segment . cCTA stenosis will be calculated for each patient as the highest cCTA stenosis category for any vessel all measurements will take place only in segments with diameter ≥2.0 mm. | 22 of the 276 enrolled subjects were excluded by the FFR/QCA Core Lab, leaving an ITD population of 254 subjects. 3 additional subjects were excluded from the ITD analysis due to missing cCTA 30%-90% stenosis by coronary CTA. | Posted | Number | 95% Confidence Interval | probablility | 1 day; Outcome measures were comparing FFRct to FFR. Incident time for FFR was dependent on the length of time on the cath procedure. FFRct was done remotely at HeartFlow's processing center in Redwood City with a turnaround time of 24 hours from CT scan. |
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| Secondary | Per-Patient Analysis: Diagnostic Performance of FFRct, Coronary CTA, and ICA | 22 of the 276 enrolled subjects were excluded from the analysis by the FFR/QCA Core Lab. | Posted | Number | 95% Confidence Interval | percentage of tests | 1 day; Outcome measures were comparing FFRct to FFR. Incident time for FFR was dependent on the length of time on the cath procedure. FFRct was done remotely at HeartFlow's processing center in Redwood City with a turnaround time of 24 hours from CT scan. |
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| Secondary | Per Vessel Diagnostic Performance of FFRct, Coronary CTA, and ICA | 22 of the 276 enrolled subjects were excluded from the analysis by the FFR/QCA Core Lab. | Posted | Number | 95% Confidence Interval | percentage of tests | 1 day; Outcome measures were comparing FFRct to FFR. Incident time for FFR was dependent on the length of time on the cath procedure. FFRct was done remotely at HeartFlow's processing center in Redwood City with a turnaround time of 24 hours from CT scan. | Vessels | Vessels |
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| Post-Hoc | Per-Patient Diagnostic Performance of FFRct in Patients With Intermediate Stenosis Severity (30%-70%) According to Coronary CTA | Patients with intermediate stenosis severity (30%-70%) according to coronary CTA. | Posted | Number | 95% Confidence Interval | percentage of tests | 1 day; Outcome measures were comparing FFRct to FFR. Incident time for FFR was dependent on the length of time on the cath procedure. FFRct was done remotely at HeartFlow's processing center in Redwood City with a turnaround time of 24 hours from CT scan. |
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Index Procedure through hospital discharge
Note: this study involved prospective data collection to validate in a blinded manner a non-invasive test therefore adverse event information is reported based only on the standard of care index procedure.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Standard of Care: ICA (Invasive Coronary Angiography) | (ICA) Invasive coronary angiography in standard of care environment. | 5 | 276 | 53 | 276 | ||
| EG001 | Standard of Care: cCTA (Coronary Computed Tomography Angio) | (cCTA) Coronary computed tomography angiography in standard of care environment. | 5 | 276 | 53 | 276 | ||
| EG002 | Standard of Care: FFR (Fractional Flow Reserve) | (FFR) Fractional flow reserve in standard of care environment. | 5 | 276 | 53 | 276 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Coronary Dissection during invasive FFR measurement requiring percutaneous coronary intervention | Injury, poisoning and procedural complications | Non-systematic Assessment |
| ||
| Transient cerebral ischemic attacks after ICA and invasive FFR measurement | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Fever | Infections and infestations | Non-systematic Assessment | Fever with prolonged hospitalization |
| |
| Angina Pectoris | Injury, poisoning and procedural complications | Non-systematic Assessment | Angina pectoris following catheterization |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Procedural Hypotension | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural Arrhythmia | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural Allergic Reaction | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural Angina/Chest Pain | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural TIA | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural Vasovagal Response | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural Blurred Vision | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural Complete Heart Block | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural Coughing | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural Dissection | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural Distal Embolism | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural Dyspnea | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural Headache | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural Numbness | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural Perforation | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural Rash/Urticaria | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural sickness during and after Adenosine | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Procedural Vomiting | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Discharge Hematoma | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Discharge Angina/Chest Pain | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Discharge Headache | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Discharge Arrhythmia | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Discharge Absence Seizure | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Discharge Blurred Vision | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Discharge Chest Tightness | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Discharge Facial and Chest Rash | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Discharge Fever | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Discharge Nosebleed | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Discharge Wind Pain | Injury, poisoning and procedural complications | Non-systematic Assessment |
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13% of patients were judged to have nonevaluable cCTA images on the basis of a pre-defined image quality score. This number may be reduced with improvement of CT acquisition techniques as well a refinement of the FFRct technology.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| VP Clinical, Quality & Regulatory Affairs | HeartFlow | 650-241-1221 | clinicalresearch@heartflow.com |
| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Unknown Hiperlipidemia Status |
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| Never Smoked |
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| Unknown |
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| cCTA vs. FFR |
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| Vessels |
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