HeartFlowNXT - HeartFlow Analysis of Coronary Blood Flow Using Coronary CT Angiography

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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HeartFlowNXT - HeartFlow Analysis of Coronary Blood Flow Using Coronary CT Angiography: NeXt sTeps

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Procedure: ICA (Invasive Coronary Angiography)
* Procedure: FFR (Fractional Flow Reserve)
* Procedure: cCTA (coronary computed tomography angiography)
* Other: FFRct Analysis (Fractional Flow Reserve Computed Tomography)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Subject providing written informed consent Scheduled to undergo a clinically indicated Invasive Coronary Angiogram (ICA) Has had ≥64 multidetector row cCTA within 60 days prior to ICA or agrees to undergo cCTA with ≥64 multidetector row cCTA within 60 days prior to ICA Exclusion Criteria: Percutaneous coronary intervention (PCI) has been performed any time prior to ICA. Prior coronary artery bypass graft (CABG) surgery Contraindication to beta blocker agents, nitrates, or adenosine, including 2nd or 3rd degree heart block; sick sinus syndrome; long QT syndrome; severe hypotension; severe asthma, severe COPD or bronchodilator-dependent COPD Suspicion of acute coronary syndrome (acute myocardial infarction and unstable angina) Recent prior myocardial infarction within 30 days prior to cCTA or between cCTA and ICA Known complex congenital heart disease Prior pacemaker or internal defibrillator lead implantation Prosthetic heart valve Tachycardia or significant arrhythmia Impaired chronic renal function (serum creatinine >1.5 mg/dl) Subjects with known anaphylactic allergy to iodinated contrast Pregnancy or unknown pregnancy status in subject of childbearing potential Body mass index >35 at time of cCTA Subject requires an emergent procedure Evidence of ongoing or active clinical instability, including acute chest pain (sudden onset), cardiogenic shock, unstable blood pressure with systolic blood pressure <90 mmHg, and severe congestive heart failure (NYHA III or IV) or acute pulmonary edema Any active, serious, life-threatening disease with a life expectancy of less than 2 months Inability to comply with study procedures

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Standard of care: FFR, ICA, cCTA, FFRct<br>(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) | Procedure: ICA (Invasive Coronary Angiography)<br>* Per the protocol, patients will have an Invasive Coronary Angiography.<br>Procedure: FFR (Fractional Flow Reserve)<br>* Per the protocol, patients will have a Fractional Flow Reserve procedure.<br>Procedure: cCTA (coronary computed tomography angiography)<br>* Per the protocol, patients will have a coronary computed tomography angiography.<br>Other: FFRct Analysis (Fractional Flow Reserve Computed Tomography)<br>* Per the protocol, patients will have a fractional flow reserve computed tomography.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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. | 

Secondary Outcome Measures

| Outcome Measure | 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. | 
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary Artery Disease Computed Fractional Flow Reserve