Validation of a Predictive Model of Coronary Fractional Flow Reserve in Patients With Intermediate Coronary Stenosis

Coronary Stenosis Clinical Trial

— FFRB  

Official title:

FFRB Study: Validation of a Predictive Model of Coronary Fractional Flow Reserve in Patients With Intermediate Coronary Stenosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03054324
• Other study ID #: 2016/2097
• Status: Recruiting
• Start date: September 2, 2016
• Est. completion date: December 31, 2018

Study information

• Verified date: March 2018
• Source: National Heart Centre Singapore
• Contact: Soo Teik Lim, MBBS
• Email: lim.soo.teik[@]singhealth.com.sg
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Coronary fraction flow reserve (FFR), the ratio of the mean coronary pressure distal to a coronary stenosis to the mean aortic pressure during maximal coronary blood flow (hyperemia), defines the hemodynamic significance of coronary artery narrowing. Noninvasive assessment of FFR via a combination of computational fluid dynamics (CFD) and coronary CT angiography CCTA (the so-called FFRCT) has potential. Coronary computed tomographic angiography is a noninvasive test for diagnosis of anatomic coronary stenosis (i.e., narrowing of a blood vessel). A new analytical model of FFR from the general Bernoulli equation (conservation of energy) (FFRB) is simple and has potential. A collaborator group has recently developed a new analytical model to quantify pressure drop, and hence FFR, based on lesion dimensions (i.e., the cross-section area along the lesion and the length of lesion) and coronary flow, with no empirical parameters. The investigators hypothesize that this new model will allow quantification of FFR (FFRB) in a cohort of human patients with intermediate coronary stenosis. The study will compare FFRB with invasive FFR measurements from invasive coronary angiography (ICAG).

Description:

Coronary fraction flow reserve (FFR), the ratio of the mean coronary pressure distal to a coronary stenosis to the mean aortic pressure during maximal coronary blood flow (hyperemia), defines the hemodynamic significance of coronary artery narrowing. Recent landmark studies showed a clear benefit of FFR in guiding percutaneous coronary intervention (PCI) for better clinical outcome and cost-effectiveness. The reference method for FFR measurement requires the use of a pressure wire inserted across the stenosis invasively. Therefore, a non-invasive method to quantify FFR is clinically desired.

Noninvasive assessment of FFR via a combination of computational fluid dynamics (CFD) and coronary CT angiography CCTA (the so-called FFRCT) has potential. Coronary computed tomographic angiography is a noninvasive test for diagnosis of anatomic coronary stenosis (i.e., narrowing of a blood vessel). However, CCTA alone does not determine whether a stenosis causes ischemia. Computational fluid dynamics (CFD), applied to CCTA images, enables computation of FFR (FFRCT). Recent studies have demonstrated the potential of FFRCT as a promising noninvasive method for identification of individual lesion with ischemia from both single centre and multi-centre prospective studies. However, the FFRCT is currently performed remotely and it takes several hours to complete the computation for each study. This potentially impedes the wider clinical application of FFRCT.

A new analytical model of FFR from the general Bernoulli equation (conservation of energy) (FFRB) is simple and has potential. The Bernoulli equation has many clinical applications. A collaborator group has recently developed a new analytical model to quantify pressure drop, and hence FFR, based on lesion dimensions (i.e., the cross-section area along the lesion and the length of lesion) and coronary flow, with no empirical parameters. The investigators validated it using in vitro and in vivo experiments and finite-element method. The study team hypothesize that this new model will allow quantification of FFR (FFRB) in a cohort of human patients with intermediate coronary stenosis. The investigators will compare FFRB with invasive FFR measurements from invasive coronary angiography (ICAG).

Aims and Objectives

Primary aim: Diagnostic performance of FFRB with CCTA data in patients with intermediate coronary artery disease (CAD), as compared to an invasive FFR reference standard (FFR<=0.80)

Secondary aims: Diagnostic performance with FFRB for lesions of intermediate stenosis severity; Determining the per-vessel correlation of FFRB value to FFR from ICA

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 132
• Est. completion date: December 31, 2018
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 98 Years

Eligibility

Inclusion Criteria:

• Aged 21-98.

• Underwent CCTA within 180 days and is scheduled to undergo coronary angiography and FFR in vessels having diameter stenosis between 30-90%, and deemed clinically indicated for evaluation.

Exclusion Criteria:

• Previous PCI

• Previous coronary artery bypass surgery

• Contraindication to beta blockers , nitroglycerin or adenosine, including second- or third-degree heart block; sick sinus syndrome; long QT syndrome; severe hypotension; asthma, chronic obstructive pulmonary disease, heart rate <50 beats/min.

• Acute coronary syndrome (acute myocardial infarction, unstable angina or unstable arrhythmias) is suspected.

• Had recent myocardial infarction within 30 days before CCTA or between CCTA and coronary angiography

• Has known complex congenital heart disease.

• Has had pacemaker or internal defibrillator leads implanted.

• Has a prosthetic heart valve or significant valvular pathology.

• Has tachycardia or significant arrhythmia; heart rate = 100 beats/min; systolic blood pressure =90 mmHg.

• Renal dysfunction (glomerular filtration rate (GFR) <30 mL/min/1.73m2).

• Allergy to iodinated contrast.

• Individuals unable to provide informed consent.

• Non-cardiac illness with life expectancy <2 years.

• Pregnant state.

• Canadian Cardiovascular Society class IV angina.

• Patients with a left ventricular ejection fraction less than 30%.

• Patients with hypertrophic cardiomyopathy.

Related Conditions & MeSH terms

• Constriction, Pathologic
• Coronary Stenosis

Intervention

Diagnostic Test:
• Fractional Flow Reserve
Coronary fraction flow reserve (FFR), the ratio of the mean coronary pressure distal to a coronary stenosis to the mean aortic pressure during maximal coronary blood flow (hyperemia), defines the hemodynamic significance of coronary artery narrowing.

Locations

Country	Name	City	State
Singapore	National Heart Centre Singapore	Singapore
Singapore	National University Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
National Heart Centre Singapore

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diagnostic performance of FFRB to invasive FFR	The diagnostic performance of FFRB with CCTA data in patients with intermediate coronary artery disease (CAD), as compared to an invasive FFR reference standard (FFR<=0.80)	6 months from CT Angiogram
Secondary	Diagnostic performance with FFRB for lesions of intermediate stenosis severity		6 months from CT Angiogram
Secondary	Per-vessel correlation of FFRB to invasive FFR		6 months from CT Angiogram