One-Dimensional Mathematical Model-Based Automated Assessment of Fractional Flow Reserve

The First Experience With Using a One-dimensional Mathematical Model With Fully Automated Algorithm of Extraction of Patient-specific Geometry From CT Images for a Noninvasive Assessment of Fractional Flow Reserve.

This study evaluates the diagnostic efficiency of an automated method of noninvasive assessment of the fractional reserve of coronary blood flow.

Fractional flow reserve is estimated with a one-dimensional mathematical model constructed by means of an automated algorithm. Noninvasive method values are thereafter compared with invasive method values.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: FFR

Detailed Description

Noninvasive assessment of Fractional Flow Reserve is almost never applied in the Russian Federation due to the relative novelty and study insufficiency, lack of the appropriate resource base, specific necessary software and trained qualified personnel.

In 2015, scientists from the Institute of Numerical Mathematics RAS in collaboration with specialists of the I.M. Sechenov First Moscow State Medical University developed a noninvasive method of fractional flow reserve assessment based on a one-dimensional mathematical model. A model is constructed based on images derived from the coronary computed tomography angiography performed by standard protocol; the method is fully automated.

The aim of our study is to evaluate the diagnostic efficiency of this technique in clinical practice.

This is a pilot study; we are planning to enroll 30 patients: 13 of them underwent 64-slice computed tomography and are included retrospectively; 17 will be included prospectively, with a 640-slice CT scan. Specialists from the Laboratory of Mathematical Modeling will process CT images and evaluate noninvasive FFR. Ischemia is confirmed if FFR < 0.80 and disproved if FFR ≥ 0.80. After that, the prospective group of patients will be hospitalized for invasive FFR assessment as a reference standard; if ischemia is proved, patients will undergo stent implantation. In the retrospective group, patients already have invasive FFR values estimated.

Statistical analysis will be performed using R programming language packages (cran-r.project.com). Continuous variables will be presented as mean values ± standard deviations, order variables will be presented as medians with interquartile ranges in parentheses. We are going to use the D'Agostino-Pearson omnibus test for the assessment of normality of distribution and construct a Q-Q Plot. We will compare these two methods with the Bland-Altman analysis and ROC-analysis and will assess the degree of correlation with the Pearson's chi-squared.

The study should result in determining the sensitivity, specificity, positive and negative predictive values of the method.

After the active phase of the research is done, we are planning to proceed observation on the prospective group of patients to verify the endpoints.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 127540
    • Daria Gognieva

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients providing written informed consent
2. Scheduled to undergo clinically-indicated non-emergent invasive coronary angiography (ICA)
3. Has undergone >640 multidetector CCTA within 60 days prior to ICA
4. No cardiac interventional therapy between the CCTA and ICA

Exclusion Criteria:

1. Prior coronary artery bypass graft (CABG) surgery
2. Prior percutaneous coronary intervention (PCI) for which suspected coronary artery lesion(s) are within a stented coronary vessel
3. Contraindication to adenosine, including 2nd or 3rd-degree heart block; sick sinus syndrome; long QT syndrome; severe hypotension, severe asthma, severe COPD or bronchodilator-dependent COPD
4. Suspicion of acute coronary syndrome (acute myocardial infarction and unstable angina)
5. Recent prior myocardial infarction within 40 days of ICA
6. Known complex congenital heart disease
7. Prior pacemaker or internal defibrillator lead implantation
8. Prosthetic heart valve
9. Significant arrhythmia or tachycardia
10. Impaired chronic renal function (serum creatinine >1.5 mg/dl
11. Patients with known anaphylactic allergy to iodinated contrast
12. Pregnancy or unknown pregnancy status
13. Body mass index >35
14. Patient requires an emergent procedure
15. 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
16. Any active, serious, life-threatening disease with a life expectancy of less than 2 months
17. Inability to comply with study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FFRct; Patients will receive cCTA, ICA, FFRct, and FFRinv per protocol.	Device: FFR; Fractional flow reserve measured during cardiac catheterization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Accuracy of FFRct	Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FFRct at the vessel level using binary outcomes whith compared to FFR as the reference standard.	through study completion, an average of 8 months

Collaborators and Investigators

• Sponsor: I.M. Sechenov First Moscow State Medical University
• Investigators: Principal Investigator: Daria Gognieva, MD, I.M. Sechenov First Moscow State Medical University (Sechenov University); Study Director: Philipp Kopylov, Professor, I.M. Sechenov First Moscow State Medical University (Sechenov University)

Publications and helpful links

General Publications

• Gognieva D, Gamilov T, Pryamonosov R, Betelin V, Ternovoy SK, Serova NS, Abugov S, Shchekochikhin D, Mitina Y, El-Manaa H, Kopylov P. One-Dimensional Mathematical Model-Based Automated Assessment of Fractional Flow Reserve in a Patient with Silent Myocardial Ischemia. Am J Case Rep. 2018 Jun 20;19:724-728. doi: 10.12659/AJCR.908449.

Helpful Links

• Am J Case Rep. 2018 Jun 20;19:724-728. doi: 10.12659/AJCR.908449.

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2017
• Primary Completion (Actual): June 5, 2019
• Study Completion (Actual): July 5, 2019

Study Registration Dates

• First Submitted: December 22, 2018
• First Submitted That Met QC Criteria: January 6, 2019
• First Posted (Actual): January 8, 2019

Study Record Updates

• Last Update Posted (Actual): May 18, 2020
• Last Update Submitted That Met QC Criteria: May 14, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: coronary computed tomography angiography; noninvasive assessment of the fractional flow reserve
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: 17-51-53160

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data disclosure is not permitted by the local ethics committee. For more information about the study, you need to contact the principal investigator.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No