CCTA-FFR Registry for Risk Prediction

CCTA-FFR Registry for Development of Comprehensive Risk Prediction Model

The investigators sought to investigate the prognostic implication of qualitative and quantitative plaque analysis on coronary CT angiography (CCTA) according to fractional flow reserve (FFR). The main objective was to develop a comprehensive risk model by using clinical risk factors, FFR and CCTA parameters.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Diagnostic test: Fractional flow reserve, Coronary CT angiography

Detailed Description

Coronary CT angiography (CCTA) is an evolving noninvasive modality in diagnosis of coronary artery disease (CAD). Its incremental prognostic value over traditional scheme of risk prediction has repeatedly been demonstrated. Beyond the assessment of CAD severity, the prognostic value of CCTA has increased with comprehensive plaque analysis. Certain plaque features on CCTA have a prognostic value in the prediction of future coronary events. The concept of fractional flow reserve (FFR) has been developed as an invasive index of the functional severity of stenosis. FFR represents maximal blood flow to the myocardium supplied by an artery with stenosis as a fraction of normal maximum flow. In moderate stenotic lesion, determining whether to perform PCI based on FFR is a current guideline, and has been proven to reduce unnecessary revascularization procedure and improve clinical prognosis. However, clinical events still occur in patients with FFR >0.80. In a recent study, the prognosis in the vessel with FFR > 0.8 was investigated. However, a comprehensive risk model according to FFR has never been investigated. Therefore, the investigators sought to investigate the prognostic implication of qualitative and quantitative plaque analysis on CCTA according to FFR. The main objective was to develop a comprehensive risk model by using clinical risk factors, FFR, and CCTA parameters.

Patients who underwent CCTA within 90 days before FFR measurement will be included. The study population will be from 2 different registries. The 3V-FFR-FRIENDS registry (NCT0620122050) enrolled a total of 1,136 patients (3,298 vessels). Among them, 299 patients who underwent CCTA within 90 days before FFR measurement will be included. The institutional registry of Tsuchiura Kyodo General Hospital included 448 patients who underwent FFR measurement and CCTA within 90 days. By retrospectively collecting clinical outcome data, coronary angiographic data, physiologic indices, and CCTA data from two registries, the CCTA-FFR Registry for Development of Comprehensive Risk Prediction Model will be created. For 3V FFR-FRIENDS registry (NCT0620122050), the collected clinical data for the previous study will be used, and 5-year outcome data will be collected from Seoul National University Hospital, Keimyung University Dongsan Medical Center, and Inje University Ilsan Paik Hospital. For the Institutional registry of Tsuchiura Kyodo General Hospital registry, the investigators will collect the baseline characteristics of participants, CCTA data, and clinical outcome data followed until Mar 2019.

• Study Type: Observational
• Enrollment (Actual): 747

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with suspected coronary artery disease who underwent coronary CT angiography within 90 days before FFR measurement will be included.

Description

Inclusion Criteria:

• Patients who underwent CCTA within 90 days before FFR measurement

Exclusion Criteria:

• Unanalyzable coronary CT angiography
• Inadequate fractional flow reserve measurement

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CCTA-FFR; Patients who underwent CCTA within 90 days before FFR measurement will be included in the present study.	Diagnostic test: Fractional flow reserve, Coronary CT angiography; Coronary CT angiography was performed as part of routine clinical practice for patients with suspected coronary artery disease and the decision to perform coronary CT angiography before invasive angiography was at the judgment of the physicians in charge.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Discrimination index of prediction model for vessel-oriented composite outcome	A risk model for vessel-oriented composite outcome, incorporating clinical, angiographic, fractional flow reserve (FFR), and coronary CT angiographic parameters will be developed. Vessel-oriented composite outcome is a composite of cardiac death, vessel-related myocardial infarction (MI), or vessel-related ischemia-driven revascularization. The target vessel will be defined as the vessel with FFR measurement.	Upto 5 years after index procedure

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Inje University; Keimyung University Dongsan Medical Center; Tsuchiura Kyodo General Hospital
• Investigators: Study Director: Bon-Kwon Koo, MD, PhD, Seoul National University Hospital; Principal Investigator: Joon Hyung Doh, MD, PhD, Inje University; Principal Investigator: Chang-Wook Nam, MD, PhD, Keimyung University Dongsan Medical Center

Publications and helpful links

General Publications

• Pijls NH, van Son JA, Kirkeeide RL, De Bruyne B, Gould KL. Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty. Circulation. 1993 Apr;87(4):1354-67. doi: 10.1161/01.cir.87.4.1354.
• Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van' t Veer M, Klauss V, Manoharan G, Engstrom T, Oldroyd KG, Ver Lee PN, MacCarthy PA, Fearon WF; FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009 Jan 15;360(3):213-24. doi: 10.1056/NEJMoa0807611.
• Nielsen LH, Botker HE, Sorensen HT, Schmidt M, Pedersen L, Sand NP, Jensen JM, Steffensen FH, Tilsted HH, Bottcher M, Diederichsen A, Lambrechtsen J, Kristensen LD, Ovrehus KA, Mickley H, Munkholm H, Gotzsche O, Husain M, Knudsen LL, Norgaard BL. Prognostic assessment of stable coronary artery disease as determined by coronary computed tomography angiography: a Danish multicentre cohort study. Eur Heart J. 2017 Feb 7;38(6):413-421. doi: 10.1093/eurheartj/ehw548.
• Cho I, Al'Aref SJ, Berger A, O Hartaigh B, Gransar H, Valenti V, Lin FY, Achenbach S, Berman DS, Budoff MJ, Callister TQ, Al-Mallah MH, Cademartiri F, Chinnaiyan K, Chow BJW, DeLago A, Villines TC, Hadamitzky M, Hausleiter J, Leipsic J, Shaw LJ, Kaufmann PA, Feuchtner G, Kim YJ, Maffei E, Raff G, Pontone G, Andreini D, Marques H, Rubinshtein R, Chang HJ, Min JK. Prognostic value of coronary computed tomographic angiography findings in asymptomatic individuals: a 6-year follow-up from the prospective multicentre international CONFIRM study. Eur Heart J. 2018 Mar 14;39(11):934-941. doi: 10.1093/eurheartj/ehx774.
• SCOT-HEART Investigators, Newby DE, Adamson PD, Berry C, Boon NA, Dweck MR, Flather M, Forbes J, Hunter A, Lewis S, MacLean S, Mills NL, Norrie J, Roditi G, Shah ASV, Timmis AD, van Beek EJR, Williams MC. Coronary CT Angiography and 5-Year Risk of Myocardial Infarction. N Engl J Med. 2018 Sep 6;379(10):924-933. doi: 10.1056/NEJMoa1805971. Epub 2018 Aug 25.
• Motoyama S, Ito H, Sarai M, Kondo T, Kawai H, Nagahara Y, Harigaya H, Kan S, Anno H, Takahashi H, Naruse H, Ishii J, Hecht H, Shaw LJ, Ozaki Y, Narula J. Plaque Characterization by Coronary Computed Tomography Angiography and the Likelihood of Acute Coronary Events in Mid-Term Follow-Up. J Am Coll Cardiol. 2015 Jul 28;66(4):337-46. doi: 10.1016/j.jacc.2015.05.069.
• Williams MC, Moss AJ, Dweck M, Adamson PD, Alam S, Hunter A, Shah ASV, Pawade T, Weir-McCall JR, Roditi G, van Beek EJR, Newby DE, Nicol ED. Coronary Artery Plaque Characteristics Associated With Adverse Outcomes in the SCOT-HEART Study. J Am Coll Cardiol. 2019 Jan 29;73(3):291-301. doi: 10.1016/j.jacc.2018.10.066.
• De Bruyne B, Baudhuin T, Melin JA, Pijls NH, Sys SU, Bol A, Paulus WJ, Heyndrickx GR, Wijns W. Coronary flow reserve calculated from pressure measurements in humans. Validation with positron emission tomography. Circulation. 1994 Mar;89(3):1013-22. doi: 10.1161/01.cir.89.3.1013.
• Berger A, Botman KJ, MacCarthy PA, Wijns W, Bartunek J, Heyndrickx GR, Pijls NH, De Bruyne B. Long-term clinical outcome after fractional flow reserve-guided percutaneous coronary intervention in patients with multivessel disease. J Am Coll Cardiol. 2005 Aug 2;46(3):438-42. doi: 10.1016/j.jacc.2005.04.041.
• Park J, Lee JM, Koo BK, Shin ES, Nam CW, Doh JH, Hwang D, Zhang J, Hu X, Wang J, Ye F, Chen S, Yang J, Chen J, Tanaka N, Yokoi H, Matsuo H, Takashima H, Shiono Y, Akasaka T. Clinical Relevance of Functionally Insignificant Moderate Coronary Artery Stenosis Assessed by 3-Vessel Fractional Flow Reserve Measurement. J Am Heart Assoc. 2018 Feb 15;7(4):e008055. doi: 10.1161/JAHA.117.008055.
• Kim CH, Yang S, Zhang J, Lee JM, Hoshino M, Murai T, Hwang D, Shin ES, Doh JH, Nam CW, Wang J, Chen SL, Tanaka N, Matsuo H, Akasaka T, Kakuta T, Koo BK. Differences in Plaque Characteristics and Myocardial Mass: Implications for Physiological Significance. JACC Asia. 2022 Mar 29;2(2):157-167. doi: 10.1016/j.jacasi.2021.11.011. eCollection 2022 Apr.
• Yang S, Hoshino M, Yonetsu T, Zhang J, Hwang D, Shin ES, Doh JH, Nam CW, Wang J, Chen S, Tanaka N, Matsuo H, Kubo T, Chang HJ, Kakuta T, Koo BK. Outcomes of non-ischaemic coronary lesions with high-risk plaque characteristics on coronary CT angiography. EuroIntervention. 2022 Oct 12:EIJ-D-22-00562. doi: 10.4244/EIJ-D-22-00562. Online ahead of print.
• Yang S, Lee JM, Hoshino M, Murai T, Choi KH, Hwang D, Kim KJ, Shin ES, Doh JH, Chang HJ, Nam CW, Zhang J, Wang J, Chen SL, Tanaka N, Matsuo H, Akasaka T, Kakuta T, Koo BK. Prognostic Implications of Comprehensive Whole Vessel Plaque Quantification Using Coronary Computed Tomography Angiography. JACC Asia. 2021 Jun 15;1(1):37-48. doi: 10.1016/j.jacasi.2021.05.003. eCollection 2021 Jun.
• Yang S, Koo BK, Hwang D, Zhang J, Hoshino M, Lee JM, Murai T, Park J, Shin ES, Doh JH, Nam CW, Wang J, Chen S, Tanaka N, Matsuo H, Akasaka T, Chang HJ, Kakuta T, Narula J. High-Risk Morphological and Physiological Coronary Disease Attributes as Outcome Markers After Medical Treatment and Revascularization. JACC Cardiovasc Imaging. 2021 Oct;14(10):1977-1989. doi: 10.1016/j.jcmg.2021.04.004. Epub 2021 May 19.
• Yang S, Koo BK, Hoshino M, Lee JM, Murai T, Park J, Zhang J, Hwang D, Shin ES, Doh JH, Nam CW, Wang J, Chen S, Tanaka N, Matsuo H, Akasaka T, Choi G, Petersen K, Chang HJ, Kakuta T, Narula J. CT Angiographic and Plaque Predictors of Functionally Significant Coronary Disease and Outcome Using Machine Learning. JACC Cardiovasc Imaging. 2021 Mar;14(3):629-641. doi: 10.1016/j.jcmg.2020.08.025. Epub 2020 Nov 25.

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2010
• Primary Completion (Actual): March 31, 2019
• Study Completion (Actual): May 31, 2019

Study Registration Dates

• First Submitted: July 22, 2019
• First Submitted That Met QC Criteria: July 27, 2019
• First Posted (Actual): July 30, 2019

Study Record Updates

• Last Update Posted (Actual): July 30, 2019
• Last Update Submitted That Met QC Criteria: July 27, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Atherosclerosis; Fractional flow reserve; Coronary CT angiography
• 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: H-1907-094-1048

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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