FAPI Imaging Assessment of Chronic Total Occlusion (FACT)

The Clinical Value of FAPI Imaging in Assessing Chronic Total Occlusion Lesions in Patients with Coronary Heart Disease (FACT Trial)

This registry will include consecutive patients presenting with at least one chronic total coronary occlusion (CTO) identified via coronary angiography or cardiac computed tomography angiography (CCTA) at our center. Due to the complexity of CTO lesions, both procedural success rates and prognosis improvements are limited. The progression and development of atherosclerotic plaques involve fibroblast activity, contributing to the formation of fibrous caps and calcified nodules through various mechanisms. Myocardial fibrosis within chronically occluded segments is strongly linked to ventricular remodeling and patient prognosis. The activation of cardiac fibroblasts (CFs) is a critical early phase in myocardial fibrosis, playing a key role in fibrotic progression. However, the role of activated CFs in CTO patients has remained unclear, mainly due to the lack of reliable in vivo assessment techniques for detecting CF activation.

Recent studies have demonstrated that radionuclide-labeled fibroblast activation protein inhibitor (FAPI) imaging is an effective and reliable technique for detecting both myocardial fibrosis and activated CFs in arterial plaques. Preliminary data suggest that FAPI imaging can characterize plaque composition and assess the extent of myocardial fibrosis in various cardiovascular conditions. However, its potential to predict the ease of CTO recanalization and subsequent clinical outcomes remains to be fully explored.

The aim of this prospective cohort study is to evaluate the predictive value of FAPI imaging in patients with at least one untreated CTO. All enrolled patients will undergo baseline assessments prior to intervention, including blood tests, clinical evaluations, and imaging studies. These imaging studies will include myocardial FDG/perfusion imaging, FAPI imaging, and resting perfusion imaging. In selected patients, additional evaluations such as stress myocardial perfusion imaging, magnetic resonance imaging (MRI), and echocardiography will also be performed.

For patients undergoing percutaneous coronary intervention (PCI), follow-up assessments will occur at 6 and 12 months. At the 6-month mark, improvements in left ventricular (LV) wall motion will be assessed using resting perfusion imaging. At 12 months, coronary angiography (CAG) will be performed on all patients to evaluate recanalization outcomes. Additionally, myocardial perfusion imaging, magnetic resonance imaging (MRI), and echocardiography may be selectively used to evaluate patients during the 12-month follow-up.

1. To evaluate the ability of FAPI imaging in predicting the difficulty of CTO recanalization.
2. To investigate the role of myocardial FAPI imaging in predicting the improvement of LV wall motion at 6 months, assessed using follow-up single-photon emission computed tomography (SPECT).

By comparing FAPI imaging with conventional prognostic assessment methods, this study aims to clarify the utility of FAPI imaging in both predicting the recanalization complexity and in assessing long-term clinical outcomes in CTO patients.

Study Overview

• Status: Recruiting
• Conditions: Chronic Total Occlusion (CTO)
• Intervention / Treatment: Diagnostic test: FAPI Imaging

• Study Type: Observational
• Enrollment (Estimated): 167

Contacts and Locations

• Study Contact: Name: Shengwen Yang, Ph.D, MD; Phone Number: +8601085231480 +8617801014018; Email: verayang1990@163.com
• Study Contact Backup: Name: Bin Tu, Ph.D MD; Phone Number: +8601085231480 +8618810682692; Email: dr_bintu@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100020
      • Recruiting
      • Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
      • Contact: Shengwen Yang, Ph.D MD; Phone Number: +8601085231480; Email: verayang1990@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients presenting with at least one coronary chronic total occlusion (CTO) on coronary angiogram who will be treated by percutaneous coronary intervention

Description

Inclusion Criteria:

• Age > 18 years
• Presence of at least one untreated CTO at basal angiography (defined as a total occlusion in any major coronary vessel or relevant side branches [reference vessel diameter ≥2.5mm or as judged by two independent interventional cardiologists], with TIMI 0 in the distal segment and at least 3 months old
• Patient has a clinical indication to perform CTO PCI
• Willing to participate and able to understand, read and sign the informed consent document.

Exclusion Criteria:

• Hypersensitivity to aspirin, clopidogrel, or -limus families / or contraindication to antiplatelet agents
• Severe hepatic dysfunction (≥3 times normal reference values)
• Severe chronic kidney disease (estimated Glomerular Filtration Rate [eGFR] <30 mL/min/1.73m2)
• Life expectancy < 1 years
• Pregnant women or women with potential childbearing

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with at least one untreated CTO at basal angiography; Total occlusion in any major coronary vessel or relevant side branches [reference vessel diameter ≥2.5mm or as judged by two independent interventional cardiologists], with TIMI 0 in the distal segment and at least 3 months old	Diagnostic test: FAPI Imaging; Studies have shown that imaging with radionuclide-labeled fibroblast activation protein inhibitor (FAPI) is a reliable technique for detecting myocardial fibrosis and activated CFs in arteries. Preliminary evidence suggests that FAPI imaging can assess plaque characteristics and the status of myocardial fibrosis in various cardiovascular diseases.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of left ventricular (LV) wall motion	SPECT images (myocardial perfusion imaging, MPI) were analyzed using QPS/QGS software. Segmental wall motion was semi-quantitatively scored using the American Heart Association (AHA) 17-segment LV model and a five-point scale. 0=normal, 1=mildly hypokinetic, 2=moderately hypokinetic, 3=severely hypokinetic, 4=akinetic, 5=dyskinetic. The improvement of LV wall motion was defined as a decrease of the wall motion score of at least 1 point score.	6 months after the procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LV end-systolic volume (ml)	LV function was assessed by modified Simpson's method.Volumes were obtained by delineation of inner and outer LV contours in end-systolic frames on cardiac SPECT, echocardiography or cardiac magnetic resonance.	6 months and 12 months after the procedure
LV end-diastolic volume (ml)	LV function was assessed by modified Simpson's method. LV end-diastolic volume was obtained by delineation of inner and outer LV contours in end-diastolic frames on cardiac SPECT, echocardiography or cardiac magnetic resonance.	6 months and 12 months after the procedure
LV ejection fraction (%)	LV function was assessed by modified Simpson's method. Ejection fraction (EF) was computed from the EDV and ESV as follows:EF=EDV-ESV/EDV on cardiac SPECT, echocardiography or cardiac MRI.	6 months and 12 months after the procedure.
Procedural success	Procedural success was defined as successful recanalization of the intended CTO lesion with DES implantation, restoration of Thrombolysis In Myocardial Infarction flow grade 3, and residual diameter stenosis <30% on visual assessment.	immediately after the procedure.

Collaborators and Investigators

• Sponsor: Lin Zhao
• Collaborators: Affiliated Beijing Chaoyang Hospital of Capital Medical University
• Investigators: Principal Investigator: Lin Zhao, Ph.D MD, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

Publications and helpful links

General Publications

• Panza JA, Ellis AM, Al-Khalidi HR, Holly TA, Berman DS, Oh JK, Pohost GM, Sopko G, Chrzanowski L, Mark DB, Kukulski T, Favaloro LE, Maurer G, Farsky PS, Tan RS, Asch FM, Velazquez EJ, Rouleau JL, Lee KL, Bonow RO. Myocardial Viability and Long-Term Outcomes in Ischemic Cardiomyopathy. N Engl J Med. 2019 Aug 22;381(8):739-748. doi: 10.1056/NEJMoa1807365.
• Perera D, Clayton T, Petrie MC, Greenwood JP, O'Kane PD, Evans R, Sculpher M, Mcdonagh T, Gershlick A, de Belder M, Redwood S, Carr-White G, Marber M; REVIVED investigators. Percutaneous Revascularization for Ischemic Ventricular Dysfunction: Rationale and Design of the REVIVED-BCIS2 Trial: Percutaneous Coronary Intervention for Ischemic Cardiomyopathy. JACC Heart Fail. 2018 Jun;6(6):517-526. doi: 10.1016/j.jchf.2018.01.024.
• Wang L, Wang Y, Wang J, Xiao M, Xi XY, Chen BX, Su Y, Zhang Y, Xie B, Dong Z, Zhao S, Yang MF. Myocardial Activity at 18F-FAPI PET/CT and Risk for Sudden Cardiac Death in Hypertrophic Cardiomyopathy. Radiology. 2023 Feb;306(2):e221052. doi: 10.1148/radiol.221052. Epub 2022 Oct 11.

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: October 5, 2024
• First Submitted That Met QC Criteria: October 22, 2024
• First Posted (Actual): October 24, 2024

Study Record Updates

• Last Update Posted (Actual): October 24, 2024
• Last Update Submitted That Met QC Criteria: October 22, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Prognosis; Imaging; Percutaneous coronary intervention; Coronary Heart Disease; Fibroblast activation protein inhibitor
• Other Study ID Numbers: 2024-772-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Only IPD used in the results publication
• IPD Sharing Access Criteria: Need a proposal that describes planned analyses and a data sharing agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No