Quantitative Flow Ratio (QFR) Guided Coronary Artery Bypass Grafting for Patients Undergoing Primary Valve Surgery With Concomitant Coronary Artery Disease (FAVOR IV-QVAS)

A Multicenter, Prospective, Randomized, Blind, Controlled Clinical Study to Compare the Efficacy of Quantitative Flow Ratio Guided and Coronary Angiography Guided Revascularization Strategy for Patients Undergoing Primary Valve Surgery With Comorbid Coronary Artery Disease

This is a multicenter, prospective, randomized, blinded, controlled clinical study in patients with planned primary valvular surgery and comorbid coronary artery lesions with diameter stenosis of ≥ 50%, to compare the effectiveness of an Quantitative Flow Ratio (QFR)-guided revascularization strategy and a coronary angiography (CAG)-guided revascularization strategy in preventing the incidence of composite outcome (MACE-5, including all-cause death, myocardial infarction, stroke, unplanned coronary revascularization, and new renal failure requiring dialysis) within 30 days after surgery. The study hypothesis is that the QFR-guided strategy can reduce the incidence of the MACE-5 within 30 days after surgery, as compared with the CAG-guided strategy.

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Valvular Heart Disease With Comorbid Coronary Artery Disease; Planned to Undergo Elective On-pump Valve Surgery Due to Primary Mitral and/or Aortic Valvular Heart Disease
• Intervention / Treatment: Device: QFR-guided strategy; Other: CAG-guided strategy

Detailed Description

It is planned to enroll 792 subjects aged ≥18 years, with no gender restriction, who plan to undergo elective open-heart valvular surgery due to primary valvular heart disease, with comorbid coronary artery lesions defined as diameter stenosis of ≥ 50% (visual estimation) that are diagnosed by CAG before the surgery.

QFR group: Calculate the QFR values of all target coronary arteries (anterior descending branch, circumflex branch, main right coronary artery or its primary branches with ≥ 1.5 mm in diameter, such as diagonal branch, intermediate branch, obtuse marginal branch, posterior descending branch and posterior branch of left ventricle) with lesions with diameter stenosis of ≥ 50% (visual estimation) suited for CABG revascularization. If QFR ≤ 0.80, then simultaneous CABG revascularization of target blood vessels will be carried out. If QFR > 0.80, then no CABG revascularization of target blood vessels will be carried out.

CAG group (control group): All target coronary arteries (anterior descending branch, circumflex branch, main right coronary artery or its primary branches with ≥ 1.5 mm in diameter, such as diagonal branch, intermediate branch, obtuse marginal branch, posterior descending branch and posterior branch of left ventricle) with lesions with diameter stenosis of ≥ 50% (visual estimation) suited for CABG revascularization will undergo simultaneous CABG revascularization.

Intervention duration: The assessments will be performed after randomization and before the surgery to guide the surgery.

No planned interim analysis.

• Study Type: Interventional
• Enrollment (Actual): 792
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • The First Affiliated Hospital of Anhui Medical University
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Medical University Union Hospital
  • Henan
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China
      • Fuwai Central China Cardiovascular Hospital
  • Hunan
    • Changsha, Hunan, China
      • The Second Xiangya Hospital of Central South University
  • Shandong
    • Jinan, Shandong, China
      • Qilu Hospital of Shandong University
    • Qingdao, Shandong, China
      • The Affiliated Hospital of Qingdao University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Changhai Hospital of Shanghai
    • Shanghai, Shanghai Municipality, China
      • Shanghai Chest Hospital
    • Shanghai, Shanghai Municipality, China, 200025
      • Ruijin Hospital Shanghai Jiao Tong University School of Medicine
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • Tianjin Chest Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • the First Affiliated Hospital Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntarily participate in the trial and provide the informed consent form;
• Male or female patients aged ≥ 18 years;
• Planned to undergo elective on-pump valve surgery due to primary mitral and/or aortic valvular heart disease (such as rheumatic, degenerative, infective, congenital valvular heart disease, etc.);
• At least one target coronary arteries (anterior descending branch, circumflex branch, main right coronary artery or its primary branches with ≥ 1.5 mm in diameter, such as diagonal branch, intermediate branch, obtuse marginal branch, posterior descending branch and posterior branch of left ventricle) with preoperative diameter stenosis of ≥ 50% by coronary angiography (visual estimation, subject to written coronary angiography report) and suited for CABG revascularization.

Exclusion Criteria:

• History of heart surgery;
• Planned second-stage PCI or CABG revascularization;
• Secondary valvular heart disease (ischemia, cardiomyopathy);
• Planned valve intervention surgery through the catheter;
• Subjects that were evaluated to have cardiogenic shock or other critical conditions that were not appropriate for the trial by study physician;
• QFR calculations cannot be carried out from preoperative coronary angiography data (such as poor projection position, inability to detect vascular boundaries, poor contrast agent filling, excessive overlap or severely distorted of vessel lesion sections, lesion involved in myocardial bridge, or lesion site within 3 mm from the ostium of the main coronary artery);
• The target coronary arteries were evaluated to be not suitable for CABG by study physician;
• Life expectancy < 3 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QFR group	Device: QFR-guided strategy; In this study, the QFR-guided strategy will be applied to in the QFR group in which calculation of the QFR values of all target coronary arteries with lesions with diameter stenosis of ≥ 50% (visual estimation) and with suitability to CABG revascularization will be carried out. If QFR ≤ 0.80, then simultaneous CABG revascularization of target blood vessels will be carried out. If QFR > 0.80, then no CABG revascularization of target blood vessels will be carried out.
Active Comparator: CAG group	Other: CAG-guided strategy; In this study, CAG-guided strategy will be used for the control group, i.e., in accordance with current guideline recommendations, all target coronary arteries with lesions with diameter stenosis of ≥ 50% (visual estimation) and suited for CABG revascularization will undergo CABG revascularization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The 30-day incidence of composite outcome (MACE-5) including all-cause death, myocardial infarction, stroke, unplanned coronary revascularization, and new renal failure requiring dialysis	within 30 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time from randomization to first occurrence of any of composite outcome (MACE-6) within 1 year	The time from randomization to first occurrence of any of composite outcome (MACE-6) including all-cause death, myocardial infarction, stroke, unplanned coronary revascularization, hospitalization or urgent visits for unstable angina pectoris, and hospitalization or urgent visits for heart failure	within 1 year after surgery
The incidence of 1-year graft failure (stenosis ≥ 50% or occlusion occurred in grafts or distal anastomosis)		at 1 year after surgery
The time from randomization to first occurrence of any of composite outcome (MACE-6) within 3 year	The time from randomization to first occurrence of any of composite outcome (MACE-6) including all-cause death, myocardial infarction, stroke, unplanned coronary revascularization, hospitalization or urgent visits for unstable angina pectoris, and hospitalization or urgent visits for heart failure	within 3 years after surgery
The incidence of 3-year graft failure (stenosis ≥ 50% or occlusion occurred in grafts or distal anastomosis)		at 3 years after surgery
Health-related quality of life	the variables are the EQ-5D scores	within 30 days, 1 year and 3 years after surgery
Cost effectiveness	the variables are the cost increased for each composite outcome reduction at 30 days after surgery and cost increased for each additional QALY at 1 year and 3 years after surgery	within 30 days, 1 year and 3 years after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of grafts per person	counted as distal anastomosis	at Day 0
The total circulatory time during the surgery	minutes	at Day 0
The total cross-clamp time during the surgery	minutes	at Day 0
The total units of erythrocyte transfusion during and after the surgery till discharge		from Day 0 to discharge day
The number of days from surgery day to discharge day		from Day 0 to discharge day
Change from baseline in the Canadian Cardiac Society (CCS) anginal status score (0-4)		at 1 year after surgery
Change from baseline in the CCS anginal status score (0-4)		at 3 years after surgery
Change from baseline in the New York Heart Association (NYHA) score (1-4)		at 1 year after surgery
Change from baseline in the NYHA score (1-4)		at 3 years after surgery

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Collaborators: Med-X Research Institute, Shanghai Jiao Tong University
• Investigators: Principal Investigator: Mario Gaudino, MD, Weill Medical College of Cornell University; Principal Investigator: Qiang Zhao, MD., Ruijin Hospital; Principal Investigator: Shengxian Tu, PhD., Med-X Research Institute, Shanghai Jiao Tong University; Study Director: Yunpeng Zhu, MD., Ruijin Hospital

Publications and helpful links

General Publications

• Zhu J, Zhu Y, Zhang W, Wang Z, Ye X, Zhou M, Li H, Qiu J, Xu H, Sun Y, Kang L, Tu S, Zhao Q. Preliminary outcomes of quantitative flow ratio-guided coronary bypass grafting in primary valve surgery: A propensity score weighted analysis. JTCVS Open. 2024 Jun 25;21:90-108. doi: 10.1016/j.xjon.2024.06.008. eCollection 2024 Oct.

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2019
• Primary Completion (Actual): September 30, 2024
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: June 5, 2019
• First Posted (Actual): June 6, 2019

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 10, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Aortic Valve Disease; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Valve Diseases
• Other Study ID Numbers: 2018CR001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

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