Clinical trial NCT05556590: Quantitative Flow Ratio on Radial Artery Graft Outcome After Coronary Artery Bypass Grafting
Official title: Impact of Preoperative Quantitative Flow Ratio on Radial Artery Graft Outcome After Coronary Artery Bypass Grafting in the ASRAB-Pilot Trial
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Artery Disease
Keywords: Coronary artery bypass grafting
Radial artery graft
Quantitative flow ratio
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2022-09-27
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: For patients enrolled in the ASRAB-pilot trial, those who with available preoperative CAG images for QFR analysis, will be enrolled in this study.

Brief summary: In coronary artery bypass grafting (CABG), the use of radial artery (RA) is recommended by the guidelines only to significantly stenosed vessel, due to its high vulnerability to competitive flow. Fractional flow reserve (FFR) is the gold standard to measure physiological significance of coronary lesions and the potential for competitive flow. This study aims to investigate whether the preoperative quantitative flow ratio (QFR) measurement, a novel coronary angiography-based FFR, is associated with RA graft failure post-CABG, and to explore the best cut-off value of QFR for RA grafts using.

Patients from ASRAB-pilot trial (NCT04310995) undergoing primary isolated CABG using RA grafts, and with preoperative coronary angiography (CAG) images available for QFR analysis will be enrolled in this prospective double-blind observational study. QFR analysis will be conducted for all RA-grafted vessels based on preoperative CAG. The primary outcome will RA graft failure (FitzGibbon Grade B,O or S) evaluated by coronary computer tomography angiography or CAG at 7 days and 6 months post-CABG.

Detailed description: Introduction:

The radial artery (RA) was first used by Carpentier for coronary artery bypass grafting (CABG) in 1971 because of a number of potential advantages, including ease of harvesting, a low propensity for wound infection, a larger diameter than other arterial grafts, and a thick, muscular wall that facilitates the construction of an anastomosis. However, early experience suggested that RA grafts were prone to spasm and functional occlusion, and their use was abandoned for many years. In the past decades, the advent of drug therapy to prevent graft spasm and the adoption of newer harvesting techniques revitalized the interest the use of radial artery. Recently several randomized trials has been conducted to prove the better graft patency over the saphenous vein (SV) and survival benefit was also observed as well. However, due to its unneglectable vulnerability to competitive flow, the recent American and European guidelines for coronary revascularization both limited the use of RA only in significantly stenosed vessels.

Fractional flow reserve (FFR) is the current gold standard to measure the physiological significance of coronary stenosis and the potential for competitive flow. The quantitative flow ratio (QFR) is a novel, intelligent, noninvasive method that enables efficient computation of the FFR from coronary angiography in good concordance with catheter-based FFR. QFR-guided percutaneous coronary intervention (PCI) has been used and showed the improved clinical outcomes in FAVOR III China trial (Comparison of Quantitative Flow Ratio-Guided and Angiography-Guided Percutaneous InterVention in Patients With cORonary Artery Disease).

The Impact of Preoperative Quantitative Flow Ratio on Radial-Artery Graft Outcome after Coronary Artery Bypass Grafting (ASRAB-QUARGO) study aims to investigate whether the preoperative QFR measurement is associated with RA graft patency 6 months after CABG, and to explore the best QFR cut-off value for guiding RA-CABG.

Methods:

Study design- The ASRAB-QUARGO is a single-centre, prospective, double-blind, observational sub-study of the ASRAB-pilot trial (NCT04310995). The study was registered and approved by the ethics committee in out institution. Informed consent was waived under permission from the ethics committee.

Outcome- The primary outcome is the association between preoperative QFR of target vessel and the RA graft outcome at 6 months after CABG. The secondary outcome is the association between preoperative QFR of target vessel and the RA graft outcome at 7 days after CABG.

Study procedures- The complete eligibility criteria for ASRAB-pilot trial is provided in the "eligibility" section. After successfully receiving primary isolated CABG, the patients from the ASRAB-pilot cohort with preoperative CAG images available for QFR analysis were enrolled in this study. QFR analysis was conducted in all vessels grafted based on preoperative CAG images. The images were sent to the core lab (CardHemo, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China) for computation of the QFR. The analysis was performed by the experienced analysts using the AngioPlus system (Pulse Medical Imaging Technology, Shanghai, China) as described \[11-15\]. QFR results were recorded by the core lab and blinded to the patient and surgeon. Apart from the investigational anti-spastic drug from the ASRAB-pilot trial, optimized medical treatment was pursued according to the current American and European guidelines, including smoking cessation counselling and the administration of antiplatelet agents, beta blockers, lipid medications, and angiotensin-converting enzyme inhibitors.

Patients underwent follow-up coronary computer tomography angiography （CCTA）6 months after surgery. Angiographic evaluations were performed by two observers (one radiologist and one cardiac surgeon) blinded to the preoperative QFR values. In the case of ambiguity or disagreement between observers, additional CAG is conducted as possible for further confirmation. For sequential grafts, each segment between two adjacent anastomoses (graft-to-graft anastomosis not included) will be defined as an independent graft and evaluated independently. For composite grafts (eg. T or Y grafts), only RAs directly anastomosed to target vessel were considered as RA grafts. Angiographic patency was graded referring to the FitzGibbon classification: 4 Grade A for widely patent, Grade B for patent with flow limited, Grade S for string sign and Grade O for occluded. Grade B, O and S were considered as diseased. MACE was defined as a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke and unplanned coronary revascularization.

Sample size- Historical data from our center indicate that graft disease (Grade B, O \& S) occurs in around 20% of grafts 6 months after CABG. We estimated an RA graft disease rate of 10% if QFR ≤ best cut-off value (0.50-0.55 assumed), and 30% if QFR \> best cut-off valve (0.5-0.55 assumed). With a power of 0.80 at an alpha level of 0.05, 118 RA grafts would be required to detect a statistically significant difference between groups. Assuming a 10% dropout rate and an average of 1.2 anastomosis per patient, sample size was defined at 110 patients. Therefore, the cohort size of ASRAB-pilot study of 150 patients is deemed adequate.

Analytic design and statistical analysis- Continuous variables were reported as mean, standard deviation, median, interquartile, minimum or maximum. For discrete categorical data, statistical description was presented as count and percentage. Missing data was treated as random missing. Unless otherwise stated, missing data was not filled in in this study.

Considering the possible heterogeneity between the sample population and the actual population for application, 2000 resampling samples were constructed through bootstrapping, and the mean value of QFR cut-off of all samples was taken as the final QFR cut-off. The determination of QFR cut-off value for a single sample adopted the minimum p-value method, taking RA, ITA or SV graft disease at 6 months after operation as endpoint index.

Considering the observational nature of this study, the cohort grouped based on the QFR cut-off may had imbalance of important factors. Therefore, the multivariate regression model and propensity scoring method were used to correct the potential confounding factors to evaluate the difference of outcome indicators between groups after the QFR cut-off grouping. The correlation between QFR and visual estimation was analyzed by the Spearman rank-order correlation coefficient. The predictive value of QFR and visual estimation for graft disease was compared by analyzing their respective ROC curve and corresponding AUC. Taking the QFR and the visual estimation as important prediction variables, a multifactor prediction model was constructed. The prediction accuracy was evaluated and compared by AUC. The prediction model was presented as nomograms, and the calibration curve and decision analysis curve were constructed.

Eligibility criteria: Inclusion Criteria:

* All patients enrolled in the ASRAB-pilot study.

Exclusion Criteria:

* Preoperative CAG not available for QFR analysis.

The inclusion and exclusion criteria of ASRAB-pilot study are attached:

Inclusion Criteria:

* Age≥18 years.
* Male or female patients.
* Have signed informed consent.
* Have successfully accepted the first RA-CABG surgery.

Exclusion Criteria:

* Previously experienced an allergy to active ingredients and/or excipients of experimental drugs.
* Hypotension (defined as systolic blood pressure \< 90mmHg or diastolic blood pressure \< 60mmHg) after surgery.
* Acute myocardial infarction, pulmonary congestion or cardiogenic shock after surgery.
* Concomitant medications with phosphodiesterase-5 inhibitors such as sildenafil, vardenafil, tadalafil, etc.
* Pathological sinus node syndrome, degree II or III atrioventricular block without cardiac pacemaker.
* Contraindications for coronary computed tomography angiography (CCTA) or coronary arteriography (CAG) examination, such as iodine allergy, etc. (note: patients with renal insufficiency or even end-stage renal disease whose hemodialysis can be tolerated by CCTA or CAG tests are eligible for inclusion).
* History or evidence of ongoing alcohol or drug abuse.
* Life expectancy \< 1 year judged by investigators.
* Other inappropriate situations judged by investigators.

Primary outcomes:
measure: 6-month radial artery graft failure
timeFrame: 6 months after surgery
measure: 7-day radial artery graft failure
timeFrame: 7 days after surgery
Secondary outcomes:
measure: Major adverse cardiovascular event (MACE)
timeFrame: within 6 months after surgery
measure: Myocardial infarction related to radial artery graft failure
timeFrame: within 6 months after surgery
measure: Unplanned coronary revascularization related to radial artery graft failure
timeFrame: within 6 months after surgery
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Ruijin Hospital
name: Qiang Zhao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ruijin Hospital
name: Yunpeng Zhu, MD
role: STUDY_DIRECTOR
affiliation: Ruijin Hospital
name: Jiaxi Zhu, MD
role: STUDY_DIRECTOR
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