Preoperative Use of Fractional Flow Reserve in CABG Use and Effectiveness of FFR-based CABG in Real-life Practice

Study Overview
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Brief Summary
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The use of fractional flow reserve (FFR) to guide coronary artery bypass graft (CABG) is controversial and not ubiquitously adopted across the units. There is no definitive evidence that the use of FFR improves early clinical outcomes after CABG, with the exception of a simplification of the procedure. FFR use may help in defining the indication to the use arterial grafts, but there is no evidence that preoperative FFR lead to any benefits in terms of patency when venous grafts are used. On these grounds a large multicentric all-comers observational study is planned. The aim is to achieve a real-life picture of the FFR practice in CABG across several European and non-European units. This study will inform on the effective use rate of FFR in the CABG practice and its clinical effectiveness when compared to standard angiography-based CABG.

Detailed Description
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Background The use of fractional flow reserve (FFR) to guide coronary artery bypass graft (CABG) is controversial. A large retrospective study on 627 patients by Toth et al. showed that FFR-guided surgery was associated with a lower number of graft anastomoses and a lower rate of on-pump surgery compared with angiography-guided coronary artery bypass graft surgery. This did not result in a higher event rate during up to 36 months of follow-up and was associated with a lower rate of angina. The six years follow-up of the same study showed that FFR-guided CABG was associated with a significant reduction in the rate of overall death or myocardial infarction at 6-year follow-up as compared with angiography-guided CABG. However, the three randomized studies on FFR-based CABG have achieved contradictive results. The FARGO (Fractional Flow Reserve Versus Angiography Randomization for Graft Optimization) and GRAFFITI (GRAft patency after FFR-guided versus angiography-guided CABG) did not report a significant impact on hard outcomes at 1 year. Conversely, the IMPAG trial support the use of preoperative FFR in total arterial CABG. Authors found a significant association between the preoperative FFR measurement of the target vessel and the anastomotic functionality at 6 months, with a cut-off of 0.78. Authors concluded that integration of FFR measurement into the preoperative diagnostic workup could lead to improved anastomotic graft function. The currently available randomized evidences might have been flawed by limitations including underpowering, entry selectivity bias, cross over among treatment, difference in the type of conduits used and presence of unexpected confounders related to surgeons' reluctance to base their surgical strategy on FFR. These drawbacks not only hamper the reliability of the results, but more importantly, reduce their translatability to the real-life clinical world. Given the lack of definitive evidences and the difficulty of RCT to capture the real-life scenario of the clinical practice, we plan to perform a large multicentric all-comers study comparing the practice of FFR in CABG across several European and non-European units. The main aim is to obtain information on Use rate of FFR in preoperative planning of surgical candidates Effective adherence to FFR guidance during elective surgery and identification of factors eventually limiting observance to FFR information Short and long-term outcomes of FFR-based CABG in comparison to standard angiography-based CABG Post hoc analysis in relation to type of conduit used, completeness of revascularization, surgeon experience, volume/outcome relationship.

Official Title
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A Real Life All-comers Retrospective Study on FFR-based CABG

Conditions
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Fracational Flow Reserve, Coronary Artery Disease, Coronary Artery Bypass Surgery

Intervention / Treatment
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* Procedure: Fractional Flow reserve


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: all-comers including both elective and urgent (and urgent in-house) isolated CABG cases Exclusion Criteria: patients undergoing emergency revascularization for iatrogenic complications or other conditions that would prevent a careful analysis of angiographic severity of the lesions

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| FFR-CABG<br>Patients with at least one intermediate stenosis that received a preoperative FFR evaluation before being referred for CABG | Procedure: Fractional Flow reserve<br>* Measurement of fractional flow reserve in the preoperative work-up for oronary artery bypass surgery<br>|
| Angio-CABG<br>Patients with at least one intermediate stenosis that did not received a preoperative FFR evaluation before being referred for CABG | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Use rate of FFR in preoperative planning of surgical candidates | Frequency and rate of usage of fractional flow reserve measurement in the routine practice of Cath labs | 10 years | 
| Effective adherence to FFR guidance during elective surgery and identification of factors eventually limiting observance to FFR information | To check if CABG operations are performed according to the guidance provided by FFR in terms of location and number of lesions to be bypassed | 10 years | 
| Survival of FFR-based CABG in comparison to standard angiography-based CABG | Comparing mortality rate among the two groups | 10 years | 
| Myocardial infarction rate in FFR-based CABG in comparison to standard angiography-based CABG | Comparing onset of myocardial infarction among the two groups | 10 years | 
| Major cardiovascular events rate in FFR-based CABG in comparison to standard angiography-based CABG | Comparing occurrence of major cardiovascular events among the two groups | 10 years | 
| Target vessel revascularization rate in FFR-based CABG in comparison to standard | Comparing perioperative mortality, myocardial infarction, major cardiovascular events, target vessel revascularization, long-term survival, long-term freedom from coronary intervention among the two groups | 10 years | 
| Freedom from coronary intervention in FFR-based CABG compared to standard angiography-based CABG | Comparing long-term freedom from coronary intervention among the two groups | 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Type of conduit used | Post-hoc analysis to investigated the use rate of arterial or venous conduit and the impact on clinical outcomes of the different conduits. This is crucial considering that the most recent randomized trial found a benefit of preoperative FFR when arterial conduits are used for CABG | 10 years | 
| Completeness of revascularization | to investigate if the use of preoperative FFR is associated to incomplete revascularization (i.e. reduced number of bypassed lesion) | 10 years | 
| Surgeon experience effect | Measuring relation between surgeon's experience (measured as number of CABG cases performed) on mortality and other outcomes. Studies have demonstrated a learning curve of at least 50 cases | 10 years | 
| Volume/outcome relationship | Measuring relation between center's experience (measured as number of CABG cases/year) and outcomes.Centers performing high volumes of these procedure might produce better outcomes. | 10 years |