Clinical trial NCT02527044: Impact of Preoperative FFR on Arterial Bypass Graft Functionality
Official title: Impact of Preoperative FFR on Arterial Bypass Graft Functionality: Towards a New CABG Paradigm
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Heart Disease
Keywords: Coronary Artery Bypass
Flow Reserve
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
First posted: 2015-08-18
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: This study was designed to evaluate the correlation between pre-operative FFR and the functionality of arterial bypass grafts six months after coronary artery bypass grafting. Patients with multi-vessel coronary artery disease will undergo both a coronary angiogram and FFR during their diagnostic workup. All patients will be referred for surgical revascularization (CABG) with planned use of arterial grafts. Six months after surgery, patients will undergo an angiogram to assess the functionality of the bypass graft and anastomosis.

Detailed description: The objective of surgical coronary revascularization is to restore blood flow supply to a myocardial territory that is ischemic or at risk of infarction, by interposing a low-resistance conduit in parallel to a major diseased coronary artery segment. The conductance of this additional conduit must be sufficient to accommodate high flow demands with minimal pressure drop at the site of distal implantation. Such a conduit may be used either as single independent graft, or assembled in a variety of sequential configurations, according to the preferred technique and based on the underlying coronary artery disease (CAD). Saphenous vein grafts (SVGs), most commonly used as single free grafts reimplanted on the aorta, are large conduits with very limited vasomotion. Their resistance to blood flow is negligible due to their large diameter, absence of muscular layer and usually short length, but their long-term patency is hindered by the development of premature atherosclerosis. In contrast, arterial grafts are usually of smaller diameter and more resistive due to their histological features. These arterial conduits are usually used in situ, as the second or third order of branches from the aorta and, therefore, have higher pressure drops compared to grafts implanted directly onto the aorta. Alternatively, the creation of composite T grafts with the free right internal thoracic artery (RITA) connected to the in situ left internal thoracic artery (LITA) can allow revascularization of all myocardium at risk. However, consequences of such a combination are that the flow supply is entirely dependent on the flow capacity of the proximal LITA, and that resistance along the graft may become a concern, particularly at the more distal anastomoses of the configuration (due to the cumulative length and distal graft tapering).

Competitive flow typically occurs when the resistance of the graft closely matches that of the native coronary artery target. In this situation, both the native coronary artery and the bypass graft contribute to distal perfusion, each providing resistance to blood flow from the other. Schematically, these resistances are arranged in parallel with input pressure at the coronary ostium or at the ostium of the graft, and output pressure at the anastomotic target site. The pressures at the two ends of the circuit are identical with only minor phasic variations in proximal pressure due to the delay in progression of the systolic pressure wave from the coronary ostium to the more distal ostium of the graft. According to Ohm's law, blood flow is directly proportional to pressure gradient and inversely proportional to resistance. Consequently, the relative contribution of the graft and of the native circulation to distal perfusion will be inversely proportional to their own resistance: if the resistance of the graft exceeds that of the native vessel (for instance, in situations of non-severely obstructive CAD), the distal territory will be predominantly perfused by the native coronary artery; if the resistance of the native vessel remains higher, the flow through the graft will be predominant; if both conduits oppose near-identical resistances to flow, their contribution to distal blood flow will be equivalent.

Many reports have consistently suggested that competitive flow in arterial bypass grafts negatively affects patency: more graft failures are observed when native coronary stenosis is less severe. Further, the misunderstanding of competitive flow also impairs multiple arterial grafting adoption rates, which remain quite low worldwide despite proven superior outcomes, due in large part to incomplete understanding of the effects of flow competition by surgeons. Current methods to evaluate coronary stenosis are: visual inspection, quantitative computerized angiography (QCA) and fractional flow reserve (FFR). Several studies have compared these three methods, demonstrating that visual assessment and QCA are of limited value for accurately predicting the significance of most intermediate narrowings and, therefore, at predicting a competition phenomenon. In contrast, FFR measures the consequence of the stenosis in terms of reduction of blood flow capacity. FFR reliably identifies stenoses associated with inducible ischemia with more than 93% accuracy, a rate higher than any other test. Despite these advantages, FFR is not widely applied especially in coronary surgery whereas in interventional cardiology, it is used near systematically. What the investigators propose in this collaborative study is a complete paradigm shift in how coronary surgery is carried out - total arterial grafting supported by a true physiologic basis, and a correlated proof of its outcomes.

Currently, indications for surgical coronary revascularization still largely rely only on visual estimation of stenoses. Unfortunately, the estimation of the true coronary lesion severity by visual estimation is especially poor for moderate lesions, i.e. between 50 to 70% stenosis. An FFR cutoff value of 0.8 is obtained in only 35% of these moderate lesions. When using saphenous vein, the impact of competition flow on graft patency is minimal in this situation but when an artery conduit is preferred, it impacts the functionality of the graft significantly.

Therefore, the investigators are proposing a prospective FFR evaluation of surgical patients with 3-vessel CAD, whose disease severity will be estimated by visual inspection during diagnostic angiogram. FFR will be performed and all values will be recorded; however, the patient, interventional cardiologist, and surgeon will be blinded to its results. All patients will then undergo coronary surgery with planned arterial revascularization. Six months after surgery, a control angiogram will be performed to evaluate functionality of the grafts. The results of this functional assessment will be correlated with the preoperative FFR values, in order to find a cutoff above which the arterial grafts are not functional, which will also be analyzed by subgroups defined according to configuration (i.e. in situ or composite).

Eligibility criteria: Inclusion Criteria:

1. All patients with multi-vessel coronary artery disease undergoing elective or urgent first time coronary artery bypass grafting (CABG).
2. All patients undergoing diagnostic angiography and suspected to have multi-vessel disease for referral to CABG
3. Patients requiring both on-pump or off-pump CABG are accepted, as long as a arterial revascularisation is planned.
4. The patients must be over the age of 18.
5. CABG is the only procedure being conducted

Exclusion Criteria:

1. Planned simultaneous surgical procedure unrelated to coronary revascularization (e.g. valve repair/replacement, aneurysmectomy, carotid endarterectomy or carotid stenting)
2. Redo CABG, or a percutaneous coronary intervention (PCI) within the last 6 months.
3. Severe renal insufficiency (preoperative creatinine \>150umol/L) contraindicating postoperative coronary angiography
4. Significant leukopenia, neutropenia, thrombocytopenia, anemia, or known bleeding diathesis
5. Women who are pregnant or are seeking to become pregnant
6. Must not have severe congestive heart failure (class III or IV New York Heart Association) at enrollment
7. Left ventricular ejection fraction less than 30%
8. Prior history of significant bleeding that might be expected to recur with CABG
9. Prisoners or institutionalized individuals
10. Geographic inaccessibility for the follow-up visits required by protocol
11. Concurrent enrollment in another clinical trial
12. Extra-cardiac illness that is expected to limit survival to less than 5 years

Primary outcomes:
measure: Correlation between pre-operative FFR and anastomosis function
timeFrame: Up to 12 months
Secondary outcomes:
measure: Correlation between pre-operative FFR and anastomosis occlusion
timeFrame: Up to 12 months
measure: Major Adverse Cardiac Events
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Bouge
country: Belgium
facility: Clinique Saint-Luc Bouge
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: David Glineur, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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