What should be the role of fractional flow reserve measurement in patients undergoing coronary artery bypass grafting?

Central MessageFFR as a guide to dictate whether a patient will benefit from CABG versus PCI and or which vessels should or not be grafted should be discouraged. FFR is useful for graft choice (arterial vs venous).See Commentaries on pages 80 and 83.Feature Editor's Introduction—Glineur and colleagues from Ottawa present a superb summary on the evidence of the use of fractional flow reserve (FFR) for coronary bypass surgery.FFR was conceived to guide percutaneous coronary interventions, a procedure that targets directly the culprit plaque and whose success is inversely related to the complexity and the numbers of the lesions treated. In this context, a tool able to identify the flow-limiting lesions and reduce the procedural complexity and the number of stents implanted makes obvious sense.Bypass surgery is intrinsically different than percutaneous coronary interventions in 2 key aspects: surgery targets the distal, normal, or almost normal portion of the target vessel; and the procedural success of bypass surgery is not influenced by target lesion complexity. In surgery, the association between the number of treated lesions and the outcome is very weak (or nonexistent in the modern era). In this setting, the use of FFR makes much less sense, especially because the use of FFR to inform surgical grafting carries the important risk of jeopardizing 2 cornerstones of the success of coronary surgery: completeness of revascularization and protection of the coronary bed from disease progression.I'm grateful to Dr Glineur and his group for this very articulated summary of such an important issue, and I'm sure that readers will echo my sentiment.Mario Gaudino, MD, MSCE FFR as a guide to dictate whether a patient will benefit from CABG versus PCI and or which vessels should or not be grafted should be discouraged. FFR is useful for graft choice (arterial vs venous). See Commentaries on pages 80 and 83. The current challenge cardiac surgeons face with regard to the role of fractional flow reserve (FFR) in their field is not insignificant. The evidence behind FFR-guided percutaneous coronary intervention (PCI) is robust, based on the FAME series of trial,1Tonino P.A. De Bruyne B. Pijls N.H. Siebert U. Ikeno F. van't Veer M. et al.Fractional flow reserve versus angiography for guiding percutaneous coronary intervention.N Engl J Med. 2009; 360: 213-224Crossref PubMed Scopus (2672) Google Scholar,2Tonino P.A. Fearon W.F. De Bruyne B. Oldroyd K.G. Leesar M.A. Ver Lee P.N. et al.Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation.J Am Coll Cardiol. 2010; 55: 2816-2821Crossref PubMed Scopus (830) Google Scholar comparing Fractional Flow Reserve versus angiographic-guided revascularization in Patients with Multivessel Coronary Artery Disease and it has become the standard of care for interventional cardiologists who currently plan their intervention based on the functional analysis of any given stenosis rather than its visual appearance in 2 dimensions at the time of coronary catheterization. They have the significant advantage of deferring and reassessing a particular lesion based on physiology. Cardiac surgeons in general are less receptive to the FFR for several reasons. First, it is not feasible to defer surgical revascularization of a borderline stenosis; second, coronary artery bypass grafting (CABG) has always been perceived to protect patients from future events by grafting moderate lesions; and third, as a surgical procedure it remains stunted in its evolution as evidenced by the use of the left internal thoracic artery and saphenous veins as the conduits of choice for the vast majority of patients. In this article, we will discuss the issues the surround the topic of FFR in CABG by performing a careful and objective analysis of the current available data, including our own, in the literature. The most commonly used methods by surgeons to estimate the severity of the coronary stenosis and the potential for competitive flow is visual estimation. The Cleveland Clinic has extensively studied the correlation between graft patency and the percent stenosis estimated by visual inspection. They found that the best patency for internal thoracic conduits is found when they are used to bypass the left anterior descending artery (LAD) territory. In fact, the same authors observed that the severity of the LAD lesion has a low influence on internal thoracic artery patency, whereas it is on the right coronary artery territory where patency relates most with the degree of stenosis.3Sabik III, J.F. Olivares G. Raza S. Lytle B.W. Houghtaling P.L. Blackstone E.H.J. Does grafting coronary arteries with only moderate stenosis affect long-term mortality?.Thorac Cardiovasc Surg. 2016; 151: 806-811Abstract Full Text Full Text PDF Scopus (15) Google Scholar,4Sabik III, J.F. Blackstone E.H. Coronary artery bypass graft patency and competitive flow.J Am Coll Cardiol. 2008; 51: 126-128Crossref PubMed Scopus (44) Google Scholar Similarly, patency rates of radial and gastroepiploic arteries are dependent on the degree of native coronary artery stenosis.5Gaudino M. Alessandrini F. Pragliola C. Cellini C. Glieca F. Luciani N. et al.Effect of target artery location and severity of stenosis on mid-term patency of aorta-anastomosed vs. internal thoracic artery-anastomosed radial artery grafts.Eur J Cardiothorac Surg. 2004; 25: 424-428Crossref PubMed Scopus (64) Google Scholar The physiologic way to assess the severity of a coronary stenosis is by using FFR.6Pijls N.H. De Bruyne B. Peels K. Van Der Voort P.H. Bonnier H.J. Bartunek J. et al.Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses.N Engl J Med. 1996; 334: 1703-1708Crossref PubMed Scopus (1613) Google Scholar FFR was first measured invasively with a catheter across the coronary stenosis with maximal hyperemia induced by the administration of adenosine mimicking conditions similar to those experienced during stress test. Therefore, it is a ratio of pressure in a vessel distal to a stenosis of interest compared with that vessel in the absence of the stenosis, and a value ≤0.8 indicates significant ischemia. More recently, instantaneous wave-free ratio has been used in planning surgical revascularization. This method has been found to be more sensitive to detect critical stenoses than FFR.7Baibhav B. Gedela M. Moulton M. Pavlides G. Pompili V. Rab T. et al.Role of invasive functional assessment in surgical revascularization of coronary artery disease.Circulation. 2018; 137: 1731-1739Crossref PubMed Scopus (5) Google Scholar The advantages of FFR are that it accounts for the size and amount of viable myocardium supplied by a specific diseased coronary artery, the quality of the vessels bypassed, their sizes, and the presence of distal disease (Figure 1). In the FAME sub-study trials8Toth G. Hamilos M. Pyxaras S. Mangiacapra F. Nelis O. De Vroey F. et al.Evolving concepts of angiogram: fractional flow reserve discordances in 4000 coronary stenoses.Eur Heart J. 2014; 35: 2831-2838Crossref PubMed Scopus (178) Google Scholar and others,9Watanabe H. Onishi K. Kakehi K. Takase T. Yamaji K. Ueno M. et al.Clinical and angiographic factors predicting fractional flow reserve and explaining the visual-functional mismatch in patients with intermediate coronary artery stenosis.Coron Artery Dis. 2020; 31: 73-80Crossref PubMed Scopus (2) Google Scholar the researchers found, in concordance with the results of the Cleveland Clinic,3Sabik III, J.F. Olivares G. Raza S. Lytle B.W. Houghtaling P.L. Blackstone E.H.J. Does grafting coronary arteries with only moderate stenosis affect long-term mortality?.Thorac Cardiovasc Surg. 2016; 151: 806-811Abstract Full Text Full Text PDF Scopus (15) Google Scholar that the LAD territory has the highest mismatch between percent stenosis and FFR ≤0.8, showing that when looking at mild to moderate stenosis of the LAD we have the highest probability of having a positive FFR compared with other branches of the coronary tree. The circumflex artery territory has a better correlation than the LAD between the visual estimation and FFR ≤0.8, but the best correlation is with the right coronary artery territory. The most common explanation is that myocardial mass supplied by the LAD is the largest compared with other territories.10Nordlund D. Heiberg E. Carlsson M. Frund E.T. Hoffmann P. Koul S. et al.Extent of myocardium at risk for left anterior descending artery, right coronary artery, and left circumflex artery occlusion depicted by contrast-enhanced steady state free precession and T2-weighted short tau inversion recovery magnetic resonance imaging.Circ Cardiovasc Imaging. 2016; 9: e004376PubMed Google Scholar In utilizing FFR to determine whether there is inducible ischemia, its pitfalls must be recognized by practitioners. FFR is based on pressure and the assumption of maximal hyperemia. For FFR to be performed accurately and reproducibly, a correct technique is of paramount importance with special care taken to identify disengagement of the catheter guide during measurement,11Aminian A. Dolatabadi D. Lefebvre P. Khalil G. Zimmerman R. Michalakis G. et al.Importance of guiding catheter disengagement during measurement of fractional flow reserve in patients with an isolated proximal left anterior descending artery stenosis.Catheter Cardiovasc Interv. 2015; 85: 595-601Crossref PubMed Scopus (12) Google Scholar correct positioning of the pressure sensor in relation to the stenosis in question, and the achievement of maximal hyperemia. Obtaining maximal hyperemia can be influenced by something as innocuous as recent intake of caffeine by a patient. Particularly relevant to CABG, FFR measurement of a stenosis may be significantly influenced by the presence of another downstream stenosis. This arises in the assessment of the left main coronary stenosis, whereby a downstream stenosis (eg, in the LAD) has a tendency to underestimate the severity of the left main stenosis (ie, higher FFR than actual).12Yong A.S. Daniels D. De Bruyne B. Kim H.S. Ikeno F. Lyons J. et al.Fractional flow reserve assessment of left main stenosis in the presence of downstream coronary stenoses.Circ Cardiovasc Interv. 2013; 6: 161-165Crossref PubMed Scopus (56) Google Scholar Another caveat of utilizing FFR in CABG is in the evaluation of vessels with predominantly diffuse atherosclerosis or microvascular dysfunction. In the presence of diffuse atherosclerosis, FFR is typically overestimated, resulting in a higher-than-expected FFR. The functional SYNTAX score, using FFR to guide PCI has been proposed to target revascularization and reclassify multivessel disease based on angiography. Although this is an attractive option, it is not feasible to defer revascularization in patients undergoing CABG because it is often a definitive invasive treatment unlike PCI, where further intervention could be deferred. It is also assumed that surgical revascularization protects a patient against future cardiovascular events, independent from the complexity of the underlying disease because it provides a secondary blood supply to the coronary tree. Two points remain to be addressed: Will a graft remain open when grafted to a moderately stenosed coronary lesion without evidence of functional stenosis by FFR? and, How would the 2 different types of conduits, arterial or venous, behave in this scenario? In the absence of data from randomized controlled trials, the routine use of FFR to dictate which vessel to graft or not to graft surgically remains unanswered. When performing a coronary revascularization procedure, the goal of the intervention is to restore blood supply to a myocardial territory that is ischemic through the interposition of a low-resistance conduit allowing adequate flow of blood over the area of stenosis of the involved coronary artery segment. This bypass conduit must be able to accommodate the high flow demands of systemic pressure with minimal pressure drop at the site of distal implantation reliably and for a prolonged period of time. The phenomenon of competitive flow occurs when the resistance to the flow of blood through the coronary bypass graft closely matches that of the native coronary artery vessel. In this situation, both the bypass conduit and the coronary artery contribute to the myocardial perfusion of a given myocardial territory. In the case of vein grafts, the pressures at the 2 ends of the conduit are identical—the absence of muscular layers and their large diameter making them the perfect compliance conduits. On the other hand, when arterial grafts are used as bypass grafts, a higher pressure at the proximal aspect rather than at the site of the distal anastomosis will always be the norm for these grafts due to the smaller diameter and the higher vasomotor tone (muscular layer) of arterial conduits. In an observational study, we found 6 times higher pressure gradients drop in arterial grafts compared with venous grafts between the aorta and the distal conduit anastomosis.13Glineur D. Poncelet A. El Khoury G. D'hoore W. Astarci P. Zech F. et al.Fractional flow reserve of pedicled internal thoracic artery and saphenous vein grafts 6 months after bypass surgery.Eur J Cardiothorac Surg. 2007; 31: 376-381Crossref PubMed Scopus (25) Google Scholar Due to these intrinsic conduit differences, competitive flow will significantly influence more arterial conduits than their venous counterparts, potentially leading to graft attrition and occlusion. This phenomenon has been widely reported in the literature14Sabik III, J.F. Lytle B.W. Blackstone E.H. Khan M. Houghtaling P.L. Cosgrove D.M. Does competitive flow reduce internal thoracic artery graft patency?.Ann Thorac Surg. 2003; 76: 1490-1496Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar, 15Glineur D. D'hoore W. de Kerchove L. Noirhomme P. Price J. Hanet C. et al.Angiographic predictors of 3-year patency of bypass grafts implanted on the right coronary artery system: a prospective randomized comparison of gastroepiploic artery, saphenous vein, and right internal thoracic artery grafts.J Thorac Cardiovasc Surg. 2011; 142: 980-988Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 16Glineur D. D'hoore W. El Khoury G. Sondji S. Kalscheuer G. Funken J.C. et al.Angiographic predictors of 6-month patency of bypass grafts implanted to the right coronary artery a prospective randomized comparison of gastroepiploic artery and saphenous vein grafts.J Am Coll Cardiol. 2008; 51: 120-125Crossref PubMed Scopus (38) Google Scholar (Figure 2). The influence of flow competition also depends on the targeted coronary artery. Indeed, arterial grafts to the LAD territory were found to better tolerate competitive flow compared with arterial conduits used to bypass the lateral or inferior walls of the heart.3Sabik III, J.F. Olivares G. Raza S. Lytle B.W. Houghtaling P.L. Blackstone E.H.J. Does grafting coronary arteries with only moderate stenosis affect long-term mortality?.Thorac Cardiovasc Surg. 2016; 151: 806-811Abstract Full Text Full Text PDF Scopus (15) Google Scholar The influence of FFR results on CABG has been studied in 2 types of trials: patency trials and in outcome-driven clinical trials. These 2 different types of trials have tried to answer very different questions: Does FFR ≤0.8 influence graft patency? or, Does not grafting a vessel with FFR >0.8 influence the clinical outcome of patients undergoing surgical coronary revascularization in a similar way to what has already been demonstrated in the cardiology literature? Botman and colleagues17Botman C.J. Schonberger J. Koolen S. Penn O. Botman H. Dib N. et al.Does stenosis severity of native vessels influence bypass graft patency? A prospective fractional flow reserve-guided study.Ann Thorac Surg. 2007; 83: 2093-2097Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar analyzed prospectively 164 patients undergoing CABG who had FFR measured during preoperative diagnostic angiogram. At 1 year, a systematic angiographic follow-up was performed. The authors concluded that bypassing lesions with FFR >0.75 resulted in a greater rate of graft occlusion (21.4% in FFR >0.75 vs 8.9% in FFR <0.75; and K. S. M. M. et flow assessment using a time flow in fractional flow reserve-guided coronary artery bypass Thorac Cardiovasc Surg. 2015; Full Text Full Text PDF PubMed Scopus Google Scholar the between preoperative FFR on LAD stenosis and the bypass graft flow They the results FFR group FFR but and group FFR In and graft flow was and and was and They concluded that as coronary stenosis severity graft flow and group studied the influence of FFR in arterial grafting in the of FFR on D. U. S. et of preoperative fractional flow reserve on arterial bypass graft the Heart J. PubMed Scopus Google Scholar patients both coronary angiography and FFR as of their diagnostic and arterial At 6 a systematic angiographic follow-up was performed. found that but not angiographic stenosis was a of arterial graft patency and at 6 performed to coronary arteries with FFR had a patency rate of in a D. M. S. et by arterial graft and Cardiovasc Interv. 2020; PubMed Scopus Google Scholar the same authors found that the FFR value to have a arterial graft is when the right coronary This is related to the between the graft or internal thoracic and the distal coronary the the the higher risk for competitive and G. De Bruyne B. F. De Vroey F. Pyxaras S. L. et al.Fractional flow reserve-guided versus coronary artery bypass graft 2013; PubMed Scopus Google Scholar in a FFR-guided versus CABG found that after FFR-guided CABG patients had a of through vs a of and greater from saphenous vein graft G. De Bruyne B. F. De Vroey F. Pyxaras S. L. et al.Fractional flow reserve-guided versus coronary artery bypass graft 2013; PubMed Scopus Google Scholar A study using the same patient by and S. De Bruyne B. G. P. et follow-up of fractional flow reserve-guided versus coronary artery bypass graft Cardiovasc Interv. 2018; PubMed Scopus (44) Google Scholar at 1 intermediate stenosis in patients by coronary angiography or angiography FFR. The authors found that patients in the FFR-guided group had and a rate of and myocardial 6 after surgery ratio The Fractional Flow Reserve versus for E.H. et al.Fractional flow reserve versus coronary artery bypass Am Coll Cardiol. 2018; PubMed Scopus Google Scholar analyzed graft patency and clinical at 6 months in patients randomized to CABG versus FFR-guided the grafts were veins patency was observed between the 2 there were in cardiac and events rate at 1 of the in the of the First, the study was at of the of patients not the to the was based on a rate of graft occlusion of after 6 months in grafts to coronary arteries with FFR and with FFR the observed rates were much at and the number of patients who follow-up angiography was which to the rate of during The after versus CABG De Bruyne B. P. F. R. et patency after FFR-guided versus coronary artery bypass the PubMed Scopus Google Scholar the influence of FFR on graft patency and clinical patients were randomized to or FFR-guided The ratio of arterial to venous grafts used was At in graft patency or in cardiac and events was of the should be when the First, the to follow-up was angiographic at 1 was performed in only of patients. surgical due to to their surgical on FFR have the of FFR in the in the FFR-guided of the vessels had FFR and of vessels had FFR the was for both clinical and angiographic Due to the was at of the of the data FFR in CABG from with and short In of graft patency, data from the of FFR on D. U. S. et of preoperative fractional flow reserve on arterial bypass graft the Heart J. PubMed Scopus Google Scholar Botman and C.J. Schonberger J. Koolen S. Penn O. Botman H. Dib N. et al.Does stenosis severity of native vessels influence bypass graft patency? A prospective fractional flow reserve-guided study.Ann Thorac Surg. 2007; 83: 2093-2097Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar and and K. S. M. M. et flow assessment using a time flow in fractional flow reserve-guided coronary artery bypass Thorac Cardiovasc Surg. 2015; Full Text Full Text PDF PubMed Scopus Google Scholar the from E.H. et al.Fractional flow reserve versus coronary artery bypass Am Coll Cardiol. 2018; PubMed Scopus Google Scholar and De Bruyne B. P. F. R. et patency after FFR-guided versus coronary artery bypass the PubMed Scopus Google Scholar rate in the 2 prospective randomized E.H. et al.Fractional flow reserve versus coronary artery bypass Am Coll Cardiol. 2018; PubMed Scopus Google De Bruyne B. P. F. R. et patency after FFR-guided versus coronary artery bypass the PubMed Scopus Google Scholar to at 1 without between the 2 whereas in the arterial grafting it was when FFR was The explanation for this significant is related to the in the types of graft used in the different trials. have and saphenous veins are not sensitive to competition flow when compared with arterial In of clinical that the 2 trials were very with significant clinical benefit of CABG was The functional SYNTAX FFR to the severity of coronary artery disease and it has been proposed by cardiologists to the revascularization The of this to CABG not by Indeed, the goal of surgical revascularization has always been to protect the patient from future events of the complexity of the underlying the SYNTAX after revascularization is a of long-term and cardiac and G. E. S. C. A. M. et SYNTAX coronary artery bypass J Cardiothorac Surg. 51: Google Scholar The use of FFR could the rate of revascularization with potential long-term for our patients. on the current evidence and the absence of data from trials to detect in clinical the use of FFR as the only guide to dictate whether a patient should become a for a surgical revascularization versus PCI and or which vessels should or not be grafted should be discouraged. FFR to be an important tool to which of graft to use (ie, arterial for lesions with an FFR venous for those with higher

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