Surgical collateralization: The hidden mechanism for improving prognosis in chronic coronary syndromes

Abstract

Central MessagePrognostic effects of treatments for chronic CAD mainly depend on infarct prevention. Coronary bypass grafting prevents myocardial infarctions through surgical collateralization.See Commentaries on pages 709 and 710. Prognostic effects of treatments for chronic CAD mainly depend on infarct prevention. Coronary bypass grafting prevents myocardial infarctions through surgical collateralization. See Commentaries on pages 709 and 710. Feature Editor's Introduction—In this issue of the Journal, Doenst and Sigusch nicely summarize the mechanisms of the protective effect of coronary bypass surgery on the coronary circulation and on clinical outcomes. Although percutaneous interventions treat only flow-limiting stenoses, bypass surgery confers long-term protection against disease progression in the entire grafted vessel (“surgical collateralization”). This key mechanistic difference likely explains the difference in outcomes between the 2 strategies and has profound implications for many aspects of modern coronary bypass practice, including the use of arterial grafts and the role of fractional flow reserve. Although the evidence summarized by the authors is not necessarily recent, Doenst and Sigusch's elegant review is an important reminder for the surgical community of the foundations and potential of the most commonly performed cardiac surgery operation, and I am sure that many readers, like me, will enjoy reading it. Mario Gaudino, MD, MSCE Coronary artery disease (CAD) causes ischemia by the generation of stenosing lesions in the vessel wall that gradually limit (chronic/inducible ischemia) or suddenly interrupt blood flow by complete vessel occlusion (acute ischemia, the main mechanism of acute myocardial infarction).1Doenst T. Haverich A. Serruys P. Bonow R.O. Kappetein P. Falk V. et al.PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.J Am Coll Cardiol. 2019; 73: 964-976Crossref PubMed Scopus (136) Google Scholar As a consequence, disease conditions associated with CAD are separated into acute or chronic coronary syndromes (the latter was formerly referred to as “stable CAD”).2Knuuti J. Wijns W. Saraste A. Capodanno D. Barbato E. Funck-Brentano C. et al.2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes.Eur Heart J. 2020; 41: 407-477Crossref PubMed Scopus (2086) Google Scholar,3Neumann F.J. Sousa-Uva M. Ahlsson A. Alfonso F. Banning A.P. Benedetto U. et al.2018 ESC/EACTS guidelines on myocardial revascularization.Eur Heart J. 2019; 40: 87-165Crossref PubMed Scopus (2910) Google Scholar Treatment of CAD generally consists of medical therapy (a combination of beta-blockers, renin-angiotensin-aldosterone system inhibitors, platelet inhibition, statins, and other cholesterol-lowering drugs together with lifestyle modifications) with the option of adding invasive treatment modalities, specifically percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG).2Knuuti J. Wijns W. Saraste A. Capodanno D. Barbato E. Funck-Brentano C. et al.2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes.Eur Heart J. 2020; 41: 407-477Crossref PubMed Scopus (2086) Google Scholar Because the limitation or interruption of blood flow to the distal myocardium is the main mechanism of CAD, treatments directed at improving or restoring blood flow have been summarized under the term of “myocardial revascularization.”2Knuuti J. Wijns W. Saraste A. Capodanno D. Barbato E. Funck-Brentano C. et al.2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes.Eur Heart J. 2020; 41: 407-477Crossref PubMed Scopus (2086) Google Scholar, 3Neumann F.J. Sousa-Uva M. Ahlsson A. Alfonso F. Banning A.P. Benedetto U. et al.2018 ESC/EACTS guidelines on myocardial revascularization.Eur Heart J. 2019; 40: 87-165Crossref PubMed Scopus (2910) Google Scholar, 4Patel M.R. Calhoon J.H. Dehmer G.J. Grantham J.A. Maddox T.M. Maron D.J. et al.ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 appropriate use criteria for coronary revascularization in patients with stable ischemic heart disease: a report of the American College of Cardiology appropriate use criteria task force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and interventions, Society of Cardiovascular Computed Tomography, and Society of Thoracic Surgeons.J Am Coll Cardiol. 2017; 69: 2212-2241Crossref PubMed Scopus (408) Google Scholar There is no doubt that revascularization is key for the treatment of acute ischemia.5Amsterdam E.A. Wenger N.K. Brindis R.G. Casey Jr., D.E. Ganiats T.G. Holmes Jr., D.R. et al.2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association task force on practice guidelines.J Am Coll Cardiol. 2014; 64: e139-e228Crossref PubMed Scopus (1894) Google Scholar For chronic coronary syndromes, it has been accepted that the detection of ischemia (by single photon emission computed tomography, cardiac magnetic resonance tomography, or FDG-positron emission tomography) and the assessment of flow relevance of individual stenoses (by fractional flow reserve [FFR], intravascular ultrasound, or OCT) are helpful guides for applying and choosing the optimal revascularization strategy.2Knuuti J. Wijns W. Saraste A. Capodanno D. Barbato E. Funck-Brentano C. et al.2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes.Eur Heart J. 2020; 41: 407-477Crossref PubMed Scopus (2086) Google Scholar,3Neumann F.J. Sousa-Uva M. Ahlsson A. Alfonso F. Banning A.P. Benedetto U. et al.2018 ESC/EACTS guidelines on myocardial revascularization.Eur Heart J. 2019; 40: 87-165Crossref PubMed Scopus (2910) Google Scholar However, despite its plausibility and worldwide acceptance, the available evidence supporting a life-prolonging effect of revascularization for chronic coronary syndromes appears less convincing than for acute coronary syndromes and appears contradictory.1Doenst T. Haverich A. Serruys P. Bonow R.O. Kappetein P. Falk V. et al.PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.J Am Coll Cardiol. 2019; 73: 964-976Crossref PubMed Scopus (136) Google Scholar Prospective randomized evidence addressing the impact of revascularization through PCI in patients with chronic coronary syndromes has not yet convincingly demonstrated a prognostic benefit.6Stergiopoulos K. Boden W.E. Hartigan P. Möbius-Winkler S. Hambrecht R. Hueb W. et al.Percutaneous coronary intervention outcomes in patients with stable obstructive coronary artery disease and myocardial ischemia: a collaborative meta-analysis of contemporary randomized clinical trials.JAMA Intern Med. 2014; 174: 232-240Crossref PubMed Scopus (214) Google Scholar,7Boden W.E. O'Rourke R.A. Teo K.K. Hartigan P.M. Maron D.J. Kostuk W.J. et al.Optimal medical therapy with or without PCI for stable coronary disease.N Engl J Med. 2007; 356: 1503-1516Crossref PubMed Scopus (3574) Google Scholar Although symptomatic relief is one key goal of revascularization,3Neumann F.J. Sousa-Uva M. Ahlsson A. Alfonso F. Banning A.P. Benedetto U. et al.2018 ESC/EACTS guidelines on myocardial revascularization.Eur Heart J. 2019; 40: 87-165Crossref PubMed Scopus (2910) Google Scholar even this effect has recently been questioned by the controversially discussed ORBITA trial, in which classic stenting was not associated with a measurable difference in symptom relief compared with mock PCI to the left anterior descending.8Al-Lamee R. Thompson D. Dehbi H.M. Sen S. Tang K. Davies J. et al.Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial.Lancet. 2018; 391: 31-40Abstract Full Text Full Text PDF PubMed Scopus (539) Google Scholar In addition, the most recent trial9Maron D.J. Hochman J.S. Reynolds H.R. Bangalore S. O'Brien S.M. Boden W.E. et al.Initial invasive or conservative strategy for stable coronary disease.N Engl J Med. 2020; 382: 1395-1407Crossref PubMed Scopus (808) Google Scholar assessing a strategy of early invasive diagnosis followed by revascularization for chronic coronary syndrome versus a conservative medical strategy reconfirmed the lack of a prognostic impact of revascularization. The trial failed to demonstrate a survival difference to medical therapy for the invasive group, which consisted of three-quarters of patients who underwent PCI and one-quarter of patients who underwent CABG. In contrast, there is repeated evidence from prospective randomized trials that CABG provides a survival benefit over PCI10Head S.J. Milojevic M. Daemen J. Ahn J.M. Boersma E. Christiansen E.H. et al.Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data.Lancet. 2018; 391: 939-948Abstract Full Text Full Text PDF PubMed Scopus (330) Google Scholar and medical therapy.11Velazquez E.J. Lee K.L. Jones R.H. Al-Khalidi H.R. Hill J.A. Panza J.A. et al.Coronary-artery bypass surgery in patients with ischemic cardiomyopathy.N Engl J Med. 2016; 374: 1511-1520Crossref PubMed Scopus (488) Google Scholar However, this advantage appears to be especially present in patient populations who are characterized by higher severity of CAD and the presence of other cardiovascular comorbidities such as diabetes mellitus or heart failure.1Doenst T. Haverich A. Serruys P. Bonow R.O. Kappetein P. Falk V. et al.PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.J Am Coll Cardiol. 2019; 73: 964-976Crossref PubMed Scopus (136) Google Scholar,12Farkouh M.E. Domanski M. Dangas G.D. Godoy L.C. Mack M.J. Siami F.S. et al.Long-term survival following multivessel revascularization in patients with diabetes: the FREEDOM follow-on study.J Am Coll Cardiol. 2019; 73: 629-638Crossref PubMed Scopus (122) Google Scholar,13Thuijs D. Kappetein A.P. Serruys P.W. Mohr F.W. Morice M.C. Mack M.J. et al.Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial.Lancet. 2019; 394: 1325-1334Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar These conditions are generally associated with higher risk of myocardial infarctions. The only prospective randomized comparison of CABG to medical therapy was performed in patients with ischemic heart failure. The Surgical Treatment of IsChemic Heart Failure trial randomized patients with impaired left ventricular function (ejection fraction <35%) to CABG or medical therapy. Patients in the CABG group lived on average 18 months longer compared with medical therapy over a 10-year observation period.11Velazquez E.J. Lee K.L. Jones R.H. Al-Khalidi H.R. Hill J.A. Panza J.A. et al.Coronary-artery bypass surgery in patients with ischemic cardiomyopathy.N Engl J Med. 2016; 374: 1511-1520Crossref PubMed Scopus (488) Google Scholar Neither ischemia14Panza J.A. Holly T.A. Asch F.M. She L. Pellikka P.A. Velazquez E.J. et al.Inducible myocardial ischemia and outcomes in patients with coronary artery disease and left ventricular dysfunction.J Am Coll Cardiol. 2013; 61: 1860-1870Crossref PubMed Scopus (136) Google Scholar nor viability testing15Bonow R.O. Maurer G. Lee K.L. Holly T.A. Binkley P.F. Desvigne-Nickens P. et al.Myocardial viability and survival in ischemic left ventricular dysfunction.N Engl J Med. 2011; 364: 1617-1625Crossref PubMed Scopus (602) Google Scholar was associated with the treatment effect of CABG on survival. Thus, both diagnostic tools were not helpful for decision-making. Therefore, one may conclude that if PCI does not prolong life and if ischemia testing is not helpful for achieving improvements in prognosis in chronic coronary syndromes, the life-prolonging effect of CABG appears to be mediated through a mechanism that is not directly related to revasularization.1Doenst T. Haverich A. Serruys P. Bonow R.O. Kappetein P. Falk V. et al.PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.J Am Coll Cardiol. 2019; 73: 964-976Crossref PubMed Scopus (136) Google Scholar We previously suggested that the survival advantage of CABG is linked to the ability of bypass grafting to reduce the incidence of new myocardial infarctions.1Doenst T. Haverich A. Serruys P. Bonow R.O. Kappetein P. Falk V. et al.PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.J Am Coll Cardiol. 2019; 73: 964-976Crossref PubMed Scopus (136) Google Scholar Figure 1 shows this effect for the majority of current randomized trials having compared CABG with PCI (Table E1). It also receives support from a plethora of recent reports that we recently reviewed.16Doenst T. Bargenda S. Kirov H. Moschovas A. Tkebuchava S. Safarov R. et al.Cardiac surgery 2019 reviewed.Thorac Cardiovasc Surg. 2020; 68: 362-375Google Scholar We suggested that a patent graft to a distal coronary artery creates a surgical collateral that may prevent the occurrence of a new infarction in case the vessel occludes proximal to bypass insertion (eg, by a ruptured plaque).1Doenst T. Haverich A. Serruys P. Bonow R.O. Kappetein P. Falk V. et al.PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.J Am Coll Cardiol. 2019; 73: 964-976Crossref PubMed Scopus (136) Google Scholar The mechanism of action is then similar to a collateral stemming from angiogenesis or arteriogenesis. Figure 2 schematically illustrates this concept. In addition to PCI, CABG not only revascularizes chronically ischemic myocardium caused by a significant stenosis but also prevents new myocardial infarctions that may originate from other nonflow-limiting lesions in the same vascular bed. The spatial distance of vessel occlusions and bypass graft insertion was analyzed by Jeon and colleagues,17Jeon C. Candia S.C. Wang J.C. Holper E.M. Ammerer M. Kuntz R.E. et al.Relative spatial distributions of coronary artery bypass graft insertion and acute thrombosis: a model for protection from acute myocardial infarction.Am Heart J. 2010; 160: 195-201Crossref PubMed Scopus (17) Google Scholar who compared 168 patients after CABG with 208 patients presenting with ST-segment elevation myocardial infarction. They quantified the median distance between vessel occlusion and graft insertion, which ranged between 11 and 49 mm depending on the grafted vessel (Figure 2), and suggested that CABG thereby protects against infarction. We suggested that this protective effect is not primarily due to the resupply of blood to chronically ischemic myocardium but by establishing an alternative pathway for blood flow in case the original vessel occludes (ie, surgical collateralization).1Doenst T. Haverich A. Serruys P. Bonow R.O. Kappetein P. Falk V. et al.PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.J Am Coll Cardiol. 2019; 73: 964-976Crossref PubMed Scopus (136) Google Scholar The Video 1 shows an angiographic example where a 13-year-old vein graft supplies a coronary territory that no longer receives blood from the meanwhile occluded native vessel, but the myocardium did not suffer an infarction from the occlusion of this native vessel.Figure 2Schematic illustration of the concept of surgical collateralization. Both PCI and CABG treat ischemia by directly eliminating the flow-limiting lesion (PCI) or by circumventing it with a bypass graft (CABG). However, because the majority of myocardial infarctions are caused by nonflow-limiting lesions, the collateral created by bypass grafting can additionally protect against infarction from nonflow-limiting stenoses. The arrows indicate blood flow to the distal myocardium, which is maintained through the bypass graft if a nonflow-limiting lesion causes native vessel occlusion. ∗The values reflect a median distance from vessel occlusion to bypass graft insertion as assessed in a comparative study of 168 patients who underwent CABG and 200 patients with acute myocardial infarction.17Jeon C. Candia S.C. Wang J.C. Holper E.M. Ammerer M. Kuntz R.E. et al.Relative spatial distributions of coronary artery bypass graft insertion and acute thrombosis: a model for protection from acute myocardial infarction.Am Heart J. 2010; 160: 195-201Crossref PubMed Scopus (17) Google Scholar LAD, Left anterior descending; CX, circumflex; RCA, right coronary artery.View Large Image Figure ViewerDownload Hi-res image Download (PPT) We further illustrated in our review that the majority (>85%) of myocardial infarctions are linked to nonflow-limiting lesions.1Doenst T. Haverich A. Serruys P. Bonow R.O. Kappetein P. Falk V. et al.PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.J Am Coll Cardiol. 2019; 73: 964-976Crossref PubMed Scopus (136) Google Scholar Figure 3 quantifies the occurrence of myocardial infarctions based on the degree of vessel stenoses before vessel occlusion. Severe stenoses (presumably flow-limiting) were the cause for myocardial infarction in less than 15%. Thus, focusing PCI to only flow-limiting lesions, as recommended to improve PCI outcomes,3Neumann F.J. Sousa-Uva M. Ahlsson A. Alfonso F. Banning A.P. Benedetto U. et al.2018 ESC/EACTS guidelines on myocardial revascularization.Eur Heart J. 2019; 40: 87-165Crossref PubMed Scopus (2910) Google Scholar,18Xaplanteris P. Fournier S. Pijls N.H.J. Fearon W.F. Barbato E. Tonino P.A.L. et al.Five-year outcomes with PCI guided by fractional flow reserve.N Engl J Med. 2018; 379: 250-259Crossref PubMed Scopus (408) Google Scholar thereby limits PCI's ability to prevent new myocardial infarctions. The result should be greater protection against new myocardial infarction from CABG than from PCI. The currently available data suggest that the treatment of chronic ischemia by normalizing blood flow (ie, revascularization) may primarily alleviate symptoms, but that prevention of new myocardial infarctions (eg, by surgical collateralization) may prolong life. The summarized recognition is paradigm shifting, but it also explains the majority of perceived controversies in the literature. The following 6 points address the main consequences that arise from it and explain the main current controversies.1.Current terminology appears inappropriate With the suggestion that an infarct-prevention mechanism (eg, surgical collateralization) prolongs life rather than revascularization of chronic ischemic myocardium,1Doenst T. Haverich A. Serruys P. Bonow R.O. Kappetein P. Falk V. et al.PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.J Am Coll Cardiol. 2019; 73: 964-976Crossref PubMed Scopus (136) Google Scholar the term “myocardial revascularization” for summarizing the invasive treatment options appears, scientifically speaking, inappropriate because the term suggests a presumed mechanism that may prevent the consideration of additional or alternative mechanisms. The term “invasive treatment of CAD” whether by PCI or CABG, may be more appropriate because it does not suggest a presumed mechanism (ie, revascularization) and allows the presence of alternative mechanisms of action (eg, surgical collateralization). A similar rationale regarding the semantics of long-established terminology resulted in the change of the term “stable CAD” to “chronic coronary syndrome.”2Knuuti J. Wijns W. Saraste A. Capodanno D. Barbato E. Funck-Brentano C. et al.2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes.Eur Heart J. 2020; 41: 407-477Crossref PubMed Scopus (2086) Google Scholar2.Patient consenting may require revision Patients with multivessel disease are required to be discussed by a heart team.3Neumann F.J. Sousa-Uva M. Ahlsson A. Alfonso F. Banning A.P. Benedetto U. et al.2018 ESC/EACTS guidelines on myocardial revascularization.Eur Heart J. 2019; 40: 87-165Crossref PubMed Scopus (2910) Google Scholar This joint recommendation is then supposed to be presented to the patient to reach the final treatment decision, which is certainly influenced by many different factors. Future informed consent may now require explaining the difference between revascularization and surgical collateralization. This difference no longer supports offering the choice between “2 types of revascularization.” It would require information on 1 less-invasive treatment option restoring blood flow by treating flow-limiting (primarily symptom-causing) lesions and 1 more invasive treatment option providing both restoration of adequate blood flow (ie, revascularization) and significant protection against new myocardial infarctions (ie, surgical collateralization).3.Grafts must stay patent One key condition for exploiting the described mechanisms of CABG is graft patency. Graft occlusion obviously eliminates any revascularizing and infarct-preventative effects. Two main directions are currently being followed to achieve this task. First, multiarterial revascularization has been associated with better graft patency and better survival.19Chikwe J. Sun E. Hannan E.L. Itagaki S. Lee T. Adams D.H. et al.Outcomes of second arterial conduits in patients undergoing multivessel coronary artery bypass graft surgery.J Am Coll Cardiol. 2019; 74: 2238-2248Crossref PubMed Scopus (45) Google Scholar Considering that the majority of patients undergoing CABG in comparative trials compared with PCI received 1 left internal thoracic artery plus veins (which is consistent with current daily practice in most surgical centers worldwide) illustrates how large the therapeutic potential of multiple arterial CABG may be. It is interesting to note in this context, that the 10-year survival curves for PCI and CABG in the SYNTAX trial did not further diverge after 5 years.13Thuijs D. Kappetein A.P. Serruys P.W. Mohr F.W. Morice M.C. Mack M.J. et al.Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial.Lancet. 2019; 394: 1325-1334Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar Although not evaluated, it is conceivable that graft occlusions may have contributed to this result. The ROMA trial, comparing multiple arterial revascularization with a strategy of left internal thoracic artery plus veins on a large scale, will provide definitive answers to this question.20Gaudino M. Alexander J.H. Bakaeen F.G. Ballman K. Barili F. Calafiore A.M. et al.Randomized comparison of the clinical outcome of single versus multiple arterial grafts: the ROMA trial-rationale and study protocol.Eur J Cardiothorac Surg. 2017; 52: 1031-1040Crossref PubMed Google Scholar Second, it has been suggested to use FFR assessment to guide coronary bypass target selection. Several smaller trials have been performed with different results.21Thuesen A.L. Riber L.P. Veien K.T. Christiansen E.H. Jensen S.E. Modrau I. et al.Fractional flow reserve versus angiographically-guided coronary artery bypass grafting.J Am Coll Cardiol. 2018; 72: 2732-2743Crossref PubMed Scopus (52) Google Scholar, 22Fournier S. Toth G.G. De Bruyne B. Johnson N.P. Ciccarelli G. Xaplanteris P. et al.Six-year follow-up of fractional flow reserve-guided versus angiography-guided coronary artery bypass graft surgery.Circ Cardiovasc Interv. 2018; 11: e006368Crossref PubMed Scopus (58) Google Scholar, 23Toth G.G. De Bruyne B. Kala P. Ribichini F.L. Casselman F. Ramos R. et al.Graft patency after FFR-guided versus angiography-guided coronary artery bypass grafting: the GRAFFITI trial.EuroIntervention. 2019; 15: e999-e1005Crossref PubMed Scopus (40) Google Scholar FFR guidance resulted in the performance of fewer grafts without significantly affecting patency rates.21Thuesen A.L. Riber L.P. Veien K.T. Christiansen E.H. Jensen S.E. Modrau I. et al.Fractional flow reserve versus angiographically-guided coronary artery bypass grafting.J Am Coll Cardiol. 2018; 72: 2732-2743Crossref PubMed Scopus (52) Google Scholar,23Toth G.G. De Bruyne B. Kala P. Ribichini F.L. Casselman F. Ramos R. et al.Graft patency after FFR-guided versus angiography-guided coronary artery bypass grafting: the GRAFFITI trial.EuroIntervention. 2019; 15: e999-e1005Crossref PubMed Scopus (40) Google Scholar From a “surgical collateralization perspective,” the omission of targets would result in less protection against future infarctions.1Doenst T. Haverich A. Serruys P. Bonow R.O. Kappetein P. Falk V. et al.PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.J Am Coll Cardiol. 2019; 73: 964-976Crossref PubMed Scopus (136) Google Scholar In other words, more open grafts should result in more protection against myocardial infarction. Assessing the distances from infarction sites to graft insertions (Figure 2) underscores this suggestion. It is further supported by coronary computed tomography investigations in patients after CABG.24Small G.R. Yam Y. Chen L L. Ahmed O. Al-Mallah M. Berman D.S. et al.Prognostic assessment of coronary artery bypass patients with 64-slice computed tomography angiography: anatomical information is incremental to clinical risk prediction.J Am Coll Cardiol. 2011; 58: 2389-2395Crossref PubMed Scopus (34) Google Scholar,25Chow B.J. Wells G.A. Chen L. Yam Y. Galiwango P. Abraham A. et al.Prognostic value of 64-slice cardiac computed tomography severity of coronary artery disease, coronary atherosclerosis, and left ventricular ejection fraction.J Am Coll Cardiol. 2010; 55: 1017-1028Crossref PubMed Scopus (221) Google Scholar These authors found that the number of unprotected coronary territories (ie, myocardial regions at risk not supplied with an open bypass graft) correlated with prognosis. Although these findings may argue against using FFR for target selection, FFR assessment may still be useful in CABG. High FFR values reflect a higher risk of graft occlusion, but all evidence thus far supports that graft occlusions in the context of high FFR values are not associated with clinical events. The occlusions appear to occur silently.21Thuesen A.L. Riber L.P. Veien K.T. Christiansen E.H. Jensen S.E. Modrau I. et al.Fractional flow reserve versus angiographically-guided coronary artery bypass grafting.J Am Coll Cardiol. 2018; 72: 2732-2743Crossref PubMed Scopus (52) Google Scholar, 22Fournier S. Toth G.G. De Bruyne B. Johnson N.P. Ciccarelli G. Xaplanteris P. et al.Six-year follow-up of fractional flow reserve-guided versus angiography-guided coronary artery bypass graft surgery.Circ Cardiovasc Interv. 2018; 11: e006368Crossref PubMed Scopus (58) Google Scholar, 23Toth G.G. De Bruyne B. Kala P. Ribichini F.L. Casselman F. Ramos R. et al.Graft patency after FFR-guided versus angiography-guided coronary artery bypass grafting: the GRAFFITI trial.EuroIntervention. 2019; 15: e999-e1005Crossref PubMed Scopus (40) Google Scholar,26Glineur D. Grau J.B. Etienne P.Y. Benedetto U. Fortier J.H. Papadatos S. et al.Impact of preoperative fractional flow reserve on arterial bypass graft anastomotic function: the IMPAG trial.Eur Heart J. 2019; 40: 2421-2428Crossref PubMed Scopus (50) Google Scholar,27Glineur 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 (60) Google Scholar However, the occlusion risk appears to depend on the type of graft (vein or artery) and the technical construction of the grafts (single vs sequential grafts).26Glineur D. Grau J.B. Etienne P.Y. Benedetto U. Fortier J.H. Papadatos S. et al.Impact of preoperative fractional flow reserve on arterial bypass graft anastomotic function: the IMPAG trial.Eur Heart J. 2019; 40: 2421-2428Crossref PubMed Scopus (50) Google Scholar,27Glineur 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 (60) Google Scholar Therefore, FFR assessment may be helpful in determining the best strategy for obtaining the highest rate of long-term patent grafts.4.Better stents will probably not lead to better survival One of the typical arguments used for explaining the lack of prognostic impact of PCI has been the use of older stents. However, on the basis of the recognitions listed, stent type should not make a difference in survival. Newer-generation drug-eluting stents have successfully reduced the rate of re-revascularizations,3Neumann F.J. Sousa-Uva M. Ahlsson A. Alfonso F. Banning A.P. Benedetto U. et al.2018 ESC/EACTS guidelines on myocardial revascularization.Eur Heart J. 2019; 40: 87-165Crossref PubMed Scopus (2910) Google Scholar,28Bonaa K.H. Mannsverk J. Wiseth R. Aaberge L. Myreng Y. Nygard O. et al.Drug-eluting or bare-metal stents for coronary artery disease.N Engl J Med. 2016; 375: 1242-1252Crossref PubMed Scopus (344) Google Scholar but they never provided a survival advantage over bare metal (older) stents or medical therapy.1Doenst T. Haverich A. Serruys P. Bonow R.O. Kappetein P. Falk V. et al.PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.J Am Coll Cardiol. 2019; 73: 964-976Crossref PubMed Scopus (136) Google Scholar,6Stergiopoulos K. Boden W.E. Hartigan P. Möbius-Winkler S. Hambrecht R. Hueb W. et al.Percutaneous coronary intervention outcomes in patients with stable obstructive coronary artery disease and myocardial ischemia: a collaborative meta-analysis of contemporary randomized clinical trials.JAMA Intern Med. 2014; 174: 232-240Crossref PubMed Scopus (214) Google Scholar,7Boden W.E. O'Rourke R.A. Teo K.K. Hartigan P.M. Maron D.J. Kostuk W.J. et al.Optimal medical therapy with or without PCI for stable coronary disease.N Engl J Med. 2007; 356: 1503-1516Crossref PubMed Scopus (3574) Google Scholar,9Maron D.J. Hochman J.S. Reynolds H.R. Bangalore S. O'Brien S.M. Boden W.E. et al.Initial invasive or conservative strategy for stable coronary disease.N Engl J Med. 2020; 382: 1395-1407Crossref PubMed Scopus (808) Google Scholar,28Bonaa K.H. Mannsverk J. Wiseth R. Aaberge L. Myreng Y. Nygard O. et al.Drug-eluting or bare-metal stents for coronary artery disease.N Engl J Med. 2016; 375: 1242-1252Crossref PubMed Scopus (344) Google Scholar On the basis of the considerations that contemporary PCI in chronic coronary syndrome only addresses the minority of infarct-causing lesions (Figure 3), it is statistically challenging to detect an infarct-preventative effect of PCI in clinical trials. In addition, even the finding of fewer myocardial infarctions with PCI in some trials may not translate into a survival impact.18Xaplanteris P. Fournier S. Pijls N.H.J. Fearon W.F. Barbato E. Tonino P.A.L. et al.Five-year outcomes with PCI guided by fractional flow reserve.N Engl J Med. 2018; 379: 250-259Crossref PubMed Scopus (408) Google Scholar,29Mehta S.R. Wood D.A. Storey R.F. Mehran R. Bainey K.R. Nguyen H. et al.Complete revascularization with multivessel PCI for myocardial infarction.N Engl J Med. 2019; 381: 1411-1421Crossref PubMed Scopus (311) Google Scholar Thus, the infarct-preventative potential with CABG appears greater (Figure 2) and may additionally be supported by the consequent use of the left internal thoracic artery to the left anterior descending artery, a graft that has excellent long-term patency to a vessel that supplies the largest part of the myocardium and in which occlusions likely cause deadly infarctions.30Bates E.R. Revisiting reperfusion therapy in inferior myocardial infarction.J Am Coll Cardiol. 1997; 30: 334-342Crossref PubMed Scopus (47) Google Scholar Any potential prognostic effect of PCI over medical therapy (as suggested by a recent network meta-analysis31Windecker S. Stortecky S. Stefanini G.G. da Costa B.R. Rutjes A.W. Di Nisio M. et al.Revascularisation versus medical treatment in patients with stable coronary artery disease: network meta-analysis.BMJ. 2014; 348: g3859Crossref PubMed Scopus (261) Google Scholar) can again be associated with a lower incidence of myocardial infarction in this group.1Doenst T. Haverich A. Serruys P. Bonow R.O. Kappetein P. Falk V. et al.PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.J Am Coll Cardiol. 2019; 73: 964-976Crossref PubMed Scopus (136) Google Scholar Thus, the link between infarct prevention and prognosis may be prevailing for PCI; only the chance to achieve it is smaller than with CABG. This notion may also explain our possibly conflicting report in which we demonstrate a survival benefit for PCI in a retrospective propensity-matched comparison with medical therapy once the amount of single photon emission computed tomography detected ischemia exceeded 15%.32Miller R.J.H. Bonow R.O. Gransar H. Park R. Slomka P.J. Friedman J.D. et al.Percutaneous or surgical revascularization is associated with survival benefit in stable coronary artery disease.Eur Heart J Cardiovasc Imaging. 2020; 21: 961-970Crossref PubMed Scopus (10) Google Scholar This study is currently the only report demonstrating a survival impact for isolated PCI (not mixed with CABG) in chronic coronary syndromes. However, we were not able to provide information on CAD severity and the incidence of myocardial infarctions. Although our data in this analysis32Miller R.J.H. Bonow R.O. Gransar H. Park R. Slomka P.J. Friedman J.D. et al.Percutaneous or surgical revascularization is associated with survival benefit in stable coronary artery disease.Eur Heart J Cardiovasc Imaging. 2020; 21: 961-970Crossref PubMed Scopus (10) Google Scholar are from an all-comers registry and likely contain many patients who are not necessarily part of generally highly selected randomized trials, we cannot exclude the possibility that the survival effect again is mediated by infarct prevention. Nevertheless, the data may also serve to support a prognostic impact of revascularization (ie, the resupply of blood to chronically ischemic territories), but considering the vast body of evidence in this field,1Doenst T. Haverich A. Serruys P. Bonow R.O. Kappetein P. Falk V. et al.PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.J Am Coll Cardiol. 2019; 73: 964-976Crossref PubMed Scopus (136) Google Scholar,3Neumann F.J. Sousa-Uva M. Ahlsson A. Alfonso F. Banning A.P. Benedetto U. et al.2018 ESC/EACTS guidelines on myocardial revascularization.Eur Heart J. 2019; 40: 87-165Crossref PubMed Scopus (2910) Google Scholar this effect would appear to be smaller for prognosis than the one preventing new infarctions.5.Medical therapy is complementary to CABG Medical therapy has made tremendous progress over time. Recent reports suggest that the main effects are again mediated though infarct prevention mainly through cholesterol-lowering strategies (and not so much by beta-blockers).33Bjorklund E. Nielsen S.J. Hansson E.C. Karlsson M. Wallinder A. Martinsson A. et al.Secondary prevention medications after coronary artery bypass grafting and long-term survival: a population-based longitudinal study from the SWEDEHEART registry.Eur Heart J. 2020; 41: 1653-1661Crossref PubMed Scopus (33) Google Scholar,34Newby D.E. Adamson P.D. Berry C. Boon N.A. Dweck M.R. Flather M. et al.Coronary CT angiography and 5-year risk of myocardial infarction.N Engl J Med. 2018; 379: 924-933Crossref PubMed Scopus (556) Google Scholar The effects are complementary as illustrated by the survival advantage of CABG over medical therapy in the Surgical Treatment of IsChemic Heart Failure trial.11Velazquez E.J. Lee K.L. Jones R.H. Al-Khalidi H.R. Hill J.A. Panza J.A. et al.Coronary-artery bypass surgery in patients with ischemic cardiomyopathy.N Engl J Med. 2016; 374: 1511-1520Crossref PubMed Scopus (488) Google Scholar Considering that patients after CABG are often less well medically treated compared with patients after PCI,35Pinho-Gomes A.C. Azevedo L. Ahn J.M. Park S.J. Hamza T.H. Farkouh M.E. et al.Compliance with guideline-directed medical therapy in contemporary coronary revascularization trials.J Am Coll Cardiol. 2018; 71: 591-602Crossref PubMed Scopus (66) Google Scholar it appears important for surgeons to stress this point. Optimal medical therapy in patients after CABG is likely to further improve CABG outcomes.6.CAD assessment must change Despite all criticism raised in this article regarding our understanding of the presumed mechanisms and our terminology for CABG and PCI, the current guidelines provide a good practical guide for decision-making. This is specifically true when all operative and interventional risks as well as long-term aspects such as graft patency and stent complications are considered. However, our ability to identify infarct-prone lesions is still wanting. Although new interventional techniques such as intravascular ultrasound, near-infrared spectroscopy, and OCT may provide new ways to identify infarct-prone lesions,3Neumann F.J. Sousa-Uva M. Ahlsson A. Alfonso F. Banning A.P. Benedetto U. et al.2018 ESC/EACTS guidelines on myocardial revascularization.Eur Heart J. 2019; 40: 87-165Crossref PubMed Scopus (2910) Google Scholar,36Waksman R. Di Mario C. Torguson R. Ali Z.A. Singh V. Skinner W.H. et al.Identification of patients and plaques vulnerable to future coronary events with near-infrared spectroscopy intravascular ultrasound imaging: a prospective, cohort study.Lancet. 2019; 394: 1629-1637Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar the advent of coronary computed tomography, computed tomography FFR,37Collet C. Onuma Y. Andreini D. Sonck J. Pompilio G. Mushtaq S. et al.Coronary computed tomography angiography for heart team decision-making in multivessel coronary artery disease.Eur Heart J. 2018; 39: 3689-3698PubMed Google Scholar and risk scores such as the Duke CAD score38Liao L. Kong D.F. Shaw L.K. Sketch Jr., M.H. Milano C.A. Lee K.L. et al.A new anatomic score for prognosis after cardiac catheterization in patients with previous bypass surgery.J Am Coll Cardiol. 2005; 46: 1684-1692Crossref PubMed Scopus (39) Google Scholar or the Leaman score1Doenst T. Haverich A. Serruys P. Bonow R.O. Kappetein P. Falk V. et al.PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.J Am Coll Cardiol. 2019; 73: 964-976Crossref PubMed Scopus (136) Google Scholar,3Neumann F.J. Sousa-Uva M. Ahlsson A. Alfonso F. Banning A.P. Benedetto U. et al.2018 ESC/EACTS guidelines on myocardial revascularization.Eur Heart J. 2019; 40: 87-165Crossref PubMed Scopus (2910) Google Scholar,37Collet C. Onuma Y. Andreini D. Sonck J. Pompilio G. Mushtaq S. et al.Coronary computed tomography angiography for heart team decision-making in multivessel coronary artery disease.Eur Heart J. 2018; 39: 3689-3698PubMed Google Scholar may be attractive noninvasive diagnostic tools that allow for better decision-making in the heart team of the future. Coronary computed tomography–derived approaches identifying unprotected coronary territories at risk correlate with prognosis in patients after CABG.24Small G.R. Yam Y. Chen L L. Ahmed O. Al-Mallah M. Berman D.S. et al.Prognostic assessment of coronary artery bypass patients with 64-slice computed tomography angiography: anatomical information is incremental to clinical risk prediction.J Am Coll Cardiol. 2011; 58: 2389-2395Crossref PubMed Scopus (34) Google Scholar,25Chow B.J. Wells G.A. Chen L. Yam Y. Galiwango P. Abraham A. et al.Prognostic value of 64-slice cardiac computed tomography severity of coronary artery disease, coronary atherosclerosis, and left ventricular ejection fraction.J Am Coll Cardiol. 2010; 55: 1017-1028Crossref PubMed Scopus (221) Google Scholar CABG provides a comprehensive treatment of CAD by revascularization of ischemic myocardium plus surgical collateralization for infarct prevention by placing a bypass graft distal to the majority of CAD lesions. Stenosed vessels often have more lesions than the severe “index” stenosis, and the majority of infarctions are caused by nonflow-limiting lesions. Because contemporary PCI is limited to the exclusive treatment of flow-limiting lesions, its infarct-preventative effect appears limited. However, improving prognosis in chronic coronary syndromes appears to be linked to infarct prevention (eg, by surgical collateralization) rather than revascularization of chronic ischemic myocardium. Thus, CABG provides superior prognostic outcomes compared with PCI in chronic coronary syndromes because of its collateralization effect. As a consequence, “myocardial revascularization” may not be an appropriate term for summarizing PCI and CABG.