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2018 ESC/EACTS Guidelines on myocardial revascularization

2018 ESC/EACTS Guidelines on myocardial revascularization Acute coronary syndromes, Antithrombotic therapy, Bare-metal stents, Coronary artery bypass grafting, Coronary artery disease, Drug-eluting stents, Guidelines, Heart Team, Myocardial infarction, Myocardial ischaemia, Myocardial revascularization, Medical therapy, Percutaneous coronary intervention, Recommendation, Revascularization, Risk stratification, Stents, Stable angina, Stable coronary artery disease, ST-segment elevation myocardial infarction, SYNTAX score The Task Force on myocardial revascularization of the European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association for Percutaneous Cardiovascular Interventions (EAPCI) TABLE OF CONTENTS ABBREVIATIONS AND ACRONYMS 4 1. PREAMBLE 7 2. INTRODUCTION 8  2.1 What is new in the 2018 Guidelines? 9 3. DIAGNOSTIC TOOLS TO GUIDE MYOCARDIAL REVASCULARIZATION 10  3.1 Non-invasive diagnostic tools 10   3.1.1 Assessment of myocardial ischaemia 10   3.1.2 Assessment of myocardial viability in patients with heart failure and coronary artery disease 10  3.2 Invasive diagnostic tools 10   3.2.1 Pressure-derived fractional flow reserve 10     3.2.1.1 Use of fractional flow reserve in patients with intermediate-grade coronary stenosis including left main stenosis 11     3.2.1.2 Use of fractional flow reserve to identify lesions requiring revascularization in patients with multivessel coronary artery disease undergoing percutaneous coronary intervention 11     3.2.1.3 Fractional flow reserve-guided management vs medical therapy in patients with coronary artery disease 11   3.2.2 Other pressure-derived indices 11   3.2.3 Use of fractional flow reserve and pressure-derived indices in patients with severe aortic stenosis 12   3.2.4 Use of intravascular imaging for diagnostic assessment of stenosis 12  3.3 Gaps in the evidence 12 4. PROCESS FOR DECISION-MAKING AND PATIENT INFORMATION 12  4.1 Patient information and informed consent 12  4.2 Multidisciplinary decision-making (Heart Team) 13  4.3 Timing of revascularization 13 5. REVASCULARIZATION FOR STABLE CORONARY ARTERY DISEASE 15  5.1 Rationale for revascularization 15  5.2 Evidence basis for revascularization 15   5.2.1 Revascularization with the use of percutaneous coronary intervention 15   5.2.2 Revascularization with the use of coronary artery bypass grafting 16  5.3 Percutaneous coronary intervention vs coronary artery bypass grafting 16   5.3.1 Criteria for decision making 16     5.3.1.1 Predicted surgical mortality 18     5.3.1.2 Anatomical complexity of coronary artery disease 18     5.3.1.3 Completeness of revascularization 20   5.3.2 Isolated proximal left anterior descending coronary artery disease 21   5.3.3 Left main coronary artery disease 21   5.3.4 Multivessel coronary artery disease 23  5.4 Gaps in the evidence 23 6. REVASCULARIZATION IN NON-ST-ELEVATION ACUTE CORONARY SYNDROME 24  6.1 Early invasive vs conservative strategy 24  6.2 Timing of angiography and intervention 24  6.3 Type of revascularization 24   6.3.1 Percutaneous coronary intervention 24     6.3.1.1 Technical aspects 24     6.3.1.2 Revascularization strategies and outcomes 24   6.3.2 Coronary artery bypass grafting 24   6.3.3 Percutaneous coronary intervention vs coronary artery bypass grafting 25  6.4 Gaps in the evidence 25 7. REVASCULARIZATION IN ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION 26  7.1 Time delays 26  7.2 Selection of reperfusion strategy 26  7.3 Primary percutaneous coronary intervention 27  7.4 Percutaneous coronary intervention after thrombolysis and in patients with late diagnosis 27  7.5 Gaps in the evidence 28 8. MYOCARDIAL REVASCULARIZATION IN PATIENTS WITH HEART FAILURE 29  8.1 Chronic heart failure 29   8.1.1 Recommendations for myocardial revascularization in patients with chronic heart failure 29   8.1.2 Ventricular reconstruction and aneurysm resection 29  8.2 Acute heart failure and cardiogenic shock 30   8.2.1 Revascularization 30   8.2.2 Mechanical circulatory support 30     8.2.2.1 Intra-aortic balloon pump 30     8.2.2.2 Extracorporeal membrane oxygenation 30     8.2.2.3 Percutaneous left ventricular assist devices 30     8.2.2.4 Surgically implanted left ventricular assist devices 30  8.3 Gaps in the evidence 31 9. REVASCULARIZATION IN PATIENTS WITH DIABETES 32  9.1 Evidence for myocardial revascularization 32  9.2 Type of myocardial revascularization 32   9.2.1. Randomized clinical trials 32   9.2.2 Meta-analysis of coronary artery bypass grafting vs percutaneous coronary intervention in patients with diabetes 32  9.3 Revascularization with the use of percutaneous coronary intervention 33  9.4 Antithrombotic pharmacotherapy 33  9.5 Metformin 33  9.6 Gaps in the evidence 33 10. REVASCULARIZATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE 33  10.1 Evidence base for revascularization and recommendations 33  10.2 Prevention of contrast-induced nephropathy 33  10.3 Gaps in the evidence 33 11. REVASCULARIZATION IN PATIENTS REQUIRING VALVE INTERVENTIONS 34  11.1 Primary indication for valve interventions 34  11.2 Primary indication for myocardial revascularization 34    11.2.1 Aortic valve disease 34    11.2.2 Mitral valve disease 34  11.3 Gaps in the evidence 35 12. ASSOCIATED PERIPHERAL ARTERY DISEASES 35  12.1 Prevention of stroke associated with carotid artery disease and myocardial revascularization 35  12.2 Associated coronary and peripheral artery diseases 36 13. REPEAT REVASCULARIZATION 36  13.1 Early graft failure 36  13.2 Acute percutaneous coronary intervention failure 37  13.3 Disease progression and late graft failure 37    13.3.1 Redo coronary artery bypass grafting or percutaneous coronary intervention 37    13.3.2 Percutaneous coronary intervention for saphenous vein graft lesions 37  13.4 Repeat percutaneous coronary intervention 37    13.4.1 Restenosis 37    13.4.2 Disease progression 38    13.4.3 Stent thrombosis 38 14. ARRHYTHMIAS 39  14.1 Ventricular arrhythmias 39    14.1.1 Revascularization for the prevention of sudden cardiac death in patients with stable coronary artery disease and reduced left ventricular function 39    14.1.2 Revascularization for the treatment of electrical storm 39    14.1.3 Revascularization after out-of-hospital cardiac arrest 40  14.2 Atrial arrhythmias 40    14.2.1 Atrial fibrillation complicating percutaneous coronary intervention 40    14.2.2 Atrial fibrillation complicating coronary artery bypass grafting 40    14.2.3 Postoperative atrial fibrillation and stroke risk 40  14.3 Gaps in the evidence 41 15. PROCEDURAL ASPECTS OF CORONARY ARTERY BYPASS GRAFTING 41  15.1 Surgical techniques 41    15.1.1 Completeness of revascularization 41    15.1.2 Conduit selection 41    15.1.3 Mammary artery harvesting 42    15.1.4 Radial artery harvesting 42    15.1.5 Saphenous vein harvesting 42    15.1.6 Construction of central anastomosis 42    15.1.7 Intraoperative quality control 42    15.1.8 On-pump and off-pump procedures 42    15.1.9 Minimally invasive and hybrid procedures 42  15.2 Reporting perioperative outcomes 43  15.3 Gaps in the evidence 43 16. PROCEDURAL ASPECTS OF PERCUTANEOUS CORONARY INTERVENTION 44  16.1 Percutaneous coronary intervention devices 44    16.1.1 Balloon angioplasty 44    16.1.2 Choice of coronary stents ABBREVIATIONS AND ACRONYMS 7 1. PREAMBLE 10 2. INTRODUCTION 11  2.1 What is new in the 2018 Guidelines? 12 3. DIAGNOSTIC TOOLS TO GUIDE MYOCARDIAL REVASCULARIZATION 13  3.1 Non-invasive diagnostic tools 13   3.1.1 Assessment of myocardial ischaemia 13   3.1.2 Assessment of myocardial viability in patients with heart failure and coronary artery disease 13  3.2 Invasive diagnostic tools 13   3.2.1 Pressure-derived fractional flow reserve 13     3.2.1.1 Use of fractional flow reserve in patients with intermediate-grade coronary stenosis including left main stenosis 13     3.2.1.2 Use of fractional flow reserve to identify lesions requiring revascularization in patients with multivessel coronary artery disease undergoing percutaneous coronary intervention 14     3.2.1.3 Fractional flow reserve-guided management vs medical therapy in patients with coronary artery disease 14   3.2.2 Other pressure-derived indices 14   3.2.3 Use of fractional flow reserve and pressure-derived indices in patients with severe aortic stenosis 15   3.2.4 Use of intravascular imaging for diagnostic assessment of stenosis 15  3.3 Gaps in the evidence 15 4. PROCESS FOR DECISION-MAKING AND PATIENT INFORMATION 15  4.1 Patient information and informed consent 15  4.2 Multidisciplinary decision-making (Heart Team) 16  4.3 Timing of revascularization 16 5. REVASCULARIZATION FOR STABLE CORONARY ARTERY DISEASE 18  5.1 Rationale for revascularization 18  5.2 Evidence basis for revascularization 18   5.2.1 Revascularization with the use of percutaneous coronary intervention 18   5.2.2 Revascularization with the use of coronary artery bypass grafting 19  5.3 Percutaneous coronary intervention vs coronary artery bypass grafting 19   5.3.1 Criteria for decision making 19     5.3.1.1 Predicted surgical mortality 21     5.3.1.2 Anatomical complexity of coronary artery disease 21     5.3.1.3 Completeness of revascularization 23   5.3.2 Isolated proximal left anterior descending coronary artery disease 24   5.3.3 Left main coronary artery disease 24   5.3.4 Multivessel coronary artery disease 26  5.4 Gaps in the evidence 26 6. REVASCULARIZATION IN NON-ST-ELEVATION ACUTE CORONARY SYNDROME 27  6.1 Early invasive vs conservative strategy 27  6.2 Timing of angiography and intervention 27  6.3 Type of revascularization 27   6.3.1 Percutaneous coronary intervention 27     6.3.1.1 Technical aspects 27     6.3.1.2 Revascularization strategies and outcomes 27   6.3.2 Coronary artery bypass grafting 27   6.3.3 Percutaneous coronary intervention vs coronary artery bypass grafting 27  6.4 Gaps in the evidence 28 7. REVASCULARIZATION IN ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION 29  7.1 Time delays 29  7.2 Selection of reperfusion strategy 29  7.3 Primary percutaneous coronary intervention 30  7.4 Percutaneous coronary intervention after thrombolysis and in patients with late diagnosis 30  7.5 Gaps in the evidence 31 8. MYOCARDIAL REVASCULARIZATION IN PATIENTS WITH HEART FAILURE 32  8.1 Chronic heart failure 32   8.1.1 Recommendations for myocardial revascularization in patients with chronic heart failure 32   8.1.2 Ventricular reconstruction and aneurysm resection 32  8.2 Acute heart failure and cardiogenic shock 33   8.2.1 Revascularization 33   8.2.2 Mechanical circulatory support 33     8.2.2.1 Intra-aortic balloon pump 33     8.2.2.2 Extracorporeal membrane oxygenation 33     8.2.2.3 Percutaneous left ventricular assist devices 33     8.2.2.4 Surgically implanted left ventricular assist devices 33  8.3 Gaps in the evidence 34 9. REVASCULARIZATION IN PATIENTS WITH DIABETES 35  9.1 Evidence for myocardial revascularization 35  9.2 Type of myocardial revascularization 35   9.2.1. Randomized clinical trials 35   9.2.2 Meta-analysis of coronary artery bypass grafting vs percutaneous coronary intervention in patients with diabetes 35  9.3 Revascularization with the use of percutaneous coronary intervention 36  9.4 Antithrombotic pharmacotherapy 36  9.5 Metformin 36  9.6 Gaps in the evidence 36 10. REVASCULARIZATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE 36  10.1 Evidence base for revascularization and recommendations 36  10.2 Prevention of contrast-induced nephropathy 36  10.3 Gaps in the evidence 36 11. REVASCULARIZATION IN PATIENTS REQUIRING VALVE INTERVENTIONS 37  11.1 Primary indication for valve interventions 37  11.2 Primary indication for myocardial revascularization 37    11.2.1 Aortic valve disease 37    11.2.2 Mitral valve disease 37  11.3 Gaps in the evidence 38 12. ASSOCIATED PERIPHERAL ARTERY DISEASES 38  12.1 Prevention of stroke associated with carotid artery disease and myocardial revascularization 38  12.2 Associated coronary and peripheral artery diseases 39 13. REPEAT REVASCULARIZATION 39  13.1 Early graft failure 39  13.2 Acute percutaneous coronary intervention failure 40  13.3 Disease progression and late graft failure 40    13.3.1 Redo coronary artery bypass grafting or percutaneous coronary intervention 40    13.3.2 Percutaneous coronary intervention for saphenous vein graft lesions 40  13.4 Repeat percutaneous coronary intervention 40    13.4.1 Restenosis 40    13.4.2 Disease progression 41    13.4.3 Stent thrombosis 41 14. ARRHYTHMIAS 42  14.1 Ventricular arrhythmias 42    14.1.1 Revascularization for the prevention of sudden cardiac death in patients with stable coronary artery disease and reduced left ventricular function 42    14.1.2 Revascularization for the treatment of electrical storm 42    14.1.3 Revascularization after out-of-hospital cardiac arrest 43  14.2 Atrial arrhythmias 43    14.2.1 Atrial fibrillation complicating percutaneous coronary intervention 43    14.2.2 Atrial fibrillation complicating coronary artery bypass grafting 43    14.2.3 Postoperative atrial fibrillation and stroke risk 43  14.3 Gaps in the evidence 44 15. PROCEDURAL ASPECTS OF CORONARY ARTERY BYPASS GRAFTING 44  15.1 Surgical techniques 44    15.1.1 Completeness of revascularization 44    15.1.2 Conduit selection 44    15.1.3 Mammary artery harvesting 45    15.1.4 Radial artery harvesting 45    15.1.5 Saphenous vein harvesting 45    15.1.6 Construction of central anastomosis 45    15.1.7 Intraoperative quality control 45    15.1.8 On-pump and off-pump procedures 45    15.1.9 Minimally invasive and hybrid procedures 45  15.2 Reporting perioperative outcomes 46  15.3 Gaps in the evidence 46 16. PROCEDURAL ASPECTS OF PERCUTANEOUS CORONARY INTERVENTION 47  16.1 Percutaneous coronary intervention devices 47    16.1.1 Balloon angioplasty 47    16.1.2 Choice of coronary stents 47    16.1.3 Bioresorbable scaffolds 48    16.1.4 Drug-coated balloons 48    16.1.5 Devices for lesion preparation 48  16.2 Invasive imaging tools for procedural guidance 48    16.2.1 Intravascular ultrasound 48    16.2.2 Optical coherence tomography 49  16.3 Specific lesion subsets 49    16.3.1 Bifurcation stenosis 49    16.3.2 Chronic total coronary occlusion 49    16.3.3 Ostial lesions 50  16.4 Vascular access 50 17. ANTITHROMBOTIC TREATMENTS 51  17.1 Percutaneous coronary intervention in stable coronary artery disease 52    17.1.1 Choice of treatment and pre-treatment 52    17.1.2 Peri-interventional treatment 52    17.1.3 Post-interventional and maintenance treatment 52  17.2 Non-ST-segment elevation acute coronary syndrome 54    17.2.1 Choice of treatment and pre-treatment 54    17.2.2 Peri-interventional treatment 54    17.2.3 Post-interventional and maintenance treatment 55  17.3 ST-segment elevation myocardial infarction 57    17.3.1 Choice of treatment and pre-treatment 57    17.3.2 Peri-interventional treatment 57    17.3.3 Post-interventional and maintenance treatment 58  17.4 Coronary artery bypass grafting 58  17.5 Special conditions 59    17.5.1 Antithrombotic therapy after percutaneous coronary intervention in patients requiring oral anticoagulation 59    17.5.2 Revascularization in patients with renal failure 61    17.5.3 Monitoring of antiplatelet drugs (platelet function testing and genotyping) 61    17.5.4 Surgery in patients on dual antiplatelet therapy 61  17.6 Gaps in the evidence 61 18. VOLUME–OUTCOME RELATIONSHIP FOR REVASCULARIZATION PROCEDURES 62  18.1 Coronary artery bypass grafting 62  18.2 Percutaneous coronary intervention 62  18.3 Training in cardiac surgery and interventional cardiology for myocardial revascularization 62 19. MEDICAL THERAPY, SECONDARY PREVENTION, AND STRATEGIES FOR FOLLOW-UP 63  19.1 Gaps in the evidence 64 20. KEY MESSAGES 64 21. EVIDENCE-BASED ‘TO DO’ AND ‘NOT TO DO’ MESSAGES FROM THE GUIDELINES 64 22. APPENDIX 68 23. REFERENCES 68 Abbreviations and acronyms Abbreviations and acronyms ABC Age, Biomarkers, Clinical History ABSORB II A Bioresorbable Everolimus-Eluting Scaffold Versus a Metallic Everolimus-Eluting Stent II AIDA Amsterdam Investigator-Initiated Absorb Strategy All-Comers ACCOAST Comparison of Prasugrel at the Time of Percutaneous Coronary Intervention or as Pretreatment at the Time of Diagnosis in Patients with Non-ST Elevation Myocardial Infarction ACS Acute coronary syndrome ACUITY Acute Catheterization and Urgent Intervention Triage strategy ADAPT-DES Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents AF Atrial fibrillation ALPHEUS Assessment of Loading With the P2Y12-Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting AMI Acute myocardial infarction AMACING A Maastricht Contrast-Induced Nephropathy Guideline ANTARCTIC Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome ARCTIC Assessment by a Double Randomization of a Conventional Antiplatelet Strategy versus a Monitoring-guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption versus Continuation One Year after Stenting ART Arterial Revascularization Trial AS Aortic stenosis ASE American Society of Echocardiography ATLANTIC Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST-Elevation Myocardial Infarction to Open the Coronary Artery ATLAS-ACS 2–TIMI 51 Anti-Xa Therapy to Lower cardiovascular events in Addition to Standard therapy in subjects with Acute Coronary Syndrome–Thrombolysis In Myocardial Infarction 51 ATOLL Acute STEMI Treated with primary PCI and intravenous enoxaparin Or UFH to Lower ischaemic and bleeding events at short- and Long-term follow-up AWESOME Angina With Extremely Serious Operative Mortality Evaluation BARC Bleeding Academic Research Consortium BARI-2D Bypass Angioplasty Revascularization Investigation 2 Diabetes BES Biolimus-eluting stent BEST Randomised Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease b.i.d. Bis in die (twice daily) BIMA Bilateral internal mammary artery BMS Bare-metal stent BRAVE Bavarian Reperfusion Alternatives Evaluation BRS Bioresorbable scaffolds BVS Bioresorbable vascular scaffold CABG Coronary artery bypass grafting CAD Coronary artery disease CARDia Coronary Artery Revascularization in Diabetes CCS Canadian Cardiovascular Society CEA Carotid endarterectomy CHA2DS2- VASc Congestive heart failure, Hypertension, Age ≥75 [Doubled], Diabetes mellitus, Prior stroke or transient ischaemic attack or thromboembolism [Doubled] – Vascular disease, Age 65–74 and Sex category [Female] CHAMPION Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition CI Confidence interval CIN Contrast-induced nephropathy CKD Chronic kidney disease CMR Cardiac magnetic resonance COMPASS Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease COURAGE Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation CPG ESC Committee for Practice Guidelines CT Computed tomography CT-FFR CT-derived fractional flow reserve CTO Chronic total occlusion CTSN Cardiothoracic Surgical Trial Network CULPRIT- SHOCK Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock CVA Cerebrovascular accident CvLPRIT Complete Versus Lesion-Only Primary PCI Trial DANAMI 3-DEFER The Third DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction: DEFERred stent implantation in connection with primary PCI DANAMI-3− PRIMULTI The Third DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction: PRImary PCI in MULTIvessel Disease DAPT Dual antiplatelet therapy DCB Drug-coated balloon DEFINE-FLAIR Define Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularization DES Drug-eluting stents DUS Duplex ultrasound EACTS European Association for Cardio-Thoracic Surgery EAPCI European Association for Percutaneous Cardiovascular Interventions EBC TWO European Bifurcation Coronary TWO ECG Electrocardiogram ECLS Extracorporeal life support ECMO Extracorporeal membrane oxygenation EES Everolimus-eluting stent EF Ejection fraction EMS Emergency medical service EROA Effective regurgitant orifice area ENTRUST- AF-PCI Evaluation of the safety and efficacy of an edoxaban-based antithrombotic regimen in patients with atrial fibrillation following successful percutaneous coronary intervention ESC European Society of Cardiology EUROCTO Randomized Multicentre Trial to Compare Revascularization With Optimal Medical Therapy for the Treatment of Chronic Total Occlusions EuroSCORE European System for Cardiac Operative Risk Evaluation EUROMAX European Ambulance Acute Coronary Syndrome Angiography EXCEL Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization FAME Fractional Flow Reserve versus Angiography for Multivessel Evaluation FDG-PET Fluorodeoxyglucose positron emission tomography FFR Fractional flow reserve FITT-STEMI Feedback Intervention and Treatment Times in ST-Elevation Myocardial Infarction FMC First medical contact FREEDOM Future Revascularization Evaluation in Patients with Diabetes Mellitus GLOBAL LEADERS Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation GP IIb/IIIa Glycoprotein IIb/IIIa GRAVITAS Gauging Responsiveness with A Verify Now assay-Impact on Thrombosis And Safety HAS-BLED Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol HEAT-PPCI How Effective are Antithrombotic Therapies in primary PCI HF Heart failure HFrEF Heart failure with reduced ejection fraction HORIZONS Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction HPR High platelet reactivity HR Hazard ratio i.v. Intravenous IABP Intra-aortic balloon pump IABP-SHOCK II Intraaortic Balloon Pump in Cardiogenic Shock II Trial ICD Implantable cardioverter defibrillator iwFR Instantaneous wave-free ratio IMA Internal mammary artery IMR Ischaemic mitral regurgitation INR International normalized ratio IRA Infarct-related artery ISAR-CABG Is Drug-Eluting-Stenting Associated with Improved Results in Coronary Artery Bypass Grafts ISAR-REACT Intracoronary Stenting and Antithrombotic Regimen Rapid Early Action for Coronary Treatment ISCHEMIA International Study of Comparative Health Effectiveness With Medical and Invasive Approaches IVUS Intravascular ultrasound imaging LAA Left atrial appendage LAD Left anterior descending LEAD Lower extremity artery disease LGE-CMR Late gadolinium enhancement cardiac magnetic resonance LIMA Left internal mammary artery LM/LMS Left main/left main stem LMWH Low-molecular-weight heparin LPR Low platelet reactivity LV Left ventricle/left ventricular LVAD Left ventricular assist device, LVEF Left ventricular ejection fraction MACCE Major adverse cardiac and cerebrovascular events MACE Major adverse cardiac events MADIT II Multicenter Automatic Defibrillator Implantation Trial II MATRIX Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX MCS Mechanical circulatory support MI Myocardial infarction MINOCA Myocardial infarction with non-obstructive coronary arteries MLA Minimal luminal area MR Mitral regurgitation MSCT Multi-slice computed tomography MT Medical therapy MVD Multivessel coronary artery disease MVO Microvascular obstruction NAC N-acetylcysteine NNT Number needed to treat NOAC Non-vitamin K antagonist oral anticoagulant NOBLE Nordic-Baltic-British Left Main Revascularization Study NSTE-ACS Non-ST-segment elevation acute coronary syndrome NSTEMI Non-ST-segment elevation myocardial infarction NYHA New York Heart Association OAC Oral anticoagulation OASIS-5 Optimal Antiplatelet Strategy for Interventions-5 OCT Optical coherence tomography OR Odds ratio ORBITA Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina PARR-2 PET and Recovery following Revascularization PCI Percutaneous coronary intervention Pd/Pa Distal coronary to aortic pressure PES Paclitaxel-eluting stent PET Positron emission tomography PF Platelet function PIONEER Prevention of bleeding in patients with AF undergoing PCI PLATFORM Prospective LongitudinAl Trial of FFRct: Outcome and Resource Impacts, PLATO Study of Platelet Inhibition and Patient Outcomes pLVAD Percutaneous left ventricular assist device p.o. Per os (orally) POSEIDON Prevention of Contrast Renal Injury with Different Hydration Strategies PPI Proton pump inhibitor PRAGUE-18 Comparison of Prasugrel and Ticagrelor in the Treatment of Acute Myocardial Infarction PRAMI Preventive Angioplasty in Acute Myocardial Infarction PRECISE-DAPT PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Anti Platelet Therapy PRECOMBAT Premier of Randomised Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease PRESERVE Prevention of Serious Adverse Events Following Angiography q.d. Quaque die (once daily) RCT Randomized controlled trial RE-DUAL Randomised Evaluation of Dual Antithrombotic Therapy with Dabigatran versus Triple Therapy with Warfarin in Patients with Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention REMEDIAL II Renal Insufficiency After Contrast Media Administration II REPLACE-2 The Randomised Evaluation in PCI Linking Angiomax to Reduced Clinical Events 2 RIVAL Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes ROMA Randomization of Single vs Multiple Arterial Grafts RR Relative risk SASSICAIA Comparison of Loading Strategies With Antiplatelet Drugs in Patients Undergoing Elective Coronary Intervention SAVR Surgical aortic valve replacement s.c. Subcutaneous SCAD Stable coronary artery disease SCD-HEFT Sudden Cardiac Death in Heart Failure Trial SES Sirolimus-eluting stent SHOCK Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock SIMA Single internal mammary artery SMART-DATE Smart Angioplasty Research Team-safety of 6-month duration of Dual Antiplatelet Therapy after percutaneous coronary intervention in patients with acute coronary syndromes SPECT Single-photon emission computed tomography SR Sinus rhythm STEEPLE Safety and Efficacy of Intravenous Enoxaparin in Elective Percutaneous Coronary Intervention Randomised Evaluation STEMI ST-segment elevation myocardial infarction STICH Surgical Treatment for Ischemic Heart Failure STICHES STICH Extension Study STS Society of Thoracic Surgeons SVG Saphenous vein graft SVR Surgical ventricular reconstruction SWEDEHEART Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies SYNTAX Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery TAP T and protrusion TAVI Transcatheter aortic valve implantation TIA Transient ischaemic attack TIMI Thrombolysis in Myocardial Infarction TLR Target lesion revascularization TOTAL Trial of Routine Aspiration Thrombectomy with PCI versus PCI Alone in Patients with STEMI TRIGGER-PCI Testing platelet Reactivity In patients underGoing elective stent placement on clopidogrel to Guide alternative thErapy with pRasugrel TRITON-TIMI 38 TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel–Thrombolysis In Myocardial Infarction TROPICAL-ACS Testing responsiveness to platelet inhibition on chronic antiplatelet treatment for acute coronary syndromes TVR Target vessel revascularization TWILIGHT Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention UFH Unfractionated heparin VA Veno-arterial VACARDS Veterans Affairs Coronary Artery Revascularization in Diabetes Study VALIDATE Bivalirudin versus Heparin in ST-Segment and Non–ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy VKA Vitamin K antagonist 1. Preamble Clinical practice guidelines summarize and evaluate all available evidence at the time of the writing process on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient with a given condition, taking into account the impact on outcome as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Clinical practice guidelines are no substitutes for textbooks, but complement them, and cover the European Society of Cardiology (ESC) Core Curriculum topics. As such they should help physicians to make decisions in their daily practice. However, final decisions should be individualized by responsible physicians and the patient. A great number of clinical practice guidelines have been issued in recent years both by the ESC as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC and joint society guidelines can be found on the ESC website (https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Guidelines-development/Writing-ESC-Guidelines). These Guidelines represent the official position of the ESC and the European Association for Cardio-Thoracic Surgery (EACTS) on this given topic and will be regularly updated. Members of this Task Force were selected by the ESC and EACTS to represent professionals involved with the medical care of patients with this pathology. Selected experts in the field undertook a comprehensive review of the published evidence for diagnosis, management (including treatment) and/or prevention of a given condition according to the ESC Committee for Practice Guidelines (CPG) and EACTS policy. A critical evaluation of diagnostic and therapeutic procedures was performed including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger populations were included, where data exist. The level of evidence and the strength of recommendation of particular treatment options were weighed and graded according to predefined scales, as outlined in Tables 1 and 2. Table 1: Classes of recommendations Table 1: Classes of recommendations Table 2: Levels of evidence Table 2: Levels of evidence The experts of the writing and reviewing panels completed declarations of interest forms on what might be perceived as real or potential sources of conflicts of interest. These forms were compiled into one file and can be found on the ESC and EACTS websites http://www.escardio.org/guidelines and http://www.eacts.org). Any changes in declarations of interest that arise during the writing period must be notified to the ESC and EACTS and updated. The Task Force received its entire financial support from the ESC and EACTS without any involvement from the healthcare industry. The CPG-ESC and EACTS supervised and coordinated the preparation of these new Guidelines produced by the joint Task Force. These entities are also responsible for the endorsement process of these Guidelines. The ESC/EACTS Guidelines underwent extensive review by a wide panel of relevant external experts. After appropriate revisions it was approved by all the experts involved in the Task Force. The finalized document was approved by the ESC CPG and EACTS for joint publication in the European Heart Journal and the European Journal of Cardio-Thoracic Surgery. The task of developing clinical practice guidelines covers not only the integration of the most recent research, but also the creation of educational tools and implementation programmes for the recommendations. To implement the guidelines, condensed pocket guidelines, summary slides, booklets with essential messages, and an electronic version for digital applications (smartphones, etc.) are produced. These versions are abridged and, thus, if needed, one should always refer to the full text version, which is freely available on the ESC and EACTS websites. The National Societies of the ESC are encouraged to endorse, translate, and implement the ESC Guidelines. Implementation programmes are needed because it has been shown that the outcome of disease may be favourably influenced by the thorough application of clinical recommendations. Surveys and registries are needed to verify that real-life daily practice is in keeping with what is recommended in the guidelines, thus completing the loop between clinical research, writing of guidelines, and implementing them in clinical practice. The guidelines do not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and where appropriate and necessary the patient's guardian or carer. It is also the health professional's responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription. 2. Introduction These Guidelines represent the third time that the ESC and EACTS have brought together cardiologists and cardiac surgeons in a joint Task Force to review the ever-increasing body of evidence, with the mission of drafting balanced, patient-centred practice Guidelines on myocardial revascularization. Summaries of the key changes in comparison with the previous Guidelines are provided in Figures 1 and 2. There is considerable overlap of the current document with other Guidelines, specifically those on stable coronary artery disease, non-ST-elevation myocardial infarction, ST-elevation myocardial infarction, heart failure, valvular heart disease and the Focused Update on Dual Antiplatelet Therapy. Unless supported by new evidence, we followed the recommendations of these Guidelines where pertinent to our Guidelines, and refer the reader to the respective sections in those documents for detailed discussion. We reserve more in-depth discussion for topics that are specific to issues pertaining to myocardial revascularization that are not covered in other Guidelines. To keep the current document concise and reader-friendly, we also moved some of the detailed descriptions of study results to the online Supplementary Data. 2.1 What is new in the 2018 Guidelines? Figure 1 View largeDownload slide New recommendations. Figure 1 View largeDownload slide New recommendations. Figure 2 View largeDownload slide Changes in class of recommendation. Figure 2 View largeDownload slide Changes in class of recommendation. 3. Diagnostic tools to guide myocardial revascularization The use of diagnostic imaging and functional testing modalities to detect patients with coronary artery disease (CAD) is discussed in detail in the clinical practice Guidelines for patients with SCAD [1]. Further diagnostic assessment of patients with obstructive CAD is critical in order to identify patients and select specific lesions that are likely to benefit from myocardial revascularization, in addition to optimal medical therapy. 3.1 Non-invasive diagnostic tools 3.1.1 Assessment of myocardial ischaemia Non-invasive diagnostic assessment of patients with CAD being considered for myocardial revascularization comprises the assessment of ischaemia and the evaluation of viability in patients with regional wall motion abnormalities or reduced ejection fraction (EF). Functional testing to assess ischaemia is critical for the assessment of stable patients with CAD. Documentation of ischaemia using functional testing before elective invasive procedures for CAD is the preferred approach. It may also have a role in the assessment of some patients presenting with acute coronary syndrome (ACS). Because of the low sensitivity of exercise electrocardiogram (ECG) testing in the assessment of patients with symptoms of angina, non‐invasive imaging is recommended as the first-line test [1]. Detection of a large area of myocardial ischaemia by functional imaging is associated with impaired prognosis of patients and identifies patients who should undergo revascularization (see section 5). In patients undergoing coronary computed tomography (CT), both CT‐derived fractional flow reserve (CT‐FFR) and CT perfusion represent possible approaches to evaluate lesion‐specific ischaemia. Although the evidence for both is limited at present, there are considerably more data from clinical investigations of CT‐FFR. A number of trials have shown that correlation between CT-derived FFR and invasive FFR is high [2, 3]. The non-randomized PLATFORM (Prospective LongitudinAl Trial of FFRct: Outcome and Resource Impacts) study showed that in patients referred for invasive angiography due to chest pain (predominantly atypical angina) and intermediate pre-test probability of CAD, assessment with CT and CT-FFR reduced the number of patients with subsequently normal invasive coronary angiograms compared with standard care [4]. Currently, clinical trial data with CT-FFR are insufficient to make a recommendation for its use in clinical practice. 3.1.2 Assessment of myocardial viability in patients with heart failure and coronary artery disease In patients with regional wall motion abnormalities or ventricular dysfunction, heart failure (HF) can be caused by stunned or hibernating myocardium and may be reversed by revascularization. Assessment of myocardial viability may be done in order to select patients that are more likely to benefit from myocardial revascularization and can be achieved with several imaging modalities: myocardial contrast echocardiography, single-photon emission CT (SPECT), and late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) all assess cellular integrity; positron emission tomography (PET) assesses cellular metabolism; and dobutamine techniques assess contractile reserve [1, 5]. Assessment of ischaemia provides incremental benefit over viability in mild to moderate CAD, but with extensive CAD viability assessment may be sufficient [6]. Patients with advanced HF and viable myocardium should first undergo revascularization with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) before being considered for mechanical circulatory support (MCS) or heart transplantation [7, 8]. The PARR-2 (PET and Recovery following Revascularization) trial included patients with severe left ventricular (LV) dysfunction being considered for revascularization or HF/transplantation workups, and randomized them to management assisted by fluorodeoxyglucose PET (FDG-PET) or standard care [6]. The primary outcome of cardiac death, myocardial infarction (MI), or recurrent hospital stay for cardiac cause at 1 year was not improved in the group managed by FDG-PET [relative risk (RR) 0.82, 95% confidence interval (CI) 0.59–1.14, P = 0.16], though the rate of compliance with the treatment recommended by FDG-PET was variable. The viability substudy of the STICH (Surgical Treatment for Ischemic Heart Failure) trial found viable myocardium in 487/601 patients (81%) and none in 114 (19%) [9]. There was a significant association between myocardial viability and outcome by univariate analysis, but not on multivariable analysis. The lack of correlation between myocardial viability and benefit from revascularization indicates that this strategy should not be the only test when selecting the optimal therapy. Recommendations for non-invasive imaging in patients with coronary artery disease and heart failure with reduced ejection fraction a Class of recommendation. b Level of evidence. CAD: coronary artery disease; CMR: cardiac magnetic resonance; HF: heart failure; PET: positron emission tomography; SPECT: single-photon emission computed tomography. Recommendations for non-invasive imaging in patients with coronary artery disease and heart failure with reduced ejection fraction a Class of recommendation. b Level of evidence. CAD: coronary artery disease; CMR: cardiac magnetic resonance; HF: heart failure; PET: positron emission tomography; SPECT: single-photon emission computed tomography. 3.2 Invasive diagnostic tools 3.2.1 Pressure-derived fractional flow reserve 3.2.1.1 Use of fractional flow reserve in patients with intermediate-grade coronary stenosis including left main stenosis Coronary pressure-derived FFR is the current standard of care for the functional assessment of lesion severity in patients with intermediate-grade stenosis (typically around 40–90% stenosis) without evidence of ischaemia in non-invasive testing, or in those with multivessel disease. Multiple studies have shown that PCI can be safely deferred if FFR is >0.75 [12–15]. The DEFER trial enrolled 325 patients scheduled for PCI of an intermediate stenosis [15]. If FFR was ≥0.75, patients were randomly assigned to deferral (defer group; n = 91) or performance (perform group; n = 90) of PCI. The composite rate of cardiac death and acute MI (AMI) in the defer and perform groups was 3.3 vs 7.9% (P = 0.21). However, most contemporary studies use an FFR cut-off of 0.80. A recent large-scale observational study supports the use of FFR >0.80 rather than 0.75 as a cut-off [16]. Indeed, the two largest studies in this field, DEFINE-FLAIR (Define Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularization DES drug-eluting stent) [17] and iFR-SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) [18], used the 0.80 cut-off for lesion selection by FFR, with favourable event rates at 1 year. Thus, 0.80 is the accepted FFR threshold for defining haemodynamically relevant lesions. Haemodynamic relevance, as defined by FFR ≤0.80, correlates poorly with diameter stenosis by visual assessment. In the FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) trial, only 35% of the 50–70% stenoses were haemodynamically relevant and, of the 71–90% stenoses, 20% were not. Only an estimated diameter stenosis >90% predicted haemodynamic relevance with high accuracy (96% correct classification). A number of studies have shown that utilization of an FFR-based assessment strategy at the time of angiography results in reclassification of the revascularization strategy (PCI, bypass surgery, or medical therapy) in a high proportion of patients with intermediate-grade lesions (>40% of patients are reclassified) [19–22]. In addition, separate and pooled analyses of the patients included in those studies have shown that the end results of ‘FFR-based reclassification’ in patients investigated at the time of diagnostic angiography is neutral overall for the number of patients indicated for revascularization [23]. A patient-level and study-level meta-analysis of 9173 lesions demonstrated that with lesions with FFR <0.75, revascularization reduced the 1-year risk of major adverse cardiac events (MACE), including a reduction in the composite risk of death and MI [24]. Thus, the FFR threshold of 0.75 is used to define more severe ischaemia that is of prognostic relevance. The presence of intermediate grade left main stem (LMS) disease is not infrequent and angiographic evaluation may be challenging. Assessment using pressure-derived FFR is more challenging in comparison with non-LMS stenosis due to the requirement for disengagement of the guiding catheter and an inability to administer intracoronary adenosine. Some observational data exist to support the use of FFR in order to decide if revascularization should be deferred or performed [25]. In the largest study, which included 230 patients with intermediate-grade LMS stenosis, only 23% showed an FFR <0.80. Treatment was deferred in patients with an FFR ≥0.80 and bypass surgery was done in patients with an FFR <0.80 [26]. Clinical outcomes at 5 years were similar in both groups. However, it is important to consider the potential influence of any untreated downstream disease in the left anterior descending (LAD) or left circumflex arteries, which may be associated with an increased risk of a false negative FFR [27]. The value of FFR to evaluate intermediate stenosis and guide selection of lesions for revascularization at the time of bypass surgery has been shown in an observational study [28]. Of the 627 patients with intermediate stenosis that were evaluated, 429 had bypass without FFR and 198 had bypass with FFR; in the latter group, the proportion of patients with three-vessel disease was reclassified from 94 to 86%. Outcomes were similar in both groups at 3 years [hazard ratio (HR) for death/MI/target vessel revascularization (TVR) = 1.03, 95% CI 0.67–1.69], though the group with FFR guidance was associated with a lower number of graft anastomoses and a lower rate of on-pump surgery compared with angiography-guided CABG surgery. 3.2.1.2 Use of fractional flow reserve to identify lesions requiring revascularization in patients with multivessel coronary artery disease undergoing percutaneous coronary intervention FFR may also be useful for the selection of lesions requiring revascularization in patients with multivessel CAD. The FAME trial showed that in patients with multivessel disease randomized to an FFR-guided PCI strategy (using a cut-off ≤0.80 to indicate requirement for PCI), outcomes at 12 months in terms of death, non-fatal MI, and repeat revascularization were superior compared with angiography-guided PCI and utilized fewer resources [29]. In addition, the 2-year composite risk of death or MI was significantly lower with the FFR-guided PCI strategy [30]. Long-term follow-up at 5 years showed broadly consistent findings, although differences between groups in relation to the primary endpoint were no longer significant [31]. This suggests that FFR-guided PCI should be the preferred management strategy in these patients. 3.2.1.3 Fractional flow reserve-guided management vs medical therapy in patients with coronary artery disease In patients with SCAD and at least one stenosis with FFR ≤0.80, the FAME 2 trial showed that PCI using drug-eluting stent (DES) implantation improved the primary endpoint of death, non-fatal MI, or urgent revascularization within 2 years compared with medical treatment alone, which was driven by a lower need for urgent revascularization [32]. The advantage of FFR-guided PCI over medical therapy alone was maintained at 3 years [33]. 3.2.2 Other pressure-derived indices FFR evaluation requires maximal and stable hyperaemia, which is usually obtained by the administration of intravenous (i.v.) adenosine. Recently, there has been renewed interest in resting indices derived from resting gradients alone [distal coronary to aortic pressure (Pd/Pa) or instantaneous wave-free ratio (iwFR)]. Two recent large-scale randomized trials showed broadly comparable results between FFR-guided and iwFR-guided revascularization strategies in patients with intermediate-grade stenosis [17, 18]. Revascularization was indicated in both trials if FFR was ≤0.80 or if iwFR was ≤0.89. In the DEFINE-FLAIR trial, the primary endpoint of MACE at 1 year occurred in 6.8% in patients randomized to iwFR-guided revascularization vs 7.0% in patients randomized to FFR-guided revascularization (P <0.001 for non-inferiority; HR 0.95, 95% CI 0.68–1.33, P = 0.78) [17]. In the iFR-SWEDEHEART trial, the primary endpoint of death from any cause, non-fatal MI, or unplanned revascularization was 6.7% in the iwFR group and 6.1% in the FFR group (P = 0.007 for non-inferiority; HR 1.12, 95% CI 0.79–1.58, P = 0.53) [18]. In this trial, 17.5% of patients had ACS at the time of presentation. There was no interaction with outcomes. Both trials are limited by having a follow-up duration of only 1 year. The SYNTAX II study (Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery), a single-arm, prospective study in patients with multivessel disease incorporating a management strategy including combined iwFR/FFR assessment of stenosis severity in addition to intravascular ultrasound (IVUS)-guided stent implantation and guideline-directed medical therapy, showed encouraging outcomes compared with a historical cohort enrolled in the SYNTAX trial [34]. Randomized trials comparing iwFR-guided revascularization with angiography-guided revascularization or medical therapy are not available. iwFR has not been extensively validated for patients with LMS stenosis. There is no adequate randomized controlled trial (RCT) data to support the use of whole-cardiac cycle Pd/Pa for the guidance of revascularization decisions. 3.2.3 Use of fractional flow reserve and pressure-derived indices in patients with severe aortic stenosis In patients with intermediate coronary stenosis and concomitant severe aortic stenosis, although some observational studies exist (see section 11), there are no adequate RCT data to support the use of FFR or iwFR for the guidance of revascularization decisions. 3.2.4 Use of intravascular imaging for the diagnostic assessment of stenosis IVUS is an ultrasound-based modality of intravascular imaging with an axial resolution of about 150 µm. IVUS imaging allows real-time tomographic assessment of vessel size, lumen area, and plaque composition and volume. In comparison with optical coherence tomography (OCT), it has more limited spatial resolution, but better penetration depth and potential advantages in terms of vessel sizing. OCT is a light-based modality of intravascular imaging with higher axial resolution compared with IVUS (15 vs 150 µm). The disadvantages of OCT imaging are that it requires complete blood clearance from the lumen for imaging and that it has more limited penetration, which can limit the assessment of complete plaque burden and may impair accurate vessel sizing. Potential clinical uses of intravascular imaging for diagnostic assessment in patients being considered for myocardial revascularization are the evaluation of stenosis severity in lesions with intermediate-grade stenosis, evaluation of lesion morphology in lesions ambiguous with angiographic assessment, and the characterization of plaque composition. The majority of the existing data from clinical trials relate to the use of intravascular imaging guidance during PCI and are discussed in section 16. The use of intravascular imaging to evaluate patients with stent failure is discussed in section 13. Regarding the assessment of intermediate-grade stenosis, a number of studies have evaluated the optimal cut-off of minimal lumen area for the identification of haemodynamically relevant lesions. One prospective registry showed overall moderate correlation of minimal lumen area with FFR values, with cut-off values for detecting haemodynamically relevant stenosis (<2.4, <2.7, and <3.6 mm2) dependent on vessel size (reference vessel diameters <3.0, 3.0–3.5, and >3.5 mm, respectively) [34a]. Generally, haemodynamic assessment with FFR should be preferred for this indication. The presence of intermediate-grade LMS disease is not infrequent and angiographic assessment may be challenging. Assessment using IVUS evaluation of intermediate-grade LMS disease in patients being considered for bypass surgery or PCI is supported by data from a number of observational studies [35–38]. In a multicentre, prospective study, revascularization was mainly deferred if the minimal luminal area (MLA) was ≥6 mm2 and performed in cases of an MLA <6 mm2 [37]. After a 2-year follow-up, cardiac death-free survival was similar in both groups (98 and 95%, respectively). Another study suggested that deferral of intervention in 131 patients with an MLA ≥7.5 mm2 showed favourable clinical outcomes [36]. In Asian patients with generally smaller heart sizes, studies have suggested that an IVUS MLA of 4.5–4.8 mm2 may be the most appropriate [38]. Recommendations on functional testing and intravascular imaging for lesion assessment a Class of recommendation. b Level of evidence. FFR: fractional flow reserve; iwFR: instantaneous wave-free ratio; IVUS: intravascular ultrasound; PCI: percutaneous coronary intervention. Recommendations on functional testing and intravascular imaging for lesion assessment a Class of recommendation. b Level of evidence. FFR: fractional flow reserve; iwFR: instantaneous wave-free ratio; IVUS: intravascular ultrasound; PCI: percutaneous coronary intervention. 3.3 Gaps in the evidence Further studies investigating the role of novel, combined, non‐invasive anatomical and functional imaging are needed, such as randomized clinical trials with CT‐FFR in patients with suspected and known CAD, as well as further clinical investigation of perfusion CT. Randomized trials comparing iwFR-based management of patients with intermediate-grade stenosis compared with medical therapy are missing. Further study of whole-cardiac cycle Pd/Pa for the guidance of revascularization in the setting of randomized clinical trials is also required. Further studies including randomized trials are needed to assess the value of functional vs anatomical guidance for CABG. 4. Process for decision-making and patient information 4.1 Patient information and informed consent Informed consent requires transparency, especially if there is debate over various treatment options. Active patient participation in the decision-making process should be encouraged. Patient information needs to be unbiased, evidence-based, up-to-date, reliable, accessible, relevant, and consistent with legal requirements. Use of terminology that the patient understands is essential. Short-term procedure-related and long-term risks and benefits—such as survival, relief of angina, quality of life, the potential need for late reintervention, the need for prevention measures, and uncertainties associated with different treatment strategies—should be thoroughly discussed. Although current recommendations are mostly based on the ability of treatments to reduce adverse events including mortality, there is growing interest in patient-reported outcome measures [40, 41]. Patients are not only interested to know how recommended treatment impacts on prognosis but also on their quality of life in the way they perceive it. A written evidence-based patient information document should be provided, potentially with decision aids. Patients must have the time to reflect on the trade-offs imposed by the outcome estimates. In order to seek a second opinion or to discuss the findings and consequences with referring physicians, enough time should be allowed—up to several days, as required—between diagnostic catheterization and intervention. These recommendations pertain to patients in a stable condition, for whom various treatment options exist and who can make a decision without the constraints of an urgent or emergent situation (Table 3). The patient’s right to decline the treatment option recommended by the Heart Team has to be respected. Patient refusal of a recommended treatment should be acknowledged in a written document after the patient has received the necessary information by the Heart Team members. In this case, the patient may be offered an alternative treatment option by the Heart Team. Table 3: Multidisciplinary decision pathways, patient informed consent, and timing of revascularization ACS Shock STEMI NSTE-ACS SCAD without ad hoc PCI indication according to Heart Team protocol SCAD with ad hoc PCI indication according to Heart Team protocol Multidisciplinary decision-making Not mandatory during the acute phase; mechanical circulatory support according to Heart Team protocol Not mandatory during the acute phase Not mandatory during the acute phase; after stabilization, recommended as in SCAD Required Not required Informed consent Witnessed verbal informed consent or family consent if possible without delay Witnessed verbal informed consent may be sufficient unless written consent is legally required Written informed consenta; in emergency cases witnessed verbal informed consent may be sufficient Written informed consenta Written informed consenta Time to revascularization Emergency: no delay Emergency: no delay Urgency: within 2 h to within 72 h depending on the risk criteria Within 2 weeks for high-risk patientsb and within 6 weeks for all other patients Ad hoc Procedure Proceed with intervention based on best evidence/availability. Ad hoc treatment of culprit lesion, staged treatment of non-culprit lesions according to institutional protocol or Heart Team decision Proceed with intervention based on best evidence/availability. Non-culprit lesions treated according to institutional protocol or Heart Team decision Proceed with intervention based on best evidence/availability. Non-culprit lesions treated according to institutional protocol or Heart Team decision Allow for enough time from diagnostic catheterization to decide on the appropriate intervention Proceed with intervention according to institutional protocol defined by Heart Team ACS Shock STEMI NSTE-ACS SCAD without ad hoc PCI indication according to Heart Team protocol SCAD with ad hoc PCI indication according to Heart Team protocol Multidisciplinary decision-making Not mandatory during the acute phase; mechanical circulatory support according to Heart Team protocol Not mandatory during the acute phase Not mandatory during the acute phase; after stabilization, recommended as in SCAD Required Not required Informed consent Witnessed verbal informed consent or family consent if possible without delay Witnessed verbal informed consent may be sufficient unless written consent is legally required Written informed consenta; in emergency cases witnessed verbal informed consent may be sufficient Written informed consenta Written informed consenta Time to revascularization Emergency: no delay Emergency: no delay Urgency: within 2 h to within 72 h depending on the risk criteria Within 2 weeks for high-risk patientsb and within 6 weeks for all other patients Ad hoc Procedure Proceed with intervention based on best evidence/availability. Ad hoc treatment of culprit lesion, staged treatment of non-culprit lesions according to institutional protocol or Heart Team decision Proceed with intervention based on best evidence/availability. Non-culprit lesions treated according to institutional protocol or Heart Team decision Proceed with intervention based on best evidence/availability. Non-culprit lesions treated according to institutional protocol or Heart Team decision Allow for enough time from diagnostic catheterization to decide on the appropriate intervention Proceed with intervention according to institutional protocol defined by Heart Team a This may not apply to countries that are not legally required to ask for written informed consent. The ESC and EACTS advocate the documentation of patient consent for all revascularization procedures. b Severe symptoms (CCS class 3), anatomy (left main disease or equivalent, three-vessel disease or proximal left anterior descending artery), or depressed ventricular function. ACS: acute coronary syndromes; CCS: Canadian Cardiovascular Society; ESC: European Society of Cardiology; EACTS: European Association for Cardio-Thoracic Surgery; NSTE-ACS: non-ST-segment elevation acute coronary syndrome; PCI: percutaneous coronary intervention; SCAD: stable coronary artery disease; STEMI: ST-segment elevation myocardial infarction. Table 3: Multidisciplinary decision pathways, patient informed consent, and timing of revascularization ACS Shock STEMI NSTE-ACS SCAD without ad hoc PCI indication according to Heart Team protocol SCAD with ad hoc PCI indication according to Heart Team protocol Multidisciplinary decision-making Not mandatory during the acute phase; mechanical circulatory support according to Heart Team protocol Not mandatory during the acute phase Not mandatory during the acute phase; after stabilization, recommended as in SCAD Required Not required Informed consent Witnessed verbal informed consent or family consent if possible without delay Witnessed verbal informed consent may be sufficient unless written consent is legally required Written informed consenta; in emergency cases witnessed verbal informed consent may be sufficient Written informed consenta Written informed consenta Time to revascularization Emergency: no delay Emergency: no delay Urgency: within 2 h to within 72 h depending on the risk criteria Within 2 weeks for high-risk patientsb and within 6 weeks for all other patients Ad hoc Procedure Proceed with intervention based on best evidence/availability. Ad hoc treatment of culprit lesion, staged treatment of non-culprit lesions according to institutional protocol or Heart Team decision Proceed with intervention based on best evidence/availability. Non-culprit lesions treated according to institutional protocol or Heart Team decision Proceed with intervention based on best evidence/availability. Non-culprit lesions treated according to institutional protocol or Heart Team decision Allow for enough time from diagnostic catheterization to decide on the appropriate intervention Proceed with intervention according to institutional protocol defined by Heart Team ACS Shock STEMI NSTE-ACS SCAD without ad hoc PCI indication according to Heart Team protocol SCAD with ad hoc PCI indication according to Heart Team protocol Multidisciplinary decision-making Not mandatory during the acute phase; mechanical circulatory support according to Heart Team protocol Not mandatory during the acute phase Not mandatory during the acute phase; after stabilization, recommended as in SCAD Required Not required Informed consent Witnessed verbal informed consent or family consent if possible without delay Witnessed verbal informed consent may be sufficient unless written consent is legally required Written informed consenta; in emergency cases witnessed verbal informed consent may be sufficient Written informed consenta Written informed consenta Time to revascularization Emergency: no delay Emergency: no delay Urgency: within 2 h to within 72 h depending on the risk criteria Within 2 weeks for high-risk patientsb and within 6 weeks for all other patients Ad hoc Procedure Proceed with intervention based on best evidence/availability. Ad hoc treatment of culprit lesion, staged treatment of non-culprit lesions according to institutional protocol or Heart Team decision Proceed with intervention based on best evidence/availability. Non-culprit lesions treated according to institutional protocol or Heart Team decision Proceed with intervention based on best evidence/availability. Non-culprit lesions treated according to institutional protocol or Heart Team decision Allow for enough time from diagnostic catheterization to decide on the appropriate intervention Proceed with intervention according to institutional protocol defined by Heart Team a This may not apply to countries that are not legally required to ask for written informed consent. The ESC and EACTS advocate the documentation of patient consent for all revascularization procedures. b Severe symptoms (CCS class 3), anatomy (left main disease or equivalent, three-vessel disease or proximal left anterior descending artery), or depressed ventricular function. ACS: acute coronary syndromes; CCS: Canadian Cardiovascular Society; ESC: European Society of Cardiology; EACTS: European Association for Cardio-Thoracic Surgery; NSTE-ACS: non-ST-segment elevation acute coronary syndrome; PCI: percutaneous coronary intervention; SCAD: stable coronary artery disease; STEMI: ST-segment elevation myocardial infarction. The patient has the right to obtain information on the level of expertise of the operator, the workload of the centre, whether all treatment options—including surgery—are available on-site, and local results in the performance of percutaneous and surgical myocardial revascularization procedures. Patients considered for revascularization should also be clearly informed of the continuing need for medical therapy, as well as lifestyle modification and other secondary prevention strategies (see section 19) [42]. 4.2 Multidisciplinary decision-making (Heart Team) The Heart Team—comprising clinical or non-invasive cardiologists, cardiac surgeons, and interventional cardiologists, as well as anaesthetists and other specialists if deemed necessary—should provide a balanced, multidisciplinary decision-making process [43]. Additional input may be needed from other specialties involved in the care of the patient. The Heart Team should meet on a regular basis to analyse and interpret the available diagnostic evidence, determine the need for myocardial revascularization, and assess the relative short- and long-term safety and effectiveness of the percutaneous and surgical options. Ad hoc meetings of the Heart Team should facilitate and support efficient clinical workflows. The need for an interdisciplinary approach is underlined by reports on (i) the underuse of revascularization procedures in 18–40% of patients with CAD [44] and (ii) inappropriate use of revascularization strategies with a lack of case discussions [45]. The marked variability in PCI-to-CABG ratios between European countries (ranging from 2.4–7.6 in 2013, for example) has raised concerns regarding the appropriate selection of revascularization strategies [46]. Rates for the inappropriate use of PCI (10–15%) [43, 47, 48] and CABG (1–2%) are reported. Multidisciplinary decision-making in a Heart Team can minimize specialty bias and prevent self-referral from interfering with optimal patient care [49]. Several reports from different centres have established that the treatment recommendations made in multidisciplinary Heart Team discussions are reproducible and implemented in the vast majority of cases (93–95%) [50, 51]. Interdisciplinary institutional protocols should be developed for common case scenarios to avoid the need for systematic case-by-case review of all diagnostic angiograms. However, complex cases—defined by the protocols—should be discussed individually. In these cases, revascularization should not be performed at the time of diagnostic angiography, to allow sufficient time to assess all available information and clearly explain and discuss the findings with the patient. The rationale for a decision and consensus on the optimal revascularization treatment should be documented on the patient’s chart. In institutions without an on-site cardiac surgery unit, collaboration with an external cardiac surgery unit is required to design protocols that define when Heart Team discussion is needed. 4.3 Timing of revascularization Patients requiring myocardial revascularization may be at increased risk of adverse events during the waiting period [52]. A recent meta-analysis of observational studies calculated that a waiting period of 3 months for surgical myocardial revascularization may be associated with the risk of 1 death among 80 patients [53]. Table 3 shows the preferred timing of revascularization depending on the clinical presentation and the extent and localization of CAD [54]. Sections 7 and 8 show additional and more specific information in this regard for patients with ACS. Ad hoc PCI is defined as a therapeutic intervention performed within the same procedure as the diagnostic coronary angiography. Ad hoc PCI is convenient, often cost-effective and safe, and is associated with fewer access site complications and lower radiation exposure [55, 56]. However, in the USA, up to 30% of patients undergoing ad hoc PCI are potential candidates for CABG [56]. This number may be lower in Europe [45]. Although it is not advisable for ad hoc PCI to represent the default approach for complex SCAD, it may be justified if a full diagnostic work-up, including functional testing, is available and the patient is adequately informed on both percutaneous and surgical myocardial revascularization options (see section 4.1). Institutional protocols developed by the Heart Team in accordance with current Guidelines should define specific anatomical criteria and clinical subsets that may be—or should not be—treated ad hoc. Stable patients with complex CAD, as reflected by a high SYNTAX score, should in general be discussed by the Heart Team and not be treated ad hoc. Recommendations for decision-making and patient information in the elective setting a Class of recommendation. b Level of evidence. PCI: percutaneous coronary intervention. Recommendations for decision-making and patient information in the elective setting a Class of recommendation. b Level of evidence. PCI: percutaneous coronary intervention. 5. Revascularization for stable coronary artery disease 5.1 Rationale for revascularization The indications for revascularization in patients with SCAD who receive guideline-recommended medical treatment are the persistence of symptoms despite medical treatment and/or the improvement of prognosis [1]. Several studies have shown that myocardial revascularization by PCI or CABG more effectively relieves angina, reduces the use of anti-anginal drugs, and improves exercise capacity and quality of life compared with a strategy of medical therapy alone during short- and long-term follow-up (Supplementary Table 1) [32, 33, 57–62]. Recently, the ORBITA (Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina) trial randomly compared PCI with placebo (sham procedure) in patients with SCAD due to single-vessel CAD (diameter stenosis >70%) and preserved LV function in the presence of moderate symptoms of angina [Canadian Cardiovascular Society (CCS) class II in 59% of patients, duration 9 months] for the first time [63]. After 6 weeks of medication optimization (mean number of anti-anginal drugs: 3) and baseline cardiopulmonary exercise testing, 200 patients were randomized (105 PCI and 95 placebo). Following a 6-week post-randomization period, the primary endpoint of increment in exercise time was not significantly different, but estimates were imprecise (PCI minus placebo 16.6 sec, 95% CI –8.9 to 42.0, P = 0.20). The dobutamine stress echocardiography peak stress wall motion score index improved with PCI (–0.09, 95% CI –0.15 to –0.04, P = 0.001). ORBITA raises the issue of whether the symptom relief of PCI in the specific setting of stable single-vessel CAD may be related at least in part to a placebo effect. Limitations of the study, as acknowledged by the investigators and outlined elsewhere, include the short observation period (6 weeks), the inclusion of patients with mild symptoms pre-randomization (CCS class 0–I in 25% of patients), the group imbalance in ostial and proximal lesions (37 vs 57%, P = 0.005), loss to follow-up after randomization, and the insufficient power to detect a true difference [64]. This precludes definite conclusions at this stage. Nevertheless, the ORBITA study underlines the value of optimal medical therapy in the management of SCAD. Three-year follow-up of the FAME 2 study indicated yearly and sustained improvement of angina (10.2 vs 28.5% at 1 month and 5.2 vs 9.7% at 3 years) in favour of FFR-guided PCI, despite considerable crossover in the medical therapy arm [33]. Among patients with multivessel disease, the assessment of frequency of angina and quality of life measures in the SYNTAX, FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus), and EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trials consistently showed early and sustained improvement for both PCI and CABG during long-term follow-up [65–67]. 5.2 Evidence basis for revascularization The indications for revascularization in patients with stable angina or silent ischaemia are summarized in the recommendation table. 5.2.1 Revascularization with the use of percutaneous coronary intervention Several meta-analyses comparing a strategy of PCI with initial medical therapy among patients with SCAD found no or only modest benefits in terms of survival or MI for an invasive strategy, taking into account the fact that up to 40% of patients crossed over after to revascularization during longer-term follow-up [91, 98, 99]. A network meta-analysis of 100 trials with 93 553 patients and 262 090 patient-years of follow-up comparing a strategy of initial medical therapy with revascularization reported improved survival using PCI with new-generation DES (everolimus: rate ratio 0.75, 95% CI 0.59–0.96; zotarolimus: rate ratio 0.65, 95% CI 0.42–1.00) compared with initial medical treatment [100]. In the FAME 2 trial [32], patients with SCAD and at least one functionally significant stenosis (invasive FFR ≤0.80) were randomly assigned to medical therapy or medical therapy plus FFR-guided PCI using new-generation DES. The 3-year report of the FAME 2 trial reported a lower incidence of the primary composite endpoints of death, MI, and urgent revascularization (10.1 vs 22.0%; P <0.001), driven by a lower incidence of urgent revascularization in the PCI group (4.3 vs 17.2%; P <0.001) and without significant differences in the rates of death and MI [33]. At 2 years of follow-up, the rate of death or MI was lower in the PCI than the medical therapy group (4.6 vs 8.0%; HR 0.56, 95% CI 0.32–0.97, P = 0.04) in a landmark analysis between 8 days and 2 years of follow-up, whereas event rates were higher during days 0–7 due to periprocedural MI (for overview of studies see Supplementary Table 2) [97]. Indications for revascularization in patients with stable angina or silent ischaemia a Class of recommendation. b Level of evidence. c With documented ischaemia or a haemodynamically relevant lesion defined by FFR ≤0.80 or iwFR ≤0.89 (see section 3.2.1.1), or >90% stenosis in a major coronary vessel. d Based on FFR <0.75 indicating a prognostically relevant lesion (see section 3.2.1.1). e In consideration of patient compliance and wishes in relation to the intensity of anti-anginal therapy. CAD: coronary artery disease; FFR: fractional flow reserve; iwFR: instantaneous wave-free ratio; LAD: left anterior descending coronary artery; LV: left ventricular; LVEF: left ventricular ejection fraction. Indications for revascularization in patients with stable angina or silent ischaemia a Class of recommendation. b Level of evidence. c With documented ischaemia or a haemodynamically relevant lesion defined by FFR ≤0.80 or iwFR ≤0.89 (see section 3.2.1.1), or >90% stenosis in a major coronary vessel. d Based on FFR <0.75 indicating a prognostically relevant lesion (see section 3.2.1.1). e In consideration of patient compliance and wishes in relation to the intensity of anti-anginal therapy. CAD: coronary artery disease; FFR: fractional flow reserve; iwFR: instantaneous wave-free ratio; LAD: left anterior descending coronary artery; LV: left ventricular; LVEF: left ventricular ejection fraction. 5.2.2 Revascularization with the use of coronary artery bypass grafting The superiority of CABG over a strategy of initial medical therapy was established in a meta-analysis of seven RCTs [68] more than two decades ago, demonstrating a survival benefit of CABG in patients with SCAD and left main (LM) or three-vessel disease, particularly when the proximal LAD coronary artery was involved, and has been corroborated in more recent studies [100, 101]. A network meta-analysis of 100 trials with 93 553 patients comparing a strategy of initial medical therapy with revascularization reported improved survival (RR 0.80, 95% CI 0.63–0.99) and a reduced risk of MI (RR 0.79, 95% CI 0.83–0.99) among patients undergoing CABG compared with initial medical treatment [100]. In the STICH trial, 1212 patients with CAD and an LV ejection fraction (LVEF) ≤35% were randomized to initial medical therapy or CABG. The extended 10-year follow-up of the STICH trial reported a significant reduction in all-cause (59 vs 66%; HR 0.84, 95% CI 0.73–0.97; P = 0.02) and cardiovascular mortality (41 vs 49%; HR 0.79, 95% CI 0.66–0.93; P = 0.006) [81]. For an overview of studies, see Supplementary Table 2. 5.3 Percutaneous coronary intervention vs coronary artery bypass grafting The recommendations for the type of revascularization (CABG or PCI) in patients with SCAD with suitable coronary anatomy for both procedures and low predicted surgical mortality are summarized below. The Heart Team should take into consideration the individual cardiac and extracardiac characteristics, in addition to patient preference, in the overall decision-making process (Figure 3). A summary of trials comparing the outcomes of patients treated with angioplasty vs CABG and bare-metal stent (BMS) vs CABG is shown in Supplementary Table 3, and of studies comparing DES and CABG in Table 4. Table 4: Randomized clinical trials comparing percutaneous coronary intervention with drug-eluting stents vs surgical revascularization Stent type and year of publication Study N Baseline characteristics Primary endpointa Secondary endpointsa Age (y) Women (%) Diabetes (%) MV disease (%) EF (%) Definition Y Results Y Death MI Revasc Stroke DES PES 2009 SYNTAX [102] 1800 65 22 25 MV 61 LM 39 - Death, MI, stroke, or repeat revasc 1 17.8 vs 12.4% 5 13.9 vs 11.4% 9.7 vs 3.8%* 25.9 vs 13.7%* 2.4 vs 3.7% SES 2011 Boudriot [103] 201 68 25 36 LM 100 65 Death, MI, or repeat revasc 1 13.9 vs 19% 1 2 vs 5% 3 vs 3% 14 vs 5.9% - SES 2011 PRECOMBAT [104] 600 62 24 32 LM 100 61 Death, MI, stroke, or TVR 1 8.7 vs 6.7%b 2 2.4 vs 3.4% 1.7 vs 1.0% 9.0 vs 4.2%* 0.4 vs 0.7% EES 2015 BEST [105] 880 64 29 41 MV 100 60 Death, MI, or TVR 2 11.0 vs 7.9% 5 6.6 vs 5.0% 4.8 vs 2.7% 13.4 vs 6.6% 2.9 vs 3.3% BES 2016 NOBLE [106] 1201 66 22 15 LM 100 60 Death, MI, or TVR 5 15.4 vs 7.2% 5 11.6 vs 9.5% 6.9 vs 1.9%*c 16.2 vs 10.4%* 4.9 vs 1.7% EES 2016 EXCEL [107] 1905 66 24 30 LM 100 57 Death, MI, or stroke 3 15.4 vs 14.7%b 3 8.2 vs 5.9% 8.0 vs 8.3% 13.4 vs 6.6%* 2.3 vs 2.9% Stent type and year of publication Study N Baseline characteristics Primary endpointa Secondary endpointsa Age (y) Women (%) Diabetes (%) MV disease (%) EF (%) Definition Y Results Y Death MI Revasc Stroke DES PES 2009 SYNTAX [102] 1800 65 22 25 MV 61 LM 39 - Death, MI, stroke, or repeat revasc 1 17.8 vs 12.4% 5 13.9 vs 11.4% 9.7 vs 3.8%* 25.9 vs 13.7%* 2.4 vs 3.7% SES 2011 Boudriot [103] 201 68 25 36 LM 100 65 Death, MI, or repeat revasc 1 13.9 vs 19% 1 2 vs 5% 3 vs 3% 14 vs 5.9% - SES 2011 PRECOMBAT [104] 600 62 24 32 LM 100 61 Death, MI, stroke, or TVR 1 8.7 vs 6.7%b 2 2.4 vs 3.4% 1.7 vs 1.0% 9.0 vs 4.2%* 0.4 vs 0.7% EES 2015 BEST [105] 880 64 29 41 MV 100 60 Death, MI, or TVR 2 11.0 vs 7.9% 5 6.6 vs 5.0% 4.8 vs 2.7% 13.4 vs 6.6% 2.9 vs 3.3% BES 2016 NOBLE [106] 1201 66 22 15 LM 100 60 Death, MI, or TVR 5 15.4 vs 7.2% 5 11.6 vs 9.5% 6.9 vs 1.9%*c 16.2 vs 10.4%* 4.9 vs 1.7% EES 2016 EXCEL [107] 1905 66 24 30 LM 100 57 Death, MI, or stroke 3 15.4 vs 14.7%b 3 8.2 vs 5.9% 8.0 vs 8.3% 13.4 vs 6.6%* 2.3 vs 2.9% Age and EF are reported as means. * P < 0.05. a Results are reported as percutaneous coronary intervention vs coronary artery bypass grafting. b Non-inferiority met. c Non-procedural MI (exclusion of periprocedural MI). BES: biolimus-eluting stents; BEST: Randomised Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease; DES: drug-eluting stents; EES: everolimus-eluting stent; EF: ejection fraction; EXCEL: Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization; LM: left main coronary artery disease; MI: myocardial infarction; MV: multivessel coronary artery disease; NOBLE: Nordic-Baltic-British Left Main Revascularization Study; PES: paclitaxel-eluting stents; PRECOMBAT: Premier of Randomised Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease; Revasc: revascularization; SES: sirolimus-eluting stents; SYNTAX: Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery; TVR: target vessel revascularization; Y: years. Table 4: Randomized clinical trials comparing percutaneous coronary intervention with drug-eluting stents vs surgical revascularization Stent type and year of publication Study N Baseline characteristics Primary endpointa Secondary endpointsa Age (y) Women (%) Diabetes (%) MV disease (%) EF (%) Definition Y Results Y Death MI Revasc Stroke DES PES 2009 SYNTAX [102] 1800 65 22 25 MV 61 LM 39 - Death, MI, stroke, or repeat revasc 1 17.8 vs 12.4% 5 13.9 vs 11.4% 9.7 vs 3.8%* 25.9 vs 13.7%* 2.4 vs 3.7% SES 2011 Boudriot [103] 201 68 25 36 LM 100 65 Death, MI, or repeat revasc 1 13.9 vs 19% 1 2 vs 5% 3 vs 3% 14 vs 5.9% - SES 2011 PRECOMBAT [104] 600 62 24 32 LM 100 61 Death, MI, stroke, or TVR 1 8.7 vs 6.7%b 2 2.4 vs 3.4% 1.7 vs 1.0% 9.0 vs 4.2%* 0.4 vs 0.7% EES 2015 BEST [105] 880 64 29 41 MV 100 60 Death, MI, or TVR 2 11.0 vs 7.9% 5 6.6 vs 5.0% 4.8 vs 2.7% 13.4 vs 6.6% 2.9 vs 3.3% BES 2016 NOBLE [106] 1201 66 22 15 LM 100 60 Death, MI, or TVR 5 15.4 vs 7.2% 5 11.6 vs 9.5% 6.9 vs 1.9%*c 16.2 vs 10.4%* 4.9 vs 1.7% EES 2016 EXCEL [107] 1905 66 24 30 LM 100 57 Death, MI, or stroke 3 15.4 vs 14.7%b 3 8.2 vs 5.9% 8.0 vs 8.3% 13.4 vs 6.6%* 2.3 vs 2.9% Stent type and year of publication Study N Baseline characteristics Primary endpointa Secondary endpointsa Age (y) Women (%) Diabetes (%) MV disease (%) EF (%) Definition Y Results Y Death MI Revasc Stroke DES PES 2009 SYNTAX [102] 1800 65 22 25 MV 61 LM 39 - Death, MI, stroke, or repeat revasc 1 17.8 vs 12.4% 5 13.9 vs 11.4% 9.7 vs 3.8%* 25.9 vs 13.7%* 2.4 vs 3.7% SES 2011 Boudriot [103] 201 68 25 36 LM 100 65 Death, MI, or repeat revasc 1 13.9 vs 19% 1 2 vs 5% 3 vs 3% 14 vs 5.9% - SES 2011 PRECOMBAT [104] 600 62 24 32 LM 100 61 Death, MI, stroke, or TVR 1 8.7 vs 6.7%b 2 2.4 vs 3.4% 1.7 vs 1.0% 9.0 vs 4.2%* 0.4 vs 0.7% EES 2015 BEST [105] 880 64 29 41 MV 100 60 Death, MI, or TVR 2 11.0 vs 7.9% 5 6.6 vs 5.0% 4.8 vs 2.7% 13.4 vs 6.6% 2.9 vs 3.3% BES 2016 NOBLE [106] 1201 66 22 15 LM 100 60 Death, MI, or TVR 5 15.4 vs 7.2% 5 11.6 vs 9.5% 6.9 vs 1.9%*c 16.2 vs 10.4%* 4.9 vs 1.7% EES 2016 EXCEL [107] 1905 66 24 30 LM 100 57 Death, MI, or stroke 3 15.4 vs 14.7%b 3 8.2 vs 5.9% 8.0 vs 8.3% 13.4 vs 6.6%* 2.3 vs 2.9% Age and EF are reported as means. * P < 0.05. a Results are reported as percutaneous coronary intervention vs coronary artery bypass grafting. b Non-inferiority met. c Non-procedural MI (exclusion of periprocedural MI). BES: biolimus-eluting stents; BEST: Randomised Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease; DES: drug-eluting stents; EES: everolimus-eluting stent; EF: ejection fraction; EXCEL: Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization; LM: left main coronary artery disease; MI: myocardial infarction; MV: multivessel coronary artery disease; NOBLE: Nordic-Baltic-British Left Main Revascularization Study; PES: paclitaxel-eluting stents; PRECOMBAT: Premier of Randomised Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease; Revasc: revascularization; SES: sirolimus-eluting stents; SYNTAX: Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery; TVR: target vessel revascularization; Y: years. Figure 3 View largeDownload slide Aspects to be considered by the Heart Team for decision-making between percutaneous coronary intervention and coronary artery bypass grafting among patients with stable multivessel and/or left main coronary artery disease. Figure 3 View largeDownload slide Aspects to be considered by the Heart Team for decision-making between percutaneous coronary intervention and coronary artery bypass grafting among patients with stable multivessel and/or left main coronary artery disease. 5.3.1 Criteria for decision-making Predicted surgical mortality, the anatomical complexity of CAD, and the anticipated completeness of revascularization are important criteria for decision-making with respect to the type of revascularization (CABG or PCI). Whether conservative therapy, PCI, or CABG is preferred should depend on the risk−benefit ratios of these treatment strategies, weighing up the risks of periprocedural complications (e.g. cerebrovascular events, blood transfusions, renal failure, new onset arrhythmias, or wound infections) against improvements in health-related quality of life, as well as long-term freedom from death, MI, or repeat revascularization. 5.3.1.1 Predicted surgical mortality To assess the predicted surgical mortality, the European System for Cardiac Operative Risk Evaluation (EuroSCORE II) (www.euroscore.org/calc.html) and the Society of Thoracic Surgeons (STS) score (http://riskcalc.sts.org) were both developed based on clinical variables to estimate the operative in-hospital or 30-day mortality risk [108–110] (Supplementary Table 4). Both scores have demonstrated their value in specific cohorts of patients undergoing CABG [111]. Calibration of the STS score is updated on a regular basis. It has been suggested that the STS score outperforms the EuroSCORE II when compared directly in a cohort of CABG patients [112], although other studies have found comparable performance of both models [113, 114]. There are no established cut-offs for low predicted surgical mortality based on the EuroSCORE II or STS score. Thus, individualized treatment decisions are needed. These decisions should respect the range of predicted surgical risks in the major RCTs that inform the choice of revascularization modality (Table 5). In these studies, the predicted surgical risk was assessed by the logistic EuroSCORE. Compared with the more recent EuroSCORE II, the logistic EuroSCORE has similar discrimination but poorer calibration and, thus, overestimates surgical mortality by roughly two-fold [115]. Table 5: Logistic EuroSCOREs in major randomized trials comparing percutaneous coronary intervention with coronary artery bypass grafting Trial EuroSCORE PCI EuroSCORE CABG SYNTAX 3.8 ± 2.6 3.8 ± 2.7 BEST 2.9 ± 2.0 3.0 ± 2.1 FREEDOM 2.7 ± 2.4 2.8 ± 2.5 PRECOMBAT 2.7 ± 1.8 2.8 ± 1.9 EXCEL Not reported Not reported NOBLE 2 (2–4) 2 (2–4) Trial EuroSCORE PCI EuroSCORE CABG SYNTAX 3.8 ± 2.6 3.8 ± 2.7 BEST 2.9 ± 2.0 3.0 ± 2.1 FREEDOM 2.7 ± 2.4 2.8 ± 2.5 PRECOMBAT 2.7 ± 1.8 2.8 ± 1.9 EXCEL Not reported Not reported NOBLE 2 (2–4) 2 (2–4) Numbers are presented as mean ± SD or median (interquartile range). BEST: Randomised Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease; CABG: coronary artery bypass grafting; EuroSCORE: European System for Cardiac Operative Risk Evaluation; EXCEL: Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization; NOBLE: Nordic-Baltic-British Left Main Revascularization Study; PCI: percutaneous coronary intervention; PRECOMBAT: Premier of Randomised Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease; SYNTAX: Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery. Table 5: Logistic EuroSCOREs in major randomized trials comparing percutaneous coronary intervention with coronary artery bypass grafting Trial EuroSCORE PCI EuroSCORE CABG SYNTAX 3.8 ± 2.6 3.8 ± 2.7 BEST 2.9 ± 2.0 3.0 ± 2.1 FREEDOM 2.7 ± 2.4 2.8 ± 2.5 PRECOMBAT 2.7 ± 1.8 2.8 ± 1.9 EXCEL Not reported Not reported NOBLE 2 (2–4) 2 (2–4) Trial EuroSCORE PCI EuroSCORE CABG SYNTAX 3.8 ± 2.6 3.8 ± 2.7 BEST 2.9 ± 2.0 3.0 ± 2.1 FREEDOM 2.7 ± 2.4 2.8 ± 2.5 PRECOMBAT 2.7 ± 1.8 2.8 ± 1.9 EXCEL Not reported Not reported NOBLE 2 (2–4) 2 (2–4) Numbers are presented as mean ± SD or median (interquartile range). BEST: Randomised Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease; CABG: coronary artery bypass grafting; EuroSCORE: European System for Cardiac Operative Risk Evaluation; EXCEL: Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization; NOBLE: Nordic-Baltic-British Left Main Revascularization Study; PCI: percutaneous coronary intervention; PRECOMBAT: Premier of Randomised Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease; SYNTAX: Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery. Despite the usefulness of these scores, there is not a single risk model that provides perfect risk assessment because the scores are limited by (i) the specific definitions used or the methodology applied, (ii) the absence of important variables such as frailty, (iii) the practicability of calculation, (iv) a failure to reflect all relevant mortality and morbidity endpoints, and (v) limited external validation. Decision-making should not be solely dependent on risk scores. These scores should be used as a guide within the multidisciplinary Heart Team discussion. To combine clinical and anatomical risk estimation, the SYNTAX II score was retrospectively derived from the SYNTAX cohort [127] and subsequently externally validated [120, 128, 129]. Nevertheless, compared with the SYNTAX score, its value in assigning patients to PCI or CABG is less well investigated. The fact that the SYNTAX II score failed to predict the outcome of the EXCEL trial raises additional concern [130]. 5.3.1.2 Anatomical complexity of coronary artery disease The SYNTAX score (http://www.syntaxscore.com) was prospectively developed for the SYNTAX trial to grade the anatomical complexity of coronary lesions in patients with LM or three-vessel disease (Table 6 and Supplementary Table 4) [116]. In the cohort of the SYNTAX trial, and subsequently in external validation cohorts, the SYNTAX score was found to be an independent predictor of long-term major adverse cardiac and cerebrovascular events (MACCE) and of death in patients treated with PCI but not CABG [117–120]. Table 6: Guide for calculating the SYNTAX score Steps Variable assessed Description Step 1 Dominance The weight of individual coronary segments varies according to coronary artery dominance (right or left). Co-dominance does not exist as an option in the SYNTAX score. Step 2 Coronary segment The diseased coronary segment directly affects the score as each coronary segment is assigned a weight depending on its location, ranging from 0.5 (i.e. the posterolateral branch) to 6 (i.e. left main in case of left dominance). Step 3 Diameter stenosis The score of each diseased coronary segment is multiplied by two in case of a stenosis 50–99% and by five in case of total occlusion. In case of total occlusion, additional points will be added as follows: Age >3 months or unknown  +1 Blunt stump        +1 Bridging          +1 First segment visible distally  +1 per non-visible segment Side branch at the occlusion +1 if <1.5 mm diameter              +1 if both <1.5 mm and ≥1.5 mm diameter             +0 if ≥1.5 mm diameter (i.e. bifurcation lesion) Step 4 Trifurcation lesion The presence of a trifurcation lesion adds additional points based on the number of diseased segments: • 1 segment +3 • 2 segments +4 • 3 segments +5 • 4 segments +6 Step 5 Bifurcation lesion The presence of a bifurcation lesion adds additional points based on the type of bifurcation according to the Medina classification [126]: Medina 1,0,0–0,1,0–1,1,0   +1 Medina 1,1,1–0,0,1–1,0,1–0,1,1  +2 Moreover, the presence of a bifurcation angle <70° adds one additional point Step 6 Aorto-ostial lesion The presence of aorto-ostial lesion segments adds one additional point Step 7 Severe tortuosity The presence of severe tortuosity proximal of the diseased segment adds two additional points Step 8 Lesion length Lesion length >20 mm adds one additional point Step 9 Calcification The presence of heavy calcification adds two additional points Step 10 Thrombus The presence of thrombus adds one additional point Step 11 Diffuse disease/ small vessels The presence of diffusely diseased and narrowed segments distal to the lesion (i.e. when at least 75% of the length of the segment distal to the lesion has a vessel diameter <2 mm) adds one point per segment number Steps Variable assessed Description Step 1 Dominance The weight of individual coronary segments varies according to coronary artery dominance (right or left). Co-dominance does not exist as an option in the SYNTAX score. Step 2 Coronary segment The diseased coronary segment directly affects the score as each coronary segment is assigned a weight depending on its location, ranging from 0.5 (i.e. the posterolateral branch) to 6 (i.e. left main in case of left dominance). Step 3 Diameter stenosis The score of each diseased coronary segment is multiplied by two in case of a stenosis 50–99% and by five in case of total occlusion. In case of total occlusion, additional points will be added as follows: Age >3 months or unknown  +1 Blunt stump        +1 Bridging          +1 First segment visible distally  +1 per non-visible segment Side branch at the occlusion +1 if <1.5 mm diameter              +1 if both <1.5 mm and ≥1.5 mm diameter             +0 if ≥1.5 mm diameter (i.e. bifurcation lesion) Step 4 Trifurcation lesion The presence of a trifurcation lesion adds additional points based on the number of diseased segments: • 1 segment +3 • 2 segments +4 • 3 segments +5 • 4 segments +6 Step 5 Bifurcation lesion The presence of a bifurcation lesion adds additional points based on the type of bifurcation according to the Medina classification [126]: Medina 1,0,0–0,1,0–1,1,0   +1 Medina 1,1,1–0,0,1–1,0,1–0,1,1  +2 Moreover, the presence of a bifurcation angle <70° adds one additional point Step 6 Aorto-ostial lesion The presence of aorto-ostial lesion segments adds one additional point Step 7 Severe tortuosity The presence of severe tortuosity proximal of the diseased segment adds two additional points Step 8 Lesion length Lesion length >20 mm adds one additional point Step 9 Calcification The presence of heavy calcification adds two additional points Step 10 Thrombus The presence of thrombus adds one additional point Step 11 Diffuse disease/ small vessels The presence of diffusely diseased and narrowed segments distal to the lesion (i.e. when at least 75% of the length of the segment distal to the lesion has a vessel diameter <2 mm) adds one point per segment number SYNTAX: Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery. Table 6: Guide for calculating the SYNTAX score Steps Variable assessed Description Step 1 Dominance The weight of individual coronary segments varies according to coronary artery dominance (right or left). Co-dominance does not exist as an option in the SYNTAX score. Step 2 Coronary segment The diseased coronary segment directly affects the score as each coronary segment is assigned a weight depending on its location, ranging from 0.5 (i.e. the posterolateral branch) to 6 (i.e. left main in case of left dominance). Step 3 Diameter stenosis The score of each diseased coronary segment is multiplied by two in case of a stenosis 50–99% and by five in case of total occlusion. In case of total occlusion, additional points will be added as follows: Age >3 months or unknown  +1 Blunt stump        +1 Bridging          +1 First segment visible distally  +1 per non-visible segment Side branch at the occlusion +1 if <1.5 mm diameter              +1 if both <1.5 mm and ≥1.5 mm diameter             +0 if ≥1.5 mm diameter (i.e. bifurcation lesion) Step 4 Trifurcation lesion The presence of a trifurcation lesion adds additional points based on the number of diseased segments: • 1 segment +3 • 2 segments +4 • 3 segments +5 • 4 segments +6 Step 5 Bifurcation lesion The presence of a bifurcation lesion adds additional points based on the type of bifurcation according to the Medina classification [126]: Medina 1,0,0–0,1,0–1,1,0   +1 Medina 1,1,1–0,0,1–1,0,1–0,1,1  +2 Moreover, the presence of a bifurcation angle <70° adds one additional point Step 6 Aorto-ostial lesion The presence of aorto-ostial lesion segments adds one additional point Step 7 Severe tortuosity The presence of severe tortuosity proximal of the diseased segment adds two additional points Step 8 Lesion length Lesion length >20 mm adds one additional point Step 9 Calcification The presence of heavy calcification adds two additional points Step 10 Thrombus The presence of thrombus adds one additional point Step 11 Diffuse disease/ small vessels The presence of diffusely diseased and narrowed segments distal to the lesion (i.e. when at least 75% of the length of the segment distal to the lesion has a vessel diameter <2 mm) adds one point per segment number Steps Variable assessed Description Step 1 Dominance The weight of individual coronary segments varies according to coronary artery dominance (right or left). Co-dominance does not exist as an option in the SYNTAX score. Step 2 Coronary segment The diseased coronary segment directly affects the score as each coronary segment is assigned a weight depending on its location, ranging from 0.5 (i.e. the posterolateral branch) to 6 (i.e. left main in case of left dominance). Step 3 Diameter stenosis The score of each diseased coronary segment is multiplied by two in case of a stenosis 50–99% and by five in case of total occlusion. In case of total occlusion, additional points will be added as follows: Age >3 months or unknown  +1 Blunt stump        +1 Bridging          +1 First segment visible distally  +1 per non-visible segment Side branch at the occlusion +1 if <1.5 mm diameter              +1 if both <1.5 mm and ≥1.5 mm diameter             +0 if ≥1.5 mm diameter (i.e. bifurcation lesion) Step 4 Trifurcation lesion The presence of a trifurcation lesion adds additional points based on the number of diseased segments: • 1 segment +3 • 2 segments +4 • 3 segments +5 • 4 segments +6 Step 5 Bifurcation lesion The presence of a bifurcation lesion adds additional points based on the type of bifurcation according to the Medina classification [126]: Medina 1,0,0–0,1,0–1,1,0   +1 Medina 1,1,1–0,0,1–1,0,1–0,1,1  +2 Moreover, the presence of a bifurcation angle <70° adds one additional point Step 6 Aorto-ostial lesion The presence of aorto-ostial lesion segments adds one additional point Step 7 Severe tortuosity The presence of severe tortuosity proximal of the diseased segment adds two additional points Step 8 Lesion length Lesion length >20 mm adds one additional point Step 9 Calcification The presence of heavy calcification adds two additional points Step 10 Thrombus The presence of thrombus adds one additional point Step 11 Diffuse disease/ small vessels The presence of diffusely diseased and narrowed segments distal to the lesion (i.e. when at least 75% of the length of the segment distal to the lesion has a vessel diameter <2 mm) adds one point per segment number SYNTAX: Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery. In the SYNTAX trial, tertiles of SYNTAX score with low, intermediate, and high anatomical complexity stratified patients into those who had similar outcomes with both PCI and CABG and those who derived significant benefit from CABG [121–123]. In subsequent RCTs, the interaction of the strata of SYNTAX score with the effect of the randomized treatment was less pronounced and did not reach statistical significance [105–107]. However, in a recent collaborative individual patient pooled analysis of randomized trials including 11 518 patients [124], the test for trend across the ordered tertiles of the SYNTAX score of the SYNTAX study was positive at P = 0.0011 (unpublished analysis), confirming the strata of the SYNTAX score as an effect modifier to be considered. There is concern about bias and inter-individual variability in calculating the SYNTAX score [125]. This should be minimized by adequate training. 5.3.1.3 Completeness of revascularization The aim of myocardial revascularization is to minimize residual ischaemia. In support of this concept, the nuclear substudy of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial demonstrated an incremental benefit in reducing the risk of death and MI by reducing residual stress-induced ischaemia from >10% of the myocardium to ≤5% [86]. In the SYNTAX trial, anatomical complete revascularization was defined as PCI or bypass of all epicardial vessels with a diameter exceeding ≥1.5 mm and a luminal reduction of ≥50% in at least one angiographic view [131]. A meta-analysis of 89 883 patients enrolled in RCTs and observational studies revealed a lower long-term mortality (RR 0.71, 95% CI 0.65–0.77, P <0.001), MI (RR 0.78, 95% CI 0.68–0.90; P = 0.001), and repeat myocardial revascularization (RR 0.74, 95% CI 0.65–0.83; P <0.001) by complete revascularization (based on anatomical definition in 87% of the patients) as compared with incomplete revascularization [132]. The benefit of complete revascularization was independent of the treatment modality. A more recent meta-analysis suggested enhanced benefit when complete revascularization is performed with state-of-the-art techniques in high-risk patients [133]. Likewise, in a post hoc analysis of the SYNTAX trial, anatomical incomplete revascularization was associated with inferior long-term outcomes after both CABG and PCI [131]. A residual SYNTAX score >8 after PCI was associated with significant increases in the 5-year risk of death and of the composite of death, MI, and stroke, and any residual SYNTAX score >0 was associated with the risk of repeat intervention [134]. In an observational study from the New York State registry that compared CABG with PCI using new-generation DES [everolimus-eluting stent (EES)] in 9223 pairs of propensity-matched patients with multivessel CAD, the significantly higher risk of MI associated with PCI as compared with CABG was not seen among matched pairs of patients in which the PCI group had complete revascularization (Pinteraction = 0.02) [135]. Consistent findings were obtained in a pooled analysis of 3212 patients of the SYNTAX, BEST (Randomised Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease), and PRECOMBAT (Premier of Randomised Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease) trials [136]. A mean SYNTAX score of 27 and an LVEF of 59% were obtained. In a propensity-matched analysis, mortality and the composite risk of death, MI, and stroke were significantly lower after PCI with complete vs incomplete revascularization. After PCI with complete revascularization, the risk of death or of the composite of death, MI, or stroke was not significantly different from that after CABG with complete revascularization (adjusted HR 1.16, 95% CI 0.83–1.63, P = 0.39, and 1.14, 95% CI 0.87–1.48, P = 0.35, respectively), whereas these risks were significantly elevated after PCI with incomplete revascularization. Functional complete revascularization is achieved when all lesions causing resting or stress-induced ischaemia are bypassed or treated by PCI. Given the limitations of non-invasive imaging techniques (see section 3), these lesions are best identified by FFR or iwFR during diagnostic angiography. For PCI, the FAME study demonstrated that the more restrictive selection of target lesions by functional guidance conferred superior long-term outcomes compared with anatomically guided lesion selection (see section 3) [31]. In contrast, leaving functionally relevant lesions untreated resulted in a high rate of reinterventions in the FAME 2 study [33]. Based on the data of the FAME and FAME 2 studies, complete revascularization based on the functional definition is the preferred strategy for PCI. The role of functional guidance for CABG is less clear [28, 137]. One of the potential benefits of CABG is protection against disease progression in proximal segments, which may be diminished by restricting the bypass targets to functionally relevant lesions. This has to be weighed against the risk of bypass closure when native vessel flow is high. Thus, for ambiguous lesions, functional testing may also help guide the surgical revascularization strategy. Recommendations on criteria for the choice between coronary artery bypass grafting and percutaneous coronary intervention a Class of recommendation. b Level of evidence. c Level of evidence refers to prediction of outcomes. EuroSCORE: European System for Cardiac Operative Risk Evaluation; CABG: coronary artery bypass grafting; CAD: coronary artery disease; LM: left main; PCI: percutaneous coronary intervention; STS: Society of Thoracic Surgeons; SYNTAX: Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery. Recommendations on criteria for the choice between coronary artery bypass grafting and percutaneous coronary intervention a Class of recommendation. b Level of evidence. c Level of evidence refers to prediction of outcomes. EuroSCORE: European System for Cardiac Operative Risk Evaluation; CABG: coronary artery bypass grafting; CAD: coronary artery disease; LM: left main; PCI: percutaneous coronary intervention; STS: Society of Thoracic Surgeons; SYNTAX: Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery. Recommendation for the type of revascularization in patients with stable coronary artery disease with suitable coronary anatomy for both procedures and low predicted surgical mortalityd a Class of recommendation. b Level of evidence. c PCI should be considered if the Heart Team is concerned about the surgical risk or if the patient refuses CABG after adequate counselling by the Heart Team. d For example, absence of previous cardiac surgery, severe morbidities, frailty, or immobility precluding CABG (also see Table 5). SYNTAX score calculation information is available at http://www.syntaxscore.com. CABG: coronary artery bypass grafting; CAD: coronary artery disease; LAD: left anterior descending coronary artery; PCI: percutaneous coronary intervention; SYNTAX: Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery. Recommendation for the type of revascularization in patients with stable coronary artery disease with suitable coronary anatomy for both procedures and low predicted surgical mortalityd a Class of recommendation. b Level of evidence. c PCI should be considered if the Heart Team is concerned about the surgical risk or if the patient refuses CABG after adequate counselling by the Heart Team. d For example, absence of previous cardiac surgery, severe morbidities, frailty, or immobility precluding CABG (also see Table 5). SYNTAX score calculation information is available at http://www.syntaxscore.com. CABG: coronary artery bypass grafting; CAD: coronary artery disease; LAD: left anterior descending coronary artery; PCI: percutaneous coronary intervention; SYNTAX: Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery. 5.3.2 Isolated proximal left anterior descending coronary artery disease Comparing CABG and PCI among patients with isolated proximal LAD disease, the available evidence suggests similar outcomes in terms of death, MI, and stroke, but a higher risk of repeat revascularization with PCI [68, 70, 73, 101, 139–144]. 5.3.3 Left main coronary artery disease The available evidence from RCTs and meta-analyses comparing CABG with PCI using DES among patients with LM disease suggests equivalent results for the safety composite of death, MI, and stroke up to 5 years of follow-up [148]. A significant interaction with time is notable, providing early benefit for PCI in terms of MI and peri-interventional stroke, which is subsequently offset by a higher risk of spontaneous MI during long-term follow-up. The need for repeat revascularization is higher with PCI than with CABG. The EXCEL trial compared CABG with PCI using new-generation DES (EES) among 1905 patients with significant LM disease [107]. At 3 years of follow-up, the primary endpoint of death, stroke, or MI occurred with similar frequency in the CABG and PCI group (14.7 vs 15.4%; HR 1.00, 95% CI 0.79–1.26, P = 0.98). The pre-planned landmark analysis from 30 days to 3 years showed a significant difference for the primary endpoint in favour of CABG (7.9 vs 11.5%, P = 0.02). The NOBLE (Nordic-Baltic-British Left Main Revascularization Study) trial compared CABG with PCI using new-generation DES [biolimus-eluting stents (BES)] among 1201 patients with significant LM disease (mean SYNTAX score of 23) [106]. At a median follow-up of 3.1 years, the primary endpoint of death, non-procedural MI, stroke, and repeat revascularization occurred more frequently in the PCI than the CABG group (29 vs 19%; HR 1.48, 95% CI 1.11–1.96, P = 0.007). A recent collaborative individual patient pooled analysis of randomized trials including 11 518 patients reviewed the currently available evidence from randomized trials comparing CABG with PCI for LM or multivessel disease [124]. The primary outcome was all-cause mortality. In the overall cohort, CABG was associated with a significant survival benefit during a mean follow-up of 3.8 ± 1.4 years (5-year all-cause mortality 11.2% after PCI vs 9.2% after CABG; HR 1.20, 95% CI 1.06–1.37, P = 0.0038). There was a linear trend for HRs of death increasing with increasing SYNTAX tertiles [P = 0.0011 for trend (unpublished analysis)]. However, among 4478 patients with LM disease, those randomly assigned to CABG or PCI with a mean follow-up of 3.4 ± 1.4 years reported similar risks for the primary outcome all-cause mortality (PCI 10.7 vs CABG 10.5%; HR 1.07, 95% CI 0.87–1.33, P = 0.52) at 5 years. There were no significant differences in mortality between PCI and CABG in subgroup analyses according to SYNTAX scores. Nevertheless, in patients with a high SYNTAX score, a trend towards better survival was noted with CABG. The proportion of patients with a high SYNTAX score was limited in view of the inclusion criteria of the respective studies. Current evidence indicates that PCI is an appropriate alternative to CABG in LM disease and low-to-intermediate anatomical complexity. Among patients with LM disease and low anatomical complexity, there is evidence that the outcomes with respect to major clinical endpoints are similar for PCI and CABG, resulting in a class I recommendation. Among patients with LM disease and high anatomical complexity, the number of patients studied in RCTs is low due to exclusion criteria; the risk estimates and CIs are imprecise, but suggest a trend towards better survival with CABG. Therefore, PCI in this setting cannot be endorsed as reflected by a class III recommendation. For PCI in LM with intermediate anatomical complexity, the previous class IIa recommendation was maintained in view of the incomplete 5-year follow-up of the two largest RCTs in this setting. 5.3.4 Multivessel coronary artery disease The observation of a survival advantage of CABG over PCI has been consistent among patients with severe three-vessel CAD (intermediate to high SYNTAX score), and has been attributed, at least in part, to the placement of bypass grafts to the mid coronary vessels providing prophylaxis against the development of new proximal disease. The BEST trial, comparing CABG with PCI using new-generation DES (EES) among patients with multivessel CAD (77% three-vessel CAD and 23% two-vessel disease, mean SYNTAX score 24), prematurely stopped enrolment after the inclusion of 880 patients due to slow recruitment [105]. At a median follow-up of 4.6 years, PCI was associated with a higher incidence of the primary endpoint (death, MI, and TVR) (15.3 vs 10.6%; HR 1.47, 95% CI 1.01–2.13, P = 0.04) than CABG. The risk of death, MI, and stroke was not statistically different between the two treatment groups (11.9 vs 9.5%; HR 1.26, 95% CI 0.84–1.89, P = 0.26), whereas repeat revascularization of any vessel (11.0 vs 5.4%; HR 2.1, 95% CI 1.28–3.41, P = 0.003) but not target lesion revascularization (5.7 vs 3.8%; HR 1.51, 95% CI 0.82–2.80, P = 0.19) was more frequent in the PCI group. CABG resulted in more complete revascularization (71.5 vs 50.9%; P <0.001) and a lower incidence of revascularization for new lesions (5.5 vs 2.3%; HR 2.47, 95% CI 1.18–5.17, P = 0.01). Consistent with findings in the overall cohort (see section 5.3.3), the collaborative individual patient pooled analysis found that in 7040 patients with multivessel disease, those assigned to CABG had significantly lower 5-year all-cause mortality than those assigned to PCI (PCI 11.5 vs CABG 8.9%; HR 1.28, 95% CI 1.09–1.49, P = 0.0019) [124]. Outcomes for the endpoint all-cause mortality were modified by two variables, diabetes and disease complexity, as assessed by the SYNTAX score. Compared with patients without diabetes (8.7 vs 8.0%; HR 1.08, 95% CI 0.86–1.36, P = 0.49), mortality was higher after PCI than CABG in patients with diabetes (15.5 vs 10.0%; HR 1.48, 95% CI 1.19–1.84, P = 0.0004, Pinteraction = 0.045). There was a gradient of risk with a stepwise increase in mortality for PCI according to SYNTAX score tertile (SYNTAX score 0–22: 10.5 vs 8.4%; HR 1.11, 95% CI 0.77–1.62, P = 0.57; SYNTAX score 23–32: 14.0 vs 9.5%; HR 1.50, 95% CI 1.09–2.08, P =0.0129; SYNTAX score >32: 19.2 vs 11.2%; HR 1.70, 95% CI 1.13–2.55, P = 0.0094). An individual patient data pooled analysis of SYNTAX and BEST, comparing CABG with PCI using DES among 1275 patients with multivessel disease in the absence of diabetes (89% three-vessel CAD, mean SYNTAX score 26), reported a lower risk of death (6.0 vs 9.3%; HR 0.65, 95% CI 0.43–0.98, P = 0.04) and MI (3.3 vs 8.3%; HR 0.40, 95% CI 0.24–0.65, P <0.001) in the CABG group at a median follow-up of 61 months [149]. The risk of death was not significantly different among patients with a low (0–22) SYNTAX score (6.0 vs 7.5%, P = 0.66), whereas the benefit of CABG over PCI was greater in patients with an intermediate-to-high (>22) SYNTAX score (7.1 vs 11.6%, P = 0.02). Another individual patient data pooled analysis of SYNTAX and BEST, comparing CABG with PCI using DES among 1166 patients with multivessel disease involving the proximal LAD (88% three-vessel CAD, mean SYNTAX score 28), reported a higher risk of the composite of death, MI, and stroke (16.3 vs 11.5%; HR 1.43, 95% CI 1.05–1.96, P = 0.02), cardiac death, MI, and repeat revascularization in the PCI group at 5 years of follow-up [147]. Of note, outcomes were not significantly different for CABG and PCI for any endpoint except for MI among the subgroup of patients with low SYNTAX score (0–22). The available evidence suggests that in multivessel CAD without diabetes and low anatomical complexity, PCI and CABG achieve similar long-term outcomes with respect to survival and the composite of death, MI, and stroke, justifying a class I recommendation for PCI. In patients with multivessel CAD and intermediate-to-high anatomical complexity, the two large trials using DES, SYNTAX and BEST, found a significantly higher mortality and a higher incidence of death, MI, and stroke with PCI in the absence of diabetes. Consistent results were also obtained for patients with multivessel CAD in the recent individual patient-level meta-analysis [124]. Thus, the previous class III recommendation for PCI in multivessel CAD and intermediate-to-high complexity was maintained. 5.4 Gaps in the evidence It remains to be determined whether revascularization by PCI improves prognosis in patients with SCAD. The ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) study (NCT01471522) is currently recruiting 5000 patients with SCAD and evidence of moderate-to-severe ischaemia detected by non-invasive imaging, who are randomized before coronary angiography to medical therapy or an invasive strategy to detect differences in the primary endpoint of death or MI. Current techniques rely on coronary angiography and the detection of ischaemia-producing lesions. However, future adverse events are related at least in part to non-flow limiting, vulnerable plaques. Better identification of vulnerable plaques and the development of appropriate treatment strategies is needed. Along the same lines, the completeness and timing of revascularization are not well defined, and neither are the roles of residual ischaemia and lesions. Moreover, we need more research on the use of the SYNTAX and other scores for informing treatment allocation, as well as dedicated trials in specific subsets. Very long-term, extended follow-up (10 years) of trials comparing PCI and CABG, particularly in the setting of LM disease, will provide further insights into the relative merits of both revascularization techniques. 6. Revascularization in non-ST-elevation acute coronary syndrome Myocardial revascularization in patients with non-ST-segment elevation ACS (NSTE-ACS) is addressed by prior Guidelines that are endorsed by the current Task Force [158]. In the present Guidelines, we discuss new evidence where previous recommendations require an update. 6.1 Early invasive vs conservative strategy An invasive strategy has become the standard of care for high-risk patients [158]. This approach allows prompt diagnosis of the underlying CAD, identification of the culprit lesion, guidance for antithrombotic management, and the assessment of the suitability of coronary anatomy for PCI or CABG. Numerous factors interplay in the decision-making process, including clinical presentation, comorbidities, risk stratification (Figure 4), and high-risk features specific for a revascularization modality such as frailty, cognitive status, estimated life expectancy, and the functional and anatomical severity of CAD. Figure 4 View largeDownload slide Selection of non-ST-elevation acute coronary syndrome treatment strategy and timing according to initial risk stratification. Figure 4 View largeDownload slide Selection of non-ST-elevation acute coronary syndrome treatment strategy and timing according to initial risk stratification. Up to 40% of NSTE-ACS patients with obstructive CAD present with multiple complex plaques [159–162] and 25% with an acute occluded coronary artery [163], so that identification of the culprit lesion may be challenging. Correlation with ECG or echo changes and the use of OCT in the 25% of NSTE-ACS patients with angiographically normal epicardial coronary arteries [164–166] may be helpful for identifying the culprit lesion, or rule out other mechanisms such as dissection or haematomas [MI with non-obstructive coronary arteries (MINOCA)] [167–169]. A routine invasive strategy in NSTE-ACS has been shown to improve clinical outcomes [170], and benefit was mainly confined to biomarker-positive patients [171] and patients with other high-risk features as defined in Figure 4. Of importance, the use of a radial approach, new-generation DES, and more effective P2Y12-inhibitors were not available or broadly implemented in these trials, and led to a magnified benefit in frail ACS populations [172, 173]. 6.2 Timing of angiography and intervention The current recommendations on the timing of angiography and intervention, as defined in Figure 4, are based on evidence discussed in detail by the prior Guidelines on NSTE-ACS [158]. Specifically, a reduction in recurrent or refractory ischaemia and length of hospital stay was found with early intervention [174, 175]. More recently, an updated collaborative meta-analysis on individual published and unpublished data (n = 5324 patients with a median follow-up of 180 days) suggested that early intervention might also be associated with decreased mortality [176]. This meta-analysis showed a statistical trend towards decreased mortality with an early invasive strategy compared with a delayed invasive strategy in unselected patients with NSTE-ACS (HR 0.81, 95% CI 0.64–1.03, P = 0.088). The survival benefit of the early invasive strategy appeared more pronounced in high-risk subsets, including elevated cardiac biomarkers at baseline (HR 0.76, 95% CI 0.58–0.996), diabetes (HR 0.67, 95% CI 0.45–0.99), a Global Registry of Acute Coronary Events risk score >140 (HR 0.70, 95% CI 0.52–0.95), and age 75 years or older (HR 0.65, 95% CI 0.46–0.93), although tests for interaction were inconclusive. 6.3 Type of revascularization 6.3.1 Percutaneous coronary intervention 6.3.1.1 Technical aspects Implantation of new-generation DES is the standard treatment strategy even when dual antiplatelet therapy (DAPT) cannot be sustained beyond 1 month post-intervention [173, 177–179] (see section 17), and the radial approach has also become the standard of care [172]. DAPT is recommended for 12 months irrespective of stent type, while in patients at high ischaemic risk not experiencing bleeding events, DAPT may be extended (see section 17). There is no evidence for any additional benefit of thrombectomy in patients undergoing PCI in the setting of NSTE-ACS [180]. While FFR is considered the invasive gold standard for the functional assessment of lesion severity in SCAD, it has been shown to be feasible, reliable, safe, and effective in NSTE-ACS patients with multivessel disease, although its prognostic value is unclear [22, 137, 181]. 6.3.1.2 Revascularization strategies and outcomes Complete revascularization of significant lesions should be attempted in multivessel disease NSTE-ACS patients, given that it was mandated in trials testing early vs late intervention [171, 182, 183] and that the prognosis of patients with incomplete revascularization is known to be worse [131, 184]. In addition, it seems that complete one-stage revascularization is associated with better clinical outcome than multistage PCI [185]. The risk of periprocedural complications of PCI defined as MI or myocardial injury, as well as that of long-term ischaemia, remains higher in NSTE-ACS than in stable patients [186, 187]. For ACS patients who have undergone PCI, revascularization procedures represent the most frequent, most costly, and earliest causes for rehospitalization [188, 189]. As in ST-elevation myocardial infarction (STEMI), routine treatment of non-culprit lesions during the primary intervention by PCI is harmful in NSTE-ACS patients with cardiogenic shock, as shown by the recently published CULPRIT-SHOCK (Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock) trial (see section 7.3) [190]. 6.3.2 Coronary artery bypass grafting Approximately 5–10% of NSTE-ACS patients require CABG [191], and they represent a challenging subgroup given their high-risk characteristics compared with patients undergoing elective CABG [192]. In the absence of randomized data, optimal timing for non-emergent CABG in NSTE-ACS patients should be determined individually. The risk of ischaemic events possibly related to suboptimal antiplatelet therapy while awaiting surgery is <0.1%, while that of perioperative bleeding complications associated with platelet inhibitors is >10% [193]. In patients with ongoing ischaemia or haemodynamic instability with an indication for CABG, emergency surgery should be performed and not postponed as a consequence of antiplatelet treatment exposure. 6.3.3 Percutaneous coronary intervention vs coronary artery bypass grafting There is no randomized comparison of PCI vs CABG in the specific setting of NSTE-ACS. The currently available evidence indirectly suggests that the criteria applied to patients with SCAD to guide the choice of revascularization modality should be applied to stabilized patients with NSTE-ACS [100, 121, 150, 194]. Recent individual-patients data analysis from the BEST, PRECOMBAT, and SYNTAX studies compared the outcome of CABG with that of PCI in 1246 patients with stabilized NSTE-ACS and multivessel or LM disease [194]. The 5-year incidence of the primary outcome—the composite of death, MI, or stroke—was significantly lower with CABG than with PCI (13.4 vs 18%, P = 0.036). The findings of this meta-analysis were consistent with the main findings of the studies included, thus supporting the concept that the principles of SCAD should apply to stabilized patients with NSTE-ACS as well. For complex cases, Heart Team discussion and use of the SYNTAX score are recommended [195], given its ability to predict death, MI, and revascularization in patients with NSTE-ACS and multivessel disease undergoing PCI. In patients with multivessel disease and diabetes in particular, recent evidence suggests a greater benefit of CABG vs PCI [196]. 6.4 Gaps in the evidence In the setting of NSTE-ACS, there are no dedicated prospective studies on the revascularization strategy with multivessel disease. Thus, current recommendations on the choice of lesions to be treated and treatment modality (PCI or CABG) are based on an analogy to findings obtained in SCAD or STEMI. Likewise, the prognostic role of FFR and iwFR in guiding myocardial revascularization needs additional clarification. Recommendations for invasive evaluation and revascularization in non-ST-elevation acute coronary syndrome a Class of recommendation. b Level of evidence. c May apply to stabilized NSTE-ACS patients. CABG: coronary artery bypass grafting; IRA: infarct-related artery; NSTE-ACS: non-ST-elevation acute coronary syndrome; PCI: percutaneous coronary intervention; SCAD: stable coronary artery disease; SYNTAX: Synergy Between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery. Recommendations for invasive evaluation and revascularization in non-ST-elevation acute coronary syndrome a Class of recommendation. b Level of evidence. c May apply to stabilized NSTE-ACS patients. CABG: coronary artery bypass grafting; IRA: infarct-related artery; NSTE-ACS: non-ST-elevation acute coronary syndrome; PCI: percutaneous coronary intervention; SCAD: stable coronary artery disease; SYNTAX: Synergy Between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery. 7. Revascularization in ST-segment elevation myocardial infarction Myocardial revascularization in patients with STEMI is addressed by the 2017 ESC Guidelines on STEMI. After reviewing the subsequent literature, the current Task Force endorses most recommendations of these Guidelines [198]. 7.1 Time delays Delays in the timely implementation of reperfusion therapy are key issues in the management of STEMI. Detailed recommendations on timelines, logistics, and pre-hospital management have been provided in the recent ESC STEMI Guidelines (Figure 5) [198]. Figure 5 View largeDownload slide Modes of patient’s medical contact, components of ischaemia time, and flowchart for reperfusion strategy selection. Figure 5 View largeDownload slide Modes of patient’s medical contact, components of ischaemia time, and flowchart for reperfusion strategy selection. A recent analysis of 12 675 STEMI patients in the FITT-STEMI (Feedback Intervention and Treatment Times in ST-Elevation Myocardial Infarction) trial emphasizes the strong impact of time delays on mortality, particularly in STEMI patients with cardiogenic shock or out-of-hospital cardiac arrest [199]. In shock without out-of-hospital cardiac arrest, every 10 min treatment delay between 60–180 min from the first medical contact resulted in 3.3 additional deaths per 100 PCI-treated patients, and in 1.3 additional deaths after out-of-hospital cardiac arrest without cardiogenic shock. In stable STEMI patients, time delays were substantially less relevant (0.3 additional deaths per 100 PCI-treated patients for every 10 min delay between 60–180 min from the first medical contact). Thus, high-risk STEMI patients with cardiogenic shock or out-of-hospital cardiac arrest are those who benefit most from expediting all steps of the care pathway. 7.2 Selection of reperfusion strategy Primary PCI, defined as percutaneous catheter intervention in the setting of STEMI without previous fibrinolysis, is the preferred reperfusion strategy. It has replaced fibrinolysis in patients with STEMI, provided it can be performed in a timely manner in high-volume PCI centres with experienced operators and 24 h/7 days a week catheterization laboratory activation [198, 200, 201]. In settings where primary PCI cannot be performed in a timely fashion, fibrinolysis should be administered as soon as possible. If first medical contact (FMC) is out-of-hospital, lysis should be implemented pre-hospital (e.g. in the ambulance) (Figure 5) [202–206]. It should be followed by transfer to PCI-capable centres for routine coronary angiography in all patients, and should be performed without delay for rescue PCI in the case of unsuccessful fibrinolysis or within 2–24 h after bolus administration [198]. Emergency CABG may be indicated in selected STEMI patients unsuitable for PCI. 7.3 Primary percutaneous coronary intervention Key points for optimizing and guiding primary PCI are summarized below. The infarct-related artery (IRA) should be systematically treated during the initial intervention. Patients with extensive CAD in vessels remote from the IRA have an adverse prognosis following primary PCI [207]. Staged PCI in patients with multivessel disease and no haemodynamic compromise is an independent predictor of survival, and more frequent ischaemic events have been reported in direct vs staged revascularization of STEMI patients with multivessel disease [208–210]. Four major randomized trials—PRAMI (Preventive Angioplasty in Acute Myocardial Infarction) [211], CvLPRIT (Complete Versus Lesion-Only Primary PCI trial) [212], DANAMI-3−PRIMULTI (The Third DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction: PRImary PCI in MULTIvessel Disease) [213], and Compare-Acute [214]—have consistently shown a benefit of complete revascularization (performed immediately or staged) as compared with IRA-only PCI in patients with STEMI and multivessel disease (for details see the Supplementary Data). A recent meta-analysis of 10 trials has shown that complete revascularization was associated with a lower risk of MACE (RR 0.57, 95% CI 0.42–0.77), due to a lower risk of urgent revascularization (RR 0.44, 95% CI 0.30–0.66), with no significant difference in mortality (RR 0.76, 95% CI 0.52–1.12) or MI (RR 0.54, 95% CI 0.23–1.27) [215]. This meta-analysis did not include Compare-Acute. Yet, similar to earlier studies, the benefit of complete revascularization over culprit-only revascularization seen in Compare-Acute was driven by a lower need for unplanned reintervention, whereas the incidences of death and recurrent MI were similar between the two strategies [214]. Most of the studies support the concept of full revascularization either during the initial hospital stay for STEMI or a staged admission [215], but it remains to be determined how clinicians can identify lesions that should be revascularized beyond the culprit lesion and whether complete revascularization should be performed in single- or multi-stage procedures. Moreover, there is a lack of evidence on the optimal timing of staged procedures. In most of the studies, staged procedures were performed during the initial hospital stay. At present, one-stage multivessel PCI during STEMI without cardiogenic shock should be considered in patients in the presence of multiple, critical stenoses or highly unstable lesions (angiographic signs of possible thrombus or lesion disruption), and if there is persistent ischaemia after PCI on the supposed culprit lesion. In patients with multivessel disease and AMI with cardiogenic shock, the recently published CULPRIT-SHOCK trial showed that a strategy with PCI of the culprit lesion only with possible staged revascularization determined a lower 30-day risk of the composite of all-cause mortality or severe renal failure compared with immediate multivessel PCI [190]. This was driven by a significant risk reduction in 30-day all-cause mortality by the culprit lesion-only strategy compared with immediate multivessel PCI (43.3 vs 51.6%; HR 0.84, 95% CI 0.72–0.98, P = 0.03). These findings need to be interpreted in light of a low 12.5% (43 out of 344 patients) crossover rate from culprit lesion-only to immediate multivessel PCI based on physicians’ judgment. Based on these findings, culprit lesion-only PCI is recommended as the default strategy in patients with AMI with cardiogenic shock. A more detailed discussion of the revascularization strategy in MI patients with cardiogenic shock is found in the Supplementary Data. In patients with STEMI, DES (in particular new-generation DES) have demonstrated better efficacy as compared with BMS and should be used as the default strategy in STEMI patients, even when DAPT cannot be sustained beyond 1 month [177, 178, 216–218] (see section 16.1.2). As discussed in section 16.4, radial access is preferred over femoral access. Delaying stenting in primary PCI has been investigated as an option to reduce microvascular obstruction (MVO) and preserve microcirculatory function in two small trials with conflicting results [219, 220]. More recently, in the larger deferred vs conventional stent implantation in patients with STEMI [The Third DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction: DEFERred stent implantation in connection with primary PCI (DANAMI 3-DEFER)] trial in 1215 STEMI patients, there was no effect on the primary clinical outcome (composite of death, non-fatal MI, or ischaemia-driven revascularization of non-IRA lesions) over a median follow-up of 42 months [221]. Routine deferred stenting was associated with a higher risk of TVR. Thrombus aspiration has been proposed as an adjunct during primary PCI to further improve epicardial and myocardial reperfusion by the prevention of distal embolization of thrombotic material and plaque debris [222]. Two landmark RCTs, which were adequately powered to detect the superiority of routine manual thrombus aspiration vs conventional PCI, showed no benefit on clinical outcomes of the routine aspiration strategy overall or in any subgroup of patients indicating high thrombotic risk [223–226]. A safety concern emerged in TOTAL (Trial of Routine Aspiration Thrombectomy with PCI versus PCI Alone in Patients with STEMI) trial with an increase in the risk of stroke [225, 227]. Taken together, these results suggest that the routine use of thrombus aspiration is not indicated. In the high-thrombus burden subgroup, the trend towards reduced cardiovascular death and increased stroke/transient ischaemic attack (TIA) provides a rationale for future trials of improved thrombus aspiration technologies in this high-risk subgroup (although statistical tests did not support significant subgroup interaction) [228]. 7.4 Percutaneous coronary intervention after thrombolysis and in patients with late diagnosis The benefits of early, routine PCI after thrombolysis were seen in the absence of an increased risk of adverse events (stroke or major bleeding). Based on data from the four most recent trials, all of which had a median delay between the start of thrombolysis and angiography of 2–6 h, a time frame of 2–24 h after successful lysis is recommended [206, 229–231]. In cases of failed fibrinolysis, or if there is evidence of re-occlusion or reinfarction with recurrence of ST-segment elevation, the patient should undergo immediate coronary angiography and rescue PCI [232]. Patients presenting between 12 and 48 h after the onset of symptoms, even if pain free and with stable haemodynamics, may still benefit from early coronary angiography and possibly PCI [233, 234]. In patients presenting days after the acute event with a completed MI, only those with recurrent angina or documented residual ischaemia—and proven viability on non-invasive imaging in a large myocardial territory—may be considered for revascularization when the infarct artery is occluded. Routine late PCI of an occluded IRA after MI in stable patients has no incremental benefit over medical therapy [235]. 7.5 Gaps in the evidence Patients undergoing primary PCI benefit from full revascularization, but the optimal timing of treatment of the non-culprit lesion is not known. More studies evaluating the assessment of non-culprit lesions by FFR or iwFR at the time of acute PCI, and studies investigating whether intravascular imaging guidance of primary PCI can improve the outcomes of STEMI patients, are needed. Future trials of improved thrombus aspiration technologies may address the role of this strategy in patients with high-risk features, such as large thrombus burden [228]. Primary percutaneous coronary intervention for myocardial reperfusion in ST-elevation myocardial infarction: indications and logistics a Class of recommendation. b Level of evidence. CCU: coronary care unit; EMS: emergency medical services; ICCU: intensive coronary care unit; MI: myocardial infarction; PCI: percutaneous coronary intervention; STEMI: ST-segment elevation myocardial infarction. Primary percutaneous coronary intervention for myocardial reperfusion in ST-elevation myocardial infarction: indications and logistics a Class of recommendation. b Level of evidence. CCU: coronary care unit; EMS: emergency medical services; ICCU: intensive coronary care unit; MI: myocardial infarction; PCI: percutaneous coronary intervention; STEMI: ST-segment elevation myocardial infarction. Primary percutaneous coronary intervention for myocardial reperfusion in ST-elevation myocardial infarction: procedural aspects (strategy and technique) a Class of recommendation. b Level of evidence. CABG: coronary artery bypass grafting; IRA: infarct-related artery; PCI: percutaneous coronary intervention; STEMI: ST-segment elevation myocardial infarction. Primary percutaneous coronary intervention for myocardial reperfusion in ST-elevation myocardial infarction: procedural aspects (strategy and technique) a Class of recommendation. b Level of evidence. CABG: coronary artery bypass grafting; IRA: infarct-related artery; PCI: percutaneous coronary intervention; STEMI: ST-segment elevation myocardial infarction. 8. Myocardial revascularization in patients with heart failure 8.1 Chronic heart failure 8.1.1 Recommendations for myocardial revascularization in patients with chronic heart failure When compared with medical therapy alone, coronary revascularization is superior in improving survival in patients with HF of ischaemic origin and is recommended in clinical practice [81, 248]. However, the optimal revascularization strategy is not defined. The choice between CABG and PCI should be made by the Heart Team after careful evaluation of the patient’s clinical status and coronary anatomy, expected completeness of revascularization (see section 5.3.1.3), myocardial viability, coexisting valvular disease, and comorbidities. Considerations relating to the need for viability testing prior to revascularization are discussed in section 3. Randomized clinical trial data comparing revascularization with medical therapy exists only for CABG in the setting of the STICH trial [81]. One analysis from this trial showed that CABG can be performed with acceptable 30-day mortality rates (5.1%) in patients with LV dysfunction (LVEF ≤35%) [249]. Extended follow-up in the STICH Extension Study (STICHES) supports a significant survival benefit of CABG combined with medical therapy vs medical therapy alone in a 10-year observation period [81]. There are currently no dedicated randomized clinical trials comparing PCI vs medical therapy in patients with HF with reduced EF (HFrEF). In addition, CABG vs PCI randomized trials have excluded patients with severe HF. In one prospective registry including 4616 patients with multivessel disease and severe HFrEF, propensity score-matched comparison revealed similar survival (mean follow-up 2.9 years) with PCI (using EES) vs CABG [250]. PCI was associated with a higher risk of MI, particularly in patients with incomplete revascularization, and repeat revascularization. CABG was associated with a higher risk of stroke. The conclusion of the study was that multivessel PCI can be a valuable option in HF patients if complete revascularization is possible. A systematic review of studies comparing revascularization with medical therapy in patients with an EF ≤40% showed that there was a significant mortality reduction with CABG (HR 0.66, 95% CI 0.61–0.72, P <0.001) and PCI (HR 0.73, 95% CI 0.62–0.85, P <0.001) vs medical therapy, though these finding are limited by the predominantly observational nature of the included studies and missing information on the completeness of revascularization [248]. A recent observational study investigated outcomes with PCI or CABG for multivessel CAD and LV dysfunction in 1738 propensity-matched patients with diabetes mellitus [251]. Similar to the findings in the absence of LV dysfunction, when CABG was compared with PCI it was associated with a significantly lower risk of MACE, which included a significant reduction in mortality. Event curves separated early during the first year and continued to separate out to 12 years. PCI should be considered in older patients without diabetes in whom complete revascularization can be achieved, whereas CABG is preferred in younger patients with more extensive CAD or those with diabetes. In patients with diabetes and LV moderate or severe dysfunction (EF <50%), CABG is associated with better long-term survival and reduced incidence of MACCE [250, 251]. 8.1.2 Ventricular reconstruction and aneurysm resection The aim of surgical ventricular reconstruction (SVR) is to restore physiological volume, and achieve an elliptical shape of the LV, by scar resection and LV wall reconstruction on a mannequin of predefined size. The aim of ventricular aneurysmectomy is to remove fibrous scars in cases of severe dilatation, thrombus formation, or as a source of life-threatening ventricular arrhythmias. The STICH trial revealed no difference in the primary outcome (total mortality or cardiac hospitalization) between patients randomly allocated to CABG vs combined CABG and SVR [252]. Subgroup analyses of patients with a less dilated LV and better LVEF showed benefit from SVR [253]. In the STICH trial, a post-operative LV end-systolic volume index ≤70 ml/m2, after CABG plus SVR, resulted in improved survival compared with CABG alone [252, 254]. In experienced centres, SVR may be done at the time of CABG if HF symptoms are more predominant than angina, and if myocardial scar and moderate LV remodelling are present. Recommendations on revascularizations in patients with chronic heart failure and systolic left ventricular dysfunction (ejection fraction ≤35%) a Class of recommendation. b Level of evidence. CABG: coronary artery bypass grafting; LV: left ventricular; NYHA: New York Heart Association; PCI: percutaneous coronary intervention. Recommendations on revascularizations in patients with chronic heart failure and systolic left ventricular dysfunction (ejection fraction ≤35%) a Class of recommendation. b Level of evidence. CABG: coronary artery bypass grafting; LV: left ventricular; NYHA: New York Heart Association; PCI: percutaneous coronary intervention. 8.2 Acute heart failure and cardiogenic shock Acute myocardial ischaemia in the setting of AMI is the antecedent event for the majority of patients with cardiogenic shock undergoing percutaneous revascularization. Mechanical complications—such as papillary muscle rupture with severe mitral valve regurgitation, ventricular septal defect, or free wall rupture—are additional precipitating causes. 8.2.1 Revascularization The SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) trial demonstrated that in patients with cardiogenic shock complicating AMI, emergency revascularization with PCI or CABG improved long-term survival when compared with initial intensive medical therapy. All-cause mortality at 6 months was lower in the group assigned to revascularization than in the medically treated patients (50.3 vs 63.1%, respectively; RR 0.80, 95% CI 0.65–0.98, P = 0.03) [258]. The revascularization strategy for patients with cardiogenic shock and multivessel disease is addressed in section 7. A subanalysis of the SHOCK trial comparing patients treated with CABG or PCI showed similar survival rates between the two subgroups [259]. There were more patients with diabetes (48.9 vs 26.9%; P = 0.02), three-vessel disease (80.4 vs 60.3%; P = 0.03), and LM coronary disease (41.3 vs 13.0%; P = 0.001) in the CABG group. The findings of this non-randomized comparison suggest that CABG should be considered in patients with cardiogenic shock who have suitable anatomy, particularly if successful PCI is not feasible. 8.2.2 Mechanical circulatory support Short-term MCS devices that are currently available are the intra-aortic balloon pump (IABP), veno-arterial extracorporeal membrane oxygenation (ECMO), and percutaneous left ventricular assist devices (pLVADs). Short-term MCS may be considered in refractory cardiogenic shock depending on patient age, comorbidities, neurological function, and the prospects for long-term survival and quality of life. 8.2.2.1 Intra-aortic balloon pump IABPs are low-cost devices that are easy to insert and remove. They moderately increase cardiac output and coronary and cerebral perfusion, while decreasing ventricular workload. In patients with cardiogenic shock complicating acute MI, the IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II) randomized trial (600 patients) showed that the use of IABPs did not reduce 30-day mortality and that there was no evidence of long-term benefit [260, 261]. A recent Cochrane review of seven trials (790 patients) showed that IABPs may have a beneficial effect on some haemodynamic parameters but did not result in survival benefits [262]. Thus, the routine use of IABPs in patients with cardiogenic shock complicating acute MI is not recommended. 8.2.2.2 Extracorporeal membrane oxygenation Veno-arterial ECMO (VA-ECMO), also known as extracorporeal life support (ECLS), in its current form is a modified form of cardiopulmonary bypass. It decompresses the venous system; increases coronary, cerebral, and peripheral perfusion; and also provides supplementary blood oxygenation. When performed percutaneously, it does not allow for LV decompression and leads to increasing LV afterload. In patients with cardiac arrest, evidence from observational trials supports better survival in patients treated with VA-ECMO compared with those without [263]. When compared with IABP, VA-ECMO provides superior circulatory support [264, 265]. Moreover, a meta-analysis of observational studies suggested that in patients with cardiogenic shock post-ACS, VA-ECMO showed a 33% higher 30-day survival compared with IABP [95% CI 14–52%, P <0.001; number needed to treat (NNT) 13] [263]. However, the low number of patients included in the analysed studies and the non-random treatment allocation are important limitations. 8.2.2.3 Percutaneous left ventricular assist devices The majority of clinical experience with currently available pLVADs is limited to two types of device: (i) a transaortic microaxial pump (Impella) that directly unloads the LV providing 2.5–5 l/min blood flow and (ii) a transseptal centrifugal assist device (TandemHeart) that unloads the LV via a cannula introduced into the left atrium through a transseptal puncture. A recent meta-analysis on MCS in cardiogenic shock included four randomized trials investigating the efficacy and safety of pLVADs vs IABP, and demonstrated similar short-term mortality despite initial beneficial effects on arterial blood pressure and peripheral perfusion, measured by serum lactate levels [266]. In all trials, a higher rate of bleeding from vascular access sites and a significantly higher incidence of limb ischaemia following pLVAD was noted. Similar outcomes were noted in an RCT of high-risk PCI in patients with impaired LV function. The 30-day incidence of major adverse events was not different for patients with pLVAD vs IABP [267]. In summary, the evidence for pLVAD is insufficient to provide a recommendation on its clinical use in cardiogenic shock. 8.2.2.4 Surgically implanted left ventricular assist devices There are limited data on surgically-implanted LV assist device (LVAD) therapy in patients with AMI and cardiogenic shock. One multicentre registry showed that despite being more critically ill prior to implantation, patients with acute MI managed with LVAD had outcomes similar to other LVAD populations [268]. A suggested algorithm for the management of patients with cardiogenic shock is shown in Figure 6. Figure 6 View largeDownload slide Algorithm for the management of patients with cardiogenic shock. Figure 6 View largeDownload slide Algorithm for the management of patients with cardiogenic shock. 8.3 Gaps in the evidence There is no RCT comparing revascularization with PCI vs CABG in patients with HF. There is limited evidence on the role of active MCS in patients with cardiogenic shock compared with standard therapy. Recommendations for the management of patients with cardiogenic shock a Class of recommendation. b Level of evidence ACS: acute coronary syndrome; CABG: coronary artery bypass grafting; IABP: intra-aortic balloon pump; NSTE-ACS: non-ST-elevation acute coronary syndrome; PCI: percutaneous coronary intervention; STEMI: ST-elevation myocardial infarction. Recommendations for the management of patients with cardiogenic shock a Class of recommendation. b Level of evidence ACS: acute coronary syndrome; CABG: coronary artery bypass grafting; IABP: intra-aortic balloon pump; NSTE-ACS: non-ST-elevation acute coronary syndrome; PCI: percutaneous coronary intervention; STEMI: ST-elevation myocardial infarction. 9. Revascularization in patients with diabetes Patients wit http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Cardio-Thoracic Surgery Oxford University Press

2018 ESC/EACTS Guidelines on myocardial revascularization

Sousa-Uva,, Miguel; Neumann,, Franz-Josef; Ahlsson,, Anders; Alfonso,, Fernando; Banning, Adrian, P; Benedetto,, Umberto; Byrne, Robert, A; Collet,, Jean-Philippe; Falk,, Volkmar; Head, Stuart, J; Jüni,, Peter; Kastrati,, Adnan; Koller,, Akos; Kristensen, Steen, D; Niebauer,, Josef; Richter, Dimitrios, J; Seferović, Petar, M; Sibbing,, Dirk; Stefanini, Giulio, G; Windecker,, Stephan; Yadav,, Rashmi; Zembala, Michael, O; Wijns,, William; Glineur,, David; Aboyans,, Victor; Achenbach,, Stephan; Agewall,, Stefan; Andreotti,, Felicita; Barbato,, Emanuele; Baumbach,, Andreas; Brophy,, James; Bueno,, Héctor; Calvert, Patrick, A; Capodanno,, Davide; Davierwala, Piroze, M; Delgado,, Victoria; Dudek,, Dariusz; Freemantle,, Nick; Funck-Brentano,, Christian; Gaemperli,, Oliver; Gielen,, Stephan; Gilard,, Martine; Gorenek,, Bulent; Haasenritter,, Joerg; Haude,, Michael; Ibanez,, Borja; Iung,, Bernard; Jeppsson,, Anders; Katritsis,, Demosthenes; Knuuti,, Juhani; Kolh,, Philippe; Leite-Moreira,, Adelino; Lund, Lars, H; Maisano,, Francesco; Mehilli,, Julinda; Metzler,, Bernhard; Montalescot,, Gilles; Pagano,, Domenico; Petronio, Anna, Sonia; Piepoli, Massimo, Francesco; Popescu, Bogdan, A; Sádaba,, Rafael; Shlyakhto,, Evgeny; Silber,, Sigmund; Simpson, Iain, A; Sparv,, David; Tavilla,, Giuseppe; Thiele,, Holger; Tousek,, Petr; , Van Belle, Eric; Vranckx,, Pascal; Witkowski,, Adam; Zamorano, Jose, Luis; Roffi,, Marco; Windecker,, Stephan; Aboyans,, Victor; Agewall,, Stefan; Barbato,, Emanuele; Bueno,, Héctor; Coca,, Antonio; Collet,, Jean-Philippe; Coman, Ioan, Mircea; Dean,, Veronica; Delgado,, Victoria; Fitzsimons,, Donna; Gaemperli,, Oliver; Hindricks,, Gerhard; Iung,, Bernard; Jüni,, Peter; Katus, Hugo, A; Knuuti,, Juhani; Lancellotti,, Patrizio; Leclercq,, Christophe; McDonagh, Theresa, A; Piepoli, Massimo, Francesco; Ponikowski,, Piotr; Richter, Dimitrios, J; Roffi,, Marco; Shlyakhto,, Evgeny; Sousa-Uva,, Miguel; Simpson, Iain, A; Zamorano, Jose, Luis; Pagano,, Domenico; Freemantle,, Nick; Sousa-Uva,, Miguel; Chettibi,, Mohamed; Sisakian,, Hamayak; Metzler,, Bernhard; İbrahimov,, Firdovsi; Stelmashok, Valeriy, I; Postadzhiyan,, Arman; Skoric,, Bosko; Eftychiou,, Christos; Kala,, Petr; Terkelsen, Christian, Juhl; Magdy,, Ahmed; Eha,, Jaan; Niemelä,, Matti; Kedev,, Sasko; Motreff,, Pascal; Aladashvili,, Alexander; Mehilli,, Julinda; Kanakakis,, Ioannis-Georgios; Becker,, David; Gudnason,, Thorarinn; Peace,, Aaron; Romeo,, Francesco; Bajraktari,, Gani; Kerimkulova,, Alina; Rudzītis,, Ainārs; Ghazzal,, Ziad; Kibarskis,, Aleksandras; Pereira,, Bruno; Xuereb, Robert, G; Hofma, Sjoerd, H; Steigen, Terje, K; Witkowski,, Adam; , de Oliveira, Eduardo Infante; Mot,, Stefan; Duplyakov,, Dmitry; Zavatta,, Marco; Beleslin,, Branko; Kovar,, Frantisek; Bunc,, Matjaž; Ojeda,, Soledad; Witt,, Nils; Jeger,, Raban; Addad,, Faouzi; Akdemir,, Ramazan; Parkhomenko,, Alexander; Henderson,, Robert
European Journal of Cardio-Thoracic Surgery , Volume 55 (1) – Jan 1, 2019

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