European Heart Journal (2010) 31, 2501–2555 ESC/EACTS GUIDELINES doi:10.1093/eurheartj/ehq277Guidelines on myocardial revascularizationThe Task Force on Myocardial Revascularization of the EuropeanSociety of Cardiology (ESC) and the European Association forCardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Associationfor Percutaneous Cardiovascular Interventions (EAPCI)‡Authors/Task Force Members: William Wijns (Chairperson) (Belgium)*, Philippe Kolh(Chairperson) (Belgium)*, Nicolas Danchin (France), Carlo Di Mario (UK),Volkmar Falk (Switzerland), Thierry Folliguet (France), Scot Garg (The Netherlands),Kurt Huber (Austria), Stefan James (Sweden), Juhani Knuuti (Finland), JoseLopez-Sendon (Spain), Jean Marco (France), Lorenzo Menicanti (Italy)Miodrag Ostojic (Serbia), Massimo F. Piepoli (Italy), Charles Pirlet (Belgium),Jose L. Pomar (Spain), Nicolaus Reifart (Germany), Flavio L. Ribichini (Italy),Martin J. Schalij (The Netherlands), Paul Sergeant (Belgium), Patrick W. Serruys(The Netherlands), Sigmund Silber (Germany), Miguel Sousa Uva (Portugal),David Taggart (UK)ESC Committee for Practice Guidelines: Alec Vahanian (Chairperson) (France), Angelo Auricchio (Switzerland),Jeroen Bax (The Netherlands), Claudio Ceconi (Italy), Veronica Dean (France), Gerasimos Filippatos (Greece),Christian Funck-Brentano (France), Richard Hobbs (UK), Peter Kearney (Ireland), Theresa McDonagh (UK),Bogdan A. Popescu (Romania), Zeljko Reiner (Croatia), Udo Sechtem (Germany), Per Anton Sirnes (Norway),Michal Tendera (Poland), Panos E. Vardas (Greece), Petr Widimsky (Czech Republic)EACTS Clinical Guidelines Committee: Philippe Kolh (Chairperson) (Belgium), Ottavio Alﬁeri (Italy), Joel Dunning(UK), Stefano Elia (Italy), Pieter Kappetein (The Netherlands), Ulf Lockowandt (Sweden), George Sarris (Greece),Pascal Vouhe (France)Document Reviewers: Peter Kearney (ESC CPG Review Coordinator) (Ireland), Ludwig von Segesser (EACTSReview Coordinator) (Switzerland), Stefan Agewall (Norway), Alexander Aladashvili (Georgia),Dimitrios Alexopoulos (Greece), Manuel J. Antunes (Portugal), Enver Atalar (Turkey), Aart Brutel de la Riviere* Corresponding authors (the two chairpersons contributed equally to this document): William Wijns, Cardiovascular Center, OLV Ziekenhuis, Moorselbaan 164, 9300 Aalst,Belgium. Tel: +32 53 724 439, Fax: +32 53 724 185, Email: firstname.lastname@example.orgPhilippe Kolh, Cardiovascular Surgery Department, University Hospital (CHU, ULg) of Liege, Sart Tilman B 35, 4000 Liege, Belgium. Tel: +32 4 366 7163, Fax: +32 4 366 7164,Email: email@example.comThe content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of theESC Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to OxfordUniversity Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC.‡ Other ESC entities having participated in the development of this document:Associations: Heart Failure Association (HFA), European Association for Cardiovascular Prevention and Rehabilitation (EACPR), European Heart Rhythm Association (EHRA), Euro-pean Association of Echocardiography (EAE).Working Groups: Acute Cardiac Care, Cardiovascular Surgery, Thrombosis, Cardiovascular Pharmacology and Drug Therapy.Councils: Cardiovascular Imaging, Cardiology Practice.Disclaimer. The ESC Guidelines represent the views of the ESC and were arrived at after careful consideration of the available evidence at the time they were written. Healthprofessionals are encouraged to take them fully into account when exercising their clinical judgement. The guidelines do not, however, override the individual responsibility of healthprofessionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and where appropriate and necessary the patient’sguardian 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.& The European Society of Cardiology 2010. All rights reserved. For Permissions please email: firstname.lastname@example.org.
2504 ESC/EACTS GuidelinesSPECT single photon emission computed tomography Table 1 Classes of recommendationsSTEMI ST-segment elevation myocardial infarctionSVG saphenous vein graftSVR surgical ventricular reconstruction Classes of Deﬁnition recommendationsTIA transient ischaemic attackTVR target vessel revascularization Class I Evidence and/or general agreementUFH unfractionated heparin that a given treatment or procedure is beneﬁcial, useful, effective.VD vessel diseaseVSD ventricular septal defect Class II Conﬂicting evidence and/or aVT ventricular tachycardia divergence of opinion about the usefulness/efﬁcacy of the givenZES zotarolimus-eluting stent treatment or procedure. Class IIa Weight of evidence/opinion is in favour of usefulness/efﬁcacy.1. Preamble Class IIb Usefulness/efﬁcacy is less wellGuidelines and Expert Consensus Documents summarize and established by evidence/opinion.evaluate all available evidence with the aim of assisting physicians Class III Evidence or general agreement thatin selecting the best management strategy for an individual the given treatment or procedure ispatient suffering from a given condition, taking into account the not useful/effective, and in some casesimpact on outcome and the risk –beneﬁt ratio of diagnostic or may be harmful.therapeutic means. Guidelines are no substitutes for textbooksand their legal implications have been discussed previously. Guide-lines and recommendations should help physicians to makedecisions in their daily practice. However, the ultimate judgementregarding the care of an individual patient must be made by his/her Table 2 Levels of evidenceresponsible physician(s). The recommendations for formulating and issuing ESC Guide- Data derived from multiple randomized Level of clinical trialslines and Expert Consensus Documents can be found on the evidence A or meta-analyses.ESC website (http://www.escardio.org/guidelines-surveys/esc-guidelines/about/Pages/rules-writing.aspx). Data derived from a single randomized Level of clinical trial Members of this Task Force were selected by the European Society evidence B or large non-randomized studies.of Cardiology (ESC) and the European Association forCardio-Thoracic Surgery (EACTS) to represent all physicians involved Level of Consensus of opinion of the experts and/or evidence C small studies, retrospective studies, registries.with the medical and surgical care of patients with coronary arterydisease (CAD). A critical evaluation of diagnostic and therapeutic pro-cedures is performed including assessment of the risk–beneﬁt ratio.Estimates of expected health outcomes for society are included,where data exist. The level of evidence and the strength of recommen- assistant-downloadable versions are useful at the point of care.dation of particular treatment options are weighed and graded accord- Some surveys have shown that the intended users are sometimesing to predeﬁned scales, as outlined in Tables 1 and 2. unaware of the existence of guidelines, or simply do not translate The members of the Task Force have provided disclosure state- them into practice. Thus, implementation programmes are neededments of all relationships that might be perceived as real or poten- because it has been shown that the outcome of disease may betial sources of conﬂicts of interest. These disclosure forms are kept favourably inﬂuenced by the thorough application of clinicalon ﬁle at European Heart House, headquarters of the ESC. Any recommendations.changes in conﬂict of interest that arose during the writingperiod were notiﬁed to the ESC. The Task Force report receivedits entire ﬁnancial support from the ESC and EACTS, without any 2. Introductioninvolvement of the pharmaceutical, device, or surgical industry. Myocardial revascularization has been an established mainstay in the ESC and EACTS Committees for Practice Guidelines are treatment of CAD for almost half a century. Coronary artery bypassresponsible for the endorsement process of these joint Guidelines. grafting (CABG), used in clinical practice since the 1960s, is arguablyThe ﬁnalized document has been approved by all the experts the most intensively studied surgical procedure ever undertaken,involved in the Task Force, and was submitted to outside special- while percutaneous coronary intervention (PCI), used for overists selected by both societies for review. The document is revised, three decades, has been subjected to more randomized clinicaland ﬁnally approved by ESC and EACTS and subsequently pub- trials (RCTs) than any other interventional procedure. PCI waslished simultaneously in the European Heart Journal and the Euro- ﬁrst introduced in 1977 by Andreas Gruentzig and by thepean Journal of Cardio-Thoracic Surgery. mid-1980s was promoted as an alternative to CABG. While both After publication, dissemination of the Guidelines is of para- interventions have witnessed signiﬁcant technological advances, inmount importance. Pocket-sized versions and personal digital particular the use of drug-eluting stents (DES) in PCI and of arterial
ESC/EACTS Guidelines 2505grafts in CABG, their role in the treatment of patients presenting important aspect of contemporary clinical practice, being of value towith stable CAD is being challenged by advances in medical treat- clinicians and patients. Over the long term, it allows quality controlment, referred to as optimal medical therapy (OMT), which and the assessment of health economics, while also serving as ainclude intensive lifestyle and pharmacological management. Fur- means for individual operators, institutions and regulatory bodies tothermore, the differences between the two revascularization strat- assess and compare performance. Numerous different models haveegies should be recognized. In CABG, bypass grafts are placed to been developed for risk stratiﬁcation, and those in current clinicalthe mid-coronary vessel beyond the ‘culprit’ lesion(s), providing use are summarized in Table 3. Comparative analyses of theseextra sources of nutrient blood ﬂow to the myocardium and offering models are limited because available studies have largely evaluatedprotection against the consequences of further proximal obstructive individual risk models in different patient populations with differentdisease. In contrast, coronary stents aim to restore the normal con- outcome measures reported at various time points. These limitationsductance of the native coronary vasculature without offering protec- restrict the ability to recommend one speciﬁc risk model; however:tion against new disease proximal to the stent. Even with this fundamental difference in the mechanisms of † The EuroSCORE validated to predict surgical mortality wasaction between the two techniques, myocardial revascularization recently shown to be an independent predictor of majorprovides the best results when focusing on the relief of ischaemia. adverse cardiac events (MACEs) in studies with both percuta-In patients presenting with unstable angina, non-ST-segment neous and surgical treatment arms.2,3 Therefore, it can beelevation acute coronary syndrome (NSTE-ACS), and ST-segment used to determine the risk of revascularization irrespective of,elevation myocardial infarction (STEMI), myocardial ischaemia is and even before, the selection of treatment strategy. It hasobvious and life-threatening. Culprit coronary stenoses are easily little role, however, in determining optimal treatment.identiﬁed by angiography in the vast majority of cases. By contrast, † The SYNTAX score has been shown to be an independent pre-in patients with stable CAD and multivessel disease (MVD) in par- dictor of MACE in patients treated with PCI but not withticular, identiﬁcation of the culprit stenosis or stenoses requires CABG.4 Therefore it has a role in aiding the selection ofanatomical orientation by angiography combined with functional optimal treatment by identifying those patients at highest riskevaluation, obtained either by non-invasive imaging before cathe- of adverse events following PCI.terization, or during the invasive procedure using pressure-derived † The National Cardiovascular Database Registry (NCDRfractional ﬂow reserve (FFR) measurements. CathPCI risk score) has been validated in PCI patients and Many conditions, stable or acute, can be treated in different ways, should only be used in this context.5including PCI or surgical revascularization. The advances in technology † The Society of Thoracic Surgeons (STS) score, and the age,imply that most coronary lesions are technically amenable to PCI; creatinine, and ejection fraction (ACEF) score have been vali-however, technical feasibility is only one element of the decision- dated in surgical patients, and therefore should only be usedmaking process, which should incorporate clinical presentation, sever- to determine surgical risk.ity of angina, extent of ischaemia, response to medical therapy, andextent of anatomical disease by angiography. Both revascularization It is important to acknowledge that no risk score can accuratelymethods carry procedure-related risks that are different to some predict events in an individual patient. Moreover, limitations existextent in nature, rate, and time domain. Thus patients and physicians with all databases used to build risk models, and differences in deﬁ-need to ‘balance short-term convenience of the less invasive PCI pro- nitions and variable content can affect the performance of risk scorescedure against the durability of the more invasive surgical approach’.1 when they are applied across different populations. Ultimately risk Formulation of the best possible revascularization approach, stratiﬁcation should be used as a guide, while clinical judgementtaking into consideration the social and cultural context also, will and multidisciplinary dialogue (Heart Team) remain essential.often require interaction between cardiologists and cardiac sur-geons, referring physicians or other specialists as desirable. Patientsneed help in taking informed decisions about their treatment, and 4. Process for decision making andthe most valuable advice will likely be provided to them by the patient informationHeart Team. Recognizing the importance of the interactionbetween (interventional) cardiologists and cardiac surgeons, the lea- 4.1 Patient informationdership of both the ESC and EACTS has given this Joint Task Force, Patient information needs to be objective and unbiased, patienttheir respective Guideline Committee, and the reviewers of this oriented, evidence based, up-to-date, reliable, understandable,document the mission to draft balanced, patient-centred, evidence- accessible, relevant, and consistent with legal requirements.driven practice guidelines on myocardial revascularization. Informed consent requires transparency, especially if there is con- troversy about the indication for a particular treatment (PCI vs. CABG vs. OMT). Collaborative care requires the preconditions3. Scores and risk stratiﬁcation, of communication, comprehension, and trust. It is essential to realize that health care decisions can no longer be based solelyimpact of comorbidity on research results and our appraisal of the patient’s circum-Myocardial revascularization is appropriate when the expected stances. Patients taking an active role throughout the decisionbeneﬁts, in terms of survival or health outcomes (symptoms, func- making process have better outcomes. However, most patientstional status, and/or quality of life), exceed the expected negative con- undergoing CABG or PCI have limited understanding of theirsequences of the procedure. Therefore, risk assessment is an disease and sometimes unreasonable expectations with regard to
2506 ESC/EACTS Guidelines Table 3 Recommended risk stratiﬁcation scores to be used in candidates for percutaneous coronary intervention or coronary artery bypass grafting Number of variables used to Score Calculation Validated outcomes Classa/levelb Ref.c calculate risk Clinical Angiographic PCI CABG EuroSCORE www.euroscore.org/calc.html 17 0 Short- and long-term mortality IIb B IB 2, 3, 6 SYNTAX Quantify coronary artery www.syntaxscore.com 0 11 (per lesion) IIa B III B 4 score disease complexity Mayo Clinic (7, 8) 7 0 MACE and procedural death IIb C III C –— Risk Score NCDR (5) 8 0 In-hospital mortality IIb B –— 5 CathPCI Parsonnet (9) 16 0 30-day mortality –— III B 9 score Operative mortality, stroke, renal failure, prolonged http://184.108.40.206/ ventilation, deep sternal STS scored 40 2 –— IB 10 STSWebRiskCalc261/ infection, re-operation, morbidity, length of stay <6 or >14 days [Age/ejection fraction (%)] + 1 ACEF score 2 0 Mortality in elective CABG –— IIb C –— (if creatinine >2 mg/dL)(11) a Class of recommendation. b Level of evidence. c References. d The STS score is undergoing periodic adjustement which makes longitudinal comparisons difﬁcult. ACEF ¼ age, creatinine, ejection fraction; CABG ¼ coronary artery bypass grafting; MACE ¼ major adverse cardiac event; NCDR ¼ National Cardiovascular Database Registry; PCI ¼ percutaneous coronary intervention; STS ¼ Society of Thoracic Surgeons.the proposed intervention, its complications, or the need for late example of a suitable and balanced patient information documentreintervention, especially after PCI. is provided in the Appendix of the online document. Informing patients about treatment choices allows them to reﬂect There is growing public demand for transparency regarding siteon the advantages and disadvantages associated with either strategy. and operator results. Anonymous treatment should be avoided. ItPatients can only weigh this information properly in the light of their is the patient’s right to know who is about to treat him or her andpersonal values and must have the time to reﬂect on the trade-offs to obtain information on the level of expertise of the operator andimposed by the estimates. The patient deserves to fully understand the volume load of the centre. In addition, the patient should bethe risks, beneﬁts, and uncertainties associated with the condition informed whether all treatment options are available at the siteand its treatment. Avoiding incomprehensible jargon, and consistent and whether surgery is offered on site or not. Non-emergent high-use of terminology that the patient understands, are mandatory. risk PCI procedures, including those performed for distal left mainInformed medical decision making should consider short-term (LM) disease, complex bifurcation stenosis involving large sideprocedure-related beneﬁts and risks as well as expected long-term branches, single remaining coronary artery, and complex chronicrisks and beneﬁts in terms of survival, relief of angina, quality of life, total occlusion (CTO) recanalization, should be performed by ade-and the potential need for late reintervention. It is equally important quately experienced operators at centres that have access to circu-that any bias of stakeholders towards various treatment options for latory support and intensive care treatment, and haveCAD is made known to the patient. Specialty bias and self-referral cardiovascular surgery on site.should not interfere with the decision process. With the exception For patients with stable CAD and multivessel or LM disease, all rel-of unstable patients or candidates for ad hoc PCI (Table 4), the evant data should be reviewed by a clinical/non-invasive cardiologist,patient should be offered enough time, up to several days as required, a cardiac surgeon, and an interventional cardiologist (Heart Team) tobetween diagnostic catheterization and intervention to reﬂect on determine the likelihood of safe and effective revascularization withthe results of the diagnostic angiogram, to seek a second opinion either PCI or CABG.4 To ensure this review, myocardial revascular-as desirable, or to discuss the ﬁndings and consequences with his ization should in general not be performed at the time of diagnosticor her referring cardiologist and/or primary care physician. An angiography, thereby allowing the Heart Team sufﬁcient time to
ESC/EACTS Guidelines 2507 Table 4 Multidisciplinary decision pathways, patient informed consent, and timing of intervention Stable with ACS Stable MVD indication for ad hoc PCIa Shock STEMI NSTE - ACSb Other ACSc Multidisciplinary Not mandatory. Not mandatory. Not required for Required. Required. According to decision making culprit lesion but predeﬁned required for non- protocols. culprit vessel(s). Informed consent Oral witnessed Oral witnessed Written informed Written informed Written informed Written informed informed consent informed consent consentd (if time consentd consentd consentd or family consent may be sufﬁcient permits). if possible without unless written delay. consent is legally required. Time to Emergency: Emergency: Urgency: within Urgency: Elective: Elective: revascularization no delay. no delay. 24 h if possible time constraints no time constraints. no time constraints. and no later than apply. 72 h. Procedure Proceed with Proceed with Proceed with Proceed with Plan most Proceed with intervention based intervention based intervention based intervention based appropriate intervention on best evidence/ on best evidence/ on best evidence/ on best evidence/ intervention according to availability. availability. availability. Non- availability. Non- allowing enough institutional culprit culprit lesions time from diagnostic protocol deﬁned by lesions treated treated according catheterization to local Heart Team. according to to institutional intervention. institutional protocol. protocol. a Potential indications for ad hoc PCI are listed in Table 5. b See also Table 12. c Other ACS refers to unstable angina, with the exception of NSTE-ACS. d This may not apply to countries that legally do not ask for written informed consent. ESC and EACTS strongly advocate documentation of patient consent for all revascularization procedures. ACS ¼ acute coronary syndrome; MVD ¼ multivessel disease; NSTE-ACS ¼ non-ST-segment elevation acute coronary syndrome; PCI ¼ percutaneous coronary intervention; STEMI ¼ ST-segment elevation myocardial infarction.assess all available information, reach a consensus, and clearly explain autonomy, beneﬁcience, non-maleﬁcience, and justice. Theand discuss the ﬁndings with the patient. Standard evidence-based informed consent process should therefore not be looked atinterdisciplinary institutional protocols may be used for common solely as a necessary legal requirement but should be used ascase scenarios, but complex cases should be discussed individually an opportunity to optimize objective decision making. Awarenessto ﬁnd the best solution for each patient. that other factors such as sex, race, availability, technical skills, The above obviously pertains to patients in a stable condition who local results, referral patterns, and patient preference, whichcan make a decision without the constraints of an emergency situ- sometimes contradict evidentiary best practice, may have anation. If potential adverse events are negligible compared with the impact on the decision making process, independently of clinicalexpected treatment beneﬁt or there is no viable alternative to emer- ﬁndings, is mandatory. The creation of a Heart Team servesgency treatment, informed decision making may not be possible. the purpose of a balanced multidisciplinary decision process.4 Patients considered for revascularization should also be clearly Additional input may be needed from general practitioners,informed of the continuing need for OMT including antiplatelet anaesthesiologists, geriatricians, or intensivists. Hospital teamsagents, statins, b-blockers, and angiotensin-converting enzyme without a cardiac surgical unit or with interventional cardiologists(ACE) inhibitors, as well as other secondary prevention strategies working in an ambulatory setting should refer to standard(Section 13). evidence-based protocols designed in collaboration with an expert interventional cardiologist and a cardiac surgeon, or seek their opinion for complex cases. Consensus on the4.2 Multidisciplinary decision making optimal revascularization treatment should be documented. Stan-(Heart Team) dard protocols compatible with the current Guidelines may beThe process for medical decision making and patient information used to avoid the need for systematic case-by-case review ofis guided by the ‘four principles’ approach to healthcare ethics: all diagnostic angiograms.
2508 ESC/EACTS Guidelines Ad hoc percutaneous coronary intervention Ad hoc PCI is deﬁned as a therapeutic interventional procedure Table 6 Recommendations for decision making andperformed immediately (with the patient still on the catheteriza- patient informationtion table) following the diagnostic procedure as opposed to astaged procedure performed during a different session. Ad hoc Classa LevelbPCI is convenient for the patient, associated with fewer access It is recommended that patients besite complications, and often cost-effective. However, in a adequately informed about the potentialreview of .38 000 patients undergoing ad hoc PCI, 30% of beneﬁts and short- and long-term risks of I C a revascularization procedure. Enough timepatients were in categories that were regarded as potential candi- should be spared for informed decisiondates for CABG. Ad hoc PCI is therefore reasonable for many making.patients, but not desirable for all, and should not automatically The appropriate revascularization strategy inbe applied as a default approach. Institutional protocols designed patients with MVD should be discussed by the I Cby the Heart Team should be used to deﬁne speciﬁc anatomical Heart Team.criteria and clinical subsets that can or cannot be treated ad hoc.Based on resources and settings, geographical differences can be a Class of recommendation.expected. Table 5 lists potential indications for ad hoc PCI. All b Level of evidence.other pathologies in stable patients, including lesions of the LM MVD ¼ multivessel disease.or proximal left anterior descending (LAD) artery and MVD invol-ving the LAD artery, should be discussed by a Heart Team beforea deferred revascularization procedure (PCI or CABG). Table 6lists the recommendations for decision making and patient symptoms, to risk stratify patients with stable angina and aninformation. acute coronary syndrome (ACS), and to help choose treatment options and evaluate their efﬁcacy. In practice, diagnostic and prog- nostic assessments are conducted in tandem rather than separ-5. Strategies for pre-intervention ately, and many of the investigations used for diagnosis also offer prognostic information.12 In elective cases, the pre-test likelihooddiagnosis and imaging of disease is calculated based on symptoms, sex, and risk factors.Exercise testing and cardiac imaging are used to conﬁrm the diag- Patients with an intermediate likelihood of obstructive CAD willnosis of CAD, to document ischaemia in patients with stable undergo exercise testing while patients with a high likelihood undergo direct invasive examination. Boundaries deﬁning inter- mediate likelihood of CAD are usually set at 10 –90% or Table 5 Potential indications for ad hoc percutaneous 20 –80%. Because of high availability and low costs, an exercise elec- coronary intervention vs. revascularization at an trocardiogram (ECG) is the most commonly used test to conﬁrm interval the anginal nature of the symptoms and to provide objective evi- dence of inducible ischaemia. Its accuracy is limited however, Ad hoc PCI especially in women.12 Many of the patients with an intermediate Haemodynamically unstable patients (including cardiogenic shock). likelihood of CAD post-exercise ECG are reclassiﬁed into higher Culprit lesion in STEMI and NSTE-ACS. or lower likelihood groups after non-invasive functional imaging. The target of revascularization therapy is myocardial ischaemia, Stable low-risk patients with single or double vessel disease (proximal LAD excluded) and favourable morphology (RCA, non-ostial LCx, mid- not the epicardial coronary disease itself. Revascularization pro- or distal LAD). cedures performed in patients with documented ischaemia Non-recurrent restenotic lesions. reduce total mortality13 through reduction of ischaemic burden.14 Discrepancies between the apparent anatomical severity Revascularization at an interval of a lesion and its functional effects on myocardial blood supply are Lesions with high-risk morphology. common, especially in stable CAD. Thus, functional assessment, Chronic heart failure. non-invasive or invasive, is essential for intermediate stenoses. Renal failure (creatinine clearance <60 mL/min), if total contrast Revascularization of lesions without functional signiﬁcance can be volume required >4 mL/kg. deferred.15 Stable patients with MVD including LAD involvement. Another indication for non-invasive imaging before revasculari- Stable patients with ostial or complex proximal LAD lesion. zation is the detection of myocardial viability in patients with Any clinical or angiographic evidence of higher periprocedural risk poor left ventricle (LV) function. Patients who have viable but dys- with ad hoc PCI. functional myocardium are at higher risk if not revascularized, while the prognosis of patients without viable myocardium is not LAD ¼ left anterior descending; LCx ¼ left circumﬂex; MVD ¼ multivessel improved by revascularization.16,17 disease; NSTE-ACS ¼ non-ST-segment elevation acute coronary syndrome; The current evidence supporting the use of various tests for the PCI ¼ percutaneous coronary intervention; RCA ¼ right coronary artery; detection of CAD is based on meta-analyses and multicentre STEMI ¼ ST-segment elevation myocardial infarction. studies (Table 7). Few RCTs have assessed health outcomes for
ESC/EACTS Guidelines 2509 Table 7 Indications of different imaging tests for the diagnosis of obstructive coronary artery disease and for the assessment of prognosis in subjects without known coronary artery diseasea Prognostic Asymptomatic Prognostic value of Symptomatic value of positive References (screening) negative result a result a Pretest likelihoodb of obstructive disease Low Intermediate High Anatomical test Invasive angiography III A III A IIb A IA IA IA 12 c MDCT angiography III B IIb B IIa B III B IIb B IIa B 17–20 MRI angiography III B III B III B III B III C III C 22 Functional test Stress echo III A III A IA III A d IA IA 12 d Nuclear imaging III A III A IA III A IA IA 12 Stress MRI III B III C IIa B III B d IIa B IIa B 12, 23–25 PET perfusion III B III C IIa B III B d IIa B IIa B 26 a For the prognostic assessment of known coronary stenosis, functional imaging is similarly indicated. b The pretest likelihood of disease is calculated based on symptoms, sex, and risk factors. c This refers to MDCT angiography, not calcium scoring. d In patients with obstructive CAD documented by angiography, functional testing may be useful in guiding the revascularization strategy based on the extent, severity, and localisation of ischaemia. CAD ¼ coronary artery disease; MDCT ¼ multidetector computed tomography; MRI ¼ magnetic resonance imaging; PET ¼ positron emission tomography.diagnostic testing and the available evidence has been derived signiﬁcant by MDCT are associated with ischaemia22 indicatinglargely from non-randomized studies. On many occasions the that MDCT angiography cannot accurately predict the haemo-choice of the test is based on local expertise and availability of dynamic signiﬁcance of coronary stenosis.the test. Although several tests can be used, it is important to In summary, MDCT is reliable for ruling out signiﬁcant CAD inavoid unnecessary diagnostic steps. patients with stable and unstable anginal syndromes and in patients When considering any test to detect CAD one must also take with low to moderate likelihood of CAD. However, MDCT angio-into account the risks associated with the test itself. The risks of graphy typically overestimates the severity of atheroscleroticexercise, pharmacological stressors, contrast agents, invasive pro- obstructions and decisions for patient management requirecedures, and cumulative ionizing radiation must be weighed further functional testing.against the risk of disease or delayed diagnosis. Magnetic resonance imaging coronary angiography In summary, documentation of ischaemia using functional testing Data suggest that MRI coronary angiography has a lower successis strongly recommended before elective invasive procedures, pre- rate and is less accurate than MDCT for the detection of CAD.18ferably using non-invasive testing before invasive angiography.5.1 Detection of coronary artery disease 5.2 Detection of ischaemiaThere are two non-invasive angiographic techniques that can The tests are based on either reduction of perfusion or inductiondirectly image coronary arteries: multidetector computed tom- of ischaemic wall motion abnormalities during exercise or pharma-ography (MDCT) and magnetic resonance imaging (MRI). cological stress. The most well-established stress imaging tech- Multidetector computed tomography coronary niques are echocardiography and perfusion scintigraphy. Bothangiography may be used in combination with either exercise stress or pharma- The studies and meta-analyses of MDCT to detect CAD have cological stress. Newer stress imaging techniques also includegenerally shown high negative predictive values (NPVs), suggesting stress MRI, positron emission tomography (PET) imaging, and com-that MDCT is excellent in excluding signiﬁcant CAD,18,19 while bined approaches. The term hybrid imaging refers to imagingpositive predictive values (PPVs) were only moderate. In the two systems in which two modalities [MDCT and PET, MDCT andmulticentre trials published, one was consistent with the results single photon emission computed tomography (SPECT)] are com-of prior meta-analyses20 but the other showed only moderate bined in the same scanner, allowing both studies to be performedNPV (83–89%).21 Only about half of the stenoses classiﬁed as in a single imaging session.
2510 ESC/EACTS Guidelines Stress imaging techniques have several advantages over conven- Meta-analysis of data obtained with PET demonstrated 92% sen-tional exercise ECG testing, including superior diagnostic perform- sitivity and 85% speciﬁcity for CAD detection, superior to myocar-ance,12 the ability to quantify and localize areas of ischaemia, and dial perfusion SPECT. Myocardial blood ﬂow in absolute units (mL/the ability to provide diagnostic information in the presence of g/min) measured by PET further improves diagnostic accuracy,resting ECG abnormalities or when the patient is unable to exer- especially in patients with MVD, and can be used to monitor thecise. For these reasons, stress imaging techniques are preferred in effects of various therapies.patients with previous PCI or CABG. In patients with angiographi-cally conﬁrmed intermediate coronary lesions, evidence of ischae- 5.3 Hybrid/combined imagingmia is predictive of future events. The combination of anatomical and functional imaging has become Stress echocardiography appealing because the spatial correlation of structural and func- Stress echocardiography is an established diagnostic test and is tional information of the fused images may facilitate a comprehen-more accurate than exercise ECG test in the detection of sive interpretation of coronary lesions and their pathophysiologicalischaemia.12 relevance. This combination can be obtained either with image The most frequently used method is a physical exercise test coregistration or with devices that have two modalities combinedtypically using a bicycle ergometer, but pharmacological stressors (MDCT and SPECT, MDCT and PET).such as dobutamine and less frequently dipyridamole can also be Single-centre studies evaluating the feasibility and accuracy ofused. The technique requires adequate training and experience combined imaging have demonstrated that MDCT and perfusionsince it is more user dependent than other imaging techniques. imaging provide independent prognostic information. No large orPooled sensitivity and speciﬁcity of exercise echocardiography multicentre studies are currently available.are reported as 80– 85% and 84–86%, respectively.12 5.4 Invasive tests Recent technical improvements involve the use of contrast In common practice, many patients with intermediate or high pretestagents to facilitate identiﬁcation of regional wall motion abnormal- CAD likelihood are catheterized without prior functional testing.ities and to image myocardial perfusion. These agents improve the When non-invasive stress imaging is contraindicated, non-diagnostic,interpretability of the images, but the technique of perfusion or unavailable, the measurement of FFR or coronary ﬂow reserve isimaging is not yet established. helpful. Even experienced interventional cardiologists cannot Perfusion scintigraphy predict accurately the signiﬁcance of most intermediate stenoses SPECT perfusion is an established diagnostic test. It provides a on the basis of visual assessment or quantitative coronary angiogra-more sensitive and speciﬁc prediction of the presence of CAD phy.27,28 Deferral of PCI15,28 or CABG27 in patients with FFR .0.80than exercise ECG.12 The reported sensitivity and speciﬁcity of is safe and clinical outcome is excellent. Thus, FFR is indicated for theexercise scintigraphy when compared with invasive angiography assessment of the functional consequences of moderate coronaryrange between 85–90% and 70 –75%, respectively.12 stenoses when functional information is lacking. Newer SPECT techniques with ECG gating improve diagnosticaccuracy in various patient populations, including women, dia- 5.5 Prognostic valuebetics, and elderly patients.23 Adding information from a simul- Normal functional imaging results are linked with excellent prog-taneously performed calcium score using MDCT may further nosis while documented ischaemia is associated with increasedincrease the accuracy.24 risk for MACE. Prognostic information obtained from MDCT Cardiovascular magnetic resonance imaging imaging is becoming available. Cardiac MRI stress testing with pharmacological stressors can beused to detect wall motion abnormalities induced by dobutamine 5.6 Detection of myocardial viabilityinfusion or perfusion abnormalities induced by adenosine. The prognosis of patients with chronic ischaemic systolic LV dysfunc-Cardiac MRI has been applied only recently in clinical practice tion is poor, despite advances in various therapies. Non-invasiveand therefore fewer data have been published compared with assessment of myocardial viability should guide patient management.other established non-invasive imaging techniques.12 Multiple imaging techniques including PET, SPECT, and dobutamine A recent meta-analysis showed that stress-induced wall motion stress echocardiography have been extensively evaluated for assess-abnormalities from MRI had a sensitivity of 83% and a speciﬁcity ment of viability and prediction of clinical outcome after myocardialof 86% in patient-based analysis, and perfusion imaging demon- revascularization. In general, nuclear imaging techniques have a highstrated 91% sensitivity and 81% speciﬁcity.25 When evaluated sensitivity, whereas techniques evaluating contractile reserve haveprospectively at multiple sites, the diagnostic performance of somewhat lower sensitivity but higher speciﬁcity. MRI has a high diag-stress perfusion MRI shows similarly high sensitivity but lower nostic accuracy to assess transmural extent of myocardial scar tissue,speciﬁcity. but its ability to detect viability and predict recovery of wall motion is Multidetector computed tomography perfusion not superior to other imaging techniques.16 The differences in per- MDCT can be used for perfusion imaging, but data obtained in formance of the various imaging techniques are small, and experi-clinical settings are scarce. ence and availability commonly determine which technique is used. Positron emission tomography Current evidence is mostly based on observational studies or Studies with myocardial perfusion PET have reported excellent meta-analyses, with the exception of two RCTs, both relating todiagnostic capabilities in the detection of CAD. The comparisons PET imaging.17 Patients with a substantial amount of dysfunctionalof PET perfusion imaging have also favoured PET over SPECT.26 but viable myocardium are likely to beneﬁt from myocardial
ESC/EACTS Guidelines 2511revascularization and may show improvements in regional and global a small nuclear substudy of the COURAGE trial (which reportedcontractile function, symptoms, exercise capacity, and long-term no overall survival beneﬁt of PCI over OMT), involving just overprognosis.16 300 patients, 100 patients with .10% ischaemic myocardium had a lower risk of death or MI with revascularization.146. Revascularization for stable 6.3 Optimal medical therapy vs.coronary artery disease percutaneous coronary interventionDepending on its symptomatic, functional, and anatomical com- The efﬁcacy of PCI (with or without stenting) vs. OMT has beenplexity, stable CAD can be treated by OMT only or combined addressed in several meta-analyses29,30,39 – 42 and a large RCT.43with revascularization using PCI or CABG. The main indications Most meta-analyses reported no mortality beneﬁt, increased non-for revascularization are persistence of symptoms despite OMT fatal periprocedural MI, and reduced need for repeat revasculariza-and/or prognosis. Over the last two decades signiﬁcant advances tion with PCI. One meta-analysis41 reported a survival beneﬁt forin all three treatment modalities have reduced many previous PCI over OMT (respective mortalities of 7.4% vs. 8.7% at antrials to historic value. average follow-up of 51 months), but this study included patients with recent MI and CABG patients in the revascularized group.6.1 Evidence basis for revascularization Another meta-analysis reported reduced mortality for PCI vs.The evidence basis for CABG and PCI is derived from RCTs and OMT, even after exclusion of MI patients [hazard ratio (HR)large propensity-matched observational registries; both have 0.82, 95% conﬁdence interval (CI) 0.68–0.99].30important strengths, but also limitations. The COURAGE RCT43 randomized 2287 patients with known By eliminating bias, individual RCTs and their subsequent signiﬁcant CAD and objective evidence of myocardial ischaemia tometa-analyses29 – 31 constitute the highest hierarchical form of OMT alone or to OMT + PCI. At a median follow-up of 4.6 years,evidence-based medicine. However, their extrapolation to routine there was no signiﬁcant difference in the composite of death, MI,clinical practice is complicated by the fact that their patient popu- stroke, or hospitalization for unstable angina. Freedom fromlations are often not representative of those encountered in normal angina was greater by 12% in the PCI group at 1 year but wasclinical practice (e.g. most RCTs of PCI and CABG in ‘multivessel’ eroded by 5 years, by which time 21% of the PCI group and 33%CAD enrolled ,10% of potentially eligible patients, most of whom of the OMT group had received additional revascularization (P ,actually had single or double vessel CAD). Analysis on an 0.001). The authors concluded that an initial strategy of PCI inintention-to-treat basis is problematic when many patients cross stable CAD did not reduce the risk of death, MI, or MACE whenover from medical therapy to revascularization or from PCI to added to OMT. The severity of CAD in COURAGE was, at most,CABG. Limited duration of follow-up (usually ,5 years) incompletely moderate, with the relative proportions of one-, two- and three-depicts the advantages of CABG, which initially accrue with time but vessel CAD being 31%, 39%, and 30%, while only 31% of patientswhich may also eventually be eroded by progressive vein graft failure. had proximal LAD disease. Furthermore, patients with LM disease In contrast, by capturing data on all interventions, large observa- were excluded and most patients had normal LV function.tional registries may more accurately reﬂect routine clinicalpractice. In the absence of randomization, however, their fundamen- 6.4 Percutaneous coronary interventiontal limitation is that they cannot account for all confounding factors, with drug-eluting stents vs. bare metalwhich may inﬂuence both the choice and the outcome of different stentsinterventions. Propensity matching for both cardiac and non-cardiac Brophy et al.,44 in an analysis of 29 trials involving 9918 patients,comorbidity can only partially mitigate this problem. Accepting this reported no difference between bare metal stent (BMS) andlimitation, independent registries have consistently reported that an balloon angioplasty in terms of death, MI, or the need forinitial strategy of CABG rather than PCI in propensity-matched CABG, but an 5% absolute reduction in restenosis with stenting.patients with MVD or LM CAD improved survival over a 3- to Subsequent meta-analyses45 of RCTs comparing DES with BMS5-year period by 5%, accompanied by a four- to seven-fold reported similar rates of death, cardiac death, and non-fatal MI,reduction in the need for reintervention.32 – 37 The differing but a signiﬁcant reduction in the need for subsequent or repeatpopulations in RCTs and registries may partly explain the apparent target vessel revascularization (TVR) with DES. In contrast,differences in the respective efﬁcacies of the two procedures, at Kirtane et al.,46 in an unadjusted analysis of 182 901 patients inleast in patients with the most severe CAD. 34 observational studies of BMS and DES, reported a signiﬁcant reduction in mortality (HR 0.78, 95% CI 0.71–0.86) and MI (HR6.2 Impact of ischaemic burden on 0.87, 95% CI 0.78 –0.97) with DES. After multivariable adjustment,prognosis the beneﬁts of DES were signiﬁcantly attenuated and the possibilityThe adverse impact of demonstrable ischaemia on clinical outcome that at least some of the clinical beneﬁt of DES might be due to[death, myocardial infarction (MI), ACS, occurrence of angina] has concomitant dual antiplatelet therapy (DAPT) could not bebeen well recognized for over two decades.13,38 While sympto- excluded. In a network meta-analysis restricted to patients withmatic patients with no or little evidence of ischaemia have no prog- non-acute CAD, sequential advances in PCI techniques were notnostic beneﬁt from revascularization, asymptomatic patients with a associated with incremental mortality beneﬁt in comparison withsigniﬁcant mass of ischaemic myocardium do.13,38 Most recently, in OMT.42
2512 ESC/EACTS Guidelines6.5 Coronary artery bypass grafting vs. be ineligible for PCI) and 198 PCI patients (considered to be atmedical therapy excessive surgical risk). At 1 year, 12.4% of CABG and 17.8% of PCI patients reached the respective primary composite endpointThe superiority of CABG to medical therapy in the management of (P , 0.002) of death (3.5% vs. 4.4%; P ¼ 0.37), MI (3.3% vs. 4.8%;speciﬁc subsets of CAD was ﬁrmly established in a meta-analysis of P ¼ 0.11), CVA (2.2% vs. 0.6%; P ¼ 0.003), or repeat revasculariza-seven RCTs,31 which is still the major foundation for contempor- tion (5.9% vs. 13.5%; P , 0.001).4 Unpublished data at 2 yearsary CABG. It demonstrated a survival beneﬁt of CABG in patients showed major adverse cardiac and cerebral event (MACCE)with LM or three-vessel CAD, particularly when the proximal LAD rates of 16.3% vs. 23.4% in favour of CABG (P , 0.001). Becausecoronary artery was involved. Beneﬁts were greater in those with PCI failed to reach the pre-speciﬁed criteria for non-inferiority,severe symptoms, early positive exercise tests, and impaired LV the authors concluded at both 14 and 2 years that ‘CABGfunction. The relevance of these ﬁndings to current practice is remains the standard of care for patients with three-vessel orincreasingly challenged as medical therapy used in the trials was LM CAD although the difference in the composite primary end-substantially inferior to current OMT. However, a recent point was largely driven by repeat revascularization’. Whethermeta-analysis reported a reduction in the HR for death with the excess of CVA in the CABG group in the ﬁrst year wasCABG vs. OMT (HR 0.62, 95% CI 0.50–0.77).30 In addition, the purely periprocedural or also due to lower use of secondary pre-beneﬁts of CABG might actually be underestimated because: ventive medication (DAPT, statins, antihypertensive agents, and ACE inhibitors) is not known.† most patients in the trials had a relatively low severity of CAD; Failure to reach criteria for non-inferiority therefore means that† analysis was conducted on an intention-to-treat basis (even all other ﬁndings are observational, sensitive to the play of chance, though 40% of the medical group crossed over to CABG); and hypothesis generating. Nevertheless, in 1095 patients with† only 10% of CABG patients received an internal thoracic artery three-vessel CAD, the MACCE rates were 14.4% vs. 23.8% in (ITA); however the most important prognostic component of favour of CABG (P , 0.001). Only in the tercile of patients with CABG is the use of one47,48 or preferably two49 ITAs. the lowest SYNTAX scores (,23) was there no signiﬁcant differ- ence in MACCE between the two groups. It is also noteworthy6.6 Percutaneous coronary intervention that the mortality and repeat revascularization rates were similarvs. coronary artery bypass grafting in the 1077 CABG registry patients, even though these patients Isolated proximal left anterior descending artery had more complex CAD. disease Taking together all 1665 patients with three-vessel CAD (1095 There are two meta-analyses of .190050 and .120051 patients, in the RCT and 570 in the registry), it appears that CABG offersboth of which reported no signiﬁcant difference in mortality, MI, or signiﬁcantly better outcomes at 1 and 2 years in patients withcerebrovascular accident (CVA), but a three-fold increase in recur- SYNTAX scores .22 (79% of all patients with three-vesselrent angina and a ﬁve-fold increase in repeat TVR with PCI at up to CAD). These results are consistent with previous registries32 – 375 years of follow-up. reporting a survival advantage and a marked reduction in the Multivessel disease (including SYNTAX trial) need for repeat intervention with CABG in comparison with PCI There have been .15 RCTs of PCI vs. CABG in MVD52 but in patients with more severe CAD.only one of OMT vs. PCI vs. CABG (MASS II).53 Most patients in Left main stenosisthese RCTs actually had normal LV function with single or CABG is still conventionally regarded as the standard of care fordouble vessel CAD and without proximal LAD disease. signiﬁcant LM disease in patients eligible for surgery, and the CASSMeta-analyses of these RCTs reported that CABG resulted in up registry reported a median survival advantage of 7 years in 912to a ﬁve-fold reduction in the need for reintervention, with patients treated with CABG rather than medically.54 While ESCeither no or a modest survival beneﬁt or a survival beneﬁt only guidelines on PCI state that ‘Stenting for unprotected LM diseasein patients .65 years old (HR 0.82) and those with diabetes should only be considered in the absence of other revasculariza-(HR 0.7).29 The 5-year follow-up of the MASS II53 study of 611 tion options’,55 emerging evidence, discussed below, suggestspatients (underpowered) reported that the composite primary that PCI provides at least equivalent if not superior results toendpoint (total mortality, Q-wave MI, or refractory angina requir- CABG for lower severity LM lesions at least at 2 years of follow-uping revascularization) occurred in 36% of OMT, 33% of PCI and and can justify some easing of PCI restrictions. However, the21% of CABG patients (P ¼ 0.003), with respective subsequent importance of conﬁrming that these results remain durable withrevascularization rates of 9%, 11% and 4% (P ¼ 0.02). longer term follow-up (at least 5 years) is vital. The SYNTAX trial While LM stenosis is a potentially attractive target for PCI In contrast to the highly selective patient populations of previous because of its large diameter and proximal position in the coronaryRCTs, SYNTAX is a 5-year ‘all comers’ trial of patients with the circulation, two important pathophysiological features may mitigatemost severe CAD, including those with LM and/or three-vessel against the success of PCI: (i) up to 80% of LM disease involves theCAD, who were entered into either the trial or a parallel nested bifurcation known to be at particularly high risk of restenosis; andregistry if ineligible for randomization.4 By having two components, (ii) up to 80% of LM patients also have multivessel CAD whereSYNTAX therefore captured real treatment decisions in a trial of CABG, as already discussed, may already offer a survival advantage.1800 patients randomized to PCI or CABG and in a registry of The most ‘deﬁnitive’ current account of treatment of LM disease1077 CABG patients (whose complexity of CAD was deemed to by CABG or PCI is from the hypothesis-generating subgroup