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Rapid detection of myo- cardial infarction by subsecond, free-breathing delayed contrast- enhancement cardiovascular magnetic resonance. Circulation. 2007; 115:236 44. 1264. Cheng AS, Pegg TJ, Karamitsos TD, et al. Cardiovascular magnetic resonance perfusion imaging at tesla for the detection of coronary artery disease: a comparison with 1. tesla. J Am Coll Cardiol. 2007; 49:2440 9. 1265. Nagata M, Kato S, Kitagawa K, et al. Diagnostic accuracy of 1. T unenhanced whole-heart coronary MR angiography performed with 3 channel cardiac coils: initial single-center experience. Radiology. 2011;259:384 92. 1266. Sakuma H, Ichikawa Y, Chino S, et al. Detection of coronary artery stenosis with whole-heart coronary magnetic resonance angiography. J Am Coll Cardiol. 2006;48:1946 50. KEY WORDS: AHA Scientific Statements n cardiovascular diagnostic techniques n coronary artery disease n coronary stenosis n minimally invasive surgical procedures n myocardial ischemia n myocardial revas- cularization n risk factors n stable angina Appendix 1. Author Relationships With Industry and Other Entities (Relevant): 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guidelines for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease Committee Member Employment Consultant Speaker s Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals by Section* Stephan D. Fihn (Chair) Veterans Health Administration Director, Office of Analytics and Business Intelligence; University of Washington Professor of Medicine and of Health Services; Head, Division of General Internal Medicine None None None None None None None (Continued) Appendix 1.


Author Relationships With Industry and Other Entities (Relevant): 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guidelines for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease Committee Member Employment Consultant Speaker s Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals by Section* Stephan D. Fihn (Chair) Veterans Health Administration Director, Office of Analytics and Business Intelligence; University of Washington Professor of Medicine and of Health Services; Head, Division of General Internal Medicine None None None None None None None (Continued) Appendix 1. Continued Committee Member Employment Consultant Speaker s Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals by Section* Julius M. Gardin (Vice Chair) Hackensack University Medical Center Professor and Chairman, Department of Internal Medicine Arena Pharmaceuticals (Expired Dec. 2008) AstraZeneca (Expired Bristol-Myers Squibb (Expired Dec. 2009) CV Therapeutics (Expired Dec. 2007) Pfizer (Expired Dec. Sanofi-aventis Takeda (Expired Bristol-Myers Squibb (Expired Dec. 2009) CV Therapeutics (Expired Dec. 2007) Pfizer (Expired Dec. Takeda (Expired None Merck (Expired Dec. None None 4.4.1.1 Jonathan Abrams University of New Mexico, Office of CME Professor of Medicine (Cardiology) None None None None None None None Kathleen Berra Stanford Prevention Research Center Clinical Trial Director Boehringer Ingelheim CV Therapeutics Gilead Sciences Novartis Pfizer Sanofi-aventis None Kai Pharmaceuticals PCNA Board Member James C. Blankenship Geisinger Medical Center Director Cardiology; Director Cardiac Catheterization Laboratory None Sanofi-aventis None Abiomed AstraZeneca Boston Scientific Conor Medsystems Kai Pharmaceutical Novartis Schering-Plough The Medicines Company None None 4.4.2.1 Apostolos P. Dallas Carilion Roanoke Memorial Hospital Director of Continuing Medical Education None None GlaxoSmithKline Johnson & Johnson Novartis Sanofi-aventis None None None 4.4.1.1 Pamela S. Douglas Duke University Medical Center Ursula Geller Professor of Research in Cardiovascular Diseases None None None Novartis None None 4.4.1.1 JoAnne M. Foody Harvard Medical School Associate Professor; Brigham and Women s/Faulkner Hospitals Abbott Amarin Gilead Merck Novartis Pfizer Sanofi-aventis None None None None None 2.2.2.2 Thomas C. Gerber Mayo Clinic Radiology, Professor of Medicine None None None None None None None Alan L. Hinderliter University of North Carolina: Division of Cardiology Associate Professor None None None None None None None Spencer B.


Continued Committee Member Employment Consultant Speaker s Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals by Section* Julius M. Gardin (Vice Chair) Hackensack University Medical Center Professor and Chairman, Department of Internal Medicine Arena Pharmaceuticals (Expired Dec. 2008) AstraZeneca (Expired Bristol-Myers Squibb (Expired Dec. 2009) CV Therapeutics (Expired Dec. 2007) Pfizer (Expired Dec. Sanofi-aventis Takeda (Expired Bristol-Myers Squibb (Expired Dec. 2009) CV Therapeutics (Expired Dec. 2007) Pfizer (Expired Dec. Takeda (Expired None Merck (Expired Dec. None None 4.4.1.1 Jonathan Abrams University of New Mexico, Office of CME Professor of Medicine (Cardiology) None None None None None None None Kathleen Berra Stanford Prevention Research Center Clinical Trial Director Boehringer Ingelheim CV Therapeutics Gilead Sciences Novartis Pfizer Sanofi-aventis None Kai Pharmaceuticals PCNA Board Member James C. Blankenship Geisinger Medical Center Director Cardiology; Director Cardiac Catheterization Laboratory None Sanofi-aventis None Abiomed AstraZeneca Boston Scientific Conor Medsystems Kai Pharmaceutical Novartis Schering-Plough The Medicines Company None None 4.4.2.1 Apostolos P. Dallas Carilion Roanoke Memorial Hospital Director of Continuing Medical Education None None GlaxoSmithKline Johnson & Johnson Novartis Sanofi-aventis None None None 4.4.1.1 Pamela S. Douglas Duke University Medical Center Ursula Geller Professor of Research in Cardiovascular Diseases None None None Novartis None None 4.4.1.1 JoAnne M. Foody Harvard Medical School Associate Professor; Brigham and Women s/Faulkner Hospitals Abbott Amarin Gilead Merck Novartis Pfizer Sanofi-aventis None None None None None 2.2.2.2 Thomas C. Gerber Mayo Clinic Radiology, Professor of Medicine None None None None None None None Alan L. Hinderliter University of North Carolina: Division of Cardiology Associate Professor None None None None None None None Spencer B. King III Saint Joseph s Heart and Vascular Institute President; Saint Joseph s Health System Executive Director Academic Affairs Medtronic (Expired None None None Merck (DSMB) Wyeth Pharmaceuticals (DSMB) (Continued) Fihn et al Stable Ischemic Heart Disease: Full Text e465 Appendix 1.


King III Saint Joseph s Heart and Vascular Institute President; Saint Joseph s Health System Executive Director Academic Affairs Medtronic (Expired None None None Merck (DSMB) Wyeth Pharmaceuticals (DSMB) (Continued) Fihn et al Stable Ischemic Heart Disease: Full Text e465 Appendix 1. Continued Committee Member Employment Consultant Speaker s Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals by Section* Paul D. Kligfield Cornell Medical Center Professor of Medicine Cardiac Science GE Healthcare MDS Pharma Services Mortara Instrument Philips Medical Systems None None None None None 2.2.1 Harlan M. Krumholz Yale University School of Medicine Harold H. Hines, Jr. Professor of Medicine and Epidemiology and Public Health None None None None None None None Raymond Y.K. Kwong Brigham & Women s Hospital Medicine, Cardiovascular Division Instructor of Medicine None None None None None None None Michael J. Lim St. Louis University Associate Professor of Medicine; Division of Cardiology, Interim Director; J. Gerard Mudd Cardiac Catheterization Laboratory, Director Bristol-Myers Squibb Cordis Sanofi-aventis Schering-Plough None None None None None 4.4.1.1 Jane A. Linderbaum Mayo Clinic Assistant Professor of Medicine None None None None None None None Michael J. Mack The Heart Hospital Baylor Plano Director None None None None None None None Mark A. Munger University of Utah College of Pharmacy Professor Pharmacotherapy and Internal Medicine; Associate Dean, Academic Affairs None Gilead None Novartis None None 4.4.3.1 Richard L. Prager University of Michigan Hospitals and Health Centers Professor of Surgery, Section of Cardiac Surgery None None None None None None None Joseph F. Sabik Cleveland Clinic Foundation Professor of Surgery Medtronic Novo Nordisk None None None None None 4.4.1.3 Leslee J. Shaw Emory University School of Medicine Professor of Medicine None None None Bracco Diagnostics None None 3.2.2.6.


Kwong Brigham & Women s Hospital Medicine, Cardiovascular Division Instructor of Medicine None None None None None None None Michael J. Lim St. Louis University Associate Professor of Medicine; Division of Cardiology, Interim Director; J. Gerard Mudd Cardiac Catheterization Laboratory, Director Bristol-Myers Squibb Cordis Sanofi-aventis Schering-Plough None None None None None 4.4.1.1 Jane A. Linderbaum Mayo Clinic Assistant Professor of Medicine None None None None None None None Michael J. Mack The Heart Hospital Baylor Plano Director None None None None None None None Mark A. Munger University of Utah College of Pharmacy Professor Pharmacotherapy and Internal Medicine; Associate Dean, Academic Affairs None Gilead None Novartis None None 4.4.3.1 Richard L. Prager University of Michigan Hospitals and Health Centers Professor of Surgery, Section of Cardiac Surgery None None None None None None None Joseph F. Sabik Cleveland Clinic Foundation Professor of Surgery Medtronic Novo Nordisk None None None None None 4.4.1.3 Leslee J. Shaw Emory University School of Medicine Professor of Medicine None None None Bracco Diagnostics None None 3.2.2.6. Joanna D. Sikkema University of Miami School of Nursing None AstraZeneca None None None None 4.4.1.1 Craig R. Smith, Jr Columbia University Chairman, Department of Surgery None None None None None None None Sidney C. Smith, Jr Center for Cardiovascular Science and Medicine Professor of Medicine; Director Eli Lilly (Expired July Sanofi-aventis (Expired Sept. 2009) AstraZeneca (Expired Bayer (Expired Oct. Fornier (Expired May Sanofi-aventis (Expired Nov. 2009) None GlaxoSmithKline (DSMB) (Expired None None 4.4.2.1 (Continued) Appendix 1.


Joanna D. Sikkema University of Miami School of Nursing None AstraZeneca None None None None 4.4.1.1 Craig R. Smith, Jr Columbia University Chairman, Department of Surgery None None None None None None None Sidney C. Smith, Jr Center for Cardiovascular Science and Medicine Professor of Medicine; Director Eli Lilly (Expired July Sanofi-aventis (Expired Sept. 2009) AstraZeneca (Expired Bayer (Expired Oct. Fornier (Expired May Sanofi-aventis (Expired Nov. 2009) None GlaxoSmithKline (DSMB) (Expired None None 4.4.2.1 (Continued) Appendix 1. Continued Committee Member Employment Consultant Speaker s Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals by Section* John A. Spertus MidAmerica Heart Institute of St. Luke s Hospital Director, Outcomes Research; University of Missouri Kansas City Gilead None None BMS/sanofi- aventis Cordis Eli Lilly Johnson & Johnson Roche Diagnostics None None 4.4.1.1 Sankey V. Williams Hospital of the University of Pennsylvania Solomon Katz Professor of General Medicine, Division of General Internal Medicine None None Johnson & Johnson Merck None None None 4.4.1.1 This table represents the relationships of committee members with industry and other entities that were reported by authors to be relevant to this document. These relationships were reviewed and updated in conjunction with all meetings and conference calls of the writing committee during the document development process. The table does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of $5% of the voting stock or share of the business entity, or ownership of $$10 000 of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person s gross income for the previous year.


A person is deemed to have a significant interest in a business if the interest represents ownership of $5% of the voting stock or share of the business entity, or ownership of $$10 000 of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person s gross income for the previous year. A relationship is considered to be modest if it is less than significant under the preceding definition. Relationships in this table are modest unless otherwise noted. *Writing committee members are required to recuse from voting on sections to which their specific relationships with industry and other entities could apply. Section numbers apply to the full-text guideline. Significant relationship. No financial benefit. The current guideline was developed during the transition in RWI policy and occurred over an extended period of time. In the interest of transparency, we provide full information on RWI existing over the entire period of guideline development, including delineation of relationships that expired .24 months before the guideline was finalized. CV indicates cardiovascular; DSMB, data safety and monitoring board; and SAQ, Seattle Angina Questionnaire. Appendix 2. Reviewer Relationships With Industry and Other Entities (Relevant): 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guidelines for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease Reviewer Representation Consultant Speaker Ownership/ Partnership/ Principal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Ralph G. Brindis Official Reviewer ACCF Board of Trustees None None None None None None Timothy D. Henry Official Reviewer AHA CV Therapeutics Sanofi-aventis None None Baxter* CV Therapeutics* None None Judith S. Hochman Official Reviewer ACCF/AHA Task Force on Practice Guidelines Eli Lilly GlaxoSmithKline None None Johnson & Johnson Merck Robert H. Jones Official Reviewer STS None None None None None None Janet B.


Reviewer Relationships With Industry and Other Entities (Relevant): 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guidelines for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease Reviewer Representation Consultant Speaker Ownership/ Partnership/ Principal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Ralph G. Brindis Official Reviewer ACCF Board of Trustees None None None None None None Timothy D. Henry Official Reviewer AHA CV Therapeutics Sanofi-aventis None None Baxter* CV Therapeutics* None None Judith S. Hochman Official Reviewer ACCF/AHA Task Force on Practice Guidelines Eli Lilly GlaxoSmithKline None None Johnson & Johnson Merck Robert H. Jones Official Reviewer STS None None None None None None Janet B. Long Official Reviewer PCNA None AstraZeneca None None None None Bruce W. Lytle Official Reviewer AATS None None None None None None Douglass A. Morrison Official Reviewer SCAI None None None None None None E. Magnus Ohman Official Reviewer AHA Abiomed Datascope Inovise* Liposcience The Medicines Company Response Biomedical CV Therapeutics* The Medicines Company* Inovise* Bristol-Myers Squibb* Daiichi-Sankyo* Eli Lilly* The Medicines Company* Millennium Pharmaceuticals* Sanofi-aventis* Schering-Plough* None None (Continued) Fihn et al Stable Ischemic Heart Disease: Full Text e467 Appendix 2.


Long Official Reviewer PCNA None AstraZeneca None None None None Bruce W. Lytle Official Reviewer AATS None None None None None None Douglass A. Morrison Official Reviewer SCAI None None None None None None E. Magnus Ohman Official Reviewer AHA Abiomed Datascope Inovise* Liposcience The Medicines Company Response Biomedical CV Therapeutics* The Medicines Company* Inovise* Bristol-Myers Squibb* Daiichi-Sankyo* Eli Lilly* The Medicines Company* Millennium Pharmaceuticals* Sanofi-aventis* Schering-Plough* None None (Continued) Fihn et al Stable Ischemic Heart Disease: Full Text e467 Appendix 2. Continued Reviewer Representation Consultant Speaker Ownership/ Partnership/ Principal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Douglas K. Owens Official Reviewer ACP GE Healthcare* None None None None None Paul Poirier Official Reviewer ACCF Board of Governors None None None None None None Amir Qaseem Official Reviewer ACP None None None None None None Joyce L. Ross Official Reviewer PCNA Kaneka America Abbott AstraZeneca* Bristol-Myers Squibb Oscient Pfizer Sanofi-aventis None None None None Timothy A. Sanborn Official Reviewer SCAI None The Medicines Company Merck None St. Jude Medical (DSMB) None None Jeffrey L. Anderson Content Reviewer ACCF/AHA Task Force on Practice Guidelines BMS/sanofi-aventis Daiichi-Sankyo Eli Lilly None None None None None William E. Boden Content Reviewer Abbott CV Therapeutics/ Gilead* Sanofi-aventis Schering-Plough Medicure Pharma None None None None Matthew Budoff Content Reviewer ACCF Imaging Council None None None None None None Kim A. Eagle Content Reviewer None None None None None None Gordon A. Ewy Content Reviewer None None None None None None Victor Ferrari Content Reviewer ACCF Imaging Council None None None None None None Raymond J. Gibbons Content Reviewer Cardiovascular Clinical Studies Lantheus Medical Imaging Medscape Molecular Insight TherOx None None Velomedix* None None Linda Gillam Content Reviewer ACCF Imaging Council Abbott Vascular Edwards Lifesciences None None None Core Lab Services None Robert A. Guyton Content Reviewer ACCF/AHA Task Force on Practice Guidelines None None None Edwards Lifesciences None None L. David Hillis Content Reviewer None None None None None None David R. Holmes Content Reviewer ACCF Interventional Scientific Council None None None None None None Hani Jneid Content Reviewer AHA Council on Clinical Cardiology None None None None None None Sanjay Kaul Content Reviewer None None None None None None Howard C. Lewin Content Reviewer ACCF Imaging Council None None Positron Imaging Partners None None None (Continued) Appendix 2.


Continued Reviewer Representation Consultant Speaker Ownership/ Partnership/ Principal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Todd D. Miller Content Reviewer AHA Council on Clinical Cardiology The Medicines Company TherOx None None Kai Pharmaceuticals King Pharmaceuticals Lantheus Medical Imaging Molecular Insight Pharmaceuticals None None L. Kristin Newby Content Reviewer AHA Council on Clinical Cardiology Adolor Biovascular CV Therapeutics Inverness Medical Johnson & Johnson Novartis Roche Diagnostics Daiichi-Sankyo None AstraZeneca BG Medicine Carvio Dx* GlaxoSmithKline* Medicare* Millennium Pharmaceuticals Schering-Plough* None None Elizabeth Ross Content Reviewer None None None None None None William S. Weintraub Content Reviewer AstraZeneca* Bayer* Bristol-Myers Squibb Cardionet Eli Lilly Pfizer* Sanofi-aventis Shionogi None None Abbott* AstraZeneca* Bristol-Myers Squibb* Otsuka* Sanofi-aventis* None 2004; Defendant; Aprotinin 2008; Defendant; Quetiapine 2008; Defendant; Celebrex This table represents the relationships of reviewers with industry and other entities that were disclosed at the time of peer review. It does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of $5% of the voting stock or share of the business entity, or ownership of $$10 000 of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person s gross income for the previous year. A relationship is considered to be modest if it is less than significant under the preceding definition. Relationships noted in this table are modest unless otherwise noted. *Significant relationship. AATS indicates American Association for Thoracic Surgery; ACCF, American College of Cardiology Foundation; ACP, American College of Physicans; AHA, American Heart Association; NIH, National Institutes of Health; PCNA, Preventive Cardiovascular Nurses Association; SCAI, Society for Cardiovascular Interventions and Angiography; and STS, Society of Thoracic Surgeons.


AATS indicates American Association for Thoracic Surgery; ACCF, American College of Cardiology Foundation; ACP, American College of Physicans; AHA, American Heart Association; NIH, National Institutes of Health; PCNA, Preventive Cardiovascular Nurses Association; SCAI, Society for Cardiovascular Interventions and Angiography; and STS, Society of Thoracic Surgeons. Fihn et al Stable Ischemic Heart Disease: Full Text e469 Appendix 3. Abbreviations List ACE 5 angiotensin-converting enzyme ACS 5 acute coronary syndrome AMI 5 acute myocardial infarction ARB 5 angiotensin-receptor blocker AV 5 atrioventricular BMI 5 body mass index BMS 5 bare-metal stent BP 5 blood pressure CABG 5 coronary artery bypass graft CAC 5 coronary artery calcium CAD 5 coronary artery disease CCS 5 Canadian Cardiovascular Society CCTA 5 coronary/cardiac computed tomography angiography CKD 5 chronic kidney disease CMR 5 cardiac magnetic resonance CT 5 computed tomography DAPT 5 dual antiplatelet therapy DES 5 drug-eluting stent ECG 5 electrocardiogram EDTA 5 ethylene diamine tetraacetic acid EECP 5 enhanced external counterpulsation EF 5 ejection fraction FDA 5 US Food and Drug Administration FFR 5 fractional flow reserve GDMT 5 guideline-directed medical therapy HDL 5 high-density lipoprotein HIV 5 human immunodeficiency virus IHD 5 ischemic heart disease LAD 5 left anterior descending LBBB 5 left bundle-branch block LDL 5 low-density lipoprotein LGE 5 late gadolinium enhancement LIMA 5 left internal mammary artery LV 5 left ventricular LVEF 5 left ventricular ejection fraction MACE 5 major adverse cardiac event MET 5 metabolic equivalent MI 5 myocardial infarction MPI 5 myocardial perfusion imaging NSTEMI 5 non ST-elevation myocardial infarction PAD 5 peripheral artery disease PCI 5 percutaneous coronary intervention PET 5 positron emission tomography PHQ 5 Patient Health Questionnaire RCT 5 randomized controlled trial SAQ 5 Seattle Angina Questionnaire SIHD 5 stable ischemic heart disease (Continued) Appendix 3.


Abbreviations List ACE 5 angiotensin-converting enzyme ACS 5 acute coronary syndrome AMI 5 acute myocardial infarction ARB 5 angiotensin-receptor blocker AV 5 atrioventricular BMI 5 body mass index BMS 5 bare-metal stent BP 5 blood pressure CABG 5 coronary artery bypass graft CAC 5 coronary artery calcium CAD 5 coronary artery disease CCS 5 Canadian Cardiovascular Society CCTA 5 coronary/cardiac computed tomography angiography CKD 5 chronic kidney disease CMR 5 cardiac magnetic resonance CT 5 computed tomography DAPT 5 dual antiplatelet therapy DES 5 drug-eluting stent ECG 5 electrocardiogram EDTA 5 ethylene diamine tetraacetic acid EECP 5 enhanced external counterpulsation EF 5 ejection fraction FDA 5 US Food and Drug Administration FFR 5 fractional flow reserve GDMT 5 guideline-directed medical therapy HDL 5 high-density lipoprotein HIV 5 human immunodeficiency virus IHD 5 ischemic heart disease LAD 5 left anterior descending LBBB 5 left bundle-branch block LDL 5 low-density lipoprotein LGE 5 late gadolinium enhancement LIMA 5 left internal mammary artery LV 5 left ventricular LVEF 5 left ventricular ejection fraction MACE 5 major adverse cardiac event MET 5 metabolic equivalent MI 5 myocardial infarction MPI 5 myocardial perfusion imaging NSTEMI 5 non ST-elevation myocardial infarction PAD 5 peripheral artery disease PCI 5 percutaneous coronary intervention PET 5 positron emission tomography PHQ 5 Patient Health Questionnaire RCT 5 randomized controlled trial SAQ 5 Seattle Angina Questionnaire SIHD 5 stable ischemic heart disease (Continued) Appendix 3. Continued SPECT 5 single-photon emission computed tomography STEMI 5 ST-elevation myocardial infarction TMR 5 transmyocardial revascularization UA 5 unstable angina UA/NSTEMI 5 unstable angina/non ST-elevation myocardial infarction Appendix 4.


Continued SPECT 5 single-photon emission computed tomography STEMI 5 ST-elevation myocardial infarction TMR 5 transmyocardial revascularization UA 5 unstable angina UA/NSTEMI 5 unstable angina/non ST-elevation myocardial infarction Appendix 4. Nomogram for Estimating 2-Year CAD Event-Free Survival (ie, Freedom From CAD Death or Nonfatal MI) by Using Percent Ischemic Myocardium in Intermediate-Likelihood Patients by Post-Stress LV CAD indicates coronary artery disease, LVEF, left ventricular ejection fraction; MI, myocardial infarction; and SPECT, single-photon emission computed tomography. Reproduced with permission from Shaw et al.276 Fihn et al Stable Ischemic Heart Disease: Full Text e471


Antithrombotic Therapy for Atrial Fibrillation CHEST Guideline and Expert Panel Report Gregory Y. H. Lip, MD; Amitava Banerjee, MD, DPhil; Giuseppe Boriani, MD, PhD; Chern en Chiang, MD, PhD; Ramiz Fargo, MD, FCCP; Ben Freedman, MD, PhD; Deirdre A. Lane, PhD; Christian T. Ruff, MD, MPH; Mintu Turakhia, MD; David Werring, PhD; Sheena Patel, MPH; and Lisa Moores, MD, FCCP BACKGROUND: The risk of stroke is heterogeneous across different groups of patients with atrial brillation (AF), being dependent on the presence of various stroke risk factors. We provide recommendations for antithrombotic treatment based on net clinical bene t for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. METHODS: Systematic literature reviews were conducted to identify relevant articles published from the last formal search perfomed for the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (9th Edition). The overall quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted, voted on, and revised until consensus was reached.


Graded recommendations and ungraded consensus-based statements were drafted, voted on, and revised until consensus was reached. RESULTS: For patients with AF without valvular heart disease, including those with paroxysmal AF, who are at low risk of stroke (eg, CHA2DS2-VASc [congestive heart failure, hypertension, age $ 75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65-74 and sex category ABBREVIATIONS: ABC = Atrial brillation Better Care; ACS = acute coronary syndrome; ACTIVE W = Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events; ACUTE = Assessment of Cardioversion Using Transesophageal Echocardiog- raphy; AFFIRM = Atrial Fibrillation Follow-up Investigation of Sinus Rhythm Management; AHRE = atrial high-rate episode; aPTT = activated partial thromboplastin time; ARISTOTLE = Apixaban for Reduction of Stroke and Other Thromboembolic Events in Atrial Fibrillation; ATRIA = Anticoagulation and Risk Factors in Atrial Fibrillation; AVERROES = Apixaban Versus Acetylsalicylic Acid (ASA) to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment; BRIDGE = Bridging Anticoagulation in Patients who Require Tem- porary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery; CAA = cerebral amyloid angiopathy; CHA2DS2-VASc = congestive heart failure, hypertension, age $75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65-74 and sex category (female); CHADS2 = congestive heart failure; hyper- tension = age; diabetes = stroke (doubled); CIED = cardiac implanted electrical device; CKD = chronic kidney disease; CMB = cerebral microbleed; COI = con icts of interest; CrCl = creatinine clearance; DAPT = dual antiplatelet therapy; ESUS = embolic stroke of unde- termined source; GRADE = Grading of Recommendations, Assess- ment, Development, and Evaluation; HAS-BLED = hypertension, abnormal renal/liver function (1 point each), stroke, bleeding history or predisposition, labile INR, elderly (0.65), drugs/alcohol concom- itantly (1 point each); HEMORR2HAGES = hepatic or renal disease, ethanol abuse, malignancy, older, reduced platelet count/function, hypertension, anemia, genetic factors, excessive fall risk, and stroke; HF = heart failure; HR = hazard ratio; ICH = intracranial hemor- rhage; INR = international normalized ratio; LAA = left atrial appendage; LAAO = left atrial appendage occlusion; LMWH = low- molecular-weight heparin; MI = myocardial infarction; MOST = Atrial Diagnostics Ancillary Study of the Mode Selection Trial; NOAC = non-vitamin K antagonist oral anticoagulant drug; OAC = oral anticoagulant; o.d.


= omni die (every day); PAD = peripheral arterial disease; PCC = prothrombin complex concentrate; PCI = percutaneous coronary intervention; PREVAIL = Prospective Ran- domized Evaluation of the Watchman LAA Closure Device In Pa- tients With Atrial Fibrillation Versus Long Term Warfarin Therapy trial; PROTECT AF = Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation; RCT = ran- domized controlled trial; RE-ALIGN = Randomized, Phase II Study to Evaluate the Safety and Pharmacokinetics of Oral Dabigatran Etexilate in Patients after Heart Valve Replacement; RE-LY = Ran- domized Evaluation of Long-term Anticoagulant Therapy with Dabigatran Etexilate; RE-VERSE AD = Reversal Effects of Idar- ucizumab on Active Dabigatran; ROCKET AF = Rivaroxaban Once daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation; RR = risk ratio; SPAF-I = Stroke Prevention in AF; TEE = transesophageal echocardiography; TIA = transient ischemic attack; t.i.d. = ter in die (three times daily); TT = thrombin time; TTE = transthoracic echocardiography; TTR = time in therapeutic range; UFH = unfractionated heparin; VKA = vitamin K antagonist AFFILIATIONS: From the Institute of Cardiovascular Sciences, Uni- versity of Birmingham, United Kingdom; Liverpool Centre for Car- diovascular Science, University of Liverpool, and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom; and Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (Dr Lip); Institute of Health Informatics, [ Evidence-Based Medicine ] (female)] score of 0 in males or 1 in females), we suggest no antithrombotic therapy. The next step is to consider stroke prevention (ie, oral anticoagulation therapy) for patients with 1 or more non-sex CHA2DS2-VASc stroke risk factors.


The next step is to consider stroke prevention (ie, oral anticoagulation therapy) for patients with 1 or more non-sex CHA2DS2-VASc stroke risk factors. For patients with a single non-sex CHA2DS2-VASc stroke risk factor, we suggest oral anticoagulation rather than no therapy, aspirin,orcombinationtherapywithaspirinandclopidogrel;andforthoseathighriskofstroke(eg, CHA2DS2-VASc $ 2 in males or $ 3 in females), we recommend oral anticoagulation rather than notherapy,aspirin,orcombinationtherapywithaspirinandclopidogrel.Wherewerecommendor suggest in favor of oral anticoagulation, we suggest using a non-vitamin K antagonist oral anti- coagulant drug rather than adjusted-dose vitamin K antagonist therapy. With the latter, it is important to aim for good quality anticoagulation control with a time in therapeutic range > 70%. Attention to modi able bleeding risk factors (eg, uncontrolled BP, labile international normalized ratios, concomitant use of aspirin or nonsteroidal antiin ammatory drugs in an anticoagulated patient, alcohol excess) should be made at each patient contact, and HAS-BLED (hypertension, abnormal renal/liver function [1 point each], stroke, bleeding history or predisposition, labile in- ternationalnormalized ratio, elderly (0.65), drugs/alcoholconcomitantly [1 point each]) score used to assess the risk of bleeding where high risk patients ($ 3) should be reviewed and followed up more frequently. CONCLUSIONS: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF with $1 non-sex CHA2DS2-VASc stroke risk factor(s). KEY WORDS: antithrombotic therapy; atrial brillation; evidence-based medicine; guidelines Note on Shaded Text: In this guideline, shaded text with an asterisk (shading appears in PDF le only) refers to recommendations that remain unchanged from the previous version of the guideline. Summary of Recommendations 1. For patients with AF, including those with paroxysmal AF, stroke risk should be assessed using a risk factor based approach, rather than an categorization into low, moderate/high risk strata.


For patients with AF, including those with paroxysmal AF, stroke risk should be assessed using a risk factor based approach, rather than an categorization into low, moderate/high risk strata. We recommend use of the CHA2DS2-VASc as a simple clinical based stroke risk score to initially identify low stroke risk patients who should not be offered antithrombotic therapy to prevent stroke and reduce mortality (Strong recommendation, moderate quality evidence). Remark: Low risk patients are generally those age < 65 and lone AF irrespective of sex (this includes those with a CHA2DS2-VASc score 0 in males, or 1 in females). 2.


Remark: Low risk patients are generally those age < 65 and lone AF irrespective of sex (this includes those with a CHA2DS2-VASc score 0 in males, or 1 in females). 2. Subsequent to this initial step, for patients with AF, including those with paroxysmal AF, we recommend stroke prevention should be offered to those AF University College London (Dr Banerjee), London, United Kingdom; Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena & Reggio Emilia, Modena University Hospital (Dr Boriani), Modena, Italy; General Clinical Research Center and Division of Cardiology, Taipei Veterans General Hospital and National Yang-Ming University (Dr Chiang), Taipei, Taiwan; Division of Pulmonary and Critical Care, Department of Internal Medicine, Riverside University Medical Center, Moreno Valley, CA, and Division of Pulmonary, Critical Care, Hyperbaric, and Sleep Medicine, Department of Internal Medicine, Loma Linda University Medical Center (Dr Fargo), Loma Linda, CA; Heart Research Institute/Charles Perkins Centre, University of Sydney and Department of Cardiology Concord Hospital, University of Sydney (Dr Freedman), Sydney, Australia; Institute of Cardiovascular Sciences, University of Bir- mingham, United Kingdom, and Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg Univer- sity (Dr Lane), Aalborg, Denmark; Cardiovascular Medicine Division, Brigham and Women s Hospital, Harvard Medical School (Dr Ruff), Boston, MA; Department of Medicine, Stanford University School of Medicine (Dr Turakhia), Stanford, CA; Stroke Research Centre, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, University College Hospitals NHS Foundation Trust (Dr Werring), London, United Kingdom; CHEST (Ms Patel), Glenview, IL; and Uniformed Services University of the Health Sciences, F. Edward Hebert School of Medicine (Dr Moores) Bethesda, MD.


Subsequent to this initial step, for patients with AF, including those with paroxysmal AF, we recommend stroke prevention should be offered to those AF University College London (Dr Banerjee), London, United Kingdom; Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena & Reggio Emilia, Modena University Hospital (Dr Boriani), Modena, Italy; General Clinical Research Center and Division of Cardiology, Taipei Veterans General Hospital and National Yang-Ming University (Dr Chiang), Taipei, Taiwan; Division of Pulmonary and Critical Care, Department of Internal Medicine, Riverside University Medical Center, Moreno Valley, CA, and Division of Pulmonary, Critical Care, Hyperbaric, and Sleep Medicine, Department of Internal Medicine, Loma Linda University Medical Center (Dr Fargo), Loma Linda, CA; Heart Research Institute/Charles Perkins Centre, University of Sydney and Department of Cardiology Concord Hospital, University of Sydney (Dr Freedman), Sydney, Australia; Institute of Cardiovascular Sciences, University of Bir- mingham, United Kingdom, and Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg Univer- sity (Dr Lane), Aalborg, Denmark; Cardiovascular Medicine Division, Brigham and Women s Hospital, Harvard Medical School (Dr Ruff), Boston, MA; Department of Medicine, Stanford University School of Medicine (Dr Turakhia), Stanford, CA; Stroke Research Centre, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, University College Hospitals NHS Foundation Trust (Dr Werring), London, United Kingdom; CHEST (Ms Patel), Glenview, IL; and Uniformed Services University of the Health Sciences, F. Edward Hebert School of Medicine (Dr Moores) Bethesda, MD. DISCLAIMER: CHEST Guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which should always be sought for any medical condition.


DISCLAIMER: CHEST Guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which should always be sought for any medical condition. The complete disclaimer for this guideline can be accessed at: http://www.chestnet.org/Guidelines-and-Resources FUNDING/SUPPORT: This study was funded in total by internal funds from the American College of Chest Physicians. CORRESPONDENCE TO: Gregory Y.H. Lip, MD, Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom; e-mail: gregory.lip@ liverpool.ac.uk Copyright 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. 1122 Evidence-Based Medicine [ 1 5 4 # 5 C H E S T N O V E M B E R 2 0 1 8 ] patients with one or more non-sex CHA2DS2-VASc stroke risk factors (score of 1 in a male or 2 in a female) (Strong recommendation, moderate quality evidence). Remark: Consideration of other less established clinical stroke risk factors, imaging (cardiac or cerebral), or biomarkers (urine, blood, or genetics) may re ne risk strati cation based on simple clinical factors. A complex risk schema using a variety of such data that could accurately place more patients in the low risk stratum not requiring anticoagulants than current simple clinically based scores (personalized medicine) should be the goal of future research, but it will be very dif cult to nd non- anticoagulated patient cohorts for prospective validation. 3. For patients with AF, we recommend bleeding risk assessment should be performed for all patients with AF at every patient contact and should initially focus on potentially modi able bleeding risk factors (Strong recommendation, low quality evidence).


For patients with AF, we recommend bleeding risk assessment should be performed for all patients with AF at every patient contact and should initially focus on potentially modi able bleeding risk factors (Strong recommendation, low quality evidence). Remark: Modi able risk factors may include: Uncontrolled blood pressure; Labile INRs (in a patient taking VKA); Alcohol excess; Concomitant use of NSAIDs or aspirin in an anticoagulated patient; bleeding tendency or predisposition (eg, treat gastric ulcer, optimize renal or liver function, etc). 4. For patients with AF, we recommend use of the HAS-BLED score to address modi able bleeding risk factors in all AF patients. Those potentially at high risk (HAS-BLED score 3) warrant more frequent and regular reviews or follow-up (Strong recommendation, moderate quality evidence). Remark: Given that bleeding risk is highly dynamic, attention to modi able bleeding risk factors should be prioritized during every patient contact and review. 5. In VKA-treated patients, we suggest the use of the HAS-BLED score for bleeding risk assessment (Weak recommendation, low quality evidence). Remark: A high HAS-BLED score ($ 3) is rarely a reason to avoid anticoagulation. The individual modi able components of the score, when reviewed with the patient, can serve to ameliorate bleed risk. 6. For patients with AF, we recommend against antiplatelet therapy alone (monotherapy or aspirin in combination with clopidogrel) for stroke prevention alone, regardless of stroke risk (Strong recommendation, moderate quality evidence). Remark: Patients with AF might have other indications for antiplatelet drugs (eg, acute coronary syndrome, stents). 7. In patients with AF who are eligible for OAC, we recommend NOACs over VKA (Strong recommendation, moderate quality evidence). Remark: Patient and caregiver preferences, cost, formulary considerations, anticipated medication adherence or compliance with INR testing and dose adjustment should be incorporated into clinical decision-making. 8.


Remark: Patient and caregiver preferences, cost, formulary considerations, anticipated medication adherence or compliance with INR testing and dose adjustment should be incorporated into clinical decision-making. 8. In patients on VKAs with consistently low time in INR therapeutic range (eg, TTR < 65%), we recommend considering interventions to improve TTR or switching to NOACs (Strong recommendation, moderate quality evidence). Remark: Action required if TTR < 65% - implement additional measures (more regular INR tests; review medication adherence; address other factors known to in uence INR control; education/counselling) to improve INR control. 9. In patients with prior unprovoked bleeding, warfarin-associated bleeding, or at high risk of bleeding, we suggest using apixaban, edoxaban, or dabigatran 110 mg (where available) as all demonstrate signi cantly less major bleeding compared with warfarin (Weak recommendation, very low quality evidence). Remark: In patients with prior gastrointestinal bleeding apixaban or dabigatran 110 mg bid may be preferable as they are the only NOACs associated without an increased risk of gastrointestinal bleeding compared with warfarin. Remark: Dabigatran 150 mg twice daily recommended in patients at high risk of ischemic stroke as only agent/ dose with superior ef cacy compared with warfarin. However, bleeding risk would need to be assessed and patients monitored. 10. For patients with non-valvular AF, when VKAs are used, we suggest the target should be INR 2.0-3.0, with attention to individual TTR, ideally 70% (Ungraded consensus-based statement). Remark: Action required if TTR sub-optimal (ie, <65- 70%) - implement additional measures (more regular INR tests; review medication adherence; address other factors known to in uence INR control; education/counseling) to improve INR control or consider an NOAC. Remark: When possible, experienced specialized anticoagulation clinics should be utilized for VKA and INR management. 11.


Remark: When possible, experienced specialized anticoagulation clinics should be utilized for VKA and INR management. 11. For patients with AF, we suggest the SAMe-TT2R2 score to aid decision-making to help identify patients likely to do well on VKA (Ungraded consensus-based statement). Remark: Those with score 0-2 are likely to achieve a good TTR. Those with score > 2 are less likely to achieve a good TTR and would require more regular INR checks, education/counseling and frequent follow- up, or alternatively, NOAC should be considered as a better management option if high medication adherence can be expected. 12. For patients with AF of greater than 48 h or unknown duration undergoing elective electrical or pharmacologic cardioversion, we recommend therapeutic anticoagulation with well-managed VKA (INR 2-3) or an NOAC using dabigatran, rivaroxaban, edoxaban, or apixaban for at least 3 weeks before cardioversion or a transesophageal echocardiography (TEE)-guided approach with abbreviated anticoagulation before cardioversion rather than no anticoagulation (Strong recommendation, moderate quality evidence). Remark: With NOACs adherence and persistence should be strongly emphasized. 13. For patients with AF of greater than 48 hours or unknown duration undergoing elective electrical or pharmacologic cardioversion, we recommend therapeutic anticoagulation (with VKA or NOAC) for at least 4 weeks after successful cardioversion to sinus rhythm rather than no anticoagulation, regardless of the baseline risk of stroke (Strong recommendation, moderate quality evidence). Remark: Decisions about anticoagulation beyond 4 weeks should be made in accordance with our risk- based recommendations for long-term antithrombotic therapy in recommendations 1 and 2, and not on the basis of successful cardioversion. 14.