PRACTICE GUIDELINE 2013 ACCF/AHA Guideline for the Management of Heart Failure: Executive Summary A Report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the American College of Chest Physicians, Heart Rhythm Society, and International Society for Heart and Lung Transplantation Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation WRITING COMMITTEE MEMBERS Clyde W. Yancy, MD, MSc, FACC, FAHA, Chairyz; Mariell Jessup, MD, FACC, FAHA, Vice Chair*y; Biykem Bozkurt, MD, PhD, FACC, FAHAy; Javed Butler, MBBS, FACC, FAHA*y; Donald E. Casey, Jr, MD, MPH, MBA, FACP, FAHAx; Mark H. Drazner, MD, MSc, FACC, FAHA*y; Gregg C. Fonarow, MD, FACC, FAHA*y; Stephen A. Geraci, MD, FACC, FAHA, FCCPk; Tamara Horwich, MD, FACCy; James L. Januzzi, MD, FACC*y; Maryl R. Johnson, MD, FACC, FAHA{; Edward K. Kasper, MD, FACC, FAHAy; Wayne C. Levy, MD, FACC*y; Frederick A. Masoudi, MD, MSPH, FACC, FAHAy#; Patrick E. McBride, MD, MPH, FACC**; John J. V. McMurray, MD, FACC*y; Judith E. Mitchell, MD, FACC, FAHAy; Pamela N. Peterson, MD, MSPH, FACC, FAHAy; Barbara Riegel, DNSc, RN, FAHAy; Flora Sam, MD, FACC, FAHAy; Lynne W. Stevenson, MD, FACC*y; W. H. Wilson Tang, MD, FACC*y; Emily J. Tsai, MD, FACCy; Bruce L. Wilkoff, MD, FACC, FHRS*yy *Writing committee members are required to recuse themselves from voting on sections to which their speci c relationships with industry and other entities may apply; see Appendix 1 for recusal information. yACCF/AHA representative. zACCF/AHA Task Force on Practice Guidelines liaison. xAmerican College of Physicians representative. kAmerican College of Chest Physicians representative. {International Society for Heart and Lung Transplantation representative. #ACCF/AHA Task Force on Performance Measures liaison. **American Academy of Family Physicians representative. yyHeart Rhythm Society representative. zzFormer Task Force member during this writing effort. This document was approved by the American College of Cardiology Foundation Board of Trustees and the American Heart Association Science Advisory and Coordinating Committee in May 2013. The American College of Cardiology Foundation requests that this document be cited as follows: Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJV, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WHW, Tsai EJ, Wilkoff BL. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:1495 539. This article has been copublished in Circulation. Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.cardiosource.org) and the American Heart Association (my.americanheart.org). For copies of this document, please contact Elsevier Inc. Reprint Department, fax (212) 633-3820, e-mail reprints@elsevier.com. Permissions: Multiple copies, modi cation, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American College of Cardiology Foundation. Please contact Elsevier s permission department at healthpermissions@elsevier.com. Journal of the American College of Cardiology 2013 by the American College of Cardiology Foundation and the American Heart Association, Inc. Published by Elsevier Inc. ACCF/AHA TASK FORCE MEMBERS Jeffrey L. Anderson, MD, FACC, FAHA, Chair; Alice K. Jacobs, MD, FACC, FAHA, Immediate Past Chairzz; Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect; Nancy M. Albert, PhD, CCNS, CCRN, FAHA; Biykem Bozkurt, MD, PhD, FACC, FAHA; Ralph G. Brindis, MD, MPH, MACC; Mark A. Creager, MD, FACC, FAHAzz; Lesley H. Curtis, PhD; David DeMets, PhD; Robert A. Guyton, MD, FACC; Judith S. Hochman, MD, FACC, FAHA; Richard J. Kovacs, MD, FACC, FAHA; Frederick G. Kushner, MD, FACC, FAHAzz; E. Magnus Ohman, MD, FACC; Susan J. Pressler, PhD, RN, FAAN, FAHA; Frank W. Sellke, MD, FACC, FAHA; Win-Kuang Shen, MD, FACC, FAHA; William G. Stevenson, MD, FACC, FAHAzz; Clyde W. Yancy, MD, MSc, FACC, FAHAzz TABLE OF CONTENTS Preamble 1497 1. Introduction 1499 1.1. Methodology and Evidence Review 1499 1.2. Organization of the Writing Committee 1499 1.3. Document Review and Approval 1499 1.4. Scope of This Guideline With Reference to Other Relevant Guidelines or Statements 1500 2. De nition of HF 1500 3. HF Classi cations 1500 4. Epidemiology 1501 5. Initial and Serial Evaluation of the HF Patient: Recommendations 1502 5.1. Clinical Evaluation 1502 5.1.1. History and Physical Examination 1502 5.1.2. Risk Scoring 1503 5.2. Diagnostic Tests 1503 5.3. Biomarkers 1503 5.4. Noninvasive Cardiac Imaging 1504 5.5. Invasive Evaluation 1505 6. Treatment of Stages A to D: Recommendations 1505 6.1. Stage A 1505 6.2. Stage B 1505 6.3. Stage C 1506 6.3.1. Nonpharmacological Interventions 1506 6.3.2. Pharmacological Treatment for Stage C HFrEF 1506 6.3.3. Pharmacological Treatment for Stage C HFpEF 1510 6.3.4. Device Therapy for Stage C HFrEF 1510 6.4. Stage D 1513 6.4.1. Water Restriction 1513 6.4.2. Inotropic Support 1513 6.4.3. Mechanical Circulatory Support 1516 6.4.4. Cardiac Transplantation 1516 7. The Hospitalized Patient: Recommendations 1516 7.1. Precipitating Causes of Decompensated HF 1517 7.2. Maintenance of GDMT During Hospitalization 1517 7.3. Diuretics in Hospitalized Patients 1517 7.4. Renal Replacement TherapydUltra ltration 1518 7.5. Parenteral Therapy in Hospitalized HF 1518 7.6. Venous Thromboembolism Prophylaxis in Hospitalized Patients 1518 7.7. Arginine Vasopressin Antagonists 1518 7.8. Inpatient and Transitions of Care 1518 8. Important Comorbidities in HF 1519 Interventional Treatments of HF: Recommendations 1519 10. Coordinating Care for Patients With Chronic HF: Recommendations 1520 11. Quality Metrics/Performance Measures: Recommendations 1520 12. Evidence Gaps and Future Research Directions 1520 References 1522 Appendix 1. Author Relationships With Industry and Other Entities (Relevant) 1533 Appendix 2. Reviewer Relationships With Industry and Other Entities (Relevant) 1536 Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 Preamble The medical profession should play a central role in evalu- ating the evidence related to drugs, devices, and procedures for the detection, management, and prevention of disease. When properly applied, expert analysis of available data on the bene ts and risks of these therapies and procedures can improve the quality of care, optimize patient outcomes, and favorably affect costs by focusing resources on the most effective strategies. An organized and directed approach to a thorough review of evidence has resulted in the production of clinical practice guidelines that assist clinicians in selecting the best management strategy for an individual patient. Moreover, clinical practice guidelines can provide a founda- tion for other applications, such as performance measures, appropriate use criteria, and both quality improvement and clinical decision support tools. The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly produced guidelines in the area of cardiovascular disease since 1980. The ACCF/AHA Task Force on Practice Guide- lines (Task Force), charged with developing, updating, and revising practice guidelines for cardiovascular diseases and procedures, directs and oversees this effort. Writing committees are charged with regularly reviewing and evalu- ating all available evidence to develop balanced, patient- centric recommendations for clinical practice. Experts in the subject under consideration are selected by the ACCF and AHA to examine subject-speci c data and write guidelines in partnership with representatives from other medical organizations and specialty groups. Writing commit- tees are asked to perform a literature review; weigh the strength of evidence for or against particular tests, treatments, or procedures; and include estimates of expected outcomes where such data exist. Patient-speci c modi ers, comorbid- ities, and issues of patient preference that may in uence the choice of tests or therapies are considered. When available, information from studies on cost is considered, but data on ef cacy and outcomes constitute the primary basis for the recommendations contained herein. In analyzing the data and developing recommendations and supporting text, the writing committee uses evidence-based methodologies developed by the Task Force (1). The Class of Recommendation (COR) is an estimate of the size of the treatment effect considering risks versus bene ts in addition to evidence and/or agreement that a given treatment or procedure is or is not useful/effective or in some situations may cause harm. The Level of Evidence (LOE) is an estimate of the certainty or precision of the treatment effect. The writing committee reviews and ranks evidence supporting each recommendation with the weight of evidence ranked as LOE A, B, or C according to speci c de nitions that are included in Table 1. Studies are identi ed as observational, retrospective, prospective, or randomized where appropriate. For certain conditions for which inadequate data are available, recommendations are based on expert consensus and clinical experience and are ranked as LOE C. When recommendations at LOE C are supported by historical clinical data, appropriate references (including clinical reviews) are cited if available. For issues for which sparse data are available, a survey of current practice among the clinicians on the writing committee is the basis for LOE C recommendations and no references are cited. The schema for COR and LOE are summarized in Table 1, which also provides suggested phrases for writing recommendations within each COR. A new addition to this methodology is separation of the Class III recommendations to delineate whether the recommendation is determined to be of no bene t or is associated with harm to the patient. In addition, in view of the increasing number of comparative effectiveness studies, comparator verbs and suggested phrases for writing recommendations for the comparative effectiveness of one treatment or strategy versus another have been added for COR I and IIa, LOE A or B only. In view of the advances in medical therapy across the spectrum of cardiovascular diseases, the Task Force has designated the term guideline-directed medical therapy (GDMT) to represent optimal medical therapy as de ned by ACCF/AHA guidelinerecommended therapies (primarily Class I). This new term, GDMT, will be used herein and throughout all future guidelines. Because the ACCF/AHA practice guidelines address patient populations (and clinicians) residing in North Amer- ica, drugs that are not currently available in North America are discussed in the text without a speci c COR. For studies performed in large numbers of subjects outside North America, each writing committee reviews the potential in uence of different practice patterns and patient populations on the treatment effect and relevance to the ACCF/AHA target population to determine whether the ndings should inform a speci c recommendation. The ACCF/AHA practice guidelines are intended to assist clinicians in clinical decision making by describing a range of generally acceptable approaches to the diagnosis, management, and prevention of speci c diseases or condi- tions. The guidelines attempt to de ne practices that meet the needs of most patients in most circumstances. The ultimate judgment regarding care of a particular patient must be made by the clinician and patient in light of all the circumstances presented by that patient. As a result, situa- tions may arise for which deviations from these guidelines may be appropriate. Clinical decision making should involve consideration of the quality and availability of expertise in the area where care is provided. When these guidelines are used as the basis for regulatory or payer decisions, the goal should be improvement in quality of care. The Task Force recognizes that situations arise in which additional data are needed to inform patient care more effectively; these areas will be identi ed within each respective guideline when appropriate. Prescribed courses of treatment in accordance with these recommendations are effective only if followed. Because lack JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary of patient understanding and adherence may adversely affect outcomes, clinicians should make every effort to engage the patient s active participation in prescribed medical regimens and lifestyles. In addition, patients should be informed of the risks, bene ts, and alternatives to a particular treatment and be involved in shared decision making whenever feasible, particularly for COR IIa and IIb, for which the bene t-to-risk ratio may be lower. The Task Force makes every effort to avoid actual, potential, or perceived con icts of interest that may arise as a result of industry relationships or personal interests among the members of the writing committee. All writing committee members and peer reviewers of the guideline are required to disclose all current healthcare-related relationships, including those existing 12 months before initiation of the writing effort. In December 2009, the ACCF and AHA implemented a new policy for relationship with industry and other entities (RWI) that requires the writing committee chair plus a minimum of 50% of the writing committee to have no relevant RWI (Appendix 1 includes the ACCF/AHA de nition of Table 1. Applying Classification of Recommendation and Level of Evidence A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective. *Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. yFor comparative effectiveness recommendations (Class I and IIa; Level of Evidence A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated. Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 relevance). These statements are reviewed by the Task Force and all members during each conference call and/or meeting of the writing committee and are updated as changes occur. All guideline recommendations require a con dential vote by the writing committee and must be approved by a consensus of the voting members. Members are not permitted to draft or vote on any text or recommendations pertaining to their RWI. Members who recused themselves from voting are indicated in the list of writing committee members, and speci c section recusals are noted in Appendix 1. Authors and peer reviewers RWI pertinent to this guideline are disclosed in Appendixes 1 and 2, respectively. Additionally, to ensure complete transparency, writing committee members comprehensive disclosure informationdincluding RWI not pertinent to this documentdis available as an online supplement. Comprehensive disclosure information for the Task Force is also available online at http://www.cardiosource.org/en/ ACC/About-ACC/Who-We-Are/Leadership/Guidelines-and- Documents-Task-Forces.aspx. The work of writing committees is supported exclusively by the ACCF and AHA without commercial support. Writing committee members volunteered their time for this activity. In an effort to maintain relevance at the point of care for practicing clinicians, the Task Force continues to oversee an ongoing process improvement initiative. As a result, in response to pilot projects, several changes to these guidelines will be apparent, including limited narrative text, a focus on summary and evidence tables (with references linked to abstracts in PubMed), and more liberal use of summary recommendation tables (with references that support LOE) to serve as a quick reference. In April 2011, the Institute of Medicine released 2 reports: Clinical Practice Guidelines We Can Trust and Finding What Works in Health Care: Standards for Systematic Reviews (2,3). It is noteworthy that the ACCF/AHA practice guide- lines are cited as being compliant with many of the proposed standards. A thorough review of these reports and of our current methodology is under way, with further enhancements anticipated. The recommendations in this guideline are considered current until they are superseded by a focused update or the full-text guideline is revised. Guidelines are of cial policy of both the ACCF and AHA. The reader is encouraged to consult the full-text guideline (4). for additional guidance and details about heart failure, because the Executive Summary contains only the recommendations. Jeffrey L. Anderson, MD, FACC, FAHA Chair, ACCF/AHA Task Force on Practice Guidelines 1.1. Methodology and Evidence Review The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted through October 2011 and includes selected other references through April 2013. The relevant data are included in evidence tables in the Data Supplement. Searches were extended to studies, reviews, and other evidence conducted in human subjects and that were published in English from PubMed, EMBASE, Cochrane, Agency for Healthcare Research and Quality Reports, and other selected databases relevant to this guideline. Key search words included but were not limited to the following: heart failure, cardiomyopathy, quality of life, mortality, hospitalizations, prevention, biomarkers, hypertension, dyslipidemia, imaging, cardiac catheterization, endomyocardial biopsy, angiotensin- converting enzyme inhibitors, angiotensin-receptor antago- nists/blockers, beta blockers, cardiac, cardiac resynchroni- zation therapy, de brillator, device-based therapy, implantable cardioverter-de brillator, device implantation, medical therapy, acute decompensated heart failure, preserved ejection fraction, terminal care and trans- plantation, quality measures, and performance measures. Additionally, the committee reviewed documents related to the subject matter previously published by the ACCF and AHA. References selected and published in this document are representative and not all-inclusive. 1.2. Organization of the Writing Committee The committee was composed of physicians and a nurse with broad expertise in the evaluation, care, and management of patients with heart failure (HF). The authors included general cardiologists, HF and transplant specialists, electrophysiolo- gists, general internists, and physicians with methodological expertise. The committee included representatives from the ACCF, AHA, American Academy of Family Physicians, American College of Chest Physicians, American College of Physicians, Heart Rhythm Society, and International Society for Heart and Lung Transplantation. 1.3. Document Review and Approval This document was reviewed by 2 of cial reviewers each nominated by both the ACCF and the AHA, as well as 1 to 2 reviewers each from the American Academy of Family Physicians, American College of Chest Physicians, Heart Rhythm Society, and International Society for Heart and Lung Transplantation, as well as 32 individual content reviewers (including members of the ACCF Adult Congenital and Pedi- atric Cardiology Council, ACCF Cardiovascular Team Council, ACCF Council on Cardiovascular Care for Older Adults, ACCF Electrophysiology Committee, ACCF Heart Failure and Transplant Council, ACCF Imaging Council, ACCF Prevention Committee, ACCF Surgeons Scienti c Council, and ACCF Task Force on Appropriate Use Criteria). All information on reviewers RWI was distributed to the writing committee and is published in this document (Appendix 2). This document was approved for publication by the gov- erning bodies of the ACCF and AHA and endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation, American College of Chest Physicians, Heart JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary Rhythm Society, and International Society for Heart and Lung Transplantation. 1.4. Scope of This Guideline With Reference to Other Relevant Guidelines or Statements This guideline covers multiple management issues for the adult patient with HF. Although there is an abundance of evidence addressing HF, for many important clinical consid- erations, this writing committee was unable to identify suf - cient data to properly inform a recommendation. The writing committee actively worked to reduce the number of LOE C recommendations, especially for Class Irecommended therapies. Despite these limitations, it is apparent that much can be done for HF. Adherence to the clinical practice guidelines herein reproduced should lead to improved patient outcomes. Although of increasing importance, children with HF and adults with congenital heart lesions are not speci cally addressed in this guideline. The reader is referred to publi- cally available resources to address questions in these areas. However, this guideline does address HF with preserved ejection fraction (EF) in more detail and similarly revisits hospitalized HF. Additional areas of renewed interest are stage D HF, palliative care, transition of care, and quality of care for HF. Certain management strategies appropriate for the patient at risk for HF or already affected by HF are also reviewed in numerous relevant clinical practice guidelines and scienti c statements published by the ACCF/AHA Task Force on Practice Guidelines, AHA, ACCF Task Force on Appropriate Use Criteria, European Society of Cardiology, Heart Failure Society of America, and the National Heart, Lung, and Blood Institute. The writing committee saw no need to reiterate the recommendations contained in those guidelines and chose to harmonize recommendations when appropriate and eliminate discrepancies. This is especially the case for device-based therapeutics, where complete align- ment between the HF guideline and the device-based therapy guideline was deemed imperative (5). Some recommendations from earlier guidelines have been updated as warranted by new evidence or a better understanding of earlier evidence, whereas others that were no longer accurate or relevant or that were overlapping were modi ed; recommendations from previous guidelines that were similar or redundant were eliminated or consolidated when possible. The present document recommends a combination of life- style modi cations and medications that constitute GDMT. GDMT is speci cally referenced in the recommendations for treatment of HF (Section 6.3.2). Both for GDMT and other recommended drug treatment regimens, the reader is advised to con rm dosages with product insert material and to evaluate carefully for contraindications and drug-drug interactions. Table 2 is a list of documents deemed pertinent to this effort and is intended for use as a resource; it obviates the need to repeat already extant guideline recommendations. Additional other HF guideline statements are highlighted as well for the purpose of comparison and completeness. 2. De nition of HF HF is a complex clinical syndrome that results from any structural or functional impairment of ventricular lling or ejection of blood. The cardinal manifestations of HF are dyspnea and fatigue, which may limit exercise tolerance, and uid retention, which may lead to pulmonary and/or splanchnic congestion and/or peripheral edema. Some patients have exercise intolerance but little evidence of uid retention, whereas others complain primarily of edema, dyspnea, or fatigue. Because some patients present without signs or symptoms of volume overload, the term heart failure is preferred over congestive heart failure. There is no single diagnostic test for HF because it is largely a clinical diagnosis based on a careful history and physical examination. The clinical syndrome of HF may result from disorders of the pericardium, myocardium, endocardium, heart valves, or great vessels, or from certain metabolic abnormalities, but most patients with HF have symptoms due to impaired left ventricular (LV) myocardial function. It should be empha- sized that HF is not synonymous with either cardiomyopathy or LV dysfunction; these latter terms describe possible structural or functional reasons for the development of HF. HF may be associated with a wide spectrum of LV functional abnormalities, which may range from patients with normal LV size and preserved EF to those with severe dilatation and/ or markedly reduced EF. In most patients, abnormalities of systolic and diastolic dysfunction coexist, irrespective of EF. EF is considered important in classi cation of patients with HF because of differing patient demographics, comorbid conditions, prognosis, and response to therapies (36) and because most clinical trials selected patients based on EF. EF values are dependent on the imaging technique used, method of analysis, and operator. As other techniques may indicate abnormalities in systolic function among patients with a preserved EF, it is preferable to use the terms preserved or reduced EF over preserved or reduced systolic function. For the remainder of this guideline, we will consistently refer to HF with preserved EF and HF with reduced EF as HFpEF and HFrEF, respectively (Table 3). 3. HF Classi cations Both the ACCF/AHA stages of HF (37) and the New York Heart Association (NYHA) functional classi cation (37,38) provide useful and complementary information about the presence and severity of HF. The ACCF/AHA stages of HF emphasize the development and progression of disease and can be used to describe individuals and populations, whereas the NYHA classes focus on exercise capacity and the symptomatic status of the disease (Table 4). Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 The lifetime risk of developing HF is 20% for Americans 40 years of age (39). In the United States, HF incidence has largely remained stable over the past several decades, with >650 ,000 new HF cases diagnosed annually (40 42). HF incidence increases with age, rising from approximately 20 per 1,000 individuals 65 to 69 years of age to >80 per 1,000 individuals among those 85 years of age (41). Approximately 5.1 million persons in the United States have clinically manifest HF, and the Table 2. Associated Guidelines and Statements Title Organization Publication Year (Reference) Guidelines Guidelines for the Management of Adults With Congenital Heart Disease ACCF/AHA 2008 (6) Guidelines for the Management of Patients With Atrial Fibrillation ACCF/AHA/HRS 2011 (7 9) Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults ACCF/AHA 2010 (10) Guideline for Coronary Artery Bypass Graft Surgery ACCF/AHA 2011 (11) Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities ACCF/AHA/HRS 2013 (5) Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy ACCF/AHA 2011 (12) Guideline for Percutaneous Coronary Intervention ACCF/AHA/SCAI 2011 (13) Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease Guideline for the Management of ST-Elevation Myocardial Infarction ACCF/AHA 2013 (16) Guidelines for the Management of Patients With Unstable Angina/ Non ST-Elevation Myocardial Infarction Guidelines for the Management of Patients With Valvular Heart Disease ACCF/AHA 2008 (18) Comprehensive Heart Failure Practice Guideline HFSA 2010 (19) Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure ESC 2012 (20) Chronic Heart Failure: Management of Chronic Heart Failure in Adults in Primary and Secondary Care Antithrombotic Therapy and Prevention of Thrombosis ACCP 2012 (22) Guidelines for the Care of Heart Transplant Recipients ISHLT 2010 (23) Statements Contemporary Definitions and Classification of the Cardiomyopathies AHA 2006 (24) Genetics and Cardiovascular Disease AHA 2012 (25) Appropriate Utilization of Cardiovascular Imaging in Heart Failure ACCF 2013 (26) Appropriate Use Criteria for Coronary Revascularization Focused Update ACCF 2012 (27) Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines Referral, Enrollment, and Delivery of Cardiac Rehabilitation/Secondary Prevention Programs at Clinical Centers and Beyond Decision Making in Advanced Heart Failure AHA 2012 (31) Recommendations for the Use of Mechanical Circulatory Support: Device Strategies and Patient Selection Advanced Chronic Heart Failure ESC 2007 (33) Oral Antithrombotic Agents for the Prevention of Stroke in Nonvalvular Atrial Fibrillation Third Universal Definition of Myocardial Infarction ESC/ACCF/AHA/WHF 2012 (35) AACVPR indicates American Association of Cardiovascular and Pulmonary Rehabilitation; AATS, American Association for Thoracic Surgery; ACCF, American College of Cardiology Foundation; ACCP, American College of Chest Physicians; ACP, American College of Physicians; AHA, American Heart Association; ASA, American Stroke Association; ESC, European Society of Cardiology; HFSA, Heart Failure Society of America; HRS, Heart Rhythm Society; ISHLT, International Society for Heart and Lung Transplantation; NHLBI, National Heart, Lung, and Blood Institute; NICE, National Institute for Health and Clinical Excellence; PCNA, Preventive Cardiovascular Nurses Association; SCAI, Society for Cardiovascular Angiography and Interventions; STS, Society of Thoracic Surgeons; and WHF, World Heart Federation. JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary prevalence continues to rise (40). In the Medicare-eligible population, HF prevalence increased from 90 to 121 per HFpEF each make up about half of the overall HF burden (43). One in 5 Americans will be >65 years of age by 2050 (44). Because HF prevalence is highest in this group, the number of Americans with HF is expected to signi cantly worsen in the future. Disparities in the epidemiology of HF have been identi ed. Blacks have the highest risk for HF (45). In the ARIC (Atherosclerosis Risk in Communities) study, incidence rate per 1,000 person-years was lowest among white women, (41,42) and highest among black men, (46) with blacks having a greater 5-year mortality rate than whites (47). HF in non-Hispanic black males and females has a prevalence of 4.5% and 3.8%, respectively, versus 2.7% and 1.8% in non-Hispanic white males and females, respectively (40). 5. Initial and Serial Evaluation of the HF Patient: Recommendations 5.1. Clinical Evaluation See Table 5 for multivariable clinical risk scores. 5.1.1. History and Physical Examination CLASS I 1. A thorough history and physical examination should be ob- tained/performed in patients presenting with HF to identify cardiac and noncardiac disorders or behaviors that might cause or accelerate the development or progression of HF. (Level of Evidence: C) 2. In patients with idiopathic dilated cardiomyopathy, a 3- generational family history should be obtained to aid in establishing the diagnosis of familial dilated cardiomyop- athy. (Level of Evidence: C) Table 3. Definitions of HFrEF and HFpEF Classification EF (%) Description I. Heart failure with reduced ejection fraction (HFrEF) 40 Also referred to as systolic HF. Randomized controlled trials have mainly enrolled patients with HFrEF, and it is only in these patients that efficacious therapies have been demonstrated to date. II. Heart failure with preserved ejection fraction (HFpEF) 50 Also referred to as diastolic HF. Several different criteria have been used to further define HFpEF. The diagnosis of HFpEF is challenging because it is largely one of excluding other potential noncardiac causes of symptoms suggestive of HF. To date, efficacious therapies have not been identified. a. HFpEF, borderline 41 to 49 These patients fall into a borderline or intermediate group. Their characteristics, treatment patterns, and outcomes appear similar to those of patients with HFpEF. b. HFpEF, improved >40 It has been recognized that a subset of patients with HFpEF previously had HFrEF. These patients with improvement or recovery in EF may be clinically distinct from those with persistently preserved or reduced EF. Further research is needed to better characterize these patients. EF indicates ejection fraction; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; and HFrEF, heart failure with reduced ejection fraction. Table 4. Comparison of ACCF/AHA Stages of HF and NYHA Functional Classifications ACCF/AHA Stages of HF (37) NYHA Functional Classification (38) A At high risk for HF but without structural heart disease or symptoms of HF None B Structural heart disease but without signs or symptoms of HF I No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF. C Structural heart disease with prior or current symptoms of HF I No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF. II Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF. III Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF. IV Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest. D Refractory HF requiring specialized interventions IV Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest. ACCF indicates American College of Cardiology Foundation; AHA, American Heart Association; HF, heart failure; and NYHA, New York Heart Association. Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 3. Volume status and vital signs should be assessed at each patientencounter.Thisincludesserialassessmentofweight,as wellasestimatesofjugularvenouspressureandthepresenceof peripheral edema or orthopnea (48 51). (Level of Evidence: B) 5.1.2. Risk Scoring CLASS IIa 1. Validated multivariable risk scores can be useful to estimate subsequent risk of mortality in ambulatory or hospitalized patients with HF (52 60). (Level of Evidence: B) 5.2. Diagnostic Tests CLASS I 1. Initial laboratory evaluation of patients presenting with HF should include complete blood count, urinalysis, serum electro- lytes (including calcium and magnesium), blood urea nitrogen, serum creatinine, glucose, fasting lipid pro le, liver function tests, and thyroid-stimulating hormone. (Level of Evidence: C) 2. Serial monitoring, when indicated, should include serum electrolytes and renal function. (Level of Evidence: C) 3. A 12-lead electrocardiogram should be performed initially on all patients presenting with HF. (Level of Evidence: C) CLASS IIa patients who present with HF (63). (Level of Evidence: C) 2. Diagnostic tests for rheumatologic diseases, amyloidosis, or pheochromocytoma are reasonable in patients presenting with HF in whom there is a clinical suspicion of these diseases. (Level of Evidence: C) See Table 6 for a summary of recommendations from this section. A. Ambulatory/Outpatient CLASS I 1. In ambulatory patients with dyspnea, measurement of B- type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) is useful to support clin- ical decision making regarding the diagnosis of HF, espe- cially in the setting of clinical uncertainty (64 70). (Level of Evidence: A) 2. Measurement of BNP or NT-proBNP is useful for establishing prognosis or disease severity in chronic HF (69,71 76). (Level of Evidence: A) CLASS IIa 1. BNP- or NT-proBNPLguided HF therapy can be useful to achieve optimal dosing of GDMT in select clinically euvole- mic patients followed in a well-structured HF disease management program (77 84). (Level of Evidence: B) CLASS IIb 1. The usefulness of serial measurement of BNP or NT-proBNP to reduce hospitalization or mortality in patients with HF is not well established (77 84). (Level of Evidence: B) 2. Measurement of other clinically available tests such as biomarkers of myocardial injury or brosis may be consid- ered for additive risk strati cation in patients with chronic HF (85 91). (Level of Evidence: B) B. Hospitalized/Acute CLASS I 1. Measurement of BNP or NT-proBNP is useful to support clinical judgment for the diagnosis of acutely decom- pensated HF, especially in the setting of uncertainty for the diagnosis (92 98). (Level of Evidence: A) Table 5. Selected Multivariable Risk Scores to Predict Outcome in HF Risk Score Reference/Link Chronic HF All patients with chronic HF Seattle Heart Failure Model (56) http://SeattleHeartFailureModel.org Heart Failure Survival Score (52) http://handheld.softpedia.com/get/Health/Calculator/HFSS-Calc-37354.shtml CHARM Risk Score (59) CORONA Risk Score (60) Specific to chronic HFpEF I-PRESERVE Score (54) Acutely decompensated HF ADHERE Classification and Regression Tree (CART) Model (53) American Heart Association Get With The Guidelines Score (58) http://www.heart.org/HEARTORG/HealthcareProfessional/GetWithTheGuidelinesHFStroke/ GetWithTheGuidelinesHeartFailureHomePage/Get-With-The-Guidelines-Heart-Failure-Home- EFFECT Risk Score (55) http://www.ccort.ca/Research/CHFRiskModel.aspx ESCAPE Risk Model and Discharge Score (61) OPTIMIZE HF Risk-Prediction Nomogram (62) ADHERE indicates Acute Decompensated Heart Failure National Registry; CHARM, Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity; CORONA,ControlledRosuvastatinMultinationalTrial in HeartFailure;EFFECT,Enhanced Feedbackfor EffectiveCardiacTreatment;ESCAPE, Evaluation Studyof Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; I-PRESERVE, Irbesartan in Heart Failure with Preserved Ejection Fraction Study; and OPTIMIZE, Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure. JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary 2. Measurement of BNP or NT-proBNP and/or cardiac troponin is useful for establishing prognosis or disease severity in acutely decompensated HF (96,99 106). (Level of Evidence: A) CLASS IIb 1. The usefulness of BNP- or NT-proBNPLguided therapy for acutely decompensated HF is not well established (107,108). (Level of Evidence: C) 2. Measurement of other clinically available tests such as biomarkers of myocardial injury or brosis may be consid- ered for additive risk strati cation in patients with acutely decompensated HF (96,101,104,105,109 115). (Level of Evidence: A) 5.4. Noninvasive Cardiac Imaging See Table 7 for a summary of recommendations from this section. CLASS I 1. Patients with suspected or new-onset HF, or those pre- senting with acute decompensated HF, should undergo a chest x-ray to assess heart size and pulmonary congestion and to detect alternative cardiac, pulmonary, and other diseases that may cause or contribute to the patient s symptoms. (Level of Evidence: C) 2. A 2-dimensional echocardiogram with Doppler should be performed during initial evaluation of patients presenting with HF to assess ventricular function, size, wall thickness, wall motion, and valve function. (Level of Evidence: C) 3. Repeat measurement of EF and measurement of the severity of structural remodeling are useful to provide information in patients with HF who have had a signi cant change in clinical status; who have experienced or recovered from a clinical event; or who have received treatment, including GDMT, that might have had a signi cant effect on cardiac function; or who may be candidates for device therapy. (Level of Evidence: C) CLASS IIa 1. Noninvasive imaging to detect myocardial ischemia and viability is reasonable in patients presenting with de novo HF, who have known coronary artery disease (CAD) and no angina, unless the patient is not eligible for revasculariza- tion of any kind. (Level of Evidence: C) Table 6. Recommendations for Biomarkers in HF Biomarker, Application Setting COR LOE References Natriuretic peptides Diagnosis or exclusion of HF Ambulatory, Acute I A 64 70,92 98 Prognosis of HF Ambulatory, Acute I A 69,71 76,96,99 106 Achieve GDMT Ambulatory IIa B 77 84 Guidance for acutely decompensated HF therapy Acute IIb C 107,108 Biomarkers of myocardial injury Additive risk stratification Acute, Ambulatory I A 85 88,96,101,104 115 Biomarkers of myocardial fibrosis Additive risk stratification Ambulatory IIb B 89 91 Acute IIb A 96,101,104,106 108,110,112 115 COR indicates Class of Recommendation; GDMT, guideline-directed medical therapy; HF, heart failure; and LOE, Level of Evidence. Table 7. Recommendations for Noninvasive Cardiac Imaging Recommendations COR LOE Patients with suspected, acute, or new-onset HF should undergo a chest x-ray I C A 2-dimensional echocardiogram with Doppler should be performed for initial evaluation of HF I C Repeat measurement of EF is useful in patients with HF who have had a significant change in clinical status or received treatment that might affect cardiac function or for consideration of device therapy I C Noninvasive imaging to detect myocardial ischemia and viability is reasonable in HF and CAD IIa C Viability assessment is reasonable before revascularization in HF patients with CAD IIa B (117 121) Radionuclide ventriculography or MRI can be useful to assess LVEF and volume IIa C MRI is reasonable when assessing myocardial infiltration or scar IIa B (122 124) Routine repeat measurement of LV function assessment should not be performed III: No Benefit B (125,126) CAD indicates coronary artery disease; COR, Class of Recommendation; EF, ejection fraction; HF, heart failure; LOE, Level of Evidence; LV, left ventricular; LVEF, left ventricular ejection fraction; and MRI, magnetic resonance imaging. Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 2. Viability assessment is reasonable in select situations when planning revascularization in HF patients with CAD (117 121). (Level of Evidence: B) 3. Radionuclide ventriculography or magnetic resonance imaging can be useful to assess left ventricular ejection fraction (LVEF) and volume when echocardiography is inad- equate. (Level of Evidence: C) 4. Magnetic resonance imaging is reasonable when assessing myocardial in ltrative processes or scar burden (122 124). (Level of Evidence: B) CLASS III: NO BENEFIT 1. Routine repeat measurement of LV function assessment in the absence of clinical status change or treatment inter- ventions should not be performed (125,126). (Level of Evidence: B) 5.5. Invasive Evaluation See Table 8 for a summary of recommendations from this section. CLASS I 1. Invasive hemodynamic monitoring with a pulmonary artery catheter should be performed to guide therapy in patients who have respiratory distress or clinical evidence of impaired perfusion in whom the adequacy or excess of intracardiac lling pressures cannot be determined from clinical assessment. (Level of Evidence: C) CLASS IIa 1. Invasive hemodynamic monitoring can be useful for carefully selected patients with acute HF who have persistent symp- toms despite empiric adjustment of standard therapies and a. whose uid status, perfusion, or systemic or pulmonary vascular resistance is uncertain; b. whose systolic pressure remains low, or is associated with symptoms, despite initial therapy; c. whose renal function is worsening with therapy; d. who require parenteral vasoactive agents; or e. who may need consideration for mechanical circulatory support (MCS) or transplantation. (Level of Evidence: C) 2. When ischemia may be contributing to HF, coronary arteri- ography is reasonable for patients eligible for revasculari- zation. (Level of Evidence: C) 3. Endomyocardial biopsy can be useful in patients presenting with HF when a speci c diagnosis is suspected that would in uence therapy. (Level of Evidence: C) CLASS III: NO BENEFIT 1. Routine use of invasive hemodynamic monitoring is not recommended in normotensive patients with acute decom- pensated HF and congestion with symptomatic response to diuretics and vasodilators (127). (Level of Evidence: B) CLASS III: HARM 1. Endomyocardial biopsy should not be performed in the routine evaluation of patients with HF. (Level of Evidence: C) 6. Treatment of Stages A to D: Recommendations 6.1. Stage A CLASS I 1. Hypertension and lipid disorders should be controlled in accordance with contemporary guidelines to lower the risk of HF (28,128 132). (Level of Evidence: A) 2. Other conditions that may lead to or contribute to HF, such as obesity, diabetes mellitus, tobacco use, and known car- diotoxic agents, should be controlled or avoided. (Level of Evidence: C) 6.2. Stage B See Table 9 for a summary of recommendations from this section. CLASS I 1. In all patients with a recent or remote history of myocardial infarction (MI) or acute coronary syndrome (ACS) and reduced EF, angiotensin-converting enzyme (ACE) inhibitors should be used to prevent symptomatic HF and reduce mortality (133 135). In patients intolerant to ACE inhibi- tors, angiotensin-receptor blockers (ARBs) are appropriate unless contraindicated (132,136). (Level of Evidence: A) 2. In all patients with a recent or remote history of MI or ACS and reduced EF, evidence-based beta blockers should be used to reduce mortality (137 139). (Level of Evidence: B) Table 8. Recommendations for Invasive Evaluation Recommendations COR LOE Monitoring with a pulmonary artery catheter should be performed in patients with respiratory distress or impaired systemic perfusion when clinical assessment is inadequate I C Invasive hemodynamic monitoring can be useful for carefully selected patients with acute HF with persistent symptoms and/or when hemodynamics are uncertain IIa C When ischemia may be contributing to HF, coronary arteriography is reasonable IIa C Endomyocardial biopsy can be useful in patients with HF when a specific diagnosis is suspected that would influence therapy IIa C Routine use of invasive hemodynamic monitoring is not recommended in normotensive patients with acute HF III: No Benefit B (127) Endomyocardial biopsy should not be performed in the routine evaluation of HF III: Harm C COR indicates Class of Recommendation; HF, heart failure; and LOE, Level of Evidence. JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary 3. In all patients with a recent or remote history of MI or ACS, statins should be used to prevent symptomatic HF and cardiovascular events (140 146). (Level of Evidence: A) 4. In patients with structural cardiac abnormalities, including LV hypertrophy, in the absence of a history of MI or ACS, blood pressure should be controlled in accordance with clinical practice guidelines for hypertension to prevent symptomatic HF (28,128 131). (Level of Evidence: A) 5. ACE inhibitors should be used in all patients with a reduced EF to prevent symptomatic HF, even if they do not have a history of MI (135,147). (Level of Evidence: A) 6. Beta blockers should be used in all patients with a reduced EF to prevent symptomatic HF, even if they do not have a history of MI. (Level of Evidence: C) CLASS IIa 1. To prevent sudden death, placement of an implantable cardioverter-de brillator (ICD) is reasonable in patients with asymptomatic ischemic cardiomyopathy who are at least 40 days post-MI, have an LVEF of 30% or less, are on appropriate medical therapy, and have reasonable expecta- tion of survival with a good functional status for more than 1 year (148). (Level of Evidence: B) CLASS III: HARM 1. Nondihydropyridine calcium channel blockers with negative inotropic effects may be harmful in asymptomatic patients with low LVEF and no symptoms of HF after MI. (Level of Evidence: C) 6.3. Stage C 6.3.1. Nonpharmacological Interventions CLASS I 1. Patients with HF should receive speci c education to facil- itate HF self-care (149 154). (Level of Evidence: B) 2. Exercise training (or regular physical activity) is recom- mended as safe and effective for patients with HF who are able to participate to improve functional status (155 158). (Level of Evidence: A) CLASS IIa 1. Sodium restriction is reasonable for patients with symp- tomatic HF to reduce congestive symptoms. (Level of Evidence: C) 2. Continuous positive airway pressure can be bene cial to increase LVEF and improve functional status in patients with HF and sleep apnea (159 162). (Level of Evidence: B) 3. Cardiac rehabilitation can be useful in clinically stable patients with HF to improve functional capacity, exercise duration, health-related quality of life, and mortality (155,157,158,163 166). (Level of Evidence: B) 6.3.2. Pharmacological Treatment for Stage C HFrEF CLASS I 1. Measures listed as Class I recommendations for patients in stages A and B are recommended where appropriate for patients in stage C. (Levels of Evidence: A, B, and C as appropriate) 2. GDMT as depicted in Figure 1 should be the mainstay of pharmacological therapy for HFrEF (134,136,137,167 182). (Level of Evidence: A) See Table 10 for oral diuretics recommended for use in the treatment of chronic HF. CLASS I 1. Diuretics are recommended in patients with HFrEF who have evidence of uid retention, unless contraindicated, to improve symptoms. (Level of Evidence: C) 6.3.2.2. ACE INHIBITORS See Table11for drugs commonlyusedfor HFrEF(stage C HF). CLASS I 1. ACE inhibitors are recommended in patients with HFrEF and current or prior symptoms, unless contraindicated, to reduce morbidity and mortality (134,167 169). (Level of Evidence: A) Table 9. Recommendations for Treatment of Stage B HF Recommendations COR LOE References In patients with a history of MI and reduced EF, ACE inhibitors or ARBs should be used to prevent HF I A 132 136 In patients with MI and reduced EF, evidence-based beta blockers should be used to prevent HF I B 137 139 In patients with MI, statins should be used to prevent HF I A 140 146 Blood pressure should be controlled to prevent symptomatic HF I A 28,128 131 ACE inhibitors should be used in all patients with a reduced EF to prevent HF I A 135,147 Beta blockers should be used in all patients with a reduced EF to prevent HF I C N/A An ICD is reasonable in patients with asymptomatic ischemic cardiomyopathy who are at least 40 d post-MI, have an LVEF 30%, and on GDMT IIa B 148 Nondihydropyridine calcium channel blockers may be harmful in patients with low LVEF III: Harm C N/A ACE indicates angiotensin-converting enzyme; ARB, angiotensin-receptor blocker; COR, Class of Recommendation; EF, ejection fraction; GDMT, guideline-directed medical therapy; HF, heart failure; ICD, implantable cardioverter-defibrillator; LOE, Level of Evidence; LVEF, left ventricular ejection fraction; MI, myocardial infarction; and N/A, not available. Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 6.3.2.3. ANGIOTENSIN-RECEPTOR BLOCKERS CLASS I 1. ARBs are recommended in patients with HFrEF with current or prior symptoms who are ACE inhibitor intolerant, unless contraindicated, to reduce morbidity and mortality (136,170,171,189). (Level of Evidence: A) CLASS IIa 1. ARBs are reasonable to reduce morbidity and mortality as alter- natives to ACE inhibitors as rst-line therapy for patients with HFrEF, especially for patients already taking ARBs for other indi- cations,unlesscontraindicated(190 195).(Level of Evidence: A) CLASS IIb 1. Addition of an ARB may be considered in persistently symptomatic patients with HFrEF who are already being treated with an ACE inhibitor and a beta blocker in whom an aldosterone antagonist is not indicated or tolerated (176,196). (Level of Evidence: A) CLASS III: HARM 1. Routine combined use of an ACE inhibitor, ARB, and aldo- sterone antagonist is potentially harmful for patients with HFrEF. (Level of Evidence: C) 6.3.2.4. BETA BLOCKERS CLASS I 1. Use of 1 of the 3 beta blockers proven to reduce mortality (e.g., bisoprolol, carvedilol, and sustained-release metoprolol succi- nate) is recommended for all patients with current or prior symptomsofHFrEF,unlesscontraindicated,toreducemorbidity and mortality (137,172 175,187). (Level of Evidence: A) 6.3.2.5. ALDOSTERONE RECEPTOR ANTAGONISTS See Table 12 for aldosterone receptor antagonists drug dosing. CLASS I 1. Aldosterone receptor antagonists (or mineralocorticoid receptor antagonists) are recommended in patients with NYHA class II IV HF and who have LVEF of 35% or less, unless contraindicated, to reduce morbidity and mortality. Patients with NYHA class II HF should have a history of prior cardiovascular hospitalization or elevated plasma natriuretic peptide levels to be consid- ered for aldosterone receptor antagonists. Creatinine should be 2.5 mg/dL or less in men or 2.0 mg/dL or less in women (or estimated glomerular ltration rate >30 ), and potassium should be less than 5.0 mEq/L. Careful monitoring of potassium, renal function, and diuretic dosing should be performed at initiation and closely followed thereafter to minimize risk of hyperkalemia and renal insuf ciency (181,182,197). (Level of Evidence: A) 2. Aldosterone receptor antagonists are recommended to reduce morbidity and mortality following an acute MI in patients who have LVEF of 40% or less who develop symp- toms of HF or have a history of diabetes mellitus, unless contraindicated (184). (Level of Evidence: B) CLASS III: HARM 1. Inappropriate use of aldosterone receptor antagonists is potentially harmful because of life-threatening hyperkalemia or renal insuf ciency when serum creatinine is greater than HFrEF Stage C NYHA Class I IV Treatment: For NYHA class II-IV patients. Provided estimated creatinine >30 mL/min and K+ <5.0 mEq/dL For persistently symptomatic African Americans, NYHA class III-IV Class I, LOE A ACEI or ARB AND Beta Blocker Class I, LOE C Loop Diuretics Class I, LOE A Hydral-Nitrates Class I, LOE A Aldosterone Antagonist Add Add Add For all volume overload, NYHA class II-IV patients Figure 1. Stage C HFrEF: evidence-based, guideline-directed medical therapy. ACEI indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin-receptor blocker; HFrEF, heart failure with reduced ejection fraction; Hydral-Nitrates, hydralazine and isosorbide dinitrate; LOE, Level of Evidence; and NYHA, New York Heart Association. JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary 2.5 mg/dL in men or greater than 2.0 mg/dL in women (or ), and/or potassium greater than 5.0 mEq/L (198,199). (Level of Evidence: B) 6.3.2.6. HYDRALAZINE AND ISOSORBIDE DINITRATE CLASS I 1. The combination of hydralazine and isosorbide dinitrate is recommended to reduce morbidity and mortality for patients self-described as African Americans with NYHA class III IV HFrEF receiving optimal therapy with ACE inhibitors and beta blockers, unless contraindicated (179,180). (Level of Evidence: A) CLASS IIa 1. A combination of hydralazine and isosorbide dinitrate can be useful to reduce morbidity or mortality in patients with current or prior symptomatic HFrEF who cannot be given an ACE inhibitor or ARB because of drug intolerance, hypoten- sion, or renal insuf ciency, unless contraindicated (188). (Level of Evidence: B) See Table 13 for a summary of the treatment bene t of GDMT in HFrEF. CLASS IIa 1. Digoxin can be bene cial in patients with HFrEF, unless contraindicated, to decrease hospitalizations for HF (202 209). (Level of Evidence: B) 6.3.2.8. OTHER DRUG TREATMENT CLASS I 1. Patients with chronic HF with permanent/persistent/ paroxysmal atrial brillation (AF) and an additional risk factor for cardioembolic stroke (history of hyper- tension, diabetes mellitus, previous stroke or transient ischemic attack, or 75 years of age) should receive chronic anticoagulant therapy* (210 216). (Level of Evidence: A) 2. The selection of an anticoagulant agent (warfarin, dabiga- tran, apixaban, or rivaroxaban) for permanent/persistent/ paroxysmal AF should be individualized on the basis of risk factors, cost, tolerability, patient preference, potential for drug interactions, and other clinical characteristics, including time in the international normalized ratio thera- peutic range if the patient has been taking warfarin. (Level of Evidence: C) CLASS IIa 1. Chronic anticoagulation is reasonable for patients with chronic HF who have permanent/persistent/paroxysmal AF but are without an additional risk factor for cardioembolic stroke* (211 213,217 219). (Level of Evidence: B) CLASS III: NO BENEFIT 1. Anticoagulation is not recommended in patients with chronic HFrEF without AF, a prior thromboembolic event, or a cardioembolic source (220 222). (Level of Evidence: B) CLASS III: NO BENEFIT 1. Statins are not bene cial as adjunctive therapy when prescribed solely for the diagnosis of HF in the absence of other indications for their use (223 228). (Level of Evidence: A) CLASS IIa 1. Omega-3 polyunsaturated fatty acid supplementation is reasonable to use as adjunctive therapy in patients with NYHA class II IV symptoms and HFrEF or HFpEF, unless contraindicated, to reduce mortality and cardiovascular hospitalizations (229,230). (Level of Evidence: B) Table 10. Oral Diuretics Recommended for Use in the Treatment of Chronic HF Drug Initial Daily Dose(s) Maximum Total Daily Dose Duration of Action Loop diuretics Bumetanide 0.5 to 1.0 mg once or twice Furosemide 20 to 40 mg once or twice Thiazide diuretics Chlorothiazide 250 to 500 mg once or twice Hydrochlorothiazide 25 mg once or twice Indapamide 2.5 mg once 5 mg 36 h Metolazone 2.5 mg once 20 mg 12 to 24 h Potassium-sparing diuretics* Amiloride 5 mg once 20 mg 24 h Sequential nephron blockade Metolazonez 2.5 to 10.0 mg once plus loop diuretic N/A N/A Hydrochlorothiazide 25 to 100 mg once or twice plus loop diuretic N/A N/A Chlorothiazide (IV) 500 to 1,000 mg once plus loop diuretic N/A N/A *Eplerenone, although also a diuretic, is primarily used in chronic HF. yHigher doses may occasionally be used with close monitoring. zSee Section 7.3. HF indicates heart failure; IV, intravenous; and N/A, not applicable. * In the absence of contraindications to anticoagulation. Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 6.3.2.9. DRUGS OF UNPROVEN VALUE OR THAT MAY WORSEN HF CLASS III: NO BENEFIT 1. Nutritional supplements as treatment for HF are not rec- ommended in patients with current or prior symptoms of HFrEF (231,232). (Level of Evidence: B) 2. Hormonal therapies other than to correct de ciencies are not recommended for patients with current or prior symp- toms of HFrEF. (Level of Evidence: C) CLASS III: HARM 1. Drugs known to adversely affect the clinical status of patients with current or prior symptoms of HFrEF are potentially harmful and should be avoided or withdrawn Table 11. Drugs Commonly Used for Stage C HFrEF Drug Initial Daily Dose(s) Maximum Dose(s) Mean Doses Achieved in Clinical Trials ACE inhibitors Fosinopril 5 to 10 mg once 40 mg once N/A Perindopril 2 mg once 8 to 16 mg once N/A Quinapril 5 mg twice 20 mg twice N/A Ramipril 1.25 to 2.5 mg once 10 mg once N/A Trandolapril 1 mg once 4 mg once N/A ARBs Aldosterone antagonists Spironolactone 12.5 to 25.0 mg once 25 mg once or twice 26 mg/d (181) Eplerenone 25 mg once 50 mg once 42.6 mg/d (184) Beta blockers Bisoprolol 1.25 mg once 10 mg once 8.6 mg/d (185) Carvedilol 3.125 mg twice 50 mg twice 37 mg/d (186) Carvedilol CR 10 mg once 80 mg once N/A Metoprolol succinate extended release (metoprolol CR/XL) Hydralazine and isosorbide dinitrate Fixed-dose combination (180) 37.5 mg hydralazine/20 mg isosorbide dinitrate 3 times daily 75 mg hydralazine/40 mg isosorbide dinitrate 3 times daily isosorbide dinitrate daily Hydralazine and isosorbide daily and isosorbide dinitrate: 20 to Hydralazine: 300 mg daily in divided doses and isosorbide dinitrate: 120 mg daily in divided doses N/A ACE indicates angiotensin-converting enzyme; ARB, angiotensin-receptor blocker; CR, controlled release; CR/XL, controlled release/extended release; HFrEF, heart failure with reduced ejection fraction; and N/A, not applicable. Table 12. Drug Dosing for Aldosterone Receptor Antagonists Eplerenone Spironolactone Initial dose (only if K 5 mEq/L) 25 mg once daily 25 mg once every other day 12.5 to 25.0 mg once daily 12.5 mg once daily or every other day Maintenance dose (after 4 wk for K 50 mg once daily 25 mg once daily 25 mg once or twice daily 12.5 to 25.0 mg once daily *After dose initiation for K , increase6.0 mEq/L, or worsening renal function, hold until K <5.0 mEq/L. Consider restarting reduced dose after confirming resolution of hyperkalemia/renal insufficiency for at least 72 h. eGFR indicates estimated glomerular filtration rate; and K , potassium. Adapted from Butler et al. (200). JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary whenever possible (e.g., most antiarrhythmic drugs, most calcium channel blocking drugs [except amlodipine], nonsteroidal anti-in ammatory drugs, or thiazolidinediones) (233 244). (Level of Evidence: B) 2. Long-term use of infused positive inotropic drugs is poten- tially harmful for patients with HFrEF, except as palliation for patients with end-stage disease who cannot be stabilized with standard medical treatment (see recommendations for stage D). (Level of Evidence: C) 6.3.2.9.1. Calcium Channel Blockers CLASS III: NO BENEFIT 1. Calcium channel blocking drugs are not recommended as routine treatment for patients with HFrEF (238,245,246). (Level of Evidence: A) See Table 14 for a summary of recommendations from this section and Table 15 for strategies for achieving optimal GDMT. 6.3.3. Pharmacological Treatment for Stage C HFpEF See Table 16 for a summary of recommendations from this section. CLASS I 1. Systolic and diastolic blood pressure should be controlled in patients with HFpEF in accordance with published clinical practice guidelines to prevent morbidity (28,247). (Level of Evidence: B) 2. Diuretics should be used for relief of symptoms due to volume overload in patients with HFpEF. (Level of Evidence: C) CLASS IIa 1. Coronary revascularization is reasonable in patients with CAD in whom symptoms (angina) or demonstrable myo- cardial ischemia is judged to be having an adverse effect on symptomatic HFpEF despite GDMT. (Level of Evidence: C) 2. Management of AF according to published clinical practice guidelines in patients with HFpEF is reasonable to improve symptomatic HF. (Level of Evidence: C) 3. The use of beta-blocking agents, ACE inhibitors, and ARBs in patients with hypertension is reasonable to control blood pressure in patients with HFpEF. (Level of Evidence: C) CLASS IIb 1. The use of ARBs might be considered to decrease hospitalizations for patients with HFpEF (248). (Level of Evidence: B) CLASS III: NO BENEFIT 1. Routine use of nutritional supplements is not recommended for patients with HFpEF. (Level of Evidence: C) 6.3.4. Device Therapy for Stage C HFrEF See Table 17 for a summary of recommendations from this section. CLASS I 1. ICD therapy is recommended for primary prevention of sudden cardiac death to reduce total mortality in selected patients with nonischemic dilated cardiomyopathy or ischemic heart disease at least 40 days post-MI with LVEF of 35% or less and NYHA class II or III symptoms on chronic GDMT, who have reasonable expectation of mean- ingful survival for more than 1 yeary (148,249). (Level of Evidence: A) 2. Cardiac resynchronization therapy (CRT) is indicated for patients who have LVEF of 35% or less, sinus rhythm, left bundle-branch block (LBBB) with a QRS duration of 150 ms or greater, and NYHA class II, III, or ambulatory IV symptoms on GDMT. (Level of Evidence: A for NYHA class III/IV (37,250 252); Level of Evidence: B for NYHA class II (253,254). 3. ICD therapy is recommended for primary prevention of sudden cardiac death to reduce total mortality in selected patients at least 40 days post-MI with LVEF of 30% or less and NYHA class I symptoms while receiving GDMT, who have reasonable expectation of meaningful survival for more than 1 yeary (255 257). (Level of Evidence: B) CLASS IIa 1. CRT can be useful for patients who have LVEF of 35% or less, sinus rhythm, a non-LBBB pattern with a QRS duration of 150 ms or greater, and NYHA class III/ambulatory class IV symptoms on GDMT (250 252,254). (Level of Evidence: A) 2. CRT can be useful for patients who have LVEF of 35% or less, sinus rhythm, LBBB with a QRS duration of 120 to 149 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT (250 254,258). (Level of Evidence: B) 3. 