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date_gregorian=2025-10-23 date_hijri=1447-05-01 document_type=guide entity=format:application/pdf entity=language:ar language=en taxonomy_l1=economy_finance taxonomy_l2=insurance validity=valid validity_confidence=0.6

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY © 2022 BY THE AMERICAN HEART ASSOCIATION, INC., THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION, AND THE HEART FAILURE SOCIETY OF AMERICA. PUBLISHED BY ELSEVIER VOL. 79, NO. 17, 2022 CLINICAL PRACTICE GUIDELINE: FULL TEXT 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines Writing Committee Members Paul A. Heidenreich, MD, MS, FACC, FAHA, HFNSA, Chair† Biykem Bozkurt, MD, PhD, FACC, FAHA, FHFSA, Vice Chair† David Aguilar, MD, MSc, FAHA$ ^{\dagger} $ Larry A. Allen, MD, MHS, FACC, FAHA, HFNSA$ ^{\dagger} $ Joni J. Byun$ ^{\dagger} $ Monica M. Colvin, MD, MS, FAHA$ ^{\dagger} $ Anita Deswal, MD, MPH, FACC, FAHA, FHFSA$ ^{\dagger} $ Mark H. Drazner, MD, MSc, FACC, FAHA, FHFSA$ ^{\dagger} $ Shannon M. Dunlay, MD, MS, FAHA, HFSA$ ^{\dagger} $ Linda R. Evers, JD$ ^{\dagger} $ James C. Fang, MD, FACC, FAHA, FHFSA$ ^{\dagger} $ Savitri E. Fedson, MD, MA$ ^{\dagger} $ Gregg C. Fonarow, MD, FACC, FAHA, FHFSA$ ^{\S} $ Salim S. Hayek, MD, FACC$ ^{\dagger} $ Adrian F. Hernandez, MD, MHS‡ Prateeti Khazanie, MD, MPH, FHFSA† Michelle M. Kittleson, MD, PhD† Christopher S. Lee, PhD, RN, FAHA, FHFSA† Mark S. Link, MD† Carmelo A. Milano, MD† Lorraine C. Nnacheta, Dr.PH, MPH† Alexander T. Sandhu, MD, MS† Lynne Warner Stevenson, MD, FACC, FAHA, FHFSA† Orly Vardeny, PHARM, DS, FAHA, FHFSA|| Amanda R. Vest, MBBS, MPH, FHFSA|| Clyde W. Yancy, MD, MSc, MACC, FAHA, FHFSA† †ACC/AHA Representative. ‡ACC/AHA Joint Committee on Clinical Practice Guidelines Liaison. §ACC/AHA Task Force on Performance Measures Representative. ||HFSA Representative. Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information. This document was approved by the American College of Cardiology Clinical Policy Approval Committee, the American Heart Association Science Advisory and Coordinating Committee, the American College of Cardiology Science and Quality Committee, and the Heart Failure Society of America Executive Committee in December 2021 and the American Heart Association Executive Committee in January 2022. The American College of Cardiology requests that this document be cited as follows: Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79:e263-e421. This article has been copublished in Circulation and the Journal of Cardiac Failure. Copies: This document is available on the websites of the American College of Cardiology (www.acc.org), the American Heart Association (professional.heart.org), and the Heart Failure Society of America (www.hfsa.org). For copies of this document, please contact the Elsevier Inc. Reprint Department via fax (212-633-3820) or e-mail (reprints@elsevier.com). Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American College of Cardiology. Requests may be completed online via the Elsevier website at https://www.elsevier.com/about/policies/author-agreement/obtaining-permission. ISSN 0735-1097/$36.00 https://doi.org/10.1016/j.jacc.2021.12.012 e264 Heidenreich et al 2022 AHA/ACC/HFSA Heart Failure Guideline JACC VOL. 79, NO. 17, 2022 MAY 3, 2022:e263-e421 ACC/AHA Joint Joshua A. Beckman, MD, MS, FAHA, FACC, Committee Chair Members Patrick T. O'Gara, MD, MACC, FAHA, Immediate Past Chair Sana M. Al-Khatib, MD, MHS, FACC, FAHA Anastasia L. Armbruster, PHARMd, FACC Kim K. Birtcher, PHARMd, MS, AACC Joaquin E. Cigarroa, MD, FACC Lisa de las Fuentes, MD, MS, FAHA Anita Deswal, MD, MPH, FACC, FAHA Dave L. Dixon, PHARMd, FACC Lee A. Fleisher, MD, FACC, FAHA Federico Gentile, MD, FACC Zachary D. Goldberger, MD, FACC, FAHA Bulent Gorenek, MD, FACC Norrisa Haynes, MD, MPH Adrian F. Hernandez, MD, MHS Mark A. Hlatky, MD, FACC, FAHA José A. Joglar, MD, FACC, FAHA W. Schuyler Jones, MD, FACC Joseph E. Marine, MD, FACC Daniel B. Mark, MD, MPH, FACC, FAHA Debabrata Mukherjee, MD, FACC, FAHA Latha P. Palaniappan, MD, MS, FACC, FAHA Mariann R. Piano, RN, PhD, FAHA Tanveer Rab, MD, FACC Erica S. Spatz, MD, MS, FACC Jacqueline E. Tamis-Holland, MD, FAHA, FACC Duminda N. Wijeysundera, MD, PhD Y. Joseph Woo, MD, FACC, FAHA Former Joint Committee member; current member during the writing effort. ABSTRACT AIM The "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure" replaces the "2013 ACCF/AHA Guideline for the Management of Heart Failure" and the "2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure." The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure. METHODS A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. STRUCTURE Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses. TABLE OF CONTENTS <table><tr><td>ABSTRACT</td><td>e264</td></tr><tr><td>TOP 10 TAKE-HOME MESSAGES</td><td>e266</td></tr><tr><td>PREAMBLE</td><td>e267</td></tr><tr><td>1. INTRODUCTION</td><td>e268</td></tr><tr><td>1.1. Methodology and Evidence Review</td><td>e268</td></tr><tr><td>1.2. Organization of the Writing Committee</td><td>e268</td></tr><tr><td>1.3. Document Review and Approval</td><td>e268</td></tr></table> 1.4. Scope of the Guideline ....e268 1.5. Class of Recommendation and Level of Evidence e270 1.6. Abbreviations e271 2. DEFINITION OF HF e272 2.1. Stages of HF e272 2.2. Classification of HF by Left Ventricular Ejection Fraction (LVEF) e275 JACC VOL. 79, NO. 17, 2022 MAY 3, 2022:e263-e421 Heidenreich et al 2022 AHA/ACC/HFSA Heart Failure Guideline e265 2.3. Diagnostic Algorithm for Classification of HF According to LVEF e277 3. EPIDEMIOLOGY AND CAUSES OF HF e278 3.1. Epidemiology of HF e278 3.2. Cause of HF e279 4. INITIAL AND SERIAL EVALUATION e279 4.1. Clinical Assessment: History and Physical Examination e279 4.1.1. Initial Laboratory and Electrocardiographic Testing e281 4.2. Use of Biomarkers for Prevention, Initial Diagnosis, and Risk Stratification e282 4.3. Genetic Evaluation and Testing e284 4.4. Evaluation With Cardiac Imaging e285 4.5. Invasive Evaluation e288 4.6. Wearables and Remote Monitoring (Including Telemonitoring and Device Monitoring) ..... e289 4.7. Exercise and Functional Capacity Testing e290 4.8. Initial and Serial Evaluation: Clinical Assessment: HF Risk Scoring e291 5. STAGE A (PATIENTS AT RISK FOR HF) e292 5.1. Patients at Risk for HF (Stage A: Primary Prevention) e292 6. STAGE B (PATIENTS WITH PRE-HF) e295 6.1. Management of Stage B: Preventing the Syndrome of Clinical HF in Patients With Pre-HF e295 7. STAGE C HF e297 7.1. Nonpharmacological Interventions e297 7.1.1. Self-Care Support in HF e297 7.1.2. Dietary Sodium Restriction e299 7.1.3. Management of Stage C HF: Activity, Exercise Prescription, and Cardiac Rehabilitation e300 7.2. Diuretics and Decongestion Strategies in Patients With HF e301 7.3. Pharmacological Treatment for HFrEF e302 7.3.1. Renin-Angiotensin System Inhibition With ACEi or ARB or ARNi e302 7.3.2. Beta Blockers e305 7.3.3. Mineralocorticoid Receptor Antagonists (MRAs) e306 7.3.4. Sodium-Glucose Cotransporter 2 Inhibitors e307 7.3.5. Hydralazine and Isosorbide Dinitrate . . e308 7.3.6. Other Drug Treatment e310 7.3.7. Drugs of Unproven Value or That May Worsen HF e311 7.3.8. GDMT Dosing: Sequencing and Uptitration e313 7.3.9. Additional Medical Therapies e316 7.3.9.1. Management of Stage C HF: Ivabradine e316 7.3.9.2. Pharmacological Treatment for Stage C HFrEF: Digoxin e316 7.3.9.3. Pharmacological Treatment for Stage C HFrEF: Soluble Guanylyl Cyclase Stimulators e317 7.4. Device and Interventional Therapies for HFrEF e318 7.4.1. ICDs and CRTs e318 7.4.2. Other Implantable Electrical Interventions e322 7.4.3. Revascularization for CAD e323 7.5. Valvular Heart Disease e324 7.6. Heart Failure With Mildly Reduced EF (HFmrEF) and Improved EF (HFimpHF) e326 7.6.1. HF With Mildly Reduced Ejection Fraction e326 7.6.2. HF With Improved Ejection Fraction e327 7.7. Preserved EF (HFpEF) e328 7.7.1. HF With Preserved Ejection Fraction e328 7.8. Cardiac Amyloidosis e331 7.8.1. Diagnosis of Cardiac Amyloidosis e331 7.8.2. Treatment of Cardiac Amyloidosis e332 8. STAGE D (ADVANCED) HF e334 8.1. Specialty Referral for Advanced HF e334 8.2. Nonpharmacological Management: Advanced HF e337 8.3. Inotropic Support e337 8.4. Mechanical Circulatory Support e339 8.5. Cardiac Transplantation e340 9. PATIENTS HOSPITALIZED WITH ACUTE DECOMPENSATED HF e341 9.1. Assessment of Patients Hospitalized With Decompensated HF e341 9.2. Maintenance or Optimization of GDMT During Hospitalization e342 9.3. Diuretics in Hospitalized Patients: Decongestion Strategy e344 e266 Heidenreich et al 2022 AHA/ACC/HFSA Heart Failure Guideline JACC VOL. 79, NO. 17, 2022 MAY 3, 2022:e263-e421 9.4a. Parenteral Vasodilation Therapy in Patients Hospitalized With HF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e345 9.4b. VTE Prophylaxis in Hospitalized Patients ... e346 9.5. Evaluation and Management of Cardiogenic Shock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e346 9.6. Integration of Care: Transsitions and Team-Based Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10. COMORBIDITIES IN PATIENTS WITH HF . . e351 10.1. Management of Comorbidities in Patients With HF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e351 10.2. Management of AF in HF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e354 11. SPECIAL POPULATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e356 11.1. Disparities and Vulnerable Populations . . . . e356 11.2. Cardio-Oncology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e358 11.3. HF and Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e360 12. QUALITY METRICS AND REPORTING . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.1. Performance Measurement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e363 13. GOALS OF CARE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.1. Palliative and Supportive Care, Shared Decision-Making, and End-of-Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e364 14. RECOMMENDATION FOR PATIENT-REPORTED OUTCOMES AND EVIDENCE GAPS AND FUTURE RESEARCH DIRECTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e367 14.1. Patient-Reported Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.2. Evidence Gaps and Future Research Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e370 REFERENCES e371 APPENDIX 1 Author Relationships With Industry and Other Entities (Relevant) e411 APPENDIX 2 Reviewer Relationships With Industry and Other Entities (Comprehensive) e414 APPENDIX 3 Appendix for Tables 3 and 4: Suggested Thresholds for Structural Heart Disease and Evidence of Increased Filling Pressures e421 TOP 10 TAKE-HOME MESSAGES 1. Guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (HFrEF) now includes 4 medication classes that include sodium-glucose cotransporter-2 inhibitors (SGLT2i). 2. SGLT2i have a Class of Recommendation 2a in HF with mildly reduced ejection fraction (HFmrEF). Weaker recommendations (Class of Recommendation 2b) are made for ARNi, ACEi, ARB, MRA, and beta blockers in this population. 3. New recommendations for HFpEF are made for SGLT2i (Class of Recommendation 2a), MRAs (Class of Recommendation 2b), and ARNi (Class of Recommendation 2b). Several prior recommendations have been renewed including treatment of hypertension (Class of Recommendation 1), treatment of atrial fibrillation (Class of Recommendation 2a), use of ARBs (Class of Recommendation 2b), and avoidance of routine use of nitrates or phosphodiesterase-5 inhibitors (Class of Recommendation 3: No Benefit). 4. Improved LVEF is used to refer to those patients with previous HFrEF who now have an LVEF >40%. These patients should continue their HFrEF treatment. 5. Value statements were created for select recommendations where high-quality, cost-effectiveness studies of the intervention have been published. 6. Amyloid heart disease has new recommendations for treatment including screening for serum and urine monoclonal light chains, bone scintigraphy, genetic sequencing, tetramer stabilizer therapy, and anticoagulation. 7. Evidence supporting increased filling pressures is important for the diagnosis of HF if the LVEF is >40%. Evidence for increased filling pressures can be obtained from noninvasive (e.g., natriuretic peptide, diastolic function on imaging) or invasive testing (e.g., hemodynamic measurement). 8. Patients with advanced HF who wish to prolong survival should be referred to a team specializing in HF. A HF specialty team reviews HF management, assesses suitability for advanced HF therapies, and uses palliative care including palliative inotropes where consistent with the patient's goals of care. 9. Primary prevention is important for those at risk for HF (stage A) or pre-HF (stage B). Stages of HF were revised to emphasize the new terminologies of “at risk” for HF for stage A and pre-HF for stage B. 10. Recommendations are provided for select patients with HF and iron deficiency, anemia, hypertension, sleep disorders, type 2 diabetes, atrial fibrillation, coronary artery disease, and malignancy. JACC VOL. 79, NO. 17, 2022 MAY 3, 2022:e263-e421 Heidenreich et al 2022 AHA/ACC/HFSA Heart Failure Guideline e267 PREAMBLE Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines with recommendations to improve cardiovascular health. These guidelines, which are based on systematic methods to evaluate and classify evidence, provide a foundation for the delivery of quality cardiovascular care. The ACC and AHA sponsor the development and publication of clinical practice guidelines without commercial support, and members volunteer their time to the writing and review efforts. Guidelines are official policy of the ACC and AHA. For some guidelines, the ACC and AHA partner with other organizations. Intended Use Clinical practice guidelines provide recommendations applicable to patients with or at risk of developing cardiovascular disease (CVD). The focus is on medical practice in the United States, but these guidelines are relevant to patients throughout the world. Although guidelines may be used to inform regulatory or payer decisions, the intent is to improve quality of care and align with patients' interests. Guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances and should not replace clinical judgment. Clinical Implementation Management, in accordance with guideline recommendations, is effective only when followed by both practitioners and patients. Adherence to recommendations can be enhanced by shared decision-making between clinicians and patients, with patient engagement in selecting interventions on the basis of individual values, preferences, and associated conditions and comorbidities. Methodology and Modernization The ACC/AHA Joint Committee on Clinical Practice Guidelines (Joint Committee) continuously reviews, updates, and modifies guideline methodology on the basis of published standards from organizations, including the National Academy of Medicine (formerly, the Institute of Medicine) (1,2), and on the basis of internal reevaluation. Similarly, presentation and delivery of guidelines are reevaluated and modified in response to evolving technologies and other factors to optimally facilitate dissemination of information to health care professionals at the point of care. Numerous modifications to the guidelines have been implemented to make them shorter and enhance “user friendliness.” Guidelines are written and presented in a modular, “knowledge chunk” format in which each chunk includes a table of recommendations, a brief synopsis, recommendation-specific supportive text and, when appropriate, flow diagrams or additional tables. Hyperlinked references are provided for each modular knowledge chunk to facilitate quick access and review. In recognition of the importance of cost-value considerations, in certain guidelines, when appropriate and feasible, an assessment of value for a drug, device, or intervention may be performed in accordance with the ACC/AHA methodology (3). To ensure that guideline recommendations remain current, new data will be reviewed on an ongoing basis by the writing committee and staff. Going forward, targeted sections/knowledge chunks will be revised dynamically after publication and timely peer review of potentially practice-changing science. The previous designations of “full revision” and “focused update” will be phased out. For additional information and policies on guideline development, readers may consult the ACC/AHA guideline methodology manual (4) and other methodology articles (5-7). Selection of Writing Committee Members The Joint Committee strives to ensure that the guideline writing committee contains requisite content expertise and is representative of the broader cardiovascular community by selection of experts across a spectrum of backgrounds, representing different geographic regions, sexes, races, ethnicities, intellectual perspectives/biases, and clinical practice settings. Organizations and professional societies with related interests and expertise are invited to participate as partners or collaborators. Relationships With Industry and Other Entities The ACC and AHA have rigorous policies and methods to ensure that documents are developed without bias or improper influence. The complete policy on relationships with industry and other entities (RWI) can be found online. Appendix 1 of the guideline lists writing committee members' relevant RWI; for the purposes of full transparency, their comprehensive disclosure information is available in a Supplemental Appendix. Comprehensive disclosure information for the Joint Committee is also available online. Evidence Review and Evidence Review Committees In developing recommendations, the writing committee uses evidence-based methodologies that are based on all available data (4,5). Literature searches focus on randomized controlled trials (RCTs) but also include registries, nonrandomized comparative and descriptive studies, case series, cohort studies, systematic reviews, and expert opinion. Only key references are cited. An independent evidence review committee is commissioned when there are $ \geq $ 1 questions deemed of e268 Heidenreich et al 2022 AHA/ACC/HFSA Heart Failure Guideline JACC VOL. 79, NO. 17, 2022 MAY 3, 2022:e263-e421 utmost clinical importance and merit formal systematic review to determine which patients are most likely to benefit from a drug, device, or treatment strategy, and to what degree. Criteria for commissioning an evidence review committee and formal systematic review include absence of a current authoritative systematic review, feasibility of defining the benefit and risk in a time frame consistent with the writing of a guideline, relevance to a substantial number of patients, and likelihood that the findings can be translated into actionable recommendations. Evidence review committee members may include methodologists, epidemiologists, clinicians, and bio-statisticians. Recommendations developed by the writing committee on the basis of the systematic review are marked “SR.” Guideline-Directed Medical Therapy The term guideline-directed medical therapy (GDMT) encompasses clinical evaluation, diagnostic testing, and both pharmacological and procedural treatments. For these and all recommended drug treatment regimens, the reader should confirm dosage with product insert material and evaluate for contraindications and interactions. Recommendations are limited to drugs, devices, and treatments approved for clinical use in the United States. Joshua A. Beckman, MD, MS, FAHA, FACC Chair, ACC/AHA Joint Committee on Clinical Practice Guidelines 1. INTRODUCTION 1.1. Methodology and Evidence Review The recommendations listed in this guideline are, whenever possible, evidence based. An initial extensive evidence review, which included literature derived from research involving human subjects, published in English, and indexed in MEDLINE (through PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline, was conducted from May 2020 to December 2020. Key search words included but were not limited to the following: heart failure; heart failure with reduced ejection fraction; heart failure with preserved ejection fraction; heart failure with mildly reduced ejection fraction; systolic heart failure; heart failure rehabilitation; cardiac failure; chronic heart failure; acute decompensated heart failure; cardiogenic shock; beta blockers; mineralocorticoid receptor antagonists; ACE-inhibitors, angiotensin and neprilysin receptor antagonist; sacubitril valsartan; angiotensin receptor antagonist; Sodium glucose co-transporter 2 or SGLT2 inhibitors; cardiac amyloidosis; atrial fibrillation; congestive heart failure; guideline-directed medical therapy; HFrEF; diabetes mellitus; cardiomyopathy; cardiac amyloidosis; valvular heart disease; mitral regurgitation; cardiomyopathy in pregnancy; reduced ejection fraction; right heart pressure; palliative care. Additional relevant studies, published through September 2021 during the guideline writing process, were also considered by the writing committee and added to the evidence tables when appropriate. This guideline was harmonized with other ACC/AHA guidelines published through December 2021. The final evidence tables are included in the Online Data Supplement and summarize the evidence used by the writing committee to formulate recommendations. References selected and published in the present document are representative and not all-inclusive. 1.2. Organization of the Writing Committee The writing committee consisted of cardiologists, HF specialists, internists, interventionalists, an electrophysiologist, surgeons, a pharmacist, an advanced nurse practitioner, and 2 lay/patient representatives. The writing committee included representatives from the ACC, AHA, and Heart Failure Society of America (HFSA). Appendix 1 of the present document lists writing committee members' relevant RWI. For the purposes of full transparency, the writing committee members' comprehensive disclosure information is available in a Supplemental Appendix. 1.3. Document Review and Approval This document was reviewed by 2 official reviewers nominated by the AHA; 1 official reviewer nominated by the ACC; 2 official reviewers from the HFSA; 1 official Joint Committee on Clinical Practice Guidelines reviewer; and 32 individual content reviewers. Reviewers' RWI information was distributed to the writing committee and is published in this document (Appendix 2). This document was approved for publication by the governing bodies of the ACC, AHA, and HFSA. 1.4. Scope of the Guideline The purpose of the “2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure” (2022 HF guideline) is to provide an update and to consolidate the “2013 ACCF/AHA Guideline for the Management of Heart Failure” (1) for adults and the “2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure” (2) into a new document. Related ACC/AHA guidelines include recommendations relevant to HF and, in such cases, the HF guideline refers to these documents. For example, the 2019 primary prevention of cardiovascular disease guideline (3) includes JACC VOL. 79, NO. 17, 2022 MAY 3, 2022:e263-e421 Heidenreich et al 2022 AHA/ACC/HFSA Heart Failure Guideline e269 recommendations that will be useful in preventing HF, and the 2021 valvular heart disease guideline (4) provides recommendations for mitral valve (MV) clipping in mitral regurgitation (MR). Areas of focus include: ■ Prevention of HF. ■ Management strategies in stage C HF, including: ■ New treatment strategies in HF, including sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitors (ARNi). ■ Management of HF and atrial fibrillation (AF), including ablation of AF. ■ Management of HF and secondary MR, including MV transcatheter edge-to-edge repair. ■ Specific management strategies, including: Cardiac amyloidosis. Cardio-oncology. ■ Implantable devices. ■ Left ventricular assist device (LVAD) use in stage D HF. The intended primary target audience consists of clinicians who are involved in the care of patients with HF. Recommendations are stated in reference to the patients and their condition. The focus is to provide the most up-to-date evidence to inform the clinician during shared decision-making with the patient. Although the present document is not intended to be a procedural-based manual of recommendations that outlines the best practice for HF, there are certain practices that clinicians might use that are associated with improved clinical outcomes. In developing the 2022 HF guideline, the writing committee reviewed previously published guidelines and related statements. Table 1 contains a list of these guidelines and statements deemed pertinent to this writing effort and is intended for use as a resource, thus obviating the need to repeat existing guideline recommendations. TABLE 1 Associated Guidelines and Statements <table><tr><td>Title</td><td>Organization</td><td>Publication Year (Reference)</td></tr><tr><td colspan="3">Guidelines</td></tr><tr><td>2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery</td><td>ACCF/AHA</td><td>2011 (6)</td></tr><tr><td colspan="3">■ Hills et al., "2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery" is now replaced and retired by the "2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization" (5)</td></tr><tr><td>2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention</td><td>ACCF/AHA/SCAI</td><td>2011 (7)</td></tr><tr><td colspan="3">■ Levine et al., "2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention," is now replaced and retired by the "2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization"(5)</td></tr><tr><td>2015 ACCF/AHA/SCAI Focused Update Guideline for Percutaneous Coronary Intervention</td><td>ACCF/AHA/SCAI</td><td>2016 (8)</td></tr><tr><td>2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease</td><td>ACC/AHA</td><td>2021 (4)</td></tr><tr><td>2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy</td><td>ACC/AHA</td><td>2020 (9)</td></tr><tr><td>2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease</td><td>ACC/AHA</td><td>2019 (3)</td></tr><tr><td>2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation</td><td>AHA/ACC/HRS</td><td>2019 (10)</td></tr><tr><td>2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults</td><td>ACC/AHA/AAPA/ABC/ACPM/AGS/AphA/ASH/ASPC/NMA/PCNA</td><td>2018 (11)</td></tr><tr><td>2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure</td><td>ACC/AHA/HFSA</td><td>2017 (2)</td></tr><tr><td>2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure</td><td>ACC/AHA/HFSA</td><td>2016 (12)</td></tr><tr><td>2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease</td><td>ACC/AHA/AATS/PCNA/SCAI/STS</td><td>2014 (13)*</td></tr><tr><td>2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk</td><td>AHA/ACC</td><td>2014 (14)</td></tr><tr><td>2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults</td><td>AHA/ACC/TOS</td><td>2014 (15)</td></tr><tr><td>2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/AphA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol</td><td>AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/AphA/ASPC/NLA/PCNA</td><td>2019 (16)</td></tr><tr><td>2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults</td><td>ACC/AHA</td><td>2014 (17)</td></tr><tr><td>2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk</td><td>ACC/AHA</td><td>2014 (18)</td></tr><tr><td>2013 ACCF/AHA Guideline for the Management of Heart Failure</td><td>ACCF/AHA</td><td>2013 (1)</td></tr><tr><td>2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction</td><td>ACCF/AHA</td><td>2013 (19)</td></tr></table> Continued on the next page e270 Heidenreich et al 2022 AHA/ACC/HFSA Heart Failure Guideline JACC VOL. 79, NO. 17, 2022 MAY 3, 2022:e263-e421 TABLE 1 Continued <table><tr><td>Title</td><td>Organization</td><td>Publication Year (Reference)</td></tr><tr><td>2012 ACCF/AHA/HRS Focused Update of the 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities</td><td>ACCF/AHA/HRS</td><td>2012 (20)</td></tr><tr><td>2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease</td><td>ACCF/AHA/ACP/AATS/PCNA/SCAI/STS</td><td>2012 (21)</td></tr><tr><td>Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women-2011 Update</td><td>AHA</td><td>2011 (22)</td></tr><tr><td>AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update</td><td>AHA/ACCF</td><td>2011 (23)</td></tr><tr><td>2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults</td><td>ACCF/AHA</td><td>2010 (24)</td></tr><tr><td>Part 9: Post-Cardiac Arrest Care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care</td><td>AHA</td><td>2010 (25)</td></tr><tr><td>Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure</td><td>NHLBI</td><td>2003 (26)</td></tr><tr><td colspan="3">Statements</td></tr><tr><td>Cardiac Amyloidosis: Evolving Diagnosis and Management</td><td>AHA</td><td>2020 (27)</td></tr><tr><td>Testing of Low-Risk Patients Presenting to the Emergency Department With Chest Pain</td><td>AHA</td><td>2010 (28)</td></tr><tr><td>Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus</td><td>AHA/ADA</td><td>2007 (29)</td></tr><tr><td>Prevention and Control of Influenza</td><td>CDC</td><td>2005 (30)</td></tr></table> *The full SIHD guideline is from 2012 (21). A focused update was published in 2014 (13). AATS indicates American Association for Thoracic Surgery; AACVPR, American Association of Cardiovascular and Pulmonary Rehabilitation; AAPA, American Association Academy of Physician Assistants; ABC, Association of Black Cardiologists; ACC, American College of Cardiology; ACCF, American College of Cardiology Foundation; ACPM, American College of Preventive Medicine; ADA, American Diabetes Association; AGS, American Geriatrics Society; AHA, American Heart Association; AphA, American Pharmacists Association; ASH, American Society of Hypertension; ASPC, American Society for Preventive Cardiology; CDC, Centers for Disease Control and Prevention; ESC, European Society of Cardiology; HFSA, Heart Failure Society of America; HRS, Heart Rhythm Society; NHLBI, National Heart, Lung, and Blood Institute; NICE, National Institute for Health and Care Excellence; NMA, National Medical Association; NLA, National Lipid Association; PCNA, Preventive Cardiovascular Nurses Association; SCAI, Society for Cardiovascular Angiography and Interventions; SIHD, stable ischemic heart disease; STS, Society of Thoracic Surgeons; TOS, The Obesity Society; and WHF, World Heart Federation. 1.5. Class of Recommendation and Level of Evidence The Class of Recommendation (COR) indicates the strength of recommendation, encompassing the estimated magnitude and certainty of benefit in proportion to risk. The Level of Evidence (LOE) rates the quality of scientific evidence supporting the intervention on the basis of the type, quantity, and consistency of data from clinical trials and other sources (Table 2) (1). JACC VOL. 79, NO. 17, 2022 MAY 3, 2022:e263-e421 Heidenreich et al 2022 AHA/ACC/HFSA Heart Failure Guideline e271 TABLE 2 Applying American College of Cardiology/American Heart Association Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care (Updated May 2019)* <table><tr><td colspan="2">CLASS (STRENGTH) OF RECOMMENDATION</td></tr><tr><td>CLASS 1 (STRONG)</td><td>Benefit >>> Risk</td></tr><tr><td colspan="2">Suggested phrases for writing recommendations:Is recommendedIs indicated/useful/effective/beneficialShould be performed/administered/otherComparative-Effectiveness Phrases†:- Treatment/strategy A is recommended/indicated in preference to treatment B-Treatment A should be chosen over treatment B</td></tr></table> <table><tr><td>CLASS 2a (MODERATE)</td><td>Benefit >> Risk</td></tr><tr><td colspan="2">Suggested phrases for writing recommendations:Is reasonableCan be useful/effective/beneficialComparative-Effectiveness Phrases†:- Treatment/strategy A is probably recommended/indicated in preference to treatment B- It is reasonable to choose treatment A over treatment B</td></tr></table> <table><tr><td>CLASS 2b (WEAK)</td><td>Benefit ≥ Risk</td></tr><tr><td colspan="2">Suggested phrases for writing recommendations:May/might be reasonableMay/might be consideredUsefulness/effectiveness is unknown/Unclear/uncertain or not well-established</td></tr></table> <table><tr><td>CLASS 3: No Benefit (MODERATE)(Generally, LOE A or B use only)</td><td>Benefit = Risk</td></tr><tr><td colspan="2">Suggested phrases for writing recommendations:Is not recommendedIs not indicated/useful/effective/beneficialShould not be performed/administered/other</td></tr></table> <table><tr><td>Class 3: Harm (STRONG)</td><td>Risk > Benefit</td></tr><tr><td colspan="2">Suggested phrases for writing recommendations:Potentially harmfulCauses harmAssociated with excess morbidity/mortalityShould not be performed/administered/other</td></tr></table> LEVEL (QUALITY) OF EVIDENCE‡ <table><tr><td>LEVEL A</td></tr><tr><td>• High-quality evidence‡, from more than 1 RCT• Meta-analyses of high-quality RCTs• One or more RCTs corroborated by high-quality registry studies</td></tr></table> <table><tr><td>LEVEL B-R</td><td>(Randomized)</td></tr><tr><td>• Moderate-quality evidence‡ from 1 or more RCTs• Meta-analyses of moderate-quality RCTs</td><td></td></tr></table> <table><tr><td>LEVEL B-NR</td><td>(Nonrandomized)</td></tr><tr><td>• Moderate-quality evidence‡ from 1 or more well-designed, well-executed nonrandomized studies, observational studies, or registry studies• Meta-analyses of such studies</td><td></td></tr></table> <table><tr><td>LEVEL C-LD</td><td>(Limited Data)</td></tr><tr><td colspan="2">• Randomized or nonrandomized observational or registry studies with limitations of design or execution• Meta-analyses of such studies• Physiological or mechanistic studies in human subjects</td></tr></table> <table><tr><td>LEVEL C-E0</td><td>(Expert Opinion)</td></tr><tr><td colspan="2">• Consensus of expert opinion based on clinical experience</td></tr></table> COR and LOE are determined independently (any COR may be paired with any LOE). A recommendation with LOE C does not imply that the recommendation is weak. Many important clinical questions addressed in guidelines do not lend themselves to clinical trials. Although RCTs are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective. * The outcome or result of the intervention should be specified (an improved clinical outcome or increased diagnostic accuracy or incremental prognostic information). For comparative-effectiveness recommendations (COR 1 and 2a; LOE A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated. The method of assessing quality is evolving, including the application of standardized, widely-used, and preferably validated evidence grading tools; and for systematic reviews, the incorporation of an Evidence Review Committee. COR indicates Class of Recommendation; E0, expert opinion; LD, limited data; LOE, Level of Evidence; NR, nonrandomized; R, randomized; and RCT, randomized controlled trial. 1.6. Abbreviations <table><tr><td>Abbreviation</td><td>Meaning/Phrase</td></tr><tr><td>ACEi</td><td>angiotensin-converting enzyme inhibitors</td></tr><tr><td>ACS</td><td>acute coronary syndrome</td></tr><tr><td>ARNi</td><td>angiotensin receptor-neprilysin inhibitors</td></tr><tr><td>ARB</td><td>angiotensin (II) receptor blockers</td></tr><tr><td>AF</td><td>atrial fibrillation</td></tr><tr><td>AL-CM</td><td>immunoglobulin light chain amyloid cardiomyopathy</td></tr><tr><td>ATTR-CM</td><td>transthyretin amyloid cardiomyopathy</td></tr><tr><td>ATTRv</td><td>variant transthyretin amyloidosis</td></tr><tr><td>ATTRwt</td><td>wild-type transthyretin amyloidosis</td></tr><tr><td>BNP</td><td>B-type natriuretic peptide</td></tr><tr><td>CABG</td><td>coronary artery bypass graft</td></tr><tr><td>CAD</td><td>coronary artery disease</td></tr><tr><td>CCM</td><td>cardiac contractility modulation</td></tr></table> Continued in the next column <table><tr><td>Abbreviation</td><td>Meaning/Phrase</td></tr><tr><td>CHF</td><td>congestive heart failure</td></tr><tr><td>CKD</td><td>chronic kidney disease</td></tr><tr><td>CMR</td><td>cardiovascular magnetic resonance</td></tr><tr><td>COVID-19</td><td>coronavirus disease 2019</td></tr><tr><td>CPET</td><td>cardiopulmonary exercise test</td></tr><tr><td>CRT</td><td>cardiac resynchronization therapy</td></tr><tr><td>CRT-D</td><td>cardiac resynchronization therapy with defibrillation</td></tr><tr><td>CRT-P</td><td>cardiac resynchronization therapy with pacemaker</td></tr><tr><td>CT</td><td>computed tomography</td></tr><tr><td>CVD</td><td>cardiovascular disease</td></tr><tr><td>CVP</td><td>central venous pressure</td></tr><tr><td>DOAC</td><td>direct-acting oral anticoagulants</td></tr><tr><td>DPP-4</td><td>dipeptidyl peptidase-4</td></tr></table> Continued on the next page e272 Heidenreich et al 2022 AHA/ACC/HFSA Heart Failure Guideline JACC VOL. 79, NO. 17, 2022 MAY 3, 2022:e263-e421 <table><tr><td>Abbreviation</td><td>Meaning/Phrase</td></tr><tr><td>ECG</td><td>electrocardiogram</td></tr><tr><td>EF</td><td>ejection fraction</td></tr><tr><td>eGFR</td><td>estimated glomerular filtration rate</td></tr><tr><td>FDA</td><td>U.S. Food and Drug Administration</td></tr><tr><td>FLC</td><td>free light chain</td></tr><tr><td>GDMT</td><td>guideline-directed medical therapy</td></tr><tr><td>HF</td><td>heart failure</td></tr><tr><td>HFimpEF</td><td>heart failure with improved ejection fraction</td></tr><tr><td>HFmrEF</td><td>heart failure with mildly reduced ejection fraction</td></tr><tr><td>HFpEF</td><td>heart failure with preserved ejection fraction</td></tr><tr><td>HFrEF</td><td>heart failure with reduced ejection fraction</td></tr><tr><td>ICD</td><td>implantable cardioverter-defibrillator</td></tr><tr><td>IFE</td><td>immunofixation electrophoresis</td></tr><tr><td>LBBB</td><td>left bundle branch block</td></tr><tr><td>LV</td><td>left ventricular</td></tr><tr><td>LVAD</td><td>left ventricular assist device</td></tr><tr><td>LVEDV</td><td>left ventricular end-diastolic volume</td></tr><tr><td>LVEF</td><td>left ventricular ejection fraction</td></tr><tr><td>LVH</td><td>left ventricular hypertrophy</td></tr><tr><td>MCS</td><td>mechanical circulatory support</td></tr><tr><td>MI</td><td>myocardial infarction</td></tr><tr><td>MR</td><td>mitral regurgitation</td></tr><tr><td>MRA</td><td>mineralocorticoid receptor antagonist</td></tr><tr><td>MV</td><td>mitral valve</td></tr><tr><td>NSAID</td><td>nonsteroidal anti-inflammatory drug</td></tr><tr><td>NSVT</td><td>nonsustained ventricular tachycardia</td></tr><tr><td>NT-proBNP</td><td>N-terminal prohormone of B-type natriuretic peptide</td></tr><tr><td>NYHA</td><td>New York Heart Association</td></tr><tr><td>QALY</td><td>quality-adjusted life year</td></tr><tr><td>QOL</td><td>quality of life</td></tr><tr><td>PA</td><td>pulmonary artery</td></tr><tr><td>PCWP</td><td>pulmonary capillary wedge pressure</td></tr><tr><td>PET</td><td>positron emission tomography</td></tr><tr><td>PPAR-$ \gamma $</td><td>peroxisome proliferator-activated receptor gamma</td></tr><tr><td>PUFA</td><td>polyunsaturated fatty acid</td></tr><tr><td>RA</td><td>right atrial</td></tr><tr><td>RASS</td><td>renin-angiotensin-aldosterone system</td></tr><tr><td>RAASi</td><td>renin-angiotensin-aldosterone system inhibitors</td></tr><tr><td>RCT</td><td>randomized controlled trial</td></tr><tr><td>RV</td><td>right ventricular</td></tr><tr><td>SCD</td><td>sudden cardiac death</td></tr></table> Continued in the next column <table><tr><td>Abbreviation</td><td>Meaning/Phrase</td></tr><tr><td>SGLT2i</td><td>sodium-glucose cotransporter-2 inhibitors</td></tr><tr><td>SPECT</td><td>single photon emission CT</td></tr><tr><td>$ ^{99m}Tc-PYP $</td><td>technetium pyrophosphate</td></tr><tr><td>TEER</td><td>transcatheter mitral edge-to-edge repair</td></tr><tr><td>TTE</td><td>transthoracic echocardiogram</td></tr><tr><td>VA</td><td>ventricular arrhythmia</td></tr><tr><td>VF</td><td>ventricular fibrillation</td></tr><tr><td>VHD</td><td>valvular heart disease</td></tr><tr><td>$ VO_2 $</td><td>oxygen consumption/oxygen uptake</td></tr><tr><td>VT</td><td>ventricular tachycardia</td></tr></table> 2. DEFINITION OF HF HF Description HF is a complex clinical syndrome with symptoms and signs that result from any structural or functional impairment of ventricular filling or ejection of blood. The writing committee recognizes that asymptomatic stages with structural heart disease or cardiomyopathies are not covered under the above definition as having HF. Such asymptomatic stages are considered at-risk for HF (stage A) or pre-HF (stage B), as explained in Section 2.1, “Stages of HF”. 2.1. Stages of HF The ACC/AHA stages of HF (Figure 1, Table 3) emphasize the development and progression of disease (1,2), and advanced stages and progression are associated with reduced survival (3). Therapeutic interventions in each stage aim to modify risk factors (stage A), treat risk and structural heart disease to prevent HF (stage B), and reduce symptoms, morbidity, and mortality (stages C and D). To address the evolving role of biomarkers and structural changes for recognition of patients who are at risk of developing HF, who are potential candidates for targeted treatment strategies for the prevention of HF, and to enhance the understanding and adoption of these classifications, the writing committee proposed the terminologies listed in Table 3 for the stages of HF. For thresholds of cardiac structural, functional changes, elevated filling pressures, and biomarker elevations, refer to Appendix 3. JACC VOL. 79, NO. 17, 2022 MAY 3, 2022:e263-e421 Heidenreich et al 2022 AHA/ACC/HFSA Heart Failure Guideline e273 TABLE 3 Stages of HF <table><tr><td>Stages</td><td>Definition and Criteria</td></tr><tr><td>Stage A: At Risk for HF</td><td>At risk for HF but without symptoms, structural heart disease, or cardiac biomarkers of stretch or injury (e.g., patients with hypertension, atherosclerotic CVD, diabetes, metabolic syndrome and obesity, exposure to cardiotoxic agents, genetic variant for cardiomyopathy, or positive family history of cardiomyopathy).</td></tr><tr><td>Stage B: Pre-HF</td><td>No symptoms or signs of HF and evidence of 1 of the following:</td></tr><tr><td></td><td>Structural heart disease*</td></tr><tr><td></td><td>■ Reduced left or right ventricular systolic function</td></tr><tr><td></td><td>■ Reduced ejection fraction, reduced strain</td></tr><tr><td></td><td>■ Ventricular hypertrophy</td></tr><tr><td></td><td>■ Chamber enlargement</td></tr><tr><td></td><td>■ Wall motion abnormalities</td></tr><tr><td></td><td>■ Valvular heart disease</td></tr><tr><td></td><td>Evidence for increased filling pressures*</td></tr><tr><td></td><td>■ By invasive hemodynamic measurements</td></tr><tr><td></td><td>■ By noninvasive imaging suggesting elevated filling pressures (e.g., Doppler echocardiography)</td></tr><tr><td></td><td>Patients with risk factors and</td></tr><tr><td></td><td>■ Increased levels of BNPs* or</td></tr><tr><td></td><td>■ Persistently elevated cardiac troponin</td></tr><tr><td></td><td>in the absence of competing diagnoses resulting in such biomarker elevations such as acute coronary syndrome, CKD, pulmonary embolus, or myopericarditis</td></tr><tr><td>Stage C: Symptomatic HF</td><td>Structural heart disease with current or previous symptoms of HF.</td></tr><tr><td>Stage D: Advanced HF</td><td>Marked HF symptoms that interfere with daily life and with recurrent hospitalizations despite attempts to optimize GDMT.</td></tr></table> *For thresholds of cardiac structural, functional changes, elevated filling pressures, and biomarker elevations, refer to Appendix 3. BNP indicates B-type natriuretic peptide; CKD, chronic kidney disease; CVD, cardiovascular disease; GDMT, guideline-directed medical therapy; and HF, heart failure. New York Heart Association (NYHA) Classification The NYHA classification is used to characterize symptoms and functional capacity of patients with symptomatic (stage C) HF or advanced HF (stage D). It is a subjective assessment by a clinician and can change over time. Although reproducibility and validity can be limited (4,5), the NYHA functional classification is an independent predictor of mortality (6,7), and it is widely used in clinical practice to determine the eligibility of patients for treatment strategies. Clinicians specify NYHA classification at baseline after the initial diagnosis and after treatment through the continuum of care of a patient with HF. Although a patient with symptomatic HF (stage C) may become asymptomatic with treatment (NYHA class I), that patient will still be categorized as stage C HF. Patients with stage C HF can be classified according to the trajectory of their symptoms (Figure 2). e274 Heidenreich et al 2022 AHA/ACC/HFSA Heart Failure Guideline JACC VOL. 79, NO. 17, 2022 MAY 3, 2022:e263-e421 FIGURE 1 ACC/AHA Stages of HF The ACC/AHA stages of HF are shown. ACC indicates American College of Cardiology; AHA, American Heart Association; CVD, cardiovascular disease; GDMT, guideline-directed medical therapy; and HF, heart failure. FIGURE 2 Trajectory of Stage C HF The trajectory of stage C HF is displayed. Patients whose symptoms and signs of HF are resolved are still stage C and should be treated accordingly. If all HF symptoms, signs, and structural abnormalities resolve, the patient is considered to have HF in remission. HF indicates heart failure; and LV, left ventricular. *Full resolution of structural and functional cardiac abnormalities is uncommon. JACC VOL. 79, NO. 17, 2022 MAY 3, 2022:e263-e421 Heidenreich et al 2022 AHA/ACC/HFSA Heart Failure Guideline e275 2.2. Classification of HF by Left Ventricular Ejection Fraction (LVEF) LVEF is considered important in the classification of patients with HF because of differing prognosis and response to treatments and because most clinical trials select patients based on ejection fraction (EF). RCTs with evidence of survival benefit in patients with HF have mainly enrolled patients with HF with an LVEF $ \leq35\% $ or $ \leq40\% $ , often labeled HF with reduced ejection fraction (HFrEF) (1). In this guideline, HFrEF is defined as LVEF $ \leq40\% $ (Table 4). HF with preserved EF (HFpEF) represents at least 50% of the population with HF, and its prevalence is increasing (2). HFpEF has been variably classified as LVEF $ >40\% $ , $ >45\% $ , or $ \geq50\% $ . Because some of these patients do not have entirely normal LVEF but also do not have major reduction in systolic function, the term preserved EF has been used. In this guideline, the threshold for HFpEF is an LVEF $ \geq50\% $ (Table 4). Patients with HF and an LVEF between the HFrEF and HFpEF range have been termed as “HF with mid-range EF” (3,4), or “HF with mildly reduced EF” (4). Because of LVEF being lower than normal, these patients are classified in this document as HF with mildly reduced EF (HFmrEF). Patients with HFmrEF are usually in a dynamic trajectory to improvement from HFrEF or to deterioration to HFrEF (Figure 3). Therefore, for patients whose EF falls into this mildly reduced category, 1 EF measurement at 1 time point may not be adequate, and the trajectory of LVEF over time and the cause is important to evaluate (Figure 3). Furthermore, the diagnosis of HFmrEF and HFpEF can be challenging. Although the classic clinical signs and symptoms of HF, together with EF of 41% to 49% or ≥50%, respectively, are necessary for the diagnosis of the HFmrEF and HFpEF, the requirements for additional objective measures of cardiac dysfunction can improve the diagnostic specificity. The signs and symptoms of HF are frequently nonspecific and overlap with other clinical conditions. Elevated natriuretic peptide levels are supportive of the diagnosis, but normal levels do not exclude a diagnosis of HFmrEF or HFpEF. To improve the specificity of diagnosing HFmrEF and HFpEF, the clinical diagnosis of HF in these EF categories should be further supported by objective measures. Therefore, the writing committee proposes the addition of evidence of spontaneous (at rest) or provokable (e.g., during exercise, fluid challenge) increased LV filling pressures (e.g., elevated natriuretic peptide, noninvasive/ invasive hemodynamic measurement) to the classifications of HFmrEF and HFpEF (Table 4). The “2013 ACCF/AHA Guideline for the Management of Heart Failure” (1) has used the HFpEF-improved terminology for those whose EF improved from a lower level to EF >40% under the subgrouping of patients with HFpEF. Others have proposed a working definition of HF-recovered EF that included a baseline LVEF ≤40%, a ≥10% increase from baseline LVEF, and a second measurement of LVEF >40% (3). Although associated with better outcomes, improvement in LVEF does not mean full myocardial recovery or normalization of LV function. In most patients, cardiac structural abnormalities, such as LV chamber dilatation and ventricular systolic and diastolic dysfunction, may persist. Furthermore, changes in LVEF might not be unidirectional; a patient may have improvement followed by a decrease in EF or vice versa depending on the underlying cause, duration of disease, adherence to the GDMT, or reexposure to cardiotoxicity (5). Therefore, the writing committee elected not to use “recovered EF” or HFpEF, even if subsequent LVEF was >50% but, rather, “HF with improved EF” (HFimpEF) as a subgroup of HFrEF to characterize these patients (Table 4, Figure 3). Importantly, EF can decrease after withdrawal of pharmacological treatment in many patients who had improved EF to normal range with GDMT (5). Trajectory of LVEF can be important, and a significant reduction in LVEF over time is a poor prognostic factor. e276 Heidenreich et al 2022 AHA/ACC/HFSA Heart Failure Guideline JACC VOL. 79, NO. 17, 2022 MAY 3, 2022:e263-e421 TABLE 4 Classification of HF by LVEF <table><tr><td>Type of HF According to LVEF</td><td>Criteria</td></tr><tr><td>HFrEF (HF with reduced EF)</td><td>■ LVEF ≤40%</td></tr><tr><td>HFimpEF (HF with improved EF)</td><td>■ Previous LVEF ≤40% and a follow-up measurement of LVEF >40%</td></tr><tr><td>HFmrEF (HF with mildly reduced EF)</td><td>■ LVEF 41%-49%■ Evidence of spontaneous or provokable increased LV filling pressures (e.g., elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement)</td></tr><tr><td>HFpEF (HF with preserved EF)</td><td>■ LVEF ≥50%■ Evidence of spontaneous or provokable increased LV filling pressures (e.g., elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement)</td></tr></table> Please see Appendix 3 for suggested thresholds for structural heart disease and evidence of increased filling pressures. HF indicates heart failure; LV, left ventricular; and LVEF, left ventricular ejection fraction. FIGURE 3 Classification and Trajectories of HF Based on LVEF See Appendix 3 for suggested thresholds for laboratory findings. The classification for baseline and subsequent LVEF is shown. Patients with HFrEF who improve their LVEF to >40% are considered to have HFimpEF and should continue HFrEF treatment. HF indicates heart failure; HFimpEF, heart failure with improved ejection fraction; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; and LVEF, left ventricular ejection fraction. *There is limited evidence to guide treatment for patients who improve their LVEF from mildly reduced (41%-49%) to ≥50%. It is unclear whether to treat these patients as HFpEF or HFmrEF. JACC VOL. 79, NO. 17, 2022 MAY 3, 2022:e263-e421 Heidenreich et al 2022 AHA/ACC/HFSA Heart Failure Guideline e277 2.3. Diagnostic Algorithm for Classification of HF According to LVEF Structural and functional alterations of the heart as the underlying cause for the clinical presentation support the diagnosis of HFmrEF and HFpEF (1) (Figure 4). The criteria for diagnosis of HFmrEF and HFpEF require evidence of increased LV filling pressures at rest, exercise, or other provocations. The criteria can be fulfilled with findings of elevated levels of natriuretic peptides, echocardiographic diastolic parameters such as an E/e' ≥15 or other evidence of elevated filling pressures, or invasive hemodynamic measurement at rest or exercise. Evidence of structural heart disease (e.g., LV structural or functional alterations) may be used to further support the diagnosis of HFpEF. Key structural alterations are an increase in left atrial size and volume (left atrial volume index) and/or an increase in LV mass (LV mass index). Exercise stress testing with echocardiographic evaluation of diastolic parameters can be helpful if the diagnosis remains uncertain (2,3). Alternatively, or in addition, invasive hemodynamics at rest or with exercise, with assessment of filling pressures (pulmonary capillary wedge pressure or LV end diastolic pressures, pulmonary artery [PA] pressures, stroke volumes, and cardiac output) can be performed to help further establish the diagnosis (4). The diagnosis of HFpEF is often challenging. A clinical composite score to diagnose HFpEF, the $ H_{2} $ PFEP score (5-7), integrates these predictive variables: obesity, atrial fibrillation (AF), age >60 years, treatment with $ \geqslant $ 2 antihypertensive medications, echocardiographic E/e' ratio >9, and echocardiographic PA systolic pressure >35 mmHg. A weighted score based on these 6 variables was used to create the composite score ranging from 0 to 9. The odds of HFpEF doubled for each 1-unit score increase (odds ratio, 1.98; 95% CI: 1.74-2.30; P<0.0001), with a c-statistic of 0.841. Scores <2 and ≥6 reflect low and high likelihood, respectively, for HFpEF. A score between 2 and 5 may require further evaluation of hemodynamics with exercise echocardiogram or cardiac catheterization to confirm or negate a diagnosis of HFpEF. The use of this H₂FPEF score may help to facilitate discrimination of HFpEF from noncardiac causes of dyspnea and can assist in determination of the need for further diagnostic testing in the evaluation of patients with unexplained exertional dyspnea (6,7). The European Society of Cardiology has developed a diagnostic algorithm (8). This involves a pretest that assesses for HF symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes, elderly, AF), and diagnostic laboratory tests, ECG, and echocardiography. In the absence of overt noncardiac causes of breathlessness, HFpEF can be suspected if there is a normal LVEF, no significant heart valve disease or cardiac ischemia, and at least 1 typical risk factor. The score used functional, morphological, and biomarker domains. The points score assigns 2 points for a major criterion or 1 point for a minor criterion within each domain, with a maximum of 2 points for each domain. e278 Heidenreich et al 2022 AHA/ACC/HFSA Heart Failure Guideline JACC VOL. 79, NO. 17, 2022 MAY 3, 2022:e263-e421 FIGURE 4 Diagnostic Algorithm for HF and EF-Based Classification The algorithm for a diagnosis of HF and EF-based classification is shown. BNP indicates B-type natriuretic peptide; ECG, electrocardiogram; EF, ejection fraction; HF, heart failure; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LVEF, left ventricular ejection fraction; LV, left ventricular; and NT-proBNP, N-terminal pro-B type natriuretic peptide. 3. EPIDEMIOLOGY AND CAUSES OF HF 3.1. Epidemiology of HF Trends in Mortality and Hospitalization for HF HF is a growing health and economic burden for the United States, in large part because of the aging population (1,2). Beginning in 2012, the age-adjusted death rate per capita for HF increased for the first time in the United States (3). A recent U.S. evaluation found total deaths caused by HF have increased from 275,000 in 2009 to 310,000 in 2014 (3) …(802,812 more chars)