2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults

HomeCirculationVol. 119, No. 142009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplementary MaterialsFree AccessReview ArticlePDF/EPUB2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in AdultsA Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation 2005 WRITING COMMITTEE MEMBERS Sharon Ann Hunt, MD, FACC, FAHA, Chair, William T. Abraham, MD, FACC, FAHA, Marshall H. Chin, MD, MPH, FACP, Arthur M. Feldman, MD, PhD, FACC, FAHA, Gary S. Francis, MD, FACC, FAHA, Theodore G. Ganiats, MD, Mariell Jessup, MD, FACC, FAHA, Marvin A. Konstam, MD, FACC, Donna M. Mancini, MD, Keith Michl, MD, FACP, John A. Oates, MD, FAHA, Peter S. Rahko, MD, FACC, FAHA, Marc A. Silver, MD, FACC, FAHA, Lynne Warner Stevenson, MD, FACC, FAHA and Clyde W. Yancy, MD, FACC, FAHA 2005 WRITING COMMITTEE MEMBERS Search for more papers by this author , Sharon Ann HuntSharon Ann Hunt Search for more papers by this author , William T. AbrahamWilliam T. Abraham Search for more papers by this author , Marshall H. ChinMarshall H. Chin Search for more papers by this author , Arthur M. FeldmanArthur M. Feldman Search for more papers by this author , Gary S. FrancisGary S. Francis Search for more papers by this author , Theodore G. GaniatsTheodore G. Ganiats Search for more papers by this author , Mariell JessupMariell Jessup Search for more papers by this author , Marvin A. KonstamMarvin A. Konstam Search for more papers by this author , Donna M. ManciniDonna M. Mancini Search for more papers by this author , Keith MichlKeith Michl Search for more papers by this author , John A. OatesJohn A. Oates Search for more papers by this author , Peter S. RahkoPeter S. Rahko Search for more papers by this author , Marc A. SilverMarc A. Silver Search for more papers by this author , Lynne Warner StevensonLynne Warner Stevenson Search for more papers by this author and Clyde W. YancyClyde W. Yancy Search for more papers by this author Originally published26 Mar 2009https://doi.org/10.1161/CIRCULATIONAHA.109.192065Circulation. 2009;119:e391–e479is corrected byCorrectionOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: March 26, 2009: Previous Version 1 Preamble (UPDATED)…e3931. Introduction (UPDATED)…e395 1.1. Evidence Review (UPDATED)…e395 1.2. Organization of Committee and Relationships With Industry (UPDATED)…e396 1.3. Review and Approval (NEW)…e396 1.4. Stages of Heart Failure (UPDATED)…e3962. Characterization of Heart Failure as a Clinical Syndrome…e397 2.1. Definition of Heart Failure…e397 2.2. Heart Failure as a Symptomatic Disorder…e397 2.3. Heart Failure as a Progressive Disorder…e3983. Initial and Serial Clinical Assessment of Patients Presenting With Heart Failure (UPDATED)…e399 3.1. Initial Evaluation of Patients…e400 3.1.1. Identification of Patients (UPDATED)…e400 3.1.2. Identification of a Structural and Functional Abnormality (UPDATED)…e401 3.1.3. Evaluation of the Cause of Heart Failure…e401 3.1.3.1. History and Physical Examination …e401 3.1.3.2. Laboratory Testing (UPDATED)…e402 3.1.3.3. Evaluation of the Possibility of Coronary Artery Disease…e402 3.1.3.4. Evaluation of the Possibility of Myocardial Disease…e403 3.2. Ongoing Evaluation of Patients…e404 3.2.1. Assessment of Functional Capacity…e404 3.2.2. Assessment of Volume Status…e404 3.2.3. Laboratory Assessment (UPDATED)…e404 3.2.4. Assessment of Prognosis (UPDATED)…e4054. Therapy…e405 4.1. Patients at High Risk for Developing Heart Failure (Stage A)…e405 4.1.1. Control of Risk…e406 4.1.1.1. Treatment of Hypertension…e406 4.1.1.2. Treatment of Diabetes…e407 4.1.1.3. Management of the Metabolic Syndrome…e407 4.1.1.4. Management of Atherosclerotic Disease…e407 4.1.1.5. Control of Conditions That May Cause Cardiac Injury…e408 4.1.1.6. Other Measures…e408 4.1.2. Early Detection of Structural Abnormalities…e408 4.2. Patients With Cardiac Structural Abnormalities or Remodeling Who Have Not Developed Heart Failure Symptoms (Stage B)…e408 4.2.1. Prevention of Cardiovascular Events…e409 4.2.1.1. Patients With an Acute Myocardial Infarction…e409 4.2.1.2. Patients With a History of MI but Normal Left Ventricular Ejection Fraction…e409 4.2.1.3. Patients With Hypertension and Left Ventricular Hypertrophy…e409 4.2.1.4. Patients With Chronic Reduction of Left Ventricular Ejection Fraction but No Symptoms…e409 4.2.1.5. Patients With Severe Valvular Disease but No Symptoms…e410 4.2.2. Early Detection of Heart Failure…e410 4.3. Patients With Current or Prior Symptoms of HF (Stage C)…e410 4.3.1. Patients With Reduced Left Ventricular Ejection Fraction (UPDATED)…e410 4.3.1.1. General Measures (UPDATED)…e410 4.3.1.2. Drugs Recommended for Routine Use…e413 4.3.1.2.1. Diuretics…e413 4.3.1.2.2. Inhibitors of the Renin-Angiotensin-Aldosterone System…e414 4.3.1.2.2.1. Angiotensin Converting Enzyme Inhibitors in the Management of Heart Failure…e415 4.3.1.2.2.2. Angiotensin Receptor Blockers…e417 4.3.1.2.2.3. Aldosterone Antagonists…e418 4.3.1.2.3. Beta-Adrenergic Receptor Blockers…e420 4.3.1.2.4. Digitalis…e422 4.3.1.2.5. Ventricular Arrhythmias and Prevention of Sudden Death (UPDATED)…e423 4.3.1.3. Interventions to Be Considered for Use in Selected Patients…e425 4.3.1.3.1. Isosorbide Dinitrate…e425 4.3.1.3.2. Hydralazine…e426 4.3.1.3.3. Hydralazine and Isosorbide Di-nitrate (UPDATED)…e426 4.3.1.3.4. Cardiac Resynchronization Therapy (UPDATED)…e426 4.3.1.3.5. Exercise Training…e427 4.3.1.4. Drugs and Interventions Under Active Investigation…e427 4.3.1.4.1. Techniques For Respiratory Support…e428 4.3.1.4.2. External Counterpulsation…e428 4.3.1.4.3. Vasopressin Receptor Antagonists…e428 4.3.1.4.4. Implantable Hemodynamic Monitors…e428 4.3.1.4.5. Cardiac Support Devices…e428 4.3.1.4.6. Surgical Approaches Under Investigation…e428 4.3.1.4.7. Nesiritide…e428 4.3.1.5. Drugs and Interventions of Unproved Value and Not Recommended…e429 4.3.1.5.1. Nutritional Supplements and Hormonal Therapies…e429 4.3.1.5.2. Intermittent Intravenous Positive Inotropic Therapy (UPDATED)…e429 4.3.2. Patients With Heart Failure and Normal Left Ventricular Ejection Fraction…e429 4.3.2.1. Identification of Patients…e430 4.3.2.2. Diagnosis…e431 4.3.2.3. Principles of Treatment…e431 4.4. Patients With Refractory End-Stage Heart Failure (Stage D) (UPDATED)…e432 4.4.1. Management of Fluid Status…e432 4.4.2. Utilization of Neurohormonal Inhibitors…e433 4.4.3. Intravenous Peripheral Vasodilators and Positive Inotropic Agents (UPDATED)…e433 4.4.4. Mechanical and Surgical Strategies…e434 4.5. The Hospitalized Patient (NEW)…e435 4.5.1. Diagnostic Strategies…e437 4.5.2. Treatment in the Hospital…e438 4.5.2.1. Diuretics: The Patient With Volume Overload…e438 4.5.2.2. Vasodilators…e438 4.5.2.3. Inotropes…e439 4.5.2.4. Other Considerations…e439 4.5.3. The Hospital Discharge…e4405. Treatment of Special Populations (UPDATED)…e441 5.1. Women and Men…e441 5.2. Ethnic Considerations…e441 5.3. Elderly Patients…e4426. Patients With Heart Failure Who Have Concomitant Disorders…e442 6.1. Cardiovascular Disorders…e443 6.1.1. Hypertension, Hyperlipidemia, and Diabetes Mellitus…e443 6.1.2. Coronary Artery Disease…e444 6.1.3. Supraventricular Arrhythmias (UPDATED)…e444 6.1.4. Prevention of Thromboembolic Events…e445 6.2. Noncardiovascular Disorders…e446 6.2.1. Patients With Renal Insufficiency…e446 6.2.2. Patients With Pulmonary Disease…e446 6.2.3. Patients With Cancer…e446 6.2.4. Patients With Thyroid Disease…e446 6.2.5. Patients With Hepatitis C and Human Immunodeficiency Virus…e446 6.2.6. Patients With Anemia…e4477. End-of-Life Considerations…e4478. Implementation of Practice Guidelines…e448 8.1. Isolated Provider Interventions…e449 8.2. Disease-Management Systems…e449 8.3. Performance Measures…e449 8.4. Roles of Generalist Physicians and Cardiologists…e450References…e450Appendix 1…e469Appendix 2…e470Appendix 3…e474Appendix 4…e474Appendix 5…e475Preamble (UPDATED)It is important that the medical profession play a significant role in critically evaluating the use of diagnostic procedures and therapies as they are introduced and tested in the detection, management, or prevention of disease states. Rigorous and expert analysis of the available data documenting relative benefits and risks of those procedures and therapies can produce helpful guidelines that improve the effectiveness of care, optimize patient outcomes, and favorably affect the overall cost of care by focusing resources on the most effective strategies. Download figureDownload PowerPointTable 1. Applying Classification of Recommendations and Level of Evidence*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. 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. Even though randomized trials are not available, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.†In 2003, the ACCF/AHA Task Force on Practice Guidelines developed a list of suggested phrases to use when writing recommendations. All guideline recommendations have been written in full sentences that express a complete thought, such that a recommendation, even if separated and presented apart from the rest of the document (including headings above sets of recommendations), would still convey the full intent of the recommendation. It is hoped that this will increase readers' comprehension of the guidelines and will allow queries at the individual recommendation level.The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of such guidelines in the area of cardiovascular disease since 1980. This effort is directed by the ACCF/AHA Task Force on Practice Guidelines, whose charge is to develop and revise practice guidelines for important cardiovascular diseases and procedures.Experts in the subject under consideration are selected from both organizations and charged with examining subject-specific data and writing or updating these guidelines. The process includes additional representatives from other medical practitioner and specialty groups where appropriate. Writing groups are specifically charged to perform a formal literature review, weigh the strength of evidence for or against a particular treatment or procedure, and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that might influence the choice of particular tests or therapies are considered, as are frequency of follow-up and cost-effectiveness. When available, information from studies on cost will be considered; however, review of data on efficacy and clinical outcomes will constitute the primary basis for preparing recommendations in these guidelines.The ACCF/AHA Task Force on Practice Guidelines makes every effort to avoid any actual, potential, or perceived conflicts of interest that might arise as a result of an outside relationship or personal interest of a member of the writing committee. Specifically, all members of the writing committee, as well as peer reviewers of the document, are asked to provide disclosure statements of all such relationships that might be perceived as real or potential conflicts of interest. Writing committee members are also strongly encouraged to declare a previous relationship with industry that may be perceived as relevant to guideline development. If a writing committee member develops a new relationship during his or her tenure, he or she is required to notify the guideline writing staff in writing. The continued participation of the writing committee member will be reviewed by the parent task force, reported orally to all members of the writing panel at each meeting, and updated and reviewed by the writing committee as changes occur. Please refer to the methodology manual for the ACCF/AHA guideline writing committees for further description and the relationships with industry policy.1 See Appendix 1 for a list of writing committee member relationships with industry and Appendix 2 for a listing of peer reviewer relationships with industry that are pertinent to this guideline.The practice guidelines produced are intended to assist healthcare providers in clinical decision making by describing a range of generally acceptable approaches for the diagnosis, management, or prevention of specific diseases or conditions. These guidelines attempt to define practices that meet the needs of most patients in most circumstances. These guideline recommendations reflect a consensus of expert opinion after a thorough review of the available, current scientific evidence and are intended to improve patient care. If these guidelines are used as the basis for regulatory/payer decisions, the ultimate goal is quality of care and serving the patient's best interests. The ultimate judgment regarding care of a particular patient must be made by the healthcare provider and patient in light of all of the circumstances presented by that patient.The 2005 guidelines were approved for publication by the governing bodies of the ACCF and the AHA and have been officially endorsed by the American College of Chest Physicians, the International Society for Heart and Lung Transplantation, and the Heart Rhythm Society. The summary article including recommendations was published inthe September 20, 2005, issues of both the Journal of the American College of Cardiology and Circulation. The full-text guideline is posted on the World Wide Web sites of the ACC (www.acc.org) and the AHA (my.americanheart.org). Copies of the full text and the summary article are available from both organizations.The current document is a re-publication of the “ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult,”2 revised to incorporate updated recommendations and text from a focused update performed during 2008.3 Recommendations have been updated with new information that has emerged from clinical trials or other ACCF/AHA guideline or consensus documents. In addition, the writing committee felt that a new section, the Hospitalized Patient, was necessary to address the increasingly recognized problem of the patient with acute decompensated heart failure, as opposed to the patient with chronic heart failure. Heart failure is now the single most common reason why patients over 65 years are admitted to the hospital, and the updated guidelines review important management principles for this population. For easy reference, this online-only version denotes sections that have been updated.Elliott M. Antman, MD, FACC, FAHA Chair, ACCF/AHA Task Force on Practice Guidelines, 2003–2005Sidney C. Smith, Jr, MD, FACC, FAHA Chair, ACCF/AHA Task Force on Practice Guidelines, 2006–20081. Introduction (UPDATED)Heart failure (HF) is a major and growing public health problem in the United States. Approximately 5 million patients in this country have HF, and over 550 000 patients are diagnosed with HF for the first time each year.4 The disorder is the primary reason for 12 to 15 million office visits and 6.5 million hospital days each year.5 From 1990 to 1999, the annual number of hospitalizations has increased from approximately 810 000 to over 1 million for HF as a primary diagnosis and from 2.4 to 3.6 million for HF as a primary or secondary diagnosis.6 In 2001, nearly 53 000 patients died of HF as a primary cause. The number of HF deaths has increased steadily despite advances in treatment, in part because of increasing numbers of patients with HF due to better treatment and “salvage” of patients with acute myocardial infarctions (MIs) earlier in life.4Heart failure is primarily a condition of the elderly,7 and thus the widely recognized “aging of the population” also contributes to the increasing incidence of HF. The incidence of HF approaches 10 per 1000 population after age 65,4 and approximately 80% of patients hospitalized with HF are more than 65 years old.8 Heart failure is the most common Medicare diagnosis-related group (i.e., hospital discharge diagnosis), and more Medicare dollars are spent for the diagnosis and treatment of HF than for any other diagnosis.9 The total estimated direct and indirect costs for HF in 2005 were approximately $27.9 billion.4 In the United States, approximately $2.9 billion annuallyis spent on drugs for the treatment of HF.41.1. Evidence Review (UPDATED)The ACCF and the AHA first published guidelines for the evaluation and management of HF in 1995 and published revised guidelines in 2001.10 Since that time, a great deal of progress has been made in the development of both pharmacological and nonpharmacological approaches to treatment for this common, costly, disabling, and potentially fatal disorder. The number of available treatments has increased, but this increase has rendered clinical decision making far more complex. The timing and sequence of initiating treatments and the appropriateness of prescribing them in combination are uncertain. The increasing recognition of the existence of clinical HF in patients with a normal ejection fraction (EF) (see Section 4.3.2.1) has also led to heightened awareness of the limitations of evidence-based therapy for this important group of patients. For these reasons, the 2 organizations believed that it was appropriate to reassess and update these guidelines, fully recognizing that the optimal therapy of HF remains a work in progress and that future advances will require that the guideline be updated again.The recommendations listed in the 2005 guideline are evidence based whenever possible. Pertinent medical literature in the English language was identified through a series of computerized literature searches (including Medline and EMBASE) and a manual search of selected articles. References selected and published in this document are representative but not all inclusive. Recommendations relevant to a class of drugs specify the use of the drugs shown to be effective in clinical trials unless there is reason to believe that such drugs have a broad class effect.In 2005, the committee elected to focus this document on the prevention of HF and on the diagnosis and management of chronic HF in the adult patient with normal or low LVEF. Other guidelines are relevant to the HF population, and include the ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction11 and the ACC/AHA 2002 Update of the Guidelines for the Management of Unstable Angina and Non-ST Elevation Myocardial Infarction.12 These guidelines have excluded HF in children, both because the underlying causes of HF in children differ from those in adults and because none of the controlled trials of treatments for HF have included children. We have not considered the management of HF due to primary valvular disease (see ACC/AHA Guidelines on the Management of Patients With Valvular Heart Disease)13 or congenital malformations, and we have not included recommendations for the treatment of specific myocardial disorders (e.g., hemochromatosis, sarcoidosis, or amyloidosis).For the 2009 focused update, late-breaking clinical trials presented at the 2005, 2006, and 2007 annual scientific meetings of the ACCF, AHA, and European Society of Cardiology, as well as selected other data, from 2005 through November 2007, were reviewed by the standing guideline writing committee along with the parent task force to identify those trials and other key data that might impact guideline recommendations. On the basis of the criteria/considerations noted earlier, recent trial data and other clinical information were considered important enough to prompt a focused update of the ACCF/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult.2 In addition, the guidelines writing committee thought that a new section on the management of the hospitalized patient with HF should be included in this update. A number of recent HF trials reviewed for this update, were, in fact, performed on hospitalized patients, and a number of newer therapies are under development for this population. Moreover, there is increasing government and other third-party payer interest in the prevention of HF hospitalizations, and rehospitalizations. Quality indicators about the process of discharging the HF patient have already been developed, and data about rehospitalizations for HF by hospital have been made public. Thus, the committee thought that a new section about this important aspect of HF care should be added to the update.When considering the new data for the focused update, the writing group faced the task of weighing evidence from studies enrolling large numbers of subjects outside North America. While noting that practice patterns and the rigor applied to data collection, as well as the genetic makeup of subjects, might influence the observed magnitude of a treatment's effect, the writing group believed that the data were relevant to formulation of recommendations for the management of HF in North America.1.2. Organization of Committee and Relationships With Industry (UPDATED)The 2005 writing committee was composed of 15 members who represented the ACCF and AHA, as well as invited participants from the American College of Chest Physicians, the Heart Failure Society of America, the International Society for Heart and Lung Transplantation, the American Academy of Family Physicians, and the American College of Physicians. Both the academic and private practice sectors were represented.For the 2009 focused update, all members of the 2005 HF writing committee were invited to participate; those who agreed (referred to as the 2009 Focused Update Writing Group) were required to disclose all relationships with industry relevant to the data under consideration1 as were all peer reviewers of the document (see Appendixes 4 and 5 for a listing of relationships with industry for the 2009 Focused Update Writing Group and peer reviewers, respectively). Each recommendation required a confidential vote by the writing group members before and after external review of the document. Writing group members who had a significant (greater than $10 000) relationship with industry relevant to a recommendation were required to recuse themselves from voting on that recommendation.1.3. Review and Approval (NEW)The 2005 Guideline document was reviewed by 3 official reviewers nominated by the ACCF, 3 official reviewers nominated by the AHA, 1 reviewer nominated by the American Academy of Family Physicians, 2 reviewers nominated by the American College of Chest Physicians, 1 reviewer nominated by the American College of Physicians, 4 reviewers nominated by the Heart Failure Society of America, and 1 reviewer nominated by the International Society for Heart and Lung Transplantation. In addition, 9 content reviewers and the following committees reviewed the document: ACCF/AHA Committee to Develop Performance Measures for Heart Failure, ACCF/AHA Committee to Revise Guidelines for the Management of Patients With Acute Myocardial Infarction, ACCF/AHA/ESC Committee to Update Guidelines on the Management of Patients with Atrial Fibrillation, ACCF/AHA Committee to Update Guidelines on Coronary Artery Bypass Graft Surgery, ACCF Committee to Develop Data Standards on Heart Failure, AHA Quality of Care and Outcomes Research Interdisciplinary Working Group Steering Committee, and AHA Council on Clinical Cardiology Committee on Heart Failure and Transplantation.The 2009 focused update was reviewed by 2 external reviewers nominated by both the ACCF and AHA, as well as a reviewer from the ACCF/AHA Task Force on Practice Guidelines, 10 organizational reviewers representing the American College of Chest Physicians, the American College of Physicians, the American Academy of Family Physicians, the Heart Failure Society of America, and the International Society for Heart and Lung Transplantation, and 14 individual content reviewers. All information about reviewers' relationships with industry was collected and distributed to the writing committee and is published in this document (see Appendix 5 for details).The 2009 focused update was approved for publication by the governing bodies of the ACCF and the AHA and endorsed by the International Society for Heart and Lung Transplantation.1.4. Stages of Heart Failure (UPDATED)The HF writing committee previously developed a new approach to the classification of HF,2 one that emphasized both the development and progression of the disease. In doing so, they identified 4 stages involved in the development of the HF syndrome. The first 2 stages (A and B) are clearly not HF but are an attempt to help healthcare providers with the early identification of patients who are at risk for developing HF. Stages A and B patients are best defined as those with risk factors that clearly predispose toward the development of HF. For example, patients with coronary artery disease, hypertension, or diabetes mellitus who do not yet demonstrate impaired left ventricular (LV) function, hypertrophy, or geometric chamber distortion would be considered Stage A, whereas patients who are asymptomatic but demonstrate LV hypertrophy (LVH) and/or impaired LV function would be designated as Stage B. Stage C then denotes patients with current or past symptoms of HF associated with underlying structural heart disease (the bulk of patients with HF), and Stage D designates patients with truly refractory HF who might be eligible for specialized, advanced treatment strategies, such as mechanical circulatory support, procedures to facilitate fluid removal, continuous inotropic infusions, or cardiac transplantation or other innovative or experimental surgical procedures, or for end-of-life care, such as hospice.This classification recognizes that there are established risk factors and structural prerequisites for the development of HF and that therapeutic interventions introduced even before the appearance of LV dysfunction or symptoms can reduce the population morbidity and mortality of HF. This classification system is intended to complement but in no way to replace the New York Heart Association (NYHA) functional classification, which primarily gauges the severity of symptoms in patients who are in Stage C or Stage D. It has been recognized for many years that the NYHA functional classification reflects a subjective assessment by a healthcare provider and can change frequently over short periods of time. It has also been recognized that the treatments used may not differ significantly across the classes. Therefore, the committee believed that a staging system was needed that would reliably and objectively identify patients during the course of their developing disease and that would be linked to treatments uniquely appropriate at each stage of illness. According to this new staging approach, patients would only be expected to either not advance at all or to advance from one stage to the next, unless progression of the disease was slowed or stopped by treatment, and spontaneous reversal of this progression would be considered unusual. For instance, although symptoms (NYHA functional class) might vary widely over time (in response to therapy or to progression of disease) in a patient who has already developed the clinical syndrome of HF (Stage C), the patient could never return to Stage B (never had HF), and therapies recommended for Stage C will be appropriate even if this patient is in NYHA class I. This new classification scheme adds a useful dimension to our thinking about HF that is similar to that achieved by staging or risk assessment systems for other disorders (e.g., those used in the approach to cancer).2. Characterization of Heart Failure as a Clinical Syndrome2.1. Definition of Heart FailureHeart failure is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. The cardinal manifestations of HF are dyspnea and fatigue, which may limit exercise tolerance, and fluid retention, which may lead to pulmonary congestion and peripheral edema. Both abnormalities can impair the functional capacity and quality of life of affected individuals, but they do not necessarily dominate th