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  1. 1. Journal of Cardiac Failure Vol. 16 No. 6 2010 HFSA 2010 Guideline Executive Summary Executive Summary: HFSA 2010 Comprehensive Heart Failure Practice Guideline HEART FAILURE SOCIETY OF AMERICA St. Paul, Minnesota Guideline Committee Members JoAnn Lindenfeld, MD1 (Chair) Nancy M. Albert, RN, PhD Debra K. Moser, RN, DNSc John P. Boehmer, MD Joseph G. Rogers, MD Sean P. Collins, MD, MSc Randall C. Starling, MD, MPH Justin A. Ezekowitz, MBBCh William G. Stevenson, MD Michael M. Givertz, MD W. H. Wilson Tang, MD Stuart D. Katz, MD John R. Teerlink, MD Marc Klapholz, MD Mary N. Walsh, MD Executive Council Douglas L. Mann, MD, President Inder S. Anand, MD Steven R. Houser, PhD J. Malcolm O. Arnold, MD Mariell L. Jessup, MD John C. Burnett, Jr., MD Barry M. Massie, MD John Chin, MD Mandeep R. Mehra, MD Jay N. Cohn, MD Mariann R. Piano RN, PhD Thomas Force, MD Clyde W. Yancy, MD Barry H. Greenberg, MD Michael R. Zile, MD ABSTRACT Heart failure (HF) is a syndrome characterized by high mortality, frequent hospitalization, reduced quality of life, and a complex therapeutic regimen. Knowledge about HF is accumulating so rapidly that individ- ual clinicians may be unable to readily and adequately synthesize new information into effective strategies of care for patients with this syndrome. Trial data, though valuable, often do not give direction for indi- vidual patient management. These characteristics make HF an ideal candidate for practice guidelines. The 2010 Heart Failure Society of America comprehensive practice guideline addresses the full range of eval- uation, care, and management of patients with HF. Key Words: Heart failure, practice guidelines. From the 1Department of Cardiology, University of Colorado Health A copy of the HFSA Comprehensive Heart Failure Practice GuidelineSciences Center, Denver, CO. can be found at The document should be cited as follows: Lindenfeld J, Albert NM, See page 506 for disclosure information.Boehmer JP, Collins SP, Ezekowitz JA, Givertz MM, Klapholz M, Moser 1071-9164/$ - see front matterDK, Rogers JG, Starling RC, Stevenson WG, Tang WHW, Teerlink JR, Ó 2010 Elsevier Inc. All rights reserved.Walsh MN. Executive Summary: HFSA 2010 Comprehensive Heart Fail- doi:10.1016/j.cardfail.2010.04.005ure Practice Guideline. J Card Fail 2010;16:475e539. 475
  2. 2. 476 Journal of Cardiac Failure Vol. 16 No. 6 June 2010 Table of Contents Section 1: Development and Implementation of a Comprehensive Heart Failure Practice Guideline.......476 Section 2: Conceptualization and Working Definition of Heart Failure ......................................................479 Section 3: Prevention of Ventricular Remodeling, Cardiac Dysfunction, and Heart Failure......................480 Section 4. Evaluation of Patients for Ventricular Dysfunction and Heart Failure.......................................481 Section 5: Management of Asymptomatic Patients with Reduced Left Ventricular Ejection Fraction...........................................................................................................................484 Section 6: Nonpharmacologic Management and Health Care Maintenance in Patients with Chronic Heart Failure ..........................................................................................................485 Section 7: Heart Failure in Patients with Reduced Ejection Fraction .........................................................486 Section 8: Disease Management, Advance Directives, and End-of-Life Care in Heart Failure .................492 Section 9: Electrophysiology Testing and the Use of Devices in Heart Failure .........................................494 Section 10: Surgical Approaches to the Treatment of Heart Failure.............................................................495 Section 11: Evaluation and Management of Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction ...............................................................................................496 Section 12: Evaluation and Management of Patients with Acute Decompensated Heart Failure................497 Section 13: Evaluation and Therapy for Heart Failure in the Setting of Ischemic Heart Disease ..............500 Section 14: Managing Patients with Hypertension and Heart Failure...........................................................502 Section 15: Management of Heart Failure in Special Populations ................................................................502 Section 16: Myocarditis: Current Treatment ..................................................................................................503 Section 17: Genetic Evaluation of Cardiomyopathy* ....................................................................................503 Acknowledgement.............................................................................................................................................505 References .........................................................................................................................................................506 Section 1: Development and Implementation of driving the development of HF guidelines are presenteda Comprehensive Heart Failure Practice Guideline in Table 1.1. The first HF guideline developed by the Heart Failure Heart failure (HF) is a syndrome characterized by high mor- Society of America (HFSA) had a narrow scope, concen-tality, frequent hospitalization, poor quality of life, multiple trating on the pharmacologic treatment of chronic, symp-comorbidities, and a complex therapeutic regimen. Knowl- tomatic left ventricular dysfunction.1 It did not consideredge about HF is accumulating so rapidly that individual clini- subsets of the clinical syndrome of HF, such as acute de-cians may be unable to readily and adequately synthesize new compensated HF and ‘‘diastolic dysfunction,’’ or issuesinformation into effective principles of care for patients with such as prevention. The subsequent comprehensive clinicalthis syndrome. Trial data, though valuable, often do not give practice guideline published in 2006 addressed a full rangeadequate direction for individual patient management. of topics including prevention, evaluation, disease manage- Given the complex and changing picture of HF and the ac- ment, and pharmacologic and device therapy for patientscumulation of evidence-based HF therapy, it is not possible with HF.2 The 2010 guideline updates and expands eachfor the clinician to rely solely on personal experience and ob- of these areas and adds a section on the Genetic Evaluationservation to guide therapeutic decisions. The situation is ex- of Cardiomyopathy published separately in 2009.3 Theacerbated because HF is now a chronic condition in most discussion of end of life management has also been consid-patients, meaning that the outcome of therapeutic decisions erably expanded. Appendix A is a comparison of the 2006might not be apparent for several years. The prognosis of in- Table 1.1. Assumptions Underlying HFSA Practicedividual patients differs considerably, making it difficult to Guidelinegeneralize. Treatments might not dramatically improvesymptoms of the disease process, yet might provide impor- Clinical decisions must be made. Correct course of action may not be readily apparent.tant reductions or delays in morbid events and deaths. The as- Multiple non-pharmacologic, pharmacologic, and device therapies aresessment of specific therapeutic outcomes is complicated by available.the potential differential impact of various cotherapies. Reasonably valid methods exist to address knowledge base and evaluate medical evidence. The complexity of HF, its high prevalence in society, and Data beyond randomized clinical trials exist that enhance medical decisionthe availability of many therapeutic options make it an ideal making.candidate for practice guidelines. Additional assumptions Uncertainties remain concerning approaches to treatment after review of totality of medical evidence. * Expert opinion has a role in management decisions when Strength of Reprinted with edits and permission from Hershberger RE, Linden- Evidence A data are not available to guide management.feld J, Mestroni L, Seidman C, Taylor MRG, Towbin JA. Genetic evalua- A consensus of experts remains the best method of managementtion of cardiomyopathy: a Heart Failure Society of America practice recommendations when Strength of Evidence A data are not availableguideline. J Card Fail 2009;15:83-97.
  3. 3. Executive Summary: Heart Failure Practice Guideline HFSA 477and 2010 guideline, summarizing the modifications, addi- and robust outcomes. However, randomized clinical trialtions, and deletions in the guideline recommendations. data, whether derived from one or multiple trials, haveAppendix B is a list of acronyms (including clinical trials) not been taken simply at face value. They have been eval-used in the 2010 guideline. uated for: (1) endpoints studied, (2) level of significance, (3) reproducibility of findings, (4) generalizability of studyHFSA Guideline Approach to Medical Evidence results, and (5) sample size and number of events on which outcome results are based. Two considerations are critical in the development ofpractice guidelines: assessing strength of evidence and de- Strength of Evidence B. The HFSA guideline processtermining strength of recommendation. Strength of evi- also considers evidence arising from cohort studies or smallerdence is determined both by the type of evidence clinical trials with physiologic or surrogate endpoints. Thisavailable and the assessment of validity, applicability, and level B evidence is derived from studies that are diverse in de-certainty of a specific type of evidence. Following the sign and may be prospective or retrospective in nature. Theylead of previous guidelines, strength of evidence in this may involve subgroup analyses of clinical trials or haveguideline is heavily dependent on the source or type of a case control or propensity design using a matched subsetevidence used. The HFSA guideline process has used three of trial populations. Dose-response studies, when available,grades (A, B, or C) to characterize the type of evidence may involve all or a portion of the clinical trial population. Ev-available to support specific recommendations (Table 1.2). idence generated from these studies has well-recognized, in- It must be recognized, however, that the evidence sup- herent limitations. Nevertheless, their value is enhancedporting recommendations is based largely on population re- through attention to factors such as pre-specification of hy-sponses that may not always apply to individuals within the potheses, biologic rationale, and consistency of findings be-population. Therefore, data may support overall benefit of tween studies and across different treatment over another but cannot exclude that some in- Strength of Evidence C. The present HFSA guidelinedividuals within the population may respond better to the makes extensive use of expert opinion, or C-level evidence.other treatment. Thus, guidelines can best serve as The need to formulate recommendations based on level Cevidence-based recommendations for management, not as evidence is driven primarily by a paucity of scientific evi-mandates for management in every patient. Furthermore, dence in many areas critical to a comprehensive must be recognized that trial data on which recommenda- For example, the diagnostic process and the steps used totions are based have often been carried out with background evaluate and monitor patients with established HF havetherapy not comparable to therapy in current use. There- not been the subject of clinical studies that formally testfore, physician decisions regarding the management of in- the validity of one approach versus another. In areas suchdividual patients may not always precisely match the as these, recommendations must be based on expert opinionrecommendations. A knowledgeable physician who inte- or go unaddressed.grates the guidelines with pharmacologic and physiologic The value of expert opinion as a form of evidence re-insight and knowledge of the individual being treated mains disputed. Many contend that expert opinion isshould provide the best patient management. a weak form of observational evidence, based on practiceStrength of Evidence A. Randomized controlled clinical experience and subject to biases and limitations. Advocatestrials provide what is considered the most valid form of believe expert opinion represents a complex synthesis ofguideline evidence. Some guidelines require at least 2 pos- observational insights into disease pathophysiology anditive randomized clinical trials before the evidence for a rec- the benefits of therapy in broad populations of patients.ommendation can be designated level A. The HFSA They stress the value of the interchange of experienceguideline committee has occasionally accepted a single ran- and ideas among colleagues, who collectively treat thou-domized, controlled, outcome-based clinical trial as suffi- sands of patients. Through contact with numerous individ-cient for level A evidence when the single trial is large ual health care providers who may discuss patients withwith a substantial number of endpoints and has consistent them, experts are exposed to rare safety issues and gain insight into the perceptions of practitioners concerning the efficacy of particular treatments across a wide spectrum Table 1.2. Relative Weight of Evidence Used to Develop HFSA Practice Guideline of HF. Despite the case that can be made for its value, recom-Hierarchy of Types of Evidence mendations based on expert opinion alone have been lim-Level A Randomized, Controlled, Clinical Trials ited to those circumstances when a definite consensus May be assigned based on results of a single trial could be reached across the guideline panel and reviewers.Level B Cohort and Case-Control Studies Post hoc, subgroup analysis, and meta-analysis HFSA Guideline Approach to Strength of Prospective observational studies or registries RecommendationLevel C Expert Opinion Observational studies-epidemiologic findings Safety reporting from large-scale use in practice Determining Strength. Although level of evidence is im- portant, the strength given to specific recommendations is
  4. 4. 478 Journal of Cardiac Failure Vol. 16 No. 6 June 2010critical. The process used to determine the strength of indi- Table 1.4. Steps in the Development of the 2010 HFSAvidual recommendations is complex. The goal of guideline Practice Guidelinedevelopment is to achieve the best recommendations for Determine the scope of the practice guidelineevaluation and management, considering not only efficacy, Form subcommittees with expertise for each guideline sectionbut the cost, convenience, side effect profile, and safety of Perform literature search relevant to each guideline section and distribute to subcommittee and committee membersvarious therapeutic approaches. The HFSA guideline com- Solicit additional relevant information from subcommittee and committeemittee often determined the strength of a recommendation members for each subsectionby the ‘‘totality of evidence,’’ which is a synthesis of all Formulate new recommendations and revise previous recommendations assigning Strength of Recommendation and Strength of Evidencetypes of available data, pro and con, about a particular ther- Form consensus of subcommittee for each section by conference callapeutic option. Assign writing of additional or revised background by subcommittee Full committee review of each section with revisions by subcommitteeTotality of Evidence. Totality of evidence includes not Review of each completed section by Executive Council with revisionsonly results of clinical trials, but also expert opinion and made by full committee and returned to Executive Council for final approval.findings from epidemiologic and basic science studies. Disseminate documentAgreement among various types of evidence, especially Update document as changes are necessaryfrom different methodologies, increases the likelihoodthat a particular therapy is valuable. Although many equateevidence-based medicine with the results of a few individ- subcommittees and the full Guideline Committee. Membersual clinical trials, the best judgment seems to be derived of each subcommittee were asked to review the search andfrom a careful analysis of all available trial data combined identify any additional relevant medical evidence for eachwith integration of results from the basic laboratory and the assigned section. Changes in recommendation and back-findings of epidemiologic studies. ground were carried out by each subcommittee with confer- ence calls directed by the Guideline Committee chair. EachScale of Strength. The HFSA guideline employs the cat- section was presented for comments and consensus ap-egorization for strength of recommendation outlined in proval to the Guideline Committee. Once subsectionsTable 1.3. There are several degrees of favorable recom- were complete, the Executive Council reviewed and com-mendations and a single category for therapies felt to be mented on each section and these comments were returnednot effective. The phrase ‘‘is recommended’’ should be to the Guideline Committee for changes and once complete,taken to mean that the recommended therapy or manage- for final approval by the Executive Council.ment process should be followed as often as possible in in-dividual patients. Exceptions are carefully delineated. Consensus. The development of a guideline involves the‘‘Should be considered’’ means that a majority of patients selection of individuals with expertise and experience toshould receive the intervention, with some discretion in- drive the process of formulating specific recommendationsvolving individual patients. ‘‘May be considered’’ means and producing a written document. The role of these ex-that individualization of therapy is indicated (Table 1.3). perts goes well beyond the formulation of recommenda-When the available evidence is considered to be insufficient tions supported by expert opinion.or too premature, or consensus fails, issues are labeled un- Experts involved in the guideline process must functionresolved and included as appropriate at the end of the rele- as a collective, not as isolated individuals. Expert opinionvant section. is not always unanimous. Interpretations of data vary. Dis- agreements arise over the generalizability and applicability Table 1.3. HFSA System for Classifying the Strength of of trial results to various patient subgroups. Experts are Recommendations influenced by their own experiences with particular thera- pies, but still generally agree on the clinical value of trial‘‘Is recommended’’ Part of routine care Exceptions to therapy should be minimized data. Discomfort with the results of trials reported as posi-‘‘Should be Majority of patients should receive the tive or negative generally focus on factors that potentially considered’’ intervention compromise the evidence. Unfortunately, there are no abso- Some discretion in application to individual patients should be allowed lute rules for downgrading or upgrading trial results or for‘‘May be considered’’ Individualization of therapy is indicated deciding that the limitations of the trial are sufficient to ne-‘‘Is not recommended’’ Therapeutic intervention should not be used gate what has been regarded as a traditionally positive or negative statistical result. The HFSA Guideline Committee sought resolution ofProcess of Guideline Development difficult cases through consensus building. An open, dy- Key steps in the development of this guideline are listed namic discussion meant that no single voice was allowedin Table 1.4. Having determined the broad scope of the cur- to dominate. Written documents were essential to this pro-rent guideline, subcommittees of the guideline committee cess, because they provided the opportunity for feedbackwere formed for each section of the guideline. A literature from all members of the group. On occasion, consensussearch with relevant key words and phrases for each of opinion was sufficient to override positive or negative re-guideline section were provided to members of the sults of almost any form of evidence. The HFSA process
  5. 5. Executive Summary: Heart Failure Practice Guideline HFSA 479had a strong commitment to recommendations based on ob- basis by physicians and other health care providers in thejective evidence rigorously reviewed by a panel of experts. field. The development and utilization of practice guidelines Issues that caused difficulty for the HFSA guideline pro- has emerged as an alternative strategy. The methodology ofcess were some of the more important ones faced by the guideline development needs improvement, but when thesecommittee, because they mirrored those that are often documents are properly conceived and formulated, their im-most challenging to clinicians in day-to-day practice. The portance to patient care seems evident. This HFSA guidelinefoundation of the HFSA guideline process was the belief on HF is designed as a ‘‘living document,’’ which will con-that the careful judgment of recognized opinion leaders tinue to serve as a resource for helping patients with these controversial areas is more likely to be correctthan ad hoc decisions made ‘‘on the spot’’ by physicians Section 2: Conceptualization and Working Defini-in practice. tion of Heart Failure The involvement of many groups in the development ofthis guideline helped avoid the introduction of bias, which HF remains a major and growing societal problem de-can be personal, practice-based, or based on financial inter- spite advances in detection and therapy.4-7 However, thereest. Committee members and reviewers from the Executive is no widely accepted characterization and definition ofCouncil received no direct financial support from the HFSA HF, probably because of the complexity of the syndrome.or any other source for the development of the guideline. The conceptualization and working definition of HF pre-Support was provided by the HFSA administrative staff, sented here emerged as these guidelines were developed.but the writing of the document was performed on a volun- They are critical to understanding HF and approaching itsteer basis primarily by the Committee. Financial relation- treatment appropriately.ships that might represent conflicts of interest were Conceptual Background. HF is a syndrome rather thancollected annually from all members of the Guideline Com- a primary diagnosis. It has many potential etiologies, di-mittee and the Executive Council. Current relationships are verse clinical features, and numerous clinical subsets. Pa-shown in Appendix C. tients may have a variety of primary cardiovascularDissemination and Continuity. The value of a practice diseases and never develop cardiac dysfunction, and thoseguideline is significantly influenced by the scope of its dis- in whom cardiac dysfunction is identified through testingsemination. The first and second HFSA guidelines were may never develop clinical HF. In addition to cardiac dys-available on the Internet, and thousands of copies were function, other factors, such as vascular stiffness, dyssyn-downloaded. The current document will be implemented chrony, and renal sodium handling, play major roles inon the Internet both for file transfer and as a hypertext the manifestation of the syndrome of HF.source of detailed knowledge concerning HF. Patients at risk for many cardiovascular diseases are at An important final consideration is the continuity of the risk for HF. Early identification and treatment of risk fac-guideline development process. The intent is to create tors is perhaps the most significant step in limiting the pub-a ‘‘living document’’ that will be updated and amended lic health impact of HF.8-10 Emphasis on primary andas necessary to ensure continuing relevance. The rapid de- secondary prevention is particularly critical because ofvelopment of new knowledge in HF from basic and clinical the difficulty of successfully treating left ventricular (LV)research and the continuing evolution of pharmacologic and dysfunction, especially when severe.8 Current therapeuticdevice therapy for this condition provides a strong mandate advances in the treatment of HF do not make preventionfor timely updates. The HFSA intends to undertake targeted any less and updates in areas where new research has impli- Although HF is progressive, current therapy may providecations for practice. Section 17: The Genetic Evaluation of stability and even reversibility. The inexorable progressionCardiomyopathy is an example of this policy. of HF from LV remodeling and dysfunction is no longer inevitable. Prolonged survival with mild to moderate LVSummary dysfunction is now possible. Therapy with angiotensin- converting enzyme (ACE) inhibitors or angiotensin receptor Practice guidelines have become a major part of the clini- blockers (ARBs), beta blockers, and cardiaccal landscape and seem likely to become more rather than resynchronization therapy (CRT) can lead to slowing or toless pervasive. Some may perceive guidelines as another partial reversal of remodeling.mechanism for process management or as another instrument Because of this prolonged survival, comorbid conditions,for cost control. But there is a more patient-centered rationale such as coronary artery disease (CAD) or renal failure, canfor their development, especially for a common, potentially progress, complicating treatment. Given this prolonged sur-debilitating, and often fatal syndrome such as HF. Despite ad- vival, considerable attention is devoted in this guideline tovances in clinical trial methodology and the extensive use of disease management, the use of multidrug therapy, and thestudies to evaluate therapeutics and the care process, essen- management of patients with HF at the end of life.tial elements of the management process remain undefinedfor many clinical problems. HF is no exception. Tradition- Working Definition. Although HF may be caused byally, management guidelines were determined on an ad hoc a variety of disorders, the following comprehensive
  6. 6. 480 Journal of Cardiac Failure Vol. 16 No. 6 June 2010guideline and this working definition focus on HF primarily Table 2.1. Additional HF Definitionsfrom the loss or dysfunction of myocardial muscle or ‘‘HF With Reduced Left A clinical syndrome characterizedinterstitium. Ventricular Ejection Fraction by signs and symptoms of HF (LVEF)’’ Sometimes: ‘‘HF and reduced LVEF. Most HF is a syndrome caused by cardiac dysfunction, With a Dilated Left Ventricle’’ commonly associated with LV generally resulting from myocardial muscle dys- chamber dilation. ‘‘HF With Preserved LVEF’’ A clinical syndrome characterized function or loss and characterized by either LV di- Sometimes: ‘‘HF With by signs and symptoms of HF lation or hypertrophy or both. Whether the a Nondilated LV’’ with preserved LVEF. Most dysfunction is primarily systolic or diastolic or commonly associated with a nondilated LV chamber. May mixed, it leads to neurohormonal and circulatory be the result of valvular disease abnormalities, usually resulting in characteristic or other causes (Section 11). symptoms such as fluid retention, shortness of ‘‘Myocardial Remodeling’’ Pathologic myocardial hypertrophy or dilation in breath, and fatigue, especially on exertion. In the response to increased absence of appropriate therapeutic intervention, myocardial stress. These HF is usually progressive at the level of both car- changes are generally accompanied by pathologic diac function and clinical symptoms. The severity changes in the cardiac of clinical symptoms may vary substantially dur- interstitium. Myocardial ing the course of the disease process and may remodeling is generally a progressive disorder. not correlate with changes in underlying cardiac function. Although HF is progressive and often fa- tal, patients can be stabilized and myocardial dys- function and remodeling may improve, either infarction (MI) in patients with atherosclerotic cardiovascu- spontaneously or as a consequence of therapy. In lar disease is a critical intervention, since occurrence of MI physiologic terms, HF is a syndrome characterized confers an 8- to 10-fold increased risk for subsequent HF.30 by either or both pulmonary and systemic venous Other modifiable risk factors include anemia, diabetes, hy- congestion and/or inadequate peripheral oxygen perlipidemia, obesity, valvular abnormalities, alcohol, cer- delivery, at rest or during stress, caused by cardiac tain illicit drugs, some cardiotoxic medications, and dysfunction. diet.37,38Additional Definitions Recommendations for Patients With Risk Factors for HF is often classified as HF with reduced systolic func- Ventricular Remodeling, Cardiac Dysfunction, andtion versus HF with preserved systolic function. Myocardial Heart Failureremodeling often precedes the clinical syndrome of HF.Additional definitions are provided in Table 2.1. 3.1 A careful and thorough clinical assessment, with ap- propriate investigation for known or potential risk fac- tors, is recommended in an effort to preventSection 3: Prevention of Ventricular Remodeling, development of LV remodeling, cardiac dysfunction, Cardiac Dysfunction, and Heart Failure and HF. These risk factors include, but are not limited to, hypertension, hyperlipidemia, atherosclerosis, dia- HF is an all-too-frequent outcome of hypertension and betes mellitus, valvular disease, obesity, physical inac-arterial vascular disease, making it a major public health tivity, excessive alcohol intake, dietary choices, andconcern.11,12 Epidemiologic, clinical, and basic research smoking. (Strength of Evidence 5 A)have identified a number of antecedent conditions that pre-dispose individuals to HF and its predecessors, LV remod- 3.2 The recommended goals for the management of spe-eling and dysfunction.13-21 Recognition that many of these cific risk factors for the development of cardiac dys-risk factors can be modified and that treating HF is difficult function and HF are shown in Table 3.1.and costly has focused attention on preventive strategies for 3.3 ACE inhibitors are recommended for prevention of HFHF. in patients at high risk of this syndrome, including Development of both systolic and diastolic dysfunction those with CAD, peripheral vascular disease, orrelated to adverse ventricular remodeling may take years stroke. Patients with diabetes and another major riskto produce significant ill effects.22-28 Although the precise factor or patients with diabetes who smoke or havemechanisms for the transition to symptomatic HF are not microalbuminuria are also at high risk and should re-clear, many modifiable factors have been identified that pre- ceive ACE inhibitors. (Strength of Evidence 5 A)dispose or aggravate the remodeling process and the devel-opment of cardiac dysfunction. Treatment of systemic 3.4 Beta blockers are recommended for patients with priorhypertension, with or without LV hypertrophy, reduces MI to reduce mortality, recurrent MI, and the develop-the development of HF.8,29-36 Prevention of myocardial ment of HF. (Strength of Evidence 5 A)
  7. 7. Executive Summary: Heart Failure Practice Guideline HFSA 481 Table 3.1. Goals for the Management of Risk Factors for the Development of Heart FailureRisk Factor Population Treatment Goal Strength of EvidenceHypertension No diabetes or renal disease !140/90 mmHg A Diabetes !130/80 mmHg A Renal insufficiency and O1g/day of 127/75 A proteinuria Renal insufficiency and #1 g/day of 130/85 A proteinuria Everyone with hypertension Limit sodium to #1500 mg/day ADiabetes See American Diabetes Association (ADA) GuidelineHyperlipidemia See National Cholesterol Education Program (NCEP) GuidelinePhysical Inactivity Everyone Sustained aerobic activity 20-30 minutes, 3- B 5 times weeklyObesity BMI O30 Weight reduction to achieve BMI !30 CExcessive alcohol intake Men Limit alcohol intake to 1-2 drink equivalents C per day Women 1 drink equivalent per day Those with propensity to abuse alcohol or Abstention with alcoholic cardiomyopathySmoking Everyone Cessation AVitamin/mineral deficiency Everyone Diet high in Kþ/calcium BPoor diet Everyone 4 or more servings of fruit and vegetables B per day; One or more servings of breakfast cereal per week Section 4. Evaluation of Patients for Ventricular concentration as part of a screening evaluation for Dysfunction and Heart Failure structural heart disease in asymptomatic patients is not recommended. (Strength of Evidence 5 B) Patients undergoing evaluation for ventricular dysfunc-tion and HF fall into 3 general groups: (1) patients at risk Table 4.1. Indications for Evaluation of Clinicalof developing HF, (2) patients suspected of having HF Manifestations of HFbased on signs and symptoms or incidental evidence of ab- Conditions Hypertensionnormal cardiac structure or function, and (3) patients with Diabetes Obesityestablished symptomatic HF. CAD (eg, after MI, revascularization) Peripheral arterial disease or cerebrovascularPatients at Risk for Heart Failure disease Valvular heart disease Patients identified to be at risk for HF require aggressive Family history of cardiomyopathy in a first-management of modifiable risk factors as outlined in Sec- degree relative History of exposure to cardiac toxinstion 3 of this guideline. Patients with risk factors may Sleep-disordered breathinghave undetected abnormalities of cardiac structure or func- Test Findings Sustained arrhythmiastion. In addition to risk factor reduction, these patients re- Abnormal ECG (eg, LVH, left bundle branch block, pathologic Q waves)quire careful assessment for the presence of symptoms of Cardiomegaly on chest X-rayHF and, depending on their underlying risk, may warrantnoninvasive evaluation of cardiac structure and function.Recommendations for Evaluation of Patients at Risk for Table 4.2. Assess Cardiac Structure and Function inHeart Failure Patients with the Following Disorders or Findings CAD (eg, after MI, revascularization)4.1 Evaluation for clinical manifestations of HF with a rou- Valvular heart disease tine history and physical examination is recommended Family history of cardiomyopathy in a first-degree relative Atrial fibrillation or flutter in patients with the medical conditions or test findings Electrocardiographic evidence of LVH, left bundle branch block, or listed in Table 4.1. (Strength of Evidence 5 B) pathologic Q waves Complex ventricular arrhythmia4.2 Assessment of Cardiac Structure and Function. Echo- Cardiomegaly cardiography with Doppler is recommended to deter- mine cardiac structure and function in asymptomatic patients with the disorders or findings listed in Table 4.2. (Strength of Evidence 5 B) Patients Suspected of Having HF4.3 Routine determination of plasma B-type natriuretic The evaluation of patients suspected of having HF fo- peptide (BNP) or N-terminal pro-BNP (NT-proBNP) cuses on interpretation of signs and symptoms that have
  8. 8. 482 Journal of Cardiac Failure Vol. 16 No. 6 June 2010 Table 4.3. Symptoms Suggesting the Diagnosis of HF 4.7 Differential Diagnosis. The differential diagnoses inSymptoms Dyspnea at rest or on exertion Table 4.5 should be considered as alternative explana- Reduction in exercise capacity tions for signs and symptoms consistent with HF. Orthopnea (Strength of Evidence 5 B) Paroxysmal nocturnal dyspnea (PND) or nocturnal cough Edema Ascites or scrotal edema Table 4.5. Differential Diagnosis for HF Symptoms andLess specific Early satiety, nausea and vomiting, abdominal Signs presentations of HF discomfort Myocardial ischemia Wheezing or cough Pulmonary disease (pneumonia, asthma, chronic obstructive pulmonary Unexplained fatigue disease, pulmonary embolus, primary pulmonary hypertension) Confusion/delirium Sleep-disordered breathing Depression/weakness (especially in the elderly) Obesity Deconditioning Malnutrition Anemialed to the consideration of this diagnosis. Careful history Hepatic failureand physical examination, combined with evaluation of car- Chronic kidney disease Hypoalbuminemiadiac structure and function, should be undertaken to deter- Venous stasismine the cause of symptoms and to evaluate the degree of Depressionunderlying cardiac pathology. Anxiety and hyperventilation syndromes Hyper or hypo-thyroidismRecommendations for Evaluation of PatientsSuspected of Having HF Patients With Established HF4.4 Symptoms Consistent with HF. The symptoms listed The evaluation of patients with an established diagnosis in Table 4.3 suggest the diagnosis of HF. It is recom- of HF is undertaken to identify the etiology, assess symp- mended that each of these symptoms be elicited in all tom nature and severity, determine functional impairment, patients in whom the diagnosis of HF is being consid- and establish a prognosis. Follow-up of patients with HF ered. (Strength of Evidence 5 B) or cardiac dysfunction involves continuing reassessment4.5 Physical Examination. It is recommended that patients of symptoms, functional capacity, prognosis, and therapeu- suspected of having HF undergo careful physical ex- tic effectiveness. amination with determination of vital signs and care- ful evaluation for signs shown in Table 4.4. (Strength of Evidence 5 B) Recommendations for the Evaluation of Patients With Established HF Table 4.4. Signs to Evaluate in Patients Suspected of 4.8 It is recommended that patients with a diagnosis of HF Having HF undergo evaluation as outlined in Table 4.6. (Strength of Evidence 5 C)Cardiac Abnormality Sign 4.9 Symptoms. In addition to symptoms characteristic ofElevated cardiac Elevated jugular venous pressure filling pressures S3 gallop HF (dyspnea, fatigue, decreased exercise tolerance, and fluid overload Rales fluid retention), evaluation of the following symptoms Hepatojugular reflux should be considered in the diagnosis of HF: Ascites Edema AnginaCardiac enlargement Laterally displaced or prominent apical impulse Symptoms suggestive of embolic events Murmurs suggesting valvular dysfunction Symptoms suggestive of sleep-disordered breathingReduced cardiac output Narrow pulse pressure Cool extremities Tachycardia with pulsus alternansArrhythmia Irregular pulse suggestive of atrial Table 4.6. Initial Evaluation of Patients With a Diagnosis of fibrillation or frequent ectopy HF Assess clinical severity of HF by history and physical examination Assess cardiac structure and function Determine the etiology of HF, with particular attention to reversible causes Evaluate for coronary disease and myocardial ischemia4.6 It is recommended that BNP or NT-proBNP levels be Evaluate the risk of life-threatening arrhythmia assessed in all patients suspected of having HF, espe- Identify any exacerbating factors for HF cially when the diagnosis is not certain. (Strength of Identify comorbidities which influence therapy Identify barriers to adherence Evidence 5 A)
  9. 9. Executive Summary: Heart Failure Practice Guideline HFSA 483 Symptoms suggestive of arrhythmias, including Assess electrical dyssynchrony (wide QRS or palpitations bundle branch block), especially when left ven- Symptoms of possible cerebral hypoperfusion, in- tricular ejection fraction (LVEF) !35% cluding syncope, presyncope, or lightheadedness Detect LV hypertrophy or other chamber enlarge- (Strength of Evidence 5 B) ment Detect evidence of myocardial infarction (MI) or4.10 Functional Capacity/Activity Level. It is recommen- ischemia ded that the severity of clinical disease and functional limitation be evaluated and recorded and the ability to Assess QTc interval, especially with drugs that perform typical daily activities be determined. This prolong QT intervals (Strength of Evidence 5 B) evaluation may be graded by metrics such as New 4.14 Chest X-Ray. It is recommended that all patients with York Heart Association (NYHA) functional class HF have a postero-anterior and lateral chest X-ray (Table 4.7) (Strength of Evidence 5 A) or by the 6- examination for determination of heart size, evidence minute walk test. (Strength of Evidence 5 C) of fluid overload, detection of pulmonary and other diseases, and appropriate placement of implanted Table 4.7. Criteria for NYHA Functional Classification in cardiac devices. (Strength of Evidence 5 B) Patients With HFClass I No limitation of physical activity. Ordinary physical 4.15 Additional Laboratory Tests. It is recommended that activity does not cause undue fatigue, palpitation, or patients with no apparent etiology of HF or no spe- dyspnea. cific clinical features suggesting unusual etiologiesClass II Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, undergo additional directed blood and laboratory palpitations, or dyspnea. studies to determine the cause of HF. (Strength ofClass III IIIA: Marked limitation of physical activity. Evidence 5 B) Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. IIIB: Marked 4.16 Evaluation of myocardial ischemia is recommended limitation of physical activity. Comfortable at rest, but minimal exertion causes fatigue, palpitation, or in those who develop new-onset LV systolic dysfunc- dyspnea. tion especially in the setting of suspected myocardialClass IV Unable to carry on any physical activity without ischemia or worsening symptoms with pre-existing discomfort. Symptoms of cardiac insufficiency present at rest. If any physical activity is undertaken, CAD. The choice of testing modality should depend discomfort is increased. on the clinical suspicion and underlying cardiac risk factors. Coronary angiography should be considered when pre-test probability of underlying ischemic4.11 Volume Status. The degree of volume excess is a key cardiomyopathy is high and an invasive coronary consideration during treatment. It is recommended intervention may be considered. (See Section 13 that it be routinely assessed by determining: for specific clinical situations and Strength of Presence of paroxysmal nocturnal dyspnea or or- Evidence) thopnea 4.17 Exercise testing for functional capacity is not recom- Presence of dyspnea on exertion mended as part of routine evaluation in patients with Daily weights and vital signs with assessment for HF. Specific circumstances in which maximal exercise orthostatic changes testing with measurement of expired gases should be Presence and degree of rales, S3 gallop, jugular considered include (Strength of Evidence 5 C): venous pressure elevation, hepatic enlargement and tenderness, positive hepatojugular reflux, Assessing disparity between symptomatic limita- edema, and ascites (Strength of Evidence 5 B) tion and objective indicators of disease severity Distinguishing non HF-related causes of func-4.12 Standard Laboratory Tests. It is recommended that tional limitation, specifically cardiac versus pul- the following laboratory tests be obtained routinely monary in patients being evaluated for HF: serum electro- Considering candidacy for cardiac transplantation lytes, blood urea nitrogen, creatinine, glucose, cal- or mechanical circulatory support cium, magnesium, fasting lipid profile (low-density Determining the prescription for cardiac rehabili- lipoprotein cholesterol, high-density lipoprotein cho- tation lesterol, triglycerides), complete blood count, serum albumin, uric acid, liver function tests, urinalysis, Addressing specific employment capabilities and thyroid function. (Strength of Evidence 5 B) 4.18 Routine endomyocardial biopsy is not recommended4.13 Electrocardiogram (ECG). It is recommended that all in cases of new-onset HF. Endomyocardial biopsy patients with HF have an ECG performed to: should be considered in patients with rapidly pro- Assess cardiac rhythm and conduction (in some gressive clinical HF or ventricular dysfunction, de- cases, using Holter monitoring or event monitors) spite appropriate medical therapy. Endomyocardial
  10. 10. 484 Journal of Cardiac Failure Vol. 16 No. 6 June 2010 biopsy also should be considered in patients sus- 4.21 It is recommended that reevaluation of electrolytes and pected of having myocardial infiltrative processes, renal function occur at least every 6 months in clini- such as sarcoidosis or amyloidosis, or in patients cally stable patients and more frequently following with malignant arrhythmias out of proportion to LV changes in therapy or with evidence of change in vol- dysfunction, where sarcoidosis and giant cell ume status. More frequent assessment of electrolytes myocarditis are considerations. (Strength of Evi- and renal function is recommended in patients with se- dence 5 C) vere HF, those receiving high doses of diuretics, those on aldosterone antagonists, and those who are clini-4.19 It is recommended that clinical evaluation at each cally unstable. (Strength of Evidence 5 C) follow-up visit include determination of the elements listed in Table 4.9. (Strength of Evidence 5 B) See Section 7 for recommendations for patients on an aldosterone receptor antagonist. These assessments should include the same symp- toms and signs assessed during the initial evaluation. (Strength of Evidence 5 B) Section 5: Management of Asymptomatic Patients Table 4.9. Elements to Determine at Follow-Up Visits of HF Patients With Reduced Left Ventricular Ejection FractionFunctional capacity and activity level LV remodeling and reduced LVEF should be distin-Changes in body weightPatient understanding of and compliance with dietary sodium restriction guished from the syndrome of clinical HF. When LVEF isPatient understanding of and compliance with medical regimen reduced (!40%), but there are no signs and symptoms ofHistory of arrhythmia, syncope, presyncope, palpitation or ICD discharge HF, the condition frequently is referred to as asymptomaticAdherence and response to therapeutic interventionsThe presence or absence of exacerbating factors for HF, including LV dysfunction (ALVD). It is important to distinguish be- worsening ischemic heart disease, hypertension, and new or worsening tween ALVD and patients categorized as NYHA Class I valvular disease HF. Although patients with NYHA Class I HF do not cur- rently have HF symptoms, they may have ALVD currently, or they may have clinical systolic HF with symptoms in the4.20 In the absence of deteriorating clinical presentation, past. In contrast, patients with ALVD have no past history repeat measurements of ventricular volume and of HF symptoms. It is now well recognized that there LVEF should be considered in these limited circum- may be a latency period when the LVEF is reduced before stances: the development of symptomatic HF. Although most atten- When a prophylactic implantable cardioverter de- tion in the HF literature has centered on patients with symp- fibrillator (ICD) or cardiac resynchronization toms, evidence now indicates that ALVD is more common therapy (CRT) device and defibrillator (CRT-D) than previously assumed. The recent realization that thera- placement is being considered in order to deter- pies aimed at symptomatic HF may improve outcomes in mine that LVEF criteria for device placement patients with ALVD has increased the importance of recog- are still met after medical therapy (Strength of nizing and treating patients with this condition. Evidence 5 B) The management of patients with ALVD focuses on con- When patients show substantial clinical improve- trolling cardiovascular risk factors and on the prevention or ment (for example, in response to beta blocker reduction of progressive ventricular remodeling. Exercise, treatment or following pregnancy in patients smoking cessation, hypertension control, as well as treat- with peripartum cardiomyopathy). Such change ment with ACE inhibitors (or ARBs) and beta blockers, may denote improved prognosis, although it all have a potential role in the treatment of this syndrome. does not in itself mandate alteration or discontin- uation of specific treatments (see Section 7). Recommendations for the Management of (Strength of Evidence 5 C) Asymptomatic Patients With Reduced LVEF In alcohol and cardiotoxic substance abusers who have discontinued the abused substance. (Strength 5.1 It is recommended that all patients with ALVD exercise of Evidence 5 C) regularly according to a physician-directed prescription to avoid general deconditioning; to optimize weight, In patients receiving cardiotoxic chemotherapy. blood pressure, and diabetes control; and to reduce car- (Strength of Evidence 5 B) diovascular risk. (Strength of Evidence 5 C) Repeat determination of LVEF is usually unnecessary 5.2 Smoking cessation is recommended in all patients in- in patients with previously documented LV dilatation cluding those with ALVD. (Strength of Evidence 5 B) and low LVEF who manifest worsening signs or symp- toms of HF, unless the information is needed to justify 5.3 Alcohol abstinence is recommended if there is current a change in patient management (such as surgery or de- or previous history of excessive alcohol intake. vice implantation). (Strength of Evidence 5 C) (Strength of Evidence 5 C)
  11. 11. Executive Summary: Heart Failure Practice Guideline HFSA 4855.4 It is recommended that all patients with ALVD with (cardiac cachexia). Measurement of nitrogen balance, hypertension achieve optimal blood pressure control. caloric intake, and prealbumin may be useful in deter- (Strength of Evidence 5 B) mining appropriate nutritional supplementation. Calo- ric supplementation is recommended. Anabolic5.5 ACE inhibitor therapy is recommended for asymptom- steroids are not recommended for cachexic patients. atic patients with reduced LVEF (!40%). (Strength of (Strength of Evidence 5 C) Evidence 5 A) 6.5 Patients with HF, especially those on diuretic therapy5.6 ARBs are recommended for asymptomatic patients with and restricted diets, should be considered for daily reduced LVEF who are intolerant of ACE inhibitors from multivitamin-mineral supplementation to ensure ade- cough or angioedema. (Strength of Evidence 5 C) quate intake of the recommended daily value of essen- Routine use of the combination of ACE inhibitors and tial nutrients. Evaluation for specific vitamin or ARBs for prevention of HF is not recommended in this nutrient deficiencies is rarely necessary. (Strength of population. (Strength of Evidence 5 C) Evidence 5 C)5.7 Beta blocker therapy should be considered in asymp- 6.6 Documentation of the type and dose of naturoceutical tomatic patients with reduced LVEF. (post-MI, products used by patients with HF is recommended. Strength of Evidence 5 B; non post-MI, Strength of (Strength of Evidence 5 C) Evidence 5 C) Naturoceutical use is not recommended for relief of Section 6: Nonpharmacologic Management and symptomatic HF or for the secondary prevention ofHealth Care Maintenance in Patients With Chronic cardiovascular events. Patients should be instructed Heart Failure to avoid using natural or synthetic products containing ephedra (ma huang), ephedrine, or its metabolites be- Nonpharmacologic management strategies represent an cause of an increased risk of mortality and morbidity.important contribution to HF therapy. They may signifi- Products should be avoided that may have significantcantly impact patient stability, functional capacity, mortal- drug interactions with digoxin, vasodilators, betaity, and quality of life. These strategies include diet and blockers, antiarrhythmic drugs, and anticoagulants.nutrition, oxygen supplementation, and management of (Strength of Evidence 5 B)concomitant conditions such as sleep apnea, insomnia, de- Recommendations for Other Therapiespression, and sexual dysfunction. Exercise training mayalso play a role in appropriate patients. Attention should 6.7 Continuous positive airway pressure to improve dailybe focused on the appropriate management of routine functional capacity and quality of life is recommendedhealth maintenance issues. in patients with HF and obstructive sleep apnea docu- mented by approved methods of polysomnography.Recommendations for Diet and Nutrition (Strength of Evidence 5 B)6.1 Dietary instruction regarding sodium intake is recom- 6.8 Supplemental oxygen, either at night or during exer- mended in all patients with HF. Patients with HF and tion, is not recommended for patients with HF in the diabetes, dyslipidemia, or severe obesity should be absence of an indication of underlying pulmonary dis- given specific dietary instructions. (Strength of Evi- ease. Patients with resting hypoxemia or oxygen desa- dence 5 B) turation during exercise should be evaluated for residual fluid overload or concomitant pulmonary dis-6.2 Dietary sodium restriction (2-3 g daily) is recommen- ease. (Strength of Evidence 5 B) ded for patients with the clinical syndrome of HF and preserved or depressed left ventricular ejection frac- 6.9 The identification of treatable conditions, such as tion (LVEF). Further restriction (!2 g daily) may sleep-disordered breathing, urologic abnormalities, be considered in moderate to severe HF. (Strength of restless leg syndrome, and depression should be con- Evidence 5 C) sidered in patients with HF and chronic insomnia. Pharmacologic aids to sleep induction may be neces-6.3 Restriction of daily fluid intake to !2 L is recommen- sary. Agents that do not risk physical dependence ded in patients with severe hyponatremia (serum so- are preferred. (Strength of Evidence 5 C) dium !130 mEq/L) and should be considered for Recommendations for Specific Activity and Lifestyle all patients demonstrating fluid retention that is diffi- Issues cult to control despite high doses of diuretic and so- dium restriction. (Strength of Evidence 5 C) 6.10 It is recommended that screening for endogenous or6.4 It is recommended that specific attention be paid to prolonged reactive depression in patients with HF be nutritional management of patients with advanced conducted following diagnosis and at periodic inter- HF and unintentional weight loss or muscle wasting vals as clinically indicated. For pharmacologic
  12. 12. 486 Journal of Cardiac Failure Vol. 16 No. 6 June 2010 treatment, selective serotonin reuptake inhibitors are setting of reduced renal function or ACE-inhibitor preferred over tricyclic antidepressants, because the therapy. (Strength of Evidence 5 B) latter have the potential to cause ventricular arrhyth- 6.17 It is recommended that patients with new- or recent- mias, but the potential for drug interactions should be onset HF be assessed for employability following considered. (Strength of Evidence 5 B) a reasonable period of clinical stabilization. An6.11 Nonpharmacologic techniques for stress reduction may objective assessment of functional exercise capacity be considered as a useful adjunct for reducing anxiety is useful in this determination. (Strength of Evi- in patients with HF. (Strength of Evidence 5 C) dence 5 B)6.12 It is recommended that treatment options for sexual 6.18 It is recommended that patients with chronic HF who dysfunction be discussed openly with both male are employed and whose job description is compati- and female patients with HF. (Strength of Evi- ble with their prescribed activity level be encouraged dence 5 C) to remain employed, even if a temporary reduction in hours worked or task performed is required. Retrain- The use of phosphodiasterase-5 inhibitors such as sil- ing should be considered and supported for patients denafil may be considered for use for sexual dysfunc- with a job demanding a level of physical exertion tion in patients with chronic stable HF. These agents exceeding recommended levels. (Strength of Evi- are not recommended in patients taking nitrate prepa- dence 5 B) rations. (Strength of Evidence 5 C) Recommendations for Exercise Testing/ExerciseRecommendations for Routine Health Care TrainingMaintenance 6.19 It is recommended that patients with HF undergo ex-6.13 It is recommended that patients with HF be advised ercise testing to determine suitability for exercise to stop smoking and to limit alcohol consumption training (patient does not develop significant ische- to #2 standard drinks per day in men or #1 standard mia or arrhythmias). drink per day in women. Patients suspected of having an alcohol-induced cardiomyopathy should be ad- If deemed safe, exercise training should be consid- vised to abstain from alcohol consumption. Patients ered for patients with HF in order to facilitate under- suspected of using illicit drugs should be counseled standing of exercise expectations (heart rate ranges to discontinue such use. (Strength of Evidence 5 B) and appropriate levels of exercise training), to in- crease exercise duration and intensity in a supervised6.14 Pneumococcal vaccine and annual influenza vaccina- setting, and to promote adherence to a general exer- tion are recommended in all patients with HF in the cise goal of 30 minutes of moderate activity/exercise, absence of known contraindications. (Strength of Ev- 5 days per week with warm up and cool down exer- idence 5 B) cises. (Strength of Evidence 5 B)6.15 Endocarditis prophylaxis is not recommended based Section 7: Heart Failure in Patients With Reduced on the diagnosis of HF alone. Consistent with the Ejection Fraction AHA recommendation, ‘prophylaxis should be given for only specific cardiac conditions, associated with There are 3 primary issues that must be considered the highest risk of adverse outcome from endocardi- when treating HF patients with reduced LVEF: (1) im- tis.’39 These are: ‘prosthetic cardiac valves; previous proving symptoms and quality of life, (2) slowing the infective endocarditis; congenital heart disease progression or reversing cardiac and peripheral dysfunc- (CHD)’ such as: ‘unrepaired cyanotic CHD, includ- tion, and (3) reducing mortality. General measures, such ing palliative shunts and conduits; completely re- as salt restriction, weight loss, lipid control, and other paired congenital heart defect with prosthetic nonpharmacologic measures are addressed in Section 6. material or device, whether placed by surgery or by Pharmacologic approaches to symptom control, including catheter intervention, during the first six months after diuretics, vasodilators, intravenous inotropic drugs, antico- the procedure; repaired CHD with residual defects at agulants, and antiplatelet agents are discussed at the end the site or adjacent to the site of a prosthetic patch or of this section. prosthetic device (which inhibit endothelialization); Two classes of agents have become the recommended cor- cardiac transplantation recipients who develop car- nerstone of therapy to delay or halt progression of cardiac diac valvulopathy.’ (Strength of Evidence 5 C) dysfunction and improve mortality: ACE inhibitors and6.16 Nonsteroidal anti-inflammatory drugs, including beta blockers. Even while these agents are underused in the cyclooxygenase-2 inhibitors, are not recommended treatment of HF, new classes of agents have been added in patients with chronic HF. The risk of renal failure that show an impact on mortality, complicating decisions and fluid retention is markedly increased in the about optimal pharmacologic therapy. These include
  13. 13. Executive Summary: Heart Failure Practice Guideline HFSA 487 Table 7.1. ACE-inhibitor, Angiotensin Receptor Blocker, and Beta-Blocker Therapy in Heart Failure with Low Ejection Fraction Mean Dose Achieved inGeneric Name Trade Name Initial Daily Dose Target Dose Clinical TrialsACE-inhibitorsCaptopril Capoten 6.25 mg tid 50 mg tid 122.7 mg/day160Enalapril Vasotec 2.5 mg bid 10 mg bid 16.6 mg/day42Fosinopril Monopril 5-10 mg qd 80 mg qd n/aLisinopril Zestril, Prinivil 2.5-5 mg qd 20 mg qd *4.5 mg/day (low dose ATLAS) 33.2 mg/day (high dose ATLAS)161Quinapril Accupril 5 mg bid 80 mg qd n/aRamipril Altace 1.25-2.5 mg qd 10 mg qd n/aTrandolapril Mavik 1 mg qd 4 mg qd n/aAngiotensin Receptor BlockersCandesartan Atacand 4-8 mg qd 32 mg qd 24 mg/day162Losartan Cozaar 12.5-25 mg qd 150 mg qd 129 mg/day163Valsartan Diovan 40 mg bid 160 mg bid 254 mg/day164Beta-blockersBisoprolol Zebeta 1.25 mg qd 10 mg qd 8.6 mg/day47Carvedilol Coreg 3.125 mg bid 25 mg bid 37 mg/day165Carvedilol Coreg CR 10 mg qd 80 mg qdMetoprolol succinate CR/XL Toprol XL 12.5-25 mg qd 200 mg qd 159 mg/day48Aldosterone AntagonistsSpironolactone Aldactone 12.5 to 25 mg qd 25 mg qd 26 mg/day60Eplerenone Inspra 25 mg qd 50 mg qd 42.6 mg/day61Other VasodilatorsFixed dose Hydralazine/ BiDil 37.5 mg hydralazine/20 mg 75 mg hydralazine/40 mg 142.5 mg hydralazine/76 mg Isosorbide dinitrate isosorbide dinitrate tid isosorbide dinitrate tid isosorbide dinitrate/day166Hydralazine Apresoline 37.5 mg qid 75 mg qid 270 mg/day167Isosorbide dinitrate Isordil 20 mg qid 40 mg qid 136 mg/day167 *No difference in mortality between high and low dose groups, but 12% lower risk of death or hospitalization in high dose group vs. low dose group.ARBs, aldosterone antagonists, and the combination of 7.2 It is recommended that other therapy be substituted forhydralazine and an oral nitrate (Table 7.1). ACE inhibitors in the following circumstances: In patients who cannot tolerate ACE inhibitors dueRecommendations for ACE-inhibitors to cough, ARBs are recommended. (Strength of There is compelling evidence that ACE inhibitors should Evidence 5 A)be used to inhibit the renin-angiotensin-aldosterone system The combination of hydralazine and an oral nitrate(RAAS) in all HF patients with reduced LVEF, whether or may be considered in such patients not toleratingnot they are symptomatic (Table 7.1). A number of large ARB therapy. (Strength of Evidence 5 C)clinical trials have demonstrated improvement in morbidityand mortality in HF patients with reduced LVEF, both Patients intolerant to ACE inhibitors from hyperka-chronically and post-MI.40-42 lemia or renal insufficiency are likely to experience the same side effects with ARBs. In these cases, the7.1 ACE inhibitors are recommended for routine adminis- combination of hydralazine and an oral nitrate tration to symptomatic and asymptomatic patients should be considered. (Strength of Evidence 5 C) with LVEF # 40%. (Strength of Evidence 5 A) ACE inhibitors should be titrated to doses used in 7.3 ARBs are recommended for routine administration to clinical trials, as tolerated during concomitant up- symptomatic and asymptomatic patients with an titration of beta blockers. (Strength of Evidence 5 C) LVEF # 40% who are intolerant to ACE inhibitors for reasons other than hyperkalemia or renal insuffi-Recommendations for Alternatives to ACE-inhibitors ciency. (Strength of Evidence 5 A) ACE inhibitors can have some troublesome side effects, in- 7.4 ARBs should be considered in patients experiencingcluding cough and angioedema, which may limit therapy with angioedema while on ACE inhibitors based on theirthese agents. ARBs have been demonstrated to be well toler- underlying risk and with recognition that angioedemaated in randomized trials of patients judged to be intolerant has been reported infrequently with ARBs. (Strengthof ACE inhibitors.43,44 Both drugs have similar effects on of Evidence 5 B)blood pressure, renal function, and potassium.43 Thus, patientsintolerant of ACE-inhibitors for these reasons may also be in- The combination of hydralazine and oral nitrates maytolerant of ARBs, and the combination of hydralazine and oral be considered in such patients not tolerating ARBnitrates should be considered for these patients. therapy. (Strength of Evidence 5 C)