Executive Summary: HFSA 2006 Comprehensive Heart Failure Practice Guideline

Article Outline

• Abstract
• Section 1: Development and Implementation of a Comprehensive Heart Failure Practice Guideline
  • Introduction
  • HFSA Guideline Approach to Medical Evidence
    • Strength of Evidence A
    • Strength of Evidence B
    • Strength of Evidence C
  • HFSA Guideline Approach to Strength of Recommendation
  • Process of Guideline Development
    • Consensus
    • Dissemination and Continuity
• Section 2: Conceptualization and Working Definition of Heart Failure
• Section 3: Prevention of Ventricular Remodeling, Cardiac Dysfunction, and Heart Failure
  • Recommendations for Patients With Risk Factors for Ventricular Remodeling, Cardiac Dysfunction, and Heart Failure
• Section 4: Evaluation of Patients for Ventricular Dysfunction and Heart Failure
  • Evaluation of Patients at Risk
  • Evaluation of Patients Suspected of Having HF
  • Initial Evaluation of Patients With HF
• Section 5: Management of Asymptomatic Patients With Reduced Left Ventricular Ejection Fraction
• Section 6: Nonpharmacologic Management and Health Care Maintenance in Patients With Chronic Heart Failure
  • Diet and Nutrition
  • Other Therapies
  • Specific Activity and Lifestyle Issues
  • Health Care Maintenance Issues
• Section 7: Heart Failure in Patients With Left Ventricular Systolic Dysfunction
  • ACE Inhibitors
  • β-Adrenergic Receptor Blockers
  • Angiotensin Receptor Blockers (ARBs)
  • Aldosterone Antagonists
  • Hydralazine and Oral Nitrates
  • Polypharmacy
  • Diuretic Therapy
  • Digoxin
  • Anticoagulants and Antiplatelets
  • Antiarrhythmic Agents
• Section 8: Disease Management in Heart Failure
  • Education and Counseling
  • Disease Management Programs
  • Advance Directives and End-of-Life Care
• Section 9: Electrophysiologic Testing and the Use of Devices in Heart Failure
  • General Considerations
  • Electrophysiologic Testing and Evaluation of Syncope
  • Prophylactic ICD Placement
  • Biventricular Resynchronization Pacing
  • Dual Chamber Pacemakers
• Section 10: Surgical Approaches to the Treatment of Heart Failure
• Section 11: Evaluation and Management of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction
• Section 12: Evaluation and Management of Patients With Acute Decompensated Heart Failure
• Section 13: Evaluation and Therapy for Heart Failure in the Setting of Ischemic Heart Disease
  • Evaluation for CAD
  • Therapy for Patients With HF and CAD
• Section 14: Managing Patients With Hypertension and Heart Failure
  • Asymptomatic or Symptomatic LV Hypertrophy or LV Dysfunction Without LV Dilation (Preserved EF)
  • Asymptomatic LV Dysfunction With LV Dilation and a Low EF
  • Symptomatic LV Dysfunction With LV Dilation and Low EF
• Section 15: Management of Heart Failure in Special Populations
  • Elderly Patients With HF
  • HF in Women
  • HF in African Americans
• Section 16: Myocarditis: Current Treatment
• Acknowledgment
• References
• Copyright

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 individual 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 individual patient management. These characteristics make HF an ideal candidate for practice guidelines. The 2006 Heart Failure Society of America comprehensive practice guideline addresses the full range of evaluation, care, and management of patients with HF.

Key Words: Heart failure, Practice guidelines

Committee Members

Kirkwood F. Adams, Jr, MD¹ (Co-Chair)

JoAnn Lindenfeld, MD² (Co-Chair)

J. Malcolm O. Arnold, MDBarry M. Massie, MD

David W. Baker, MDMandeep R. Mehra, MD

Denise H. Barnard, MDAlan B. Miller, MD

Kenneth Lee Baughman, MDDebra K. Moser, RN, DNSc

John P. Boehmer, MDJ. Herbert Patterson, PharmD

Prakash Deedwania, MDRichard J. Rodeheffer, MD

Sandra B. Dunbar, RN, DSNJonathan Sackner-Bernstein, MD

Uri Elkayam, MDMarc A. Silver, MD

Mihai Gheorghiade, MDRandall C. Starling, MD, MPH

Jonathan G. Howlett, MDLynne Warner Stevenson, MD

Marvin A. Konstam, MDLynne E. Wagoner, MD

Marvin W. Kronenberg, MD

Executive Council

Gary S. Francis, MD, President

Michael R. Bristow, MD, PhDPeter P. Liu, MD

Jay N. Cohn, MDDouglas L. Mann, MD

Wilson S. Colucci, MDIleana L. Piña, MD

Barry H. Greenberg, MDSusan J. Pressler, RN, DNS

Thomas Force, MDHani N. Sabbah, PhD

Harlan M. Krumholz, MDClyde W. Yancy, MD

Table of Contents

Section 1: Development and Implementation of a Comprehensive Heart Failure Practice Guideline11

Section 2: Conceptualization and Working Definition of Heart Failure13

Section 3: Prevention of Ventricular Remodeling, Cardiac Dysfunction, and Heart Failure14

Section 4: Evaluation of Patients for Ventricular Dysfunction and Heart Failure14

Section 5: Management of Asymptomatic Patients With Reduced Left Ventricular Ejection Fraction17

Section 6: Nonpharmacologic Management and Health Care Maintenance in Patients With Chronic Heart Failure18

Section 7: Heart Failure in Patients With Left Ventricular Systolic Dysfunction19

Section 8: Disease Management in Heart Failure24

Section 9: Electrophysiologic Testing and the Use of Devices in Heart Failure27

Section 10: Surgical Approaches to the Treatment of Heart Failure27

Section 11: Evaluation and Management of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction28

Section 12: Evaluation and Management of Patients With Acute Decompensated Heart Failure29

Section 13: Evaluation and Therapy for Heart Failure in the Setting of Ischemic Heart Disease32

Section 14: Managing Patients With Hypertension and Heart Failure33

Section 15: Management of Heart Failure in Special Populations34

Section 16: Myocarditis: Current Treatment35

References35

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Section 1: Development and Implementation of a Comprehensive Heart Failure Practice Guideline 

Introduction 

Heart failure (HF) is a syndrome characterized by high mortality, frequent hospitalization, poor quality of life, and a complex therapeutic regimen. Knowledge about HF is accumulating so rapidly that individual clinicians may be unable to synthesize new information into effective principles of patient care. Trial data, though valuable, often do not give adequate direction for individual patient management.

Given the complex and changing picture of HF and the accumulation of evidence-based HF therapy, it is not possible for the clinician to rely solely on personal experience and observation to guide therapeutic decisions. The prognosis of individual patients differs considerably, making it difficult to generalize. Treatments might not dramatically improve symptoms of the disease process, yet might provide important reductions or delays in morbid events and deaths. The assessment of specific therapeutic outcomes is complicated by the potential differential impact of various cotherapies.

The complexity of HF, its high prevalence in society, and the availability of evidence supporting certain therapeutic options make it an ideal candidate for practice guidelines. The first HF guideline developed by the Heart Failure Society of America (HFSA) had a narrow scope, concentrating on the pharmacologic treatment of chronic, symptomatic left ventricular dysfunction.¹ It did not consider subsets of the clinical syndrome of HF, such as acute decompensated HF and “diastolic dysfunction,” or issues such as prevention. The current comprehensive guideline addresses the full range of evaluation, care and management of patients with HF, including acute HF, disease management, and HF in special populations. It represents a continuation of important contributions already made to the field of HF guidelines by HFSA members.², ³, ⁴, ⁵, ⁶

HFSA Guideline Approach to Medical Evidence 

Two considerations are critical in the development of practice guidelines: assessing level of evidence and determining strength of recommendation. Strength of evidence is determined both by the type of evidence available and the assessment of validity, applicability, and certainty of a specific type of evidence. Following the lead of previous guidelines, strength of evidence in this guideline is heavily dependent on the source or type of evidence used. The HFSA guideline process has used three grades (A, B, or C) to characterize the type of evidence available to support specific recommendations (Table 1.2).

Table 1.2. Relative Weight of Evidence Used to Develop HFSA Practice Guideline

Hierarchy of Types of Evidence
Level A	Randomized, Controlled, Clinical Trials
	May be assigned based on results of a single trial
Level B	Cohort and Case-Control Studies
	Post hoc, subgroup analysis, and meta-analysis
	Prospective observational studies or registries
Level C	Expert Opinion
	Observational studies–epidemiologic findings
	Safety reporting from large-scale use in practice

It must be recognized, however, that the evidence supporting recommendations is based largely on population responses that may not always apply to individuals within the population. Therefore, data may support overall benefit of 1 treatment over another but cannot exclude that some individuals within the population may respond better to the other treatment. Thus guidelines can best serve as evidence-based recommendations for management, not as mandates for management in every patient. Furthermore, it must be recognized that trial data on which recommendations are based have often been carried out with background therapy not comparable to therapy in current use. Therefore, physician decisions regarding the management of individual patients may not always precisely match the recommendations. A knowledgeable physician who integrates the guidelines with pharmacologic and physiologic insight and knowledge of the individual being treated should provide the best patient management.

Randomized controlled clinical trials provide what is considered the most valid form of guideline evidence. The HFSA Guideline Committee typically has accepted a single randomized, controlled, outcome-based clinical trial as sufficient for level A evidence. However, randomized clinical trial data, whether derived from one or multiple trials, have not been taken simply at face value. They have been evaluated for: (1) endpoints studied, (2) level of significance, (3) reproducibility of findings, (4) generalizability of study results, and (5) sample size and number of events on which outcome results are based.⁷

The HFSA guideline process also considers evidence arising from cohort studies or smaller clinical trials with physiologic or surrogate endpoints. This level B evidence is derived from studies that are diverse in design and may be prospective or retrospective in nature. They may involve subgroup analyses of clinical trials or have a case-control or propensity design using a matched subset of trial populations. Dose-response studies, when available, may involve all or a portion of the clinical trial population. These types of evidence have well-recognized, inherent limitations. Nevertheless, their value may be weighed through attention to factors such as prespecification of hypotheses in cohort analyses and replication of findings within different populations.

The present HFSA guideline makes extensive use of expert opinion, or C-level evidence. The need to formulate recommendations based on level C evidence is driven primarily by a paucity of scientific evidence in many areas critical to a comprehensive guideline. For example, the diagnostic process and the steps used to evaluate and monitor patients with established HF have not been the subject of clinical studies that formally test the validity of one approach versus another. In areas such as these, recommendations must be based on expert opinion or go unaddressed.

HFSA Guideline Approach to Strength of Recommendation 

Although level of evidence is important, the strength given to specific recommendations is critical. The process used to determine the strength of individual recommendations is complex. The goal of guideline development is to achieve the best recommendations for evaluation and management, considering not only efficacy, but the cost, convenience, side effect profile, and safety of various therapeutic approaches. The HFSA Guideline Committee often determined the strength of a recommendation by the “totality of evidence,” which is a synthesis of all types of available data, pro and con, about a particular therapeutic option.

Most guidelines have several strengths, ranging from “recommended,” to “should or may be considered,” to “not recommended.” The HFSA guideline employs the categorization outlined in Table 1.3. When the available evidence is considered to be insufficient or too premature, or consensus fails, issues are labeled unresolved and included as appropriate at the end of the relevant section.

Table 1.3. HFSA System for Classifying the Strength of Recommendations

Process of Guideline Development 

Key steps in the development of this guideline are listed in Table 1.4.⁸ Having determined the broad scope of the current guideline, members of the Guideline Committee were asked to identify the relevant medical evidence in assigned sections. Sources identified were reviewed by the Committee as a whole and then by the Executive Council of the HFSA. Evidence was then evaluated for relative value and strength, as described earlier.

Table 1.4. Steps in the Development of the HFSA Practice Guideline

The process of moving from ideas of recommendations to a final document includes many stages of evaluation and approval. Every section, once written, had a lead reviewer and 2 additional reviewers. After a rewrite, each section was assigned to another review team, which led to a version reviewed by the Committee as a whole and then the HFSA Executive Council, representing 1 more level of expertise and experience. Out of this process emerged the final document.

The development of a guideline involves the selection of individuals with expertise and experience to drive the process of formulating specific recommendations and producing a written document. The role of these experts goes well beyond the formulation of recommendations supported by expert opinion.

Experts involved in the guideline process must function as a group, not as isolated individuals. Expert opinion is not always unanimous. Interpretations of data vary. Disagreements arise over the generalizability and applicability of trial results to various patient subgroups. Experts are influenced by their own experiences with particular therapies, but still generally agree on the clinical value of trial data. Discomfort with the results of trials reported as positive or negative generally focus on factors that potentially compromise the evidence. There are no absolute rules for downgrading or upgrading trial results or for deciding that the limitations of the trial are sufficient to negate what has been regarded as a traditionally positive or negative statistical result.

The HFSA Guideline Committee sought resolution of difficult cases through consensus building. Written documents were essential to this process, because they provided the opportunity for feedback from all members of the group. On occasion, consensus of Committee opinion was sufficient to override positive or negative results of almost any form of prior evidence.

The involvement of many groups in the development of this guideline helped avoid the introduction of bias, which can be personal, practice-based, or based on financial interest. Committee members and reviewers from the Executive Council received no direct financial support from the HFSA or any other source for the development of the guideline. Administrative support was provided by the HFSA staff, and the writing of the document was performed on a volunteer basis by the Committee. Financial relationships that might represent conflicts of interest were collected for all members of the Guideline Committee and of the Executive Council, who were asked to disclose potential conflicts and recuse themselves from discussions when necessary.

The value of a practice guideline is significantly influenced by the scope of its dissemination. The current document will be implemented on the Internet both for file transfer and as a hypertext source of detailed knowledge concerning HF. Development of concise summaries of the recommendations in card format and translation of the recommendations to portable computing devices is envisioned.

An important final consideration is the continuity of the guideline development process. The intent is to create a “living document” that will be updated and amended as necessary to ensure continuing relevance. The rapid development of new knowledge in HF from basic and clinical research and the continuing evolution of pharmacologic and device therapy for this condition provides a strong mandate for timely updates. The HFSA intends to undertake targeted reviews and updates in areas where new research has implications for practice.

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Section 2: Conceptualization and Working Definition of Heart Failure 

HF is a syndrome rather than a primary diagnosis. It has many potential etiologies, diverse clinical features, and numerous clinical subsets. Patients may have a variety of primary cardiovascular diseases and never develop cardiac dysfunction, and those in whom cardiac dysfunction is identified through testing may never develop clinical HF. In addition to cardiac dysfunction, other factors, such as vascular stiffness and renal sodium handling, play major roles in the manifestation of the syndrome of HF.

Patients at risk for many cardiovascular diseases are at risk for HF. Early identification and treatment of risk factors is perhaps the most significant step in limiting the public health impact of HF.⁹, ¹⁰ Emphasis on primary and secondary prevention is particularly critical because of the difficulty of successfully treating left ventricular (LV) dysfunction, especially when severe.⁹, ¹⁰

Although HF is progressive, current therapy may provide stability and even reversibility. Therapy with angiotensin-converting enzyme (ACE) inhibitors (or angiotensin receptor blockers [ARB]) and β-blockers can lead to partial reversal or to slowing of remodeling. Because of this prolonged survival, comorbid conditions, such as coronary artery disease or renal failure, can progress, complicating treatment.

Although HF may be caused by a variety of disorders, this working definition focuses on HF due primarily to the loss or dysfunction of myocardial muscle or interstitium.

HF is a syndrome caused by cardiac dysfunction, generally resulting from myocardial muscle dysfunction or loss and characterized by LV dilation or hypertrophy. Whether the dysfunction is primarily systolic or diastolic or mixed, it leads to neurohormonal and circulatory abnormalities, usually resulting in characteristic symptoms such as fluid retention, shortness of breath, and fatigue, especially on exertion. In the absence of appropriate therapeutic intervention, HF is usually progressive at the levels of cardiac function and clinical symptoms. The severity of clinical symptoms may vary substantially during the course of the disease process and may not correlate with changes in underlying cardiac function. Although HF is progressive and often fatal, patients can be stabilized, and myocardial dysfunction and remodeling may improve, either spontaneously or as a consequence of therapy.

In physiologic terms, HF is a syndrome characterized by elevated cardiac filling pressure and/or inadequate peripheral oxygen delivery, at rest or during stress, caused by cardiac dysfunction.

HF is often classified as HF with abnormal systolic function versus HF with preserved systolic function. Although not truly equivalent, these classifications often consider normal systolic function and normal ejection fraction to be the same. Myocardial remodeling often precedes the clinical syndrome of HF. Additional definitions are provided in Table 2.1.

Table 2.1. Additional HF Definitions

“HF With Reduced LVEF”	A clinical syndrome characterized by signs and symptoms of HF and reduced LVEF. Most commonly associated with LV chamber dilation.
Sometimes:
“HF With a Dilated Left Ventricle”
“HF With a Preserved LVEF”	A clinical syndrome characterized by signs and symptoms of HF with preserved LVEF. Most commonly associated with a nondilated LV chamber. May be the result of valvular disease or other causes (Section 11).
Sometimes:
“HF With a Nondilated LV”
“Myocardial Remodeling”	Pathologic myocardial hypertrophy or dilation in response to increased myocardial stress. These changes are generally accompanied by pathologic changes in the cardiac interstitium. Myocardial remodeling is generally a progressive disorder.

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Section 3: Prevention of Ventricular Remodeling, Cardiac Dysfunction, and Heart Failure 

Epidemiologic, clinical, and basic research have identified a number of antecedent conditions that predispose individuals to HF and its predecessors, LV remodeling and dysfunction.¹¹, ¹², ¹³, ¹⁴, ¹⁵, ¹⁶, ¹⁷, ¹⁸, ¹⁹ Recognition that many of these risk factors can be modified and that treating HF is difficult and costly has caused attention to focus on preventive strategies for HF. Treatment of systemic hypertension, with or without LV hypertrophy, reduces the development of HF.⁹, ²⁰, ²¹, ²², ²³, ²⁴, ²⁵, ²⁶, ²⁷ Prevention of myocardial infarction (MI) in patients with atherosclerotic cardiovascular disease is a critical intervention, since occurrence of MI confers an 8- to 10-fold increased risk for subsequent HF.²⁴ Other modifiable risk factors include diabetes, hyperlipidemia, obesity, valvular abnormalities, alcohol, certain illicit drugs, and some cardiotoxic medications.²⁸ ACE inhibitors are recommended for use in patients at high risk for the development of HF, and β-blockers are recommended for patients with prior MI.

Recommendations for Patients With Risk Factors for Ventricular Remodeling, Cardiac Dysfunction, and Heart Failure 

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Section 4: Evaluation of Patients for Ventricular Dysfunction and Heart Failure 

Patients undergoing evaluation for ventricular dysfunction and HF fall into 3 general groups: (1) patients at risk of developing HF, (2) patients suspected of having HF based on signs and symptoms or incidental evidence of abnormal cardiac structure or function, and (3) patients with symptomatic HF.

Evaluation of Patients at Risk 

Patients identified as at risk for HF require aggressive management of modifiable risk factors. Patients with risk factors may have undetected abnormalities of cardiac structure or function. In addition to risk factor reduction, these patients require careful assessment for the presence of symptoms of HF and, depending on their underlying risk, may warrant noninvasive evaluation of LV structure and function.

Evaluation of Patients Suspected of Having HF 

The evaluation of patients suspected of having HF focuses on interpretation of signs and symptoms that have led to the consideration of this diagnosis. A careful history and physical examination, combined with evaluation of cardiac structure and function, should be undertaken to determine the cause of symptoms and to evaluate the degree of underlying cardiac pathology.

Initial Evaluation of Patients With HF 

The evaluation of patients with an established diagnosis of HF is undertaken to identify the etiology, assess symptom nature and severity, determine functional impairment, and establish a prognosis. Follow-up of patients with HF or ventricular dysfunction involves continuing reassessment of symptoms, functional capacity, prognosis, and therapeutic effectiveness.

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Section 5: Management of Asymptomatic Patients With Reduced Left Ventricular Ejection Fraction 

LV remodeling and reduced EF should be distinguished from the syndrome of clinical HF. When LVEF is reduced (<40%), but there are no signs and symptoms of HF, the condition frequently is referred to as asymptomatic LV dysfunction (ALVD). It is now well recognized that there may be a latency period when the EF is reduced before the development of symptomatic HF. Although most attention in the HF literature has centered on patients with symptoms, evidence now indicates that ALVD is more common than overt HF. The recent realization that therapies aimed at symptomatic HF may improve outcomes in patients with ALVD has increased the importance of recognizing and treating patients with this condition.

The management of patients with ALVD focuses on controlling cardiovascular risk factors and on the prevention or reduction of progressive ventricular remodeling. Exercise, smoking cessation, hypertension control, as well as treatment with ACE inhibitors (or ARBs) and β-blockers, all have a potential role in the treatment of this syndrome.

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Section 6: Nonpharmacologic Management and Health Care Maintenance in Patients With Chronic Heart Failure 

Nonpharmacologic management strategies represent an important contribution to HF therapy. They can significantly impact patient stability, functional capacity, mortality, and quality of life.

Diet and Nutrition 

In addition to the primary concern of controlling body weight, dietary concerns focus on restricting salt and fluid intake.

Other Therapies 

Specific Activity and Lifestyle Issues 

HF is a syndrome with an enormous impact on the quality of life of patients and families. HF can affect employment, relationships, leisure activities, eating, sleeping, and sexual activity—to name just a few critical areas. Physicians have a significant opportunity to improve their patients' quality of life by initiating discussion regarding these issues and providing education, feedback, and support.

Health Care Maintenance Issues 

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Section 7: Heart Failure in Patients With Left Ventricular Systolic Dysfunction 

There are 3 primary issues that must be considered when treating HF patients with LV systolic dysfunction: (1) improving symptoms and quality of life, (2) slowing the progression of cardiac and peripheral dysfunction, and (3) reducing mortality. General measures, such as salt restriction, weight loss, lipids control, and other nonpharmacologic measures are addressed in Section 6. Pharmacologic approaches to symptom control, including diuretics, vasodilators, intravenous inotropic drugs, anticoagulants, and antiplatelet agents, are discussed at the end of this section.

Two classes of agents have become the recommended cornerstone of therapy to delay or halt progression of cardiac dysfunction and improve mortality: ACE inhibitors and β-blockers. Even though these agents are underused in the treatment of HF, new classes of agents have been added that show an impact on mortality, complicating decisions about optimal pharmacologic therapy. These include ARBs, aldosterone antagonists, and the combination of hydralazine and an oral nitrate.

ACE Inhibitors 

There is compelling evidence that ACE inhibitors should be used to inhibit the renin-angiotensin system in all HF patients with LV systolic dysfunction, whether or not they are symptomatic. Several large clinical trials have demonstrated improvement in morbidity and mortality in HF patients with LV dysfunction, both chronically and post-MI.²⁹, ³⁰, ³¹

β-Adrenergic Receptor Blockers 

β-blocker therapy remains a major advance in the treatment of patients with LV systolic dysfunction. Along with ACE inhibitors, this class of drug is now established as routine therapy in patients with LV systolic dysfunction. This therapy is well tolerated by a large majority of patients with HF, even those with comorbid conditions such as diabetes mellitus, chronic obstructive lung disease, and peripheral vascular disease.

Angiotensin Receptor Blockers (ARBs) 

Both ACE inhibitors and ARBs inhibit the renin-angiotensin-aldosterone system, but by different mechanisms. ACE inhibitors block the enzyme responsible for converting angiotensin I to angiotensin II and for degrading various kinins. However, during chronic therapy, angiotensin II levels are not completely suppressed by ACE inhibitors. ARBs block the effects of angiotensin II on the AT1 receptor, independent of the source of angiotensin II production. The addition of ARBs to ACE inhibitors in patients with chronic HF might provide additional blockade of the renin-angiotensin-aldosterone system, and clinical trials demonstrate added therapeutic benefit. ARBs have been demonstrated to be well tolerated in randomized trials of patients judged to be intolerant of ACE inhibitors by their clinicians, although these primarily reflect intolerance from cough, skin rashes, and angioedema. Both drugs have similar effects on blood pressure, renal function, and potassium.

Aldosterone Antagonists 

Sustained activation of aldosterone appears to play an important role in the pathophysiology of HF.³², ³³ Although ACE inhibition may transiently decrease aldosterone secretion, there are diverse stimuli other than angiotensin II for the production of this hormone.³⁴ Studies suggest a rapid return of aldosterone to levels similar to those before ACE inhibition.³⁵ Aldosterone-receptor blockers have been shown to be effective in post MI HF patients already on standard therapy. The selective aldosterone antagonist, eplerenone avoids some of the potential side effects of spironolactone, but creatinine clearance and potassium must be carefully monitored.

Hydralazine and Oral Nitrates 

Polypharmacy 

Polypharmacy is required for optimal management to slow progression and improve outcome in patients with LV systolic dysfunction. An ACE inhibitor plus a β-blocker is standard background therapy. An ARB can be substituted for an ACE inhibitor if indicated or desired. An ARB can be added to an ACE inhibitor in individuals in whom β-blocker is contraindicated or not tolerated. The optimal choice of additional drug therapy to further improve outcome in patients already treated with 2 of these 3 drugs is not firmly established. The choice among agents may be influenced by the patient's age, renal function, serum potassium, racial background, and severity of the clinical syndrome. Certain combinations require careful monitoring.

Diuretic Therapy 

Loop and distal tubular diuretics are necessary adjuncts in the medical therapy for HF when symptoms are due to sodium and water retention. Diuretics reduce congestive symptoms and signs and can be titrated as needed to restore euvolemia and to reach an estimated “dry” weight goal for the patient. Relief of signs and symptoms must be achieved without causing side effects, particularly symptomatic hypotension or worsening renal function. Loop diuretics, which act on the ascending limb of the renal medullary loop of Henle, are considered the diuretic class of choice for the treatment of HF.

Digoxin 

Although little controversy exists as to the benefit of digoxin in patients with symptomatic LV systolic dysfunction and concomitant atrial fibrillation, the debate continues over its role in patients with normal sinus rhythm.

Anticoagulants and Antiplatelets 

Patients with HF are recognized to be at increased risk for arterial or venous thromboembolic events. In addition to atrial fibrillation and poor ventricular function, which promote stasis and increase the risk of thrombus formation, patients with HF have other manifestations of hypercoagulability. Evidence of heightened platelet activation, increased plasma and blood viscosity, and increased plasma levels of fibrinopeptide A, β-thromboglobulin, d-dimer, and von Willebrand factor have been found in many patients.³⁶, ³⁷, ³⁸ Though data are scarce or conflicting, warfarin, aspirin, and clopidogrel all have potential roles in therapy for HF patients at risk for thromboembolic events.

Antiarrhythmic Agents 

Ventricular arrhythmias are common in HF patients, and sudden cardiac death continues to account for a significant proportion of the mortality in this syndrome. Despite the obvious clinical need, antiarrhythmic drug therapy remains ineffective at reducing mortality in patients with HF. Furthermore, virtually all antiarrhythmic agents have been shown to have adverse hemodynamic effects sufficient to have negative consequences in patients with HF.

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Section 8: Disease Management in Heart Failure 

Education and Counseling 

The majority of HF care is done at home by the patient and family or caregiver. If these individuals do not know what is required or fail to see its importance, they will not participate effectively in care. For this reason, comprehensive education and counseling are the foundation for all HF management. The goals of education and counseling are to help patients, their families and caregivers acquire the knowledge, skills, strategies, and motivation necessary for adherence to the treatment plan and effective participation in self-care. The inclusion of family members and other caregivers is especially important, because HF patients often suffer from cognitive impairment, functional disabilities, multiple comorbidities, and other conditions that limit their ability to fully comprehend, appreciate, or enact what they learn.³⁹, ⁴⁰, ⁴¹, ⁴², ⁴³, ⁴⁴

Disease Management Programs 

HF disease management programs fall into three broad categories: (1) HF clinics,⁴⁵, ⁴⁶, ⁴⁷, ⁴⁸, ⁴⁹, ⁵⁰, ⁵¹, ⁵², ⁵³, ⁵⁴, ⁵⁵, ⁵⁶, ⁵⁷, ⁵⁸, ⁵⁹ (2) care delivered in the home or to patients who are at home,⁶⁰, ⁶¹, ⁶², ⁶³, ⁶⁴, ⁶⁵, ⁶⁶, ⁶⁷, ⁶⁸, ⁶⁹, ⁷⁰, ⁷¹, ⁷², ⁷³, ⁷⁴, ⁷⁵, ⁷⁶ and (3) telemonitoring.⁷⁷, ⁷⁸, ⁷⁹, ⁸⁰, ⁸¹, ⁸², ⁸³ HF clinics are disease management programs in which service is provided primarily in an outpatient clinic setting where patients come to receive care from practitioners with expertise in HF. HF clinics provide optimization of drug therapy, patient and family/caregiver education, and counseling, emphasis on self-care, vigilant follow-up, early attention to signs and symptoms of fluid overload, coordination of care with other providers, and increased access to the health care provider. Studies of HF disease management using the clinic and home-based care models provide convincing evidence that it is possible to significantly reduce rehospitalization rates and costs and improve functional status and quality of life for HF patients.

Advance Directives and End-of-Life Care 

Premature death from progressive decompensated HF or sudden cardiac death is frequent in HF, which has a worse prognosis than many common cancers.⁸⁴ The high mortality rate in HF makes advance directives and end-of-life care important issues in this population. However, recent advances in HF treatment have resulted in substantial reductions in mortality when proven therapies are applied. These advances apply both to the risk of sudden death and death from progressive heart failure. It is mandatory that discussions about advance directives occur in this context and that utilization of end of life care occur after full and appropriate application of evidence-based pharmacologic and nonpharmacologic treatments. These treatments must be allowed time to be beneficial, and issues such as access to care, compliance, and knowledge about HF must be addressed. Moreover, clinicians must recognize that use of end-of-life care does not mandate abandonment of HF therapies, which may effectively ease symptoms and continue to improve quality of life. Patients with HF and their caregivers often do not appreciate the severity or terminal nature of their illness. HF is a chronic disease, but can progress to a terminal condition. When patients develop a persistent pattern of refractory HF despite aggressive medical therapy, it is important to acknowledge this development.

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Section 9: Electrophysiologic Testing and the Use of Devices in Heart Failure 

Perhaps no area of HF therapy has changed more in recent years than the use of implanted devices as a treatment option. Critical issues in the selection of patients to receive these devices include the severity of the disease and the status of underlying medical therapy.

General Considerations 

Electrophysiologic Testing and Evaluation of Syncope 

Prophylactic ICD Placement 

Biventricular Resynchronization Pacing 

Dual Chamber Pacemakers 

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Section 10: Surgical Approaches to the Treatment of Heart Failure 

Despite advances in medical management of HF, there remain circumstances in which surgical procedures are the only or the best treatment option. These include heart transplantation, the longest accepted surgical therapy, and procedures that (1) repair the heart, (2) reshape it, or (3) replace all or part of heart function.

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Section 11: Evaluation and Management of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction 

A substantial number of patients with HF have preserved LVEF, variably defined as an LVEF >40%, >45%, or >50%.⁸⁵, ⁸⁶ HF with preserved LVEF is not a distinct condition, but rather a syndrome with numerous possible causative or comorbid conditions, including hypertension, diabetes mellitus, vascular stiffness, renal impairment, and atrial fibrillation. The ventricle in HF with preserved LVEF is characterized by hypertrophy,⁸⁷ increased extracellular matrix,⁸⁸ and abnormal calcium handling with delayed relaxation.⁸⁹, ⁹⁰ Activation of the neurohormonal milieu, including the renin-angiotensin system and the sympathetic nervous system, is common. The diagnosis of HF with preserved LVEF can be made by the combination of (1) clinical signs and symptoms of HF and (2) findings of preserved or relatively preserved LVEF using an imaging method.

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Section 12: Evaluation and Management of Patients With Acute Decompensated Heart Failure 

Studies demonstrate that the majority of patients hospitalized with HF have evidence of systemic hypertension on admission and commonly have preserved LVEF. Most hospitalized patients have significant volume overload, and congestive symptoms predominate. Patients with severely impaired systolic function, reduced blood pressure, and symptoms resulting from poor end-organ perfusion are in the distinct minority. Natural history studies have shown that acute decompensated HF (ADHF) represents a period of high risk for patients, during which their likelihood of death and rehospitalization is significantly greater than for a comparable period of chronic, but stable HF.⁹¹

There is a paucity of controlled clinical trial data to define optimal treatment for patients with acute HF. The few trials conducted have focused primarily on symptom relief, not outcomes, and have mainly enrolled patients with reduced EF who were not hypertensive.

Relief of congestion and volume overload generally is accomplished with sodium and fluid restriction and the use of diuretics. Intravenous vasodilators may be added. Agents to consider for the improvement of hemodynamic parameters include intravenous nitroglycerin, sodium nitroprusside, and nesiritide. The use of inotropes should be severely limited. Discharge evaluation and planning for follow-up are important factors in reducing readmission.

12.2.Hospital admission is recommended for patients presenting with ADHF when the clinical circumstances listed in Table 12.1 (a) are present.

Table 12.1. Recommendations for Hospitalizing Patients Presenting With ADHF

Recommendation	Clinical Circumstances
(a)Hospitalization Recommended	Evidence of severely decompensated HF, including:
	•Hypotension
	•Worsening renal function
	•Altered mentation
	Dyspnea at rest
	•Typically reflected by resting tachypnea
	•Less commonly reflected by oxygen saturation <90%
	Hemodynamically significant arrhythmia
	•Including new onset of rapid atrial fibrillation
	Acute coronary syndromes
(b)Hospitalization Should Be Considered	Worsened congestion
	•Even without dyspnea
	•Typically reflected by a weight gain ≥5 kilograms
	Signs and symptoms of pulmonary or systemic congestion
	•Even in the absence of weight gain
	Major electrolyte disturbance
	Associated comorbid conditions
	•Pneumonia
	•Pulmonary embolus
	•Diabetic ketoacidosis
	•Symptoms suggestive of transient ischemic accident or stroke
	Repeated ICD firings
	Previously undiagnosed HF with signs and symptoms of systemic or pulmonary congestion

12.4.Patients admitted with ADHF should be carefully monitored. It is recommended that the items listed in Table 12.4 be assessed at the stated frequencies. (Strength of Evidence = C)

Table 12.4. Monitoring Recommendations for Patients Admitted for ADHF

Frequency	Value	Specifics
At least daily	Weight	Determine after voiding in the morning
		Account for possible increased food intake due to improved appetite
At least daily	Fluid intake and output
More than daily	Vital signs	Including orthostatic blood pressure
At least daily	Signs	Edema
		Ascites
		Pulmonary rales
		Hepatomegaly
		Increased jugular venous pressure
		Hepatojugular reflux
		Liver tenderness
At least daily	Symptoms	Orthopnea
		Paroxysmal nocturnal dyspnea
		Nocturnal cough
		Dyspnea
		Fatigue
At least daily	Electrolytes	Potassium
		Sodium
At least daily	Renal function	BUN
		Serum creatinine

12.23.It is recommended that criteria in Table 12.7 be met before a patient with HF is discharged from the hospital. (Strength of Evidence = C)

Table 12.7. Discharge Criteria for Patients with HF

Recommended for all HF patients	•Exacerbating factors addressed.
	•At least near optimal volume status achieved.
	•Transition from intravenous to oral diuretic successfully completed.
	•Patient and family education completed.
	•At least near optimal pharmacologic therapy achieved (Sections 7 and 11)
	•Follow-up clinic visit scheduled, usually for 7–10 days
Should be considered for patients with advanced HF or recurrent admissions for HF	•Oral medication regimen stable for 24 hours
	•No intravenous vasodilator or inotropic agent for 24 hours
	•Ambulation before discharge to assess functional capacity after therapy
	•Plans for postdischarge management (scale present in home, visiting nurse or telephone follow up generally no longer than 3 days after discharge)
	•Referral for disease management

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Section 13: Evaluation and Therapy for Heart Failure in the Setting of Ischemic Heart Disease 

The most common cause of chronic heart failure HF is no longer hypertension or valvular heart disease; it is coronary artery disease (CAD). Managing HF in patients with CAD or a history of CAD is significantly different than managing HF from primary cardiomyopathy. Antiplatelet agents, smoking cessation, and lipid-lowering therapy are particularly important interventions in patients with HF from CAD.⁹² HF in the setting of CAD is a heterogeneous condition with several factors contributing to LV systolic dysfunction and HF symptoms. After an MI, there is loss of functioning myocytes, development of myocardial fibrosis, and subsequent LV remodeling, resulting in chamber dilatation and neurohormonal activation—all leading to progressive dysfunction of the remaining viable myocardium.⁹³ This well-recognized process may be ameliorated after an acute MI by myocardial revascularization,⁹⁴, ⁹⁵, ⁹⁶ and by medical therapy with ACE inhibitors or ARBs,⁹⁷, ⁹⁸ β-blockers,⁹⁹ and aldosterone antagonists.¹⁰⁰

The majority of patients surviving an MI have significant atherosclerotic disease in coronary arteries other than the infarct-related vessel.¹⁰¹ Another important mechanism for systolic dysfunction with additive effects on LV performance is myocardial hibernation,¹⁰² a process in which myocardial contraction is downregulated in response to chronic reduction in myocardial blood supply.

In addition to risk factor reduction, therapy is based on the use of antiplatelets, ACE inhibitors (or ARBs), and β-blockers, with other agents used to relieve symptoms such as angina.

Evaluation for CAD 

Therapy for Patients With HF and CAD 

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Section 14: Managing Patients With Hypertension and Heart Failure 

Blood pressure is a simple measurement that assesses the interaction of heart function with vascular impedance. When heart function is normal the impedance is the main determinant of blood pressure and therefore pressure (systolic and mean) becomes a powerful risk factor for development of LV hypertrophy, increased myocardial oxygen consumption, coronary atherosclerosis, and subsequent HF.¹⁰³, ¹⁰⁴ Control of blood pressure in this setting is critical to prevent the development and progression of LV dysfunction.¹⁰⁵

When LV function is impaired, the relationship between impedance and cardiac function becomes more complex. Increases of impedance may impair LV emptying and thus not be reflected in a higher pressure. Under those circumstances therapy is aimed at lowering impedance, not at the blood pressure. Indeed, blood pressure may rise in response to effective therapy that improves LV emptying or reverses remodeling even if the impedance is reduced.

Asymptomatic or Symptomatic LV Hypertrophy or LV Dysfunction Without LV Dilation (Preserved EF) 

Asymptomatic LV Dysfunction With LV Dilation and a Low EF 

Symptomatic LV Dysfunction With LV Dilation and Low EF 

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Section 15: Management of Heart Failure in Special Populations 

Heart failure is a major problem in women, African Americans, and the elderly of both sexes and any race. The clinical conclusions based on trial data derived from predominately younger white male study populations generally apply equally to these groups. However, there are etiologic or pathophysiologic considerations specific to some of these groups that warrant attention if care is to be optimized. In the case of African Americans, who previously have been shown to not respond as well to ACE inhibitor therapy as whites, an indication now exists to consider the combination of hydralazine and isosorbide dinitrate as part of standard therapy.

Elderly Patients With HF 

HF in Women 

HF in African Americans 

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Section 16: Myocarditis: Current Treatment 

Myocarditis is a distinct clinical entity with a wide variety of cardiac manifestations including HF. Potential etiologies may include toxins, medications, physical agents, and, most importantly, infections. The most common forms appear to be postviral in origin. Ongoing myocardial inflammation may result in dilated cardiomyopathy, restrictive cardiomyopathy, or acute LV failure without dilatation. Controversy continues to surround the best approach to the management of patients considered to have myocarditis.

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Acknowledgment 

The Guideline Committee would like to thank the Executive Council for their review and comments; Barbara Riegel, RN, DNSc, (University of Pennsylvania) for her input in writing the Disease Management section; and Bart Galle, PhD, and Cheryl Yano (HFSA staff) for their administrative support.

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• 1 Heart Failure Program, University of North Carolina–Chapel Hill, Chapel Hill, North Carolina
• 2 Department of Cardiology, University of Colorado Health Sciences Center, Denver, Colorado