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

Abstract

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 readily and adequately synthesize new information into effective principles of care for patients with this syndrome. 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 situation is exacerbated because HF is now a chronic condition in most patients, meaning that the outcome of therapeutic decisions might not be apparent for several years. 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. Additional assumptions driving the development of HF guidelines are presented in Table 1.1Table 1.1Assumptions Underlying HFSA Practice GuidelineClinical decisions must be made.Lack of action is not an option.Correct course of action may not be readily apparent.Reasonably valid methods exist to address knowledge base and evaluate medical evidence.Data beyond randomized clinical trials exist that enhance medical decision making.Uncertainties remain concerning approaches to treatment after review of totality of medical evidence.Expert opinion has a role in management decisions.Experts with interest and commitment to the clinical problem and guideline process must be available. Open table in a new tab 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.1Guideline Committee for the Heart Failure Society of American HFSA guidelines for the management of patients with heart failure caused by left ventricular systolic dysfunction—pharmacological approaches.J Card Fail. 1999; 5: 357-382Abstract Full Text PDF PubMed Scopus (40) Google Scholar 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. It represents a continuation of important contributions already made to the field of HF guidelines by HFSA members.2Konstam M.A. Dracup K. Baker D. Bottorff M. Brooks N.H. Dacey R.A. et al.Evaluation and care of patients with left ventricular systolic dysfunction. Agency for Health Care Policy and Research, US Department of Health and Human Services, Rockville, MD1994Google Scholar, 3Guidelines for the evaluation and management of heart failure Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure).Circulation. 1995; 92: 2764-2784Crossref PubMed Google Scholar, 4Hunt S.A. Baker D.W. Chin M.H. Cinquegrani M.P. Feldman A.M. Francis G.S. et al.ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the International Society for Heart and Lung Transplantation; Endorsed by the Heart Failure Society of America.Circulation. 2001; 104: 2996-3007Crossref PubMed Scopus (1127) Google Scholar, 5The treatment of heart failure Task Force of the Working Group on Heart Failure of the European Society of Cardiology.Eur Heart J. 1997; 18: 736-753Crossref PubMed Scopus (402) Google Scholar, 6Liu P. Arnold M. Belenkie I. Howlett J. Huckell V. Ignazewski A. et al.The 2001 Canadian Cardiovascular Society consensus guideline update for the management and prevention of heart failure.Can J Cardiol. 2001; 17: 5E-25EPubMed Google Scholar HFSA Guideline Approach to Medical Evidence Two considerations are critical in the development of practice guidelines: assessing strength 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 1.2Relative Weight of Evidence Used to Develop HFSA Practice GuidelineHierarchy of Types of Evidence Level ARandomized, Controlled, Clinical Trials May be assigned based on results of a single trial Level BCohort and Case-Control Studies Post hoc, subgroup analysis, and meta-analysis Prospective observational studies or registries Level CExpert Opinion Observational studies–epidemiologic findings Safety Reporting from large-scale use in practice Open table in a new tab 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 one 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. Strength of Evidence A. Randomized controlled clinical trials provide what is considered the most valid form of guideline evidence. Some guidelines require at least 2 positive randomized clinical trials before the evidence for a recommendation can be designated level A. 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.7Califf R.M. Considerations in the design, conduct, and interpretation of quantitative clinical evidence.in: Topol E.J. Comprehensive cardiovascular medicine. Lippincott-Raven, Philadelphia1998: 1203-1221Google Scholar Strength of Evidence B. 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. Strength of Evidence C. 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. The value of expert opinion as a form of evidence remains disputed. Many contend that expert opinion is a weak form of observational evidence, based on practice experience and subject to biases and limitations. Advocates believe expert opinion represents a complex synthesis of observational insights into disease pathophysiology and the benefits of therapy in broad populations of patients. They stress the value of the interchange of experience and ideas among colleagues, who collectively treat thousands of patients. Through contact with numerous individual health care providers who may discuss patients with 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 of HF. Despite the case that can be made for its value, recommendations based on expert opinion alone have been limited to those circumstances when a definite consensus could be reached across the guideline panel and reviewers. HFSA Guideline Approach to Strength of Recommendation Determining Strength. 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. Totality of Evidence. Totality of evidence includes not only results of clinical trials, but also expert opinion and findings from epidemiologic and basic science studies. Agreement among various types of evidence, especially from different methodologies, increases the likelihood that a particular therapy is valuable. Although many equate evidence-based medicine with the results of a few individual clinical trials, the best judgment seems to be derived from a careful analysis of all available trial data combined with integration of results from the basic laboratory and the findings of epidemiologic studies. Scale of Strength. 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. There are several degrees of favorable recommendations and a single category for therapies felt to be not effective. The phrase “is recommended” should be taken to mean that the recommended therapy or management process should be followed as often as possible in individual patients. Exceptions are carefully delineated. “Should be considered” means that a majority of patients should receive the intervention, with some discretion involving individual patients. “May be considered” means that individualization of therapy is indicated (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 1.3HFSA System for Classifying the Strength of Recommendations“Is recommended”Part of routine careExceptions to therapy should be minimized“Should be considered”Majority of patients should receive the interventionSome discretion in application to individual patients should be allowed“May be considered”Individualization of therapy is indicated“Is not recommended”Therapeutic intervention should not be used Open table in a new tab Process of Guideline Development Key steps in the development of this guideline are listed in Table 1.4.8Adams K.F. Development and implementation of heart failure practice guidelines.in: Braunwald E. Heart failure: a companion to Braunwald's heart disease. Elsevier, Philadelphia2004: 567-578Google Scholar 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 1.4Steps in the Development of HFSA Practice GuidelineDetermine the scope of the practice guidelineIdentify the medical evidence relevant to the guidelineSpecify the type of evidence and relative weight of evidenceFormulate the strength of evidence usedEstablish therapeutic justification for the recommended therapiesFormulate recommendations of specific strengthCreate the initial documentDevelop a review process for the documentDisseminate the practice guidelineDetermine the life cycle of the document Open table in a new tab 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 two 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 one more level of expertise and experience. Out of this process emerged the final document. Consensus. 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 collective, 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. Unfortunately, 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. An open, dynamic discussion meant that no single voice was allowed to dominate. Written documents were essential to this process, because they provided the opportunity for feedback from all members of the group. On occasion, consensus of opinion was sufficient to override positive or negative results of almost any form of evidence. The HFSA process had a strong commitment to recommendations based on objective evidence rigorously reviewed by a panel of experts. Issues that caused difficulty for the HFSA guideline process were some of the more important ones faced by the committee, because they mirrored those that are often most challenging to clinicians in day-to-day practice. The foundation of the HFSA guideline process was the belief that the careful judgment of recognized opinion leaders in these controversial areas is more likely to be correct than ad hoc decisions made “on the spot” by physicians in practice. 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. Support was provided by the HFSA administrative staff, but the writing of the document was performed on a volunteer basis primarily by the committee. Financial relationships that might represent conflicts of interest were collected annually from all members of the guideline committee and the Executive Council. Current relationships are shown in Table 1.5.Table 1.5Guideline Committee and Executive Council Disclosure InformationName/CompanyConsultantScientific Advisory BoardOfficer, Board Member, Trustee, Owner, EmployeeResearch SupportLecturerRoyaltiesOther CompensationStocks or Bonds >$10,000Stock OptionsOtherKirkwood F. Adams Abbott✓ Actelion✓ Amgen✓✓ AstraZeneca✓✓✓ Biosite✓ Bristol-Myers Squibb✓✓ GlaxoSmithKline✓✓ Myogen✓✓✓ NitroMed✓ Novacardia✓ Otsuka America✓✓✓ Pfizer✓ Sanofi-Synthelabo✓✓ Scios✓✓✓ Vasogen✓Malcolm J. Arnold Pfizer✓✓ Sanofi-Synthelabo✓✓David W. Baker NoneDenise Barnard Actelion✓ Amgen✓ AstraZeneca✓ GlaxoSmithKline✓ Novartis✓ Orion Pharma Corp.✓ Pfizer✓ Vasogen✓Kenneth L. Baughman NoneJohn P. Boehmer Guidant✓✓✓✓ Impulse Dynamics✓ Medtronic✓Events Comm. Orqis✓ Paracor✓ Titan Pharmaceutical✓Michael R. Bristow ARCA Discovery✓✓✓ AstraZeneca✓ C2R✓ Cardiac Dimensions✓ Covalent✓ CVRx✓ Genzyme✓ GlaxoSmithKline✓ Guidant✓ Merck✓ Mitsubishi✓ Mylan✓ Myogen✓✓✓ Novartis✓ Scios✓Jay N. Cohn Hypertension Diagnostics✓✓✓ Medtronic✓ NitroMed✓✓✓ Novartis✓Wilson Colucci Abbott✓ AstraZeneca✓ GlaxoSmithKline✓ Pharmacia✓Prakash C. Deedwania AstraZeneca✓✓✓ Pfizer✓✓Sandra B. Dunbar NoneUri Elkayam Amgen✓✓✓ Astella✓ GlaxoSmithKline✓✓✓ Otsuka✓✓ Pfizer✓ Savacor✓✓ Scios✓✓✓Thomas Force Merck✓ Schering Plough✓Gary S. Francis GlaxoSmithKline✓ Medtronic✓ Merck✓DSMB Otsuka✓✓ Pfizer✓ SciosDSMBMihai Gheorghiade GlaxoSmithKline✓✓ Medtronic✓ Otsuka✓✓ PBL✓✓ Pfizer✓ Sigma Tau✓Barry H. Greenberg AstraZeneca✓ CHF Solutions✓✓ GlaxoSmithKline✓✓✓ Merck✓ Novartis✓ Pfizer✓Jonathan G. Howlett AstraZeneca✓✓✓✓ Merck Frosst Canada✓✓ Novartis✓✓✓ Ortho Biotech✓✓✓✓ Pfizer✓Marvin A. Konstam Actelion✓ AstraZeneca✓✓ GlaxoSmithKline✓✓ Guidant✓ Medtronic✓ Merck✓✓ Novartis✓ Orqis Medical✓ Otsuka✓ Pfizer✓✓✓Marvin W. Kronenberg NoneHarlan M. Krumholz CV Therapeutics(Data)✓ United Healthcare✓✓ VHA, Inc.✓✓JoAnn Lindenfeld Novartis✓✓✓ Pfizer✓✓✓ AstraZeneca✓✓ Novacardia✓ Medtronic✓✓ Guidant✓✓ St Jude Medical✓ Otsuka✓Peter P. Liu Aventis-Sanofi✓ Pfizer✓Douglas L. Mann Acorn Cardiovascular✓✓ AstraZeneca✓ Biosite✓ Guidant✓ Pfizer✓Barry M. Massie Abbott✓ Bristol-Myers Squibb✓✓ GlaxoSmithKline✓✓ Novacardia✓✓ Novartis✓ Sanofi-Synthelabo✓✓✓Mandeep R. Mehra AstraZeneca✓✓ Bristol-Myers Squibb✓✓ Fujisawa Healthcare✓✓ GlaxoSmithKline✓✓ Guidant✓✓ Medtronic✓✓ Merck✓✓ Novartis✓✓ Pfizer✓✓ Roche✓✓ Scios✓✓Alan B. Miller Abbott✓ AstraZeneca✓✓ Bristol-Myers Squibb✓✓ CV Therapeutics✓ GlaxoSmithKline✓✓ King✓ Medtronic✓✓ Myogen✓ NitroMed✓✓ Novartis✓ Pfizer✓✓ Sanofi✓ Wyeth✓Debra K. Moser NoneJ. Herbert Patterson NoneIleana L. Piña AstraZeneca✓✓ Biosite✓ GlaxoSmithKline✓ Novartis✓Susan J. Pressler NoneRichard J. Rodeheffer NoneHani N. Sabbah Acorn Cardiovascular✓✓ Amgen✓ AnGes✓ AstraZeneca✓ BioControl✓✓ CV Therapeutics✓✓ CVRx✓✓ Guidant✓ Impulse Dynamics✓✓Jonathan Sackner-Bernstein Cephalon✓✓ GlaxoSmithKline✓✓✓ Otsuka✓ Pfizer✓Marc A. Silver CardioDynamics✓ GlaxoSmithKline✓ Medcon✓ Scios✓Randall C. Starling Acorn Cardiovascular✓✓ Cardiomens✓✓ Medtronic✓✓✓ Myocor✓✓ Novartis✓✓✓ Roche✓✓Lynne W. Stevenson Medtronic✓✓✓ Scios✓Lynne E. Wagoner GlaxoSmithKline✓ Medtronic✓ Scios✓ Wyeth✓Clyde W. Yancy GlaxoSmithKline✓✓ Scios✓✓✓ Open table in a new tab Dissemination and Continuity. The value of a practice guideline is significantly influenced by the scope of its dissemination. The first HFSA guideline was available on the Internet, and thousands of copies were downloaded. 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. Summary Practice guidelines have become a major part of the clinical landscape and seem likely to become more rather than less pervasive.9Woolf S.H. Practice guidelines: a new reality in medicine. I. Recent developments.Arch Intern Med. 1990; 150: 1811-1818Crossref PubMed Google Scholar Some may perceive guidelines as another mechanism for process management or as another instrument for cost control. But there is a more patient-centered rationale for their development, especially for a common, potentially debilitating, and often fatal syndrome such as HF. Despite advances in clinical trial methodology and the extensive use of studies to evaluate therapeutics and the care process, essential elements of the management process remain undefined for many clinical problems. HF is no exception. Traditionally, management guidelines were determined on an ad hoc basis by physicians and other health care providers in the field. The development and utilization of practice guidelines has emerged as an alternative strategy. The methodology of guideline development needs improvement, but when these documents are properly conceived and formulated, their importance to patient care seems evident. This HFSA guideline on HF is designed as a “living document,” which will continue to serve as a resource for helping patients with heart failure.