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2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure
A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America
* Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information.
† ACC/AHA Task Force on Clinical Practice Guidelines Liaison.
Biykem Bozkurt
Footnotes
* Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information. † ACC/AHA Task Force on Clinical Practice Guidelines Liaison.
* Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information.
* Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information. ‡ ACC/AHA Representative.
* Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information.
Gerasimos S. Filippatos
Footnotes
* Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information.
* Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information.
* Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information. ‡ ACC/AHA Representative.
* Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information.
* Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information. ¶ HFSA Representative.
* Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information.
* Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information. ¶ HFSA Representative.
* Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information.
* Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information. ‡ ACC/AHA Representative.
* Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information. † ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ‡ ACC/AHA Representative. § ACP Representative. ‖ ISHLT Representative. ¶ HFSA Representative. # CHEST Representative. ** ACC/AHA Task Force on Performance Measures Representative. †† AAFP Representative.
Former Task Force member; current member during the writing effort.
‡
Joaquin E. Cigarroa, MD, FACC
Lesley H. Curtis, PhD, FAHA
Lee A. Fleisher, MD, FACC, FAHA
Federico Gentile, MD, FACC
Samuel Gidding, MD, FAHA
Mark A. Hlatky, MD, FACC
John Ikonomidis, MD, PhD, FAHA
José Joglar, MD, FACC, FAHA
Susan J. Pressler, PhD, RN, FAHA
Duminda N. Wijeysundera, MD, PhD
Table of Contents
Preamble 630
1.
Introduction 632
1.1.
Methodology and Evidence Review 632
1.2.
Organization of the Writing Group 632
1.3.
Document Review and Approval 632
6.
Initial and Serial Evaluation of the HF Patient 632
6.3.
Biomarkers 633
6.3.1.
Biomarkers for Prevention: Recommendation 634
6.3.2.
Biomarkers for Diagnosis: Recommendation 634
6.3.3.
Biomarkers for Prognosis or Added Risk Stratification: Recommendations 634
7.
Treatment of Stages A to D 635
7.3.
Stage C 635
7.3.2.
Pharmacological Treatment for Stage C HF With Reduced Ejection Fraction: Recommendations 635
7.3.2.10.
Renin-Angiotensin System Inhibition With Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker or ARNI: Recommendations 635
7.3.2.11.
Ivabradine: Recommendation 635
7.3.3.
Pharmacological Treatment for Stage C HFpEF: Recommendations 639
9.
Important Comorbidities in HF 640
9.2.
Anemia: Recommendations 640
9.5.
Hypertension (New Section) 640
9.5.1.
Treating Hypertension to Reduce the Incidence of HF: Recommendation 640
9.5.2.
Treating Hypertension in Stage C HFrEF: Recommendation 641
9.5.3.
Treating Hypertension in Stage C HFpEF: Recommendation 641
9.6.
Sleep-Disordered Breathing: Recommendations 641
Appendix 1
Author Relationships With Industry and Other Entities (Relevant) 643
Appendix 2
Reviewer Relationships With Industry and Other Entities (Comprehensive) 644
Appendix 3
Abbreviations 645
References 646
Preamble
Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health. These guidelines, which are based on systematic methods to evaluate and classify evidence, provide a cornerstone for quality cardiovascular care. The ACC and AHA sponsor the development and publication of guidelines without commercial support, and members of each organization volunteer their time to the writing and review efforts. Guidelines are official policy of the ACC and AHA.
Intended Use
Practice guidelines provide recommendations applicable to patients with or at risk of developing cardiovascular disease. The focus is on medical practice in the United States, but guidelines developed in collaboration with other organizations may have a global impact. Although guidelines may be used to inform regulatory or payer decisions, their intent is to improve patients’ quality of care and align with patients’ interests. Guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances and should not replace clinical judgment.
Clinical Implementation
Guideline recommended management is effective only when followed by healthcare providers and patients. Adherence to recommendations can be enhanced by shared decision making between healthcare providers and patients, with patient engagement in selecting interventions based on individual values, preferences, and associated conditions and comorbidities.
Methodology and Modernization
The ACC/AHA Task Force on Clinical Practice Guidelines (Task Force) continuously reviews, updates, and modifies guideline methodology on the basis of published standards from organizations including the Institute of Medicine (
Committee on Standards for Systematic Reviews of Comparative Effectiveness ResearchInstitute of Medicine (U.S.) Finding What Works in Health Care: Standards for Systematic Reviews.
) and on the basis of internal reevaluation. Similarly, the presentation and delivery of guidelines are reevaluated and modified on the basis of evolving technologies and other factors to facilitate optimal dissemination of information at the point of care to healthcare professionals. Given time constraints of busy healthcare providers and the need to limit text, the current guideline format delineates that each recommendation be supported by limited text (ideally, <250 words) and hyperlinks to supportive evidence summary tables. Ongoing efforts to further limit text are underway. Recognizing the importance of cost-value considerations in certain guidelines, when appropriate and feasible, an analysis of the value of a drug, device, or intervention may be performed in accordance with the ACC/AHA methodology (
ACC/AHA statement on cost/value methodology in clinical practice guidelines and performance measures: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and Task Force on Practice Guidelines.
To ensure that guideline recommendations remain current, new data are reviewed on an ongoing basis, with full guideline revisions commissioned in approximately 6-year cycles. Publication of new, potentially practice-changing study results that are relevant to an existing or new drug, device, or management strategy will prompt evaluation by the Task Force, in consultation with the relevant guideline writing committee, to determine whether a focused update should be commissioned. For additional information and policies regarding guideline development, we encourage readers to consult the ACC/AHA guideline methodology manual (
Further evolution of the ACC/AHA clinical practice guideline recommendation classification system: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
ACCF/AHA clinical practice guideline methodology summit report: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
The evolution and future of ACC/AHA clinical practice guidelines: a 30-year journey: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
AHA/ACC/HHS strategies to enhance application of clinical practice guidelines in patients with cardiovascular disease and comorbid conditions: from the American Heart Association, American College of Cardiology, and U.S. Department of Health and Human Services.
The Task Force strives to avoid bias by selecting experts from a broad array of backgrounds. Writing committee members represent different geographic regions, sexes, ethnicities, races, intellectual perspectives/biases, and scopes of clinical practice. The Task Force may also invite organizations and professional societies with related interests and expertise to participate as partners, collaborators, or endorsers.
Relationships With Industry and Other Entities
The ACC and AHA have rigorous policies and methods to ensure that guidelines are developed without bias or improper influence. The complete relationships with industry and other entities (RWI) policy can be found online. Appendix 1 of the current document lists writing committee members’ relevant RWI. For the purposes of full transparency, writing committee members’ comprehensive disclosure information is available online. Comprehensive disclosure information for the Task Force is also available online.
Evidence Review and Evidence Review Committees
When developing recommendations, the writing committee uses evidence-based methodologies that are based on all available data (
Further evolution of the ACC/AHA clinical practice guideline recommendation classification system: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
ACCF/AHA clinical practice guideline methodology summit report: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
The evolution and future of ACC/AHA clinical practice guidelines: a 30-year journey: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
). Literature searches focus on randomized controlled trials (RCTs) but also include registries, nonrandomized comparative and descriptive studies, case series, cohort studies, systematic reviews, and expert opinion. Only key references are cited.
An independent evidence review committee (ERC) is commissioned when there are 1 or more questions deemed of utmost clinical importance that merit formal systematic review. This systematic review will strive to determine which patients are most likely to benefit from a drug, device, or treatment strategy and to what degree. Criteria for commissioning an ERC and formal systematic review include: a) the absence of a current authoritative systematic review, b) the feasibility of defining the benefit and risk in a time frame consistent with the writing of a guideline, c) the relevance to a substantial number of patients, and d) the likelihood that the findings can be translated into actionable recommendations. ERC members may include methodologists, epidemiologists, healthcare providers, and biostatisticians. When a formal systematic review has been commissioned, the recommendations developed by the writing committee on the basis of the systematic review are marked with“SR”.
Guideline-Directed Management and Therapy
The term guideline-directed management and therapy (GDMT) encompasses clinical evaluation, diagnostic testing, and pharmacological and procedural treatments. For these and all recommended drug treatment regimens, the reader should confirm the dosage by reviewing product insert material and evaluate the treatment regimen for contraindications and interactions. The recommendations are limited to drugs, devices, and treatments approved for clinical use in the United States.
Class of Recommendation and Level of Evidence
The Class of Recommendation (COR) indicates the strength of the recommendation, encompassing the estimated magnitude and certainty of benefit in proportion to risk. The Level of Evidence (LOE) rates the quality of scientific evidence that supports the intervention on the basis of the type, quantity, and consistency of data from clinical trials and other sources (Table 1) (
Further evolution of the ACC/AHA clinical practice guideline recommendation classification system: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
ACCF/AHA clinical practice guideline methodology summit report: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
Table 1Applying Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care* (Updated August 2015)
2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
) (2013 HF guideline) in areas in which new evidence has emerged since its publication. For this update and future heart failure (HF) guidelines, the Heart Failure Society of America (HFSA) has partnered with the ACC and AHA to provide coordinated guidance on the management of HF.
The scope of the focused update includes revision to the sections on biomarkers; new therapies indicated for stage C HF with reduced ejection fraction (HFrEF); updates on HF with preserved ejection fraction (HFpEF); new data on important comorbidities, including sleep apnea, anemia, and hypertension; and new insights into the prevention of HF.
This focused update represents the second part of a 2-stage publication; with the first part having been published as the “2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure” (
2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America.
), which introduced guidance on new therapies, specifically for the use of an angiotensin receptor–neprilysin inhibitor (ARNI) (valsartan/sacubitril) and a sinoatrial node modulator (ivabradine). That focused update was published concurrently with the European Society of Cardiology’s complete guideline, “2016 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure” (
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.
To identify key data that influence guideline recommendations, the Task Force and members of the 2013 HF guideline writing committee reviewed clinical trials that were presented at the annual scientific meetings of the ACC, AHA, and European Society of Cardiology and other scientific meetings and that were published in peer-reviewed format from April 2013 through November 2016. The evidence is summarized in tables in the Online Data Supplement. All recommendations (new, modified, and unchanged) for each clinical section are included to provide a comprehensive assessment. The text explains new and modified recommendations, whereas recommendations from the previous guideline that have been deleted or superseded no longer appear. Please consult the full-text version of the 2013 HF guideline (
2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
) for text and evidence tables supporting the unchanged recommendations and for clinical areas not addressed in this focused update. Individual recommendations in this focused update will be incorporated into the full-text guideline in the future. Recommendations from the prior guideline that remain current have been included for completeness, but the LOE reflects the COR/LOE system used when the recommendations were initially developed. New and modified recommendations in this focused update reflect the latest COR/LOE system, in which LOE B and C are subcategorized for greater specificity (
Further evolution of the ACC/AHA clinical practice guideline recommendation classification system: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
ACCF/AHA clinical practice guideline methodology summit report: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
). The section numbers correspond to the full-text guideline sections.
1.2 Organization of the Writing Group
For this focused update, representative members of the 2013 HF guideline writing committee were invited to participate. They were joined by additional invited members to form a new writing group, which is referred to as the 2017 HF focused update writing group. Members were required to disclose all RWI relevant to the data under consideration. The group was composed of experts representing general cardiologists, HF and transplantation specialists, electrophysiologists, pharmacists, and general internists. The 2017 HF focused update writing group included representatives from the ACC, AHA, and HFSA, as well as the American Academy of Family Physicians, American College of Chest Physicians, American College of Physicians, and International Society for Heart and Lung Transplantation.
1.3 Document Review and Approval
The focused update was reviewed by 2 official reviewers each nominated by the ACC, AHA, and HFSA; 1 reviewer each from the American Academy of Family Physicians, American College of Chest Physicians, and International Society for Heart and Lung Transplantation; and 19 individual content reviewers. Reviewers’ RWI information is published in this document (Appendix 2).
This document was approved for publication by the governing bodies of the ACC, AHA, and HFSA.
6. Initial and Serial Evaluation of the HF Patient
6.3 Biomarkers
Assays for BNP (B-type natriuretic peptide) and NT-proBNP (N-terminal pro-B-type natriuretic peptide), which are both natriuretic peptide biomarkers, have been used increasingly to establish the presence and severity of HF. In general, both natriuretic peptide biomarker values track similarly, and either can be used in patient care settings as long as their respective absolute values and cutpoints are not used interchangeably. Notably, BNP, but not NT-proBNP, is a substrate for neprilysin. Therefore, ARNI increases BNP levels (
). Note that the type of natriuretic peptide assay that has been performed must be considered during interpretation of natriuretic peptide biomarker levels in patients on ARNI. In 2 studies with ARNI, NT-proBNP levels were reduced (
The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial.
A substantial evidence base exists that supports the use of natriuretic peptide biomarkers to assist in the diagnosis or exclusion of HF as a cause of symptoms (e.g., dyspnea, weight gain) in the setting of chronic ambulatory HF (
Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group.
The diagnostic accuracy of plasma BNP and NTproBNP in patients referred from primary care with suspected heart failure: results of the UK natriuretic peptide study.
Balion C, Don-Wauchope A, Hill S, et al. Use of Natriuretic Peptide Measurement in the Management of Heart Failure [Internet]. 13(14)-EHC118-EF ed. Rockville, MD: 2013.
N-terminal pro-B-type natriuretic peptide testing improves the management of patients with suspected acute heart failure: primary results of the Canadian prospective randomized multicenter IMPROVE-CHF study.
), especially when the cause of dyspnea is unclear. The role of natriuretic peptide biomarkers in population screening to detect incident HF is emerging (
Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left ventricular dysfunction.
Screening the population for left ventricular hypertrophy and left ventricular systolic dysfunction using natriuretic peptides: results from the Dallas Heart Study.
Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study.
). Obesity may be associated with lower natriuretic peptide concentrations, and this may modestly reduce diagnostic sensitivity in morbidly obese patients (
Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study.
2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
Effect of B-type natriuretic peptide-guided treatment of chronic heart failure on total mortality and hospitalization: an individual patient meta-analysis.
Does B-type natriuretic peptide-guided therapy improve outcomes in patients with chronic heart failure? A systematic review and meta-analysis of randomized controlled trials.
N-terminal pro-B-type natriuretic peptide-guided, intensive patient management in addition to multidisciplinary care in chronic heart failure: a 3-arm, prospective, randomized pilot study.
Management of chronic heart failure guided by individual N-terminal pro-B-type natriuretic peptide targets: results of the PRIMA (Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) study.
Heart failure outcomes and benefits of NT-proBNP-guided management in the elderly: results from the prospective, randomized ProBNP outpatient tailored chronic heart failure therapy (PROTECT) study.
Brain natriuretic peptide-guided treatment does not improve morbidity and mortality in extensively treated patients with chronic heart failure: responders to treatment have a significantly better outcome.
N-terminal pro-B-type natriuretic peptide-guided treatment for chronic heart failure: results from the BATTLESCARRED (NT-proBNP-Assisted Treatment To Lessen Serial Cardiac Readmissions and Death) trial.
Improved pharmacological therapy of chronic heart failure in primary care: a randomized Study of NT-proBNP Guided Management of Heart Failure–SIGNAL-HF (Swedish Intervention study–Guidelines and NT-proBNP AnaLysis in Heart Failure).
BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial.
Rapid Emergency Department Heart Failure Outpatients Trial (REDHOT II): a randomized controlled trial of the effect of serial B-type natriuretic peptide testing on patient management.
Rationale and design of PRIMA II: A multicenter, randomized clinical trial to study the impact of in-hospital guidance for acute decompensated heart failure treatment by a predefined NT-PRoBNP target on the reduction of readmIssion and Mortality rAtes.
), there are insufficient data to inform specific guideline recommendations related to natriuretic peptide–guided therapy or serial measurements of BNP or NT-proBNP levels for the purpose of reducing hospitalization or deaths in the present document.
Like natriuretic peptides, cardiac troponin levels may be elevated in the setting of chronic or acute decompensated HF, suggesting myocyte injury or necrosis (
). Troponins I and T respond similarly for acute coronary syndromes and acute decompensated HF. Elevations in either troponin I or T levels in the setting of acute HF are of prognostic significance and must be interpreted in the clinical context (
2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
Serial measurement of cardiac troponin T using a highly sensitive assay in patients with chronic heart failure: data from 2 large randomized clinical trials.
), multiple other biomarkers, including those of inflammation, oxidative stress, vascular dysfunction, and myocardial and matrix remodeling, have been implicated in HF (
). Biomarkers of myocardial fibrosis, soluble ST2 receptor, and galectin-3 are predictive of hospitalization and death and may provide incremental prognostic value over natriuretic peptide levels in patients with HF (
Head-to-head comparison of serial soluble ST2, growth differentiation factor-15, and highly-sensitive troponin T measurements in patients with chronic heart failure.
). Strategies that combine multiple biomarkers may ultimately prove beneficial in guiding HF therapy in the future, but multicenter studies with larger derivation and validation cohorts are needed (
Serial measurements of midregion proANP and copeptin in ambulatory patients with heart failure: incremental prognostic value of novel biomarkers in heart failure.
Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics.
This section categorizes the role of biomarkers into prevention, diagnosis, prognosis, and added risk stratification to clarify evidence-based objectives of their use in clinical practice.
6.3.1 Biomarkers for Prevention: Recommendation
Tabled
1Biomarkers: Recommendation for Prevention of HF
COR
LOE
Recommendation
Comment/Rationale
IIa
B-R
For patients at risk of developing HF, natriuretic peptide biomarker–based screening followed by team-based care, including a cardiovascular specialist optimizing GDMT, can be useful to prevent the development of left ventricular dysfunction (systolic or diastolic) or new-onset HF
PONTIAC (NT-proBNP selected prevention of cardiac events in a population of diabetic patients without a history of cardiac disease): a prospective randomized controlled trial.
, patients at risk of HF (identified by the presence of hypertension, diabetes mellitus, or known vascular disease [e.g., stage A HF]), but without established left ventricular systolic dysfunction or symptomatic HF at baseline, were randomly assigned to receive screening with BNP testing or usual primary care. Intervention-group participants with BNP levels of ≥50 pg/mL underwent echocardiography and were referred to a cardiovascular specialist who decided on further investigation and management. All patients received further coaching by a specialist nurse who emphasized individual risk and the importance of adherence to medication and healthy lifestyle behaviors. BNP-based screening reduced the composite endpoint of asymptomatic left ventricular dysfunction (systolic or diastolic) with or without newly diagnosed HF
. Similarly, in another small, single-center RCT, accelerated up-titration of renin-angiotensin-aldosterone system antagonists and beta blockers reduced cardiac events in patients with diabetes mellitus and elevated NT-proBNP levels but without cardiac disease at baseline
PONTIAC (NT-proBNP selected prevention of cardiac events in a population of diabetic patients without a history of cardiac disease): a prospective randomized controlled trial.
. Developing a standardized strategy to screen and intervene in patients at risk of HF can be difficult because of different definitions of HF risk, heterogeneity of prevalence in different populations, variable duration until clinical HF or left ventricular dysfunction develops, and variable interventions for risk factor modification or treatment. Further studies are needed to determine cost-effectiveness and risk of such screening, as well as its impact on quality of life (QoL) and mortality rate.
Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group.
The diagnostic accuracy of plasma BNP and NTproBNP in patients referred from primary care with suspected heart failure: results of the UK natriuretic peptide study.
Balion C, Don-Wauchope A, Hill S, et al. Use of Natriuretic Peptide Measurement in the Management of Heart Failure [Internet]. 13(14)-EHC118-EF ed. Rockville, MD: 2013.
Natriuretic peptide biomarker testing in the setting of chronic ambulatory HF provides incremental diagnostic value to clinical judgment, especially when the etiology of dyspnea is unclear
Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group.
The diagnostic accuracy of plasma BNP and NTproBNP in patients referred from primary care with suspected heart failure: results of the UK natriuretic peptide study.
Balion C, Don-Wauchope A, Hill S, et al. Use of Natriuretic Peptide Measurement in the Management of Heart Failure [Internet]. 13(14)-EHC118-EF ed. Rockville, MD: 2013.
. In emergency settings, natriuretic peptide biomarker levels usually have higher sensitivity than specificity and may be more useful for ruling out than ruling in HF
Balion C, Don-Wauchope A, Hill S, et al. Use of Natriuretic Peptide Measurement in the Management of Heart Failure [Internet]. 13(14)-EHC118-EF ed. Rockville, MD: 2013.
. Although lower values of natriuretic peptide biomarkers exclude the presence of HF, and higher values have reasonably high positive predictive value to diagnose HF, clinicians should be aware that elevated plasma levels for both natriuretic peptides have been associated with a wide variety of cardiac and noncardiac causes (Table 2)
Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study.
High levels of plasma brain natriuretic peptide and interleukin-6 after optimized treatment for heart failure are independent risk factors for morbidity and mortality in patients with congestive heart failure.
Comparison of copeptin, B-type natriuretic peptide, and amino-terminal pro-B-type natriuretic peptide in patients with chronic heart failure: prediction of death at different stages of the disease.
Measurement of baseline levels of natriuretic peptide biomarkers and/or cardiac troponin on admission to the hospital is useful to establish a prognosis in acutely decompensated HF
Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT). A multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath.
Higher levels of natriuretic peptide biomarkers on admission are usually associated with greater risk for clinical outcomes, including all-cause and cardiovascular mortality, morbidity, and composite outcomes, across different time intervals in patients with decompensated HF
Balion C, Don-Wauchope A, Hill S, et al. Use of Natriuretic Peptide Measurement in the Management of Heart Failure [Internet]. 13(14)-EHC118-EF ed. Rockville, MD: 2013.
Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT). A multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath.
. Similarly, abnormal levels of circulating cardiac troponin are commonly found in patients with acute decompensated HF, often without obvious myocardial ischemia or underlying coronary artery disease (CAD), and this is associated with worse clinical outcomes and higher risk of death
Cardiac troponin I is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure.
. Furthermore, not all patients may need biomarker measurement for prognostication, especially if they already have advanced HF with established poor prognosis or persistently elevated levels of biomarkers in former settings. Therefore, assays of natriuretic peptide biomarkers for incremental prognostication should not preclude good clinical judgment; an individualized approach to each patient is paramount.
IIa
B-NR
During a HF hospitalization, a predischarge natriuretic peptide level can be useful to establish a postdischarge prognosis
Triage after hospitalization with advanced heart failure: the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) risk model and discharge score.
Lowered B-type natriuretic peptide in response to levosimendan or dobutamine treatment is associated with improved survival in patients with severe acutely decompensated heart failure.
A novel discharge risk model for patients hospitalised for acute decompensated heart failure incorporating N-terminal pro-B-type natriuretic peptide levels: a European coLlaboration on Acute decompeNsated Heart Failure: ELAN-HF Score.
Admission, discharge, or change in B-type natriuretic peptide and long-term outcomes: data from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) linked to Medicare claims.
Predischarge natriuretic peptide biomarker levels and the relative change in levels during hospital treatment are strong predictors of the risk of death or hospital readmission for HF
Triage after hospitalization with advanced heart failure: the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) risk model and discharge score.
Lowered B-type natriuretic peptide in response to levosimendan or dobutamine treatment is associated with improved survival in patients with severe acutely decompensated heart failure.
A novel discharge risk model for patients hospitalised for acute decompensated heart failure incorporating N-terminal pro-B-type natriuretic peptide levels: a European coLlaboration on Acute decompeNsated Heart Failure: ELAN-HF Score.
Admission, discharge, or change in B-type natriuretic peptide and long-term outcomes: data from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) linked to Medicare claims.
. Several studies have suggested that predischarge natriuretic peptide biomarker levels had higher reclassification and discrimination value than clinical variables in predicting outcomes
A novel discharge risk model for patients hospitalised for acute decompensated heart failure incorporating N-terminal pro-B-type natriuretic peptide levels: a European coLlaboration on Acute decompeNsated Heart Failure: ELAN-HF Score.
Admission, discharge, or change in B-type natriuretic peptide and long-term outcomes: data from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) linked to Medicare claims.
. Patients with higher predischarge levels and patients who do not have a decrease in natriuretic peptide biomarker levels during hospitalization have worse outcomes
A novel discharge risk model for patients hospitalised for acute decompensated heart failure incorporating N-terminal pro-B-type natriuretic peptide levels: a European coLlaboration on Acute decompeNsated Heart Failure: ELAN-HF Score.
Admission, discharge, or change in B-type natriuretic peptide and long-term outcomes: data from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) linked to Medicare claims.
. Although observational or retrospective studies have suggested that patients with natriuretic peptide biomarker reduction had better outcomes than those without any changes or with a biomarker rise
Lowered B-type natriuretic peptide in response to levosimendan or dobutamine treatment is associated with improved survival in patients with severe acutely decompensated heart failure.
, targeting a certain threshold, value, or relative change in these biomarker levels during hospitalization may not be practical or safe for every patient and has not been tested in a prospective large-scale trial. Clinical assessment and adherence to GDMT should be the emphasis, and the prognostic value of a predischarge value or relative changes does not imply the necessity for serial and repeated biomarker measurements during hospitalization.
IIb
B-NR
In patients with chronic HF, measurement of other clinically available tests, such as biomarkers of myocardial injury or fibrosis, may be considered for additive risk stratification
Measurement of the interleukin family member ST2 in patients with acute dyspnea: results from the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) study.
Usefulness of soluble concentrations of interleukin family member ST2 as predictor of mortality in patients with acutely decompensated heart failure relative to left ventricular ejection fraction.
Biomarkers of myocardial fibrosis (e.g., soluble ST2 receptor, galectin-3, high-sensitivity cardiac troponin, and others) are predictive of hospitalization and death in patients with HF and also are additive to natriuretic peptide biomarker levels in their prognostic value
Usefulness of soluble concentrations of interleukin family member ST2 as predictor of mortality in patients with acutely decompensated heart failure relative to left ventricular ejection fraction.
Incremental value of biomarkers to clinical variables for mortality prediction in acutely decompensated heart failure: the Multinational Observational Cohort on Acute Heart Failure (MOCA) study.
*Other biomarkers of injury or fibrosis include soluble ST2 receptor, galectin-3, and high-sensitivity troponin.
ACC indicates American College of Cardiology; AHA, American Heart Association; ADHF, acute decompensated heart failure; BNP, B-type natriuretic peptide; COR, Class of Recommendation; ED, emergency department; HF, heart failure; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; and pts, patients.
2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group.
Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial.
2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group.
Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group.
Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the Survival and Ventricular Enlargement Trial. The SAVE Investigators.
Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators.
A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group.
2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study.
Safety and efficacy of eplerenone in patients at high risk for hyperkalemia and/or worsening renal function: analyses of the EMPHASIS-HF study subgroups (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure).
Angiotensin-converting enzyme (ACE) inhibitors reduce morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). Randomized controlled trials (RCTs) clearly establish the benefits of ACE inhibition in patients with mild, moderate, or severe symptoms of HF and in patients with or without coronary artery disease
Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group.
Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group.
Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the Survival and Ventricular Enlargement Trial. The SAVE Investigators.
Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators.
A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group.
. ACE inhibitors can produce angioedema and should be given with caution to patients with low systemic blood pressures, renal insufficiency, or elevated serum potassium. ACE inhibitors also inhibit kininase and increase levels of bradykinin, which can induce cough but also may contribute to their beneficial effect through vasodilation. Angiotensin receptor blockers (ARBs) were developed with the rationale that angiotensin II production continues in the presence of ACE inhibition, driven through alternative enzyme pathways. ARBs do not inhibit kininase and are associated with a much lower incidence of cough and angioedema than ACE inhibitors; but like ACE inhibitors, ARBs should be given with caution to patients with low systemic blood pressure, renal insufficiency, or elevated serum potassium. Long-term therapy with ARBs produces hemodynamic, neurohormonal, and clinical effects consistent with those expected after interference with the renin-angiotensin system and have been shown in RCTs
to reduce morbidity and mortality, especially in ACE inhibitor–intolerant patients. In ARNI, an ARB is combined with an inhibitor of neprilysin, an enzyme that degrades natriuretic peptides, bradykinin, adrenomedullin, and other vasoactive peptides. In an RCT that compared the first approved ARNI, valsartan/sacubitril, with enalapril in symptomatic patients with HFrEF tolerating an adequate dose of either ACE inhibitor or ARB, the ARNI reduced the composite endpoint of cardiovascular death or HF hospitalization significantly, by 20%
. The benefit was seen to a similar extent for both death and HF hospitalization and was consistent across subgroups. The use of ARNI is associated with the risk of hypotension and renal insufficiency and may lead to angioedema, as well.
I
ACE-I: A
The use of ACE inhibitors is beneficial for patients with prior or current symptoms of chronic HFrEF to reduce morbidity and mortality
Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group.
Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group.
Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the Survival and Ventricular Enlargement Trial. The SAVE Investigators.
Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators.
A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group.
Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials.
ACE inhibitors have been shown in large RCTs to reduce morbidity and mortality in patients with HFrEF with mild, moderate, or severe symptoms of HF, with or without coronary artery disease
Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group.
Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group.
Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the Survival and Ventricular Enlargement Trial. The SAVE Investigators.
Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators.
A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group.
Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials.
. ACE inhibitors should be started at low doses and titrated upward to doses shown to reduce the risk of cardiovascular events in clinical trials. ACE inhibitors can produce angioedema and should be given with caution to patients with low systemic blood pressures, renal insufficiency, or elevated serum potassium (>5.0 mEq/L). Angioedema occurs in <1% of patients who take an ACE inhibitor, but it occurs more frequently in blacks and women
. Patients should not be given ACE inhibitors if they are pregnant or plan to become pregnant. ACE inhibitors also inhibit kininase and increase levels of bradykinin, which can induce cough in up to 20% of patients but also may contribute to beneficial vasodilation. If maximal doses are not tolerated, intermediate doses should be tried; abrupt withdrawal of ACE inhibition can lead to clinical deterioration and should be avoided. Although the use of an ARNI in lieu of an ACE inhibitor for HFrEF has been found to be superior, for those patients for whom ARNI is not appropriate, continued use of an ACE inhibitor for all classes of HFrEF remains strongly advised.
I
ARB: A
The use of ARBs to reduce morbidity and mortality is recommended in patients with prior or current symptoms of chronic HFrEF who are intolerant to ACE inhibitors because of cough or angioedema
Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial.
. Long-term therapy with ARBs in patients with HFrEF produces hemodynamic, neurohormonal, and clinical effects consistent with those expected after interference with the renin-angiotensin system
Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial.
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