2021 Update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction J O U R N A L.
INTRODUCTION
Heart failure (HF) is an increasingly prevalent condition, with its prevalence rising rapidly The disease places a substantial burden on healthcare resources and is associated with significant morbidity, mortality, and a markedly reduced quality of life Nevertheless, important breakthroughs have redefined opportunities to alter the natural history of HF through a broad range of medical therapies, devices, and care strategies.
This focused ECDP update supplements the 2017 ECDP with data from emerging studies and continues to provide succinct, practical guidance for managing patients with heart failure with reduced ejection fraction (HFrEF) It preserves a concise, structured format to deliver evidence-based, actionable recommendations clinicians can readily apply in daily practice.
Pivotal Issues in the 2017 ECDP was preserved, and their associated treatment algorithms and tables have been updated to accommodate this new, evolving evidence.
Ten Pivotal Issues in HFrEF
1 How to initiate, add, or switch therapies to new evidence-based guideline-directed treatments for
2 How to achieve optimal therapy given multiple drugs for HF including augmented clinical assessment (e.g., imaging data, biomarkers, and filling pressures) that may trigger additional changes in guideline-directed therapy.
3 When to refer to an HF specialist.
4 How to address challenges of care coordination.
5 How to improve medication adherence.
6 What is needed in specific patient cohorts: African
Americans, older adults, and the frail.
7 How to manage your patients’costs and access to HF medications.
8 How to manage the increasing complexity of HF.
9 How to manage common comorbidities.
10 How to integrate palliative care and the transition into hospice care.
METHODS
The original 2017 ACC ECDP was drafted using a struc- tured format that was created subsequent to the release of the 2016 and 2017 ACC/AHA/HFSA focused updates of the
Beginning with the 2013 ACCF/AHA heart failure guideline, the evolution of the Evidence‑Based Clinical Decision Process (ECDP) involved developing questions to identify evidence gaps and convening a multidisciplinary panel to conduct a literature review that aggregates current evidence addressing contemporary heart failure care The references were reviewed by the ECDP Chair and Vice Chair, yielding an agreed compendium Print copies of the compendium were distributed to every panel member before the live roundtable held on July 19, 2016, at the ACC Heart House The HF roundtable brought together cardiologists, internists, emergency physicians, hospitalists, nurses, patient‑advocacy group representatives, pharmacists, fellows‑in‑training, quality‑improvement experts, epidemiologists, and biostatisticians.
Since the 2017 ECDP publication, numerous clinical trials have reported updated evidence that informs the clinical management of patients with HFrEF These studies have expanded knowledge on biomarkers and imaging, on managing comorbidities, and on overcoming challenges in care coordination Moreover, the COVID-19 pandemic has significantly affected outpatient management of chronic diseases such as HFrEF, and this impact warrants consideration in this document.
To integrate emerging data with established logic for treating HFrEF, the ACC organized structured discussions on new therapies, unanswered questions, adherence, and implementation strategies, and the College also hosted multidisciplinary panel discussions, archived online for broader access at https://www.acc.org/tools-and-practice-support/quality-programs/succeed-in-managing-heart-failure-initiative/emerging-strategies-for-heart-failure-roundtable, to disseminate evolving strategies in heart failure management Building on these discussions, a writing committee was formed to provide practical guidance aimed at closing gaps in HF treatment For the 2021 update, the committee met in mid-2020 via confidential conference calls attended only by writing committee members and ACC staff; when consensus was required, decisions were made by a roll-call vote or email-generated ballot, with a simple majority prevailing, and the Chair’s prerogative reconciled the final decision in the event of a tie.
In accordance with ACC policy, the formal peer-review process was completed and included a public comment period to gather additional feedback; after reconciling all comments, this document was approved for publication by the Clinical Policy Approval Committee.
The American College of Cardiology (ACC) and the Solution Set Oversight Committee (SSOC) recognize the importance of avoiding real or perceived relationships with industry (RWI) or other entities that may influence clinical policy To support this commitment, the ACC maintains a comprehensive database that tracks all relevant relationships for ACC members and all individuals participating in ACC activities, including those involved in the development of electronic clinical decision support products (ECDPs).
ECDPs follow ACC RWI Policy in determining what con- stitutes a relevant relationship, with additional vetting by the SSOC.
ECDP writing groups must be chaired or co-chaired by an individual with no relevant RWI Although vice chairs and writing group members may have relevant RWI, they must constitute less than 50% of the writing group, preserving unbiased leadership Relevant disclosures for the writing group, external reviewers, and related parties must be provided to ensure transparency and integrity throughout the process.
SSOC members can be found inAppendixes 1 and 2 To ensure complete transparency, a full list of disclosure in- formation, including relationships not pertinent to this document, is available in Supplemental Appendix 1.
Participants are discouraged from acquiring relevant RWI throughout the writing process.
ASSUMPTIONS AND DEFINITIONS
General Clinical Assumptions
1 Although many topics are generalizable to all patients with HF, the focus of this effort, including pathway recommendations, is on patients with HFrEF.
2 Although some of the recommendations may be rele- vant to patients hospitalized with acute HF or in those with left ventricular ejection fractions (LVEFs) higher than 40%, this document mainly focuses on the man- agement of patients with chronic ambulatory HFrEF with LVEF#40%.
3 The expert consensus writing committee endorses the evidence-based approaches to HF therapy and man- agement enumerated in the 2013 ACC/AHA HF guide- line (3) and the subsequent 2016 and 2017 ACC/AHA/
4 These algorithms assume the clinician will seek input as needed from a pharmacist, a cardiologist, an HF specialist, and/or a disease management program, and/ or other relevant medical specialists (e.g., endocrinol- ogists or nephrologists) to guide clinical management.
5 In all cases, patient preferences and values, in part- nership with evidence-based clinical judgment, should guide clinical decision-making.
6 At any point in time, these suggestions and algorithms may be superseded by new data.
De fi nitions
Heart failure is categorized into four stages to guide risk assessment and treatment: Stage A includes individuals at high risk for heart failure who have no structural heart disease or HF symptoms; Stage B includes people with structural heart disease but no signs or symptoms of heart failure; Stage C includes those with structural heart disease who have had prior or current symptoms of heart failure; and Stage D refers to refractory heart failure requiring specialized interventions.
GDMT: Guideline-directed medical therapy, repre- senting treatment options supported for use by clinical practice guidelines.
In HFrEF (heart failure with reduced ejection fraction), the clinical diagnosis of heart failure is defined by a left ventricular ejection fraction (LVEF) of less than 40% The New York Heart Association (NYHA) functional classification provides four levels of symptom-related limitation: Class I – no limitation of physical activity; ordinary physical activity does not cause heart failure symptoms Class II – slight limitation; comfortable at rest, but ordinary physical activity results in heart failure symptoms Class III – marked limitation; comfortable at rest, but less than ordinary activity leads to symptoms Class IV – unable to perform any physical activity without symptoms, or symptoms of heart failure at rest.
Optimal therapy: Treatment provided at either the target or the highest-tolerated dose for a given patient.Target dose:Doses targeted in clinical trials.
DESCRIPTION AND RATIONALE: ANSWERS TO
How to Initiate, Add, or Switch to New Evidence-Based Guideline-Directed Therapy
Guideline-Directed Therapy for HFrEF
Chronic heart failure with reduced ejection fraction (HFrEF) is treated with guideline-directed therapies, including ARNIs, ACE inhibitors, ARBs, beta-blockers, loop diuretics, aldosterone antagonists, hydralazine/isosorbide dinitrate, and ivabradine, with ivabradine acting as a selective If channel blocker for the sinoatrial node pacemaker current With the exception of loop diuretics, these therapies have demonstrated in randomized controlled trials that they improve symptoms, reduce hospitalizations, and prolong survival Digoxin in modern HFrEF has limited new data and is primarily used for rate control in patients with atrial fibrillation who have low blood pressure.
Following the publication of the 2017 ECDP focused on optimizing therapy for HFrEF, more data have emerged to support an expanded role for ARNIs in pa- tients with HFrEF These data include their use as a de novo therapy in some patients naive to ACEIs or ARB therapies (7–10), evidence for rapid improvement in patient-reported outcome measures (e.g., symptoms, physical functioning, and quality of life), and the
Figure 1 outlines ten pivotal issues in heart failure with reduced ejection fraction (HFrEF) It documents the reverse remodeling effect of ARNIs in chronic HFrEF, independent of background therapy with ACE inhibitors or ARBs (11) It is not yet clear that de novo initiation is best for all patients with HFrEF—for example, those with hypotension or very advanced heart failure—and we also recognize access challenges for some patients related to payer coverage and associated costs.
Since the publication of the 2017 ECDP, an important development has been the FDA's approval of an SGLT2 inhibitor and its addition to the armamentarium of medications for treating patients with HFrEF The DAPA-HF trial, or Study to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events in Patients with Heart Failure, investigates the impact of dapagliflozin on cardiovascular outcomes and helps expand therapeutic options for heart failure with reduced ejection fraction.
Worsening HF or CV Death in Patients with Chronic HF) trial, dapagliflozin demonstrated a reduction in CV death and HF hospitalization in patients with and without type
Type 2 diabetes (T2D) commonly coexists with heart failure with reduced ejection fraction (HFrEF) The EMPEROR-Reduced trial (Empagliflozin Outcome Trial in Patients With Chronic HFrEF) demonstrated that empagliflozin reduces heart‑failure hospitalizations and cardiovascular death in patients with chronic HFrEF, with benefits observed in patients both with and without diabetes These findings support a favorable class effect of SGLT2 inhibitors in HFrEF, independent of diabetes status.
With these developments, it is important to provide updated guidance on when to add, switch, and titrate all therapies for heart failure with reduced ejection fraction (HFrEF) to achieve maximally tolerated—and ideally target—doses, as outlined in Figure 1 and Table 1.
T A B L E 1 Starting and Target Doses of Select GDMT and Novel Therapies for HF (choice and timing of each therapy and in whom they should be added discussed in the text)*
Bisoprolol 1.25 mg once daily 10 mg once daily
Carvedilol 3.125 mg twice daily 25 mg twice daily for weight