Review ArticleBeyond Stage C: Considerations in the Management of Patients With Heart Failure Progression and Gaps in Evidence
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Lay Summary
The number of people living with poor heart-pump function is increasing. The medical and device therapies that are used for people with this disease called heart failure are based on clinical trial data. However, an increasing number of people progress to end-stage disease; the typically used therapies may no longer be tolerated or beneficial, and these people are not well represented in the clinical trial data. This review article summarizes existing clinical trial data, discusses how and
The Challenges of Identifying Patients With Severe and Advanced Heart Failure
The identification of patients who are progressing from stage C to stage D HF is both clinically important and economically impactful. These patients have a high burden of symptoms, are at significant risk of hospitalization and death, and commonly require substantial health care resources. However, accurate identification of this population in daily clinical practice can be challenging and elusive.
The ACC/AHA and the European Society of Cardiology have proposed indicators of advanced disease (
Referral to Advanced Heart Failure Teams
Timely and appropriate referral to an advanced HF specialist for either consultation or comanagement is important to ensure timely interventions for advanced HF. A summary of indicators that should prompt referral have been published by several societies and bodies of experts,15,16 including the popular acronym I NEED HELP.15 A summary of important reasons to refer to an advanced HF center includes: inability to walk 1 block without dyspnea (not better attributable to pulmonary or other
Clinical Trials of Medical Therapies Targeting Neurohormonal Modulation for Patients With Severe and Advanced Heart Failure
Data from multiple clinical trials provide the foundation that supports current evidence-based therapies for most patients with symptomatic HF. These include ACEi (ACE inhibitors)/angiotensin receptor blockers (ARBs)/or ARNIs, evidenced-based beta-blockers, mineralocorticoid receptor antagonists (MRAs), sodium–glucose cotransporter 2 (SGLT2) inhibitors, and vericiguat; and, in some cases, ivabradine, combination hydralazine plus isosorbide dinitrate and digoxin. These therapies are widely
Clinical Trials of Inotropic Therapies for Patients With Severe and Advanced Heart Failure
In addition to neurohormonal modulation, there has been significant interest in the role of inotropic therapy for the treatment of HFrEF.31 Given that reduced contractility is often a pathophysiological hallmark of severe and advanced HF, medications that increase contractility offer the possibility of improving outcomes. However, clinical trials, historically, have not shown a mortality benefit for this class of medications. For example, the OPTIME-CHF (Outcomes of a Prospective Trial of
Implantable Cardioverter Defibrillators and Cardiac Resynchronization Therapy
Causes of death in patients with severe and advanced HF include not only hemodynamic failure but also ventricular arrhythmias leading to sudden cardiac death. Patients with NYHA class IV symptoms were excluded from landmark trials of ICD therapy in HFrEF,35,36 and the AHA/ACC/HFSA guidelines do not support use of an ICD if overall survival is estimated to be less than 1 year.
Compared to ICDs, which improve mortality rates but not symptoms, the mechanistic underpinnings of CRT fundamentally
Considerations for a Practical Approach to Medical Management in Severe and Advanced Heart Failure
Fig. 2 displays considerations for the approach to management of patients progressing to severe or advanced HF: identifying and addressing reversible causes for worsening HF, optimizing volume status and medical and device therapy, and managing comorbid conditions. Practically, this often entails escalating medical therapy via titration to blood pressure and symptoms, typically with a focus on diuretic therapy and use of medications with fewer blood pressure-lowering effects (largely MRAs and
Hospitalizations for Acute Heart Failure Complicated by Cardiogenic Shock
Acute exacerbations of HF are more common and often more severe as HF progresses. These acute decompensated states may be complicated by cardiogenic shock (CS) and account for up to 30% of CS cases.46 A broader discussion of CS is beyond the scope of this review, but a few points are worth mentioning. CS has historically been defined as a primary cardiac disorder that results in both clinical and biochemical manifestations of tissue hypoperfusion. More recently, the Society for Cardiovascular
Considerations for Future Directions
There are notable ways in which the field of advanced HF can improve to meet the needs of this growing population of patients. These are highlighted in Table 2 and summarized here. First, a standardized and actionable definition of severe and advanced HF should be created, a definition that can be used to identify like populations for clinical research, and we recommend society- and/or government-based efforts be focused in this space. The essential components of such a definition include: (1)
Conclusions
The number of patients living with severe and advanced HF is growing and is expected to increase over time. The existing clinical trial evidence concerning how to manage this population medically is insufficient, and the HF community needs to identify ways to better recognize and phenotype these patients in order to improve current care and enroll participants in clinical trials of medical therapies and devices for HF.
Sources of Funding
There are no funding sources to report.
Disclosures
The following relationships exist related to this manuscript: SR serves on the DSMB committee for Abbott and as a consultant for Medtronic. ADV reports research funding through his institution from the American Heart Association, Amgen, AstraZeneca, Bayer, Intra-Cellular Therapies, American Regent, the NHLBI, Novartis, and PCORI and also provides consulting services for Amgen, AstraZeneca, Bayer, CareDx, InnaMed, LivaNova, Mardil Medical, Novartis, Procyrion, scPharmaceuticals, Story Health,
References (65)
- et al.
2022 AHA/ACC/HFSA Guideline or the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
J Card Fail
(2022) - et al.
Characteristics and outcomes of patients with heart failure and discordant findings by right-sided heart catheterization and cardiopulmonary exercise testing
Am J Cardiol
(2014) - et al.
Validity and reliability of the NYHA classes for measuring research outcomes in patients with cardiac disease
Heart Lung
(2002) - et al.
Comparing LCZ696 with enalapril according to baseline risk using the MAGGIC and EMPHASIS-HF risk scores
J Am Coll Cardiol
(2015) - et al.
Registry Evaluation of Vital Information for VADs in Ambulatory Life (REVIVAL): rationale, design, baseline characteristics, and inclusion criteria performance
J Heart Lung Transplant
(2020) - et al.
Comparison of accuracy of estimation of cardiac output by thermodilution versus the fick method using measured oxygen uptake
Am J Cardiol
(2022) - et al.
Advanced (stage D) heart failure: a statement from the Heart Failure Society of America Guidelines Committee
J Card Fail
(2015) - et al.
Sacubitril/valsartan in advanced heart failure with reduced ejection fraction: rationale and design of the LIFE trial
JACC Heart Fail
(2020) - et al.
Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study
Lancet
(2010) - et al.
Ambulatory inotrope infusions in advanced heart failure: a systematic review and metaanalysis
JACC Heart Fail
(2018)
Expected vs actual outcomes of elective initiation of inotropic therapy during heart failure hospitalization
Mayo Clin Proc Innov Qual Outcomes
3-year outcomes of transcatheter mitral valve repair in patients with heart failure
J Am Coll Cardiol
MitraClip in secondary mitral regurgitation as a bridge to heart transplantation: 1-year outcomes from the International MitraBridge Registry
J Heart Lung Transplant
Sustained efficacy of pulmonary artery pressure to guide adjustment of chronic heart failure therapy: complete follow-up results from the CHAMPION randomised trial
Lancet
Haemodynamic-guided management of heart failure (GUIDE-HF): a randomised controlled trial
Lancet
Advanced heart failure: epidemiology, diagnosis, and therapeutic approaches
JACC Heart Fail
Map the gap: regional mapping to assess distribution of heart failure mortality and advanced heart failure treatment facilities
J Card Fail
The impact of health care disparities on patients with heart failure
J Card Fail
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
J Am Coll Cardiol
Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial
Lancet
Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-convertingenzyme inhibitors: the CHARM-Alternative trial
Lancet
Effects of high-dose versus lowdose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, doubleblind trial
Lancet
Universal Definition and Classification of Heart Failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure
J Card Fail
Identifying treatments for stage C2 heart failure
JAMA Cardiol
Forecasting the impact of heart failure in the United States: a policy statement from the
American Heart Association. Circ Heart Fail
Prevalence and prognostic significance of heart failure stages: application of the American College of Cardiology/American Heart Association heart failure staging criteria in the community
Circulation
Assessment of omecamtiv mecarbil for the treatment of patients with severe heart failure: a post hoc analysis of data from the GALACTIC-HF Randomized Clinical Trial
JAMA Cardiol
Development of advanced heart failure: a population-based study
Circ Heart Fail
Nomenclature and criteria for diagnosis of diseases of the heart and blood vessels
J Am Med Assoc
Efficacy and safety of sacubitril/valsartan in high-risk patients in the PIONEER-HF Trial
Circ Heart Fail
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 Am Coll Cardiol
Effects of enalapril on mortality in severe congestive heart failure
N Engl J Med
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Funding sources: There are no funding sources to report.