Review Article
Beyond Stage C: Considerations in the Management of Patients With Heart Failure Progression and Gaps in Evidence

https://doi.org/10.1016/j.cardfail.2023.02.015Get rights and content

Highlights

  • The number of patients living with severe and advanced heart failure is growing and is expected to increase over time.

  • Patients who have progressed beyond stage C heart failure are underrepresented in clinical trials, and there is a lack of high-quality evidence to guide clinical decision making.

  • We provide an approach to the medical management of patients with severe and advanced heart failure based on limited current data and the clinical experiences of the authors who specialize in heart failure.`

ABSTRACT

Despite treatment with contemporary medical therapies for chronic heart failure (HF), there has been an increase in the prevalence of patients progressing to more advanced disease. Patients progressing to and living at the interface of severe stage C and stage D HF are underrepresented in clinical trials, and there is a lack of high-quality evidence to guide clinical decision making. For patients with severe HF phenotypes, the medical therapies used for patients with less advanced stages of illness are often no longer tolerated or provide inadequate clinical stability. The limited data on these patients highlights the need to increase formal research characterizing this high-risk population. This review summarizes existing clinical trial data and incorporates our considerations for approaches to the medical management of patients advanced “beyond stage C” HF.

Section snippets

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,

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