Outpatient Worsening Heart Failure as a Target for Therapy: A Review

Abstract

Importance: Hospitalizations for worsening heart failure (WHF) represent an enormous public health and financial burden, with physicians, health systems, and payers placing increasing emphasis on hospitalization prevention. In addition, maximizing time out of the hospital is an important patient-centered outcome. In this review, we discuss the concept of outpatient WHF, highlight the rationale and data for the outpatient treatment of WHF as an alternative to hospitalization, and examine opportunities and strategies for developing outpatient "interceptive" therapies for treatment of worsening symptoms and prevention of hospitalization.

Observations: Worsening heart failure has traditionally been synonymous with an episode of in-hospital care for worsening symptoms. While WHF often leads to hospitalization, many patients experience WHF in the outpatient setting and carry a similarly poor prognosis. These findings support WHF as a distinct condition, independent of location of care. For those that are hospitalized, most patients have an uncomplicated clinical course, with diuretics as the only intravenous therapy. Although complicated scenarios exist, it is conceivable that improved tools for outpatient management of clinical congestion would allow a greater proportion of hospitalized patients to receive comparable care outside the hospital. Most patients with WHF have a gradual onset of congestive signs and symptoms, offering a potential window in which effective therapy may abort continued worsening and obviate the need for hospitalization. To date, outpatient WHF has received minimal attention in randomized clinical trials, but this high-risk group possesses key features that favor effective clinical trial investigation.

Conclusions and relevance: As the public health and economic burdens of heart failure continue to grow, recognizing the entity of outpatient WHF is critical. Efforts to reduce heart failure hospitalization should include developing effective therapies and care strategies for outpatient WHF. The outpatient WHF population represents a major opportunity for therapeutic advancements that could fundamentally change heart failure care delivery.

Figure 1.. Conceptual Framework for Worsening Heart Failure (WHF)

Worsening heart failure may be managed in both the outpatient and inpatient settings, as determined by many factors. Studying the inpatient vs outpatient WHF populations in randomized clinical trials presents specific advantages and disadvantages for successful clinical trial execution. ED indicates emergency department; HF, heart failure; IV, intravenous.

Figure 2.. Heart Failure (HF) Randomized Clinical Trials Describing All-cause Mortality Rates for Patients With Worsening Heart Failure (WHF) Categorized by the Location of Care

Worsening HF is associated with a high subsequent risk of death, irrespective of treatment as an outpatient, inpatient, or in the emergency department (ED). The outpatient WHF definition in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) was signs and/or symptoms consistent with HF and outpatient treatment with intravenous decongestive therapy. The outpatient WHF definition in the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial was 1 or more of the following without associated hospitalization or ED visit: (1) sustained increase in diuretic dose for 1 month, (2) intravenous treatment for HF, and (3) the addition of a new drug for treating WHF. Data from Skali et al and Okumura et al.

Figure 3.. Schematic Representation of the Time Course of Decompensation

This representation highlights traditional randomized clinical trial enrollment and treatment strategies compared with the proposed approach of introducing the study intervention upstream of hospitalization in the outpatient worsening heart failure (WHF) setting. The randomized clinical trials listed are representative examples of each strategy (ie, lists are not all-inclusive). The orange dashed line represents the severity of decompensation. ED indicates emergency department.