In-hospital worsening heart failure: a clinically relevant endpoint?

Abstract

Outcome measures used for the clinical evaluation of patients with acute heart failure differ between studies and may neither adequately address the characteristic presenting symptoms and signs nor reflect the pathophysiological processes involved. In-hospital worsening of heart failure (WHF) is associated with poor outcomes and thus a potential endpoint conveying clinically meaningful prognostic information. Current definitions of WHF are based on the combination of worsening symptoms and signs and the intensification of treatment during admission. Definitions vary across studies and do not fully account for baseline therapy or circumstances in which there is failure to respond to treatment. Further, there are limited data to inform healthcare professionals as to which patients are most at risk of developing in-hospital WHF. In this opinion piece, we review the definitions for WHF used in recent and ongoing clinical trials and propose a novel definition, which captures failure to respond to treatment as well as clinical worsening (deterioration of symptoms and signs) of the patient's condition. Such a definition, applied consistently across studies, would help clarify the characteristics of patients likely to develop in-hospital WHF, allow comparative assessments of the effectiveness of interventions, and help guide appropriate patient management in order to improve outcomes.

Keywords: Acute heart failure; Endpoints; Worsening heart failure.

Figure 1

In‐hospital worsening heart failure (WHF) and reported outcomes in recent clinical trials. Kaplan–Meier estimates of (A) cumulative risk of death or heart failure (HF) hospitalization through Day 30 by occurrence of WHF through Day 7, shown with 95% confidence intervals and number of subjects at risk in VERITAS.12 (B) Survival for patients with and without WHF within 7 days of admission.14 (C) Risk of all‐cause mortality through Day 180 shown with number of subjects at risk in RELAX‐AHF.17 (D) Observed all‐cause mortality up to 1 year post‐index hospitalization in ADHERE.19 ADHERE, Acute Decompensated Heart Failure National Registry; HR, hazard ratio; RELAX‐AHF, serelaxin in acute heart failure; VERITAS, Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Studies. Figure (A) reproduced with permission from Cotter et al.11; Figure (B) reproduced with permission from Weatherley et al.14; Figure (C) reproduced with permission from Metra et al.17; Figure (D) reproduced with permission from DeVore et al.19

Figure 2

Change in dyspnoea score by study day in patients with/without in‐hospital worsening heart failure (WHF). Mean patient‐reported dyspnoea change score over time on a Likert scale, in patients with and without in‐hospital WHF.11 i.v., intravenous. Figure reproduced with permission: Cotter G et al.11. © 2009 Karger AG, Basel.

Figure 3

Irrespective of definition, in‐hospital worsening heart failure (WHF) is associated with poor outcomes for patients with heart failure. The definition of in‐hospital WHF varies across studies but is consistently associated with adverse outcomes including longer length of stay, increased rate of re‐hospitalization, higher mortality rate, and greater economic burden.11, 12, 14, 15, 17, 19, 37