Elsevier

American Heart Journal

Volume 170, Issue 2, August 2015, Pages 298-305
American Heart Journal

Clinical Investigation
Heart Failure
Worsening heart failure during hospitalization for acute heart failure: Insights from the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF)

https://doi.org/10.1016/j.ahj.2015.04.007Get rights and content

Background

Despite initial in-hospital treatment of acute heart failure (HF), some patients experience worsening HF (WHF). There are limited data about the outcomes and characteristics of patients who experience in-hospital WHF.

Methods and Results

We assessed the characteristics and outcomes of patients with and without WHF in the ASCEND-HF trial. Worsening HF was defined as at least 1 symptom or sign of new, persistent, or WHF requiring additional intravenous inotropic/vasodilator or mechanical therapy during index hospitalization. We assessed the relationship between WHF and 30-day mortality, 30-day mortality or HF hospitalization, and 180-day mortality. We also assessed whether there was a differential association between early (days 1-3) vs late (day ≥4) WHF and outcomes. Of 7,141 patients with acute HF, 354 (5%) experienced WHF. Patients with WHF were more often male and had a history of atrial fibrillation or diabetes, lower blood pressure, and higher creatinine. After risk adjustment, WHF was associated with increased 30-day mortality (odds ratio 13.37, 95% CI 9.85-18.14), 30-day mortality or HF rehospitalization (odds ratio 6.78, 95% CI 5.25-8.76), and 180-day mortality (hazard ratio 3.90, 95% CI 3.14-4.86) (all P values < .0001). There was no evidence of a difference in outcomes between early and late WHF (all P values for comparison ≥ .2).

Conclusions

Worsening HF during index hospitalization was associated with worse 30- and 180-day outcomes. Worsening HF may represent an important patient-centered outcome in acute HF and a focus of future treatments.

Section snippets

Methods

ASCEND-HF enrolled 7,141 patients with acute HF within 24 hours of their first intravenous HF-related therapy. ASCEND-HF was a randomized, double-blind, placebo-controlled trial of nesiritide in addition to standard care. The study design and results have been previously reported.7, 17 The 2 primary end points were a composite of all-cause mortality or HF readmission up to 30 days after randomization and the change in early dyspnea relief after study drug initiation. Each participating center's

Results

Worsening HF occurred in 354 (5%) patients enrolled in ASCEND-HF. The baseline characteristics of patients with and without WHF are presented in Table I. Patients with WHF were more often male and white with a history of atrial fibrillation, diabetes, and HF admission compared with those without WHF. There was similar use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and β-blockers in patients with and without WHF, but higher rates of aldosterone antagonism and

Discussion

In the largest clinical trial of acute HF, we characterized the end point of WHF, providing insight into a key population that has been poorly studied. Patients who experienced WHF had markedly worse outcomes at 30 and 180 days. Specifically, patients with WHF had more than a 13-fold increase in 30-day mortality and nearly a 7-fold increase in 30-day mortality or rehospitalization for HF. By 180 days, 41.5% of patients with WHF had died compared with 11.3% of patients without WHF. We found no

Conclusions

The results from this retrospective analysis of a large, international, clinical trial of patients with acute HF patients extend the findings of previous smaller acute HF studies. Worsening HF is strongly associated with significantly increased risk of rehospitalization and mortality at 30 and 180 days. Worsening HF portends a poor prognosis regardless of whether it occurs early or late during hospitalization. Worsening HF in hospitalized patients with acute HF represents a patient-centered

Disclosures

The ASCEND-HF study was funded by Scios. This analysis was funded by the Duke Clinical Research Institute.

All authors have approved the final article.

Kelly receives funding from Duke's T32 Training grant (National Institutes of Health Ruth L. Kirschstein NRSA Institutional Research Training Grant: 5 T32 HL 7101-39). Mentz receives honoraria from Thoratec and research support from Amgen, AstraZeneca, BMS, GSK, Gilead, Novartis, Otsuka, and ResMed. Hasselblad has hothing to report. Ezekowitz

Acknowledgement

Ms Elizabeth Cook and Ms Morgan deBlecourt provided editorial assistance.

References (21)

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Clinical Trial Registration: ClinicalTrials.gov; unique identifier: NCT00475852.

Guest Editor: W. H. Wilson Tang, MD served as guest editor for this article.

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