Assessment of dyspnea in acute decompensated heart failure: insights from ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) on the contributions of peak expiratory flow.

Abstract

OBJECTIVES:

This study hypothesized that peak expiratory flow rate (PEFR) would increase with acute heart failure (AHF) treatment over the first 24 h, related to a Dyspnea Index (DI) change and treatment effect.

BACKGROUND:

Dyspnea is a key symptom and clinical trial endpoint in AHF, yet objective assessment is lacking.

METHODS:

In a clinical trial substudy, 421 patients (37 sites) underwent PEFR testing at baseline, 1, 6, and 24 h after randomization to nesiritide or placebo. DI (by Likert scale) was collected at hours 6 and 24.

RESULTS:

Patients were median age 70 years, and 34% were female; no significant differences between nesiritide or placebo patients existed. Median baseline PEFR was 225 l/min (interquartile range [IQR]: 160 to 300 l/min) and increased to 230 l/min (2.2% increase; IQR: 170 to 315 l/min) by hour 1, 250 l/min (11.1% increase; IQR: 180 to 340 l/min) by hour 6, and 273 l/min (21.3% increase; IQR: 200 to 360 l/min) by 24 h (all p < 0.001). The 24-h PEFR change related to moderate or marked dyspnea improvement by DI (adjusted odds ratio: 1.04 for each 10 l/min improvement [95% confidence interval (CI): 1.07 to 1.10]; p < 0.01). A model incorporating time and treatment over 24 h showed greater PEFR improvement after nesiritide compared with placebo (p = 0.048).

CONCLUSIONS:

PEFR increases over the first 24 h in AHF and could serve as an AHF endpoint. Nesiritide had a greater effect than placebo on PEFR, and this predicted patients with moderate/marked improvement in dyspnea, thereby providing an objective metric for assessing AHF. (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure [ASCEND-HF]; NCT00475852).

• Authors: Justin A Ezekowitz, Adrian F Hernandez, Christopher M O'Connor, Randall C Starling, Guy Proulx, Mason H Weiss, Jeffrey A Bakal, Robert M Califf, John J V McMurray, Paul W Armstrong
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 59 Issue 16 Pg. 1441-8 (Apr 17 2012) ISSN: 1558-3597 [Electronic] United States
• PMID: 22497823 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Natriuretic Agents
• Natriuretic Peptide, Brain

Topics

• Acute Disease
• Aged
• Aged, 80 and over
• Disease Progression
• Dose-Response Relationship, Drug
• Dyspnea (diagnosis, etiology, physiopathology)
• Female
• Follow-Up Studies
• Heart Failure (complications, drug therapy, physiopathology)
• Humans
• Male
• Middle Aged
• Natriuretic Agents (administration & dosage, therapeutic use)
• Natriuretic Peptide, Brain (administration & dosage, therapeutic use)
• Peak Expiratory Flow Rate (drug effects, physiology)
• Prospective Studies
• Treatment Outcome