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

J Am Coll Cardiol. 2012 Apr 17;59(16):1441-8. doi: 10.1016/j.jacc.2011.11.061.


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).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Natriuretic Agents
  • Natriuretic Peptide, Brain

Associated data