title: 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: OBJECTIVE
  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.affiliation: University of Alberta, Edmonton, Canada. jae2@ualberta.ca
authors.forename: Justin A
authors.initials: JA
authors.lastname: Ezekowitz
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.forename: Randall C
authors.initials: RC
authors.lastname: Starling
authors.forename: Guy
authors.initials: G
authors.lastname: Proulx
authors.forename: Mason H
authors.initials: MH
authors.lastname: Weiss
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bakal
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004417:Dyspnea / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D045283:Natriuretic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage / Q000627:therapeutic use*; D010366:Peak Expiratory Flow Rate / Q000187:drug effects / Q000502:physiology*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D045283:Natriuretic Agents; D020097:Natriuretic Peptide, Brain