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

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