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CLINICAL RESEARCH: HEART FAILURE

Timing of Immunoreactive B-Type Natriuretic Peptide Levels and Treatment Delay in Acute Decompensated Heart Failure

An ADHERE (Acute Decompensated Heart Failure National Registry) Analysis

Alan S. Maisel, MD, FACC^_*,,_*, William F. Peacock, MD, N. McMullin, MD, Robert Jessie, MD, FACC, Gregg C. Fonarow, MD, FACC^¶, Janet Wynne, MS^|| and Roger M. Mills, MD, FACC^||

^_* Veterans Administration, San Diego, California
University of California, San Diego, California
The Cleveland Clinic, Cleveland, Ohio
Virginia Commonwealth University Medical Center, Medical College of Virginia, Richmond, Virginia
^¶ University of California, Los Angeles, Los Angeles, California
^|| Scios Inc., Mountain View, California.

Manuscript received February 21, 2008; revised manuscript received May 9, 2008, accepted May 12, 2008.

^_* Reprint requests and correspondence: Dr. Alan S. Maisel, San Diego VA Medical Center, 3340 La Jolla Village Drive, San Diego, California 92161. (Email: amaisel{at}ucsd.edu).

Objectives: We undertook this analysis to determine whether there is a relationship between the time to measurement of immunoreactive B-type natriuretic peptide (iBNP) and early intervention for acutely decompensated heart failure (ADHF) and whether these variables are associated with morbidity and mortality in ADHF patients.

Background: Although natriuretic peptides (NPs) can aid emergency department (ED) physicians in the diagnosis of ADHF, the relationship between the time to measurement of NP levels and time to treatment is not clear. In addition, the impact of time to treatment on clinical outcomes has not been demonstrated.

Methods: Patients from ADHERE (Acute Decompensated Heart Failure National Registry) who were admitted to the ED and who received intravenous diuretics were included. Recordings of iBNP levels and the timing of intravenous diuretic therapy were documented. Patients were divided by quartiles of time to treatment and iBNP levels, creating 16 categories.

Results: In 58,465 ADHF episodes from 209 hospitals, patients with the longest average time to iBNP draw also had the longest time to treatment. Mean ED time increased with increased time-to-treatment quartiles. Rales on initial examination were associated with early recognition of HF and earlier institution of therapy. The later the treatment took place, the fewer patients were asymptomatic at the time of hospital discharge. Within the time-to-treatment quartiles, mortality increased with increasing iBNP. Treatment delay was independently, but modestly, associated with increased in-hospital mortality with a risk-adjusted odds ratio 1.021, 95% confidence interval 1.010 to 1.033, and p < 0.0001, per every 4-h delay.

Conclusions: In the ED setting, delayed measurement of iBNP levels and delay in treatment for ADHF were strongly associated. These delays were linked with modestly increased in-hospital mortality, independent of other prognostic variables. The adverse impact of delay was most notable in patients with greater iBNP levels (Registry for Acute Decompensated Heart Failure Patients; NCT00366639).

Key Words: B-type natriuretic peptide • heart failure • mortality • registries • diuretics

Abbreviations and Acronyms   ADHERE = Acute Decompensated Heart Failure National Registry   ADHF = acute decompensated heart failure   CI = confidence interval   ED = emergency department   GEE = generalized estimating equation   HF = heart failure   iBNP = immunoreactive B-type natriuretic peptide   ICU = intensive care unit

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