A combined clinical and biomarker approach to predict diuretic response in acute heart failure.
BACKGROUND
Poor diuretic response in acute heart failure is related to poor clinical outcome. The underlying mechanisms and pathophysiology behind diuretic resistance are incompletely understood. We evaluated a combined approach using clinical characteristics and biomarkers to predict diuretic response in acute heart failure (AHF).


RESULTS
We investigated explanatory and predictive models for diuretic response--weight loss at day 4 per 40 mg of furosemide--in 974 patients with AHF included in the PROTECT trial. Biomarkers, addressing multiple pathophysiological pathways, were determined at baseline and after 24 h. An explanatory baseline biomarker model of a poor diuretic response included low potassium, chloride, hemoglobin, myeloperoxidase, and high blood urea nitrogen, albumin, triglycerides, ST2 and neutrophil gelatinase-associated lipocalin (r(2) = 0.086). Diuretic response after 24 h (early diuretic response) was a strong predictor of diuretic response (β = 0.467, P < 0.001; r(2) = 0.523). Addition of diuretic response after 24 h to biomarkers and clinical characteristics significantly improved the predictive model (r(2) = 0.586, P < 0.001).


CONCLUSIONS
Biomarkers indicate that diuretic unresponsiveness is associated with an atherosclerotic profile with abnormal renal function and electrolytes. However, predicting diuretic response is difficult and biomarkers have limited additive value. Patients at risk of poor diuretic response can be identified by measuring early diuretic response after 24 h.
Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Jozine M
JM
ter Maaten
Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Mattia A E
MA
Valente
University of Brescia, Brescia, Italy.
Marco
M
Metra
Department of Cardiovascular Sciences, "Sapienza" University of Rome, Rome, Italy.
Noemi
N
Bruno
Duke University Medical Center, Durham, NC, USA.
Christopher M
CM
O'Connor
Clinical Military Hospital, Medical University, Wroclaw, Poland.
Piotr
P
Ponikowski
University of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
John R
JR
Teerlink
Momentum Research, Durham, NC, USA.
Gad
G
Cotter
Momentum Research, Durham, NC, USA.
Beth
B
Davison
University of Hull, Kingston upon Hull, UK.
John G
JG
Cleland
Brigham and Women's Hospital, Boston, MA, USA.
Michael M
MM
Givertz
Merck Research Laboratories, Rahway, NJ, USA.
Daniel M
DM
Bloomfield
University of Iowa Carver College of Medicine Cardiovascular Research Center, Iowa City, IA, USA.
Howard C
HC
Dittrich
Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Dirk J
DJ
van Veldhuisen
Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.|University Medical Center Groningen, Department of Epidemiology, University of Groningen, Groningen, The Netherlands.
Hans L
HL
Hillege
Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Kevin
K
Damman
Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. a.a.voors@umcg.nl.
Adriaan A
AA
Voors
D000208:Acute Disease; D050197:Atherosclerosis / Q000150:complications*; D015415:Biomarkers / Q000378:metabolism; D017326:Clinical Trials, Phase III as Topic; D004232:Diuretics / Q000008:administration & dosage* / Q000627:therapeutic use; D004573:Electrolytes / Q000378:metabolism; D005665:Furosemide / Q000008:administration & dosage* / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007674:Kidney Diseases / Q000150:complications; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D004232:Diuretics; D004573:Electrolytes; D005665:Furosemide
Biomarkers; Diuretic response; Heart failure; Prediction