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Eur Heart J. 2014 May 14;35(19):1284-93. doi: 10.1093/eurheartj/ehu065. Epub 2014 Feb 28.

Diuretic response in acute heart failure: clinical characteristics and prognostic significance.

Author information

  • 1Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
  • 2Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
  • 3University of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
  • 4Duke University Medical Center, Durham, NC, USA.
  • 5University of Brescia, Brescia, Italy.
  • 6Medical University, Clinical Military Hospital, Wroclaw, Poland.
  • 7Momentum Research, Durham, NC, USA.
  • 8University of Hull, Kingston upon Hull, UK.
  • 9Brigham and Women's Hospital, Boston, MA, USA.
  • 10Merck Research Laboratories, Rahway, NJ, USA.
  • 11Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
  • 12Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands Department of Epidemiology, University Medical Center Groningen, Groningen, Hanzeplein 1, 9713 GZ, The Netherlands.



Diminished diuretic response is common in patients with acute heart failure, although a clinically useful definition is lacking. Our aim was to investigate a practical, workable metric for diuretic response, examine associated patient characteristics and relationships with outcome.


We examined diuretic response (defined as Δ weight kg/40 mg furosemide) in 1745 hospitalized acute heart failure patients from the PROTECT trial. Day 4 response was used to allow maximum differentiation in responsiveness and tailoring of diuretic doses to clinical response, following sensitivity analyses. We investigated predictors of diuretic response and relationships with outcome. The median diuretic response was -0.38 (-0.80 to -0.13) kg/40 mg furosemide. Poor diuretic response was independently associated with low systolic blood pressure, high blood urea nitrogen, diabetes, and atherosclerotic disease (all P < 0.05). Worse diuretic response independently predicted 180-day mortality (HR: 1.42; 95% CI: 1.11-1.81, P = 0.005), 60-day death or renal or cardiovascular rehospitalization (HR: 1.34; 95% CI: 1.14-1.59, P < 0.001) and 60-day HF rehospitalization (HR: 1.57; 95% CI: 1.24-2.01, P < 0.001) in multivariable models. The proposed metric-weight loss indexed to diuretic dose-better captures a dose-response relationship. Model diagnostics showed diuretic response provided essentially the same or slightly better prognostic information compared with its individual components (weight loss and diuretic dose) in this population, while providing a less biased, more easily interpreted signal.


Worse diuretic response was associated with more advanced heart failure, renal impairment, diabetes, atherosclerotic disease and in-hospital worsening heart failure, and predicts mortality and heart failure rehospitalization in this post hoc, hypothesis-generating study.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email:


Cardiorenal syndrome; Diuretic resistance; Diuretics; Heart failure; Mortality; Prognosis; Rehospitalization; Renal dysfunction; Worsening renal function

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