Rapid and Highly Accurate Prediction of Poor Loop Diuretic Natriuretic Response in Patients With Heart Failure

Circ Heart Fail. 2016 Jan;9(1):e002370. doi: 10.1161/CIRCHEARTFAILURE.115.002370.

Abstract

Background: Removal of excess sodium and fluid is a primary therapeutic objective in acute decompensated heart failure and commonly monitored with fluid balance and weight loss. However, these parameters are frequently inaccurate or not collected and require a delay of several hours after diuretic administration before they are available. Accessible tools for rapid and accurate prediction of diuretic response are needed.

Methods and results: Based on well-established renal physiological principles, an equation was derived to predict net sodium output using a spot urine sample obtained 1 or 2 hours after loop diuretic administration. This equation was then prospectively validated in 50 acute decompensated heart failure patients using meticulously obtained timed 6-hour urine collections to quantify loop diuretic-induced cumulative sodium output. Poor natriuretic response was defined as a cumulative sodium output of <50 mmol, a threshold that would result in a positive sodium balance with twice-daily diuretic dosing. Following a median dose of 3 mg (2-4 mg) of intravenous bumetanide, 40% of the population had a poor natriuretic response. The correlation between measured and predicted sodium output was excellent (r=0.91; P<0.0001). Poor natriuretic response could be accurately predicted with the sodium prediction equation (area under the curve =0.95, 95% confidence interval 0.89-1.0; P<0.0001). Clinically recorded net fluid output had a weaker correlation (r=0.66; P<0.001) and lesser ability to predict poor natriuretic response (area under the curve =0.76, 95% confidence interval 0.63-0.89; P=0.002).

Conclusions: In patients being treated for acute decompensated heart failure, poor natriuretic response can be predicted soon after diuretic administration with excellent accuracy using a spot urine sample.

Keywords: diuretic resistance; diuretics; heart failure; poor natriuretic response; sodium.

Publication types

  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Acute Disease
  • Administration, Intravenous
  • Aged
  • Biomarkers / urine
  • Bumetanide / administration & dosage
  • Bumetanide / adverse effects
  • Bumetanide / therapeutic use*
  • Drug Monitoring / methods*
  • Drug Resistance
  • Female
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Heart Failure / urine
  • Humans
  • Male
  • Middle Aged
  • Models, Biological*
  • Natriuresis / drug effects*
  • Predictive Value of Tests
  • Prospective Studies
  • Reproducibility of Results
  • Sodium / urine*
  • Sodium Potassium Chloride Symporter Inhibitors / administration & dosage
  • Sodium Potassium Chloride Symporter Inhibitors / adverse effects
  • Sodium Potassium Chloride Symporter Inhibitors / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Urinalysis

Substances

  • Biomarkers
  • Sodium Potassium Chloride Symporter Inhibitors
  • Bumetanide
  • Sodium