Natriuretic Equation to Predict Loop Diuretic Response in Patients With Heart Failure

J Am Coll Cardiol. 2021 Feb 16;77(6):695-708. doi: 10.1016/j.jacc.2020.12.022.

Abstract

Background: Most acute decompensated heart failure admissions are driven by congestion. However, residual congestion is common and often driven by the lack of reliable tools to titrate diuretic therapy. The authors previously developed a natriuretic response prediction equation (NRPE), which predicts sodium output using a spot urine sample collected 2 h after loop diuretic administration.

Objectives: The purpose of this study was to validate the NRPE and describe proof-of-concept that the NRPE can be used to guide diuretic therapy.

Methods: Two cohorts were assembled: 1) the Diagnosing and Targeting Mechanisms of Diuretic Resistance (MDR) cohort was used to validate the NRPE to predict 6-h sodium output after a loop diuretic, which was defined as poor (<50 mmol), suboptimal (<100 mmol), or excellent (>150 mmol); and 2) the Yale Diuretic Pathway (YDP) cohort, which used the NRPE to guide loop diuretic titration via a nurse-driven automated protocol.

Results: Evaluating 638 loop diuretic administrations, the NRPE showed excellent discrimination with areas under the curve ≥0.90 to predict poor, suboptimal, and excellent natriuretic response, and outperformed clinically obtained net fluid loss (p < 0.05 for all cutpoints). In the YDP cohort (n = 161) using the NRPE to direct therapy mean daily urine output (1.8 ± 0.9 l vs. 3.0 ± 0.8 l), net fluid output (-1.1 ± 0.9 l vs. -2.1 ± 0.9 l), and weight loss (-0.3 ± 0.3 kg vs. -2.5 ± 0.3 kg) improved substantially following initiation of the YDP (p < 0.001 for all pre-post comparisons).

Conclusions: Natriuretic response can be rapidly and accurately predicted by the NRPE, and this information can be used to guide diuretic therapy during acute decompensated heart failure. Additional study of diuresis guided by the NRPE is warranted.

Keywords: diuretics; heart failure; natriuretic response; sodium.

Publication types

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

MeSH terms

  • Aged
  • Biomarkers / urine
  • Cohort Studies
  • Drug Monitoring / methods*
  • Female
  • Heart Failure / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Models, Biological*
  • Natriuresis / drug effects*
  • Proof of Concept Study
  • Sodium / urine*
  • Sodium Potassium Chloride Symporter Inhibitors / therapeutic use*
  • Urinalysis

Substances

  • Biomarkers
  • Sodium Potassium Chloride Symporter Inhibitors
  • Sodium