Determinants of Diuretic Responsiveness and Associated Outcomes During Acute Heart Failure Hospitalization

An Analysis From the NHLBI Heart Failure Network Clinical Trials

NHLBI Heart Failure Clinical Trials Network Investigators

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Poor response to loop diuretic therapy is a marker of risk during heart failure hospitalization. We sought to describe baseline determinants of diuretic response and to further explore the relationship between this response and clinical outcomes. Methods and Results: Patient data from the National Heart, Lung, and Blood Institute Heart Failure Network ROSE-AHF and CARRESS-HF clinical trials were analyzed to determine baseline determinants of diuretic response. Diuretic efficiency (DE) was defined as total 72-hour fluid output per total equivalent loop diuretic dose. Data from DOSE-AHF was then used to determine if these predictors of DE correlated with response to a high- versus low-dose diuretic strategy. At 72 hours, the high-DE group had median fluid output of 9071 ml (interquartile range: 7240–11775) with median furosemide dose of 320 mg (220–480) compared with 8030 ml (6300–9915) and 840 mg (600–1215) respectively for the low DE group. Cystatin C was independently associated with DE (odds ratio 0.36 per 1mg/L increase; 95% confidence interval: 0.24–0.56; P < 0.001). Independently from baseline characteristics, reduced fluid output, weight loss and DE were each associated with increased 60 day mortality. Among patients with estimated glomerular filtration rate below the median, those randomized to a high-dose strategy had improved symptoms compared with those randomized to a low-dose strategy. Conclusions: Elevated baseline cystatin C, as a biomarker of renal dysfunction, is associated with reduced diuretic response during heart failure hospitalization. Higher loop diuretic doses are required for therapeutic decongestion in patients with renal insufficiency. Poor response identifies a high-risk population.

Original languageEnglish (US)
JournalJournal of Cardiac Failure
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

National Heart, Lung, and Blood Institute (U.S.)
Diuretics
Hospitalization
Heart Failure
Clinical Trials
Sodium Potassium Chloride Symporter Inhibitors
Cystatin C
Furosemide
Glomerular Filtration Rate
Renal Insufficiency
Weight Loss
Biomarkers
Odds Ratio
Confidence Intervals

Keywords

  • Acute heart failure
  • congestion
  • cystatin C
  • loop diuretic
  • renal failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{916287945a42494e9cde29c7d1465f86,
title = "Determinants of Diuretic Responsiveness and Associated Outcomes During Acute Heart Failure Hospitalization: An Analysis From the NHLBI Heart Failure Network Clinical Trials",
abstract = "Background: Poor response to loop diuretic therapy is a marker of risk during heart failure hospitalization. We sought to describe baseline determinants of diuretic response and to further explore the relationship between this response and clinical outcomes. Methods and Results: Patient data from the National Heart, Lung, and Blood Institute Heart Failure Network ROSE-AHF and CARRESS-HF clinical trials were analyzed to determine baseline determinants of diuretic response. Diuretic efficiency (DE) was defined as total 72-hour fluid output per total equivalent loop diuretic dose. Data from DOSE-AHF was then used to determine if these predictors of DE correlated with response to a high- versus low-dose diuretic strategy. At 72 hours, the high-DE group had median fluid output of 9071 ml (interquartile range: 7240–11775) with median furosemide dose of 320 mg (220–480) compared with 8030 ml (6300–9915) and 840 mg (600–1215) respectively for the low DE group. Cystatin C was independently associated with DE (odds ratio 0.36 per 1mg/L increase; 95{\%} confidence interval: 0.24–0.56; P < 0.001). Independently from baseline characteristics, reduced fluid output, weight loss and DE were each associated with increased 60 day mortality. Among patients with estimated glomerular filtration rate below the median, those randomized to a high-dose strategy had improved symptoms compared with those randomized to a low-dose strategy. Conclusions: Elevated baseline cystatin C, as a biomarker of renal dysfunction, is associated with reduced diuretic response during heart failure hospitalization. Higher loop diuretic doses are required for therapeutic decongestion in patients with renal insufficiency. Poor response identifies a high-risk population.",
keywords = "Acute heart failure, congestion, cystatin C, loop diuretic, renal failure",
author = "{NHLBI Heart Failure Clinical Trials Network Investigators} and Kiernan, {Michael S.} and Stevens, {Susanna R.} and Tang, {W. H.Wilson} and Javed Butler and Anstrom, {Kevin J.} and Birati, {Edo Y.} and Grodin, {Justin L.} and Divya Gupta and Margulies, {Kenneth B.} and Shane LaRue and D{\'a}vila-Rom{\'a}n, {Victor G.} and Hernandez, {Adrian F.} and {de las Fuentes}, Lisa",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.cardfail.2018.02.002",
language = "English (US)",
journal = "Journal of Cardiac Failure",
issn = "1071-9164",
publisher = "Churchill Livingstone",

}

TY - JOUR

T1 - Determinants of Diuretic Responsiveness and Associated Outcomes During Acute Heart Failure Hospitalization

T2 - An Analysis From the NHLBI Heart Failure Network Clinical Trials

AU - NHLBI Heart Failure Clinical Trials Network Investigators

AU - Kiernan, Michael S.

AU - Stevens, Susanna R.

AU - Tang, W. H.Wilson

AU - Butler, Javed

AU - Anstrom, Kevin J.

AU - Birati, Edo Y.

AU - Grodin, Justin L.

AU - Gupta, Divya

AU - Margulies, Kenneth B.

AU - LaRue, Shane

AU - Dávila-Román, Victor G.

AU - Hernandez, Adrian F.

AU - de las Fuentes, Lisa

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Poor response to loop diuretic therapy is a marker of risk during heart failure hospitalization. We sought to describe baseline determinants of diuretic response and to further explore the relationship between this response and clinical outcomes. Methods and Results: Patient data from the National Heart, Lung, and Blood Institute Heart Failure Network ROSE-AHF and CARRESS-HF clinical trials were analyzed to determine baseline determinants of diuretic response. Diuretic efficiency (DE) was defined as total 72-hour fluid output per total equivalent loop diuretic dose. Data from DOSE-AHF was then used to determine if these predictors of DE correlated with response to a high- versus low-dose diuretic strategy. At 72 hours, the high-DE group had median fluid output of 9071 ml (interquartile range: 7240–11775) with median furosemide dose of 320 mg (220–480) compared with 8030 ml (6300–9915) and 840 mg (600–1215) respectively for the low DE group. Cystatin C was independently associated with DE (odds ratio 0.36 per 1mg/L increase; 95% confidence interval: 0.24–0.56; P < 0.001). Independently from baseline characteristics, reduced fluid output, weight loss and DE were each associated with increased 60 day mortality. Among patients with estimated glomerular filtration rate below the median, those randomized to a high-dose strategy had improved symptoms compared with those randomized to a low-dose strategy. Conclusions: Elevated baseline cystatin C, as a biomarker of renal dysfunction, is associated with reduced diuretic response during heart failure hospitalization. Higher loop diuretic doses are required for therapeutic decongestion in patients with renal insufficiency. Poor response identifies a high-risk population.

AB - Background: Poor response to loop diuretic therapy is a marker of risk during heart failure hospitalization. We sought to describe baseline determinants of diuretic response and to further explore the relationship between this response and clinical outcomes. Methods and Results: Patient data from the National Heart, Lung, and Blood Institute Heart Failure Network ROSE-AHF and CARRESS-HF clinical trials were analyzed to determine baseline determinants of diuretic response. Diuretic efficiency (DE) was defined as total 72-hour fluid output per total equivalent loop diuretic dose. Data from DOSE-AHF was then used to determine if these predictors of DE correlated with response to a high- versus low-dose diuretic strategy. At 72 hours, the high-DE group had median fluid output of 9071 ml (interquartile range: 7240–11775) with median furosemide dose of 320 mg (220–480) compared with 8030 ml (6300–9915) and 840 mg (600–1215) respectively for the low DE group. Cystatin C was independently associated with DE (odds ratio 0.36 per 1mg/L increase; 95% confidence interval: 0.24–0.56; P < 0.001). Independently from baseline characteristics, reduced fluid output, weight loss and DE were each associated with increased 60 day mortality. Among patients with estimated glomerular filtration rate below the median, those randomized to a high-dose strategy had improved symptoms compared with those randomized to a low-dose strategy. Conclusions: Elevated baseline cystatin C, as a biomarker of renal dysfunction, is associated with reduced diuretic response during heart failure hospitalization. Higher loop diuretic doses are required for therapeutic decongestion in patients with renal insufficiency. Poor response identifies a high-risk population.

KW - Acute heart failure

KW - congestion

KW - cystatin C

KW - loop diuretic

KW - renal failure

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U2 - 10.1016/j.cardfail.2018.02.002

DO - 10.1016/j.cardfail.2018.02.002

M3 - Article

JO - Journal of Cardiac Failure

JF - Journal of Cardiac Failure

SN - 1071-9164

ER -