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 journalArticlepeer-review

35 Scopus citations


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
Pages (from-to)428-438
Number of pages11
JournalJournal of Cardiac Failure
Issue number7
StatePublished - Jul 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Inc.


Funding: This research was supported in part by grants from the National Institutes of Health (coordinating center: U10 HL084904 ; regional clinical centers: U01 HL084861 , U10 HL110312 , 13 U10 HL110342 , U10 HL110262 , U10 HL110302 , U10 HL110309 , U10 HL110336 , U10 HL110338 ). J. Butler: research support from the National Institutes of Health, European Union, and Food and Drug Administration; consultant to Amgen, Bayer, Celladon, Covis Medtronic, Janssen, Novartis, Relypsa, Stealthpeptide, Takeda, and Trevena. D.A. Hernandez: research support from Amgen, Astrazeneca, BMS, GSK, Novartis, and Janssen; honoraria from Amgen, Novartis, and Janssen. All other authors have nothing to disclose.

FundersFunder number
National Institutes of HealthU10 HL110338, U10 HL110309, U10 HL110262, U10 HL084904, 13 U10 HL110342, U01 HL084861, U10 HL110302, U10 HL110336
U.S. Food and Drug Administration
National Heart, Lung, and Blood InstituteU10HL110312
Takeda Pharmaceuticals U.S.A.
European Commission


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


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