Determinants of Diuretic Responsiveness and Associated Outcomes During Acute Heart Failure Hospitalization: An Analysis From the NHLBI Heart Failure Network Clinical Trials

• Type of Material: Article
• Authors: Michael S. Kiernan, Tufts Medical Center; Susanna R. Stevens, Duke Clinical Research Institute; W.H. Wilson Tang, Cleveland Clinic Foundation; Javed Butler, Emory University; Kevin J. Anstrom, Duke Clinical Research Institute; Edo Y. Birati, University of Pennsylvania; Justin L. Grodin, University of Texas; Divya Gupta, Emory University; Kenneth B. Margulies, Stony Brook University; Shane Larue, Washington University; Victor G. Davila-Roman, Washington University; Adrian F. Hernandez, Duke Clinical Research Institute; Lisa De Las Fuentes, Washington University
• Language: English
• Date: 2018-07-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.cardfail.2018.02.002
• Title of Journal or Parent Work: Journal of Cardiac Failure
• ISSN: 1071-9164
• Volume: 24
• Issue: 7
• Start Page: 428
• End Page: 438
• Grant/Funding Information: J Butler - research support from the National Institutes of Health, European Union; and the FDA, and is a consultant to Amgen, Bayer, Celladon, Covis Medtronic, Janssen, Novartis, Relypsa, StealthPeptide, Takeda, and TrevenaD A Hernandez - Research: Amgen, AstraZeneca, BMS, GSK, Novartis, Janssen, Honorarium: Amgen, Novartis, Janssen.; 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)
• Keywords: Cardiovascular System & Cardiology; CYSTATIN-C; MARKERS; LIMITATIONS; FUROSEMIDE; loop diuretic; ULTRAFILTRATION; CREATININE; DYSPNEA RELIEF; Life Sciences & Biomedicine; Cardiac & Cardiovascular Systems; Acute heart failure; renal failure; SURVIVAL; Science & Technology; TOLVAPTAN; RENAL DYSFUNCTION; cystatin C; congestion
• Research Categories: Health Sciences, General; Health Sciences, Medicine and Surgery

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.