PMID- 33573739
OWN - NLM
STAT- MEDLINE
DCOM- 20210920
LR  - 20220218
IS  - 1558-3597 (Electronic)
IS  - 0735-1097 (Print)
IS  - 0735-1097 (Linking)
VI  - 77
IP  - 6
DP  - 2021 Feb 16
TI  - Natriuretic Equation to Predict Loop Diuretic Response in Patients With 
      Heart Failure.
PG  - 695-708
LID - S0735-1097(20)38108-0 [pii]
LID - 10.1016/j.jacc.2020.12.022 [doi]
AB  - 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.
CI  - Copyright (c) 2021 American College of Cardiology Foundation. Published by Elsevier 
      Inc. All rights reserved.
FAU - Rao, Veena S
AU  - Rao VS
AD  - Department of Internal Medicine, Section of Cardiovascular Medicine, Yale 
      University School of Medicine, New Haven, Connecticut, USA.
FAU - Ivey-Miranda, Juan B
AU  - Ivey-Miranda JB
AD  - Department of Internal Medicine, Section of Cardiovascular Medicine, Yale 
      University School of Medicine, New Haven, Connecticut, USA; Department of Heart 
      Failure, Hospital de Cardiologia, Instituto Mexicano del Seguro Social, Mexico 
      City, Mexico.
FAU - Cox, Zachary L
AU  - Cox ZL
AD  - Department of Pharmacy, Vanderbilt University Medical Center, Nashville, 
      Tennessee, USA.
FAU - Riello, Ralph
AU  - Riello R
AD  - Heart and Vascular Center, Yale New Haven Hospital, New Haven, Connecticut, USA.
FAU - Griffin, Matthew
AU  - Griffin M
AD  - Department of Internal Medicine, Section of Cardiovascular Medicine, Yale 
      University School of Medicine, New Haven, Connecticut, USA.
FAU - Fleming, James
AU  - Fleming J
AD  - Department of Internal Medicine, Section of Cardiovascular Medicine, Yale 
      University School of Medicine, New Haven, Connecticut, USA.
FAU - Soucier, Richard
AU  - Soucier R
AD  - Department of Internal Medicine, Section of Cardiovascular Medicine, Yale 
      University School of Medicine, New Haven, Connecticut, USA.
FAU - Sangkachand, Prasama
AU  - Sangkachand P
AD  - Heart and Vascular Center, Yale New Haven Hospital, New Haven, Connecticut, USA.
FAU - O'Brien, Margaret
AU  - O'Brien M
AD  - Heart and Vascular Center, Yale New Haven Hospital, New Haven, Connecticut, USA.
FAU - LoRusso, Francine
AU  - LoRusso F
AD  - Heart and Vascular Center, Yale New Haven Hospital, New Haven, Connecticut, USA.
FAU - D'Ambrosi, Julie
AU  - D'Ambrosi J
AD  - Heart and Vascular Center, Yale New Haven Hospital, New Haven, Connecticut, USA.
FAU - Churchwell, Keith
AU  - Churchwell K
AD  - Heart and Vascular Center, Yale New Haven Hospital, New Haven, Connecticut, USA.
FAU - Mahoney, Devin
AU  - Mahoney D
AD  - Department of Internal Medicine, Section of Cardiovascular Medicine, Yale 
      University School of Medicine, New Haven, Connecticut, USA.
FAU - Bellumkonda, Lavanya
AU  - Bellumkonda L
AD  - Department of Internal Medicine, Section of Cardiovascular Medicine, Yale 
      University School of Medicine, New Haven, Connecticut, USA.
FAU - Asher, Jennifer L
AU  - Asher JL
AD  - Department of Comparative Medicine, Yale University School of Medicine, New 
      Haven, Connecticut, USA.
FAU - Maulion, Christopher
AU  - Maulion C
AD  - Department of Internal Medicine, Section of Cardiovascular Medicine, Yale 
      University School of Medicine, New Haven, Connecticut, USA.
FAU - Turner, Jeffrey M
AU  - Turner JM
AD  - Department of Medicine, Division of Nephrology, Yale University School of 
      Medicine, New Haven, Connecticut, USA.
FAU - Wilson, F Perry
AU  - Wilson FP
AD  - Clinical and Translational Research Accelerator, Yale University School of 
      Medicine, New Haven, Connecticut, USA.
FAU - Collins, Sean P
AU  - Collins SP
AD  - Department of Emergency Medicine, Vanderbilt University Medical Center, 
      Nashville, Tennessee, USA.
FAU - Testani, Jeffrey M
AU  - Testani JM
AD  - Department of Internal Medicine, Section of Cardiovascular Medicine, Yale 
      University School of Medicine, New Haven, Connecticut, USA. Electronic address: 
      jeffrey.testani@yale.edu.
LA  - eng
GR  - R01 HL128973/HL/NHLBI NIH HHS/United States
GR  - R21 HL143092/HL/NHLBI NIH HHS/United States
GR  - R01 DK113191/DK/NIDDK NIH HHS/United States
GR  - R01 HL139629/HL/NHLBI NIH HHS/United States
GR  - R01 HL148354/HL/NHLBI NIH HHS/United States
GR  - L30 HL115790/HL/NHLBI NIH HHS/United States
GR  - K23 HL114868/HL/NHLBI NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
GR  - T32 HL007950/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Validation Study
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Biomarkers)
RN  - 0 (Sodium Potassium Chloride Symporter Inhibitors)
RN  - 9NEZ333N27 (Sodium)
SB  - IM
CIN - J Am Coll Cardiol. 2021 Feb 16;77(6):709-712. PMID: 33573740
CIN - J Am Coll Cardiol. 2021 Jun 1;77(21):2757-2758. PMID: 34045033
CIN - J Am Coll Cardiol. 2021 Jun 1;77(21):2758-2759. PMID: 34045035
MH  - Aged
MH  - Biomarkers/urine
MH  - Cohort Studies
MH  - Drug Monitoring/*methods
MH  - Female
MH  - Heart Failure/*drug therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Models, Biological
MH  - Natriuresis/*drug effects
MH  - Proof of Concept Study
MH  - Sodium/*urine
MH  - Sodium Potassium Chloride Symporter Inhibitors/*therapeutic use
MH  - Urinalysis
PMC - PMC8114781
MID - NIHMS1663088
OTO - NOTNLM
OT  - diuretics
OT  - heart failure
OT  - natriuretic response
OT  - sodium
COIS- Funding Support and Author Disclosures This study was supported by National 
      Institutes of Health (NIH) grants K23HL114868, L30HL115790, R01HL139629, 
      R21HL143092, R01HL128973, and R01HL148354 (to Dr. Testani); R01DK113191 and 
      P30DK079210 (to Dr. Wilson); and 5T32HL007950 (to Dr. Griffin). The funding 
      source had no role in study design, data collection, analysis, or interpretation. 
      The contents of this paper are solely the responsibility of the authors and do 
      not necessarily represent the official view of NIH. Dr. Rao has a patent 
      treatment of diuretic resistance (US20200079846A1) issued to Yale and Corvidia 
      Therapeutics Inc. with royalties paid to Yale University; has (with Dr. Testani) 
      a patent method for measuring renalase (WO2019133665A2) issued to Yale; and has 
      received personal fees from Translational Catalyst. Dr. Riello has received 
      consulting fees from Janssen, Johnson & Johnson, Pfizer, and Portola; and has 
      served on advisory boards for AstraZeneca, Janssen, Johnson & Johnson, Medicure, 
      and Portola. Ms. Mahoney has received personal fees from Sequana Medical. Dr. 
      Collins has received grants from the NIH, Patient-Centered Outcomes Research 
      Institute, Agency for Healthcare Research and Quality, and AstraZeneca; and has 
      received personal fees from Ortho Clinical, Boehringer Ingelheim, Roche, and 
      Relypsa Medical. Dr. Testani has (with Dr. Rao) a patent method for measuring 
      renalase (WO2019133665A2) issued to Yale; has received personal fees from 
      Reprieve Medical, AstraZeneca, Novartis, Cardionomic, Bayer, MagentaMed, W.L. 
      Gore, and Windtree Therapeutics; has received grants and personal fees from 
      Bristol Myers Squibb, 3ive Labs, Boehringer Ingelheim, Sanofi, and FIRE1; has 
      received grants from Otsuka, Abbott, and Merck outside of the submitted work; and 
      has patents for treating diuretic resistance filed and issued. All other authors 
      have reported that they have no relationships relevant to the contents of this 
      paper to disclose.
EDAT- 2021/02/13 06:00
MHDA- 2021/09/21 06:00
PMCR- 2022/02/16
CRDT- 2021/02/12 05:40
PHST- 2020/09/18 00:00 [received]
PHST- 2020/12/02 00:00 [revised]
PHST- 2020/12/07 00:00 [accepted]
PHST- 2021/02/12 05:40 [entrez]
PHST- 2021/02/13 06:00 [pubmed]
PHST- 2021/09/21 06:00 [medline]
PHST- 2022/02/16 00:00 [pmc-release]
AID - S0735-1097(20)38108-0 [pii]
AID - 10.1016/j.jacc.2020.12.022 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2021 Feb 16;77(6):695-708. doi: 10.1016/j.jacc.2020.12.022.