title: Rapid and Highly Accurate Prediction of Poor Loop Diuretic Natriuretic Response in Patients With Heart Failure.
abstract: BACKGROUND
  Removal of excess sodium and fluid is a primary therapeutic objective in acute decompensated heart failure and commonly monitored with fluid balance and weight loss. However, these parameters are frequently inaccurate or not collected and require a delay of several hours after diuretic administration before they are available. Accessible tools for rapid and accurate prediction of diuretic response are needed.
  
  
  RESULTS
  Based on well-established renal physiological principles, an equation was derived to predict net sodium output using a spot urine sample obtained 1 or 2 hours after loop diuretic administration. This equation was then prospectively validated in 50 acute decompensated heart failure patients using meticulously obtained timed 6-hour urine collections to quantify loop diuretic-induced cumulative sodium output. Poor natriuretic response was defined as a cumulative sodium output of <50 mmol, a threshold that would result in a positive sodium balance with twice-daily diuretic dosing. Following a median dose of 3 mg (2-4 mg) of intravenous bumetanide, 40% of the population had a poor natriuretic response. The correlation between measured and predicted sodium output was excellent (r=0.91; P<0.0001). Poor natriuretic response could be accurately predicted with the sodium prediction equation (area under the curve =0.95, 95% confidence interval 0.89-1.0; P<0.0001). Clinically recorded net fluid output had a weaker correlation (r=0.66; P<0.001) and lesser ability to predict poor natriuretic response (area under the curve =0.76, 95% confidence interval 0.63-0.89; P=0.002).
  
  
  CONCLUSIONS
  In patients being treated for acute decompensated heart failure, poor natriuretic response can be predicted soon after diuretic administration with excellent accuracy using a spot urine sample.
authors.affiliation: From the Department of Internal Medicine (J.M.T., M.C., F.P.W., L.B., D.J., C.R.P.) and Program of Applied Translational Research (J.M.T., J.S., S.C., V.R., C.O., O.L., A.K., F.P.W., C.R.P.), Yale University School of Medicine, New Haven, CT; Piedmont Heart Institute, Fayetteville, GA (A.D.); and Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic, OH (W.H.W.T.). jeffrey.testani@yale.edu.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Testani
authors.affiliation: From the Department of Internal Medicine (J.M.T., M.C., F.P.W., L.B., D.J., C.R.P.) and Program of Applied Translational Research (J.M.T., J.S., S.C., V.R., C.O., O.L., A.K., F.P.W., C.R.P.), Yale University School of Medicine, New Haven, CT; Piedmont Heart Institute, Fayetteville, GA (A.D.); and Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic, OH (W.H.W.T.).
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Hanberg
authors.affiliation: From the Department of Internal Medicine (J.M.T., M.C., F.P.W., L.B., D.J., C.R.P.) and Program of Applied Translational Research (J.M.T., J.S., S.C., V.R., C.O., O.L., A.K., F.P.W., C.R.P.), Yale University School of Medicine, New Haven, CT; Piedmont Heart Institute, Fayetteville, GA (A.D.); and Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic, OH (W.H.W.T.).
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.affiliation: From the Department of Internal Medicine (J.M.T., M.C., F.P.W., L.B., D.J., C.R.P.) and Program of Applied Translational Research (J.M.T., J.S., S.C., V.R., C.O., O.L., A.K., F.P.W., C.R.P.), Yale University School of Medicine, New Haven, CT; Piedmont Heart Institute, Fayetteville, GA (A.D.); and Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic, OH (W.H.W.T.).
authors.forename: Veena
authors.initials: V
authors.lastname: Rao
authors.affiliation: From the Department of Internal Medicine (J.M.T., M.C., F.P.W., L.B., D.J., C.R.P.) and Program of Applied Translational Research (J.M.T., J.S., S.C., V.R., C.O., O.L., A.K., F.P.W., C.R.P.), Yale University School of Medicine, New Haven, CT; Piedmont Heart Institute, Fayetteville, GA (A.D.); and Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic, OH (W.H.W.T.).
authors.forename: Chukwuma
authors.initials: C
authors.lastname: Onyebeke
authors.affiliation: From the Department of Internal Medicine (J.M.T., M.C., F.P.W., L.B., D.J., C.R.P.) and Program of Applied Translational Research (J.M.T., J.S., S.C., V.R., C.O., O.L., A.K., F.P.W., C.R.P.), Yale University School of Medicine, New Haven, CT; Piedmont Heart Institute, Fayetteville, GA (A.D.); and Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic, OH (W.H.W.T.).
authors.forename: Olga
authors.initials: O
authors.lastname: Laur
authors.affiliation: From the Department of Internal Medicine (J.M.T., M.C., F.P.W., L.B., D.J., C.R.P.) and Program of Applied Translational Research (J.M.T., J.S., S.C., V.R., C.O., O.L., A.K., F.P.W., C.R.P.), Yale University School of Medicine, New Haven, CT; Piedmont Heart Institute, Fayetteville, GA (A.D.); and Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic, OH (W.H.W.T.).
authors.forename: Alexander
authors.initials: A
authors.lastname: Kula
authors.affiliation: From the Department of Internal Medicine (J.M.T., M.C., F.P.W., L.B., D.J., C.R.P.) and Program of Applied Translational Research (J.M.T., J.S., S.C., V.R., C.O., O.L., A.K., F.P.W., C.R.P.), Yale University School of Medicine, New Haven, CT; Piedmont Heart Institute, Fayetteville, GA (A.D.); and Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic, OH (W.H.W.T.).
authors.forename: Michael
authors.initials: M
authors.lastname: Chen
authors.affiliation: From the Department of Internal Medicine (J.M.T., M.C., F.P.W., L.B., D.J., C.R.P.) and Program of Applied Translational Research (J.M.T., J.S., S.C., V.R., C.O., O.L., A.K., F.P.W., C.R.P.), Yale University School of Medicine, New Haven, CT; Piedmont Heart Institute, Fayetteville, GA (A.D.); and Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic, OH (W.H.W.T.).
authors.forename: F Perry
authors.initials: FP
authors.lastname: Wilson
authors.affiliation: From the Department of Internal Medicine (J.M.T., M.C., F.P.W., L.B., D.J., C.R.P.) and Program of Applied Translational Research (J.M.T., J.S., S.C., V.R., C.O., O.L., A.K., F.P.W., C.R.P.), Yale University School of Medicine, New Haven, CT; Piedmont Heart Institute, Fayetteville, GA (A.D.); and Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic, OH (W.H.W.T.).
authors.forename: Andrew
authors.initials: A
authors.lastname: Darlington
authors.affiliation: From the Department of Internal Medicine (J.M.T., M.C., F.P.W., L.B., D.J., C.R.P.) and Program of Applied Translational Research (J.M.T., J.S., S.C., V.R., C.O., O.L., A.K., F.P.W., C.R.P.), Yale University School of Medicine, New Haven, CT; Piedmont Heart Institute, Fayetteville, GA (A.D.); and Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic, OH (W.H.W.T.).
authors.forename: Lavanya
authors.initials: L
authors.lastname: Bellumkonda
authors.affiliation: From the Department of Internal Medicine (J.M.T., M.C., F.P.W., L.B., D.J., C.R.P.) and Program of Applied Translational Research (J.M.T., J.S., S.C., V.R., C.O., O.L., A.K., F.P.W., C.R.P.), Yale University School of Medicine, New Haven, CT; Piedmont Heart Institute, Fayetteville, GA (A.D.); and Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic, OH (W.H.W.T.).
authors.forename: Daniel
authors.initials: D
authors.lastname: Jacoby
authors.affiliation: From the Department of Internal Medicine (J.M.T., M.C., F.P.W., L.B., D.J., C.R.P.) and Program of Applied Translational Research (J.M.T., J.S., S.C., V.R., C.O., O.L., A.K., F.P.W., C.R.P.), Yale University School of Medicine, New Haven, CT; Piedmont Heart Institute, Fayetteville, GA (A.D.); and Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic, OH (W.H.W.T.).
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
authors.affiliation: From the Department of Internal Medicine (J.M.T., M.C., F.P.W., L.B., D.J., C.R.P.) and Program of Applied Translational Research (J.M.T., J.S., S.C., V.R., C.O., O.L., A.K., F.P.W., C.R.P.), Yale University School of Medicine, New Haven, CT; Piedmont Heart Institute, Fayetteville, GA (A.D.); and Section of Heart Failure and Cardiac Transplantation, Cleveland Clinic, OH (W.H.W.T.).
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
mesh_terms: D000208:Acute Disease; D061605:Administration, Intravenous; D000368:Aged; D015415:Biomarkers / Q000652:urine; D002034:Bumetanide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods*; D004351:Drug Resistance; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009318:Natriuresis / Q000187:drug effects*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D012964:Sodium / Q000652:urine*; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D016482:Urinalysis
chemical_list: D015415:Biomarkers; D049994:Sodium Potassium Chloride Symporter Inhibitors; D002034:Bumetanide; D012964:Sodium
keywords: diuretic resistance; diuretics; heart failure; poor natriuretic response; sodium