title: Determinants and impact of the natriuretic response to diuretic therapy in heart failure with reduced ejection fraction and volume overload.
abstract: OBJECTIVE
  The objective of this study was to investigate determinants of the natriuretic response to diuretics in decompensated heart failure (HF) and the relationship with decongestion, neurohumoral activation and clinical outcome in the contemporary era of HF management.
  
  
  RESULTS
  In this prospective, single-centre cohort study, consecutive patients with decompensated HF (n = 54) and left ventricular ejection fraction 45% received protocol-driven diuretic therapy until complete disappearance of congestion signs. Urine was collected during three consecutive 24-h intervals. Natriuretic response was defined as absolute natriuresis (mmol) per mg of intravenous bumetanide administered. Natriuresis was 146 mmol (76-206 mmol), 74 mmol (37-167 mmol) and 74 mmol (53-134 mmol) per mg intravenous bumetanide administered during the first, second and third 24-h interval, respectively. Diastolic blood pressure (beta = 23.048 +/- 10.788; P-value = 0.036), plasma aldosterone (beta = -25.722?11.560; P-value=0.029), and combination therapy with acetazolamide (beta = 103.241 +/- 40.962; P-value = 0.014) were independent predictors of the natriuretic response. Patients with a stronger natriuretic response demonstrated more pronounced decreases in plasma NT-proBNP levels (P-value = 0.025), while a weaker response was associated with higher peak plasma aldosterone levels (P-value = 0.013) and plasma renin activity (P-value = 0.033). Natriuresis per loop diuretic dose predicted freedom from all-cause mortality or HF readmissions, independently of baseline renal function (HR 0.40, 95% CI 0.16-0.98; P-value = 0.045).
  
  
  CONCLUSIONS
  More effective natriuresis in decompensated HF patients with reduced ejection fraction and volume overload is associated with better decongestion, less neurohumoral activation and predicts favourable clinical outcome independently from renal function per se. Acetazolamide warrants further evaluation in large prospective trials to increase the natriuretic response to loop diuretics.
authors.forename: Frederik H
authors.initials: FH
authors.lastname: Verbrugge
authors.forename: Matthias
authors.initials: M
authors.lastname: Dupont
authors.forename: Philippe B
authors.initials: PB
authors.lastname: Bertrand
authors.forename: Petra
authors.initials: P
authors.lastname: Nijst
authors.forename: Joris
authors.initials: J
authors.lastname: Penders
authors.forename: Joseph
authors.initials: J
authors.lastname: Dens
authors.forename: David
authors.initials: D
authors.lastname: Verhaert
authors.forename: Pieter
authors.initials: P
authors.lastname: Vandervoort
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
authors.forename: Wilfried
authors.initials: W
authors.lastname: Mullens
mesh_terms: D000368:Aged; D002034:Bumetanide / Q000494:pharmacology / Q000627:therapeutic use; D015331:Cohort Studies; D004232:Diuretics / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011446:Prospective Studies; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000627:therapeutic use; D013318:Stroke Volume / Q000187:drug effects*
chemical_list: D004232:Diuretics; D049994:Sodium Potassium Chloride Symporter Inhibitors; D002034:Bumetanide