title: Worsening Renal Function during Management for Chronic Heart Failure with Reduced Ejection Fraction: Results From the Pro-BNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study.
abstract: OBJECTIVE
  To assess prognostic meaning of worsening renal failure (WRF) occurring during management of chronic heart failure (HF) with reduced ejection fraction.
  
  
  BACKGROUND
  When WRF develops during titration of HF medical therapy, it commonly leads to less aggressive care.
  
  
  METHODS
  A total of 151 patients enrolled in a prospective, randomized study of standard of care (SOC) HF therapy versus SOC plus a goal N-terminal pro-B type natriuretic peptide (NT-proBNP) < 1000 pg/mL were examined. Cardiovascular (CV) event (defined as worsening HF, hospitalization for HF, significant ventricular arrhythmia, acute coronary or cerebral ischemia, or CV death) at 1 year relative to WRF (defined as any reduction in estimated glomerular filtration rate) 90 days postenrollment were tabulated.
  
  
  RESULTS
  Those developing WRF by 3 months had an average 14% reduction in estimated glomerular filtration rate. There was no difference in incidence of WRF between study arms (43% in SOC, 57% in NT-proBNP, P = .29). During the first 3 months of therapy titration, incident WRF was associated with numerically fewer CV events at 1 year compared with those without WRF (mean 0.81 vs 1.16 events, P = .21). WRF was associated trend toward fewer CV events in the SOC arm (hazard ratio 0.45, 95% confidence interval 0.16-1.24, P = .12); the NT-proBNP-guided arm had numerically lower CV event rates regardless of WRF. Subjects with NT-proBNP <1000 pg/mL and WRF received higher doses of guideline directed medical therapies, lower doses of loop diuretics, and had significantly lower CV event rates (P < .001).
  
  
  CONCLUSIONS
  Modest degrees of WRF are common during aggressive HF with reduced ejection fraction management, but we found no significant association with CV outcomes. HF care guided by NT-proBNP was not associated with more WRF compared with SOC, and led to benefit regardless of final renal function.
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts; Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: Nasrien E
authors.initials: NE
authors.lastname: Ibrahim
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts; Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: Hanna K
authors.initials: HK
authors.lastname: Gaggin
authors.affiliation: Massachusetts General Hospital Biostatistics Center, Boston, Massachusetts.
authors.forename: Dustin J
authors.initials: DJ
authors.lastname: Rabideau
authors.affiliation: Cardiology Division, Veterans Administration Connecticut Healthcare System, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Parul U
authors.initials: PU
authors.lastname: Gandhi
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Aditi
authors.initials: A
authors.lastname: Mallick
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts; Harvard Clinical Research Institute, Boston, Massachusetts. Electronic address: jjanuzzi@partners.org.
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D002908:Chronic Disease; D015331:Cohort Studies; D018450:Disease Progression; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000032:analysis*; D010045:Outpatients / Q000706:statistics & numerical data; D010446:Peptide Fragments / Q000032:analysis*; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000503:physiopathology*; D018570:Risk Assessment; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000502:physiology*; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D004232:Diuretics; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: Heart failure; biomarkers; renal failure