title: The Importance of Worsening Heart Failure in Ambulatory Patients: Definition, Characteristics, and Effects of Amino-Terminal Pro-B-Type Natriuretic Peptide Guided Therapy.
abstract: The goal of this study was to define and assess the significance of worsening heart failure (WHF) in patients with chronic ambulatory heart failure with reduced ejection fraction (HFrEF).
  
  
  
  WHF has been identified as a potentially relevant clinical event in patients with acute heart failure (HF) and is increasingly used as an endpoint in clinical trials. No standardized definition of WHF exists. It remains uncertain how WHF relates to risk for other HF events or how treatment may affect WHF.
  
  
  
  A total of 151 symptomatic patients with chronic HFrEF were randomized to standard of care HF management or a goal to lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations ≤1,000 pg/ml in addition to standard of care. WHF was prospectively defined as: 1) new or progressive symptoms and/or signs of decompensated HF; and 2) unplanned intensification of diuretic therapy.
  
  
  
  Over a mean follow-up of 10 months, 45 subjects developed WHF. At baseline, patients developing incident WHF had higher ejection fraction (31% vs. 25%; p = 0.03), were more likely to have jugular venous distension and edema (p < 0.02), were less likely to receive angiotensin-converting enzyme inhibitors or received these agents at lower doses (p < 0.04), and also received higher loop diuretic doses (p < 0.001). Occurrence of WHF was strongly associated with subsequent HF hospitalization/cardiovascular death (hazard ratio, landmark analysis: 18.8; 95% confidence interval: 5.7 to 62.5; p < 0.001). NT-proBNP-guided care reduced the incidence of WHF in adjusted analyses (hazard ratio: 0.52; p = 0.06) and improved event-free survival (log-rank test p = 0.04).
  
  
  
  In chronic HFrEF, WHF was associated with substantial risk for morbidity and mortality. NT-proBNP-guided care reduced risk for WHF.
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Aditi
authors.initials: A
authors.lastname: Mallick
authors.affiliation: Cardiology Division, VA Connecticut Healthcare System, West Haven, and Yale 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; Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: Hanna K
authors.initials: HK
authors.lastname: Gaggin
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Nasrien
authors.initials: N
authors.lastname: Ibrahim
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts; Harvard Clinical Research Institute, Boston, Massachusetts. Electronic address: jjanuzzi@mgh.harvard.edu.
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
mesh_terms: D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000553:Ambulatory Care / Q000379:methods*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality*; D018450:Disease Progression; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010347:Patient Care Planning; D010446:Peptide Fragments / Q000097:blood*; D016016:Proportional Hazards Models; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000627:therapeutic use*; D059039:Standard of Care; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D010446:Peptide Fragments; D049994:Sodium Potassium Chloride Symporter Inhibitors; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: biomarkers; chronic heart failure; worsening heart failure