N-terminal pro brain natriuretic peptide-guided management in patients with heart failure and preserved ejection fraction: findings from the Trial of Intensified versus standard medical therapy in elderly patients with congestive heart failure (TIME-CHF)

Eur J Heart Fail. 2013 Oct;15(10):1148-56. doi: 10.1093/eurjhf/hft076. Epub 2013 May 8.


Aims: To assess the effects of an NT-proBNP-guided medical management on 18-month outcomes in patients with heart failure (HF) and preserved LVEF ( HFpEF).

Methods and results: Patients with HFpEF (LVEF >45%; n = 123) and HF with reduced LVEF (HFrEF; LVEF ≤45%; n = 499) with age ≥60 years, NYHA class ≥ II, and elevated NT-proBNP (>400 ng/L or >800 ng/L depending on age) were randomized to medical therapy titrated only to reduce symptoms to NYHA ≤II (symptom-guided) or also to reduce NT-proBNP below the inclusion threshold (NT-proBNP-guided) during a 6-month period. Patients were followed for an additional 12 months. Despite similar treatment escalation, NT-proBNP reduction and symptom relief were less in HFpEF than in HFrEF. Hospitalization-free survival at 18 months was worse in HFpEF than in HFrEF (P = 0.02), while survival and HF hospitalization-free survival did not differ. Among HFpEF patients, NT-proBNP reduction and symptom relief were similar in the symptom-guided (n = 59) and NT-proBNP-guided (n = 64) group despite more aggressive treatment in the NT-proBNP-guided group. In contrast to effects in HFrEF, NT-proBNP-guided management tended to worsen 18-month outcomes in HFpEF, with P-values for the interactions between LVEF stratum and management strategy of 0.2 for hospitalization-free survival, 0.03 for survival, and 0.01 for HF hospitalization-free survival.

Conclusions: Outcomes in HFpEF were not better than in HFrEF, and opposite effects of NT-proBNP-guided management were observed in HFpEF compared with HFrEF. These preliminary findings suggest that, in contrast to HFrEF, NT-proBNP-guided therapy may not be beneficial in HFpEF. Trial registration ISRCTN43596477.

Keywords: Biomarker; Heart failure; Natriuretic peptide; Preserved ejection fraction.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Aged
  • Aged, 80 and over
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Disease Management
  • Diuretics / therapeutic use
  • Female
  • Heart Failure / blood
  • Heart Failure / drug therapy*
  • Hospitalization
  • Humans
  • Male
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Sodium Potassium Chloride Symporter Inhibitors / therapeutic use*
  • Spironolactone / therapeutic use*
  • Stroke Volume
  • Treatment Outcome


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Diuretics
  • Peptide Fragments
  • Sodium Potassium Chloride Symporter Inhibitors
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Spironolactone

Associated data

  • ISRCTN/ISRCTN43596477