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Original research article
Prognosis and NT-proBNP in heart failure patients with preserved versus reduced ejection fraction
  1. Khibar Salah1,2,
  2. Susan Stienen1,3,
  3. Yigal M Pinto1,
  4. Luc W Eurlings4,
  5. Marco Metra5,
  6. Antoni Bayes-Genis6,
  7. Valerio Verdiani7,
  8. Jan G P Tijssen1,
  9. Wouter E Kok1
  1. 1 Heart Centre, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amasterdam, The Netherlands
  2. 2 Department of Radiology and Nuclear Medicine, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands
  3. 3 INSERM, Centre d’Investigation Cliniques Plurithématique, Université de Lorraine, CHRU de Nancy, Nancy, France
  4. 4 Department of Cardiology, VieCuri Medical Centre, Venlo, The Netherlands
  5. 5 Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Cardiology, University of Brescia, Brescia, Italy
  6. 6 Department of Cardiology, CIBERCV, Hospital Universitari Germans Trias i Pujol, Barcalona, Spain
  7. 7 Department of Internal Medicine and Emergency, Careggi University Hospital, Florence, Italy
  1. Correspondence to Khibar Salah, AMC, Amsterdam 1105 AZ, The Netherlands; k.salah{at}


Background We assessed the prognostic significance of absolute and percentage change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients hospitalised for acute decompensated heart failure with preservedejection fraction (HFpEF) versus heart failure with reduced ejection fraction (HFrEF).

Methods Patients with left ventricular ejection fraction ≥50% were categorised as HFpEF (n=283), while those with <40% as were categorised as HFrEF (n=776). Prognostic values of absolute and percentage change in NT-proBNP levels for 6 months all-cause mortality after discharge were assessed separately in patients with HFpEF and HFrEF by multivariable adjusted Cox regression analysis. Comorbidities were compared between heart failure groups.

Results Discharge NT-proBNP levels predicted outcome similarly in HFpEF and HFrEF: for any 2.7-factor increase in NT-proBNP levels, the HR for mortality was 2.14 for HFpEF (95% CI 1.48 to 3.09) and 1.96 for HFrEF (95% CI 1.60 to 2.40). Mortality prediction was equally possible for NT-proBNP reduction of ≤30% (HR 4.60, 95% CI 1.47 to 14.40 and HR 3.36, 95% CI 1.93 to 5.85 for HFpEF and HFrEF, respectively) and for >30%–60% (HR 3.28, 95% CI 1.07 to 10.12 and HR 1.79, 95% CI 0.99 to 3.26, respectively), compared with mortality in the reference groups of >60% reductions in NT-proBNP levels. Prognostically relevant comorbidities were more often present in patients with HFpEF than patients with HFrEF in low (≤3000 pg/mL) but not in high (>3000 pg/mL) NT-proBNP discharge categories.

Conclusions Our study highlights—after demonstrating that NT-proBNP levels confer the same relative risk information in HFpEF as in HFrEF—the possibility that comorbidities contribute relatively more to prognosis in patients with HFpEF with lower NT-proBNP levels than in patients with HFrEF.

  • acute decompensated Heart failure
  • prognosis
  • preserved left ventricle ejection fraction
  • NT-proBNP

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  • Contributors KS, WEK and YMP had the idea for the project, designed the collaborative analysis and undertook searches of published work. KS and SS collected the individual patient data and prepared for analysis. Statistical analysis and elaboration of figures was done by KS, WEK and JGPT. KS wrote the paper with important contribution from WEK, SS and YMP and input from MM. LWE, AB-G, JGPT, MM and VV provided valuable comments on the report. All principal investigators shared individual patient data and had an opportunity to contribute to the interpretation of results and to the redrafting of the report. All authors reviewed and revised the manuscript and approved the final version.

  • Funding LWE and YMP received research funding for their original study from the Dutch Heart Foundation, Dutch Organisation for Scientific Research (NWO), the Royal Dutch Academy of Arts and Sciences (KNAW) – Interuniversity Cardiology Institute of the Netherlands, Pfizer, Astra-Zeneca, Medtronic and Roche Diagnostics.

  • Competing interests YMP is a recipient of payments for lectures including service on speakers’ bureaus and research grants from Roche Diagnostics. YMP has an unrelated biomarker patent and stocks in a university spinoff company. WEK received a grant (2010B97) from the Dutch Heart Foundation for the PRIMA II study and has participated in advisory board meetings of Roche Diagnostics and Novartis. MM is a member of the board in Corthera and Novartis and receives payment for lectures including service on speakers’ bureaus from Servier or Stroder.

  • Ethics approval All studies were approved by the ethical committees in their respective centres.11 18 20 21

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This article has been corrected since it first published online. The open access licence type has been amended.

  • Patient consent for publication Not required.