Long-Term Prognostic Significance of Plasma B-Type Natriuretic Peptide Level in Patients With Acute Heart Failure With Reduced, Mid-Range, and Preserved Ejection Fractions

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Plasma B-type natriuretic peptide (BNP) is an important prognostic marker in patients with acute heart failure (AHF). However, it is unclear which BNP parameter, on admission, at discharge, or change during hospitalization, has the highest predictive performance for long-term adverse outcomes, and whether its prognostic impact differs according to the new European heart failure (HF) phenotype classification by left ventricular ejection fraction: heart failure with reduced ejection fraction (HFrEF), heart failure with mid-range ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF). We examined 1,792 patients with AHF consisting of 860 (48%) HFrEFs, 318 (18%) HFmrEFs, and 614 (34%) HFpEFs. Prognostic performance of each BNP parameter was assessed by the Harrell c-index. During a median follow-up of 664 days, 344 (19%) patients died. Discharge BNP had the highest c-index (0.69) for mortality among all BNP parameters (p <0.001). In multivariate Cox proportional hazard modeling, discharge BNP was associated with mortality in HFrEF, HFmrEF, and HFpEF patients with significant interaction (hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.57 to 2.41; HR 1.76, 95% CI 1.10 to 2.82; HR 1.46, 95% CI 1.12 to 1.91, respectively; p = 0.011 for interaction). Moreover, the c-index of discharge BNP for mortality in HFrEF patients (0.72) was higher than that in HFmrEF patients (0.68) and HFpEF patients (0.65). Similar results were obtained for mortality or HF rehospitalization as alternative outcomes, except there was no statistically significant interaction among HF phenotypes. In conclusion, discharge BNP is a more reliable marker than other BNP parameters on long-term outcome prediction in patients with AHF, but its prognostic impact may be weakened in HFmrEF and HFpEF compared with HFrEF.

Section snippets

Methods

We retrospectively analyzed the combined pooled data of the 2 Japanese prospective AHF registries: the West Tokyo Heart Failure (WET-HF) registry obtained from June 2005 to April 2016, and the National Cerebral and Cardiovascular Center Acute Decompensated Heart Failure (NaDEF) registry obtained from January 2013 and August 2015. Details of these registries have been described previously. Briefly, the WET-HF registry is a multicenter, observational, ongoing, prospective cohort registry that

Results

The clinical characteristics of the total population and the HF phenotypes are summarized in Table 1. HFrEF patients had lower age and systolic blood pressure, and lower prevalence of atrial fibrillation and hypertension than patients with other HF phenotypes. Meanwhile, HFrEF patients showed a higher prevalence of men and previous HF, a higher hemoglobin level, and a more frequent use of oral medications for HF. The distributions of admission BNP, discharge BNP, and log-transformed BNP change

Discussion

In the present study, we found that discharge BNP is more reliable than admission BNP and BNP change for predicting long-term adverse outcomes in patients with AHF. Importantly, a significant interaction was observed on the risk of long-term mortality between discharge BNP and new HF phenotypes, with lower HR in HFmrEF and HFpEF patients compared with HFrEF patients.

The optimal timing of BNP measurement (on admission, at discharge, or both) for future outcome prediction after hospitalization

Acknowledgment

The authors are grateful for the contributions of all the investigators, clinical research coordinators, data managers, and laboratory technicians involved in the WET-NaDEF collaboration project.

Disclosures

Toshiyuki Nagai is supported by grants from the Daiichi Sankyo Foundation of Life Science and the Mochida Memorial Foundation for Medical and Pharmaceutical Research. Shun Kohsaka received unrestricted research grant for Department of Cardiology, Keio University School of Medicine from Bayer

References (29)

  • J.J. Hsu et al.

    Heart failure with mid-range (borderline) ejection fraction: clinical implications and future directions

    JACC Heart Fail

    (2017)
  • D.A. Pascual-Figal et al.

    Mid-range left ventricular ejection fraction: clinical profile and cause of death in ambulatory patients with chronic heart failure

    Int J Cardiol

    (2017)
  • S.L. Chow et al.

    Role of biomarkers for the prevention, assessment, and management of heart failure: a scientific statement from the American Heart Association

    Circulation

    (2017)
  • C.W. Yancy et al.

    2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines

    Circulation

    (2013)
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    The WET-NaDEF collaboration project was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (Japan Society for the Promotion of Science [JSPS KAKENHI]), in Tokyo, Japan, Grant 23591062 and 26461088 awarded to TY; a Japan Health Labour Sciences Research in Tokyo, Grant 14528506 awarded to TY; and the Sakakibara Clinical Research Grant for Promotion of Sciences, Japan, 2012, 2013, and 2014 awarded to TY; a grant from the Japan Agency for Medical Research and Development, in Tokyo, Grant 201439013C awarded to SK; a grant from the Japan Cardiovascular Research Foundation, in Bunkyo-Ku, Grant 24-4-2 awarded to TA; and a Grant-in-Aid for Young Scientists from JSPS KAKENHI, Grant 15K19402, awarded to TN.

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