Incremental value of biomarkers to clinical variables for mortality prediction in acutely decompensated heart failure: The Multinational Observational Cohort on Acute Heart Failure (MOCA) study

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Abstract

Aim

This study aims to evaluate the incremental value of plasma biomarkers to traditional clinical variables for risk stratification of 30-day and one-year mortality in acutely decompensated heart failure (ADHF).

Methods and results

Through an international collaborative network, individual patient data on 5306 patients hospitalized for ADHF were collected. The all-cause mortality rate was 11.7% at 30 days and 32.9% at one year. The clinical prediction model (age, gender, blood pressure on admission, estimated glomerular filtration rate < 60 mL/min/1.73 m2, sodium and hemoglobin levels, and heart rate) had a c-statistic of 0.74 for 30-day mortality and 0.73 for one-year mortality. Several biomarkers measured at presentation improved risk stratification when added to the clinical model. At 30 days, the net reclassification improvement (NRI) was 28.7% for mid-regional adrenomedullin (MR-proADM; p < 0.001) and 25.5% for soluble (s)ST2 (p < 0.001). At one year, sST2 (NRI 10.3%), MR-proADM (NRI 9.1%), amino-terminal pro-B-type natriuretic peptide (NT-proBNP; NRI 9.1%), mid-regional proatrial natriuretic peptide (MR-proANP; NRI 7.4%), B-type natriuretic peptide (NRI 5.5%) and C-reactive protein (CRP; NRI 5.3%) reclassified patients with ADHF (p < 0.05 for all). CRP also markedly improved risk stratification of patients with ADHF as a dual biomarker combination with MR-proADM (NRI 36.8% [p < 0.001] for death at 30 days) or with sST2 (NRI 20.3%; [p < 0.001] for one-year mortality).

Conclusion

In this study, biomarkers provided incremental value for risk stratification of ADHF patients. Biomarkers such as sST2, MR-proADM, natriuretic peptides and CRP, reflecting different pathophysiologic pathways, add prognostic value to clinical risk factors for predicting both short-term and one-year mortality in ADHF.

Introduction

The care of patients with acutely decompensated heart failure (ADHF) is complex, involving clinical assessment and risk prediction as integral parts of daily clinical practice. Indeed, ADHF is associated with a very high mortality rate, and clinical risk stratification after hospitalization for ADHF remains a relevant challenge, in order to best identify those patients likely to encounter serious complications, and to potentially better allocate resources in order to mitigate this considerable risk. Several demographic and clinical factors, co-morbidities, and biochemical variables are associated with short- or mid-term mortality in ADHF, including measures of renal function and blood pressure as well as other relevant predictors [1], [2], [3], [4], [5], [6]. In recent years, a growing focus has been given to novel blood-based biomarkers for their ability to risk stratify patients with ADHF, and with this, an abundance of different assays has emerged, many reportedly associated with increased mortality in heart failure [7], [8].

Over the past several years, B-type natriuretic peptide (BNP) and its N-terminal precursor fragment (NT-proBNP) have become the biomarker “gold standards” for predicting risk, with studies demonstrating value of either test for risk stratification of ADHF [5], [9], [10], [11], [12]. Importantly, the value of natriuretic peptides as well as other novel markers has however been studied with variable depth. Indeed, the value of any biomarker for risk prediction in ADHF, analyzed in an unbiased and thorough manner, should clearly depend on the degree to which it adds to the prognostic information provided by standard risk factors and other available markers [13], [14], [15].

Accordingly, the purpose of this study was to equitably assess the individual and added value of various novel biomarkers to traditional clinical variables and to each other for risk stratification of patients with ADHF, using data from a large, collaborative global, multicenter patient cohort. Furthermore, we used the most recent and appropriate statistical tools, including reclassification and discrimination analyses.

Section snippets

Material and methods

The Multinational Observational Cohort on Acute heart failure (MOCA) study was performed in accordance with the ethical guidelines of the declaration of Helsinki and all patients provided written consent to the individual studies. In the MOCA database, individual patient data was coded without possibility of person identification. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.

Results

Clinical characteristics of the study population are in Table 1, and data on the original cohorts are in Supplemental Table 1. In MOCA, the mean age of the study population was 75 years and 43% were women. Prior history of heart failure was present in fewer than half of the subjects, and an ischemic cause of heart failure was present in approximately 56%. Consistent with the de novo presentation in a majority of patients, medications such as β-adrenergic blockers, angiotensin converting enzyme

Discussion

Numerous reports of biomarker testing for prognosis have suggested potential utility of a wide array of assays when measured in patients with heart failure. With the growing number of manuscripts in this subject area, clinicians and investigators alike are left with uncertainty about the leading candidates for clinical use in this arena. Recent statements call for, among other things, a more standardized, thorough, and rigorous approach to evaluating heart failure biomarkers, including

Conflicts of interest

JL speaker's honoraria from Abbott, consultant fees from Roche Diagnostics; JLJ grants from Roche Diagnostics, Siemens Diagnostics, Critical Diagnostics, Thermo-Fisher Diagnostics, consultant fees from Roche Diagnostics, Critical Diagnostics; V-PH consultant fees from Roche Diagnostics; WFP research grants from Abbott, Alere, Baxter, Brahms, Novartis, The Medicine's Company; consultant fees from Abbott, Alere, Lily, The Medicine's Company, speaker's honoraria from Abbott, Alere; ownership

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    1

    JL and EG equally contributed to the present work.

    2

    GREAT—Global research on acute conditions team http://www.greatnetwork.org/.

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