Multimarker strategy for the prediction of 31 days cardiac death in patients with acutely decompensated chronic heart failure

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Abstract

Background

To investigate the combined prognostic value of admission serum levels of B-type natriuretic peptide (BNP), cardiac troponin I (cTnI) and high sensitivity C-reactive protein (hs-CRP), in patients hospitalized because of acutely decompensated severe (New York Heart Association class III/IV) low-output chronic heart failure (CHF).

Methods

A total of 577 consecutive patients recruited in the 5 participating centers, were studied. Cardiac mortality by 31 days was the prespecified primary study end point.

Results

A total of 102 (17.7%) patients died by 31 days. When the study patients were divided according to the number of elevated study biomarkers, there was a significant gradual increased risk of 31-day cardiac death with increasing in the number of elevated biomarkers (p < 0.001). The value of the discriminant C statistic for the Cox regression analysis, increased significantly when each of the study biomarkers was incorporated with the other risk predictors into a Cox regression model, with the highest C statistic value for the Cox regression model that included all the study biomarkers (p < 0.001). By multivariate Cox regression analysis, elevated serum levels of BNP (p = 0.002), cTnI (p < 0.001) and hs-CRP (p = 0.02) were independent predictors of the study end point.

Conclusions

In conclusion, in patients hospitalized for acute decompensation of severe (NYHA III/IV) low-output CHF, BNP, cTnI and hs-CRP upon admission offers enhanced early risk stratification. With increasing number of elevated biomarkers, the risk of 31-day cardiac death increases gradually that implies treatment intensification, and closer follow-up.

Introduction

Chronic heart failure (CHF) is a growing health-care burden in developed countries. Rates of hospitalization increase steadily both in Europe [1] and the United States [2], [3], while mortality following hospital discharge reaches one third of patients within the first year post hospitalization [4], [5] and a striking 65–75% 5 years after admission [5]. Therapeutic choices have evolved, some of them being of considerable cost, and the need is urgent to easily, reliably and cost-effectively stratify acutely ill CHF patients in such a way that those at highest risk receive the most intensive interventions.

In this context, many biomarkers have been tested as risk stratifying tools [6]. Perhaps the most established one is B-type natriuretic peptide (BNP), a marker of failed myocardium and volume overload [7] that plays a pivotal role in the neurohumoral milieu accompanying heart failure. Elevated circulating levels of BNP upon admission for acutely decompensated CHF, during hospitalization, and upon discharge, have consistently been proven to independently predict increased morbidity, mainly rates of readmission, and also excess mortality during varying follow-up periods [8], [9], [10]. Cardiac troponins I and T (cTnI and cTnT) represent specific markers of myocardial necrosis with a well-recognized contribution to the evaluation of patients with acute coronary syndromes. However, minor myocardial injury seems to accompany the failing heart [11], too, and troponin levels have demonstrated prognostic value in the setting of acute heart failure [12], [13], [14], [15]. It has been previously recognized the fundamental role of inflammation in the pathophysiology and prognosis of heart failure [6] and the prototype acute phase reactant C-reactive protein (CRP) may contribute in these processes [6], [16], [17], [18].

Taking into consideration the relation of the above-mentioned biomarkers to heart failure, their use in combination has inadequately been studied in the setting of acutely decompensated low-output CHF. The purpose of the present study was to prospectively investigate the combined prognostic value of the admission serum levels of BNP, cTnI and hs-CRP in patients hospitalized because of acutely decompensated severe (New York Heart Association class III/IV) low-output CHF.

Section snippets

Study population

From September 2004 through January 2006 consecutive patients who were hospitalized, in each of the 5 participating centers, because of acute decompensation of severe (NYHA class III/IV) low-output CHF, were eligible for the study. All patients had the diagnosis of NYHA class III/IV CHF  3 months before, and a left ventricular ejection fraction < 35% estimated by two-dimensional echocardiography or radionuclide ventriculography ≥ 3 months before study entry. Confirmation of left ventricular

Baseline characteristics

A total of 577 consecutive eligible patients were recruited. Patient baseline characteristics and concomitant drug therapy during the 31 days of follow-up are presented in Table 1. Exacerbated congestion (61.9%) or acute pulmonary edema (38.1%) was the reason for hospitalization of the study patients. The significant associations of the baseline clinical characteristics with the values of BNP, cTnI and hs-CRP upon presentation are presented in Table 2. Patients with: age ≥ 75 years, acute

Discussion

The present study, using robust statistical methods that included multivariate Cox and discrimination analysis, demonstrated: 1) the ability of each one of the studied biomarkers, BNP, cTnI and hs-CRP, to independently predict early cardiac death in the setting of acute decompensation of low-output CHF; and 2) the gradual increase in mortality with increasing number, from none to three, of elevated biomarkers.

The first finding is in accordance with previous studies that evaluated the prognostic

Acknowledgement

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [22].

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