Page 36 - Biomarkers for risk stratification and guidance in heart failure

Multimarker risk score in emergency department dyspnea
DISCUSSION
We investigated 5 biomarkers (hs-cTnT, hs-CRP, Gal-3, Cys-C and NT-proBNP)
with a distinct pathophysiological background for short-term risk stratification
in 603 patients with dyspnea presenting to the ED. Hs-cTnT, hs-CRP, Cys-C and 2 NT-proBNP were independent predictors of 90-day all-cause mortality and risk
increased substantially as more biomarkers were elevated above cutpoint.
Moreover, we present a simple and straightforward score for short-term risk stratification based on biomarkers in combination with clinical risk factors. This MARKED-risk score is able to identify patients with very low, intermediate and
excessive high risk for both short- and long-term mortality.
Because the evaluation of dyspneic patients in the ED is difficult and an accurate diagnosis cannot always be acquired promptly, a non-diagnosis-specific risk score is helpful in clinical practice. Especially for decision making in an acute setting, short-term risk assessment is important. Several biomarkers have been found useful for prognostification in the evaluation of dyspneic patients, but single biomarkers may not provide sufficient precision. Therefore, we hypothesized that a multi-marker approach could improve risk stratification in this setting of a heterogeneous patient population. Thus, we examined 5 established biomarkers, (i.e. hs-cTnT, hs-CRP, Cys-C, Gal-3 and NT-poBNP) for risk assessment in ED dyspnea.
Cardiac troponin T is elevated in various chronic24-26 and acute27-29 conditions such as heart failure, renal failure, pulmonary embolism and acute dyspnea and is undoubtedly associated with adverse outcome in these settings and even in the general population30. CRP, a marker of inflammation, is known to be elevated in both patients with acute13, 31 and chronic 31, 32 heart failure. CRP elevations in heart failure are related to functional status and prognosis32, 33. It was previously already shown that CRP has additive prognostic value to other established biomarkers such as NT-proBNP, haemoglobin and BUN in patients presenting with dyspnea to the ED34, 35. Gal-3, a marker that is linked to fibrosis and inflammation, is involved in heart failure, cancer and renal disease and is predictive of all-cause mortality in the general population36. Although its diagnostic role in HF is of limited value 12, Gal-3 is a reasonable prognostic marker for short- to intermediate-term outcome in HF12, 37, but less so for long-term risk prediction38, 39. Cystatin C, a marker for renal function which strongly reflects glomerular filtration rate40, is a strong prognostic biomarker in acute HF independent of NT-proBNP 41 and troponin
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