Panel of emerging cardiac biomarkers contributes for prognosis rather than diagnosis in chronic heart failure.

BACKGROUND: As complex disease, heart failure is associated with various pathophysiological and biochemical disorders. No single biomarker is able to display all these characteristics. Therefore, we evaluated a multimarker panel together with the biochemical gold-standard NT-proBNP. Part of the panel are markers for angiogenesis (Endostatin, IBP-4, IBP-7, sFlt-1 as antiangiogenetic factors and PLGF as angiogenectic factor), myocyte stress (GDF-15), extracellular matrix remodelling (galectin-3, mimecan and TIMP-1), inflammation (galectin-3) and myocyte injury (hs-TnT). METHODS: All markers (Roche Diagnostics, Penzberg, Germany) were assessed in a cohort of 149 patients with chronic heart failure and 84 healthy controls. RESULTS: All markers were positively correlated with ln NT-proBNP (each p < 0.05). Furthermore, they were significantly elevated in patients with chronic heart failure (each p < 0.05). All markers increased significantly with severity of LV dysfunction and severity of New York Heart Association class (each p < 0.05), except for PLGF and Mimecan (each p = NS). With the exception of endostatin, mimecan and PLGF, all other markers were further significant predictors for all-cause mortality in a 3-year follow-up. In a multimarker approach of the five biomarkers with the best performance (NT-proBNP, hs-TnT, TIMP-1, GDF-15 and IBP-4), the event rate was superior to NT-proBNP alone and increased significantly and progressively with the number of elevated biomarkers. CONCLUSION: All emerging markers increased stepwise with the severity of symptoms and LV dysfunction and offer important prognostic information in chronic heart failure, except for PLGF and mimecan. Five biomarkers with different pathophysiological background incorporated additive prognostic value in heart failure. Prognostication in heart failure may be further improved through a multimarker approach.

Equal performance of novel N-terminal proBNP (Cardiac proBNP®) and established BNP (Triage BNP®) point-of-care tests.

BACKGROUND: Recently, a novel point-of-care test (POCT) for N-terminal proBNP (NTproBNP) has been introduced (Cardiac proBNP®, Roche). AIM: The aim was to compare the novel POCT for NTproBNP with the established POCT for BNP. METHODS: NTproBNP and BNP were assessed in 222 individuals with chronic heart failure (n = 151) or controls (n = 71) with both POCTs. RESULTS: NTproBNP and BNP were closely correlated upon regression analysis (r = 0.93; p < 0.01). NTproBNP and BNP were both correlated with ejection fraction and New York Heart Association stage. Receiver operating characteristic analysis yielded satisfying and equivalent predictive values for the detection of left ventricular dysfunction (ejection fraction <40%; NTproBNP: area under the curve 0.97; BNP: area under the curve 0.96; p > 0.05) and presence of New York Heart Association stage >2 (area under the curve 0.92 vs 0.91 for NT-proBNP and BNP, respectively; p > 0.05). CONCLUSION: The NTproBNP POCT allows biochemical detection of heart failure with satisfactory predictive values, is equivalent to the BNP POCT and will improve near-patient testing.

High-sensitive troponin T in chronic heart failure correlates with severity of symptoms, left ventricular dysfunction and prognosis independently from N-terminal pro-b-type natriuretic peptide.

BACKGROUND: Troponin T is an established marker of myocardial ischemia. We speculated that the role of the new high-sensitive troponin T (hs-cTnT) might expand towards non-ischemic myocardial disease, indicate disease severity and allow for prognostication in chronic heart failure. METHODS: Hs-cTnT (Roche Diagnostics, Mannheim, Germany) was assessed in 233 individuals with chronic heart failure (n=149) or healthy controls (n=84). RESULTS: Hs-cTnT was significantly elevated in patients with chronic heart failure [0.018 ng/mL, interquartile range (IQR) 0.009-0.036 ng/mL, vs. controls 0.003 ng/mL, 0.003-0.003 ng/mL, p<0.001] and positively correlated with N-terminal pro-b-type natriuretic peptide (NT-proBNP) (r=0.79, p<0.001). Hs-cTnT increased stepwise and signitificantly according to clinical (NYHA stage) as well as functional (LV ejection fraction, fluid retention) severity (each p<0.001). At a binary cutpoint of 0.014 ng/mL, hs-TropT was a significant predictor of all-cause mortality and all-cause mortality or rehospitalization for congestive heart failure (each p≤0.01). Of note, the prognostic value of hs-TropT was independent and additive to that of NT-proBNP. CONCLUSIONS: Hs-cTnT increases stepwise with the severity of symptoms and LV dysfunction and offers important prognostic information in chronic heart failure, independently from and additive to NT-proBNP. The utility of hs-cTnT expands beyond acute myocardial ischemia and towards chronic heart failure.

N-terminal pro-brain natriuretic peptide from fresh urine for the biochemical detection of heart failure and left ventricular dysfunction.

AIMS: Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) is a strong biochemical marker of heart failure and left ventricular dysfunction (LVD). Due to renal arterio-venous clearance of NT-proBNP and the correlation of plasma concentrations with renal function, we hypothesized that NT-proBNP may have potential as a urinary marker. The objective of this study was to assess urinary concentrations of NT-proBNP and to identify the predictive value of urinary NT-proBNP for detecting LVD and heart failure. METHODS AND RESULTS: N-terminal pro-brain natriuretic peptide (Elecsys proBNP((R)), Roche) was assessed simultaneously in fresh spot urine and plasma from 191 individuals. In patients with heart failure (n = 149), urinary and plasma NT-proBNP concentrations were positively correlated (r = 0.79, P < 0.001), but urinary NT-proBNP was significantly lower than plasma NT-proBNP (42 +/- 25 vs. 1389 +/- 325 pg/mL, P < 0.001). Upon receiver operating curve analysis, urinary NT-proBNP detected LV dysfunction (ejection fraction <40%) with a sensitivity of 91% and a specificity of 98% at a cutpoint of 22 pg/mL [area under the curves (AUC) 0.98]. At the same cutpoint, symptomatic heart failure (NYHA-class > 2) was detected with a sensitivity of 97% and specificity of 98% (AUC 0.99) and clinical signs of fluid retention were detected with a sensitivity and specificity of 98% each (AUC 0.99). CONCLUSION: N-terminal pro-brain natriuretic peptide concentrations were markedly lower in the urine than in the plasma. However, urinary NT-proBNP levels increased stepwise with the severity of heart failure and LVD, and therefore yielded satisfactory predictive values for the detection of significant LVD and symptomatic heart failure. Measurement of urinary NT-proBNP is a novel, promising, and simple method for the biochemical detection of heart failure.