N-terminal pro B type natriuretic peptide is superior to B-type natriuretic peptide to predict mortality in Classical Low Flow, Low Gradient Aortic Stenosis
Mohamed Salah Annabi1, Abdellaziz Dahou1, Jutta Bergler-Klein2, Ian G. Burwash3, Stefan Orwat4, Helmut Baumgartner4, Philip Bartko2, Julia Mascherbauer2, Gerald Mundigler2, Philippe Pibarot1, Marie-Annick Clavel1.
1Quebec Heart and Lung Institute, Québec-ville, QC, Canada, 2Vienna General Hospital, Vienna, Austria, 3Ottawa Heart Institute, Ottawa, ON, Canada, 4University Hospital of Muenster, Muenster, Germany.
OBJECTIVE: B-type natriuretic (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) are considered equally predictive of mortality. However, while BNP is cleared in a few minutes, NT-pro-BNP remains detectable several weeks. We thus aimed to compare the predictive values of both biomarkers in a population of classical low-flow, low-gradient aortic stenosis (CLF-AS).
METHODS: Among 343 patients with CLF-AS recruited in the TOPAS study, 147 had BNP, 199 had NT-proBNP measured at baseline and 107 had both. Activation ratios (BNPratio and NT-proBNPratio) were calculated by dividing the measured values by the maximal expected value for age and sex.
RESULTS: After a median follow up of 3.3 years, 72 patients died among the patients who had both biomarkers. After adjusting for age, sex, Euroscore, projected aortic valve area at normal flow rate (i.e. actual AS severity), and treatment (medical, surgical or transcatheter aortic valve replacement) (i.e. background model), Log[NT-proBNPratio] (HR=1.67, 95%CI [1,26-2.21], p<0.001) but not Log[BNPratio] (HR=1.28, [0.95-1.72], p=0.10) was found to be an independent predictor of all cause mortality. For NT-proBNPratio, the areas under the curves (AUC) to predict 1-year and 3-years mortality were respectively 0.68±0.05 and 0.65±0.05 (p=0.01 for both). Adding NT-proBNPratio to the background model resulted in a significantly improved reclassification (Net reclassification index 0.71, p=0.008), but not with BNPratio (0.38, p.15). When analysing survival in patients with either biomarkers, we found that in the subgroup of pseudo-severe AS patients who remained under medical management, those who had a baseline NT-proBNPratio > 11 had 1-year and 2-year survival of 62.7±6.5% and 46±6.7% respectively vs 95.5±4.4% and 86.4±7.3% for patients with NTpro-BNPratio <11 (LogRank p=0.002). There was no such association using BNP.
CONCLUSIONS: In a head-to-head biomarker comparison, NT-pro BNP was superior and should be preferred to BNP to predict total mortality in a population of CLF-AS.
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