6097Aminoterminal proB-type natriuretic peptide: a key parameter to optimise therapeutic management of low-flow, low-gradient aortic stenosis

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Abstract Background B-type natriuretic peptide (BNP) and aminoterminal-proBNP (NT-proBNP) are well established surrogates of LV function impairment. However, data are scarce regarding their prognostic value to risk-stratify patients with classical low-flow, low-gradient aortic stenosis (LFLG-AS, with low left ventricular [LV] ejection fraction). Methods The TOPAS study is a prospective observational cohort of 240 patients with aortic valve area <0.6 cm2/m2, mean gradient<40 mmHg and LVEF<50%. True severe AS was adjudicated using flow independent grading schemes. Results BNP significantly predicted one-year (area under the receiver operating-characteristic curve [AUC]) 0.62±0.04, p=0.026) but not three-year mortality. After adjustment for the severity of AS, initial treatment (aortic valve replacement [AVR] vs. conservative management [ConsRx]), age, sex and the EuroSCORE (Model#1), BNP-ratio>550 pg/ml had a trend to predict time to death (HR=2.14 [1.00–4.58], p=0.05). In contrast, NT-proBNP ratio significantly predicted both one and three-year mortality (AUC=0.67±0.04 and 0.66±0.05, both p=0.001), and independently predicted time to death (HR=1.39 per 1 unit of Log transformed NT-proBNP [1.11–1.74], p=0.004). In a head-to-head comparison (108 patients with both biomarkers), the AUCs to predict one and thre-year mortality were significantly higher with NT-proBNP versus BNP (p<0.009). NT-proBNP but not BNP independently predicted mortality and significantly improved Model#1 (Likelihood ratio test Chi2=15.95, p<0.001). The category-free net reclassification index of NT-proBNP was 0.71 (p=0.008) versus 0.38 (p=0.15) for BNP. Furthermore, there was a marked survival benefit associated with AVR in patients with NT-proBNP ≥1700 pg/ml (adjusted hazard ratio (aHR) associated to AVR vs conservative management=0.52 [0.31–0.85], p=0.009), while those<1700 pg/ml had excellent one-year survival under ConsRx (only one death [4.5±4.4%] at one year as compared to 23 [37±6.2%] for ConsRx-NTproBNP>1700, aHR=0.11 [0.01–0.83], p=0.033). The survival benefit associated with AVR interacted with NT-proBNP (p<0.001) but not with true or pseudosevere AS (p=0.53 for interaction), suggesting that NT-proBNP might identify moderate AS patients but sufficiently severe valvulo-ventricular disease to justify AVR. Survival according to NT-proBNP and AVR Conclusion NT-proBNP appears to be an excellent biomarker for the clinical purpose of risk-stratifying classical LFLG-AS. A threshold of 1700 pg/ml i.e. close to the diagnostic threshold for heart failure in acute dyspnea, was a strong independent determinant of the survival benefit associated with aortic valve replacement. Our findings suggest that NT-proBNP should be preferred over BNP. Acknowledgement/Funding Canadian Institute of Health Research

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