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Introduction: In degenerative mitral regurgitation (MR), brain natriuretic peptide (BNP) is a surrogate biomarker of the consequences of MR on the left ventricle (LV) and left atrium (LA). LV global longitudinal strain (GLS), quantified by 2-D speckle-tracking imaging (2DSt) improved the detection of subclinical LV dysfunction. We aimed at evaluating the impact of BNP on outcome and its relationship with GLS, in asymptomatic patients with degenerative MR.Methods and results: Comprehensive transthoracic echocardiography including 2DSt quantification was performed in 135 consecutive asymptomatic patients (60±14 years, 55% of male) with moderate to severe degenerative MR (61% with severe MR) and preserved LV function. Simultaneously, blood sample was drawn and plasma BNP level was measured. BNP widely varied over patients (mean=61±70, range: 5-439, median= 41pg/ml) and was correlated with age (r=0.28, p=0.009), indexed LV end-systolic diameter (r=0.30, p=0.0006), indexed LA volume (r=0.51, p<0.0001), E/Ea ratio (r=0.33, p<0.0001), systolic pulmonary pressure (r=0.24, p=0.006) and GLS (r=-0.54, p<0.0001). On multiple regression analysis, only indexed LA volume and GLS were independently associated with BNP (β=1.1±0.4, p=0.002 and β=-6.6±1.4, p<0.001, respectively). During follow-up (mean=23±19 months), 54 events occurred resulting in a 4-year cardiac event-free survival=50±6%. According to the median of BNP, patients with high BNP level had significant reduced event-free survival (21±8% vs. 75±6%, p<0.0001). A GLS<23% was also associated with a lower event-free survival (85±6% vs. 33±7%, p<0.0001). In Cox multivariate analysis, after adjustment for age, sex, E/Ea ratio and indexed end-systolic diameter, only indexed LA volume (hazard ratio [HR]=1.01, 95% confidence interval [CI]: 1.0-1.3, p=0.036), GLS<23% (HR=3.3, 95%CI: 1.1-9.9, p=0.03) and BNP<41pg/ml (HR=3.5, 95%CI: 1.7-7.2, p=0.001) were independent determinants of cardiac event-free survival. In addition, compared to the first quartile of BNP (<19pg/ml), second (19-41pg/ml), third (42-70pg/ml) and fourth (71-439pg/ml) quartiles of BNP were associated with a 3.5-, 10- and 11-fold increase in risk of cardiac events (p=0.06, p<0.0001 and p<0.0001, respectively).Conclusion: In asymptomatic degenerative MR, LV longitudinal function and LA volume are the main determinants of BNP release. BNP is a powerful independent predictor of cardiac events. Assessment of plasma BNP level, LA volume, and LV longitudinal function may help to improve risk stratification and the management of these patients.