Background: Mitral regurgitation (MR) is one of the most common valvular heart disease with high morbidity and mortality. Recent studies in patients with organic MR emphasized the role of cardiopulmonary exercise test (CPET) and NT-proBNP in predicting need of surgery or hospitalization for atrial fibrillation (AF) and heart failure (HF). Since most part of patients with moderate to severe organic MR have normal cardiopulmonary functional capacity and low NT-proBNP level we sought to evaluate the prognostic role of echocardiographic variables in this setting. Methods: Between September 2006 and December 2012 patients with moderate to severe organic MR (regurgitant volume (RV) > 40 ml) were evaluated. All patients underwent complete echocardiographic evaluation with 3 methods of MR quantification (PISA, doppler and volumetric methods), cardiopulmonary exercise test and NT-proBNP measurement. Only patients with normal CPET (peak VO2 > 85% of predicted) and low NT-proBNP level (<150 pg/ml) were included in the study. First event rates were estimated with the Kaplan-Meier method, Cox proportional hazards modeling for long-term first events predictors Results: Among 78 patients with moderate to severe organic MR evaluated, 31 had normal CPET (peak VO2>85% of predicted) and low NT-pro BNP level (<150 pg/ml) and were included in the study. NT-proBNP was 69±29 pg/ml (median 74 pg/ml, 25%-75% 55-95), peak VO2 was 27±5 ml/kg/min, RV (Regurgitant Volume) mean (average of 3 quantification methods) 55±15 ml/beat, ERO (Effective Regurgitant Orifice) mean 0,30±0,08 cm2, end diastolic left ventricular (EDLV) volume 165±31 ml, EDLV volume/BSA (Body Surface Area) 89±15 ml/m2, end systolic left ventricular (ESLV) volume 43±18 ml, ESLV volume/BSA 23±9 ml/m2; LA volume 77±26 ml, LA volume/BSA 41±11 ml/m2, LV mass 198±34 g, LV mass/BSA 106±14 g/m2.19 patients (41%) underwent surgery correction of MR and 4 patients (10%) developed new AF. At univariate analysis predictors of need of surgery and/or AF were LV mass (p=0,01), E velocity (p=0,001), EDLV volume (p<0,001), ESLV volume (p=0,001), ERO mean (0<0,001), RV mean (p<0,001). Independent predictors of need of surgery/AF were E velocity (p<0,001), ESLV volume (p=0,02), ERO mean (p=0,006), RV mean (p=0,002) Conclusions: In patients with moderate to severe organic mitral regurgitation, normal cardiopulmonary functional capacity and low NT-proBNP level, E velocity, ESLV volume, ERO, RV, RV/LA volume ratio and PVF reversal are strictly related to need of surgery and/or new AF during follow-up and should be carefully assessed and evaluated.