Abstract Background Due to its dynamic character, the diagnosis of left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) often requires extensive exercise testing. Mitral valve alterations represent structural parameters that are not affected by load or contractility and influence left ventricular outflow tract (LVOT) gradients. The residual portion of the mitral valve extending past its coaptation (RML) has been postulated as a necessity to exhibit LVOTO. Purpose This study aims to assess the impact of RML length on the likelihood of LVOTO in HCM patients. Methods This is a cross-sectional, multi-center, registry-based analysis conducted at two HCM referral centers. The study included HCM patients with valid standardized transthoracic echocardiographic examinations. Blinded investigators performed post-processing echocardiographic analyses. LVOTO was defined as resting or dynamic peak LVOT gradients ≥30 mmHg. Results Among 270 HCM patients studied (43% women, mean age 58±14 years), 131 patients (49%) exhibited LVOTO, with 76 (28%) having undergone septal reduction therapy (SRT). Patients with obstructive HCM exhibited a more pronounced end-diastolic interventricular septum (IVSd) thickness (2.2±0.4 vs. 1.8±0.5 cm; p<0.001) and higher left ventricular ejection fraction (LVEF) (65±9 vs. 62±10%; p=0.009) compared to those without LVOTO (nHCM). Obstructive HCM patients demonstrated longer anterior (29±4 vs. 26±4 mm; p<0.001), posterior (23±4 vs. 20±4 mm; p<0.001), and residual mitral leaflets (11±3 vs. 7±3 mm; p<0.001) than nHCM patients. Multivariable logistic regression analysis adjusting for age, IVSd thickness, LVEF, anterior, and posterior mitral leaflet length identified RML length as an independent predictor of LVOTO [OR=1.47 (95% CI 1.30-1.66); p<0.001]. The area under the receiver-operating characteristic curve for RML length in identifying LVOTO was 0.82 (95% CI 0.77-0.87). RML length ≥9 mm demonstrated 73% sensitivity and 77% specificity in identifying obstructive HCM patients. Notably, these results remained statistically significant in sensitivity analyses selectively performed in HCM patients who had previously undergone SRT as well as in those who were SRT-naïve, respectively. Conclusions This study indicates RML length as an independent predictor of LVOTO in HCM patients. Moreover, RML length demonstrated high diagnostic accuracy in identifying LVOTO among HCM patients. Prospective studies are warranted to assess the added value of RML length in the diagnostic work-up of HCM patients.Figure:Diagnostic Accuracy of RML