Use of Sex-Specific Thresholds for Low Flow in Assessment of Prognosis in Concordantly and Discordantly Graded Aortic Valve Stenosis

Abstract Objective Assessment of flow is important in grading of aortic valve stenosis (AS). Sex-specific thresholds for low flow were recently proposed (stroke volume index <40 ml/m² in men and <32 ml/m² in women, respectively). We tested the prognostic association of these cut-offs in AS patients with concordantly and discordantly graded AS based on pressure recovery adjusted aortic valve area. Methods Data from 1353 patients (38.6% women) with asymptomatic mild-moderate AS and preserved left ventricular ejection fraction enrolled in the Simvastatin and Ezetimibe in AS study was used. Discordantly graded AS (DGASEL) was defined as combined pressure recovery adjusted aortic valve area (energy loss) <1.0 cm² and mean aortic gradient <40 mmHg and concordantly graded mild-moderate AS as combined EL ≥1.0 cm² and mean aortic gradient <40mmHg. Patients were further grouped into normal and low flow. Outcome was assessed using both Kaplan-Meier curves and Cox regression analyses with concordantly graded AS with normal flow as comparator. Results In the total study population, mild-moderate AS with normal flow was present in 915 patients, mild-moderate AS with low flow in 253 patients, DGASEL with normal flow in 57 patients and DGASEL with low flow in 126 patients. During a median of 4.3 years follow-up, survival free of death and/or hospitalization for heart failure was significantly lower in patients with DGASEL irrespective of flow compared to those with mild-moderate AS with normal flow (both P<0.05, Figure). In Cox regression analysis, after adjustment for hypertension, age, sex, heart rate, randomized study treatment, aortic valve replacement and degree of aortic valve calcification, DGASEL with normal or low flow were both associated with increased risk of combined death and hospitalization for heart failure (P<0.05) (Table). However, no prognostic difference was found between groups with normal vs. low flow within groups of discordantly or concordantly graded AS. Conclusions Identification of low flow by the proposed sex-specific thresholds of stroke volume index <40 ml/m² in men and <32 ml/m² in women needs more validation before inclusion in clinical guidelines. Figure. Kaplan-Meier plot of event-free survival from combined death and heart failure hospitalization in groups of patients with mild-moderate AS normal flow, mild-moderate AS low flow, DGASEL with normal flow and DGASEL with low flow. Table. Association of combined death and hospitalization for heart failure in groups of concordantly and discordantly graded AS with normal and low flow. Multivariable Cox analysis.