BACKGROUND: Little is known about sex-related differences amongst patients with paradoxical low-flow aortic stenosis (PLF AS). Objective: to examine whether there is a difference between women and men regarding the impact on outcomes and threshold of low-flow.
METHODS AND RESULTS: We analyzed the clinical, Doppler-echocardiographic and outcome data prospectively collected in 1490 patients with severe AS and preserved left-ventricular ejection fraction (LVEF) who underwent AVR in a large tertiary referral Canadian center. In our cohort, there were 946 (63%) men and 544 (37%) women. Normal flow was present in 1006 (67%) and PLF in 484 (33%) patients. Baseline characteristics according to sex and flow-status are shown in table 1. During a median follow-up of 2.4 [1.04-4.29] years 167 patients died. Overall, patients with PLF had increased 30-day (10 [2.3%] vs 8 [0.9%], p=0.03) and cumulative all-cause mortality (hazard ratio [HR]=1.60 [95% CI: 1.17-2.18], p < 0.01). PLF remained independently associated to increased mortality after multivariate adjustment for clinical variables, LVEF and mean gradient (HR=1.53 [95% CI: 1.11-2.11], p < 0.01). Altogether, women had higher 30-day mortality than men (2.3% vs 0.8%, p=0.026), but similar cumulative mortality (p=0.39). Using the guidelines threshold of 35 ml/m2, PLF was associated with increased mortality in women (HR=1.95 [95% CI: 1.18-3.22], p < 0.01) but not in men (HR=1.25 [95% CI: 0.79-1.85], p=0.39). Using spline curve analysis, optimal thresholds were obtained for men (40 ml/m2, panel A) and women (32 ml/m2, panel B). Using these sex-specific thresholds, PLF was independently associated with increased mortality in both women (adjusted HR=2.05 [95% CI: 1.21-3.47], p < 0.01) and men (adjusted HR=1.54 [95% CI 1.02-2.32], p=0.042) (panel C) and improved risk stratification in the whole cohort. In univariate analysis, women with PLF had higher overall mortality than men with PLF (HR=1.37 [1.08-.74], p=0.009), but this difference was no longer significant after adjusting for age, surgical risk score and LVEF (HR=1.17 [0.92-1.50], p=0.21).
CONCLUSION: In patients with severe AS and preserved LVEF undergoing AVR, PLF is associated with increased overall mortality using the guidelines SVi cut-point (< 35 ml/m²) in the whole cohort and in women, but not in men. Defining PLF using the sex-specific thresholds of 40 ml/m2 for men and 32 ml/m2 for women predicted mortality in both sex categories. Our results provide support to the utilization of sex-specific thresholds to define low-flow and enhance risk stratification in AS.