Valvulo-arterial impedance in patients with severe aortic stenosis and bicuspid aortic valve

Abstract Background Valvulo-arterial impedance (Zva) is an integrated measure of global left ventricular (LV) afterload, combining both valvular and arterial load. Recent studies have identified Zva as a marker of worse LV remodeling and of adverse outcomes in patients with severe aortic stenosis (AS) and tricuspid aortic valves (TAV). However, its prognostic significance in patients with severe AS and bicuspid aortic valve (BAV) remains unclear. Purpose To evaluate the association between Zva and all-cause mortality in patients with severe AS and BAV, and to examine the relationship between Zva and markers of LV remodeling. Methods A total of 164 patients (age 63±14 years, 60% male) with severe AS and BAV were included from two Centers. Severe AS was defined as an aortic valve area (AVA) 1.0 cm or an AVA index 0.6 cm. The Zva was calculated as: (systolic arterial blood pressure (SBP) + aortic valve mean pressure gradient (AV MPG) ) / stroke volume index (SVi). Receiver operating characteristic (ROC) curve analysis was performed to identify the Zva threshold associated with mortality. The study outcome was all-cause mortality, with aortic valve replacement (AVR) accounted for during follow-up as a time-dependent covariate. Results Over a median follow-up of 9.8 years (IQR 8.0-13.0), 27 patients (16.5%) died, and 131 patients (79.9%) underwent AVR. The optimal cut-off value of Zva associated with the outcome derived from the maximal Youden index was 5 mmHg/mL/m2. Patients with a Zva ≥5 mmHg/mL/m2 were older, more often symptomatic, and had a higher prevalence of hypertension and diabetes, compared to those with a Zva 5 mmHg/mL/m2 (Table 1). Patients with Zva ≥5 mmHg/mL/m2 also presented with larger left atrial volume index (LAVI), worse LV ejection fraction (LVEF), greater LV mass index, and larger LV end-systolic and LV end-diastolic volumes, even after indexing for body surface area (BSA) (Figure 1A). Unadjusted 10-year survival was significantly lower in patients with Zva ≥5 mmHg/mL/m2 (73.5% vs. 89.6%, p=0.004) (Figure 1B). In univariate analysis, Zva ≥5 mmHg/mL/m2 was associated with worse survival (HR 2.677; 95%CI 1.245-5.756; p=0.012) together with age, hypertension, diabetes, coronary artery disease, NYHA class, LVEF, LV mass and LV end-diastolic and LV end-systolic volumes. After adjustment (selection based on the number of events) for NYHA class and AVR (as a time-dependent covariate), Zva ≥5 mmHg/mL/m2 remained independently associated with all-cause mortality (HR 2.400; 95%CI 1.038-5.552; p=0.041) (Figure 1C). Conclusion In patients with severe AS and BAV, a Zva ≥5 mmHg/mL/m² was independently associated with more pronounced LV remodeling and worse long-term survival. Zva may therefore serve as an additional tool for risk stratification and help identify patients who could benefit from earlier intervention.