Abstract In patients with aortic stenosis (AS) evaluating left ventricular (LV) systolic function is challenging due to the influence of increased afterload on traditional measures. Myocardial work (MW) analysis, a novel echocardiographic method, adjusts myocardial deformation to instantaneous LV pressure, providing a more accurate reflection of LV contractile state. Notably, prolonged LV pressure overload induces significant backward effects beyond the LV; the classification of this extravalvular cardiac damage effectively represents the cardiopulmonary system's involvement in AS. Both MW analysis and cardiac damage staging may possess significant prognostic value in the clinically complex cohort of transcatheter aortic valve replacement (TAVR) candidates. Thus, our objective was to evaluate the prognostic value of MW analysis and cardiac damage staging in TAVR patients. We enrolled 314 patients (79±6 years, 40% female) prior to TAVR. Echocardiographic assessments were conducted one day before the procedure. LV ejection fraction (EF) was calculated, global longitudinal strain (GLS) was measured using speckle-tracking echocardiography. LV pressure was estimated from systolic blood pressure and transaortic mean gradient, and global constructive work (GCW) was quantified using dedicated software. Based on echocardiographic data, we determined the extent of cardiac damage associated with AS, categorizing patients into Stage 0 (no cardiac damage), Stage 1 (LV damage), Stage 2 (mitral valve or left atrial damage), Stage 3 (pulmonary artery vasculature or tricuspid valve damage), or Stage 4 (right ventricular damage). The primary endpoint was all-cause mortality, reached by 69 patients during a median follow-up period of 25 months. Preprocedural EF was 47±13 %, GLS was -12.3±4.2 %, GCW was 2043±769 mmHg%. 14 (5%) patients were classified as Stage 0, 61 (20%) as Stage 1, 133 (43%) as Stage 2, 22 (7%) as Stage 3, and 74 (24%) as Stage 4. GCW showed a decline through AS Stages (from Stage 0-4: 2963±652 vs. 2154±621 vs. 2174±706 vs. 2044±827 vs. 1553±757 mmHg%; p<0.001). Using univariate Cox analysis GCW (HR 0.968 [95% CI 0.938-0.998] per 100 unit change; p=0.034) and AS Staging (HR 1.236 [95% CI 1.016-1.505]; p=0.034) were associated with all-cause mortality, while EF (HR 0.982 [95% CI 0.964-1.001]; p=NS) and GLS (HR 1.047 [95% CI 0.989-1.108]; p=NS) were not. In multivariate Cox regression models, both GCW (HR 0.958 [95% CI 0.923-0.994] per 100 unit change; p=0.022) and AS cardiac damage staging (HR 1.281 [95% CI 1.040-1.577]; p=0.020) were significant independent predictors of all-cause mortality. In TAVR patients, preoperative GCW values continuously decreased across all AS Stages. GCW and AS Staging showed strong association with all-cause mortality in our cohort, while EF and GLS did not. Furthermore, GCW and AS Staging had higher prognostic value than any other echocardiographic measure, highlighing their role in preprocedural assessment before TAVR.
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