YComparison of non-invasive and invasive cardiac damage staging in patients with clinically significant aortic stenosis

Abstract Background Cardiac damage staging derived from transthoracic echocardiography (TTE) is an additive clinical tool to enhance risk stratification and therapeutic decision making in patients with clinically significant (i.e. ≥moderate) aortic stenosis (AS). However, it is not able to differentiate prognosis among patients in Stage 3 and 4. The optimal strategy and timing of intervention in patients with moderate and asymptomatic severe (m/asAS) remains controversial. Purpose To compare the accuracy in risk stratification of the cardiac damage staging derived from TTE and right heart catheterization (RHC) in patients with clinically significant AS, divided in those with m/asAS and those with symptomatic severe AS (ssAS). At first, all stages were considered; then, we focused on patients in stage 3 and 4. Methods Observational cohort study of patients with clinically significant AS undergoing TTE and RHC from 2016-2020. AS grading was based on current guidelines evaluating the TTE closest to the RHC (maximum time interval 3 months). Patients were divided in those with m/asAS and ssAS. Cardiac damage staging (Stage 0-4) was derived both from TTE and RHC. Kaplan Mayer (KM) curves and log-rank tests were used to compare the survival according to each cardiac damage stage in both cohorts. Area under the receiver-operating characteristics curve (AUC) analysis and Delong’s test were used to compare the accuracy in prognostic stratification. Results 432 patients were included (183 with m/asAS and 249 with ssAS). According to TTE-derived cardiac damage staging, 42 (9.7%) patients were classified in Stage 0; 99 (22.9%) in Stage 1; 160 (37%) in Stage 2; 68 (15.7%) in Stage 3 and 63 (14.6%) in Stage 4. Median follow-up was 3.1 [2-6.1] years. KM curves showed the validity of cardiac damage staging in both cohorts (p<0.01 in patients with masAS and p=0.01 in those with ssAS). Overall, there was no statistically significant difference in prognostic accuracy between the cardiac staging system derived from TTE and RHC in both cohorts (AUC 0.713, 95%CI 0.63-0.80 for TTE and AUC 0.733, 95%CI 0.64-0.83 for RHC in m/asAS, p=0.758 and AUC 0.633, 95%CI 0.56-0.71 for TTE and AUC 0.677, 95%CI 0.60-0.75 for RHC in ssAS, p=0.258). Considering only patients in Stage 3 and 4, RHC-derived cardiac staging system showed significant higher diagnostic accuracy than TTE-derived in both cohorts (AUC 0.782, 95%CI 0.66-0.91 for RHC and AUC 0.540, 95%CI 0.38-0.71 for TTE in m/asAS, p=0.01 and AUC 0.699, 95%CI 0.58-0.81 for RHC and AUC 0.51, 95%CI 0.38-0.65 for TTE in ssAS, p=0.02). Conclusions Compared to the TTE-derived, RHC-derived cardiac staging system showed a similar accuracy in stratifying the prognosis of both patients with m/asAS and ssAS, being significantly more accurate in patients in Stage 3 and 4. The evaluation of right heart chambers appears to be pivotal in risk stratification of patients with clinically significant AS.Survival curves of study populationROC curves of TTE and RHC stratification