METHODS
Study population and design
This was a single-center retrospective study conducted from 2012 to 2018 at the La Timone Hospital, Marseille, France. The study included consecutive patients at intermediate-risk treated for severe symptomatic AS. All patients have been subjected to a pre-operative multi-disciplinary ”Heart Team” evaluation to validate the indication of either TAVR with S3-THV or RDAVR with INTUITY. Based on the 2017 European Society of Cardiology and European Association for Cardio-Thoracic surgery (ESC/EACTS) guidelines, intermediate surgical risk was defined by EUROSCORE II≥4% [16] and clinical evaluation by “Heart Team”. The study was approved by the La Timone Hospital review Board (protocol number RGPD/AP-HM 2019-48) with written informed consent obtained from each participant.
Procedural characteristics
Depending on the vascular routes evaluated by computed tomography (CT) , TAVR was performed via trans-femoral, trans-subclavian, trans-aortic or trans-apical approach. The size of the prosthesis was selected by a multidisciplinary team, based on the CT scanned aortic annulus size. The procedure was performed under general or local anesthesia. Fluoroscopic guidance was used to guide prosthesis positioning and deployment. Prosthesis position and function were evaluated with angiography and transthoracic echocardiography (TTE).
For RDAVR, after standard aortotomy, the aortic valve leaflets were removed concomitant with calcium debridement. Three equidistant guiding sutures were placed through the nadir of the annulus and then placed in corresponding positions through the sewing ring of the prosthesis. Using the guiding sutures, the valve and attached delivery system were lowered onto the annulus and secured into position under direct vision. The balloon catheter was then inflated to deploy the stent frame in a controlled fashion. On deployment, the prosthesis was fixed in a supra-annular position with the 3 guiding sutures and the aortotomy was closed. Prosthesis position and function were evaluated with per-operative trans-esophageal echocardiography.
Endpoints
Based on the recent PARTNER 3 study, the primary endpoint was a composite criterion comprising all-cause mortality, disabling stroke and hospitalization at two years. Rehospitalization was defined as any hospitalization related to the procedure, the valve, or congestive heart failure (CHF).
The secondary endpoints included : 1/ life-threatening and major bleeding, defined as a drop in the haemoglobin level of at least 3.0 g/dl or requiring transfusion of more than two units of red blood cells, or causing hospitalization or permanent injury, or requiring surgery 2/ moderate or severe PPM at one month follow-up (FU), defined by an iEOA≤0,85cm2/m2 and iEOA<0,65cm2/m2respectively; 3/ PVR≥2/4 at one-month FU; 4/ PM implantation at two-years. All outcomes were defined according to the Valve Aortic Research Consortium-2 definitions [17].
Follow-up assessments
All patients had a clinical examination, neurological examination, 12-lead electrocardiogram and TTE at discharge, thirty days, one year and two years. Patients who had suspected stroke after the procedure underwent serial neurologic examinations by physician specialist.
Statistical analysis
The initial clinical and echographic characteristics were first described and compared according to both groups. Quantitative variables are presented as means (±SD) and compared using Student t-test when appropriate. Categorical variables are presented as numbers (percentages) and compared using chi-squared test when appropriate (Fisher test otherwise).
To reduce confounding by indication, analysis of the endpoints was based on a propensity score matching. The propensity score model was built using a logistic regression model including all variables known to be related to the endpoints and/or to the type of procedure (TAVR or RDAVR) regardless of their statistical significance. Appendix
This model allowed to calculate for each patient the probability of RDAVR procedure. Using the propensity score, RDAVR patients were matched to TAVR patients. An optimal 1:1 matching algorithm on the basis of the propensity score was applied. Analyses of all outcomes were then performed on the matched population.
The analysis of the occurrence of the primary composite endpoint and of all-cause death was performed using time-to-event approach. Univariate Cox models were built to estimate hazard ratios with their 95% confidence intervals. The analysis of the occurrence of secondary outcomes was performed using time-to-event approach taking into account the competing risk of death. Univariate Fine and Gray model were built to estimate cause-specific hazard ratios with 95% confidence intervals. Analysis of the occurrence of early outcomes (major bleeding, PPM and PVR) was performed by using univariate logistic regression models, allowing estimation of odds ratios with 95% confidence intervals. All tests were two-sided, and P values less than 0.05 were considered to indicate statistical significance. Statistical analyses were performed using R software, version 3.4.1.