MATERIALS AND METHODS

Study design and population
SAVI-1 and SAVI-2 are prospective, all-comers, multicentre registries conducted in 17 (SAVI-1) and 26 (SAVI-2) centres in Europe and Argentina, but predominantly in Germany. The study design and population of SAVI-1 has been described previously [6]. SAVI-2 has a similar design. Treatment and follow-up were according to the standard of care at the respective hospital. Clinical follow-up, including echocardiographic assessment, was scheduled at discharge or after 7 days, whichever was earlier; at 30 days, a telephone follow-up was conducted (for SAVI-1, clinical and echocardiographic follow-up was scheduled at 30 days). The last registry follow-up was at 12 months, including clinical and (voluntary) echocardiographic assessments. Each registry was scheduled to enrol 250 patients.
The inclusion criteria were broad to allow for an all-comers population and included all patients with severe aortic stenosis, native annulus diameter from ≥21 up to ≤27 mm, informed consent signature, and willingness to return for follow-up visits. Excluded were patients not eligible for TAVI with ACURATE TATM as per the instructions for use. The registry was approved by the respective ethic committees.

Study device
The ACURATE TATM valve has been previously described [4, 5]. In brief, it is a self-expanding nitinol prosthesis with porcine leaflets. Stabilizer arches serve to orientate the prosthesis within the ascending aorta during the deployment phase and avoid its tilting. The diabolo-shape facilitates self-alignment and self-centering of the prosthesis, and a PET skirt contributes to preventing paravalvular leaks (PVL). The prosthesis is available in three different sizes, S, M and L. The delivery system has a crossing profile of 33 F. Commissures of the prosthesis can be placed adjacent to the patients commissure and thus the valve is placed in a truely anatomical manner.

Endpoints and definitions
The primary endpoint of SAVI-1 was the rate of major cardiac and cerebrovascular events (MACCE) at 30 days and 1 year, defined as composite of death, myocardial infarction, reintervention, and stroke. The primary endpoint of SAVI-2 was the incidence of all-cause mortality at 30 days. Secondary end-points according to the Valvular Academic Research Consortium-2 (VARC-2) guidelines [7] were: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and other TAVI-related complications (i.e. valve-in-valve, conversion to open heart, coronary obstruction, unplanned use of cardiopulmonary bypass, ventricular septal perforation, mitral valve apparatus damage/dysfunction, cardiac tamponade, endocarditis, valve thrombosis, valve migration/embolization) at 30 days and 1 year. Functional improvement from baseline was assessed via the New York Heart Association (NYHA) functional classification at the 30-day and 1-year follow-ups. We intend to compare safety and performance outcomes between SAVI-1 and -2.

Statistical analysis
No formal sample size calculation was conducted. Data were analysed according to the Intention-to-Treat population, which included all patients in whom an implant was attempted. Patients who received a prosthesis other than the study valve (e.g. conversion to open heart, valve-in-valve) were excluded from echocardiographic follow-up, but included in safety assessments. Data are presented using descriptive statistical methods. For quantitative variables, means and standard deviations (SD) were calculated, and for categorical data absolute and relative frequencies. When appropriate, 95% CIs were calculated. Event estimates were calculated using the Kaplan–Meier method; the log-rank test was used to compare overall mortality. Cox proportional hazards regression analysis was used to explore the association between SAVI-1 and SAVI-2. Data analysis was performed using SAS V9.3 (SAS Institute Cary, NC, USA).