Outcomes and Hemodynamic Performances of Transcatheter Aortic Valve Replacement With Two Generations of Self-expanding Transcatheter Aortic Valves

The aim of this study was to investigate the hemodynamic and clinical performance of the Evolut R compared with its direct predecessor, CoreValve, in Taiwanese population. This study included all consecutive patients who underwent TAVR with either the CoreValve or Evolut R between March 2013 to December 2020. Thirty-day Valve Academic Research Consortium-2 (VARC-2)-dened outcomes and hemodynamic performances were investigated. There were no signicant differences in baseline demographic characteristics between patients receiving CoreValve (n= 117) or Evolut R (n=117). Aortic valve-in-valve procedures for failed surgical bioprosthesis and procedures under conscious sedation were performed signicantly more often with Evolut R. Pre-dilatation was performed signicantly more often and contrast media volume was signicantly higher with CoreValve. Stroke (0% vs 4.3%, p = 0.024) and the need for emergent conversion to open surgery (0% vs 5.1%, P = 0.012) were signicantly lower in Evolut R than CoreValve recipients. Evolut R signicantly reduce 30-day composite safety endpoint (4.3% vs 15.4%, p = 0.004). In conclusion, advancements in transcatheter valve technologies have resulted in improved outcomes for patients undergoing TAVR with self-expanding valves. With new-generation Evolut R, device success was high and signicantly reduced 30-day composite safety endpoint after TAVR compared with CoreValve.

being increasingly used also in this lower risk population [4][5][6] . In Taiwan, the CoreValve transcatheter aortic bioprosthesis (Medtronic, Minneapolis, MN, USA) was the rst commercially available valve approved in December 2012, and the second-generation self-expanding Evolut R valve (Medtronic) was available in March 2017 7 . To date, more than 1000 TAVR procedures using self-expanding Medtronic devices have been performed in Taiwan. The continuous device iterations, along with growing operator experience and re nement of procedural techniques, have played a major role in improving the safety and e cacy of TAVR procedures.
We performed a single-center study, comparing the Evolut R with its direct precursor, the CoreValve, with regard to 30-day Valve Academic Research Consortium-2 (VARC-2)-de ned safety and e cacy outcomes.  9 . Adjunct pharmacologic therapy included heparin during the procedure and aspirin (100 mg/day) inde nitely and clopidogrel (75 mg/day) for 3-6 months following the procedure. Valve size was selected according to ranges of perimeter-derived annulus diameters based on CT recommended by the manufacturer.

Methods
Echocardiographic assessment. Standardized transthoracic echocardiography was performed before and after TAVR by board-certi ed cardiologists. The calculation of effective ori ce area (EOA) required calculation of LV stroke volume using the outer-to-outer diameter of the stented valve paired with the pulsed wave Doppler placed just apical to the stented valve recommended by Hahn et al 10 .
Study endpoints. All clinical endpoints of this study were de ned according to the VARC-2 criteria 11 .
"Device success" was de ned as the absence of procedural mortality (≤72 h postprocedure) and correct positioning of a single prosthetic heart valve into the proper anatomical location and intended performance of the prosthetic heart valve [no prosthesis-patient mismatch and mean aortic valve gradient < 20 mmHg or peak velocity < 3 m/s, and no moderate or severe prosthetic valve regurgitation (PVL)]. Following valve deployment, assessment of valve function was performed using transthoracic echocardiography. VARC-2 proposed using the AKIN system for the reporting of acute kidney injury (AKI). AKI was de ned as an absolute (< 48 hours) reduction in kidney function and de ned as: stage 2increase in serum creatinine to 200-299% (2.0-2.9 x increase compared with baseline) or urine output < 0.5 ml/kg/h for > 12 h but < 24 h and stage 3 -increase in serum creatinine to > 300% (> 3 x increase compared with baseline) or serum creatinine of > 4.0 mg/dL with an acute increase of at least 0.5 mg/dL or the new need for renal replacement therapy post TAVR. The 30-day-combined safety endpoint is a combined endpoint de ned by VARC-2 as a composite of all-cause mortality, major stroke, life-threatening or disabling bleeding, acute stage 2 or 3 kidney injury including renal replacement therapy, major vascular complications, coronary artery obstruction requiring intervention, and repeat procedure for valve-related dysfunction.
Statistical analysis. Continuous variables were expressed as mean ± standard deviation (SD), and analyzed with the Student's t test or the Wilcoxon rank sum test, depending on the variable distribution. Categorical variables were compared using the chi-square test with Yates' correction for continuity or the Fisher's exact test. For all comparisons, p value < 0.05 was considered statistically signi cant. The data were analyzed using SPSS software, version 24.0 (IBM, Armonk, NY, USA).

Results
Baseline characteristics. The demographic and echocardiographic characteristics are displayed in Table  1. The mean age of the population was 80.8 ± 8.8 years and the mean logistic EuroSCORE was 18.3%.

Discussion
During the past several years, technological advancement of Evolut R was built on the well-established foundation of the CoreValve platform, forti ed with lower delivery pro le (14)(15)(16) to reduce vascular complications and alternative TAVR access necessity, enhanced Nitinol frame geometry to enable better housing inside the aortic root, and a complete recapturable platform that allows optimized implantation depth upon deployment. Our results support short-term e cacy and safety performance of the Evolut-R compare with the CoreValve. Evolut R signi cantly reduce 30-day composite safety endpoint, driven by numerically lower deaths, major stroke, life-threatening or disabling bleeding, and acute stage 2 or 3 kidney injury including renal replacement therapy.
The InLine sheath used in the Evolut R system has a lower pro le (14)(15)(16) than CoreValve (18 French), which lowered the need for alternative TAVR access, which has historically been associated with inferior outcomes in patients undergoing TAVR, from 7.7-2.6%. Pre-dilatation was observed signi cantly more often in the CoreValve group, which may be responsible for longer procedure duration and increased contrast agent administration. The higher volume of contrast use is one of the underlying mechanisms leading to acute kidney injury which remains one of the strongest predictors of short-and long-term mortality after TAVR.
Valve malposition may still occur even after all necessary precautions have been taken, while prosthesis migration and embolization were associated with a four-fold higher mortality and three-fold higher stroke rate at 30 days 12 . Compared to CoreValve, a key feature of the Evolut-R is the option to fully recapture and to reposition the valve during deployment. There were 3 cases (2.6%) in the CoreValve treated patient requiring the implantation of a second valve, and one (0.9%) in the Evolut R group. In addition, the option to recapture allowed a less ventricular implantation depth, resulting in a numerically lower incidence of new pacemaker implantation and moderate PVL in the Evolut R recipients.
Left ventricular perforation is the most serious complications of TAVR, usually occurs as a direct trauma by the Amplatz Super Stiff guidewire, which was used exclusively for the deployment of CoreValve. Amplatz. Super Stiff guidewire are not designed for TAVR procedures and the operators must bend the wire to achieve the optimal shape to sit safely in the ventricle for TAVR, during which procedure the central core can be damaged or the desired shape may not be achieved, A pooled analysis of causes of perioperative mortality after TAVR (12 studies examining 1223 patients) showed that 10.1% of deaths at one month were due to pericardial tamponade while 39% of "in-lab" mortality was due to cardiac perforation causing pericardial tamponade 13 . Notably, the adoption of a dedicated pre-shaped Con da Brecker guidewire, features a continuous, tapered core and pre-shaped curve, in the Evolut R recipients reduce the risk of left ventricular perforation, which necessitated emergent cardiac surgery, from 5.1% in the CoreValve group to none in the Evolut R recipients.
The primary goal of TAVR is to achieve the maximum ori ce area with a minimum ow velocity. Given severe prosthesis-patient mismatch (PPM) was associated with increased risk of 1-year mortality (hazard ratio: 1.19) and heart failure re-hospitalization (hazard ratio: 1.12) following TAVR in 62,125 patients enrolled in the STS/ACC TVT Registry 14 , there has been a concern regarding PPM in Asian patients with small aortic annulus. Studies in east Asian populations demonstrated Sapien 3 valve had smaller EOA (2.07 ± 0.61 vs. 1.70 ± 0.49 cm 2 , p < 0.001) 15 and caused PPM about 1.92 times 16 more than Sapien XT valve. Thus, TAVR with supra-annular self-expanding was associated with superior hemodynamic outcomes compared with balloon-expandable valves in patients with small aortic annulus. These ndings pave the way for further trials regarding appropriate prosthesis selection for TAVR in patients with in East Asian population with small aortic annulus.

Limitations
Our study was only a single-center investigation and was limited by its retrospective and observational design. In addition, the results of CoreValve could have been affected by the learning curve of TAVR in the early stages, thus the bene t of Evolut R might have been overstated to some extent.   Criteria between CoreValve and Evolut R system.