INTRODUCTION

Over the past decade, the self-expandable CoreValve (Medtronic Ltd, United States) and the balloon-expandable SAPIEN valve (Edwards Lifesciences Ltd, United States) were the valves most commonly used for transcatheter aortic valve implantation (TAVI).¹

There are few studies comparing Evolut PRO (Medtronic Ldt, United States) vs SAPIEN 3 (Edwards Lifesciences Ltd, United States), like the SMART trial for small aortic annulI² and the ALSTER-TAVI all-comers registry.³ However, comparative randomized clinical trials are lacking. Therefore, we designed the present randomized study to provide a head-to-head comparison between these 2 valves regarding procedural data and in-hospital outcomes especially paravalvular leak (PVL). Although the transcatheter heart valves used in this trial are not the latest generation valves of the CoreValve and SAPIEN families (currently, the Evolut-Pro plus and the SAPIEN Ultra), this is the first randomized clinical trial to compare a self-expanding valve with an outer skirt to a balloon expandable valve (with an outer skirt too).

METHODS

PVL assessment

Immediate PVL was semi-quantitatively assessed using Seller's criteria 7: 0/4 (absent); 1/4 (mild); 2/4 (moderate); 3/4 (moderate- to-severe); and 4/4 (severe).⁷ Transvalvular pressure gradients were obtained invasively using the pullback method. Aortic regurgitation index (AR index) was calculated.⁸

In case of significant PVL ≥ grade II, if needed, balloon postdilatation using the VACS III or NUCLEUS balloon (NuMED, United States) or else implantation of second valve was used. TTE was performed at discharge to quantify PVL according to the main VARC-2 criteria.⁹

Assessment of anatomical factors possibly associated with PVL

The following measurements were supported by Philips software (Philips Medical, The Netherlands): the left ventricular outflow tract/ascending aorta (LVOT/AAo) angle was defined as the angle between the axis of the first 4 cm of the ascending aorta (contact surface with the upper part of the prosthesis), and the LVOT axis (the valve landing zone) indicated by a line perpendicular to the plane of the aortic valve annulus).¹⁰

Aortic angulation (AA) angle was defined as the angle between the horizontal plane and the plane of aortic annulus.¹¹ We categorized it into < 48° and ≥ 48°.¹²

Both angles were measured in the optimal fluoroscopic deployment position with all 3 coronary cusps in the same plane (figure 1). Valve implantation depth was assessed in the deployment position on the fluoroscopy from the native aortic annular margin on the side of both the non-coronary cusp (NCC) and left coronary cusp to the proximal edge of the deployed valve on the corresponding side¹³ (figure 2). Aortic root calcification was fluoroscopically assessed as inexistent, mild (small, isolated calcification spots), moderate (multiple large calcification spots) or severe (extensive calcification).¹³ Presence or absence of LVOT and mitral annular calcification were also noted.

Figure 1. Measurement of different angles. AA, aortic angulation (49.62º). B: LVOT/AAo angle (18.74º). AAo, ascending aorta; LVOT, left ventricular outflow tract. 

Figure 2. Measurement of implantation depth in the Evolut PRO value. A: [A = 1.17 mm associated with the NCC, and B = 4.91 mm associated with the LCC], and SAPIEN 3. B: [A = 5.65 mm associated with the NCC, and B = 7.31 mm associated with the LCC]. Note high implantation associated with the NCC due to increased LVOT/AAo angle in the Evolut PRO (A) but not in the SAPIEN 3 valve (B). AAo, ascending aorta; LCC, left coronary cusp; LVOT, left ventricular outflow tract; NCC, non-coronary cusp. 

RESULTS

DISCUSSION

In this study 2 important findings were made. First, implantation of the Evolut PRO valve was associated with a higher risk of significant PVL compared to the SAPIEN 3 valve. Secondly, the rate of PPI was equal in both groups. Otherwise, both types of valves yielded similar outcomes.

Reducing PVL is an important challenge regarding TAVI as it is associated with worse outcomes especially with the current use of these devices in lower-risk patients.¹⁴

A randomized comparison between the CoreValve and SAPIEN XT valves in the CHOICE trial revealed a lower rate of moderate-to-severe PVL in the SAPIEN XT group.¹⁵ In the SOLVE-TAVI trial, the non-inferiority of 2 devices (SAPIEN 3 and Evolut R) was reported in terms of their primary efficacy composite endpoint (death, stroke, paravalvular regurgitation, and new pacemaker implantation).¹⁶ Currently, the SAPIEN 3 Ultra and Evolut PRO+ have been developed with early favorable outcomes.¹⁷

In our study, relevant PVL (≥ grade II) was more common in patients who received the Evolut PRO compared to the SAPIEN 3 valve (9.6% vs 6.8%, respectively). Enríquez-Rodríguez et al. reported a lower rate (2.5%) of moderate to severe PVL with the SAPIEN 3 valves possibly due to the presence of an external sealing cuff.¹⁸

Obviously, anatomical factors are important for the occurrence of PVL. We observed that larger LVOT/AAo angles were associated with a higher rate of PVL, particularly with the Evolut PRO valve. Sherif et al. demonstrated that the risk of PVL increases with larger LVOT/AAo angles.¹⁰ We also observed that the LVOT/AAo angle affects implantation depth in association with the NCC with the Evolut PRO, but not with the SAPIEN 3 valves. It is quite conceivable that implantation depth impacts the rate of PVL.

Sherif et al. were the first ones to report on the association between increased AA angles and postoperative PVL with self-expanding valves.¹⁰ A subsequent retrospective study conducted by Abramowitz et al. described a higher rate of complications (eg, postoperative PVL in patients with horizontal aortas (defined by an AA ≥ 48º as seen on the cardiac CT scan) who received self-expanding valves.¹¹ We observed that AA angles impacted PVL in patients who received Evolut PRO valves even if these angles were < 48º with no significant differences in the rate of PVL for AA angles < 48^º or ≥ 48^º.

In this study we also observed 6 patients with AA angles ≤ 30º (3 patients with Evolut PRO and 3 patients with SAPIEN 3). All of them were free of PVL immediately after valve deployment. One could speculate that AA angles ≤ 30º are the best for Evolut PRO valve implantation, but the small size of the sample prevents us from drawing any definitive conclusions.

In our study, the rates of device success determined by the absence of a significant PVL (≥ grade II) at hospital discharge, need for a second valve, valve embolization, the performance of the prosthetic heart valve, and the mortality rate according to VARC definition⁹ were 86% and 98% with the Evolut PRO and SAPIEN 3 valve, respectively. Similarly, Li et. al found a high device success rate for both the SAPIEN 3 and the Evolut R valve (94% and 96%, respectively).¹⁹

We found similar rates of postoperative conduction defects and PPI for both Evolut PRO and SAPIEN 3 valve types (7.8% and 5.1%, respectively). Popma et al.²⁰ and Vlastra et al.²¹ reported lower rates of PPI with new generation balloon expandable valves compared to new-generation self-expanding valves. The comparable rates of conduction defects and PPI with either valve in our study was probably due to the lower implantation depth of Evolut PRO valves.

Li et al. reported higher rates of postdilatation of up to 30% with the Evolut R compared to the SAPIEN 3 valve.¹⁹ This was not seen in our study (15.7% and 5.1%, respectively; P = .35). This was probably so thanks to the proper positioning of the Evolut PRO valve and routine predilatation in all our cases.

In this study, in-hospital mortality was similar in both valve groups. Li et al. also reported that mortality was not associated with the type of valve implanted.¹⁹ The CHOICE trial also showed a comparable mortality rate with the use of older-generation valves (Core- Valve and SAPIEN XT).¹⁵

The rates of stroke were similar for both the Evolut PRO and the SAPIEN 3 valve and lower compared to those seen with older generation devices.¹⁵,¹⁹,²²,²³ The operators' experience and improved delivery systems are likely to account for the reduced risk of thromboembolic complications.

Regardless of the type of valve used, acute kidney injury seemed to be slightly more common in our study (5.9% and 3.5% for the Evolut PRO and the SAPIEN 3, respectively) than previously reported. Husser et al.²⁴ noted a rate of 2.7% in SAPIEN 3 valves while Kodali et al.²⁵ reported rates of 1.7%. However, large multicenter studies usually have stricter inclusion criteria so the baseline kidney function of the patients included was better.¹⁹

Despite increased sheath/femoral artery ratios with the Evolut PRO valve, the rate of bleeding or vascular complications was similar compared to the SAPIEN 3 valve. Similar results were reported by Li et al.¹⁹ and Panchal et al.²⁶

CONCLUSIONS

This randomized study demonstrated comparable procedural and in-hospital outcomes for the Evolut PRO and SAPIEN 3 valves except for a significantly higher rate of PVL associated with the Evolut PRO valves. The PVL reported was associated with the LVOT/AAo angle in Evolut PRO group, which also impacted negatively the implantation depth of this type of valve.

AUTHORS' CONTRIBUTIONS

Idea and design: H. M. Elnaggar, M. S. Mahmoud, W. Schoels, and Y. T. Kishk. Administrative support: W. Schoels, M. Kullmer, and M. Dia. Provision of study materials or patients: M. S. Mahmoud, M. Algowhary, and H. M. Elnaggar. Data collection and assembly: M. S. Mahmoud, M. Kullmer, and M. Dia. Data analysis and interpretation: M. S. Mahmoud, Y. T. Kishk, M. Algowhary, and H. M. Elnaggar. Manuscript drafting and final approval: all authors.