Initial Results of Intra-Annular Self-Expandable Valves

Background Navitor, an intra-annular self-expanding heart valve (IA-SEV), is the third transcatheter heart valve introduced in Japan (in April 2022) as the next generation of the Portico valve ahead of other Asian countries. Objectives The purpose of this study was to assess the patient–prosthesis mismatch (PPM) after IA-SEV implantation in Asian patients. Methods All clinical data were collected from the database of an ongoing prospective Japanese multicenter registry (OCEAN-TAVI [Optimised Catheter Valvular Intervention transcatheter aortic valve implantation]). The primary endpoint was the rate of no PPM; the secondary endpoint included the rate of in-hospital mortality and hemodynamics after IA-SEV implantation. Results A total of 463 patients (median age 86; 69.7% female) were enrolled in the registry. The percentages of implanted valves sized 23 mm, 25 mm, 27 mm, and 29 mm were 26.1% (n = 121), 41.7% (n = 193), 22.9% (n = 106), and 9.3% (n = 43), respectively. The primary endpoint of no PPM was achieved in 91.7% of the entire cohort and in 87.3%, 94.2%, 91.4%, and 93.0% of each valve size. The rate of in-hospital mortality was 1.9%. Postprocedural mean pressure gradient was 8.3 ± 4.3 mm Hg. The overall rate of pacemaker implantation was 9.7%; the incidence of pacemaker rate tended to be reduced when dividing the first and second half of operator experiences (13.0% vs. 8.0%; P = 0.08). Conclusions The initial results for the IA-SEV were excellent regarding hemodynamics and reduction of paravalvular leakage regardless of valve size. The IA-SEV is a useful transcatheter heart valve, especially for Asian patients with a high prevalence of small annulus.

2][3][4][5][6] It is now positioned as a useful treatment for AS comparable to surgical aortic valve replacement.Navitor (Abbott) is an intra-annular self expandable valve (IA-SEV), which was launched in April 2022 as the next-generation device of the Portico valve (Abbott) and the third valve after the SAPIEN (Edwards Lifesciences) and Evolut (Medtronic) series introduced in Japan.The features of IA-SEV include a cylindershaped frame, an intra-cellular valve with good hemodynamics, a large cell design useful for coronary artery access, and a NaviSeal skirt (Abbott) that significantly reduces paravalvular leakage (PVL).The delivery system, the FlexNav system (Abbott), is steerable, low profile, and has excellent passability, enabling valve recapture and repositioning.
IA-SEV was first introduced in Japan in Asia and has been successively introduced in other Asian countries.Because Asian individuals are smaller in size and have smaller aortic complexes than Western individuals, IA-SEV was considered to be useful because of its favorable hemodynamic characteristics.
We report the early results of patients prospectively enrolled and receiving an IA-SEV implant in a Japanese multicenter large-scale registry.

METHODS
STUDY POPULATION.All clinical data were collected from the database of an ongoing prospective Japanese multicenter registry (OCEAN-TAVI [Optimised Catheter Valvular Intervention transcatheter aortic valve implantation]). 7,8This trial is registered with the University Hospital Medical Information Network The degree of PVL was classified into 3 grades: nontrivial, mild, and equal or greater than moderate.
Postprocedural valve performance was evaluated by using the effective orifice area (EOA), indexed EOA, and incidence of patient-prosthesis mismatch (PPM).TAVR With Intra-Annular Self-Expandable Valves postoperative hemodynamics were analyzed based on echocardiographic examinations performed within 1 week of the day after TAVI in all cases.
In the current IA-SEV proctoring system in Japan, operators must perform 3 procedures first with proctor present, and the fourth and later patients can be treated independently.In this analysis, the early experience was defined as the first half of all cases and the late experience as the last half of all cases in the number of cases at each institution.If the number of cases was odd, one more case of early experience was added.All facilities in the proctoring phase with <3 cases were considered to have early experience.
The primary endpoint was the rate of no PPM, and the secondary endpoint was the rate of in-hospital mortality, hemodynamics after implantation, and differences in pacemaker implantation rates between early and late experiences.The incidence of ischemic stroke was 2.6%, disabling stroke was 1.3%, all bleeding was 8.9%, acute kidney injury was 4.5% (acute kidney injury stage 3 was 0.4%), and major vascular complications were low at 0.2% (Table 3).New-onset complete left bundle branch block was seen in 24.6%.The rate of pacemaker implantation was 9.7%.The incidence of inhospital mortality was 1.9%.early and late experience at each facility showed that the rate was 13.0% in the early period and 8.0% in the late period (P ¼ 0.0845), indicating a learning curve, although it was not statistically significant (Figure 2).

DISCUSSION
In this report, we present real-world data on IA-SEV from a multicenter registry by an Asian cohort.The main findings are as follows: 1) postprocedural hemodynamics were excellent even in small size valves, and the overall no PPM rate was 91.7% (87.3% in 23 mm valves); 2) the characteristics of the delivery system showed that vascular and hemorrhagic complications were low; 3) the NaviSeal was very effective in reducing PVL, with PVL below mild in >90% of patients in all sizes; and 4) a learning curve was observed for the pacemaker rate, which is expected to decrease as the technique matures.
IA-SEV is the third transcatheter heart valve launched in Japan (after the balloon-expandable valve and the supra-annular self-expandable valve [SA-SEV]).In our results, postprocedural mPG was 9.0 mm Hg at 23 mm, 8.3 mm Hg at 25 mm, 7.9 mm Hg at 27 mm, and 7.3 mm Hg at 29 mm valve sizes.Not only were the values in the single digits for all valve sizes, but they also became smaller as the valve diameter increased.The former generation IA-SEV (PORTICO) was also reported to have good hemodynamics. 12,13e PORTICO IDE study demonstrated the comparison between IA-SEV and commercially available valves including balloon expandable valves and SA-SEV for the patients extreme and high risk of surgery with severe AS. 14 The results showed that the IA-SEV had better hemodynamics (EOA and mPG) at 2 years compared with the balloon-expandable valve.The SA-SEV and IA-SEV were comparable in hemodynamics after 1 year.The reason why hemodynamics equivalent to SA-SEV can be obtained despite the intra-annular valve type is that the valve platform is cylindrical in shape, which allows the valve to open and close widely.15 It is well known that Japanese individuals are clearly smaller than their Western counterparts in terms of body size and valve ring anatomy, 16 and it  has been reported that Japanese patients often receive implants with smaller valves than their Western counterparts.7 In our study, almost two thirds of all cases were small size valves (23 mm and 25 mm).Conversely, in a study in Western countries, the proportion of the larger size (27 mm and 29 mm) valves comprised almost 70%.15 Our OCEAN-TAVI registry previously reported that the patients with small annulus had remarkably higher residual pressure gradient after implantation of balloon expandable valves.17 A recent report also suggests that narrow valve annulus may be a risk for structural valve deterioration in terms of long-term prognosis.18 These reports indicate that the use of the smallest IA-SEV (23 mm) provides good hemodynamics and is less likely to produce PPM, characteristics that make it very easy to use for Asian subjects with small body sizes.
The current IA-SEV uses the FlexNav delivery system, which is a hydrophilic-coated, extremely steerable, low-profile system that is easy to deliver.In a clinical trial using this delivery system, 19 major vascular complications were reportedly 5.0%, which seems to be less than the vascular complications in high-intermediate risk patients in the past. 1,2In this study, all vascular complications were 2.6%, and major vascular complications were 0.2%, which are very low, and we can realize the advantages of this In our report, the rate of pacemaker implantation (PMI) was 9.7%, indicating a learning curve trend.The pacemaker rate for the SA-SEV was 17.4% even in lowrisk patients. 6In the PORTICO NG trial 15 in the United States and Europe, the rate was 19.0%.It has been reported that the use of intracardiac echocardiography (ICE) in SA-SEV implantation can significantly reduce the PMI rate. 20,21The participating centers in this study compared centers that implanted valves using ICE (4 centers) with those that did not (19 centers).The PMI rate in the ICE group was 12.4%, while the PMI rate in the non-ICE group was 8.7% (P ¼ 0.2257), with no significant difference between the 2 groups.Therefore, for IA-SEV implantation, the use of ICE did not seem to play a role in decreasing the PMI rate.In SA-SEV, a large size valve has been described as an independent determinant of PMI. 22 speculate that there are numerous reasons for the lower PMI rate, including the fact that more small sized valves were implanted than recorded in the previous paper, 15    TRANSLATIONAL OUTLOOK: This study was a short-term observation, but longer term follow-up of the valve will elucidate the hemodynamic benefits on freedom from structural valve deterioration.

(
UMIN000020423).The study protocol of the OCEAN-TAVI registry was approved by the local institutional review boards of the participating centers, and written informed consent was obtained from all patients before undergoing TAVR.The diagnosis of AS, indications for TAVR, and transcatheter heart valve selection were determined by individual local heart teams.The IA-SEV was launched in April 2022, and 463 patients with AS were treated by TAVR using IA-SEV.In Japan, the indication for this valve is limited to the native valve only; therefore, in this cohort, patients receiving a transcatheter aortic valve in the surgical aortic valve procedure and a transcatheter aortic valve in the transcatheter valve procedure were not enrolled.DATA DEFINITION AND CLINICAL ENDPOINTS.The OCEAN-TAVI registry data set includes: baseline patient characteristics; laboratory data; echocardiographic data; procedural variables; and clinical outcomes with respect to mortality, rehospitalization, and other clinical adverse events.Information regarding the occurrence and/or causes of adverse events was obtained from either the medical records of each center or treating hospital, or by contacting the patient's family members.An electronic data capture system was used for the collection of the required materials, and all data were assessed via a self-audit by the site.All clinical endpoints, procedural data, complications, postprocedural parameters, and in-hospital events were defined by using

A
B B R E V I A T I O N S A N D A C R O N Y M S AS = aortic stenosis EOA = effective orifice area IA-SEV = intra-annular self expandable valve ICE = intracardiac echocardiography mPG = mean pressure gradient PMI = pacemaker implantation PPM = patient-prosthesis mismatch PVL = paravalvular leakage SA-SEV = supra-annular selfexpandable heart valve

FIGURE 1
FIGURE 1 Preprocedural and Postprocedural Hemodynamics and AR and PVL system.The PORTICO NG (Evaluation of the Portico NG [Next Generation] Transcatheter Aortic Valve in High and Extreme Risk Patients With Symptomatic Severe Aortic Stenosis) study 15 showed that PVL was very well suppressed because of the outer cuff (ie, Naviseal) in IE-SAV.In our study, mild or less PVL was >90% in all sizes, indicating the effectiveness of this treatment.In the PORTICO-I trial, 12 the grade of PVL was better at 1 year than at 30 days after valve implantation, indicating that PVL decreases with time.Because our data in this study were based on the measurement of PVL immediately after implantation, PVL is expected to decrease further after 30 days and 1 year.

FIGURE 2
FIGURE 2 Pacemaker Learning Curve

Table 2
PROCEDURE AND COMPLICATION DATA.The size of the IA-SEV was 23 mm in 26.1%, 25 mm in 41.7%, 27 mm in 22.9%, and 29 mm in 9.3%.Among all sizes, the numbers of small sized valves (23 mm and 25 mm) totaled 314 cases, accounting for 67.8%.Most of the patients (86.8%) were treated while they were under conscious sedation.A transfemoral approach was used in 97.6% of cases, and 11 (2.4%) patients
frequency of no PPM was 87.5% for the smallest valve size (23 mm) but reached >90% for larger valves.AR ¼ aortic regurgitation.
(A) Preprocedural and postprocedural hemodynamics and paravalvular leakage (PVL) in each valve size.Each left panel shows the preprocedural/postprocedural mean pressure gradient (mPG) and aortic valve area (effective orifice area [EOA]).Compared with preprocedural findings, hemodynamics (mPG and EOA) and PVL significantly improved after the transcatheter aortic valve implantation procedure in each valve size.*P < 0.0001.Values are mean AE SD. (B) The percentage of severe patient-prosthesis mismatch (PPM), moderate PPM, and no PPM for each valve.In the entire cohort, severe PPM was 2.6%, and no PPM was 91.7%.For each valve size, the Mollmann H, Linke A, Nombela-Franco L, et al.Procedural safety and device performance of the Porticoä valve from experienced TAVI centers: 30-day outcomes in the multicenter CONFIDENCE registry.J Clin Med.2022;11:4839.14.Makkar RR, Cheng W, Waksman R, et al.Selfexpanding intra-annular versus commercially available transcatheter heart valves in high and extreme risk patients with severe aortic stenosis (PORTICO IDE): a randomized, controlled, noninferiority trial.Lancet.2020;396:669-683.15.Reardon MJ, Chehab B, Smith D, et al. 30-day clinical outcomes of a self-expanding transcatheter aortic valve: the international PORTICO NG study.J Am Coll Cardiol Intv.2023;16:681-689.16.Watanabe Y, Hayashida K, Takayama M, et al.First direct comparison of clinical outcomes between European and Asian cohorts in transcatheter aortic valve implantation: the Massy study group vs. the PREVAIL JAPAN trial.J Cardiol.2015;65:112-116.The latestgeneration IA-SEV has been launched; however, the clinical data and valve hemodynamics for Asian cohorts were not yet clear.COMPETENCY IN PATIENT CARE: The IA-SEV has excellent valve hemodynamics even in smaller size (low incidences of PPM, and low mean pressure gradient).This valve has efficacy for Asian cohorts with small-size anatomy as well as Western cohorts.