Expanding our horizons for the use of transcatheter self-expanding valves: what does the future hold?

KEYWORDS:

• Structural heart intervention
• aortic stenosis
• transcatheter aortic valve implantation
• self-expanding bioprosthesis
• balloon-expandable bioprosthesis
• aortic valve

1. Introduction

Technological progresses and improved operator experience have contributed to transcatheter aortic valve implantation (TAVI) wide spreading. Indications have been expanded while old-generation platforms have been replaced by new ones and we currently have a huge number of devices available for use [1].

For classification purposes and easier reference in literature, TAVI devices are usually grouped into bigger categories. The distinction between balloon-expandable (BE) and self-expanding (SE) devices is based on the different mechanism of deployment, namely deformation by balloon inflation and valve unsheathing. Even if BE devices show better outcomes in terms of permanent pacemaker implantation (PPI) rates and residual para-valvular leaks (PVL), they require a more meticulous sizing to avoid mechanical damage of the aortic annulus and their use is less favorable in small annuli [2]. In these settings, SE devices can prove more beneficial. However, as TAVI expands to low-risk younger patients, further improvement and technical innovation are definitively expected to overcome some limitations of SE devices.

2. Strengths and weaknesses of new generation SE devices

Table 1 provides an overview on current generation SE devices. These include the Corevalve Evolut platform (Medtronic, Minneapolis, Minnesota, USA) with its iterations R/PRO/PRO⁺, the Acurate neo platform (Boston Scientific, Marlborough, Massachusetts, USA) with its iteration neo2, the Portico and the Navitor valves (Abbott, Chicago, Illinois, USA), the Allegra valve (NVT, New Valve Technology, Morges, Switzerland), the Hydra valve (SMT, Sahajanand Medical Technologies Ltd., Sahajanand Estate, Wakhariawadi, Near Dabholi, India) and the VenusA-Plus valve (Venus Medtech Inc., Hangzhou, China). All consist of a nitinol stent frame with a diamond cell design holding three leaflets made of either porcine or bovine pericardial tissue. Nitinol alloy has shapes memory properties, thus enabling valve deployment through progressive stent unsheathing.

Table 1. New generation self-expanding transcatheter aortic valve devices

DEVICE	FRAME	LEAFLETS	EXT. WRAP	SIZES	RECAPTURE/REPOSITION	RETRIEVABLE	ACCESS SIZE	SUPRA-ANNULAR
CoreValve Evolut R/PRO/PRO+Medtronic	nitinol	porcine		yes*	23–26-29-34	yes/yes*^1	yes	yes
Acurate neo/neo 2Boston Scientific	nitinol	porcine		yes*	23–25-27	no/yes*^2 top-down deployment	no	yes
AllegraNew Valve Technology	nitinol	bovine		no	23–27-31	yes/yes occlusion free deployment	yes	yes
HydraSMT	nitinol	bovine		yes	22–26-30		yes	yes
VenusA-PlusVenus Medtech	nitinol	porcine	porcine	no	23–26-29-32	yes/yes*^1	yes	yes
PorticoAbbott	nitinol	bovine		no	23–25-27-29	yes/yes*^1	yes	intra-annular
NavitorAbbott	nitinol	bovine		yes**	23–25-27-29	yes/yes	yes	intra-annular

* external wrap is present on Evolut Pro 23–26-29 and all sizes of Evolut Pro+ (including 34); Acurate neo platform includes an external wrap that is even wider for neo 2.

** NaviSeal Cuff actively synchronizes to the cardiac cycle, seals, and mitigates Paravalvular Leak by expanding to fill calcification-related gaps between the annulus and the valve.

*¹ up to 80% deployment.

*² even after completing the 1^st step (release of upper crown and stabilization arches), it is still

possible to adjust the position by gentle pulling/pushing movements (but not completely recapture/re-sheath the valve).

The Evolut, Portico, Navitor, Hydra and VenusA-Plus platforms share a flared design and their unsheathing process consists in progressively releasing the proximal (inflow) to distal (outflow) portion of the stent.

Conversely, the Acurate neo and Allegra technologies have a more unique shape and unsheathing mechanism. In the top-down deployment of the Acurate neo platform the stabilization arches and the upper crown are opened first (in order to achieve immediate axial self-alignment and supra-annular anchoring), followed by opening of the inflow stent. The Allegra valve has a three-step occlusion-free release: the mid portion holding the leaflets is opened first, followed by the sequential opening of the inflow and the outflow portion. The stent shape has a more convex outflow tract that limits interaction with the ascending aorta.

2.1. Strengths

2.1.1 Supra-annular design

With the exception of the Portico and Navitor devices, all the other SE valves have a supra-annular design. The advantage of intra-annular devices is to provide immediately functioning leaflets during deployment; however, the supra-annular design provides better hemodynamic performances both on immediate and long-term outcomes. In fact, the supra-annular position preserves leaflets coaptation also in challenging anatomies at risk for stent under-expansion such as small annuli and valve-in-valve (ViV) settings; this ensures large effective orifice areas (EOA) and low mean gradients, thus reducing the risk of patient-prosthesis mismatch (PPM) [3,4]. The TAVI SMALL international registry, including 859 patients with small annuli treated with a SE valve, showed that pre-discharge gradients were consistently low in every group, with a slight benefit in favor of the Evolut R (8.1 mm Hg) and Evolut PRO (6.9 mm Hg) compared to the Acurate neo (9.6 mm Hg) and Portico (8.9 mm Hg) groups (p < 0.001) [5]. Furthermore, leaflet coaptation in the supra-annular position while avoiding geometric distortion and leaflet pin-wheeling also provides more favorable flow dynamics at the level of the neosinus, which may translates into improved valve durability (a primary goal for the future of TAVI) [6]. In fact, lower degrees of mechanical stress on the cusps and faster blood wash out from the neosinus prevent from structural valve deterioration and leaflet thrombosis, which are the main features leading to late valve dysfunction and failure [7].

2.1.2 Device repositioning and recapture

Immediate procedural success as well as optimal valve function and long-term outcomes are highly dependent on the implantation depth, but this is not always predictable with SE valves [8]. Nevertheless, SE devices, with the exception of the Acurate neo, are recapturable and repositionable, thus favoring a more precise and accurate deployment in challenging anatomies at higher risk for suboptimal valve positioning or sudden valve displacement.

2.2. Weaknesses

2.2.1 Low radial force

If compared to stainless steel or cobalt-chromium alloy used for BE stents, nitinol has less radial force. This explains a lower incidence of mechanical complications such as annular rupture (0.13% for SE vs 0.25% for BE valves) and a significantly lower risk of emergent cardiac surgery and in-hospital mortality (p < 0.001) [9]. However, in extremely calcified anatomies, valves with low radial force can have asymmetrical or even under-expansion thus reducing device performance and causing poorer sealing with higher risk of PVL. For this reason, pre- and post-dilatation are frequently required despite a higher risk of cerebral embolization.

2.2.2. High design profile

Valves with a high profile, despite favoring a harmonious implantation in the ascending aorta, may also interfere with the surrounding structures, especially in small anatomies, and make coronary access uneasy.

2.2.3 Low predictable valve positioning

Implantation depth is an important determinant of outcomes. Despite the contemporary refinements in valve technologies and implantation techniques, SE valves still demonstrate less accurate positioning compared to BE devices. This is also reflected by the nonnegligible rate of valve migration/embolization reported. Yet, multiple implantation attempts are also associated to a greater amount of contrast used which is responsible for acute kidney injury after TAVI.

3. What the future holds for SE devices

As transcatheter treatments expand to patients with longer life expectancy, lifelong management of their aortic valve disease needs to be taken into consideration. At this purpose, long-term outcomes become extremely important and common issues related to SE valves (including coronary access, PPI, PVL) need to be fixed.

Further optimization of current devices and implantation techniques have a not negligible role in order to improve device performance and enlarge the audience for SE devices.

3.1. Optimization of current technologies

3.1.1. Implementation of coronary access

Uneasy coronary access has been described in a significant proportion of patients with SE devices [10]. Selective coronary engagement through diamond cells can be particularly challenging, especially for operators who are less familiar with structural interventions. Moreover, the position of commissural posts after implantation can be completely random [11]. A prosthetic post directly facing coronary orifices makes coronary engagement difficult even in prostheses with large cells and reduces feasibility of the BASILICA technique (bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction) in case of future ViV and TAVI-in-TAVI procedures [12]. Accordingly, commissural alignment is a primary goal for SE valves; at this purpose, new implantation techniques have been described [13,14]. Nevertheless, a not negligible percentage of coronary ostia can still not be reached. Moreover, commissural alignment is based on CT scan studies which calculate the degree of over-imposition but no in vivo studies are available to demonstrate that this approach increases the rate of coronary reengagement.

3.1.2. Implementation of valve sealing and reduction of PVL

PVL has been largely associated with poor outcome after TAVI and some data suggest that even mild residual periprosthetic regurgitation can negatively impact patients outcomes at follow-up. For this reason, minimization of PVL is one of the key element to improve outcomes after TAVI. New generation SE valves have an improved sealing technology with external skirts with variable thickness and length. A promising technology is represented by the NaviSeal Cuff of the Navitor valve which actively synchronizes to the cardiac cycle, seals, and mitigates PVL by expanding to fill calcification-related gaps between the annulus and the valve.

3.1.3. Reduction of post procedural conduction disturbances and pacemaker implantation

Conduction disturbances represent the Achille’s heel of TAVI since their incidence does not decrease over the years and, rather, tends to remain high due to the progressive augmentation of radial force [15]. Given proximity with the His bundle, depth of implantation is an important determinant of pacemaker implantation rates and few millimeters can make a huge difference. Each device has a specific implantation depth to target [8]. Parallax errors may affects accuracy during implantation of SE valves in the standard co-planar 3 cusps view. As an alternative, the ‘cusp-overlap approach’ has been recently suggested. This view helps to center the delivery catheter across the aortic valve, eliminates parallax of the delivery system and enables prosthesis implantation at a higher depth. In addition, it also visually elongates the left ventricle outflow tract, thus ideally identifying the course of the conduction system. Retrospective analysis show that the 30-days incidence of PPI after Evolut implantation with this technique is significantly reduced (6.4% vs 17.8%, p = 0.004) [16]. A prospective study sponsored by Medtronic (Optimize PRO, NCT04091048) is currently ongoing.

A critical issue for implantation depth is also related to the delivery systems. These rarely give an optimal performance in a wide range of anatomy and, especially in complex cases with horizontal aorta and tortuosity, does not allow a valid coaxial alignment between the THV and the native annulus thus promoting interference with the conduction system. Enhanced torquability, flexibility and adjustable steering of delivery catheters would allow a more precise positioning also in complex anatomies with additional positive effects on procedural time and PPI rates.

3.2. New devices

Completely new transcatheter heart valves are also under investigation. Among these, the 6 months results of the first-in-man feasibility study of the BIOVALVE (Biotronik, Buelach, Switzerland) have been recently published. Despite structural similarities with its predecessors, preliminary short-term results are not encouraging, since procedural success only reaches 75% [17]. However, in the highly competitive current TAVI market, new devices should be overall innovative to emerge. Devices affected by limitations of a first-in-man experience, including the use in a very high-risk population and a learning curve at its very beginning, are still far from the future of TAVI. At this purpose, more economic investment, larger studies and longer follow-up will be necessary.

4. Conclusions

TAVI market currently offers a wide choice of SE devices. In order to compete with BE ones, matching the best device to each patient is a main goal. But since TAVI indications are expanding, further implementation is needed. Optimization of implantation techniques is the first step to improve results, but innovation is equally necessary.

TAVI represents a dynamic, constantly evolving field of interest for interventional cardiology. According to 2017 European guidelines, TAVI is recommended (class IB) for patients with severe symptomatic aortic stenosis (AS) at high or prohibitive risk for surgery [18]. However, current practice has already gone further and TAVI is used in intermediate to low surgical risk patients, bicuspid aortic valves (BAV), valve-in-valve (ViV) and pure aortic regurgitation (AR) cases [1,19–21].

Despite few head-to-head comparisons and most of the evidence coming from metanalysis and retrospective studies, BE TAVI devices have been always considered superior to SE ones thanks to quicker procedural times, lower incidence of acute kidney injury, lower rate of PPI and less significant PVL, which all translate into shorter hospital stays and improved long-term outcomes [2].

Nevertheless, in the era of tailored medicine, is it inconceivable not to have an alternative. At this purpose, SE valves proved to be even superior to BE ones in specific settings. Larger EOA and lower post-procedural mean gradients obtained with SE devices are more suitable for small annuli and degenerated surgical bioprostheses [5].

Accordingly, all catheterization laboratories should be definitively equipped with both BE and SE devices in order to offer the best treatment for each patient.

However, some issues related to the use of SE devices still need to be addressed and further implementation aims to parallel expanding indications to TAVI. Some niche indications to TAVI, such as aortic valve disease in bicuspid morphology, have not found yet the ideal device. Optimization of existing platforms and implantation techniques are already in progress, but unmet needs are still waiting for strikingly new innovative technologies.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A peer reviewer on this manuscript is a proctor for the Medtronic self-expanding valve and Edwards Lifesciences balloon-expandable valve. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.