It has been 22 years since the first transcatheter aortic valve implantation (TAVI) was introduced. Since then, the landscape has undergone drastic changes. Initially limited to inoperable patients, TAVI indications have progressively expanded, becoming the treatment of choice for patients over 75 years of age today. This shift has been driven by technical advances, favorable durability data, and a growing body of scientific evidence supporting TAVI’s inclusion in major clinical practice guidelines. Most of the current evidence has been provided by observational registries and clinical trials involving prostheses that have been available on the market for many years, such as the SAPIEN® (Edwards Lifesciences, USA) and Evolut® (Medtronic, USA) devices​(3 Myvalv vs Sapien y Ev…). 

As expected, new prostheses are emerging in the market, aiming to establish themselves as viable alternatives in TAVI. One such example is the Myval® prosthesis (Meril Life Sciences Pvt. Ltd., India), featuring an intra-annular balloon-expandable design intended to demonstrate similar clinical benefits. 

The LANDMARK clinical study we are analyzing today aims to demonstrate that the Myval® prosthesis is not inferior to widely used contemporary prostheses (Edwards SAPIEN® and Medtronic Evolut®). This trial is randomized, prospective, and multicentric, conducted across 31 hospital centers in 16 countries, including Spain. 

Patients selected for the study were adults with severe symptomatic aortic stenosis, indicated for TAVI according to the evaluation of the local heart team. They also required an anatomical compatibility to implant the three prostheses included in the trial, with access mandated via the transfemoral route. Patients were randomly assigned in a 1:1 ratio to receive the Myval® prosthesis or a contemporary prosthesis (50% distribution for Edwards SAPIEN® and 50% for Medtronic Evolut® within this group). Following randomization, device sizing (determined by pre-procedural computed tomography analysis), implantation technique (projection used, need for pre/post-dilatation, etc.), and post-procedural monitoring (including pacemaker requirement) were left to the discretion of the investigative team at each center. 

The primary endpoint at 30 days was a composite of seven events: all-cause mortality, stroke, major bleeding, acute kidney injury, major vascular complications, moderate or severe aortic insufficiency, and permanent pacemaker implantation, according to the Valve Academic Research Consortium-3 (VARC-3) criteria. Key secondary endpoints included the individual components of the primary endpoint, in addition to functional class evaluation, quality of life, and hemodynamic parameters of valve function assessed via echocardiography. 

A total of 768 patients were included in the study, with 384 randomly assigned to the Meril Myval® prosthesis group and the remaining 384 to the contemporary prosthesis group. Women constituted 48% of the participants, with an average age of 80 years and an average STS score of 2.6% (indicating low surgical risk, <4%). There were no significant differences between both groups regarding these or other baseline characteristics. In the intention-to-treat analysis, the Meril Myval® prosthesis met the primary endpoint of non-inferiority at 30 days, with an incidence of 25% in the Meril Myval® group versus 27% in the contemporary prosthesis group. The risk difference was −2.3%, with an upper 95% confidence interval limit of 3.8% (p for non-inferiority <0.0001). No significant differences were observed in the individual components of the primary endpoint. 

The authors concluded that in individuals with severe, symptomatic aortic stenosis, the transcatheter Meril Myval® valve achieved its primary endpoint at 30 days. 

COMMENTARY: 

In recent years, several randomized trials have compared different TAVI valves. The major studies include: 

• SOLVE-TAVI (2020): Compared the self-expandable Medtronic Evolut R® valve and the balloon-expandable Edwards SAPIEN 3®, achieving equivalence in the combined primary endpoint at 30 days. 

• SCOPE I and II: Evaluated the Boston AcurateNeo® device, which failed to demonstrate non-inferiority against Medtronic Evolut R® and Edwards SAPIEN 3®, considered standards for their durability and extensive evidence. 

• PORTICO-IDE: Demonstrated non-inferiority of the Abbott Portico® valve compared to standard valves. 

Now added to this list is the LANDMARK trial, which evaluated the balloon-expandable Meril Myval® prosthesis against Edwards SAPIEN® and Medtronic Evolut®, demonstrating non-inferiority in the 30-day efficacy and safety combined endpoint. Notable findings include a lower pacemaker rate than traditional rates in both groups, 15% with Meril Myval® compared to 17% with contemporary prostheses (p = 0.49), which, while low, remains considerably higher than with conventional surgical prostheses. Additionally, if we examine other primary endpoint events, these also had a low incidence, likely reflecting technique improvements: 

• All-cause mortality: 2% in both groups (p = 1.0). 

• Stroke: 3% in both, only 1% disabling (p = 1.0). 

• Major vascular complications: 2% in both groups (p = 0.6). 

• Moderate or severe regurgitation: 3% with Meril Myval® versus 5% with the other prostheses (p = 0.58). 

In interventional cardiology, non-inferiority trials are common to validate new devices and facilitate their adoption in clinical practice. However, while most studies focus exclusively on transfemoral access, mainly performed by interventional cardiologists, it cannot be overlooked that these results are extrapolated to non-transfemoral accesses, such as transcarotid or transaxillary routes. These approaches, in certain Spanish centers like ours, are managed entirely by cardiac surgeons. 

At the University Hospital of A Coruña (CHUAC), we have performed over 480 non-transfemoral TAVI procedures since 2009. For the first ten years, the transapical route was predominantly used, whereas in the last 190 cases, the transcarotid route has been preferred. With this approach, 30-day mortality was 1.6%, despite the high surgical risk of the patients (EuroSCORE II of 7% and an average age of 82 years). The stroke rate was 0.8%, major vascular complications 1.6%, and permanent pacemaker implantation rate 12%. In general, these results are comparable or even superior to those achieved in this trial. Although more than 80% of the implanted prostheses were of the Edwards SAPIEN 3® type, around 10% were Meril Myval® prostheses, providing us with a comparative experience basis between the two. 

It is noteworthy that this clinical trial included a patient population with lower surgical risk than previous studies (average STS score 2.6%). Another distinguishing feature is its notable anatomical variability, with 7% of bicuspid valves and 32% small annuli, likely reflecting the broad current indication of TAVI across different patient profiles. 

The study has some limitations. The main one is selection bias, as only 15% of patients were included in participating centers, all with favorable anatomies for the prostheses. This may limit the generalizability of the results. Additionally, there were more crossovers in the Meril Myval® group (15 vs. 5), primarily due to the lack of available prosthetic sizes. Finally, patients with 23 mm Medtronic Evolut® prostheses were not included, which may have underestimated the benefit of the supra-annular design in small annuli. 

In my opinion, the Meril Myval® prosthesis has two significant advantages over others; the first is the availability of intermediate and even extra-large sizes (accessible with any access type), and the second is the simplicity of the system, which comes preloaded (extravasculature) on the balloon (particularly relevant for non-transfemoral access): 

1. Availability of Intermediate Sizes: With 1.5 mm increments instead of the usual 3 mm, Myval® improves adaptation to the patient’s aortic annulus. Precise adjustment is crucial, as an oversized prosthesis increases the risk of complications, while an undersized one may lead to paravalvular insufficiency or embolization. In the LANDMARK study, 48% of Myval® patients received an intermediate prosthesis, associated with a lower rate of prosthetic insufficiency and a larger aortic valve area at 30 days compared to Edwards SAPIEN®. Additionally, Myval® offers extra-large sizes (30.5 and 32 mm) for annuli up to 840 mm², which may be helpful in patients with non-calcified pure aortic insufficiency or mitral or tricuspid valve-in-valve procedures. Although the LANDMARK study did not include patients with large annuli, future results are expected from a registry dedicated to this group. 
2. System Simplicity with Preloaded Balloon Prosthesis: The Meril Myval® system’s extravascular preloading simplifies the TAVI process, being especially useful for non-transfemoral accesses like the transcarotid route, commonly performed in CHUAC’s cardiac surgery service. In this access, the space between the supraaortic trunks and the aortic annulus is much more limited than in transfemoral access. Myval®’s design eliminates cumbersome steps to position the balloon within the prosthesis in a restricted space, simplifying the procedure and reducing risks. The intravascular loading of prostheses, as with Edwards SAPIEN 3®, includes maneuvers requiring space, and it warrants special attention when the distance between the aortic annulus and the distal end of the introducer is limited, i.e., in non-transfemoral peripheral accesses. 

As therapeutic options in TAVI continue to expand, treatment personalization is becoming increasingly important, choosing the most suitable prosthesis according to the patient’s anatomy. Thus, we have moved from searching for the “patient for implantation” to finding “the best implant for each patient.” In this context, the Meril Myval® prosthesis has made significant progress with positive 30-day results compared to other prostheses. Nevertheless, further studies and long-term follow-up are needed to determine its definitive place in clinical practice. 

Finally, I would like to once again encourage all cardiac surgeons interested in the TAVI field not to give up on their goal. It is crucial to take advantage of all training opportunities, stay updated, and, with determination, promote the implementation of non-transfemoral access in their hospitals. These approaches, due to their surgical nature, are particularly suitable for our specialty, and our results support us. 

REFERENCE: 

Baumbach A, van Royen N, Amat-Santos IJ, Hudec M, Bunc M, et al. LANDMARK comparison of early outcomes of newer-generation Myval transcatheter heart valve series with contemporary valves (Sapien and Evolut) in real-world individuals with severe symptomatic native aortic stenosis: a randomised non-inferiority trial. Lancet. 2024 Jun 22;403(10445):2695-2708. doi: 10.1016/S0140-6736(24)00821-3.