The Evolution of TAVR and the Quest for Versatility
Since the inception of transcatheter aortic valve replacement (TAVR), the landscape has been dominated by a few established platforms, primarily the balloon-expandable SAPIEN series and the self-expanding Evolut series. While these devices have revolutionized the treatment of symptomatic severe aortic stenosis, particularly in high-risk and elderly populations, the search for next-generation valves that offer greater sizing precision and comparable long-term efficacy continues. The LANDMARK trial represents a pivotal moment in this evolution, evaluating the Myval balloon-expandable transcatheter heart valve (THV) series against these established contemporary standards.
Highlights
The following points summarize the primary findings of the 1-year LANDMARK trial report:
1. Clinical Noninferiority: The Myval THV series was found to be noninferior to contemporary SAPIEN and Evolut valves regarding a composite endpoint of all-cause mortality, stroke, and hospitalizations.
2. Hemodynamic Performance: Both the novel and established platforms demonstrated excellent and comparable hemodynamic profiles at the 1-year mark.
3. Quality of Life: Significant and sustained improvements in quality of life, measured by the SF-12 survey, were observed across both study arms.
4. Sizing Innovation: The Myval series introduces unique intermediate sizes, potentially allowing for more precise matching of patient anatomy.
The Clinical Challenge: Why New THV Platforms Matter
Despite the success of current TAVR devices, clinicians often encounter anatomical challenges where standard sizing might lead to suboptimal outcomes, such as paravalvular leak or prosthesis-patient mismatch. The Myval THV series was designed to address some of these gaps by offering a broader range of sizes, including ‘extra’ and ‘intermediate’ options.
Previously, the LANDMARK trial established the 30-day early safety of the Myval system. However, for a new device to be integrated into standard clinical practice, evidence of mid-term durability and clinical efficacy is essential. This 1-year report provides the necessary data to assess whether the initial safety profile translates into sustained clinical benefits.
LANDMARK Study Design: A Rigorous Multi-Center Comparison
The LANDMARK trial was an open-label, randomized, noninferiority trial conducted across 31 hospitals in Europe, New Zealand, and Brazil. A total of 768 participants with symptomatic severe native aortic stenosis were enrolled and randomly assigned in a 1:1 ratio to receive either the Myval THV series or a contemporary THV (either the SAPIEN or Evolut series).
Study Population
The participants had a mean age of 80 years, with a balanced gender distribution (48% women). The median Society of Thoracic Surgeons (STS) Predicted Risk of Mortality score was 2.6%, indicating a population that, while elderly, was generally at low to intermediate surgical risk. This demographic profile reflects the contemporary shift of TAVR into broader patient populations.
Endpoints and Methodology
The primary composite endpoint at 1 year included:
1. All-cause mortality.
2. All strokes.
3. Procedure- or valve-related hospitalizations.
An extended composite endpoint, as recommended by the Valve Academic Research Consortium-3 (VARC-3), also incorporated quality-of-life assessments using the 12-Item Short Form Health Survey (SF-12). The analysis was conducted on an intention-to-treat basis, with a prespecified noninferiority margin of 10.89% for the 1-year exploratory analysis.
1-Year Results: Clinical Efficacy and Hemodynamic Parity
The 1-year outcomes of the LANDMARK trial confirm that the Myval THV series performs on par with the current market leaders. The Kaplan-Meier estimates for freedom from the composite endpoint at 365 days were nearly identical: 87.0% for the Myval group and 86.9% for the contemporary THV group.
Statistical Significance
The difference in the composite endpoint was -0.1% (1-sided 95% CI: 3.9%), which easily met the criteria for noninferiority (P < 0.0001). This suggests that the novel balloon-expandable platform is as effective as the SAPIEN and Evolut series in preventing major adverse clinical events during the first year post-implantation.
Quality of Life and Extended Endpoints
When evaluating the extended composite endpoint—which adds quality-of-life metrics to the clinical outcomes—there were no significant differences between the two groups. Freedom from the extended composite endpoint was 80.5% in the Myval arm compared to 77.3% in the contemporary arm (difference: 3.2%; 95% CI: -2.9% to 9.2%; P = 0.33). Both groups experienced a significant improvement in physical and mental health scores from baseline to one year, highlighting the profound impact of successful TAVR on elderly patients’ functional status.
Expert Commentary: Interpreting the Versatility of the Myval Series
The results of the LANDMARK trial are particularly significant due to the Myval’s ‘versatility’ in sizing. Unlike traditional platforms that offer limited size increments, the Myval series includes intermediate sizes (e.g., 21.5 mm, 24.5 mm, 27.5 mm). In clinical practice, this allows for a more tailored approach to the aortic annulus, potentially reducing the risk of annular rupture from over-sizing or paravalvular regurgitation from under-sizing.
From a mechanistic perspective, the Myval THV utilizes a cobalt-chromium frame and a bovine pericardial tissue valve, similar to the SAPIEN architecture. The parity in results suggests that the structural integrity and hemodynamic function of this novel frame design are robust. However, experts note that while 1-year data are encouraging, longer-term follow-up (up to 5 or 10 years) will be required to assess the true durability and the incidence of structural valve deterioration compared to the long-term data available for SAPIEN and Evolut.
Clinical Implications and Practice Gaps
For clinicians, the LANDMARK trial provides evidence-based confidence in using the Myval platform. The availability of an additional, noninferior balloon-expandable valve increases the options for heart teams when planning interventions. This is especially relevant in healthcare systems where cost-effectiveness and device availability may influence treatment choices.
Despite the positive results, some questions remain. The trial was not powered to detect small differences in rare complications, such as specific types of valve thrombosis or the need for permanent pacemakers. Furthermore, the 1-year timeframe, while standard for regulatory noninferiority, is only the beginning of the valve’s lifecycle in a patient.
Conclusion
The 1-year report from the LANDMARK trial establishes the Myval THV series as a clinically comparable alternative to the most widely used contemporary transcatheter heart valves. With noninferiority demonstrated in all-cause mortality, stroke, and hospitalization rates, and a demonstrated improvement in patient quality of life, the Myval platform offers a versatile and effective solution for the management of symptomatic severe aortic stenosis. As the field move towards more personalized valve selection, the expanded sizing options of the Myval series may play an increasingly important role in optimizing patient outcomes.
Funding and ClinicalTrials.gov
The LANDMARK trial was sponsored by Meril Life Sciences Pvt. Ltd. The trial is registered at ClinicalTrials.gov with the identifier NCT04275726.
References
1. Serruys PW, Tobe A, van Royen N, et al. 1-Year Outcomes of Novel Balloon-Expandable vs Contemporary Transcatheter Heart Valves in Severe Aortic Stenosis: The LANDMARK Trial. J Am Coll Cardiol. 2025;S0735-1097(25)10159-9. doi:10.1016/j.jacc.2025.10.076.
2. VARC-3 Writing Committee. Valve Academic Research Consortium 3: Updated Endpoint Definitions for Aortic Valve Clinical Research. J Am Coll Cardiol. 2021;77(21):2717-2746.
3. Mack MJ, Leon MB, Thourani VH, et al. Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients. N Engl J Med. 2019;380(18):1695-1705.
4. Popma JJ, Deeb GM, Yakubov SJ, et al. Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients. N Engl J Med. 2019;380(18):1706-1715.