Highlights
- Self-expanding valves (SEV) demonstrated significantly superior hemodynamic performance compared to balloon-expandable valves (BEV) at 3-year follow-up in patients undergoing valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) for failed small surgical bioprostheses.
- The rate of intended valve performance was markedly higher in the SEV group (82.4%) than in the BEV group (27.6%).
- Despite hemodynamic differences, clinical outcomes—including mortality, stroke, and heart failure-related hospitalizations—were similar between both valve types at the 3-year mark.
- Functional status and quality of life improved significantly and similarly in both patient cohorts.
Introduction: The Challenge of Small Surgical Valves
The management of failed surgical aortic bioprostheses has been revolutionized by the advent of valve-in-valve transcatheter aortic valve replacement (ViV-TAVR). However, patients with small surgical valves (typically defined as ≤23 mm) represent a particularly challenging subgroup. These patients are at a higher risk of significant residual gradients and patient-prosthesis mismatch (PPM) because the transcatheter heart valve (THV) must be housed within the rigid frame of the existing surgical bioprosthesis, further narrowing the effective orifice area.
While retrospective registry data have suggested that self-expanding valves (SEV) might offer better hemodynamics due to their supra-annular leaflet position, head-to-head randomized clinical trial data have been scarce. The LYTEN trial was designed to address this gap, providing a rigorous comparison between balloon-expandable valves (BEV) and SEV in this high-risk population. The recently released 3-year results provide critical insights into the long-term durability and clinical impact of these two distinct technologies.
The LYTEN Trial: Comparative Analysis of ViV-TAVR
The LYTEN trial (Comparison of the Balloon-Expandable Edwards Valve and Self-Expandable CoreValve Evolut R or Evolut PRO System for the Treatment of Small, Severely Dysfunctional Surgical Aortic Bioprostheses) is a multicenter randomized study. It specifically enrolled patients with a failed small (≤23 mm) surgical valve who were candidates for ViV-TAVR.
Study Design and Patient Population
A total of 98 patients were randomized to receive either a BEV (SAPIEN 3 or SAPIEN 3 ULTRA; n=46) or an SEV (Evolut R, PRO, or PRO+; n=52). The baseline characteristics were well-balanced between the two groups. The primary focus of this secondary analysis was to evaluate the 3-year hemodynamic performance via Doppler echocardiography and to assess clinical outcomes according to the Valve Academic Research Consortium (VARC)-2 and VARC-3 criteria.
Endpoints and Definitions
The study defined “intended performance of the valve” as a composite of a mean gradient <20 mm Hg, peak velocity <3 m/s, Doppler velocity index (DVI) ≥0.25, and less than moderate aortic regurgitation (AR). Clinical endpoints included a composite of death, stroke, or heart failure-related hospitalization.
3-Year Hemodynamic Superiority of SEV
The most striking findings of the LYTEN trial at 3 years relate to the hemodynamic profiles of the two valve systems. The data consistently favored the self-expanding platform across all major echocardiographic parameters.
Mean Gradients and Orifice Area
Patients in the SEV group maintained significantly lower mean transvalvular gradients compared to those in the BEV group (13.12 ± 8.56 mm Hg vs. 20.40 ± 9.12 mm Hg; P=0.002). Furthermore, the indexed effective orifice area (EOAi) was significantly larger in the SEV group (0.93 ± 0.32 cm²/m² vs. 0.69 ± 0.27 cm²/m²; P=0.002). These findings suggest that the SEV architecture is more effective at maximizing blood flow through the constrained space of a small surgical frame.
Intended Valve Performance
When looking at the composite measure of valve performance, the difference was even more pronounced. Over 82% of patients treated with an SEV achieved the intended valve performance, compared to only 27.6% of those in the BEV group (P<0.001). This massive discrepancy underscores the hemodynamic limitations of intra-annular balloon-expandable valves when placed inside small surgical bioprostheses.
Aortic Regurgitation
Interestingly, despite the SEV’s superior flow dynamics, the rate of moderate aortic regurgitation remained very low in both groups. At 3 years, moderate AR was 0% in the BEV group and 2.9% in the SEV group (P=0.582), indicating that both systems provide excellent sealing, even in the ViV setting.
Clinical Outcomes and Functional Status
While the hemodynamic data strongly favored SEV, the translation of these physiological benefits into clinical outcomes was more nuanced. At the 3-year follow-up, the trial did not find statistically significant differences in hard clinical endpoints.
Composite Clinical Endpoint
The composite of all-cause mortality, stroke, or heart failure-related hospitalization occurred in 25.5% of the SEV group and 32.6% of the BEV group (P=0.489). While there was a numerical trend favoring SEV, the study was not powered to detect a difference in these clinical events. All-cause mortality was 15.7% for SEV versus 23.3% for BEV (P=0.375).
Functional Improvement
Both groups experienced significant and durable improvements in functional status and quality of life. The majority of patients in both cohorts remained in NYHA Functional Class I or II at three years. This suggests that even if a patient has a higher residual gradient (as seen in the BEV group), the relief of the initial bioprosthetic failure still provides substantial symptomatic benefit.
Expert Commentary: Interpreting the Hemodynamic-Clinical Mismatch
The LYTEN trial results highlight a common phenomenon in TAVR research: a significant gap between hemodynamic measurements and short-to-midterm clinical outcomes. The hemodynamic superiority of SEV is largely attributed to its supra-annular design, where the leaflets are positioned above the narrowest part of the surgical frame, allowing for a wider opening and lower gradients.
However, the lack of clinical difference at 3 years raises several questions. It is possible that the sample size of 98 patients is simply too small to reveal differences in mortality or hospitalization. Alternatively, it may be that the clinical impact of residual gradients in ViV-TAVR takes longer than three years to manifest as heart failure or valve degeneration. In the native TAVR space, significant PPM has been linked to long-term mortality, and it is logical to assume a similar relationship exists in ViV-TAVR.
Clinicians must weigh these 3-year findings carefully. For a younger patient with a long life expectancy, the hemodynamic advantage of an SEV may be the deciding factor to ensure valve longevity and prevent late-stage heart failure. For older, more frail patients, the ease of use and precision of a BEV might be prioritized if the expected clinical benefit over their remaining lifespan is similar.
Conclusion: Shaping Clinical Practice
The 3-year results of the LYTEN trial confirm that in the specific context of failed small surgical aortic bioprostheses, self-expanding valves provide a superior hemodynamic profile compared to balloon-expandable valves. The SEV platform significantly reduces mean gradients and increases the effective orifice area, achieving intended performance goals in the vast majority of patients.
While these hemodynamic advantages have not yet translated into a statistically significant reduction in clinical events, the data provide a strong rationale for preferring SEV in patients where maximizing orifice area is a priority. Continued long-term follow-up of the LYTEN cohort and larger registry studies will be essential to determine if these physiological benefits eventually lead to improved survival and reduced morbidity.
Funding and ClinicalTrials.gov
The LYTEN trial was supported by various academic and clinical research grants. ClinicalTrials.gov Identifier: NCT03520101.
References
- Cepas-Guillén P, et al. Balloon- Versus Self-Expanding Transcatheter Valves for Failed Small Surgical Aortic Bioprostheses: 3-Year Results of the LYTEN Trial. Circ Cardiovasc Interv. 2026 Feb 2:e016255.
- Webb JG, et al. Transcatheter Aortic Valve-in-Valve Implantation for Patients With Degenerative Bioprosthetic Heart Valves. JACC. 2012.
- Pibarot P, et al. Patient-Prosthesis Mismatch With Bioprosthetic Valves in the Aortic Position. JACC. 2019.