Transcatheter aortic valve replacement (TAVR) has become the preferred therapeutic option for symptomatic severe aortic stenosis (AS) over the past decade. Numerous studies affirm the noninferiority or superiority of TAVR compared to surgical aortic valve replacement (SAVR) across various procedural risk scenarios [1, 2, 3, 4, 5, 6, 7]. Improvements in interventional techniques, procedural proficiency, and innovations in transcatheter heart valve (THV) design have significantly contributed to enhanced clinical outcomes.

In China, the reported incidence of valvular heart disease ranges from 2.5 to 3.2 per thousand, though this is likely underestimated. With over 290 million people aged 60 years or older, more than 100 medical centers in China now perform TAVR procedures for severe AS [8, 9, 10]. Comparative analysis of TAVR candidates in China and Western nations reveals several distinctions. Notably, there is a higher prevalence of bicuspid aortic valve (BAV), a greater incidence of type 0 valves, substantial aortic valve calcification, a higher frequency of aortic regurgitation (AR) relative to AS, a significant proportion of cases attributed to rheumatic causes, and narrower femoral artery diameters [11, 12]. BAV patients often exhibit oval valve annuli, trapezoidal valve leaflets, asymmetric valve structure, and pronounced calcification, leading to issues such as valve distortion, displacement, and incomplete attachment. Furthermore, TAVR in patients with irregular and severely calcified BAVs has been associated with an increased risk of short-term aortic root rupture and moderate-to-severe AR [13, 14, 15, 16, 17]. Inadequate THV expansion and sizing also raise concerns about durability and thrombosis [18]. However, it is crucial to note that most landmark randomized clinical trials thus far have excluded BAV patients [19]. Previous registries have shown comparable outcomes of TAVR between BAV and tricuspid aortic valve (TAV) patients [20, 21], but these registries were limited in detailed information regarding various BAV morphologies, which may affect the outcomes after TAVR [13].

With ongoing device innovation and the accumulation of evidence-based medical data, the scope of TAVR application has steadily expanded. In 2015, the The Food and Drug Administration (FDA) approved the SAPIEN 3 transcatheter aortic valve (Edwards Lifesciences, Irvine, CA, USA) for patients experiencing symptomatic severe AS at high risk for SAVR surgery. This device addressed issues such as paravalvular leakage (PVL) and introduced a smaller sheath and improved delivery system. In 2019, the PARTNER 3 trial results were officially published [6], providing an evidence-based foundation for TAVR utilization in low-risk patients. SAPIEN 3 has emerged as the only TAVR technology globally proven to be superior to SAVR in the primary endpoint of randomized controlled clinical trials for low-risk patients [6]. In May 2023, the National Medical Products Administration (NMPA) of China approved SAPIEN 3 for use in patients with severe symptomatic AS who are at high risk for or ineligible for open-heart surgery.

However, it is worth noting that the China TAVR consensus [11] still considers TAVR in BAV patients as a relative indication [22]. Given the current literature’s insufficient evidence, this study aims to address this significant clinical issue by evaluating the safety and efficacy of the transfemoral SAPIEN 3 balloon expandable THVs in TAVR for AS patients, especially those with BAV stenosis, based on real-world clinical data from consecutively enrolled patients in China who underwent implantation of this system.

This study is a pioneering multi-center, real-world investigation aimed at assessing the safety and efficacy of SAPIEN 3 balloon-expandable THVs in TAVR for AS patients in China. Our findings strongly support the safety and feasibility of this prosthesis in challenging BAV anatomies, resulting in excellent valve performance and a notably low incidence of significant PVL. These results challenge existing contraindications and relative indications for TAVR, underscoring the potential of this approach in diverse patient populations as the field of TAVR continues to evolve.

Over the past decade, there has been a remarkable surge in the adoption of TAVR, leading to a paradigm shift in the management of severe AS [27, 28, 29]. In China, where the population is aging, there is a growing burden of degenerative valvular diseases, including AS. Additionally, Chinese patients seeking TAVR often exhibit a higher frequency of bicuspid valve morphology and more severe leaflet calcification [12], presenting unique challenges. Although TAVR was introduced later in China compared to other regions, the procedure has witnessed rapid development in recent years [30, 31]. Being the first and only approved balloon-expandable TAVR valve system in China, the SAPIEN 3 THVs have accumulated substantial clinical data and experience over a 3-year period. Our research findings provide significant insights into the efficacy and safety of SAPIEN 3 balloon-expandable THVs in treating AS across the Chinese population.

BAV anatomy can present unique challenges for TAVR, even with advances in THV design and increased operator experience, especially in Chinese AS patients with a high proportion of bicuspid valves. Historically, BAV has been considered a relative contraindication for TAVR, and these patients were excluded from major randomized trials comparing TAVR with SAVR [14]. In propensity score–matched results from the early Bicuspid AS TAVR multicenter registry, TAVR in patients with BAV stenosis was associated with a higher frequency of adverse procedural events compared to those with TAV stenosis [32, 33]. However, these differences were mainly observed in patients treated with early-generation devices, and no significant differences in procedural complications were noted when using new-generation devices [20]. In a continuous series of multicenter studies, the new-generation Lotus™ Valve System (Boston Scientific, Natick, MA, USA) demonstrated safety and feasibility in treating AS patients with BAV anatomies, resulting in excellent valve performance and a low incidence of significant PVL. However, it is important to note that this conclusion is based on products that have been withdrawn from the market and a relatively small sample size [34]. Notably, balloon-expandable THVs may offer specific advantages by providing a greater opening force to ensure circular expansion and minimize PVL [14].

Our study indicates no significant differences in 30-day mortality, procedural mortality, procedural success, coronary artery occlusion, THV-in-THV deployment, and permanent pacemaker implantation between patients with BAV stenosis and TAV stenosis who underwent TAVR with transfemoral SAPIEN 3 balloon-expandable THVs. Additionally, the incidence of moderate PVL did not significantly differ between BAV and TAV patients. While the Sievers’ classification, which considers the number and location of raphe, is commonly used to characterize various BAV morphologies [35], the successful outcomes of TAVR may be more dependent on factors such as overall calcium burden and the presence of calcified raphe, which can hinder optimal device expansion [13]. In our cohort of BAV stenosis patients, the proportion of patients with (Type 1) or without raphe (Type 0) was similar, and nearly half of the patients (40.4%) exhibited severe calcification of the leaflets.

The higher conversion to open-heart surgery rate observed in BAV stenosis patients in this cohort is consistent with results from the Society of Thoracic Surgeons–American College of Cardiology Transcatheter Valve Therapy Registry (STS/ACC TVT Registry), which confirmed a higher rate (BAV vs. TAV: 0.90% vs. 0.40%, p = 0.03) [36]. BAV anatomy often involves larger dimensions of all components of the aortic valve complex, a nontubular (flared or tapered) shape, more extensive calcification, the presence of a calcified raphe, heterogeneous calcium distribution, and asymmetrical morphology of the aortic valve complex and coronary anomalies, which can be procedural challenges for TAVR [14]. The newest generation of THVs could help to further improve short-term outcomes in patients with BAV stenosis to more closely match those of TAV [14].

This study has several important inherent limitations that merit acknowledgment. Given its retrospective nature, the analysis is susceptible to potential unmeasured confounders. Furthermore, it exclusively focuses on patients who underwent the TAVR procedure, which may introduce selection bias, necessitating caution when interpreting the results. Additionally, BAV anatomy is highly heterogeneous, with patients exhibiting variable degrees of valve calcification, including raphe calcification when present. Consequently, the findings of this study should not be extrapolated to the entire BAV population [37]. The anatomical risk of TAVR in BAV AS should be carefully evaluated [13]. Moreover, the relatively short follow-up duration may not adequately capture long-term outcomes, particularly concerning durability and thrombosis. Finally, many baseline characteristics, such as cardiovascular risk factors, detailed CT measurements, and comorbidities like peripheral artery disease (PAD) and chronic kidney disease (CKD), were not assessed. To gain more comprehensive insights into the safety and efficacy of TAVR in BAV patients, future research should consider larger prospective studies with extended follow-up periods.

In conclusion, our study contributes to the growing body of evidence surrounding TAVR, within the Chinese population. It addresses crucial clinical questions and provides valuable insights into the safety and efficacy of the transfemoral SAPIEN 3 balloon-expandable THVs, particularly in the context of BAV stenosis, offering reference for clinicians and researchers in this rapidly evolving field. Further research and ongoing evaluation of TAVR technologies and techniques are essential to refine patient selection, optimize procedural outcomes, and enhance the management of AS in diverse patient populations.

The original data provided by Edward Lifescience. The code used for data analysis can be obtained by contacting authors.

JD, SZW, and XBP designed the research study and revised it critically for important intellectual content. JD and ZPL searched and organized the literature, were the main drafters of the manuscript, and critically revised the important content. PJW and YMY participated in data collection and screening. GZZ and WBOY helped analyzing data. SGL, YQX, JYW, and DHX participated in the data interpretation. FWZ and GJZ assisted in literature retrieval and participated in revising important content of the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This trial adhered to the principles of the Declaration of Helsinki. The Institutional Review Board of the Chinese Academy of Medical Sciences, Fuwai Hospital, granted approval for this study (ethical approval number: 2022-1829), and all participants received a waiver of informed consent.

This evaluation study is supported by the following aspects: CAMS Innovation Fund for Medical Sciences (2021-I2M-1-065); National Key R&D Program of China (2022YFC2503400); National High Level Hospital Clinical Research Funding (2022-GSP-GG-18; 2023-GSP-RC-04; 2023-GSP-RC-17; 2023-GSP-QN-28); National Key R&D Program of China (2023YFC2412705); Development Project of National Major Scientific Research Instrument (82327801); Sanming Project of Medicine in Shenzhen (SZSM202011013).

The authors declare no conflict of interest.

We have not utilized any form of AI or AI-assisted technologies in the process of writing this scientific paper.