Patients with bicuspid aortic valves (BAV) are predisposed to the development of aortic stenosis. We performed a pairwise meta-analysis, comparing the efficacy of transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) in patients with BAV.
Medical databases were queried to pool comparative studies of interest. Single-arm studies, conference presentations, animal studies, and studies that involved patients with tricuspid aortic morphology were excluded. Outcomes were pooled as risk ratios (RRs) with their 95% confidence intervals (CI) using the random effects model in R.
There were 60,858 patients with BAV (7,565 TAVR, 53,293 SAVR) included. Compared with SAVR, TAVR was associated with a significantly lower risk of 30-day major bleeding (RR 0.29, 95%CI 0.13 to 0.63, p=0.01) but a higher risk of new permanent pacemaker placement (RR 2.17, 95%CI 1.03 to 4.58, p=0.04). No significant differences were seen with other explored outcomes, including 30-day/mid-term mortality, stroke, acute kidney injury, major vascular complications, paravalvular leak, and conduction abnormalities.
In conclusion, in patients with BAV, TAVR is associated with a lower risk of 30-day major bleeding but has an increased risk for permanent pacemaker implantation when compared with SAVR. Future large-scale randomised trials comparing both the short- and long-term outcomes of SAVR and TAVR in patients with BAV are needed to assess the efficacy of each modality in a controlled population across long follow-up durations.
Introduction
Individuals with bicuspid aortic valves (BAV) are at an elevated risk for developing aortic stenosis.1 Currently, transcatheter aortic valve replacement (TAVR) has emerged as a less invasive alternative to surgical aortic valve replacement (SAVR), demonstrating non-inferior to superior outcomes across patients of various risk levels.2 Less clear, however, are the outcomes of these modalities in BAV patients, as this population has been relatively underrepresented in many large studies. Due to the growing use of TAVR, we performed an updated pairwise meta-analysis on TAVR in comparison to SAVR in patients with BAV.
Method
This study did not require institutional review board approval or informed patient consent as only published-study level data, not individual patient data, were utilised. An extensive search was conducted in the PubMed, Embase, Scopus, and Cochrane Library databases, without restriction, to identify studies comparing the safety and efficacy of TAVR and SAVR in patients with BAV. Specifically, comparative studies comparing SAVR and TAVR in patients with BAV were searched for. Single-arm studies, conference presentations, animal studies, and studies that involved patients with tricuspid aortic morphology were excluded. Outcomes were pooled as risk ratios (RRs) with their 95% confidence intervals (CIs) using the random effects model in R.
Results
We pooled 60,858 patients (7,565 TAVR, 53,293 SAVR) from seven observational cohort studies (table 1). Compared with SAVR, TAVR was associated with a significantly lower risk of 30-day major bleeding (RR 0.29, 95%CI 0.13 to 0.63, p=0.01) but a higher risk of new permanent pacemaker placement (RR 2.17, 95%CI 1.03 to 4.58, p=0.04). There were no significant differences between the two modalities with regards to 30-day mortality (RR 1.07, 95%CI 0.48 to 2.39, p=0.85), stroke (RR 1.02, 95%CI 0.77 to 1.34, p=0.88), acute kidney injury (RR 0.88, 95%CI 0.40 to 1.92, p=0.69), major vascular complications (RR 1.03, 95%CI 0.07 to 15.43, p=0.97), paravalvular leak (RR 2.33, 95%CI 0.13 to 41.70, p=0.34), conduction abnormalities (RR 2.76, 95%CI 0.37 to 20.50, p=0.16), or mid-term mortality (RR 1.18, 95%CI 0.30 to 4.60, p=0.36).
Table 1. Summary of included studies and pooled pairwise meta-analysis
| First author/year | Study period | Country | Type of study | TAVR patients | SAVR patients |
|---|---|---|---|---|---|
| Elbadawi/2019 | 2012–2016 | USA | Retrospective, PSM | 975 | 975 |
| Husso/2021 | 2008–2017 | Finland | Retrospective, PSM | 75 | 75 |
| Majmundar/2022 | 2016–2018 | USA | Retrospective, PSM | 1,393 | 1,393 |
| Mentias/2020 | 2015–2017 | USA | Prospective, PSM | 699 | 699 |
| Sanaiha/2022 | 2012–2019 | USA | Retrospective | 3,855 | 52,476 |
| Soud/2020 | 2011–2014 | USA | Retrospective, PSM | 68 | 68 |
| Tsai/2020 | 2013–2018 | Taiwan | Retrospective, PSM | 48 | 82 |
| Pooled pairwise meta-analysis | |||||
| Primary outcome | RR, 95%CI | p value | I2 | ||
| 30-day mortality | 1.07, 0.48 to 2.39 | 0.85 | 77.6 | ||
| 30-day stroke | 1.02, 0.77 to 1.34 | 0.88 | 0.0 | ||
| 30-day acute kidney injury | 0.88, 0.40 to 1.92 | 0.69 | 94.6 | ||
| 30-day major bleeding | 0.29, 0.13 to 0.63 | 0.01* | 96.9 | ||
| 30-day major vascular complications | 1.03, 0.07 to 15.43 | 0.97 | 54.3 | ||
| 30-day paravalvular leak | 2.33, 0.13 to 41.70 | 0.34 | 37.3 | ||
| 30-day conduction abnormalities | 2.76, 0.37 to 20.50 | 0.16 | 96.2 | ||
| New permanent pacemaker | 2.17, 1.03 to 4.58 | 0.04* | 73.3 | ||
| Mid-term mortality | 1.18, 0.30 to 4.60 | 0.36 | 0.0 | ||
| *Significant, p<0.05 Key: CI = confidence interval; PSM = propensity-score matched; RR = risk ratio; SAVR = surgical aortic valve replacement; TAVR = transcatheter aortic valve replacement |
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Discussion
We present an updated meta-analysis of 60,858 patients with BAV undergoing TAVR and SAVR. Our results showed TAVR to be associated with a lower risk of 30-day major bleeding but posed a higher risk of new permanent pacemaker implantation. Of note, there was no significant difference with regards to mortality or stroke between the two groups.
The lower risk of 30-day major bleeding in TAVR can be explained due to it being a minimally invasive procedure when compared with SAVR.3 SAVR requires the use of cardiopulmonary bypass and has a large incision that increases risk of haemorrhagic complications. Conversely, TAVR does not need cardiopulmonary bypass and has a small incision performed in the groin or chest that is associated with a lower risk of blood loss. Another reason for a lower risk of major bleeding is that the native valve and tissue can be preserved to a greater extent in TAVR, while more tissue may need to be removed in SAVR.4 The greater need for new permanent pacemakers in TAVR patients is likely associated with a new valve being inserted into the old valve, which can disrupt the cardiac conduction system, along with catheter use that can contribute to heart block.5
The lack of significant differences in certain outcomes between TAVR and SAVR may be attributed to a variety of factors. One key consideration is the small sample size and the limited number of studies, which could have reduced the statistical power to detect differences in these outcomes between the two groups. Consequently, larger studies or a greater number of smaller studies may be required to reveal potential differences in these outcomes. Due to the lack of individual patient data, we are unable to assess differences in operative technique/TAVR access route, patient baseline comorbidities, and adherence to post-operative medical regimen/follow-up, which may have influenced clinical outcomes. Future studies should seek to ascertain the risks and benefits of these procedures in a randomised cohort with standardised follow-up protocols.
There are limitations in this study that must be considered. First, there is a lack of randomised trials on this topic, pointing to a large gap in contemporary literature. Consequently, all the studies pooled in this meta-analysis were prospective and retrospective cohort studies, in which operators predetermined patient intervention without randomisation. This poses an elevated risk of confounding and treatment-allocation bias. We attempted to control for confounding variables by prioritising propensity-matched cohorts, when provided by the original studies, and predetermining the use of random-effects statistics, which more conservatively estimates effect sizes. Furthermore, there were no available data on long-term outcomes up to 10 years or more. This made it difficult to understand the long-term effects of TAVR compared with SAVR and long-term durability for each modality. Finally, the studies included in this paper span across three different counties, and may introduce confounding bias due to vastly different health systems in terms of accessibility, technology, resources, and expertise.
To conclude, in patients with BAV, TAVR is associated with a lower risk of 30-day major bleeding but increased risk for permanent pacemaker implantation when compared with SAVR. Future, large-scale randomised trials comparing both the short- and long-term outcomes of SAVR and TAVR in patients with BAV are needed to assess the efficacy of each modality in a controlled population across long follow-up durations.
Key messages
- In patients with bicuspid aortic valves, transcatheter aortic valve replacement (TAVR) is associated with a lower risk of 30-day major bleeding, but has an increased risk for permanent pacemaker implantation, when compared with surgical aortic valve replacement (SAVR)
- No difference is observed for mortality/stroke
- Future large-scale randomised trials comparing both the short- and long-term outcomes of SAVR and TAVR in patients with BAV are needed to assess the efficacy of each modality in a controlled population across long follow-up durations
Conflicts of interest
None declared.
Funding
None.
Study approval
No institutional review board approval was necessary for this project as no individual patient data were used.
References
1. Pujari SH, Agasthi P. Aortic stenosis. In: StatPearls. Treasure Island, FL: StatPearls Publishing, 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557628/
2. Prendergast B, Redwood S, Patterson T et al. TAVR versus SAVR in aortic stenosis. J Am Coll Cardiol 2021;77:1162–4. https://doi.org/10.1016/j.jacc.2021.01.012
3. Zhang D, Mao X, Liu D, Zhang J, Luo G, Luo L. Transcatheter vs surgical aortic valve replacement in low to intermediate surgical risk aortic stenosis patients: a systematic review and meta-analysis of randomized controlled trials. Clin Cardiol 2020;43:1414–22. https://doi.org/10.1002/clc.23454
4. Grigorios T, Stefanos D, Athanasios M et al. Transcatheter versus surgical aortic valve replacement in severe, symptomatic aortic stenosis. J Geriatr Cardiol 2018;15:76–85. https://doi.org/10.11909/j.issn.1671-5411.2018.01.002
5. Bob-Manuel T, Nanda A, Latham S, Pour-Ghaz I, Skelton WP 4th, Khouzam RN. Permanent pacemaker insertion in patients with conduction abnormalities post transcatheter aortic valve replacement: a review and proposed guidelines. Ann Transl Med 2018;6:11. https://doi.org/10.21037/atm.2017.10.21
