Rapid deployment technology versus conventional sutured bioprostheses in aortic valve replacement

Abstract Objectives Despite the benefits of rapid deployment aortic valve prostheses (RDAVR), conventional sutured valves (cAVR) are more commonly used in the treatment for aortic stenosis. Given the paucity of randomized studies, this study aimed to synthesize available data to compare both treatment options. Methods A systematic search of Pubmed, OVID, and MEDLINE was conducted to retrieve comparative studies for RDAVR versus cAVR in the treatment of aortic stenosis. Out of 1773 returned titles, 35 papers were used in the final analysis, including 1 randomized study, 1 registry study, 6 propensity‐matched studies, and 28 observational studies, incorporating a total of 10,381 participants (RDAVR n = 3686; cAVR n = 6310). Results Random‐effects meta‐analysis found no difference between the two treatment groups in terms of operative mortality, stroke, or bleeding (p > .05). The RDAVR group had reduced cardiopulmonary bypass (standardized mean difference [SMD]: −1.28, 95% confidence interval [CI]: [−1.35, −1.20], p < .001) and cross‐clamp times (SMD: −1.05, 95% CI: [−1.12, −0.98], p < .001). Length of stay in the intensive care unit was also shorter in the RDAVR group (SMD: −0.385, 95% CI: [−0.679, −0.092], p = .010). The risk of pacemaker insertion was higher for RDAVR (odds ratio [OR]: 2.41, 95% CI: [1.92, 3.01], p < .001) as was the risk of paravalvular leak (PVL) at midterm follow‐up (OR: 2.52, 95% CI: [1.32, 4.79], p = .005). Effective orifice area and transvalvular gradient were more favorable in RDAVR patients (p > .05). Conclusions Despite the benefits of RDAVR in terms of reduced operative time and enhanced recovery, the risk of pacemaker insertion and midterm PVL remains a significant cause for concern.


| INTRODUCTION
Surgical aortic valve replacement (AVR) remains the established treatment modality for severe aortic valve stenosis. The introduction of rapid deployment AVR prostheses (RDAVR), particularly sutureless valves, in the last two decades has offered an alternative technique implantation during surgical AVR. A panel of international experts on sutureless, rapid deployment and stented bioprostheses recommended its use for isolated AVR in elderly patients with severe comorbidities and aortic wall conditions such as calcified root and porcelain aorta. 1 Other benefits of RDAVR in comparison to conventional sutured AVR (cAVR) include reduced operation time with reduced cross-clamp and cardiopulmonary bypass times, as well as favorable effective orifice area (EOA) and hemodynamic outcomes. 2,3 Current guidelines do not make specific recommendations for the use of RDAVR. 4 cAVR). Operative times were reported to be significantly lower in the RDAVR groups in both studies. Only the study by Borger and colleagues reported on paravalvular leak (PVL) and found there to be no significant difference between the two groups. 8 In the current era of evidence-based medicine, pairwise metaanalyses are increasingly used to synthesize the results of different trials evaluating the same intervention(s) to obtain an overall estimate of the treatment effect of one intervention relative to the control. 9 Given the paucity of comparative data between the two bioprosthetic classes for the surgical management of aortic stenosis, data synthesis of available evidence will help provide a more robust analysis. This systematic review and meta-analysis aims to comprehensively compare postoperative outcomes in patients undergoing cAVR and RDAVR.

| METHODS
This study was conducted in accordance with the Prescribed Reported Items for Systematic Reviews and Meta-analysis (PRISMA) 10 and Assessing the methodological quality of systematic reviews (AMSTAR) Guidelines. Ethical approval was not required to conduct this study, neither was informed consent.

| Search strategy
The EMBASE AND MEDLINE databases were searched for relevant articles published after January 1, 2000 were, thus taking into account the implementation of RDAVR prostheses. Search terms incorporated "aortic valve replacement" or derivatives of its terms (e.g., prosthesis, surgery, and AVR). "Rapid-deployment" or "sutureless" were terms added to the search, as well as specifically named prostheses (Perceval, Intuity, 3F Enable). The full search strategy can be found in the Appendix A (I).

| Screening
Selected articles were screened for title and abstract by two reviewers (S. R. and I. H.), and conflicts were resolved through discussion. Selected studies were checked by a third reviewer (M. Y. S.). Studies were included from the full-text screening if there was a full-text article comparing cAVR and sAVR at least for the intraoperative parameters (e.g., cardio-pulmonary bypass time, cross-clamp time, etc.), and patient demographics for each group. Both retrospective and prospective studies were considered. Case reports were excluded.

| Inclusion
Only studies in the English language were considered, and studies on patients above 18 years of age at the time of the operation. Studies incorporating two comparable treatment groups, receiving RDAVR in one study arm and cAVR in the other, were considered. Conventional AVR protheses were selected based upon the mention of any of the leading market prostheses (e.g. perimount, Trifecta, etc). For RDAVR, studies incorporating either (or a combination) of the known prostheses by name (perceval, intuity, 3F-enable) were included. Studies reporting measurable short and/or long-term outcome data were considered.

| Exclusion
Case reports were excluded. Studies that lacked clarity in design or where separation between covariates/outcomes of the RDAVR and cAVR groups were not considered. Papers displaying an element of bias thus favoring one group over the other were excluded. Study cohorts that consisted of any non-AVR patients were not strictly excluded, unless non-AVR patients were included along with AVR patients and were not analyzed as separate groups.

| Outcome measures
These were divided into three categories: Operative measures: cardiopulmonary bypass time, aortic crossclamp time.

| Data extraction
Data from selected studies following full-text screening were extracted according to a structured protocol into predefined a summary

| Statistical analysis
The Newcastle-Ottawa Scale was used to assess the quality of nonrandomized studies, with particular focus on comparability of patient groups and patient selection bias. It is a well-validated and standardized screening tool for the risk of bias.
The odds ratio (OR) was used as the summary statistic for binary outcomes (e.g., mortality, stroke, and pacemaker insertion) whereas continuous outcomes (e.g., hospital stay and transvalvular gradient) were analyzed using reported means and standard deviations (SD) thus yielding a standardized mean difference (SMD). A randomeffects model was chosen over a fixed-effects model due to the expected heterogeneity between the studies. Heterogeneity was investigated using Cochrane's test and the I 2 statistic. Funnel plots were generated to assess for publication bias. Peter's test for small studies was conducted to rule out large effects from potentially nonsignificant studies. Meta-regression analysis was used to investigate the effects of covariates, including patient and operative characteristics. Statistical analyses were conducted using the Stata 13.0 software (Stata Corp.).

| RESULTS
From our search, we identified 1608 articles, of which 1513 were excluded based on title and abstract screening, as shown in Figure 1A. Full texts were obtained for the remaining 95 articles, and 35 were included in our final analysis, satisfying the inclusion/exclusion criteria. Study characteristics of the included papers are shown in Table 1.

| Publication bias
Publication bias was assessed using the Peter's test. The results of the analysis are shown in the funnel plot in Figure 1B

| Pacemaker implantation
There was a statistically significant difference in pacemaker implantation between the two arms which favored cAVR when con- There was a significant amount of heterogeneity within subgroups and overall (I 2 = 90%) ( Figure 5C).

| Peak gradient across valve
Similarly, peak gradient across the valve favored RDAVR over cAVR Indeed, reduced ITU stay was a significant finding in this study. Although further ITU-specific data were not available for meta-analysis, such as ventilator time and the incidence of complications (e.g., pneumonia and renal failure), the significantly reduced time in ITU acts as a surrogate for reduced complications in the RDAVR group.
As well as patient benefits, reduced hospital stay in the context of AVR can contribute to recognizable cost-benefits. 50

| Pacemaker incidence
In many studies (including those in this analysis), permanent pacemaker (PPM) implantation is used as a surrogate for the incidence of grade III atrioventricular block. Although it serves as a reliable and measurable outcome, it should be noted that institutions vary on the guidance for PPM insertion and their use can also be warranted for other cardiac disrhythmias, thus creating a potential source of heterogeneity.
Despite this, meta-analysis of PPM implantation revealed no evidence of heterogeneity (I 2 = 0%, p = .662), thus suggesting, statistically, potentially consistent PPM protocols across the studies.
From our findings, RDAVR unfortunately performs worse with regards the rate of PPM insertion in the early postoperative phase, reflecting compression of calcium against the bundle branch located at the base of the interleaflet triangle between the right and noncoronary cusps and the right fibrous trigone-leading to heart block. As RDAVR prostheses are designed to sit below the level of the aortic annulus, similar to the design of TAVI prostheses, 51 this complication is more likely, 52,53 in contrast with conventional valves which are implanted in the supra-or intra-annular position. The incidence is increased in the event of valve oversizing, which is often performed to offset the risk of para-valvular leakage, 54 especially in the hands of surgeons who in the early phases of RDAVR implementation at their respective units. 55

| Echocardiographic outcomes
PVL has a recognized incidence following RDAVR, also confirmed in this study-more than the risk post-cAVR. Although data on patient functional status were not available for meta-analysis, untreated severe PVL has been shown in some cases to result in left ventricle pressure and volume overload with leading to symptoms of heart failure, especially if the receiving chamber is noncompliant. 56 In spite of this, the hemodynamic benefits of RDAVR have also been confirmed, namely in the form of better iEOA and transvalvular gradient compared with cAVR. This has particular benefit in patients at risk of patient-prosthesis mismatch, especially in the context of small aortic roots. 12 These findings emphasize the need for accurate patient selection in the context of AVR prosthesis choice, tailored toward annular profile, patient habitus, and functional status.

| RDAVR compared with TAVI
According to National Audit Data, the number of surgical AVR has been increasing in steadily over the last decade. This is despite the recent expansion of risk-categories encompassed by TAVI treatment, which continues to provide a significant alternative to all forms of surgical AVR, by avoiding sternal trauma altogether.
RDAVR has the potential to facilitate minimally invasive AVR through the ease of implantation and avoidance of annular stitching.
When compared with TAVI, a previously reported propensitymatched analysis (n = TAVI 538 vs. sutureless 385) demonstrated improved long-term outcomes in RDAVR compared with TAVI, despite the increased need for blood transfusions in the short term. 57 Furthermore, one randomized trial of TAVI with an early-generation valve in 280 patients demonstrated that TAVI was not inferior to surgery with more than 5 years of follow-up. 58 Meta-analysis found that sutureless valves result in improved perioperative survival compared with TAVI, albeit with only six studies analyzed, adding further weight to using sutureless valves as a viable option, especially for minimally invasive approaches. 59

| Strengths and limitations
This study benefits from strict inclusion criteria, a large pooled analysis and subgrouping according to clinically relevant variables. However, the findings should be taken with some caution. The statistical heterogeneity may reflect the differing pathologies between patient groups, including the size of aortic roots. Despite the increased risk of midterm PVL detected echocardiographically, studies lacked data on functional outcome in these patients. Finally, all included studies were comparative, however the main limitation in the present work is the lack of randomized studies (only one valid RCT was incorporated).

| Conclusion
Despite the benefits of RDAVR in terms of reduced operative time and enhanced recovery, the risk of pacemaker insertion in the short-term, and PVL in the long-term, remains a significant cause for concern. There is a strong need for larger multicentre RCTs with long-term follow-up to provide conclusive evidence about the safety and efficacy of RDAVR. Inclusion criteria:

MEDLINE
• Written in English. This can include studies where the initial data collection was run in a different language but the data extraction and analysis were written in English.
• Published in a peer-reviewed journal.
• The study cohort consisted of patients 18 years of age or older at the time of the operation.
• The study cohort consisted of patients who have aortic stenosis or other aortic valve disease which requires replacement using either sutureless technique or conventional aortic valve replacement.
• Outcome measures of complications, mortality or morbidity were a primary aim.
• At least 10 patients in the study cohort were undergoing AV replacement using sutureless technique or conventional valve replacement.
• The study included two treatment arms, sutureless aortic valve replacement and conventional sutured aortic valve replacement, which were being compared.
Exclusion criteria: • Not written in English.
• Not published in a peer-reviewed journal, as well as abstracts without full articles, editorials, case reports, case series and conference proceedings.
• The study cohort consisted of patients younger than 18 years of age at the time of operation.
• The study cohort consisted of any non-aortic valve replacement patients, or if non-AVR patients were included along with AVR patients and were not analyzed as a separate group.
• Study cohorts also included patients undergoing transcatheter or transapical surgeries without separate analysis for the sutureless or conventional aortic valve replacement procedures. SALMASI ET AL.