Early and Long-Term Clinical and Echocardiographic Outcomes of Sutureless vs. Sutured Bioprosthesis for Aortic Valve Replacement

Objective: The goal of this manuscript is to compare clinical and echocardiographic outcomes of patients undergoing aortic valve replacement (AVR) with Perceval sutureless bioprosthesis (SU-AVR) and sutured bioprosthesis (SB). Methods: Following the PRISMA statement, data were extracted from studies published after August 2022 and found in PubMed/MEDLINE, EMBASE, CENTRAL/CCTR, ClinicalTrials.gov, SciELO, LILACS, and Google Scholar. The primary outcome of interest was post-procedural permanent pacemaker implantation, and the secondary outcomes were new left bundle branch block (LBBB), moderate/severe paravalvular leak (PVL), valve dislocation (pop-out), need for a second transcatheter heart valve, 30-day mortality, stroke, and echocardiographic outcomes. Results: Twenty-one studies were included in the analysis. When SU-AVR was compared to other SB, mortality ranged from 0 to 6.4% for Perceval and 0 to 5.9% for SB. Incidence of PVL (Perceval 1–19.4% vs. SB 0–1%), PPI (Perceval 2–10.7% vs. SB 1.8–8.5%), and MI (Perceval 0–7.8% vs. SB 0–4.3%) were comparable. In addition, the stroke rate was lower in the SU-AVR group when compared to SB (Perceval 0–3.7% vs. SB 1.8–7.3%). In patients with a bicuspid aortic valve, the mortality rate was 0–4% and PVL incidence was 0–2.3%. Long-term survival ranged between 96.7 and 98.6%. Valve cost analysis was lower for the Perceval valve and higher for sutured bioprosthesis. Conclusions: Compared to SB valves, Perceval bioprosthesis has proved to be a reliable prosthesis for surgical aortic valve replacement due to its non-inferior hemodynamics, implantation speed, reduced cardiopulmonary bypass time, reduced aortic cross-clamp time, and shorter length of stay.


Introduction
The advent of sutureless valves for aortic valve replacement (SU-AVR) has enabled surgery in patients who would otherwise not be surgical candidates due to frailty or prolonged surgical procedures.
SU-AVR self-expanding Perceval aortic bioprosthesis (LivaNova Group, Milan, Italy) was developed to combine the advantages of transcatheter aortic valve replacement (TAVR) [1] procedure, allowing for fast implantation with no need for suturing, with

Material and Methods
This review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines ( Figure 1) [10]. The following databases were searched for studies meeting our inclusion criteria and published by 28 February 2023: PubMed/MEDLINE, Embase, SciELO, LILACS, CCTR/CENTRAL, Google Scholar, and grey literature. We searched for the following terms: ["Heart Valve Prosthesis Implantation" OR "rapid-deployment aortic valve" OR "sutureless aortic valve" OR "Perceval" NOT "Enable"] AND [''Sutured versus Sutureless" OR ''Bioprosthesis versus Sutureless"]. The following steps were taken for study selection: (1) the identification of titles of records through database search; (2) the removal of duplicates; (3) the screening and selection of abstracts; and (4) the assessment for eligibility through full-text papers. Data are available upon reasonable request.

Inclusion Criteria
Studies were included if any of the following criteria were met: (1) reported outcomes of Perceval compared with other heart valve prostheses or procedures; (2) reported analysis of complications using Perceval valve ( Figure 2); (3) reported off-label experience; and (4) reported learning curve analysis.

Data Collection
Data collection was conducted on 8 March 2023. One author (AD) screened the articles and reviewed them three times. The results were reviewed by another author (SS). Discrepancies were arbitrated by the third author to achieve consensus (MB). The primary reported outcomes of the study included (a) clinical trials outcomes investigating SU-AVR; (b) SU-AVR vs. other stented bioprostheses (c) SU-AVR in bicuspid aortic valves; (d) long-term outcomes of SU-AVR (valve durability); and (e) hospital costs.

Surgical Technique for Perceval Sutureless Valve Implantation
The most performed surgical approach for SU-AVR implantation is full sternotomy. Following heparin administration, standard central aortic and right atrial venous cannulation are initiated. After the institution of cardiopulmonary bypass (CPB), the aorta is cross-clamped and antegrade and/or retrograde cardioplegia is delivered. Aortotomy is performed, and the aortic valve is removed, with care taken for adequate removal of annular calcification and debridement. Therefore, the valve is implanted at the annulus level through three guiding stitches that are later removed, and the valve is ballooned at 4 atmospheres. After correct valve deployment and testing of the valve, the aorta is closed in standard fashion. Surgical centers with advanced expertise in minimally invasive cardiac surgery [8] find SU-AVR to be suitable for minimally invasive aortic valve replacement with either ministernotomy or right minithoracotomy.

Results
After excluding duplicates and non-eligible studies, 21 studies were included in the analyses.

Hospital Costs Outcomes
Three studies were included in the cost analysis. Hospital costs outcomes ranged in US dollars from $12,825 for SU-AVR and $13,543 for SB (Table 6).

Summary of Findings
(1) SU-AVR had a lower incidence of in-hospital complications and overall mortality when compared to SB. (2) SU-AVR had the lowest hospital costs when compared to SB bioprosthesis.

Comments
This manuscript highlighted the most up-to-date outcomes from clinical studies, including the benefits and pitfalls of SU-AVR over SB for aortic valve replacement. In this context, we reported short-and long-term clinical and echocardiographic outcomes. In addition, we also reported the overall hospital costs for each of the valves. Based on the findings from this study, we hypothesize that patients and surgeons can benefit from these outcomes by aiding in the surgical decision process based on the individual patient risk profile.

Outcomes of Sutureless Valves
SU-AVR have made a significant advancement in the last decade and its design has been accepted as the preferred treatment of choice for patients with aortic valve disease who qualify for aortic valve replacement. In addition, TAVR has proven its non-inferiority when compared to other SB [46][47][48]. The strongest points of these valves include (a) the noninferior hemodynamics outcomes; (b) a friendly implant in hostile annulus environments, such as endocarditis and reoperations; and (c) facilitating future valve-in-valve TAVR as sinus struts protect coronary ostia from obstruction and Nitinol cage expandable. In this study, we found and pointed out important clinical and procedural outcomes when SU-AVR is compared to other bioprostheses. We found that outcomes such as stroke, PPI, PVL, and echocardiographic reports are non-inferior to SU-AVR when compared to SB [6][7][8]. However, a future clinical trial comparing SB and SU-AVR will give more insight into the right choice of patient. When compared to other SB, the latest revealed higher CPB and aortic cross-clamp (AXC) time, higher incidence of stroke rate, and bleeding. The increased incidence of PPI in the Perceval group when compared to SB remains a burden and is mainly operator depended [46,[49][50][51][52]. In this context, the learning curve plays a major role and the SB has been used for a longer period: therefore, the operator is more experienced in valve implantation.

Long-Term Clinical Outcomes
Long-term clinical outcomes reported an overall cardiac death incidence of 1.4-3.3%, a valve explant incidence of 0-1.5%, an incidence of paravalvular leak of 0-1% and a stroke incidence of 0-0.8%. In addition, risk predictors for SU-AVR that impact all-cause death included female sex [53]. On the other hand, SB outcomes at 5-year follow-up have shown an overall incidence of cardiac death of 2-2.6%, repeat intervention of 3-3.7%, and structural valve deterioration of 1-1.3% [32]. In addition, risk predictors for all-cause mortality include age, creatinine level, presence of CAD, and NYHA class [54]. This review highlights long-term clinical outcomes, including repeat intervention, cardiac death, incidence of stroke, and major paravalvular leaks.

Long-Term Echocardiographic Outcomes
Long-term echocardiographic outcomes of SU-AVR evidenced a preserved EF of around 60%, a mean transvalvular gradient of 8.8-9.3 mmHg, and an EOA of 1.8. Echocardiographic risk predictors for all-cause death in SU-AVR included left ventricle dysfunction of grade 3 [32]. Other studies using SB have shown an EF of 62% and a mean gradient of 20.6 mmHg [55], while risk predictors for death included the E/e' index. This review is the largest study describing long-term echocardiographic outcomes in medical literature, providing new insights into outcomes, including transvalvular gradients and EOA.

Reported Cost Outcomes
The reported cost outcomes of SU-AVR are lower compared to SB. In this context, patients in developing countries have a higher incidence of rheumatic aortic valve disease, while hospitals have limited budgets. Therefore, SU-AVR satisfies both criteria, including hostile aortic roots after rheumatic disease and lower economic costs compared to other bioprostheses. However, these outcomes are difficult to measure due to different hospital costs among different countries and the annual currency inflation.

Comparison with Other Literature Reviews
When compared to the study by Powell et al. [9], this study review provides new insights into long-term echocardiographic and clinical outcomes. In this context, outcomes from this review provide clear answers to questions, such as what is the reintervention rate in patients undergoing SU-AVR? Can sutureless valves be removed if reintervention is necessary? What is the long-term evolution of transvalvular gradients? How does post-operative paravalvular leak impact long-term prognosis?

Comparison with Our Previous Study
When compared to our previous review, this study provides an update on short-and long-term outcomes after SU-AVR implantation, including an 8-year follow-up clinical study in patients undergoing SU-AVR replacement.
This study provides an update of the literature review on bicuspid valves and on short-and long-term outcomes when compared to our previous publication [2]. Once more, this review confirms the good clinical outcomes of the Perceval valve from the literature. In addition, a meta-analysis done by our group [4] evidenced that sutureless valves when compared to other bioprosthesis have similar 30-day stroke, AKI, major bleeding, PPI, PPM, and post-operative aortic valve area. In the follow-up, we observed a higher risk of mortality (hazard ratio: 1.74; 95% CI: 1.26-2.40; p < 0.001) with other bioprosthesis compared to sutureless valves.
The strong points of this study include an update on current publications for sutureless valves and a 360-degree view of the prosthesis when compared to other bioprostheses.

Future Perspectives
SU-AVR have been proven to be a good alternative for old and frail patients undergoing aortic valve replacement. However, SU-AVR has been proven to be a good ''marriage" in patients undergoing minimally invasive AVR. In this context, this review may contribute to opening a new point of discussion on whether the use of SU-AVR can expand to younger patients, not amenable to aortic valve repair and undergoing minimally invasive SAVR. While patients benefit from minimally invasive cardiac surgery, the procedure itself can be lengthy when compared to traditional AVR. Therefore, the use of a SU-AVR can better suit this patient profile by reducing the duration of the AVR surgical procedure as well as reducing the post-operative complications rate.

Conclusions
The Perceval bioprosthesis has proved to be a reliable prosthesis for conventional SAVR and mini-SAVR due to its implantation speed, reduced CPB time, reduced AXC time, and shorter intensive care unit and hospital length of stay. In addition, its adoption in hostile roots, and its usage in reinterventions coupled with the low profile render it a formidable tool in the surgical armamentarium. Perceval implantation expectation is zero PVL. Anything above that is likely due to a sub-optimal implant and should be revised. Clearly, this is related to adequate annular debridement and familiarity with optimal implant technique.

Learning Objectives
What do we already know about the Perceval sutureless valve? What do we already know about sutureless valves? 1. Sutureless valves have a recognized role in cardiac surgery for aortic valve replacement. 2. Transcatheter aortic valve implantation (TAVR) has emerged as a suitable alternative for aortic valve replacement (AVR).
What does this study add to the literature? 1. SU-AVR surgical indications include (a) patients undergoing cardiac surgery for aortic valve stenosis, (b) mixed valve pathology (stenosis/regurgitation) and (c) reinterventions.
2. SU-AVR have better clinical and echocardiographic outcomes when compared to SB. 3. Instead of adopting the less efficient way of thinking "sutureless better than TAVR or vice versa", cardiologists should consider the initial pre-interventional risk profile and patient life expectancy when referring patients for these treatments.

Conflicts of Interest:
The authors declare no conflict of interest.