Early results of the Sorin^® Perceval S sutureless valve: systematic review and meta-analysis

Introduction

Aortic stenosis (AS) is the most common valvular disorder, resulting in decreased life expectancy in symptomatic individuals (1,2).

Surgical aortic valve replacement (AVR) has long been the definitive therapy in treating symptomatic AS. Transcatheter aortic valve implantation (TAVI) has become an accepted alternative to surgery in treating high-risk or non-operative individuals with severe AS (3). The emergence of TAVI has led to renewed interest in developing artificial valves not requiring sutures to secure the valve in position. Rapid deployment employing a radial force to secure the valve within the annulus has significantly reduced implantation time.

In the 1960s, Magovern pioneered a sutureless heart valve made from titanium using a ball-in-cage design; and achieved a reduction in cardiopulmonary bypass time (CPB) (4). Implantation of this novel valve continued into the 1980s. However, the potential for paravalvular leak and embolisation limited it’s further development (4,5). The TAVI technology has been adopted in sutureless valves, which can be deployed under direct vision via conventional or minimally invasive approaches without the need of a catheter. Minimally invasive AVR (MAVR) has demonstrated similar results to conventional AVR in regards to clinical outcomes, with the added benefit of improved patient satisfaction (6).

Currently, MAVR is limited to select cardiac centers. They can require specialised equipment and surgeons may experience a steep learning curve (7). MAVR is attributed to longer aortic cross-clamp (ACC) and CPB time, which inherently links to a higher risk of adverse events, especially amongst a high-risk surgical group (8). Therefore, the use of sutureless valves may be advantageous in the setting of MAVR by potentially reducing the operating time.

At present the Perceval (Sorin, Saluggia, Italy, CE approved 2011, FDA approved 2016) is the only true sutureless valve available for the implantation. It’s direct competitor, the Intuity Elite (Edwards Lifesciences, Irvine, US, CE approved 2014, FDA approved 2016) is a rapid deployment aortic valve prosthesis requires 3 sutures to secure the valve to the annulus. Both valves are bioprosthetic and are anchored to the aortic annulus with an expandable metal stent frame.

The Perceval features an inflow ring designed to sit at the level of the annulus and an outflow ring, which sits at the level of the sinotubular junction. The outward flexion of the winged struts, connects the two rings and occupies the sinuses of Valsalva (Figure 1). Perceval aortic valve prosthesis is currently available in four sizes: S (19–21 mm), M (22–23 mm), L (24–25 mm), and XL (27 mm).

Figure 1 Sorin Perceval S sutureless valve (Sorin, Saluggia, Italy).

As the worldwide use of the Perceval valve continues to rise, there are no comprehensive reviews, assessing the efficacy and safety of the Perceval valve. Therefore we have performed this meta-analysis to assess the safety, clinical, and survival benefits of Perceval valve.

Methods

Search strategy

An electronic database search of four databases (MEDLINE, EMBASE, PubMed, Cochrane) was performed starting from January 2000 to December 2016. To attain the maximal search yield, we used the following free text “Perceval” or “sutureless” and “aortic valve replacement”. We identified further relevant studies after reviewing the reference lists of all retrieved articles and the Sorin Perceval website (http://www.livanova.sorin.com/products/cardiac-surgery/aortic/perceval).

Outcomes

The primary end points included procedural success rate, 30-day mortality, cerebrovascular accident, permanent pacemaker insertion, paravalvular leak (mild, moderate and severe), re-operation, and the length of hospital and intensive care stay. The secondary end points included echocardiographic findings including mean post-operative gradients (mmHg), mean long-term gradients, effective orifice area (EOA), New York Heart Association (NYHA) functional class improvement from baseline, and survival at 1-, 2-year, and longer. Additional outcomes included the procedural approach (minimally invasive vs. conventional sternotomy), valve sizes used, and ACC and CPB times.

Selection criteria

All patients undergoing implantation of the Perceval valve were eligible for this meta-analysis. The patient selection criteria for Perceval valve implantation varied with each institution. Only observational studies were included in this review. Case reports, case series with less than thirty patients, recent abstracts, expert opinions and editorial reports were excluded.

Data analysis and critical appraisal

Two reviewers (KS, SL) separately appraised the selected studies using a standardised data table. The relevant data extracted from the articles’ text, tables, and figures was tabulated. Any discrepancies were resolved by discussion. The quality of scoring of observational studies used in meta-analyses can be controversial; therefore each article was analysed in accordance with the critical review checklist from the Dutch Cochrane Centre, as suggested by the MOOSE group (9).

Quality appraisal included: (I) a clear definition of study population; (II) a clear definition of outcomes and outcome assessment; (III) independent assessment of outcome parameters; (IV) sufficient duration period for follow-up; (V) no selective loss during follow-up; and (VI) identification of important confounders and prognostic factors.

Intervention

Despite some variation, similar steps were performed at different centers. The surgical approach was via a right anterior thoracotomy, mini-sternotomy or full sternotomy. In general, a transverse aortotomy was made 1.5 to 2 cm above the sinotubular junction. The aortic valve leaflets were excised and the annulus was either semi-debrided or fully debrided. Three guiding sutures, commonly 4-0 monofilament, were passed at the nadir of the aortic annulus. An appropriately sized prosthesis was collapsed onto the dual holder. Each guiding thread is passed through eyelets on the prosthesis inflow ring, to allow for accurate seating of the prosthetic valve onto the debrided annulus. A deflated post-dilation catheter was placed across the prosthesis and the balloon was inflated at 4 atmospheres for 30 s, as per the manufacturer’s recommendations. Warm sterile saline at 37 degree Celsius was poured within the aortic root to allow for fixing of the nitinol stent and ensure optimal valve sealing. Following closure of the aortotomy, a transesophageal echocardiography was performed to assess the correct implantation of the prosthesis and exclude the presence of a paravalvular leak.

Results

Quality of the studies

After removal of duplicated studies, the titles and abstracts of 66 publications were identified as described in the search strategy. An initial review of these abstracts identified 24 potentially relevant articles. After applying the inclusion and exclusion criteria, 14 articles were reviewed (10-23) (See Figure 2 PRISMA diagram). A total of 2,505 patients were represented in this study, of which 2,205 patients had undergone AVR using the Perceval valve. Quality assessment using the MOOSE criteria (9) checklist is summarised in Table S1.

Figure 2 PRISMA diagram.

Table S1 Quality assessment of included studies
Full table

Quality of evidence

All 14 studies were observational, which included 7 prospective (11,14,16,19-22) and 7 retrospective studies (10,12,13,15,17,18,23). There were no randomized controlled trials. The mean follow-up time was 6 to 8 months for 3 studies (15,18,19), 10 to 16 months for 5 studies (10,11,13,21,22), and 18 to 24 months for 3 studies (12,20,23), as seen in Table 1.

Table 1 Study characteristics
Full table

One study compared conventional AVR, sutureless valve implantation and TAVI (14). Shrestha et al. (22) compared patients receiving conventional aortic valves to patients receiving the Perceval valve. The study by Villa (12) chose to stratify patient groups to the size of the valve implanted. Patients with a “S” size valve were compared to patients implanted with a “L” sized valve. Three studies (13,15,19) compared the minimally invasive to full sternotomy surgical approach. All studies originated from specialised tertiary referral centers. Eleven centers reported results in greater than 100 patients (range, 120–314) (11-23). Seven studies presented multi-center data (12,13,15-17,19,23).

Seven studies published explicit inclusion criteria (13,15,16,18,19,21,22). The definition of patients not suitable for the Perceval valve varied between institutions. For example, Flameng et al. (21) chose to include only those patients with an aortic annulus between 19 to 23 mm; whereas Meuris et al. (16) excluded patients with intraoperative annulus diameters greater than 23 mm. The operative technique was defined in ten studies (10,12-16,18).

Overall, 61.5% of patients were female. The mean age was 78.7 years old (range, 76.6–80.4 years old). The mean body surface area was 1.78 m² (range, 1.6–1.85 m²). The mean of patients with AS was 57.9% (range, 56.1–76.7%). The reported mean left ventricular ejection fraction was 56.9%. Hypertension and hyperlipidemia were reported in the majority of patients, 77.6 and 63.4% respectively. Additional comorbidities included chronic lung disease (18.7%), diabetes (28.1%), coronary artery disease (22.6%), peripheral vascular disease (18.7%), atrial fibrillation (15.9%) and chronic renal impairment (12.8%). The mean NYHA Class III or IV reported was 70.9% (range, 47.7–100%). European System for Cardiac Operative Risk Evaluation (EuroSCORE) was inconsistently reported; logistic versus additive, hence a mean could not be calculated (see Table S2).

Table S2 Baseline characteristics
Full table

Median sternotomy approach was used most frequently for valve implantation (weighted mean 75.2%; range, 15.3–100%). The Perceval valve size “M” was used in 46.4% of patients (range, 32–78.1%). The weighted mean ACC and CPB times for an isolated AVR were 39.7 minutes (range, 17–59.3 minutes) and 64.2 minutes (range, 35–92.3 minutes) respectively. Additional cardiac procedures were performed in 42.6% of patients (range, 9.7–100%) (see Table 2).

Table 2 Operative characteristics
Full table

Assessment of safety

The 30-day mortality rate was 2.3% (pooled weighted mean, 95% CI, 1.44–3.25%) (Figure 3A). The pooled rate of pacemaker implantation 6.76% (95% CI, 4.68–8.86%) (Figure 3B) and the pooled rate of cerebrovascular accidents was 1.73% (95% CI, 1.23–2.22%) (Figure 3C). Table 3 provides a summary of additional perioperative outcomes including atrial fibrillation, pericardial tamponade, myocardial infarction, reoperation, explantation of the sutureless valve, exploration for bleeding, infection, length of intensive care unit stay and hospital stay.

Figure 3 Patients undergoing perceval sutureless valve insertion, forest plots indicate: (A) 30-day mortality; (B) pacemaker insertion; (C) cerebrovascular accidents. Out, outcomes; Treat; treatment.

Table 3 Procedural outcomes
Full table

Haemodynamic outcomes

Prior to MAVR, the pooled baseline mean gradient was 32.9 mmHg (95% CI, 24.4–41.5 mmHg) and the post-operative pooled mean gradient improved to 8.02 mmHg (95% CI, 5.12–8.00 mmHg). The weight mean pre-operative EOA was 0.75 cm² (range, 0.7–0.8 cm²), which improved to 1.51 cm² (range, 1.4–1.6 cm²). The pooled post-operative indexed EOA was 0.85 cm²/m² (range, 0.80–0.90 cm²/m²). Patient prosthesis mismatch (PPM) was defined and reported in only one study (12). The pooled mean of moderate to severe paravalvular leak was 1.9% (95% CI, 0.97–3.7%). Table 4 shows a summary of haemodynamic measurements including follow-up gradients.

Table 4 Echocardiography measurements and clinical data following Perceval S implantation
Full table

Long-term outcomes

Post-operative NYHA Class improvement of one or two classes occurred in 87.8% of patients (95% CI, 81.0–92.5%). Survival at 1-year was a pooled weighted mean of 90.4% (95% CI, 87.2–93.7%). Loss to follow-up, reoperation, and endocarditis were inconsistently reported. Survival beyond 1-year was reported variably in the included studies, with the longest period of survival, 5-year reported in two studies (11,16) for a weighted mean of 83% (range, 71.3–85.5%) (see Table 5).

Table 5 NYHA functional class and survival data in patients post Perceval S insertion
Full table

Discussion

As life expectancy improves, the prevalence of severe AS increases. Subsequently, patients are of higher risk due to their age and other comorbidities. In the past several years, TAVI has emerged as an established alternative to conventional AVR, particularly in the high-risk surgical cohort. TAVI has shown that rapid deployment and anchoring of the aortic valve without sutures, is feasible and safe. The advantage of the Perceval valve is that rapid deployment is achieved under direct visualisation in a semi-debrided annulus. The procedure can be performed using a minimally invasive approach, potentially reducing morbidity and mortality. This meta-analysis of the Perceval valve has demonstrated excellent initial results, which are comparable to conventional AVR.

In a cohort consisting of near octogenarians (mean age 78.5 years old), we found that the early postoperative outcomes are promising, as the 30-day mortality rate was 2.34% and the cerebrovascular event rate of 1.37%. This is in the context of a concomitant procedure rate of 42.5%. This result is similar to another recently published meta-analysis which demonstrated an acceptable early mortality rate of 2.1% and stroke rate of 1.4%, when compared to conventional AVR (24).

Interestingly, the pacemaker rate was 6.76% and is higher than in conventional AVR (3.6%) (25). One theory is that the radial force applied during deployment of the sutureless valve may be a precipitant for a higher pacemaker implantation rate (26) Pacemaker rates following after TAVI have ranged between 9% to 42% (27,28) and have been associated with the continued expansion of the valve following implantation. This has resulted in conduction blocks occurring days after TAVI (29). However recently, there is evidence to suggest that the depth of placement of the Perceval has a correlation with a higher pacemaker implantation rate (30). Yanagawa et al. have shown a reduction in pacemaker implantation from 28% to 0% by the placement of guiding sutures millimeters higher than the manufacturer recommendation resulting in a slightly shallower valve position with respect to the aortic annulus (31).

Additional adverse events related to valve implantation are very low. There was one reported case of endocarditis in the perioperative phase after the sutureless valve was explanted (23). Overall rates of reoperation (1.43%) and early infection (<1%) rates are low, further supporting the safe early outcomes.

Long ACC and CPB times are associated with increased perioperative mortality (8). Our analysis has shown that the Perceval valve has significantly reduced the ACC and CPB times when compared to conventional AVR. The weighted mean ACC and CPB times for isolated AVR was 39.7 and 64.2 minutes respectively, which were less than the established conventional AVR times of 76 and 106 minutes respectively (15).

Overall, there were 1,022 patients that underwent Perceval valve implantation via median sternotomy, representing a weighted mean of 75.2%. Several studies undertook a primarily minimally invasive approach (15,18) with no concomitant cardiac surgical procedure. Currently, minimally invasive approaches have been associated with longer ACC and CPB time, with no concise evidence to suggest reduced mortality and improved survival rates (32,33).

Even with the use of a rapid deployment valve, studies using the right thoracotomy approach were found to have longer ACC and CPB times, compared to the median sternotomy approach (see Table 2). This could be explained by difficult access, inability in debriding the aortic annulus effectively, patient selection and operator experience in minimally invasive surgery.

Early haemodynamic values have been promising with weighted mean valve gradient of 12.1 mmHg and post-operative EOA of 1.51 cm². Several studies have shown further improvement at 1 and 2 years with weighted mean gradients of 10.1 and 9.9 mmHg respectively (see Table 5). Moderate to severe paravalvular leak was noted to be a pooled mean of 1.9%. Several authors advocate the need for proper annular decalcification or potential replacement with a conventional aortic valve at the time of implantation if there is significant paravalvular leak (19,20). In one study, severe paravalvular leak was not corrected at the time of surgery, and in those patients the leak remained stable with no further intervention at a later date (13). Though the early results with the Perceval valve suggest excellent haemodynamic results, demonstrating stable mean gradients up to at least 2 years, the long-term follow-up data was limited in most instances and not statistically comparable to other sutureless valves such as the Intuity (Edwards LifeSciences, Irvine, Calif, USA) or conventional valves such as the Mosaic (Medtronic, Inc., Minneapolis, Minn, USA).

This study is limited by several factors. The majority of the studies reviewed in this meta-analysis have only reported early survival and haemodynamics outcomes. The available long-term data is limited to a very small cohort of patients. Although the early haemodynamic data was encouraging, the data cannot be stratified to a particular valve type or size. The studies presented were observational and in many instances, they involve the same specialised centers; thereby causing a sample selection and publication bias. Additional limiting factors to consider were the proportion of isolated AVRs to concomitant procedures, bias introduced by surgical approach and the experience of the surgeon. Further randomised controlled trials at specialised centers with extensive experience in implanting Perceval valves are required to validate the data in this meta-analysis (34). The Perceval Sutureless Implant vs. Standard Aortic Valve Replacement (PERSIST-AVR) trial (http:livanova.sorin.com), will be the first such large international multicenter trial to adequately compare the efficacy and performance of the Perceval valve to conventional AVR.

Conclusions

This systematic review and meta-analysis has demonstrated that early clinical and haemodynamic performance of the Perceval valve is satisfactory and comparable to that of conventional AVR. However, the long-term durability and haemodynamic data for the Perceval valve is somewhat limited. Large-scale randomised studies are recommended to accurately assess long-term durability and complications associated with the Perceval valve.

Acknowledgements

None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

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