Transannular bovine jugular vein monocusp for the reconstruction of severe right ventricular outflow tract obstruction

Objective Severe right ventricular outflow tract obstruction in tetralogy of Fallot and variants necessitates the use of transannular patch in a significant proportion of children undergoing repair. We have used a Contegra monocusp together with delamination of native leaflet tissue in order to create a functioning pulmonary valve. Methods In total, 18 (2017-2022) consecutive Contegra monocusp implantations were included. Median age and weight were 3.65 [2.00; 9.43] months and 6.12 [4.30; 8.22] kg, respectively. Nine of 18 patients had undergone palliation. Native pulmonary leaflet tissue was recruited to create a single posterior cusp. Contegra monocusp selection was based on the goal to achieve a neoannulus of Z value ≈ 0. Monocusp sizes implanted were 16 [14; 18] mm. Patch plasty of left pulmonary artery (LPA) (9), right pulmonary artery (RPA) (2), and both LPA-RPA (5) were often performed. Results All patients survived the operation and were discharged home in good health. Median ventilation time and hospital stay were 2 [1; 9] and 12.5 [9; 54] days, respectively. Follow-up duration was 30.68 [3.47; 60.47] months and 100% complete. One patient with well-corrected right ventricular outflow tract died 9.4 months postoperatively, possibly of aspiration. One child with membranous pulmonary atresia needed reoperation (conduit insertion) at 3.5 months of follow-up. Five needed catheter interventions: supravalvar stent (2), LPA stent (3), and RPA stent (1), most of them in the earlier half of the experience. Pulmonary annulus changed from preoperative –3.91 [–5.98; –2.23] to –0.10 [–1.44; 1.92] at discharge; growing proportionally to –0.13 [–3.52; 2.73] at follow-up. Kaplan–Meier freedom from composite dysfunction was 79.25 (95% confidence interval, +13.68%, –31.44%) at 36 months. Conclusions Recruitment of native leaflets, optimal Contegra monocusp, and commissuroplasty provide an easily replicable technique for achieving a competent, proportionally growing neopulmonary valve. Longer follow-up is needed to determine its impact on delaying a pulmonary valve replacement. Video Abstract

The severity of the pulmonary annular hypoplasia, the number and quality of pulmonary leaflet tissue available, and also the adequacy of pulmonary valve function achieved after repair determine the long-term outcome after repair of tetralogy of Fallot (TOF). 1 Despite restrictive strategies, a significant proportion of TOF repairs involve a transannular patch. Although the overall early mortality remains low, 1,2 the pulmonary valve function influences the early-and long-term postoperative course. [3][4][5] Various monocusp techniques using homograft, 6 xenograft, 7,8 polytetrafluoroethylene (PTFE; 0.1 mm), 5,9 and Contegra monocusp 10 have been described. We have used the Contegra monocusp with a goal to achieve a neopulmonary annular Z-value of approximately 0 and added pulmonary reconstructive techniques including delamination, native leaflet tissue recruitment, and optimization of Contegra free leaflet margin size by commissural plication to achieve pulmonary competence. The purpose of this study is to describe our technique and review the mid-term results of a using a Contegra monocusp transannular patch for right ventricular outflow tract (RVOT) reconstruction in children with severe forms of TOF and its variants.

METHODS Institutional Review Board Statement
The study design was conducted in accordance with the Declaration of Helsinki and approved by the Cantonal Ethics Committee of Z€ urich, Switzerland (BASEC protocol code no. 2017-01321) with an amendment dt. 11.11.2020. Informed consent was obtained from the patients' parents.

Patients
Eighteen consecutive Contegra monocusp transannular patch insertions performed during repair of severe forms of TOF and its variants by a single surgeon (H.D.) (2017-2022) were included in the study. All patients received postoperative aspirin. Demographic, clinical, operative, and follow-up data were retrospectively collected from digital hospital database as well as from external referring physicians (Table 1).

Decision-Making
Based on preoperative echo and intraoperative Z-score measurements, 11 the following algorithm guided the decision-making approach to the pulmonary annulus: Z score approximately !À2: provided the pulmonary leaflets were normally laid with bi/tricuspid configuration, an annulus-sparing approach was preferred. Z score À2 to À3: If the pulmonary valve was pliable, a trial with annulus-sparing approach, aggressive commissurotomy, and intraoperative balloon dilatation was undertaken. If the postrepair RVOT z score was<À2 and the right ventricle-to-pulmonary artery gradient was>20 to 25 mm Hg (mean Doppler gradient) with right ventricular/left ventricular pressure ratio of >0.65 to 7, a transannular approach was justified. In case of transversely oriented pulmonary valve with 2 well-formed cusps and a small annulus, a pulmonary valve cusp augmentation with autologous pericardium as proposed by Sung and colleagues was preferred. 3,12 Z score <À3: Extreme pulmonary annular hypoplasia with dysplastic, nonpliable and nodular leaflets necessitated a transannular monocusp reconstruction.

Abbreviations and Acronyms
Chronology of Surgical Steps Figure 1, A-F shows the schematic representation of our technique of Contegra monocusp implantation. After establishing moderately hypothermic cardiopulmonary bypass, the ductal ligament is divided and the pulmonary tree is extensively mobilized. Upper infundibulotomy is performed on a cardioplegic heart and accessory infundibular muscles are transected (often with electrocautery to prevent coronary fistula). The pulmonary valve is inspected and sized using olive tip probes. For a severely hypoplastic pulmonary trunk with dysplastic pulmonary valve, a Contegra monocusp transannular patch is chosen.

Choosing Contegra Monocusp Size
Considering that a child needs a 10-mm pulmonary annulus, and his native annulus is 4 mm, the size of the Contegra monocusp chosen is calculated as follows: The appropriately sized Contegra is ordered for saline irrigation. During this time, ventricular septal defect closure is performed.

Delamination and Creating a Dorsal Leaflet
Native pulmonary leaflet tissue is analyzed. Using a combination of take-down of the commissure, delamination, fusion of leaflets, and leaflet thinning, a dorsal neopulmonary leaflet is created (Figure 1, A).

Neopulmonary Root Creation
Contegra monocusp is sutured beginning at the left-sided commissure with the monocusp lying on its back, followed by suturing of the right-sided margin ( Figure 1, A-C). Thereafter, the proximal tongue is fashioned so as to match the ventriculotomy. Due to excessive height of the leaflets, monocusp commissures need to be higher than the native leaflet commissures in order to ensure Contegra free leaflet edge to the native leaflet apposition.

Commissural Plasty
In our experience, for a given Contegra monocusp size, the corresponding free leaflet margin is too redundant to be competent. Hence, commissural plication of the monocusp to the native leaflet commissure is undertaken in order to reduce its redundancy ( Figure 1, D and E). A harmonic coaptation at the commissures and not-too much redundancy of the monocusp are key to achieving valve competence ( Figure 2, A).

Enlargement of Pulmonary Annulus (PA) Bifurcation
The PA bifurcation may be enlarged by separate patches on the left PA or right PA or both to match the size of the neopulmonary root. Creating an enlarged bifurcation to match the enlarged root is equally critical. We have used different autologous and xenogenic pericardial patches ( Table 2) for branch PA enlargement but have preferred spongiosa-free Contegra patches lately due to their elasticity, hemostatic nature, and smooth inner wall.

Intraoperative Findings
Intraoperative findings are summarized in Table 2.

Echocardiography: Pitfall
Although the measurement of RVOT gradient can be performed conventionally by continuous-wave Doppler, the estimation of neopulmonary valve regurgitation must take into consideration the fact that the Contegra monocusp is displaced caudally to the junction of right ventricular (RV) body to the RV infundibulum. This addition of contractile part to the neopulmonary trunk may cause a reversal of flow in pulmonary side branches, even when no significant regurgitation is present. Hence, corroborative evidence with color Doppler estimation of the vena contracta and the extent of regurgitation into RV cavity is mandatory. The observed regurgitation was graded as grade 1 to 3 for mild, moderate, and severe. 13

Statistical Analysis
Data are presented as median [range]. Survival was determined using Kaplan-Meier curves. Z scores were calculated according to Pettersen and colleagues. 11 Statistical analysis was performed using Microsoft Excel 2019 and GraphPad Prism 9.5.0.

RESULTS
All children survived the operation. The median follow-up duration was 100% complete at 30.68 [3.47-60.47] months.

Mortality
One child in good clinical and cardiac status died at home while breast feeding (9.4 months postoperatively), probably due to aspiration. No autopsy was performed. An echocardiography 3 weeks before death showed a mean gradient of 18 mm Hg and a mild pulmonary regurgitation (PR). No arrhythmias were reported. Kaplan-Meier survival of our cohort was 93.3% (95% confidence interval [CI], þ5.7, -32.1) at 36 months.

Reoperation
One child with pulmonary atresia ventricular septal defect (case no. 8, performed in 2018) needed reoperation with implantation of a Contegra valved conduit for residual pulmonary artery stenosis at 3.5 months after total correction. A freestanding Contegra leaflet implanted posteriorly in addition to the Contegra monocusp was in retrospect an error. All 16 remaining children are alive, thriving, and free of reoperation. Freedom from reoperation is 94.4% (95% CI, þ4.8, -27.8) at 36 months.

DISCUSSION
Since transannular patching remains a necessity, postoperative acute PR manifests as inotropic dependence, prolonged ventilation, and intensive care unit and hospital stay. 3,5 Although long-term consequences of chronic PR continue to be debated, there is increasing consensus that it (in tandem with other operative insults such as myocardial scars) negatively impacts long-term outcome. [14][15][16] Hence, various pulmonary valve reconstructive techniques have been used, to avoid extremes of gradient and regurgitation. The lesser the amount of native tissue available, the greater is the amount of foreign tissue necessary to create a functioning neopulmonary valve. For severely hypoplastic annulus with a dysplastic valve, an anterior monocusp is preferred to a conduit in infancy for obvious reasons.

Homograft Monocusp
Although the use of homograft monocusp dates back to 1968, 7,8 the results have been inconsistent, partly because it was only used as an onlay patch without resorting to significant reconstructive techniques. 6,8,9 Nath and colleagues 9 reported their experience of 131 pulmonary homograft monocusp implantations and showed good early outcome (ventilation and hospital stay of 1 and 6.5 days, respectively). Early mortality was 2.3% and late mortality was 4%. At a median follow-up of 5 years, 73% monocusp suffered from moderate or severe regurgitation. Freedom from pulmonary valve replacement was 85 AE 10.3% at 10 years.

PTFE Monocusp
Turrentine and Brown popularized 5,17 the PTFE (0.1 mm) monocusp and reported improved perioperative outcome in terms of duration of mechanical ventilation, intensive care unit, and hospital stay, even when 80.8% suffered moderate or severe regurgitation and 24.5% needed replacement at a follow-up of 10.9 AE 5.8 years.
This procedure requires precise measurements of the monocusp and the overlying patch so as to achieve reasonable competence. This makes the outcome operator dependent and maybe difficult for surgeons in their learning curve.
Miyazaki and colleagues 18 reported on a multiinstitutional Japanese experience, with a PTFE valved patch and bulging sinuses in 534 patients. They reported excellent 10-year freedom from reoperation of 93% and freedom from moderate or severe regurgitation of 78% at a median follow-up of 4.6 years. Our present experience closely replicates the Japanese results.

Other Monocusp Techniques
Monocusp created from autologous or xeno-pericardium, 4 Dacron, and right atrial appendage have also been described with varying short-and long-term results.

Contegra Monocusp
Chiappini and colleagues 10 first reported use of Contegra monocusp as a transannular patch. They reported good outcomes, with approximately 36.4% showing moderate or severe PR at 28 months' follow-up. Contegra enjoys long-term familiarity to surgeons with excellent reported outcomes. 19 The multiple sizes, off-the-shelf availability, naturally defined relationship between the cusp and the sinus, greater height, increased leaflet coaptation, and adequate tissue proximal and distal to the valve makes it attractive for use as a monocusp, notwithstanding its cost. The Contegra valve leaflets are the more pliable of all xenogeneic tissues with low inertia, which means that   10,20 We have built on the concept of Contegra monocusp, by proposing a simple technique based on following pillars: 1. The addition of deficient circumference by the Contegra monocusp with a goal of achieving a Z value z 0. The monocusp thus presented possesses excessive free leaflet margin, which needs to be shortened, by using commissural plication between the Contegra and the native leaflet.
2. The larger coaptation area between the redundant leaflet and the anteriorly displaced conal septum may continue to provide competence with patient growth in the medium term ( Figure 4). 3. The better the quality of native leaflet tissue and better the coaptation to the Contegra monocusp, the better the stimulus for the native leaflet to grow. 4. Time will tell whether this delayed progression of significant regurgitation helps delay the need for a pulmonary valve replacement.

Methods
This manuscript describes the technique and efficacy of Contegra® monocusp & native leaflet recruitment, for the reconstruction of severe RVOT Obstruction.

Results
Contegra® monocusp, anteriorly displaced conal septum and reconstructed remnants of native leaflet enable optimum enlargement and reasonable neo-pulmonary valve function in the short and mediuim term.

Implication
Contegra® monocusp provides a good option for reconstruction in select cases of severe RVOTO.

Flow Dynamics of Contegra Monocusp
The anterocephalic displacement of the conal septum in TOF creates an angle of approximately 45 between the RVOT and the pulmonary bifurcation. Furthermore, since the monocusp together with its sinus mimics the anatomy of an aortic sinus, it may be presumed that similar da Vinci vortices 21 are at play in the Contegra monocusp (Figure 2, B). These eddy currents on the one hand distend the sinus outwards and on the other hand flap the leaflet dorsally. Even when no significant native leaflet tissue is available, the conal septal shelf provides a cushion for the monocusp to fall back upon and create pulmonary competence. Considering the severe RVOT obstruction with little native pulmonary tissue in our cohort, a duration of mechanical ventilation and hospital stay of 2 and 12.5 days was gratifying. Although the neopulmonary annulus grew commensurate with the child's growth, the valve has continued to function very well in 14 of 16 surviving monocusps (excluding 1 patient who died and 1 who needed replacement). We believe that the good early outcome and the hope of better mid-term outcome justify the costs involved and the sacrifice of a complete Contegra conduit. However, all the hypothesis about the long-term outcome needs to be validated with longer follow-up in a larger cohort of patients.

Contegra Patches for Branch PA Plasty
We have used different patch materials (autologous and xenogeneic) for branch PA reconstruction (Table 2). However, of late, we have relied on spongiosa denuded Contegra patches. While being guarded about its long-term impact, we have 5 reinterventions in autologous pericardial plasty (2) and xenopericardial plasty (3) and none in the group with Contegra patches (5).

Future Outlook
Although the advantages of having a competent pulmonary valve have been well documented, its impact on long-term survival is unknown. Despite this, the general logic in favor of creating a functioning pulmonary valve justifies the quest for developing products and strategies that allow off-the-shelf, reasonably priced, and easy-tolearn concepts, which would help push behind the need for a complete valve by a decade or two. This in turn should allow putting in an adult-sized valve and thus better valve survival. These endeavors would go a long way in improving the morbidity and mortality of these complex patients. Democratization would necessitate translating this concept to a synthetic construct and industrializing it. The PTFE monocusp described by some Japanese groups 18,22,23 has achieved excellent results; unfortunately, however, they remain unavailable for worldwide dissemination.

Limitations
This retrospective analysis of our technique has inherent limitations of a single-institutional, retrospective observational study. The decision to go transannular is not based on any one objective criteria but involves subjectivity of the operating surgeon. Although echocardiography is the obvious diagnostic modality, the extra-anatomic position of the monocusp subjects it to fallacies in interpretation if standard criteria of regurgitation are used. Last but not the least, the long-term outcome of this approach is still a matter of conjecture.

CONCLUSIONS
Contegra monocusp provides a simple, easily available transannular monocusp patch that helps reconstruct a reasonably functioning neopulmonary valve in severe form of TOF and variants. The neopulmonary annulus continues to grow proportionately in the medium term while maintaining competence, thanks to a redundant Contegra leaflet and the anteriorly displaced conal septum abutting each other. Despite the high material cost of the monocusp, the impact of smooth early postoperative course and a prospect of delayed need for a pulmonary valve makes it an attractive option. Apart from documenting the long-term outcome of our approach, future efforts should be directed at developing similar prosthetic constructs leading to industrialization and easy availability (Video Abstract).