Pulmonary valve replacement after right ventricular outflow tract reconstruction with homograft vs Contegra®: a case control comparison of mortality and morbidity

The use of a valved conduit between the right ventricle and the pulmonary artery (RV-PA) for right ventricular outflow tract (RVOT) reconstruction in congenital heart diseases was introduced by Ross and Somerville in 1966 [1]. Since then, the practice has gained in both popularity and use. Currently, cryopreserved homografts, and particularly pulmonary homografts (PH), are considered first-choice conduits. Regrettably, there is both a lack of availability [2] (especially in the smallest sizes more suitable for newborns) and an issue of early degeneration, particularly in younger patients [3, 4]. These obstacles prompted the development of alternative options. One such solution is Contegra®, a bovine jugular vein xenograft, which was introduced in 1999 by Medtronic® Inc. (Minneapolis, MN, USA). Contegra® showed excellent results in early, mid, and long term studies [5‐9], so that some centers started recommending it as the preferred conduit for RVOT reconstruction [6]. This optimism has been tempered by several negative reports [10‐12] revealing development of distal stenosis, aneurysms of the conduit, and a greater risk of endocarditis. Some teams, such as Göber et al. did not recommend its routine use [12].

Furthermore, whether homografts or Contegra®, RV-PA conduits lack growth potential. This, combined with their degeneration and/or calcification over time, poses a serious problem when used in young patients with a great growing potential, therefore requiring multiple RV-PA conduit replacements [13]. Despite the issues, and the number of years the surgery has existed, the RV-PA conduit replacement procedure’s results remain unknown, and poorly studied in the field of comparison between homografts and Contegra®. The purpose of this study is therefore to compare the surgical morbidity and mortality of Contegra® and homograft replacement in a pediatric population.

In many CHD cases, both RVOT reconstruction and the Ross procedure require the implantation of a RV-PA valved conduit. Despite advancements, it is likely that in most patients, this conduit will need to be replaced during their childhood, especially since early replacement of the conduit could prevent irreversible structural myocardial changes [21]. The feasibility of such a procedure is important to consider when implanting RV-PA conduits. Conduits like Carpentier-Edwards conduit, a porcine-valved Dacron conduit, are considered easy and safe to replaced [22] because they are easily pealed from the surrounding tissue. For this reason, some teams still use it in RVOT reconstruction.

Most surgeons consider PH as the “gold standard” for RVOT reconstruction, but it is not the “perfect conduit”. Despite providing good hemodynamic results without the need for anticoagulation [23], the increasing demand over the last 30 years and limited availability could lead to a shortage [2]. Furthermore, worries were raised concerning its durability, especially in younger patients [24, 25]. Wells et al. found a failure rate of PH of about 40% after 10 years [24], which concurrence with Boethig et al.’s findings of a 46% degeneration rate in patients older than 10 years of age, and a degeneration rate of 65% in younger patients after merely five years [26]. Several modes of conduit failure have been described, including shrinkage of the conduit, early calcifications, RVOT aneurysm, conduit valve insufficiency [24, 25, 27, 28], and outgrowth, although the latter occurs less than expected [3, 24]. Risks factors for homograft failure have been extensively studied. They include younger aged recipients, smaller homograft diameter, the use of aortic homograft in older patients, low weight at implantation, truncus arteriosus and an extra-anatomic position [3, 24, 28, 29]. Moreover, in 2010, Christenson et al. showed that the performances of non ABO-matched homografts were significantly worse than ABO-matched homografts, especially for younger children [23]. In Belgium, the homografts are never ABO-matched. Studies have shown that replaced homograft performs as well as the first homograft [13, 30]. Technical considerations may influence the surgeon’s preference for a conduit. PH implantation requires additional prosthetic or pericardial patches to connect to the right ventricle. All these considerations may render the PH imperfect for newborns [31].

Given the aforementioned considerations, the Contegra® conduit was introduced in 1999 for RVOT reconstruction. In Belgium, Contegra® has been available since May 2000 and since then, unsupported Contegra® conduits have been used. Contegra® is a bovine jugular vein conduit with a native triple-leaflet valve stored in diluted and buffered glutaraldehyde. This retains leaflets and conduit wall compliance and likely renders Contegra® non-antigenic [32]. This differs from cryopreservation which does not eliminate the antigenic expression in homografts [33]. Unlike PH, Contegra® is readily available in sizes ranging from 12 mm to 22 mm. Moreover, studies are optimistic, showing good hemodynamic results [34]. Some authors even consider Contegra® as a valid alternative to homografts [5, 6, 8, 23, 34‐37], even in newborns [31]. In 2011, Brown et al. described a freedom from explantation for Contegra® at both five and ten years of 97% and 90% respectively, versus 81% and 69% for PHs [35]. It has been observed that degradation is characterized by less calcification [6, 7, 34]. As for technical considerations, Contegra® because of the abundance of tissue on both sides of the valve, does not need additional material for proximal hoods and distal pasties. Suturing is simple, the material is resistant to suture tear and very flexible, therefore, making its surgical handling easy. Concerns were raised due to a specific complication with Contegra®: stenosis at the distal anastomosis which causes proximal conduit dilation and the formation of an aneurysm in small sized conduits [10‐12, 38], so that some authors discouraged its use [10]. Since the modification of the operative technique as proposed by Corno et al. in 2008, this complication has become rarer [8, 38]. Few cases of pseudo aneurysm of the right ventricle after Contegra® implantation have been reported [39]. Such a complication occurred once in the present study. The seven-and-a-half-year-old patient underwent a Rastelli procedure six years earlier with the implantation of a 18 mm Contegra®, to correct a transposition of the great arteries with ventricular septal defect and pulmonary stenosis. The pre-operative transesophageal echocardiography showed a dilation of the right ventricle and a subaortic membrane. The false aneurysm was located between the ventriculotomy and the Contegra® which was entirely disconnected from the ventricle. The Contegra® was removed and replaced by an 18 mm Contegra®. More recently, Ugaki et al. reported a further complication: endocarditis, which occurred in 9% of the Contegra® implanted, 10 times more often than what is observed with homografts, particularly in children older than three years [40]. Another source of concern is the risk of thrombus formation as reported by Tiete et al. [12, 41] and for which they recommend a prophylactic anticoagulation. All patients with a Contegra® received low molecular weight heparin during two months after the implantation in our center, which might explain the small incidence (2 cases; 3.3%) of Contegra® replacement due to thrombosis.

Low surgical mortality is reported and death rate is identical between homograft and Contegra® replacements, confirming other reports that proclaim it to be a safe procedure [13, 27, 42]. It suggests that the type of replaced conduit does not influence the perioperative mortality. The overall operative complication rate was approximately 14%, even though the patients underwent multiple sternotomies. This rate was not influenced by the type of conduit in place during the redo procedure and this result corroborates with other reports on the fact that, if approached meticulously in specialized centers, repeat sternotomy can be performed with a minor subsequent morbidity and mortality [43, 44]. Allografts and xenografts differ in the host immunogenic response, and when implanting a xenograft, one could expect a greater inflammatory reaction. For Wojtalik et al. the three reasons for potential immunogenicity and antigenicity of Contegra® are: a big surface of contact with host tissues, cellular remnants (whole endothelial layer) within the implant and heterogeneous graft fixation by glutaraldehyde [45]. This can cause more adherences (therefore affecting the surgery duration), and ultimately more rejections than homografts. No difference was observed in terms of duration, bleeding or transfusion between the two groups. From an operative point of view, calcifications are observed in the two groups, but in the Contegra® group, they tend to be less extensive than the ones observed in the explanted homografts group. Both groups present adherences. Their dissection and the explantation of the conduit were easier in the Contegra® group thanks to a cleavage plane well defined by the tunica externa of the bovine jugular vein, which once removed, allows an easy and safe dissection. Finally, no difference in post-operative morbidity was observed between the two groups, suggesting that the perioperative course is not affected by the type of the explanted conduit.

In conclusion, the “perfect RV-PA conduit” is yet to be found, and both Contegra® or homografts used in pediatric RVOT reconstruction will require explantation and replacement. Multiple RVOT reconstruction with RV-PA conduit replacement can be performed safely with a low surgical morbidity or mortality. We showed that the type of conduit does not influence these results. Therefore, the choice of conduit for RVOT reconstruction should not be influenced by the future surgical risk during the replacement procedure.