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Ann Thorac Surg 2005;79:618-624
© 2005 The Society of Thoracic Surgeons


Original article: Cardiovascular

Early Results of the Bovine Jugular Vein Graft Used for Reconstruction of the Right Ventricular Outflow Tract

Hitendu H. Dave, MDa,*, Alexander Kadner, MDa, Felix Berger, MDb, Burkhardt Seifert, PhDc, Ali Dodge-Khatami, MD, PhDa, Dominique Béttex, MDd, René Prêtre, MDa

a Clinic for Cardiovascular Surgery, University Hospital Zurich,Zurich, Switzerland
b Department of Cardiology, Children's Hospital Zurich, Zurich, Switzerland
c Department of Biostatistics, University of Zurich, Zurich, Switzerland
d Department of Cardiovascular Anesthesia, University Hospital Zurich, Zurich, Switzerland

Accepted for publication July 29, 2004.

* Address reprint requests to Dr Dave, Clinic for Cardiovascular Surgery, D Hoer 45, University Hospital Zurich, Ramistrasse 100, Zurich CH–8091, Switzerland (E-mail: hitendu.dave{at}kispi.unizh.ch).


    Abstract
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 
BACKGROUND: This study is an assessment of early results of bovine jugular vein grafts (BJV) used to reconstruct the right ventricular outflow tract.

METHODS: Ninety-three consecutive BJV implantations performed between May 2001 and August 2003 were included in this study. The median age was 7.2 years. Indications included various forms of tetralogy of Fallot and pulmonary atresia (56 patients), aortic valve disease requiring a Ross procedure (21 patients), truncus arteriosus (8 patients), d-transposition of the great arteries with ventricular septal defect and pulmonary stenosis (5 patients) and miscellaneous (3 patients). Additional plasty of the intrapericardial pulmonary arteries was performed in 41 patients. Follow-up was complete with a mean duration of 20.3 ± 5.8 months.

RESULTS: There were 3 patients (3.2%) with early deaths and 2(2.2%) with late deaths, but none were related to the bovine jugular vein grafts. Twelve bovine jugular vein grafts needed reintervention; 11 were due to development of a stenotic membrane at the anastomosis site and one was due to somatic outgrowth of the child (10 conduit replacements and two balloon dilatations). Overall freedom from reintervention was 91.6% and 83.5% at 12 and 24 months, respectively. Small size (≤ 14 mm) conduits show respective rates of 80.7% and 63.6%, whereas larger sizes were 98% and 96%, free from reintervention at 12 and 24 months.

CONCLUSIONS: Bovine jugular vein grafts, when used for reconstruction of the right ventricular outflow tract, showed good early-term results. Attrition of small size bovine jugular vein grafts, due to development of a stenotic process at the anastomotic site needs to be closely observed. Longer follow-up is needed to allow a more definitive comparison with other established options.


    Introduction
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 
Nearly one third of patients born with congenital cardiac malformations have some form of right or left ventricular outflow tract obstruction. A significant proportion of patients with right ventricular outflow obstruction eventually need reconstruction of the native right ventricular outflow tract (RVOT) with a valved conduit. Many patients with congenital valvular aortic stenosis ultimately undergo a Ross procedure, which also requires a valved conduit, to reestablish the right-sided continuity. A huge amount of data has been gathered with the use of various conduits on the right side, only to show that a conduit with long survival still has not been found [1–5]. Homografts have achieved the best results so far, and these are considered the standard against which new conduits should be evaluated [1]. Homografts continue to show degeneration over time, sometimes early; the gap between demand and supply tends to increase. With this backdrop, we started using the bovine jugular vein graft (BJV) as a valved conduit for RVOT reconstructions. These veins present valves composed of three thin leaflets and sinuses that look like a semilunar root and can be obtained in a wide range of sizes.


    Material and Methods
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 
Permission to proceed with this study was granted by our Institutional Review Board. After obtaining informed patient or parent consent, 93 consecutive patients prospectively underwent implantation of a BJV (Contegra [Medtronic, Minneapolis, MN]) between May 2001 and August 2003 with perioperative clinical and echocardiographic evaluation. Only unsupported conduits (without external supporting rings) were used. Median age and weight were 7.2 years (range, 3 days to 40 years) and 19.8 kg (1.9 kg to 97 kg), respectively (Fig 1). Indications for BJV implantation are shown in Table 1. Patients with first time BJV implantations were sorted into three basic groups. The first group consisted of patients requiring a valved conduit for an RVOT pathology (usually an obstruction) at initial operation (n = 34); the second group included those patients requiring a valved conduit for severe pulmonary insufficiency, years after primary correction (n = 32); and the last group represented those patients who required a conduit to replace the pulmonary root used as an autograft (n = 21).



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Fig 1. Age distribution. (BJV = bovine jugular vein graft.)

 

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Table 1. Indications for Bovine Jugular Vein Graft Implantations
 
Technique of Implantation
After completing the left heart repair on a cardioplegic heart, the BJV implantation was performed during the phase of myocardial reperfusion. Whenever possible, as in the vast majority of patients, we attempted to keep the pulmonary bifurcation intact. The main pulmonary artery was always completely transected to allow a harmonious end-to-end anastomosis of the graft to the pulmonary bifurcation.

The diameter of the BJV was mostly determined according to the diameter of the PA bifurcation, although the distance between the conal septum and pulmonary bifurcation was also taken into consideration at times. The BJV was not oversized in regard to the pulmonary bifurcation. Our series showed a bi-modal distribution of the BJV conduits used, with peaks at 12 and 22 mm (Fig 2). In 4 low-weight neonates (< 2.5 kg), the BJV was downsized to 8 mm by resecting a strip of the conduit along with one leaflet of the valve. The graft was intended to be as short and straight as possible. The distal end of the conduit was trimmed a little beyond the level of the commissures. The distal anastomosis was performed with continuous polypropylene suture, taking bites preferably through the intima media layers of the BJV and avoiding the external spongiosa. As already described by our group [6], the proximal end of the graft was cut with only a slight bevel in orthotopic implantations (typically as a part of the Ross procedure or in chronic pulmonary insufficiency after repair of tetralogy of Fallot). An additional triangular patch made of graft material was often used to enlarge the onlay part of the graft to accommodate the large infundibular opening. The proximal end of the graft was cut with a much longer bevel whenever a more heterotopic implantation on the right ventricle was necessary. This group included patients in which the conal septum was inexistent (truncus arteriosus) or not usable for BJV insertion (such as in a Rastelli operation). In these patients the incision in the infundibulum was extended cranially as much as possible (lateral to the aorta) so that the BJV could lie on the left side and have a more anatomic disposition. The implantation of the BJV was done more in an end-to-side fashion so that the graft maintains a straight direction and the plane of the valve annulus remains perpendicular to the graft direction. In longstanding severe pulmonary insufficiency, in which the right ventricular infundibulum is severely dilated in relation to the diameter of the pulmonary bifurcation, the discrepancy between the RV opening and the proximal diameter of the BJV was corrected when needed by tightening a running Prolene (Ethicon, Somerville, NJ) pursestring suture passed at the level of the proximal anastomosis in a technique similar to a DeVega annuloplasty. In cases of akinesia or dyskinesia of the anterior wall of the right ventricle (typically found after a tetralogy of Fallot repair), a strip of ventricular wall was resected to remodel the right ventricle.



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Fig 2. Size distribution of bovine jugular vein graft (BJV) implants: absolute numbers (top) and with respect to body surface area (bottom).

 
Forty-one patients underwent concomitant reconstruction or enlargement of the pulmonary bifurcation or pulmonary branches, using a patch of the native pulmonary artery wall, a patch of the BJV itself, or a patch of autologous pericardium (in order of preference).

Anticoagulation Regime
All patients routinely received 10 IU/kg/h of heparin infusion early postoperatively, followed by low molecular weight heparin (until hospital discharge). Aspirin is given postoperatively for a period of 3 months, starting from the first postoperative day.

Follow-Up
All patients more than 3.5 kg underwent intraoperative transesophageal echocardiography. All patients underwent a transthoracic echocardiography during hospital stay and during a routine control between 3 and 6 months. A questionnaire related to the function of the BJV was filled out prospectively during these examinations. Serial controls were then scheduled every 6 to 12 months depending on the pathology.

While correlating the existing gradients (measured during cardiac catheterization being performed for unrelated indications) with the Doppler estimated gradients, we observed that a mild turbulent flow of up to 2.3 m/s is typically observed through the BJV valve, where no real gradient existed. This flow acceleration leads to a calculated overestimation of an inexisting systolic gradient. Hence we considered a Doppler estimated gradient of 20 mm Hg for the BJVs as acceptable. Angiography was performed when the estimated gradient exceeded 40 mm Hg, to delineate the obstruction and attempt dilatation. In cases of failed dilatation or recurrent stenosis, surgical correction was performed. Clinical and echocardiographic follow-up was complete. The mean duration of follow-up was 20.3 ± 5.8 months (range, 10 to 32 months).

Statistical Methods
Continuous variables in this study are presented as mean ± standard deviations, median, or range as appropriate. We used the log rank test to compare the results between the groups (smaller [≤ 14 mm] grafts vs larger grafts). P values ≤ 5% were considered as statistically significant. Kaplan-Meier survival curves for the survivors were used to analyze survival of grafts; these graphs are presented with 95% confidence interval bars.


    Results
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 
There were 3 of 93 patients (3.2%) with early deaths and 2 of 93 (2.2%) with late deaths, and none were related to the BJV grafts. Perioperative deaths occurred in patients with absent pulmonary valve syndrome, truncus arteriosus, and type IV pulmonary atresia, which were due to low cardiac output. The two late deaths were caused by respiratory obstructive disease (preterm infant, esophageal atresia, status after repair of tetralogy of Fallot) and myocardial failure (after correction of complex pulmonary atresia with right ventricular failure).

As of June 2004, with a mean follow-up of 20.3 ± 5.8 months, 86.4% and 88.6% of patients were free from BJV reintervention and reoperation, respectively. Reinterventions on 11 BJVs were performed because of stenosis at the anastomotic site (five times at the distal anastomosis, two times at the proximal, and four times at both levels). One 8-mm BJV implanted in a neonate (2.5 kg) for truncus arteriosus got relatively stenotic for the size of the patient (11 kg) and needed explantation. Although balloon dilatation was attempted in most of these patients, some relief was obtained in only 4 for a mean duration of 5.5 months (durations, 11, 4, 3, and 4 months for each of the 4 patients). Two patients, 1 with a 16-mm BJV and 1 with a 20-mm BJV continued to be observed 8.5 months after balloon dilatation, each for proximal anastomotic site stenosis. Balloon dilatation failed in most cases because of the elastic character of the stenosis with immediate recoil after deflation or a floating membrane after successful dilatation.

Eight patients needed nine replacements of BJVs because of stenosis 15.5 ± 5.6 months after primary repair, whereas one 8-mm graft was replaced 21 months postimplantation after the patient outgrew the BJV. Of the surviving 78 BJV grafts (excluding the 10 explanted grafts), 61 (78.2%) had echocardiographic estimated mean gradients of <20 mm Hg. Seventeen of 78 grafts (21.8%) had estimated mean gradients of 24.3 ± 4.4 mm Hg without evidence of morphologic stenosis. Seventy-two patients (92.3%) had a trace of or mild BJV valve insufficiencies, and 6 patients (7.7%) had moderate valve insufficiencies. The degree of insufficiency did not progress over time. One patient (with a 20-mm BJV) had graft leaflet endocarditis develop after a lower limb infection with staphylococcus 20 months after implantation, which lead to a temporary rise in gradients. This patient was successfully treated with antibiotic therapy. In a few patients we observed early postoperative echogenic shadow (situated near the leaflets) < 1 mm in diameter that we interpreted as a small thrombus. All of these disappeared before hospital discharge. In 1 patient this so-called thrombus measured 4 mm in diameter and was hence administered warfarin and this also regressed with time. We did not encounter major thrombosis of the BJV during our experience.

Survival of the Bovine Jugular Vein Graft
The Kaplan Meier survival curve for the BJV grafts revealed a freedom from reintervention of 91.6 ± 5.9% and 83.5 ± 8.9%, and a freedom from reoperation of 94.1 ± 5% and 85.7 ± 8.6% (% ± 95% confidence interval) at 12 and 24 months, respectively (Fig 3). For BJV > 14 mm, the freedom from reintervention was 98% (+2.0, –3.9) & 96% (+4.0, –5.4) and the freedom from reoperation was 100%, at 12 and 24 months respectively. In BJV ≤ 14 mm, it was 80.7 ± 13.9% & 63.6 ± 18.8% (freedom from reintervention) and 84.0 ± 12.9% & 63.1 ± 18.9% (freedom from reoperation) (% ± 95% CI), respectively (Fig 4). Log rank test comparing the performance of the small versus the large BJV showed a significant difference in their freedom from reintervention (p = 0.0004), and the freedom from reoperation (p < 0.0001).



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Fig 3. Kaplan Meier survival curve for all bovine jugular vein grafts. (CI = confidence interval; Reint = reintervention; Reop = reoperation.)

 


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Fig 4. Kaplan Meier survival curves for bovine jugular vein graft (BJV) sizes > 14 mm (top) versus ≤ 14 mm (bottom). {15956.618.gr7} = freedom from reoperation; {blacksquare} = freedom from reintervention. (CI = confidence interval; Reop = reoperation; Reint = reintervention.)

 
Bovine Jugular Vein Graft Failure
Ten BJV were explanted and replaced by another BJV (9 times) or homograft (1 time). One explanted BJV was 8 mm in diameter, seven of the explanted grafts were 12 mm, and two were 14 mm (Table 2). Two BJVs (16 and 20 mm) implanted during a Ross procedure developed proximal anastomotic site stenosis 8 and 12 months after implantation. They continued to remain palliated at 8.5 months after balloon dilatation (Table 2). Surprisingly, the four downsized grafts (8 mm diameter) have shown good function; three of them continue to be followed at a mean duration of 17 months after implantation. The cause for BJV obstruction in all cases has been the development of a circumferential stenotic membrane (Fig 5) at the conduit anastomotic sites (Table 2). The stenotic membrane in the explants showed the same macroscopic characteristics as that of a subaortic membrane. The graft itself maintained a pliable wall without signs of macroscopic calcification; the leaflets appeared thin and normal (Fig 6). On microscopic examination, the conduit showed a thin pseudointima, consisting of fibrin and macrophages devoid of endothelium. It also showed a giant cell reaction at the junction between the media and the adventitia [7].


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Table 2. Bovine Jugular Vein Graft Reinterventions
 


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Fig 5. (a) Membranous stenosis at proximal and (b) distal bovine jugular vein graft anastomosis site.

 


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Fig 6. Bovine jugular vein graft showing normal valve leaflets at 1 year after implantation.

 

    Comment
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 
Conduit implantation for RVOT reconstruction constitutes approximately 15% to 20% of all congenital cardiac operations at a center with a classic congenital work load. Homografts have shown the best results so far, with overall survivals of appoximately 84% and 31% at 5 and 15 years, respectively [8]. Young age at implantation, and the need for a small homograft have consistently been recognized as risk factors for accelerated failure [2, 3, 9–12]. A chronic problem pertaining to the use of homografts is the scarcity of suitably sized homografts and the consistency of its quality. Xenograft aortic or pulmonary valves and conduits have failed to match the results of the homograft valved conduits [13]. Recently the bovine jugular vein conduit (consisting of a centrally located valvular apparatus with three sinuses and three valve cusps) has been proposed as an alternative to homografts [6, 13, 14]. The valve leaflets are particularly thin and present a large area of coaptation. The conduit wall is pliable and presents good handling characteristics. The graft retains excellent elastic properties that result in significant systolic expansion, which therefore reduces mechanical stress on the valve leaflets. These properties also make the BJV more forgiving (regarding size and length discrepancies) with respect to the RVOT anatomy.

Bovine Jugular Vein Function and Survival
In our experience the BJV showed good systolic and diastolic function early postoperatively, as assessed by transesophageal echocardiography. The echocardiogram estimated gradients of as much as 20 mm Hg without any morphologic stenosis were considered acceptable. With time, the gradual increase in gradients that we have observed in some of the small BJV grafts parallel the evolution of gradients in homografts [4]. The diastolic function of the BJV valve remains excellent in all the patients in our series, and in those with slight regurgitation, it did not worsen over time. We have not encountered any instance of aneurysmal dilatation or conduit thrombosis needing explantation, as has been reported by others [14].

The freedom from BJV conduit reintervention of 91.6 ± 5.9% and 83.5 ± 8.9% at 12 and 24 months, respectively (Fig 4), is comparable with the early results of homografts [1, 15]. However, the robustness of this finding is hampered by a relatively wide confidence interval, particularly for the smaller sized grafts. A larger number of patients at risk, at longer follow-up segments, will allow us to draw more definitive comparative conclusions. However, our series presents the advantage of emanating from a single center with homogenous indications and implantation techniques, and with a prospective echocardiographic evaluation.

The freedom from reintervention or systolic dysfunction at a mean follow-up of 20.3 months was good for grafts larger than 14 mm. This group of patients showed a trend toward good results comparable with that of homografts. The freedom from reintervention was poorer for the small sizes, especially in the 12-mm group (Fig 4). However, this attrition rate still compares favorably with the rate of corresponding homografts [16, 17] and other conduits [5]. The exact reason for the early deterioration of the BJV function may be different from that of homografts. In all of our patients, we found a circumferential membrane leading to severe stenosis, similar to the one found in subaortic stenosis. The graft itself, including the leaflets, showed minimal structural deformation. The creation of local turbulence may be one of the important factors responsible for the development of the stenosing membrane. Interestingly, the four patients with downsized BJVs (to 8 mm) have functioned well. A better matching of the size of the graft to the pulmonary artery diameter may provide a solution to reduce local turbulent flow and subsequent development of the fibrotic membrane. As noted by others [14], it is likely that the relative profile of the stenotic membrane becomes critical in small conduits in comparison with larger ones, necessitating early reintervention. It is also our assumption that the plane of the valve annulus should remain perpendicular to the graft direction. A bevel that is too short results in traction on the convex part of the graft with caudal rotation of the annular plane and compression at the leaflet level. This deformation of the graft is prone to occur when a longitudinal infundibulotomy is made for insertion of the graft, as in a truncus arteriosus repair or in a Rastelli operation. Lengthening the onlay part of the graft by the addition of a patch may solve the problem. However, the implantation of the BJV in an end-to-side fashion (a technique that we later adopted) preserves the native straight configuration of the graft and results in an optimal disposition of the valve leaflets. The early obstruction of small BJV grafts remains a cause for concern. The fact that the obstruction was due to the formation of a membrane, most probably induced by turbulent flows and not by a degenerative process, should be viewed as a positive finding. The good integration of the xenograft tissue to the body, in absence of any important external reaction or calcific degeneration, could favorably impact long-term function. If the large BJV conduits continue to maintain good function over long-term follow-ups, their logistic advantages and good handling characteristics could make it an important conduit in the armamentarium for use in RVOT reconstructions.


    References
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

  1. Stark J, Bull C, Stajevic M, Jothi M, Elliott M, de Leval M. Fate of subpulmonary homograft conduits: determinants of late homograft failure J Thorac Cardiovasc Surg 1998;115(3):506-514.[Abstract/Free Full Text]
  2. Clarke DR, Bishop DA. Allograft degeneration in infant pulmonary valve allograft recipients Eur J Cardiothorac Surg 1993;7(7):365-370.[Abstract]
  3. Tweddell JS, Pelech AN, Frommelt PC, et al. Factors affecting longevity of homograft valves used in right ventricular outflow tract reconstruction for congenital heart disease Circulation 2000;102(19 Suppl 3):III130-5.
  4. Salim MA, DiSessa TG, Alpert BS, Arheart KL, Novick WM, Watson Jr DC. The fate of homograft conduits in children with congenital heart disease: an angiographic study Ann Thorac Surg 1995;59(1):67-73.[Abstract/Free Full Text]
  5. Aupecle B, Serraf A, Belli E, et al. Intermediate follow-up of a composite stentless porcine valved conduit of bovine pericardium in the pulmonary circulation Ann Thorac Surg 2002;74(1):127-132.[Abstract/Free Full Text]
  6. Dave H, Kadner A, Bauersfeld U, Berger F, Turina M, Pretre R. Early results of using the bovine jugular vein for right ventricular outflow reconstruction during the Ross procedure Heart Surg Forum 2003;5(6):390-392.
  7. Kadner A, Dave H, Bettex D, Turina MI, Prêtre R. Formation of a stenotic fibrotic membrane at the distal anastomosis of bovine jugular vein grafts (Contegra) after RVOT reconstruction J Thorac Cardiovasc Surg 2004;127:285-286.[Free Full Text]
  8. Stark J. The use of valved conduits in pediatric cardiac surgery Pediatr Cardiol 1998;19(4):282-288.[Medline]
  9. Bando K, Danielson GK, Schaff HV, Mair DD, Julsrud PR, Puga FJ. Outcome of pulmonary and aortic homografts for right ventricular outflow tract reconstruction J Thorac Cardiovasc Surg 1995;109(3):509-517.[Abstract/Free Full Text]
  10. Razzouk AJ, Williams WG, Cleveland DC, et al. Surgical connections from ventricle to pulmonary arteryComparison of four types of valved implants. Circulation 1992;86(Suppl 5):II154-8.
  11. Schorn K, Yankah AC, Alexi-Meskhishvili V, Weng Y, Lange PE, Hetzer R. Risk factors for early degeneration of allografts in pulmonary circulation Eur J Cardiothorac Surg 1997;11(1):62-69.[Abstract]
  12. Hawkins JA, Bailey WW, Dillon T, Schwartz DC. Midterm results with cryopreserved allograft valved conduits from the right ventricle to the pulmonary arteries J Thorac Cardiovasc Surg 1992;104(4):910-916.[Abstract]
  13. Breymann T, Thies WR, Boethig D, Goerg R, Blanz U, Koerfer R. Bovine valved venous xenografts for RVOT reconstruction: results after 71 implantations Eur J Cardiothorac Surg 2002;21(4):703-710.[Abstract/Free Full Text]
  14. Boudjemline Y, Bonnet D, Massih TA, et al. Use of bovine jugular vein to reconstruct the right ventricular outflow tract: early results J Thorac Cardiovasc Surg 2003;126(2):490-497.[Abstract/Free Full Text]
  15. Dearani JA, Danielson GK, Puga FJ, et al. Late follow-up of 1,095 patients undergoing operation for complex congenital heart disease utilizing pulmonary ventricle to pulmonary artery conduits Ann Thorac Surg 2003;75:399-410.[Abstract/Free Full Text]
  16. Niwaya K, Knott Craig CJ, Lane MM, et al. Cryopreserved homograft valves in the pulmonary position: risk analysis for intermediate-term failure J Thorac Cardiovasc Surg 1999;117(1):141-146.[Abstract/Free Full Text]
  17. Yankah AC, Alexi-Meskhishvili V, Weng Y, Schorn K, Lange PE, Hetzer R. Accelerated degeneration of allografts in the first two years of life Ann Thorac Surg 1995;60(Suppl 2):S71-6.



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