Asian Cardiovasc Thorac Ann 2005;13:361-365
© 2005 Asia Publishing EXchange Ltd
Mid-Term Experience with Valved Bovine Jugular Vein Conduits
Malgorzata Pawelec-Wojtalik, PhD,
Wojciech Mrówczy
ski, PhD1,
Andrzej Wodziski, PhD1,
Michal Wojtalik, PhD1,
Jacek Henschke, PhD1,
Girish K Sharma, PhD1
Department of Pediatric Radiology
1 Department of Pediatric Cardiac Surgery, Poznan University of Medical Sciences, Poznan, Poland
For reprint information contact: Wojciech Mrówczyski, PhD Tel: 48 61 849 1277 Fax: 48 61 866 9130 Email: wjmrow{at}amp.edu.pl, Department of Pediatric Cardiac Surgery, Poznan University of Medical Sciences, 27/33 Szpitalna, Poznan 60-572, Poland.
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ABSTRACT
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From June 1999 to January 2004, 43 children underwent implantation of a valved bovine jugular vein conduit and correction of complex congenital heart defects. Median age was 1.98 years (range, 11 days – 13.3 years). There were 7 early deaths (16.3%) unrelated to conduit failure or thrombosis. Median follow-up of 36 survivors was 24 months (range, 1–48 months, quartile range, 12–48 months), total follow-up was 78 patient-years. There were 3 late deaths (8.3%) due to infection, pulmonary thromboembolism, and sudden cardiac arrest after re-operation to repair a right ventricular outflow tract aneurysm. There were 2 conduit explantations due to dysfunction and suspected endocarditis. Three patients underwent balloon dilatation of distal stenoses. The mean peak gradient through the pulmonary anastomosis was 15 mm Hg (range, 3–42 mm Hg) among patients free from re-intervention. No severe valve regurgitation was observed. Freedom from re-intervention was 72% at 48 months. This conduit remains a good alternative to homografts. Causes of distal stenosis must be clarified, guidelines for prophylactic anticoagulation must be created, and the role of percutaneous balloon dilatation established.
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INTRODUCTION
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The introduction of the Contegra valved bovine jugular vein conduit (Medtronic, Inc., Minneapolis, MN, USA) in 1999 gave rise to a number of studies on this novel means of right ventricle outflow tract (RVOT) reconstruction in children. Early results were promising.1–4 However, recent studies indicate potential drawbacks connected with implantation of this conduit.5–6 These conflicting results are not surprising with the experience of longer follow-up, and might be attributable to differences in congenital heart disease spectra, surgical techniques, or solutions to conduit-related problems in various studies. Thus, further observations are necessary to assess medium and long-term outcome and to recognize possible complications. This report describes experience with the Contegra conduit implanted by a single surgeon over a 5-year period at one institution.
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PATIENTS AND METHODS
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This study was a prospective, non-randomized, non-blinded clinical trial performed as part of a multicenter investigation controlled by the Federal Drug Administration. Between June 1999 and January 2004, 43 children (26 males and 17 females) underwent correction of complex congenital heart defects with reconstruction of the RVOT using a Contegra conduit. Median age was 1.98 years (range, 11 days – 13.3 years); 6 patients were neonates, 7 were infants, and 30 were older children including 13 over 4-years old. Median body weight was 12 kg (range, 2.3–52 kg), and body surface area was 0.5 m2 (range, 0.18–1.5 m2). The Ethics Committee on Human Research approved the study protocol. Informed consent was obtained from the parents or representatives.
Surgery was performed under general anesthesia through a midline sternotomy. Both venae cavae were cannulated through the right atrium or directly. Moderately hypothermic (24–28°C) cardiopulmonary bypass was instituted. Aortic arch anomalies were addressed under deep hypothermia and total circulatory arrest. The bypass apparatus was primed with blood containing fluids in the case of patients < 20 kg and hematocrit < 40%. Aortic crossclamping and multiple doses of St Thomas’ Hospital crystalloid cardioplegia were employed in all patients (initial dose: 20 mL·kg–1, then 10 mL·kg–1 every 30 min). Correction techniques depended on the particular defects present, but Contegra implantation was used for RVOT reconstruction in all procedures. Distal anastomosis was performed before declamping the aorta, proximal anastomosis was carried out on a beating heart. Continuous polypropylene sutures were used. The graft valve was positioned as distally as possible. After the operation, all patients were transferred to the intensive care unit, and anticoagulation with continuous heparin infusion (50 IU·kg–1 every 4 hours) was carried out for 2 days. Subsequently, oral aspirin (5 mL·kg–1) was administered throughout the follow-up. Follow-up examinations were scheduled at 1, 3, and 6 months and then yearly. A physical examination and assessment of conduit function by transthoracic Doppler echocardiography were carried out. The peak pressure gradient across the distal anastomosis and conduit valve insufficiency (4-level scale) were measured.
The normality of variable distribution was assessed by the Shapiro-Wilk test. A p value < 0.05 indicated the lack of a normal distribution in all studied variables. Thus, median, quartiles, and ranges described the variables. The Kaplan-Meier method was applied to assess the survival rate and probability of freedom from conduit-related events (need for redo surgery or balloon dilatation).
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RESULTS
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Congenital heart defects in the studied population are shown in Table 1
. Contegra implantation was preceded by other cardiac procedures in 13 patients: 10 underwent a modified Blalock-Taussig anastomosis, including one with bilateral systemic-to-pulmonary shunts; aortic commissurotomy was carried out in 2; and correction of coarctation of the aorta and ventricular septal defect closure was performed in one. One patient had suffered idiopathic intracranial hemorrhage complicated by sepsis and aortic valve endocarditis after a neurosurgical procedure. Another child developed Kawasaki disease with endocarditis that caused severe aortic valve incompetence. Both underwent a rescue Ross procedure because of acute left ventricular failure.
There were 7 early deaths (16.3%) unrelated to conduit failure or thrombosis. These children, all < 4-years old, died from low cardiac output syndrome complicated by pneumonia and sepsis, despite optimal medical therapy. Extracorporeal membrane oxygenation was not available. The autopsies revealed patent grafts and ischemic changes in the myocardium. Table 2 shows early complications and procedure-related morbidity. One child required a bidirectional shunt because of intractable right ventricular failure and inability to wean from bypass after correction of double-outlet right ventricle. Pulmonary complications, sepsis, and delayed sternal closure were more frequent among younger patients with complex defects.
The median follow-up of the 36 survivors was 24 months (range, 1–48 months; quartile range, 12–48 months), total follow-up was 78 patient-years. There were 3 late deaths (late mortality, 8.3%). The survival rate at 48 months was 91%. A child with truncus arteriosus and DiGeorge syndrome died 3 months postoperatively from pneumonia, sepsis, and multi-organ failure. Another patient died suddenly 4 months after a Ross procedure; the autopsy revealed pulmonary thromboembolism. A patient with a complex aortic valve defect underwent successful re-operation for pseudoaneurysm of the RVOT one year after the primary Ross correction. He died of sudden cardiac arrest one day after the procedure. There were 2 re-operations unrelated to conduit dysfunction: a patient with transposition of the great arteries and pulmonary stenosis required reconstruction of the mitral valve (2.5 years after Contegra implantation), and another with pulmonary stenosis underwent epicardial pacemaker implantation 11 months postoperatively because of complete atrioventricular block. Most children were in New York Heart Association functional class I during follow-up. A patient with tetralogy of Fallot (TOF) and absent pulmonary valve syndrome was bed-ridden due to ventilator dependency. He was in functional class IV from early follow-up. The mean New York Heart Association functional class at the end of follow-up among the 27 patients free from re-intervention was I (range, I II).
First-degree valve insufficiency of the conduit was observed throughout the follow-up. Second-degree regurgitation occurred in 13.9% of patients at 1 month postoperatively and in 31.25% after 3 years. Third- and 4th-degree regurgitation were not encountered. The median peak pressure gradient in the distal anastomosis was < 16 mm Hg during follow-up (Figure 1). Most children had a gradient < 30 mm Hg throughout the study period. Gradients exceeding 45 mm Hg were observed after 6–12 months in 5 patients, and after 3 years in one; they underwent various re-interventions. Freedom from re-intervention is shown in Figure 2. There were 4 re-operations due to conduit dysfunction. In 2 patients (aortic stenosis/insufficiency; TOF), the conduit was removed and replaced with a homograft (after 11 and 21 months) because of severe distal graft stenosis and suspicion of endocarditis on echocardiography. Another child with TOF presented with stenosis of the implant 12 months postoperatively; 2 degenerated leaflets were removed. A patient with RVOT pseudoaneurysm underwent repair with a Dacron patch to replace the proximal part of the conduit. During surgery, it was noted that the valve was unchanged and there was no distal stenosis, which was confirmed later at autopsy. Balloon angioplasty was performed in 3 patients (truncus arteriosus; aortic stenosis/insufficiency; TOF) due to distal graft stenosis after 13, 14, and 38 months. It was successful in 2 cases where a decrease of peak gradient was observed (from 71 to 28 mm Hg, and from 95 to 12 mm Hg). The gradient did not change significantly (51 vs. 45 mm Hg) in the patient with TOF. All dilatations were performed in children < 4-years old with ventriculoarterial discordance.
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DISCUSSION
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The outstanding properties of glutaraldehyde-fixed bovine conduits noted in most short-term studies confirm its suitability for RVOT reconstruction.1–4,7 Longer follow-up is still limited, and the number of patients with Contegra devices varied from 20 to 71 in recent reports.2,4–5,7 Mean follow-up ranged from 10.2 to 19.8 months.5–6 The follow-up in our series is one of the longest, but the power of the study is diminished by early patient attrition with only 36 on longer follow-up. Early mortality was higher than that observed in other centers (16.3% vs. 9.7% and 7%).2,8 There have also been reports of no postoperative mortality.1,3,6–7 However, the mean age was much higher than in centers operating on complex defects in infancy.1–2,4–5,7–8 Differences in mortality rates might be due to patient selection.1 One of the virtues of bovine jugular vein conduit is its availability in various sizes, which prevents over-sizing that can promote early graft dysfunction by compression or kinking.9 Nevertheless, a degree of upsizing cannot be avoided when the 12-mm Contegra is implanted in neonates. Besides diameter discrepancy, the height of the integral valve can necessitate tailoring a longer conduit than is ideal, although this was usually not problematic.3
Anticoagulation was instituted in all patients. Currently, heparin is not prescribed in all centers; sometimes low-molecular-weight heparin is used.6 We believe that our strategy helped to avoid the early thrombotic events encountered by others.6,8 Complement activation by glutaraldehyde-treated grafts and the presence of preformed xenograft antibodies might give rise to clot formation.10–12 Thus, prolongation of prophylaxis beyond the early postoperative period is essential because of the slow endothelialization of this conduit. Most centers prescribe aspirin until 6 months after implantation.1,6 The uncertainty of complete endothelialization of the graft and the possibility of non-laminar flow at the distal anastomosis, favoring thrombus formation, forced us to maintain antiplatelet treatment during the entire follow-up. One late death (after 3 months) in our study was probably caused by pulmonary thromboembolism despite anticoagulation, but it is not certain whether the graft was the source of the emboli. In the study by Boudjemline and colleagues,8 a 16-month-old patient died of conduit thrombosis and multiple pulmonary emboli 2 weeks after Contegra implantation; this proven conduit-related death indicates the necessity of prolonged anticoagulation therapy.
Intact conduit function is vital for an uneventful long-term outcome and the patient’s quality of life. Short-term studies show good functioning of this conduit.1,3 Reports of only low-grade (trivial and mild) conduit valve regurgitation are in agreement with our results.1–4,6,7 However, severe valve insufficiency due to graft stenosis was observed in 6 patients by Meyns and colleagues.5 Mean peak pressure gradients not exceeding 16 mm Hg were described in several studies.1,3,7 However, higher peak gradients were encountered during longer observations.2,4–5 The nature of this phenomenon is still unclear. Superfluous proliferation of neointima at the distal connection (observed in explanted conduits), probably due to unfavorable blood flow, might be the explanation.13 Despite the excellent properties of the bovine conduit, there is a potential mismatch between the compliance of the Contegra and the pulmonary artery, especially in neonates. This discrepancy may influence graft patency.14 There is also an immunological hypothesis.15 Inflammatory cells in explanted grafts (8 and 12 months postoperatively) were found on microscopic examination.13 We previously reported significantly increased numbers of activated T cells 12 months after implantation of a Contegra prosthesis.16 This might have been involved in the conduit failure in our 5 patients, as graft dysfunction occurred at approximately 1 year after the operation; however, the small number of patients precludes any statistical analysis.
Continuous progression of distal stenosis has been described, with a 50% chance of severe narrowing at 24 months after Contegra implantation.5 In contrast, Breymann and colleagues2 reported 90% freedom from explantation. Patients in our study had a 78% probability of freedom from re-intervention at the same time. There was only one patient with a pressure gradient of 30–45 mm Hg after unsuccessful angioplasty. The roles of patient age and conduit size as factors accelerating graft dysfunction are uncertain.5,8 The majority of graft failures (3 redo surgery, 1 balloon dilatation) in our series occurred in older patients with larger graft sizes. Our good results in younger children are in contrast to experience from Belgium.5 Different surgical techniques might be an explanation for this discrepancy as 30% of homograft failures can be attributed to technical issues.9 Narrowing of the pulmonary anastomosis is not the only adverse event encountered after Contegra implantation. The presence of a prosthesis can promote RVOT aneurysm formation.6,17 This complication was observed in one of our patients, but no distal stenosis, intact morphology of the valve, and a wide pulmonary anastomosis were found. The aneurysm might have been caused by improper suturing of the graft to the muscle of the right ventricle.
Three cases of Contegra endocarditis have been described.3,5 Two children had echocardiographic signs of endocarditis in our study; graft culture was positive in one. Microscopic examination of the other specimen revealed an inflammatory process excluding endocarditis. It seems that exact diagnosis of the process underlying graft failure can sometimes be difficult. The usual treatment for a failing conduit is explantation and replacement with a homograft when the peak gradient exceeds 50 mm Hg and there is significant elevation of right ventricular pressure.5–6,17 This was carried out in 2 of our patients. One child underwent removal of 2 degenerated valve leaflets through a small incision in the graft. This was the first redo surgery and the behavior of the Contegra during adhesion release was unknown, so a less invasive procedure was chosen. The conduit remained patent during the rest of the follow-up, and moderate pulmonary insufficiency was observed. Balloon dilatation is the second option for conduit stenosis.5–6 It offers potentially lower mortality than redo surgery and can be repeated. It was successful in 2 of the 3 cases in this study. The Contegra proved its efficacy in two rescue procedures due to aortic valve endocarditis, and this conduit remains a good alternative to homografts. However, a longer follow-up is needed, causes of distal stenosis should be clarified, guidelines for prophylactic anticoagulation must be created, and the role of percutaneous balloon dilatation should be established.
This work was funded by Medtronic, Inc., Minneapolis, MN, USA.
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REFERENCES
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- Bove T, Demanet H, Wauthy P, Goldstein JP, Dessy H, Viart P, et al. Early results of valved bovine jugular vein conduit versus bicuspid homograft for right ventricular outflow tract reconstruction. Ann Thorac Surg 2002;74:536–41.[Abstract/Free Full Text]
- Meyns B, Van Garsse L, Boshoff D, Eyskens B, Mertens L, Gewillig M, et al. The Contegra conduit in the right ventricular outflow tract induces supravalvular stenosis. J Thorac Cardiovasc Surg 2004;128:834–40.[Abstract/Free Full Text]
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ABSTRACT
INTRODUCTION
