Eur J Cardiothorac Surg 2007;32:209-214. doi:10.1016/j.ejcts.2007.04.036
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved
Compared fate of small-diameter Contegras® and homografts in the pulmonary position
Nicodème Sinzobahamvyaa,*,
Boulos Asfoura,
Margaretha Boscheinenb,
Joachim Photiadisa,
Christoph Finkc,
Ehrenfried Schindlerd,
Victor Hraskaa,
Anne Marie Brechera
a Department of Pediatric Thoracic and Cardiovascular Surgery, Congenital Cardiac Center (‘Deutsches Kinderherzzentrum’), Sankt Augustin, Germany
b Department of Pediatric Cardiology, Congenital Cardiac Center (‘Deutsches Kinderherzzentrum’), Sankt Augustin, Germany
c Department of Cardiac Intensive Care, Congenital Cardiac Center (‘Deutsches Kinderherzzentrum’), Sankt Augustin, Germany
d Department of Anesthesiology and Critical Care Medicine, Congenital Cardiac Center (‘Deutsches Kinderherzzentrum’), Sankt Augustin, Germany
Received 16 February 2007;
received in revised form 25 April 2007;
accepted 30 April 2007.
* Corresponding author. Address: Deutsches Kinderherzzentrum, Asklepios Klinik, Arnold-Janssen-Strasse, 29 53757 Sankt Augustin, Germany. Tel.: +49 2241 249601; fax: +49 2241 249602. (Email: n.sinzobahamvya{at}asklepios.com).
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Abstract
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Objective: This study analyzes whether small-diameter Contegras behave in the same way as small-diameter homografts, when implanted for the first time in pulmonary position. Methods: Small-diameter conduits include 12 and 14 mm Contegras and 8–14 mm homografts. Graft dysfunction is defined as right ventricular outflow tract obstruction with peak echo-Doppler gradient > 40 mmHg, or grade III/IV graft regurgitation. Graft failure is defined as need for conduit replacement or need for catheter or surgical reintervention. Thirty-eight patients who received small Contegras (n
= 25) and small homografts (n
= 13) from October 2002 to end December 2006 were studied. The most frequent indication was pulmonary atresia and ventricular septal defect (n
= 20; 10 associated with major aorto-pulmonary collateral arteries), followed by truncus arteriosus (n
= 12). Most patients’ characteristics were comparable except that recipients of homografts were smaller (p for body area = 0.014). Survival, freedom from graft dysfunction, failure and explantation were estimated by the Kaplan–Meier method. The log-rank test was used to compare outcomes. Results: There were three early and four late deaths. No death was graft related. Survival was 80 ± 8.2% for patients with Contegras and 77 ± 11.7% for those with allografts: p
= 0.82. Mean follow-up duration is 22 ± 16 months. Freedom from dysfunction for Contegra conduits decreased in the first 6 months and stabilized at 58 ± 11% from month 14. For homografts it decreased only 1 year after implantation, down to 35 ± 19.7% from month 31: p
= 0.61. Freedom from Contegra failure diminished the first 16 months to level out at 57 ± 13%. No homograft failed the first 2 years. With a p-value of 0.14, homografts tended to fail less frequently. Five grafts were explanted. Freedom from explantation was similar (p
= 0.98): 90 ± 6.7% for Contegras and 75 ± 21.6% for homografts at year 3. Conclusion: In the first 4 years after pulmonary implantation of small-diameter Contegras and homografts, the fate of both conduits was statistically similar, in spite of different behavior. As Contegra is ‘off-the-shelf’ available, it constitutes a sound alternative to homograft for right ventricular outflow tract reconstruction in neonates and infants.
Key Words: Valved conduits • Contegra • Homograft • Right ventricular outflow tract reconstruction
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1. Introduction
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Shortage of small-diameter valved homografts forces pediatric cardiac surgeons to look for alternative conduits for early repair of congenital lesions. The bovine jugular vein graft (Contegra of Medtronic Inc., Minneapolis, MN, USA) introduced in clinical practice in 1999 was first used in our unit in October 2002. We continued to resort to allografts according to their availability. Until end December 2006, overall 94 Contegras and 35 homografts have been concomitantly implanted in pulmonary position.
According to our previous experience [1], small homografts with z-value at least two constitute the best-valved conduits in the pulmonary position for neonates and young infants. Publications on Contegra usually include all ages of patients and all graft sizes (12–22 mm). Whether small sized Contegras behave the same way as small sized allografts has been not analyzed so far. This study compares durability and function of these small-valved conduits used for right ventricular outflow tract (RVOT) reconstruction in very young children, in the first 4 years after implantation.
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2. Patients and methods
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2.1 Definitions
Only patients who received grafts in pulmonary position as first valved conduits are considered. Small-diameter Contegras are the 12 and 14 mm internal annular diameter Contegras. Accordingly, the size of small-diameter allografts ranges from 8 to 14 mm in this study. Graft size was normalized to the patient's body surface area: z-value. Early survivors are patients who were discharged from hospital and who survived at least 30 days after operation. Graft dysfunction is considered to be present in case of peak echo-Doppler gradient greater than 40 mmHg by two-dimensional echocardiography, at any RVOT/conduit level or if grade III/IV graft (pulmonary) regurgitation is detected. Graft failure is defined as the need for conduit replacement or the need for interventional dilatation and/or stenting for right ventricular outflow tract obstruction (RVOTO). Excluded are catheter reinterventions for narrowing (hypoplasia) of pulmonary arteries not involving the distal graft anastomosis.
2.2 Patients – diagnoses
From October 2002 to end December 2006, a total of 38 patients received small-valved conduits as first valved graft in the pulmonary position. Table 1A shows the different sizes of the 25 Contegras and the 13 pulmonary (n
= 5) and aortic (n
= 8) homografts. The great majority (55% = 21/38) were 12 mm in diameter with a mean z-value of 2.6. No supported Contegra model was used. The most frequent indication/lesion for RVOT reconstruction (see Table 1B) was pulmonary atresia and ventricular septal defect (PA/VSD): 52% = 20/38, followed by truncus arteriosus: 32% = 12/38. Common was PA/VSD association with major aorto-pulmonary collateral arteries (PA/VSD/MAPCAs, n
= 10), conduit being implanted after unifocalization as primary (n
= 7) or staged (n
= 3) procedure. The main patients’ characteristics according to type of conduit are given in Table 2
to allow comparison. In particular, graft z-value was statistically similar (p
= 0.44), even if patients who received homografts were smaller (p for body area = 0.014) and somewhat younger (p
= 0.09) at the time of operation. Age ranged from 5 to 780 days. Overall there were 11 neonates, five among them in the homograft group.
2.3 Surgical technique and management
Conduits were implanted with moderate hypothermic cardiopulmonary bypass and intermittent cardioplegic cardiac arrest using St-Thomas II (n
= 34) or Bretschneider (n
= 4) solution. Aortic cross-clamping time, similar (p
= 0.79) for both types of conduits ranged from 20 to 187 min (Table 2). Guidelines from Medtronic for rinsing Contegras and from homograft banks for thawing homografts were meticulously followed. Both pulmonary arteries were dissected/mobilized to the hilum and the pulmonary artery bifurcation or the unifocalized pulmonary artery was then opened to such extend to match the diameter of the chosen conduit. Grafts were cut as short as possible from valve commissures at distal end. They were placed as lateral and left as possible. The distal anastomosis was usually performed under cardioplegic cardiac arrest, using 7/0 or 6/0 continuous running polypropylene suture with an everting technique. The proximal anastomosis was performed on the beating heart. To cover the ventriculotomy, proximal tube tissue of implant (Contegra) or a hood made of pericardium (Homograft) was used. To facilitate chest re-entry, if reoperation became necessary, heart was routinely covered by a Gore-Tex membrane. It is to be noted that of the 10 cases with PA/VSD/MAPCAs, VSD was left open totally (n
= 4) or partially (fenestrated patch) (n
= 2) in six patients. Comprehensive Aristotle score for each procedure varied between 11 and 21. The score tended to be higher in patients who received Contegras (p
= 0.14, see Table 2). On 10 occasions, the sternum was closed secondarily. Two patients needed immediate extracorporeal membrane oxygenation (ECMO) support, the first because of respiratory failure (PA/VSD/MAPCAs), the second because of acute right ventricular failure (PA/Ebstein's anomaly), both in the Contegra group. Five patients suffered from several episodes of pulmonary hypertensive crises. For two, NO therapy was required for more than 3 days. The median duration of postoperative endotracheal intubation for early survivors was 4 days. It was similar for both types of implants: p
= 0.39 (Table 2). Patients were routinely treated with aspirin 2 mg/kg daily for 3 months.
2.4 Follow-up: evaluation of conduit function
Hospital survivors were seen in outpatient clinics by pediatric cardiologists at least every 6 months for the first 2 years. Follow-up for the Contegra group of patients was a part of an evaluating program for the whole cohort of Contegra implants. As previously reported [1], echo-Doppler peak pressure gradient was calculated using the simplified Bernoulli equation, and graft insufficiency was graded by mapping the dimensions of the regurgitation jet. If a problem was detected or suspected, cardiac catheterization and angiocardiography was performed. Indication for conduit replacement was grade 3/4 regurgitation with dilatation of right ventricle, or RVOT obstruction not amenable for interventional dilatation, with right ventricle pressure at least 75% of the systemic pressure. Interventional dilatation was considered when peak echo-Doppler gradient was >40 mmHg.
2.5 Data analysis
Data were collected as part of a protocol after implantation for the Contegra patients and retrospectively for the homograft group. Emphasis was put on echocardiography, cardiac catheterization and findings at reintervention. The actual assessment took place from November 2006 to January 2007. Continuous variables are expressed as mean ± standard deviation (SD) and median with range (minimum–maximum). Variables for the two groups of conduits are compared using two-tailed unpaired t-test. Kaplan–Meier curves for actuarial survival, freedom from dysfunction, failure and explantation of conduits are calculated using the GraphPad Prism (San Diego, CA, USA). End points are time of death, first diagnosis of conduit dysfunction, interventional or surgical reintervention and conduit replacement, respectively. The log-rank test is used to estimate the statistical difference between the two types of conduits. The significance level is set at a p value of 
0.05.
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3. Results
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3.1 Survival
There were three early deaths: early mortality of 8% for both conduit groups. The first, a 5-day old neonate with PA and Ebstein's anomaly of the tricuspid valve underwent biventricular repair with RVOT reconstruction by means of a 12 mm Contegra. Because of elevated pulmonary artery pressure, this was observed to start to dilate with weaning from cardio-pulmonary bypass; it was then wrapped into a Gore-Tex sleeve. ECMO assistance was required because of acute right ventricular failure. But it had to be discontinued on the third postoperative day, due to progressive cerebral hemorrhage. The second case was a 33 days infant with truncus arteriosus type II who received a 10 mm aortic homograft. He suffered from intractable recurrent pulmonary hypertensive crises and died on postoperative day 3. The last patient, aged 5 months, with PA/VSD/MAPCAs and associated DiGeorge syndrome, underwent one stage repair, with unifocalization, VSD partial closure and implantation of a 12 mm Contegra. Low cardiac output syndrome ensued. He died after 12 days from multi-organ failure.
Four patients died late, all in the first postoperative year. Details are given in Table 3
. No death was graft related. Actuarial survival was similar (p
= 0.82) for both Contegra (80 ± 8.2% beyond 1 year) and homografts (77 ± 11.7%) recipients.
3.2 Follow-up: freedom from graft dysfunction
Follow-up is 100% complete. The mean duration of observation for all early survivors is 22 months ± 16 months. It is not statistically different (p
= 0.39) for both types of conduits (see Table 2). In this period, heart catheterization and angiocardiography was performed 32 times in 16 patients, most (n
= 16) in seven cases of PA/VSD/MAPCAs.
Freedom from dysfunction decreased rapidly in the first 6 months, slowly thereafter to stabilize from month 14 at 58 ± 11% for Contegra conduits (Fig. 1
). It remained unaffected the first year for homografts, to progressively decrease afterwards down to 35% ± 19.7% from month 31. Rate of dysfunction of both grafts was not statistically different: p
= 0.61. Dysfunction (Table 4
) was due to obstruction (n
= 9) or to regurgitation (n
= 4) with aneurysmal conduit dilatation in two Contegra cases.
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Fig. 1. Kaplan–Meier estimate of freedom from graft dysfunction after implantation of small-diameter 25 Contegras and 13 homografts. Vertical bars represent standard error of the mean (SEM).
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3.3 Freedom from graft failure
Interventional dilatation (with stent insertion on seven occasions) was required to treat obstruction in nine cases. This allowed us to postpone surgical reintervention for five patients beyond the date of last assessment. One homograft was replaced without prior catheter intervention.
Freedom from failure for Contegra conduits decreased continuously the first 16 months to level out at 57 ± 13% (Fig. 2
) the following 2 years. No homograft failed the first 2 years. With a p value of 0.14, homografts tended to fail less frequently than Contegras.
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Fig. 2. Kaplan–Meier estimate of freedom from graft failure after implantation of small-diameter 25 Contegras and 13 homografts. Vertical bars represent standard error of the mean (SEM).
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3.4 Freedom from graft explantation
Three Contegras and two homografts have been replaced. Table 5
gives underlying lesions and type of second implant. Contegras were grossly dilated and no calcification was detected. Homografts had shrunk and were diffusely calcified. Contegras were used to replace homografts. Vice versa, homografts were implanted in the place of Contegras. As shown by Fig. 3
, fate of both grafts was similar: p
= 0.98, with freedom from explantation at year 3 of 90 ± 6.7% for Contegras and 75 ± 21.6% for homografts.
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Fig. 3. Kaplan–Meier estimate of freedom from graft explantation after implantation of small-diameter 25 Contegras and 13 homografts. Vertical bars represent standard error of the mean (SEM).
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3.5 Graft function at last follow-up
Of the 31 survivors, 26 have still their initial conduit. For the 18 Contegra grafts, echocardiography shows normal function in 2, regurgitation Grade 1 in 11 and Grade 2 in 5. One patient, scheduled for reintervention, has a 47 mmHg peak echo-gradient at the distal anastomosis. At this level, two other patients exhibit 30–39 mmHg gradients. For the eight allografts, regurgitation is Grade 1 in 3, Grade 2 in 2 and Grade 3 in 2. One patient has no regurgitation but gradient of 28 mmHg through the implant. At the last follow-up, only one patient has a gradient above 30 mmHg (39 mmHg) across the homograft.
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4. Discussion
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To date there is no prospective randomized controlled study to compare function and durability of Contegra against homografts. Current shortage of small-diameter allografts would render this trial difficult to undertake. The multi-institutional prospective study from the Congenital Heart Surgeons Society [2] examined risk factors for failure or dysfunction of homografts, Contegras, decellularized allografts and porcine heterografts initially implanted in pulmonary position in patients aged less than 2 years. But patients in whom VSD was not totally closed (8 in our study) were excluded. Bové et al. [3] retrospectively compared 41 Contegras and 36 surgically downsized bicuspid pulmonary homografts used for RVOT reconstruction for patients aged 6 days to 13 years. Four of these grafts were implanted as second-valved conduits replacing degenerated first homografts. Boethig and colleagues [4] also retrospectively compared 52 homografts, 31 porcine xenografts and 108 Contegras. But the three patient cohorts were operated in successive periods, starting with the homograft cohort. Patients of all ages and consequently all graft sizes were included. This work is the first to compare all small sized homografts and Contegras implanted as first RVOT valved conduit over the same time and in the same unit.
As shown in Table 2, the two groups of patients are not quite comparable. The number of homografts is twice lower. This is due to the on-going shortage of small-diameter allografts. We always tried our best to get some for the very small (<2.5 kg) neonates, assuming that the 12 mm Contegra might reveal itself not only to be too large but also too long. Accordingly, body surface area of homografts recipients is significantly smaller (p
= 0.014) and age tends to be younger (0.09). There is also relatively more cases of MAPCAs unifocalization in the Contegra group (9/25) than in the homograft group (1/13): p
= 0.12. Nevertheless other parameters are not statistically different, in particular, the conduit z-value, so that the two types of small-diameter grafts may be compared. But this work is still hampered by the small number of patients and the heterogenicity of cardiac lesions requiring implantation of small-valved conduits, so that results have to be accepted with caution.
This study shows similar (not different) durability and function in the first 4 years of both types of small-valved conduits with equivalent patients’ survival, freedom from graft dysfunction, failure and explantation, p value ranging from 0.14 to 0.98. This finding is in accordance with the two above-mentioned retrospective studies [3,4] that also concluded to comparable outcomes in different sets of patients. However, conduit behavior somewhat varies as illustrated by Tables 4 and 5. Noteworthy is aneurysmal dilatation in two cases of 12 mm Contegra, absence of any calcification in the three explanted Contegras and its presence in the two replaced allografts. It is also to be noted that Contegras tended to fail earlier. But interventional dilatation allowed to prolong their lifespan so that freedom from explantation was identical (p
= 0.98) for both types of conduits. Interestingly, no graft was explanted after unifocalization.
Among the factors limiting the longevity of valved conduits, especially homografts and Contegras, small size of the graft is the most frequently cited critical factor [1,5–7]. Conduit z-value is crucial. Following Tweddell and coauthors [5], we demonstrated [1] that a z-value less than 2 was a risk factor for homograft failure and dysfunction. Karamlou for the Congenital Heart Surgeons Society [2] recently indicated that pulmonary valved conduit durability can be improved by using grafts with z-scores between 1 and 3. With the exception of one pulmonary homograft (Table 1A), all other conduits in this study had z-value above 1. This may explain similar outcomes, regardless of indication for graft implantation.
In this series, Contegra was regularly used in cases with stenosis of peripheral pulmonary arteries and pulmonary hypertension, in particular after MAPCAs unifocalization. There were three instances of Contegra dilatation, but none in the PA/VSD/MAPCAs group. Most authors recommend to implant aortic homograft in such conditions and to renounce the bovine jugular vein conduit, as this is intended to function under low pressure. Maybe supported Contegra models would be indicated in such condition. In view of the shortage of small-sized homografts, our experience indicates that the alternative use of Contegra in such setting is justified. This observation requires further investigation and assessment.
In spite of the shortcomings of this study, we may conclude that in the first 4 years after pulmonary implantation of small-diameter Contegras and homografts, the fate of both types of conduits, was statistically not different. As Contegra is ‘off-the-shelf’ available, it constitutes an attractive valuable alternative to homograft for RVOT reconstruction in neonates and infants. Further observation is needed to see whether the fate of the two grafts remains similar in longer follow-up.
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References
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- Sinzobahamvya N, Wetter J, Blaschczok HC, Cho MY, Brecher AM, Urban AE. The fate of small-diameter homografts in the pulmonary position. Ann Thorac Surg 2001;72:2070-2076.[Abstract/Free Full Text]
- Karamlou T, Blackstone EH, Hawkins JA, Jacobs ML, Kanter KR, Brown JW, Mavroudis C, Caldarone CA, Williams WG, McCrindle BW, the Pulmonary Conduit Working Group for the members of the Congenital Heart Surgeons Society Can pulmonary conduit dysfunction and failure be reduced in infants and children less than age 2 years at initial implantation?. J Thorac Cardiovasc Surg 2006;132:829-838.[Abstract/Free Full Text]
- Bové T, Demanet H, Wauthy P, Goldstein JP, Dessy H, Viart P, Devillé A, Deuvaert FE. Early results of valved bovine jugular vein conduit versus bicuspid homograft for right ventricular outflow tract reconstruction. Ann Thorac Surg 2002;74:536-541.[Abstract/Free Full Text]
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- Tweddell JS, Pelech AN, Frommelt PC, Mussatto KA, Wyman JD, Fedderly RT, Berger S, Frommelt MA, Lewis DA, Friedberg DZ, Thomas Jr. JP, Sachdeva R, Litwin SB. Factors affecting longevity of homograft valves used in right ventricular outflow tract reconstruction for congenital heart disease. Circulation 2000;102(Suppl. III):130-135.
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Abstract
1. Introduction
