HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Toru Ishizaka Richard G. Ohye Takaaki Suzuki Eric J. Devaney Edward L. Bove Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ishizaka, T. Articles by Bove, E. L. Search for Related Content PubMed PubMed Citation Articles by Ishizaka, T. Articles by Bove, E. L. Related Collections Congenital - cyanotic

Eur J Cardiothorac Surg 2003;23:715-718
© 2003 Elsevier Science NL

Premature failure of small-sized Shelhigh No-React porcine pulmonic valve conduit model NR-4000

Section of Cardiac Surgery, Division of Pediatric Cardiovascular Surgery, F7830 C.S. Mott Children's Hospital, 1500 East Medical Center Drive, The University of Michigan Health System, Ann Arbor, MI 48109, USA

Received 20 November 2002; received in revised form 7 January 2003; accepted 22 January 2003.

^* Corresponding author. Tel.: +1-734-936-4978; fax: +1-734-763-7353
e-mail: ohye{at}med.umich.edu

	Abstract

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 
Objective: Given the limited availability of small-sized cryopreserved pulmonary homografts, we implanted a series of Shelhigh No-React porcine pulmonic valve conduits (SPVC). The aim of this study was to evaluate the short-term performance following implantation. Methods: From February 2000 to September 2000, the SPVC was implanted 25 times in 24 patients in the right ventricular outflow tract (RVOT) to correct congenital anomalies. The anatomical malformations were TOF/PA in eight patients, TGA/VSD/PS in four, truncus arteriosus in four, IAA/VSD/AS or AA in four, l-TGA/VSD in two and other in two. Age at operation was 2.8±3.9 years (mean±SD), including 12 patients under 1 year. The median conduit size was 14 mm (range, 10–18). Results: At a mean follow-up of 23±5 months, two late deaths (8%) have occurred. Although they were not primarily conduit related, both showed severe conduit stenosis. Twenty-one conduits (84%) showed mild to severe conduit stenosis, regurgitation or both. Two patients underwent balloon dilatation for distal conduit stenosis. Twelve conduits (48%) in 11 patients were removed at a median of 12 months (range, 2–18 months) due to RVOT obstruction in 11 and free conduit insufficiency with pseudoaneurysm in one. The typical findings of the explanted conduits were prominent intimal peel formation at the distal anastomosis without calcification. The actuarial freedom from reintervention at 18 months was 48±10%. Conclusions: Our experience of the SPVC with the diameter of 14 mm or less has revealed a high incidence of distal conduit stenosis due to intimal peel formation resulting in early conduit failure. These findings have led us to abandon its use when other options are available.

Key Words: Right ventricular outflow tract • Conduit • Xenograft • Shelhigh No-React porcine pulmonic valve conduit

	1. Introduction

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 
Given the limited availability of small-sized cryopreserved pulmonary homografts, we implanted a series of the Shelhigh (Shelhigh Inc., Millburn, NJ) No-React^® porcine pulmonic valve conduit (SPVC). Reports of the clinical experience with the SPVC are few and results vary [1,2]. The aim of this study is to evaluate the short-term performance after its implantation at our institution.

	2. Materials and methods

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 
2.1. Patients
From February 2000 to September 2000, the SPVC was implanted 25 times in 24 patients in the right ventricular outflow tract (RVOT) to correct congenital anomalies at The C.S. Mott Children's Hospital, The University of Michigan Medical Center, Ann Arbor, MI. The anatomical malformations were tetralogy of Fallot with pulmonary atresia in eight patients, d-transposition of the great arteries with VSD and pulmonary stenosis in four, truncus arteriosus in four, interrupted aortic arch with VSD and aortic stenosis or aortic atresia in four, l-transposition of the great arteries with VSD and pulmonary stenosis in two, double outlet left ventricle in one, and complete AVSD with pulmonary stenosis and heterotaxy syndrome in one. Age at operation was 2.8±3.9 years (mean±SD), including 12 patients under 1 year. Weight at operation was 12.1±14.4 kg. The median conduit size was 14 mm (range, 10–18 mm).

The SPVC is an FDA-approved medical device and did not require institutional review board (IRB) approval or informed consent for implantation. However, appropriate IRB approval was obtained as required prior to undertaking this retrospective analysis.

2.2. Surgical technique
Thirteen conduits were inserted at the initial repair. Other portions of the repair were done according to the underlying pathology using standard techniques. The SPVC was inserted between RV and PA in all the patients, including two with corrected transposition, who underwent Senning and Rastelli operations. The remaining 12 conduits were used to replace a previously placed conduit. One patient received the SPVC twice. In this patient, the SPVC was replaced at the time of repair of a pseudoaneurysm 1 month following the primary repair of aortic atresia, VSD, and interrupted aortic arch. The distal anastomosis was performed with a continuous polypropylene suture. Five patients with tetralogy of Fallot, pulmonary atresia and aorto-pulmonary collateral arteries and one patient with truncus arteriosus and discontinuous pulmonary arteries underwent concomitant unifocalization. The distal SPVC anastomosis was made to an anterior patch augmentation of the unifocalized central pulmonary artery in four patients, and directly to the confluence in two. Branch pulmonary arterioplasty was also necessary in three other patients. The proximal end of the conduit was tailored and anastomosed to a vertical ventriculotomy with a continuous polypropylene suture.

2.3. Follow-up
Follow-up was accomplished by direct contact with the referring cardiologist and included clinical examination and Doppler echocardiography after IRB permission was obtained. Low-dose aspirin was administered as antiplatelet therapy in all of the patients following the implantation of the SPVC. When non-invasive testing showed evidence of significant conduit dysfunction, cardiac catheterization was performed. Obstruction gradients greater than 50 mmHg were considered as significant and treated by transcatheter or surgical intervention.

2.4. Statistical analysis
Data are presented as means with standard deviations. Time-related freedom from conduit failure was calculated using Kaplan–Meier estimates. Comparison of the survival data was performed using the log–rank test. All statistical analyses were performed using Stat-view statistical software version 5.0. (SAS Institute Inc., Cary, NC).

	3. Results

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 
Echocardiographic assessment at the time of hospital discharge in all the patients demonstrated that the mean peak gradient across the valve was 8±11 mmHg (median, 0; range 0–33 mmHg). The valve insufficiency, graded on a scale of 0–4, was 0 in 10, 1 in 11, 2 in two, 3 in one, and 4 in one patient.

Follow-up was complete in all patients with a mean duration of 23±5 months. There were two late deaths (8%) at 5 and 8 months following the initial procedure. One patient with truncus arteriosus and DiGeorge syndrome died of sepsis secondary to appendicitis. Although the cause of the death was not considered as primarily conduit related, the post mortem examination in this patient demonstrated severe stenosis with a luminal diameter of 3 mm (10 mm SPVC) due to significant neointimal proliferation. The other patient died after mitral valve replacement for mitral stenosis in a complete AVSD with heterotaxy syndrome. This patient's SPVC conduit had been previously successfully ballooned for distal stenosis. One patient with d-transposition of the great arteries presented with a dilated cardiomyopathy and underwent heart transplantation 12 months after the initial repair. This patient's SPVC (16 mm) showed neither stenosis nor insufficiency at the time of the transplant. Two patients (including the one patient above) underwent balloon dilatation for distal conduit stenosis. Twelve conduits (48%) in 11 patients were removed at a median time of 12 months (range, 2–18 months). The indications for reoperation were RVOT obstruction in 11 and free conduit insufficiency with pseudoaneurysm in 1. The site of the obstruction, confirmed both angiographically and at the time of surgery, was proximal (RV) in one patient, distal in seven (Fig. 1 ), and throughout the length of the conduit in 3 (Fig. 2 ). The macroscopic appearance of the explanted SPVC conduit, which had the marked concentric obstruction throughout the length of the conduit, is shown in Fig. 3 . Neointimal proliferation with circumferential laminar thrombus formation is seen. Histological examination of the typical obstruction of the distal anastomosis showed dense fibrosis with chronic inflammation without any calcification (Fig. 4 ).

View larger version (158K): [in this window] [in a new window]   Fig. 1. Right ventricular angiogram in a patient 25 months following implantation of the SPVC (14 mm) demonstrating a tight stenosis at the distal anastomosis (lateral projection).

View larger version (104K): [in this window] [in a new window]   Fig. 2. Right ventricular angiogram in a patient 9 months following implantation of the SPVC (14 mm) demonstrating stenosis throughout the entire length of the conduit (lateral projection).

View larger version (95K): [in this window] [in a new window]   Fig. 3. Marked conduit obstruction by proliferative luminal fibrous peel with laminar thrombus formation between the conduit wall and peel (viewed from below).

View larger version (115K): [in this window] [in a new window]   Fig. 4. Dense fibrosis with chronic inflammation at the distal conduit stenosis. Hematoxylin and eosin stain (x20).

View larger version (81K): [in this window] [in a new window]   Fig. 5. Distribution of conduit diameters and incidence of conduit failure.

View larger version (18K): [in this window] [in a new window]   Fig. 6. Freedom from conduit failure for the entire series, for conduits with diameter of 14 mm or less, and for conduits larger than 14 mm.

	4. Discussion

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

The SPVC is a porcine pulmonic valve. In all SPVCs implanted in this study, the distal conduit was a segment of porcine pulmonary artery. Proximally, a skirt of bovine pericardial tissue is attached to allow for tailoring to the ventriculotomy. It is pretreated with an aldehyde-based detoxification process called "No-React^®" for the purpose of reducing or delaying the onset of calcification. Although the details of the proprietary "No-React^®" process are not available, the treatment involves (1) aldehydes cross-linkage, (2) a detoxification process in solutions of natural endogenous substances, and (3) incubation with surfactant. Subcutaneous implantation of bovine pericardial strips or porcine aortic valve cusps in rats demonstrated that this "No-React^®" process has advantages in attenuating calcification and the host's inflammatory response over the conventional gultaraldehyde pretreatment [4,5].

Reports of the clinical experience with the SPVC are limited and results vary [1,2]. The discrepancies in their results may be explained by markedly different patient populations and therefore different sized conduits. Our results of the SPVC with the diameter of 14 mm or less was 50 and 17% at 12 and 18 months, which is similar to the results of Pearl et al. In addition, their histologic findings of neointimal peel formation are also similar to our experience.

Regarding the mechanism of conduit failure defined by angiography or surgical pathology, our series is notable for the absence of focal valvular stenosis, conduit kinking, sternal compression, or somatic outgrowth (defined as diffuse stenosis without a specific site of obstruction) [6,7]. Rather, extensive pseudointimal formation at the distal anastomosis or throughout the conduit was the two principal causes of conduit obstruction. The Shelhigh Company initially felt that these distal conduit stenoses were a result of endocarditis at the distal anastomosis due to thrombus formation at the suture line. At that time, they recommended an interrupted or everting suture technique to minimize thrombus formation.

Recent reports of freedom from reoperation for cryopreserved homograft have demonstrated rates of 80 and 41% at 5 and 10 years (diameter less than 15 mm) [8]; 91, 67, and 22% at 1, 2, and 5 years (mean diameter 9±2 mm) [9]; and 91, 72, and 62% at 1, 5, and 10 years (diameter 8–13 mm) [10]. Compared with these data, our results of the SPVC with the diameter of 14 mm or less are unsatisfactory. Currently, our first choice for RVOT reconstruction in neonates and infants is cryopreserved pulmonary homograft. When homograft is not available, our preferences include downsizing a larger pulmonary homograft to a bicuspid valve, the Hancock^® porcine valved conduit, and the Contegra^® bovine juglar vein prosthesis on a research protocol.

Limitations of this study include its retrospective nature and single institution bias. Since the time of this study, the Shelhigh Company has replaced the distal porcine pulmonary artery with a sleeve of bovine pericardium treated with the No-React^® process (the Model NR-4000PA).

In conclusion, our experience with the SPVC has revealed a high incidence of early conduit failure due to the neointimal peel formation, especially in sizes 14 mm or below. These findings have led us to abandon its use when other options are available.

	Footnotes

 
Presented at the 16th Annual Meeting of the European Association for Cardio-thoracic Surgery, Monte Carlo, Monaco, September 22–25, 2002.

	References

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 

1. Masetti P., Ussia G.P., Gazzolo D., Marianeschi S.M., Abella R.F., Cipriani A., Labia C., Iorio F.S., Marcelletti C. Aortic pulmonary autograft implant: medium-term follow-up with a note on a new right ventricular pulmonary artery conduit. J Card Surg 1998;13:173-176.[Medline]
2. Pearl J.M., Cooper D.S., Bove K.E., Manning P.B. Early failure of the Shelhigh pulmonary valve conduit in infants. Ann Thorac Surg 2002;74:542-549.[Abstract/Free Full Text]
3. Bove E.L., Beekman R.H., Snider A.R., Callow L.B., Underhill D.J., Rocchini A.P., Dick M., II, Rosenthal A. Repair of truncus arteriosus in the neonate and young infant. Ann Thorac Surg 1989;47:499-506.[Abstract]
4. Abolhoda A., Yu S., Oyarzun R., McCormick J.R., Bogden J.D., Gabbay S. Calcification of bovine pericardium: glutaraldehyde versus No-React biomodification. Ann Thorac Surg 1996;62:169-174.[Abstract/Free Full Text]
5. Abolhoda A., Yu S., Oyarzun R., Allen K.R., McCormick J.R., Han S., Kemp F.W., Bogden J.D., Lu Q., Gabbay S. No-React detoxification process: a superior anticalcification method for bioprostheses. Ann Thorac Surg 1996;62:1724-1730.[Abstract/Free Full Text]
6. Wells W.J., Arroyo H., Jr, Bremner R.M., Wood J., Starnes V.A. Homograft conduit failure in infants is not due to somatic outgrowth. J Thorac Cardiovasc Surg 2002;124:88-96.[Abstract/Free Full Text]
7. Sano S., Karl T.R., Mee R.B.B. Extracardiac valved conduits in the pulmonary circuit. Ann Thorac Surg 1991;52:285-290.[Abstract]
8. Lange R., Weipert J., Homann M., Mendler N., Paek S., Holper K., Meisner H. Performance of allografts and xenografts for right ventricular outflow tract reconstruction. Ann Thorac Surg 2001;71:S365-S367.[Abstract/Free Full Text]
9. Perron J., Moran A.M., Gauvreau K., delNido P.J., Mayer J.E., Jonas R.A. Valved homograft conduit repair of the right heart in early infancy. Ann Thorac Surg 1999;68:542-548.[Abstract/Free Full Text]
10. Sinzobahamvya N., Wetter J., Blaschczok H.C., Cho M.-Y., Brecher A.M., Urban A.E. The fate of small diameter homografts in the pulmonary position. Ann Thorac Surg 2001;72:2070-2076.[Abstract/Free Full Text]

This article has been cited by other articles:

				W.-H. Kim, S. K. Min, C. H. Choi, J. R. Lee, Y. J. Kim, E.-J. Bae, and C. I. Noh Follow-Up of Shelhigh Porcine Pulmonic Valve Conduits Ann. Thorac. Surg., December 1, 2007; 84(6): 2047 - 2050. [Abstract] [Full Text] [PDF]

				A. J. Rastan, T. Walther, I. Daehnert, J. Hambsch, F. W. Mohr, J. Janousek, and M. Kostelka Bovine jugular vein conduit for right ventricular outflow tract reconstruction: evaluation of risk factors for mid-term outcome. Ann. Thorac. Surg., October 1, 2006; 82(4): 1308 - 1315. [Abstract] [Full Text] [PDF]

				D. M. McMullan, G. Oppido, N. Alphonso, A. D. Cochrane, Y. d. d'Acoz, and C. P. Brizard Evaluation of downsized homograft conduits for right ventricle-to-pulmonary artery reconstruction J. Thorac. Cardiovasc. Surg., July 1, 2006; 132(1): 66 - 71. [Abstract] [Full Text] [PDF]

				C. Schreiber, S. Sassen, M. Kostolny, J. Horer, J. Cleuziou, M. Wottke, K. Holper, F. Fend, A. Eicken, and R. Lange Early graft failure of small-sized porcine-valved conduits in reconstruction of the right ventricular outflow tract. Ann. Thorac. Surg., July 1, 2006; 82(1): 179 - 185. [Abstract] [Full Text] [PDF]

				A. Dodge-Khatami Invited commentary. Ann. Thorac. Surg., July 1, 2006; 82(1): 185 - 186. [Full Text] [PDF]

				J. W. Brown, M. Ruzmetov, M. D. Rodefeld, P. Vijay, and M. W. Turrentine Right Ventricular Outflow Tract Reconstruction With an Allograft Conduit in Non-Ross Patients: Risk Factors for Allograft Dysfunction and Failure Ann. Thorac. Surg., August 1, 2005; 80(2): 655 - 664. [Abstract] [Full Text] [PDF]

				J. A. Quintessenza, J. P. Jacobs, V. O. Morell, J. M. Giroud, and R. J. Boucek Initial Experience With a Bicuspid Polytetrafluoroethylene Pulmonary Valve in 41 Children and Adults: A New Option For Right Ventricular Outflow Tract Reconstruction Ann. Thorac. Surg., March 1, 2005; 79(3): 924 - 931. [Abstract] [Full Text] [PDF]

				V. Gober, P. Berdat, M. Pavlovic, J.-P. Pfammatter, and T. P. Carrel Adverse Mid-Term Outcome Following RVOT Reconstruction Using the Contegra Valved Bovine Jugular Vein Ann. Thorac. Surg., February 1, 2005; 79(2): 625 - 631. [Abstract] [Full Text] [PDF]

				D. Boethig, W.-R. Thies, H. Hecker, and T. Breymann Mid term course after pediatric right ventricular outflow tract reconstruction: a comparison of homografts, porcine xenografts and Contegras Eur. J. Cardiothorac. Surg., January 1, 2005; 27(1): 58 - 66. [Abstract] [Full Text] [PDF]

				B. Meyns, L. Van Garsse, D. Boshoff, B. Eyskens, L. Mertens, M. Gewillig, S. Fieuws, E. Verbeken, and W. Daenen The Contegra conduit in the right ventricular outflow tract induces supravalvular stenosis J. Thorac. Cardiovasc. Surg., December 1, 2004; 128(6): 834 - 840. [Abstract] [Full Text] [PDF]

				Y. Boudjemline, D. Bonnet, and D. Sidi Reply to the Editor J. Thorac. Cardiovasc. Surg., February 1, 2004; 127(2): 611 - 611. [Full Text] [PDF]

				Y. Boudjemline, C. Beyler, D. Bonnet, and D. Sidi Surprising outcome similarities between Contegra(R) bovine jugular vein conduit and Shelhigh No-React(R) porcine pulmonary valve conduit: role of immunologic reaction Eur. J. Cardiothorac. Surg., November 1, 2003; 24(5): 850 - 851. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Toru Ishizaka Richard G. Ohye Takaaki Suzuki Eric J. Devaney Edward L. Bove Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ishizaka, T. Articles by Bove, E. L. Search for Related Content PubMed PubMed Citation Articles by Ishizaka, T. Articles by Bove, E. L. Related Collections Congenital - cyanotic