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J Thorac Cardiovasc Surg 1994;107:1162-1164
© 1994 Mosby, Inc.

LETTERS TO THE EDITOR

Invited letter concerning: Accelerated degeneration of aortic allografts in infants and young children

The Children's Hospital
University of Colorado Health Sciences Center
Department of Surgery
Division of Cardiothoracic Surgery
Denver, CO 80218

To the Editor:

The letter from Dr Gallo and his associates hints at the Denver experience with aortic valve allograft reconstruction of the left ventricular outflow tract (LVOT) in young children. Gallo's group reported the case of an infant girl who had undergone surgical repair of truncus arteriosus at 1 month of age and subsequently had severe truncal valve regurgitation. The aortic root was replaced with a cryopreserved aortic allograft at 3 months of age. Echocardiography 3 months after aortic root replacement demonstrated a severely regurgitant and calcified allograft that required explantation. Allograft degeneration is a troublesome phenomenon in recipients less than 3 years of age, as evidenced by its prevalence in intermediate-term follow-up of pediatric recipients of aortic valve allografts who presented for LVOT reconstruction in Denver. The prevalence of aortic allograft fibrocalcification and valvular insufficiency warrants reexamination of the surgical options available for young children with congenital anomalies of the LVOT.

At The Children's Hospital and the University of Colorado Health Sciences Center in Denver, 55 children have had LVOT reconstruction with a cryopreserved aortic valve allograft for aortic root replacement. Forty patients were 3 to 17 years of age and 15 children were less than 3 years old at operation. Ages of the 40 older children ranged from 3 to 17.9 years (mean 10.7 years). Preoperative diagnoses included recurrent subvalvular aortic stenosis in 19 patients, multilevel aortic stenosis with insufficiency in 8, multilevel aortic stenosis in 5, aortic insufficiency in 5, and aortic stenosis with hypoplastic anulus in 3 children. LVOT gradients in patients with aortic stenosis were 20 to 100 mm Hg (mean 55 mm Hg) at cardiac catheterization. Thirty-eight children (95%) had undergone a previous cardiac operation. Standard aortic root replacement ¹ was performed in 11 allograft recipients (27%) and the remaining 29 (73%) required extended aortic root replacement in which the allograft mitral leaflet was used to enlarge the LVOT. ² Aortic valve allografts of 15 to 23 mm (mean 21 mm) internal diameter were implanted in patients who weighed 10.3 to 88.4 kg (mean 35.8 kg) at operation. There were three hospital deaths (7%) and 62% (23/37) of the operative survivors had postoperative complications. One child underwent cardiac transplantation 30 hours after aortic root replacement because of left ventricular failure. Thirty-six remaining children have been followed up clinically for 5 months to 7.5 years (mean 3.0 years). One child was lost to follow-up 20 months after the operation. No late deaths have occurred. Two patients (6%) who were 3 years of age or older at operation have undergone cardiac reoperation. Candida tropicalisendocarditis developed in a 14-year-old boy and he required allograft replacement 4 months after extended aortic root replacement. One 12-year-old boy who had an aortic root replacement and concurrent right ventricular outflow tract reconstruction with an aortic and a pulmonary valve allograft, respectively, underwent cardiac transplantation 3.7 years after the operation because of myocardial failure. In both cases, primary allograft degeneration was not observed.

The ages of the 15 children who were younger than 3 years old at operation ranged from 1 day to 2.1 years (mean 7.6 months). Preoperative diagnoses included multilevel aortic stenosis with insufficiency in seven, multilevel aortic stenosis in six, and truncal valve insufficiency in two. Ten patients (67%) had undergone prior cardiac operations and presented for aortic root replacement with LVOT gradients of 45 to 100 mm Hg (mean 75 mm Hg) measured at cardiac catheterization. Intraoperatively, seven children required extended aortic root replacement, four had standard aortic root replacement, and four underwent aortic root replacement with concurrent proximal extension with a polytetrafluoroethylene patch and aortic arch replacement. ³ Internal diameter of the implanted aortic valve allografts ranged from 10 to 17 mm (mean 13 mm). The valve conduits were implanted in patients weighing 2.8 to 12.4 kg (mean 5.9 kg). There were three early deaths (20%) and 83% (10/12) of the recipients had postoperative complications. Twelve operative survivors have been followed up clinically for 4 months to 5.6 years (mean 2.3 years) with one late death (8%) that was not valve related. Six of 11 remaining children (54%) who were less than 3 years old at operation have had allograft degeneration that led to valve replacement 3 months to 3.7 years after aortic root replacement (mean 1.9 years). One child currently is in stable condition receiving low-dose cyclosporine therapy that was initiated with echocardiographic findings of progressive allograft calcification and mild regurgitation.

No statistically significant difference is detected between the two age groups when the prevalences of hospital death, early postoperative complication, or late postoperative mortality are compared (p > 0.10 by ² analysis for independent samples). However, the proportion of children who required allograft explantation was significantly higher in the younger (6/11) versus older (2/35) age groups (p < 0.01 by ² test for independent samples). Fig. 1 illustrates the significant difference in follow-up between the older and younger patient groups when the prevalence of allograft failure leading to explantation is examined.

View larger version (17K): [in this window] [in a new window]   Fig. 1. Freedom from allograft degeneration that required explantation in patients less than 3 years of age at operation compared with patients 3 years of age or older.

Cryopreserved aortic allografts continue to be the preferred valve conduit for LVOT reconstruction. With the exception of one of the younger children who underwent placement of a mechanical aortic valve prosthesis at another institution, all reoperations of the patients herein involved implantation of a second allograft. The older patient underwent reoperative extended aortic root replacement as did two of the younger recipients. Two children had pulmonary autograft procedures and one underwent reoperative aortic root replacement.

Although a correlation between prevalence of allograft degeneration and failure and young recipient age is increasingly obvious, the exact cause is undetermined. The etiology of valve failure might be based on an immune mechanism. ⁴ So that this response is avoided in young patients who require LVOT reconstruction, pulmonary autografts are recommended as a surgical option. In addition to the fact that the technique is difficult in young children and infants, it was not an option for Gallo and his colleagues, whose patient had truncus arteriosus. Use of nonviable allografts or xenografts could also provide suitable palliation while avoiding a potential immune response. If implantation of a viable valve allograft is inevitable, antiinflammatory agents or low-dose immunosuppressive drugs are recommended as postoperative therapy in patients less than 3 years of age. To date, there is no adequate substitute for valve allografts, particularly in the pediatric population, in which surgical options are extremely limited.

References

1. Somerville J, Ross D. Homograft replacement of aortic root with reimplantation of coronary arteries: results after one to five years. Br Heart J 1982;47:473-82.[Abstract/Free Full Text]
   
2. Clarke DR. Extended aortic root replacement with cryopreserved allografts: Do they hold up? Ann Thorac Surg 1991;52:669-75.[Abstract]
   
3. St. Cyr JA, Campbell DN, Fullerton DA, Grosso M, Bishop DA, Clarke DR. Cryopreserved allograft repair of aortic hypoplasia and interrupted aortic arch. Ann Thorac Surg 1992;53:1110-3.[Abstract]
   
4. Clarke DR, Campbell DN, Hayward AR, Bishop DA. Degeneration of aortic valve allografts in young recipients. J THORAC CARDIOVASC SURG 1993;105:934-42.[Abstract]
   

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