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Ann Thorac Surg 2005;80:1628-1633
© 2005 The Society of Thoracic Surgeons

Original article: Cardiovascular

Pediatric Autograft Aortic Root Replacement: A Prospective Follow-Up Study

Johanna J.M. Takkenberg, MD, PhD a , * , Arie Pieter Kappetein, MD, PhD a , Lex A. van Herwerden, MD, PhD a , Maarten Witsenburg, MD, PhD a , Lenny Van Osch-Gevers, MD, PhD b , Ad J.J.C. Bogers, MD, PhD a

a Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, the Netherlandsand
b Department of Pediatric Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands

Accepted for publication April 26, 2005.

* Address correspondence to Dr Takkenberg, Department of Cardiothoracic Surgery, Bd563, Erasmus University Medical Center, PO Box 2040, Rotterdam, 3000CA the Netherlands (Email: j.j.m.takkenberg{at}erasmusmc.nl).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: The autograft procedure offers children who require aortic valve replacement the advantage of an autologous valve that has growth potential and does not require anticoagulation. However, the autograft procedure is a double valve operation and its durability depends on the lifetime of both the autograft and the pulmonary valve substitute. We present our clinical experience with pediatric autograft aortic root replacement.

METHODS: Between September 1988 and September 2003, 47 children (mean age, 8 years; standard deviation, 5 years; range, 3 months to 15 years) underwent autograft aortic root replacement. Perioperative characteristics and annual follow-up information were collected prospectively.

RESULTS: The male to female ratio was 32 to 15. Eighty-nine percent of patients had congenital aortic valve disease, 47% of patients previously underwent cardiac surgery, and 43% had an aortic valve balloon dilatation. Concomitant left ventricular outflow tract enlargement was performed in 19 patients. In all cases the pulmonary valve was replaced using an allograft. There were no hospital deaths. Mean follow-up was 6.1 years (median 5.4; range, 1 month to 15 years; total of 284 patient years). During follow-up 3 patients died. Cumulative survival was 95% at 1 year and 93% at 12 years. One patient had endocarditis of the pulmonary allograft develop. Three patients required reoperation; two patients for allograft degeneration at 9.4 and 12.8 years, and 1 for combined autograft dilatation and allograft degeneration at 7.7 years postoperatively. Freedom from valve-related reoperation was 86% at 12 years.

CONCLUSIONS: Pediatric autograft aortic root replacement is associated with acceptable mortality and reoperation rates in the first decade postoperatively. It allows most children to grow into adulthood without the need for anticoagulation and additional valve replacements.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
The autograft procedure, introduced by Donald Ross [1] in 1967, is performed mostly in young patients. It entails transplantation of the patient's own pulmonary valve to aortic position and replacement of the pulmonary valve, usually with a donor valve or bioprosthesis [2]. Potential advantages are the use of the patient's own valve with favorable hemodynamic characteristics, low endocarditis risk, low thrombogenicity, avoidance of anticoagulant therapy, and the alleged growth potential of the autograft valve in children. However, the autograft procedure is a technically demanding operation that requires replacement of both the aortic and the pulmonary valve. Also, the autograft in the aortic position and the valve substitute in the right ventricular outflow tract may develop structural failure with time. Thus the durability of the autograft procedure depends on the lifetime of both valve substitutes.

There have been several recent reports of progressive dilatation of the neoaortic root after autograft aortic root replacement (the modified Ross procedure) in adults. This has resulted in a decrease of the use of the procedure or change to subcoronary and inclusion cylinder surgical implantation techniques [3–5]. Although dilatation of the aortic root may be an important limitation of the Ross procedure for adult patients, for the growing child the diameter increase may actually be beneficial. However, if neoaortic dilatation results in aortic regurgitation and reoperation, or increased risk of aortic dissection, then even in children the risk-benefit ratio of an autograft procedure may change unfavorably. In this light we report from our ongoing prospective cohort study an update of the clinical and echocardiographic results with autograft aortic root replacement in patients under the age of 16 [6–8].


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Acknowledgments
 References
 
Between September 1988 and September 2003, 141 consecutive patients underwent autograft aortic root replacement at Erasmus University Medical Center. Of these patients, 47 were younger than 16 years at the time of operation. The preoperative characteristics of these 47 pediatric patients are displayed in Table 1. Institutional review board approval was obtained for this prospective follow-up study; the institutional review board waived informed consent.


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  		Table 1. Preoperative Patient Characteristics
 
Operation
All surgical procedures were performed on cardiopulmonary bypass with moderate hypothermia. Crystalloid cardioplegia and topical cooling were used for myocardial protection. The autograft root including a small rim of right ventricular muscle was placed on the left ventricular outflow tract and annulus. No attempts were made to wrap the autograft or reinforce the base of the autograft. The pulmonary root was replaced by an allograft in all patients [6]. Details on the allograft characteristics are displayed in Table 2. In 4 patients the allograft was tailored from a tricuspid to a bicuspid valve to obtain adequate right ventricular outflow tract allograft size matching. The allograft diameter in Table 2 represents the diameter as measured after tailoring.


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  		Table 2. Allograft Characteristics
 
Follow-Up
All patients who received an autograft at Erasmus University Medical Center were prospectively followed-up by annual telephone interviews (patients aged 18 years and older) or through visits to their pediatric cardiologist, or both. Echocardiographic follow-up in patients younger than 18 years was obtained annually at the time of visit to the pediatric cardiologist. The echocardiographic studies were done by one experienced technician and evaluated by one of three dedicated pediatric cardiologists. After patients turned 18 years of age they became part of our ongoing prospective standardized echocardiographic protocol. The details of this protocol were previously described [9].

Statistical Methods
Descriptive statistical analysis of perioperative data was done. Continuous data are presented as mean ± 1 standard deviation, and comparison was done using the unpaired t test. Categorical data are presented as proportions. Comparison was done using Fisher's exact test or the chi2 test. Cumulative survival and freedom from reoperation or reintervention were analyzed using the Kaplan-Meier method. For all analyses, SPSS 11.0 for Windows statistical software (SPSS, Chicago, IL) was used.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Acknowledgments
 References
 
Operative details are displayed in Table 3. All patients survived the operation and the subsequent hospital stay. One patient who had a complete atrioventricular block develop after extensive resection of a subvalvular stenosis required postoperative implantation of a permanent pacemaker. No other events were documented.


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  		Table 3. Perioperative Data
 
Mean follow-up was 6.1 years (median, 5.4 years; range, 1 month to 15.1 years; total of 284 patient years) and was complete for 46 of the 47 patients (98%). During follow-up 3 patients died. One patient died 6 weeks postoperatively due to sepsis (who was readmitted 5 days after discharge with fever and died during the subsequent hospitalization), 1 patient died 6 months postoperatively due to recurrent rheumatic fever, and 1 patient died of heart failure (a non-valve related cardiac death) 1.8 years postoperatively. Cumulative survival was 95% (standard error, 3.2) at 1 year and 93% (standard error, 4.0) at 5, 10, and 12 years (Fig 1).



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  		Fig 1. Cumulative survival (solid line) and freedom from autograft and allograft-related reoperation (interrupted line).

 
Autograft procedure-related reoperations were necessary in 3 patients. One patient underwent autograft replacement in combination with allograft replacement at 7.7 years postoperative for dilatation and regurgitation of the autograft, as well as degeneration of the cryopreserved pulmonary allograft. At the time of the autograft procedure this child was 15 years old and presented with combined aortic stenosis and regurgitation of a bicuspid valve after previous balloon dilatation and surgical valvotomy. One patient who was 4 years old at the time of the autograft procedure required mitral valve replacement and tricuspid valve repair 6.9 years postoperatively for severe mitral and tricuspid valve regurgitation (not autograft or pulmonary allograft-related). The same patient required isolated replacement of a degenerated aortic allograft in the pulmonary position 12.8 years after the autograft procedure. Finally, 1 patient (age 12 years at the time of the autograft procedure) had endocarditis of a degenerated cryopreserved aortic allograft develop 8.8 years postoperatively, shortly after the incision of an axillary abscess. Initially the patient was treated successfully with antibiotics, and eventually (ie, 9.4 years postoperatively) the degenerated allograft was replaced. At the time of reoperation no signs of active endocarditis were found. All 3 patients survived the reoperations. Overall freedom from autograft and allograft reoperation was 100% at 5 years and 85.6% (standard error, 9.5) at 10 and 12 years (Fig 1).

No other autograft or pulmonary allograft valve-related events occurred; in particular there were no bleeding occurrences, thromboembolic complications, nonstructural valve failures, or valve thromboses.

One patient underwent mitral valve replacement and tricuspid valve repair 7 years after the autograft procedure. The anterior mitral valve leaflet showed a central tear, most likely caused by enucleation of a subaortic stenosis at the time of the autograft procedure.

At last follow-up, most patients (still alive and without reoperations) were in the New York Heart Association functional class I (n = 36; 90%), 4 patients (10%) were in the New York Heart Association functional class II.

Table 4 shows aortic and pulmonary regurgitation at the last echocardiographic follow-up of all surviving patients. The 4 children who had moderate aortic regurgitation at their last echocardiographic examination (grade 3+) were 11, 12, 12, and 12 years old at the time of their autograft operation.


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  		Table 4. Echocardiographic Outcome at Last Follow-Up
 
Figure 2 shows progression of echocardiographic aortic regurgitation (AR) with time since the operation (ie, 189 observations in 43 patients). A linear function best described the observed progression: aortic regurgitation(t)= 0.08*t + 0.71, indicating an initial aortic regurgitation of 0.71 grade and an annual increase of 0.08 grade (t = time since operation in years). The 4 children who had moderate aortic regurgitation at their last echocardiographic examination (grade 3+) were 11, 12, 12, and 12 years old at the time of their autograft operation.



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  		Fig 2. Progression of aortic regurgitation after autograft aortic root replacement. The dots represent actual observations (ie, 189 observations in 43 patients); the line shows the linear function that was constructed using the actual observations and describes progression of aortic regurgitation during the years. (AR = aortic regurgitation; AVR = aortic valve replacement.)

 
Table 4 also shows that 3 children had severe pulmonary regurgitation at their last echocardiographic examination. Their age at autograft operation was 3 months, 4 months, and 12 years. One of these patients died shortly after this echocardiographic examination due to chronic right and left heart failure. The other 2 patients have not yet required reoperation on the pulmonary valve. Seven patients had a Doppler gradient of > 30 mm Hg (of which none were > 60 mm Hg) greater than the right ventricular outflow tract at the time of their last echocardiographic examination. Their ages at the time of the autograft procedure were 4 months, 4, 12, 13, 14, 15, and 15 years. Three of these patients have thereafter undergone replacement of their pulmonary allograft. Of the 4 patients with a "bicuspidalized" allograft at last echocardiographic follow-up, 3 patients had mild pulmonary regurgitation. No significant pulmonary gradient was observed.

Figure 3 shows progression of echocardiographic pulmonary regurgitation with time since the operation (ie, 119 observations in 40 patients). A linear function best described the observed progression: pulmonary regurgitation(t)= 0,05*t + 0.71, indicating an initial pulmonary regurgitation of 0.71 grade and an annual increase of 0.05 grade.



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  		Fig 3. Progression of pulmonary allograft regurgitation. The dots represent actual observations (ie, 119 observations in 40 patients); the line shows the linear function that was constructed using the actual observations and describes progression of pulmonary regurgitation during the years. (PR = pulmonary regurgitation.)

 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Acknowledgments
 References
 
These prospective study results show that pediatric autograft aortic root replacement is associated with acceptable mortality and reoperation rates in the first decade postoperatively and it allows most children to grow into adulthood without the need for anticoagulation and additional valve replacements. However it is obvious from recent reports [10, 11] that the durability of the Ross procedure is indeed limited, and children who undergo a Ross procedure most likely have a considerable risk to undergo at least one reoperation of the aortic or pulmonary valve, or both, during the remainder of the patient's life.

The autograft procedure is considered to be a technically demanding procedure because two valves require replacement. This is reflected by the relatively long perfusion and aortic cross-clamp times in our report. However, there were no operative deaths, no perioperative myocardial infarctions, and no need for reoperation due to persistent bleeding. Only 1 patient required a permanent pacemaker. Other authors report comparable early outcome with operative mortality ranging from 0 to 4.5% [10–13].

Although operative mortality was absent in our pediatric cohort, there were 3 deaths in the first 2 years after the autograft procedure. Beyond 2 years, no further deaths were observed and late survival thus far seems to follow a trajectory comparable with the general age-matched population. This is in accordance with other pediatric Ross series in which the survival range was 100% at 5 years [10], 96% at 7 years [12], and 92% at 10 years [13].

Only 1 older child in our clinical experience so far required reoperation of a dilating autograft at 7.7 years after the initial procedure. In addition, 4 older children had moderate aortic regurgitation at their last echocardiographic examination. All 4 children had a previous surgical aortic valvotomy, and 3 also had a previous aortic valve balloon dilatation. The indication for autograft operation in these 4 patients was combined aortic regurgitation and stenosis in 2, aortic regurgitation in 1, and aortic stenosis in 1. Three of these 4 patients had a bicuspid valve and 1 patient had a tricuspid valve. Laudito and colleagues [10] reported that older children with preoperative predominant aortic regurgitation are at increased risk of autograft failure [10]. Autograft failure (defined as reoperation or > grade 2+ aortic regurgitation) occurred in 5 older children in our series, but these small numbers do not allow us to draw any conclusions with regard to the possible association between patient age, preoperative hemodynamic diagnosis, and durability of the autograft procedure. Thus far the progression of aortic regurgitation with time seems to be linear and slow (Fig 2; 0.08 grade per year).

The durability of the autograft in children can be considered good when compared with adult patients. In our own experience (ie, 47 children and 94 adult patients), we find that at 10 years, postoperative freedom from autograft reoperation is 93% in patients younger than 16 years of age versus 79% in those 16 years of age and older (p = 0.05; log-rank test, unpublished data). Elkins and colleagues [13] reported a comparable 92% freedom from autograft reoperation at 10 years after the procedure in 167 patients younger than 18 years of age. A recent update of Dr Kouchoukos' series of 119 older children and younger adults (mean age, 31 years) shows that autograft reoperation mainly occurs in adult patients. Of the 11 autograft reoperations, 10 were done in patients aged 16 years or older at the time of the autograft procedure [11]. Possible explanations for a better performance of the autograft in younger children compared with older children and adults include the ability of the autograft of a young child to better adapt to systemic pressures, and the alleged growth potential of the autograft in the growing child. Thus far the latter explanation remains speculative.

The longevity of the pulmonary allograft is another important factor that needs to be addressed when evaluating the durability of the autograft procedure. In our pediatric cohort, 3 patients required reoperation of their degenerated allograft, another 8 patients had severe pulmonary insufficiency or an important right ventricular outflow tract gradient, or both. It suggests that the lifetime of the allograft in the pulmonary position may be shorter than the lifetime of the autograft. However, this is not confirmed by other reports, of which most show an allograft reoperation rate comparable with or even lower than the autograft reoperation rate [11–13]. So far, the 4 tailored ("bicuspidalized") allografts show a good function at a mean follow-up of 2 years. Longer follow-up is required to assess whether tailoring is of influence on the durability of the pulmonary allograft. Although there was no reoperative mortality in our experience, replacement of a degenerated pulmonary allograft in the presence of an autograft is a major operation. The emergence of percutaneous techniques to replace the pulmonary valve [14] may provide a less invasive option to treat allograft degeneration.

Freedom from any valve-related reoperation in our pediatric cohort was 86% at 12 years of age, implying that most children who undergo autograft aortic root replacement grow into adulthood without the need for anticoagulation or reoperation. For growing children there are currently no valve substitutes available that are superior to the autograft with regard to hemodynamic profile, growth potential, durability, and occurrence of valve-related events. In the future, tissue-engineered heart valves that are still in the experimental phase of development may provide patients who require aortic valve replacement with a valve substitute that is the next best thing to nature [15]. In particular, children are potential beneficiaries of the development of tissue-engineered valves, if indeed this new exciting technique will result in a durable living valve that has the potential to grow with the child. However, until the safety and efficacy of these valves have been proven, the autograft procedure remains the procedure of choice in growing children who require aortic valve replacement.

In conclusion, our experience with pediatric autograft aortic root replacement yields excellent operative results and is associated with a good patient survival and low reoperation and valve-related event rates in the first decade after the procedure. However, one can expect that given their excellent survival most children who undergo autograft aortic root replacement will eventually require an autograft or allograft reoperation, or both, during their lifetime.


   Acknowledgments
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
References
 
We thank Marijke Rozema-Botermans and Liz van der Velden-Macauley for their excellent secretarial assistance.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Ross DN. Replacement of aortic and mitral valves with a pulmonary autograft Lancet 1967;2(7523):956-958.[Medline]
  2. Takkenberg JJ, Dossche KM, Hazekamp MG, et al. Report of the Dutch experience with the Ross procedure in 343 patients Eur J Cardiothorac Surg 2002;22(1):70-77.[Abstract/Free Full Text]
  3. Luciani GB, Casali G, Favaro A, et al. Fate of the aortic root late after Ross operation Circulation 2003;108(Suppl 1):II61-II67.
  4. Sievers H, Dahmen G, Graf B, et al. Midterm results of the Ross procedure preserving the patient's aortic root Circulation 2003;108(Suppl 1):II55-II60.
  5. Hokken RB, Takkenberg JJ, van Herwerden LA, et al. Excessive pulmonary autograft dilatation causes important aortic regurgitation Heart 2003;89(8):933-934.[Free Full Text]
  6. Hokken RB, Cromme-Dijkhuis AH, Bogers AJ, et al. Clinical outcome and left ventricular function after pulmonary autograft implantation in children Ann Thorac Surg 1997;63(6):1713-1717.[Abstract/Free Full Text]
  7. Bogers AJ, Takkenberg JJ, Kappetein AP, et al. Is there a place for pediatric valvotomy in the autograft era? Eur J Cardiothorac Surg 2001;20(1):89-94.[Abstract/Free Full Text]
  8. Bogers AJ, Kappetein AP, Roos-Hesselink JW, Takkenberg JJ. Is a bicuspid aortic valve a risk factor for adverse outcome after an autograft procedure? Ann Thorac Surg 2004;77(6):1998-2003.[Abstract/Free Full Text]
  9. Willems TP, Takkenberg JJ, Steyerberg EW, et al. Human tissue valves in aortic positiondeterminants of reoperation and valve regurgitation. Circulation 2001;103(11):1515-1521.[Abstract/Free Full Text]
  10. Laudito A, Brook MM, Suleman S, et al. The Ross procedure in children and young adultsa word of caution. J Thorac Cardiovasc Surg 2001;122(1):147-153.[Abstract/Free Full Text]
  11. Kouchoukos NT, Masetti P, Nickerson NJ, et al. The Ross procedurelong-term clinical and echocardiographic follow-up. Ann Thorac Surg 2004;78(3):773-781.[Abstract/Free Full Text]
  12. Lupinetti FM, Duncan BW, Lewin M, et al. Comparison of autograft and allograft aortic valve replacement in children J Thorac Cardiovasc Surg 2003;126(1):240-246.[Abstract/Free Full Text]
  13. Elkins RC, Lane MM, McCue C. Ross operation in childrenlate results. J Heart Valve Dis 2001;10(6):736-741.[Medline]
  14. Bonhoeffer P, Boudjemline Y, Qureshi SA, et al. Percutaneous insertion of the pulmonary valve J Am Coll Cardiol 2002;39(10):1664-1669.[Abstract/Free Full Text]
  15. Yacoub MH, Takkenberg JJ. Will heart valve tissue engineering change the world? Nat Clin Pract Cardiovasc Med 2005;2(2):60-61.[Medline]



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