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Original Articles: Pediatric Cardiac

Right Ventricular Outflow Tract Reconstruction in Ross Patients: Does the Homograft Fare Better?

Section of Cardiothoracic Surgery, James W. Riley Hospital for Children and Indiana University School of Medicine, Indianapolis, Indiana

Accepted for publication July 1, 2008.

^_* Address correspondence to Dr Brown, Section of Cardiothoracic Surgery, Indiana University School of Medicine, 545 Barnhill Dr, EH 215, Indianapolis, IN 46202-5123 (Email: jobrown{at}iupui.edu).

Presented at the Poster Session of the Fifty-third Annual Meeting of the Southern Thoracic Surgical Association, Tucson, AZ, Nov 8–11, 2006.

	Abstract

Top Abstract Introduction Material and Methods Results Comment Footnotes References

 
Background: In the Ross aortic valve replacement (AVR) procedure, the right ventricular outflow tract (RVOT) conduit is inserted in an orthotopic position. In complex congenital RVOT obstruction, the right ventricular-pulmonary artery (RV-PA) conduit is placed in a more heterotopic position. We hypothesized that durability of homograft RVOT reconstruction in the Ross AVR is improved secondary to orthotopic positioning and the ability to oversize the RV-PA homograft conduit in the Ross AVR.

Methods: Between June 1993 and May 2007, 183 consecutive patients (mean age, 23.3 ± 15.2; median, 22; range, 1 month to 61 years) underwent Ross AVR with RVOT reconstruction using a cryopreserved pulmonary homograft (n = 156), decellularized pulmonary homograft (n = 22), and bovine jugular vein conduit (n = 5).

Results: Three patients died (2 early, 1 late; mean follow-up, 5.7 ± 3.3 years). Twenty-four patients (13%) had a peak systolic RVOT gradient exceeding 20 mm Hg, 5 (3%) had a gradient exceeding 40 mm Hg, and 7 (4%) had more than 2+ RVOT insufficiency. Eight patients (4%) underwent conduit replacement for RV dysfunction. Freedom from RVOT reoperation at 10 years is 96%. Freedom from RV failure and dysfunction are 98% and 96% at 5 years and 96% and 93% at 10 years, respectively. Independent predictors of pulmonary homograft RV-PA conduit dysfunction are smaller (< 14 mm) RVOT conduit size (p = 0.03) and follow-up exceeding 5 years (p = 0.05).

Conclusions: Stenosis and regurgitation of the RV-PA conduit in adults and children following Ross AVR is infrequent. The most logical reasons for the superior performance of the homograft in Ross patients are: (1) orthotopic positioning, (2) older age of implant, and (3) the ability to significantly oversize the homograft in Ross patients.

	Introduction

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Replacement of the aortic valve with a pulmonary autograft (Ross AVR) requires the satisfactory replacement of the transplanted pulmonary valve and artery [1–5]. In most Ross series, pulmonary homografts are used exclusively for autograft replacement. The prevalence and predictors of late pulmonary homograft dysfunction after the Ross procedure are still unclear [6, 7]. Since their introduction into clinical practice in 1962 by Donald Ross [1], pulmonary homograft performance has been described in numerous publications [6, 7].

The use of alternatives to pulmonary homografts in the right ventricular outflow tract (RVOT) position in patients undergoing a Ross procedure has been described [2, 8, 9]. Alternative conduits, including porcine stented or stentless valved conduit [8], Gore-Tex monocusp valved conduits (W. L. Gore & Associates, Flagstaff, AZ) [4], and bovine jugular venous valve conduits [2, 9], have yet to show equivalencies to pulmonary homografts in terms of availability, hemodynamic performance, and durability.

In patients undergoing the Ross AVR, the RVOT conduit is inserted in an orthotopic position rather than in the more heterotopic position used in the repair of complex congenital RVOT obstruction. We hypothesized that durability of RVOT reconstruction in patients undergoing the Ross AVR is improved secondary to orthotopic positioning and the ability to oversize the homograft size at implantation. The purpose of this study was to review our institutional midterm experience to assess RVOT hemodynamics, mortality rate, and reoperative frequency after Ross AVR.

	Material and Methods

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Between June 1993 and May 2007, 183 consecutive patients underwent a Ross AVR at the Indiana University Hospitals, including the James W. Riley Hospital for Children in Indianapolis. There were 125 male patients (68%) and 58 female patients (32%) with a mean age of 23.3 ± 15.2 years (median, 22 years; range, 1 month to 61 years). Six patients (3%) were younger than 1 year, 80 (44%) were between 1 and 19 years, and 97 were older than 19 years (53%). Isolated aortic valve disease was present in 167 patients, and 16 pediatric patients had more complex, multilevel left ventricular outflow tract (LVOT) obstruction. A total of 119 previous cardiac surgical or balloon procedures were performed in 84 patients (46%); surgical valvotomy and transventricular balloon valvuloplasty were the most frequent surgical procedures performed before a Ross AVR. Of 86 pediatric patients, 58 (67%) had a previous cardiac procedure, whereas only 26 adults (27%) had prior aortic valve procedures (p = 0.01). Patients' preoperative aortic valve pathologies are presented in Table 1.

The Indiana University Institutional Review Board approved the study and waived the need to obtain patient consent for the study. Hospital records were retrospectively reviewed, including operative records as well as preoperative and postoperative catheterization and echocardiography data. Transthoracic M-mode, two-dimensional, color-flow, and Doppler echocardiograms were obtained in all patients before hospital discharge and annually thereafter. The degree of autograft and neopulmonary regurgitation was quantitated as none/trivial, mild, moderate, and severe [10]. The peak velocity flow across both semilunar valves was also assessed.

RV conduit failure was defined as explant of the valve for any reason or late death (occurring > 30 days postoperatively) as a result of any cause. RV conduit dysfunction was defined as moderate or greater stenosis (a peak gradient > 40 mm Hg) or pulmonary insufficiency exceeding 2+ on echocardiography. Neopulmonary insufficiency was defined echocardiographically as moderate when there was a broad regurgitant jet less than the annulus width associated with diastolic color Doppler flow reversal from the distal main pulmonary artery. A regurgitant jet that encompassed the entire annulus width associated with diastolic flow reversal in the branch pulmonary arteries was graded as severe. Neopulmonary stenosis was defined as a transvalvular peak instantaneous pressure gradient > 40 mm Hg or a mean gradient of > 30 mm Hg. The follow-up echo in which the patient first met one or both of these dysfunction criteria was recorded as the end of satisfactory conduit life and the beginning of RV conduit dysfunction.

Operative Technique
Standard techniques of cardiopulmonary bypass were used, with bicaval cannulation, moderate hypothermia, and antegrade and retrograde cold blood potassium cardioplegia. A standard full-root technique was used for all Ross patients, as previously described [4, 11]. When a Ross-Konno procedure (n = 14) was performed, the autograft was harvested with a 1- to 1.5-cm extension of attached RV infundibular free wall muscle for use in patching the septoplasty incision. The RVOT was then reconstructed with an appropriately oversized (4 to 8 mm larger than the autograft) cryopreserved pulmonary homograft (CryoLife Inc, Marrietta, GA; n = 156) or a decellularized pulmonary homograft (SynerGraft; CryoLife Inc, n = 22), or glutaraldehyde-preserved bovine jugular vein with integral venous valve (Contegra, Medtronic, Inc, Minneapolis, MN; n = 5). The patients were separated from cardiopulmonary bypass in the usual manner, and intraoperative transesophageal echocardiography was routinely performed.

At the time of the Ross AVR, 92 additional procedures were performed in 59 patients (32%). All concomitant procedures are reported in Table 2. Fifty-two procedures were performed in patients who had preoperative aortic annular dilatation, consisting of reduction of the aortic annulus in 35, and ascending aorta replacement with synthetic graft in 17. The aortic annulus was reduced from 30.2 ± .6 mm preoperatively to 24.6 ± 2.2 mm postoperatively (p = 0.17). The aortic annulus in patients with a Konno procedure was enlarged from 10.2 ± 3.2 mm preoperatively to 19.9 ± 3.8 mm postoperatively (p = 0.05).

Mean and peak aortic and pulmonary gradients were measured by Doppler echocardiography. The grade of aortic and right ventricular-pulmonary artery (RV-PA) conduit regurgitation was evaluated with color Doppler, using a 5-grade semi-quantitative scale (0, absent; 1, trivial; 2, mild; 3, moderate; 4, severe) according to the ratio of the width of the regurgitant jet at its origin to the LVOT and RVOT diameter [10]. Aortic and RV-PA conduit lesions were classified as predominant stenosis and predominant regurgitation according to the conclusive judgment of the operating surgeon after summarizing preoperative hemodynamic data and intraoperative findings.

	Results

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Mortality and Morbidity
There were two (1.1%) early deaths and one (0.6%) late death. A 48-year-old patient with severe bicuspid aortic stenosis and micronodular cirrhosis with a history of hepatitis C underwent Ross AVR and coronary artery bypass grafting of the right coronary artery. The patient had a cardiac arrest postoperatively and died 4 days later of multisystem organ failure secondary to liver and pulmonary failure, hepatorenal syndrome, and sepsis. One neonate with critical aortic stenosis underwent an emergency Ross-Konno procedure, aortic arch patch augmentation, and atrial and ventricular septal defect closure. This neonate required extracorporeal membrane oxygenation (ECMO) support and had an intercerebral hemorrhage while being weaned from ECMO support 5 days postoperatively. One pediatric patient died 6 months after a Ross-Konno procedure from aspiration pneumonia. Overall survival estimated by the Kaplan-Meier method, including early mortality, was 98% at 1, 5, and 10 years.

Low-cardiac output syndrome occurred in 5 patients (3%) postoperatively, and all 5 required ECMO. One patient died (early death described above). The second case occurred in a 6-week-old neonate with preoperative severe aortic insufficiency (AI) and an aortic valve mass. This preoperative pathology was thought to be due to an anticardiolipin antibody problem with calcified vegetations on the aortic valve. This patient could not be weaned from bypass after a Ross AVR and was placed on ECMO support. No recovery of ventricular function occurred during the next 4 days, and an orthotopic cardiac transplantation was performed on postoperative day 5. This child continues to do well 8 years after transplantation. The other 3 patients were successfully weaned from ECMO and are long-term survivors. Additional morbidity included reexploration for bleeding in 1 patient and complete heart block requiring permanent pacemaker insertion in 2 patients (1%), both of whom required a Ross-Konno procedure.

Reoperations
Eight patients (4%) required reoperation for significant obstruction of the pulmonary homograft (n = 6) as severe pulmonary regurgitation (n = 2). The mean time between the initial Ross AVR and RVOT reoperation was 6.4 ± 3.4 years (range, 6 months to 11 years). Patients reoperated on for pulmonary homograft stenosis or regurgitation received a second standard pulmonary homograft implantation (n = 2), a bovine pericardial valve (n = 1), a decellularized pulmonary homograft (SynerGraft; n = 1), bovine jugular vein conduit (Contegra; n = 1), porcine nonstented aortic bioprosthesis (Medtronic Freestyle; n = 1), or the RVOT was reconstructed with Gore-Tex monocusp (n = 2), respectively.

Two additional patients (1 pediatric and 1 adult) will undergo a planned balloon intervention because of a pulse Doppler gradient of 50 mm Hg or more across the pulmonary homograft. Freedom from RVOT reintervention was 98% at 5 years and 96% at 10 years (Fig 1).

View larger version (9K): [in this window] [in a new window]   Fig 1. Actuarial freedom from neopulmonary conduit reoperation in patients with Ross procedure.

A transesophageal echocardiogram was routinely performed in the operating room after Ross AVR. The most recent follow-up echocardiogram revealed neopulmonary regurgitation as none or trivial in 140 patients (77%), mild pulmonary regurgitation in 34 (19%), and moderate in 7 (4%). The peak neopulmonary pressure gradient was 23.3 ± 11.2 mm Hg (range, 0 to 60 mm Hg). No patient had important flow acceleration (obstruction) across the RVOT reconstruction. A peak systolic RVOT gradient exceeding 20 mm Hg was seen in 24 patients (13%), and a gradient exceeding 40 mm Hg was seen in 5 (3%). RVOT insufficiency exceeding 2+ was noted in 7 (4%) patients.

Freedom from RV failure and dysfunction was 98% and 96% at 5 years and 96% and 93% at 10 years, respectively (Fig 2). The independent predictors of RV dysfunction were smaller (< 14 mm) RVOT conduit size (p = 0.03) and length of follow-up exceeding 5 years (p = 0.05).

View larger version (13K): [in this window] [in a new window]   Fig 2. Actuarial freedom from neopulmonary conduit failure (diamonds) and dysfunction (squares) in patients with Ross procedure.

During follow-up, 14 patients (9%) required reoperation on the pulmonary autograft, one of whom had two procedures. All reoperations for autograft insufficiency or ascending aortic dilation, or both, occurred at a median interval of 6 years (mean, 5.9 ± 2.2; range, 2 to 10 years). Autograft annuloplasty with resection of an ascending aortic aneurysm and ascending aorta replacement with synthetic graft was performed in 6 patients (4%), and aortic root replacement with a mechanical prosthetic composite graft was done in 7 (4%). One patient had repair of a LV pseudoaneurysm below the Ross valve. All patients survived reoperation. Therefore, among the 14 reoperated on patients, 7 have prosthetic cardiac valves and 7 their native autograft valve. Actuarial freedom from reoperation on pulmonary autograft was 98% at 5 years and 92% at 10 years. At the latest follow-up, 96% of patients had their original Ross valve.

	Comment

Top Abstract Introduction Material and Methods Results Comment Footnotes References

 
The Ross AVR is now an established technique with excellent results in managing aortic valve disease [1–5, 11–13]. In most of the late follow-up reports of Ross AVR procedures, autograft-related problems and complications of RV-PA conduits mainly govern the long-term results and need for reoperation [3–5, 14]. Homografts continue to be the most commonly used conduits for the RVOT reconstruction during Ross AVR, despite some late problems [15, 16]. An array of possible alternatives or modification of homografts has been tried or postulated [17]. The development of cryopreservation as a method of tissue conservation has enabled longer storage and thus increased availability. Advantages over alternative conduits include ease of use and good hemodynamics. Although homografts used as a pulmonary conduit in congenital heart diseases may be exposed to hemodynamic factors that may adversely affect their longevity (pulmonary artery branch stenoses, unequal vascular distribution), patients who undergo a Ross procedure are generally free of pulmonary vascular disease and thus are a better model for studying homograft-related factors that might have an influence on valve dysfunction or failure.

Pulmonary homografts were the RV-PA conduit of our choice for reconstruction in Ross AVR procedures from the beginning and remain so even today. More recently, demand has increased for more a durable RV-PA conduit for non-Ross RVOT reconstruction [18]. In late 2000 we started using the Contegra bovine jugular vein conduit, porcine stentless aortic root xenografts (Medtronic Freestyle), and a new decellularized pulmonary homograft (SynerGraft) for non-Ross RVOT reconstruction [2, 8, 17, 19].

Pulmonary homograft regurgitation requiring replacement after Ross AVR has been rare in our experience, with only 1 infant requiring RVOT valve replacement. Homograft stenosis has been reported in a small percentage of patients in most large series (1% to 5%) [5, 13, 14, 16], with infants having the highest rate of up to 25% at 4 years [12]. To date, 8 patients (4%) in our series have required reoperation for pulmonary homograft dysfunction. The primary reason for this low incidence of significant obstruction in our Ross AVR homografts is the opportunity to oversize the pulmonary homograft by as much as 10 mm in diameter, and this oversizing makes up for the expected shrinkage of the pulmonary homograft in most cases [20]. In our smallest infants we have occasionally used a bovine jugular vein conduit because it has not shown a tendency to shrink after implantation and we believe it may be more durable [18].

Aortic homografts calcify more quickly when placed in the RVOT [15, 21]. This was linked to the higher elastin and intrinsic calcium content of the aortic wall [22]. Of the mechanical factors, homograft size has been found to be a significant factor that influences durability in most studies [14–16], and our results are consistent with these results as homograft diameter was found to be an independent predictor of late stenosis. This is especially true in the pediatric Ross AVR population. Indeed, children aged younger 3 years have an accelerated growth and can quickly outgrow their valve. This was the reason why we aggressively oversized the implanted homograft in Ross AVR patients, regardless of the patients' pulmonary annulus size. Forbess and colleagues [16], whose samples included 29% children aged younger than 1 year, found homograft size, rather than patient age, to be the most important independent predictor for pulmonary homograft failure, defined as the need for homograft replacement.

Stark and colleagues [23] found cryopreservation, rather than antibiotic sterilization, to be detrimental to the late function of the homograft. Interestingly, homografts preserved in antibiotic-nutrient solution functioned well in the experience of Ross [1] and in subsequent reports [24]. Although viability was thought to be desirable for homografts in the aortic position for preserved collagen synthesis by donor fibroblasts and, thus, increased resistance to mechanical stress, endothelial cell viability seems detrimental in pulmonary homografts, where it may induce an immune response in the host that may ultimately lead to valve or conduit failure. Decellularized pulmonary homografts were developed to eliminate or reduce this immune response. Preliminary results using the CryoLife SynerGraft have been encouraging [19]; however, they are more expensive than cryopreserved homografts.

Early and intermediate clinical results with the Contegra conduit for congenital non-Ross RVOT reconstruction and during Ross AVR procedures are encouraging [2, 9, 17, 25]. In two series of the Contegra in the Ross AVR, the hemodynamic performance of the Contegra graft was better than that of the homograft, even though the homografts had bigger diameters than the Contegra conduits [25, 26]. Studies of complex congenital repair of the RVOT using the Contegra conduit have also documented improved performance compared with pulmonary homografts [2, 27–29]. Infrequent complications in the form of nonfatal and fatal thrombosis, aneurysmal dilation, confluence stenosis, and endocarditis requiring reoperation have been described for the Contegra used for congenital RVOT reconstruction [27, 30]. The incidence is low and durability is greater [29].

Our preference to date has been to use a standard cryopreserved pulmonary homograft for RVOT reconstruction in Ross AVR patients whenever an appropriate size graft is available. The older age of the typical Ross AVR patient, the orthotopic position, and the ability to oversize the pulmonary allograft may all increase its longevity in the Ross AVR patient. Laminar flow through a homograft in the orthotopic position may be less destructive to the valve than in situations where the flow is turbulent, as in a conduit sutured to the RV infundibulum. Heterotopic placement of the RV-PA conduit also potentially subjects the conduit to compression by the sternal closure. In addition, conditions requiring heterotopic placement of the RV-PA conduit, such as pulmonary atresia, may have other distal pulmonary artery abnormalities affecting early and late conduit performance.

In conclusion, we have demonstrated in this review that the midterm function of the pulmonary homograft used to replace the autograft for Ross AVR has been excellent, with freedom from RVOT dysfunction/replacement at 98% and 96% at 5 years and 96% and 93% at 10 years, respectively. We continue to use the pulmonary homograft as our RVOT conduit of choice during the Ross AVR. Very little follow-up data exist to support the use of alternate RV-PA conduits for the Ross AVR procedure.

	Footnotes

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^_* Drs Brown and Ruzmetov contributed equally to the study.

	References

Top Abstract Introduction Material and Methods Results Comment Footnotes References

 

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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): John W. Brown Mark Ruzmetov Mark D. Rodefeld Mark W. Turrentine Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brown, J. W. Articles by Turrentine, M. W. Search for Related Content PubMed PubMed Citation Articles by Brown, J. W. Articles by Turrentine, M. W. Related Collections Congenital - cyanotic