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a Departments of Cardiology and Cardiac Surgery, Children's Hospital Boston, Boston, Massachusetts
b Departments of Pediatrics and Surgery, Harvard Medical School, Boston, Massachusetts
Accepted for publication April 27, 2009.
* Address correspondence to Dr McElhinney, Department of Cardiology, Children's Hospital, Boston, MA 02115 (Email: doff.mcelhinney{at}cardio.chboston.org).
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| Abstract |
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Methods: We conducted a retrospective chart review including baseline data, operative data, and cross-sectional follow-up on children younger than 10 years of age undergoing a first conduit reoperation (n = 180), comparing conduit replacement (n = 147, 82%) with conduit augmentation (n = 33, 18%).
Results: There were no differences between the two groups with respect to age, size, or hemodynamic variables. Augmentation was less often performed in patients with an aortic homograft and by one surgeon. At conduit 2, cardiopulmonary bypass time was longer in replacement patients (101 ± 35 versus 71 ± 34 minutes; p < 0.001); cardiac intensive care unit stay was not different. Early mortality was 0.5%, and overall 10-year survival was 95%. Freedom from reoperation was 80% at 5 years and 39% at 10 years, whereas freedom from reintervention (reoperation or catheter intervention) was 55% at 5 years and 26% at 10 years, with no differences between groups. Aortic homograft as a first conduit was associated with shorter freedom from reoperation. Limiting analysis to conduits that were replaced at conduit 2, undersized conduits were associated with shorter freedom from reoperation and smaller body surface area, and undersized conduits were associated with shorter freedom from reintervention.
Conclusions: Freedom from a second conduit reoperation after a first conduit replacement was shorter in smaller children and undersized conduits. Conduit augmentation offers similar clinical outcomes in selected patients.
Children with many forms of congenital heart disease undergo biventricular repair with a right ventricle to pulmonary artery (RV-PA) conduit. However, evidence-based decisions about conduit reintervention are difficult to formulate due to the nebulous outcome literature and long-term nature of many important outcomes. Children undergoing biventricular repair with RV-PA conduits present unique problems related to optimizing for small, but growing, chest size, conduit-branch PA size mismatch, and RV incision size. In children, reintervention on dysfunctional conduits is primarily aimed at relieving conduit stenosis, because the consequences of conduit regurgitation are often well tolerated until young adulthood. Freedom from conduit reoperation in mixed cohorts can range anywhere from 60% to 90% at 5 years and 29% to 72% at 10 years [1–6]. Therefore, young infants receiving conduits for initial palliation may require multiple reoperations. Factors previously identified to predict conduit longevity include patient age, primary anatomic diagnosis, type of conduit, conduit size, conduit diameter Z-score (standard deviations above or below average pulmonary valve size relative to body surface area), distal PA stenosis, and higher RV systolic pressure [1–10]. In certain settings, the cost of multiple reoperations and conduit availability are prohibitive. In examining the literature, most reports on conduit longevity focus only on infants or combine primary operations with reoperation and include patients of various ages and with various conduit types. With so many variables, it is difficult to assess the effect of different management strategies on outcomes. Studies that stratify analysis by patient age and reoperative status may help minimize the confounding effects of these variables and help inform decisions on specific populations.
Patch augmentation of RV-PA conduits is an alternative to complete conduit replacement for the treatment of conduit obstruction. Using readily available autologous, xenograft, or synthetic materials, patches can be crafted to relieve conduit obstruction with the possibility of a more straightforward operative and postoperative course, albeit at the cost of conduit regurgitation. The longevity of augmented conduits relative to replaced conduits is not well described. In this study of young children undergoing a first conduit reoperation (ie, a second conduit operation, conduit 2), we hypothesized that although operative and perioperative outcomes such as duration of cardiopulmonary bypass and intensive care unit stay would be shorter for patients undergoing conduit augmentation at the time of conduit 2, compared with those undergoing conduit replacement, freedom from further reoperation (conduit 3) or reintervention after conduit augmentation would be shorter. The primary hypothesis was that freedom from conduit 3 was significantly shorter after conduit augmentation compared with conduit replacement.
| Material and Methods |
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Surgical Procedure
The conduit augmentation procedure generally consisted of a longitudinal incision along the entire length of the anterior portion of the RV-PA conduit across both RV and PA anatomoses, although there was variation in the extent of the incision. The homograft valve was often excised. An onlay patch was crafted from expanded polytetrafluoroethylene, polyethylene terephthalate fiber (Dacron), or homograft for each patient and sewn into this incision, thereby increasing the diameter. The size of the patch was not standardized.
Data Analysis
The primary outcome was freedom from conduit 3 after conduit 2. Secondary outcomes included survival and a composite outcome of freedom from conduit 3 or conduit dilation (freedom from conduit reintervention) after conduit 2. We also analyzed demographic, anatomic, and procedural factors including age at original conduit operation, original conduit type, original conduit size, original conduit Z-score (based on previously published normative echocardiographic data [11]), diagnosis, type of repair at conduit 2 (replacement versus augmentation), surgeon, bypass time, cardiac intensive care unit stay, age at conduit 2, body surface area at conduit 2, and size of replacement at conduit 2. Baseline variables were compared using Student's t test or
2 analysis as appropriate. Primary and secondary outcomes were analyzed using Kaplan-Meier analysis and multivariable Cox regression analysis. Multivariate models were constructed using independent variables with significance levels up to a probability value of 0.1 by univariate analysis, and significance in the final model was determined for probability values less than or equal to 0.05. Outcome analyses were also performed with adjustment for age and surgeon at conduit 2. Data are presented as mean ± standard deviation, median with interquartile range, or frequency (percent of total).
| Results |
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Among patients who underwent conduit replacement at conduit 2, the conduit was an aortic homograft in 89, a pulmonary homograft in 42, a nonvalved synthetic tube graft in 13, and a valved synthetic graft in 3. The mean nominal conduit diameter was 17.9 ± 2.9 mm, and the mean conduit Z-score was 1.9 ± 1.3. Among patients undergoing conduit augmentation at conduit 2, patch material included expanded polytetrafluoroethylene in 17, Dacron in 9, and homograft tissue in 7. Patch size and configuration, as well as procedures to tailor the PA bifurcation, depended on the surgeon and specific case, and the completed diameter of the augmented conduit was not routinely measured. Among the 5 surgeons responsible for these 180 procedures, one performed augmentation in 3% of conduit 2 procedures (p = 0.04), another performed augmentation in 40% of conduit 2 procedures (p = 0.02), and the other 3 surgeons performed conduit augmentation in about 20% of their respective cases.
Perioperative Outcomes
All conduit 2 patients underwent surgery with cardiopulmonary bypass and recovered in the cardiac intensive care unit. Total pump time was significantly longer in patients who underwent conduit replacement compared with augmentation (101 ± 35 versus 71 ± 34 minutes; p < 0.001). There was no difference in length of cardiac intensive care unit stay between patients who underwent replacement (2.3 ± 3.6 days) and those who underwent augmentation (1.8 ± 0.8 days; p = 0.23). There was 1 early death (
30 days) at conduit 2 in the replacement group (not significantly different).
Follow-Up
Follow-up was available on 161 of the total 180 conduit 2 patients, 129 in the conduit replacement group and 32 who underwent augmentation. Median follow-up duration was 7.3 years (interquartile range, 3.9 to 10.9) with no difference between the two groups. Including the early death, 11 patients died and 1 underwent heart transplant during follow-up, all of whom were in the replacement group. Overall survival by Kaplan-Meier analysis was 99% at 1 year, 96% at 5 years, and 95% at 10 years, as presented in Figure 1.
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Transcatheter Conduit Procedures After Conduit 2
Transcatheter dilation or stenting of an obstructed RV-PA conduit was performed in 85 patients after conduit 2, 71 in the replacement group and 14 in the augmentation group. Fifty-two of these patients subsequently underwent conduit 3. At the time of the first transcatheter procedure after conduit 2, the peak systolic gradient across the conduit was 54 ± 20 mm Hg, with no difference between conduit replacement and augmentation groups (Table 2). Overall, freedom from any conduit reintervention (conduit 3 or conduit dilation or stenting) after conduit 2 was 98% at 1 year, 55% at 5 years, and 26% at 10 years. There was no difference in freedom from conduit reintervention between the replacement and augmentation groups (log rank test p = 0.09; Fig 3). The use of a pulmonary homograft at the original conduit operation (β = 1.6; 95% confidence interval, 1.1 to 2.4; p = 0.04) was associated with longer freedom from reintervention on multivariate analysis. When conduit replacement patients were considered separately, smaller conduit Z-score (β = 0.79; 95% confidence interval, 0.71 to 0.88; p < 0.001) and smaller body surface area at the time of conduit 2 (β = 0.27; 95% confidence interval, 0.09 to 0.82; p = 0.02) were associated with decreased freedom from conduit reintervention on multivariable analysis. These analyses were not affected by controlling for surgeon.
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Reintervention After Right Ventricle to Pulmonary Artery Conduit Operations
Freedom from conduit reoperation after conduit 2, called conduit 3, was 80% at 5 years and 39% at 10 years. At our institution, transcatheter conduit dilation and/or stenting is often performed in an effort to relieve RV-PA conduit obstruction and to minimize RV work before referral for conduit reoperation. In this series, almost two thirds of patients who underwent conduit 3 had a prior transcatheter intervention. Including angioplasty and stenting of the conduit, freedom from conduit reintervention after conduit 2 was 55% at 5 years and 26% at 10 years. The only predictor of longer freedom from conduit reoperation or reintervention after conduit 2 was use of a pulmonic homograft at the original conduit placement. Among patients in this series who underwent conduit replacement at conduit 2, smaller body surface area and smaller conduit Z-score were associated with shorter freedom from subsequent reoperation and reintervention. Primary diagnosis and other previously demonstrated variables were not associated with freedom from reintervention.
Studies of broader cohorts undergoing primary conduit placement or reoperation report overall freedom from reoperation ranging from 60% to 90% at 5 years [1–6]. Reported risk factors for reoperation included smaller conduit diameter, conduit type, younger age, and diagnosis of transposition of the great arteries, depending on the series. Specific studies focusing on freedom from reoperation after conduit replacement found that younger age, smaller conduit, use of homograft, and diagnosis of truncus arteriosus were risk factors for a repeat conduit replacement after a first conduit replacement [1, 2, 4–10]. In our cohort, we found that use of a pulmonic homograft as the original conduit was associated with conduit reoperation and reintervention. Although it is not entirely clear why original conduit type should affect second conduit outcomes, conduit allosensitization may be considered. Some authors have described accelerated fibrocalcification in aortic homografts, and other authors have ascribed these changes to an immune-mediated phenomenon based on circumstantial data such as immunologic (eg, blood group or HLA type) mismatches between graft and patient [12, 13]. Our data are unable to address the possible role of allosensitization.
Although it is intuitive that smaller conduits would be associated with shorter freedom from reoperation, conduit size is a complex variable. Many patients needing RV-PA conduits have PA anomalies predisposing them to multiple stenoses. Optimizing a conduit to minimize mismatch between the conduit and patient or PA size may theoretically help reduce total pulmonary arterial impedance and RV work. Karamlou and coworkers [14] and Askovich and associates [15] found that a conduit size more than 2.5 standard deviations above the mean normal pulmonary annulus diameter (Z-score >2.5) was associated with diminished freedom from reoperation. In patients with tetralogy of Fallot or truncus arteriosus, Wells and colleagues [16] found that valvar area thickening and shrinkage led to conduit stenosis in 53% of patients, whereas somatic outgrowth was responsible in only 8%. McMullan and associates [17] showed that surgically restricting oversized conduits in an effort to optimize matching of the conduit to PA size in patients with truncus arteriosus was associated with freedom from significant conduit stenosis or regurgitation. Therefore, conclusions from our data on young children that bigger is better should not be drawn without additional investigation.
Survival After Right Ventricle to Pulmonary Artery Conduit Operations
In our series, there was 1 early death (0.5%) and 95% survival at 10 years by Kaplan-Meier analysis. Although all 11 of the deaths in this series aggregated to the replacement group, we believe that this finding was stochastic, given that nearly all were far removed from the conduit 2 surgery and that most patients had undergone a conduit reoperation after conduit 2. Single-center series on mixed cohorts undergoing primary and repeat RV-PA conduits have reported early postoperative mortality of 4% to 10% and late survival ranging from 66% to 94% at 10 years [1–10]. Early mortality is substantially lower after conduit replacement than after primary conduit placement, with estimates ranging from 0.9% to 1.7%. Multivariate analyses, excluding era effects, have identified risk factors for death to include male sex, older age at repair, RV hypertension after the repair, and certain diagnoses including truncus arteriosus, transposition of the great arteries, and congenitally corrected transposition.
Conduit Augmentation
Of the 180 children in this series, 18% underwent conduit augmentation at conduit 2. Augmentation was less likely to be performed in patients with an aortic homograft and more likely in pulmonic homografts. As anticipated, even when patients undergoing ventricular septal defect closure concomitant with conduit 2 (almost all of whom had conduit replacement) were excluded, the duration of cardiopulmonary bypass was more than 30 minutes shorter in the augmentation group on average. Intensive care unit stay was not different between groups. In contrast to our hypothesis, however, freedom from reoperation and from any conduit reintervention after conduit 2 were not significantly different between patients who underwent augmentation and those who underwent conduit replacement. Although patients with conduit augmentation were almost invariably left with conduit regurgitation after conduit 2, almost all of the patients undergoing subsequent reintervention in both groups had RV-PA obstruction, and did not undergo reintervention for regurgitation. Moreover, the degree of conduit obstruction was comparable in the two groups both in patients who did and did not undergo reintervention.
We found only one study that looked at the role of conduit augmentation for obstructed RV-PA conduits. Our findings differ somewhat from those of Mohammadi and colleagues [18], who observed that patch augmentation in a cohort with a wider age range was associated with higher rates of conduit dysfunction leading to reoperation. This difference may be related to the relatively narrow age range, the need for another conduit surgery in relatively short succession, or the higher proportion of pulmonary homografts in the augmentation group of our cohort. Pulmonary homografts have been associated with increased longevity and absence of accelerated fibrocalcification. As such, supple pulmonary homografts may be more amenable to patch augmentation than other types of conduits. Patch augmentation may offer a useful and perhaps more cost-effective alternative to conduit replacement for conduit reoperation in selected young children, especially in resource-poor settings.
Limitations
Retrospective data collection and incomplete follow-up after conduit 2 in 19 of 180 patients are important limitations of the study. The inability to ascertain reintervention in these patients and their preponderance in the conduit replacement group risks underestimating freedom from reoperation or reintervention after conduit replacement. Another limitation is possible selection bias in the use of conduit augmentation. The bias in selection of patients with aortic homografts for replacement rather than augmentation was almost certainly based on technical considerations, as discussed above. Furthermore, a number of surgeons performed the procedures examined in this report, and idiosyncratic preferences for one procedure or technical differences may have biased the findings. In an effort to minimize this bias, we adjusted for surgeon and patient age in our outcome analyses. We were also unable to systematically assess the degree or incidence of fibrocalcification in explanted or augmented homografts. Although these limitations may make it difficult to generalize our findings, the data support the conclusion that acute and intermediate outcomes do not differ dramatically between children undergoing conduit augmentation and replacement of an obstructed first RV-PA conduit.
Conclusions
Freedom from a third RV-PA conduit operation after second conduit operation in young children was 80% at 5 years and 39% at 10 years in this series. Smaller body surface area and undersized conduits were independently associated with shorter freedom from reoperation and any reintervention. Augmentation of the original RV-PA conduit at the time of reoperation for conduit obstruction may be a reasonable strategy in certain patients, and is associated with shorter cardiopulmonary bypass time, similar postoperative course, and similar freedom from reoperation and reintervention. Further study will be necessary to determine characteristics of patients more likely to benefit from augmentation or replacement.
| Acknowledgments |
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J. S. Tweddell Invited commentary. Ann. Thorac. Surg., August 1, 2009; 88(2): 580 - 580. [Full Text] [PDF] |
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