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The treatment of aortic valve disease in children and adolescents requires an individualized approach to provide a long-term solution with optimal hemodynamic profile. The role of aortic leaflet reconstruction techniques is evolving.
We retrospectively reviewed the charts of 58 patients who underwent aortic valve tricuspidalization either by an Ozaki procedure (neo-tricuspidalization) or single leaflet reconstruction between 2015 and 2019. Immediate operative results as well as hospital and short-term outpatient follow-up data were evaluated.
Fifty-eight patients underwent leaflet reconstruction with 40 (69%) receiving a neo-tricuspidalization and 18 patients (31%) undergoing single leaflet reconstruction, using either a glutaraldehyde fixed autologous pericardium or tissue engineered bovine pericardium (CardioCel; Admedus, Queensland, Australia). The median age at the time of surgery was 14.8 years (interquartile range, 10.6-16.8 years). Twenty-three patients (40%) had isolated aortic regurgitation. The peak velocity across the aortic valve decreased from 3.4 ± 1.2 meters per second (m/s) preoperatively to 2.0 ± 0.4 m/s (P < .001) after surgery and remained stable (2.2 ± 0.7 m/s) during a median echocardiographic follow-up of 14.1 months (7.2-20.1 months) for the whole cohort. Freedom from reoperation or moderate and greater aortic regurgitation at 1, 2, and 3 years was 94.2% ± 3.3%, 85.0% ± 5.8%, and 79.0% ± 8.0%, respectively, with no difference between the neo-tricuspidalization and single leaflet reconstruction groups (P = .635). There were 6 late reoperations (10%) of which 3 were due to endocarditis.
Aortic leaflet reconstruction provides acceptable short-term hemodynamic outcomes and proves the utility of this technique as an adjunctive strategy for surgical treatment of aortic valve disease in children and young adults.
Aortic leaflet reconstruction techniques can be applied in children and young adults with acceptable immediate hemodynamic outcomes. These short-term outcomes must be weighed against the need for late reoperation after the Ross procedure, disappointing long-terms result of various aortic valve repair techniques, and important anticoagulation related morbidity following mechanical valve replacement.
Children and young adults with aortic valve disease continue to present a challenging pathology to manage. They require an individualized treatment approach based on the aortic valve anatomy, associated cardiac lesions, previous valve interventions, patient size and age at the time of intervention, as well as surgeon experience. The management strategy pursued must consider the durability provided to minimize the need for repetitive procedures, as well as the morbidity associated with lifelong anticoagulation therapy.
Balloon valvotomy or open surgical valvotomy are used as the initial intervention in neonates and children with aortic valve stenosis, but regardless of initial strategy many require further surgical intervention within 10 years.
The small size of the child at this stage often prohibits the use of an adult size prosthesis and therefore management strategies have evolved to include the use of either aortic leaflet repair or reconstruction until annular growth allows for a more durable prosthesis placement. Recent literature reports favorable comprehensive outcomes for the use of multiple techniques of aortic valve repair in children,
have reported extensively on the excellent outcomes for their technique of autologous pericardial aortic valve reconstruction. However, a study evaluating the outcomes in a younger population had a mean age of 47.8 ± 11.2 years.
Therefore, the feasibility and outcomes of this aortic valve reconstruction technique has not been studied in children and young adults.
We evaluated the immediate hemodynamic results and short-term outcomes for children and young patients who have undergone aortic leaflet replacement to determine the utility of this technique in the armamentarium of those managing aortic valve disease in pediatric populations.
Under institutional review board-approved protocols, we retrospectively reviewed the charts of 58 patients who underwent either neo-tricuspidalization (Ozaki procedure) or single leaflet reconstruction (SLR), with preservation and rotation of native leaflets, between 2015 and 2019. Immediate operative results as well as hospital and short-term outpatient follow-up data were evaluated.
Data were abstracted from inpatient hospital records, operative reports, follow-up, and clinic notes. Preadmission and immediate postrepair (intraoperative) echocardiograms were reviewed to assess immediate hemodynamic results of the repair. Follow-up echocardiograms were reviewed to assess durability over time. Severity of valvar stenosis was reported as peak velocity in meters per second (m/s). Aortic regurgitation (AR) was graded from 0 to 4 with grade 0 = none, grade 1 = trivial, grade 2 = mild, grade 3 = moderate, and grade 4 = severe.
Following median sternotomy, a large piece of autologous pericardium was harvested. This was then treated with 0.6% glutaraldehyde solution for 10 minutes, followed by rinsing in saline 3 × 6 minutes each.
For patients aged 15 years or younger, the glutaraldehyde treatment was limited to 5 minutes. Tissue engineered bovine pericardium (CardioCel; Admedus, Queensland, Australia) was used in absence of native pericardium or due to regulatory restrictions on glutaradehyde use.
After cardiac arrest with cold blood cardioplegia, a transverse aortotomy was performed. Retraction sutures were placed at each commissure for better exposure and to simulate the pressurized state of the aorta. The valvar anatomy was then inspected taking into account the number and position of commissures and raphes, leaflet geometry, and quality of the leaflet tissue. Based on this assessment a decision was made as whether to perform an Ozaki procedure or SLR with preservation of the native aortic valve tissue.
In the case of neo-tricuspidalization, native leaflets were excised and leaflet replacement carried out in a manner as described by Ozaki and colleagues (Video 1).
Both of the fused leaflets were detached from a commissure/raphe along the annular level to an extent at which the leaflets could be rotated and brought high enough to form new commissures. Particular attention was paid for these to be of equal height compared with the reference commissure. The new leaflet was then measured and fashioned similar to the description by Hammer and colleagues.
Lengths of silk suture were then used to estimate the required free edge length and geometric height of the new leaflet. These were then used as a guide to fashion a neo-cusp from either autologous glutaraldehyde-treated pericardium or bovine pericardium. The newly fashioned leaflet was then sewn to the annulus and aortic wall with either running 5–0 or 4–0 polypropylene suture, starting at the nadir of the new sinus with the neo-cusp folded into the outflow tract, and then carrying the suture line up to its respective commissures. It was secured to each commissure by passing a pledgeted polypropylene suture through the leaflet and out of the aortic wall. The height of the neo-cusp was then trimmed to an appropriate length and valve geometry as well as coaptation was reassessed.
Categorical data are presented as percentage and continuous nonnormally distributed data are presented as median and interquartile range (IQR) or mean. Differences within a group, for normally distributed continuous variables, were compared by 2-tailed Student t tests and nonnormally distributed variables were compared by Wilcoxon test. Freedom from reoperation and moderate or greater AR was estimated by Kaplan-Meier analysis. Differences between groups were analyzed by log-rank test.
Analyses were performed using R version 2018 (R Foundation for Statistical Computing, Vienna, Austria) and IBM SPSS software version 21.0 (IBM-SPSS Inc, Armonk, NY).
A total of 58 patients underwent aortic leaflet reconstruction surgery between 2015 and early 2019. The median age and weight of patients at the time of operation was 14.8 years (IQR, 10.6-16.8 years) and 53.5 kg (IQR, 32.9-67.8 kg). There were 23 balloon valvuloplasties performed in 22 patients before indexed surgery and 11 previous cardiac operations. The majority of patients (60%) had either isolated aortic stenosis in 14 (24%) or mixed pathology in 21 (36%) at the time of valve repair. The remaining 23 patients (40%) had AR. Details of the preoperative aortic valve anatomy and patient characteristics can be found in Table 1.
Table 1Demographic characteristics of patient cohort (N = 58)
Values are presented as median (interquartile range) or (%). CAT, Common arterial trunk; DORV, double-outlet right ventricle; AS, aortic stenosis; PAB, pulmonary artery band; ASO, arterial switch operation; TGA, transposition of the great arteries.
Of 58 patients, 40 patients (69%) underwent an Ozaki procedure. The remaining 18 patients (31%) underwent SLR. The material used for leaflet reconstruction was split, with 26 patients (45%) receiving autologous pericardium and 32 patients (55%) bovine pericardium (CardioCel). Twelve patients (21%) had concomitant procedures performed at the time of aortic valve surgery (Table 2). The median bypass and crossclamp times of those patients undergoing isolated Ozaki or SLR were 130.5 minutes (IQR, 113.5-142.5 minutes) and 103.5 minutes (IQR, 90.5-111 minutes), respectively. Forty patients (69%) were extubated on the day of surgery. The median intensive care unit and hospital length of stay was 1 day (IQR, 1-2 days) and 5 days (IQR, 4-7 days), respectively. Further perioperative characteristics can be found in Table 2.
Table 2Operative characteristics (N = 58)
Single leaflet reconstruction
Patients with concomitant procedures
Mitral valve repair
Supravalvar AS repair
Resection of subaortic membrane
PA debanding/septal myectomy/ASD creation
Manougian root enlargment/supravalvar AS repair
Bypass time (min)
Crossclamp time (min)
Postoperative aortic valve peak velocity (m/s)
Postoperative aortic regurgitation degree
ICU length of stay (d)
Hospital length of stay (d)
Values are presented as n (%) or median (interquartile range). RV-PA, Right ventricular to pulmonary artery; AS, aortic stenosis; PDA, patent ductus arteriosus; PA, pulmonary artery; ASD, atrial septal defect; ICU, intensive care unit.
Follow-up was complete in all but 1 patient. Statistical comparison shows that both Ozaki procedure and SLR were able to achieve significant reduction in aortic valve peak velocity from 3.4 ± 1.2 m/s to 2.0 ± 0.4 m/s immediately following repair (t test P < .001) and this did not significantly increase (2.2 ± 0.7 m/s) over a median echocardiographic follow up of 14.1 months (IQR, 7.2-20.1 months) (Figure 1).
When evaluated separately, both Ozaki procedure and SLR groups were able to achieve a significant reduction in aortic valve peak velocity following repair: Ozaki group from 3.1 ± 1.1 m/s to 1.9 ± 0.4 m/s (t test P < .001) and SLR group from 4.1 ± 1.2 m/s preoperatively to 0.8 ± 0.4 m/s postoperatively (t test P < .001). Although aortic valve peak velocities immediately following repair and at follow-up in patients where autologous pericardium was used were not different (1.91 ± 0.38 vs 1.83 ± 0.77; t test P = .68) there was a significant increase in velocity of patients repaired with bovine pericardium over time (2.13 ± 0.42 vs 2.58 ± 0.56; t test P = .002) (Figure 2).
Correlations of annular size and aortic valve peak velocity after Ozaki procedure at follow-up were examined using correlation analysis for both types of patch material. The correlation coefficients were compared with a 2-sided Fisher independent z test (P = .2338) and Zou confidence interval (95% CI), –0.9257 to 0.2087. No significant difference was observed. (Figure 3).
Of 44 patients with moderate or greater AR before repair, all were reduced to mild or less immediately after surgery (44 vs 0; Wilcoxon P < .001). All but 2 patients, both from the SLR group, had mild or less AR at the final follow-up.
There was 1 early reoperation after neo-tricuspidalization with partial right neo-cusp detachment that was addressed on the first postoperative day without need for further interventions. This represents a technical failure; hence, it was considered separately from late reoperations, which were due to either endocarditis or structural valve degeneration.
Six patients (10%) required late reoperation (Ozaki group n = 4 and SLR group n = 2). A summary of indications and time to reintervention for the entire cohort is presented in Table 3.
Table 3Summary of indications and time to reintervention for the entire cohort
For the Ozaki procedure, reoperations were due to endocarditis in 3 patients and structural valve degeneration (decreased mobility and calcification of bovine pericardial leaflet) in 1 patient. One patient had successful preservation of the initial neo-tricuspidalization after developing group A Streptococcus endocarditis associated with varicella zoster virus infection. This patient had reoperation following 6 weeks of antibiotic treatment with closure of periannular abscess cavities. Of the other 2 patients with endocarditis, 1 received a mechanical valve implantation and one had a homograft root replacement for associated aortic root destruction. The patient with degenerated bovine pericardial leaflets and reduced neo-cusp mobility had mechanical valve replacement. Of the 2 reoperations in the SLR group, 1 patient underwent a Ross procedure and another with the neo-cusp perforation was able to undergo repair with a patch closure.
The durability of the repair was investigated as freedom from either late reoperation or moderate and greater AR at 1, 2, and 3 years and was 94.2% ± 3.3%, 85.0% ± 5.8%, and 79.0% ± 8.0%, respectively, without a difference when evaluated according to surgical technique (P = .635) or leaflet material used (P = .464) (Figures 4 and 5). When patients who underwent neo-tricuspidalization with autologous pericardium were evaluated separately, the freedom from reoperation and moderate or greater AR was 87.5% at the time of final follow-up (Figure 6).
There was 1 mortality in a patient with a history of prior heart transplant for dilated cardiomyopathy and severely impaired left ventricle function, 5.6 months after discharge following aortic valve reconstruction surgery. The transplant was complicated by infective endocarditis of the donor heart requiring resection of a vegetation and resultant AR. This patient also experienced heart block requiring permanent pacemaker placement after heart transplant. At the time of aortic valve surgery, his left ventricular shortening fraction was 13% with left ventricular end diastolic diameter of 56.5 mm and left ventricular end systolic diameter of 48.9 mm. He underwent neo-tricuspidalization and was discharged after 28 days. A 5-month follow-up echocardiogram demonstrated only mild AR and peak transvalvar velocity of 2.8 m/s. His clinical condition was improved with left ventricle shortening fraction of 19%, left ventricular end diastolic diameter of 42.4 mm and left ventricular end systolic diameter 34.5 mm. His death occurred outside the hospital and therefore the exact details remain uncertain.
The management of aortic valve disease in the pediatric population presents a significant challenge with the overall goals of preserving the left ventricle function and minimizing the number of procedures required over a lifetime. However, multiple factors influence which interventional strategies can be applied, most importantly the patient's underlying cardiac anatomy and the age at which they reach indications for aortic valve intervention. Aortic leaflet replacement techniques can provide a useful alternative for patients with particular anatomic challenges.
The initial management strategy for aortic stenosis in the neonatal population has historically been the use of balloon valvuloplasty; however, several publications have advocated for the superior freedom from reoperation provided by surgical valve repair.
Many centers, including our own, have transitioned to a policy of surgical valvotomy for the initial management of aortic stenosis apart from neonates presenting with either severe left ventricular impairment and/or poor clinical condition in which case a balloon valvotomy is still considered a valuable alternative.
The choice of the next operation is another area of even more significant debate. The Ross procedure clearly provides several advantages.
Further studies have suggested use of an inclusion technique as a primary procedure, that while protecting the autograft from dilation, also fixes the aortic root diameter and can only be applied in patients with an adequately sized pulmonary valve.
Our center has recently published data reporting on the subannular technique for autograft placement that demonstrates protection of the autograft from dilation and also allows for continued somatic growth of the aortic annulus; however, it is unclear if this benefit extends beyond the first decade after surgery.
The advantages of the Ross procedure are also conflicted by the potential future need for reintervention on the right ventricular to pulmonary artery conduit with a reported freedom from homograft reintervention of 87.5% at 20 years.
Another option is placement of a mechanical prosthesis with or without annular enlargement. This provides acceptable freedom from reoperation, most recently found to be 78.4% ± 6.9% at 10 years in a cohort with a median age of 16 years (IQR, 12-22.8 years) with younger age acting as a significant independent predictor for reoperation. The rate of thromboembolism was found to be 0.66% per patient-year and bleeding 0.83% per patient year in a cohort managed on warfarin anticoagulation with goal international normalized ratio of 2.0 to 3.0. In this study 33% of patients were also treated with aspirin and 1 with clopidogrel.
has shown a substantial late mortality of 1.55% per patient year in nonelderly patients undergoing mechanical aortic valve replacement, with mean life expectancy just more than half of the age-matched general population. This difference has been even more significant in younger population.
There are patients in whom mechanical aortic valve replacement or the Ross procedure is not applicable. For example, patients with previous truncus arteriosus repair and others lacking a suitable pulmonary autograft, will not have a viable option for the Ross procedure. Also, many pediatric patients will not have an adequate aortic annular size to accommodate a prosthesis that will be large enough to avoid reoperation following significant patient growth. Furthermore, implantation of a small stented valve fixes the annulus, making reimplantation surgery challenging due to the necessity of performing an annular enlargement. These patients, in whom a definitive adult size aortic valve replacement procedure cannot be performed, have the most to benefit from leaflet replacement techniques.
Our investigation has shown that both an Ozaki procedure and SLR can be performed in pediatric populations, with annular size as small as 6.7 mm (SLR), with excellent immediate hemodynamic outcomes. We believe that the advantages of the Ozaki procedure with increased free margin length of the neo-cusps as discussed by Ozaki and colleagues
will have an even greater utility in pediatric populations. We anticipate that with annular and sinotubular junction growth, the coaptation may potentially be preserved by the excess of effective coaptation height at the time of initial repair.
An additional advantage of this technique is anticipated preservation of annular dynamic parameters and unhindered growth of the aortic annulus, which allows for further aortic leaflet reconstruction surgery. Also, continued aortic annular growth allows for the avoidance of aortic root enlargement techniques when aortic valve replacement becomes necessary in the future.
A recognized area of concern in our study is the 5% incidence of infective endocarditis. Etnel and colleagues
recently published a meta-analysis of the outcomes after aortic valve replacement in children reporting a rate of endocarditis of 0.40% per year (IQR, 0.22%-0.73% per year) following Ross, 0.45% per year (IQR, 0.27%-0.75% per year) following mechanical prosthesis, and 0.66% per year (IQR, 0.25%-1.75% per year) following homograft aortic valve replacement.
reported 13 cases of infective endocarditis requiring aortic valve reoperation among 850 cases (1.5%) after a mean follow-up of 53.7 ± 28.2 months. This brings into question the propensity of the leaflet material for bacterial inoculation. A study investigating the high incidence of right heart endocarditis in patients with congenital heart disease after surgery or percutaneous pulmonary valve implantation compared 3 different materials for valved stents. Bovine pericardium was found to have the lowest propensity of bacterial adhesion in comparison to bovine jugular vein and porcine pericardium.
It is unclear which factors contributed to incidence of endocarditis in our cohort. One patient developed a vegetation following infection with varicella zoster virus, which is a described complication.
Another patient developed endocarditis as a consequence of poor dental hygiene. Additional follow-up and comparison of incidence of endocarditis following alternative valve operations at our institution will be required to discern this definitively.
The variability in patient pathologic substrates and aortic valve repair techniques performed makes a meaningful comparison of our results with the literature difficult to carry out. One center has published freedom from reintervention at 1, 5, and 7 years of 97%, 87%, and 80%, respectively, for patients undergoing valve repair. Multiple techniques were used in these patients, which included leaflet extension, tricuspidization, commissurotomy, leaflet thinning, triangular resection, subcommissural annuloplasty, free-edge plication, and leaflet perforation repair.
Also, a more recent article described results of aortic valve repair in a population with a median age of 9.79 years (IQR, 0.1-28.7 years). Techniques used in this population included commissurotomy shaving (38%), leaflet replacement (40%), leaflet extension (11%), and neocommissure creation (11%) with a freedom from reoperation at 1, 5, and 7 years of 89%, 70%, and 57%, respectively.
The most common reason for reoperation in this study was substantial AR. These outcomes must be considered with caution given the fundamental differences in the repair techniques used in these studies and our patient cohort.
Identification of an optimal leaflet replacement material is a particularly difficult endeavor. This is likely to be the “Achilles' heel” of leaflet replacement surgeries in young patients rather than surgical technique per se. Scarce clinical evidence exists in determining which biomaterial for aortic leaflet replacement would be optimal.
Glutaraldehyde fixed autologous pericardium has provided acceptable durability in elderly patients following the Ozaki procedure; however, the results from this study cannot be directly extrapolated to pediatric populations. It has been shown that biomaterials are prone to more rapid degeneration in younger patients, especially children.
the use of CardioCel in patients with congenital aortic valve disease (median age, 9 years) was associated with unsatisfactory mid-term results. In our series, the explanted bovine patch material showed evidence of calcification on histopathology (Figure 7). However, it was unclear whether this process started within the patch or it extended from either the aortic annulus or suture line.
We have demonstrated better performance of autologous pericardium compared to bovine pericardium with lower gradient across the aortic valve at final follow-up. However, we did not observe a significant difference in terms of material used for a composite outcome measure of AR, endocarditis, or reoperation rate. However, a 100% freedom from moderate to severe AR at follow-up in the Ozaki group where autologous pericardium was used (n = 20) could be an indicator of favorable midterm results.
Our study has limitations inherent to any retrospective review. Particularly, our study does not allow for the direct comparison of this cohort with patients receiving alternative procedures at our institution and relies on the extrapolation of previously published outcome data. Future directions of investigation will need to validate midterm durability, the influence of different materials used for cusp reconstruction, and the timing of progression to definitive aortic valve operations.
Complex aortic valve repair using aortic leaflet replacement techniques can be applied in children and young adults with acceptable immediate hemodynamic outcomes. The guarded need for reintervention of this technique must be weighed against the need for late autograft reintervention, pulmonary homograft replacement, and the anticoagulation-related morbidity of aortic valve replacement. In addition, aortic leaflet replacement techniques may offer utility in pediatric patients with anatomy unsuitable for aortic valve replacement.
Conflict of Interest Statement
Mr Martin Kostolny has proctorship contract with TERUMO EUROPE NV, Belgium. All other authors have nothing to disclose with regard to commercial support.
The initial echocardiogram clips shows a bicuspid aortic valve with poor coaptation and severe aortic regurgitation in a 6-year old female patient. The native aortic valve leaflets are resected and sizers used to measure intercommissural distance and to mark a midpoint on the native annulus for position of new commissures. A template of corresponding size is then used to create each neo-cusp with marking of dots for suturing. Starting at the midpoint of the right coronary sinus, the neo-cusp is secured to the annulus with a running polypropylene suture with a 3:1 suturing ratio between cusp and annulus initially. After suturing the last marker dot, the suture is then passed through the aortic wall 2 mm below the level of the commissure. The left coronary neo-cusp is then placed in a similar fashion and both commissural sutures and wing extension passed through a felt pledget outside the aortic wall and tied thus creating the right/left commissure. The noncoronary neo-cusp is then placed in identical fashion with creation of the left/noncoronary and then non/right coronary commissure last. Immediate postoperative echocardiography reveals well opening neo-cusps with trivial central regurgitation. Video available at: https://www.jtcvs.org/article/S0022-5223(19)32356-6/fulltext.
Outcomes after balloon dilation of congenital aortic stenosis in children and adolescents.
Aortic valve disease continues to be a challenging problem in pediatric patients. We continuously search for new innovations, as our best options are imperfect. In this issue of the Journal, Wiggins and colleagues1 from Great Ormond Street present their short-term results using the Ozaki procedure (neotricuspidization) and other valve reconstruction techniques in children and young adults. This is currently the largest retrospective single-center review in children and young adults, comprising 58 patients from 2015 to 2019.
In this issue of the Journal, Wiggins and colleagues1 present their work studying the utility of aortic valve leaflet reconstruction in children and young adults with aortic valve disease. Using data from a high-volume, single center, the authors studied 58 patients over a 4-year period who underwent either an aortic valve neo-tricuspidization procedure (Ozaki) or a single-leaflet reconstruction. The authors found that these 2 techniques can be performed safely with acceptable short-term hemodynamics in a population of patients that remains a significant clinical challenge.
A sustained long-term treatment strategy for the treatment of aortic valve disease in the pediatric population is inevitable. Thus, this strategy should involve the entire current armamentarium of available treatment options that need to be applied individually in each and every case. The requirements for the ideal valve substitute are well known, whereas such a valve is still not available.1 A myriad of factors influence the decision-making in this population that starts with the anatomy of the valve, concomitant cardiac lesions, previous interventions, patient needs and choice, and particularly the expertise of the surgical team.