CONGENITAL: AORTIC VALVE

The utility of aortic valve leaflet reconstruction techniques

in children and young adults
Luke M. Wiggins, MD,a Branko Mimic, MD, PhD,b Richard Issitt, PhD,c,d Slobodan Ilic, MD, PhD,e
Beatrice Bonello, MD,f Jan Marek, MD,f and Martin Kostolny, MDa

ABSTRACT Progression of Aortic Stenosis

CONG
Significant reduction between pre-op and immediately post-op P < .001

6
Objectives: The treatment of aortic valve disease in children and adolescents re-

Aortic Valve Peak Velocity (m/s)

quires an individualized approach to provide a long-term solution with optimal 4

hemodynamic profile. The role of aortic leaflet reconstruction techniques is

evolving. 2

Methods: We retrospectively reviewed the charts of 58 patients who

0
underwent aortic valve tricuspidalization either by an Ozaki procedure Preoperative Postoperative Follow-Up

(neo-tricuspidalization) or single leaflet reconstruction between 2015 and 2019. Timepoint

No significant difference in AS between materials at follow-up (P > .05)

Immediate operative results as well as hospital and short-term outpatient Box plots depicting peak aortic valve velocities preop-
follow-up data were evaluated. eratively, immediately postoperatively, and at follow-
up for the entire cohort.
Results: Fifty-eight patients underwent leaflet reconstruction with 40 (69%)
receiving a neo-tricuspidalization and 18 patients (31%) undergoing single leaflet
Central Message
reconstruction, using either a glutaraldehyde fixed autologous pericardium or tis-
Aortic leaflet reconstruction techniques may
sue engineered bovine pericardium (CardioCel; Admedus, Queensland, offer a valuable alternative in children and
Australia). The median age at the time of surgery was 14.8 years (interquartile young adults with aortic valve disease.
range, 10.6-16.8 years). Twenty-three patients (40%) had isolated aortic regurgi-
tation. The peak velocity across the aortic valve decreased from 3.4
1.2 meters Perspective
per second (m/s) preoperatively to 2.0
0.4 m/s (P<.001) after surgery and re- Aortic leaflet reconstruction techniques can be
mained stable (2.2
0.7 m/s) during a median echocardiographic follow-up of applied in children and young adults with
14.1 months (7.2-20.1 months) for the whole cohort. Freedom from reoperation acceptable immediate hemodynamic outcomes.
or moderate and greater aortic regurgitation at 1, 2, and 3 years was These short-term outcomes must be weighed
against the need for late reoperation after the
94.2%
3.3%, 85.0%
5.8%, and 79.0%
8.0%, respectively, with no dif- Ross procedure, disappointing long-terms result
ference between the neo-tricuspidalization and single leaflet reconstruction of various aortic valve repair techniques, and
groups (P ¼ .635). There were 6 late reoperations (10%) of which 3 were due important anticoagulation related morbidity
to endocarditis. following mechanical valve replacement.

Conclusions: Aortic leaflet reconstruction provides acceptable short-term

See Commentaries on pages 2379,
hemodynamic outcomes and proves the utility of this technique as an adjunctive
2380, and 2381.
strategy for surgical treatment of aortic valve disease in children and young adults.
(J Thorac Cardiovasc Surg 2020;159:2369-78)

Children and young adults with aortic valve disease on the aortic valve anatomy, associated cardiac lesions, pre-
continue to present a challenging pathology to manage. vious valve interventions, patient size and age at the time of
They require an individualized treatment approach based intervention, as well as surgeon experience. The manage-
ment strategy pursued must consider the durability provided
From the Divisions of aPediatric Cardiothoracic Surgery and fCardiology, cDigital
to minimize the need for repetitive procedures, as well as
Research Environment, and dPerfusion Service, Great Ormond Street Hospital, the morbidity associated with lifelong anticoagulation
London, United Kingdom; bEast Midlands Congenital Heart Centre, University therapy.
Hospitals of Leicester, Leicester, United Kingdom; and eDepartment of Pediatric
Cardiac Surgery, University Children’s Hospital, Belgrade, Serbia.
Received for publication May 10, 2019; revisions received Sept 6, 2019; accepted for
publication Sept 22, 2019; available ahead of print Dec 19, 2019. Scanning this QR code will take
Address for reprints: Luke M. Wiggins, MD, Division of Pediatric Cardiothoracic you to the article title page to
Surgery, Great Ormond Street Hospital, Great Ormond St, London, United
access supplementary informa-
Kingdom WC1N 3JH (E-mail: Luke.m.wiggins@gmail.com).
0022-5223/$36.00 tion.
Copyright Ó 2019 by The American Association for Thoracic Surgery
https://doi.org/10.1016/j.jtcvs.2019.09.176

The Journal of Thoracic and Cardiovascular Surgery c Volume 159, Number 6 2369
 Congenital: Aortic Valve Wiggins et al

After cardiac arrest with cold blood cardioplegia, a transverse aortot-

omy was performed. Retraction sutures were placed at each commissure
Abbreviations and Acronyms for better exposure and to simulate the pressurized state of the aorta. The
AR ¼ aortic regurgitation valvar anatomy was then inspected taking into account the number and po-
SLR ¼ single leaflet reconstruction sition 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
Balloon valvotomy or open surgical valvotomy are used valve tissue.
In the case of neo-tricuspidalization, native leaflets were excised and
CONG

as the initial intervention in neonates and children with

leaflet replacement carried out in a manner as described by Ozaki and col-
aortic valve stenosis, but regardless of initial strategy
leagues (Video 1).9 Multiple 5–0 polypropylene sutures were used to
many require further surgical intervention within implant newly created cusps in patients weighing <20 kg.
10 years.1-3 The small size of the child at this stage often The SLR technique was carried out in a way similar to the description by
prohibits the use of an adult size prosthesis and therefore Pr^etre and colleagues.10 Both of the fused leaflets were detached from a
management strategies have evolved to include the use of commissure/raphe along the annular level to an extent at which the leaflets
could be rotated and brought high enough to form new commissures.
either aortic leaflet repair or reconstruction until annular
Particular attention was paid for these to be of equal height compared
growth allows for a more durable prosthesis placement. with the reference commissure. The new leaflet was then measured and
Recent literature reports favorable comprehensive fashioned similar to the description by Hammer and colleagues.11 Lengths
outcomes for the use of multiple techniques of aortic of silk suture were then used to estimate the required free edge length and
valve repair in children,4 although the durability of many geometric height of the new leaflet. These were then used as a guide to
fashion a neo-cusp from either autologous glutaraldehyde-treated
repair techniques is still debated.5
Ozaki and colleagues6,7 have reported extensively on the
excellent outcomes for their technique of autologous peri-
cardial aortic valve reconstruction. However, a study evalu-
ating the outcomes in a younger population had a mean age
of 47.8
11.2 years.8 Therefore, the feasibility and out-
comes 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.

METHODS
Under institutional review board-approved protocols, we retrospec-
tively reviewed the charts of 58 patients who underwent either neo-tricus-
pidalization (Ozaki procedure) or single leaflet reconstruction (SLR), with
preservation and rotation of native leaflets, between 2015 and 2019. Imme-
diate operative results as well as hospital and short-term outpatient follow-
up data were evaluated.
Data Collection
Data were abstracted from inpatient hospital records, operative reports,
follow-up, and clinic notes. Preadmission and immediate postrepair (intra-
operative) echocardiograms were reviewed to assess immediate hemody-
namic 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 ¼ none, grade 1 ¼ trivial, grade
2 ¼ mild, grade 3 ¼ moderate, and grade 4 ¼ severe.
Operative Details
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 3 6 minutes each.9 For patients
aged 15 years or younger, the glutaraldehyde treatment was limited to 5 mi-
nutes. Tissue engineered bovine pericardium (CardioCel; Admedus,
Queensland, Australia) was used in absence of native pericardium or due
to regulatory restrictions on glutaradehyde use.
VIDEO 1. 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 mea-
sure 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 commis-
sure. The noncoronary neo-cusp is then placed in identical fashion with cre-
ation 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.

2370 The Journal of Thoracic and Cardiovascular Surgery c June 2020

Wiggins et al Congenital: Aortic Valve

TABLE 1. Demographic characteristics of patient cohort (N ¼ 58) TABLE 2. Operative characteristics (N ¼ 58)
Characteristic Result Characteristic Result
Age at operation (y) 14.8 (10.6-16.8) Technique
Weight (kg) 53.5 (32.9-67.8) Ozaki 40 (69)
Single leaflet reconstruction 18 (31)
Preoperative aortic valve peak velocity (m/s) 3.4 (2.3-4.2)
Patients with concomitant procedures 12 (21)
Preoperative aortic regurgitation 3 (3-4) RV-PA conduit 1

CONG
Preoperative aortic valve annular diameter* (mm) 21 (18-23.5) Mitral valve repair 1
Supravalvar AS repair 1
Preoperative aortic annular Z score 1.11 (–0.1 to 3.2)
Reduction aortoplasty 3
Previous intervention 23 (40) Resection of subaortic membrane 2
Aortic valve anatomy PDA ligation 1
Monocuspid 8 PA debanding/septal myectomy/ASD creation 1
Bicuspid 34 Septal myectomy 1
Tricuspid 15 Manougian root enlargment/supravalvar 1
Quadricuspid 1 AS repair
Previous operations 11 (19) Cusp material
Aortic valve repair 2 Autologous pericardium 26 (45)
Heart transplant 1 Bovine pericardium 32 (55)
CAT repair with repair of truncal valve 1 Bypass time (min) 130.5 (113.5-142.5)
Subaortic membrane resection 1
Crossclamp time (min) 103.5 (90.5-111)
DORV repair 1
Coarctation repair 1 Postoperative aortic valve peak velocity (m/s) 2 (1.75-2.4)
Surgical aortic valvotomy 1 Postoperative aortic regurgitation degree 1 (0-1)
Supravalvar AS repair 1
ICU length of stay (d) 1 (1-2)
PAB/coarctation repair 1
Aortic valve repair after previous ASO for TGA 1 Hospital length of stay (d) 5 (4-7)
Values are presented as median (interquartile range) or (%). CAT, Common arterial Values are presented as n (%) or median (interquartile range). RV-PA, Right ventric-
trunk; DORV, double-outlet right ventricle; AS, aortic stenosis; PAB, pulmonary ar- ular to pulmonary artery; AS, aortic stenosis; PDA, patent ductus arteriosus; PA, pul-
tery band; ASO, arterial switch operation; TGA, transposition of the great arteries. monary artery; ASD, atrial septal defect; ICU, intensive care unit.
*n ¼ 55.
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
pericardium or bovine pericardium. The newly fashioned leaflet was then and patient characteristics can be found in Table 1.
sewn to the annulus and aortic wall with either running 5–0 or 4–0 polypro-
pylene 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 RESULTS
commissures. It was secured to each commissure by passing a pledgeted
Operative Characteristics
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 Of 58 patients, 40 patients (69%) underwent an Ozaki
geometry as well as coaptation was reassessed. procedure. The remaining 18 patients (31%) underwent
SLR. The material used for leaflet reconstruction was split,
Statistical Analysis with 26 patients (45%) receiving autologous pericardium
Categorical data are presented as percentage and continuous nonnor- and 32 patients (55%) bovine pericardium (CardioCel).
mally distributed data are presented as median and interquartile range Twelve patients (21%) had concomitant procedures
(IQR) or mean. Differences within a group, for normally distributed contin-
performed at the time of aortic valve surgery (Table 2).
uous variables, were compared by 2-tailed Student t tests and nonnormally
distributed variables were compared by Wilcoxon test. Freedom from reop- The median bypass and crossclamp times of those patients
eration and moderate or greater AR was estimated by Kaplan-Meier anal- undergoing isolated Ozaki or SLR were 130.5 minutes
ysis. Differences between groups were analyzed by log-rank test. (IQR, 113.5-142.5 minutes) and 103.5 minutes (IQR,
Analyses were performed using R version 2018 (R Foundation for Sta- 90.5-111 minutes), respectively. Forty patients (69%)
tistical Computing, Vienna, Austria) and IBM SPSS software version 21.0
were extubated on the day of surgery. The median intensive
(IBM-SPSS Inc, Armonk, NY).
care unit and hospital length of stay was 1 day (IQR,
Demographic Characteristics 1-2 days) and 5 days (IQR, 4-7 days), respectively. Further
A total of 58 patients underwent aortic leaflet reconstruction surgery be- perioperative characteristics can be found in Table 2.
tween 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 pa- Echocardiographic Follow-up
tients before indexed surgery and 11 previous cardiac operations. The ma- Follow-up was complete in all but 1 patient. Statistical
jority of patients (60%) had either isolated aortic stenosis in 14 (24%) or comparison shows that both Ozaki procedure and SLR

The Journal of Thoracic and Cardiovascular Surgery c Volume 159, Number 6 2371
 Congenital: Aortic Valve Wiggins et al

Progression of Aortic Stenosis group from 4.1
1.2 m/s preoperatively to 0.8
0.4 m/s
Significant reduction between pre-op and immediately post-op P < .001
postoperatively (t test P < .001). Although aortic valve
6
peak velocities immediately following repair and at
Aortic Valve Peak Velocity (m/s)

follow-up in patients where autologous pericardium was

used were not different (1.91
0.38 vs 1.83
0.77; t test
4 P ¼ .68) there was a significant increase in velocity of pa-
tients repaired with bovine pericardium over time
CONG

(2.13
0.42 vs 2.58
0.56; t test P ¼ .002) (Figure 2).

2 Correlations of annular size and aortic valve peak veloc-
ity after Ozaki procedure at follow-up were examined using
correlation analysis for both types of patch material. The
0 correlation coefficients were compared with a 2-sided
Preoperative Postoperative Follow-Up
Fisher independent z test (P ¼ .2338) and Zou confidence
Timepoint interval (95% CI), –0.9257 to 0.2087. No significant differ-
No significant difference in AS between materials at follow-up (P > .05) ence was observed. (Figure 3).
FIGURE 1. Box plots depicting aortic valve peak velocities preopera- Of 44 patients with moderate or greater AR before repair,
tively, immediately postoperatively, and at follow-up for the entire cohort. all were reduced to mild or less immediately after surgery
(44 vs 0; Wilcoxon P < .001). All but 2 patients, both
were able to achieve significant reduction in aortic valve from the SLR group, had mild or less AR at the final
peak velocity from 3.4
1.2 m/s to 2.0
0.4 m/s immedi- follow-up.
ately following repair (t test P < .001) and this did not There was 1 early reoperation after neo-tricuspidalization
significantly increase (2.2
0.7 m/s) over a median echo- with partial right neo-cusp detachment that was addressed
cardiographic follow up of 14.1 months (IQR, 7.2- on the first postoperative day without need for further inter-
20.1 months) (Figure 1). ventions. This represents a technical failure; hence, it was
When evaluated separately, both Ozaki procedure and considered separately from late reoperations, which were
SLR groups were able to achieve a significant reduction due to either endocarditis or structural valve degeneration.
in aortic valve peak velocity following repair: Ozaki group Six patients (10%) required late reoperation (Ozaki
from 3.1
1.1 m/s to 1.9
0.4 m/s (t test P<.001) and SLR group n ¼ 4 and SLR group n ¼ 2). A summary of

Progression of Aortic Stenosis

Significant reduction between pre-op and immediately post-op P < .001

Autologous Pericardium Bovine Pericardium

6
Aortic Valve Peak Velocity (m/s)

Preoperative Postoperative Follow-Up Preoperative Postoperative Follow-Up

Timepoint
No significant difference in AS between materials at follow-up (P > .05) but increase in
CardioCel compared to immediately post-op (P = .002)
FIGURE 2. Box plots depicting the median and interquartile ranges of aortic valve peak velocities in meters per second preoperatively (blue), immediately
postoperatively (red), and at follow-up (green) stratified by leaflet material used for repair. AS, Aortic stenosis.

2372 The Journal of Thoracic and Cardiovascular Surgery c June 2020

Wiggins et al Congenital: Aortic Valve

Preoperative Annulus Size and Aortic Valve Velocity at Follow Up for Ozaki Procedure
Data split for the material used in the index operation

Autologous Pericardium Bovine Pericardium

Aortic Valve Peak Velocity (m/s)

CONG
2

20 25 30 18 20 22 24
Aortic Annulus Size (mm)
FIGURE 3. Correlations of annular size (millimeters) and aortic valve peak velocity (meters per second) after Ozaki procedure at follow-up was examined
using correlation analysis for both types of leaflet material.

indications and time to reintervention for the entire cohort is neo-cusp perforation was able to undergo repair with a
presented in Table 3. patch closure.
For the Ozaki procedure, reoperations were due to endo- The durability of the repair was investigated as freedom
carditis in 3 patients and structural valve degeneration from either late reoperation or moderate and greater AR at
(decreased mobility and calcification of bovine pericardial 1, 2, and 3 years and was 94.2%
3.3%, 85.0%
5.8%,
leaflet) in 1 patient. One patient had successful preservation and 79.0%
8.0%, respectively, without a difference
of the initial neo-tricuspidalization after developing group when evaluated according to surgical technique (P ¼ .635)
A Streptococcus endocarditis associated with varicella zos- or leaflet material used (P ¼ .464) (Figures 4 and 5). When
ter virus infection. This patient had reoperation following patients who underwent neo-tricuspidalization with
6 weeks of antibiotic treatment with closure of periannular autologous pericardium were evaluated separately, the
abscess cavities. Of the other 2 patients with endocarditis, 1 freedom from reoperation and moderate or greater AR was
received a mechanical valve implantation and one had a ho- 87.5% at the time of final follow-up (Figure 6).
mograft root replacement for associated aortic root destruc- There was 1 mortality in a patient with a history of prior
tion. The patient with degenerated bovine pericardial heart transplant for dilated cardiomyopathy and severely
leaflets and reduced neo-cusp mobility had mechanical impaired left ventricle function, 5.6 months after discharge
valve replacement. Of the 2 reoperations in the SLR group, following aortic valve reconstruction surgery. The trans-
1 patient underwent a Ross procedure and another with the plant was complicated by infective endocarditis of the

TABLE 3. Summary of indications and time to reintervention for the entire cohort
Patients requiring Index Indication for Time to
reoperation surgery Material reintervention re-intervention (mo) Reintervention
1* SLR Bovine pericardium Neo-cusp perforation 2.8 Patch repair
2* Ozaki Bovine pericardium Endocarditis 9.1 Valve repair
3 Ozaki Bovine pericardium Endocarditis/root abscess 11.0 Homograft root replacement
4 Ozaki Autologous pericardium Endocarditis 19.6 Mechanical prosthesis implantation
5 SLR Autologous pericardium SVD 20.4 Ross procedure
6 Ozaki Bovine pericardium SVD 27.8 Mechanical prosthesis implantation
Values are presented as time from initial cusp replacement surgery to reintervention in months. SLR, Single leaflet reconstruction; SVD, structural valve degeneration (reduced
neo-cusp mobility). *Successful preservation of the initial leaflet reconstruction surgery.

The Journal of Thoracic and Cardiovascular Surgery c Volume 159, Number 6 2373
 Congenital: Aortic Valve Wiggins et al

Cohort Freedom from Reintervention or ≥ Moderate AR Split

by Index Operation

Freedom from Reintervention or ≥ Moderate AR (%)

100

80
CONG

60

40

20

0 Log-rank, P = .635

0 1 2 3 4
Years
At Risk (Censored)
Ozaki 40 (0) 29 (9) 10 (27) 1 (35) 0 (36)
SLR 18 (0) 13 (4) 9 (6) 6 (9) 0 (14)
Cumulative Events
Ozaki 0 2 3 4 4
SLR 0 1 3 3 4
Estimate freedom % (95% CI)
Ozaki 94.4 (86.9-100.0) 89.7 (78.2-100.0) 74.4 (46.3-100.0)
SLR 93.3 (80.7-100/0) 76.4 (52.7-100.0) 76.4 (52.7-100.0)
FIGURE 4. This Kaplan-Meier curve depicts freedom from reoperation and  moderate aortic regurgitation (AR) at follow-up, stratified by index operation
(Ozaki vs single leaflet reconstruction [SLR]). 95% CI, 95% Confidence interval.

donor heart requiring resection of a vegetation and resultant strategies can be applied, most importantly the patient’s un-
AR. This patient also experienced heart block requiring per- derlying cardiac anatomy and the age at which they reach
manent pacemaker placement after heart transplant. At the indications for aortic valve intervention. Aortic leaflet
time of aortic valve surgery, his left ventricular shortening replacement techniques can provide a useful alternative
fraction was 13% with left ventricular end diastolic diam- for patients with particular anatomic challenges.
eter of 56.5 mm and left ventricular end systolic diameter The initial management strategy for aortic stenosis in the
of 48.9 mm. He underwent neo-tricuspidalization and was neonatal population has historically been the use of balloon
discharged after 28 days. A 5-month follow-up echocardio- valvuloplasty; however, several publications have advo-
gram demonstrated only mild AR and peak transvalvar ve- cated for the superior freedom from reoperation provided
locity of 2.8 m/s. His clinical condition was improved with by surgical valve repair.12,13 More recent re-evaluations of
left ventricle shortening fraction of 19%, left ventricular balloon valvuloplasty have revealed very poor outcomes
end diastolic diameter of 42.4 mm and left ventricular end when urgent/emergent aortic valve replacement is required
systolic diameter 34.5 mm. His death occurred outside the following this technique.14 Many centers, including our
hospital and therefore the exact details remain uncertain. own, have transitioned to a policy of surgical valvotomy
for the initial management of aortic stenosis apart from ne-
DISCUSSION onates presenting with either severe left ventricular impair-
The management of aortic valve disease in the pediatric ment and/or poor clinical condition in which case a balloon
population presents a significant challenge with the overall valvotomy is still considered a valuable alternative.
goals of preserving the left ventricle function and mini- The choice of the next operation is another area of even
mizing the number of procedures required over a lifetime. more significant debate. The Ross procedure clearly pro-
However, multiple factors influence which interventional vides several advantages.15 However, an increasing number

2374 The Journal of Thoracic and Cardiovascular Surgery c June 2020

Wiggins et al Congenital: Aortic Valve

Cohort Freedom from Reintervention or ≥ Moderate AR Split

by Material Used

Freedom from Reintervention or ≥ Moderate AR (%)

100

80

CONG
60

40

20

0 Log-rank, P = .464

0 1 2 3 4
Years
At Risk (Censored)
Bovine
32 (0) 23 (6) 14 (14) 6 (21) 0 (26)
pericardium
Autologous
26 (0) 19 (7) 5 (19) 1 (23) 0 (24)
pericardium

Cumulative Events
Bovine
0 3 4 5 6
pericardium
Autologous
0 0 2 2 2
pericardium
Estimate freedom % (95% CI)
Bovine pericardium 89.5 (78.2-100.0) 85.0 (71.3-98.7) 75.6 (54.3-96.8)
Autologous pericardium 81.8 (59.0-100.0)
FIGURE 5. Kaplan-Meier curve depicting freedom from reoperation and moderate or severe aortic regurgitation (AR) following complex aortic valve
repair stratifed by leaflet material (autologous pericardium vs bovine pericardium). 95% CI, 95% Confidence interval.

of reports have shown significant incidence of autograft the potential future need for reintervention on the right ven-
dilation within the first 2 decades following Ross proced- tricular to pulmonary artery conduit with a reported
ure.16,17 This late complication can be addressed by per- freedom from homograft reintervention of 87.5% at
forming a valve-sparing aortic root procedure in some 20 years.22
patients.18 Further studies have suggested use of an inclu- Another option is placement of a mechanical prosthesis
sion technique as a primary procedure, that while protecting with or without annular enlargement. This provides accept-
the autograft from dilation, also fixes the aortic root diam- able freedom from reoperation, most recently found to be
eter and can only be applied in patients with an adequately 78.4%
6.9% at 10 years in a cohort with a median age
sized pulmonary valve.19 Our center has recently published of 16 years (IQR, 12-22.8 years) with younger age acting
data reporting on the subannular technique for autograft as a significant independent predictor for reoperation. The
placement that demonstrates protection of the autograft rate of thromboembolism was found to be 0.66% per
from dilation and also allows for continued somatic growth patient-year and bleeding 0.83% per patient year in a cohort
of the aortic annulus; however, it is unclear if this benefit ex- managed on warfarin anticoagulation with goal interna-
tends beyond the first decade after surgery.20 The Ross oper- tional normalized ratio of 2.0 to 3.0. In this study 33% of
ation was also shown to have suboptimal results when used patients were also treated with aspirin and 1 with clopidog-
in a population with bicuspid aortic valves and AR.21 The rel.23 A recently published meta-analysis with microsimula-
advantages of the Ross procedure are also conflicted by tion by Korteland and colleagues24 has shown a substantial

The Journal of Thoracic and Cardiovascular Surgery c Volume 159, Number 6 2375
 Congenital: Aortic Valve Wiggins et al

Ozaki - Autologous Pericardium Subgroup

Freedom from Reintervention or ≥ Moderate AR (%)

100

80
CONG

60

40

20

0 Estimate freedom % (95% CI) 87.5 (64.6-100.0)

0 1 2 3
Years
At Risk (Censored)
20 (0) 14 (6) 3 (16) 0 (19)
Cumulative Events
0 0 1 1
FIGURE 6. Kaplan-Meier curve depicting freedom from reoperation and moderate to severe aortic regurgitation (AR) in patients undergoing Ozaki pro-
cedure where autologous pericardium was used for leaflet reconstruction. 95% CI, 95% Confidence interval.

late mortality of 1.55% per patient year in nonelderly pa- colleagues25 will have an even greater utility in pediatric
tients undergoing mechanical aortic valve replacement, populations. We anticipate that with annular and sinotubu-
with mean life expectancy just more than half of the age- lar junction growth, the coaptation may potentially be pre-
matched general population. This difference has been served by the excess of effective coaptation height at the
even more significant in younger population. time of initial repair.25 This has been shown to be a strong
There are patients in whom mechanical aortic valve predictor of aortic valve repair durability.26 An additional
replacement or the Ross procedure is not applicable. For advantage of this technique is anticipated preservation of
example, patients with previous truncus arteriosus repair annular dynamic parameters and unhindered growth of
and others lacking a suitable pulmonary autograft, will the aortic annulus, which allows for further aortic leaflet
not have a viable option for the Ross procedure. Also, reconstruction surgery. Also, continued aortic annular
many pediatric patients will not have an adequate aortic growth allows for the avoidance of aortic root enlargement
annular size to accommodate a prosthesis that will be large techniques when aortic valve replacement becomes neces-
enough to avoid reoperation following significant patient sary in the future.
growth. Furthermore, implantation of a small stented valve A recognized area of concern in our study is the 5% inci-
fixes the annulus, making reimplantation surgery chal- dence of infective endocarditis. Etnel and colleagues27
lenging due to the necessity of performing an annular recently published a meta-analysis of the outcomes after
enlargement. These patients, in whom a definitive adult aortic valve replacement in children reporting a rate of en-
size aortic valve replacement procedure cannot be per- docarditis of 0.40% per year (IQR, 0.22%-0.73% per year)
formed, have the most to benefit from leaflet replacement following Ross, 0.45% per year (IQR, 0.27%-0.75% per
techniques. year) following mechanical prosthesis, and 0.66% per
Our investigation has shown that both an Ozaki proced- year (IQR, 0.25%-1.75% per year) following homograft
ure and SLR can be performed in pediatric populations, aortic valve replacement.27 Ozaki and colleagues7 reported
with annular size as small as 6.7 mm (SLR), with excellent 13 cases of infective endocarditis requiring aortic valve re-
immediate hemodynamic outcomes. We believe that the ad- operation among 850 cases (1.5%) after a mean follow-up
vantages of the Ozaki procedure with increased free margin of 53.7
28.2 months. This brings into question the pro-
length of the neo-cusps as discussed by Ozaki and pensity of the leaflet material for bacterial inoculation. A

2376 The Journal of Thoracic and Cardiovascular Surgery c June 2020

Wiggins et al
FIGURE 7. Histopathology of explanted right coronary CardioCel patch
(Admedus, Queensland, Australia) stained with Alcian blue/periodic acid
Schiff.
study investigating the high incidence of right heart endo-
carditis in patients with congenital heart disease after sur-
gery or percutaneous pulmonary valve implantation
compared 3 different materials for valved stents. Bovine
pericardium was found to have the lowest propensity of bac-
terial adhesion in comparison to bovine jugular vein and
porcine pericardium.28 It is unclear which factors contrib-
uted to incidence of endocarditis in our cohort. One patient
developed a vegetation following infection with varicella
zoster virus, which is a described complication.29 Another
patient developed endocarditis as a consequence of poor
dental hygiene. Additional follow-up and comparison of
incidence of endocarditis following alternative valve opera-
tions 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 reinter-
vention at 1, 5, and 7 years of 97%, 87%, and 80%, respec-
tively, for patients undergoing valve repair. Multiple
techniques were used in these patients, which included
leaflet extension, tricuspidization, commissurotomy, leaflet
thinning, triangular resection, subcommissural annulo-
plasty, free-edge plication, and leaflet perforation repair.2
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 replace-
ment (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.4 The
most common reason for reoperation in this study was sub-
stantial AR. These outcomes must be considered with
The Journal of Thoracic and Cardiovascular Surgery c Volume 159, Number 6
Congenital: Aortic Valve
caution given the fundamental differences in the repair tech-
niques 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 clin-
ical evidence exists in determining which biomaterial for
CONG
aortic leaflet replacement would be optimal.30 An increased
risk of long-term recurrent AR following aortic valve repair
has been associated with the use of a patch in a number of
studies that used a variety of materials.31,32
Glutaraldehyde fixed autologous pericardium has pro-
vided 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.33 In
a recently published study by Nordmeyer and colleagues,34
the use of CardioCel in patients with congenital aortic valve
disease (median age, 9 years) was associated with unsatis-
factory mid-term results. In our series, the explanted bovine
patch material showed evidence of calcification on histopa-
thology (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 ma-
terial used for a composite outcome measure of AR, endo-
carditis, 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 ¼ 20) could be
an indicator of favorable midterm results.
Limitations
Our study has limitations inherent to any retrospective re-
view. 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 reconstruc-
tion, and the timing of progression to definitive aortic valve
operations.
CONCLUSIONS
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 tech-
nique must be weighed against the need for late autograft
reintervention, pulmonary homograft replacement, and the
anticoagulation-related morbidity of aortic valve
2377
 Congenital: Aortic Valve
replacement. In addition, aortic leaflet replacement tech-
niques 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
CONG
nothing to disclose with regard to commercial support.
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Key Words: aortic valve repair, aortic leaflet reconstruction