Analysis of Indications for Surgical
Closure of Subarterial Ventricular Septal
Defect Without Associated Aortic Cusp
Prolapse and Aortic Regurgitation
Kin-shing Lun, MBBS, Hung Li, MD, Maurice Ping Leung, MD,
Adolphus Kai-tung Chau, MBBS, Tak-cheung Yung, MBBS, Clement Shui-wah Chiu,
and Yiu-fai Cheung, MBBS
Subarterial ventricular septal defect (VSD) is relatively
common in Orientals. We reviewed the outcome of 214
patients (137 males) who were followed for 8.6 5.2
years (range 0.1 to 24.3) and addressed the issue re-
garding the necessity and optimum timing of closing
subarterial defects before development of aortic valve
deformities. Demographic data, transthoracic and trans-
esophageal echocardiographic findings, cardiac cathe-
terization results, and operative findings were reviewed.
Kaplan-Meier actuarial analysis was performed to as-
sess the development of aortic valve complications over
time. Seventy-five patients with heart failure and pulmo-
nary hypertension underwent surgical closure of VSD at
the age of 2.4 2.9 years. No patient had aortic cusp
prolapse before operation and none developed aortic
cusp prolapse or aortic regurgitation (AR) on follow-up.
In contrast, of the 139 asymptomatic patients managed
conservatively, 102 (73%) developed aortic cusp pro-
S ubarterial ventricular septal defect (VSD) is rela-
tively common among Orientals. 13
Associated
aortic cusp prolapse and aortic regurgitation (AR)
occur with an incidence of 44% to 79%4 6 and tend to
progress once developed.7 Early surgical repair of the
defect has been advocated as soon as these aortic
valvar complications are detected.8,9 Nevertheless, the
necessity or timing of surgical closure of septal de-
fects without concomitant aortic valvar deformities
remains controversial.6,8 11 In our institution, the in-
dication for surgery is congestive heart failure or
significant aortic cusp prolapse with or without asso-
ciated AR. This approach provides the opportunity to
study the natural history of the development and pro-
gression of aortic cusp prolapse and AR, and to com-
pare the occurrence of these complications in patients
who underwent surgery early with those who were
From the Division of Pediatric Cardiology and Cardiothoracic Surgery,
Grantham Hospital, The University of Hong Kong, Aberdeen, Hong
Kong, China. Dr. Li is supported by a research grant from the Institute
of Cardiovascular Science and Medicine, Faculty of Medicine, the
University of Hong Kong, China. Manuscript received October 2,
2000; revised manuscript received and accepted January 2, 2001.
Address for reprints: Yiu-fai Cheung, MBBS, Division of Pediatric
Cardiology, Department of Pediatrics, Grantham Hospital, 125
Wong Chuk Hang Road, Aberdeen, Hong Kong, China. E-mail:
xfcheung@hkucc.hku.hk.
1266 2001 by Excerpta Medica, Inc. All rights reserved.
The American Journal of Cardiology Vol. 87 June 1, 2001
MBBS,
lapse, 78% of whom (80 of 102) developed AR. The
prevalence of aortic cusp prolapse and AR at 1, 5, 10,
and 15 years old was 8%, 30%, 64%, and 83%, and 3%,
24%, 45%, and 64%, respectively. Significant prolapse
or AR prompted surgical closure of VSD with (n 22) or
without (n 26) valvoplasty in 48 of 102 patients
(47%). The size of the VSD was significantly larger in
patients with heart failure (9.6 3.3 mm) or aortic cusp
prolapse (11.7 4.1 mm) compared with those without
heart failure (4.5 1.4 mm, p <0.001). All patients
with aortic cusp prolapse and all but 1 with heart failure
had a defect size of >5 mm. In conclusion, subarterial
VSD of >5 mm should be closed as early as possible to
prevent development of aortic cusp prolapse and AR.
Asymptomatic patients with small defects <5 mm could
be managed conservatively. 2001 by Excerpta Med-
ica, Inc.
(Am J Cardiol 2001;87:1266 1270)
managed conservatively. In this study, we reviewed
the outcome of 214 patients with subarterial VSD, and
in the light of our findings, attempted to address the
issue regarding the necessity and optimum timing of
closing subarterial defects before development of aor-
tic valve deformities.
METHODS
Patients: The clinical records of 214 consecutive
patients (137 males, 77 females) who were diagnosed
with subarterial VSDs between June 1975 and Octo-
ber 1999 in our institution were reviewed. The diag-
nosis of subarterial VSD was based primarily on 2-di-
mensional echocardiography,12,13 although angiocar-
diography had been the diagnostic modality in earlier
years. Serial clinical and echocardiographic assess-
ments were performed during outpatient follow-up.
Symptomatic infants were followed every 4 to 8
weeks, whereas asymptomatic patients were assessed
every 6 to 12 months. The following data were re-
trieved from the records: demographic data, transtho-
racic and transesophageal echocardiographic findings,
cardiac catheterization results, and surgical findings.
Patients with defects that occur in association with
more complex cardiac lesions, such as tetralogy of
Fallot, double outlet ventricle, or transposition of the
great arteries, were excluded.
0002-9149/01/$see front matter
PII S0002-9149(01)01517-X
 Patients were categorized into 3 groups for com-
parison. Group I consisted of 75 patients who under-
went surgical closure of the defect for symptomatic
heart failure. Group II comprised 102 asymptomatic
patients who did not undergo initial surgical closure
and developed aortic cusp prolapse with or without
AR. Group III comprised 37 patients who were man-
aged medically but did not develop any valvar com-
plications.
Echocardiographic and hemodynamic assessment:
Videotape recordings of transthoracic and transesoph-
ageal echocardiograms, performed using a Hewlett-
Packard Sonos 1000/1500 ultrasound machine (An-
dover, Massachusetts), and angiographic recordings
were reviewed. The size of septal defect was taken as
the largest diameter measured either on echocardio-
gram, angiogram, or at surgery in patients without
aortic cusp prolapse. For patients with significant cusp
prolapse, the size measured at surgery was taken.
Cardiac catheterization was performed in 139 patients
(46 in group I, 82 in group II, and 11 in group III). The
pulmonary arterial pressure was documented and the
pulmonary to systemic flow ratio (Qp/Qs) calculated.
Prolapse of aortic cusp was graded on a 3-point
scale5,14,15: mild (buckling of aortic cusp with minimal
herniation, aortic cusp protrudes slightly into defect
only during early systole), moderate (prolapse of cusp
with obvious herniation into the septal defect), and
severe (prolapse of cusp and its sinus through the
defect into the right ventricular outflow tract during
systole and diastole).
The degree of AR on aortography was graded on a
4-point scale.16 Using color Doppler echocardiogra-
phy, the degree was graded6 as: trivial (slight AR
under the aortic valve), mild (AR not reaching the tip
of mitral valve leaflet), moderate (AR reaching the tip
of mitral valve leaflet), and severe (AR beyond the tip
of mitral valve leaflet). A regurgitant index was de-
rived from the ratio of the maximal diameter of re-
gurgitant jet to that of the left ventricular outflow tract
immediately below the aortic valve.17,18
Surgery: The transpulmonary approach was used.
Aortic cusp prolapse was identified and graded using
guidelines similar to those set for echocardiograms, by
visualizing through the defect during infusion of car-
dioplegic solution into the coronary sinus. A trans-
verse aortotomy would be made when aortic valve
exploration was required. Aortic valvoplasty would be
performed if cusp prolapse and AR were of moderate
to severe degree. A stay suture would then be placed
in the corpus Arantii of the normal leaflets and the
center of the prolapsed leaflet, while excessive valve
tissue was plicated and sutured with pledgets to the
commissural margins close to the aortic wall.19 The
septal defect was closed with a prosthetic patch.
Statistical analysis: Results are expressed as
mean SD unless otherwise specified. The develop-
ment of aortic valve complications with time was
analyzed by Kaplan-Meier actuarial survival analysis,
and comparisons between patient groups were per-
formed using log-rank test. Differences in variables
among groups were compared by simple analysis of
CONGENITAL HEART DISEASE/SURGICAL CLOSURE OF SUBARTERIAL VSD
FIGURE 1. Box plot of size of VSD by patient groups. Bold lines,
medians in each group. All patients in group II and all but 1 pa-
tient in group I had a VSD size >5 mm.
variance or unpaired Students t tests, where appro-
priate. A p value 0.05 was considered significant.
All statistical analyses were performed using SPSS
Version 8.0 (SPSS, Inc, Chicago, Illinois).
RESULTS
Patients: The age at initial presentation was 2.8
0.3 years (range 1 day to 17.4 years). The patients had
been followed for 8.6 5.2 years (range 0.1 to 24.3)
and their age at latest follow-up was 12.5 7.1 years
(range 0.3 to 39.7).
Group I patients underwent surgical closure of
septal defect at 2.4 2.9 years (median 1.3, range
0.05 to 11.7). None had aortic valve involvement at
the time of surgery. Associated structural cardiac
anomalies included persistent arterial duct (n 22),
atrial septal defect or patent foramen ovale (n 20),
coarctation of aorta (n 18), valvar pulmonary ste-
nosis (n 6) and interrupted aortic arch (n 3). Of
the 102 patients in group II, 48 (47%) eventually
required closure of the defect with (n 22) or without
(n 26) aortic valvoplasty due to progression of
aortic cusp prolapse or development of significant AR.
The age at operation was 9.8 4.8 years (median 9.4,
range 1.5 to 21.9). None of the group III patients
required surgery.
Hemodynamic and morphologic variables: Systolic
pulmonary arterial pressure was significantly higher in
group I patients (59.2 23.2 mm Hg) compared with
patients in group II (28.2 11.0 mm Hg) and group
III (30.6 10.3 mm Hg) (p 0.001). Similarly, the
Qp/Qs ratio was significantly greater in group I pa-
tients (3.0 1.5) than those in group II (1.6 0.6)
and group III (1.7 0.7) (p 0.001). The size of the
septal defect was significantly larger in group I (9.6
3.3 mm) and group II (11.7 4.1 mm) patients
compared with those in group III (4.5 1.4 mm) (p
0.001) (Figure 1). All patients in group II and all but
1 in group I had a defect size of 5 mm.
1267
 Aortic cusp prolapse: Of the 139 patients who were
managed conservatively (groups II and III), 102
(73%) developed aortic valve prolapse. The preva-
lence of aortic cusp prolapse at 1, 5, 10, and 15 years
old was 8%, 30%, 64%, and 83%, respectively. The
right coronary cusp was involved in 98 patients,
whereas 4 patients had additional involvement of the
noncoronary cusp. The degree of prolapse was mild in
68 patients, moderate in 25, and severe in 9 patients.
In contrast, none of the group I patients developed this
complication (p 0.001) (Figure 2). All of the aortic
valves were tricuspid.
Aortic regurgitation: Eighty of the 102 patients
(78%) who had prolapse of aortic cusp developed AR.
Sixteen patients already had both aortic cusp prolapse
and AR at first presentation. The prevalence of AR at
1, 5, 10, and 15 years old was 3%, 24%, 45%, and
64%, respectively (Figure 2). The degree of AR was
trivial in 17 patients, mild in 58, moderate in 4, and
severe in 1. The severity of AR progressed with time,
with worsening of AR noted in 50% of patients over a
5-year follow-up period (Figure 2). In contrast, none
of the group I patients developed AR after surgical
closure of the defect (p 0.001, Figure 2).
Surgical outcome: There was no operative mortal-
ity. All patients in group I were free of aortic valvar
complications postoperatively. The impact of surgical
repair on severity of AR is shown in Figure 3. AR
improved in 64% of group II patients (27 of 42) who
already had AR preoperatively and remained trivial or
mild in 29% (12 of 42). The AR index decreased from
21.2 16.9% to 10.9 10.1% (p 0.001) within 1
week of operation. Two patients eventually required
prosthetic valve replacement at 8 and 14 years, respec-
tively, after aortic valvoplasty; 1 of these patients died
2 years after reoperation due to thromboembolism.

DISCUSSION
This study shows that subarterial ventricular de-
fects 5 mm in size are free from development of
aortic cusp deformities and AR. For larger defects,
early surgical closure completely prevents the occur-
rence of these complications. In contrast, a conserva-
tive approach resulted in 64% of our patients devel-
oping aortic cusp prolapse and 45% developing AR by
10 years of age. It is quite convincing that a small
subgroup would not develop aortic valvar complica-
tions even when followed to adulthood. The 37 pa-
tients in group III have been followed for 6.9 5.8
years (range 0.3 to 24.3); 12 of them have been
followed for 15 years. Similarly, 10% of the 315
patients aged 15 to 35 years in the study of Tohyama
et al6 did not develop any valvar complications. Clin- FIGURE 2. Kaplan-Meier analysis of (A) freedom from aortic cusp
ical or imaging criteria that helped to identify this prolapse with age, (B) freedom from AR with age, and (C) free-
subgroup have not been previously available. Our data dom from progression of severity of AR with follow-up duration.
suggest, however, that subarterial defects 5 mm are
unlikely to be associated with aortic valve deformities
or regurgitation (Figure 1). We argue therefore that and AR are conflicting.20 22 Some investigators have
defects 5 mm in size do not require surgical closure suggested an inverse relation between defect size and
in the absence of heart failure symptoms. frequency of aortic cusp deformities.20,21 By using
Reports on the influence of the size of subarterial echocardiography and Doppler color flow to assess the
defects on the development of aortic cusp prolapse size of the defects, Sim et al20 reported that patients

1268 THE AMERICAN JOURNAL OF CARDIOLOGY VOL. 87 JUNE 1, 2001


FIGURE 3. Impact of surgery on aortic regurgitation. *Patients
who required prosthetic valvar replacement despite aortic valvo-
plasty.
without involvement of the aortic valve have appar-
ently larger defects than those with valve deformity.
However, the range of the defect size reported is large
and overlaps significantly between the 2 groups. Fur-
thermore, the use of Doppler color flow might have
underestimated the actual defect size in patients with
reduction of left-to-right shunt secondary to signifi-
cant aortic cusp prolapse. This probably also explains
the similar observation of an earlier study that as-
sessed the defect size by angiographic and hemody-
namic information obtained from cardiac catheteriza-
tion.21 In contrast, in the surgical series reported by
Ishikawa et al,22 the frequency of aortic cusp prolapse
correlates positively with the defect size that was
measured intraoperatively. Our findings, based on
echocardiographic and intraoperative measurements,
concur with those of the latter study.
Previous studies have related the development of
aortic valvar complications to other hemodynamic
variables. The severity of AR has been shown to relate
positively to the ratio of pulmonary to systemic blood
flow,6 further supporting that larger defects are pre-
disposed to a greater degree of AR. Our study fails to
reveal this relation. One possible explanation is that
cardiac catheterization was usually performed after
development of cusp prolapse with a subsequent re-
duction in Qp/Qs ratio. This applies especially to
group II patients who were usually catheterized after
echocardiographic documentation of aortic cusp pro-
lapse. Momma et al4 reported that patients with pul-
monary hypertension rarely develop cusp prolapse or
regurgitation. Although it is true that none of our
group I patients who had pulmonary hypertension and
congestive heart failure developed aortic cusp pro-
lapse, early surgical repair of the larger defects may
have precluded this group from being followed long
CONGENITAL HEART DISEASE/SURGICAL CLOSURE OF SUBARTERIAL VSD
enough for cusp prolapse to develop. Furthermore,
normal pulmonary arterial pressure may not necessar-
ily predispose to aortic valvar complications, as illus-
trated by our group II and III patients. This suggests
that apart from flow velocity and pressure drop across
the defect, the volume of flow may also play an
important role in the pathogenesis of aortic cusp pro-
lapse.
The high incidence of aortic valvar complications
in this study agrees with the findings of previous
studies.4,6,23,24 Aortic cusp prolapse occurred in 73%
of our patients, whereas 78% of those with cusp pro-
lapse developed various degrees of AR. The progres-
sive course of these complications is clearly demon-
strated in this longitudinal, although retrospective,
study and concurs with the findings of cross-sectional
studies.4,6,25 The lack of anatomic support for the
aortic cusp and the Venturi effect in relation to a large
left-to-right shunt predispose to progression of cusp
prolapse and AR.4,26,27 Early closure of the defect in
the presence of cusp prolapse even in the absence of
AR has therefore been advocated to prevent further
progression of aortic valve deformities.8,9 The encour-
aging surgical outcome in this and other studies sup-
ports this proposition,8,9,28 and the use of intraopera-
tive transesophageal echocardiography has further im-
proved the result.15 Our findings further confirm that
early surgical closure of large defects in symptomatic
patients completely prevents the occurrence of aortic
valvar complications.
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