Keywords aortic regurgitation - aneurysm - aorta/aortic
Introduction
Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly, primarily caused by the
congenital absence of elastic and muscular tissue in the aortic wall of the sinus
of Valsalva.[1 ] It may also be acquired, with infective endocarditis of the aortic valve as the
most common cause.[2 ] The incidence of SVA is higher in Eastern populations than in Western ones,[1 ] and 65 to 80% of SVA patients are male.[3 ] SVA was first described by Hope in 1839.[4 ] The first report of successful surgical repair was reported by Lillehei et al in
1957.[5 ] Since then, several reports have described SVA repair techniques, and at present,
there is still debate regarding the optimal method of surgical repair.
At Samsung Medical Center, we recently established a prudent repair technique based
on a dual approach. In this study, we reviewed our 22-year experience with SVAs to
investigate the determinants of the development of significant aortic regurgitation
(AR) and long-term survival after surgical repair.
Materials and Methods
Study Patients
During the 22-year period from January 1995 to December 2016, 71 patients (31 females
and 40 males) underwent surgical repair of SVA with (n = 60, 84.5%) or without rupture (n = 11, 15.5%). Patients with aortic root or ascending aortic dilatation or connective
tissue disease were excluded. The median age at the time of operation was 33.3 years
(range: 11.8–62.7 years). Our Institutional Review Board approved this study, and
the need for patient consent was waived (IRB number; SMC 2019-02-020).
At the time of admission, 57 patients (80.3%) were symptomatic. Major symptoms were
dyspnea on exertion in 41 patients (57.7%, most common), followed by chest discomfort
or pain, palpitation, fever, chills, and fatigue. In total, 14 patients (19.7%) were
asymptomatic and diagnosed incidentally during routine examinations.
The origins of the SVAs and the exit site of ruptured SVAs are summarized in [Table 1 ]. The right coronary sinus was the most common site of origin of the aneurysm (n = 59, 83.1%). The aneurysms ruptured into the right ventricle (RV) in 42 patients
and into the right atrium (RA) in 18 patients. No patients experienced the formation
of a fistula into the pulmonary trunk or the pericardial sac.
Table 1
Sinus of origin and exit site of the ruptured SVA in all patients (n = 71)
Sinus of origin
Patients (n )
Unruptured
Ruptured
Chamber of rupture
RA
RV
LV
Right coronary sinus
59
9
50
10
40
0
Noncoronary sinus
10
2
8
8
0
0
Left coronary sinus
2
0
2
0
2
0
Total
71
11
60
18
42
0
Abbreviations: LV, left ventricle; RA, right atrium; RV, right ventricle; SVA, sinus
of Valsalva aneurysm.
Ventricular septal defect (VSD) was the most common coexisting cardiac lesion. There
were 48 patients (67.6%) with VSDs, including the subarterial type in 41 patients,
the perimembranous type in 3, the muscular outlet type in 1, and the total conal defect
type in 3. AR (≥ grade I) was the second most common cardiac malformation (n = 45, 63.4%), followed by right ventricular outflow tract (RVOT) obstruction in 10
patients (14.1%), infective endocarditis in 9 (12.7%), and bicuspid aortic valve in
5 (7.0%). The AR severity was grade I in 14 patients, grade II in 13, grade III in
7, and grade IV in 11.
Operative Procedures
Surgical repair was performed under cardiopulmonary bypass (CPB) with moderate hypothermia.
Median sternotomy was used in all patients. The left ventricle was vented. After the
ascending aorta was cross-clamped, the RA or the main pulmonary artery was opened
to clamp the fistula opening and antegrade cardioplegia was infused through the root
cannula. If there was AR (≥ grade I), the ascending aorta was opened obliquely and
cardioplegia was delivered either directly via the coronary ostia or in a retrograde
manner via the coronary sinus, depending on the surgeon's preference. Cold crystalloid
cardioplegia (n = 5), Custodiol histidine-tryptophan-ketoglutarate solution (n = 15), and cold blood cardioplegia (n = 51) were used for myocardial protection.
Surgery was performed through an aortotomy in 15 patients (21.1%), the chamber of
termination (RA or RV) in 5 (7.0%), and the dual approach (both RA/RV and aortic sides)
in 51 (72.8%). The aortotomy group was defined as patients who underwent surgical
repair of SVA through aortotomy only. The exit site group was defined as patients
who underwent surgical repair of SVA through the chamber of termination only. The
dual approach group was defined as patients who underwent surgical repair of SVA through
the dual approach (both the RA/RV and aortic sides). Excluding 11 patients who underwent
aortic valve replacement (AVR) during the first SVA repair operation, the surgical
approaches involved an aortotomy in 9 patients (aortotomy group; 9/60, 15.0%), the
chamber of termination (RA or RV) in 5 (exit site group; 5/60, 8.3%), and the dual
approach (both RA/RV and aortic side) in 46 (dual approach group; 46/60, 76.7%). Several
methods for the surgical repair of SVA including primary or patch closure with a glutaraldehyde-fixed
autologous pericardial patch, a bovine pericardial patch or a Dacron patch (DuPont,
Wilmington, Delaware, United States) are summarized in [Table 2 ].
Table 2
Surgical repair of SVA (patients who underwent aortic valve replacement during the
first operation were excluded) (n = 60; 9 in the aortotomy group, 5 in the exit site group, and 46 in the dual approach
group)
Primary
Autologous pericardial patch
Bovine
Dacron
Total
Aorta side
9
29
14
3
55
Aortotomy group
2
4
3
0
9
Dual approach group
7
25
11
3
46
Exit side
45
3
1
2
51
Exit site group
5
0
0
0
5
Dual approach group
40
3
1
2
46
Abbreviation: SVA, sinus of Valsalva aneurysm.
An illustration depicting the underlying pathology (with or without VSD) as well as
the types of repair is summarized in [Table 3 ]. VSD closure was performed primarily (n = 4) or by patching (n = 44) through the RA, the RV, or the main pulmonary artery ([Table 4 ]).
Table 3
Surgical repair of SVA (patients who underwent aortic valve replacement during the
first operation were excluded) (n = 60; with or without VSD)
VSD type
Dual approach group
Aortotomy group
Exit site group
Total
Subarterial
26
7
3
36
Perimembranous
1
1
0
2
Muscular outlet
1
0
0
1
Total conal defect
2
0
0
2
No VSD
16
1
2
19
Abbreviations: SVA, sinus of Valsalva aneurysm; VSD, ventricular septal defect.
Table 4
Profile of patients with VSD (n = 48)
VSD type
Patch closure
Primary closure
Total
Dacron
Bovine
Autologous pericardial patch
Subarterial
35
3
0
3
41
Perimembranous
2
0
0
1
3
Muscular outlet
1
0
0
0
1
Total conal defect
1
1
1
0
3
Total
39
4
1
4
48
Abbreviation: VSD, ventricular septal defect.
Over the 22-year study period, our institution has used several methods for the surgical
repair of SVA through aortotomy only, through the chamber of termination only, or
via a dual approach (both the RA/RV and aorta sides). In the past 3 years, we have
established a prudent repair technique using a dual approach that is based on a transaortic
procedure. Our anatomic correction comprises (1) resection of the ruptured or unruptured
aneurysmal sac, (2) patch closure of the defect in the sinus of origin through the
aortotomy, (3) direct suture closure of the distal end of the remaining sac margin
through the chamber of termination, and (4) correction of coexisting cardiac lesions,
such as VSD closure using the patch or direct suture technique.
Aortic valvuloplasty (AVP) was performed using Trusler's technique in 28 patients
(39.4%), and AVR was performed at the first operation in 11 patients (15.5%) with
mechanical valves (n = 9) or tissue valves (n = 2). The most common abnormality of the aortic valve in patients who underwent AVP
or AVR was prolapse of the right coronary or noncoronary sinus. The overall profile
of the patients with or without aortic valve procedures is summarized in [Table 5 ].
Table 5
Profile of all patients, with or without aortic valve procedures (n = 71)
Preoperative AR
Aortic valve procedure (No.)
Aortic valvuloplasty (No.)
Aortic valve replacement (No.)
Total
No (grade 0)
22
2
2
26
Minimal (grade I)
9
4
1
14
Mild (grade II)
1
12
0
13
Moderate (grade III)
0
5
2
7
Severe (grade IV)
0
5
6
11
Total
32
28
11
71
Abbreviation: AR, aortic regurgitation.
Ten patients (14.1%) required RVOT reconstruction for RVOT obstruction, while nine
patients (12.7%) with infective endocarditis required vegetation removal with aortic
valve intervention.
The mean aortic cross-clamp time was 109.9 ± 54.4 minutes (median: 104, range: 25–351
minutes), and the mean CPB time was 144.8 ± 65.3 minutes (median: 134, range: 45–469
minutes). Patients who did not undergo aortic valve procedures were given aspirin
for 3 months postoperatively.
End Points, Definitions, and Follow-up
The primary end point of this study was freedom from significant AR. The secondary
end point was overall survival. Significant AR was defined as moderate or severe postoperative
AR (≥ grade III/IV) based on echocardiographic follow-up. The AVP group was defined
as patients who underwent surgical repair of SVA with AVP. The no-AVP group was defined
as patients who underwent surgical repair of SVA without AVP or AVR. The AR group
was defined as patients diagnosed with significant AR postoperatively. The no-AR group
was defined as patients who did not have significant AR postoperatively.
Baseline clinical data were collected from medical records and databases. The echocardiographic
follow-up was performed at our outpatient department. Follow-up clinical data were
acquired through telephone interviews and medical records reviews. To obtain complete
follow-up data, including mortality, information was collected from the National Registry
of Births and Deaths using each patient's unique personal identification number.
Statistical Analysis
This retrospective study was designed to investigate the determinants contributing
to the development of significant AR and long-term survival after surgical repair.
For each of the baseline characteristics, we obtained the hazard ratio (HR) and its
95% confidence interval (CI) using a univariate Cox's regression. The Kaplan–Meier's
survival method was used to draw survival curves for various survival outcomes along
with 5-, 10-, and 15-year survival probabilities for freedom from AR. A log-rank test
was used to test the differences in survival curves among groups. All tests were two
tailed.
A p -value of less than 0.05 was considered statistically significant. The statistical
analysis was performed using SPSS, version 22.0 (SPSS, Chicago, Illinois, United States)
and the R programming language, version 3.3.1 (R Foundation for Statistical Computing,
Vienna, Austria).
Results
Baseline Characteristics
The baseline characteristics of the patients in the two groups (the AR group and the
no-AR group) are summarized in [Table 6 ]. Patients with bicuspid aortic valves had a tendency to develop significant postoperative
AR, and after adjustments, the incidence of bicuspid aortic valves was noted to be
significantly higher in the AR group than in the no-AR group (HR for the AR group:
5.119; 95% CI: 1.029–25.471; p = 0.046). There were no patients with infective endocarditis in the AR group.
Table 6
Baseline characteristics of patients (n = 71)
Variables
p -Value
HR
Lower 95% CI
Upper 95% CI
Age
0.722
1.290
0.319
5.221
Female gender
0.411
1.706
0.478
6.094
Infective endocarditis
0.435
–
–
–
VSD
0.366
2.047
0.434
9.661
Preoperative AR
0.114
3.507
0.741
16.600
RVOT obstruction
0.994
0.993
0.125
7.891
Bicuspid aortic valve
0.046
5.119
1.029
25.471
Ruptured SVA
0.720
0.750
0.155
3.626
Abbreviations: AR, aortic regurgitation; CI, confidence interval; HR, hazard ratio;
RVOT, right ventricle outflow tract; SVA, sinus of Valsalva aneurysm; VSD, ventricular
septal defect.
Overall Clinical Outcomes
There was no early mortality. Postoperative complications included postoperative bleeding
(n = 1), neurologic complications (n = 2; seizure on the first postoperative day in one patient, new-onset subdural hemorrhage
on the 13th postoperative day in one), and wound infection (n = 1). The median mechanical ventilator support time was 9.0 hours (range: 0.8–135.5
hours), the median intensive care unit stay was 1 day (range: 0.3–10.3 days), and
the median postoperative hospital stay was 7 days (range: 4–58 days).
During the follow-up period (median: 65.4 months, range: 0.3–237.9 months), there
were three late deaths. The causes of late deaths were underlying disease (gastric
cancer) in one case (5.5 years after operation with the dual approach) and unknown
in two cases (14.2 years after operation with the dual approach and 16.7 years after
operation with AVR). The overall survival is summarized in [Fig. 1A ].
Fig. 1 (A) Overall survival (n = 71). (B) Freedom from significant AR (excluding 11 patients who underwent AVR during
the first operation) (n = 60). (C) Freedom from significant AR in the aortotomy group, the exit site group,
and the dual approach group (n = 60). (D) Freedom from significant AR in the AVP group and the no-AVP group (n = 60). (E) Freedom from significant AR according to the severity of preoperative
AR (n = 60). (F) Freedom from significant AR according to the severity of preoperative
AR, divided into two groups (≤ grades II vs. ≥ grades III) (n = 60). AR, aortic regurgitation; AVP, aortic valvuloplasty; AVR, aortic valve replacement.
When 11 patients with AVR during the first SVA repair operation were excluded, 10
patients (10/60, 16.7%) had recurrent or newly developed significant AR. Among these
10, 1 patient underwent reoperation for AVR during the follow-up period (after 9 months).
Freedom from significant AR of the patients is summarized in [Fig. 1B–D ]. In the AVP and no-AVP groups, freedom from significant AR according to the severity
of preoperative AR is summarized in [Fig. 1E ]. When the patients with preoperative AR were reclassified into two groups (no preoperative
AR, grades I and II vs. grades III and IV preoperative AR), freedom from significant
AR in the patients with low-grade preoperative AR (≤ grade II) was significantly higher
than those with high-grade preoperative AR (≥ grade III) (p = 0.014; [Fig. 1F ]).
Among the 26 patients with low-grade preoperative AR (grade I or II) when the patients
with no preoperative AR were excluded, the patients in the AVP group had a tendency
to develop significant postoperative AR, but freedom from significant AR did not differ
statistically (p = 0.125; [Fig. 2A ]). Among the 13 patients with grade II preoperative AR, those in the AVP group had
a tendency to develop postoperative significant AR, but their freedom from significant
AR did not differ statistically from that of the patients in the no-AVP group (p = 0.387; [Fig. 2B ]). Among the 26 patients who underwent AVP (omitting 2 patients without preoperative
AR), freedom from significant AR did not differ statistically between the two severity
groups (grades I and II vs. grades III and IV, p = 0.460; [Fig. 3 ]).
Fig. 2 (A) Freedom from significant AR in patients (AVP group vs. no-AVP group) with low-grade
preoperative AR (grade I or II) (n = 26). (B) Freedom from significant AR in patients (AVP group vs. no-AVP group) with
mild preoperative AR (grade II) (n = 13). AR, aortic regurgitation; AVP, aortic valvuloplasty.
Fig. 3 Freedom from significant AR in patients with AVP classified according to the severity
of preoperative AR, divided into two groups (grades I and II vs. grades III and IV)
(n = 26). AR, aortic regurgitation; AVP, aortic valvuloplasty.
Discussion
SVA is a rare cardiac anomaly responsible for ∼0.15 to 1.5% of congenital cardiac
surgeries involving CPB.[6 ] Moustafa et al reported that the site of origin of the SVA was the right coronary
sinus in 69.8% of patients, the noncoronary sinus in 25.6%, and the left coronary
sinus in 4.7%.[2 ] In this study, the right coronary sinus was the most common site of origin of the
aneurysm (n = 59, 83.1%), followed by the noncoronary sinus (n = 10, 14.1%) and the left coronary sinus (n = 2, 2.8%).
Patients with unruptured SVAs are usually asymptomatic.[3 ] If patients with unruptured SVAs do not have any complications, such as RVOT obstruction,
compression of the ostia of coronary arteries, abnormal cardiac rhythms, embolic events,
or infection, SVAs are usually diagnosed only incidentally.[7 ]
[8 ] In our study, 14 patients (19.7%) were asymptomatic, and they were diagnosed incidentally
during routine examinations.
Coexisting cardiac abnormalities are common in patients with congenital and ruptured
or unruptured SVAs. VSD is the most common associated lesion, occurring in 12 to 53%
of SVA patients.[2 ]
[9 ] In our study, 48 patients (67.6%) had a VSD. AR is also commonly associated disorder
with VSD,[1 ] and it is more common in patients with ruptured SVA.[2 ] In our study, AR (≥ grade I) was the second most common cardiac malformation (n = 45, 63.4%).
Surgery for anatomic correction is the mainstay of treatment for SVA.[1 ]
[3 ]
[9 ]
[10 ] The primary goals of surgical repair of SVAs are to close the SVAs without distorting
the aortic sinus, remove the aneurysmal sac, correct any associated intracardiac abnormalities,
and prevent residual AR. Previous reports have described various methods for the surgical
repair of SVAs,[10 ]
[11 ] and several publications have demonstrated that SVAs can be surgically repaired
with low-risk and excellent long-term outcomes.[11 ]
[12 ]
[13 ]
[14 ]
[15 ]
[16 ] Yacoub et al used the transaortic technique with a series of interrupted sutures
through the crest of the ventricular septum and the annulus of the aortic cusp to
plicate the dilated sinus of Valsalva.[10 ] Another study found that transaortic repair of SVAs with an optimal geometric design
of the sinus of Valsalva could reduce the incidence of postoperative AR.[14 ] In contrast, Jung et al demonstrated that the transaortic approach may cause a high
risk of postoperative AR by distorting the aortic sinus geometry.[11 ] Thus, the optimal surgical correction method remains a controversial issue because
of the rarity of SVAs. Controversies regarding strategies for the surgical procedure
persist, particularly regarding the operative approach (transaortic or nontransaortic)
and the surgical technique (primary closure or patch closure)[11 ] and the decision to undergo concomitant surgical procedures, such as aortic valve
repair or replacement.
The advantages of the nontransaortic approach include minimizing the risk of aortic
sinus distortion by preserving the geometry of the sinus of Valsalva and avoiding
the use of foreign materials in the aortic sinus.[11 ] However, this technique cannot reach the origin of the SVA, and it is impossible
to perform before the onset of the SVA in the cusp.[10 ] Careful inspection of the coronary ostia to determine the optimal position, patency,
and the anatomy of the aortic root complex and aortic valve status is possible using
the transaortic approach, and an aortic valve intervention, such as AVP or AVR, can
be performed only through an aortotomy.[3 ]
[11 ] Postoperative AR, either residual or progressive, is an important risk factor that
affects a patient's prognosis,[1 ]
[12 ] and it can have a critical influence on postoperative cardiac function.[1 ] Although there is a minor risk of VSD or recurrent fistula,[11 ]
[17 ] AR either new or recurrent can result in a risk of early or late complications after
surgical correction.[11 ] Therefore, careful inspection to determine whether to perform aortic valve intervention
is a very important step in the surgical repair of SVA. The key point of our surgical
strategy is resolving the lack or defect of the aortic media in the sinus of Valsalva,
which is the major pathological cause of ruptured or unruptured SVA.
AVP was performed in patients with preoperative AR diagnosed as grade III (moderate)
or IV (severe), based on the surgeon's preference. AVR was performed during the first
operation when it was impossible to repair the aortic valve via AVP, as in cases of
infective endocarditis. The most common abnormality of the aortic valve among the
patients who underwent AVP or AVR was prolapse of the right coronary sinus or noncoronary
sinus.
According to previous reports, surgical outcomes for SVA are excellent and satisfactory.[2 ]
[10 ]
[11 ] Our survival rates at 5, 10, and 15 years were 100, 97, and 89%, respectively, which
are not inferior to that of previous reports.
The baseline characteristics of the patients in the AR group and the no-AR group did
not differ significantly, except for the incidence of bicuspid aortic valve, which
was significantly higher in the AR group than in the no-AR group. The combination
of bicuspid aortic valve and SVA is rare and could be explained by the abnormal flow
pattern of the dysplastic valve against the aortic wall,[18 ] and it is believed to be related to significant postoperative AR.
Freedom from significant AR did not differ significantly among the three surgical
technique groups. There was no correlation between the degree of postoperative AR
and the SVA repair method. Thus, the transaortic approach including aortotomy could
be a risk factor for significant postoperative AR, but the risk is not statistically
higher. [Fig. 1C ] shows that the Kaplan–Meier's curve was reversed after 10 years between the dual
approach group and the aortotomy group. However, a limited number of patients were
at risk during the period, and the data could not be statistically significant. In
a recently published article, Luo et al demonstrated that routine aortotomy for simple
ruptured SVAs has been remained a controversial issue, and the variable approaches
such as aortotomy, right atriotomy, and pulmonary arteriotomy could be viable options.[19 ]
The important finding in this study is that patients with low-grade preoperative AR
(grade I or II; those with no preoperative AR were excluded) who underwent AVP had
a tendency to develop significant postoperative AR, but freedom from significant AR
did not differ statistically. Another impressive result is that patients with grade
II preoperative AR who underwent AVP had a tendency to develop significant postoperative
AR, but their freedom from significant AR did not differ statistically from that of
patients who did not undergo AVP. This finding indicates that aortic valve intervention,
such as AVP, in patients with low-grade preoperative AR can improve the outcome of
postoperative AR, and AVP can be recommended for those patients.
Additionally, among the 26 patients who underwent AVP (omitting 2 patients with no
preoperative AR), freedom from significant AR did not differ statistically between
the two groups (grades I and II vs. grades III and IV). This reflects the possibility
of improving the outcome by performing AVP to reduce AR in patients with high-grade
preoperative AR.
Therefore, concomitant aortic valve repair should be recommended not only for patients
with moderate or severe preoperative AR (grades III and IV) but also for those with
minimal or mild preoperative AR (grades I and II), whose aortic valve geometry needs
correction.
This study has several limitations. First, freedom from significant AR was significantly
higher in the no-AVP group than in the AVP group. This difference may have occurred
because the patients in the AVP group had a tendency to have more severe preoperative
AR than those in the no-AVP group. Second, the follow-up period might not have been
long enough to permit an investigation of the long-term clinical outcomes of overall
survival and freedom from AR. Third, this was a small retrospective study with only
71 patients, and its statistical power may be limited. One goal of future research
should be to perform a prospective multicenter large study with long-term close follow-up
of the development of significant AR.
Conclusion
Surgical repair of SVA with or without rupture can be performed safely using the dual
approach technique. Concomitant aortic valve repair can be performed without difficulty
and should be recommended not only for patients with moderate or severe preoperative
AR (grades III and IV) but also for those with minimal or mild preoperative AR (grades
I and II), whose aortic valve geometry needs correction. Long-term close follow-up
for the development of significant AR is mandatory.