Keywords aortic valve - aortic valve replacement - prosthesis
Introduction
Aortic valve replacement (AVR) is one of the most frequently performed open heart
surgeries.[1 ] With the increase in patients undergoing AVR, patients who require redo AVR due
to structural valve degeneration (SVD), prosthetic valve endocarditis, paravalvular
leak or thrombosis/pannus formation are also increasing. With the increase in the
number of patients using aortic valve bioprostheses and recent advances in valve-in-valve
transcatheter aortic valve implantation (ViV-TAVI), an increase in the number of patients
with failing bioprostheses is to be expected.
In previous studies, the in-hospital mortality rate of redo AVR after surgical AVR
ranged from 2 to 18%, averaging around 5%.[2 ]
[3 ] However, these studies are outdated, and their study populations were heterogeneous
with various surgical indications. Therefore, the present study evaluated recent clinical
outcomes of redo AVR after surgical AVR for failing prostheses.
Patients and Methods
Patient Enrollment
The study protocol was reviewed by our Institutional Review Board and approved as
a minimal risk retrospective study (Approval Number: H-2202–061–1299) that did not
require individual consent on February 18, 2022. From January 2010 to December 2021,
392 consecutive patients underwent redo AVR after surgical AVR in four tertiary centers.
None of the patients had underwent coronary artery bypass grafting as a primary procedure.
Of these patients, 66 who had severe mitral or tricuspid valve disease and 2 who underwent
intended concomitant coronary artery bypass graft were excluded. Thus, this study
enrolled 324 patients (62.1 ± 13.8 years; 145 males and 179 females).
The indications for redo SVR were (1) non-SVD (n = 84), (2) SVD (n = 151), (3) prosthetic valve endocarditis (n = 82), and (4) thrombosis (n = 7).
Operative Strategy
The procedures were performed using various approaches, including median sternotomy
(n = 303), upper partial sternotomy (n = 19), or right anterior thoracotomy (n = 2). One-hundred and twenty of the patients underwent redo AVR with a mechanical
valve, and the other 204 patients underwent bioprosthetic redo AVR. Two different
types of rapid deployment/sutureless valve were used (Sorin Perceval [n = 3] and Edwards Intuity [n = 5]). The surgical approach and type of prosthesis were selected at the discretion
of the attending surgeon.
Evaluation of Early and Long-Term Clinical Outcomes
Operative mortality was defined as death within 30 days of operation or during the
same hospitalization period. Postoperative low cardiac output syndrome was defined
as the need for mechanical or inotropic support to maintain systolic blood pressure
>90 mm Hg after correcting reversible factors.
Regular (3- to 6-month intervals) postoperative follow-up was performed at the outpatient
clinic. The patient's condition was checked via telephone if they did not attend the
scheduled clinic visit. Cardiac death was defined as any death of a cardiac origin,
including sudden death. Aortic valve-related events (AVREs) were defined as following;
(1) cardiac death, (2) congestive heart failure, (3) reoperation for aortic valve,
(4) thromboembolism,[5 ] major bleeding that caused death, hospitalization, or need for a transfusion, (5)
prosthetic aortic valve endocarditis, and (6) permanent pacemaker implantation following
AVR.
The clinical follow-up period ended on April 30, 2022. The median follow-up duration
was 51 months (interquartile range: 16.8–79.0 months). The completeness of follow-up
was 94.1% (305 out of 324) for overall survival and other long-term clinical outcomes.
Statistical Analysis
Statistical analyses were performed using R version 4.0.3 (R Foundation for Statistical
Computing) and SAS (version 9.4; SAS institute, Cary, North Carolina, United States).
The two groups were compared using the Chi-square test or Fisher's exact test and
Student's t -test for categorical and continuous variables, respectively. Survival rates were
estimated using the Kaplan–Meier method.
Logistic regression analysis was performed to evaluate the factors associated with
operative mortality. Risk factors for longitudinal data were analyzed using a multivariate
Cox proportional hazards model.
The patients were divided into subgroups according to the presence of preoperative
endocarditis. The cumulative incidences of cardiac death and AVRE were estimated with
noncardiac death as a competing risk for the events. The cumulative incidences of
composite of thromboembolism and bleeding were estimated with all-cause death as a
competing risk for the events. The cumulative incidences of the two groups for each
event were compared using the Fine–Gray test. Variables with a p- value <0.10 in the univariate analyses were entered into multivariate models. A p- value <0.05 was considered statistically significant.
To balance the patients for differences in baseline characteristics, inverse probability
of treatment weight (IPTW) analysis was used. The following preoperative variables
were entered into the logistic regression model: age, sex, body surface area, hypertension,
diabetes mellitus, history of stroke, chronic kidney disease, coronary artery disease,
dyslipidemia, atrial fibrillation, and left ventricular ejection fraction (LVEF).
A clustered Cox regression analysis of overall survival based on the IPTW analysis
was performed.
Results
Patient Characteristics and Operative Data
The baseline patients characteristics are presented in [Table 1 ]. Redo AVR was performed in 242 patients for reasons other than prosthetic valve
endocarditis (nonendocarditis group) and the other 82 patients underwent redo AVR
due to endocarditis (endocarditis group). Patients in the nonendocarditis group were
younger, more likely to be male, and have diabetes mellitus, a history of stroke,
and atrial fibrillation than the endocarditis group ([Table 1 ]). There were no significant differences in preoperative characteristics between
the two groups after IPTW adjustment. The aortic cross clamp time was longer and tricuspid
valve procedures were performed more frequently in the endocarditis group after IPTW
adjustment ([Table 1 ]).
Table 1
Preoperative and operative data of the study patients before and after inverse probability
of treatment weighting (IPTW)
Before IPTW, n (%)
IPTW-adjusted, %
Variables
All
Nonendocarditis group (n = 242)
Endocarditis group (n = 82)
p- Value
Nonendocarditis group (n = 242)
Endocarditis group (n = 82)
p- Value
Age (y)
62.1 ± 13.8
60.9 ± 14.1
65.8 ± 12.2
0.005
62.1 ± 14.1
60.6 ± 14.4
0.195
Female, n (%)
145 (44.8%)
81 (33.3%)
64 (79.0%)
<0.001
44.2
43.0
0.754
Body surface area (m2 )
1.8 ± 1.6
1.7 ± 1.2
2.0 ± 2.4
0.268
1.7 ± 1.2
1.8 ± 1.3
0.607
Risk factors, n (%)
Hypertension
115 (35.5%)
81 (33.5%)
34 (42.0%)
0.203
36.0
31.8
0.246
Diabetes mellitus
63 (19.4%)
37 (15.2%)
26 (32.1%)
0.002
18.3
17.8
0.863
History of stroke
50 (15.5%)
26 (10.7%)
24 (29.6%)
<0.001
15.1
18.8
0.099
Chronic kidney disease[a ]
54 (16.7%)
37 (15.2%)
17 (21.0%)
0.302
18.0
22.7
0.116
Coronary artery disease
20 (6.2%)
12 (4.9%)
8 (9.9%)
0.110
6.9
6.0
0.793
Dyslipidemia
54 (16.7%)
44 (18.1%)
10 (12.3%)
0.228
42.5
12.9
0.569
Atrial fibrillation
100 (30.9%)
83 (34.3%)
17 (20.7%)
0.031
31.1
23.8
0.163
LVEF
60.9 ± 10.4
61.6 ± 9.8
58.7 ± 11.9
0.055
61.1 ± 9.7
60.7 ± 9.7
0.527
CPB time (min)
197.5 ± 91.6
189.5 ± 87.4
221.6 ± 99.6
0.006
177.8 ± 81.7
260.7 ± 92.0
<0.001
ACC time (min)
133.3 ± 68.0
126.6 ± 62.3
153.3 ± 80.1
0.007
124.0 ± 62.5
201.5 ± 79.0
<0.001
Concomitant procedure, n (%)
Mitral valve procedure
68 (21.0%)
50 (20.7%)
18 (22.0%)
0.095
27.6
42.1
0.030
Tricuspid valve procedure
56 (17.3%)
52 (21.5%)
4 (4.9%)
0.008
23.8
7.9
0.380
Aorta procedure[b ]
38 (11.7%)
30 (12.4%)
8 (9.8%)
0.728
8.2
10.5
0.533
Arrhythmia surgery
12 (3.7%)
10 (4.1%)
2 (2.4%)
0.732
1.7
0.0
<0.001
CABG
2 (0.6%)
1 (0.4%)
1 (1.2%)
>0.999
0.0
0.0
0.249
Abbreviations: ACC, aortic cross clamp; CABG, coronary artery bypass grafting; CPB,
cardiopulmonary bypass; LVEF, left ventricular ejection fraction.
a Chronic kidney disease was defined as the definition of chronic kidney disease by
The Kidney Disease: Improving Global Outcomes Work Group.
b Aorta procedure was defined as ascending aorta replacement or reduction plasty.
Early Results
Operative mortality occurred in 15 patients (4.6%) overall. Excluding the patients
with endocarditis, the operative mortality of redo AVR decreased to 2.5% (6 of 242
patients), whereas that of redo AVR in patients with endocarditis increased to 11.0%
(9 of 82 patients). In the nonendocarditis group, the operative mortality was 1.3%
(2 of 151 patients) for SVD, and 4.8% (4 of 84 patients) for non-SVD. The operative
mortality was significantly higher in the endocarditis group (11.0% vs. 2.5%, p = 0.004).
[Table 2 ] summarizes the postoperative complications. There were significant differences in
the operative mortality rate and incidences of postoperative acute kidney injury,
stroke, and respiratory complications between the two groups ([Table 2 ]). After applying the IPTW procedure, the endocarditis group also had significantly
worse clinical outcomes in operative mortality and postoperative acute kidney injury
than the nonendocarditis group, whereas the other postoperative outcomes were comparable.
Table 2
Early clinical outcomes
Before IPTW, n (%)
IPTW-adjusted, %
Variables
All
Nonendocarditis group (n = 242)
Endocarditis group (n = 82)
p- Value
Nonendocarditis group (n = 242)
Endocarditis group (n = 82)
p- Value
Operative mortality
15(4.6%)
6 (2.5%)
9(11.0%)
0.004
3.0
10.2
0.013
For nonstructural valve dysfunction (n = 84)
4 (4.8%)
For structural valve degeneration (n = 151)
2 (1.3%)
For thrombosis (n = 7)
0 (0%)
Complications, n (%)
Low cardiac output syndrome
28 (8.6%)
18 (7.4%)
10 (12.3%)
0.171
7.6
11.1
0.330
Bleeding
16 (4.9%)
10 (4.1%)
7 (7.3%)
0.559
4.6
3.6
>0.999
Acute kidney injury
48 (14.8%)
26 (10.7%)
22 (26.8%)
0.001
11.6
23.2
0.011
New-onset AF
44 (13.6%)
36 (14.9%)
8 (9.8%)
0.326
14.9
9.4
0.217
Mediastinitis
2 (0.7%)
1 (0.5%)
1 (1.4%)
0.438
0.3
0.8
0.432
Stroke
16 (4.9%)
8 (3.3%)
8 (9.8%)
0.042
2.9
7.0
0.175
CAVB
9 (2.8%)
7 (2.9%)
2 (2.4%)
0.823
3.9
1.8
0.461
PPM insertion
13 (4.0%)
9 (3.7%)
4 (4.9%)
0.891
3.8
3.2
>0.999
Respiratory
2 (0.6%)
24 (9.9%)
16 (9.5%)
0.037
10.6
12.9
0.072
Infective endocarditis
2 (0.6%)
2 (0.8%)
0 (0.0%)
0.992
1.6
0.0
0.576
Abbreviations: AF, atrial fibrillation; CAVB, complete atrioventricular block; IPTW,
inverse probability of treatment weighting; PPM, permanent pacemaker.
The results of the univariate and multivariate logistic regression analyses for operative
mortality are shown in [Table 3 ]. Independent risk factors of operative mortality were the presence of preoperative
endocarditis (hazard ratio [HR]: 3.990; 95% confidence interval [CI]: 1.343–12.580;
p = 0.014), longer cardiopulmonary bypass time (HR: 1.006; 95% CI: 1.000–1.011; p = 0.037), and lower LVEF (HR: 0.956; 95% CI: 0.918–0.998; p = 0.034).
Table 3
Logistic regression analysis for factors associated with operative mortality
Factors associated with operative mortality
Variables[a ]
Univariate analysis
Multivariable analysis
HR [95% CI]
p- Value
HR [95% CI]
p- Value
Endocarditis group
4.849 [1.693–14.895]
0.004
3.990 [1.343–12.580]
0.014
CPB time
1.006 [1.001–1.011]
0.011
1.006 [1.000–1.011]
0.037
LVEF
0.946 [0.911–0.987]
0.007
0.956 [0.918–0.998]
0.034
Abbreviations: CPB, cardiopulmonary bypass, LVEF, left ventricular ejection fraction.
a All variables in [Table 1 ] were analyzed and factors that entered into the multivariable analysis were shown.
Long-Term Survival
Late death occurred in 53 patients including 10 cardiac deaths. The 1- and 5-year
overall survival rates were 93.4 and 83.5%, respectively ([Fig. 1A ]). In the nonendocarditis group, the overall survival at 1- and 5-years was 96.2
and 88.2%, respectively ([Fig. 1B ]). Kaplan–Meier curves showed that the overall survival was higher in the nonendocarditis
group (p < 0.001). The freedom from cardiac death at 1- and 5-years was 98.1 and 96.2%, respectively
([Fig. 2A ]). In the nonendocarditis group, the freedom from cardiac death at 1- and 5-years
was 100.0 and 98.8%, respectively ([Fig. 2B ]). Kaplan–Meier curves showed that the freedom from cardiac death was higher in the
nonendocarditis group (p = 0.010). Multivariate analysis showed that age and the presence of endocarditis
and LVEF were significantly associated with overall survival ([Table 4 ]). In the competing risk analysis for cardiac death, the endocarditis group was associated
with increased risk (HR: 10.260, 95% CI: 2.137–49.268; p = 0.004, [Table 4 ]). After IPTW, the clustered Cox regression also revealed that the endocarditis group
had poorer overall survival (HR: 2.238; 95% CI: 1.161–4.314; p = 0.016; [Supplementary Table S1 ] and [Supplementary Fig. S1 ] [available in the online version]).
Fig. 1 Kaplan–Meier curve (unweighted) for overall survival (A ) in all patients and (B ) according to the presence of preoperative prosthetic valve endocarditis.
Fig. 2 Kaplan–Meier curve (unweighted) for cardiac death (A ) in all patients and (B ) according to the presence of preoperative prosthetic valve endocarditis.
Table 4
Cox proportional hazards models for factors associated with overall survival and competing
risk analysis for factors associated with cardiac death
Factors associated with overall survival
Variables[a ]
Univariate analysis
Multivariable analysis
HR [95% CI]
p- Value
HR [95% CI]
p- Value
Age (y)
1.069 [1.039–1.099]
<0.001
1.065 [1.035–1.095]
<0.001
Endocarditis group
2.654 [1.539–4.577]
<0.001
2.107 [1.198–3.709]
0.010
LVEF
0.967 [0.946–0.989]
<0.001
0.961 [0.940–0.984]
<0.001
Factors associated with cardiac death
Variables[a ]
Univariate analysis
Multivariable analysis
HR [95% CI]
p- Value
HR [95% CI]
p- Value
Age
1.078 [1.010–1.151]
0.024
1.087 [1.012–1.167]
0.023
Endocarditis group
12.800 [2.717–60.310]
0.001
10.260 [2.137–49.268]
0.004
LVEF
0.927 [0.890–0.967]
<0.001
0.918 [0.874–0.964]
<0.001
Abbreviations: AF, atrial fibrillation; LVEF, left ventricular ejection fraction.
a All variables in [Table 1 ] were analyzed and factors that entered into the multivariable analysis were shown.
Aortic Valve-Related Events
During follow-up, AVRE occurred in 65 patients including cardiac death in 10, congestive
heart failure in 20, reoperation for the aortic valve in 11, and prosthetic AV endocarditis
in 9 patients.
The 1- and 5-year rates of freedom from AVRE were 91.4 and 76.8%, respectively ([Fig. 3A ]). The 5-year rates of freedom from AVRE in the nonendocarditis and endocarditis
groups were 93.8 and 79.7%, respectively ([Fig. 3B ]). Although there were significant differences in AVRE between the two groups in
the log-rank test (p = 0.010), there was no significant difference in AVRE after IPTW adjustment. The
multivariate analyses showed that the endocarditis was not an independent risk factor
for AVRE (HR: 1.456; 95% CI: 0.792–2.710; p = 0.236). Instead, the presence of chronic kidney disease was associated with AVRE
([Table 5 ]).
Fig. 3 Kaplan–Meier curve (unweighted) for aortic valve-related events (A ) in all patients and (B ) according to the presence of preoperative prosthetic valve endocarditis.
Table 5
Competing risk analysis for factors associated with aortic valve-related event (AVRE)
Factors associated with AVRE
Variables[a ]
Univariate analysis
Multivariable analysis
HR [95% CI]
p- Value
HR [95% CI]
p- Value
CKD
2.050 [1.220–3.450]
0.007
2.030 [1.183–3.480]
0.010
LVEF
0.977 [0.955–0.998]
0.035
0.978 [0.956–1.000]
0.067
Endocarditis group
1.790 [1.080–2.990]
0.024
1.456 [0.782–2.710]
0.236
Male gender
1.690 [1.030–2.750]
0.036
1.280 [0.713–2.300]
0.408
History of stroke
1.670 [0.934–2.970]
0.084
1.291 [0.698–2.390]
0.415
Abbreviations: CKD, chronic kidney disease; LVEF, left ventricular ejection fraction.
a All variables in [Table 1 ] were analyzed and factors that entered into the multivariable analysis were shown.
Comment
This study demonstrated three main findings. First, the clinical outcomes of redo
AVR for nonendocarditis were excellent with 2.5% operative mortality. In particular,
the mortality of redo AVR for SVD was very low at 1.5%. Second, endocarditis, prolonged
cardiopulmonary bypass time, and low LVEF were independent risk factors in redo AVR.
Third, redo AVR was associated with better overall survival and lower risk of cardiac
death in younger patients with an acceptable LVEF without endocarditis.
As the proportion of patients undergoing bioprosthetic AVR is increasing,[4 ] increasing numbers of patients are expected to require redo AVR.[5 ]
[6 ] Based on reports of a relatively high risk of redo surgical AVR with around 5% operative
mortality,[1 ] ViV-TAVI has been increasingly used. Although some previous observational studies
found that ViV-TAVI was associated with lower early mortality than redo AV,[7 ]
[8 ] those were not randomized controlled trials. In addition, those studies were based
on the administrative hospital-discharge database, which has limited information about
the existing bioprosthetic valve size. In patients with smaller bioprostheses, surgery
may be preferred over intervention due to patient–prosthesis mismatch; however, the
reoperation of smaller existing prostheses can be technically more demanding due to
the possible need for annular enlargement.[9 ] Moreover, compared with our patients, the patients in those studies tended to undergo
previous coronary artery bypass grafting more frequently (∼3% vs. 15–20%), which can
confer a relatively higher risk for redo surgery.[10 ]
[11 ] In addition, Deharo et al included patients with previous endocarditis.[7 ]
Recent meta-analyses that directly compared ViV-TAVI and surgery showed that the early[12 ] and mid-term[13 ] all-cause mortalities were comparable. There has been concern regarding the mid-
and long-term results of ViV-TAVI because of the higher postoperative pressure gradient
compared with surgery.[14 ]
[15 ] Regarding that, ViV-TAVI is challenging in patients with small bioprostheses (<21 mm)
in terms of hemodynamic performance[16 ] and Asians are tend to implant smaller bioprostheses at the index procedure. In
our study, 290 patients (89.5%) had bioprostheses less than or equal to 21 mm. Hawkins
et al[17 ] have also emphasized that patients with life expectancy longer than the duration
of TAVI valve and unsuitable anatomy for ViV-TAVI should be considered as a surgical
AVR candidate. Regarding reported mortality rates of 12 and 29–32% at 1 and 3 years
after ViV TAVI,[18 ]
[19 ] we observed relatively high 1- and 5-year overall survival rates of redo AVR (96.2
and 88.2%) in the nonendocarditis group. In addition, early studies suggested high
rates of device malposition, elevated transvalvular gradients, and coronary obstruction.[20 ]
[21 ]
Consistent with other studies,[1 ]
[22 ]
[23 ] the operative mortality of redo AVR in our study was 4.6%. Mortality around 5% was
observed with heterogeneous surgical patients, including reoperation involving aortic
surgery[22 ]
[23 ] and various surgical indications.[1 ] Moreover, most of those studies were published before 2010. After excluding the
patients with prosthetic valve endocarditis, the operative mortality in our study
fell to 2.5%, and decreased further to 1.5% for the patient with SVD. Our data show
that the operative mortality of prosthetic aortic valve endocarditis is up to 11.0%.
Prosthetic valve endocarditis is one of the most important indications of redo AVR
and its reported mortality rate is between 5 and 17%.[24 ]
[25 ] In numerous previous studies, prosthetic valve endocarditis as an indication for
redo AVR was a risk factor for early mortality, which is similar to our findings.[1 ]
[26 ]
[27 ]
The reported results after redo AVR are associated with the timing and indications
of reoperation, cardiac/noncardiac risk factors, and the type of valve implanted.[26 ]
[27 ]
[28 ] In our study, the multivariate analysis showed that preoperative prosthetic valve
endocarditis, prolonged cardiopulmonary bypass time, and low preoperative LVEF were
independent risk factors for operative mortality. In particular, a reduced LVEF is
a well-known risk factor for early mortality, which is similar to our results.[5 ]
[27 ] These findings show the importance of a comprehensive preoperative evaluation of
the candidates for redo cardiac surgery.
As technological advances have led to the introduction of transcatheter valve implantation
in selected patients who require redo cardiac surgery, a thorough understanding of
the operative outcomes and risk factors of redo AVR is essential. Although redo cardiac
surgery is technically demanding, surgical advances and standardized intensive care
unit protocols to minimize perioperative complication help reduce the associated morbidity.
Minimally invasive surgical techniques continue to be developed and new surgical devices
have been introduced, including sutureless valves, rapid deployment valves, and automated
suture fasteners, such as Cor-Knot.[1 ] Minimally invasive surgery can facilitate access to redo surgery, expanding the
surgical options to make redo surgery safer. In addition, the introduction of new
surgical devices can help reduce aortic cross clamp time, and avoid the dissection
of a previous aortotomy site and annulus injury during hand-tying. Moreover, the postoperative
cardiac intensive care protocols have been developed and standardized.[29 ] As a re-evaluation of recent clinical outcomes of redo AVR was needed, we conducted
this study to re-assess the contemporary results of redo AVR.
Several limitations of this study must be noted. First, it was limited by its retrospective
design. As the patients were not randomized to the interventions, there was selection
bias. However, we applied IPTW analysis to minimize bias. Second, the indications
for valve selection for redo AVR might have affected the clinical outcomes. However,
due to the retrospective nature of the study, we could not delineate the precise indications
for valve selection. Finally, we did not compare the clinical outcomes of redo AVR
and ViV-TAVI.
In conclusion, the early and long-term clinical outcomes of redo AVR for nonendocarditis
were excellent. Our findings suggest that patients without endocarditis, especially
with an acceptable ejection fraction, can be treated with redo AVR safely. However,
the long-term results of redo AVR and ViV-TAVI are needed to establish the superiority
of redo AVR with degenerated bioprosthetic aortic valves.
