Keywords
aortic valve - aortic root - bioprosthesis - surgery
Introduction
There is general agreement regarding performing surgery on operable patients with
severe aortic regurgitation accompanying aortic root aneurysms > 5.0 to 5.5 cm,[1]
[2] a large left ventricle, and left ventricular dysfunction. Standard surgical management
is a Bentall procedure in which either a bioprosthesis or a mechanical prosthesis
is incorporated within a polyester graft (composite graft).
Although the Bentall procedure is associated with low mortality and morbidity, bioprostheses
deteriorate, more rapidly in the younger patient, requiring reoperation, and mechanical
prostheses require life-long anticoagulation with its risks. The alternative is an
aortic valve-sparing operation. We and others have shown that it is possible to achieve
successful aortic root repair in more than 95% of cases—with less than 1% mortality
and 92 to 98% freedom from aortic valve reoperation at 5 years[3]
[4]
[5]
[6]
[7]
[8]—using the valve-sparing reimplantation operation first described by David for aortic
root aneurysms with or without aortic valve regurgitation and with improved subsequent
modifications.[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10] However, there are few studies evaluating outcomes following a reimplantation procedure
compared with the Bentall procedure at 8 to 10 years.[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
Therefore, we evaluated early and late outcomes of a reimplantation procedure compared
with a Bentall procedure and how surgery, either early or late in the disease process,
influenced success.
Materials and Methods
Patients
From January 2000 to January 2017, 1,159 patients underwent aortic valve reimplantation
with aortic root replacement or Bentall operation at Cleveland Clinic. Of these, 516
were excluded for age > 70 years or < 18 years, aortic valve reoperation, aortic valve
stenosis, infective endocarditis, aortic dissection, emergency surgery, or abnormal
cusp number (unicuspid, bicuspid, and quadricuspid). Of the remaining 643 patients,
448 had an aortic valve reimplantation procedure, and 195 underwent a Bentall operation
that incorporated either a bioprosthesis (n = 147, 75%) or a mechanical prosthesis (n = 48, 25%). Mean age at operation was 48 ± 13 years and 58 ± 10 years in the reimplantation
and Bentall groups, respectively, with male predominance ([Table 1]).
Table 1
Preoperative patient characteristics
Characteristics
|
Unmatched cohorts
|
Propensity-matched cohorts
|
Reimplantation
(n = 448)
|
Bentall
(n = 195)
|
Std. Diff. (%)
|
Reimplantation
(n = 100)
|
Bentall
(n = 100)
|
Std. Diff. (%)
|
n
[a]
|
No. (%) or mean ± SD
|
n
[a]
|
No. (%) or mean ± SD
|
n
[a]
|
No. (%) or mean ± SD
|
n
[a]
|
No. (%) or mean ± SD
|
Demographics:
|
|
|
|
|
|
|
|
|
|
|
Age (y)
|
448
|
48 ± 13
|
195
|
58 ± 10
|
88
|
100
|
58 ± 8.0
|
100
|
56 ± 10
|
–12
|
Female
|
448
|
85 (19)
|
195
|
21 (11)
|
–23
|
100
|
12 (12)
|
100
|
13 (13)
|
3.0
|
Height (cm)
|
448
|
182 ± 10
|
195
|
179 ± 10
|
–22
|
100
|
181 ± 9.0
|
100
|
179 ± 11
|
–16
|
BMI (kg•m–2)
|
444
|
27 ± 5.1
|
192
|
29 ± 5.9
|
37
|
99
|
29 ± 5.2
|
98
|
29 ± 6.0
|
–5.8
|
NYHA functional class:
|
414
|
|
179
|
|
33
|
91
|
|
87
|
|
7.9
|
I
|
|
263 (64)
|
|
82 (46)
|
|
|
42 (46)
|
|
37 (43)
|
|
II
|
|
129 (31)
|
|
83 (46)
|
|
|
42 (46)
|
|
42 (48)
|
|
III
|
|
21 (5.1)
|
|
14 (7.8)
|
|
|
7 (7.7)
|
|
8 (9.2)
|
|
IV
|
|
1 (0.24)
|
|
0 (0)
|
|
|
0 (0)
|
|
0 (0)
|
|
Aortic dimensions
[b]:
|
|
|
|
|
|
|
|
|
|
|
Root diameter (cm)
|
448
|
5.0 ± 0.52
|
195
|
5.2 ± 0.74
|
33
|
100
|
5.1 ± 0.61
|
100
|
5.1 ± 0.65
|
–9.5
|
Root area/height ratio
|
448
|
11 ± 2.3
|
195
|
12 ± 3.5
|
41
|
100
|
12 ± 2.8
|
100
|
12 ± 2.9
|
–4.2
|
Ascending diameter (cm)
|
445
|
4.5 ± 0.90
|
194
|
4.9 ± 1.0
|
39
|
99
|
4.8 ± 0.86
|
99
|
4.8 ± 0.92
|
–4.5
|
Aortic valve pathology:
|
|
|
|
|
|
|
|
|
|
|
AR grade
|
448
|
|
195
|
|
114
|
100
|
|
100
|
|
14
|
None
|
|
186 (42)
|
|
14 (7.2)
|
|
|
13 (13)
|
|
13 (13)
|
|
Mild
|
|
42 (9.4)
|
|
6 (3.1)
|
|
|
4 (4.0)
|
|
3 (3.0)
|
|
Moderate
|
|
97 (22)
|
|
39 (20)
|
|
|
24 (24)
|
|
20 (20)
|
|
Severe
|
|
123 (27)
|
|
136 (70)
|
|
|
59 (59)
|
|
64 (64)
|
|
Mitral valve regurgitation:
|
444
|
|
192
|
|
–4.3
|
98
|
|
98
|
|
–2.8
|
None
|
|
349 (79)
|
|
147 (77)
|
|
|
74 (76)
|
|
73 (74)
|
|
Mild
|
|
46 (10)
|
|
26 (14)
|
|
|
10 (10)
|
|
13 (13)
|
|
Moderate
|
|
20 (4.5)
|
|
12 (6.3)
|
|
|
5 (5.1)
|
|
5 (5.1)
|
|
Severe
|
|
29 (6.5)
|
|
7 (3.7)
|
|
|
9 (9.2)
|
|
7 (7.2)
|
|
Ventricular morphology and function:
|
|
|
|
|
|
|
|
|
|
|
LV mass index (g•m−2)
|
402
|
116 ± 42
|
178
|
142 ± 47
|
57
|
87
|
136 ± 52
|
93
|
139 ± 51
|
7.5
|
Ejection fraction (%)
|
439
|
57 ± 5.8
|
191
|
54 ± 7.4
|
–44
|
98
|
55 ± 6.0
|
99
|
55 ± 7.0
|
3.4
|
Cardiac rhythm:
|
|
|
|
|
|
|
|
|
|
|
AF or flutter
|
440
|
24 (5.5)
|
191
|
19 (9.9)
|
17
|
98
|
8 (8.2)
|
97
|
9 (9.3)
|
4.0
|
Coronary artery stenosis:
|
|
|
|
|
|
|
|
|
|
|
Left circumflex artery ≥ 50%
|
446
|
15 (3.4)
|
190
|
18 (9.5)
|
25
|
99
|
9 (9.1)
|
97
|
5 (5.2)
|
–15
|
LAD ≥ 50%
|
447
|
27 (6)
|
193
|
32 (17)
|
34
|
100
|
16 (16)
|
100
|
13 (13)
|
–8.5
|
Right coronary artery ≥ 50%
|
448
|
15 (3.3)
|
191
|
21 (11)
|
30
|
100
|
9 (9)
|
98
|
8 (8.2)
|
–3.0
|
Left main disease ≥ 50%
|
446
|
0 (0)
|
190
|
3 (1.6)
|
18
|
99
|
0 (0)
|
100
|
2 (2)
|
20
|
Preoperative ICD
|
448
|
1 (0.22)
|
195
|
0 (0)
|
—
|
—
|
—
|
—
|
—
|
—
|
Preoperative pacemaker
|
448
|
1 (0.22)
|
195
|
1 (0.51)
|
—
|
—
|
—
|
—
|
—
|
—
|
Noncardiac comorbidities:
|
|
|
|
|
|
|
|
|
|
|
Hypertension
|
447
|
309 (69)
|
195
|
156 (80)
|
25
|
100
|
80 (80)
|
100
|
81 (81)
|
2.5
|
Peripheral arterial disease
|
448
|
24 (5.4)
|
195
|
14 (7.2)
|
7.5
|
100
|
8 (8.0)
|
100
|
5 (5.0)
|
–12
|
Pharmacologically treated diabetes
|
445
|
15 (3.4)
|
195
|
15 (7.7)
|
19
|
100
|
6 (6.0)
|
100
|
5 (5.0)
|
–4.4
|
COPD
|
448
|
52 (12)
|
195
|
21 (11)
|
–2.7
|
100
|
12 (12)
|
100
|
12 (12)
|
0.0
|
History of smoking
|
448
|
180 (40)
|
195
|
96 (49)
|
18
|
100
|
54 (54)
|
100
|
50 (50)
|
–8.0
|
Creatinine (mg•dL–1)
|
446
|
0.95 ± 0.21
|
194
|
1.04 ± 0.48
|
24
|
100
|
0.98 ± 0.25
|
99
|
1.0 ± 0.62
|
14
|
Abbreviations: AF, atrial fibrillation; AR, aortic regurgitation; BMI, body mass index;
COPD, chronic obstructive pulmonary disease; ICD, implantable cardioverter-defibrillator;
LAD, left anterior descending coronary artery; LV, left ventricle; NYHA, New York
Heart Association; SD, standard deviation; Std Diff, standardized difference (Bentall-Reimplantation).
a Patients with data available.
b Echocardiographic.
Operative techniques included previously described modifications[4]
[11] of David's reimplantation method, which entails mobilizing the aortic valve, reimplanting
it into a polyester tube graft, attaching coronary buttons, and replacing the aneurysmal
aorta,[3]
[8]
[9]
[10]
[12] including plegeted sutures in the left ventricular outflow tract and use of a Hegar
dilator. Concomitant mitral valve surgery was performed in 35 patients (7.8%), coronary
artery bypass grafting in 31 (6.9%), and 34 (7.6%) required circulatory arrest ([Table 2]).
Table 2
Operative details
Detail
|
Unmatched cohorts
|
Propensity-matched cohorts
|
Reimplantation
(n = 448)
|
Bentall
(n = 195)
|
Std. Diff. (%)
|
Reimplantation
(n = 100)
|
Bentall
(n = 100)
|
Std. Diff. (%)
|
n
[a]
|
No. (%) or mean ± SD
|
n
[a]
|
No. (%) or mean ± SD
|
n
[a]
|
No. (%) or mean ± SD
|
n
[a]
|
No. (%) or mean ± SD
|
Concomitant procedures:
|
|
|
|
|
|
|
|
|
|
|
Descending aorta grafting
|
448
|
5 (1.1)
|
195
|
1 (0.51)
|
–6.7
|
100
|
0 (0)
|
100
|
1 (1.0)
|
14
|
CABG
|
448
|
31 (6.9)
|
195
|
43 (22)
|
44
|
100
|
19 (19)
|
100
|
14 (14)
|
–13
|
Ablation procedure for AF
|
448
|
21 (4.7)
|
195
|
21 (11)
|
23
|
100
|
8 (8.0)
|
100
|
9 (9.0)
|
3.6
|
Mitral valve repair
|
448
|
34 (7.6)
|
195
|
9 (4.6)
|
–12
|
100
|
9 (9.0)
|
100
|
6 (6.0)
|
–11
|
Mitral valve replacement
|
448
|
1 (0.22)
|
195
|
3 (1.5)
|
14
|
100
|
1 (1.0)
|
100
|
3 (3.0)
|
14
|
Tricuspid valve repair
|
448
|
7 (1.6)
|
195
|
1 (0.51)
|
–10
|
100
|
2 (2.0)
|
100
|
1 (1.0)
|
–8.2
|
Support:
|
|
|
|
|
|
|
|
|
|
|
Circulatory arrest
|
448
|
34 (7.6)
|
195
|
27 (14)
|
|
100
|
9 (9)
|
100
|
14 (14)
|
|
Circulatory arrest time (min)
|
34
|
18 ± 13
|
27
|
16 ± 7.4
|
|
9
|
12 ± 3.1
|
14
|
18 ± 7.7
|
|
Myocardial ischemic time (min)
|
448
|
106 ± 37
|
195
|
95 ± 36
|
|
100
|
114 ± 34
|
100
|
96 ± 36
|
|
CPB time (min)
|
448
|
127 ± 43
|
195
|
117 ± 45
|
|
100
|
136 ± 40
|
100
|
116 ± 44
|
|
Abbreviations: AF, atrial fibrillation; CABG, coronary artery bypass grafting; CPB,
cardiopulmonary bypass; SD, standard deviation; Std Diff, standardized difference
(Bentall-Reimplantation).
a Patients with data available.
Data
Patient characteristics and operative details were abstracted prospectively into the
Cleveland Clinic Thoracic Aorta Database, data that are approved for use in research
by the institutional review board, with patient consent waived.
Endpoints
Endpoints were (1) postoperative in-hospital mortality and adverse events defined
by the Society of Thoracic Surgeons national database (https://www.sts.org/registries-research-center/sts-national-database), (2) longitudinal postoperative aortic valve regurgitation and stenosis and left
ventricular reverse remodeling, (3) reoperation on the aortic valve or thoracic aorta,
and (4) time-related mortality.
Transthoracic echocardiography was used to assess postoperative aortic valve regurgitation,
mean aortic valve gradient, and left ventricular mass index.[13] Echocardiography was performed routinely before index hospital discharge and at
referring physician discretion during follow-up. A total of 1,759 echocardiograms
were available for 591 patients (92% of the study cohort) ([Supplementary Fig. S1]). No data in this report are based on intraoperative transesophageal echocardiography,
which was routinely performed. Interpretation of follow-up echocardiograms was obtained
at as many time points as available for each patient. Echocardiographic data were
censored at time of aortic valve or thoracic aorta reintervention, death, or final
follow-up.
Systematic follow-up performed at 2, 5, 10, 15, and 20 years was used to identify
aortic valve reinterventions. In the reimplantation group, 50% were followed > 10.5
months, 25% > 4.2 years, and 5% > 11 years; in the Bentall group, 50% were followed > 3.6
months, 25% > 4.5 years, and 5% > 12 years.
Adding supplemental vital status information obtained before November 2011 (Social
Security Death Master File)[14] to systematic follow-up, in the reimplantation group 50% of patients were followed > 2.8
years, 25% > 6 years, and 10% > 9 years, and in the Bentall group 50% of patients
were followed > 2.4 years, 25% > 7 years, and 10% > 11 years.
Data Analysis
SAS statistical software (SAS version 9.2; SAS Institute, Cary, NC) and R version
3.3.1 were used for analysis. Continuous variables are summarized as mean ± standard
deviation or as 15th/50th (median)/85th percentiles when values are skewed; comparisons
are based on the Wilcoxon rank-sum nonparametric test. Categorical data are summarized
using frequencies and percentages; comparisons are based on the chi-squared test or
Fisher's exact test. Uncertainty is expressed by confidence limits equivalent to ± 1
standard error (68%).
Variables associated with Reimplantation versus a Bentall Procedure
A parsimonious model for reimplantation versus a Bentall procedure was developed using
logistic regression, with variable selection from preoperative patient variables and
intended concomitant procedures listed in [Supplementary Appendix S1]. Variable selection, with p-value criterion for retention of variables in the model of 0.05, used bootstrap bagging
with 500 bootstrap data sets.[15] Frequency of occurrence of variables related to reimplantation versus Bentall procedure
was ascertained (aggregation step) and indicated the reliability of each variable.
Variables with bootstrap reliability ≥ 50% were retained in the final model.
Prior to multivariable analysis, we employed fivefold multiple imputation[16] using a Markov chain Monte Carlo technique.
For complementary analysis, random forest classification[17] was performed to assess possible nonlinear relationships between likelihood of reimplantation
and continuous patient characteristics, using risk-adjusted partial-dependency plots.[18] All variables listed in [Supplementary Appendix S1] were included in the analysis, without variable selection. Owing to a strong correlation
among different expressions of aortic root size, we performed separate analyses with
(1) aortic root diameter, (2) root area/height ratio, and (3) both root diameter and
area/height ratio. Missing data were imputed using “on the fly” random forest imputation.[19]
Longitudinal Data Analysis
Postoperative and follow-up transthoracic echocardiograms were analyzed for temporal
pattern of change using a nonlinear multiphase mixed-effects cumulative logistic regression
model for longitudinal ordinal data and a nonlinear mixed-effects regression model
for continuous data, both with patient as the random effect.[20]
Time-Related Events
Freedom from aortic valve reintervention and survival were assessed nonparametrically
by the Kaplan–Meier estimator and time-varying instantaneous risk of death by a multiphase
parametric hazard model.[21]
Development and Use of Propensity Score
Because patient characteristics differed for reimplantation versus a Bentall procedure,
propensity-matched cohorts were compared using the parsimonious model of variables
associated with reimplantation, other patient demographic variables, symptoms, cardiac
and noncardiac comorbidities, and procedure variables that might be related to unrecorded
selection factors (41 variables, [Supplementary Table S1] , c-statistic = 0.91; [Supplementary Appendix S1]). A propensity score was calculated for each patient by solving the model for the
probability of being in the reimplantation group and used to match Bentall cases 1:1
by greedy matching. Bentall cases whose propensity scores deviated > 0.10 from those
of reimplantation cases were considered unmatched. This process yielded 100 well-matched
pairs (51% of possible matches; see [Table 1] and [Supplementary Figs. S2A] and [S2B]).
Results
Selection of Reimplantation versus a Bentall Procedure
Patients were more likely to undergo reimplantation than a Bentall procedure ([Supplementary Fig. S3], and see [Table 1]) if they were asymptomatic (64% vs. 46%, p = 0.0008), younger than age 50 years ([Supplementary Fig. S4A]), had less preoperative aortic regurgitation, better left ventricular function ([Supplementary Fig. S4B]), smaller aortic root ([Supplementary Fig. S4C]) or smaller aortic root/height ratio ([Supplementary Fig. S4D]), and were operated on more recently ([Supplementary Fig. S4E]).
Safety of Reimplantation versus a Bentall Procedure
Hospital mortality was 0.22% (1/448) after reimplantation and 0% (0/195) after a Bentall
procedure ([Table 3]). Among propensity-matched patients, occurrence of in-hospital adverse events, including
stroke, renal failure requiring dialysis, reoperation for postoperative bleeding,
and postoperative atrial fibrillation, was similar between groups ([Table 3]). However, the reimplantation group had a median postoperative length of stay that
was 1 day shorter.
Table 3
In-hospital outcomes
Outcome
|
Unmatched cohorts
|
Propensity-matched cohorts
|
Reimplantation (n = 448)
|
Bentall
(n = 195)
|
Reimplantation (n = 100)
|
Bentall
(n = 100)
|
p-Value
|
n
[a]
|
No. (%) or 15th/50th/85th percentiles
|
n
[a]
|
No. (%) or 15th/50th/85th percentiles
|
n
[a]
|
No. (%) or 15th/50th/85th percentiles
|
n
[a]
|
No. (%) or 15th/50th/85th percentiles
|
Hospital death
|
448
|
1 (0.22)
|
195
|
0 (0)
|
100
|
0 (0)
|
100
|
0 (0)
|
—
|
Stroke
|
448
|
1 (0.22)
|
195
|
1 (0.51)
|
100
|
1 (1.0)
|
100
|
0 (0)
|
> 0.9
|
Reoperation for valve dysfunction
|
448
|
1 (0.22)
|
195
|
0 (0)
|
100
|
1 (1.0)
|
100
|
0 (0)
|
> 0.9
|
Reoperation for bleeding
|
448
|
8 (1.8)
|
195
|
8 (4.1)
|
100
|
1 (1.0)
|
100
|
4 (4.0)
|
0.4
|
Renal failure requiring dialysis
|
445
|
1 (0.22)
|
194
|
1 (0.52)
|
100
|
0 (0)
|
99
|
1 (1.0)
|
0.5
|
Prolonged ventilation (> 24 h)
|
447
|
19 (4.3)
|
181
|
13 (7.2)
|
100
|
2 (2.0)
|
97
|
7 (7.2)
|
0.1
|
New-onset atrial fibrillation
|
417
|
104 (25)
|
172
|
77 (45)
|
90
|
36 (40)
|
88
|
41 (47)
|
0.4
|
Postoperative ICD
|
447
|
6 (1.3)
|
195
|
3 (1.5)
|
100
|
3 (3)
|
100
|
0 (0)
|
> 0.9
|
Postoperative pacemaker
|
447
|
8 (1.8)
|
194
|
13 (6.7)
|
100
|
2 (2)
|
100
|
6 (6)
|
0.001
|
Transfusions:
|
|
|
|
|
|
|
|
|
|
Red blood cell
|
448
|
113 (25)
|
195
|
58 (30)
|
100
|
18 (18)
|
100
|
32 (32)
|
0.02
|
Platelets
|
409
|
130 (32)
|
164
|
65 (40)
|
84
|
33 (39)
|
91
|
37 (41)
|
0.8
|
Fresh frozen plasma
|
448
|
93 (21)
|
195
|
44 (23)
|
100
|
26 (26)
|
100
|
26 (26)
|
> 0.9
|
Any transfused product
|
448
|
191 (43)
|
195
|
93 (48)
|
100
|
44 (44)
|
100
|
51 (51)
|
0.3
|
Length of stay:
|
448
|
|
195
|
|
100
|
|
100
|
|
|
Intensive care unit (h)
|
|
22/28/73
|
|
23/46/96
|
|
22/27/98
|
|
23/47/97
|
0.08
|
Postoperative (d)
|
|
5.0/6.1/9.0
|
|
5.2/7.2/11
|
|
5.1/6.1/10
|
|
5.2/7.1/12
|
0.01
|
Abbreviation: ICD, implantable cardioverter-defibrillator.
a Patients with data available.
Effectiveness of Valve Reimplantation
Among all 448 patients who underwent aortic valve reimplantation, freedom from severe
aortic regurgitation was 96% at 5 years and 95% at 8 years ([Fig. 1A]), 10-year freedom from aortic valve reintervention was 98% with 5 patients undergoing
aortic valve reintervention, all for aortic regurgitation secondary to cusp dysfunction
([Fig. 1B]), and 5- and 10-year survival was 97 and 95% ([Fig. 1C]). Higher likelihood of postoperative aortic regurgitation was associated with higher
preoperative grade of aortic regurgitation ([Fig. 2A]; p < 0.0001); however, neither preoperative aortic root diameter ([Fig. 2B]; p = 0.3) nor area/height ratio ([Fig. 2C]; p = 0.14) was associated with greater regurgitation. Mean gradient was 7 mm Hg at 5
and 8 years after surgery ([Supplementary Fig. S5]), and left ventricular mass, 120 g·m–2 at time of surgery was 104 g·m–2 at 5 years and 105 g·m–2 at 8 years after surgery ([Supplementary Fig. S6]). In patients who had both aortic valve reimplantation and mitral valve repair,
freedom from reoperation was 100% at 10 years, not significantly different from that
of patients having reimplantation alone (p = 0.5).
Fig. 1 Outcomes after a reimplantation procedure. (A) Postoperative prevalence of severe aortic regurgitation (AR). Solid lines represent
the longitudinal trend in each grade, and symbols represent grouped data without regard
to repeated measures to provide crude verification of model fit. (B) Freedom from aortic valve reintervention. Each symbol represents a reintervention
and vertical lines 68% confidence limits equivalent to ± 1 standard error. Numbers
below horizontal axis represent patients still being followed. (C) Survival. Each symbol represents a death and vertical bars 68% confidence limits
equivalent to ± 1 standard error. Solid line within a 68% confidence band represents
parametric estimates. Numbers below horizontal axis represent patients still being
followed.
Fig. 2 Relationship of severe postoperative aortic regurgitation (AR) to preoperative variables.
Format is as in [Fig. 1A]. (A) Greater preoperative severity of AR was associated with more severe late AR. (B) Preoperative aortic root diameter was not associated with severe postoperative AR.
(C) Preoperative aortic root area/height ratio was not associated with severe postoperative
AR.
Fig. 3 Outcomes in propensity-matched cohorts of patients after undergoing reimplantation
versus a Bentall procedure. (A) Aortic regurgitation (AR). Solid lines represent parametric estimates of percentage
of patients (mean effect) with severe AR after surgery. Symbols represent data grouped
(without regard to repeated measurements) within time frames to provide a crude verification
of model fit. (B) Temporal trend of aortic valve (AV) mean gradient. Symbols represent data grouped
(without regard to repeated measurements) within time frames to provide a crude verification
of model fit. (C) Left ventricular (LV) mass index. Format is as in panel B. (D) Freedom from reoperation on the aortic valve. Solid lines represent parametric estimates.
Symbols are nonparametric Kaplan–Meier estimates, and vertical bars represent 68%
confidence limits. (E) Survival. Format is as in panel D.
Outcomes of Reimplantation versus Bentall Procedure
The propensity-matched reimplantation group, which consisted of patients with Bentall-like
preoperative characteristics ([Supplementary Table S1]), demonstrated significantly more severe postoperative aortic regurgitation than
the Bentall group; at 8 years, prevalence was 7.2% compared with 0% in the Bentall
group (p = 0.02; [Fig. 3A]). The reimplantation group experienced a lower mean gradient ([Fig. 3B]) and a rapid early decrease in mass index ([Fig. 3C]) compared with the Bentall group (p = 0.04 and p = 0.007, respectively), although as time progressed, the difference narrowed (p = 0.8 for the late phase). At 10 years, there was no statistically significant difference
in freedom from reintervention on the aortic valve (reimplantation, 98%; Bentall,
100%, p = 0.8; [Fig. 3D]). There was also no significant difference in survival between the matched reimplantation
and Bentall groups at 10 years (p = 0.8; [Fig. 3E]).
Discussion
Principal Findings
The current study shows a high level of repair success (> 95%) and low mortality for
patients undergoing reimplantation for aortic root aneurysms with or without aortic
regurgitation. Specifically, mortality was 0.22%, repair success high, and freedom
from reintervention 98% at 10 years. This study discerned potential benefits of early
intervention with valve reimplantation before a large root developed with potential
tearing of cusps, more severe aortic regurgitation, or symptoms.
Reimplantation versus Bentall Procedure
The Bentall group of patients experienced excellent outcomes; however, patients undergoing
reimplantation with more advanced disease were more likely to experience severe late
aortic regurgitation compared with those undergoing a Bentall procedure, despite the
negligible difference in valve reintervention and survival.
Clearly, for aortic root reimplantation, high mortality would negate the benefit of
preventing aortic dissection or rupture, heart failure, and late death; however, in
this study we have shown that the operation is as safe as the Bentall procedure. Importantly,
reimplantation circumvents potential for prosthetic degeneration of bioprosthetic
composite grafts and the need for anticoagulation therapy for mechanical composite
grafts.
The decision to attempt and the subsequent success at completing a valve reimplantation
was influenced by several factors. More symptomatic patients and patients with worse
left ventricular dysfunction and more severe aortic regurgitation had lower success,
but larger aortic root size did not influence reimplantation success, although a smaller
cross-sectional area/height ratio was associated with greater likelihood of successful
reimplantation. We inform patients who have aortic root aneurysms with tricuspid valves
and moderate or less aortic valve regurgitation that they will have a 90 to 95% chance
of valve preservation, and if less than mild regurgitation, a greater than 95% chance.
Indeed, this study confirms high success in this group of patients. In an earlier
paper, we reported that only 2% of patients had an increase in aortic regurgitation
after surgery.[11]
We believe that the reason for less success with more severe regurgitation is the
greater likelihood of more severe lacerations, perforations, torn cusps, stretched
cusps, and prolapse of more than one cusp, making a long-term durable repair more
difficult to achieve, and an additional argument for earlier surgery.[22]
Long-Term Durability
We compared outcomes of reimplantation with those of a propensity-matched population,
which showed no early or late increased risk of mortality and without risk of late
failure of biological Bentalls.[12] Previously, we found that late risk for new dissection after reimplantation was
only 1.4%, and most were in the descending aorta and associated with a connective
tissue disorder.[8] If patients with aortic cross-sectional area-to-height ratio > 10 are not operated
on, late survival is reduced partly because the risk of dissection increases without
surgery.[23]
Clinical Implications
Based on this study, > 95% freedom from reoperation and severe regurgitation at 10
years can be expected for tricuspid aortic valves with reimplantation. Critical to
the success of aortic valve repairs is addressing the CLASS schema factors (Commissures,
Leaflets, Anulus, Sinutubular junction, and Sinuses) that contribute to aortic valve
competence[8]
[11]; the reimplantation procedure also braces the root and aortic valve, which is analogous
to use of anuloplasty for mitral valve repair.[24] Use of commissure figure-of-8 sutures to repair cusp prolapse during reimplantation
improves valve repair success.
We believe the modifications we use with pledgets in the left ventricular outflow
tract, use of a 30-mm tube graft in most patients, and reducing anular size based
on body surface area using Hegar dilators results in a reproducible and reliable procedure
with good late valve function.[4]
[11]
Limitations
This is a single-institution observational study comparing reimplantation with Bentall
composite valve grafts. We did not have a control arm of medically treated patients
with enlarged aortas and aortic regurgitation. There are, however, reports of medically
treated patients with enlarged aortas, but with associated risk of dissection or rupture;
most of these patients transition to surgery.[25]
Conclusion
This study demonstrates that reimplantation or root replacement with a Bentall type
procedure, with or without aortic regurgitation, can be performed with excellent early
and late outcomes, leading us to recommend reimplantation more often in patients who
present with even moderately severe or severe aortic regurgitation and significantly
enlarged aortic roots. A key to success is learning a reproducible procedure by the
methods we use.
Editor's Commentary
Tirone E. David, MD, FRCSC
Division of Cardiac Surgery, Toronto General Hospital, University of Toronto, Toronto,
Ontario, Canada
This study compared the outcomes of reimplantation of the aortic valve with Bentall
procedure with mechanical as well as bioprosthetic valves. Although the sample size
is relatively large (particularly for the reimplantation group) the proportion of
patients followed beyond 1 year was very small (50% of reimplantation was followed > 10.5
months and 50% of Bentall > 3.6 months). Thus, interpretation of outcomes at 10 years
should be made with caution. In addition, patients with mechanical valves likely had
valve-related complications such as bleeding and stroke and were not accounted for.
Patients with bioprosthetic valve did not have any valve failure because of short
follow-up. Based on the data presented the authors should have concluded that these
two operations provide similar result up to 10 years and reimplantation was not better
than Bentall.