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Surgical aortic arch intervention at the time of extended ascending aortic replacement is associated with increased mortality
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Surgical aortic arch intervention at the time of extended ascending aortic replacement is associated with increased mortality
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i
SURGICAL AORTIC ARCH INTERVENTION AT THE TIME OF EXTENDED
ASCENDING AORTIC REPLACEMENT IS ASSOCIATED WITH INCREASED
MORTALITY
by
Michael E. Bowdish, MD
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSTIY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(APPLIED BIOSTATISTICS AND EPIDEMIOLOGY)
May 2019
Copyright 2019 Michael E. Bowdish, MD
ii
TABLE OF CONTENTS
DEDICATION iii
ACKNOWLEDGEMENTS iv
ABSTRACT v
INTRODUCTION 1
METHODS 2
RESULTS 5
DISCUSSION 9
CONCLUSIONS 15
REFERENCES 16
TABLES 20
FIGURE LEGENDS 27
FIGURES 28
iii
DEDICATION
This work is dedicated to my wonderful wife, Margarita, and son, Matthew, for their
endless love and support.
iv
ACKNOWLEDGEMENTS
I would like to thank my advisor, mentor, and friend, Dr. Wendy Mack for being a great
mentor and encouraging me to pursue a master’s degree in applied Biostatistics and
Epidemiology. In addition, I would like to thank my committee members, Dr. Meredith Franklin
and Dr. Sandrah Eckel. Last, I would like to thank all the professors for tolerating a full-time
faculty member in their classes – I truly enjoyed learning about a new discipline and look
forward to continuing to work together as colleagues.
v
ABSTRACT
Objective: To compare outcomes of hemiarch versus total arch repair during extended ascending
aortic replacement.
Methods: Between 2004 and 2017, 261 patients underwent hemiarch (n=149, 57%) or total arch
repair (aortic debranching or Carrell patch technique, n=112, 43%) in the setting of extended
replacement of the ascending aorta. Median follow up was 17.2 (IQR 4.2–39.1) months.
Multivariable models considering preoperative and intraoperative factors associated with
mortality and aortic reintervention were constructed.
Results: Survival was 89.0, 81.3, and 73.5% vs. 76.4, 69.5, and 61.7% at 1, 3, and 5 years in the
hemiarch versus total arch groups, respectively (log-rank p=0.010). After adjustment for
preoperative and intraoperative factors, the presence of a total arch repair (adjusted HR 2.53,
95% CI 1.39 – 4.62, p=0.003), and increasing age (adjusted HR per 10 years of age, 1.76, 95%
CI 1.37 – 2.28, p<0.001) were associated with increased mortality. The cumulative incidence of
aortic reintervention with death as a competing outcome was 2.6, 2.6, and 4.4% and 5.0, 10.3,
and 11.9% in the hemiarch and total arch groups, respectively. After adjustment, the presence of
a total arch repair was significantly associated with need for aortic reintervention (SHR 3.21,
95% CI 1.01 – 10.2, p=0.047).
Conclusions: Overall survival after aortic arch repair in the setting of extended ascending aortic
replacement is excellent, however, total arch repair and increasing age are associated with higher
mortality and reintervention rates. A conservative approach to aortic arch repair can be prudent,
especially in those of advanced age.
1
INTRODUCTION
The optimal approach to aortic arch repair in the setting of ascending aortic disease
remains controversial and continues to evolve, especially in the setting of acute aortic dissection.
While some advocate for replacement of the entire aortic arch during extended replacement of
the ascending aorta,
1-3
others restrict aortic arch repair to those settings in which aortic pathology
exists.
4-6
Proponents of the former approach argue that a more aggressive approach to the aortic
arch prevents the need for subsequent reintervention and potentially leads to better long-term
outcomes. Others argue that absent aortic arch pathology, total arch replacement is associated
with increased morbidity and mortality and may not decrease the need for further aortic
reintervention or result in improved long-term survival.
Our custom at the University of Southern California has been to perform a hemiarch
operation whenever possible, as long as it fully addresses the indication for operation. Total arch
replacements are reserved for aortic dissections with tears in the arch, or aneurysms and other
aortic arch pathology that involve the aortic branches. This study compares our results with
hemiarch vs. total arch replacements in 261 consecutive operations for primary ascending aortic
pathology. The primary objective was to develop a multivariable model to estimate the effect of
important preoperative and operative variables on mortality and need for aortic reintervention.
2
METHODS
This was a systematic retrospective cohort study of patients undergoing surgical aortic arch
intervention in the setting of extended ascending aortic pathology at our institution between
March 2004 and August 2017. Patients who underwent isolated ascending aortic replacement
with a closed distal anastomosis were excluded. The Institutional Review Board of the
University of Southern California Health Sciences Campus approved this study (HS-17-00621)
and waived the requirement for patient consent.
Patients baseline demographics, operative characteristics, and perioperative outcomes were
identified through our research database. The primary endpoints were mortality and need for
aortic reintervention. All medical records from our electronic medical record system were
reviewed. Postoperative complications were defined according to standard guidelines.
7
All
variables are defined in Supplemental Table 1. Indication for surgery was divided into dissection,
aneurysm, and “other”. The dissection category included acute and chronic dissection, while the
aneurysm category included both primary aneurysms and pseudoaneurysms. The “other”
category included infections, porcelain aortas, and aorto-esophageal fistulas. Follow up was
considered complete as of the date of last contact.
The entire cohort was divided into two categories based on type of surgical aortic arch repair.
Hemiarch repair was defined as replacement of the undersurface of the aortic arch, without aortic
arch vessel reconstruction. Total arch repair was defined as the need for re-implantation of aortic
arch vessels either as a contiguous patch (i.e. Carrel technique) or the need for prosthetic aortic
3
arch vessel debranching. We also included in the category of total arch repair 4 cases where only
the innominate artery was reimplanted because of the similar complexity of that procedure.
Patients undergoing both emergent/urgent and elective procedures were included as well as
patients with concomitant cardiac procedures.
Our approach to aortic dissection repair has been previously described.
4,8
For both hemiarch and
total arch repairs, we prefer axillary artery cannulation with antegrade cerebral perfusion with
mild to moderate hypothermia depending on extent of anticipated repair. In general, we cool to
27°C for hemiarch repair and 24 to 22°C for total arch repair. The decision to proceed with
hemiarch versus total arch is made based on presence or absence of aortic arch pathology
(dissection with intimal tear, aneurysm, infection). Our general approach to hemiarch and total
arch repair (both carrel patch and debranching techniques) is demonstrated in Figure 1.
Statistical analyses were performed using STATA Version 15 (Statistical Software, College
Station, TX) and R version 3.4.3 (https://www.R-project.org/). Preoperative and operative
characteristics and postoperative outcomes are summarized with descriptive statistics. For
continuous variables, comparisons between groups were conducted based on normality with
either a two-sample independent t-test or Wilcoxon rank sum test. Categorical comparisons were
by Chi square or Fisher’s exact tests. Overall survival analyses were conducted by Kaplan-Meier
methods, with log-rank comparison between surgical treatment groups. Cox proportional hazard
modeling was conducted to identify pre- and intraoperative factors associated with overall
mortality. All variables with a univariable p value <0.2 were considered in creating a
multivariable Cox proportional hazard model of overall mortality. The independent variable of
4
interest was type of aortic arch repair (hemiarch versus total arch). Model diagnostics included
use of Schoenfeld residuals to examine the proportional hazard assumption, martingale residuals
to assess linearity, and Cox-Snell residuals to examine overall model fit. Influential observations
were identified through use of delta beta and likelihood displacement. The proportional hazard
assumption was found to be violated by the “other” category of surgical indication, therefore the
final multivariable model is stratified by this covariate. A sensitivity analysis excluding key
influential observations, and a separate analysis excluding the “other” category of surgical
indication, confirmed the primary findings (see supplemental material). Results are presented as
hazard ratio (HR) and 95% confidence intervals. Non-parametric estimates of the cumulative
incidence of aortic reintervention were calculated.
9
The need for aortic reintervention was
analyzed using competing risks with considered death a competing outcome and are presented as
sub-hazard ratios (SHR) and 95% confidence intervals.
10
Statistical tests with a two-sided p
value less than 0.05 were considered statistically significant.
5
RESULTS
A total of 261 patients are included in this study, of which 149 (57%) underwent hemiarch and
112 (43%) underwent total arch repair. Preoperative and operative characteristics are shown in
Tables 1 and 2. In the overall cohort, median age was 60.6 (IQR 52.7 – 70.0) with a
predominance of males, smokers, and those with hypertension. Acute aortic dissection was the
predominant indication for surgery (66.3%). Those undergoing hemiarch and total arch repair
were of similar age and body mass index (BMI), and had similar frequencies of hyperlipidemia,
chronic obstructive pulmonary disease, chronic dialysis, previous stroke, and history of heart
failure. Those undergoing hemiarch repair were more likely to be males, have hypertension,
diabetes, peripheral artery disease, a prior myocardial infarction, and dissection as the operative
indication.
Operative characteristics are notable for a similar proportion of reoperative surgery in both
groups (35.7 vs. 25.7%, p=0.16, total arch vs. hemiarch). Type of proximal aortic repair was
likewise similar in both groups with relatively equal distribution of isolated aortic replacement
(at sinotubular junction), aortic replacement with aortic valve replacement, and aortic root
replacement. Those undergoing hemiarch replacement were more likely to have an
urgent/emergent operative indication and to have shorter cardiopulmonary bypass, aortic cross
clamp, and antegrade cerebral perfusion times. Cerebral protection was used with similar
frequency in both groups, with axillary cannulation and antegrade cerebral perfusion
predominating in our recent series. Thirty-one (11.9%) of those undergoing total arch
replacement had an elephant trunk procedure.
6
In-hospital and 30-day mortality were significantly higher in those undergoing total arch
replacement. In-hospital mortality was 5.4% in the hemiarch group versus 13.4% in the total arch
group (p=0.024). 30-day mortality was 4.7% in the hemiarch group versus 14.3% in the total
arch group (p=0.018). Vocal cord paralysis was more common in the total arch group, while
other perioperative outcomes (use of ECMO, stroke, paraplegia, reoperation for bleeding,
pneumonia, open chest) were similar between groups.
Median follow-up was 17.2 months (IQR 4.2 – 39.1). Overall survival based on Kaplan-Meier
estimates was 83.6, 76.2, and 68.2% at 1, 3, and 5 years, respectively (Figure 2A and
Supplemental Table 2). Survival for those undergoing hemiarch repair was 89.0, 81.2, and
73.5% at 1, 3, and 5 years while survival for those undergoing total arch repair was 76.4, 69.5,
and 61.7% at 1, 3, and 5 years (log rank p=0.010, Figure 2B and Supplemental Table 2).
To assess the association of type of aortic repair on overall mortality, a multivariable Cox
proportional hazard model was fitted to control for confounding bias by pre and intraoperative
factors (Figure 3 and Supplemental Table 3). Unadjusted hazard ratios are shown in
Supplemental Table 3. Adjustments were made for age, gender, presence of antegrade cerebral
perfusion, prior myocardial infarction, preoperative renal failure, peripheral artery disease,
chronic lung disease, hyperlipidemia, hypertension, and concomitant coronary artery bypass
grafting. The presence of a total arch repair was associated with a 2.53 time increase in mortality
(adjusted HR 2.53, 95% CI 1.38 – 4.62, p = 0.003) as compared to a hemiarch repair. The other
strong predictor of mortality in this analysis was increasing age, with a 1.76 time increase per 10
7
years of age (HR 1.76, 95% CI 1.37 – 2.28, p<0.001). Testing for an interaction between age and
type of aortic repair was not statistically significant (interaction HR 0.942, 95% CI 0.56 – 1.60,
p=0.824). Age did not appear to confound the association of operative type on mortality, bue was
an important predictor. While the other factors were not significant, they were left in the final
model due to their level of significance on univariable analysis and clinical plausibility as a
confounder. However, removal of each non-significant covariate did not alter the overall
assessment of the relationship of either type of aortic arch repair or age in relationship to
mortality. Predicted survival curves demonstrating the strong relationship with mortality between
type of aortic repair (total arch or hemiarch) and age are shown in Figure 4.
The cumulative incidence of the need for aortic reintervention with death as a competing
outcome is shown in Figure 5. Fourteen patients underwent aortic reintervention (4 hemiarch, 10
total arch). The median time to aortic reintervention was 505 days (IQR 152 – 505) days in the
hemiarch group and 437.4 days (IQR 84 – 437.5) in the total arch group. Of the hemiarch
reintervention, 2 required a descending thoracic endograft, 1 aortic valve replacement, and 1 re-
replacement of the ascending aorta. Of the aortic reintervention in the total arch group, 7
required a descending thoracic endograft, 2 of which included aortic arch endografts, 2 open
aortic arch repairs, and 1 aortic root replacement. The cumulative incidence of aortic
reintervention with death as a competing outcome was 2.6, 2.6, and 4.4% at 1, 2, and 3 years in
the hemiarch group and 5.0, 10.3, and 11.9% in the total arch group. The total arch group was
3.19 times more likely to require aortic reintervention (sub-hazard ratio (SHR) 3.10, 95% CI 1.00
– 10.1, p=0.049) in a univariable competing risk model (death as competing outcome). After
adjustment for age, the presence of a total arch repair remained significantly associated with
8
need for aortic reintervention (SHR 3.21, 95% CI 1.01 – 10.2, p=0.047). Age was not associated
with the need for aortic reintervention (SHR 0.90, 95% CI 0.65 – 1.23, p=0.50).
9
DISCUSSION
Operations in the setting of extended ascending aortic replacement can range in complexity from
hemiarch to total arch replacement. The proponents of the hemiarch repair cite its technical
simplicity, perceived durability, shorter circulatory arrest times, and potential for lower
morbidity
11,12
. Those who prefer the total arch repair believe that the reintervention rate should
be lower with complete replacement leading to improved long-term survival.
13-15
There are two principle findings of this study. The first is that, total arch replacement at the time
of extended ascending aortic replacement is associated with increased mortality and
reintervention rates when compared with hemiarch replacement. Second, age is associated with
increasing mortality regardless of the extent of repair. Collectively, our data suggest that
mortality and reintervention rates are higher in the total arch group, making the hemiarch
procedure the preferred procedure as long as it adequately addresses the aortic pathology,
especially in those of advanced age.
The baseline characteristics of those undergoing hemiarch and total arch replacement were
somewhat different in this series. Those undergoing hemiarch replacement were more commonly
male, hypertensive, diabetic, had peripheral arterial disease and a prior myocardial infarction. In
addition, those undergoing hemiarch repair were more likely to have been done emergently and
have an aortic dissection as opposed to an aortic aneurysm as the operative indication. Our
assessment is that the hemiarch group in this study appeared somewhat “sicker” than the total
arch group, and that would be consistent with our philosophy of only performing a total arch
replacement during extended ascending aortic replacement when clinically indicated.
10
In-hospital and 30 day mortality were 5.4 and 4.7% in the hemiarch group and 13.4 and 14.3% in
the total arch groups. These results, as well as our overall survival at 1, 3, and 5 years of 83.6,
76.2, and 68.2% are comparable to previously published studies.
12,16-18
While our study did not
focus on perioperative outcomes, we had relatively low stroke rates (3.4 vs 5.4%, hemiarch vs
total arch, p=0.43), as well as similar rates of paraplegia, need for postoperative extracorporeal
membrane oxygenation, and reoperations for bleeding between groups. These results are similar
to others reported in the literature as well as rates of paraplegia.
12,19-23
The primary objective was to develop a multivariable model to estimate the effect of important
preoperative and operative variables on mortality and need for aortic reintervention in the setting
of aortic arch surgery at the time of extended ascending aortic replacement. By Kaplan-Meier
estimates, there was a clear difference in survival between those undergoing a hemiarch versus a
total arch repair (log-rank p=0.012). To examine this relationship further, a multivariable Cox
proportional hazard model was created which adjusted for baseline characteristics between
groups. In this analysis, the presence of a total arch repair was associated with a 2.5 time increase
in the likelihood of death during the follow up period as compared to the hemiarch group (HR
2.53, 95% CI 1.38-4.62, p=0.003). In addition to type of aortic repair, increasing age was also
highly associated with mortality during the follow up period – with a 1.8 time increase per 10-
year increase in age (HR 1.76 per 10 years of age, 95% CI 1.37-2.28, p<0.001). Other factors of
significance or borderline significance on univariable modeling were not associated with
mortality on multivariable modeling (gender, use of antegrade cerebral perfusion, previous
myocardial infarction, renal failure, chronic lung disease, peripheral arterial disease,
hyperlipidemia, hypertension, and concomitant coronary artery bypass grafting). It is also
11
notable that the effect of age was constant in both the hemiarch and total arch groups, as
assessment of an interaction term was not significant.
The central figure of this manuscript (Figure 3) demonstrates the powerful effect of type of
repair and age. This figure puts the impact of the age and type of aortic repair estimates on
mortality in perspective based on our multivariable model. The predicted hazard for mortality for
a 50-year-old undergoing a hemiarch repair is 17.1 (HR 17.1, 95% CI 4.8 – 61.5), while the
predicted hazard for mortality for a 70-year-old undergoing the same repair is 53.3 (HR 53.3,
95% CI 18.9 – 319.4). Similarly, the predicted hazard for mortality for a 50-year-old undergoing
a total arch repair is 43.4 (HR 43.3, 95% CI 10-181), while the predicted hazard for mortality for
a 70-year-old undergoing the same repair is 134.9 (HR 134.9, 95% CI 20-909). One can also
compare across repair types – in a 50-year-old the hazard was 17.1 for a hemiarch and 43.4 for a
total arch, and in a 70-year-old, the hazard was 53.3 with a hemiarch and 134.9 with a total arch.
It was not our intention in this study to examine indication for repair (dissection, aneurysm,
other) in detail as we wanted to look at a comprehensive aortic experience in the setting of
extended ascending aorta replacement. However, indication is known to be a strong risk factor
for mortality in other studies
17,22
and was included in our multivariable modeling. While
indication was not associated with overall survival in this analysis, this variable violated the
proportionality assumptions of Cox proportional hazard modeling. Therefore, our final
multivariable model referenced above was “stratified” by indication. However, to confirm our
primary findings that age and type of repair were highly associated with mortality and that this
was not influenced by indication, three sensitivity analyses were performed (Supplemental Table
12
4). As can be seen in Supplement Table 4, stratification by the indication variable in the model
resulted in an improvement in model fit with a lower AIC and BIC as compared to the non-
stratified model (AIC 562 to 448, BIC 608 to 487). The violation of proportionality occurred in
the “other” indication for surgery (infections, porcelain aortas, and aorto-esophageal fistulas,
n=16). As this group is admittedly a bit “unique” we performed the analysis excluding these
observations, with similar finding for presence of a total arch repair and age per 10 years (both
remained highly significant, and this model had worse fit than the indication stratified model).
Finally, we fit our final model separately, in the cohorts only with aortic dissections and only
with aneurysms, again with similar findings that total arch replacement and age per 10 years
were both associated with increased mortality. Our findings on the effect of age on overall
outcomes is be supported by recent literature publications.
13,24
Type of aortic arch repair at time of extended ascending aortic replacement is thought to
influence the need for subsequent aortic reintervention.
5,13,14,24,25
In this study, we utilized
competing risk model with death as a competing risk to determine estimates of aortic
reintervention rates. As one cannot definitively determine that those who died would not have
needed aortic reintervention, considering death as a competing risk is appropriate. However,
competing risk analyses of these type are a bit difficult to interpret in the context of the literature
as the vast majority of studies have not utilized this methodology.
Despite a more extensive aortic repair, those undergoing total arch replacement at the time of
extended ascending aorta replacement had markedly higher reintervention rates (2.6, 2.6, and
4.4% at 1, 2, and 3 years in the hemiarch group and 5.0, 10.3, and 11.9% in the total arch group).
13
After adjustment for age (the other strong predictor in the mortality model), those with a total
arch repair were 3.2 times as likely to need aortic reintervention as compared to the hemiarch
group (SHR 3.21, 95% CI 1.01 – 10.2, p=0.047). Age itself was not associated with the need for
aortic reintervention (SHR 0.90, 95% CI 0.65 – 1.23, p=0.50).
There are numerous limitations to this study. First, this study is subject to all the limitation of a
retrospective, non-protocoled study. Second, while presence of a total arch repair and age were
variables of significance, the lack of a factor as significant could be due to small sample size and
a type II error. Third, we lack power to examine different types of aortic arch repair. Fourth, the
lack of accurate anatomic data from preoperative and postoperative computed tomography
imaging makes assessment of these variables as it relates to mortality or need for aortic
reintervention impossible. Fifth, there is a potential third group of interest we did not include in
this study – those who had non-extended ascending aortic replacements with an aortic cross
clamp in place. Sixth, the difference in survival may be due to higher perioperative mortality in
the total arch group despite appropriately modeling to assess the continued adjusted risk over
time. Seventh, surgeon bias and preference largely dictated when to intervene on aortic arch in
extended ascending aortic replacement and type of aortic arch repair chosen – while one could
consider attempting to control for this with multilevel modeling, this is not widely embraced in
the surgical literature. Last, the limited number of endovascular interventions in this study make
any assessment of this technology in our practice difficult, although it is being increasingly
utilized.
14
The optimal approach to aortic arch repair in the setting of ascending aortic disease remains
controversial and continues to evolve. While some advocate for extensive replacement of the
aortic arch during extended replacement of the ascending aorta, others prefer a more tempered
approach absent true pathology. While this study cannot directly compare the two philosophical
approaches of aortic arch repair outlined above, as aortic arch repair was only performed in this
study when clinically indicated, if addressing all aortic pathology present at the time of operation
is adequate, we have might expect to see similar survival and reintervention rates between these
two groups. On the other hand, if more isolated pathology only requiring hemiarch replacement
of the aorta truly progresses, then one may see a higher reintervention and possibly mortality rate
in the less aggressively managed “hemiarch” group. The fact we found higher rates of mortality
and reintervention in the total arch group, when we only addressed the aortic arch when
pathology was present suggests that this group represents a group of patients with disease distinct
from those with isolated ascending aortic pathology and that those with arch pathology
inherently have more advanced disease which is likely to both decrease survival and increase the
need for further aortic reintervention. This effect was particularly prominent in those of advanced
age.
15
CONCLUSIONS
In conclusion, our data suggests that mortality and reintervention rates are higher with total arch
replacement in the setting of extended ascending aortic replacement, making the hemiarch
procedure the preferred procedure as long as it adequately addresses the aortic pathology,
especially in those of advanced age. The rationale for extending ascending aortic repair to
include a total arch replacement in order to decrease reintervention may not be valid.
16
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With Right Axillary Artery Cannulation and a Presewn Multibranched Graft. Ann Thorac Surg.
2011;92(3):889-897. doi:10.1016/j.athoracsur.2011.04.067.
19
23. Apostolakis E, Koletsis EN, Dedeilias P, et al. Antegrade Versus Retrograde Cerebral
Perfusion in Relation to Postoperative Complications Following Aortic Arch Surgery for Acute
Aortic Dissection Type A. J Card Surg. 2008;23(5):480-487. doi:10.1111/j.1540-
8191.2008.00587.x.
24. Rice RD, Sandhu HK, Leake SS, et al. Is Total Arch Replacement Associated With
Worse Outcomes During Repair of Acute Type A Aortic Dissection? Ann Thorac Surg.
2015;100(6):2159-2166. doi:10.1016/j.athoracsur.2015.06.007.
25. Crawford ES, KIRKLIN JW, Naftel DC, Svensson LG, Coselli JS, Safi HJ. Surgery for
acute dissection of ascending aorta. Should the arch be included? J Thorac Cardiovasc Surg.
1992;104(1):46-59.
20
TABLES
Table 1. Preoperative characteristics
a
Characteristic Overall Cohort
(n = 261)
Total Arch
(n = 112)
Hemia Arch
(n = 149)
p value
Age, years (Q25, Q75) 60.6 (52.7, 70.0) 63.1 (53.4, 70.2) 59.5 (52.6, 69) 0.428
BMI, kg/m
2
±SD 27.4 (24.4, 31.6) 27.3 (24, 29.8) 27.5 (24.4, 32.3) 0.258
Male, n (%) 181 (69.4) 68 (60.7) 113 (75.8) 0.009
Smoking History, n (%) 204 (78.2%) 93 (83.0%) 111 (74.5%) 0.098
Hypertension, n (%) 177 (67.8%) 66 (58.9%) 111 (74.5%) 0.008
Diabetes, n (%) 31 (11.9%) 8 (7.1%) 23 (15.4%) 0.040
Hyperlipidemia, n (%) 68 (26.1%) 25 (22.3%) 43 (28.9%) 0.234
Previous cardiac
surgery, n (%)
Preop chronic dialysis,
n (%)
10 (3.8%) 4 (3.6%) 6 (4.0%) 0.850
Peripheral artery
disease, n (%)
28 (10.7%) 7 (6.3%) 21 (14.1%) 0.043
Previous stroke, n (%) 20 (7.7%) 8 (7.1%) 12 (8.1%) 0.784
History of MI, n (%) 21 (8.1%) 3 (2.7%) 18 (12.1%) 0.006
Heart failure, n (%) 43 (16.5%) 17 (15.2%) 26 (17.5%) 0.624
Primary Indication
<0.0001
Type A Dissection, n
(%)
173 (66.3%) 60 (53.6%) 113 (75.8%)
Aneurysm, n (%) 72 (27.6%) 46 (41.1%) 26 (17.5%)
Other, n (%) 16 (6.1%) 6 (5.4%) 10 (6.7%)
a
Continuous variables are expressed as median and interquartile range; group differences
tested with two-sample Wilcoxon rank sum test. Categorical variables are expressed as
frequency (percent); group differences tested with Chi Square or Fisher’s exact test.;
Abbreviations: BMI - body mass index
21
Table 2. Operative Characteristics
a
Characteristic Total
(n = 261)
Total Arch
(n = 112)
Hemiarch
(n = 149)
p value
Reoperative sternotomy 81 (31.0) 40 (35.7) 41 (27.5) 0.157
Emergent/urgent
operation
205 (78.5) 76 (67.9) 129 (86.6) <0.0001
Proximal aortic repair
0.304
Isolated ascending 90 (34.5) 44 (39.3) 46 (30.9)
Aortic valve
replacement
96 (36.8) 42 (37.5) 54 (36.2)
Aortic root
replacement
68 (26.1) 23 (20.5) 45 (30.2)
Valve sparing root
replacement
7 (2.7) 3 (2.7) 4 (2.7)
Concomitant CABG 37 (14.2) 15 (13.4) 22 (14.8) 0.753
Femoral artery 26 (10.0%) 13 (11.6%) 13 (8.7%)
Deep hypothermic
circulatory arrest (Y/N)
50 (19.22%) 20 (17.9%) 30 (20.1%) 0.644
Operative times (min)
CPB time (min) 184 (145,
233)
213.5 (167,
282)
166 (140,
215)
<0.0001
Aortic Cross-clamp time
(min)
93.5 (67,
146)
110 (75,
170)
87 (61, 141) 0.0019
Antegrade cerebral
perfusion time (min)
23 (17, 32) 30 (22, 46) 19 (14.5, 27) <0.0001
Deep hypothermic
circulatory arrest (min)
11 (3, 19) 15.5 (6.5,
21.5)
9 (3, 15) 0.1088
Lowest core
temperature (C)
26 (24, 28.4) 25 (23, 27.3) 27 (24.8,
28.7)
0.001
Era of operation 0.018
2004 – 2012 82 (31.4%) 44 (39.3%) 38 (25.5%)
2013 – 2017 179 (68.6%) 68 (60.7%) 111 (74.5%)
a
Continuous variables are expressed as median and interquartile range; group differences
tested with two-sample Wilcoxon rank sum test. Categorical variables are expressed as
frequency (percent); group differences tested with Chi Square or Fisher’s exact test.
Abbreviations: CABG – Coronary artery bypass grafting
22
Table 3. Perioperative and Follow-up Outcomes
a
Outcome
Total
(n = 261)
Total Arch
(n = 112)
Hemiarch
(n = 149)
p value
Perioperative
In-hospital mortality 23 (8.8) 15 (13.4) 8 (5.4) 0.024
30-d mortality 23 (8.8) 16 (14.3) 7 (4.7) 0.018
Length of stay (days) 14.9 (7,17) 18.1 (8,
17.5)
11.7 (7, 17) 0.061
MCS Postoperatively 7 (2.7) 4 (3.6) 3 (2) 0.441
Stroke 11 (4.2) 6 (5.4) 5 (3.4) 0.426
Paraplegia 8 (3.1) 4 (3.6) 4 (2.7) 0.681
Open Chest 23 (8.8) 10 (8.9) 13 (8.7) 0.511
Reoperation for Bleeding 12 (4.6) 6 (5.4) 6 (4.0) 0.612
Vocal Cord Paralysis 29 (11.1) 23 (20.5) 6 (4.0) <0.0001
Pneumonia 18 (6.9) 7 (6.3) 11 (7.4) 0.721
Follow-up
Overall Mortality 61 (23.4) 36 (32.1) 25 (16.8) 0.004
Re-intervention Any 14 (5.4) 10 (8.9) 4 (2.7) 0.027
a
Continuous variables are expressed as median and interquartile range; group differences
tested with two-sample Wilcoxon rank sum test. Categorical variables are expressed as
frequency (percent); group differences tested with Chi Square or Fisher’s exact test.
23
Supplemental Table 1. Definition of Variables
Variable Definition
Preoperative characteristics
Male Male sex
Smoking history History of previous or current smoking
Hypertension Diagnosis of hypertension established before
admission with or without blood pressure
medications
Diabetes Diagnosis of diabetes mellitus established
before admission
Hyperlipidemia Diagnosis of hyperlipidemia established
before admission
Previous cardiac surgery History of any previous cardiac surgery
Preop chronic dialysis Patients maintained on chronic hemodialysis
due to end-stage renal disease before
admission
History of stroke History of a cerebrovascular accident
History of MI History of myocardial infarction
Heart failure History of heart failure
Operative characteristics
Reoperative sternotomy History of sternotomy before admission
Emergent/ urgent operation Aortic repair performed within 48 hours of
admission
Concomitant CABG Concomitant coronary artery bypass grafting
with conduit
Femoral artery Use of the femoral artery for arterial
cannulation for cardiopulmonary bypass
CPB time Cardiopulmonary bypass time
Perioperative and Follow up outcomes
Length of stay Length of hospital stay in days
MCS postoperatively Mechanical circulatory system required
postoperatively
Stroke Symptomatic cerebrovascular accident
Open chest Delayed sternal closure after aortic repair
24
Supplemental Table 2. Confidence intervals for time dependent figures
1 year
(95% CI)
3 year
(95% CI)
5 year
(95% CI)
Figure 1
Overall Cohort 83.6 (78.3-87.7) 76.2 (69.3 – 81.7) 68.2 (59.1 – 75.7)
Figure 2
Hemiarch Repair 89.0 (82.4 – 93.3) 81.3 (72.1 – 87.7) 73.5 (60.6 – 82.8)
Total Arch Repair 76.4 (67.1 – 83.5) 69.5 (58.3 – 78.2) 61.7 (48.3 – 72.6)
Figure 4
180 days
(95% CI)
365 days
(95% CI)
730 days
(95% CI)
Hemiarch Repair 0.017 (0.003 – 0.054 0.015 (0.007 – 0.069) -----
Total Arch Repair 0.028 (0.008 – 0.074) 0.050 (0.018 – 0.106) 0.103 (0.050 – 0.181)
25
Supplemental Table 3. Hazard ratios and 95% confidence intervals for all variables
consider for univariable and multivariable Cox proportional hazard model predictive of
overall mortality
1
Continuous variables are expressed as mean±SD; Categorical variables are expressed as
frequency.
2
P-values from Cox or competing risks regression are univariate.
*Abbreviations: CI – confidence interval, min – minutes
Univariable Analysis Multivariable Analysis
Variable Cox Proportional Hazard
Regression
2
Cox Proportional Hazard
Regression
2
HR (95% CI) p-value
1
HR (95% CI) p-value
2
Total Arch 1.9 (1.14 – 3.17) 0.014 2.53 (1.38 – 4.62) 0.003
Sex (male) 0.70 (0.42 – 1.18) 0.183 0.81 (0.45 – 1.45) 0.476
Age per 10 years 1.87 (1.48 – 2.36) <0.001 1.76 (1.37 – 2.28) <0.001
Antegrade Cerebral
Perfusion
0.67 (0.39 – 1.15) 0.146 0.69 (0.38 – 1.27) 0.227
BMI
Under/Normal REFERENCE
Overweight 0.75 (0.35 – 1.59) 0.457
Morbidly Obese 0.79 (0.41 – 1.54) 0.498
Reoperation 1.08 (0.64 – 1.8) 0.784
Emergent Operation 0.89 (0.50 – 1.56) 0.673
Concomitant CABG 2.72 (1.55 – 4.77) <0.0001 1.47 (0.71 – 3.03) 0.297
Hypertension 1.43 (0.81 – 2.53) 0.220 1.79 (0.89 – 3.61) 0.101
Hyperlipidemia 1.57 (0.93 – 2.66) 0.091 1.28 (0.62 – 2.24) 0.620
Diabetes 0.86 (0.39 – 1.89) 0.700
Chronic Lung Disease 1.60 (0.79 – 3.26) 0.194 0.75 (0.34 – 1.66) 0.478
Peripheral Arterial
Disease
2.36 (1.24 – 4.46) 0.008 1.75 (0.79 – 3.91) 0.170
Smoking History 1.17 (0.66 – 2.09) 0.587
Renal Failure 3.70 (1.47 – 9.28) 0.005 1.76 (0.62 – 5.07) 0.289
Preoperative CVA 0.86 (0.31 – 2.37) 0.767
Prior MI 1.91 (0.94 – 3.89) 0.074 2.26 (0.93 – 5.50) 0.072
Congestive Heart
Failure
1.40 (0.77 – 2.53) 0.272
Indication
Aneurysm REFERENCE
Dissection 0.48 (0.29 – 0.82) 0.006
Other 0.61 (0.21 – 1.74) 0.351
26
Supplemental Table 4. Sensitivity Analysis to Examine Influence of Indication
Preliminary Model
(with indication),
n=261
Final Model stratified
on Indication,
n=261
Preliminary Model
excluding “other
category” of
indication variable,
n=244
Preliminary Model
Dissection Only, n=172
Preliminary Model
Aneurysm Only, n=72
Variable
HR (95% CI) p HR (95% CI) p HR (95% CI) p HR (95% CI) p HR (95% CI) p
Total Arch 2.31 (1.28-
4.20
0.006 2.53 (1.38-
4.62)
0.003 2.94 (1.56-
5.58)
0.001 2.45 (1.09-
5.54)
0.031 3.11 (1.00-
9.63)
0.048
Age per 10
years
1.80 (1.40-
2.32)
<0.001 1.76 (1.37-
2.28)
<0.001 1.71 (1.31-
2.22)
<0.001 1.70 (1.16-
2.50)
0.007 1.91 (1.20-
3.02)
0.006
Sex (male) 0.86 (0.48-
1.53)
0.602 0.81 (0.45-
1.45)
0.476 0.66 (0.35-
1.24)
0.198 0.99 (0.37-
2.69)
0.985 0.48 (0.17-
1.36)
0.170
Antegrade
Cerebral
Perfusion
0.69 (0.38-
1.26)
0.232 0.69 (0.38-
1.26)
0.227 0.56 (0.31-
1.02)
0.059 0.74 (0.28-
1.98)
0.549 0.45 (0.17-
1.15)
0.095
Concomitant
CABG
1.40 (0.68-
2.90)
0.364 1.47 (0.71-
3.04)
0.297 1.80 (0.86-
3.80)
0.121 1.65 (0.59-
4.62)
0.339 1.88 (0.52-
6.76)
0.335
Hypertension 1.69 (0.84-
3.40)
0.139 1.79 (0.89-
3.61)
0.101 1.66 (0.81-
3.39)
0.164 1.25 (0.43-
3.66)
0.678 2.68 (0.86-
8.36)
0.090
Hyperlipidemia 1.15 (0.61-
2.19)
0.665 1.18 (0.62-
2.24)
0.620 1.27 (0.65-
2.48)
0.483 2.12 (0.89-
5.06)
0.089 0.61 (0.18-
2.11)
0.439
Chronic Lung
Disease
0.75 (0.34-
1.65)
0.479 0.75 (0.34-
1.66)
0.478 0.79 (0.34-
1.80)
0.572 1.18 (0.40-
3.50)
0.69 (0.17-
2.78)
0.603
Peripheral
Arterial
Disease
1.70 (0.76-
3.80)
0.194 1.75 (0.79-
3.92)
0.179 2.10 (0.88-
5.04)
0.095 1.99 (0.55-
7.23)
0.296 1.97 (0.48-
8.07)
0.344
Renal Failure 1.57 (0.55-
4.49)
0.404 1.77 (0.62-
5.07)
0.289 2.26 (0.75-
6.75)
0.145 0.71 (0.13-
3.75)
0.682 11.8 (2.01-
69.5)
0.006
Prior MI 0.36 (0.97-
5.75)
0.059 2.26 (0.93-
5.50)
0.289 1.42 (0.52-
3.85)
0.494 1.54 (0.45-
5.21)
0.492 0.64 (0.07-
5.94)
0.696
Indication
Aneurysm REF REF
Dissection 0.55 (0.39-
1.03)
0.060 0.68 (0.36-
1.27)
0.229
Other 0.50 (0.15-
1.42)
0.178 EXCLUDED
Model Fit: AIC 561.7 448.1 504.8
Model Fit: BIC 608.1 487.3 546.7
27
FIGURE LEGENDS
Figure 1. Graphical representation of surgical technique for hemiarch aortic replacement (A),
Carrel patch technique (B), and aortic arch debranching (C).
Figure 2. A) Kaplan-Meier survival estimate for overall survival for entire cohort of 261 patients
with 95% confidence intervals. B) Kaplan-Meier analysis of survival stratified by type of aortic
arch repair with 95% confidence intervals. Log-Rank comparison between strata 0.012.
Figure 3. Forest plot of variables associated with overall mortality after multiple variable
adjusted Cox-proportional hazard modeling (bars represent 95% confidence intervals).
Figure 4. Cox proportional hazard survival estimates for hypothetical 40, 50, 60, and 70-year-
old patient undergoing total arch and hemi arch replacement.
Figure 5. Non-parametric estimates of cumulative incidence of the probability of reoperation
with death as a competing outcome for presence (dashed line) or absence (solid line) of any
aortic reintervention. See Online Appendix Table 2 for confidence intervals.
28
FIGURES
Figure 1
A
B C
Carell Patch Technique
Hemiarch Technique
Aortic Arch Debranching
29
Figure 2
A
B
30
Figure 3
31
Figure 4
32
Figure 5
Abstract (if available)
Abstract
Objective: To compare outcomes of hemiarch versus total arch repair during extended ascending aortic replacement. ❧ Methods: Between 2004 and 2017, 261 patients underwent hemiarch (n=149, 57%) or total arch repair (aortic debranching or Carrell patch technique, n=112, 43%) in the setting of extended replacement of the ascending aorta. Median follow up was 17.2 (IQR 4.2–39.1) months. Multivariable models considering preoperative and intraoperative factors associated with mortality and aortic reintervention were constructed. ❧ Results: Survival was 89.0, 81.3, and 73.5% vs. 76.4, 69.5, and 61.7% at 1, 3, and 5 years in the hemiarch versus total arch groups, respectively (log-rank p=0.010). After adjustment for preoperative and intraoperative factors, the presence of a total arch repair (adjusted HR 2.53, 95% CI 1.39 – 4.62, p=0.003), and increasing age (adjusted HR per 10 years of age, 1.76, 95% CI 1.37 – 2.28, p<0.001) were associated with increased mortality. The cumulative incidence of aortic reintervention with death as a competing outcome was 2.6, 2.6, and 4.4% and 5.0, 10.3, and 11.9% in the hemiarch and total arch groups, respectively. After adjustment, the presence of a total arch repair was significantly associated with need for aortic reintervention (SHR 3.21, 95% CI 1.01 – 10.2, p=0.047). ❧ Conclusions: Overall survival after aortic arch repair in the setting of extended ascending aortic replacement is excellent, however, total arch repair and increasing age are associated with higher mortality and reintervention rates. A conservative approach to aortic arch repair can be prudent, especially in those of advanced age.
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Bowdish, Michael E.
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Core Title
Surgical aortic arch intervention at the time of extended ascending aortic replacement is associated with increased mortality
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Keck School of Medicine
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Master of Science
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Applied Biostatistics and Epidemiology
Publication Date
05/02/2019
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