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Abstract

OBJECTIVES

This study investigates the impact of bilateral antegrade cerebral perfusion (ACP) time on outcomes in aortic arch surgery.

METHODS

In total, 961 patients underwent either hemiarch (n = 385) or total arch replacement (n = 576) with bilateral ACP and moderate hypothermia management between 2006 and 2020 across 2 aortic centres. ACP time was categorized into 4 groups (≤30 min: n = 169, 30–60 min: n = 298, 60–90 min: n = 261, >90 min: n = 233). Inverse probability of treatment weighting yielded a well-balanced cohort among the 4 groups except for the cannulation site. Adjusted cubic spline and multivariable logistic analysis were performed, controlling for surgical procedure, cannulation site and cardiopulmonary bypass (CPB) time, to identify the relationship between ACP time and major in-hospital complications including mortality, stroke, acute renal failure and prolonged ventilation.

RESULTS

There remained a significant difference in surgical procedures and CPB time in the matched cohort. The incidences of mortality and stroke did not show significant trend (P = 0.052 and 0.717, respectively). Cubic spline curves showed that odds ratios did not increase linearly for any complications with increasing ACP time. Furthermore, ACP time, even exceeding 90 min, was not associated with complication rates [mortality: odds ratio = 1.459 (0.368–6.049), P = 0.595; stroke: 0.310 (0.058–1.635), P = 0.166; renal failure: 1.744 (0.521–6.094), P = 0.374; prolonged ventilation: 1.502 (0.535–4.286), P = 0.442], whereas CPB time was associated with mortality and prolonged ventilation.

CONCLUSIONS

Even when ACP time exceeded 90 min, it was not associated with major in-hospital complications, questioning its validity as a marker for surgical insult.

graphic
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Aortic arch repair, Bilateral antegrade cerebral perfusion, Brain protection, Total arch replacement, Hemiarch replacement, Cerebral protection

INTRODUCTION

Utilization of antegrade cerebral perfusion (ACP) has become increasingly more common compared to other cerebral protection strategies in aortic arch surgery [1]. ACP time is frequently analysed for its association with surgical outcomes, particularly mortality and stroke [2–7]. In several studies, bilateral ACP has been shown to be superior to unilateral ACP in patients needing prolonged ACP time (>30–50 min), such as in complex aortic dissection repair [2–5], and has been endorsed by current guidelines [8]. Further studies have indicated that ACP time with circulatory arrest up to 80–90 min did not significantly increase the risk of mortality or stroke [6, 7]. However, due to recent advancements in surgical techniques, such as the frozen elephant trunk (FET) procedure, it is not uncommon to encounter cases where ACP time exceeds 90 min in arch surgery [8, 9]. In such cases, according to the current guidelines, bilateral ACP may be indicated. Nevertheless, the impact of prolonged bilateral ACP time exceeding 90 min on major organ systems has not been sufficiently elucidated. We hypothesized that there is no association between prolonged ACP time and postoperative major complications in aortic arch surgery. Therefore, we examined the impact of prolonged bilateral ACP time on in-hospital outcome during aortic arch surgery.

PATIENTS AND METHODS

This study was approved by the Institutional Review Boards of Columbia University Irving Medical Center and the University of Bologna with the waiver of consent (Columbia; number AAAU0575; most recent approval date 4 April 2022; Bologna, 121/2022/Disp/AUOBo).

Study design and patient selection

This study was a multi-centre retrospective analysis, including all patients who underwent aortic arch surgery at our 2 centres between January 2006 and July 2020. Inclusion criteria for this retrospective, multi-centre study were patients who underwent hemiarch or total arch replacement (TAR) with bilateral ACP and moderate hypothermia management with an intraoperative lowest temperature between 21.1°C and 28.0°C [10]. Exclusion criteria were usage of other cerebral perfusion strategies, including isolated use of retrograde cerebral perfusion, unilateral ACP and circulatory arrest. To mitigate possible confounding from temperature management, cases with lowest temperature below 21°C or above 28°C were also excluded. Additionally, patients with missing exposure variables were excluded from the study (Fig. 1). Baseline characteristics, operative details and in-hospital postoperative complications were collected through the electronic medical record of both institutions. Definitions of the postoperative complications followed those of the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database. The distribution of ACP time is shown in Supplementary Material, Fig. S1. ACP time ranged from 4 to 314 min [median; 63 min (interquartile range; 36–89)]. Previous studies have indicated that ACP time with circulatory arrest up to 80–90 min did not significantly increase the risk of mortality or stroke [6, 7]. Therefore, to focus on cases with ACP time exceeding 90 min and to minimize differences in sample size across the groups, we divided the data into 4 groups as shown below: ACP≤30 min, 30<ACP ≤ 60 min, 60<ACP ≤ 90 min and ACP>90 min. The primary end-points included major postoperative complications: in-hospital mortality, stroke, acute renal failure and prolonged ventilation. Additionally, a subgroup analysis was performed to evaluate the association between ACP time and major postoperative complications in patients without acute aortic dissection.

Consort diagram of patients undergoing aortic arch replacement with bilateral antegrade cerebral perfusion.
Figure 1:

Consort diagram of patients undergoing aortic arch replacement with bilateral antegrade cerebral perfusion.

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Aortic arch procedure

Surgical indications generally followed guidelines at the time [11, 12]. All aneurysmal segments larger than 4.5 cm were typically replaced at the index procedure, or when not reachable, at subsequent aortic interventions. The details of aortic arch procedures at each institution have been previously described [13–16]. The choice of arterial cannulation sites and degree of induced hypothermia depended on the complexity and extent of arch replacement and surgeon preference [13]. Upon cessation of systemic perfusion, the bilateral cerebral perfusion was established either with axillary or direct innominate artery cannulation in combination with left carotid artery cannulation. The left subclavian artery was not routinely perfused. Near-infrared spectroscopy was utilized for the monitoring of regional oxygen saturation in the frontal lobes, and nasopharyngeal temperature was measured during surgery. Distal systemic perfusion was temporarily halted until the distal aortic anastomosis was completed. After the distal anastomosis was completed, systematic perfusion was resumed immediately from the side branch of the graft. For TAR, the supra-aortic vessels were individually reconstructed using a multi-branch graft. The sequence of distal and supra-aortic reconstruction was determined by the extent of arch replacement and surgeon preference. If the left subclavian artery was deep, distal anastomosis was proximalized into zone 2 [16]. The indication for FET was determined by taking several factors into consideration such as extent of aneurysm to be resected, location of primary tear, distal malperfusion and surgeon preference.

Statistical analysis

Continuous variables were expressed as mean (standard deviation) or median (interquartile range) depending on normality, which was tested via the Shapiro–Wilk test, and were compared using Kruskal–Wallis test because none of the continuous variables follow a normal distribution. Categorical variables were expressed as counts and percentages and were compared using χ2 test or Fisher’s exact test when appropriate. Furthermore, linear-by-linear test was performed to examine the trend between ACP time and incidences of in-hospital mortality, stroke, renal failure and prolonged ventilation. Propensity score-based matching weight method, which is an extension of inverse probability of treatment weighting (IPTW) technique, was used to construct balanced 4 groups of patients categorized by ACP time [17]. Covariates included in the multinomial logistic regression model to generate propensity score consisted of baseline characteristics including age, sex, diabetes, chronic kidney disease, hypertension, cerebrovascular disease, connective disorder disease, previous cardiac surgery, left ventricular ejection fraction (LVEF), aneurysm, acute aortic dissection, elective status, cardiogenic shock, concomitant procedures such as coronary artery bypass grafting, aortic root surgery, aortic valve surgery and mitral surgery, surgical era, lowest temperature and cannulation site. Standardized mean differences (SMD) of 6 pairwise comparisons were calculated to assess the balance between the 4 groups after applying the IPTW technique. The averages of SMD values for variables used in the matching algorithms were all under 0.1, indicating balance among groups. The Bonferroni post-hoc multiple comparisons were performed, with a P-value of 0.083 as the significance cut-off. Multivariable logistic regression analysis using the weighted sample was performed to determine the association between ACP and postoperative major complications, with cannulation site, surgical procedure and cardiopulmonary bypass (CPB) time controlled for. Variables entered into the models followed 2 criteria: (i) SMD>0.1 for variables used as covariates for IPTW or (ii) a P-value remaining significant in matched cohorts for other variables. CPB-related factors, such as CPB time, cross-clamp time and lower body ischaemia time, were considered for collinearity, with only ACP and CPB time being included. Variance inflation factor (VIF) was assessed to prevent multicollinearity (all VIF < 3). Cubic spline interpolation with 4 knots as appropriate was used to clarify the possible non-linear association between ACP time and end-point outcomes with TAR, CPB time, lowest temperature, cannulation site and surgical era controlled for. A P-value of 0.05 was deemed significant for all analyses, except for multiple pairwise comparisons. All statistical analyses were performed using R version 4.3.0 (R Foundation for Statistical Computing, Vienna, Austria) and JMP® software (version 13.2.0; SAS Institute, Cary, NC, USA).

RESULTS

Patient characteristics and operative details: all patients

A total of 961 patients were included in the study (ACP time ≤30 min: n = 169, 30–60 min: n = 298, 60–90 min: n = 261, >90 min: n = 233) (Fig. 1). Baseline and operative characteristics for all patients are listed in Supplementary Material, Tables S1 and S2. Procedure indication was acute type A aortic dissection in 323 patients (33.6%), and malperfusion in the coronary, brain, renal, intestinal or extremity was rare. TAR was performed in 576 patients (59.9%), and more underwent ACP time > 90 min.

In-hospital postoperative complications: all patients

In-hospital mortality was lowest for ACP time ≤ 30 min (7.1%) and highest for ACP > 90 min (13.3%), but there was no significant trend (P = 0.688). The incidence of stroke was 7.3% (P = 0.417). The incidence of acute renal failure was highest for ACP > 90 min, while that of prolonged ventilation was highest for ACP time between 30 and 60 min. However, neither showed a significant trend (P = 0.821 and 0.420, respectively) (Supplementary Material, Table S3).

In-hospital complications in IPTW-adjusted groups

IPTW created well-balanced groups with SMD < 0.10 except for cannulation site (Tables 1 and 2). There remained a significant difference in the type of aortic arch surgery and variables related to CPB (Table 2). In-hospital mortality was lowest for ACP time ≤ 30 min (9.1%) and highest for ACP > 90 min (19.7%). The incidences of in-hospital mortality and stroke did not show a significant trend (P = 0.052 and 0.717, respectively), whereas the incidences of acute renal failure and prolonged ventilation showed a significant trend among the 4 groups (P = 0.001 and 0.011, respectively) (Table 3). In multivariable logistic regression, when analysed with ACP time of ≤30 min used as the reference, ACP time is not associated with any of these complications, even when exceeding 90 min [mortality, odds ratio—OR = 1.459 (0.368–6.049), P = 0.595; stroke, OR = 0.310 (0.058–1.635), P = 0.166; renal failure, OR = 1.744 (0.521–6.094), P = 0.374; prolonged ventilation, OR = 1.502 (0.535–4.286), P = 0.442], whereas CPB time was associated with mortality and prolonged ventilation (Table 4). Furthermore, adjusted cubic spline curves showed that ORs do not increase linearly for any complication with increasing ACP time (Fig. 2).

Adjusted restricted cubic spline curves with 95% confidence intervals for odd ratios of major complications with antegrade cerebral perfusion time: (A) in-hospital mortality; (B) stroke; (C) acute renal failure and (D) prolonged ventilation.
Figure 2:

Adjusted restricted cubic spline curves with 95% confidence intervals for odd ratios of major complications with antegrade cerebral perfusion time: (A) in-hospital mortality; (B) stroke; (C) acute renal failure and (D) prolonged ventilation.

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Table 1:
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Baseline characteristics in IPTW-adjusted groups

ACP ≤ 30 min
(n = 84.7)		30 < ACP ≤ 60 min
(n = 86.6)		60 < ACP ≤ 90 min
(n = 86.2)		ACP > 90 min
(n = 81.8)		P-valueSMD
Age63.86 (54.08, 73.00)65.0 (56.6,71.4)65.7 (55.8,71.4)65.6 (54.4,73.0)0.9310.043
Female27.2 (32.1)24.9 (28.7)24.8 (28.8)24.0 (29.4)0.9080.039
Diabetes5.5 (6.5)7.6 (8.8)6.4 (7.5)6.2 (7.5)0.9250.043
Hypertension58.6 (69.1)61.1 (70.6)60.9 (70.6)60.8 (74.3)0.8080.058
CKD5.0 (5.9)5.6 (6.4)4.4 (5.1)4.1 (5.1)0.9420.035
CVD8.0 (9.4)7.3 (8.5)7.8 (9.0)6.7 (8.2)0.9860.024
Connective tissue disorder2.0 (2.4)1.8 (2.1)2.9 (3.3)1.7 (2.1)0.8420.042
Previous cardiac surgery23.8 (28.0)24.1 (27.9)27.7 (32.1)21.4 (26.2)0.7170.065
LVEF58.00 (55.00, 61.00)60.0 (55.0,62.0)59.8 (55.0,63.0)60.0 (55.0,63.0)0.9100.037
Elective status41.4 (48.9)49.7 (57.3)47.4 (56.1)42.8 (52.4)0.4710.097
Cardiogenic shock2.3 (2.8)2.3 (2.7)1.8 (2.1)3.1 (3.8)0.8450.051
Concomitant surgery50.2 (59.2)49.3 (57.0)50.9 (59.0)44.4 (54.2)0.8120.057
Aneurysm44.9 (53.0)45.7 (52.8)50.1 (58.1)43.0 (52.6)0.7480.056
Acute aortic dissection34.5 (40.7)31.2 (36.0)30.4 (35.3)30.1 (36.8)0.7730.059
Surgical era0.9730.067
 2006–201017.5 (20.7)17.3 (20.0)19.8 (22.9)15.9 (19.4)
 2011–201530.7 (36.3)33.6 (38.8)29.0 (33.7)31.2 (38.2)
 2016–202036.5 (43.1)35.7 (41.2)37.4 (43.4)34.7 (42.4)
ACP ≤ 30 min
(n = 84.7)		30 < ACP ≤ 60 min
(n = 86.6)		60 < ACP ≤ 90 min
(n = 86.2)		ACP > 90 min
(n = 81.8)		P-valueSMD
Age63.86 (54.08, 73.00)65.0 (56.6,71.4)65.7 (55.8,71.4)65.6 (54.4,73.0)0.9310.043
Female27.2 (32.1)24.9 (28.7)24.8 (28.8)24.0 (29.4)0.9080.039
Diabetes5.5 (6.5)7.6 (8.8)6.4 (7.5)6.2 (7.5)0.9250.043
Hypertension58.6 (69.1)61.1 (70.6)60.9 (70.6)60.8 (74.3)0.8080.058
CKD5.0 (5.9)5.6 (6.4)4.4 (5.1)4.1 (5.1)0.9420.035
CVD8.0 (9.4)7.3 (8.5)7.8 (9.0)6.7 (8.2)0.9860.024
Connective tissue disorder2.0 (2.4)1.8 (2.1)2.9 (3.3)1.7 (2.1)0.8420.042
Previous cardiac surgery23.8 (28.0)24.1 (27.9)27.7 (32.1)21.4 (26.2)0.7170.065
LVEF58.00 (55.00, 61.00)60.0 (55.0,62.0)59.8 (55.0,63.0)60.0 (55.0,63.0)0.9100.037
Elective status41.4 (48.9)49.7 (57.3)47.4 (56.1)42.8 (52.4)0.4710.097
Cardiogenic shock2.3 (2.8)2.3 (2.7)1.8 (2.1)3.1 (3.8)0.8450.051
Concomitant surgery50.2 (59.2)49.3 (57.0)50.9 (59.0)44.4 (54.2)0.8120.057
Aneurysm44.9 (53.0)45.7 (52.8)50.1 (58.1)43.0 (52.6)0.7480.056
Acute aortic dissection34.5 (40.7)31.2 (36.0)30.4 (35.3)30.1 (36.8)0.7730.059
Surgical era0.9730.067
 2006–201017.5 (20.7)17.3 (20.0)19.8 (22.9)15.9 (19.4)
 2011–201530.7 (36.3)33.6 (38.8)29.0 (33.7)31.2 (38.2)
 2016–202036.5 (43.1)35.7 (41.2)37.4 (43.4)34.7 (42.4)

ACP: antegrade cerebral perfusion; CKD: chronic kidney disease; CVD: cerebrovascular disease; LVEF: left ventricular ejection fraction; SMD: standardized mean differences.

Table 1:
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Baseline characteristics in IPTW-adjusted groups

ACP ≤ 30 min
(n = 84.7)		30 < ACP ≤ 60 min
(n = 86.6)		60 < ACP ≤ 90 min
(n = 86.2)		ACP > 90 min
(n = 81.8)		P-valueSMD
Age63.86 (54.08, 73.00)65.0 (56.6,71.4)65.7 (55.8,71.4)65.6 (54.4,73.0)0.9310.043
Female27.2 (32.1)24.9 (28.7)24.8 (28.8)24.0 (29.4)0.9080.039
Diabetes5.5 (6.5)7.6 (8.8)6.4 (7.5)6.2 (7.5)0.9250.043
Hypertension58.6 (69.1)61.1 (70.6)60.9 (70.6)60.8 (74.3)0.8080.058
CKD5.0 (5.9)5.6 (6.4)4.4 (5.1)4.1 (5.1)0.9420.035
CVD8.0 (9.4)7.3 (8.5)7.8 (9.0)6.7 (8.2)0.9860.024
Connective tissue disorder2.0 (2.4)1.8 (2.1)2.9 (3.3)1.7 (2.1)0.8420.042
Previous cardiac surgery23.8 (28.0)24.1 (27.9)27.7 (32.1)21.4 (26.2)0.7170.065
LVEF58.00 (55.00, 61.00)60.0 (55.0,62.0)59.8 (55.0,63.0)60.0 (55.0,63.0)0.9100.037
Elective status41.4 (48.9)49.7 (57.3)47.4 (56.1)42.8 (52.4)0.4710.097
Cardiogenic shock2.3 (2.8)2.3 (2.7)1.8 (2.1)3.1 (3.8)0.8450.051
Concomitant surgery50.2 (59.2)49.3 (57.0)50.9 (59.0)44.4 (54.2)0.8120.057
Aneurysm44.9 (53.0)45.7 (52.8)50.1 (58.1)43.0 (52.6)0.7480.056
Acute aortic dissection34.5 (40.7)31.2 (36.0)30.4 (35.3)30.1 (36.8)0.7730.059
Surgical era0.9730.067
 2006–201017.5 (20.7)17.3 (20.0)19.8 (22.9)15.9 (19.4)
 2011–201530.7 (36.3)33.6 (38.8)29.0 (33.7)31.2 (38.2)
 2016–202036.5 (43.1)35.7 (41.2)37.4 (43.4)34.7 (42.4)
ACP ≤ 30 min
(n = 84.7)		30 < ACP ≤ 60 min
(n = 86.6)		60 < ACP ≤ 90 min
(n = 86.2)		ACP > 90 min
(n = 81.8)		P-valueSMD
Age63.86 (54.08, 73.00)65.0 (56.6,71.4)65.7 (55.8,71.4)65.6 (54.4,73.0)0.9310.043
Female27.2 (32.1)24.9 (28.7)24.8 (28.8)24.0 (29.4)0.9080.039
Diabetes5.5 (6.5)7.6 (8.8)6.4 (7.5)6.2 (7.5)0.9250.043
Hypertension58.6 (69.1)61.1 (70.6)60.9 (70.6)60.8 (74.3)0.8080.058
CKD5.0 (5.9)5.6 (6.4)4.4 (5.1)4.1 (5.1)0.9420.035
CVD8.0 (9.4)7.3 (8.5)7.8 (9.0)6.7 (8.2)0.9860.024
Connective tissue disorder2.0 (2.4)1.8 (2.1)2.9 (3.3)1.7 (2.1)0.8420.042
Previous cardiac surgery23.8 (28.0)24.1 (27.9)27.7 (32.1)21.4 (26.2)0.7170.065
LVEF58.00 (55.00, 61.00)60.0 (55.0,62.0)59.8 (55.0,63.0)60.0 (55.0,63.0)0.9100.037
Elective status41.4 (48.9)49.7 (57.3)47.4 (56.1)42.8 (52.4)0.4710.097
Cardiogenic shock2.3 (2.8)2.3 (2.7)1.8 (2.1)3.1 (3.8)0.8450.051
Concomitant surgery50.2 (59.2)49.3 (57.0)50.9 (59.0)44.4 (54.2)0.8120.057
Aneurysm44.9 (53.0)45.7 (52.8)50.1 (58.1)43.0 (52.6)0.7480.056
Acute aortic dissection34.5 (40.7)31.2 (36.0)30.4 (35.3)30.1 (36.8)0.7730.059
Surgical era0.9730.067
 2006–201017.5 (20.7)17.3 (20.0)19.8 (22.9)15.9 (19.4)
 2011–201530.7 (36.3)33.6 (38.8)29.0 (33.7)31.2 (38.2)
 2016–202036.5 (43.1)35.7 (41.2)37.4 (43.4)34.7 (42.4)

ACP: antegrade cerebral perfusion; CKD: chronic kidney disease; CVD: cerebrovascular disease; LVEF: left ventricular ejection fraction; SMD: standardized mean differences.

Table 2:
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Aortic pathology and surgical management detail in IPTW-adjusted groups

ACP ≤30 min
(n = 84.7)		30 < ACP ≤ 60 min
(n = 86.6)		60 < ACP ≤ 90 min
(n = 86.2)		ACP > 90 min
(n = 81.8)		P-valueSMD
Aortic pathology
Aortic aneurysm44.9 (53.0)45.7 (52.8)50.1 (58.1)43.0 (52.6)0.7480.056
Acute aortic dissection34.5 (40.7)31.2 (36.0)30.4 (35.3)30.1 (36.8)0.7730.059
 Type A AAD34.5 (40.7)29.7 (34.3)27.4 (31.7)25.2 (30.8)0.2900.114
 Type B AAD0.0 (0.0)c,d1.4 (1.7)3.1 (3.6)4.9 (6.0)0.0130.213
 Other5.3 (6.3)9.7 (11.2)5.7 (6.7)8.7 (10.6)0.3060.112
Malperfusion
 Coronary0.6 (0.8)0.4 (0.5)0.7 (0.8)0.0 (0.0)0.7180.069
 Brain3.6 (4.2)a1.7 (2.0)0.4 (0.5)1.8 (2.2)0.1240.131
 Renal0.7 (0.8)0.0 (0.0)0.0 (0.0)0.1 (0.1)0.2640.076
 Intestine0.7 (0.8)0.0 (0.0)0.1 (0.1)0.0 (0.0)0.2830.075
 Extremity2.4 (2.8)2.1 (2.5)4.3 (5.0)3.5 (4.3)0.6220.081
Lowest temperature25.0 (24.0,26.0)25.0 (25.0,26.0)25.0 (25.0,26.0)25.0 (25.0,26.0)0.4410.095
Cannulation site0.8950.134
 Aorta22.2 (26.2)21.8 (25.1)19.9 (23.1)17.1 (20.9)
 Axillary19.2 (22.6)22.6 (26.1)24.1 (28.0)22.5 (27.5)
 Femoral21.8 (25.8)20.9 (24.1)19.8 (23.0)24.6 (30.1)
Brachiocephalic/Carotid21.5 (25.4)21.3 (24.6)22.4 (25.9)17.6 (21.5)
Concomitant surgery50.2 (59.2)49.3 (57.0)50.9 (59.0)44.4 (54.2)0.8120.057
 CABG9.8 (11.6)7.3 (8.4)11.4 (13.2)9.9 (12.1)0.6440.080
 MV surgery1.3 (1.5)2.0 (2.3)2.1 (2.5)1.3 (1.6)0.9230.043
 AV surgery14.9 (17.6)10.8 (12.5)d17.3 (20.1)14.1 (17.3)0.3770.104
 Bentall28.9 (34.1)34.7 (40.1)27.7 (32.1)23.8 (29.1)0.2710.123
Aortic surgery
 Hemiarch76.9 (90.8)a,b,c45.5 (52.6)d,e6.7 (7.8)f1.4 (1.7)<0.001
 TAR7.8 (9.2)a,b,c41.0 (47.4)d,e79.5 (92.2)f80.4 (98.3)<0.001
 Frozen elephant trunk2.0 (2.4)a,b,c14.1 (16.3)d,e37.4 (43.4)42.7 (52.2)<0.001
Cardiopulmonary bypass
 ACP time24.0 (19.0,27.0)a,b,c45.0 (36.0,52.0)d,e75.0 (67.0,82.0)f111.0 (98.0,132.0)<0.001
 CPB time172.0 (138.0,217.4)a,b,c194.0 (162.0,225.7)d,e215.0 (180.0,265.3)f231.0 (195.0,279.0)<0.001
 Cross-clamp time112.2 (70.2,156.3)a,b,c124.0 (98.0,161.0)d,e141.0 (104.0,191.0)144.0 (109.7,199.2)<0.001
 LBI time27.0 (22.0,31.0)a,b,c40.0 (34.0,49.0)d,e46.0 (38.0,61.6)f52.0 (41.0,75.0)<0.001
ACP ≤30 min
(n = 84.7)		30 < ACP ≤ 60 min
(n = 86.6)		60 < ACP ≤ 90 min
(n = 86.2)		ACP > 90 min
(n = 81.8)		P-valueSMD
Aortic pathology
Aortic aneurysm44.9 (53.0)45.7 (52.8)50.1 (58.1)43.0 (52.6)0.7480.056
Acute aortic dissection34.5 (40.7)31.2 (36.0)30.4 (35.3)30.1 (36.8)0.7730.059
 Type A AAD34.5 (40.7)29.7 (34.3)27.4 (31.7)25.2 (30.8)0.2900.114
 Type B AAD0.0 (0.0)c,d1.4 (1.7)3.1 (3.6)4.9 (6.0)0.0130.213
 Other5.3 (6.3)9.7 (11.2)5.7 (6.7)8.7 (10.6)0.3060.112
Malperfusion
 Coronary0.6 (0.8)0.4 (0.5)0.7 (0.8)0.0 (0.0)0.7180.069
 Brain3.6 (4.2)a1.7 (2.0)0.4 (0.5)1.8 (2.2)0.1240.131
 Renal0.7 (0.8)0.0 (0.0)0.0 (0.0)0.1 (0.1)0.2640.076
 Intestine0.7 (0.8)0.0 (0.0)0.1 (0.1)0.0 (0.0)0.2830.075
 Extremity2.4 (2.8)2.1 (2.5)4.3 (5.0)3.5 (4.3)0.6220.081
Lowest temperature25.0 (24.0,26.0)25.0 (25.0,26.0)25.0 (25.0,26.0)25.0 (25.0,26.0)0.4410.095
Cannulation site0.8950.134
 Aorta22.2 (26.2)21.8 (25.1)19.9 (23.1)17.1 (20.9)
 Axillary19.2 (22.6)22.6 (26.1)24.1 (28.0)22.5 (27.5)
 Femoral21.8 (25.8)20.9 (24.1)19.8 (23.0)24.6 (30.1)
Brachiocephalic/Carotid21.5 (25.4)21.3 (24.6)22.4 (25.9)17.6 (21.5)
Concomitant surgery50.2 (59.2)49.3 (57.0)50.9 (59.0)44.4 (54.2)0.8120.057
 CABG9.8 (11.6)7.3 (8.4)11.4 (13.2)9.9 (12.1)0.6440.080
 MV surgery1.3 (1.5)2.0 (2.3)2.1 (2.5)1.3 (1.6)0.9230.043
 AV surgery14.9 (17.6)10.8 (12.5)d17.3 (20.1)14.1 (17.3)0.3770.104
 Bentall28.9 (34.1)34.7 (40.1)27.7 (32.1)23.8 (29.1)0.2710.123
Aortic surgery
 Hemiarch76.9 (90.8)a,b,c45.5 (52.6)d,e6.7 (7.8)f1.4 (1.7)<0.001
 TAR7.8 (9.2)a,b,c41.0 (47.4)d,e79.5 (92.2)f80.4 (98.3)<0.001
 Frozen elephant trunk2.0 (2.4)a,b,c14.1 (16.3)d,e37.4 (43.4)42.7 (52.2)<0.001
Cardiopulmonary bypass
 ACP time24.0 (19.0,27.0)a,b,c45.0 (36.0,52.0)d,e75.0 (67.0,82.0)f111.0 (98.0,132.0)<0.001
 CPB time172.0 (138.0,217.4)a,b,c194.0 (162.0,225.7)d,e215.0 (180.0,265.3)f231.0 (195.0,279.0)<0.001
 Cross-clamp time112.2 (70.2,156.3)a,b,c124.0 (98.0,161.0)d,e141.0 (104.0,191.0)144.0 (109.7,199.2)<0.001
 LBI time27.0 (22.0,31.0)a,b,c40.0 (34.0,49.0)d,e46.0 (38.0,61.6)f52.0 (41.0,75.0)<0.001

AAD: acute aortic dissection; ACP: antegrade cerebral perfusion; AV: aortic valve; CABG: coronary artery bypass grafting; CPB: cardiopulmonary bypass; LBI: lower body ischaemia; MV: mitral valve; SMD: standardized mean differences; TAR: total arch replacement.

Alphabets indicate P < 0.05 in following comparisons in post-hoc 2-way comparison with Bonferroni correction: a, ACP ≤ 30 min versus 30<ACP ≤ 60; b, ACP ≤ 30 versus 60<ACP ≤ 90; c, ACP ≤ 30 versus ACP > 90; d, 30<ACP ≤ 60 versus 60<ACP ≤ 90; e, 30<ACP ≤ 60 versus ACP > 90; f, 60<ACP ≤ 90 versus ACP > 90.

Table 2:
Open in new tab

Aortic pathology and surgical management detail in IPTW-adjusted groups

ACP ≤30 min
(n = 84.7)		30 < ACP ≤ 60 min
(n = 86.6)		60 < ACP ≤ 90 min
(n = 86.2)		ACP > 90 min
(n = 81.8)		P-valueSMD
Aortic pathology
Aortic aneurysm44.9 (53.0)45.7 (52.8)50.1 (58.1)43.0 (52.6)0.7480.056
Acute aortic dissection34.5 (40.7)31.2 (36.0)30.4 (35.3)30.1 (36.8)0.7730.059
 Type A AAD34.5 (40.7)29.7 (34.3)27.4 (31.7)25.2 (30.8)0.2900.114
 Type B AAD0.0 (0.0)c,d1.4 (1.7)3.1 (3.6)4.9 (6.0)0.0130.213
 Other5.3 (6.3)9.7 (11.2)5.7 (6.7)8.7 (10.6)0.3060.112
Malperfusion
 Coronary0.6 (0.8)0.4 (0.5)0.7 (0.8)0.0 (0.0)0.7180.069
 Brain3.6 (4.2)a1.7 (2.0)0.4 (0.5)1.8 (2.2)0.1240.131
 Renal0.7 (0.8)0.0 (0.0)0.0 (0.0)0.1 (0.1)0.2640.076
 Intestine0.7 (0.8)0.0 (0.0)0.1 (0.1)0.0 (0.0)0.2830.075
 Extremity2.4 (2.8)2.1 (2.5)4.3 (5.0)3.5 (4.3)0.6220.081
Lowest temperature25.0 (24.0,26.0)25.0 (25.0,26.0)25.0 (25.0,26.0)25.0 (25.0,26.0)0.4410.095
Cannulation site0.8950.134
 Aorta22.2 (26.2)21.8 (25.1)19.9 (23.1)17.1 (20.9)
 Axillary19.2 (22.6)22.6 (26.1)24.1 (28.0)22.5 (27.5)
 Femoral21.8 (25.8)20.9 (24.1)19.8 (23.0)24.6 (30.1)
Brachiocephalic/Carotid21.5 (25.4)21.3 (24.6)22.4 (25.9)17.6 (21.5)
Concomitant surgery50.2 (59.2)49.3 (57.0)50.9 (59.0)44.4 (54.2)0.8120.057
 CABG9.8 (11.6)7.3 (8.4)11.4 (13.2)9.9 (12.1)0.6440.080
 MV surgery1.3 (1.5)2.0 (2.3)2.1 (2.5)1.3 (1.6)0.9230.043
 AV surgery14.9 (17.6)10.8 (12.5)d17.3 (20.1)14.1 (17.3)0.3770.104
 Bentall28.9 (34.1)34.7 (40.1)27.7 (32.1)23.8 (29.1)0.2710.123
Aortic surgery
 Hemiarch76.9 (90.8)a,b,c45.5 (52.6)d,e6.7 (7.8)f1.4 (1.7)<0.001
 TAR7.8 (9.2)a,b,c41.0 (47.4)d,e79.5 (92.2)f80.4 (98.3)<0.001
 Frozen elephant trunk2.0 (2.4)a,b,c14.1 (16.3)d,e37.4 (43.4)42.7 (52.2)<0.001
Cardiopulmonary bypass
 ACP time24.0 (19.0,27.0)a,b,c45.0 (36.0,52.0)d,e75.0 (67.0,82.0)f111.0 (98.0,132.0)<0.001
 CPB time172.0 (138.0,217.4)a,b,c194.0 (162.0,225.7)d,e215.0 (180.0,265.3)f231.0 (195.0,279.0)<0.001
 Cross-clamp time112.2 (70.2,156.3)a,b,c124.0 (98.0,161.0)d,e141.0 (104.0,191.0)144.0 (109.7,199.2)<0.001
 LBI time27.0 (22.0,31.0)a,b,c40.0 (34.0,49.0)d,e46.0 (38.0,61.6)f52.0 (41.0,75.0)<0.001
ACP ≤30 min
(n = 84.7)		30 < ACP ≤ 60 min
(n = 86.6)		60 < ACP ≤ 90 min
(n = 86.2)		ACP > 90 min
(n = 81.8)		P-valueSMD
Aortic pathology
Aortic aneurysm44.9 (53.0)45.7 (52.8)50.1 (58.1)43.0 (52.6)0.7480.056
Acute aortic dissection34.5 (40.7)31.2 (36.0)30.4 (35.3)30.1 (36.8)0.7730.059
 Type A AAD34.5 (40.7)29.7 (34.3)27.4 (31.7)25.2 (30.8)0.2900.114
 Type B AAD0.0 (0.0)c,d1.4 (1.7)3.1 (3.6)4.9 (6.0)0.0130.213
 Other5.3 (6.3)9.7 (11.2)5.7 (6.7)8.7 (10.6)0.3060.112
Malperfusion
 Coronary0.6 (0.8)0.4 (0.5)0.7 (0.8)0.0 (0.0)0.7180.069
 Brain3.6 (4.2)a1.7 (2.0)0.4 (0.5)1.8 (2.2)0.1240.131
 Renal0.7 (0.8)0.0 (0.0)0.0 (0.0)0.1 (0.1)0.2640.076
 Intestine0.7 (0.8)0.0 (0.0)0.1 (0.1)0.0 (0.0)0.2830.075
 Extremity2.4 (2.8)2.1 (2.5)4.3 (5.0)3.5 (4.3)0.6220.081
Lowest temperature25.0 (24.0,26.0)25.0 (25.0,26.0)25.0 (25.0,26.0)25.0 (25.0,26.0)0.4410.095
Cannulation site0.8950.134
 Aorta22.2 (26.2)21.8 (25.1)19.9 (23.1)17.1 (20.9)
 Axillary19.2 (22.6)22.6 (26.1)24.1 (28.0)22.5 (27.5)
 Femoral21.8 (25.8)20.9 (24.1)19.8 (23.0)24.6 (30.1)
Brachiocephalic/Carotid21.5 (25.4)21.3 (24.6)22.4 (25.9)17.6 (21.5)
Concomitant surgery50.2 (59.2)49.3 (57.0)50.9 (59.0)44.4 (54.2)0.8120.057
 CABG9.8 (11.6)7.3 (8.4)11.4 (13.2)9.9 (12.1)0.6440.080
 MV surgery1.3 (1.5)2.0 (2.3)2.1 (2.5)1.3 (1.6)0.9230.043
 AV surgery14.9 (17.6)10.8 (12.5)d17.3 (20.1)14.1 (17.3)0.3770.104
 Bentall28.9 (34.1)34.7 (40.1)27.7 (32.1)23.8 (29.1)0.2710.123
Aortic surgery
 Hemiarch76.9 (90.8)a,b,c45.5 (52.6)d,e6.7 (7.8)f1.4 (1.7)<0.001
 TAR7.8 (9.2)a,b,c41.0 (47.4)d,e79.5 (92.2)f80.4 (98.3)<0.001
 Frozen elephant trunk2.0 (2.4)a,b,c14.1 (16.3)d,e37.4 (43.4)42.7 (52.2)<0.001
Cardiopulmonary bypass
 ACP time24.0 (19.0,27.0)a,b,c45.0 (36.0,52.0)d,e75.0 (67.0,82.0)f111.0 (98.0,132.0)<0.001
 CPB time172.0 (138.0,217.4)a,b,c194.0 (162.0,225.7)d,e215.0 (180.0,265.3)f231.0 (195.0,279.0)<0.001
 Cross-clamp time112.2 (70.2,156.3)a,b,c124.0 (98.0,161.0)d,e141.0 (104.0,191.0)144.0 (109.7,199.2)<0.001
 LBI time27.0 (22.0,31.0)a,b,c40.0 (34.0,49.0)d,e46.0 (38.0,61.6)f52.0 (41.0,75.0)<0.001

AAD: acute aortic dissection; ACP: antegrade cerebral perfusion; AV: aortic valve; CABG: coronary artery bypass grafting; CPB: cardiopulmonary bypass; LBI: lower body ischaemia; MV: mitral valve; SMD: standardized mean differences; TAR: total arch replacement.

Alphabets indicate P < 0.05 in following comparisons in post-hoc 2-way comparison with Bonferroni correction: a, ACP ≤ 30 min versus 30<ACP ≤ 60; b, ACP ≤ 30 versus 60<ACP ≤ 90; c, ACP ≤ 30 versus ACP > 90; d, 30<ACP ≤ 60 versus 60<ACP ≤ 90; e, 30<ACP ≤ 60 versus ACP > 90; f, 60<ACP ≤ 90 versus ACP > 90.

Table 3:
Open in new tab

In-hospital outcome in IPTW-adjusted groups

ACP≤30 min
(n = 84.7)		30<ACP ≤ 60 min
(n = 86.6)		60<ACP ≤ 90 min
(n = 86.2)		ACP>90 min
(n = 81.8)		P-valueP-value (linear-by-linear trend analysis)
In-hospital mortality7.7 (9.1)c9.6 (11.1)e11.7 (13.6)16.1 (19.7)0.0560.052
Stroke7.7 (9.1)6.6 (7.7)8.2 (9.5)5.5 (6.7)0.9310.717
Acute renal failure9.3 (11.0)c13.1 (15.1)e16.0 (18.5)20.8 (25.4)0.0140.001
Prolonged ventilation16.5 (19.5)c21.8 (25.2)e23.6 (27.3)30.9 (37.8)0.0070.011
ACP≤30 min
(n = 84.7)		30<ACP ≤ 60 min
(n = 86.6)		60<ACP ≤ 90 min
(n = 86.2)		ACP>90 min
(n = 81.8)		P-valueP-value (linear-by-linear trend analysis)
In-hospital mortality7.7 (9.1)c9.6 (11.1)e11.7 (13.6)16.1 (19.7)0.0560.052
Stroke7.7 (9.1)6.6 (7.7)8.2 (9.5)5.5 (6.7)0.9310.717
Acute renal failure9.3 (11.0)c13.1 (15.1)e16.0 (18.5)20.8 (25.4)0.0140.001
Prolonged ventilation16.5 (19.5)c21.8 (25.2)e23.6 (27.3)30.9 (37.8)0.0070.011

ACP: antegrade cerebral perfusion.

Alphabets indicate P < 0.05 in following comparisons in post-hoc 2-way comparison with Bonferroni correction: c, ACP ≤ 30 min versus ACP > 90; e, 30 < ACP ≤ 60 versus ACP > 90.

Table 3:
Open in new tab

In-hospital outcome in IPTW-adjusted groups

ACP≤30 min
(n = 84.7)		30<ACP ≤ 60 min
(n = 86.6)		60<ACP ≤ 90 min
(n = 86.2)		ACP>90 min
(n = 81.8)		P-valueP-value (linear-by-linear trend analysis)
In-hospital mortality7.7 (9.1)c9.6 (11.1)e11.7 (13.6)16.1 (19.7)0.0560.052
Stroke7.7 (9.1)6.6 (7.7)8.2 (9.5)5.5 (6.7)0.9310.717
Acute renal failure9.3 (11.0)c13.1 (15.1)e16.0 (18.5)20.8 (25.4)0.0140.001
Prolonged ventilation16.5 (19.5)c21.8 (25.2)e23.6 (27.3)30.9 (37.8)0.0070.011
ACP≤30 min
(n = 84.7)		30<ACP ≤ 60 min
(n = 86.6)		60<ACP ≤ 90 min
(n = 86.2)		ACP>90 min
(n = 81.8)		P-valueP-value (linear-by-linear trend analysis)
In-hospital mortality7.7 (9.1)c9.6 (11.1)e11.7 (13.6)16.1 (19.7)0.0560.052
Stroke7.7 (9.1)6.6 (7.7)8.2 (9.5)5.5 (6.7)0.9310.717
Acute renal failure9.3 (11.0)c13.1 (15.1)e16.0 (18.5)20.8 (25.4)0.0140.001
Prolonged ventilation16.5 (19.5)c21.8 (25.2)e23.6 (27.3)30.9 (37.8)0.0070.011

ACP: antegrade cerebral perfusion.

Alphabets indicate P < 0.05 in following comparisons in post-hoc 2-way comparison with Bonferroni correction: c, ACP ≤ 30 min versus ACP > 90; e, 30 < ACP ≤ 60 versus ACP > 90.

Table 4:
Open in new tab

Multivariable logistic regression for all major complications for all patients

In-hospital mortality
Stroke
Acute renal failure
Prolonged ventilation
OR, 95% CIP-valueOR, 95% CIP-valueOR, 95% CIP-valueOR, 95% CIP-value
TAR1.198 (0.404–3.596)0.7442.436 (0.691–8.880)0.1681.240 (0.481–3.210)0.6551.223 (0.546–2.734)0.622
CPB time1.006 (1.001–1.010)0.0130.999 (0.992–1.005)0.7931.004 (0.999–1.008)0.0911.005 (1.001–1.009)0.010
ACP time (compared to ACP≤30 min)
30<ACP≤60 min1.106 (0.365–3.376)0.8570.608 (0.170–2.044)0.4261.256 (0.486–3.376)0.6451.222 (0.552–2.727)0.621
60<ACP≤90 min1.071 (0.279–4.216)0.9200.535 (0.119–2.412)0.4131.287 (0.397–4.300)0.6761.066 (0.393–2.924)0.900
ACP>90 min1.459 (0.368–6.049)0.5950.310 (0.058–1.635)0.1661.744 (0.521–6.094)0.3741.502 (0.535–4.286)0.442
Cannulation site (compared to aorta cannulation)
Axillary0.782 (0.272–2.244)0.6442.417 (0.603–12.494)0.2362.066 (0.863–5.303)0.1131.820 (0.865–3.952)0.120
Femoral1.947 (0.271–5.176)0.1636.461 (1.810–32.316)0.0092.343 (0.968–6.085)0.0672.950 (1.406–6.436)0.005
Brachiocephalic/Carotid1.333 (0.500–3.678)0.5672.219 (0.543–11.503)0.2871.584 (0.623–4.221)0.3401.210 (0.542–2.734)0.642
In-hospital mortality
Stroke
Acute renal failure
Prolonged ventilation
OR, 95% CIP-valueOR, 95% CIP-valueOR, 95% CIP-valueOR, 95% CIP-value
TAR1.198 (0.404–3.596)0.7442.436 (0.691–8.880)0.1681.240 (0.481–3.210)0.6551.223 (0.546–2.734)0.622
CPB time1.006 (1.001–1.010)0.0130.999 (0.992–1.005)0.7931.004 (0.999–1.008)0.0911.005 (1.001–1.009)0.010
ACP time (compared to ACP≤30 min)
30<ACP≤60 min1.106 (0.365–3.376)0.8570.608 (0.170–2.044)0.4261.256 (0.486–3.376)0.6451.222 (0.552–2.727)0.621
60<ACP≤90 min1.071 (0.279–4.216)0.9200.535 (0.119–2.412)0.4131.287 (0.397–4.300)0.6761.066 (0.393–2.924)0.900
ACP>90 min1.459 (0.368–6.049)0.5950.310 (0.058–1.635)0.1661.744 (0.521–6.094)0.3741.502 (0.535–4.286)0.442
Cannulation site (compared to aorta cannulation)
Axillary0.782 (0.272–2.244)0.6442.417 (0.603–12.494)0.2362.066 (0.863–5.303)0.1131.820 (0.865–3.952)0.120
Femoral1.947 (0.271–5.176)0.1636.461 (1.810–32.316)0.0092.343 (0.968–6.085)0.0672.950 (1.406–6.436)0.005
Brachiocephalic/Carotid1.333 (0.500–3.678)0.5672.219 (0.543–11.503)0.2871.584 (0.623–4.221)0.3401.210 (0.542–2.734)0.642

ACP: antegrade cerebral perfusion; CI: confidence interval; CPB: cardiopulmonary bypass; OR: odds ratio; TAR: total arch replacement.

Table 4:
Open in new tab

Multivariable logistic regression for all major complications for all patients

In-hospital mortality
Stroke
Acute renal failure
Prolonged ventilation
OR, 95% CIP-valueOR, 95% CIP-valueOR, 95% CIP-valueOR, 95% CIP-value
TAR1.198 (0.404–3.596)0.7442.436 (0.691–8.880)0.1681.240 (0.481–3.210)0.6551.223 (0.546–2.734)0.622
CPB time1.006 (1.001–1.010)0.0130.999 (0.992–1.005)0.7931.004 (0.999–1.008)0.0911.005 (1.001–1.009)0.010
ACP time (compared to ACP≤30 min)
30<ACP≤60 min1.106 (0.365–3.376)0.8570.608 (0.170–2.044)0.4261.256 (0.486–3.376)0.6451.222 (0.552–2.727)0.621
60<ACP≤90 min1.071 (0.279–4.216)0.9200.535 (0.119–2.412)0.4131.287 (0.397–4.300)0.6761.066 (0.393–2.924)0.900
ACP>90 min1.459 (0.368–6.049)0.5950.310 (0.058–1.635)0.1661.744 (0.521–6.094)0.3741.502 (0.535–4.286)0.442
Cannulation site (compared to aorta cannulation)
Axillary0.782 (0.272–2.244)0.6442.417 (0.603–12.494)0.2362.066 (0.863–5.303)0.1131.820 (0.865–3.952)0.120
Femoral1.947 (0.271–5.176)0.1636.461 (1.810–32.316)0.0092.343 (0.968–6.085)0.0672.950 (1.406–6.436)0.005
Brachiocephalic/Carotid1.333 (0.500–3.678)0.5672.219 (0.543–11.503)0.2871.584 (0.623–4.221)0.3401.210 (0.542–2.734)0.642
In-hospital mortality
Stroke
Acute renal failure
Prolonged ventilation
OR, 95% CIP-valueOR, 95% CIP-valueOR, 95% CIP-valueOR, 95% CIP-value
TAR1.198 (0.404–3.596)0.7442.436 (0.691–8.880)0.1681.240 (0.481–3.210)0.6551.223 (0.546–2.734)0.622
CPB time1.006 (1.001–1.010)0.0130.999 (0.992–1.005)0.7931.004 (0.999–1.008)0.0911.005 (1.001–1.009)0.010
ACP time (compared to ACP≤30 min)
30<ACP≤60 min1.106 (0.365–3.376)0.8570.608 (0.170–2.044)0.4261.256 (0.486–3.376)0.6451.222 (0.552–2.727)0.621
60<ACP≤90 min1.071 (0.279–4.216)0.9200.535 (0.119–2.412)0.4131.287 (0.397–4.300)0.6761.066 (0.393–2.924)0.900
ACP>90 min1.459 (0.368–6.049)0.5950.310 (0.058–1.635)0.1661.744 (0.521–6.094)0.3741.502 (0.535–4.286)0.442
Cannulation site (compared to aorta cannulation)
Axillary0.782 (0.272–2.244)0.6442.417 (0.603–12.494)0.2362.066 (0.863–5.303)0.1131.820 (0.865–3.952)0.120
Femoral1.947 (0.271–5.176)0.1636.461 (1.810–32.316)0.0092.343 (0.968–6.085)0.0672.950 (1.406–6.436)0.005
Brachiocephalic/Carotid1.333 (0.500–3.678)0.5672.219 (0.543–11.503)0.2871.584 (0.623–4.221)0.3401.210 (0.542–2.734)0.642

ACP: antegrade cerebral perfusion; CI: confidence interval; CPB: cardiopulmonary bypass; OR: odds ratio; TAR: total arch replacement.

Subgroups analysis in patients without acute aortic dissection

A total of 607 patients were included in this subgroup analysis (Supplementary Material, Tables S4–S6). In IPTW-adjusted groups, no major complications showed a significant trend among the 4 groups (Supplementary Material, Tables S7–S9). Furthermore, ACP time is not associated with any of these complications, even when exceeding 90 min (mortality, OR = 2.785 [0.318–43.93], P = 0398; stroke, OR = 0.324 [0.031–4.368], P = 0.358; renal failure, OR = 1.798 [0.357–10.252], P = 0.489; prolonged ventilation, OR = 2.815 [0.614–14.717], P = 0.197), whereas CPB time was associated with in-hospital mortality and prolonged ventilation (mortality, OR = 1.007 [1.002–1.014], P = 0012; prolonged ventilation, OR = 1.007 [1.002–1.013], P = 0.005) (Supplementary Material, Table S10).

DISCUSSION

Our study showed that, in performing complex arch procedures at our aortic programmes, prolonged ACP time beyond 90 min did not significantly increase the in-hospital mortality and any other major organ complications.

To our knowledge, our study is the first to have a sufficient cohort size to examine the association between postoperative complications and prolonged bilateral ACP time of over 90 min. The discussion regarding ACP strategy is still ongoing in several literature [18–20], and ACP time varies widely depending on several factors including type of aortic pathology, surgical techniques and surgical strategy in aortic arch surgery. Previous multi-centre studies have reported a wide range of ACP times, ranging from 30.7 to 160.7 min, with variation observed across different studies [7–9, 21–24]. However, while several previous studies reported that ACP strategy can be safely applied with up to 80–90 min in patients undergoing aortic arch replacement [6, 7], the safety of longer ACP durations remains uncertain. In the present study, approximately 25% of all patients received ACP time exceeding 90 min. Our patients who required a prolonged ACP time exceeding 90 min typically underwent TAR with FET, which is a procedure that has been increasingly utilized. We believe this study is valuable for cases requiring prolonged ACP time because our findings indicate that postoperative major complications do not increase linearly with extended ACP time and that ACP time is not an independent risk factor for major postoperative organ complications.

We showed that prolonged bilateral ACP time beyond 90 min does not significantly increase the incidence of stroke. In cases of ACP time beyond 90 min, the incidence of stroke was 6.7%, which is comparable to the outcome reported for patients underwent aortic surgery in STS database [1]. Compared to previous studies, enrolling bilateral and unilateral ACP strategies, which showed that ACP time up to 90 min does not increase permanent stroke in arch replacement [6, 7], our study joined more recent studies by enrolling only patients undergoing bilateral ACP, which may have offered further brain protection particularly in the setting of prolonged ACP compared to unilateral ACP [2–5]. Our finding is consistent with a previous study which showed that although cerebral positron emission tomography showed hypometabolism in the occipital areas related to ACP time, bilateral ACP maintained adequate cerebral perfusion without evidence of ischaemic brain injury [25]. Our data may support a speculation that the primary aetiology of stroke in aortic arch replacement with ACP is due to embolization rather than hypoperfusion or microangiopathy [26, 27].

Similar to stroke, ACP time was not associated with any other major organ dysfunctions in the present study. The cubic spline curves showed that the adjusted OR did not increase with ACP time for these complications. Furthermore, multivariable logistic analysis showed that ACP time, even when exceeding 90 min, was not a risk factor for in-hospital mortality, acute renal failure and prolonged ventilation. Conversely, CPB time was independently associated with in-hospital mortality and prolonged ventilation. We believe that CPB time is a more comprehensive indicator of overall surgical complexity than ACP time, contributing to increased risks for complications such as in-hospital mortality and prolonged ventilation. This belief is supported by several previous studies, which have reported that CPB time was associated with postoperative morbidity and mortality in aortic arch surgery [28, 29]. Therefore, our data showed that ACP time may not be a suitable variable to address the surgical impact of arch surgery on outcomes.

Limitations

This study has several limitations. First, this is a retrospective study at 2 large-volume aortic centres, limiting generalization of the findings. Additionally, even with our large numbers of patients undergoing aortic arch surgery, the incidences of complications were small, limiting the statistical power of our analysis, particularly for post-hoc sample size analysis based on 2-group chi-square analysis. Second, although we used IPTW model in the present study, the low size after the IPWT analysis indicates that a significant portion of the study sample is not represented in the IPTW analysis. Third, only patients who underwent arch surgery with lower temperatures of 21.1 –28.0°C were included to reduce the impact of temperature management, and thus we could not determine how much of a role the degree of hypothermia contributed to outcomes in this study. Additionally, our dataset did not include the perfusion pressure and flow rate in each case. Fourth, it remains unknown how many patients were complicated with reversible brain oedema without permanent defect. Fifth, we included patients who underwent either hemiarch or TAR and those with various types of aortic disease, such as aortic dissection and aneurysm. Although we matched the number of patients with aneurysm or acute aortic dissection and those requiring concomitant surgery, the heterogeneity among these conditions could lead to varying proportions of surgical procedures and intraoperative outcomes across the 4 groups, which may impact our study findings. Sixth, although we incorporated the era into the matching algorithm to reduce the impact of variations in clinical management over different eras, we also acknowledge that differences in preoperative and intraoperative decision-making as well as perioperative management among surgeons and between institutions were not assessed. Finally, while our study demonstrates that ‘prolonged ACP time’, defined as ACP time exceeding 90 min, is not a risk factor for major organ complications, the results should be interpreted within the context of our practice, where ACP times are distributed as shown in Supplementary Material, Fig. S1. Additionally, we were unable to establish a safe threshold for ACP time in aortic arch surgery based on this study, as the number of cases requiring extremely prolonged ACP times, such as beyond 120 min, is limited.

CONCLUSION

We showed that ACP time with bilateral ACP was not an independent risk factor for postoperative major organ complications, even with prolonged use beyond 90 min. Thus, ACP time may not be a suitable variable to address the surgical impact of arch surgery on outcomes.

SUPPLEMENTARY MATERIAL

Supplementary material is available at EJCTS online.

FUNDING

H.T. was supported by the Rudin Foundation.

Conflict of interest: Hiroo Takayama was consultant for Artivion and Edwards.

DATA AVAILABILITY

The data underlying this article will be shared on reasonable request to the corresponding author.

Author contributions

Yu Hohri: Investigation; Writing—original draft. Kavya Rajesh: Investigation; Writing—original draft. Giacomo Murana: Writing—review & editing. Sabrina Castagnini: Investigation. Edoardo Bianco: Investigation. Yanling Zhao: Formal analysis; Writing—review & editing. Paul Kurlansky: Formal analysis; Writing—review & editing. Davide Pacini: Supervision. Hiroo Takayama: Project administration; Supervision

Reviewer information

European Journal of Cardio-Thoracic Surgery thanks Yoshito Inoue and the other anonymous reviewers for their contribution to the peer review process of this article.

REFERENCES

1

Itagaki
S
,
Chikwe
J
,
Sun
E
,
Chu
D
,
Toyoda
N
,
Egorova
N.
Impact of cerebral perfusion on outcomes of aortic surgery: the Society of Thoracic Surgeons Adult Cardiac Surgery Database analysis
.
Ann Thorac Surg
2020
;
109
:
428
–
35
.

Google Scholar

Crossref
Search ADS
PubMed

 
2

Angeloni
E
,
Melina
G
,
Refice
SK
 et al.
Unilateral versus bilateral antegrade cerebral protection during aortic surgery: an updated meta-analysis
.
Ann Thorac Surg
2015
;
99
:
2024
–
31
.

Google Scholar

Crossref
Search ADS
PubMed

 
3

Malvindi
PG
,
Scrascia
G
,
Vitale
N.
Is unilateral antegrade cerebral perfusion equivalent to bilateral cerebral perfusion for patients undergoing aortic arch surgery?
Interact CardioVasc Thorac Surg
2008
;
7
:
891
–
7
.

Google Scholar

Crossref
Search ADS
PubMed

 
4

Preventza
O
,
Simpson
KH
,
Cooley
DA
 et al.
Unilateral versus bilateral cerebral perfusion for acute type A aortic dissection
.
Ann Thorac Surg
2015
;
99
:
80
–
7
.

Google Scholar

Crossref
Search ADS
PubMed

 
5

Angleitner
P
,
Stelzmueller
ME
,
Mahr
S
,
Kaider
A
,
Laufer
G
,
Ehrlich
M.
Bilateral or unilateral antegrade cerebral perfusion during surgery for acute type A dissection
.
J Thorac Cardiovasc Surg
2020
;
159
:
2159
–
67.e2
.

Google Scholar

Crossref
Search ADS
PubMed

 
6

Keeling
WB
,
Tian
D
,
Farrington
W
 et al. ;
ARCH International Investigators
.
Prolonged periods of antegrade cerebral perfusion are safe during elective arch surgery
.
Ann Thorac Surg
2023
;
115
:
387
–
94
.

Google Scholar

Crossref
Search ADS
PubMed

 
7

Zierer
A
,
El-Sayed Ahmad
A
,
Papadopoulos
N
,
Moritz
A
,
Diegeler
A
,
Urbanski
PP.
Selective antegrade cerebral perfusion and mild (28°C-30°C) systemic hypothermic circulatory arrest for aortic arch replacement: results from 1002 patients
.
J Thorac Cardiovasc Surg
2012
;
144
:
1042
–
9
.

Google Scholar

Crossref
Search ADS
PubMed

 
8

Ogino
H
,
Okita
Y
,
Uchida
N
 et al. ;
J-Open Cardiac Aortic Arch Disease Replacement Surgical Therapy Study Investigators
.
Comparative study of Japanese frozen elephant trunk device for open aortic arch repairs
.
J Thorac Cardiovasc Surg
2022
;
164
:
1681
–
92.e2
.

Google Scholar

Crossref
Search ADS
PubMed

 
9

Leone
A
,
Beckmann
E
,
Martens
A
 et al.
Total aortic arch replacement with frozen elephant trunk technique: results from two European institutes
.
J Thorac Cardiovasc Surg
2020
;
159
:
1201
–
11
.

Google Scholar

Crossref
Search ADS
PubMed

 
10

Yan
TD
,
Bannon
PG
,
Bavaria
J
 et al.
Consensus on hypothermia in aortic arch surgery
.
Ann Cardiothorac Surg
2013
;
2
:
163
–
8
.

Google Scholar

PubMed
OpenURL Placeholder Text

 
11

Isselbacher
EM
,
Preventza
O
,
Hamilton Black
JH
 et al.
2022 ACC/AHA guideline for the diagnosis and management of aortic disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines
.
Circulation
2022
;
146
:
e334
–
482
.

Google Scholar

Crossref
Search ADS
PubMed

 
12

Erbel
R
,
Aboyans
V
,
Boileau
C
 et al.
2014 ESC guidelines on the diagnosis and treatment of aortic diseases: document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC)
.
Eur Heart J
2014
;
35
:
2873
–
926
.

Google Scholar

PubMed
OpenURL Placeholder Text

 
13

Yamabe
T
,
Zhao
Y
,
Kurlansky
PA
 et al.
Extent of aortic replacement and operative outcome in open proximal thoracic aortic aneurysm repair
.
JTCVS Open
2022
;
12
:
1
–
12
.

Google Scholar

Crossref
Search ADS
PubMed

 
14

Di Marco
L
,
Berardi
M
,
Murana
G
 et al.
Early outcome and mid-term survival after open arch repair using selective antegrade cerebral perfusion
.
Asian Cardiovasc Thorac Ann
2021
;
2184923211028782
.

Google Scholar

OpenURL Placeholder Text

 
15

Takayama
H
,
Hohri
Y
,
Brinster
DR
 et al.
Open, endovascular or hybrid repair of aortic arch disease: narrative review of diverse strategies with diverse options
.
Eur J Cardiothorac Surg
2024
;
65
:
ezae179
.

Google Scholar

Crossref
Search ADS
PubMed

 
16

Leone
A
,
Di Marco
L
,
Coppola
G
 et al.
Open distal anastomosis in the frozen elephant trunk technique: initial experiences and preliminary results of arch zone 2 versus arch zone 3
.
Eur J Cardiothorac Surg
2019
;
56
:
564
–
71
.

Google Scholar

Crossref
Search ADS
PubMed

 
17

Yoshida
K
,
Hernández-Díaz
S
,
Solomon
DH
 et al.
Matching weights to simultaneously compare three treatment groups: comparison to three-way matching
.
Epidemiology
2017
;
28
:
387
–
95
.

Google Scholar

Crossref
Search ADS
PubMed

 
18

Berger
T
,
Rylski
B
,
Czerny
M
,
Kreibich
M.
Selective antegrade cerebral perfusion: how to perfuse?
Eur J Cardiothorac Surg
2023
;
63
:
ezad139
.

Google Scholar

Crossref
Search ADS
PubMed

 
19

Wahba
A.
Antegrade cerebral perfusion-in pursuit of the holy grail of perfusion in type A aortic dissection
.
Eur J Cardiothorac Surg
2021
;
60
:
1445
–
6
.

Google Scholar

Crossref
Search ADS
PubMed

 
20

Pacini
D
,
Murana
G.
New EACTS/STS guidelines on the diagnosis and treatment of aortic ‘organ’ diseases: are you ready for prime time?
Eur J Cardiothorac Surg
2024
;
65
:
ezae196
.

Google Scholar

Crossref
Search ADS
PubMed

 
21

Weiss
G
,
Tsagakis
K
,
Jakob
H
 et al.
The frozen elephant trunk technique for the treatment of complicated type B aortic dissection with involvement of the aortic arch: multicentre early experience
.
Eur J Cardiothorac Surg
2015
;
47
:
106
–
14; discussion 114
.

Google Scholar

Crossref
Search ADS
PubMed

 
22

Zierer
A
,
El-Sayed Ahmad
A
,
Papadopoulos
N
 et al.
Fifteen years of surgery for acute type A aortic dissection in moderate-to-mild systemic hypothermia
.
Eur J Cardiothorac Surg
2017
;
51
:
97
–
103
.

Google Scholar

Crossref
Search ADS
PubMed

 
23

Mestres
C-A
,
Tsagakis
K
,
Pacini
D
 et al. ;
IEOR Registry Group
.
One-stage repair in complex multisegmental thoracic aneurysmal disease: results of a multicentre study
.
Eur J Cardiothorac Surg
2013
;
44
:
e325
–
31
.

Google Scholar

Crossref
Search ADS
PubMed

 
24

Milewski
RK
,
Pacini
D
,
Moser
GW
 et al.
Retrograde and antegrade cerebral perfusion: results in short elective arch reconstructive times
.
Ann Thorac Surg
2010
;
89
:
1448
–
57
.

Google Scholar

Crossref
Search ADS
PubMed

 
25

Pacini
D
,
Di Marco
L
,
Leone
A
 et al.
Cerebral functions and metabolism after antegrade selective cerebral perfusion in aortic arch surgery
.
Eur J Cardiothorac Surg
2010
;
37
:
1322
–
31
.

Google Scholar

Crossref
Search ADS
PubMed

 
26

Berger
T
,
Kreibich
M
,
Mueller
F
 et al.
Risk factors for stroke after total aortic arch replacement using the frozen elephant trunk technique
.
Interact CardioVasc Thorac Surg
2022
;
34
:
865
–
71
.

Google Scholar

Crossref
Search ADS
PubMed

 
27

Leshnower
BG
,
Rangaraju
S
,
Allen
JW
,
Stringer
AY
,
Gleason
TG
,
Chen
EP.
Deep hypothermia with retrograde cerebral perfusion versus moderate hypothermia with antegrade cerebral perfusion for arch surgery
.
Ann Thorac Surg
2019
;
107
:
1104
–
10
.

Google Scholar

Crossref
Search ADS
PubMed

 
28

Ghoreishi
M
,
Sundt
TM
,
Cameron
DE
 et al.
Factors associated with acute stroke after type A aortic dissection repair: an analysis of the Society of Thoracic Surgeons National Adult Cardiac Surgery Database
.
J Thorac Cardiovasc Surg
2020
;
159
:
2143
–
54.e3
.

Google Scholar

Crossref
Search ADS
PubMed

 
29

Preventza
O
,
Coselli
JS
,
Garcia
A
 et al.
Moderate hypothermia at warmer temperatures is safe in elective proximal and total arch surgery: results in 665 patients
.
J Thorac Cardiovasc Surg
2017
;
153
:
1011
–
8
.

Google Scholar

Crossref
Search ADS
PubMed

 

ABBREVIATIONS

    ABBREVIATIONS
     
  • ACP

    Antegrade cerebral perfusion

    •  
  • CPB

    Cardiopulmonary bypass

    •  
  • FET

    Frozen elephant trunk

    •  
  • IPTW

    Inverse probability of treatment weighting

    •  
  • LVEF

    Left ventricular ejection fraction

    •  
  • SMD

    Standardized mean differences

    •  
  • STS

    Society of Thoracic Surgeons

    •  
  • TAR

    Total arch replacement

    •  
  • VIF

    Variance inflation factor

© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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Topic:
Subject
Organ Protection (Acquired Cardiac) Aortic Disorders
Issue Section:
CONVENTIONAL AORTIC SURGERY
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