Predictors of Type 1a Endoleak After Hybrid Thoracic Endovascular Aortic Repair for Aortic Arch Diseases

Abstract

Background: This study analyzed the risk factors for type 1a endoleak after hybrid thoracic endovascular repair (TEVAR) for aortic arch diseases based on preoperative patient characteristics and multidetector computed tomography measurements.

Methods and Results: In all, 213 patients who underwent proximal landing zone 1 and 2 hybrid TEVAR for aortic arch pathologies (zone 1, n=82 [38.5%]; zone 2, n=131 [61.5%]; median age 72 years) between May 2008 and February 2020 were enrolled in this study; the median follow-up period was 6.0 years. The rates of type 1a endoleak at 1, 3, 5, and 10 years were 1.4%, 1.4%, 4.1%, and 4.1%, respectively. Multivariate Cox proportional hazard regression analysis revealed that the angle of the aortic arch was a significant risk factor for type 1a endoleak (hazard ratio 1.08; 95% confidence interval 0.85–0.99; P=0.045). The estimated area under the curve in receiver operating characteristic curve analysis was 0.76, and the cut-off value of the aortic arch angle was 95°.

Conclusions: It is essential to prevent type 1a endoleak, the most severe complication of hybrid TEVAR. The risk factor for type 1a endoleak in this study was a sharper angle of the aortic arch (≤95°). For patients at high risk of type 1a endoleak, it is necessary to consider alternative procedures depending on a patient’s surgical risk.

Thoracic endovascular repair (TEVAR) of aortic arch disease is increasingly gaining acceptance, yet it remains a challenging procedure with sobering long-term results due to high reintervention rates.^1–3 TEVAR is associated with aortic events that do not occur with conventional total arch replacement (TAR). Among these, type 1a endoleak requiring reintervention must be prevented. Factors contributing to type 1a endoleak include a large and short proximal landing zone (LZ), a steep arch angle, a large stent graft diameter, small stent graft oversizing, a bird-beak configuration, and LZ 1.^4–6 Consequently, preoperative planning, which includes measurements and stent graft selection, is crucial in preventing type 1a endoleak.^2,5,7 However, no specific numerical values have been reported for individual parameters on preoperative multidetector computed tomography (MDCT). The aim of this study was to analyze the risk factors for type 1a endoleak based on preoperative patients characteristics and MDCT measurements.

Methods

Ethics Statement, Study Design, and Study Population

All procedures in this study were conducted according to the principles of the Declaration of Helsinki and were approved by the Medical Ethics Committee of Osaka University School of Medicine (No. 08218-11). This retrospective and observational cohort study included 213 patients who underwent proximal LZ 1 and 2 hybrid TEVAR for aortic arch pathologies between May 2008 and March 2020. Informed consent was obtained from all patients before the procedure.

Modality and Measurements

All patients underwent contrast-enhanced MDCT with 3-dimensional (3D) reconstruction using an image processing workstation (Aquarius Intuition; TeraRecon, San Mateo, CA, USA) to evaluate the adequacy of the proximal and distal LZs, the inflow artery, the aortic arch, and the access route before the operation. MDCT images were acquired with a slice thickness of <1 mm. Routine follow-up with MDCT was performed within 1 week before discharge, at 6 months after the procedure, and yearly thereafter.

The proximal LZ, aortic arch angle, and the distance from the top of the arch to the brachiocephalic artery (BCA) or left common carotid artery (LCCA) were measured on MDCT pre- and postoperatively using the 3D workstation.

We drew a centerline of the aortic arch on 3D MDCT images. The distance to BCA and LCCA was defined as the distance from the landing point of the BCA and LCCA to the apex of the aortic arch (Figure 1A). The angulation of the top of the aortic arch (θ) was calculated in 30-mm ranges using vector inner products ( · = || · || cos θ, where || and || were 15 mm in length along the median centerline and θ was the angle between vector a and vector b; Figure 1B).⁸

Figure 1.

Three-dimensional reconstruction images. (A) Calculation of the length from the top of the arch to the brachiocephalic artery (BCA) or left common carotid artery (LCCA). The distance to BCA (blue arrow) and LCCA (red arrow) was defined as the distance from the landing point of the BCA and LCCA to the apex of the aortic arch. (B) Calculation of angulation of the arch. The angulation of the top of the aortic arch (θ) was calculated in 30-mm ranges using vector inner products ( · = || · || cos θ, where || and || were 15 mm in length along the median centerline and θ was the angle between vector a and vector b).

Indications

Indications for surgical procedures were aortic diameter expansion of ≥5 mm in 6 months, a maximum aortic diameter >55 mm, aneurysm rupture, any sized saccular aneurysm, malperfusion syndrome, or an initial diameter >40 mm in type B aortic dissection.

The aortic anatomical conditions for these interventions were a proximal LZ diameter ≤42 mm and length ≥20 mm and a proximal stent graft size ≤46 mm with 10–20% oversizing. The diameter of the proximal LZ was according to the instructions for use. We first determined whether zone 2 landing TEVAR was possible. If the proximal landing was inappropriate in zone 2, we performed zone 1 landing TEVAR. However, in high-risk patients with zone 0 landing, these interventions were performed with an LZ length of 16–20 mm in the saccular aneurysm and type B dissection.

Surgical Procedures

Zone 1 landing hybrid TEVAR was performed via an extra-anatomical bypass from the right axillary artery (AxA) to the LCCA and left AxA using a T-shaped ringed 8-mm expanded polytetrafluoroethylene graft. In patients who underwent zone 2 landing hybrid TEVAR, the LSA was intentionally covered without revascularization or an extra-anatomical bypass (from the right to left AxA or from the LCCA to the left AxA). The stent graft devices were then deployed, as described previously.⁵

Definitions

The primary endpoint of interest in this study was type 1a endoleak. Secondary endpoints were aortic events: known or suspected events, such as stroke, aneurysm enlargement ≥5 mm in diameter, or any case of endoleak, stent graft migration, aortic rupture, aortic dissection, and prosthetic infection. In cases of dissection, type 1a endoleak was defined as persistent false lumen perfusion at the level of the proximal entry tear in aortic dissections.

Follow-up

At the Osaka University Graduate School of Medicine, patients were followed up with MDCT examinations at least once every 3 months in the first year and then every 6 months or 1 year thereafter. Patients were followed up until they died, and the occurrence of late complications was confirmed by the patients or their families.

Statistical Analyses

Results are expressed as the mean±SD or as the median with interquartile range (IQR) depending on the normality of data distribution, which was assessed using the Shapiro-Wilk test. Comparisons were performed using the Mann-Whitney U test. Categorical variables are presented as counts and percentages, and were compared using the Chi-squared test or Fisher’s exact test. Curves for all-cause mortality, aorta-related death rates, aortic event rates, and type 1a endoleak rates were estimated using the Kaplan-Meier product limit method and compared using log-rank tests. Estimates are provided with 95% confidence interval (CIs). Univariate and multivariate Cox proportional hazards regression analyses were performed to examine the risk factors for type 1a endoleak throughout the follow-up period. Significant risk factors with P<0.1 in univariate logistic regression and Cox proportional hazards regression analyses were incorporated into the corresponding multivariate analyses. To test the discriminatory value of independent predictors of type 1a endoleak, we used the area under the curve (AUC) method. We also used receiver operating characteristic (ROC) analysis to investigate the cut-off value for each factor that maximized the AUC for type 1a endoleak.

All P values are 2-sided, and statistical significance was set at P<0.05. Statistical analyses were performed using JMP statistical software, version 16.0.0 for MacOS X (SAS Institute Inc., Cary, NC, USA).

Results

Baseline Characteristics

The mean follow-up period was 6.0 years (IQR 2.8–9.7 years). Preoperative patient characteristics are presented in Table 1. The median patient age at the time of surgery was 72 years (IQR 66–78 years). Of the 213 patients in the study, 42 (19.7%) were female and 69 (32.4%) had a dissection. Of the 69 cases of dissection, 21 (9.9%) had an acute and subacute phase, and 48 (22.5%) had a chronic phase. Twenty-five (11.7%) patients had a history of cardiovascular surgery, and 33 (15.5%) patients underwent emergency procedures. The median EuroSCORE II was 2.7% (IQR 2.1–4.1%).

Table 1.

Preoperative Patient Characteristics (n=213)

Age (years)	72 [65–78]
Age ≥80 years	43 (20.2)
Female sex	42 (19.7)
Aortic pathologies
Aneurysm	144 (67.6)
Dissection	69 (32.4)
Acute and subacute	21 (9.9)
Chronic	48 (22.5)
Preoperative complications
Cerebrovascular disease	25 (11.7)
Coronary artery disease	44 (20.7)
CKD Stage ≥4	30 (14.1)
COPD	19 (8.9)
Ejection fraction ≤40%	1 (0.5)
Previous median sternotomy	11 (5.2)
Emergency	33 (15.5)
EuroSCORE II (%)	2.7 [2.1–4.1]

Data are presented as the median [interquartile range] or n (%). CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease.

Preoperative Measurements and Stent Grafts

Preoperative measurements and stent grafts are presented in Table 2. The median maximum diameter of the aorta was 51 mm (IQR 44–60 mm). The median diameter and length of the proximal LZ were 31 mm (IQR 29–34 mm) and 20 mm (IQR 17–24 mm), respectively. The mean angle of the aortic arch was 113±18°, and the median length from the top of the arch to the BCA or LCCA was 28 mm (IQR 21–36 mm). There were no significant differences in the length of the proximal LZ and the angle of the aortic arch between zone 1 and 2 landing TEVAR (Supplementary Table).

Table 2.

Preoperative Measurements and Stent Grafts (n=213)

Preoperative measurements
Maximum aortic diameter (mm)	51 [44–60]
Diameter of proximal LZ (mm)	31 [29–34]
Length of proximal LZ (mm)	20 [17–24]
Angle of arch (°)	113±18
Length from top of arch to BCA or LCCA (mm)	28 [21–36]
Stent grafts
Type of proximal stent grafts
TAG	74 (34.7)
CTAG	88 (41.3)
Relay Plus	16 (7.5)
Relay NBS	10 (4.7)
Zenith TX2	15 (7.0)
Zenith TXD	2 (0.9)
Talent	6 (2.8)
Valiant	2 (0.9)
No. stent grafts	1.4±0.6
Proximal stent graft
Diameter (mm)	36 [34–38]
Oversizing rate (%)	14 [10–18]

Data are presented as the mean±SD, median [interquartile range], or n (%). BCA, brachiocephalic artery; CTAG, conformable thoracic aortic graft; LCCA, left common carotid artery; LZ, landing zone.

For proximal stent grafting, TAG and conformable thoracic aortic graft (CTAG) devices (W.L. Gore & Associates, Inc., Flagstaff, AZ, USA) were used in 74 (34.7%) and 88 (41.3%) patients, respectively; Relay Plus and Relay NBS (Terumo Aortic, Inchinnan, UK) devices were used in 16 (7.5%) and 10 (4.7%) patients, respectively; Cook Zenith TX2 and Cook Zenith TXD (Cook Medical, Bloomington, IN, USA) devices were used in 15 (7.0%) and 2 (0.9%) patients, respectively; and Medtronic Talent and Valiant (Medtronic, Inc., Santa Rosa, CA, USA) devices were used in 6 (2.8%) and 2 (0.9%) patients, respectively.

Operative, Early (30-Day), and Late Outcomes

Data for operative, early (30-day), and late outcomes are presented in Table 3. All procedures were successful, and zone 1 and 2 hybrid TEVAR was performed in 82 (38.5%) and 131 (61.5%) patients, respectively. The median operative time was 160 min (IQR 130–204 min). The median postoperative hospital stay was 10 days (IQR 8–16 days), and the discharge rate to home was 95.3% (n=203). Two (0.9%) patients had a stroke, and another 2 (0.9%) patients had spinal cord injury in the early phase. However, there were no patients with stroke or spinal cord injury in the late phase.

Table 3.

Operative, Early (30-Day), and Late Outcomes (n=213)

Procedure
Zone 1 landing hybrid TEVAR	82 (38.5)
Zone 2 landing hybrid TEVAR	131 (61.5)
Procedure success	213 (100)
Operative time (min)	160 [130–204]
Hospital stay (days)	10 (8–16)
Discharge to home	203 (95.3)
Death
30-day death	1 (0.5)
Late death	38 (17.8)
Early (30-day) aortic events
Complications
Stroke	2 (0.9)
Spinal cord injury	2 (0.9)
Abdominal embolic event	1 (0.5)
Aneurysm rupture	1 (0.5)
Endoleaks
Type 1a	3 (1.4)
Type 1b	1 (0.5)
Late aortic events
RTAD	1 (0.5)
Distal SINE	3 (1.4)
Stent graft infection	1 (0.5)
Bypass graft occlusion	1 (0.5)
Endoleaks
Type 1a	4 (1.9)
Type 1b	2 (0.9)

Data are presented as the median [interquartile range] or n (%). RTAD, retrograde type A dissection; SINE, stent graft-induced new entry; TEVAR, thoracic endovascular aortic repair.

Survival and Aortic Events

The estimated death rates at 1, 3, 5, and 10 years were 4.0% (95% CI 2.1–7.2%), 10.7% (95% CI 7.1–15.9%), 13.7% (95% CI 9.5–19.4%), and 26.4% (95% CI 19.1–35.3%), respectively (Figure 2A). The estimated aorta-related death rates at 1, 3, 5, and 10 years were 1.4% (95% CI 0.5–4.3%), 1.4% (95% CI 0.5–4.3%), 1.4% (95% CI 0.5–4.3%), and 1.4% (95% CI 0.5–4.3%), respectively (Figure 2B).

Figure 2.

Kaplan-Meier of estimates of (A) all-cause death, (B) aorta-related death, (C) aortic events, and (D) type 1a endoleaks. Solid lines indicate estimated rates and shaded areas indicate 95% confidence intervals (CI). (A) The estimated death rates at 1, 3, 5, and 10 years were 4.0% (95% CI 2.1–7.2%), 10.7% (95% CI 7.1–15.9%), 13.7% (95% CI 9.5–19.4%), and 26.4% (95% CI 19.1–35.3%), respectively. (B) The estimated aorta-related death rates at 1, 3, 5, and 10 years were 1.4% (95% CI 0.5–4.3%), 1.4% (95% CI 0.5–4.3%), 1.4% (95% CI 0.5–4.3%), and 1.4% (95% CI 0.5–4.3%), respectively. (C) The estimated aortic events rates at 1, 3, 5, and 10 years were 4.7% (95% CI 2.5–8.5%), 7.3% (95% CI 4.4–11.7%), 10.0% (95% CI 6.4–15.2%), and 11.1% (95% CI 7.1–16.9%), respectively. (D) The cumulative type 1a endoleak rates at 1, 3, 5, and 10 years were 1.4% (95% CI 0.5–4.3%), 1.4% (95% CI 0.5–4.3%), 4.1% (95% CI 2.0–8.5%), and 4.1% (95% CI 2.0–8.5%), respectively.

Aortic events occurred in 21 patients (Table 3). The estimated aortic events rates at 1, 3, 5, and 10 years were 4.7% (95% CI 2.5–8.5%), 7.3% (95% CI 4.4–11.7%), 10.0% (95% CI 6.4–15.2%), and 11.1% (95% CI 7.1–16.9%), respectively (Figure 2C).

Type 1a Endoleak

Seven (3.3%) patients experienced a type 1a endoleak (3 in the early phase, 4 in the late phase). Four patients with type 1a endoleak were successfully treated with open surgical repair, whereas 1 underwent branched TEVAR. The other 2 patients were followed up without additional intervention.

Figure 2D shows Kaplan-Meier curves for cumulative type 1a endoleak rates. At 1, 3, 5, and 10 years, the cumulative type 1a endoleak rates were 1.4% (95% CI 0.5–4.3%), 1.4% (95% CI 0.5–4.3%), 4.1% (95% CI 2.0–8.5%), and 4.1% (95% CI 2.0–8.5%), respectively.

Comparisons of outcomes between patients with and without type 1a endoleak are presented in Table 4. There were no significant differences in patient characteristics. The median diameter of the proximal LZ was significantly larger in the group with type 1a endoleak group than in the group without type 1a endoleak (P=0.011). The mean angle of the aortic arch was significantly smaller in the group with type 1a endoleak group than in the group without (P=0.021). The median length from the top of the arch to the BCA or LCCA in was significantly shorter in the group with type 1a endoleak group (P=0.041). The number of patients in whom the Relay NBS was used was significantly greater in the group with type 1a endoleak (P<0.001).

Table 4.

Comparisons of Anatomical and Operative Parameters Between Patients With and Without Type 1a Endoleak

	Type 1a endoleak		P value
	Yes (n=7; 3.3%)	No (n=206; 96.7%)
Preoperative patient characteristics
Age (years)	65 [61–71]	73 [66–78]	0.40
Female sex	3 (42.9)	39 (18.9)	0.16
Aneurysm	4 (57.1)	140 (68.0)	0.62
Emergency procedure	0	33 (16.0)	0.12
Preoperative measurements
Maximum aortic diameter (mm)	57 [51–63]	51 [43–60]	0.26
Diameter of proximal LZ (mm)	33 [30–38]	31 [29–34]	0.011
Length of proximal LZ (mm)	18 [16–19]	20 [17–24]	0.09
Angle of arch (°)	99±13	113±18	0.021
Length from top of arch to BCA or LCCA (mm)	22 [18–24]	28 [21–36]	0.041
Procedure
Zone 2 landing hybrid TEVAR	5 (71.4)	126 (61.2)	0.60
Type of stent grafts
TAG	1 (14.3)	73 (35.4)	0.10
CTAG	0	88 (42.7)	0.020
Relay Plus	0	16 (7.8)	0.29
Relay NBS	4 (57.1)	6 (2.9)	<0.001
Zenith TX2	1 (14.3)	14 (6.8)	0.59
Zenith TXD	0	2 (1.0)	0.71
Talent	1 (14.3)	5 (2.4)	0.18
Valiant	0	2 (1.0)	0.75
Proximal stent graft
Diameter (mm)	40 [36–42]	36 [34–38]	0.005
Oversize rate (%)	13 [11–21]	14 [10–18]	0.79

Data are presented as the mean±SD, median [interquartile range], or n (%). Abbreviations as in Tables 2,3.

Risk factors for type 1a endoleak are presented in Table 5. In the multivariate Cox proportional hazard regression analysis, the angle of the aortic arch (hazard ratio [HR] 1.08; 95% CI 0.85–0.99; P=0.045) was a significant risk factor for type 1a endoleak. The estimated AUC in ROC curve analysis was 0.76, and the cut-off value for the angle of the aortic arch was 95° (sensitivity: 85.9%; specificity: 42.9%; Figure 3). Cut-off values for the diameter of the proximal LZ, the length of the proximal LZ, the length from the top of the arch to the BCA or LCCA, and the proximal diameter of the stent graft are shown in the Supplementary Figure.

Table 5.

Risk Factors for Type 1a Endoleak

	Univariate		Multivariate
	P value	HR (95% CI)	P value	HR (95% CI)
Preoperative measurements
Diameter of proximal LZ	0.011	1.35 (1.07–1.74)	0.60	1.15 (0.69–2.06)
Length of proximal LZ	0.09	0.84 (0.63–1.03)	0.06	0.77 (0.52–1.01)
Angle of arch	0.021	0.96 (0.92–1.00)	0.045	0.92 (0.85–0.99)
Length from top of arch to BCA or LCCA	0.041	0.90 (0.79–0.99)	0.07	0.89 (0.72–1.00)
Landing zone: Zone 2	0.60	1.53 (0.30–7.87)
Stent graft
Relay NBS	<0.001	22.2 (1.94–99.8)	0.07	5.51 (0.85–35.7)
Proximal diameter	0.005	1.36 (1.09–1.70)	0.22	1.39 (0.82–2.48)
Oversize rate	0.79	0.99 (0.90–1.09)

CI, confidence interval; HR, hazard ratio. Other bbreviations as in Table 2.

Figure 3.

Receiver operating characteristic (ROC) curve for the angle of the aortic arch to predict type 1a endoleak. The estimated area under the curve (AUC) was 0.76; the cut-off value for the angle of the aortic arch was 95° (sensitivity 85.9%, specificity 42.9%).

Discussion

Total arch repair (TAR) for aortic arch diseases has traditionally been associated with high mortality and postoperative complication rates, particularly in elderly patients and those with severe preoperative comorbidities.^9,10 Because of its minimal invasiveness, hybrid TEVAR has better short-term results and is associated with less loss of activities of daily living than traditional aortic arch surgery.^9,11,12 In recent years, hybrid TEVAR has been developed and widely adopted as an alternative approach to traditional arch surgery. Early outcomes have shown promising results compared with traditional total arch repair.¹³ However, a specific complication of hybrid TEVAR is the occurrence of endoleaks, which can lead to poor long-term outcomes. In particular, type 1a endoleaks have a high risk of further enlarging the postoperative aneurysm, necessitating reintervention.^1,11,14–21 Reintervention for type 1a endoleaks is challenging and often associated with suboptimal outcomes.²² Therefore, it is crucial to prevent type 1a endoleaks in the initial hybrid TEVAR procedure.

The 30-day mortality rate in the present study was 0.5%, and the 10-year aortic-related mortality rate was 1.4%. Compared with other literature reporting a 30-day mortality rate of 10% and a 10-year aortic-related mortality rate of 15% for TAR, the early and long-term outcomes in this study are satisfactory. In addition, the incidence of cerebral infarction in the present study was 0.9%, which is significantly lower than the reported 3–7% for TAR in other studies.^18,23–26

To prevent type 1a endoleak, appropriate proximal LZs were defined as having a length >15 mm and a diameter of 18–42 mm (based on Instruction for Use). In the present study, type 1a endoleaks were observed in 9 patients (3.3%; 3 in the early phase, 4 in the late phase). Previous studies have reported the causes of type 1a endoleak as being a larger and shorter proximal LZ, an acute arch angle, a larger stent graft diameter, small stent graft oversizing, bird-beak configurations, and zone 1 landing.^4,5,27 The causes of type 1a endoleak in the present study were broadly consistent with these previous reports and were found to be dependent on the stent graft device.

Univariate analysis in this study suggested that a larger and shorter LZ, acute arch angle, larger stent graft diameter, and the use of the Relay NBS as a stent graft were risk factors for type 1a endoleak. Furthermore, multivariate analysis indicated that an acute arch angle (HR 1.08; 95% CI 0.85–0.99; P=0.0446) was a risk factor for type 1a endoleak, with a cut-off value of ≤95° (AUC 0.76, sensitivity 85.9%, specificity 42.9%). Although a previous study reported that a steep arch angle is a risk factor for type 1a endoleak, there have been no studies that specifically reported on the angle of the aortic arch.²⁸ The novelty of the present study is that we calculated the cut-off value for the aortic arch angle as a risk factor for the development of type 1a endoleak using ROC curve analysis.

In our previous study, we reported that no type 1a endoleak was observed in zone 0 hybrid TEVAR without cardiopulmonary bypass. We believe that this was due to the longer proximal LZ length in zone 0 hybrid TEVAR compared with zones 1 and 2 hybrid TEVAR, resulting in fewer bird-beak configurations.⁷ Moreover, in our study, elderly patients treated in zone 0 without the need for cardiopulmonary bypass did not experience decreased activities of daily living or lifetime loss. Therefore, in the case of a sharper angle of the aortic arch (≤95°) in zones 1 and 2, we strongly recommended zone 0 hybrid TEVAR without cardiopulmonary bypass. However, the incidence of cerebral infarction in zone 0 landing hybrid TEVAR has been reported to be higher than in zone 1 and 2 landing TEVAR, so the choice of which TEVAR to perform is a trade-off of potential surgical risks.¹⁹ Our previous study showed that the incidence of cerebral infarction in zone 0 hybrid TEVAR without cardiopulmonary bypass was 0%, and postoperative aortic events may be reduced by accurate preoperative assessment of the ascending aorta.

Study Limitations

This study has some limitations. First, it was a retrospective study, and the sample size is small. Second, there is a bias in the stent grafts used. Third, some patients had relatively short follow-up periods, and there were few occurrences of type 1a endoleak. Therefore, future research will need to equalize or limit the number of stent grafts used.

Conclusions

It is essential to prevent type 1a endoleak, the most severe complication of hybrid TEVAR. The risk factor for type 1a endoleak in this study was a sharper angle of the aortic arch (≤95°). For patients at high risk of type 1a endoleak, it is necessary to consider alternative procedures according to a patient›s individual surgical risk.

Acknowledgments

None.

Sources of Funding

This study did not receive any specific funding.

Disclosures

Y.S. is a member of Circulation Journal’s Editorial Team. The remaining authors have no conflicts of interest to declare.

IRB Information

This study was approved by the Medical Ethics Committee of Osaka University School of Medicine (No. 08218-11).

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circj.CJ-24-0580

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