What we have learned from in-vitro studies of the chimney endovascular technique for treatment of complex abdominal aortic aneurysms: A systematic review

Abstract

Background

A considerable number of patients with abdominal aortic aneurysms (AAA) is not eligible for standard endovascular repair. These complex cases require alternative surgical approaches including the readily available chimney graft endovascular aneurysm repair (Ch-EVAR) or sealing (Ch-EVAS). The optimal configuration for Ch-EVAR or Ch-EVAS is important for success but not yet known.

Objective

The aim of the present study was to analyze current data of the outcomes of in-vitro chimney graft treatment in complex AAA.

Methods

A systematic review following PRISMA guidelines was conducted including studies reporting on gutter size, main graft compression, and chimney graft compression in in-vitro configurations.

Results

The search resulted in 285 articles. 11 studies considering 219 individual tests could be included. Gutter size was comparable between Ch-EVAR and Ch-EVAS configurations. In Ch-EVAR set-ups, the deployed BECG were Advanta V12, VIABAHN®, and BeGraft. One type of SECG was used: VIABAHN®. The four types of main grafts (MG) deployed were: Endurant™ I/II; EXCLUDER Conformable AAA Endoprosthesis and AAA Endoprosthesis, and AFX™ Endovascular AAA Delivery System. In the EVAS-configurations, the Nellix® EVAS system was deployed. In general, SECG presented smaller gutters with higher chimney graft compression. 30% main grafts oversizing seems to give the smallest gutters without high risk of infolding of MG. Oversizing, EndoAnchors, and secondary endobag filling (in Ch-EVAS) reduced gutter sizes. CG ballooning during the entire polymer injection in Ch-EVAS prevented CG compression.

Conclusion

In-vitro investigations provide insight in optimal Ch-EVAR and Ch-EVAS configurations for simulated complex AAA repair. The findings above might aid physicians in their planning to potential CG set-ups and can be used in future research to refine the most optimal configuration for chimney graft technique in complex AAA.

Keywords

in-vitro chimney graft main graft endovascular aneurysm repair EVAS abdominal aortic aneurysms gutter compression

Introduction

Over the last decades, endovascular aneurysm repair (EVAR) has broadened the surgical scope for standard treatment for abdominal aortic aneurysms (AAA) due to the minimal invasive character and significant decrease in 30-day mortality compared to open surgery (De Bruin et al., 2010; Wanhainen et al., 2019). Unfortunately, a considerable proportion of patients with AAA are not suitable for standard EVAR due to the aneurysmal anatomy outside the instructions for use (IFU) (Greenberg et al., 2003). Besides custom-made fenestrated or branched EVAR, the chimney graft (CG) technique (Ch-EVAR) offers a feasible option to treat patients with a challenging anatomy of the aortic neck, including juxta- or pararenal aneurysms. In Ch-EVAR set-up, a stent is deployed into the visceral and/or renal arteries parallel to the aortic endograph to preserve flow and enlarge proximal sealing. Ch-EVAS combines CG technique with endovascular aneurysm sac sealing using Nellix® EVAS system (Endologix, Irvine, CA, USA). Although oversizing is important for apposition of stent grafts against the aortic wall, it can cause compression of CG and MG (leading to reduced flow, graft thrombosis, and even occlusion) and may cause MG infolding. (Mestres et al., 2012)

In the PERICLES registry, 517 patients were treated with Ch-EVAR at 13 European and U.S. centers from 2008 to 2014 and a primary patency rate of 94.1% with low overall mortality was observed. By use of Ch-EVAR, the neck length was successfully extended and a significant postoperative aneurysmal sac shrinkage was observed (Donas et al., 2015). Ch-EVAR is used for elective cases globally and can be used for bailout procedures due to the off-the-shelf availability in case fenestrated or branched EVAR is not applicable due to the manufacturing time or financial capabilities in low and middle-income countries. (Coscas et al., 2011; Meekel et al., 2020; Valdivia et al., 2019)

Favorable short to midterm results were noticed in this study, with the notion that the results varied in the abdominal stent-configurations depending on the CG combinations and number of stented vessels. Long-term complications and reinterventions lurk due to potential gutter formation and stent compression (Pecoraro et al., 2016). Unfavorable long-term survival was observed in certain chimney/endograft combinations following long-term data of the PERICLES registry. Use of non-BECG led to lower incidence of type Ia endoleaks. Other risk factors for survival included center volume and oversizing; however, no specific advices could be extracted from the long-term clinical data (Scali et al., 2018). Hence, the most optimal configuration for Ch-EVAR in patients with certain clinical characteristics has not yet been found.

In-vitro studies offer a unique way to pursuing the best configuration, since different combinations can be tested in a controlled benchtop setting, with non-varying anatomies and baseline characteristics. Previously published studies on the most optimal Ch-EVAR/Ch-EVAS combinations fail to present common conclusions. Therefore, a systematic review is required. In this systematic review, the outcomes of controlled in vitro studies are considered in different Ch-EVAR/Ch-EVAS combinations. The aim was to present an overview of the gutter sizes, CG-compression, MG-compression, and other outcomes that might adversely affect clinical outcomes when using the CG technique in in-vitro models. After analyzing the data, we sought to present an overview of the different in-vitro outcomes for the tested CG configurations. These outcomes might be used to aid vascular surgeons for their decisions in the treatment of AAA using different Ch-EVAR set-ups or for further design and optimize Ch-EVAR configurations for clinical use.

Methods

Literature search

The search and data-extraction have been conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) checklist. (Page et al., 2021) PUBMED, EMBASE, and WEB of SCIENCE have been searched on October 12, 2020, and on April 20, 2021. The data were collected and deduplicated using Endnote X9.1 (Clarivate Analytics, Philadelphia, PA). Thesaurus terms and free-text words, including synonyms and closely related words, were used for the following concepts: “Juxtarenal Abdominal Aortic Aneurysm” (jAAA), “Chimney Graft,” and “In Vitro.” No restrictions were applied for language or publication date. The search strategies can be found in Supplementary Figure 1.

Article selection

Titles and abstracts were screened by two independent researchers (JPM and BLT) for relevance and included when matching the following criteria: (i) treatment of juxtarenal or pararenal AAA; (ii) EVAR/EVAS-procedures; (iii) endovascular procedures included CG; (iv) in-vitro studies considering 3D-printed or molded models resembling human AAA; and (v) CG deployed in visceral and/or renal arteries. Case reports, literature reviews, and studies without an in-vitro set-up were excluded. Additionally, studies with the following characteristics were excluded: (i) animal studies, (ii) open procedures, and (iii) no CG, (iv) computational analysis of clinical CT scans (including computational fluid dynamics (CFD)). The data was extracted and managed in a table using Microsoft^® Excel^® 2020 (version 16.40, Microsoft Corporation, Redmond, WA, USA).

Data extraction

Data was extracted by two investigators independently using a standard template (JPM and BLT). The following data were extracted from the relevant articles: author, journal, publication year, study design, number and type of CG and MG used, and details on aortic model (diameter and material). Furthermore, the following outcomes were extracted: (i) gutter size; (ii) CG-compression; iii) MG-compression; (iv) oversizing; (v) location of the gutters; and (vi) (risk of) complications. CG compression and MG compression are defined as decreases of the intraluminal area of the graft (measured perpendicular to the central luminal line) of 30%, as compared to the regular area of the measured graft. This was in line with literature that used 30% as a cutoff value for CG-stenosis and renal artery stenosis and carotid stenosis. (Persu et al., 2014; Takahashi et al., 2016; Zou et al., 2016)

Results

Search results

The search strategy identified 285 records after removal of duplicates. 274 studies were excluded based on title and abstract. The final selection consisted of 11 relevant articles with total of 94 in-vitro configurations and 219 individual tests. (Boersen et al., 2017; De Bruin et al., 2013; Meekel et al., 2020; Mestres et al., 2012; Mestres et al., 2017; Niepoth et al., 2014; Niepoth et al., 2013; Overeem et al., 2018; Shukuzawa et al., 2019; Taneva et al., 2019; Van Schaik et al., 2019) Figure 1 depicts a flow diagram of the search strategy. The study characteristics of all included studies are shown in Table 1. All studies reported on outcomes of using the CG technique in in-vitro models for the treatment of complex AAA. The characteristics studied in each paper substantially differed from each other. The majority of the articles reported on the use of EVAR in 3D-models that simulated human anatomy of complex AAA (De Bruin et al., 2013; Meekel et al., 2020; Mestres et al., 2012; Mestres et al., 2017; Niepoth et al., 2013; Overeem et al., 2018; Taneva et al., 2019), two articles used EVAS (Niepoth et al., 2014; Van Schaik et al., 2019), and one study (Boersen et al., 2017) used both EVAR- and EVAS configurations. All studies used silicone models. Nine articles analyzed optimal configurations for different set-ups with balloon expandable (BE) CG and self-expanding (SE) CG. (Boersen et al., 2017; De Bruin et al., 2013; Meekel et al., 2020; Mestres et al., 2012; Mestres et al., 2017; Niepoth et al., 2014; Overeem et al., 2018; Shukuzawa et al., 2019; Van Schaik et al., 2019) In two of these studies the most favorable extend of MG oversizing was also investigated. (Mestres et al., 2012; Mestres et al., 2017) One study investigated additional procedures to reduce gutter volume in Ch-EVAR by the use of EndoAnchors (EA) (Niepoth et al., 2013) and one study investigated an additional procedure to reduce gutter volume in Ch-EVAS by the use of secondary endobag filling. (Van Schaik et al., 2019) Four study groups investigated the renal artery flow. (Boersen et al., 2017; Niepoth et al., 2014; Overeem et al., 2018; Shukuzawa et al., 2019) Study details including types and sizes of CG and MG, number of used stents, and outcomes are depicted in Table 1.

Figure 1.

Flow diagram of search.

Table 1.

Summary of experimental studies on the outcomes of different CG in EVAR-configurations.

Author, paper (year)	In-vitro evaluation			Grafts and configurations			Deployment characteristics		Outcome measures
	MG type	Size model (mm)	Tests (N)	Set-ups	MG size (mm)	CG size (mm	Over-sizing degree ¹ (%)	Number of CG	Gutters (smallest)	MG-compression	CG-compression	Additional
Meekel, JEVT (2020) (Meekel et al., 2020)	EVAR	1924	57	ABX/GE VSE/GE VBX/GEABX/GCE VSE/GCE VBX/GCE	GE 23, 28.5GCE 23, 26.5, 28.5	ABX 6, 12VSE 6, 13VBX 6, 10, 12	20%, 40%	1	Smallest gutters with small CG/MG.GCE smaller gutters than GE. GCE with VSE superior	-	Small CG/MG combinations: Only VBX showed <30% compression.Large CG/MG combinations: All CG showed <30% compression	-
Taneva, JEVT (2019) (Taneva et al., 2019)	EVAR	27	9	ABX/ED VBX/ED BeGraft/ED	ED 36	ABX 6VBX 6BeGraft 6	30%	1	No significant differences. Smallest gutter areas in VBX/ED, highest gutter areas BeGraft/ED.	No infolding observed	In all set-ups CG compression >30%. 31, 38 and 37% for VBX, BeGraft and ABX, respectively (significantly different between VBX and BeGraft)
de Bruin, JEVT (2013) (De Bruin et al., 2013)	EVAR	1924	16	ABX/GE VSE/GE	GE 23, 28.5	ABX 6, 12VSE 6, 13	20%	1	Smaller gutter areas in VSE/GE versus ABX/GE at top of sealing zone in 23 mm MG (p = 0.021). No significant differences in gutter areas at bottom of sealing zone (p = 0.77) gutter sizes did not differ between 23- and 28.5-mm MG.	A significant higher MG compression in 12/13 mm CG set-ups (43%) compared to 6 mm CG set-ups (21%). The combination of 23 mm MG with 12/13 mm ABX/VSE led to MG compression >50%	No significant disparities for CG compression between ABX and VSE. Higher CG compression in 12/13 mm CG (34%) vs 6 mm CG (27%).In 7 out 16 set-ups CG compression >30% (no specific combinations). All were <45%	In this study, the length of the sealing zone did not influence the outcomes
Mestres, EJVEVS (2012) (Mestres et al., 2012)	EVAR	18, 20, 22, 25 and 27 mm (inner dm aorta)	36	ABX/GE VSE/GE ABX/ED VSE/ED	GE 26, 28.5, 31ED 26, 28.5, 31	ABX 6VSE 6	15%, 30%, 40%	1	Smaller gutter areas with OS 30–40%.Smaller gutters areas in VSE versus ABX.Smaller gutters areas in ED versus GE.Smallest gutters in VSE/ED combination	Median MG-compression in all groups <30%. MG OS of ≥30% increases MG compression.17% and 13% MG compression (Excluder) and 23% and 17% MG compression (Endurant) for MG OS 30% and 40%, respectively.17% and 100% infolding (Excluder) and 0% and 17% infolding (Endurant) for MG OS 30% and 40%, respectively	Median CG-compression in all groups <30%.Higher CG compression in VSE (23%) vs. ABX (9%).Higher VSE CG compression in ED (35%) vs. GE (17%)	Decrease in gutter areas when OS increased: 11.5, 6.2 and 4.3 mm^2; p < 0.001, respectively
Mestres, JVS (2017) (Mestres et al., 2017)	EVAR	18, 20, 22, 25 and 27 mm (inner dm aorta)	36	VSE/GEBeGraft/ED	GE 26, 28.5, 31ED 26, 28.5, 31	VSE 6, 8BeGraft 6, 8	15%, 30%, 40%	2/3	Smaller gutter areas in VSE/GE versus BeGraft/ED.No significant disparities for 15, 30, 40% MG OS.VSE/GE: 7.6, 6.7, 12.8 mm² for two CG; 13.6, 19.3, 14.4 mm² for three CG; for 15, 30, 40% OS, respectively.BeGraft/ED: 23.3, 22.9, 14.8 mm² for two CG; 40.5, 23.3, 21.7 mm² for two CG for 15, 30, 40% OS, respectively	In 2-CG set-up: 100% (VSE/GE) and 33% (BeGraft/ED) infolding for MG OS 40%.In 3-CG set-up: 67% (VSE/GE) infolding for MG OS 30% and 100% (VSE/GE) and 67% (BeGraft/ED) infolding for MG OS 30% and 40%, respectively.In other set-ups no infolding	In 2- and 3-CG set-up no median CG compression >30%.No significant disparities for 15%, 20% or 30% MG OS.Higher CG compression in VSE/GE (15%) vs BeGraft/ED (2%).VSE/GE 26, 19, 11% for two CG, and 27, 3, 15% for three CG for 15, 30, 40% OS.BeGraft/ED: 3, 0, 2% for two CG, and 4, 2, 1% for three CG for 15, 30, 40% OS, respectively	Significant increased risk of infolding in MG with progressive increment of MG oversizing: 0, 0, 67% (p = 0.015) for two CG, and 0, 33, 83% (p = 0.018) for three CG, for 15, 30 and 40% OS, respectively)
Overeem, JEVT (2018) (Overeem et al., 2018)	EVAR	26	3	ABX/EDVSE/EDBeGraft/ED	ED 32	ABX 6VSE 6BeGraft 6	20%	2	Significant differences in gutter volume during cycle in all configurations.Smallest gutter volumes in VSE/ED, highest gutter volumes ABX/ED.	-	Highest D-ratio in VSE/ED (1.26–1.48) and D-ratio in ABX/ED.Lowest D-ratio in BeGraft/ED: 1.08–1.17Highest CG surface area in VSE/ED.	-
Shukuzawa, J Art Org (2019) (Shukuzawa et al., 2019)	EVAR	24	36	ABX/GEVSE/GE	GE 28.5, 31	ABX 6VSE 6	20%, 30%	2	Smaller gutter areas in all set-ups for MG OS 30% vs. 20%	-	-	-
Niepoth, JEVT (2013) (Niepoth et al., 2013)	EVAR	19 24	12	ABX/GEABX/GE +Aptus (EA)	GE 23, 28.5	ABX 6	20%	1	Smaller gutter volumes after applying EA at both supra- and infrarenal positions versus ABX/GE.	Median MG-compression in all groups <30%. No alterations in MG compression after EA deployment	In most set-ups CG compression >50%. CG ballooning subsequent to EA deployment reduced CG compression to <50% in all set-ups
Boersen, JVS (2017) (Boersen et al., 2017)	EVAR/EVAS	26	7 (including one control)	ABX/EDVSE/EDABX/AFXVSE/AFXABX/NellixVSE/Nellix	ED 32AFX 34Nellix 150	ABX 6VSE 6	20%, 30%	2	Smallest gutter volumes in VSE/Nellix. Highest gutter volumes in ABX/AFX.Smaller gutter volumes in VSE versus ABX (in both Ch-EVAR and Ch-EVAS)	-	Higher CG compression in VSE (D-ratio 2.0) vs ABX (D-ratio 1.4).Similar CG compression for Ch-EVAR (D-ratio 1.4) and Ch-EVAS in ABX.Higher CG compression for Ch-EVAR (D-ratio 2.2) vs Ch-EVAS (D-ratio 1.8) in VSE.	CG compression only minimally restricted renal artery flow (391 vs 455 mL/min for the right renal artery and 424 vs 410 mL/min for the left renal artery, for the stented vs. control renal arteries, respectively)

ABX indicates Advanta V12 BECG; CG, Chimney graft; D-ratio, The ratio of the length of the major and minor axes of the CG surface area; EA, EndoAnchors; BeGraft, BeGraft BECG, ED, Medtronic Endurant(-II); GCE, Gore Conformable Excluder; GE, Gore Excluder; MG, Main graft; Nellix, Endologix Nellix; OS, Oversizing; TP1, Table position 1 (start of endograft); TP2, Table position 2 (top of the sealing zone); TP3, Table position 3 (bottom of the sealing zone); VBX, Viabahn BECG; and VSE, Viabahn SECG.

In the included studies, the different types of MG deployed in EVAR were: Endurant™ (II) (Medtronic, Dublin, Ireland); EXCLUDER® AAA Endoprosthesis (GORE®, Newark, DE, USA); EXCLUDER® Conformable AAA Endoprosthesis (GORE®, Newark, DE, USA); and AFX™ Endovascular AAA Delivery System (Endologix, Irvine, CA, USA). These were abbreviated as ED, GE, GCE, and AFX, respectively. EVAS was performed using the Nellix® EVAS system (Endologix). Additionally, one study (Niepoth et al., 2013) used EndoAnchors (Medtronic) to minimize the gutter size, abbreviated as EA. The different CG deployed in Ch-EVAR or Ch-EVAS were: Advanta V12 (Getinge AB, Gothenburg, Sweden); VIABAHN® VBX Balloon Expandable Endoprosthesis (GORE®), VIABAHN® Self Expanding Endoprosthesis (GORE®); and BeGraft/BeGraft+ (Bentley Innomed, Hechingen, Germany). These were abbreviated as ABX, VBX, VSE, and BeGraft, respectively.

Ch-EVAR

Three studies (De Bruin et al., 2013; Meekel et al., 2020; Taneva et al., 2019) determined the gutter characteristics with different types of set-ups in Ch-EVAR configurations. In the first study (Meekel et al., 2020), use of the GCE with VSE seemed to be superior to the other tested combinations. This combination showed small gutter sizes, no other gutter type than type A3 gutters (which are correlated with low endoleak incidence), and low CG compression. In the next study (Taneva et al., 2019), all set-ups showed a CG compression of over 30% without MG infolding, and a significant higher CG compression for the BeGraft compared to the VBX. The third study (De Bruin et al., 2013) presented a significant higher MG compression in the larger CG compared to the smaller sized CG, especially in combination with the 23 mm MG.

One study (Mestres et al., 2012) aimed to identify the most optimal oversizing degree (15%, 30%, and 40%). A decrease in gutter areas was noticed when the degree of oversizing was increase. 30% oversizing generally resulted in the best apposition of the CG/MG, 40% oversizing frequently showed MG infolding. However, in a different study group the average gutter area was significantly larger with 30% MG oversizing than with 20%. (Niepoth et al., 2014)

Another study assessed dynamic behavior of the CG during the cardiac cycle. Ch-EVAR configurations were deployed using physiologic flow. (Overeem et al., 2018) Gutter characteristics and D-ratio (the ratio between the lengths of the major and minor axes as proxy for compression) were assessed. During the cardiac cycle, gutter volumes and D-ratio altered significantly in all set-ups.

The feasibility of EA usage to reduce gutter sizes was investigated in a jAAA model. (Niepoth et al., 2013) At the bottom of the sealing zone a significant reduction of the gutter size was observed when the EA were applied at both supra- and infrarenally, compared to configurations without EA, without increased MG compression. Additionally, CG balloon dilation subsequently to EA placement led to a CG compression of less than 50% in each configuration, compared to mostly >50% without subsequent CG ballooning.

Ch-EVAS

There is only a small number of studies available that analyzed the outcomes of CG technique in Ch-EVAS configurations. (Boersen et al., 2017; Niepoth et al., 2014; Van Schaik et al., 2019) One study investigated the feasibility and optimal CG-balloon timing of Ch-EVAS in a flow model to simulate varying renal ischemia time. (Niepoth et al., 2014) Half-way ballooning during polymer curing mostly led to higher gutters in the ABX configurations. The authors suggested that balloon dilatation of CG should occur during the entire period of polymer injection and curing to prevent CG compression. The authors of a second study that compared EVAR and EVAS concluded that CG compression in these set-ups only minimally restricted renal artery flow. (Boersen et al., 2017) A third study concluded that secondary endobag filling ensured reduction of the gutter volume; however, further CG compression was also noticed in six out of eight models, especially in VSE set-ups. (Van Schaik et al., 2019)

Discussion

Due to the parallel configuration, gutter formation occurs in CG configurations and in itself is not problematic. However, if specific gutter types (A1, A2, or B1) are not detected and treated, patients may suffer from type Ia and Ib endoleaks (Overeem et al., 2017). It is therefore important to strive for the smallest and lowest number of gutters possible. Several considerations need to be considered when deciding upon using CG technique to treat patients with juxta- and pararenal AAA. Since numerous suggestions have been published and numerous types of CG and MG with each of their own “Instructions of Use” (IFU) are available on the market. Nonetheless, Ch-EVAR and Ch-EVAS setups are mostly used outside IFU. Therefore, there seems to be a clear need for advice on optimizations considering the decision on use of different types of MG and CG.

Many studies evaluated the outcomes for the use of either BECG or SECG. Most SECG configurations show smaller gutters but this may come at the expense of higher CG compression. BECG are known for their high radial force (Donas et al., 2012), which might lead to a lower compression rate of the CG than the SECG. Similarly, in Ch-EVAS configurations, higher CG compression was found in SECG compared to BECG. (De Bruin et al., 2013; Van Schaik et al., 2019) However, in one study, the authors found higher CG compression in BECG compared to SECG if the CG were ballooned during the full period of curing of the EVAS polymer. Contrarily to these findings, and in line with the results of the primary two Ch-EVAS studies, if the CG were ballooned only half time during the period of curing, the CG compression seemed to be, again, higher in SECG (Table 2).

Table 2.

Summary of experimental studies on the outcomes of different CG in EVAS-configurations.

Author, paper (year)	In-vitro evaluation			Grafts and Configurations			Deployment characteristics		Outcome measures
	MG type	Size model (mm)	Tests (N)	Set-ups	MG size (mm)	CG size (mm)	Over-sizing degree ¹ (%)	Number of CG	Gutters (smallest)	MG-compression	CG-compression	Additional
Niepoth, JEVT (2014) (Niepoth et al., 2014)	EVAS	25	8	ABX/NellixVSE/Nellix	Nellix 180	ABX 7VSE 8	-	2	Smaller gutter areas at the bottom of the sealing zone and smaller gutter volumes in ABX versus VSE. No differences for ABX versus V SE in gutter areas at the top of the sealing zone.Smaller gutter areas at TP2 in full-time ballooning during polymer curing versus half-time ballooning	-	Higher CG compression in ABX (42%) vs. VSE (22%).Higher CG compression in half-time ballooning during polymer curing versus full-time ballooning
Boersen, JVS (2017) (Boersen et al., 2017)	EVAR/EVAS	26	7 (including one control)	ABX/EDVSE/EDABX/AFXVSE/AFXABX/NellixVSE/Nellix	ED 32AFX 34Nellix 150	ABX 6VSE 6	20%, 30%	2	Smallest gutter volumes in VSE/Nellix. Highest gutter volumes in ABX/AFX.Smaller gutter volumes in VSE versus ABX (in both Ch-EVAR and Ch-EVAS)	-	Higher CG compression in VSE (D-ratio 2.0) vs ABX (D-ratio 1.4).Similar CG compression for Ch-EVAR (D-ratio 1.4) and Ch-EVAS in ABX.Higher CG compression for Ch-EVAR (D-ratio 2.2) vs Ch-EVAS (D-ratio 1.8) in VSE.	CG compression only minimally restricted renal artery flow (391 vs 455 mL/min for the right renal artery and 424 vs 410 mL/min for the left renal artery, for the stented vs. control renal arteries, respectively)
van Schaik, JEVT (2019) (Van Schaik et al., 2019)	EVAS	19 24	-	ABX/NellixVSE/Nellix	Nellix 180	ABX 6VSE 6	-	2	Smaller gutter areas and volumes in VSE versus ABX after primary fill.Secondary endobag filling reduced gutter volume in both VSE and ABX.	-	Higher CG compression in VSE versus ABX after primary fill. Secondary endobag increased CG compression strongly in VSE, but not in ABX.

Several studies evaluated the effect of MG oversizing. From these studies it can be deduced that 30% oversizing seems optimal with smallest gutters and without occurrence of MG infolding. The decrease in gutter size that follows oversizing was in line with the clinical findings of de Blic et al. who found that over 25% oversizing reduced the gutter size, yet, no differences in endoleaks were observed. (De Blic et al., 2018) MG compression and MG infolding mostly arise as a consequence of excessive (>30%) oversizing or the use of relatively large CG (Mestres et al., 2012; Mestres et al., 2017). Although there is no general consensus on the advised maximum MG compression, literature agrees on the increased risk of flow deprivation, in-stent thrombosis, MG infolding, and potentially collapse as a consequence of increased MG compression. (De Blic et al., 2018; Mestres et al., 2017; Moulakakis et al., 2013)

Out of the 11 studies included, one directly compared both Ch-EVAR and Ch-EVAS configurations and found the smallest gutters in Ch-EVAS combined with SECG (Boersen et al., 2017) which was in line with the clinical findings as presented by Mazzaccaro et al. (Mazzaccaro et al., 2019). Stenson et al. proposed that Ch-EVAS set-up could be used in selected cases, since lower therapeutic failure was observed than in straightforward EVAS during 2 years follow-up. (Stenson et al., 2020) These results were not backed by Zoethout et al. which showed similar disappointing results for Ch-EVAS comparable to regular EVAS within IFU, with a trend towards ongoing migration at 3 years follow-up. (Zoethout et al., 2019)

Placement of EA at both suprarenal and infrarenal positions seems to decrease gutter size without effecting CG or MG compression. (Niepoth et al., 2013) These results were supported by clinical evidence of the effect of EA on fixation and sealing in standard and complex EVAR. (Jordan et al., 2014; Qamhawi et al., 2020)

The overview of different in-vitro CG configurations presents many potentially clinically important outcomes; however, no direct bench-to-bedside translation can be made upon these results. The current review is limited by high heterogeneity between the studies, therefore pooling studies is impossible. Unfortunately, only 11 studies could be included, therefore some investigations were only performed by a single study (EA for instance). The different types of CG could be divided in two big groups: BECG or SECG. General conclusions were drawn based upon this division; however, the CG within these groups differ in fabrics and characteristics. The difference in CG undoubtedly limits the strength of these results. Despite these limitations, this overview might guide physicians in their decision for different configurations to treat different jAAA anatomies, since in-vitro experiments create an environment in which controlled, repeatable and comparable experiments can be performed.

The CG technique is a relative novel but feasible approach in the treatment of juxta- and pararenal AAA, but many lessons are yet to be learnt. For future research on this subject, a standard protocol for in vitro studies including study design and measurement parameters is recommended to make a meta-analysis of all the outcomes possible. Next, the use of computational fluid dynamics or 4D flow magnetic resonance imaging data includes changes during the cardiac cycle and blood clotting in the analyses, which are parameters that might be included in the experimental in vitro setting. Using 4D imaging data might also exclude discussions on whether 2D D-ratios as a proxy for compression or 2D graft areas to calculate graft compression should be used. Further research is needed to determine the optimal set-up in the increasing number of different combinations of MG and CG and the specific adjustments needed within these combinations to increase safety and clinical outcomes. Determining the optimal model can also be used for investigations of branched or fenestrated devices.

Conclusion

The objective of the current systematic review is to provide an overview of different Ch-EVAR and Ch-EVAS configurations for simulated complex AAA repair in an in vitro setting. In vitro studies offer the opportunity to test multiple CG and MG combinations with different sizing. Based upon the limited number of studies with considerable heterogeneity, the optimal configuration is not found. Further investigations are still required to establish the most optimal configuration for CG technique in complex AAA.

Supplemental Material

Supplemental Material - What we have learned from in-vitro studies of the chimney endovascular technique for treatment of complex abdominal aortic aneurysms: A systematic review

Supplemental Material for What we have learned from in-vitro studies of the chimney endovascular technique for treatment of complex abdominal aortic aneurysms: A systematic review by Jorn P Meekel, Bich L Tran, Theodorus G van Schaik, Konstantinos P Donas, Gergana T Taneva, Vincent Jongkind, and Kak K Yeung in Vascular

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Bich L Tran

Gergana T Taneva

Supplemental Material

Supplemental material for this article is available online.

Appendix

References

Boersen

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