Systematic Review and Meta-Analysis of Ex-Situ and In-Situ Fenestrated Stent-Grafts for Endovascular Repair of Aortic Arch Pathologies

Abstract

Purpose:

To gain insight into safety and efficacy of in situ and ex-situ fenestration techniques for total endovascular arch repair. The term ex-situ fenestration is referring to physician-modified stent-graft technique where fenestration is performed on a back table.

Methods:

Electronic search was conducted according to PRISMA (Preferred Reporting Items for Systematic review and Meta-analyses) guidelines from 2000 to 2020. The main outcomes measured were 30-day mortality, stroke, aortic-related mortality, and reintervention rates.

Results:

Fifteen studies were eligible: 7 ex-situ fenestration (189 patients) and 8 in-situ fenestration (149 patients). In ex-situ group, dissection was the main pathology treated and proximal sealing zones were Z0 or 1 in 53.5% of patients. In in-situ group, dissection and aneurysm were equally represented in around 40% of cases and proximal sealing zones were Z0 or 1 in 46.5% of patients. Cumulative 30-day all-cause mortality was similar in both groups: 3.8% (95% confidence interval [CI]: 1.7%–8.2%) and 3.8% (95% CI: 1.6%–8.9%), respectively, in ex-situ and in-situ groups and stroke rate of 2.8% (95% CI: 1.1%–7%) and 5.3% (95% CI: 2.6%–10.5%). After a 11.1 ± 2.6 months mean follow-up for ex-situ and 16.7 ± 2.3 months for in-situ group, there were 5.2 and 1.4 reinterventions per 100 patients-years, respectively, for ex-situ and in situ groups. Aortic-related mortality rates of, respectively, 3.2% (95% CI: 1.3%–7.4%) and 2.6% (95% CI: 0.9%–7.3%) were noted in ex-situ and in situ groups.

Conclusion:

The reported data show favorable short-term results of both ex-situ and in-situ fenestration techniques with low mortality and strokes rates. However, durability is still questionable given the lack of long-term data. Both options may have their place in arch repair beyond the spectrum of emergent and urgent cases, on condition that results stand the test of time.

Clinical Impact

In situ and ex-situ fenestration techniques have been initially developed to overcome emergency or as a bail out techniques however giving the promessing favorable short term results indications of these techniques may be extended to elective patients ineligible to customized stent-grafts and possibly in the futur to more elective cases as an option for total endovascular arch repair.

Keywords

stent-graft aortic arch pathologies physician-modified stent-graft fenestrated stent-graft home-made stent-graft surgeon-modified stent-graft meta-analysis

Introduction

While the first publications on custom-made fenestrated stent-graft (SG) in the arch indeed reported the feasibility of the technique and encouraging results,^1,2 long manufacturing time, ineligibility based on anatomical criteria, lack of accessibility to customized devices in some centers, along with reputed difficulty in perfect deployment, and orientation of fenestration all led to the emergence of ex-situ and in situ fenestration technologies. The term ex-situ fenestration is referring to physician-modified stent-graft technique where fenestration is performed on a back table. Initially described as bail-out techniques, ex-situ and in-situ fenestration concepts now offer a wide range of possibilities to modify standard SG³ and an increasing number of series reports have been published.

To date, the respective place of ex-situ and in-situ techniques in arch repair, notably elective cases, remains controversial, and debatable; hence, the need for a comprehensive review. Proponents of the competing endovascular technique, namely customized devices, question the durability of the modified devices, and the viability of long-term outcomes which could be impacted by device integrity alteration and lack of quality control.

The present study aims to perform a comprehensive meta-analysis of the available literature with regard to the early and mid or late outcomes of ex-situ and in-situ fenestrated stent-grafts to determine whether it is a safe and effective option in total endovascular arch pathology management.

Materials and Methods

Search Strategy

This review was planned and performed in accordance with the PRISMA (Preferred Reporting Items for Systematic review and Meta-analyses) guidelines,⁴ and the protocol was prospectively registered in PROSPERO as CRD 42020156501. An electronic search was conducted in MEDLINE, EMBASE, and Cochrane databases to determine all studies pertaining to total endovascular arch repair from 2000 to 2020. The following search terms “aneurysm,” “dissection,” “intramural hematoma,” “aort*,” “arch,” “endovascular,” “endoluminal,” “stent graft,” “TEVAR,” “thoracic endovascular aortic repair,” “fenestrat*,” “physician modified,” “home-made,” “laser,” “radiofrequency,” and the following Medical Subject Heading terms: “aortic aneurysm, thoracic,” “aortic aneurysm,” “aortic dissection,” “dissection,” “aorta, thoracic,” “endovascular surgery,” “endovascular aneurysm repair,” and “stent or stent graft” were used in combination with the Boolean operators AND or OR. The reference lists of the selected articles as well as published abstracts from major vascular meetings were also scrutinized to identify additional relevant studies not found through the electronic search strategy. A first selection level on the basis of titles and abstracts was conducted followed by a full-text review to confirm or infirm eligibility (full search strategy is available in the Supplemental Appendix). Two reviewers independently analyzed all records, with disagreement resolved after discussion by a third.

Selection Criteria

Studies were considered eligible if the following criteria were present: (1) total endovascular arch repair, (2) entire or partial arch coverage, (3) more than 5 patients treated, and (4) sufficient data of early and short- or mid-term outcomes. Exclusion criteria comprised: (1) technical notes, experimental studies and case reports of less than 5 patients; (2) Non-English-language articles; (3) commentaries, editorials and review articles; (4) studies reporting on feasibility of fenestrated SG and those with insufficient or only early outcomes data; (5) reports of only scalloped stent-grafts; (6) combination of fenestrated and surgical, fenestrated and hybrid, fenestrated, and parallel graft repair where data regarding fenestrated stent-graft could not be separated from the rest of the cohort; (7) open fenestrated stent-graft or hybrid prosthesis series; and (8) semi-custom-made stent-grafts series. Studies including hybrid repair as a part of ex-situ or in-situ fenestration procedure were not excluded. For duplicate data, the study with the highest number of patients and longest follow-up period was chosen.

Data Collection

Two authors analyzed the selected articles and extracted data concerning patient characteristics, pathology treated, operative details, and outcomes of interest. Divergences were discussed and resolved by the lead author. The main end points were as follows: 30-day mortality, stroke, aortic-related mortality, and reintervention. The quality of evidence was assessed by the 2 above-mentioned authors using GRADE tool.⁵

Definitions

Technical success of the procedure was defined on an intention-to-treat basis. It implied accurate SG deployment with preservation of branch stent patency without surgical conversion or additional unplanned intervention, death, or endoleak in the first 24 hours after index procedure.

Technical success of fenestration implied accurate deployment with preservation of branch patency in the absence of conversion or endoleak.

Fenestration-related complications comprised type Ic or III endoleak, thrombosis, or stenosis.

Stroke: both minor and major strokes occurring during hospitalization were considered. Transient ischemic attacks were not considered in the incidence evaluation of this complication.

Early reintervention corresponded to stent-graft-related iterative procedure occurring within 30 days.

Late aortic-related reintervention comprised all secondary procedures occurring more than 30 days after index endovascular repair, whether related to stent-graft, target vessel, or to aortic treated segment. Reinterventions unrelated to the aorta were ignored.

Statistical Analysis

Pooled statistics of patients and procedure characteristics were calculated and presented as weighted frequencies with 95% confidence intervals (CIs) for categorical variables and as weighted means with standard deviation for continuous variables. A pooled proportion meta-analysis of outcomes for each group was completed and data expressed as frequencies with 95% CI.

Heterogeneity across studies was investigated by calculating I² statistics. High heterogeneity (I²>50%) indicated the use of a random effects model, low heterogeneity (I²<50%) that of a fixed effects model. Publication bias was evaluated through visual inspection of funnel plots and calculation of Egger regression test. To evaluate the impact of the number of fenestrations on stroke rate a subgroup analysis was conducted by pooling and comparing available subgroup data. A 2-sided p<0.05 was considered statistically significant. All statistical analysis was performed using Comprehensive Meta-Analysis Software version 2 (Biostat, Littlewood, New Jersey)

Results

A total of 520 articles were initially identified through literature search and then screened. Of these 15 met the inclusion criteria and were retained for this review^6–20: 7 studies, with a total of 189 patients, focused on ex-situ technique, and 8 studies with a total of 149 patients examined in-situ technique. All studies were retrospective and all but one reported single-center experience. Figure 1 recaps literature search results.

Ex situ Fenestration Group

Patient characteristics

The most common pathology treated was dissection (60.6%) followed by degenerative aneurysm (21.3%). The procedure was performed urgently or emergently in 40.1% of patients. The disease involved mainly proximal and mid arch (58.6%) (Table 1). Surgical risk status, according to the American Society of Anesthesiologists score, was mentioned in only 3 studies.^15,17,19 It was graded as 3, 4, or 5 for 81.4% of cases.

Table 1.

Descriptive Characteristics of the Included Studies in In-Situ and Ex-Situ Fenestrated Stent-Graft Groups.

Author	n patients	Age (years)	Emergent or urgent	Pathology			Lesion location		Landing zone			Number of fenestrations		Fenestration technique
Author	n patients	Age (years)	Emergent or urgent	Aneurysm	Dissection	Other	Proximal or mid arch	Distal arch	0	1	2	1	2 or more	Fenestration technique
In situ fenestration
Redlinger et al⁶	22	57 (37–83)	22	4	12	6	2	20	2	1	19	22	0	Laser
Tse et al⁷	10	74	1	8	0	2	1	9	0	1	9	10	0	Radiofrequency
Katada et al⁸	12	NR	0	8	4	0	12	0	12	0	0	0	12	Puncture
Hongo et al⁹	17	NR	NR	17	0	0	17	0	17	0	0	17	0	Puncture
Shang et al¹⁰	10	48.1 (40–67)	0	1	9	0	2	8	10	0	0	0	10	Biopsy needle
Xiao Hui et al¹¹	18	52.6 ± 6.5	4	0	18	0	0	18	0	0	18	18	0	Puncture with guidewire 0.014
Liu et al¹²	23	66 ± 11	18	12	0	11	14	9	3	11	9	9	14	Laser
Xiang et al¹³	37	55.1 (31–78)	21	9	27	1	12	25	6	5	26	26	11	Outback catheter
Cumulative data (weighted average, 95% CI)	149	55.7 ± 3.5	40.1% (19.3%–65.2%)	41.3% (20.3%–65.9%)	43.6% (19.5%–71.2%)	–	36.8% (14.9%–65.9%)	63.2% (34.1%–85.1%)	35.9% (11.6%–70.6%)	10.6% (4.3%–23.6%)	51% (22.7%–78.6%)	58.5% (30.5%–86.4%)	17.4% (5.9%–28.8%)
Ex situ fenestration
Zheng et al¹⁴	61	NR	NR	3	51	7	26	35	6	20	35	40	21	—
Canaud et al¹⁵	36	74.7 ± 9	11	18	9	9	25	11	16	9	11	36	0	—
Zhu et al¹⁶	20	51.7 (18–83)	6	0	20	0	0	20	0	1	19	20	0	—
Zhu et al¹⁷	10	62 (45–81)	NR	6	1	3	10	0	5	5	0	0	10	—
Li et al¹⁸	32	58.2 ± 11.2	NR	5	15	12	3	29	0	3	29	32	0	—
Kuo et al¹⁹	13	65	5	1	11	1	13	0	13	0	0	0	13	—
Canaud et al²⁰	17	69.6 (23–83)	2	7	10	0	17	0	17	0	0	0	17	—
Cumulative data (weighted average, 95% CI)	189	63.6 ± 3.5	29.1% (20.3%–39.9%)	21.3% (8.7%–43.5%)	60.6% (33.4%–82.5%)	—	58.6% (27.8%–83.8%)	41.4% (16.2%–72.2%)	36.2% (11%–72.2%)	17.3% (7.8%–34%)	41.6% (16%–72.7%)	48.3% (23%–73.7%)	18.6% (7.3%–30%)

Data are presented as n (%) or mean± standard deviation or median (interquartile range).

Abbreviations: CI, confidence interval; NR, not reported.

Technical aspects and operative data

Fenestration technique was performed using all available stent-grafts with a majority of Valiant® (46.6%). Different configuration types were adopted: single fenestration in 48.3%; double or more fenestrations in 18.6%, for a total of 258 target vessels preserved. This corresponds to a mean fenestration/patient ratio of 1.5 ± 0.2. Proximal sealing zones were Z0 or 1 in 53.5% of patients (Table 1). Mean procedure duration was 114.9 ± 39 minute with a mean time for stent-graft modification of 46 minute (range: 14–125 minute) and a mean fluoroscopy time of 31.6 ± 10.9 minute.

Early Outcomes

Technical success rate of fenestration per total patients was 94.4% (95% CI: 88.9%–97.2%; I²: 0%) and per all target vessels 95.4% (95% CI: 90.8%–97.8%; I²: 4.6%). This led to intraoperative conversion for target vessels loss in 4.1% of patients (95% CI: 1.8%–8.8%; I²: 0%) (Table 2).

Table 2.

Early Outcomes Data for In-Situ and Ex-Situ Fenestrated Stent-Grafts.

Author	Technical success rate of fenestration per all patients	Technical success rate of fenestration per all target vessels	30-day mortality	Stroke	Early fenestration related complication	Early endoleak type I	Early aortic related reintervention
In situ fenestration
Redlinger et al⁶	22 (97.8)	22 (97.8)	1 (4.5)	0 (2.2)	0 (2.2)	0 (2.2)	1 (4.5)
Tse et al⁷	6 (60)	6 (60)	1 (10)	0 (4.5)	0 (4.5)	0 (4.5)	0 (4.5)
Katada et al⁸	11 (91.7)	33 (97.1)	0 (3.8)	0 (3.8)	0 (3.8)	1 (8.3)	0 (3.8)
Hongo et al⁹	17 (97.2)	17 (97.2)	0 (2.8)	1 (5.9)	0 (2.8)	0 (2.8)	1 (5.9)
Shang et al¹⁰	8 (80)	26 (92.9)	0 (4.5)	0 (4.5)	0 (4.5)	0 (4.5)	0 (4.5)
Xiao Hui et al¹¹	18 (97.4)	18 (97.4)	0 (2.6)	0 (2.6)	0 (2.6)	0 (2.6)	0 (2.6)
Liu et al¹²	23 (97.9)	23 (97.9)	0 (2.1)	1 (4.3)	0 (2.1)	0 (2.1)	0 (2.1)
Xiang et al¹³	35 (94.6)	53 (96.4)	0 (1.3)	3 (8.1)	0 (1.3)	0 (1.3)	0 (1.3)
Cumulative data (weighted average, 95% CI)	88.7% (80.2%–93.8%)	94% (86.3%–97.5%)	3.8% (1.6%–8.9%)	5.3% (2.6%–10.5%)	2.8% (1%–7.1%)	3.4% (1.3%–8.3%)	3.6% (1.5%–8.4%)
Ex situ fenestration
Zheng et al¹⁴	61 (99.2)	88 (99.4)	1 (1.6)	0 (0.8)	0 (0.8)	0 (0.8)	0 (0.8)
Canaud et al¹⁵	36 (98.6)	36 (98.6)	2 (5.6)	1 (2.8)	1 (2.8)	1 (2.8)	0 (1.4)
Zhu et al¹⁶	18 (90)	18 (90)	0 (2.4)	0 (2.4)	0 (2.4)	0 (2.4)	0 (2.4)
Zhu et al¹⁷	9 (90)	9 (90)	1 (10)	0 (4.5)	0 (4.5)	0 (4.5)	0 (4.5)
Li et al¹⁸	30 (93.8)	30 (93.8)	0 (1.5)	0 (1.5)	0 (1.5)	2 (6.3)	0 (1.5)
Kuo et al¹⁹	13 (96.4)	38 (98.7)	0 (3.6)	0 (3.6)	0 (3.6)	0 (3.6)	0 (3.6)
Canaud et al²⁰	16 (94.1)	36 (97.3)	0 (2.8)	1 (5.9)	0 (2.8)	0 (2.8)	0 (2.8)
Cumulative data (weighted average, 95% CI)	94.4% (88.9%–97.2%)	95.4% (90.8%–97.8%)	3.8% (1.7%–8.2%)	2.8% (1.1%–7%)	2.4% (0.9%–6.1%)	3.5% (1.5%–7.8%)	2.1% (0.7%–5.8%)

Data are presented as n (%).

Abbreviations: CI, confidence interval; NR, not reported.

Cumulative 30-day/in hospital all-cause mortality was 3.8% (95% CI: 1.7%–8.2%; I²: 0%). Stroke rate was 2.8% (95% CI: 1.1%–7%; I²: 0%) (Table 2). Subgroup analysis of stroke rate according to number of fenestrations per patient indicated no significant difference in stroke rate between 1 fenestration or more: 2% vs 4.2%, p=0.412. Early fenestration-related complications were observed at a cumulative rate of 2.4% (95% CI: 0.9%–6.1%; I²: 0%). In particular, 3.5% (95% CI: 1.5%–7.8%; I²: 0%) type I endoleak were detected post-operatively. Early reintervention was required in 2.1% of patients (95% CI: 0.7%–5.8%; I²: 0%) (Table 2).

Short to Mid-term Outcomes

Mean follow-up was 11.1 ± 2.6 months for a total of 294.1 patient-years of follow-up with no studies providing mid-term follow-up of more than 3 years (Table 3). One case of graft infection was reported which was treated with open repair. Postoperative course proved fatal.

Table 3.

Short or Mid-Term Outcomes for In-Situ and Ex-Situ Fenestrated Stent-Grafts.

Author	Follow-up, months	Late all-cause mortality	Late aortic related mortality	Late fenestration related complication	Late aortic related reintervention	Freedom from any branch stenosis or occlusion	Late endoleak type I
In situ fenestration
Redlinger et al⁶	11 (1–40)	2 (9.1)	0 (2.2)	0 (2.2)	2 (9.1)	22 (97.8)	0 (2.2)
Tse et al⁷	12 (1–33)	0 (4.5)	0 (4.5)	0 (4.5)	0 (4.5)	6 (60)	0 (4.5)
Katada et al⁸	15 (2–41)	NR	NR	NR	NR	11 (91.7)	NR
Hongo et al⁹	21.7 (1.5–62.3)	5 (29.4)	0 (2.8)	0 (2.8)	0 (2.8)	17 (97.2)	0 (2.8)
Shang et al¹⁰	5.4 ± 3.7	0 (4.5)	0 (4.5)	1 (10)	0 (4.5)	8 (80)	0 (4.5)
Xiao Hui et al¹¹	38 (24–52)	0 (2.6)	0 (2.6)	0 (2.6)	0 (2.6)	18 (97.4)	0 (2.6)
Liu et al¹²	10.5 ± 5.7	0 (2.1)	0 (2.1)	0(2.1)	0 (2.1)	23(97.9)	NR
Xiang et al¹³	21 (19–33)	0 (1.3)	0 (1.3)	1 (2.7)	1 (2.7)	36 (97.3)	0 (1.3)
Cumulative data (weighted average, 95% CI)	16.7 ± 2.3	11.4% (6%–20.6%)	2.6% (0.9%–7.3%)	3.6% (1.4%–8.8%)	4.5% (1.9%–9.9%)	91.2% (81.1%–96.1%)	2.1% (0.5%–4.7%)
Ex situ fenestration
Zheng et al¹⁴	12	0 (0.8)	0 (0.8)	0 (0.8)	0 (0.8)	61 (99.2)	0 (0.8)
Canaud et al¹⁵	11.4 ± 6	3 (8.3)	1 (2.8)	0 (1.4)	3 (8.3)	35 (97.2)	1 (2.8)
Zhu et al¹⁶	7.5 (2–14)	0 (2.4)	0 (2.4)	0 (2.4)	0 (2.4)	19 (95)	0 (2.4)
Zhu et al¹⁷	13.3 (6–19)	0 (4.5)	0 (4.5)	0 (4.5)	1 (10)	9 (90)	0 (4.5)
Li et al¹⁸	8.3 ± 5.3	1 (3.1)	1 (3.1)	1 (3.1)	0 (1.5)	29 (90.6)	NR
Kuo et al¹⁹	20 (3–28)	3 (23.1)	1 (7.7)	0 (3.6)	5 (38.5)	13 (96.4)	2 (15.4)
Canaud et al²⁰	7 ± 2	0 (2.8)	0 (2.8)	0 (2.8)	0 (2.8)	16 (94.1)	0 (2.8)
Cumulative data (weighted average, 95% CI)	11.1 ± 2.6	7.5% (3.9%–13.9%)	3.2% (1.3%–7.4%)	2.4% (0.9%–6.2%)	7.8% (3.1%–17.9%)	94.3% (89%–97.2%)	1.5% (0.4%–3.4%)

Data are presented as n (%) or mean ± standard deviation or median (interquartile range).

Abbreviations: CI, confidence interval; NR, not reported.

Cumulative mid-term reintervention rate was 7.8% (95% CI: 3.1%–17.9%; I²: 63.6%) corresponding to 5.2 reinterventions per 100 patient-years with a cumulative rate of fenestration-related complications of only 2.4% (95% CI: 0.9%–6.2%; I²: 0%). Type I endoleak was detected in follow-up CT scans at a cumulative rate of 1.5% (95% CI: 0.4%–3.4%; I²: 0%). Cumulative mid-term all-cause mortality was 7.5% (95% CI: 3.9%–13.9%; I²: 31.8%) with an aortic-related mortality rate of 3.2% (95% CI: 1.3%–7.4%; I²: 0%) (Table 3). All 3 outcomes (endoleak, reintervention, aortic-related mortality showed a low level of evidence according to GRADE approach (Table 4).

Table 4.

Overall GRADE Quality Assessment of the Different Early and Mid-Term Outcomes.

Studies (n)	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Quality
30-day all-cause mortality
15	Observational studies	Serious	Not serious	Not serious	Not serious	Undetected	⊗⊗⊗○Moderate
Stroke
15	Observational studies	Serious	Not serious	Not serious	Not serious	Undetected	⊗⊗⊗○Moderate
Technical success
15	Observational studies	Serious	Not serious	Not serious	Serious	Undetected	⊗⊗○○low
Early endoleak
15	Observational studies	Serious	Not serious	Not serious	Serious	Undetected	⊗⊗○○low
Late endoleak
12	Observational studies	Very Serious	Not serious	Not serious	Serious	Strongly suspected	⊗○○○Very low
Aortic-related mortality
14	Observational studies	Very serious	Not serious	Not serious	Serious	Strongly suspected	⊗○○○Very low
Stent-related reintervention
14	Observational studies	Very serious	Not serious	Not serious	Serious	Strongly suspected	⊗○○○Very low

In-situ Fenestration Group

Patient characteristics

Dissection and degenerative aneurysm were equally represented in around 40% of patients as an indication for in situ fenestration. Almost 70% of patients were referred for elective repair and only 29.1% treated in an emergency or urgent setting. Distal arch was mainly involved in 63.2% of patients (Table 1). Surgical risk status, according to the American Society of Anesthesiologists score, was not mentioned.

Technical aspects and operative data

Different devices were used with 33% corresponding to Valiant® stent-grafts. SG design consisted in single (58.5%) and double or more (17.4%) fenestrations for a total of 223 target vessels preserved and a mean fenestration/patient ratio of 1.46 ± 0.19. Proximal sealing of the graft was achieved in Z0 or 1 in 46.5% of patients (Table 1). Various perforation methods were used, including needle, wire, laser, and radiofrequency. Mean repair time was 270.4 ± 36 minute with a mean fluoroscopy time of 51.9 ±13.3 minute. Mean fenestration time was not mentioned by any of the studies.

Early Outcomes

Technical success rate of fenestration per total patients was 88.7% (95% CI: 0.2%–93.8%; I²: 49.7%) and per all target vessels 94% (95% CI: 86.3%–97.5%; I²: 54.9%). Conversion to correct target vessel events was required in 5.7% of patients (95% CI: 2.6%–11.9%; I²: 0%) (Table 2).

Cumulative 30-day/in-hospital all-cause mortality was 3.8% (95% CI: 1.6%–8.9%; I²: 0%). Stroke occurred post-operatively at a cumulative rate of 5.3% (95% CI: 2.6–10.5%; I²: 0%) (Table 2) with, similarly to ex-situ cohort, no significant difference when stratified according to number of fenestration (1 vs more than one): 3.9% vs 4.2%, p=0.950. Cumulative early fenestration-related complication was 2.8% (95% CI: 1%–7.1%; I²: 0%) while type I endoleak was found in 3.4% of patients (95% CI: 1.3%–8.3%; I²: 0%). Early reintervention rate either surgical or endovascular was 3.6% (95% CI: 1.5%–8.4%; I²: 0%) (Table 2).

Short to Mid-term Outcomes

Mean follow-up period was 16.7 ± 2.3 months for a total of 266.9 patient-years of follow-up. Only one study provided mid-term follow-up of more than 3 years (Table 3). No graft infection was reported out of the 149 patients treated. Cumulative mid-term reintervention rate was 4.5% (95% CI: 1.9%–9.9%; I²: 0%) corresponding to 1.4 reinterventions per 100 patient-years with a cumulative incidence of fenestration-related complications of 3.6% (95% CI: 1.4%–8.8%; I²: 0%). At some point during follow-up, there was 2.1% of type I endoleak (95% CI: 0.5%–4.7%; I²: 0%).

Cumulative mid-term all-cause mortality was 11.4% (95% CI: 6%–20.6%; I²: 46.6%) with an aortic-related mortality rate of 2.6% (95% CI: 0.9%–7.3%; I²:0%) (Table 3). All 3 outcomes (endoleak, reintervention, and aortic-related mortality) showed a low level of evidence according to GRADE approach (Table 4).

Discussion

Ex-situ and in-situ fenestration techniques were initially conceived to overcome emergency or as a bail out,²¹ but in point of fact 60% or more of indications have turned out to be elective, echoing broad acceptance of the treatment and, one can suppose, its effectiveness. Even though first reports of these techniques were focused on left subclavian artery (LSA) preservation, the present review revealed that proximal sealing zone was Z0 or Z1 in almost 50% of patients in both groups. This breakthrough toward hemi or total arch endovascular repair again echoes the validity of the technique. Advantages and disadvantages of the 2 techniques are summarized in Table 5.

Table 5.

Main Advantages and Disadvantages of Ex-Situ And In-Situ Fenestration Techniques.

	Advantages	Disadvantages
In-situ	Immediate stent-graft availability	Temporary ischemic period
In-situ	Immediate stent-graft availability	Risk of fabric embolisationHigher cost compared to ex-situ fenestration related notably to the device for fenestration
Ex-situ	No ischemic time	Risk of stent-graft integrity destabilization
Ex-situ	Possibility of fenestration reinforcement	Risk of stent-graft contamination

A high technical success rate was noted with both techniques. The few failures reported were related to either hostile anatomy of the target vessel—namely severe tortuosity, acute angle of target vessel takeoff from aortic arch, anterior or posterior shift of takeoff axis of supra-aortic trunks with regard to the arch axis, and/or hostile anatomy of the arch with high tortuosity and severe arch angulation.

The use of 3D fusion imaging maybe helpful to improve technical feasibility given the relatively fixed configuration of aortic arch but more evidence is needed to confirm this benefit.²² Besides, for in-situ fenestration the availability of steerable and/or robotic sheaths helps orientate the puncture device at a 90°angle to the endograft,^23,24 thus increasing fenestration feasibility, even if the angle between the target vessel and the arch is more acute. For ex-situ technique, the pre-loaded guidewire through LSA fenestration is an artifice which allows proper orientation of the fenestration toward the LSA, and consequently facilitates alignment of the SG to the target vessels.²⁵

In the short term, the main issue which hinders wide acceptance and spread of total endovascular arch repair remains the risk of stroke. Our review revealed that both techniques can be performed safely, as evidenced by a low stroke rate (2.8% ex-situ; 5.3% in-situ) and low early-related fenestration complications.

Stroke mechanisms invoked are mainly embolic, from atherosclerotic debris or air captured in the SG.²⁶ Data analysis showed that the use of more than one fenestration device incurred more stroke risk in ex-situ group (2% versus 4.2%). Even if the difference was not statistically significant, this result probably suggests that, rather than air embolism, the need for snare, guide wire, and device manipulation, as well as tracking, is the main contributive mechanism in the occurrence of this complication. The trick of preloaded wire running through the fenestration helps proper orientation.²⁵

The above-mentioned stroke occurrence was roughly twice as high in in-situ group compared to ex-situ. This can be explained by the temporary cerebral ischemia time inherent to the technique of fenestration and constitutes an additional potential mechanism of stroke, along with embolic mechanism.²⁵ Different brain protection techniques are thus proposed, either by establishing an extracorporeal circulation¹⁰ or by external flow derivation methods—including prosthetic bypass⁹ and temporary shunt,¹³ or by combination of internal bypass with external derivation.²⁷ Early mortality rate of 3.8% in both groups compares well with that of 5.3% after open repair as reported in a recent meta-analysis,²⁸ and is even genuinely favorable, considering that endovascular approach was limited to high-risk patients contraindicated for open repair.

One concern pinpointed by opponents of these techniques is the lack of quality control and the risk of device infection related to manipulations. This review showed that modifying SG did not seem to expose to a greater risk of contamination. Although rare, this event cannot be neglected because it can be associated with severe consequences hence the importance of prevention.

The low reintervention rate after both ex-situ and in-situ techniques (7.8% and 4.5%, respectively), along with the low aortic-related mortality during follow-up noted similarly in both groups (3.2% and 2.6%, respectively), could suggest relative durability, stability, and promise. However, the lack of sufficient hindsight and adequate late data should incite caution, since the mean follow-up was less than 24 months in both groups.

When analyzing the technique of in-situ fenestration, it is interesting to note that different methods have been developed, categorized as mechanical or physical, each with its own technical difficulties and concerns.³ Mechanical methods encompass wires and various needles, while physical methods include laser and radiofrequency perforation. Mechanical approach needs graft stabilization such as the “squid-capture” technique described by Hongo et al⁹ and also raises concerns about substantial fabric damage.²⁹ Physical approach provides a quicker method of perforation with a more regular and cleaner aspect of fenestration,⁶ but an acute takeoff angle from the arch vessels can cause difficulties. Besides, the risk of fabric filament embolization mitigates the attractivity of these techniques.

Ethical aspect of these techniques needs to be highlighted. Given that such procedures remain off label, it is recommended that modified SG be performed in emergency cases or within the frame work of investigational studies approved by institutional review board.

Limitations

The weakness of the available data generated a number of limitations and thus invites caution in result interpretation. First, the heterogeneity of the techniques used to perform fenestration within in-situ group. Second, the lack of adjustment for significant confounders according to pathology, proximal landing zone, and indication (emergent or elective), which might have caused differences in outcome occurrence. Metaregression could have helped but was unfortunately not feasible, given the absence of data in the different subgroups. Third, the absence of comparative studies, making it impossible to perform proportional comparative meta-analysis. Fourth, inconsistency across series in the definition of outcomes which may have biased the pooled analysis. This is partly related to the absence of reporting standards for arch treatment. Last, but not least, the relatively limited follow-up in both groups, might conceal more adverse events, consequently questioning technique durability.

Conclusion

As of today, the role of in-situ and ex-situ fenestration in arch repair is yet to be decisively defined, and controversy related to the durability of such devices is still rife. Nevertheless, the present review provides some valuable insights into the feasibility, safety, and efficacy of both techniques. The low early mortality and stroke rates, along with the acceptable mid-term results, may support the utility and appropriateness of the 2 techniques for arch repair beyond the spectrum of emergent or urgent use, on condition that these results stand the test of time. A better understanding of indications for one technique or the other in terms of anatomy, location, and pathology through well-designed studies will be particularly helpful.

Supplemental Material

sj-docx-1-jet-10.1177_15266028231157639 – Supplemental material for Systematic Review and Meta-Analysis of Ex-Situ and In-Situ Fenestrated Stent-Grafts for Endovascular Repair of Aortic Arch Pathologies

Supplemental material, sj-docx-1-jet-10.1177_15266028231157639 for Systematic Review and Meta-Analysis of Ex-Situ and In-Situ Fenestrated Stent-Grafts for Endovascular Repair of Aortic Arch Pathologies by Mourad Boufi, Georgiana Alexandru, Myriam Tarzi, Molka Zlitni, Houda Taghi and Anderson D. Loundou in Journal of Endovascular Therapy

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 iD

Mourad Boufi

Supplemental Material

Supplemental material for this article is available online.

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