Physician-Modified Endografts for the Treatment of Thoracic Aortic Pathologies Involving the Aortic Arch

Abstract

Objective:

This study aimed to evaluate the outcomes of physician-modified endografts (PMEGs) for the treatment of thoracic aortic pathologies involving the aortic arch.

Methods:

A retrospective single-center study was performed on consecutive patients with thoracic aortic pathologies treated by PMEGs between February 2018 and May 2022. Data on baseline characteristics, operative procedure, and follow-up information were collected. The endpoints included technical success, complications, mortality, overall survival, re-intervention, and target vessel instability.

Results:

This study comprised 173 patients (mean age=58±13, range=28–83, 148 men) with thoracic aortic pathologies, including 44 thoracic aortic aneurysms, 113 aortic dissections (9 type A, 4 residual type A, 75 type B, 32 non-A non-B), 3 aortic intramural hematomas, and 13 penetrating aortic ulcers. Thirty-five of the patients had PMEGs with 3 fenestrations, 32 had 2 fenestrations, and 106 had 1 single fenestration. Technical success was 98% (170/173), and the 30-day mortality was 2% (3/173). Perioperative complications included stroke (n=3, 2%), retrograde type A dissection (RTAD; n=3, 2%) and renal injury (n=3, 2%). Seven deaths (4%) were noted during a median follow-up of 11 (range=1–52) months. Eleven cases of re-intervention were stent-related. There were 5 type Ia endoleaks (3%), 2 type III endoleaks (1%) from the innominate artery (IA), and 3 type Ic endoleaks (2%) from the left subclavian arteries. One case of IA stent-graft (SG) stenosis was noted because of mural thrombus. Estimate rates of overall survival, freedom from secondary intervention, and freedom from target vessel instability at 2 years were 93.4% (95% confidence interval [CI]=88.7%–98.1%), 80.7% (95% CI=73.3%–88.1%), and 89.0% (95% CI=80.4%–97.6%), respectively.

Conclusions:

Physician-modified endografts showed promising immediate therapeutic results in the treatment of thoracic aortic pathologies involving the aortic arch. Our study demonstrates that the technique is feasible and produces acceptable results. Long-term outcomes are required for further refinement of this technical approach to confirm technical success and durability over time as a valuable option for endovascular aortic arch repair in specialized centers.

Clinical impact

Our short- and mid-term outcomes of physician-modified endografts in 173 patients showed promising results compared to other branched/fenestrated techniques and backed up the endovascular repair of the aortic arch. Meanwhile, the technical expertise pointed out in our manuscript, including preloaded guidewire, diameter-reducing wire and inner mini-cuffs, provided reference and technical guidance for our peers. Most importantly, it demonstrated that the PMEG, as a device whose components were all commercially available, might be a better option for emergency surgery and for centers who had no access to custom-made devices.

Keywords

physician-modified endograft thoracic endovascular aortic repair aortic arch

Introduction

Thoracic endovascular aortic repair (TEVAR) has been shown to have better outcomes in terms of mortality and morbidity when compared with open repair for thoracic aorta pathologies.^1,2 According to the recommendations in 2018, TEVAR in zones 1 and 2 is advised for patients with suitable anatomy, and endovascular repair in zone 0 for the aortic arch is recommended to be considered in patients unfit for open surgery and with suitable anatomy.³ However, an intact aortic segment, the so-called landing zone, is required for the endovascular repair. The stent-graft (SG) landing zone can easily cover the branch arteries of the aortic arch in cases of complicated thoracic aortic diseases involving aortic arch lesions. There have been several methods proposed for revascularizing arch branch arteries for TEVAR. These included parallel technique, hybrid arch procedures,^4–6 and branched or fenestrated endovascular repair.⁷ The parallel technique and hybrid procedures are less invasive than conventional surgery but have higher rates of endoleaks, re-intervention and 30-day mortality compared with branched or fenestrated repair.^8–11 Branched and fenestrated techniques include custom-made devices (CMDs), in situ fenestrations (ISFs) and physician-modified endografts (PMEGs) with back-table modification.¹² Due to restrictions in designing and manufacturing, custom-made endografts take a 6-week to 8-week development and delivery period, which is inappropriate for urgent surgery. Moreover, they have been in shortage in many countries. Therefore, due to the unmet medical need for an immediate, effective solution based on the predictable aorta and branch anatomy, ISFs and PMEGs were developed as replacements for CMDs. However, an essential problem with the ISF process is the likelihood of extra lesions from laser or needle piercing. Meanwhile, the ISF procedure—from stents deployment to puncture—extends the time of cerebral ischemia.⁵ A substantial number of studies demonstrated that the PMEGs with back-table modification performed in expert centers could provide acceptable mortality and morbidity rates, even in an emergency.^13–16 As PMEGs demand very specialized endovascular tools and expertise due to their extraordinary complexity, more evidence and clinical experience is required to support the feasibility, efficacy, and safety of this technique. This study aimed to evaluate the outcomes of PMEGs for TEVAR of thoracic aortic pathologies involving the aortic arch.

Materials and Methods

Patient Cohort

A retrospective study was approved by the institutional review board. Informed consent was waived due to the retrospective nature of this study. Patients with thoracic aortic pathologies treated by PMEGs with proximal landing zone between 0 and 2 were included. Patients undergoing zone 0 TEVAR were American Society of Anesthesiologists score class 3 or 4 and were deemed unfit for open surgery, discussed by a multidisciplinary team. All patients had appropriate anatomy for a PMEGs, with the length of the landing zone was ≥20 mm and the diameter of it was ≤38 mm. Criteria for the treatment were (1) the distance between the lesion and the left subclavian artery (LSA) was ≤15 mm, (2) thoracic aortic aneurysm with diameter of ≥55 mm or a risk of rupture (increase in diameter of ≥5 mm per year), (3) thoracic aortic dissection with suitable anatomy, and (4) aortic intramural hematoma and penetrating aortic ulcer with requirement of distal aortic arch repair.

Demographic information was collected, including age, gender, past medical history, history of surgery related to aortic disorders, smoking history, and body mass index. A thin-slice computerized tomography angiography (CTA) scan was preoperatively performed on each patient and downloaded in DICOM format. The axial and coronal view, as well as 3-dimensional reconstruction of the total aorta were obtained based on the CTA by OsiriX DICOM Viewer (Pixmeo SARL, Bernex, Geneva, Switzerland). The geometry of aortic arch and branches was thoroughly evaluated for formulating the position of fenestrations in accordance with centerline analysis. The duration of the procedure and the type of main endograft and bridging SGs were both included in the intraoperative data. Early outcomes included technical success, 30-day mortality, procedural complications, early re-intervention, length of hospital stay, and intensive care unit (ICU) stay. A follow-up CTA scan was performed and viewed at 1, 6, and 12 months, and annually thereafter for the mid-term outcomes, including the evidence of aneurysm enlargement, false lumen perfusion, endoleaks, target vessel patency, and branch instability. Secondary intervention and overall survival were also collected for mid-term outcomes.

Devices

Main endografts were selected, including Zenith ZTEG (Cook Medical Inc., Bloomington, IN, USA), Valiant (Medtronic Vascular, Santa Rosa, CA, USA), and Ankura (LifeTech, Shenzhen, China). The main endografts’ delivery system should be able to enter the aortic arch and the morphology matches the patients’ aortic anatomy. The self-expandable bridging SGs were selected, including Endurant Limb (Medtronic Vascular, Santa Rosa, CA, USA), Ankura Iliac extension (LifeTech), Viabahn (W.L. Gore & Associates, Flagstaff, AZ, USA), Fluency (Bard Peripheral Vascular, Tempe, AZ, USA), Omnilink Elite (Abbott Vascular, Santa Clara, CA, USA), and Precise (Cordis, Miami Lakes, FL, USA). The specific information is shown in Table 2. The size of the devices was determined by the extent of lesions and the vessel diameter.

Back-Table Modification

The main endograft of the proper size was selected and unsheathed in the usual manner on a back table. The fenestrations were obtained by a cautery device in accordance with the measurement from preoperative 3-dimensional reconstruction, and then, they were marked and reinforced by a platinum tungsten alloy loop obtained from an embolization coil (Cook Medical Inc., Bloomington, IN, USA). Subsequently, the endograft was tightened by a vessel loop and re-sheathed into the original sheath. The fenestration was designed to have a diameter that is 1 to 2 mm less than the projected bridging SG.

For PMEGs with multi-fenestration, a diameter-reducing wire was utilized (Figure 1D). After the fenestrations were fashioned, a V-18 wire (Boston Scientific, Bloomington, IN, USA) was placed at 6:00 position opposite to them. The endograft was constrained over the V-18 wire using loops of 3-0 Prolene sutures, and then re-sheathed. It was able to be unsheathed partially with the aid of the diameter-reducing wire for adjusting position and orientation before fenestration alignment.

Occasionally, a stiff hydrophilic guidewire was used as a preloaded guidewire in the setting of complicated architecture of the aorta and the arch (Figure 2C). The criteria of preloaded guidewire application were the observation of collapse and/or distortion of the aortic arch and the descending aorta under the 3-dimensional reconstruction. The guidewire was inserted from the distal endograft and traveled through, traversed the fenestration, proceeded to the cephalad external endograft, and then re-sheathed together with it. Moreover, 3 to 5 mm inner mini-cuffs trimmed from Viabahn SGs were sewed on the fenestrations (Figure 3C) while the primary entry tear of the dissection was closed to the targeted vessel or aneurysms involvement of branches existed. The diameter of the mini-cuffs was aligned with the fenestrations’ diameter, which was 1 to 2 mm smaller than the bridging stents.

Endovascular Procedure

All patients underwent the surgery in a hybrid operating room while under general anesthesia.

The procedure for PMEGs with 3 fenestrations was described, for instance, as follows. The unilateral femoral artery, left common carotid artery (LCCA), and left branchial artery were exposed as accesses for aortic aorta, the LCCA, and the LSA, respectively. The innominate artery (IA) access required the right branchial artery, the right common carotid or the right subclavian artery exposure on the basis of bridging SGs diameter and the vessel patency.

Heparin of 100 U/kg was administered. A pigtail catheter with gold markers was introduced via femoral approach into the aorta over a floppy loach guidewire, and advanced to the proximal aortic arch. Digital subtraction angiography (DSA) was used to monitor the lesion site and the catheter position (Figure 1B, 2B, 3B, and 4B). Then the floppy guidewire was exchange to a stiff one with the tip curved on the aortic valve. After that, the endograft modified on a back table was introduced over the stiff guidewire to the aortic arch via the femoral approach and unsheathed partially with the fenestrations obtained (Figure 5A). Once the target vessels were catheterized and the fenestrations were accessed, the loach guidewire was removed and exchanged for a stiff guidewire and a 10F sheath (Figure 5B). After that, the aortic endograft was entirely deployed with precise apposition between the fenestrations and the target vessels by removing the diameter-reducing wire (Figure 5C). To minimize cerebral ischemia, the bridging SGs were sequentially deployed starting with the LCCA, followed by the IA and LSA (Figure 5D), which were deployed 3 to 5 mm into the main endograft and dilated by percutaneous transluminal angioplasty balloon catheters. A completion angiography of the thoracic aorta and each branch was performed (Figure 1E, 2E, 3D, and 4E).

For double-fenestrated PMEGs, there was no obvious difference in technique steps. For PMEGs with single fenestration, the alignment was in a different way without a diameter-reducing wire. After being delivered into the aortic arch, a short section of the endograft was unsheathed as the fenestrations were just revealed. The unsheathed shuttle-shaped portion provided space for endograft movement and positioning (Figure 4D). Once the fenestrations were accessed, the endograft was deployed completely in the precise apposition. Other steps were the same as mentioned above.

When the preloaded guidewire was employed for the complex morphology of the aorta and aortic arch, a loach guidewire was initially introduced into the descending aorta via left common carotid access and snared out from the femoral artery, with a catheter followed. The stiff hydrophilic guidewire was passed from the femoral access to the targeted vessel site over the catheter, assisting the deployment of the aortic endograft and the catheterization of the targeted vessel. To prevent the preloaded guidewire from becoming entangled with the stiff guidewire during movement, the surgeon held the handle to maintain a stable orientation.

Vessel bypass was performed before SGs implantation if required.

Definitions

The technical success was defined as significantly effective treatment with lesion exclusion, targeted vessel patency and without endoleaks. Renal injury was defined as acute kidney injury diagnosed perioperatively. Target vessel instability meant absence of type Ic endoleak, type III endoleak from the connection between the bridging SG and the main endograft, SGs flattened with over 50% stenosis or occlusion, or any migration that affects the structure of devices.

Statistical Analysis

SPSS software (version 22.0; IBM Corporation, Armonk, NY, USA) was used to analyze data. Continuous data conforming to normal distribution were expressed as the mean±standard deviation if normally distributed, or as median and interquartile range (IQR). Normal distribution was identified by skewness, kurtosis, and normally plots with Shapiro-Wilk test. Categorical variables were expressed as counts and percentages, compared by Pearson chi-square, continuity correction or Fisher exact test. A 2-sided α<0.0167 by Bonferroni correction was considered as a statistically significant value of pairwise comparison. Overall survival, freedom from secondary intervention, and from stent instability were estimated with Kaplan-Meier analysis curve.

Results

Demographics of the Patients

From February 2018 to May 2022, a total of 173 patients (mean age=58±12, range=28–83, 148 men) with thoracic aortic disorders were treated with PMEGs in our tertiary referral center. A significant number of patients had cardiovascular risk factors, including hypertension (n=148, 86%), smoking (n=87, 50%), previous stroke (n=25, 14%), overweight (n=82, 47%), and other factors summarized in Table 1. Indications for therapy included thoracic aortic aneurysm (n=44, 25%), aortic dissection (n=113, 65%; type A, n=2; residual type A, n=4; type B, n=75; non-A non-B, n=32), aortic intramural hematoma (n=3, 2%), and penetrating aortic ulcer (n=13, 8%).

Table 1.

Baseline Characteristics (N=173).

Age, years	58±12, 28–83
Men	148 (86)
Smoker	87 (50)
Hypertension	147 (85)
Dyslipidemia	32 (18)
Chronic obstructive airway disease	16 (9)
Atrial fibrillation	5 (3)
Coronary artery disease	17 (10)
Myocardial infarction	3 (2)
Myocardial infarction within 30 days	0
Unstable angina	2 (1)
Previous PTCA or stent	16 (9)
Previous PTCA or stent within 6 weeks	0
Previous stroke	25 (14)
Previous transient ischemic attack	1 (1)
Connective tissue disorder	7 (4)
Peripheral artery diseases	18 (10)
Previous aortic surgery	20 (12)
Overweight and obesity (BMI>24.9 kg/m²)^a	81 (47)
Diseases
Thoracic aortic aneurysm	44 (25)
Aortic dissection	113 (65)
Aortic intramural hematoma	3 (2)
Penetrating aortic ulcer	13 (8)
Extent of the pathology
Aortic arch	60(35)
Descending aorta	113(65)

Abbreviations: BMI, body mass index; PTCA, percutaneous transluminal coronary angioplasty.

WHO defines overweight and obesity¹⁷ as follows: overweight is a BMI greater than or equal to 25; and obesity is a BMI greater than or equal to 30. Continuous variables are presented as mean ± standard deviation, range. Categorical variables were presented as count (percentage).

Procedural Data

There were 3 emergency surgeries and 170 elective surgeries. Thirty-five of the patients had PMEGs with 3 fenestrations, 31 had 2 fenestrations and 107 had 1 single fenestration. Inner mini-cuffs were employed in 16 cases (35 cuffs in total, 9 on IA fenestrations, 13 on LCCA fenestrations, and 13 on LSA fenestrations). The preloaded guidewires were applied in 6 cases (3 on triple fenestrated [9%, 3/35] and 3 on double-fenestrated [9%, 3/32] endografts). The artery bypass was performed in 11 cases. Details are shown in Table 2. The technical success rate was 98% (170/173). Two cases of fenestration failure were converted to chimney technique. During the catheterization in these cases, the guidewire failed to entry the endograft through the fenestration, so that, a parallel SG was applied. One was successful with lesion exclusion and the other had an RTAD. One case of type Ia endoleak and 4 cases of type Ic endoleak were observed by intraoperative angiography and embolized with coils. There were 3 cases of RTAD occurring intraoperatively and having total aortic arch replacement with the frozen elephant trunk technique. The median duration of surgery was 165 minutes (IQR=120–227).

Table 2.

Operative Procedure (N=173).

Technical success	170 (98)
Median duration of procedure, minutes	165, 120–227
Contrast use, mL	96, 84–146
Cumulative air kerma, Gy	1.1, 0.7–1.8
Intraoperative complications
Endoleak	5 (3)
Retrograde type A dissection	3 (2)
Proximal landing zone
Zone 0	44 (25)
Zone 1	25 (14)
Zone 2	103 (60)
Zone 3	1 (1)
Reconstruction branch
IA+LCCA+LSA	35 (20)
IA+LCCA	8 (5)
LCCA+LSA	21 (12)
LSA+ectopic left vertebral artery	2 (1)
IA	1 (1)
LCCA	4 (2)
LSA	101 (58)
Ectopic right subclavian artery	1 (1)
Cervical debranching
LCCA-LSA	8 (5)
Right common carotid artery-right subclavian artery	1 (1)
Common carotid artery-axillary	2 (1)
Devices
Main stent-graft
Valiant	51 (29)
Ankura	112 (65)
Zenith TX2	10 (6)
Bridging stent-graft	N=243
Endurant limb	14 (6)
Ankura (iliac extension)	3 (1)
Viabahn	34 (14)
Fluency	183 (75)
Precise	3 (1)
Omnilink Elite	3 (1)
Record blur	3 (1)

Continuous variables are presented as median and interquartile range. Categorical variables were presented as count (percentage).

Abbreviations: IA, innominate artery; LCCA, left common carotid artery; LSA, left subclavian artery.

Early Outcomes

Thirty-day mortality was 2% (3/173), with 2 cases of cardiac shock and 1 case of cardioembolic stroke. Renal injury (n=3, 2%), stroke (n=3, 2%), arrhythmia (n=3, 2%), and other adverse events were reported as perioperative complications in Table 3. Two patients had a minor stroke without significant vascular occlusion, and 1 had a major stroke with basilar artery occlusion and died of it. The early stent-related intervention rate was 1% (n=2), and the remaining early interventions (n=3, 2%) included thrombosis in cerebral infarction, and removal of thrombus of lower limb, and clearance of axillary hematoma. Outcomes of PMEGs with multi-fenestration and single fenestration were compared in Table 4. Pairwise comparison showed that PMEGs with 3 fenestrations had a significantly higher rate of renal injury (p=0.001) than that with single fenestration.

Table 3.

Early Perioperative Outcomes (N=173).

30-day mortality	3 (2)
Perioperative complications
Cardiac failure	3 (2)
Respiratory failure	3 (2)
Stroke	3 (2)
Renal injury	3 (2)
Arrhythmia	3 (2)
Early re-intervention
Stent-graft-related	2 (1)
Non–stent-graft-related	3 (2)
Intensive care unit stay	71 (41)
Length of intensive care unit stay, hours	14, 11–36
Median length of hospital stay, days	15.7, 11.7–20.6

Continuous data conforming to normal distribution were presented as mean±standard deviation, range, if normally distributed, or as median and interquartile range. Categorical variables were presented as count (percentage).

Table 4.

Comparison Among Outcomes of Physician-Modified Endograft With Various Fenestrations.

	Three-fenestrated PMEG	Two-fenestrated PMEG	Single-fenestrated PMEG	p value^a
Early outcomes	N=35	N=32	N=106
Stroke	2 (5.7)	1 (3.1)	0	0.056
Renal injury	3 (8.6)	0	0	0.014^b
Retrograde type A dissection	2 (5.7)	1 (3.1)	1 (0.9)	0.162
Median duration of procedure, minutes	260	187.5	125	<0.001^b
Mid-term outcomes	N=34	N=30	N=106
Secondary intervention	9 (26.5)	7 (23.3)	17 (16.0)	0.354
Stent-graft related	4 (11.8)	3 (10.0)	4 (3.8)	0.118
Non–stent-graft related	5 (14.7)	4 (13.3)	13 (12.3)	0.898

Categorical variables were presented as count (percentage).

Abbreviation: PMEG, physician-modified endograft.

By Pearson chi-squire or Fisher exact test.

A 2-sided α<0.05 was considered a statistically significant value. Pairwise comparison showed that PMEGs with 3 fenestrations had a significantly higher rate of renal injury (p<0.001) than that with single fenestration.

Follow-up

The follow-up information was listed as mid-term outcomes in Table 5. Seven deaths (4%) were noted during a median follow-up of 11 (IQR=4–24) months. Two patients died of stroke at 3 months and 3 years, and 5 patients died in ill-defined conditions. During the follow-up, 21 patients (12%) required a secondary intervention, 11 (6%) of which were stent-related. There were 8 patients requiring endoleak repair (Table 6). Two patients required re-stenting due to aneurysmal dilatation at the proximal or distal end of the aortic endograft. And 1 case of bridging SG stenosis was noted as a result of mural thrombus and was treated by extra stent implantation at 2 months. Nine patients underwent endovascular repair of the remaining descending thoracic and/or abdominal aorta in an intended secondary stage. One patient had an RTAD and underwent the frozen elephant trunk technique at 1.5 months. Endoleaks were observed in 10 (6%) cases: 5 patients (3%) had a type Ia endoleak and 2 patients (1%) had a type III endoleak from the IA bridging SGs, which were treated with coils embolization; 3 patients (2%) had a type Ic endoleak from the LSA, with 1 coil embolization and 2 self-sealing.

Table 5.

Mid-Term Outcomes (N=170).

Median follow-up, months	11, 4-24
Mortality	7 (4)
Secondary intervention
Stent-related	11 (6)
Secondary stage	9 (5)
Endoleaks
Type Ia	5 (3)
Type Ic from the LSA	3 (2)
Type III from bridging stent-graft for the IA	2 (1)
Reintervention	8 (5)
Targeted vessel stenosis	1 (1)
Retrograde type A dissection	1 (1)

Continuous variables are presented as median and interquartile range. Categorical variables were presented as count (percentage).

Abbreviations: IA, innominate artery; LSA, left subclavian artery.

Table 6.

Management of Endoleaks During Follow-Up Period.

No.	Pathology	Branches stented	Secondary intervention
No.	Pathology	Branches stented	Timing, months	Type of endoleak	Treatment
1	Dissection	IA+LCCA+LSA	3, 6	III from the IA	Coil embolization
2	Dissection	IA+LCCA+LSA	3	Ia	Coil embolization
3	Aneurysm	IA+LCCA+LSA	7	Ia	Coil embolization
4	Dissection	IA+LCCA	2	Ia	Coil embolization
5	Aneurysm	IA+LCCA+LSA	17	III from the IA	Coil embolization
6	Aneurysm	LCCA+LSA	4	Ia	Coil embolization
7	Dissection	LSA	3, 6	Ia	Coil embolization
8	Dissection	LSA	1	Ic from the LSA	Redo LSA stenting

Abbreviation: IA, innominate artery; LCCA, left common carotid artery; LSA, left subclavian artery.

The estimate overall survival rate was 96.5% (95% confidence interval [CI]=93.8%–99.2%), 95.2% (95% CI=91.9%–98.5%), 95.2% (95% CI=91.9%–98.5%), and 93.4% (95% CI=88.7%–98.1%) in 1 and 6 months, and in 1 and 2 years, respectively (Figure 6A). The estimate rate of freedom from secondary intervention was 97.1% (95% CI=94.6%–99.6%), 88.8% (95% CI=83.5%–94.1%), 83.6% (95% CI=76.9%–90.3%), and 80.7% (95% CI=73.3%–88.1%) in 1 and 6 months, and in 1 and 2 years, respectively (Figure 6B). The estimate rate of freedom from target vessel instability was 99.9% (95% CI=98.7%–100%), 97.7% (95% CI=95.2%–100%), 96.0% (95% CI=91.9%–100%), and 89.0% (95% CI=80.4%–97.6%) in 1 and 6 months, and in 1 and 2 years, respectively (Figure 6C).

Discussion

Indications for TEVAR have been expanding as the development of fenestrated and branched techniques for extending landing zone. Results of CMDs for thoracic aortic diseases involving aortic arch have been reported in certain centers. The multi-center experience of Cook Arch Branched devices (Cook Medical Inc., Bloomington, IN, USA) on 27 patients was reported in 2016 by Spear et al,¹⁸ with 100% technical success, 11.1% stroke, 18.5% endoleaks, 22.2% secondary re-intervention, and 3.7% overall mortality in a median 12-month follow-up period. Recently a study by Czerny et al¹⁹ on 43 patients using Relay Branch system (Terumo Aortic, Sunrise, FL, USA) was published in 2021, with 9% in-hospital mortality, 7% disabling stroke, 4% endoleaks, and 3% aortic-related deaths during a median follow-up of 16 months. These devices were designed for TEVAR in zone 0, with double-side inner branches for IA and LCCA, and the LSA required revascularization by carotid-subclavian bypass. Recently, a global experience of 3-branched devices was updated in 2021 by Tenorio et al,²⁰ with 100% technical success, 5% mortality, 5% stroke, and 18% aortic-related re-intervention during a median follow-up of 3.2 months. The CMDs for total endovascular repair of aortic arch lesions in selected centers showed high technical success and acceptable rates of mortality and morbidity. However, the 6-week to 8-week development and delivery time is inappropriate with urgent surgery and many countries have no access to such CMDs. In view of these constraints, “off-the-shelf” techniques have a broader accessibility for the time being.

The positive outcomes of our study supported the efficiency of PMEGs, with 2% 30-day mortality, 2% stroke, 98% technical success rate, 6% endoleaks, and a re-intervention rate of 6% related to stents over a median 11-month follow-up. This coincided with the recent research by Canaud et al¹³ in 2022 whose experience with the double-fenestrated PMEGs for total arch TEVAR was reported with 2% 30-day mortality, 4% stroke and 4% endoleak rate, 97% technical success rate, and a re-intervention rate of 8% during the 24-month follow-up period. Our study also showed comparable results of other small cohort studies on PMEGs.^14–16 In addition, comparison with the ISFs according to a systematic review,²¹ with rates of technical success (98% vs 94%), stroke (2% vs 6%), and especially in 30-day mortality (2% vs 11%), further confirmed that the PMEG was a feasible and reproducible strategy for thoracic aortic pathologies.

Endoleaks have been a major issue of re-intervention especially for PMEGs, as type III endoleaks primarily occurred at the junction of bridging SGs and fenestrations. According to a comprehensive review by Canonge et al,²² the incidence of type III endoleaks ranged from 0 to 5% in PMEGs with fenestration reinforcement or bridging stents. It was relatively low with a 1% rate of type III endoleaks in our experience, which was probably due to our extraordinary use of inner mini-cuffs. For aortic arch aneurysms, the disparity of diameter between the aneurysm and the sealing zone results in a gap, which creates a bridging length between the fenestrations and the orifice of the targeted vessels. In this situation, the risk of bridging SGs instability would increase, as they are continuously hit by the blood flow from the vertical direction. We applied inner mini-cuffs to overcome these difficulties, as they were sewed on the fenestrations to increase radial and friction force for SGs adhesion. The inner mini-cuffs were also used when the primary entry tear of the dissection was close to the targeted vessel, and thus reduced the risk of false lumen reperfusion due to type III endoleaks.

The RTAD is one of the most severe complications of TEVAR. It is mainly because of the fragile membrane of the true lumen, particularly in acute phase of type B dissection, which could not bear the radial force from the deployed endograft. According to a systemic review from Chen et al,²³ RTAD had a relatively low incidence rate (2.5%) but a high mortality rate (37.1%). In our study, 2 cases (1.2%) of RTAD occurred intraoperatively and one (0.6%) after a follow-up of 18 months. All the patients with RTAD immediately underwent the frozen elephant trunk technique for total arch replacement and survived during the follow-up period. We preferably selected endografts with a 0% to 5% diameter oversize of the proximal landing zone for aortic dissections. Interestingly, some experts advocated undersized endografts to reduce the likelihood of RTAD, and though the collapsed true lumen of aortic dissections allowed the endograft to be held in place,²⁴ but we believed that this strategy could potentially increase the chance of endoleaks, and needed to be carefully balanced.

Stroke is another area of concern as a common neurologic complication in completely endovascular repair of aortic arch, with a rate ranging from 0% to 20%,²⁵ while the stroke rate (2%) in our study was much lower. Compared with another experience on fenestrated PMEGs¹⁶ where the stroke rate was 10%, it should be mentioned that the lower rate of risk factors in our patients’ demographics, including age (58 vs 75.1 years), dyslipidemia (18% vs 31%), and coronary artery diseases (10% vs 33%), probably reduced stroke occurrence through atherosclerotic thrombosis. We consider that the mural thrombus might be dislodged by devices contacting the aortic wall during deployment, and thus flow into cerebral circulation. Particularly in the setting of proximal landing in zone 0 and zone 1, in addition to guidewire and catheter’s manipulations, the delivery system of the endograft could also dislodge arteriosclerotic thrombus. In our early study, a patient who had previous cerebral infarction died of an irreversible major stroke. We learned a lesson from the bad result and considered the “shaggy” aortic arch, with thrombus thickness over 5 mm, or mural thrombus presence in more than two-thirds of the arch, as a contraindication of total endovascular repair in our subsequent practice.

Technical success remained satisfactory (98.3%), and some technical details need to be highlighted. During single-fenestration procedure in our study, a short proximal section of the aortic endograft was unsheathed with the fenestration obtained. The shuttle-shaped structure of the unsheathed portion was created by the tension at both ends, and because the maximal diameter of this structure was still less than the vessel diameter, blood could flow through a gap between the endograft and the vascular wall instead of migrating the device. In the case of multi-fenestrated endograft, by the same token, while the longer proximal section with more fenestrations was unsheathed, it could be restricted by the diameter-reducing wire into a thinner barrel structure to avoid blood flow impingement. In addition, to overcome anatomy difficulties in tortuous arteries, our experience was the application of the preloaded guidewire. In some cases, the twisted aorta made it difficult for the endograft to advance to the thoracic aorta in the correct orientation for alignment by rotating the delivery system. Whereas with the traction of the preloaded guidewire, the fenestrations could be turned to the proper orientation endovascularly and placed precisely at the orifice of the targeted vessels when the endograft was delivered into the aortic arch. This effectively aided in the alignment of fenestrations and contributed to a significant reduction in the total duration of the procedure.

Many studies indicated positive results for PMEGs,^22,26 but nevertheless, the outcomes for the treatment of the aortic arch were recent. Although these data have established PMEG’s mid-term durability, they had a short median follow-up period of less than 3 years and lacked long-term results. Therefore, the long-term persistence of PMEG remains to be witnessed.

To our best knowledge, this is the first time that a significant cohort of patients has been retrospectively researched utilizing PMEGs including 3 fenestrations. However, there are several limitations to our study. Primarily, selection bias cannot be avoided as the disadvantage of single-center retrospective study. In addition, there is no control group restricting comparisons with the patient cohort that underwent traditional surgery or other TEVARs. Moreover, the follow-up is relative shorter because all the procedures were performed less than 5 years ago. Some patients were followed up in local hospitals, and thus, some detailed data were subject to bias during follow-up.

Conclusion

Physician-modified endografts have good immediate therapeutic results and are very promising for the treatment of thoracic aortic pathologies including aortic arch lesions. Our clinical results demonstrate the feasibility of the technique and acceptable outcomes. Long-term follow-up is needed for further refinement of this technical approach to confirm technical success and durability over time as a valuable option for endovascular aortic arch repair in specialized centers.

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

Xiaoqiang Li

Min Zhou

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