Embryogenesis and Adult Life in the Absence of Intrinsic Apoptosis Effectors BAX, BAK, and BOK.

Intrinsic apoptosis, reliant on BAX and BAK, has been postulated to be fundamental for morphogenesis, but its precise contribution to this process has not been fully explored in mammals. Our structural analysis of BOK suggests close resemblance to BAX and BAK structures. Notably, Bok-/-Bax-/-Bak-/- animals exhibited more severe defects and died earlier than Bax-/-Bak-/- mice, implying that BOK has overlapping roles with BAX and BAK during developmental cell death. By analyzing Bok-/-Bax-/-Bak-/- triple-knockout mice whose cells are incapable of undergoing intrinsic apoptosis, we identified tissues that formed well without this process. We provide evidence that necroptosis, pyroptosis, or autophagy does not substantially substitute for the loss of apoptosis. Albeit very rare, unexpected attainment of adult Bok-/-Bax-/-Bak-/- mice suggests that morphogenesis can proceed entirely without apoptosis mediated by these proteins and possibly without cell death in general.

Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest Trial (GOT ICE): A Randomized Clinical Trial Comparing Outcomes After Aortic Arch Surgery.

BACKGROUND: Deep hypothermia has been the standard for hypothermic circulatory arrest (HCA) during aortic arch surgery. However, centers worldwide have shifted toward lesser hypothermia with antegrade cerebral perfusion. This has been supported by retrospective data, but there has yet to be a multicenter, prospective randomized study comparing deep versus moderate hypothermia during HCA. METHODS: This was a randomized single-blind trial (GOT ICE [Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest]) of patients undergoing arch surgery with HCA plus antegrade cerebral perfusion at 4 US referral aortic centers (August 2016-December 2021). Patients were randomized to 1 of 3 hypothermia groups: DP, deep (≤20.0 °C); LM, low-moderate (20.1-24.0 °C); and HM, high-moderate (24.1-28.0 °C). The primary outcome was composite global cognitive change score between baseline and 4 weeks postoperatively. Analysis followed the intention-to-treat principle to evaluate if: (1) LM noninferior to DP on global cognitive change score; (2) DP superior to HM. The secondary outcomes were domain-specific cognitive change scores, neuroimaging findings, quality of life, and adverse events. RESULTS: A total of 308 patients consented; 282 met inclusion and were randomized. A total of 273 completed surgery, and 251 completed the 4-week follow-up (DP, 85 [34%]; LM, 80 [34%]; HM, 86 [34%]). Mean global cognitive change score from baseline to 4 weeks in the LM group was noninferior to the DP group; likewise, no significant difference was observed between DP and HM. Noninferiority of LM versus DP, and lack of difference between DP and HM, remained for domain-specific cognitive change scores, except structured verbal memory, with noninferiority of LM versus DP not established and structured verbal memory better preserved in DP versus HM (P = 0.036). There were no significant differences in structural or functional magnetic resonance imaging brain imaging between groups postoperatively. Regardless of temperature, patients who underwent HCA demonstrated significant reductions in cerebral gray matter volume, cortical thickness, and regional brain functional connectivity. Thirty-day in-hospital mortality, major morbidity, and quality of life were not different between groups. CONCLUSIONS: This randomized multicenter study evaluating arch surgery HCA temperature strategies found low-moderate hypothermia noninferior to traditional deep hypothermia on global cognitive change 4 weeks after surgery, although in secondary analysis, structured verbal memory was better preserved in the deep group. The verbal memory differences in the low- and high-moderate groups and structural and functional connectivity reductions from baseline merit further investigation and suggest opportunities to further optimize brain perfusion during HCA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02834065.

SMAD4: A critical regulator of cardiac neural crest cell fate and vascular smooth muscle development.

BACKGROUND: During embryogenesis, cardiac neural crest-derived cells (NCs) migrate into the pharyngeal arches and give rise to the vascular smooth muscle cells (vSMCs) of the pharyngeal arch arteries (PAAs). vSMCs are critical for the remodeling of the PAAs into their final adult configuration, giving rise to the aortic arch and its arteries (AAAs). RESULTS: We investigated the role of SMAD4 in NC-to-vSMC differentiation using lineage-specific inducible mouse strains. We found that the expression of SMAD4 in the NC is indelible for regulating the survival of cardiac NCs. Although the ablation of SMAD4 at E9.5 in the NC lineage led to a near-complete absence of NCs in the pharyngeal arches, PAAs became invested with vSMCs derived from a compensatory source. Analysis of AAA development at E16.5 showed that the alternative vSMC source compensated for the lack of NC-derived vSMCs and rescued AAA morphogenesis. CONCLUSIONS: Our studies uncovered the requisite role of SMAD4 in the contribution of the NC to the pharyngeal arch mesenchyme. We found that in the absence of SMAD4+ NCs, vSMCs around the PAAs arose from a different progenitor source, rescuing AAA morphogenesis. These findings shed light on the remarkable plasticity of developmental mechanisms governing AAA development.

Long-term outcomes for hybrid aortic arch repair.

OBJECTIVE: Since its inception in the early 2000s, hybrid arch repair (HAR) has evolved from novel approach to well-established treatment modality for aortic arch pathology in appropriately selected patients. Despite this nearly 20-year history of use, long-term results of HAR remain to be determined. As such, objectives of this study are to detail the long-term outcomes for HAR within an expanded classification scheme. METHODS: From August 2005 to August 2022, 163 consecutive patients underwent HAR at a single referral institution. Operative approach was selected according to an institutional algorithm and included zone 0/1 HAR in 25% (n = 40), type I HAR in 34% (n = 56), and type II/III HAR in 41% (n = 67). Specific zone 0/1 technique was zone 1 HAR in 31 (78%), zone 0 with innominate snorkel (zone 0S HAR) in 7 (18%), and zone 0 with single side-branch endograft (zone 0B HAR) in 2 (5%). The 30-day and long-term outcomes, including overall and aortic-specific survival, as well as freedom from reintervention, were assessed. RESULTS: The mean age was 63 ± 13 years and almost one-half of patients (47% [n = 77]) had prior sternotomy. Presenting pathology included degenerative aneurysm in 44% (n = 71), residual dissection after prior type A repair in 38% (n = 62), chronic type B dissection in 12% (n = 20), and other indications in 6% (n = 10). Operative outcomes included 9% mortality (n = 14) at 30 days, 5% mortality (n = 8) in hospital, 4% stroke (n = 7), 2% new dialysis (n = 3), and 2% permanent paraparesis/plegia (n = 3). The median follow-up was 44 month (interquartile range, 12-84 months). Overall survival was 59% and 47% at 5 and 10 years, respectively, whereas aorta-specific survival was 86% and 84% at the same time points. At 5 and 10 years, freedom from major reintervention was 92% and 91%, respectively. Institutional experience had a significant impact on both early and late outcomes: comparing the first (2005-2012) and second (2013-2022) halves of the series, 30-day mortality decreased from 14% to 1% (P = .01) and stroke from 6% to 3% (P = .62). Improved operative outcomes were accompanied by improved late survival, with 78% of patients in the later era vs 45% in the earlier era surviving to 5 years. CONCLUSIONS: HAR is associated with excellent operative outcomes, as well as sustained protection from adverse aortic events as evidenced by high long-term aorta-specific survival and freedom from reintervention. However, surgeon and institutional experience appear to play a major role in achieving these superior outcomes, with a five-fold decrease in operative mortality and a two-fold decrease in stroke rate in the latter half of the series. These long-term results expand on prior midterm data and continue to support use of HAR for properly selected patients with arch disease.

Total aortic arch repair with double-fenestrated physician-modified endografts, at least 3-year follow-up.

OBJECTIVE: This study aims to report the efficacy and safety of double-fenestrated physician-modified endovascular grafts (PMEGs) for total aortic arch repair with at least 3 years of follow-up. METHODS: All consecutive patients with a pathological aortic arch who underwent aortic arch repair combined with a homemade double-fenestrated stent graft from 2017 to 2020 were reviewed. RESULTS: 74 patients were treated for pathological arch conditions with a double-fenestrated PMEG. Of these, 81% were male, the mean age was 69.9 years, and 59% were classified as American Society of Anesthesiology 3 or 4. Thirty-five percent were treated for a postdissection aneurysm, 36% for a degenerative aneurysm, and 14% for acute type B dissection. Fifteen percent had supra-aortic trunk dissection. Fenestration on the subclavian artery was performed in 96%; if not, a carotid-subclavian bypass was carried out. Technical success was 100%. The proximal landing zone is consistently in zone 0. Early outcomes revealed a 3% occurrence of type 1 endoleak, which was successfully treated by prompt reintervention. One retrograde dissection occurred, and one patient died from hemorrhage on an iliac conduit. A 5% stroke rate was reported. During long-term follow-up (mean time 40.7 months), one type 1 endoleak appeared and was successfully treated; no type 2 or type 3 endoleak requiring intervention occurred. No stent fractures or migrations were reported. Four percent of patients required reintervention, but no surgical conversion to open surgical repair was needed on the aortic arch. No patient died from a cause related to the main procedure. CONCLUSIONS: Total aortic arch repair with double-fenestrated PMEGs is associated with acceptable early and midterm major morbidity and mortality. It is suitable for the main aortic pathologies. Moreover, it is easily available for emergency situations.

Comparison of bare and nonbare stent grafts during thoracic endovascular aneurysm repair of the aortic arch.

OBJECTIVE: We compared the outcomes of patients treated with nonbare stents (NBS) and proximal bare stents (PBS) endografts with a proximal landing zone in the aortic arch during thoracic endovascular aortic repair (TEVAR). METHODS: We conducted a retrospective cohort, observational, multicenter study that included 361 consecutive TEVAR procedures undertaken between November 2005 and December 2021. TEVAR patients with both BS and NBS Relay stent graft configurations with proximal landing in zones 1, 2, or 3 were enrolled. Preoperative anamnestic and morphological data, clinical outcomes, and aortic modifications 30 days after surgery and at the latest follow-up available were collected. The primary outcome was freedom from proximal endoleak (type IA) comparing the two configurations. Total and detailed endoleak rates, clinical and technical success, intraoperative additional maneuvers, major adverse events, and reinterventions were secondary outcomes. RESULTS: The median follow-up was 4.9 (interquartile range, 2.0-8.1) years. No statistically significant difference between NBS and PBS patients concerning 30-day major adverse events, retrograde aortic dissection, disabling stroke, or late type IA endoleak (10.8% vs 7.8%; P = .597). Aneurysmal disease (P = .026), PLZ diameter of >34 mm (P = .026), aortic tortuosity index of >1.4 (P = .008), type III aortic arch (P = .068), and PLZ thrombus (P = .014) identified as risk factors by univariate Cox regression analysis. PLZ thrombus was the only type IA endoleak risk factor at multivariate Cox regression (P = .016). CONCLUSIONS: We found no statistically significant difference in freedom from type IA endoleak, retrograde dissection, or disabling stroke observed between the NBS and the BS configuration of the Relay endograft. Proximal landing zone thrombotic apposition was a prominent risk factor for type IA endoleak after TEVAR.

The outcomes of aortic arch repair between open surgical repair and debranching endovascular hybrid surgical repair: A systematic review and meta-analysis.

BACKGROUND: At present, open surgical aortic arch repair (OAR) and debranching hybrid surgical aortic arch repair (HAR) serve as significant therapeutic approaches for aortic arch aneurysm or dissection. It remains unclear which technique is preferable. Our study aimed to compare the short-term and long-term outcomes of these two procedures. METHODS: To identify comparison studies of debranching HAR and OAR, a systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases was performed from January 2002 to April 2022. This study was registered on PROSPERO (CRD42020218080). RESULTS: Sixteen publications (1316 patients), including six propensity score-matching (PSM) analysis papers, were included in this study. Compared with the HAR group, the patients who underwent OAR were younger (OAR vs HAR: 67.53 ± 12.81 vs 71.29 ± 11.0; P < .00001), had less coronary artery disease (OAR vs HAR: 22.45% vs 32.6%; P = .007), less chronic obstructive pulmonary disease (OAR vs HAR: 16.16% vs 23.92%; P = .001), lower rates of previous stroke (OAR vs HAR: 12.46% vs 18.02%; P = .05), and a lower EuroSCORE (European System for Cardiac Operative Risk Evaluation) score (OAR vs HAR: 6.27 ± 1.04 vs 6.9 ± 3.76; P < .00001). HAR was associated with less postoperative blood transfusion (OAR vs HAR: 12.23% vs 7.91%; P = .04), shorter length of intensive care unit stays (OAR vs HAR: 5.92 ± 7.58 days vs 4.02 ± 6.60 days; P < .00001) and hospital stays (OAR vs HAR: 21.59 ± 17.54 days vs 16.49 ± 18.45 days; P < .0001), lower incidence of reoperation for bleeding complications (OAR vs HAR: 8.07% vs 3.96%; P = .01), fewer postoperative pulmonary complication (OAR vs HAR: 14.75% vs 5.02%; P < .0001), and acute renal failure (OAR vs HAR: 7.54% vs 5.17%; P = .03). In the PSM subgroup, the rates of spinal cord ischemic (OAR vs HAR: 5.75% vs 11.49%; P = .02), stroke (OAR vs HAR: 5.1% vs 17.35%; P = .01), and permanent paraplegia (OAR vs HAR: 2.79% vs 6.08%; P = .006) were lower in the OAR group than that in the HAR group. Although there was no statistically significant difference in 1-year survival rates (HAR vs OAR: hazard ratio [HR]: 1.54; P = .10), the 3-year and 5-year survivals were significantly higher in the OAR group than that in the HAR group (HAR vs OAR: HR: 1.69; P = .01; HAR vs OAR: HR: 1.68; P = .01). In the PSM subgroup, the OAR group was also significantly superior to the HAR group in terms of 3-year and 5-year survivals (HAR vs OAR: HR: 1.73; P = .04; HAR vs OAR: HR: 1.67; P = .04). The reintervention rate in the HAR group was significantly higher than that in the OAR group (OAR vs HAR: 8.24% vs 16.01%; P = .01). The most common reintervention was postoperative bleeding (8.07%) in the OAR group and endoleak (9.67%) in the HAR group. CONCLUSIONS: Our meta-analysis revealed that debranching HAR was associated with fewer perioperative complications than the OAR group, except for postoperative permanent paraplegia, reintervention, and stroke events. The OAR group demonstrated better 3-year and 5-year survivals than the debranching HAR group. However, patients in the OAR group had fewer comorbid factors and were younger than those in the HAR group. High-quality studies and well-powered randomized trials are needed to further evaluate this evolving field.

Proximal sealing in the aortic arch for inner curve disease using the Custom Relay® Scalloped and Fenestrated stent graft.

OBJECTIVE: This study aims to analyze early and midterm results of custom-made proximal scallop and fenestrated stent-grafts for thoracic endovascular aortic repair (TEVAR) with proximal landing zone (PLZ) in the aortic arch. METHODS: All consecutive patients treated with the custom made proximal scalloped and fenestrated Relay stent grafts (Terumo Aortic Bolton Medical Inc., Sunrise, USA) in ten Italian centers between January 2014 and December 2022 were included. The primary endpoints were technical success, incidence of intraoperative major adverse events (MAEs), deployment accuracy, and rate of early neurological complications, endoleaks (Els) and retrograde aortic dissection. RESULTS: During the study period, 49 patients received TEVAR with Relay custom-made endograft in Italy were enrolled. The median patient age was 70.1 years (interquartile range, 23-86 years) and 65.3% were male. The indication for treatment was atherosclerotic aneurysms in 59.2% of cases and penetrating aortic ulcer in 22.4%. The endograft configuration was proximal fenestration in 55.1% and scallop in 44.9%. The PLZ was zone 0 in 25 cases (51%), zone 1 in 14 cases (28.6%), and zone 2 in 10 cases (20.4%). The supra-aortic debranching procedures were 38 (77.5%). Technical success was 97.9% (48/49) due to one case (2.0%) of inaccurate deployment. Intraoperatively, one (2.0%) type Ia and one (2.0%) type III Els were detected. There were no cases of in-hospital mortality, MAEs and retrograde dissection. Three (6.1%) minor strokes (National Institutes of Health Stroke Scale score≤4) were observed. At a mean follow-up time of 36.3 + 21.3 months the rate of type I-III Els and reintervention was 4.1%, respectively. Four patients (8.2%) died during the follow-up period, one (2.1%) from abdominal aortic rupture and three (6.1%) for non-aortic causes. CONCLUSIONS: Our early and midterm outcomes suggest that scalloped and fenestrated TEVAR may provide an acceptable alternative treatment option for aortic arch pathologies. Large-scale studies are needed to assess the long-term durability of this technique.

Branched and fenestrated endovascular aortic arch repair in patients with native proximal aortic landing zone.

OBJECTIVE: Fenestrated and branched thoracic endovascular repair (f/bTEVAR) have been successfully applied in patients with diverse aortic arch pathologies. The aim of this study is to present the early and mid-term outcomes of patients with native proximal aortic landing (NPAL) managed with f/bTEVAR. METHODS: A single-center retrospective analysis of patients with NPAL, managed with f/bTEVAR, between September 1, 2011, and June 30, 2022, was conducted. All patients were treated with custom-made devices (Cook Medical) with landing within Ishimaru zones 0 to 2. Primary outcomes were technical success, mortality, stroke, and retrograde type A dissection at 30 days. Follow-up outcomes were considered secondary. RESULTS: A total of 126 patients were included (69.8% males; mean age, 70.8 ± 4.2 years; 18.3% urgent). The main indications (60.4%) for repair were aortic arch (29.4%) and thoracoabdominal aortic aneurysms (31.0%). Seventy-two patients (57.1%) were managed with fTEVAR. Proximal landing in zone 0 and 1 was chosen in 97.6%. Technical success was 94.4%, and 30-day mortality was 11.9%. Strokes were diagnosed in 13.5% of patients and major strokes were identified in 7.9% cases. Retrograde type A dissection rate was 3.9%. The multivariate analysis confirmed landing in Ishimaru zone 0 as an independently related factor for stroke (P = .005), whereas stroke (P < .001), pericardial effusion (P < .001), and acute kidney injury (P < .001) were independently related to 30-day mortality. Mean follow-up was 17.5 ± 9.3 months. The estimated survival rate and the freedom from reintervention rate were 72.6% (standard error, 4.4%) and 46.4% (standard error, 6.0%) at 24-month follow-up, respectively. CONCLUSIONS: Stroke rate after endovascular arch repair was alarming among patients with NPAL. Proximal landing to zone 0 was related to higher risk of stroke. Reinterventions were common within the 24-month follow-up.

Outcomes of thoracic endovascular aortic repair with physician-manufactured partial micropore stent grafts for aortic arch pathologies.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) has been used extensively in the management of thoracic aortic diseases. Numerous efforts have been made to enhance clinical outcomes through the use of stent grafts. This study aimed to investigate the effectiveness and safety of physician-manufactured partial micropore stent grafts (PSMGs) in TEVAR. METHODS: Between December 2017 and June 2022, data were collected from 56 patients who underwent TEVAR using physician-manufactured PSMGs. The evaluation encompassed technical success, perioperative and follow-up morbidity and mortality, stroke incidence, and branch artery patency. RESULTS: In this investigation, 56 patients received treatment with physician-manufactured PSMGs. Of these patients, 46 were male, with a mean age of 62.1 ± 11.2 years. Aortic pathologies comprised aortic dissection (n = 31 [55.4%]), aortic aneurysms (n = 10 [17.9%]), penetrating aortic ulcer (n = 8 [14.3%]), and intramural hematoma (n = 7 [12.5%]). During a median follow-up of 18 months (interquartile range, 13-25 months), the stroke rate, supra-aortic branch patency rate, and endoleak rate were 0%, 100%, and 7.1%, respectively. There were no occurrences of all-cause mortality, stroke, or the necessity for open conversion. CONCLUSIONS: TEVAR with physician-manufactured PSMGs is a viable alternative for addressing aortic arch pathologies in proficient medical centers. The approach demonstrates favorable branch patency, a low complication rate, and minimal postoperative mortality.

Comparative study of left vertebral artery revascularization in patients with and without aberrant left vertebral anatomy.

OBJECTIVE: Left vertebral artery revascularization is indicated in surgery involving zone 2 of the aortic arch and is typically accomplished indirectly via subclavian artery revascularization. For aberrant left vertebral anatomy, direct revascularization is indicated. Our objective was to compare the outcomes of direct vertebral artery revascularization with indirect subclavian artery revascularization for treating aortic arch pathology and to identify predictors of mortality. METHODS: A retrospective cohort study was conducted at a single tertiary hospital, including patients who underwent open or endovascular vertebral artery revascularization from 2005 to 2022. Those who underwent direct vertebral revascularization were compared with those who were indirectly revascularized via subclavian artery revascularization. The outcomes of interest were a composite outcome (any of death, stroke, nerve injury, and thrombosis) and mortality. Univariate logistic regression models were fitted to quantify the strength of differences between the direct and indirect revascularization cohorts. Cox regression was used to identify mortality predictors. RESULTS: Of 143 patients who underwent vertebral artery revascularization, 21 (14.7%) had a vertebral artery originating from the aortic arch. The median length of stay was 10 days (interquartile range, 6-20 days), and demographics were similar between cohorts. The incidence of composite outcome, bypass thrombosis, and hoarseness was significantly higher in the direct group (42.9% vs 18.0%, P = .019; 33.3% vs 0.8%, P < .0001; 57.1% vs 18.0%, P < .001, respectively). The direct group was approximately three times more likely to experience the composite outcome (odds ratio, 3.41; 95% confidence interval, 1.28, 9.08); similarly, this group was approximately six times more likely to have hoarseness (odds ratio, 5.88; 95% confidence interval, 2.21, 15.62). There was no significant difference in mortality rates at 30 days, 1, 3, 5, and 10 years of follow-up. Age, length of hospital stay, and congestive heart failure were identified as predictors of higher mortality. After adjusting for these covariates, the group itself was not an independent predictor of mortality. CONCLUSIONS: Direct vertebral revascularization was associated with higher rates of composite outcome (death, stroke, nerve injury, and thrombosis), bypass thrombosis and hoarseness. Patients with aberrant vertebral anatomy are at higher risks of these complications compared with patients with standard arch anatomy. However, after adjusting for other factors, mortality rates were not significantly different between the groups.

Outcomes for Children With Vascular Ring Repair Using a Simple Surgical Approach.

INTRODUCTION: Vascular Rings (VRs) are congenital malformations of the aortic arch that can compress the trachea and esophagus producing symptoms. Approximately, 5%-10% of patients experience persistent symptoms postrepair and 9% require reintervention. There are various approaches to repair-simple ligation and division of the ring or more complex procedures. Our objective was to describe outcomes for VR repair using a "simple" surgical approach. METHODS: We identified patients who underwent VR repair from 2012 to 2022 at our institution. Clinical and surgical data, demographics, intraoperative, and postoperative outcomes were extracted from their electronic medical records. Outcomes were analyzed and regression analysis was used to identify risk factors for residual symptoms after repair. RESULTS: Ninety three patients with VR repair were included. Prevalence of symptoms were reduced following surgery (80% preoperative versus 13% postoperative, P 0.03). Tracheomalacia also decreased from 16% to 7% postrepair. No deaths were reported in our cohort and 2% of our patients required reintervention. Multivariable regression analysis showed that preoperative tracheomalacia was associated with having persistent symptoms after VR repair (odds ratio 6.2, 95% CI 1.02-37.6). CONCLUSIONS: Our institutional experience using a simple surgical approach showed a significant decrease in symptoms, a very low reintervention rate and no mortality. Preoperative tracheomalacia can be a risk factor for persistent symptoms postrepair. We believe a simple surgical approach for children with complete VR repair can be effective in relieving symptoms.

Target Vessel-Related Outcomes in Patients Managed With Branch Thoracic Aortic Endovascular Repair.

INTRODUCTION: Data on target vessel (TV)-related outcomes in patients managed with branched thoracic endovascular aortic repair (BTEVAR) are limited. This study aimed to present the TV-related outcomes of BTEVAR in patients managed for aortic arch pathologies at 30 days and during follow-up. METHODS: A retrospective analysis of consecutive patients, managed between September 1, 2011, and June 30, 2022, with custom-made aortic arch endografts (Cook Medical, Bloomington, IN, USA), presenting at least one branch configuration, were eligible. Primary outcomes were technical success, TV-related patency, and reinterventions at 30 days. RESULTS: In total, 255 TVs were revascularized using branches: 107 innominate arteries (IAs), 108 left common carotid arteries (LCCAs), and 40 left subclavian arteries (LSAs). Covered stents were used as bridging stents of which 10.2% were balloon expandable. Relining, using bare-metal stents (BMS), was performed in 14.0% of IAs, 35.2% of LCCAs, and 22.5% of LSAs. Technical success on case basis was 99.2%; no failure was related to unsuccessful TV bridging. At 30 day follow-up, no TV occlusion was detected. In 5.6% of cases, a type Ic or III endoleak, attributed to TVs, was recorded. Two patients needed early branch-related reintervention. The mean follow-up was 18.3±9.2 months. Freedom from TV instability was 94.6% (standard error [SE] 2.5%] at 12 months. No TV stenosis or occlusion was detected up to 48 months of follow-up. Freedom from TV-related reinterventions was 95.4% [SE 2.4%] at 12 months. CONCLUSION: TV stenosis or occlusion in BTEVAR cases is rare and TV-related reinterventions and instability events are mainly attributed to type Ic and III endoleak formation. CLINICAL IMPACT: Previous studies focusing on target vessel (TV) outcomes after endovascular aortic arch repair are limited. In this study, including 255 TVs revascularized using branched arch devices, bridging was performed with covered stents, of which 90% were self-expanding. Relining was at the discretion of the operator and was 14% for the innominate, 35.2% for the left common carotid and 22.5% for the left subclavian artery branches. No 30-day occlusion was detected. The freedom from TV instability was almost 95% at 12 months. TV instability and reintervention were mainly attributed to endoleaks type Ic and IIIc.

Early and Midterm Outcomes of Endovascular Aortic Arch Repair Using In Situ Laser Fenestration.

INTRODUCTION: The aim of this study is to present single-center outcomes in patients treated with in situ laser fenestration thoracic endovascular aortic repair (LFTEVAR) for various aortic arch pathologies and assess the impact of increasing experience. METHODS: The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement was followed. A retrospective analysis of prospectively collected single aortic center data was conducted, including baseline information and peri- and post-operative outcomes of consecutive patients managed with LFTEVAR for aortic arch pathologies. Patients were enrolled from April 1, 2017 to January 31, 2023. The cohort was dichotomized to compare early (2017-2019) and late experience (2020-2023). Primary outcomes were peri-operative mortality and cerebrovascular morbidity. RESULTS: Thirty patients were included (63.3% males, mean age 69.8±9.6 years); 21.4% presented with aortic ruptures. Aortic aneurysm involving the aortic arch was the most frequent pathology (53.3%). Forty target vessels (TVs) were revascularized, including 19 left subclavian arteries (47.5%) and 17 left common carotid arteries (42.5%). Double fenestrations were performed in 10 patients. The proximal landing zone was Ishimaru zone 0 in 5 patients (16.7%) and zone 1 in 13 patients (43.3%). Technical success was 93%. No spinal cord ischemia was recorded, and 3 patients (10%) suffered a post-operative stroke, of which 1 was major (3.3%). The median follow-up was 12 months (range=1-48 months). Thirty-day and follow-up mortality rates were 13.5% and 15.3%, respectively. Target vessel instability was 10%, of which 3.8% required reintervention. There was no statistically significant difference in outcomes between the early and late experience groups. CONCLUSIONS: Laser fenestration thoracic endovascular aortic repair of the aortic arch performed in experienced aortic centers is associated with low early mortality and stroke rates. It is a safe and effective therapeutic option in patients considered unfit for open repair. CLINICAL IMPACT: Custom-made devices for arch pathologies requiring urgent repair are not an option because of manufacturing delays. Off-the-shelf devices with single branch arch prostheses, and outside IFU techniques such as parallel-grafts and surgeon-modified endografts have been proposed in this setting. Another off-the-shelf alternative is in situ laser fenestration thoracic endovascular repair (LFTEVAR), which addresses many limitations of the other off-the-shelf options. Our study reports the outcomes of 30 patients treated with LFTEVAR, showing that it is a viable therapeutic option in patients considered unfit for open repair acknowledging that sufficient experience with complex endovascular aortic repair is mandatory to achieve acceptable outcomes in these high-risk patients with challenging aortic anatomies.

The Initial Results of Physician-Modified Fenestrated-Branched Endovascular Repairs of the Aortic Arch and Lessons Learned From the First 21 Cases.

INTRODUCTION: Physician-modified fenestrated-branched endovascular aortic repair (PM-FBEVAR) for the aortic arch provides a minimally invasive treatment option for patients who are too high-risk for open repair. Improvements in technique are gained with ongoing experience with these complex repairs. This study aims to describe outcomes of arch PM-FBEVAR and technical lessons. MATERIALS AND METHODS: A retrospective review of consecutive patients who underwent PM-FBEVAR with zone 0 proximal sealing at a single institution between January 2019 and July 2023 was performed. Cases completed using initial techniques (early technique) were compared with cases using the current techniques (current technique). Modification technique changed to include a self-orienting spine trigger wire and anatomically specific fenestrations or inner branches in the current group. The primary outcome was in-hospital mortality. Secondary outcomes included technical success and 30 day stroke. RESULTS: A total of 21 patients underwent arch PM-FBEVAR, with 7 in the early group and 14 in the current group. Severe comorbidities were present in both groups including chronic obstructive pulmonary disease (COPD) (43% vs 36%), prior open ascending aortic repair (57% vs 43%), and prior stroke (86% vs 21%), respectively. Technical success was the same (86% vs 86%, p=1.0). Fluoroscopy time (56 vs 24 min, p=0.012) and in-hospital death (43% vs 0%, p=0.026) were significantly lower in the current group. A 30 day stroke rate (29% vs 7%, p=0.247) was non-significantly decreased in the current group. All-cause mortality was 100% vs 7% during median follow-up of 8 and 6 months (p<0.001). Three deaths in the early group were related to their aortic arch repair including aortic rupture during endograft advancement and 2 postoperative strokes. CONCLUSION: There is a significant learning curve associated with aortic arch PM-FBEVAR. This study suggests that gained experience, use of the spine trigger wire technique, and precise creation of fenestrations or inner branches can lead to a shorter procedure time and lower complications. CLINICAL IMPACT: Physician modified fenestrated branched endografting is feasible for the aortic arch. The high rate of stroke and perioperative mortality was reduced with incorporation of self-orienting spine trigger wire and anatomically specific inner branch creation.

Anatomical Feasibility of the "Canaud Technique" for Physician-Modified Thoracic Endovascular Grafts for the Treatment of Aortic Arch Disease.

PURPOSE: Thoracic endovascular aortic repair (TEVAR), originally conceived for deployment distal to the left subclavian artery (LSA), has been recently extended to more proximal landing zones. Among total endovascular solutions, the "Canaud technique" for Physician-Modified Thoracic Endovascular Grafts (C-PMEGs) has gained acceptance with good early results. The aim of this study is to report the proportion of patients with zone 0, 1, and 2 aortic arch lesions that could theoretically be treated with a C-PMEG. MATERIALS AND METHODS: Computed tomography angiography (CTA) of all consecutive patient candidates to open, hybrid, or endovascular arch repair from January 2009 to July 2023 at our Institution were analyzed. The assessment of feasibility of C-PEMG was conducted following previously extensively described anatomical criteria. RESULTS: During the study period, 209 consecutive patients were candidates for an open, hybrid, or endovascular aortic arch repair. Of them, 164 patients had a preoperative CTA scan eligible for analysis. One hundred twenty-six patients were male (76.8 %), with a mean age of 67 ± 10.8 years. Ninety-four patients (57.3%) were affected by atherosclerotic aneurysms, 48 post-dissecting aneurysms (29.3%) and 22 penetrating aortic ulcers (PAUs) (13.4%). Twenty patients (12.2%) were suitable for double-fenestrated C-PMEG, and 34 patients (20.7%) for single-fenestrated C-PMEG, totaling 32.9% of the entire cohort. The combination of supra-aortic trunks (SAT) bypass or the use of covered stent in IA or left common carotid artery (LCCA) as adjunctive maneuvers, would extend the C-PMEGs feasibility to 69 patients (42.1%). The use of an iliac graft conduit in 3 (1.8%) patients with inadequate ileo-femoral accesses would increase the C-PMEG suitability to 72 patients (43.9%). The main reason for exclusion was excessive ascending aortic diameter in 78 patients (47.6%). CONCLUSIONS: The use of C-PMEG was shown to be theoretically feasible in a percentage of patients ranging from 32.9 to 43.9% affected by aortic arch aneurysms, dissections, and PAU. The main reason for exclusion was the dimension of the ascending aorta. The C-PMEG technique is a viable option in aortic arch lesions endovascular treatment. An off-the-shelf device with similar characteristics could also be used in emergency, avoiding the limitations of physician modifications (such as time for back-table procedure, sterility, off-label use). CLINICAL IMPACT: Thoracic endovascular aortic repair (TEVAR) has been extended to more proximal landing zones for the treatment of aortic arch aneurysm, dissections, penetrating aortic ulcers. Among total endovascular solutions, the "Canaud technique" for Physician-Modified Thoracic Endovascular Grafts (C-PMEGs) has gained acceptance with good early results. The anatomical feasibility in 164 consecutive patients was 69 patients (42.1%), with the combination of supra-aortic trunks (SAT) bypass or the use of covered stent in IA or left common carotid artery (LCCA) as adjunctive maneuvers, showing that the C-PMEG technique is a viable option in aortic arch lesions endovascular treatment.

Technical Aspects of Exclusive Transfemoral Route for Total Endovascular Arch Repair: A Custom-Made Device With Only Upward-Facing Inner Branches for Aortic Arch Treatment.

PURPOSE: The purpose was to demonstrate a new arch endograft configuration to allow total endovascular aortic arch repair exclusive from transfemoral approach. TECHNIQUE: The custom-made multi-branched arch endograft (Cook Medical, Bloomington, Indiana) features 3 inner branches (IBs) for supra-aortic vessels incorporation and complete endovascular arch repair. Traditionally, the innominate and left carotid branches are anterograde IBs, requiring upper access for incorporation of these vessels, and the left subclavian branch is an upward-facing IB that can be incorporated from transfemoral access. We report a novel device configuration with only upward-facing IBs, allowing exclusive transfemoral route for total endovascular arch repair. Technical aspects, implantation technique, and limitations are described thoroughly. CONCLUSION: Herein is described an arch endograft configuration that simplifies endovascular aortic arch repair, allowing supra-aortic vessel incorporation through a transfemoral route only. This innovative design may serve as another alternative in selected patients. CLINICAL IMPACT: This innovative endograft design, with only upward-facing inner branches, simplifies the total endovascular aortic arch repair by allowing for a exclusively transfemoral approach. This may reduce procedural complexity and minimizes risks associated with multiple access points. It provides another alternative, particularly beneficial for selected high-risk patients for open repair, potentially expanding the applicability of endovascular treatments for aortic arch pathologies.

Physician Modified Fenestrated Endografts for Endovascular Aortic Arch Repair in Zone 0.

OBJECTIVE: This multicentre study aimed to assess the early and midterm outcomes of physician modified fenestrated endografts (PMEGs) for endovascular aortic arch repair in zone 0. METHODS: Between 2018 and 2022, a retrospective study was conducted in three centres of consecutive patients undergoing endovascular aortic arch repair in zone 0 with PMEGs. Endpoints included technical success, 30 day mortality rate, major adverse events, secondary interventions, stent stability, target vessel patency, and overall survival. RESULTS: A total of 54 patients (mean age 63 years; 45 males) with aortic arch pathology were included, comprising aortic dissections (n = 32; 59%) and aortic arch aneurysms (n = 22; 41%). Technical success was 98%. One patient died from stroke within 30 days. Major adverse events included stroke (n = 4; 7%), retrograde type A dissection (RTAD) (n = 3; 6%), and acute kidney injury (n = 2; 4%). During a median follow up of 12 months, there were two deaths (4%) of unknown cause at one month and 1.5 months, and no aortic related death. Type Ia, type Ic, and type IIIc endoleaks were observed in two (4%), three (6%), and two (4%) patients, respectively. No vessel stenosis was observed. Re-intervention was required in 10 patients (19%). Estimates of overall survival, freedom from secondary intervention, and freedom from target vessel instability at one year were 94.2% (standard error [SE] 3.3%), 81.8% (SE 6.0%), and 92.0% (SE 4.5%), respectively. CONCLUSION: This study has demonstrated the efficacy of PMEGs for zone 0 endovascular aortic arch repair, with acceptable technical success and mortality rates. Stroke, RTAD, and re-intervention rates remain a concern for endovascular therapy. A larger population and long term outcomes are required to assess the safety and durability of this technique as a beneficial choice for endovascular aortic arch repair in specialised centres.

Branch Thrombus after Endovascular Treatment with Arch Branched Devices for Aortic Arch Pathologies.

OBJECTIVE: The aim of this study was to describe the occurrence of branch thrombosis following endovascular treatment of aortic arch pathology using an arch branched device (ABD) and to determine whether this is influenced by clinical and geometric parameters. METHODS: In this retrospective observational study of patients treated with an ABD in three centres, the primary endpoint was thrombus formation within a branch during follow up. Secondary endpoints were technical success, serious adverse events (SAEs), early and late death, stroke, and re-interventions. Geometric measurements (tortuosity index and curvature) were determined on pre-operative and post-operative computed tomography angiographies. RESULTS: Thirty nine patients were treated and 68 antegrade branches were analysed (innominate artery, n = 27; common carotid artery [CCA], n = 40; left subclavian artery [LSA], n = 1). Thrombus was identified within seven branches (10%) on surveillance imaging (innominate artery, n = 6; CCA, n = 1; LSA, n = 0; p = .021) and was associated with a wider distal bridging stent diameter (median 14.0 mm [interquartile range {IQR} 2.0] vs. 8.7 mm [IQR 5.9]; p = .026), a higher degree of reversed tapering (4.3 mm [IQR 1.4] vs. 1.2 mm [IQR 2.8]; p = .023), use of polyethylene terephthalate (Dacron) covered (vs. expanded polytetrafluoroethylene) bridging stents (23% vs. 2%; p = .011), and higher body mass index (BMI) (32.1 kg/m2 [IQR 7.5] vs. 25.7 kg/m2 [IQR 5.4]; p = .029), but not with pre-operative or post-operative tortuosity index or curvature or alterations. Regarding secondary outcomes, the technical success rate was 97%, SAEs occurred in 15 patients (38%), early and late death rates were 8% and 23%, respectively, and early and late stroke rates were 5% and 23%, respectively. CONCLUSION: The risk of developing branch thrombosis after endovascular intervention with an ABD is considerable, especially of innominate artery branches, characterised by Dacron covered large diameter bridging stents, and in patients with a high BMI. Large prospective studies are required to analyse factors associated with branch thrombosis.

Sex Comparative Analysis of Branched and Fenestrated Endovascular Aortic Arch Repair Outcomes.

OBJECTIVE: Female sex is a risk factor for adverse events after endovascular aortic repair. Sex comparative early and midterm outcomes of fenestrated and branched endovascular aortic arch repair (F/B-Arch) are presented. METHODS: A single centre retrospective sex comparative analysis of consecutive patients managed with F/B-Arch was conducted according to STROBE. Primary outcomes were sex comparative technical success, death, and cerebrovascular morbidity at 30 days. Kaplan-Meier estimates were used for follow up outcomes. RESULTS: Among 209 patients, 38.3% were women. Coronary artery disease (p < .001) and previous myocardial infarction (p = .001) were more common in women. Non-native proximal aortic landing was higher in women (women: 51.3%; men: 31.8%, p = .005) and the aortic dissection rate was lower (28.8% vs. 48.1%, p = .005). Proximal landing to Ishimaru zones showed no difference (zone 0: p = .18; zone 1: p = .47; zone 2: p = .39). Graft configurations were equally distributed. In total, 416 supra-aortic trunks were bridged. The median number of revascularisations per patient was two (interquartile range 1, 3), with no difference between sexes (p = .54). Technical success (women: 97.5%; men: 96.9%, p = .80), 30 day mortality rate (women: 10%; men: 9.3%, p = .86), and cerebrovascular morbidity (women: 11.3%; men: 17.1%, p = .25) were similar. Women presented more access related complications (women: 32.5%; men: 16.3%, p = .006), without affecting access related re-interventions (p = .55). Survival (women: 81.1%, 95% confidence interval [CI] 76.3 - 85.9%; men: 79.8%, 95% CI 76.0 - 83.6%) and freedom from re-intervention (women: 56.6%, 95% CI 50.4 - 62.8%; men: 55.3%, 95% CI 50.1 - 60.5%) at 12 months were similar (log rank, p = .40 and p = .41, respectively). CONCLUSION: Both sexes presented similar outcomes after F/B-Arch. Appropriate patient selection may decrease the effect of sex in F/B-Arch outcomes.