Healing of Prosthetic Arterial Grafts

Numerous synthetic biomaterials have been developed as vascular substitutes. In vitro, ex vivo and in vivo studies have demonstrated that in animals, selected materials, i.e., Dacron and ePTFE (expanded polytetrafluoroethylene) grafts, are successfully incorporated in both the large and the small caliber host arteries through a process which is generally referred to as graft healing. Morphologically, this process consists of a series of complex events including fibrin deposition and degradation, monocyte-macrophage recruitment and flow-oriented cell-layer generation, this last event being the complete endothelialization of the arterial substitute. In contrast to experimental animals, the flow surface of synthetic vascular grafts remains unhealed in humans, particularly in the small caliber conduits. Healing in man consists of graft incorporation by the perigraft fibrous tissue response with a surface covered by more or less compacted, cross-linked fibrin. It is therefore obvious that: i) marked differences in graft healing exist between animals and man; and ii) the usual mechanisms of graft endothelialization are partially ineffective in man. In order to guarantee the patency of synthetic vascular grafts for human small artery bypass, new strategies and approaches have recently been attempted. In particular, the endothelial cell seeding approach has been successfully accomplished in animals and is being experimented in human clinical studies. The problems and results of this biological approach are outlined in this paper

Development of a Rotation Device for Microvascular Endothelial Cell Seeding

A rotation device (RD) specifically designed to achieve sterile endothelial cell (EC) seeding of vascular grafts has been developed. The basic characteristics of the RD include: small dimensions, fully autoclavable components, and perfectly sealed graft holders. These features make it possible to maintain sterility during all the steps of EC seeding. This was documented by negativity of all bacteriological assays performed . Moreover, the RD can simultaneously support three vascular grafts with different lengths (20, 40, and 60 cm) and diameters (4-8 mm). EC seeding is performed in the climatized chamber (37 °C; 5 % C02) with constant rotation (0.1 -3 rpm). The rotation cycle can be completed automatically. The practical efficacy of the RD was investigated by seeding 2 x 105/cm2 of human microvascular EC on 20 cm length, 4 mm internal diameter (ID) fibronectin- coated polytetrafluoroethylene (ePTFE) grafts for 24 and 48 hours respectively . Further, the effect of a highly viscous plasma expander, i.e., haemagel, on cell retention was also evaluated. Results were not as favorable as expected. However, it should be emphasized that after 48 hours of eel! incubation by using the RD, 42 % of the initially seeded EC were still present and approximately 15 % were fully spread over the graft surface. Moreover, the 10 minute perfusion with haemagel did not decrease the number of adherent microvascular EC

Cook Zenith Alpha Endograft: A Protocol to Minimise Limb Graft Occlusion

Objective: Numerous articles have reported an increased incidence of limb graft occlusion (LGO) with the Cook Zenith Alpha endograft compared with other endografts in endovascular aortic aneurysm repair (EVAR). The present study aimed to assess the rate of LGO after EVAR in particular with the Cook Zenith Alpha device when adhering to a standardised protocol designed to prevent limb related complications. Methods: This was a non-sponsored retrospective study performed in two university vascular surgery centres employing the same protocol for limb complication prevention during EVAR from 2016 to 2019. The protocol encompassed: (1) angioplasty of any common or external iliac artery with > 50% stenosis before endograft navigation; (2) proximal sealing zone of limbs at the same level of the flow divider with minimum overlap, which is more restrictive than the Cook Zenith Alpha instructions for use; (3) semi-compliant kissing ballooning of limbs; (4) limb stenting for any residual tortuosity, kinking, or stenosis; and (5) adjunctive common and external iliac stenting for residual stenosis or dissection after EVAR. Patients enrolled in this study were treated with standard aortobi-iliac EVAR. Follow up was performed by clinical visit and duplex ultrasonography at discharge, six months, and yearly thereafter. The primary endpoint was to evaluate the LGO rate with different EVAR devices (Cook Zenith Alpha, Gore C3, and Medtronic Endurant) and to determine potential risk factors for LGO associated with the Zenith Alpha. Results: In the study period, 547 EVARs were considered: 233 (42.6%) Cook Zenith Alpha, 196 (35.8%) Gore Excluder, and 118 (21.6%) Medtronic Endurant. The mean follow up was 44 ± 23 months, and the five year freedom from LGO was 97 ± 3%, without differences between groups (97 ± 2%, 95 ± 3%, and 100% with Cook Zenith Alpha, Medtronic Endurant, and Gore Excluder, respectively; p = .080). In the Zenith Alpha group, intra-operative adjunctive iliac artery angioplasty, iliac artery stenting, or iliac limb stenting was performed in 8%, 3.4%, and 9.7% of cases, respectively. Analysis of potential risk factors for LGO identified external iliac artery distal landing and large main bodies (ZIMB 32 – 36) to be independently associated with LGO during follow up (hazard ratio [HR] 18, 95% confidence interval [CI] 3 – 130, p = .004; and HR 12, 95% CI 1.2 – 130, p = .030, respectively). Conclusion: The present experience with a protocol for limb complication prevention allows achievement of a low rate of LGO at five years with Zenith Alpha endografts similar to other endografts. Specific risk factors for the Cook Zenith Alpha endograft are external iliac artery distal landing and the use of a large main body (ZIMB 32 – 36)

In-vivo vascular application via ultra-fast bioprinting for future 5D personalised nanomedicine

The design of 3D complex structures enables new correlation studies between the engineering parameters and the biological activity. Moreover, additive manufacturing technology could revolutionise the personalised medical pre-operative management due to its possibility to interplay with computer tomography. Here we present a method based on rapid freeze prototyping (RFP) 3D printer, reconstruction cutting, nano dry formulation, fast freeze gelation, disinfection and partial processes for the 5D digital models functionalisation. We elaborated the high-resolution computer tomography scan derived from a complex human peripheral artery and we reconstructed the 3D model of the vessel in order to obtain and verify the additive manufacturing processes. Then, based on the drug-eluting balloon selected for the percutaneous intervention, we reconstructed the biocompatible eluting-freeform coating containing 40\u2009nm fluorescent nanoparticles (NPs) by means of RFP printer and we tested the in-vivo feasibility. We introduced the NPs-loaded 5D device in a rat's vena cava. The coating dissolved in a few minutes releasing NPs which were rapidly absorbed in vascular smooth muscle cell (VSMC) and human umbilical vein endothelial cell (HUVEC) in-vitro. We developed 5D high-resolution self-dissolving devices incorporating NPs with the perspective to apply this method to the personalised medicine

Simultaneous versus staged approach in transcatheter aortic valve implantation for severe stenosis and endovascular aortic repair for thoracic and abdominal aortic aneurysm

Objectives: Thoracic/abdominal aortic aneurysms and aortic stenosis may be concomitant diseases requiring both transcatheter aortic valve implantation (TAVI) and endovascular aneurysm repair (T/EVAR) in high-risk patients for surgical approaches, but temporal management is not clearly defined yet. The aim of the study was to analyse outcomes of simultaneous versus staged TAVI and T/EVAR. Methods: Retrospective observational multicentre study was performed on patients requiring TAVI and T/EVAR from 2016 to 2022. Patients were divided into 2 groups: 'Simultaneous group' if T/EVAR + TAVI were performed in the same procedure and 'Staged group' if T/EVAR and TAVI were performed in 2 steps, but within 3 months. Primary outcomes were technical success, 30-day mortality/major adverse events and follow-up survival. Secondary outcomes were procedural metrics and length of stay. Results: Forty-four cases were collected; 8 (18%) had T/EVAR and 36 (82%) had EVAR, respectively. Upon temporal determination, 25 (57%) and 19 (43%) were clustered in Simultaneous and Staged groups, respectively. In Staged group, median time between procedures was 72 (interquartile range-IQR: 57-87) days. Preoperative and intraoperative figures were similar. There was no difference in 30-day mortality (Simultaneous: 0/25 versus Staged: 1/19; P = 0.43). Pulmonary events (Simultaneous: 0/25 versus Staged: 5/19; P = 0.01) and need of postoperative cardiac pacemaker (Simultaneous: 2/25 versus Staged: 7/19; P = 0.02) were more frequent in Staged patients. The overall length of stay was lower in the Simultaneous group [Simultaneous: 7 (IQR: 6-8) versus Staged: 19 (IQR: 15-23) days; P = 0.001]. The median follow-up was 25 (IQR: 8-42) months and estimated 3-year survival was 73% with no difference between groups (Simultaneous: 82% versus Staged: 74%; P = 0.90). Conclusions: Both Simultaneous or Staged T/EVAR and TAVI procedures are effective with satisfactory outcomes. Despite the small numbers, simultaneous repair seems to reduce length of stay and pulmonary complications, maintaining similar follow-up survival

Urgent endovascular repair of juxtarenal/pararenal aneurysm by off-the-shelf multibranched endograft

Objective: To report outcomes of urgent juxtarenal/pararenal aneurysms (J/P-AAAs) managed by off-the-shelf multibranched thoracoabdominal endografts (Cook, T-branch). Methods: In this observational, multicenter, retrospective study, patients with J/P-AAAs treated by urgent endovascular repair by T-branch in 23 European aortic centers, from 2013 to 2023, were analyzed. Contained J/P-AAAs rupture, presence of related symptoms, and aneurysm diameter of >70 mm were considered as indication for urgent repair. Technical success (TS), spinal cord ischemia (SCI), and 30-day/hospital mortality were assessed as early outcomes. Survival, freedom from reinterventions, and target artery instability (TAI) were evaluated during follow-up. Results: Overall, 197 patients (J-AAAs, n = 64 [33%]; P-AAAs, n = 95 [48%]; previous failed endovascular aneurysm repair (EVAR), n = 38 [19%]) were analyzed. The mean age and aneurysm diameter was 75 ± 8 years and 76 ± 4 mm, respectively. The American Society of Anesthesiologists score was 3 and 4 in 118 (60%) and 79 (40%) patients. Rupture, symptoms, and diameter of >70 mm were present in 51 (26%), 110 (56%), and 53 (27%) patients, respectively. An adjunctive proximal thoracic endograft was used in 28 cases (14%). The mean aortic coverage between the upper portion of the endograft and the lowest renal artery was 154 ± 49 mm. Single-stage repair and cerebrospinal fluid drainage were reported in 144 (73%) and 53 (27%) cases, respectively. TS was achieved in 182 (92%) cases (rupture, 84% vs no rupture, 95%; P = .02). Failures consist of TA loss (11 [6%]: renal artery, 9; celiac trunk, 2), type I to III endoleaks (2 [1%]), and 24-h mortality (2 [1%]). Rupture was a risk factor for technical failure (P = .02; odds ratio [OR], 3.8; 95% confidence interval [CI], 1.1-12.1). Overall, 15 patients (8%) had persistent SCI (rupture, 14% vs no rupture, 5%) with 11 (6%) , of paraplegia (rupture, 10% vs no rupture, 5%; P = .001). Rupture (P = .04; OR, 3.1; 95% CI, 1.1-8.9) and adjunctive proximal thoracic endograft (P = .01; OR, 4.1; 95% CI, 1.3-12.9) were risk-factors for SCI. Twenty-two patients (11%) died within 30 days or during a prolonged hospitalization. Previous failed EVAR (P = .04; OR, 3.6; 95% CI, 1.1-12.3), paraplegia (P < .001; OR, 9.9; 95% CI, 1.6-62.2) and postoperative mesenteric complications (P = .03; OR, 10.4; 95% CI, 1.2-93.3), as well as cardiac (P = .03; OR, 8.2; 95% CI, 2.0-33.0) and respiratory (P < .001; OR, 10.1; 95% CI, 2.9-35.2) morbidities were associated with 30-day/hospital mortality. The mean follow-up was 19 ± 5 months. The estimated 3-year survival and freedom from reinterventions was 58% and 77%, respectively. TAI occurred in 27 patients (14%) (occlusion, 15; endoleak, 14) with an estimated 3-year freedom from TAI of 72%. Conclusions: Urgent repair of J/P-AAAs by T-branch is feasible and effective with satisfactory TS and 30-day/hospital mortality in high-risk patients. However, extensive aortic coverage is necessary, leading to a non-negligible SCI rate, especially in case of aortic rupture or when adjunctive thoracic endografts are necessary. Previous failed EVAR and postoperative mesenteric complications, as well as cardiac and respiratory morbidities were associated with 30-day/hospital mortality and should be subjected to more research for the purposes of improving outcomes

The sac evolution imaging follow-up after endovascular aortic repair: An international expert opinion-based Delphi consensus study

Objective: Management of follow-up protocols after endovascular aortic repair (EVAR) varies significantly between centers and is not standardized according to sac regression. By designing an international expert-based Delphi consensus, the study aimed to create recommendations on follow-up after EVAR according to sac evolution. Methods: Eight facilitators created appropriate statements regarding the study topic that were voted, using a 4-point Likert scale, by a selected panel of international experts using a three-round modified Delphi consensus process. Based on the experts’ responses, only those statements reaching a grade A (full agreement $75$80% and full disagreement &lt;5%) were included in the final document. Results: One-hundred and seventy-four participants were included in the final analysis, and each voted the initial 29 statements related to the definition of sac regression (Q1-Q9), EVAR follow-up (Q10-Q14), and the assessment and role of sac regression during follow-up (Q15-Q29). At the end of the process, 2 statements (6.9%) were rejected, 9 statements (31%) received a grade B consensus strength, and 18 (62.1%) reached a grade A consensus strength. Of 27 final statements, 15 (55.6%) were classified as grade I, whereas 12 (44.4%) were classified as grade II. Experts agreed that sac regression should be considered an important indicator of EVAR success and always be assessed during follow-up after EVAR. Conclusions: Based on the elevated strength and high consistency of this international expert-based Delphi consensus, most of the statements might guide the current clinical management of follow-up after EVAR according to the sac regression. Future studies are needed to clarify debated issues. (J Vasc Surg 2024;80:937-45.