The Impact of Seasonality on Prosthetic Arteriovenous Vascular Access Graft Thrombosis

Highlights Abstract Introduction: Arteriovenous prosthetic grafts are susceptible to recurrent thrombotic occlusions mainly due to venous outflow disease secondary to neointimal hyperplasia. Maintenance of vascular access for dialysis is a perpetual challenge for both patients and health care systems. In regions with hotter climates, there is a clinical impression that episodes of prosthetic arteriovenous vascular access graft thrombosis are more frequent during hot dry summers secondary to dehydration and increased blood viscosity. Seasonality of thrombotic events has been observed in multiple vascular beds. However, a seasonal pattern or any association of arteriovenous graft thrombosis with temperature and relative humidity levels has never been fully demonstrated. Methods: Data were collected prospectively from January 2014 until December 2020 but analyzed retrospectively. In this 7-year timeframe, 289 episodes of arteriovenous graft thrombosis were identified from 142 grafts fashioned. Results: No monthly variation (P = 0.35) or seasonal variation (P = 0.91) was identified. No statistically significant correlation between episodes of thrombosis and mean monthly temperature and mean relative humidity was noted. Conclusion: No evidence was identified to support this theory. However, multiple issues with assessments of events must be conceded. Graft thrombosis is multifactorial in nature, and venous outflow disease contributes toward a significant number of these events. Within our local cohort, a low primary patency rate was identified, which further contributes to graft interventions. Relatively small numbers were recruited, and therefore, potential correlations could have been missed.

Antithrombotic Management in Adult Kidney Transplantation – A European survey study

In kidney transplantation (KTx), renal graft thrombosis (RGT) is one of the main reasons for early graft loss. Although evidence-based guidance on prevention of RGT is lacking, thromboprophylaxis is widely used. The aim of this survey was to obtain a European view of the different thromboprophylactic strategies applied in KTx. An online 22-question survey, addressed to KTx professionals, was distributed by e-mail and via platforms of the European Society for Organ Transplantation. Seventy-five responses (21 countries, 51 centers) were received: 75% had over 10 years’ clinical experience, 64% were surgeons, 29% nephrologists and 4% urologists. A written antithrombotic management protocol was available in 75% of centers. In 8 (16%) of centers respondents contradicted each other regarding the availability of a written protocol. Thromboprophylaxis is preferred by 78% of respondents, independent of existing antithrombotic management protocols. Ninety-two percent of respondents indicated that an anticipated bleeding risk is the main reason to discontinue chronic antithrombotic therapy preoperatively. Intraoperatively, 32% of respondents administer unfractionated heparin (400 – 10.000 international units with a median of 5000) in selected cases. Despite an overall preference for perioperative thromboprophylaxis in KTx, there is a high variation within Europe regarding type, timing and dosage, most likely due to the paucity of high-quality studies. Further research is warranted in order to develop better guidelines.

Designing Cardiovascular Implants Taking in View the Endothelial Basement Membrane

Insufficient endothelialization of cardiovascular grafts is a major hurdle in vascular surgery and regenerative medicine, bearing a risk for early graft thrombosis. Neither of the numerous strategies pursued to solve these problems were conclusive. Endothelialization is regulated by the endothelial basement membrane (EBM), a highly specialized part of the vascular extracellular matrix. Thus, a detailed understanding of the structure–function interrelations of the EBM components is fundamental for designing biomimetic materials aiming to mimic EBM functions. In this review, a detailed description of the structure and functions of the EBM are provided, including the luminal and abluminal interactions with adjacent cell types, such as vascular smooth muscle cells. Moreover, in vivo as well as in vitro strategies to build or renew EBM are summarized and critically discussed. The spectrum of methods includes vessel decellularization and implant biofunctionalization strategies as well as tissue engineering-based approaches and bioprinting. Finally, the limitations of these methods are highlighted, and future directions are suggested to help improve future design strategies for EBM-inspired materials in the cardiovascular field.

453 An unexpected finding in an asymptomatic patient planned for non-cardiac surgery

Aims Left ventricular (LV) aneurysms and pseudoaneurysms are two complications of myocardial infarction, either symptomatic or silent, leading to death or serious morbidity in several cases and often precluding non-cardiac surgery. Here the differential diagnosis is challenging and multimodality imaging is often needed to assess the risk of heart rupture. Methods and results A 71 years-old woman was referred to our Cardiology Department for a preoperative evaluation before lung lobectomy. Her past medical history included multiple cardiovascular risk factors and abdominal aorta aneurysm. She also had severe peripheral arterial disease treated with femoral popliteal bypass surgery in June 2021. In August 2021 she suffered from vascular graft thrombosis requiring a redo surgery. During hospitalization, she was found to have a lung adenocarcinoma. The patient had an unremarkable cardiological history and was asymptomatic. EKG was unremarkable. Transthoracic echocardiography revealed a mildly impaired LV systolic function (EF = 40%), an inferolateral basal wall akinesia and a huge aneurysm with intracavitary thrombus and a wide neck arising right below the posterior mitral annulus. The annular distortion caused by the expanding aneurysm contributed to the development of mitral regurgitation (MR) by displacing the annulus and subvalvular apparatus, resulting in restriction of the posterior mitral valve leaflet, coaptation failure, and moderate MR. Coronary angiography demonstrated a severe 3-vessel coronary artery disease. To further characterize the aneurysm, a cardiac magnetic resonance was carried out. T1 weighted inversion recovery LGE 2-chamber and short axis views showed transmural LGE of the inferior wall and confirmed the presence of a saccular dilatation with thin wall, wide neck (5 × 6 cm) and large intracavitary thrombus at high risk of rupture. Since the presence of metastatic lesions was excluded, the patient underwent cardiac surgery followed by elective lobectomy. Intraoperative findings were consistent with LV aneurysm with a thin myocardial wall. Aneurysm and related thrombus were removed and the orifice was closed with a Dacron patch. In the same setting a myocardial revascularization with two coronary artery bypass grafts was also performed. Surgery was successfully performed without any complication. Intraoperative transesophageal echocardiography clearly revealed the aneurysm and witnessed the reduction of MR after the restoration of LV inferolateral wall geometry. Conclusions Our case highlights the importance of thorough evaluation prior to non-cardiac surgery using multimodality imaging, especially when incidental echocardiographic findings in asymptomatic patients occur. A careful pre-operative assessment of patients planned for non-cardiac surgery is the key to favourable postoperative outcome.

Abelacimab Reduces Thrombus Propagation in a Baboon Model of Vascular Graft Thrombosis

Background: Factor XI (FXI) inhibition demonstrated strong efficacy in preventing thrombus formation in preclinical and clinical models of arterial and venous thrombosis. However, the effect of FXI inhibition in halting the progression of a formed clot remains largely unknown. Aims: This study aims to test whether abelacimab, a dual-acting FXI and activated FXI (FXIa) monoclonal antibody, is effective in halting clot formation and downstream growth when administered before or during active clot formation in an established baboon femoral arterio-venous (AV) shunt model. Methods: Three baboons had a chronic femoral AV shunt put in place; platelet and fibrin deposition inside and distal to collagen- or collagen + tissue factor (TF)-coated vascular grafts were measured at baseline (control), in a therapeutic setting, where abelacimab (1 mg/kg, intravenously) was administered 30 minutes after thrombus initiation, and in a preventative setting within the first 48 h and 1 week (144 - 216 h) post-administration. Pharmacodynamic effect was measured by activated partial thromboplastin time (aPTT). Results: Consistent with its half-life of 20 to 30 days, single iv administration of abelacimab at a dose of 1 mg/kg resulted in long-lasting (> 4-week) aPTT prolongation (> 2-fold). Administration of abelacimab 30 minutes after initiation of thrombosis using grafts coated either with collagen or with collagen + TF quickly halted downstream propagation of platelet and fibrin deposition compared to control. Further, downstream propagation of platelet and fibrin deposition was markedly reduced when clotting was induced by collagen, or collagen + tissue factor after abelacimab administration. Conclusions: These data suggest that abelacimab, a dual-acting anti-FXI/FXIa monoclonal antibody with a single long-lasting iv injection has the potential to slow down the growth and reduce the size of thrombi when admistered before or after clot induction. Data indicate a potential for therapeutic benefit of targeting FXI both in therapeutic and preventive settings. Sponsored by: Anthos Therapeutics Inc., 55 Cambridge Parkway, Suite 103, Cambridge, MA 02142 Figure 1 Figure 1. Disclosures Wallisch: Aronora Inc,: Current Employment. Khder: Anthos Therapeutics: Consultancy; Novartis: Current equity holder in publicly-traded company, Other: Retiree. Bloomfield: Anthos Therapeutics: Current Employment. Gruber: Aronora Inc.: Current Employment, Current equity holder in publicly-traded company; Oregon Health and Science University: Current Employment.