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Despite advances in prevention, detection, and treatment, cardiovascular disease is a leading cause of mortality and represents a major health problem worldwide. Artificial intelligence and machine learning have brought new insights to the management of vascular diseases by allowing analysis of huge and complex datasets and by offering new techniques to develop advanced imaging analysis. Artificial intelligence–based applications have the potential to improve prognostic evaluation and evidence-based decision making and contribute to vascular therapeutic decision making. In this scoping review, we provide an overview on how artificial intelligence could help in vascular surgical clinical decision making, highlighting potential benefits, current limitations, and future challenges.

Cardiovascular diseases represent a major cause of morbidity and mortality, necessitating research to improve diagnostics, and to discover and test novel preventive and curative therapies. All of which warrant experimental models that recapitulate human disease. The translation of basic science results to clinical practice is a challenging task. In particular for complex conditions such as cardiovascular diseases, which often result from multiple risk factors and co-morbidities. This difficulty might lead some individuals to question the value of animal research, citing the translational 'valley of death', which largely reflects the fact that studies in rodents are difficult to translate to humans. This is also influenced by the fact that new, human-derived in vitro models can recapitulate aspects of disease processes. However, it would be a mistake to think that animal models cannot provide a vital step in the translational pathway as they do provide important pathophysiological insights into disease mechanisms particularly on a organ and systemic level. While stem cell-derived human models have the potential to become key in testing toxicity and effectiveness of new drugs, we need to be realistic, and carefully validate all new human-like disease models. In this position paper, we highlight recent advances in trying to reduce the number of animals for cardiovascular research ranging from stem cell-derived models to in situ modelling of heart properties, bioinformatic models based on large datasets, and improved current animal models, which show clinically relevant characteristics observed in patients with a cardiovascular disease. We aim to provide a guide to help researchers in their experimental design to translate bench findings to clinical routine taking the replacement, reduction and refinement (3R) as a guiding concept. [Abstract copyright: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions please email: journals.permissions@oup.com.]

Abdominal aortic aneurysms (AAAs) are progressive dilatations of the abdominal aorta that, if left untreated, can rupture with lethal consequences. Imaging-based patient monitoring is required to select patients eligible for surgical repair. In this work, we present a model based on implicit neural representations (INRs) to model AAA progression. We represent the AAA wall over time as the zero-level set of a signed distance function (SDF), estimated by a multilayer perception that operates on space and time. We optimize this INR using automatically extracted segmentation masks in longitudinal CT data. This network is conditioned on spatiotemporal coordinates and represents the AAA surface at any desired resolution at any moment in time. Using regularization on spatial and temporal gradients of the SDF, we ensure proper interpolation of the AAA shape. We demonstrate the network's ability to produce AAA interpolations with average surface distances ranging between 0.72 and 2.52 mm from images acquired at highly irregular intervals. The results indicate that our model can accurately interpolate AAA shapes over time, with potential clinical value for a more personalised assessment of AAA progression., FIMH 2023 (submitted)

Supplemental material, sj-docx-3-jet-10.1177_15266028231165731 for Initial Clinical Experience With AneuFix Injectable Biocompatible Elastomer for Translumbar Embolization of Type 2 Endoleaks by Stefan P. M. Smorenburg, Rutger J. Lely, Bas-Jeroen van Kelckhoven, Erik G. Vermeulen, Kak Khee Yeung, Rombout R. Kruse, Martin Kraai, Chrit M. Stassen, Michael J. Jacobs and Arjan W. J. Hoksbergen in Journal of Endovascular Therapy

Supplemental material, sj-docx-1-jet-10.1177_15266028231165731 for Initial Clinical Experience With AneuFix Injectable Biocompatible Elastomer for Translumbar Embolization of Type 2 Endoleaks by Stefan P. M. Smorenburg, Rutger J. Lely, Bas-Jeroen van Kelckhoven, Erik G. Vermeulen, Kak Khee Yeung, Rombout R. Kruse, Martin Kraai, Chrit M. Stassen, Michael J. Jacobs and Arjan W. J. Hoksbergen in Journal of Endovascular Therapy

Supplemental material, sj-docx-1-jet-10.1177_15266028231165731 for Initial Clinical Experience With AneuFix Injectable Biocompatible Elastomer for Translumbar Embolization of Type 2 Endoleaks by Stefan P. M. Smorenburg, Rutger J. Lely, Bas-Jeroen van Kelckhoven, Erik G. Vermeulen, Kak Khee Yeung, Rombout R. Kruse, Martin Kraai, Chrit M. Stassen, Michael J. Jacobs and Arjan W. J. Hoksbergen in Journal of Endovascular Therapy

Supplemental material, sj-docx-2-jet-10.1177_15266028231165731 for Initial Clinical Experience With AneuFix Injectable Biocompatible Elastomer for Translumbar Embolization of Type 2 Endoleaks by Stefan P. M. Smorenburg, Rutger J. Lely, Bas-Jeroen van Kelckhoven, Erik G. Vermeulen, Kak Khee Yeung, Rombout R. Kruse, Martin Kraai, Chrit M. Stassen, Michael J. Jacobs and Arjan W. J. Hoksbergen in Journal of Endovascular Therapy

Supplemental material, sj-docx-2-jet-10.1177_15266028231165731 for Initial Clinical Experience With AneuFix Injectable Biocompatible Elastomer for Translumbar Embolization of Type 2 Endoleaks by Stefan P. M. Smorenburg, Rutger J. Lely, Bas-Jeroen van Kelckhoven, Erik G. Vermeulen, Kak Khee Yeung, Rombout R. Kruse, Martin Kraai, Chrit M. Stassen, Michael J. Jacobs and Arjan W. J. Hoksbergen in Journal of Endovascular Therapy

Supplemental material, sj-docx-3-jet-10.1177_15266028231165731 for Initial Clinical Experience With AneuFix Injectable Biocompatible Elastomer for Translumbar Embolization of Type 2 Endoleaks by Stefan P. M. Smorenburg, Rutger J. Lely, Bas-Jeroen van Kelckhoven, Erik G. Vermeulen, Kak Khee Yeung, Rombout R. Kruse, Martin Kraai, Chrit M. Stassen, Michael J. Jacobs and Arjan W. J. Hoksbergen in Journal of Endovascular Therapy

Supplemental material, sj-docx-2-jet-10.1177_15266028221120360 for Long-Term Outcomes of Nonoperative and Surgical Management of Paget-Schroetter Syndrome by Frank Hoexum, Vincent Jongkind, Hans M. E. Coveliers, Willem Wisselink and Kak Khee Yeung in Journal of Endovascular Therapy

Supplemental material, sj-docx-2-jet-10.1177_15266028221120360 for Long-Term Outcomes of Nonoperative and Surgical Management of Paget-Schroetter Syndrome by Frank Hoexum, Vincent Jongkind, Hans M. E. Coveliers, Willem Wisselink and Kak Khee Yeung in Journal of Endovascular Therapy

sj-docx-3-jet-10.1177_15266028221120360 for Long-Term Outcomes of Nonoperative and Surgical Management of Paget-Schroetter Syndrome by Frank Hoexum, Vincent Jongkind, Hans M. E. Coveliers, Willem Wisselink and Kak Khee Yeung in Journal of Endovascular Therapy

Supplemental material, sj-docx-1-jet-10.1177_15266028221120360 for Long-Term Outcomes of Nonoperative and Surgical Management of Paget-Schroetter Syndrome by Frank Hoexum, Vincent Jongkind, Hans M. E. Coveliers, Willem Wisselink and Kak Khee Yeung in Journal of Endovascular Therapy

Supplemental material, sj-docx-1-jet-10.1177_15266028221120360 for Long-Term Outcomes of Nonoperative and Surgical Management of Paget-Schroetter Syndrome by Frank Hoexum, Vincent Jongkind, Hans M. E. Coveliers, Willem Wisselink and Kak Khee Yeung in Journal of Endovascular Therapy

Smooth muscle cells (SMCs) are the predominant cell type in the aortic media. Their contractile machinery is important for the transmission of force in the aorta and regulates vasoconstriction and vasodilation. Mutations in genes encoding for the SMC contractile apparatus proteins are associated with aortic diseases, such as thoracic aortic aneurysms. Measuring SMC contraction in vitro is challenging, especially in a high-throughput manner, which is essential for screening patient material. Currently available methods are not suitable for this purpose. This paper presents a novel method based on electric cell-substrate impedance sensing (ECIS). First, an explant protocol is described to isolate patient-specific human primary SMCs from aortic biopsies and patient-specific human primary dermal fibroblasts for the study of aortic aneurysms. Next, a detailed description of a new contraction method is given to measure the contractile response of these cells, including the subsequent analysis and suggestion for comparing different groups. This method can be used to study the contraction of adherent cells in the context of translational (cardiovascular) studies and patient and drug screening studies.

Personalised 3D vascular models are valuable for diagnosis, prognosis and treatment planning in patients with cardiovascular disease. Traditionally, such models have been constructed with explicit representations such as meshes and voxel masks, or implicit representations such as radial basis functions or atomic (tubular) shapes. Here, we propose to represent surfaces by the zero level set of their signed distance function (SDF) in a differentiable implicit neural representation (INR). This allows us to model complex vascular structures with a representation that is implicit, continuous, light-weight, and easy to integrate with deep learning algorithms. We here demonstrate the potential of this approach with three practical examples. First, we obtain an accurate and watertight surface for an abdominal aortic aneurysm (AAA) from CT images and show robust fitting from as little as 200 points on the surface. Second, we simultaneously fit nested vessel walls in a single INR without intersections. Third, we show how 3D models of individual arteries can be smoothly blended into a single watertight surface. Our results show that INRs are a flexible representation with potential for minimally interactive annotation and manipulation of complex vascular structures., Comment: MICCAI STACOM 2022

This dataset supports the findings of the vascular e-Learning during the COVID-19 pandemic survey (the EL-COVID survey). The General Data Protection Regulation (GDPR) of the European Union was taken into consideration in all steps of data handling. The survey was approved by the institutional ethics committee of the Primary Investigator and an online English survey consisting of 18 questions was developed ad-hoc. A bilingual English-Mandarin version of the questionnaire was developed according to the instructions of the Chinese Medical Association in order to be used in mainland People's Republic of China. Differences between the two questionnaires were minor and did affect the process of data collection. Both questionnaires were hosted online. The EL-COVID survey was advertised through major social media. All national and regional contributors contacted their respective colleagues through direct messaging on social media or by email. Eight national societies or groups supported the dissemination of the EL-COVID survey. The data provided demographics information of the EL-COVID participants and an insight on the level of difficulty in accessing or citing previously attended online activities and whether participants were keen on citing these activities in their Curricula Vitae. A categorization of additional comments made by the participants are also based on the data. The survey responses were filtered, anonymized and submitted to descriptive analysis of percentage. (C) 2021 Published by Elsevier Inc.

INTRODUCTION: Thoracic sympathectomy is performed in the management of a variety of disorders of the upper extremity. To evaluate the contemporary results of thoracic sympathectomy for upper extremity ischemia a systematic review of the literature was conducted.EVIDENCE AQUISITION: We performed a PubMed, EMBASE and Cochrane search of the literature written in the English language from January 1975 to December 2015. All articles presenting original patient data regarding the effect of treatment on symptoms or on the healing of ulcers were eligible for inclusion. Individual analyses for Primary Raynaud's Disease (PRD) and Secondary Raynaud's Phenomenon (SRP) were performed.EVIDENCE SYNTHESIS: We included 6 prospective and 23 retrospective series with a total of 753 patients and 1026 affected limbs. Early beneficial effects of thoracic sympathectomy were noticed in 63-100% (median 94%) of all patients, in 73-100% (median 98%) of PRD patients and in 63-100% (median 94%) of SRP patients. The beneficial effect was noted to lessen over time. Long-term beneficial effects were reported in 13-100% (median 75%) of all patients, in 22-100% (median 58%) of PRD patients, and in 13-100% (median 79%) of SRD patients. Complete or improved ulcer healing was achieved in 33-100% and 25-67% respectively, of all patients.CONCLUSIONS: Thoracic sympathectomy can be beneficial in the treatment of upper extremity ischemia in select patients. Although the effect in patients with PRD will lessen over time, it may still reduce the severity of symptoms. In SRD, effects are more often long-lasting. In addition, thoracic sympathectomy may maximize tissue preservation or prevent amputation in cases of digital ulceration.

Background: LoeysDietz syndrome is a connective tissue disorder accompanied by lifethreatening vascular abnormalities such as aneurysms and dissections. Recognising the acute clinical picture is essential for rapid diagnosis and treatment. Case description: We describe three members of a family with a typical acute presentation of LoeysDietz syndrome, but without the characteristic physical abnormalities. A 40yearold man presented with a type B aortic dissection and was treated with medication. Shortly afterwards he required emergency surgery for a ruptured aneurysm of the left common iliac artery. He subsequently developed a type A aortic dissection and progressive dilatation of his thoracoabdominal aorta, for which surgical repair was performed. His sister and brother also presented with type B aortic dissections and both underwent surgery for thoracoabdominal aortic aneurysms. They died at the age of 50 and 53 respectively. Clinical genetic investigation revealed a mutation of the type 2 receptor of the transforming growth factor beta (TGFβ) gene. Conclusion: LoeysDietz syndrome is a rare hereditary condition accompanied by acute clinical symptoms. Physical characteristics of the syndrome may be absent. Timely recognition is essential for appropriate treatment and a good prognosis.

Background: LoeysDietz syndrome is a connective tissue disorder accompanied by lifethreatening vascular abnormalities such as aneurysms and dissections. Recognising the acute clinical picture is essential for rapid diagnosis and treatment. Case description: We describe three members of a family with a typical acute presentation of LoeysDietz syndrome, but without the characteristic physical abnormalities. A 40yearold man presented with a type B aortic dissection and was treated with medication. Shortly afterwards he required emergency surgery for a ruptured aneurysm of the left common iliac artery. He subsequently developed a type A aortic dissection and progressive dilatation of his thoracoabdominal aorta, for which surgical repair was performed. His sister and brother also presented with type B aortic dissections and both underwent surgery for thoracoabdominal aortic aneurysms. They died at the age of 50 and 53 respectively. Clinical genetic investigation revealed a mutation of the type 2 receptor of the transforming growth factor beta (TGFβ) gene. Conclusion: LoeysDietz syndrome is a rare hereditary condition accompanied by acute clinical symptoms. Physical characteristics of the syndrome may be absent. Timely recognition is essential for appropriate treatment and a good prognosis.

The exact pathways leading to AAA remain unclear, despite extensive research. So far, AAA treatment is mainly surgical, either in the elective setting to prevent rupture or in the acute setting of symptomatic and ruptured AAA. The risk of progressive aortic dilation and rupture can be modified by smoking cessation, thrombocyte aggregation inhibitors, statins and antihypertensives in case of hypertension are advised, albeit to varying extent. In this light, there is a need for a better understanding of the pathophysiology of AAA. Therefore, the aim was to lay the foundation for comprehensive research in AAA pathophysiology, starting from a different perspective using live human aortic tissue to understand AAA better and potentially find new therapeutic targets. In Chapter 2, a systematic review was performed, in which the aim was to identify potential prognostic markers (circulating biomarkers, biomechanical properties and genetic mutations) for AAA growth and rupture. Factors with an increased AAA expansion risk included AAA diameter, seropositivity for chlamydophila pneumonia, S-elastin peptides, inverse fluorodeoxyglucose uptake, and intraluminal thrombus size. Factors with an increased AAA rupture risk included peak wall stress and AAA diameter. Unfortunately, cautious clinical interpretation of the conclusions was advised, due to the nature of the original studies and high heterogeneity between the studies, which might also reflect the complex a multifactorial nature of AAA pathophysiology. In Chapter 3, a novel protocol was provided in which live aortic tissue sections were preserved for over 60 days. The ex vivo tissues contained live patient-specific leukocytes and macrophages, and alterations in RNA expression of different genes in these tissues was observed as result of ex vivo tissue stimulation using TGF-β. The current sectioning and preservation protocol was implemented for further stimulation studies, as presented in the following chapters. In Chapter 4, live aortic tissue sections from AAA patients and non-dilated aortas were compared using nanoindentation. This technique tests the hardness of materials on a microscopic scale. A decrease in microscopic stiffness in the medial layer (in outside to inside direction) was observed in live tissues of AAA patient compared to non-dilated live aortic tissue sections. Furthermore, decreased SMC levels, collagen and fibroblasts were found in the tissue sections of AAA patients. This decrease in cellular and extracellular structures was correlated to the reduction in microscopic stiffness in the medial layer. Chapter 5 illustrated how seeded endothelial cells and SMC form confluent multilayers mimick an the wall using a new protocol. Next, a progressive parallel cytoskeletal organization was observed over time. Also, nanoindentation was again used, and micromechanical properties and visco-elastic properties comparable to biological vascular structures were observed. In Chapter 6, SMC were seeded and electric cell-substrate impedance sensing was performed after stimulation with calcium-ion-binding ionomycin. This study shows a subgroup of AAA patients who present impaired SMC contractility in sporadic AAA, which further underlines the multifactorial nature of AAA. Furthermore, a decreased maximum contractility was observed in patients who underwent open redo repair after endovascular aneurysm repair and patients that were currently smoking. Next, perivascular adipose tissue (PVAT) was studied, following the increased interest in PVAT. In Chapter 7, a higher intra-individual PVAT density was observed around the aneurysm in AAA patients. These findings were further supported by a correlation between increased intra-individual PVAT density and increased aortic diameter after adjustment for confounders. Chapter 8 demonstrated increased expression of pro-inflammatory and aortic wall disruptive genes (PTPRC, CXCL8, LCK, CCL5 and MMP9), while a lower anti-inflammatory gene expression (PPARG) was observed. Co-culturing of non-dilated aortic tissue with PVAT of AAA patients led to increased expression of MMP9 and SMTN, which are known to be involved in aneurysmal formation and progression.

Acute limb ischemia is a serious condition where the blood flow to the affected limb is insufficient for its need. The condition is both limb and life threatening and requires urgent intervention. Currently the most commonly used treatment for acute limb ischemia is catheter directed intra-arterial thrombolysis. It is a minimally invasive therapy, but it has the drawback of being time consuming and it carries a risk of (major) bleeding. This thesis focuses on contrast-enhanced sonothrombolysis (CEST) for acute peripheral arterial thrombosis. CEST is a form of thrombolysis where ultrasound contrast agents (a.k.a. microbubbles) and ultrasound are used to enhance thrombolysis. After intravascular administration, microbubbles follow the flow of blood to the site of the thrombus. Under influence of ultrasound, microbubbles start to oscillate. When the ultrasound pressure gets high enough, the microbubbles will destabilize and eventually burst, causing microstreams in the surrounding fluid and with it shear stress to the surface of the thrombus. Part I of this thesis is focused on results of current clinical practice for thrombolysis in peripheral arterial occlusion and on what we know about CEST for this pathology. Although CEST has been used in an experimental setting in patients with ischemic stroke and myocardial infarction, no investigations have been done in patients with peripheral arterial thrombosis. In part II of this thesis we present the results of various preclinical trials on the use of CEST for peripheral arterial thrombosis. We developed a porcine model for investigating CEST in acute peripheral arterial occlusion and used this model to investigate different aspects of microbubbles and with it different protocols for CEST. In part III of this thesis we present the results of the first clinical trial testing the safety and feasibility of CEST in acute peripheral arterial occlusion. We found CEST to be feasible in a clinical setting and there were no serious adverse events related to the experimental treatment in this small trial of 20 patients.