Background

Ischemic heart disease is one of the most prevalent diseases in the world, with a global incidence of 126.5 million in 2017.¹ While there are several other and less invasive revascularization techniques, coronary artery bypass grafting (CABG) remains the designated revascularization method in patients with multi-vessel coronary artery disease, compromising annually 10.800 CABG’s in The Netherlands.^2,3

CABG can be performed either with the help of cardiopulmonary bypass (on-pump), or without (off-pump). While off-pump coronary artery bypass grafting (OPCAB) is proven not to be beneficial to on-pump coronary artery bypass grafting (ONCAB) in the overall population, significantly fewer major adverse events were noted in the high-risk population.^3-6 Next to that, it is notable that in studies with OPCAB procedures in which aortic manipulation was minimized, the stroke rate is significantly lower than in cross-clamped ONCAB procedures in the overall population.^7,8

However, bypass graft failure remains a challenge in OPCAB. Studies show that 10-15% of vein grafts are occluded within one year after the procedure and that after 10 years only 50% of vein grafts remain free of significant stenosis.⁹ Early graft failure is most commonly caused by surgical technical errors leading to thrombosis, while late graft failure mainly arises from the progression of atherosclerosis and intimal hyperplasia. To minimize bypass graft failure, and to increase the feasibility of OPCAB surgery with a no-aortic touch handling and in a minimally invasive setting, a laser-assisted anastomotic device was developed: The Elana Heart Bypass System. This method ensures a 100% non-occlusive mechanical coronary anastomosis, securing the donor to the target vessel in a side-to-side anastomosis by the forced strength of a clip (see Figure 1).

The standardized arteriotomy minimizes the possibility of technical error, thus minimizing the chance of early graft failure. An overview of the construction of an anastomosis using Elana can be found in Figure 2. The first generations of the Elana Heart Bypass have already been evaluated successfully in both in vitro and in vivo animal studies.^10–13 Currently, a Phase II clinical trial using the medium-sized Elana Heart Clip is in progress at St. Antonius Hospital in Nieuwegein.

Figure 1: (Left) The Elana Heart Clip Medium, (Right) The Elana Heart Laser Catheter Medium

Figure 2: Procedural steps of CABG using the Elana Heart Bypass System. (A) Upper fork is opened using the general applicator, (B) Upper fork is inserted intraluminal into the graft, (C) Laser catheter is inserted through distal opening of graft and laser punches anastomotic opening in graft wall, (D) Wall tissue segment is flushed off laser catheter tip, (E) Lower fork is opened using coronary applicator and forks are insert intraluminal in the target vessel, (F) Laser catheter laser punches anastomotic opening in target vessel and laser catheter including wall tissue segment is removed from graft, (G) Distal end of graft is trimmed and clipped, anastomosis is now functional.

The project

1. Arteriotomy size
   The success of revascularization through CABG in the long term is partly dictated by the incidence of late graft failure. Late graft failure can be caused by the occurrence of turbulent blood flow in the coronary artery due to a mismatch between the diameters of the graft vessel, donor vessel, and/or the arteriotomy.¹⁴ The diameter of human vessels can vary between patients due to numerous factors including length, weight, size of vascularized area, and disease. As such, the ideal arteriotomy size differs per patient and anastomosis.Even though the Elana Heart Bypass System creates a standardized arteriotomy, the system should be able to serve a broad range of vessel sizes. To achieve this, it is possible to produce multiple sizes of the Elana Heart Clip and the Elana Heart Laser Catheter so multiple sizes of arteriotomies can be created. Currently, we have developed and produced small and medium-sized clip and laser catheter.

   From the current literature, it is recommended to have a sufficient caliber match between the donor and graft vessel as well as the arteriotomy that the laser creates. Consequently, this match has a positive impact on the flow patterns and ultimately the graft patency (success). However, it is still unknown in what range of mismatch is sufficient to minimize the disturbed flow patterns and thus the late graft failure. 
   The first objective of this project is to use a computational model of the anastomosis created with Elana to calculate (i) the range of vessel diameters that can be treated with the currently existing Elana Heart Clip, sizes small and medium, without creating excessively turbulent blood flows and (ii) the optimal arteriotomy sizes on which possible new sizes of the Elana Heart Clip can be based. This project includes the development of a computer-based model as well as the physical validation of this model (in vitro/in vivo).

2. Thermal damage due to laser energy
   The arteriotomy of the Elana anastomosis is created by the Elana Heart Laser Catheter. Essentially, the laser catheter punches a tissue segment out of the vessel wall. The energy released by the laser can potentially damage surrounding tissue which can have numerous consequences for the patient including intimal hyperplasia, bleeding, and thrombogenesis. We know that the blood flow absorbs a large portion of this energy. However, the exact relationship between laser energy dissipation, restricted blood flow due to stenosis, occurrence and extent of tissue damage, and possible complement activation remains unknown.The second objective of this project is to use a (computational) model with the current arteriotomy sizes to model the thermal damage caused by the Elana Heart Laser Catheter in several worst-case scenarios. Also here physical validation of the model may be appropriate.

About AMT Medical

AMT Medical is a clinical-stage medical device company developing a highly innovative and unique heart bypass system. We are a research-driven organization aiming to bring innovation to the generally conservative world of coronary bypass surgery. Our diverse multidisciplinary team includes (biomedical) engineers, a technical physician, cleanroom production, and more. Together we are working towards the improvement and validation of our product, so it can be marketed in Europe and the US.

We have two offices, located in Ede and Utrecht. In Ede, our production team works to produce all products for (pre)clinical studies. In Utrecht, our (pre)clinical team is working on R&D projects. The office in Utrecht features a lab where experiments can be performed (cadaver tissue and equipment are available). For this project, we would like to have you at our office in Utrecht.

Your profile

As a graduate student with AMT Medical, you will work with our (pre-)clinical team to improve and/or validate the product, to ensure the safety of the procedure. You are an ambitious and resourceful student with a high interest in the cardiovascular field. Your skillset includes:

• In the final phase of a Master’s degree in biomedical engineering or related
• Experience with finite element modeling and/or other forms of computational fluid dynamics modeling
• Knowledge of soft tissue response to damage
• Fluent in Dutch and English
• Ability to work independently
• Previous experience in surgical settings is a pre

As mentioned, this project will be carried out within our (pre-)clinical team based in our office in Utrecht.
Relocation to Utrecht may be a requirement.

Contact

If you have a question about the project or if you are interested in the position, please send your resume and motivation letter to joyce.rops@amt-medical.nl and glenn.bronkers@amt-medical.nl

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