Laser-assisted coronary anastomotic connector : a journey into the development and preclinical evaluation

Abstract

Coronary artery bypass grafting (CABG) is the gold standard therapy for patients with multivessel coronary artery disease. Bypass surgery is routinely performed via a sternotomy on an arrested heart with aortic clamping and the use of cardiopulmonary bypass (CPB). Off-pump coronary artery bypass (OPCAB) surgery can potentially reduce the morbidity associated with the use of CPB (thromboembolic complications, excessive retain of fluid, blood transfusions, and activation of the immune system) and can be of benefit for patients at high risk for complications associated with CPB and aortic manipulation. Minimally invasive CABG (thoracoscopic or robotic-assisted surgery) reduces the size of the incision and hence reduces patient recovery time, hospital stay, and morbidity rates. Despite the potential benefits for (a subset of) patients in need for coronary revascularization, adoption of these techniques has not been widespread. One of the reasons is that conventional hand suturing of the anastomosis in an off-pump less invasive approach is technically very challenging. Hence, simplifying and automating the anastomosis construction with a connector could be the missing link toward expansion of minimally invasive CABG.

The aim of the research in this thesis is to develop and evaluate a new coronary anastomotic connector based on the unique principles of the Excimer Laser-Assisted Nonocclusive Anastomosis (ELANA) technique. This technology enables a nonocclusive connection of a graft to an artery. Following the hand-sutured connection of both vessels, an extravascular excimer laser catheter punches an opening into the target artery. Consequently, temporary occlusion of the artery is not necessary, in contrast to the conventional hand-sutured anastomotic technique, hence simplifying the bypass procedure.

The first two ELANA-based coronary anastomotic prototype connectors were demonstrated to be feasible on relatively large arteries (inner diameter [ID] 2.4 mm) in an acute rabbit model. Moreover, in a porcine OPCAB model, proper healing with minimal intimal hyperplasia was found at the long-term (6 months follow-up). However, although the connection of graft to target was sutureless, sutures were still required to connect the graft to the connector.

Subsequent design modifications enabled a complete sutureless construction onto clinically relevant, small caliber coronaries (ID 1.4-1.6 mm). This prototype, the Trinity Clip, was demonstrated to be applicable on human diseased ex vivo coronaries and in addition, the feasibility via a minimal invasive approach was showed in a porcine model. However, the technique should be optimized by dedicated application tools, more specifically a flexible laser and versatile applicator, and optimization of visualization by video-scopic assistance.

In a preclinical safety study, a simplified, fast, and standardized connection onto small caliber coronaries was demonstrated in the porcine OPCAB model. However, the long-term patency rate was inferior to the hand-sewn anastomosis. However, the results may be related to a design-change halfway the study (the connector is 20% heavier and longer), which resulted in distortion of the connector. This could be improved by the removal or downsizing of the spring of the connector. Provided the technical limitations can be addressed, this connector could fill the missing link toward expansion of minimally invasive CABG.