An assessment of the use of the ABSORB bioresorbable vascular scaffold in the treatment of ‘false’ coronary bifurcations

Abstract

Introduction
The use of a bioresorbable scaffold has potential advantages when used to treat coronary bifurcation disease. We investigated the influence of sizing strategy on the performance of the ABSORB bioresorbable vascular scaffold (BVS) in this setting. In addition,  we evaluated the effect of elective BVS implantation on coronary microvasculature and inflammation. Finally the role of wall shear stress (WSS) in coronary bifurcation disease was reviewed and a novel method for determining WSS with the ABSORB BVS described.
Methods
The ABC-1 trial (Absorb in Bifurcation Coronary study) was a pilot trial which enrolled thirty-eight patients with ‘false’ coronary bifurcation lesions (Medina X,X,O classification) undergoing elective percutaneous coronary intervention (PCI). Patients were randomised in randomly permutated blocks of varying lengths to receive a BVS based either on the proximal or distal reference vessel diameter. Peripheral arterial blood samples were drawn before the procedure. Optical coherence tomography (OCT) imaging and pressure wire studies were performed before and after BVS implantation. Nine months after the index procedure, seventeen patients returned for blood sampling, intracoronary imaging and physiological assessment. Microvascular resistance was assessed using the Index of Microcirculatory Resistance (IMR). Serum concentrations of IL-6, CRP, sCD40L and MCP-1 were measured before scaffold implantation and at 9 month follow-up using enzyme-linked immunosorbent assays (ELISA). Wall shear stress distribution was calculated in two cases (1 in each randomisation arm) using the principles of Computational Fluid Dynamics (CFD).
Results
37 patients were recruited in the study out of whom 19 were randomised to a proximal sizing strategy and 18 to a distal one. Procedural complication rates were 89.4% and 94.4% respectively (p=0.58). In the distal-sizing arm, there was a greater incidence of significant strut malapposition (defined as a malapposition  distance >300 μm) at the proximal end of the scaffold (2.3% versus 0.8%, p=0.023). The incidence of distal edge dissections was numerically greater in the proximal-sizing group but was not statistically significant (31.3% vs 11.8%, p=0.17). At follow up, there were fewer uncovered struts (1.1% v 7.2%, p=0.001) in the distal cohort. PCI was accompanied by an immediate reduction in IMR of 8.6 (p=0.02). Mean CFR improved by 0.9 from pre to postprocedural levels (p=0.02). At follow up, FFR remained significant lower compared to pre-procedural values (0.92 v 0.78, p=0.001). In contrast, there was no significant improvement in CFR or IMR at follow up compared to preprocedural values (p=0.58 and p=0.30 respectively). The changes in the median levels of inflammatory markers from baseline to follow up were as follows: CRP (1 to 2.1, p=0.53), IL-6 (1.1 to 1, p=0.81), MCP-1 (47.2 to 36.4, p=0.06) and sCD40L (82.6 to 80.6, p=0.53). The Spearman correlation coefficients between baseline marker levels and neoinitimal burden along with the corresponding p value were as follows: CRP (0.30, p=0.34); IL-6 (0.49, p=0.10), MCP-1 (-0.22, p=0.48); sCD40L (0, p=0.99). Similarly, the coefficients and p values between follow up levels and neointimal burden were as follows: CRP (0.41, p=0.19); IL-6 (0.52, p=0.08), MCP-1 (-0.77, p=0.81); sCD40L (-0.06, p=0.86).
Conclusion
The provisional approach with a modified ‘PSP’ strategy is safe and feasible when using the ABSORB BVS in bifurcations. Both proximal and distal sizing strategies have similar procedural complication rates. While a proximal sizing strategy is associated with less significant malapposition immediately after implantation, there are fewer uncovered struts with a distal sizing strategy at medium term follow up. Scaffold implantation does not appear to adversely affect the coronary microcirculation. Levels of preprocedural inflammatory mediators did not correlate with the amount of neointimal coverage detected on OCT at 9 months. In addition, there was no significant change between baseline and follow up levels of inflammatory biomarkers after elective BVS implantation.. Finally, computational flow modelling can be used to assess the haemodynamic impact of different bifurcation stenting strategies with the ABSORB BVS.

Date of Award	Sept 2017
Original language	English
Awarding Institution	University of Brighton
Supervisor	Dr James Cockburn (Supervisor) & David Hildick-Smith (Supervisor)