Coronary Artery Vessel Healing Pattern, Short and Long Term, After Implantation of the Everolimus‐Eluting Bioresorbable Vascular Scaffold

Abstract

BackgroundAlthough the Absorb bioresorbable vascular scaffold is increasingly used in daily clinical practice for the treatment of coronary artery disease, the exact vascular healing pattern and the resorption process in humans is unknown because histological data are derived only from animal studies.Methods and ResultsWe have obtained 4 autopsies (5 scaffolds) since August 2013. Duration of bioresorbable vascular scaffold implantation ranged from 3 to 501 days. All autopsies and histological assessments were performed by dedicated cardiovascular pathologists. At 1 week after bioresorbable vascular scaffold implantation, struts were covered with a fine layer of fibrin and platelets. At 113 days, the scaffold struts were fully covered with smooth muscle cells. Hyaline eosinophilic and proteoglycan material infiltrating the scaffold struts was observed at 501 days after implantation. At all time points, we observed the presence of multinuclear foreign body giant cells adjacent to the scaffold struts.ConclusionsResorption and healing processes after bioresorbable vascular scaffold implantation in human patients mirror those observed in porcine models. The presence of multinucleated foreign body giant cells at both short‐ and long‐term follow‐up needs further investigation and may be related to a low‐grade absorptive inflammatory response to the polymer.

Location-Specific Comparison Between a 3D In-Stent Restenosis Model and Micro-CT and Histology Data from Porcine In Vivo Experiments

“…The total extent of growth in the simulation is similar to the in vivo data, even though the detailed local distribution of growth differs. Also, as well as in our previous model,57 neointimal growth can be observed far away from the struts, similarly to experimental data 1,4,22,32…”

“…However, many models predict neointimal formation exclusively around the struts. This does not agree well with the experimental data, which shows a more even neointima 1,4,22,32. To validate the models on a location-specific level, and to make predictions about restenosis development in real vessels, a more realistic arterial geometry has to be considered, ideally comparing restenosis progression in vivo and in silico in exactly the same arteries.…”

MicroRNAs and Endothelial (Dys) Function

“…The specific application of miR‐based agents to the vasculature, for instance during PCI, can be considered as an effective therapeutic strategy. The direct intravascular delivery could be combined to new‐generation bioresorbable stents with biodegradable scaffolds (Ellis et al, ; Kraak et al, ; Santulli, ). Other potential alternatives include the stabilization of miR‐based agents: various chemical modifications of nucleotides can enhance their stability in vivo , for instance by using cholesterol‐conjugated, 2′‐O‐methyl–modified antagomiRs; miR‐based drugs can be also conjugated to targeting molecules including antibodies, peptides, or other bioactive molecules, which may promote the specific homing to the site of the injury.…”

Undiscovered pathology of transient scaffolding remains a driver of failures in clinical trials

“…Currently, it is unclear whether the plaque regression is a true phenomenon due to the disappearance of the scaffold, which is ultimately replaced by connective tissue[ 56 ]. The documented trend toward a reversal of atherosclerosis, lumen enlargement, and progressive hyaline arteriosclerosis[ 58 ] (mediating so-called OCT-phenomenon of the “golden tubes”[ 59 ]) after placement of BVS resembles the previously delineated histologic findings in animals[ 59 - 62 ] and human autopsies[ 63 ].…”