Vascular Response to Experimental Stent Malapposition and Under-Expansion

Abstract

Up to 80% of all endovascular stents have malapposed struts, and while some impose catastrophic events others are inconsequential. Thirteen stents were implanted in coronary arteries of seven healthy Yorkshire pigs, using specially-designed cuffed balloons inducing controlled stent malapposition and under-expansion. Optical coherence tomography (OCT) imaging confirmed that 25% of struts were malapposed (strut-wall distance <strut thickness) to variable extent (max. strut-wall distance malapposed group 0.51 ± 0.05 mm vs. apposed group 0.09 ± 0.05 mm, p = 2e-3). Imaging at follow-up revealed malapposition acutely resolved (<1% of struts remained malapposed at day 5), with strong correlation between lumen and the stent cross-sectional areas (slope = 0.86, p < 0.0001, R (2) = 0.94). OCT in three of the most significantly malapposed vessels at baseline showed high correlation of elastic lamina area and lumen area (R (2) = 0.96) suggesting all lumen loss was related to contraction of elastic lamina with negligible plaque/intimal hyperplasia growth. Simulation showed this vascular recoil could be partially explained by the non-uniform strain environment created from sub-optimal expansion of device and balloon, and the inability of stent support in the malapposed region to resist recoil. Malapposition as a result of stent under-expansion is resolved acutely in healthy normal arteries, suggesting existing animal models are limited in replicating clinically observed persistent stent malapposition.

Keywords: Malapposition; Optical coherence tomography; Pre-clinical model; Stent; Stent under-expansion.

Figure 1

(A) Finite-element simulation show that at low inflation pressures the cuffed tri-folded balloon expands first in the extremities of the device slightly larger than the inner diameter of the vessel. The vessel must compensate by (B) stretching radially outwards, pulling tissue at margins inwards creating axial strain. For the middle region, the expansion of the device in proximal and distal regions creates axial tensile strain. At some time-point t₂, this axial strain caused a negative radial strain (inward) of ~2% (0.05mm radial inwards displacement) at this midpoint. (C) Ex-vivo deployment of the generic stent (used animal study) in an explanted swine coronary artery of 3.1mm inner diameter (3.3mm outer diameter), shows that nominal inflation the device created some overstretch in the proximal and distal segments, and partial shrinkage in the middle segment indicating a lumen diameter and cross-sectional area shrinkage of 3% and 6%.

Figure 2

The expansion of the modified balloon (A; from QCA), generated ranges of stent under-expansion (B; min stent /reference lumen CSA) and malapposition (B; maximum strut-wall displacement within the stent by OCT), in all 13 vessels analyzed (C). Note struts with Wall Distance >0.1mm are malapposed.

Figure 3

Volume rendered reconstructions of the lumen using proprietary off-line analysis (St. Jude) for a vessel implanted with 2.5mm/3.0mm cuff and achieving a minimum stent expansion ratio (stent/reference lumen CSA) of 50.7% at baseline. (A) At baseline, the lumen appears dilated in middle under-expanded segment, which then (B) recoils onto the stent as observed at early (5 day) follow-up.

Figure 4

Normalized lumen CSA (lumen-to-mean vessel reference lumen area ratio) versus stent expansion ratio (stent-to-mean vessel reference lumen area ratio) at baseline (blue) and follow up (red), with piecewise linear regression lines plotted of the fixed effects estimates after adjustment for measurements nested in vessels and animals.. For day 0 optimal knots in the piecewise linear model were found at stent expansion ratio = 0.86 (Stent expansion ratio = 86%; R² = 0.85). Follow-up showed strong, linear and positive correlation between stent and lumen cross-sections (R² = 0.94).

Figure 5

Luminal area shrinkage follows vessel elastic recoil as determined by mapping the lumen cross-sectional area to the EEL cross sectional area manually traced in OCT frames of three of the extremely malapposed vessels (malapposition at baseline >4*strut-widths). Lumen and EEL CSA normalized to the reference non-stented lumen dimension in each vessel correlated with near unity linear regression slopes close to 1 (β_{vessel 1} = 0.84 (blue), β_{vessel 2} = 0.95 (yellow), β_{vessel 3} = 0.97 (black)).