The role of preexisting pathology in the development of neointimal hyperplasia in coronary artery bypass grafts

Abstract

Objective: Saphenous vein grafts (SVG) used for coronary artery bypass surgery (CABG) often develop a gradual luminal narrowing over the first year due to neointimal hyperplasia (NH). Although the basic science of NH is well studied, our clinical understanding of this issue is limited. The purpose of this cohort study was to investigate clinical risk factors for NH by monitoring luminal narrowing within SVG using multichannel CT angiography (CTA).

Methods: Thirty patients underwent CABG involving SVG (N = 44) and arterial grafts (N = 36). Patient variables were recorded and the baseline quality of each conduit determined intraoperatively by analyzing surplus segments for intima-media thickness ratio (IMT) by histology and matrix metalloproteinase-2 by enzyme-linked immunosorbent assay. Percent luminal narrowing (%LN) was calculated for each patent graft by comparing the CTA appearance on day 5 to a repeat study at 1 y.

Results: Compared with arterial grafts, SVG showed significantly higher IMT at baseline (0.9 +/- 0.65 versus 0.22 +/- 0.17, P < 0.0001) and more %LN over the first year (6.9 +/- 7.5 versus 25.3 +/- 13.3% LN, P< 0.0001). Of all of the measured variables, the only significant predictors of %LN included baseline IMT (r = 0.58, P = 0.002) and matrix metalloproteinase-2 levels (r = 0.60, P = 0.002) in SVG.

Conclusions: The degree of NH at baseline, a phenomenon exclusive to SVG and not found in arterial grafts, was significantly related to the development of lumen loss in the conduit over the first year after CABG. The study of SVG using serial CTA may provide unique insights into the natural history of SVG remodeling and to identify factors that influence the long-term function of this conduit.

FIG. 1

Representative 3D reconstructions of a SVG obtained using serial multi-channel CTA at 5 d (A) and 1 y (B). At 5 d the luminal diameter was measured at four points along the graft (os, proximal, middle, and distal) and the % change at 1 y was calculated and averaged as the mean % LN. (Color version of figure is available online.)

FIG. 2

A Kaplan-Meier survival curve analysis of graft patency rate over 1 y. Patency was determined at two time points, 1 and 52 wk, using CT angiography. SVG performed significantly poorer compared with arterial grafts.

FIG. 3

Using hematoxylin and eosin staining of surplus graft segments and imaging software, intraoperative graft intimal, and medial thickness was measured and an intima-media ratio was calculated. Intimal thickening showed a strong linear correlation with the degree of LN at 1 y.

FIG. 4

Intraoperative MMP-2 graft tissue levels assessed in homogenized surplus graft segments using ELISA. MMP-2 tissue level was found to show a strong linear correlation with both the intraoperative intima-media ratio (A) and the degree of LN at 1 y (B).