Cardiac allograft vasculopathy: real or a normal morphologic variant?

Abstract

Background: Naive coronary vessels may appear to have intimal thickening histologically characteristic of cardiac allograft vasculopathy (CAV). This study appraises the experimental and clinical impact of this observation.

Methods: Tissue sections from 12 naive hearts of miniature swine, 13 native porcine hearts of recipients of heterotopic cardiac allografts, 3 native human hearts and 3 human hearts with CAV were compared with light microscopy and morphometric analysis. Results were also compared with morphometric data previously gathered from 3 grafts in a standard experimental model of CAV (rejectors) and 3 grafts harvested from swine rendered tolerant to their donor hearts (chimeras).

Results: In the naive and native porcine hearts, the prevalence of CAV "mimics" was 0% to 6.94% (mean +/- SD: 1.99 +/- 1.97%) and 0% to 7.57% (2.97 +/- 2.20%), respectively (p = 0.12). The prevalence of CAV in the grafts of porcine rejectors and chimeras was 9.9% to 14.8% (12.4 +/- 2.5%) and 0.6% to 4.5% (2.6 +/- 2.0%), respectively (p < 0.05). CAV in the chimeras was similar in prevalence to that of the naive and native hearts. In native human hearts and human grafts, the prevalence was 1.86% to 2.00% (1.95 +/- 0.08%) and 9.09% to 17.50% (12.80 +/- 4.29%), respectively (p = 0.01).

Conclusions: Smooth muscle bundles inside the internal elastic laminae are similarly prevalent in human and porcine coronary vasculature. Their histologic similarity to intimal thickening of CAV could lead to an inaccurate distinction between graft tolerance and CAV in both clinical and experimental studies of heart transplantation.

Figure 1

Porcine coronary arteries of three naïve (A–C) and three native (D–F) hearts. The vessels reveal morphologic features of CAV in experimental grafts (elastic stains) (arrows mark internal elastic laminae). (A–C) Myocardium, x200; (D–E) Myocardium, x600; (F) Epicardium x600.

Figure 2

Typical features of CAV seen in two porcine heterotopic allografts (elastic stains) (arrows mark internal elastic laminae). (A) Myocardium in a rejector’s graft, x200; (B) Myocardium in a graft from a chimeric recipient, x320.

Figure 3

A scatter plot comparing the prevalence of vessels with intimal thickening in the non-transplanted and transplanted porcine hearts. The prevalence in the grafts of the rejectors is higher than that of the chimeric animals as well as that of the naïve and native hearts.

Figure 4

Human coronary arteries of three native hearts. The vessels reveal morphologic features that could be confused with those CAV (elastic stains) (arrows mark internal elastic laminae). (A) Epicardium, 50; (B) Myocardium, x200; (C) Myocardium, 400.

Figure 5

Typical features of CAV seen in three human orthotopic allografts (elastic stains) (arrows mark internal elastic laminae). (A) Epicardium, 100; (B) Myocardium, x100; (C) Myocardium, 200.

Figure 6

A scatter plot comparing the prevalence of vessels with intimal thickening in the native human hearts. The prevalence in the human grafts is higher than that of the native human hearts.