Cardiac Allograft Vasculopathy: Real or a Normal Morphologic Variant?

Houser, Stuart; Muniappan, Ashok; Allan, James; Sachs, David; Madsen, Joren

doi:10.1016/j.healun.2006.11.012

« Previous Next »The Journal of Heart and Lung Transplantation
Volume 26, Issue 2 , Pages 167-173, February 2007

Cardiac Allograft Vasculopathy: Real or a Normal Morphologic Variant?

Stuart Houser, MD
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Reprint requests: Stuart Houser, MD, Department of Pathology, Massachusetts General Hospital, Boston, MA 02114. Telephone: 617-724-7810. Fax: 617-720-5718.
Ashok Muniappan, MD
- Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
James Allan, MD
- Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
David Sachs, MD
- Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Joren Madsen, MD, DPhil
- Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Received 21 September 2005; received in revised form 21 September 2006; accepted 13 November 2006.

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.