Lack of Relationship Between Microvascular and Macrovascular Disease in Heart Transplant Recipients

Abstract

A key determinant of long-term survival in heart transplant recipients is the development of coronary vasculopathy. Both coronary macrovascular and microvascular disease are prognostically important. However, the relationship between these in transplant patients and the determinants of microvascular disease are not known. We reviewed the simultaneously obtained endomyocardial biopsies and intravascular ultrasound (IVUS) images of coronary arteries in 33 heart transplant recipients. Coronary microvascular disease was classified by light microscopy into four grades based on thickening of endothelial cell layer and stenotic versus nonstenotic medial wall thickening. Macrovascular disease was evaluated from IVUS studies and assigned into one of five grades based on the Stanford classification. Coronary microvascular and macrovascular diseases were compared. Age at transplantation was 26 (18) years; 67% were men, and the average time to posttransplantation study was 4 years. Endomyocardial biopsy revealed more advanced grade C and D microvascular disease in 45% and 36% of the patients, respectively. However, IVUS analysis for macrovascular disease revealed mostly lesser changes with grade 1 in 12%, grade 2 in 61%, and grade 3 in 21%. There was no significant correlation between grades of microvascular and macrovascular disease (P=0.10). Microvascular disease correlated positively with donor age (P=0.06) and treatment with tacrolimus (0=0.02) and statins (P=0.05). There is a poor relationship between coronary microvascular and macrovascular disease in patients with cardiac transplants, likely indicating divergent pathogenetic mechanisms. Microvascular disease increases with donor age. There is an intriguing positive relationship between microvascular disease and treatment with statins and tacrolimus.