247: Relationship between Microvascular and Macrovascular Disease in Heart Transplant Recipients

Purpose: Coronary macrovascular disease as demonstrated by coronary angiography or intravascular ultrasound (IVUS) is related to long-term survival in heart transplant recipients, and there is evidence that coronary microvascular disease (MVD) on endomyocardial biopsies is prognostically important as well. However, the relationship between these in transplant patients and the determinants of MVD are not known. Methods and Materials: We reviewed the simultaneously obtained endomyocardial biopsies and IVUS images of the coronary arteries in 33 heart transplant recipients. MVD was classified by light microscopy into 4 grades based on endothelial cell layer and vascular wall thickening. Macrovascular disease was evaluated from IVUS studies and assigned into one of 5 grades based on the Stanford classification. MVD and macrovascular disease were compared. Results: Patient characteristics: age at transplant 26+ 18 years, 67% men, average time post transplant to study 4 years. Concomitant medications: statins 68%, ACEI 49%, calcium channel blockers (CCB) 68%, Tacrolimus 59%, Sirolimus 35%, Mycophenolate 62%, prednisone 38%. Biopsy results for MVD: normal 6%, nonstenotic wall thickening 12%, both endothelial layer thickening and stenotic wall thickening 45%, and stenotic wall thickening with a normal endothelial layer 36%. IVUS analysis revealed grade 3 changes in 21% and grade 4 changes in 6%. There was no significant correlation between grades of micro and macrovascular disease (p= 0.10). There were higher grades of MVD compared to macrovascular changes. MVD correlated positively with donor age (p= 0.06) and treatment with tacrolimus (p= 0.02) and a statin (p= 0.05) but not with recipient age, gender, diabetes or treatment with ACEI, CCB, mycophenolate, or prednisone. Conclusions: 1) There is a poor relationship between coronary micro and macrovascular disease in patients with cardiac transplants, likely indicating divergent pathogenetic mechanisms. 2) MVD increases with donor age. 3) There is an intriguing relationship between MVD and treatment with statin and tacrolimus.