Discordant Microvascular and Epicardial Disease in Cardiac Allograft Vasculopathy

Abstract

Angiography and intravascular ultrasound (IVUS) of the epicardial coronary vasculature are routinely undertaken for cardiac allograft vasculopathy (CAV) assessment. Microvascular disease is common in CAV and may occur independently of epicardial disease. The purpose of this study was to examine the relationship between microvascular disease, epicardial disease and microvascular dysfunction in heart transplant (HT) patients. A retrospective analysis was performed of HT patients who underwent coronary angiography, IVUS, and endomyocardial biopsy (EMB). Epicardial CAV was defined as ISHLT CAV1-3 on angiography and maximal intimal thickness (MIT) ≥0.5 mm on IVUS. Microvascular disease was defined as Hiemann et al. microvasculopathy grade B-D on EMB. Capillary density (CD) was quantified on EMB by manual count of CD31 stained vessels per 0.6 mm2. Microvascular dysfunction was defined as index of microcirculatory resistance (IMR) ≥20. Fifty-two patients were evaluated: 37 (72%) males, mean age 50.6 ± 14.3 years, 2.6 ± 4.5 years post-HT. Invasive coronary studies and EMB were performed at mean 33 ± 55 days apart. Microvasculopathy was present in 13 (25%) patients and epicardial CAV in 20 (63%) patients on angiography and 37 (71%) on IVUS. Of 25 patients who underwent invasive hemodynamics, 15 (60%) had microvascular dysfunction. Microvasculopathy prevalence did not differ between patients with and without epicardial CAV or microvascular dysfunction (Figure). Discordant microvascular and epicardial disease was observed in 27 (52%) patients by angiography and 32 (62%) by IVUS. Isolated evaluation with angiography, IVUS and IMR missed microvasculopathy in 10 (19%), 4 (8%) and 3 (12%) patients, respectively. There was no difference in mean CD between patients with and without epicardial CAV or correlation of CD with MIT or IMR. There is high discordance of microvascular and epicardial disease in CAV. Assessment by angiography and IVUS alone may under-detect microvascular disease.