Assessment of Cardiac Allograft Vasculopathy (CAV) by Optical Coherence Tomography (OCT)

Cardiac allograft vasculopathy (CAV) represents the leading cause of late morbidity and mortality in heart transplant recipients and accounts for a second of all-cause mortality at 3 years. Development of CAV is a complex process involving intimal thickening, atherosclerosis, thrombosis and vasculitis by histology, but ultimately, intimal hyperplasia is the predominant cause of lumen narrowing, leading to ischemia and graft failure. In distinction from general coronary atherosclerosis, which is marked by focal and eccentric fibrofatty atheroma, CAV affects diffusely the entire coronary vasculature with marked intimal proliferation and concentric vascular thickening and fibrosis.

Optical coherence tomography (OCT), compared with IVUS, is more sensitive for early detection of CAV. OCT is a new generation catheter-based modality that acquires images at a spatial resolution of 10-20 μm which is 10-fold greater than that of IVUS. OCT could obviously identify the layer of media as a lower-echoic line, which could not be identified by IVUS. When assessing the quality of an intracoronary structure accurately, OCT seems to have more potential than IVUS.

The endothelial cells of the cardiac vasculature express human leukocyte antigens (HLA) and others, such as vimentin and major histocompatibility complex (MHC) class I-related chain A (MICA), and appear to be primary targets of cell-mediated and humoral immune responses after heart transplant (HTx). Circulating antibodies mediate rejection through complement activation and fixation on graft endothelium, thereby predisposing the patient to graft loss, accelerated cardiac allograft vasculopathy, and death. The rate of allosensitized patients (patients with circulating antibodies against donor antigens) on waiting lists is increasing as a consequence of growing numbers of retransplants and assist-device implantations. Allosensitization is a consequence of exposure to disparate HLA molecules during pregnancy, blood/platelet transfusions, or after cardiac repairs with homograft material, but may occur in some patients even without any of these triggers from unknown reasons.

Orthotopic heart transplantation is accompanied by sympathetic and parasympathetic denervation. The subsequent heart rate is usually higher and the circadian variation is low due to elimination of the vagus nerve effect. It is known that persistent increase in heart rate contributes to the pathogenesis of vascular diseases.

AIMS OF THE PROJECT The aim of this study is to use OCT imaging for identification of patients with early rapid progression of cardiac allograft vasculopathy (rapid progressors) and to identify the critical risk factors responsible for CAV progression. The impact of conventional and HTx-specific risk factors, such as donor-specific antibodies (using the most sensitive methods for its measurement) or rapid heart rate (using repeated Holter monitoring) will be studied in a prospective, national-level cohort study. The implication of OCT results will lead to adjustment of immunosuppressive therapy in one year after heart transplant to prevent further progression of the disease in CAV rapid progressors.