Cardiac Allograft Vasculopathy: A Review of Risk Factors and Pathogenesis

Abstract

Heart transplant remains the gold standard therapy for patients with end stage heart disease and offers improved survival and quality of life. Significant progress has been achieved in improving one year mortality after heart transplantation. Nonetheless, long-term graft survival has not changed significantly over the past few decades. Long term survival of heart transplant recipients is limited by chronic rejection, cardiac allograft vasculopathy (CAV), and malignancy. CAV is a major contributor for graft failure and mortality after the first year of in heart transplant recipients. CAV is a proliferative vasculopathy characterized by diffuse myointimal hyperplasia and progressive narrowing of the graft vessels. Both immune dependent and independent factors have been shown to contribute to the pathogenesis of CAV. Understanding these risk factors is essential in developing preventative and therapeutic strategies. Angiography with Intravascular ultrasound (IVUS) has become the key diagnostic tool in the early detection of CAV as well as prognostication. Echocardiographic assessment of allograft function in conjunction with coronary angiographic findings are used in assessing the severity of CAV. Adjustment of immunosuppression and statins remain the initial steps in the management of CAV. Retransplantation is the definitive treatment for severe CAV, however, the paucity of organs along with increased mortality associated with retransplantation makes it a less desirable option. Although significant progress has been achieved in the understanding of pathogenesis, risk factors for CAV and plaque morphology, knowledge gaps still persists and further research is warranted. Progress is still needed in developing diagnostic modalities that could detect early CAV, as well as preventative and therapeutic strategies that will facilitate graft tolerance and immune modulation. This review focuses on summarizing the pathogenesis and risk factors for CAV.