Pediatric Coronary Allograft Vasculopathy-A Review of Pathogenesis and Risk Factors

Abstract

Coronary allograft vasculopathy is the current leading cause for late graft loss following cardiac transplantation. Its pathogenesis is multifactorial, including immune, constitutional and genetic factors, metabolism, infection, as well as potential injury from routine immunosuppressive therapy. Children represent a patient group with unique differences: their pretransplant history rarely includes ischemic heart disease and risk factors for atherosclerotic heart disease, but many are presensitized from use of allograft material during reconstructive cardiac surgeries. Compared with older children and adults, infants and young children show significantly lower rates of graft vasculopathy that may be related to the relative immaturity of their immune system. This review summarizes the current concepts of coronary allograft vasculopathy derived mainly from animal models and adult clinical observations. It provides an overview of confirmed risk factors and explains their interactions. The characteristics and unique clinical findings among pediatric transplant recipients will be explored within the context of recent, albeit limited, scientific investigations.

Improved Detection of Cardiac Allograft Vasculopathy

“…This finding is likely related to several issues, including the relative naiveté of the infantile immune system leading to increased graft accommodation, younger age of donors, and less frequent rejection (and specifically, rejection with hemodynamic compromise) in these patients(7,8). Furthermore, children undergoing heart transplant tend to have less obesity, diabetes, hyperlipidemia, and hypertension than do typical adult transplant recipients, thus creating a healthier host environment for graft longevity(2,3).…”

“…CAV is a chronic graft complication caused by immune and nonimmune processes (2)(3)(4). Earlier studies showed that factors such as donor age, recipient age, human leukocyte antigen (HLA) mismatch, allosensitization, frequent cellular rejection, and rejection with hemodynamic compromise are associated with increased risk of CAV in children (1,(5)(6)(7)(8).…”

Predictors of cardiac allograft vasculopathy in pediatric heart transplant recipients

“…CAV remains a leading cause of graft loss and mortality among late survivors of heart transplantation . Despite improvements of post‐transplant management in the current era, one‐third of pediatric patients develop CAV within 10 yr of transplant .…”

Heart Transplant in Children: What a Primary Care Provider Needs to Know

“…It is believed to be a result of chronic immune rejection and nonimmune factors like hypertension, dyslipidemia, and diabetes. 18 CAV is the leading cause of graft failure in heart transplant recipients and can be definitively treated by retransplantation only, although certain therapies such as the use of statins and incorporating sirolimus into the immunosuppression regimen have been shown to be beneficial in halting or slowing the progression of CAV. 19 Patients with more discrete stenosis undergo revascularization of the coronary arteries by angioplasty and stent placement as a palliative solution and bridge to retransplantation.…”