Endothelial Dysfunction and Cytomegalovirus Replication in Pediatric Heart Transplantation

Abstract

Background-Cardiac allograft vasculopathy is the major limiting factor to the long-term success of pediatric heart transplantation. Cytomegalovirus (CMV) has been shown to be a significant risk factor for the development of cardiac allograft vasculopathy. Recent work has demonstrated CMV DNA in leukocytes in the absence of direct allograft infection, suggesting that vascular changes may not be limited to the allograft. Method and Results-Systemic arterial endothelial function was assessed with high-resolution ultrasound to determine brachial artery flow-mediated dilation in 50 pediatric heart transplant recipients (8 to 17 years of age; 27 male). Patients were separated into 2 groups according to CMV status: those without evidence of CMV replication after transplantation (nϭ38; 19 male) and patients with evidence of viremia after transplantation (nϭ12; 8 male). No patient had detectable viremia at the time of study. Flow-mediated dilation was significantly impaired in patients with evidence of CMV replication after transplantation (6.64Ϯ1.12%, meanϮSE) compared with those without (9.48Ϯ0.56%; Pϭ0.02). This difference remained after adjustment for age, time since transplantation, and medication. Pretransplantation recipient and donor CMV status and traditional CMV risk were not associated with flow-mediated dilation. Conclusions-CMV replication after cardiac transplantation is associated with chronic endothelial dysfunction in the systemic circulation in children. The implication for both systemic and coronary vascular health requires prospective evaluation.

Does Cytomegalovirus Serology Impact Outcome After Pediatric Heart Transplantation?

“…Recently, investigators have suggested that CMV replication results in endothelial dysfunction as measured with brachial artery flowmediated dilation in children after heart transplantation. 11 Some studies in adults demonstrated that recipient seropositivity status was correlated with either overt CAV detected by coronary angiography or more rapid lumen loss identified by intravascular ultrasound. [12][13][14] Until recently, little had been reported about the relationship of CMV serology and clinical outcomes in pediatric heart transplantation.…”

Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives

“…The pathophysiological factors leading to endothelial dysfunction that are especially relevant to the development of vascular disease include the following (2, 43, 213, 330, 338, 492, 493): Activation by cytokines;Stimulation by free radicals/ROS or oxidative stresses and the advanced glycation end products generated in diabetes and aging;Chronic smoking and hypertension;Chronic exposure to hyperhomocysteinemia and/or hypercholesterolemia;Increased plasma levels of oxidized low-density lipoprotein (LDL) and its accumulation within the vessel wall, as well as infection by bacteria, viruses, and other pathogens with the release of their products (251, 435, 528, 618). …”

Association of cytomegalovirus infection with hypertension risk: a meta-analysis

“…CMV infection is associated with various chronic inflammatory diseases, including cardiovascular diseases (CVDs) [8] such as myocarditis, atherosclerosis, and coronary artery disease [9–11]. Hypertension is an important cause of CVDs, and recent studies [12–18] have shown that patients with a CMV infection have an increased risk of EH; however, the association between CMV and EH remains unclear, and thus the effect of CMV infection on blood pressure is controversial.…”