Eosinophilic inflammation in spontaneous coronary artery dissection: A potential therapeutic target?

Spontaneous coronary artery dissection (SCAD), defined as non-traumatic, non-iatrogenic dissociation of coronary vessel wall resulting from intimal disruption or intramural hemorrhage, represents an important cause of sudden death and myocardial infarction among young or middle-aged women without conventional risk factors for atherosclerosis. On histopathological examination, SCAD is featured by prominent eosinophilic infiltration of the adventitia or periadventitial layer of coronary artery. It has been estimated that approximately 15-30% of SCAD patients experience recurrent episodes of dissection despite medical therapy. Preliminary evidence suggests that injury to the vascular endothelium and myocytes in the arterial wall may be explained by cytotoxic products released from eosinophils in response to inflammatory mediators. In addition, neovascularization of vasa vasorum and dilatation of intimal capillaries may be stimulated by localized eosinophils. Newly formed fragile vasa vasorum may disrupt due to high intraluminal pressure from the interconnected capillary network, leading to the expansion of intramural hemorrhage. It is hypothesized that anti-inflammatory therapy targeting eosinophilic coronary periarteritis would be effective in preventing the recurrence of SCAD by promoting the healing of dissection. The article delineates the biological plausibility, empirical data, and future perspective regarding eosinophilic inflammation as a potential therapeutic target for SCAD.

Effect and Safety of TNF Inhibitors in Immunoglobulin-Resistant Kawasaki Disease: a Meta-analysis.

Previous studies showed that tumor necrosis factor (TNF) inhibitors might decrease the rate of coronary artery abnormalities in pediatrics with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD). Therefore, we aimed to evaluate the effect and safety of TNF inhibitors in IVIG-resistant KD. We undertook a meta-analysis of clinical trials identified in systematic searches of PubMed, EMBASE, Cochrane Database, and Google scholar through May 2016. Five studies were included. Overall, rate of coronary artery aneurysm was comparable between groups (relative risk (RR), 1.05; 95 % confidence interval (95 % CI), 0.60 to 1.81; P = 0.87). No significant differences were recorded between groups in coronary artery Z scores (standardized mean difference (SMD), 0.27; 95 % CI, -0.30 to 0.85; P = 0.35). Meanwhile, TNF inhibitors were not associated with a significant decreased risk of treatment resistance compared with IVIG treatment (RR, 0.65; 95 % CI, 0.37 to 0.15; P = 0.14). However, days of fever was significantly reduced in the TNF inhibitor group (SMD, -0.66; 95 % CI, -0.90 to -0.41; P < 0.001). Additionally, risk of serious adverse events was similar between groups. Therefore, TNF inhibitors could shorten the duration of fever in IVIG-resistant KD. However, TNF inhibitors appear to have no cardioprotective effect in patients with IVIG-resistant KD.

Evidence for superantigen involvement in cardiovascular injury due to Kawasaki syndrome.

Kawasaki syndrome (KS), the major cause of acquired heart disease in children, is an acute multisystem vasculitis frequently associated with the development of myocarditis and coronary artery abnormalities. Despite the widely held belief that KS is an infectious disease, its etiology has remained elusive. Recently, we and others have reported the selective expansion of V beta 2+ T cells in the peripheral blood of most patients in the acute, but not in the convalescent, phase of KS. These data were consistent with the concept that this illness is triggered by a bacterial superantigen. We report here that a patient who died of acute KS had selective expansion of V beta 2+ T cells in her myocardium and coronary artery. Sequence analysis of TCR beta-chain genes of V beta 2+ T cells from the myocardium showed extensive junctional region diversity. These observations, along with the demonstration of V beta 2 expansion in both the CD4+ and CD8+ T cell subsets, support the concept that the activation of infiltrating V beta 2+ T cells are involved in the cardiovascular damage associated with KS.