Guidelines for Diagnosis and Management of Cardiovascular Sequelae in Kawasaki Disease (JCS 2008) - Digest Version - : – Digest Version –

Recent studies indicate that magnetic resonance imaging (MRI) after the administration of contrast material can be used to distinguish between reversible and irreversible myocardial ischemic injury regardless of the extent of wall motion or the age of the infarct. We hypothesized that the results of contrast-enhanced MRI can be used to predict whether regions of abnormal ventricular contraction will improve after revascularization in patients with coronary artery disease. Gadolinium-enhanced MRI was performed in 50 patients with ventricular dysfunction before they underwent surgical or percutaneous revascularization. The transmural extent of hyperenhanced regions was postulated to represent the transmural extent of nonviable myocardium. The extent of regional contractility at the same locations was determined by cine MRI before and after revascularization in 41 patients. Contrast-enhanced MRI showed hyperenhancement of myocardial tissue in 40 of 50 patients before revascularization. In all patients with hyperenhancement the difference in image intensity between hyperenhanced regions and regions without hyperenhancement was more than 6 SD. Before revascularization, 804 of the 2093 myocardial segments analyzed (38 percent) had abnormal contractility, and 694 segments (33 percent) had some areas of hyperenhancement. In an analysis of all 804 dysfunctional segments, the likelihood of improvement in regional contractility after revascularization decreased progressively as the transmural extent of hyperenhancement before revascularization increased (P<0.001). For instance, contractility increased in 256 of 329 segments (78 percent) with no hyperenhancement before revascularization, but in only 1 of 58 segments with hyperenhancement of more than 75 percent of tissue. The percentage of the left ventricle that was both dysfunctional and not hyperenhanced before revascularization was strongly related to the degree of improvement in the global mean wall-motion score (P<0.001) and the ejection fraction (P<0.001) after revascularization. Reversible myocardial dysfunction can be identified by contrast-enhanced MRI before coronary revascularization.

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children. Transfection experiments showed that the C allele of itpkc_3 reduces splicing efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease. This finding provides new insights into the mechanisms of immune activation in Kawasaki disease and emphasizes the importance of activated T cells in the pathogenesis of this vasculitis.