Cardiovascular pathology in 2 young adults with sudden, unexpected death due to coronary aneurysms from Kawasaki disease in childhood

Abstract

Purpose Coronary artery aneurysms (CAA) may remain silent after Kawasaki disease (KD) until adulthood when myocardial ischemia can lead to sudden death. We postulated that there would be young adults with sudden, unexpected death due to CAA from KD who would have a state-mandated autopsy performed by the San Diego County Medical Examiner’s Office (SDCMEO). Methods We reviewed all autopsy cases <35 years of age from 1997–2012 at the SDCMEO with a cardiovascular cause of death (n=154). Results We found 2 cases meeting inclusion criteria. Case 1 was a 22-year-old Korean male with chronic ischemic changes due to a partially occluded and diffusely calcified 15mm aneurysm at the bifurcation of the left main coronary artery. Interview of the mother revealed that this patient had been diagnosed with KD complicated by giant aneurysms at age two years. Case 2 was a 30-year-old Hispanic male with myocardial infarction due to thrombosis of a calcified left anterior descending artery aneurysm. Histologic findings included diffuse myocardial fibrosis and a recanalized aneurysm in the right coronary artery. Interview of the family revealed a KD-compatible illness in childhood. Immunohistochemical staining showed expression of transforming growth factor β pathway molecules in the aneurysmal arterial wall. Conclusions In a medical examiner’s office serving a population of approximately 3 million people, 2 of 154 (1.3%) cardiovascular deaths in persons <35 years were attributed to cardiovascular complications of KD in childhood. Antecedent KD should be considered in the evaluation of all cases of sudden, unexpected death in young adults.

Galectin-3 is a marker of myocardial and vascular fibrosis in Kawasaki disease patients with giant aneurysms

“…In this study, Gal-3 expression was demonstrated in the walls of both coronary and systemic artery aneurysms and the histologic details of fibrosis in these tissues have been previously reported by our group for Cases 4-7 [6,26]. Thus, these late convalescent KD subjects with giant aneurysms had both myocardial and arterial wall fibrosis, and it is likely that both these tissue sources contributed to the elevated Gal-3 levels reported here.…”

“…The dotted lines represent uncertainty about this time period for which we have no data. from autopsies of young adult KD patients has been demonstrated by immunohistochemistry [6]. Myofibroblasts in KD patients may remain activated and cause progressive luminal narrowing of coronary artery to the point of total occlusion [33].…”

“…Myocarditis is associated with coronary artery vasculitis in the majority of KD cases based on histologic studies of autopsies and endomyocardial biopsies [3][4][5]. Emerging recognition of the long-term significance of myocardial fibrosis in young adults following KD is based largely on case reports from cardiac transplantation and small series of autopsy cases [6].…”

“…Gal-3 is expressed by fibroblasts [10] and inflammatory cells including monocytes/macrophages [11][12][13]. Gal-3 is recognized as a marker of heart failure and cardiovascular events [14][15][16], and autopsies in young adults late after KD onset have demonstrated bridging fibrosis throughout the myocardium and arteries [6]. We postulated that Gal-3 may participate in the pathogenesis of myocardial and vascular fibrosis and the remodeling of CAAs following acute KD.…”

Adjunctive Testing in the Evaluation of Adults After Kawasaki Disease

“…Autopsy data and examination of explanted hearts following cardiac transplantation in individuals with a history of KD demonstrate the development of extensive myocardial fibrosis secondary either to microvascular ischemia or diffuse post-inflammatory changes ( Figure 5). 4,72 Although MRI with late gadolinium enhancement is effective in identifying regional wall abnormalities, detection of diffuse fibrosis has been more problematic, though recent studies offer promise. In studies of adults with either systemic sclerosis or rheumatoid arthritis, myocardial T1 mapping with extracellular volume quantification was effective in detecting persistent myocardial inflammation as well as diffuse fibrosis, and similar studies in KD are in progress.…”