History Of Kawasaki Disease Research Articles

Long Term Outcomes of Left Atrial Reservoir Function in Children with a History of Kawasaki Disease.

BackgroundDecreased left atrial (LA) reservoir function is reported to be associated with elevated left ventricular (LV) end diastolic pressure and LV diastolic dysfunction. Echocardiographic parameters that reflect LA reservoir function include LA total emptying fraction [(maximum LA volume - minimum LA volume) / maximum LA volume], peak LA longitudinal strain (PLALS) at systole, and LA stiffness index (E/E´/PLALS). We aimed to investigate the long-term outcomes of LV diastolic function in children with a history of Kawasaki disease (KD) (KDHx group) by assessing LA reservoir function.MethodsRetrospectively, echocardiograms performed at a mean follow-up period of 5 years after the acute phase of KD in 24 children in the KDHx group were compared to those from 20 normal control subjects. LA total emptying fraction, PLALS, LA stiffness index, LV peak longitudinal systolic strain (ε), and strain rate (SR) were evaluated with conventional echocardiographic parameters.ResultsThe mean age at long term follow-up echocardiography in children in the KDHx group was 6.8 years. Five children (20.8%) had coronary artery lesions (CALs) in the acute stage of KD. No children showed CALs at a mean follow-up period of 5 years after the acute phase of KD. There were no significant differences in the conventional echocardiographic parameters and in LA total emptying fraction, PLALS, LA stiffness index, LV peak longitudinal systolic ε, and SR, between the children in the KDHx and control group.ConclusionLV diastolic function assessed by LA reservoir function parameters at long-term follow-up in children in the KDHx group appears to be favorable.

Evaluation of myocardial deformation in patients with Kawasaki disease using speckle-tracking echocardiography during mid-term follow-up.

We explored left ventricular mechanics using speckle-tracking echocardiography in 35 patients with a history of Kawasaki disease at least 6 months after the acute phase. We also included 30 healthy children as controls. Strain data sets were acquired for the quantification of left ventricular global strain, segmental strain, and left ventricular ejection fraction. The mean age of our patients was 25.6±15.4 months. At a median follow-up of 57.5 months (16.5-98.2), although both values were in the normal range, the mean left ventricular ejection proportion of patients (57.3%) was a little lower than that of controls (p⩽0.05). Patient strain values at the basal inferoseptal (20.0), basal anterolateral (19.5), apical septal (23.3), and apical inferior (24.0) segments were lower compared with controls. In all, seven patients had coronary aneurysms during follow-up. Kawasaki disease patients with pyuria had lower left ventricular strain at the mid anterior, mid anteroseptal, apical anterior, and apical inferior segments and global longitudinal strain compared with patients with no pyuria (p⩽0.05). In children with a history of Kawasaki disease, impairment of left ventricular mechanics occurs especially within the left anterior descending artery territories.

High Sensitivity C Reactive Protein (hs-CRP) in Adolescent and Young Adult Patients with History of Kawasaki Disease.

For children with a history of Kawasaki disease (KD), low grade inflammation was generally reported to be associated with persistent coronary artery lesions (CAL). However, this association has not been clearly demonstrated to hold true in KD adolescents and young adults (10-25 years of age). We enrolled 104 subjects into our study, who were separated into the following 3 groups and controls: 1): 22 KD patients with angiography-confirmed CAL which persisted for an average of 12.5 years after onset of KD; 2) 38 KD patients with regressed aneurysms; 3) 44 KD patients without any coronary complications from the disease onset; and 4) 31 age-matched (18.7 ± 1.88 years old) healthy controls. Plasma levels of high-sensitivity C reactive protein (hs-CRP) were measured for all participants. Plasma levels of hs-CRP were significantly higher in KD patients than in the controls, regardless of their coronary severity. However, there was no significant difference in hs-CRP levels among KD patients with different severities of CAL. Of the candidate risk factors of elevated hs-CRP such as body mass index, gender, coronary severity, and levels of high-density lipoprotein-cholesterol, linear regression analysis showed the only independent predictor of hs-CRP levels was BMI (β = 0.306, p = 0.01), rather than patient grouping (p = 0.091). Our study found that levels of hs-CRP are significantly higher in adolescent and young adult patients with a history of KD, compared with age-matched controls. Low grade inflammation may play a minor role when KD patients enter into adulthood. body mass index (BMI), rather than coronary severity, was independently associated with the elevation of hs-CRP levels, one of biomarkers for further cardiovascular event. Therefore, ongoing control and management of BMI may be one of beneficial strategies that can be employed to help avoid elevation of hs-CRP levels in KD patients. Adolescents; High sensitivity-C reactive protein; Kawasaki disease; Young adult.

Analysis of Arterial Endothelial Function Assessed by the Non-invasive Method of Flow-Mediated Dilatation in Patients with a History of Kawasaki Disease: A Review of the Literature

Kawasaki disease, which was first reported by Kawasaki (1967), is an acute, febrile, pediatric illness that occasionally causes coronary artery lesions. Kawasaki disease is characterized by systemic vacuities, although the etiology remains unknown. Whether Kawasaki disease is a risk factor for the early progression of atherosclerosis in adolescents and young adults has been discussed for a long time. Endothelial function has been studied in patients with a history of Kawasaki disease by many investigators. Measurement of the percentage of flow-mediated dilatation (%FMD) is a non-invasive method for evaluation of endothelial function. This review focuses on the 15 published articles found in our literature search pertaining to %FMD measurements in patients with a history of Kawasaki disease.

Usefulness of Single Photon Emission Computed Tomography/Computed Tomography Fusion-Hybrid Imaging to Evaluate Coronary Artery Disorders in Patients with a History of Kawasaki Disease.

The coronary arterial lesions of Kawasaki disease are mainly dilative lesions, aneurysms, and stenotic lesions formed before, after, and between aneurysms; these lesions develop in multiple branches resulting in complex coronary hemodynamics. Diagnosis of myocardial ischemia and infarction and evaluation of the culprit coronary arteries and regions is critical to evaluating the treatment and prognosis of patients. This study used hybrid imaging, in which multidetector computed tomographic (CT) images for coronary CT angiography (CCTA) and stress myocardial perfusion single-photon emission CT (SPECT) images were fused. We investigated the diagnosis of blood vessels and regions responsible for myocardial ischemia and infarction in patients with complex coronary arterial lesions; in addition, we evaluated myocardial lesions that developed directly under giant coronary artery aneurysms. The subjects were 17 patients with Kawasaki disease with multiple coronary arterial lesions (median age, 18.0 years; 16 male). Both CCTA using 64-row CT and adenosine-loading myocardial SPECT were performed. Three branches, the right coronary artery (RCA), left anterior descending branch (LAD), and left circumflex branch, were evaluated with the conventional side-by-side interpretation, in which the images were lined up for diagnosis, and hybrid imaging, in which the CCTA and SPECT images were fused with computer processing. In addition, the myocardial lesions directly under giant coronary artery aneurysms were investigated with fusion imaging. Images sufficient for evaluation were acquired in all 17 patients. In the RCA, coronary arterial lesions were detected with CCTA in 16 patients. The evaluations were consistent between the side-by-side and fusion interpretation in 14 patients, and the blood vessel responsible for the myocardial ischemic region was identified in 2 patients. In the left circumflex branch, coronary arterial lesions were confirmed with 3-dimensional CT in 5 patients, and the the culprit coronary arteries for myocardial ischemia/infarction were confirmed with the fusion interpretation but not with the side-by-side interpretation. In the LAD, coronary arterial lesions were present in all patients, and the diagnosis was made with the fusion interpretation in 10 patients. In the LAD, small-range infarct lesions were detected directly under the giant coronary artery aneurysm in 8 patients, but were not confirmed with the side-by-side interpretation. Fusion imaging was capable of accurately evaluating myocardial ischemia/infarction as cardiovascular sequelae of Kawasaki disease and confirming the culprit coronary arteries. In addition, analysis of fusion images confirmed that small-range infarct lesions were concomitantly present directly under giant coronary artery aneurysms in the anterior descending coronary artery.

Rotational Atherectomy and Stent Implantation in an 11-Year-Old Boy with a History of Kawasaki Disease

Rotational Atherectomy and Stent Implantation in an 11-Year-Old Boy with a History of Kawasaki Disease

Persistent high fever for more than 10 days during acute phase is a risk factor for endothelial dysfunction in children with a history of Kawasaki disease

BackgroundEndothelial dysfunction has previously been reported in children with a history of Kawasaki disease, but the determinants of endothelial function in Kawasaki disease patients are still unknown. In this study, we investigated endothelial function in Kawasaki disease patients and attempted to identify risk factors for persistent endothelial dysfunction. MethodsUsing high-resolution ultrasound, we measured the percent flow-mediated dilatation, an arterial response to reactive hyperemia, to evaluate endothelial function in 67 patients with a history of Kawasaki disease and 28 age- and sex-matched control subjects. We divided the Kawasaki disease patients into a group with impaired endothelial function (the percent flow-mediated dilatation below −2 standard deviations of the control group) and a group with normal endothelial function (the percent flow-mediated dilatation more than −2 standard deviations of control). Logistic multiple regression analysis was performed to identify independent predictors of impaired endothelial function. ResultsIn Kawasaki disease patients, the percent flow-mediated dilatation was significantly lower than in the control subjects (9.8±3.6%, compared with 13.1±3.4%, p<0.01). In 13 Kawasaki disease patients (3 patients with coronary artery lesions and 10 patients without coronary artery lesions), the percent flow-mediated dilatation was below −2 standard deviations of control. Logistic multiple regression analysis showed that a febrile period of longer than 10 days during the acute phase was the significant risk factor for endothelial dysfunction (odds ratio: 8.562; 95% confidence interval: 1.366–53.68). Presence of coronary artery lesions was not a determinant of endothelial dysfunction. ConclusionsSystemic endothelial dysfunction exists in children with a history of Kawasaki disease, and a febrile period of longer than 10 days during the acute phase is an independent predictor of endothelial dysfunction irrespective of coronary artery involvement.

Anomalous origin and aneurysm of the right coronary artery associated with congenital bicuspid aortic valve: MDCT findings.

Anomalous origin of the coronary artery taking an interarterial course can cause myocardial infarction or sudden death. Association of anomalous origin of the coronary artery with congenital bicuspid aortic valve is rare, and only a few cases have been reported with imaging findings. Coronary artery aneurysms found in young adults are usually non-atherosclerotic. We report MDCT findings of anomalous origin and aneurysm of the right coronary artery associated with congenital bicuspid aortic valve in a 33-year-old man with a history of Kawasaki disease in the childhood, and the key role of MDCT in exact diagnosis and successful management of the complicated disease.

Z-Value of Mitral Annular Plane Systolic Excursion Is a Useful Indicator to Predict Left Ventricular Stroke Volume in Children: Comparing Longitudinal and Radial Contractions.

The purpose of our study was to explore the pumping mechanism of the left ventricle (LV) and to examine the role of longitudinal LV contraction in LV stroke volume (LVSV) compared to a radial LV contraction. We examined 890 consecutive children without structural heart disease including 395 patients with a history of Kawasaki disease (KD). We measured the mitral annular plane systolic excursion (MAPSE), the LV end-diastolic and end-systolic dimension (LVDd), the LV radial wall displacement (LVRWD) and the LV stroke volume (LVSV). The LVSV was determined by the Doppler method. The z-values of MAPSE, LVDd, LVRWD and LVSV were calculated by the mean values and standard deviations (SDs) based upon BSA every 0.1 m(2) . We evaluated the relationship between the z-LVSV and the geometrical factors. The z-value of the MAPSE was the most powerful determinant for the z-values of the LVSV of all of the geometrical factors (β = 0.36, P < 0.0001). However, the z-values of the LVRWD did not contribute to those of the LVSV. The longitudinal LV contraction contributes more to the LVSV than the radial LV contraction, even in subjects without heart failure. Evaluation of longitudinal LV contraction using the MAPSE z-value is useful for assessing global LV function in children with various body sizes.

Abstract O.63: Novel Use Of Fractal Analysis In Kawasaki Disease For Risk Prediction

Introduction: Fractal based analysis of vascular branching complexity is known to have a prognostic role in cardiovascular risk prediction and suboptimal Fractal Dimensions of retinal vessels has been shown to correlate with coronary mortality. We hypothesize that Kawasaki disease permanently alters the fractal pattern of the retinal vasculature reflecting suboptimal microcirculatory development and attendant coronary risk. Objectives: We calculated and compared the Zone Fractal Dimension(D f ) of children with a history of Kawasaki disease with a matched cohort Methods: All subjects underwent high resolution digital retinal photography and disc-as well as macular centered photographs were digitized and used for measurement of D f using a standardized validated program performed by a single trained grader. Retinal vascular dimensions were also measured Results: Fifty subjects and 100 controls were examined. Subjects had a D f f 1.506 while controls had a Df of 1.432(P&lt;0.001). Cases were controlled for age, gender and ethnicity. Conclusion: In adult studies, a D f exceeding 1.47 has been shown to be sub-optimally high with resultant associated coronary risk. This suggests that the long term cardiovascular risks of Kawasaki disease may not only be conferred through coronary flow factors but systemic microcirculatory mal-development.

Abstract 188: Carotid Artery Strain in Young Adults with a History of Kawasaki Disease

Background: Measuring carotid strain is a noninvasive way to assess the mechanical properties of the arterial wall. Whether there is an association between carotid strain and coronary artery status after Kawasaki disease (KD) is unknown. Methods: We enrolled 82 young adults, ages 15 to 30 yrs, with a history of KD (58% male), as well as 16 healthy controls (HC) of similar age (56% male). Carotid wall strain was measured from cine loops of common carotid artery B-mode ultrasound data using an offline optical flow analysis algorithm. Strain was normalized for age (Z-score) using a regression equation derived from a separate series of healthy young adults. Subjects were categorized based on their worst coronary artery status (normal, transiently dilated, aneurysm). Results: The mean age of KD subjects and HC at the time of carotid measurements was 25 ± 8 and 28 ± 8 years, respectively (p=0.30). Mean time since onset of KD was 20 ± 8 yrs. KD subjects with transiently dilated coronary arteries had significantly higher carotid strain compared to those with normal coronaries (p=0.002) and to HC (p=0.01) (Figure); those with CAA had a nonsignificant trend toward lower carotid strain compared to other groups. KD subjects with normal coronaries had carotid strain similar to HC. Conclusion: Young adults with a history of KD with normal coronary arteries also have normal carotid artery strain. Individuals with a history of transiently dilated coronary arteries had a paradoxical trend toward higher carotid strain. Thus, KD patients whose dilated coronary arteries return to normal may have healthier vasculature compared to other KD patients. The significance of this finding merits further study.

Abstract 224: Repeat Coronary Artery Bypass Grafting in an Adult Case of Kawasaki Disease

Background: The incidence of giant coronary artery aneurysm as a complication of Kawasaki disease is approximately 0.35%. Kawasaki disease was first described in 1967. However, only a few studies have reported on adult cases of cardiovascular sequelae in Kawasaki disease. Adult cases of coronary stenosis due to Kawasaki disease shows a predilection for the age range of late teens to the twenties; elderly onset, such as around the age of 60 years, is rare. Case report: A 62-year-old woman with a history of coronary artery bypass grafting (two-vessel bypass) was diagnosed with a coronary artery aneurysm and concomitant Kawasaki disease at another hospital at the age of 48 years. A reoperation was recommended owing to re-strangulation, but the patient opted for progress observation. At the age of 53 years, the patient experienced respiratory pain during laborious work, and coronary angiography was indicated. We therefore performed coronary artery bypass grafting (four-vessel bypass) for there to base Kawasaki disease, calcification of advanced, restenosis, coronary flow was observed. The postoperative course was good, and the patient has remained without restenosis for 9 years after the surgery. Conclusion: The progress of patients with a history of Kawasaki disease in adulthood has not been established; these patients therefore require periodical follow-up examinations. Moreover, because coronary artery involvement in Kawasaki disease is a risk factor for myocardial infarction, careful attention should be paid to lifestyle-related diseases.

Abstract 187: Endothelial Cell Function in Young Adults with History of Kawasaki Disease

Background: The endothelium is a single layer of epithelial cells that lines the blood vessels and is a major component in maintaining vascular homeostasis. Impaired endothelial cell (EC) function can contribute to cardiovascular disease states, but whether there is an association between endothelial dysfunction and the presence of coronary artery aneurysms after Kawasaki disease (KD) is unknown. Methods: We enrolled 110 teens and young adults, ages 16 to 30 years, with a history of KD (61% male), as well as 30 healthy controls (HC, 53% male). EC function (reactive hyperemic response after a 5 minutes brachial artery occlusion) was measured using the EndoPAT 2000. Reactive hyperemia index (RHI) and PAT ratios were determined. KD subjects were categorized based on their worst coronary artery status (normal, transiently dilated/resolved aneurysm, aneurysm). Results: The mean age of KD subjects and HC at the time of EndoPAT was 25 ± 9 and 26 ± 7 years, respectively (p=0.42). Mean time since onset of KD was 23 ± 19 years. Subjects with a history of transiently dilated/resolved aneurysms had a higher mean lnRHI compared to other KD subjects (0.91 vs 0.74, p=0.01) and HC (0.72, p=0.02). When PAT ratio was evaluated as a function of time after occlusion release, those with transiently dilated/resolved aneurysms had a trend toward a more favorable profile while other groups appeared similar (Figure). Conclusion: Most young adults with a history of KD have normal EC function. Individuals with a history of transiently dilated coronary arteries had a paradoxical trend toward better EC function, which may indicate healthier vasculature. The significance of this finding merits further study.

Abstract O.18: Histopathological Analysis Of Sudden Death Adults With Coronary Artery Aneurysms

Histopathological study on coronary arterial lesions of adult autopsy cases who had a history of Kawasaki disease (KD) in childhood or who had coronary artery aneurysms (CAANs) was performed to analyze the relationship between post-inflammatory arterial lesions and atherosclerosis. Materials and Methods: Five autopsy cases who contracted KD at childhood and 11 autopsy cases who had giant CAANs at autopsy although a history of KD was not confirmed were included in this study. The age at death ranged from 18 to 57 years old. Forty-eight coronary artery (CA) branches from 16 autopsies were histologically examined focusing on the atherosclerosis which developed on the post-inflammatory lesions. Results: CAANs occurred in 30 arteries among 48 CA branches. CAANs were classified into 2 types; dilated CAANs (22 branches) and recanalized CAANs (8 branches). Dilated CAANs: The early atherosclerotic lesions, which corresponded to Type III or less of AHA classification, were seen in 16 CAs, and among them 6 branches had thrombotic luminal occlusion caused by the intimal erosion. On the other hand, the advanced atherosclerotic lesions corresponding to Type IV or more were observed in 6 of 22 branches and thrombotic occlusion of the lumen was observed in 5 of 6 CA branches. The cause of those thrombotic occlusion was estimated the rupture of atheroma. Recanalized CAANs: All atherosclerotic lesions developed in the recanalized CAANs were classified to the early lesions. Thrombotic occlusion was seen in 1 of 8 branches. Non-CAANs: There were 18 CAs with no aneurysm formation. The majority of Non-CAANs (16 of 18 branches) showed early atherosclerotic lesions (Type I or II), but 2 branches of 1 patient showed the advanced atherosclerotic lesion and the lumen was occluded by the fresh thrombus caused by intimal erosion. Conclusion: This histological study targeted at the post-inflammatory CA lesions in adult suggests two things: 1) Though advanced atherosclerotic lesions were often observed in the dilated CAANs, the atherosclerosis in the recanalized CAANs and Non-CAANs was still in early stage. 2) The erosion of the intima plays an important role in a formation of the thrombotic occlusion in the post-inflammatory arterial lesions even in adulthood.

Abstract 190: Continuous Vascular Remodeling Related To Development Of Arteriosclerosis Or Atherosclerosis In Kawasaki Disease ~ Immunohistochemical Study using an Animal Model ~

Background: Atherosclerotic coronary heart disease has recently emerged as a clinical issue among young individuals with a history of Kawasaki disease (KD), which is a systemic vasculitis unique to children. However, whether or not and how KD promotes atherosclerosis remains unclear. We hypothesized that, analogous to the pathogenesis of arteriosclerosis or atherosclerosis, endothelial injury and the resultant intimal thickening are induced in coronary arteries after attenuation of vasculitis. Methods: We used a rabbit model of KD developed by Onouchi et al. and performed histopathological analysis of the coronary arteries at acute (1, 3, 5, and 7 days) and chronic (3 months) phases of the disease. Results: In these rabbit models, a pan-arteritis with significant intimal cellular hypertrophy was histologically detected in the acute phase, and arterial intimal thickening was observed during the chronic phase. Immunohistochemical analysis of the coronary arteries revealed that the thickened intimal lesions observed during the chronic phase comprised abundant α-smooth muscle actin (α-SMA)-positive cells, most of which concomitantly expressed vascular cell adhesion molecule-1 and nuclear factor-κB. Although macrophages positive for RAM11 were barely detected, macrophage colony stimulating factor was strongly expressed in migrating smooth muscle cells in the intimal layer. In addition, the accumulation of proteoglycan as extracellular matrix was distinctly visible in the thickened intima, indicating progressive accumulation of lipids and proliferation of smooth muscle cells within the lesion. Conclusions: These findings suggest that, in KD-associated vasculitis, the migration of α-SMA-positive cells into the thickened intima might induce continuous vascular inflammation and remodeling, which might progress to coronary arteriosclerosis or atherosclerosis.

Abstract O.55: Utility of Adenosine Cardiac Stress MRI to Evaluate Ischemia in Patients with Kawasaki Disease

Background: Patients with Kawasaki Disease (KD) and a history of coronary artery disease (CAD) are at risk of myocardial ischemia/infarction. Adenosine stress cardiac MRI (CMR) has been increasingly used in adults to evaluate for atherosclerotic CAD. This modality has not been widely used in the evaluation of CAD in children and young adults, but may be useful in those with a history of KD. Methods: Patients with a history of Kawasaki disease and a clinical indication for a stress cardiac MRI were prospectively enrolled in the study. SSFP cine and delayed enhancement CMR (DE-CMR) were performed in a standard manner. Adenosine stress perfusion was performed with administration of adenosine (140 ug/kg/min) for 2-4 minutes and gadolinium (0.1 mmol/kg) using a standard adult protocol. Results: A total of 13 procedures were performed between 2010 and 2014 on 8 patients with a history of KD (ages 8 to 22, 3F/5M). Seven of eight patients presented with chest pain. Seven of eight patients had documented moderate to giant aneurysms and one had a previous coronary bypass operation. Scans were performed 3-16 years after initial episodes of KD. Three of 16 (19%) scans demonstrated inducible regional ischemia in the distribution of coronary abnormalities. Of these, all underwent cardiac catheterization and 1 patient subsequently underwent coronary bypass surgery. All patients with negative scans were followed clinically with no evidence of further symptoms. Conclusion: As a non-invasive imaging modality, adenosine cardiac stress MRI is feasible in patients with KD and coronary abnormalities and may obviate the need for invasive studies in order to rule out significant CAD. Further studies are needed to evaluate this imaging modality as a more definitive test in the evaluation of KD and chest pain.

Abstract 199: Vasospastic Angina In A School Child Long After Kawasaki Disease

Though it has been already reported that the endothelial function was impaired in patients with a history of Kawasaki disease (KD) and coronary artery aneurysms, vasospastic angina has been rarely reported, especially in school child. A 13-year-old school child referred to us because of repeated chest pain on exercise and reverse redistribution in myocardial perfusion scan. His past history included KD at 2 years of age that was complicated by resistance to initial immunoglobulin treatment and he was left with coronary aneurysms; left main trunk (LMT) of 6.1mm, left anterior descending artery (LAD) of 6.0mm, and right coronary artery (RCA) of 6.0mm. He received oral warfarin treatment in addition to aspirin for 2 years and since then aspirin alone. Coronary angiogram at 7 years old showed LMT aneurysm of 6.1mm starting from orifice extending to bifurcation and regression of RCA aneurysm. He joined baseball club since 8 years old and has been doing well without any symptoms. In this summer, he started complain chest pain after 10 minutes of running 2-3 times a week that lasts for about 30 minutes. Though exercise stress test using treadmill did not show any abnormal electrocardiographic finding, stress myocardial perfusion scan using Thallous chloride-201Tl showed an area of reverse redistribution in the LAD territory. Baseline coronary angiogram at this time showed basically the same finding as that in the last study, intact RCA without stenosis and LMT aneurysm without any stenosis. However, provocative study using intra-coronary administration of 100 ug of acetylcholine, showed diffuse coronary artery spasm in all LCA branches and he indeed complained the same chest pain as that felt in exercise. In addition, intra-coronary administration of nitroglycerine completely reversed coronary spasm and chest pain. Conclusion: Vasospastic angina with chest pain can occurred in the school child with coronary artery aneurysms without coronary stenosis long after KD.

Abstract 75: High Sensitivity C Reactive Protein in Adolescent and Young Adult Patients with Kawasaki Disease Late After Onset

Background: In children with history of Kawasaki disease (KD), low grade inflammation was ever reported to be associated with persistent coronary artery lesions (CAL). However, this issue had rarely been checked in adolescents and young adults (10-25 years old). Methods and Results: The study cohort was comprised of 104 subjects: 22 KD patients with angiography-confirmed CAL, which persisted at an average of 12.5 years after onset of KD, 38 KD patients with regressed aneurysms, 44 KD patients without any coronary complications from the disease onset and 31 age-matched (18.7 ± 1.88 years old) healthy controls. Plasma levels of high-sensitivity C reactive protein (hs-CRP) were measured for all participants with a commercially available high-sensitivity method (Immulite, Simens, USA). Plasma levels of hs-CRP were significantly higher in KD patients, regardless of the severity of coronary artery involvement, than controls. However, there was no difference of hs-CRP level between each KD patient groups including any severity of coronary artery lesions. After adjustment for confounding factors such as body mass index, gender and levels of HDL-c, linear regression analysis showed the only independent predictor of logarithmically transformed hs-CRP levels was BMI (β=0.32, p=0.007), rather than patient grouping (p=0.126). Conclusion: Levels of hs-CRP are significantly higher in adolescent and young adult KD patients than age-matched controls. However, we failed to detect significant difference among patients with different severities of CAL. The results implied, in Taiwan, low grade inflammation might play a minor role on the persistence of coronary lesions in KD.

Abstract 202: Emergence and Characterization of Premature Acute Coronary Syndrome in Young Adults with a Confirmed History of Kawasaki Disease in Japan: Clinical and Mechanistic Insight.

Background: Sporadic cases of acute coronary syndrome (ACS) have been reported in adults with coronary sequelae presumably due to Kawasaki disease (KD). However, ACS in adults with a confirmed (whether followed-up or lost to follow-up) as well as unconfirmed history of KD is poorly characterized. Methods: To investigate ACS in such adults after KD during 2000-10, a nationwide survey was conducted in Japan. Results: A total of 67 patients (median age 35 yo, male 76%) were recruited. A diagnosis of KD was made in 32 during acute illness (Group A), in which 17 were lost to follow up. A KD diagnosis was made retrospectively in the other 35 patients from coronary imaging at ACS (Group B). Overall, 67 patients were characterized by demonstrable thrombosis (74%) as well as the presence of giant aneurysms (GAN) (≥8mm) (38%), severe stenosis (&gt;75%) (38%) and IVUS-derived calcification (92%) in culprit lesions. Group A represented younger age at ACS (26.5 yo vs. 40 yo in group B, p&lt;.001), lower conventional coronary risks (87% vs 65%, p=.043), low percentage of severe stenosis (25% vs. 50%, p=.302) and high proportion of IVUS-derived calcification (86% vs. 100%, p=.335). In group A, patients who were followed up before ACS represented a higher proportion of GAN in culprit lesions (69% vs. 29% in KD patients lost to follow up, p=.030) as well as a shorter interval from acute KD (20 y vs. 27 y, p=.008) and higher percentage of medication before ACS (87% vs. 0%, p&lt;.001). In the convalescence of acute KD in group A, the vessel size of prospective culprit lesion was 6.0-7.9mm in 36% and ≥8mm in 64%. Coronary angio, IVUS and MDCT of cases in 3 categories are presented. Conclusions: Premature ACS in young adults with a confirmed history of KD, significant coronary sequelae just after acute KD and low coronary risks is emerging in Japan. ACS in this population comprises two subtypes: ACS with GAN in culprit lesions in adults followed up for KD, as in childhood myocardial infarction in KD, and ACS in adults lost to follow up, characterized by the absence of GAN or severe stenosis and the presence of IVUS-derived calcification in culprit lesions, which was unmasked in this population. The present findings may give an insight into mechanisms in ACS, screening and medication, as well as recognition of KD in adulthood.

Abstract O.60: Kawasaki Disease Complicated by Coronary Artery Aneurysms: Mortality and 40-year Outcomes

Background: Long-term outcomes and life expectancy for children with a previous history of Kawasaki disease (KD), particularly those with coronary artery aneurysms (CAA), remain to be determined. Methods: An inception cohort of all patients with KD assessed at The Hospital for Sick Children in Toronto between 1978 and 2013 was assembled. Patient outcomes were obtained throughout their pediatric and adult clinical follow-up as long as available. Prevalence of outcomes over time was modelled with Kaplan-Meier survival curves. Life tables from Statistics Canada were used to obtain age/gender specific cumulative mortality for the general population. Results: The cohort included 2,623 KD patients, of whom 410 (16%) had coronary artery involvement (215 dilatation, 57 non-giant CAA and 138 giant CAA). Average follow-up for patients with coronary artery involvement was 6.7 years (13.3 years for giant CAA); 57 and 34 patients had at least 15 and 25 years of follow-up, respectively. No patients with coronary artery dilatation or non-giant CAA had revascularization or a myocardial infarct. Freedom from revascularization (14 events) for patients with giant CAA was 90±6%, 87±7% and 80±13% at 10, 20 and 40 years of follow-up. Freedom from myocardial infarct (11 events) was 94±4%, 92±5% and 89±7% at 5, 20 and 40 years. For patients without coronary artery involvement, 3 (0.1%) deaths were recorded, one secondary to complications of macrophage activation syndrome during the acute phase of KD and 2 from cancer. No deaths were noted for patients with coronary artery dilatation or non-giant CAA, although clinical follow-up was more limited. For patients with giant CAA, 3 deaths (2.2%) were noted, 2 related to CAA complications and 1 from non-medical cause. Cumulative mortality for patients with giant CAA was 1.5% at 10 years of age (expected mortality 0.7%, HR: 2.2 (0.3-11.5), p=0.08) and 3.1% at 40 years of age (expected 2.3%, HR: 1.3 (0.4-4.0), p=0.37). Conclusions: Despite risks of myocardial infarction and revascularization, patients with giant CAA had life-expectancy similar to that of the general population up to the fourth decade of life. Additional follow-up will be necessary to determine if these trends continue into later decades.