bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P300: Circulating MicroRNAs Associated with Glycemic Impairment and Progression in Asian Indians
Authors: Flowers Elena , Aouizerat Bradley E , Gadgil Meghana , Kanaya Alka M
Published: July 2021

Introduction:
Asian Indians experience a high incidence of type 2 diabetes (T2D), but factors associated with glycemic progression from normal to pre-diabetes to diabetes in this population are not fully understood. Circulating microRNAs (miRs) appear to be implicated in T2D etiology in other racial groups.

Hypothesis:
Circulating miRs are associated with glycemic impairment and progression in participants in the Metabolic Syndrome and Atherosclerosis in South Asians Living in America (MASALA) study.

Methods:
Participants were 128 Asian Indians age 45-84 years without cardiovascular disease and not taking diabetes medications. Oral glucose tolerance tests were performed at baseline and after 2.5 years. Glycemic progression was defined as (1) progression from normal to impaired fasting glucose (fasting glucose 100-125 mg/dl) or diabetes (2-hour glucose ≥200 mg/dl, fasting glucose ≥126 mg/dl or diabetes medication use) or (2) from impaired glucose tolerance (2-hour glucose 140-199 mg/dl) to diabetes (see above). Circulating miRs from plasma collected during the enrollment visit were measured using the Firefly Circulating microRNA assay. Unadjusted and multivariate-adjusted logistic regression models were created to determine the relationship between circulating miRs and glycemic impairment and progression.

Results:
The mean age was 57 ± 8 years and 48% (n=62) were men. Glycemic impairment was present in 57% (n=73) at baseline. The prevalence of glycemic progression after 2.5 years was 24% (n=23). Two circulating miRs were associated with glycemic impairment and seven with glycemic progression after 2.5 years (see Table).

Conclusions:
To our knowledge, this is the first study to investigate circulating miRs associated with glycemic impairment in the high risk Asian Indian racial group. Individual miRs were significantly associated with both glycemic impairment and glycemic progression. Further studies are needed to determine whether miR(s) might be useful clinical biomarkers for incident T2D in this population.
Abstract P322: Soda Consumption is Associated With Carotid Intima-Media Thickness Among Middle-Aged Mexican Women
Authors: Arvizu Mariel , Monge Adriana , Thamez Martha , Ortiz-Panozo Eduardo , Yunes Elsa , Catzín-Kuhlmann Andres , Cantu-Brito Carlos , López-Ridaura Ruy , Lajous Martin
Published: July 2021

Introduction:
Soda intake is associated with cardiovascular disease. Other sweetened drinks often considered healthy alternatives to sodas could have a similar impact on cardiovascular risk.

Hypothesis:
Sugar-sweetened beverages commonly consumed by Hispanics have a negative influence on cardiovascular risk.

Methods:
We evaluated the cross-sectional relationship of sweetened beverages and common carotid intima-media thickness (CIMT) in 1,054 disease-free women without diabetes, high cholesterol, history of stroke and/or myocardial infarction, from the Mexican Teachers’ Cohort. Beverage intake was estimated from a validated food-frequency questionnaire in 2008 and 4 years later, CIMT measurements were performed by neurologists. We defined subclinical atherosclerosis as CIMT ≥0.8mm or presence of plaque and beverage intake was categorized in quartiles of servings/day.

Results:
Mean (±SD) soda intake was 0.5 ± 0.7 servings/day among 45.2 ± 4.7 year old women and atherosclerosis prevalence was 8.7%. After adjusting for age, smoking, secondhand smoke, physical activity, oral contraception, menopausal status, SES, and diet, % change of CIMT per 1 serving/day of soda was 1.3 (95% CI 0.2-2.3). Comparing extreme quartiles of soda intake, we observed a 3.5% (95% CI 1.1-5.8; p-trend=0.003) increase in CIMT (Figure). Intake of artificially-sweetened soda, fruit infused water, and juice was not associated to CIMT. None of the beverages were associated to subclinical atherosclerosis.

Conclusions:
In this cross-sectional study, soda intake was associated to increased CIMT while artificially-sweetened soda, fruit water, or juice intakes were not. Our results support prior results on the adverse consequences of soda intake in cardiovascular health.

Keywords:
sugar-sweetened beverages, cardiovascular risk, intima media thickness, cross-sectional
Abstract P356: The Temporal Relationship Between Body Mass Index and DNA Methylation: Longitudinal Epigenome-Wide Association From the Bogalusa Heart Study
Authors: Sun Dianjianyi , Xu Xiaojing , Fu Xiaoying , Li Shengxu , Fernandez Camilo , Li Liming , Su Shaoyong , Wang Xiaoning , Chen Tao , Lian Yun , Li Quan-Zhen , Chen Wei , Srinivasan Sathanur , Berenson Gerald
Published: July 2021

Obesity, as a metabolic disorder, can be either a cause or consequence of epigenetic alterations, but their temporal relationship is unknown. This study assessed the hypothesis that BMI and DNA methylation changes mutually influence each other, dependent on different methylation sites in the human genome. Peripheral leukocyte DNA methylation data on 294,840 CpG sites filtered from 485,577 sites generated by Illumina 450K BeadChip were analyzed in two discovery cohorts (585 whites and 245 blacks) and a longitudinal cohort (95 whites and 43 blacks followed 3.2 years) in the Bogalusa Heart Study (BHS) and 2 replication cohorts (450 twins in Chinese National Twin Study, 456 blacks in Georgia Prevention Institute Epigenetics of Obesity Study). BMI was significantly associated with methylation levels at cg17260706 (negatively), cg13562284 (negatively) and cg15721584 (positively) consistently in the discovery cohorts, and these associations were replicated in both 450 Chinese twins and 456 blacks in the same directions. The temporal relationship analyses in a cross-lagged path analysis model showed a one-directional relation from BMI to methylation changes at cg17260706 in BCL9L gene in both races as seen in the figure. The temporal relationship was different in blacks versus whites for the other two CpGs. In longitudinal analysis of BMI measured 4 or more times over 40 years in the BHS, childhood (p<0.05) and adulthood BMI (p<0.01) and its long-term burden (p<0.01) and increasing trend (p<0.01) were all negatively associated with the methylation level at cg17260706 in 615 whites and 276 blacks. In addition, an SNP in the BCL9L gene (rs586763) was associated with the methylation level at cg17260706 (p<0.05) in blacks only; decreasing slopes of the methylation level at cg17260706 with increasing BMI were significantly different in three genotype groups in blacks (p<0.05), but not in whites. In conclusion, higher BMI results in lower methylation levels at cg17260706 in the BCL9L gene.
Abstract P383: Relationship of Body Mass Index With Total Mortality, Cardiac Mortality and Risk of Hospitalization in Patients With Chronic Heart Failure
Authors: Sharma Abhishek , Lavie Carl J , Borer Jeffrey S , Vallakati Ajay , Lopez-Jimenez Francisco , Arbab-Zadeh Armin , Mukherjee Debabrata Mukherjee , Lichstein Edgar
Published: July 2021

Objective:
To investigate the relationship of body mass index (BMI) with total mortality, cardiac mortality and risk of hospitalization in patients with chronic heart failure (HF).

Methods:
A systematic search of studies published between 1966 to January 31, 2014 was conducted using Pub Med, CINAHL, Cochrane CENTRAL and the Web of Science databases. Studies reporting rate of total mortality, cardiac mortality and risk of hospitalization in patients with HF in various BMI categories [<20 kg/m2 (low); 20-24.9 kg/m2 (normal reference); 25-29.9 kg/m2 (overweight); 30-34.9 kg/m2 (obese); >=35 kg/m2 (severely obese)] were identified. Event rates were compared using a forest plot of relative risk using a random effects model assuming inter-study heterogeneity.

Results:
Two study authors independently reviewed the 124 articles and identified 6 for final analyses (N=22807). After mean follow up of 2.85 years, the risk of total mortality, cardiovascular (CV) mortality and of hospitalization was highest among patients with low BMI (RR 1.27 [95% CI 1.17 - 1.37]; 1.20 [95% CI 1.01 -1.43]; 1.19 [95% CI 1.09 - 1.30] respectively). Risk of cardiac mortality and hospitalization was lowest in overweight patients (RR0.79 [95% CI 0.70-0.90] and 0.92 [95% CI 0.86-0.97] respectively). Increasing degree of obesity failed to achieve a statistically significant effect on CV mortality (0.82 [0.64-1.05] and 0.71 [0.50-1.01] for obese and severely obese, respectively) and on hospitalization (0.99 [0.92-1.07] and 1.28 [0.88-1.87] for obese and severely obese, respectively)

Conclusion:
Risk of total mortality, cardiac mortality and hospitalization was highest among chronic HF patients who were underweight as defined by low BMI, whereas risk of cardiac mortality and hospitalization was lowest in the overweight. Further prospective studies are needed to investigate this association and apparent “overweight paradox” and explore potential underlying mechanisms for this association.
Abstract P386: Pre-hospitalization Medication Use in Black and White Medicare Beneficiaries Hospitalized With Heart Failure
Authors: Levitan Emily B , Van Dyke Melissa K , Chen Ligong , Kilgore Meredith L , Brown Todd M , Durant Raegan W , Safford Monika M
Published: July 2021

Background:
Guidelines for treatment of heart failure (HF) with reduced ejection fraction recommend use of β-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), aldosterone antagonists, diuretics, digoxin, and, for blacks, the combination of hydralazine and isosorbide dinitrate. Race-specific treatment guidelines, differences in pathophysiology, comorbidities, and contraindications, and patient and provider preferences may result in differential use of these medications in blacks and whites with HF.
Objectives:
To examine differences in pre-hospitalization medication use among black and white Medicare beneficiaries hospitalized for HF.
Methods:
Medicare beneficiaries with fee-for-service and pharmacy coverage who had HF hospitalizations (inpatient claims for ≥1 overnight stay with HF as the primary discharge diagnosis, discharged alive) between 2007 and 2011 were identified in the Medicare national 5% sample. More than 98% of Medicare beneficiaries hospitalized for HF had prior inpatient or outpatient diagnoses of HF. Characteristics and medication use in the year prior to hospitalization were assessed through Medicare data. We compared pre-hospitalization medication use between black and white beneficiaries in the overall population with HF (n = 42,721) and in the subpopulation with documented systolic dysfunction (n = 9,702) with a χ
2
test.
Results:
Use of β-blockers and aldosterone antagonist was similar between blacks and whites (
Table
). Blacks were more likely to use ACE inhibitors, ARBs, and hydralazine. Whites were more likely to use diuretics and digoxin. Results were consistent when the population was limited to those with documented systolic dysfunction.
Conclusions:
Blacks were as likely as or more likely than whites to receive pharmacologic heart failure therapies with the exception of diuretics, which were none the less commonly used, and digoxin. Additional research is needed to determine the causes and implications of these differences.
Abstract 105: Platelet-Neutrophil Aggregates play a crucial role in regulating vasculitis in Kawasaki Disease
Authors: Ueno Kentaro
Published: July 2021

Objective:
Circulating platelet-neutrophil aggregates play a crucial role in amplifying acute inflammation and could promote adverse effects involving vascular injury. The aim of this study was to clarify the role of platelet-neutrophil aggregates in patients with Kawasaki disease (KD).

Methods:
We analyzed 40 patients with KD (30 intravenous immunoglobulin [IVIG] responders and 10 IVIG non-responders), 7 febrile patients with bacterial infections, and 9 normal volunteers. Thirty-three patients with KD were treated with IVIG alone, and remaining seven were treated with IVIG plus prednisolone. We evaluated the rate of platelet-neutrophil aggregates and measured the platelet factor 4 (PF4) and β-thromboglobulin (β-TG) levels in patients with KD.

Results:
The rate of platelet-neutrophil aggregates was significantly higher in patients with KD than in both patients with bacterial infection and normal volunteers. There was a trend toward increased rate of platelet-neutrophil aggregates within 2 or 3 days after IVIG than before IVIG. The rate of platelet-neutrophil aggregates was significantly higher in patients who showed coronary artery abnormalities (CAA) than in those who showed without CAA and was correlated with PF4 and β-TG levels in patients with KD. Comparing time course analysis, the rate of platelet-neutrophil aggregates was significantly decreased in patients treated with IVIG plus prednisolone than in those treated with IVIG alone.

Conclusions:
Our findings demonstrate that platelet-neutrophil aggregates play a crucial role in regulating vasculitis, and are involved in the development of CAA. Additional prednisolone treatment in the acute phase of KD might have a potential role in inhibiting amplified reciprocal inflammatory activation by suppressing platelet-neutrophil aggregates.
Abstract 108: New Assessment Of Comprehensive Coagulation Function Using Clot Waveform Analysis In Patients With Kawasaki Disease In The Acute Phase
Authors: Yoshizawa Hiroyuki , Nogami Keiji , Matsumoto Tomoko , Hayashi Tamaki , Shima Midori
Published: July 2021

Background:
Hypercoagulability for Kawasaki disease (KD) in the acute phase is known, through many reports based on the change of the individual coagulation factor. Little information on the assessment of comprehensive coagulation function of this disease is described, however. A recent developed clot waveform analysis (CWA), defines changes in light transmittance that occur during the process of clot formation, can assess comprehensive coagulation function qualitatively and quantitatively by measuring the parameters. In this study, we have investigated the clotting dynamics of acute-phase KD by CWA. Method: The subjects were 43 patients of KD with treatment of intravenous γ-globulin (IVIG), at onset ranged from 3 months to 5 years old (median 1.8 years old). Normal pooled plasma (NP) was prepared from 20 healthy individuals. Blood samples were collected at three points of time; before the IVIG administration (Pre), after 1 week of IVIG (1W), and after 1 month of IVIG (1M). Cases with anticoagulant medication were excluded. CWA was performed using MDA-II™, and parameters, clotting time (CT), maximum coagulation velocity (dT/dt,
Abstract 122: Sivelestat Sodium Hydrate Treatment for Patients with Kawasaki Disease refractory to initial intravenous immunoglobulin therapy
Authors: Ebata Ryota , Yasukawa Kumi , Saito Yuko , Higashi Kouji , Takada Nobuyuki , Takechi Fumie , Saito Naoki , Kobayashi Hironobu , Shimojo Naoki
Published: July 2021

Background:
There are still no definite treatments for refractory Kawasaki disease (KD). In this pilot study, we evaluated the safety and efficacy of a new protocol consisting of sivelestat sodium hydrate (SSH) combined with additional intravenous immune globulin (IVIG) for KD patients who were resistant to initial IVIG therapy.

Methods:
We prospectively collected clinical data of KD patients who were resistant to initial IVIG (2g/kg for one day) and received SSH (0.2mg/kg/hour for consecutive 5 days) combined with additional IVIG (2g/kg for one day) as a second-line therapy at Chiba University hospital between December 2006 and March 2014. We defined patients who remained febrile (37.5°C or more of an axillary temperature) after 36 to 48 hours after start of initial IVIG therapy or who had recrudescent fever associated with other symptoms of Kawasaki disease as being resistant to initial IVIG.

Results:
Thirty five KD patients were enrolled in this study. No serious adverse effect was noted. The median total duration of fever was 8 days (range 6 to 17 days) and the incidence of coronary artery lesion (CAL) was 5.7% (2 of 35 patients). Among a total of 35 patients, 24 (69%) of them responded promptly to be afebrile 36 to 48 hours after the start of the additional IVIG with SSH. One of these 24 patients developed CAL. The other 11 (31%) failed to become afebrile 36 to 48 hours after the start of the additional IVIG with SSH therapy. Of these 11 patients, one developed CAL. Before initial IVIG, there was no difference in demographic and laboratory data except the age, body weight and % Neutrophils. However, after initial IVIG therapy, there appeared significant difference in % Neutrophils and C-reactive protein levels and both of which were higher in additional IVIG with SSH therapy non-responders than in responders.

Conclusions:
Additional IVIG combined with SSH for the additional treatment of KD patients who were refractory to initial IVIG therapy was safe and the incidence of CAL is acceptable considering the severity of patients in this study.
Abstract 125: Steroid Treatment in the Acute Phase of Kawasaki Disease in Mexican Children. Are they Useful?
Authors: Garcia-Dominguez Miguel , Garrido-Garcia Luis M
Published: July 2021

Background:
Intravenous immunoglobulin (IVIG) and aspirin is the standard initial therapy in the treatment of Kawasaki disease (KD), which is proven to decrease the incidence of coronary artery aneurysms from 25% to less than 5%. There is increasing evidence for steroid therapy as adjunctive primary therapy with IVIG especially in those patients who are at increased risk of coronary artery aneurysms and in patients with risk of IVIG resistance. However, clinical trials evaluating the use of corticosteroids plus IVIG have produced confusing results.

Objective:
To evaluate the clinical efficacy and safety of steroids plus intravenous immunoglobulin (IVIG) combination therapy (IVIG+S) for the initial treatment of patients with KD to prevent coronary artery aneurysms (CAA) compared with the standard treatment with intravenous immunoglobulin plus aspirin (IVIG+A) in a Children’s Hospital in Mexico City.

Material and Methods:
An observational, comparative, retrospective and case-control study of all patients treated with IVIG for KD in our Institution from August 1995 to May 2014. The clinical presentation, laboratory results and coronary artery abnormalities in the IVIG+S and the IVIG+A groups were analyzed and compared.

Results:
We studied 295 patients with KD treated with IVIG, 136 (46.1%) received IVIG+A treatment and 159 (53.9%) received IVIG+S treatment. We didn’t found adverse reactions in the patients treated with steroids. The IVIG+S group were older 43.25 ± 43.04 than the non-steroid group 32.07 ± 24.51 (p < 0.008). Steroids were commonly use in incomplete cases (p < 0.059) and in patients with cardiac complications at diagnosis: pericardial effusion (p < 0.056) and pericarditis (p < 0.013). The steroid group has slightly more days of fever after the IVIG treatment 1.27 ± 1.51 days vs. 0.93 ± 0.924 days (p < 0.028). We found no difference in the development of CAA in both groups. (p = 0.221)

Conclusions:
There were no differences in the development of CAA with the use of steroids in the initial treatment of KD. Nevertheless steroids were used more commonly in incomplete forms of KD and in more severely affected patients, which could reflect the lack of difference in the development of CAA in both groups.
Abstract 168: Evaluation Of Coronary Arterial Sequelae Due To Kawasaki Disease Using Optical Coherence Tomography
Authors: Kakimoto Nobuyuki , Suzuki Hiroyuki , Kubo Takashi , Suenaga Tomohiro , Takeuchi Takashi , Shibuta Shoichi , Ino Yasushi , Akasaka Takashi , Yoshikawa Norishige
Published: July 2021

Objectives:
Optical coherence tomography (OCT) is an intracoronary arterial imaging modality employing near-infrared light to create images. OCT makes it possible to distinguish the three layers of the coronary arterial wall. However, few previous studies have used OCT to evaluate coronary arterial lesions (CAL) in Kawasaki disease (KD). Here we report the use of OCT to evaluate CALs in KD.

Patients and Methods:
Fifteen patients aged between 11 and 29 years were admitted to undergo coronary angiography (CAG) for follow-up of KD. The male : female ratio was 11:4. Their ages at disease onset and when OCT was performed were 1m - 10y11m (median; 1y2m), and 11y1m - 29y3m (median; 16y2m), respectively. The interval between disease onset and OCT examination was 5y1m - 24y4m (median; 13y2m). Repeated CAG was performed on the basis of the criteria stipulated in the guidelines for cardiovascular sequelae in KD (JCS 2008). At the time of the latest CAG, we performed not only regular CAG but also IVUS and OCT (C7 OCT imaging system, St Jude Medical, St. Paul, MN, USA) for coronary arteries between December 2012 and August 2014.

Results:
We demonstrated fresh thrombus, stenosis, fibrotic intimal thickening with lamellar calcification and partial disappearance of the tunica media in CAL. Fibrotic intimal thickening and disruption of the tunica media are demonstrated in all patients. In addition, OCT demonstrated intimal thickening and disruption of the tunica media in completely regressed lesions and even in regions where CAG had shown normal coronary arterial walls in the acute phase.

Conclusions:
Our data suggest that fibrotic intimal thickening and disruption of the tunica media may be basic changes of coronary arterial sequelae in KD. The use of OCT for evaluation of KD vasculitis may clarify the mechanisms responsible for coronary arterial sequelae and be useful for prognostication of CAL.
Abstract 178: Measurements of coronary aneurysms due to Kawasaki Disease by Dual-Source Computed Tomography (DSCT)
Authors: Tsujii Nobuyuki , Tsuda Etsuko , Kanzaki Suzu , Kurosaki Kenichi
Published: July 2021

Background:
Diameters of coronary artery aneurysms (CAAs) due to KD in the acute phase can strongly predict long-term prognosis of coronary artery lesions. Recently, Computed Tomography Angiography (CTA) has been used in the diagnosis of coronary artery lesion (CAL).

Purpose:
The purpose of this study was to determine whether measurements of coronary artery diameters by CTA using DSCT can be used instead of coronary angiograms (CAG) during cardiac catheterization.

Methods:
Twenty five pts (22 males and 3 females) with CAL due to KD were evaluated. Their ages ranged from 5 months to 38 years (median 11years). CTA was performed between July 2007 and July 2013, and CAG was done within one year. A prospective Electrocardiogram (ECG) -triggered CTA was performed on a DSCT (SOMATOM® Definition (from July 2007 to October 2009) or SOMATOM® Definition Flash (from October 2009 to July 2013); Siemens Healthcare, Germany). ECG-gated scans were performed in 19 cases and Flash Spiral scans in 6 cases. Two pediatric cardiologists measured the diameters of CAAs twice in each maximum intensity projection (MIP), curved multi planer reconstruction (MPR) and CAG. We measured 161 segments in total (segment1-3,5-7,11,13). Diagnostic accuracy was expressed as κ coefficient. A Bland-Altman analysis was also used to assess the inter-observer, intra-observer and inter-material agreement.

Results:
The visualization capability of coronary arteries was excellent. One segment was not visualized by CTA. Detection rate in CTA, comparing with CAG, was 99.7%, and the diagnostic quality of CTA was excellent (κ=0.93). Excellent inter-observer agreement for diameters of CAAs was obtained for MIP, MPR and CAG and for the intra-observer agreement. The inter-modality agreement was also excellent (MPR-CAG : y=0.9x+0.40, r=0.97 ,p<0.01 MIP-CAG : y=1.0x+0.1, r=0.94, p<0.01). We also studied the diameters in normal segments. We also obtained good correlation between inter-observer, intra-observer and inter-modality (MPR-CAG : y=1.0x, r=0.89 , p<0.01 MIP-CAG : y=1.0x+0.1, r=0.88, p<0.01).

Conclusion:
We found a significant good correlation in the measurements of coronary artery between CTA and CAG. Measurement of the diameters of coronary artery by CTA is reliable and useful.
Abstract 199: Vasospastic Angina In A School Child Long After Kawasaki Disease
Authors: Kudo Yoshiyuki , Suda Kenji , Kishimoto Shintaro , Yoshimoto Hironaga , Matsuishi Toyojiro , Nishihara Shigetaka
Published: July 2021

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 201: Risk Factors Of Persistent Coronary Artery Dilatation In Taiwanese Children With Kawasaki Disease.
Authors: Liu Ming-Yu , Liu Hsin-Min , Lin Ming-Tai , Chen Chun-An , Chiu Shuenn-Nan , Lu Chun-Wei , Wang Jou-Kou , Wu Mei-Hwan
Published: July 2021

Background:
Kawasaki disease (KD) is an acute, systemic vasculitis disease of childhood, which may lead to cardiovascular complications, particularly coronary artery (CA) dilatation or aneurysm formation, and could result in morbidity and mortality. The Z score of coronary artery decreased from initial value within first few 2-3 months after fever onset. We follow the echocardiographic measurements of KD patients over time, and attempt to find the associated factors of persistent dilated coronary artery.

Methods:
Initial presentations, clinical laboratory data, echocardiography measurements and treatment were obtained from the patients with acute Kawasaki disease over 4 years period in a single medical center hospital. The patients were divided into 3 groups according to the initial maximum Z score of any coronary artery which were normalized for body surface area. We followed the echocardiography regularly at initial acute phase, 2-4 week, 5-12week, and > 3 months after fever onset. The maximal Z score of any coronary artery branches > +2 at any time were defined as having abnormalities.

Results:
We included total 169 patients with acute KD during 2008-2012. A maximal Z score for any of the coronary artery branches greater than +2 at acute phase was noted in 31.4% (53 of 169) of patients. During the following-up period, all except one patients (1 of 138) of the patients with initial maximal Z score <+2.5, the coronary artery have no abnormality at the end of following up. In contrast, the patients with initial maximal Z score≧+2.5 were more likely to have persistent coronary abnormalities over time (5 of 31, P<0.001). We also found hypoalbuminemia (P=0.006) and unresponsiveness to initial intravenous immunoglobulin treatment (P<0.001) associated with deteriorated or persistent CA abnormality within one month of disease onset.

Conclusion:
Coronary artery dilatation with Z score≧+2.5 at acute phase of Kawasaki disease, hypoalbuminemia and IVIG unresponsiveness are significantly associated with persistent CA abnormality at one month after KD onset. That indicated how to avoid IVIG unresponsiveness at the initial treatment of KD is a critical issue.
Abstract 220: Magnetic Resonance Imaging in Children with Cardiac Complications of Kawasaki Disease: a Comparison with Echocardiography and Conventional Coronary Angiography
Authors: Khoury Michael , Manlhiot Cedric , Grosse-Wortmann Lars , Yoo Shi-Joon , Seed Michael , Redington Andrew N , McCrindle Brian W
Published: July 2021

Background:
MRI is a potentially sensitive, specific, and non-invasive imaging modality that may be used in the detection and monitoring of KD cardiac complications. Its utility relative to the more commonly used imaging modalities of echocardiography and conventional coronary angiography has not been optimally established.

Methods:
We compared concomitant clinical data, echocardiography, MRI, and angiography findings for children with coronary artery aneurysms.

Results:
MRI and angiograms were performed within 1 month of each other for 15 patients (mean age 7 years, 80% male) at a mean of 4.2 years after diagnosis. Coronary artery bypass grafting (CABG) had been performed in 8 patients (53%). For 7 patients (47%), aneurysms were seen on MRI that were not seen on echocardiography. Wall motion abnormalities were reported in 7 subjects (47%). These were characterized on both echocardiography and MRI for all. MRI identified perfusion defects in 6 patients (40%) and evidence of myocardial scar in 9 patients (60%). Extra-cardiac aneurysms were identified in 5 patients (33%) on MRI. MRI showed strong correlation with angiograms regarding aneurysm location. MRI was limited in the assessment of bypass grafts in 4 of the 8 (50%) patients who had undergone CABG. Three patients (20%) had stenosis or thrombosis identified on angiography that were not appreciated on MRI. Angiograms provided added information regarding flow, stenoses, vascular morphology and/or calcification in 8 patients (53%). Collateral artery anatomy that was not appreciated on echo and MRI were reported on angiograms in 3 patients (20%).

Conclusions:
MRI provides a valuable and comprehensive assessment of the cardiac sequelae of KD, though is limited in its assessment of CABG, stenoses, and thrombosis. MRI may be an important component of non-invasive imaging surveillance of children with important coronary artery involvement.
Abstract 221: Use of Statins in Patients with Coronary Artery Aneurysms: A Pilot Study from the North American Kawasaki Disease Registry
Authors: Khoury Michael , Portman Michael A , Manlhiot Cedric , Fournier Anne , Dillenburg Rejane F , Dancea Adrian B , Renaud Claudia , Greenway Steven C , Kutty Shelby , Beaulieu Emilie , McCrindle Brian W ,   North American Kawasaki Disease Registry
Published: July 2021

Background:
Statins have been considered as therapy for children with coronary artery aneurysms (CAA) after Kawasaki disease (KD), due to potential beneficial pleiotropic effects which might influence chronic vascular processes and inflammation.

Methods:
The North American Kawasaki Disease Registry was queried to identify patients who have received statins in the first 6 months following the convalescent phase of KD. Each identified patient was matched by age, gender and CAA z score to 3 patients who were statin-naïve (controls). Linear regression models adjusted for repeated measures and maximum coronary involvement were used to determine an association of statin use with longitudinal changes in coronary artery diameter z-score. Kaplan-Meier analysis was used to compare freedom from angiographically-confirmed stenosis or interventions.

Results:
Of 29 patients with KD and CAA (maximum coronary artery z-score >10) who received statins at any time (of n=621, 5%), 10 (9 males) patients were started within 6 months of the acute KD episode. The mean age at KD was 6.3±3.4 years (5.4±3.5 for controls, p=0.57). Mean maximum CAA z-score was 36±14 (vs. 29±16, p=0.20); 90% of statin patients and 87% of matched controls had CAAs in 3 or more branches. Linear regression analysis of 442 serial echocardiograms showed that maximum CAA z-score decreased by -1.5 (95%CI: -2.7; -0.4) SD/year (p=0.008) for control patients compared to -2.9 (95%CI: -4.4; -1.4) SD/year (p<0.001) for statin treated patients. The difference between the rate of change of CAA z-score for statin vs. control patients did not reach statistical significance (controls vs. statins: +1.4 SD/year, 95%CI: -0.6; +3.4, p=0.18). n=7 patients (3 on statin, 4 controls) developed stenosis or had revascularization, with no significant difference between groups (HR for statin group: 2.2 (0.4-11.4), p=0.41).

Conclusions:
This underpowered pilot study suggests that equipoise likely exists with regards to statin therapy in children with KD and CAA, and that a formal registry-nested trial might be considered.
Abstract 28: African American Race is Not Protective Against Coronary Artery Involvement in Kawasaki Disease
Authors: Williams Emily P , Kelleman Michael S , Mahle William T
Published: July 2021

It has been previously reported that African American race may be protective against coronary artery aneurysm development in Kawasaki Disease (KD). We aimed to test this with our own cohort of KD patients from a large pediatric cardiology practice. Data from 250 subjects diagnosed with KD and followed as outpatients with surveillance echocardiography over a two-year period were analyzed. Twelve patients were excluded due to incomplete records or an unconfirmed diagnosis. Race designated by parent was recorded. Charts were reviewed for any coronary involvement (ectasia or aneurysm) and coronary Z-score greater than 2.5 at the time of diagnosis and at subsequent follow-up visits. Odds rations were calculated comparing each racial group to others for any coronary involvement and for coronary Z-score > 2.5. Of 238 included patients, 44.5% were African American, 37.4% were non-Hispanic white, 10.5% were Hispanic, and 7.6% identified with other racial designations. Approximately 21.9% of African American patients had any coronary involvement and 9.5% had a coronary Z-score > 2.5. Approximately 21.4% of non-Hispanic whites had any coronary involvement and 13.5% of non-Hispanic whites had a coronary Z-score > 2.5. Twenty-eight percent of Hispanic patients had any coronary involvement and 12% had a coronary Z-score > 2.5%. Of patients that identified with other racial designations, 38.9% had coronary involvement and 22.2% had a coronary Z-score > 2.5. No statistically significant odds ratios were identified. Relative to reference group (non-Hispanic whites) African American patients had nearly identical rates of 1) any coronary involvement, or 2) coronary Z-score > 2.5. KD occurs commonly in African-American children. Given equal risk for late coronary sequelae vigilance and strict adherence to consensus guidelines is essential.
Abstract 33: A Meta-analysis Of Three Genome-wide Association Studies Identifies A Novel Susceptibility Locus For Kawasaki Disease.
Authors: Johnson Todd A , Wu Jer-Yuarn , Yoon Dankyu , Hata Akira , Kubo Michiaki , Takahashi Atsushi , Tsunoda Tatsuhiko , Ozaki Kouichi , Tanaka Toshihiro , Chen Chien-Hsiun , Lee Yi-Ching , Chang Li-Ching , Chang Chun-Ping , Hong Young Mi , Jang Gi Young , Yun Sin Weon , Yu Jeong Jin , Lee Kyung-Yil , Kim Jae-Jung , Lee Jong-Keuk , Chen Yuan-Tsong , Onouchi Yoshihiro ,   Japan Kawasaki Disease Genome Consortium,   Korean Kawasaki Disease Genetics Consortium,   Taiwan Kawasaki Disease Genetics Consortium
Published: July 2021

Background:
Although genome-wide association studies (GWAS) have conclusively identified several susceptibility genes / loci for Kawasaki disease (KD), a large part of the genetic etiology of this disease have not been unraveled and, above all, its marked predilection for East Asian populations have not been explained.

Objective:
To identify genetic variants commonly associated with KD in the East Asian populations, we conducted a meta-analysis of three GWASes from Japan, Korea and Taiwan.

Methods:
In the GWAS analyses, we genotyped 6322 subjects (1236 cases and 5086 controls) using either Illumina 550K or Affymetrix SNP 6.0 platforms and then imputed untyped genotypes using Impute2 or minimac software with 1000 Genomes Project’s East Asian population (JPT, CHB and CHS) reference haplotype data. We then performed a meta-analysis using a weighted-average method with inverse-variance weights and selected representative SNPs in 49 top associated loci, which were then genotyped in 4798 independent subjects (2151 cases and 2747 controls). Finally, we combined the data for the three GWASes and follow up studies in a meta-analysis.

Results:
SNPs within previously identified susceptibility loci showed significant association in the meta-analysis of the GWASes (ITPKC: rs28493229, P = 3.07 x 10-9; CASP3: rs2720377, P = 2.66 x 10-9; BLK: rs2736340, P = 1.23 x 10-16; CD40: rs1883832, P = 1.76 x 10-8; HLA class2: rs189914842, P = 4.57 x 10-11). In a meta-analysis of the three GWASes and follow-up studies, we observed a genome-wide significant level of association at a SNP in a chromosomal region different from the six known loci (P = 6.49 x 10-9).

Conclusion:
The meta-analysis of three GWAses and follow-up studies successfully identified a new SNP significantly associated with KD. Further investigation of the region where the SNP is located toward specification of the susceptibility gene, the responsible variant, as well as its effect on gene function is warranted.

Acknowledgement:
T.A.J., J.Y.W. and D.Y. equally contributed to this work and J.K.L., Y.T.C., and Y.O. are co-directing this project.
Abstract 54: The Correlation Between IgE And The Level Of Interleukin-21 In Kawasaki Disease
Authors: Lee Hae-Yong
Published: July 2021

Purpose:
It has been reported that serum level of immunoglobulin E (IgE) is increased in patients with Kawasaki disease (KD) after acute phase. However the exact mechanism of increasing IgE is yet to be revealed. We investigated whether the interleukin-21 (IL-21) could be related with the high IgE in KD. Instead of IL-4, IL-21 was focused in this study because it has been reported that its level is increased in various autoimmune vasculitis.

Methods:
From June 2008 to June 2010, 49 patients with KD admitted in Wonju Severance Christian Hospital and 13 controls with high fever due to unknown infection who had no history of KD were included in this study. The sera from patients and controls were collected and checked in terms of immunoglobulin E (Chemiluminescent method, Siemens, Munich, Germany) and IL-21 (ELISA, eBioscience, San Diego, USA).

Results:
The median age of patients with KD was 3 years of age (range: 0.4-10) and that of controls was 7 years of age (range: 1-12). The group of patients with KD was composed of 39 complete KD and 10 incomplete KD. Among patients with KD, 10 patients had coronary arterial dilatation (CAD) and 39 patients had no coronary complications. The median value of IL-21 in patients with KD was significantly increased as 466 pg/mL (range: 0-1544) while that value in controls was <62.5 pg/mL (range: 0- 825 pg/mL) (
P
< 0.01). We could not find the significant correlation between the serum level of IgE and that of IL-21 in patients with KD (Spearman R=0.2,
P
= 0.08) though 30% of patients with KD showed increased IgE more than 100 IU/mL. In addition, our data showed no significant difference between CAD group and non CAD group in terms of serum IL-21.

Conclusion:
Our data showed firstly that IL-21 is increased in patients with KD. There was no significant correlation between high IgE and the level of IL-21.
Abstract O.41: Assessment of Kawasaki Disease Risk Scores for Predicting Coronary Artery Aneurysms at a North American Center
Authors: Son Mary Beth F , Gauvreau Kimberlee , Kim Susan , Tang Alexander , Dedeoglu Fatma , Fulton David R , Lo Mindy S , Sundel Robert P , Newburger Jane W
Published: July 2021

Aim:
To assess the performance of established Japanese risk scores (RS) to identify patients (pts) with Kawasaki disease (KD) at high-risk for developing coronary artery aneurysms (CAA).

Methods:
We reviewed clinical, laboratory and echocardiographic (echo) data for pts with KD treated with IVIG from 1/2006 to 5/2014. We defined CAA as z score ≥2.5 in the right coronary artery (RCA) or left anterior descending artery (LAD) at 4-8 weeks of illness. Relationships with Kobayashi, Sano, Egami and Harada RS and CAA were examined. The maximum z score of LAD or RCA (zMax) at baseline was a covariate in logistic regression. The discrimination of each model was assessed using the c statistic.

Results:
Of 268 pts with complete data, 173 (65%) were male and median age was 3.1 y (range 0.1-14.1 y). At diagnosis, 74 (28%) had ≤3 classical criteria for KD, and 70 pts (26%) received IVIG retreatment. On baseline echo, 75 pts (27%) had a zMax ≥ 2.0. CAA occurred in 15 pts (5.6%). The Harada RS predicted development of CAA (low risk = 0% (0/80), high risk=9% (12/140), p=0.005), but the Kobayashi, Sano, and Egami RS were not associated with CAA. CAA were associated with baseline zMax ≥2.0
vs.
<2.0 (12 [16%] vs. 3 [2%], respectively, p<0.001) and as a covariate in logistic regression (Table 1).

Conclusions:
With the exception of the Harada score, established RS were ineffective at predicting the development of CAA at a cosmopolitan center. Baseline z scores were highly associated with CAA. However, adding baseline z scores to a logistic regression model did not improve discrimination of the RS.
Abstract O.53: Occult Coronary Artery Dilatation: An Unrecognized Category Of Coronary Involvement
Authors: Rached-d'Astous Soha , Rached-d'Astous Nour , Dallaire Frederic , Dahdah Nagib
Published: July 2021

Background:
The current definition of Coronary artery dilatation (CAD), Z-score >2.5, in KD may omit patients at higher risk of later complications. We propose a category of occult CAD with a Z-score variation ≥ 2 for the same CA on 2 different echocardiograms, but absolute Z-score < 2.5. We compared this new category with cases of CAD and normal CA.

>Method:
A retrospective review included 337 patients diagnosed with KD in our institution. Echographic data were retrieved for the fist year following diagnosis. Patients were classified in three categories: definite CA dilatation (dCAD) with Z-score ≥ 2.5, occult CA dilatation (oCAD) and normal CA (nCA). We compared inflammatory profile, IVIG treatment resistance, and timing of CA involvement.

Results:
There were 26.3% patients with nCA, 32.2% with oCAD and 41.1% with dCAD.Patients with KD incomplete diagnostic criteria represented 35%, 14% and 17% for NCAD, OCAD and DCAD groups respectively (p=0.008). Median time for CAD was 7 and 9.5 days for dCAD and oCAD respectively (p=0.2). A Jonckheere trend test identified a progression of inflammatory parameters through the three groups for Platelet count (p< 0.001), Albumin (p = 0.007), ESR (p = 0.04), but not for CRP (p = 0.76) and WBC (p = 0.16). There was a significant difference in treatment resistance, with 5%, 19% and 31% for NCAD, OCAD and DCAD respectively (p=0,002).

Conclusion:
OCAD group appears like a distinctive subgroup of KD patients showing intermediate inflammatory profiles and treatment respond in the NCAD to DCAD spectrum. Recent Z-score equations, more accurate for young patients’ CA size than former linear equations, may explain the high incidence of dCAD in this report. Further studies are needed to define the profile and propensity to complications of this subpopulation.
Abstract O.55: Utility of Adenosine Cardiac Stress MRI to Evaluate Ischemia in Patients with Kawasaki Disease
Authors: Campbell Michael J , Barker Piers , Li Jennifer
Published: July 2021

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 O.63: Novel Use Of Fractal Analysis In Kawasaki Disease For Risk Prediction
Authors: Lim Terence C W , Cheung Carol Y , Quek Swee Chye , Ong Peng Guan , Wong Inez B , Grignani Robert G , Wong Tien Y
Published: July 2021

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<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.