bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 206: Coronary Artery Thrombosis in an Infant with Kawasaki Disease without Giant Coronary Aneurysm and Iron Deficiency Anemia: a Case Report
Authors: Natesirinilkul Rungrote , Charoenkwan Pimlak , Sittiwangkul Rekwan , Silvilairat Suchaya , Prongpot Yupada
Published: July 2021

The major complication of Kawasaki disease is coronary aneurysm which can cause acute coronary disease in early adulthood. There are some reports of coronary artery thrombosis during the period of active Kawasaki disease in infants with giant coronary aneurysm. This report demonstrated a 5-month-old male infant who presented high-grade fever for 7 days. He was treated as urinary tract infection for 6 days before referral. At admission, he had fever, red lips and swelling of both feet, then was diagnosed Kawasaki disease. His EKG showed ST elevation at lead II, III and AVF. His initial echocardiogram revealed coronary dilatation with perivascular brightness; RCA 2.7 mm (Z-score 4.38), LMCA 2.88 mm (Z-score 2.83) and LAD 2.7 mm (Z-score 5.79). There was a clot 2.5 X 2.5 mm in LAD. However, his LV systolic function was normal (EF 76%). His blood test showed low hemoglobin as 8.9 g/dL and MCV as 61.9 fL, high white cell count 20,400/mm3 and platelet count as 606,000/mm3. His initial ESR and CRP elevated at 91 mm/hr and 52 mg/L, respectively. The cardiac enzymes were normal; CKMBmass 2.9 ng/mL (0-3) and troponin-T 0.004 ng/mL (< 0.4). He received IVIG 2.3 g/kg and aspirin 79 mg/kg/day and was closely monitored the vital signs and cardiac enzymes. His fever completely disappeared within 24 hours after treatment, then aspirin was decreased to 6 mg/kg/day. Also, he received intravenous heparin for 4 days, and then was switched to Enoxaparin. He was discharged uneventfully on day 22 of admission. Further blood test confirmed the diagnosis of iron deficiency anemia as follow; serum iron 30 [[Unable to Display Character: ɥ]]g/dL, transferrin-iron binding capacity 446 [[Unable to Display Character: ɥ]]g/dL and transferrin saturation 6.7% (< 16). He received iron supplement for 4 months. The clot in coronary artery gradually decreased in size and finally disappeared in seven months after diagnosis. So, the Enoxaparin was discontinued. He received low-dose aspirin for total course 15 months. His thrombophilia work up was unremarkable. Anemia which is one of the supplementary criteria for atypical Kawasaki disease should be properly evaluated for the cause. The study to find the association between iron deficiency anemia, which was reported as a risk for thromboembolic events, and severity of Kawasaki disease should be further investigated.
Abstract 208: Follow-up Study in Kawasaki Disease By Treadmill Exercise Test And Echocardiography
Authors: Park Sin-Ae , Park Kichul , Park Jee Won
Published: July 2021

Kawasaki disease (KD) may result in coronary aneurysm formation and increased risk of cardiovascular complications such as ischemic heart disease. Therefore, the early detection, non-invasive monitoring and long-term follow-up of myocardial ischemia are essential. This study sought to determine the ischemic heart disease by treadmill exercise test and two-dimensional echocardiography. Three hundred and four patients with a history of KD from 1995 to 2005 were retrospectively analyzed. Among them fifty patients who agree with the study underwent exercise test and 2D-echocardiography. The patients were followed for 11.6 years(8 to 17) from disease onset. The coronary artery ectasia regressed in 21 patients. No stenotic lesion could be found in the coronary artery in follow-up echocardiography. And no significant ischemic changes were detected. There is no evidence of persisting coronary ectasia and dysfunction of cardiac perfusion in patients with previous KD in this study. However, these patients should be counselled to avoid potential risk factors for other complication such as atherosclerosis and long term follow up is needed into adult life.
Abstract 217: Difference of Coronary Artery Lesions or associated Pathogens between the Two Phenotypes of Kawasaki Disease
Authors: Yoon Kyung Lim , Youn Song Ee , Han Mi Young , Cha Sung Ho
Published: July 2021

Introduction:
There are several reports that coronary artery lesions (CALs) are increased/or not increased in patients who predominantly showed arthritis in patients with Kawasaki disease (KD). Patients with eczematoid skin lesions which seem like atopic dermatitis have not been reported in association with CALs. We intended to evaluate the risk of development of CALs in patients with two different phenotypes.

Materials and methods:
We retrospectively reviewed the medical records in 220 patients who diagnosed as KD and received IVIG treatment in Kyung Hee University Hospital at Gangdong from August 2006 to December 2013. In both patients groups (6 patients with arthritis and 52 patients with eczematoid skin lesion), we reviewed the state of coronary artery, clinical characteristics, associated viral or bacterial infections.

Results:
In patients with eczematoid lesions (52/220, 23.6%), the ages of patients were significantly older, the duration of fever was longer, and the prevalence of CAL was significantly higher than that of controls (
P
=.000,
P
=.041,
P
=.033, respectively). In patients with arthritis (6/220, 3%), there were higher incidence of methylprednisolone or infliximab therapy (
P
=.000,
P
=.004, respectively), and higher incidence of viral infection like
influenza A
and
B, rhinovirus, parainfluenza 2, metapneumovirus,
and
coronavirus OC43
(
P
=.018).

Conclusions:
The incidence of CAL was higher in group of eczematoid skin lesion in KD patients than in group of patients with arthritis. Associated viral infections were higher in arthritis group, therefore, it is better to find associated pathogens aggressively that might be a certain trigger of the development of KD in this group of patients.
Abstract 222: North American Kawasaki Disease Registry - Advancing Clinical Research Through Collaboration
Authors: McCrindle Brian W ,   North American Kawasaki Disease Registry
Published: July 2021

Background:
Clinical research in children with Kawasaki disease (KD), particularly those with coronary artery aneurysms (CAA), is challenging due to the limited number of patients available at any single institution. This has resulted in imperfect evidence for optimal management and considerable practice variation.

Methods:
The North American Kawasaki Disease Registry (NAKDR) was started in July 2013 to determine the prevalence, patient-level and pharmacological risk factors for outcomes of CAA after KD. The NAKDR enrolls KD patients diagnosed from 1999-2013 with CAA (defined as any segment with a z-score >2.5). The NAKDR and its internet-based data entry portal are maintained at The Hospital for Sick Children in Toronto. Local ethics approvals and bilateral data sharing agreements are necessary for participation. Participation in the NAKDR is currently unfunded and voluntary. In September 2014, a survey on the future of the NAKDR was sent to all participating centers (response rate: 54%).

Results:
45 sites have been invited, of which 37 (82%) agreed to participate. As of September 2014, 20 sites are actively submitting data; 17 are still being initiated; 706 cases have been submitted. The majority (90%) of members indicated that they wished to continue enrolling newly diagnosed patients and continue follow-up on patients already enrolled. Members were split (45% for, 55% against) as to whether the NAKDR should be expanded to include all KD patients, regardless of CAA status. Finally, while most NAKDR members (60%) indicated that site reimbursement was not an absolute condition for future participation, most members suggested that potential funding sources should be sought to expand/facilitate activities. At term, the NAKDR is expected to comprise ~1,400 patients and, if moving forward, add ~120 new KD patients with CAA per year.

Conclusions:
The NAKDR is an important tool for clinical research in children with CAAs after KD, and its success represents broad support from clinicians. The next step will be to formalize the NAKDR leadership structure, create standard operating procedures, and pursue prospective studies and funding.
Abstract 3: Kawasaki Disease in Algerian Children: A Clinical Study
Authors: Boudiaf Houda , Achir Moussa
Published: July 2021

Background:
Kawasaki disease (KD) is an acute multisystem vasculitis of unknown etiology that occurs predominantly in infants and young children. The incidence of KD is increasing worldwide ; however the epidemiological data available for Algerian patients remains insufficient

Objective:
To describe the demographic, clinical, and laboratory features of Algerian children with KD and to highlight the practical difficulties.

Methods:
This retrospective study included children admitted with Kawasaki disease at the only pediatric tertiary referral hospital in Algiers over a period of 8 years from January 2006 to December 2013.

Results
: 108 patients with KD, with a mean age of 31 months (range: 8-84 months)were identified. There were 63 boys and 45 girls (sex ratio: 1.4). The clinical data were similar to previously described studies, with some difference: the cervical lymphadenopathy was less frequent :25%(27/108). 22%( 24/108) of children had evidence of cardiac complications: 20%( 22/108) had coronary artery abnormalities ; one child had mitral regurgitation, one had pericardial effusion. Of the 22 children with coronary abnormalities , 9 had coronary dilatation, 13 had coronary aneurysms (10 small and medium, 3 giant). These abnormalities regressed in 13 cases on follow up. During this period, catheter and surgical coronary intervention were performed to treat coronary ischemia in one patient, two years after onset. The only independent variable for prediction of coronary involvement was fever duration at the time of initial presentation(p=0.016). The therapeutic used in this study included an immunoglobulin treatment for only 63%(69/108) of the children, half of which received it within the first ten days of the onset of the disease.

Conclusion:
This work demonstrates the necessity of a registry that will allow better appreciation of the incidence of this disease and improve the diagnosis and treatment of KD in Algeria
Abstract 78: An Incomplete Kawasaki Disease Child With Initial Presentation Of Murmur
Authors: Eun Lucy Y , Choi Yunjung , Sung Mindong , Jung Jo Won , Choi Jae Young
Published: July 2021

Abstract:
Kawasaki disease(KD) is acute vasculitis in childhood. The authors report the 12-month-old girl with initial presentation of cardiac murmur who was diagnosed incomplete KD.

Case:
A 12-month-old girl with history of 3 days fever up to 38°C and upper respiratory symptoms including rhinorrhea visited a pediatric clinic. Cardiac murmur was noticed, then she was referred to Pediatric Cardiology clinic. She had loss of appetite and her growth curve showed severely underweight of 8.4kg(less than 3p) compared to height 78cm(50~75p).

On hospital day 1, laboratory studies revealed a white blood cell (WBC) 9.4(seg73%, Lym23%)x 103/uL, hemoglobin concentration(Hb) of 5.5 g/dL with hematocrit(Hct) 21%, platelet count 426,000/uL. And laboratory results included ESR 2mm/hr, C-reactive protein 0.05mg/L, AST/ALT 31/19 IU/L, Ferritine 13 ng/mL, TIBC 510ug/dL, Transferrin Saturation Index 2.5% and MCV 50.4fL, MCH 13.4pg, MCHC 26.5g/dL. She had grade II-III/VI end-systolic & early diastolic murmur. The echocardiography showed left main coronary artery dilatation and pericaridial effusion.

Based on diagnosis of incomplete Kawasaki disease and iron deficiency anemia, she treated with IVIG(IV gamma globulin), acetylsalicyclic acid, packed RBC transfusion and supplement of oral iron. On hospital day 2, repeat laboratory studies revelaed Hb 6.5 g/dL, and the murmur decreased rapidly. 6 days later Hb was 9.3 g/dL. Pro-BNP was 352 pg/ml on hospital day 1 and repeat studies revealed 978 pg/ml on hospital day 2, 84pg/ml on hospital day 8.

The patient was discharged 8 days after admission(on day 11 of her illness) without fever.

After 1 month of discharge, she had gained weight to 10.5kg and laboratory study results Hb 11.0 g/dL.

And follow-up echorcardiography showed improvement of coronary arteries.

The authors report one child presenting with heart murmur under incomplete Kawasaki disease.
Abstract 86: Pentraxin 3 Can Be A Candidate For Biomarker Of Kawasaki Disease
Authors: Katsube Yasuhiro , Akao Miharu , Hashimoto Yoshiaki , Hashimoto Kouji , Watanabe Makoto , Abe Masanori , Ikegami Ei , Kamisago Mitsuhiro , Fukazawa Ryuji , Ogawa Shunichi
Published: July 2021

Background:
Kawasaki disease (KD) is a systemic vasculitis and the leading cause of acquired heart disease. There are some cases that show unresponsiveness to initial intravenous immunoglobulin (IVIG) and require addition treatment. High incidence of coronary artery lesions (CAL) is seen in unresponsive cases. Pentraxin 3 (PTX3) is produced at the site of vascular inflammation, and used as a new biomarker for vasculitis. The aim of this study is to explore the application of PTX3 to KD. Methods: 128 patients with KD are enrolled. Blood samples are collected at before IVIG and 1, 3, 6 month later from the onset of KD. PTX3 values are compared with IVIG unresponsive scoring system by Kobayashi et al. (Circulation, 2006). Results: Mean values of PTX3 before IVIG and 1, 3, 6 month were respectively 25.1*, 7.1*, 3.8, 3.6 ng/ml (asterisk shows statistical significance with age-matched control: 3.6). Mean values of PTX3 in unresponsiveness (n=20) and responsiveness (n=108) at before IVIG and 1, 3, 6 month were 46.8* vs. 20.9, 9.1* vs. 6.7, 4.2 vs. 3.7, 3.9 vs. 3.5 ng/ml (asterisk shows statistical significance between two groups). There is statistical positive correlation between PTX3 and score points by Kobayashi et al. (r=0.602, p=0.000). According to the statistical analysis, the area under the ROC curve (AUC) was 0.87 and sensitivity and specificity of PTX3 as IVIG unresponsiveness prediction were 90 and 81 %, if cut off value was set as 28 ng/ml. Conclusions: 1. vasculitis continues at least 1 month after onset of disease. 2. PTX3 can be a candidate biomarker for prediction of unresponsiveness in patients with KD.
Abstract 90: Serum Kawasaki Disease-specific Microbe-associated Molecular Patterns are Derived from in Vitro and in Vivo Biofilms
Authors: Kusuda Takeshi , Nakashima Yasutaka , Kenji Murata , Kanno Shunsuke , Saito Mitsumasa , Tanaka Tamami , Mizuno Yumi , Ouchi Kazunobu , Waki Kenji , Hara Toshiro
Published: July 2021

Background:
We have found that serum KD-specific molecules possess molecular structures common to microbe-associated molecular patterns (MAMPs) from several bacteria by liquid chromatography-mass spectrometry (LC-MS) analysis. In the present study, we have extensively searched for the culture conditions that reproducibly produce MAMPs common to serum KD specific molecules.

Methods:
Yersinia pseudotuberculosis, spore-forming bacteria and pathogenic bacteria were obtained from KD patients. Others were purchased from American Type Culture Collection. Microbes were cultured in a variety of conditions (medium, temperature, duration, shaking and biofilm formation). For biofilm formation, a various kind of oil/butter was added to the culture medium. Extraction from in vitro samples (culture supernatants, bacteria cells, and biofilms) as well as in vivo biofilm samples (teeth, tongue, nasal cavity, or rectum) was performed with ethyl acetate. Samples were analyzed by HPLC and MS (Esquire 6000 electrospray ionization). Human coronary artery endothelial cells (HCAECs) were employed for cytokine assay. The concentrations of cytokines were measured by EC800 cell analyzer with a BD™ Cytometric Bead Array.

Results:
Serum KD-specific molecules showed m/z and MS/MS fragmentation patterns almost identical to those of MAMPs obtained from the biofilms formed in vitro (Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis, Staphylococcus aureus) or in vivo. Not culture supernatants but biofilm extracts from these bacteria, especially cultured in the presence of butter, induced proinflammatory cytokines by HCAECs.

Conclusions:
Extensive analysis by LC-MS/MS revealed that serum KD-specific molecules common to MAMPs were mostly derived from biofilms in vitro and in vivo. This report offers novel insight into the pathogenesis of KD.
Abstract 94: Diagnostic value of D-dimer and fibrinogen degradation products In Kawasaki disease
Authors: Motomura Hideki , Fukunaga Hirofumi , Nakagaki Mari , Hashimoto Kunio , Hasuwa Tomoyuki , Moriuchi Hiroyuki
Published: July 2021

Background:
Echocardiography remains the cornerstone of diagnosis of cardiac complications in patients with Kawasaki disease (KD), and is also useful for the diagnosis of incomplete KD (i-KD). Since echocardiographic evaluation is based on somewhat subjective assessment by pediatric cardiologists, objective diagnostic measures by which general pediatricians can screen high-risk patients or make diagnosis of i-KD are desired.

Objective:
To assess D-dimer and fibrinogen degradation products (FDP) as possible markers of coronary vascular damage in KD patients.

Design/Methods:
Between June 2008 and March 2014, we recruited 121 KD patients: 86 with complete KD (c-KD) treated with intravenous immunoglobulin (IVIG), 10 with c-KD treated only with aspirin (a-KD), 16 with i-KD fulfilling four major criteria, and seven with severe refractory KD (s-KD). Control patients included five with Henoch-Schonlein purpura (HSP), 15 with fibrile convulsion (FC), and 39 with pneumonia. We retrospectively checked their medical records, echocardiography, and blood test results on admission and after IVIG therapy.

Results:
Peak D-dimer values (normal range < 1.0 μg/ml) were significantly higher in c-KD (2.9±2.4) than in a-KD (1.1±0.7), FC (0.8±0.4) and pneumonia (1.3±1.1) groups (p < 0.05). Peak FDP value in the c-KD group was 6.8±4.7 μg/ml (< 5.0). Peak D-dimer and FDP values were the highest in the HSP group, followed by the s-KD group, and were comparable between the i-KD and c-KD groups. D-dimer values (2.9±1.4) at post IVIG were higher than those on admission (1.8±1.1) (p < 0.0001), while there was no significant change in FDP values. There was no significant difference in D-dimer or FDP values between KD with cardiac finding(s) and without. WBC and CRP values had no correlation with those of FDP or D-dimer.

Receiver operating characteristic analysis determined a cut-off value of 1.1 μg/ml for D-dimer for c-KD, with the area under the curve (AUC) 0.85, sensitivity 0.95, specificity 0.59 and probability 0.44. Similarly, a cut-off value for FDP was determined as 2.5 μg/ml with AUC 0.90, sensitivity 0.89, specificity 0.70 and probability 0.40.

Conclusions:
Elevated D-dimer and FDP values help assist diagnosis of i-KD, but cannot predict cardiac complications in KD patients.
Abstract O.02: Validation of Kawasaki Disease Incidence Assessment as Derived from Health System Administrative Databases vs. Active Retrospective Surveillance in Ontario, Canada
Authors: Manlhiot Cedric , O’Shea Sunita , Bernknopf Bailey , Labelle Michael , Mathew Mathew , Chahal Nita , McCrindle Brian W
Published: July 2021

Introduction:
Historically, 2 methods have been used to determine the incidence of Kawasaki disease (KD): active or passive surveillance, or the use of administrative databases. Given the increasing regulatory requirements, mainly around patient privacy, periodic retrospective surveillances have become increasingly challenging. Administrative databases are not curated datasets and doubts have been cast on their accuracy.

Methods:
The Hospital for Sick Children has been conducting retrospective triennial surveillances of KD since 1995 by contacting all hospitals in Ontario and manually reviewing all cases through chart review, reconciling inter-hospital transfers and multiple readmissions. We queried the Canadian hospital discharge database (Canadian Institute for Health Information) for hospitalizations associated with a diagnosis of KD between 2004-9. The administrative dataset was manually reviewed; patient national health number, institution and dates of admission/discharge were used to identify inter-hospital transfers, readmission and follow-up episodes.

Results:
The Canadian hospital discharge database reported 1,685 admissions during the study period (281±44 per year) for Ontario. Manual review of the dataset identified 219 (13%) as inter-hospital transfers (56, 26%), readmissions (122, 56%), admissions for follow-up of coronary artery aneurysms (14, 6%) or hospital admissions not related to KD (27, 12%). When these admissions were removed, the total number of incident cases for the study period was 1,466 (244±45 per year). The retrospective triennial surveillance identified 1,373 KD cases during the same period (229±33 per year). The Canadian hospital discharge database overestimated the number of cases in all 6 years by an average of 6.7±5.9%. The overestimation likely comes from patients who were originally diagnosed with KD but in whom the diagnosis of KD was subsequently excluded (historically ~5-6%).

Conclusions:
Reliance on administrative data to determine incidence of KD is possible and accurate; data should be manually reviewed to remove non-incident cases and estimates should be adjusted to reflect the expected proportion of patients in whom the diagnosis of KD will be subsequently excluded.
Abstract O.08: Rashless Kawasaki Disease (KD): Colorado’s Experience
Authors: Anderson Marsha S , Dominguez Samuel R , Heizer Heather R , Jone Pei-Ni , Davidson Jesse , Glode Mary P
Published: July 2021

Objective:
Published studies describe Incomplete KD, but rashless KD has not been well characterized. We describe a 10 year experience with rashless KD patients, diagnosed based on the presence of a compatible illness and coronary artery lesions (CALs).

Methods:
We prospectively collected cases of rashless KD with CALs diagnosed at Children’s Hospital Colorado from 7/1/2004-6/30/2014. Patient charts were reviewed for demographic, clinical, laboratory, and diagnostic information.

Results:
11 patients were identified (median age 3.7 yrs), representing 10.3% (11/107) of all KD patients with CALs diagnosed during the same time period. Diagnosis was made on median day of illness (DOI) 8 (range 4-17 days), and patients had a median of 4 (range 2-7) healthcare contacts prior to diagnosis. All patients (100%) had the presence or history of conjunctival injection and 8/11 (72.7%) had oral changes. Five patients had only 2 major clinical features in addition to fever; 1 patient had one. All patients had very elevated inflammatory markers. Infectious Disease consultants suspected KD and recommended treatment prior to echocardiogram (ECHO) results in 8/11 (72.7%), recommended treatment if ECHO abnormal in 2/11 (18.1%), and in 1/11 (9.2%) KD was thought to be unlikely, but the diagnosis was made by ECHO.

Conclusions:
10.3% of KD patients with CALs at our institution presented without a rash. As rash is often considered a defining characteristic of KD, some children with rashless KD are likely not being identified and treated. Providers should consider the diagnosis of KD in patients with unexplained fever, conjunctivitis, and elevated inflammatory markers.
Abstract O.16: Comprehensive Genotyping Of The FCGR2/3 Locus Reveals A Novel Association Of FCGR2C-ORF With Susceptibility To Kawasaki Disease
Authors: Kuijpers Taco W , Tacke Carline E , Nagelkerke Sietse Q , Breunis Willemijn B , Hoang Long T , Png Eileen , Geissler Judy , Tanck Michael W , Ellis Justine A , Ponsonby Anne L , Davila Sonia , Khor Chiea C , de Boer Martin , van der Heijden Joris , Fijnvandraat Karin , van der Schoot E. , van den Berg Timo K , Yeung Rae S , Levin Michael L , Burgner David , Shimizu Chisato , Burns Jane C , Hibberd Martin L
Published: July 2021

The human FCGR2/3 locus contains highly homologous genes encoding the five major receptors for IgG (Fc-gamma receptors, FcγRs). In two prior GWAS on Kawasaki disease (KD), a SNP in FCGR2A (131H>R; rs1801274) was identified to be associated with disease susceptibility. However, the FCGR2/3 locus contains multiple single nucleotide polymorphisms (SNPs) and copy number variations (CNVs), which were not covered by the detection platforms used in the GWAS. In this study we therefore focused on further fine-mapping of this locus to investigate the association of the different genetic variations with KD susceptibility. A highly accurate and validated multiplex ligation-dependent probe amplification (MLPA) assay was used to analyze all functionally relevant SNPs and CNVs within this locus. In a genetic association study involving case-control and family-based testing with 1028 patients with KD, the previous finding of FCGR2A-131H as a susceptibility marker for KD was confirmed (OR 1.16; 95%CI 1.08-1.32, meta-P = 0.01). In addition, we found a novel significant association of the FCGR2C-ORF haplotype with susceptibility to KD (OR 1.34; 95% confidence interval 1.11-1.62, meta-P = 0.003). FCGR2C-ORF leads to the expression of an extra, functionally activating FcγR (i.e. FcγRIIc) on myeloid cell types and NK cells. Being absent in Asian individuals, the FCGR2C-ORF haplotype only contributed to KD susceptibility in European subjects, independent of the established association with FCGR2A-H131R. We did not find any significant association of CNV of the locus with susceptibility to KD.

Our data point to an important role of the activating FcγRs in KD pathology. We hypothesize that the identified functional SNPs might alter the balance between the activating and inhibitory FcγRs leading to unbalanced inflammation and KD.
Abstract O.18: Histopathological Analysis Of Sudden Death Adults With Coronary Artery Aneurysms
Authors: Takahashi Kei , Oharaseki Toshiaki , Yokouchi Yuki , Enomoto Yasunori , Hayashi Kino , Asakura Kumiko , Saito Kazuyuki , Takada Aya
Published: July 2021

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 O.23: Lysyl Oxidase Expression In The Patients With Kawasaki Disease
Authors: Shimizu Chisato , YunJing Huang Cassidy , Phan-Huy Anne , Salgado Andrea , Antonio Lilia , Kanegaye John T , Tremoulet Adriana H , Franco Alessandra , Burns Jane C
Published: July 2021

Background:
Histologic study of inflamed coronary arteries from the Kawasaki disease (KD) patients shows infiltration by immune effector cells, IL-17-producing myofibroblasts, and breaks in the internal elastic lamina. Transcripts from genes associated with cell trafficking (e.g. paxillin) are elevated in whole blood from acute KD patients. Lysyl oxidase (LOX) is a multifunctional protein affecting affecting “monocyte and smooth muscle cell migration, elastogenesis, and endothelial-to-mesenchymal transition. LOX promotes cell motility through paxillin phosphorylation, which influences T-cell trafficking via the calcium signaling pathway. We investigated the role of LOX in the pathogenesis of KD.

Methods:
Agilent microarray data using whole blood were analyzed for differential expression of enzymes in the LOX family (LOX, LOX-like (L)1-4) in acute and convalescent KD samples (n=19). LOXL1 results were validated using RT-PCR in an independent cohort (n=20). LOXL1 transcripts levels were measured in KD whole blood, peripheral blood mononuclear cells (PBMC), T-cell clones, B-cell lines, and myeloid dendritic cells from acute KD patients. Immunohistochemical staining for LOXL1 was performed on coronary arteries from a KD patient who died on illness day 7.

Result:
LOXL1 expression by microarray was 3.2-fold higher in acute than convalescent samples (p<0.001) and was validated in an independent cohort by RT-PCR (5.4-fold higher, p<0.001). LOXL1 transcripts levels were 2-35 times higher in PBMC compared to whole blood (n=8). KD T cell clones had higher LOXL1 transcript levels than B-cells and dendritic cells. Immunohistochemical staining showed LOXL1-expressing inflammatory cells and smooth muscle cells in the coronary artery walls.

Conclusion:
LOXL1 may increase inflammation in acute KD by promoting the motility of infiltrating T cells and smooth muscle cells through focal adhesion formation. However, LOXL1 may also participate in arterial wall repair by crosslinking collagen and elastin. Statins inhibit focal adhesion formation and thus cell trafficking but not the crosslinking mediated by LOXL1. Studies of LOXL1 protein levels and paxillin phosphorylation in PBMC may further our understanding of their role in KD pathogenesis.
Abstract O.43: Partial and Complete Non-response to Intravenous Immunoglobulin in the Acute Treatment of Kawasaki Disease: A Matched Case-control Study
Authors: Downie Mallory L , Manlhiot Cedric , Latino Giuseppe A , Collins Tanveer H , Chahal Nita , Yeung Rae S , McCrindle Brian W
Published: July 2021

Introduction:
Patients non-responsive to intravenous immunoglobulin (IVIG) in the acute phase of Kawasaki disease (KD) are usually considered a single patient group; however, response to second-line therapy varies significantly. We sought to characterize the pattern of temperature response to IVIG infusion, and to define whether the profile was associated with response to second-line therapy in non-responders.

Methods:
Patients non-responsive to IVIG (temperature >37.5°C >24 hours after the end of IVIG) were identified. Each IVIG non-responder was matched to a IVIG-responsive control patient of the same age and gender, and with the same duration of fever prior to IVIG. Hourly temperature profiles were obtained from immediately before the start of the IVIG infusion until complete defervescence.

Results:
n=202 patients non-responsive to IVIG were matched (total n=404). For all, temperature reduced by 0.17 (0.06)°C per g/hr IVIG (p=0.006). Important variation in the temperature profile was noted for patients who did not defervesce with IVIG. Thus, non-responders were further classified as partial non-responders (31%) (temperature decreased to <37.5°C within 24 hours of the end of IVG infusion, but fever recurred) and complete non-responders (69%) (temperature consistently >37.5°C throughout IVIG treatment). The temperature profile during IVIG infusion was similar between complete and partial responders [(EST: -0.26 (0.11)°C per g/hr IVIG (p=0.02) for complete responders vs. EST: -0.20 (0.09)°C (p=0.02) for IVIG responders (responders vs. partial non-responders, p=0.65)]. In complete non-responders, IVIG was not associated with significant decreases in temperature (EST: -0.11 (0.14)°C, p=0.43). Factors associated with complete (vs. partial) non-response included presence of infectious symptoms, differences in multiple laboratory values and IVIG brand. Defervescence in partial non-responders was achieved with a second IVIG dose for 88% of patients compared to only 47% of complete non-responder (p<0.001).

Conclusions:
Non-response to initial IVIG can be further characterized by the temperature profile, and complete non-responders may require more aggressive second-line therapy.
Abstract O.61: Coronary Artery Stenosis Risk and Progression in Kawasaki Disease Patients: Experience at a U.S. Tertiary Pediatric Center
Authors: Patel Alok , Bruce Margaret , Harrington Whitney , Portman Michael
Published: July 2021

Objective:
Risk and natural progression of coronary artery stenosis in Kawasaki Disease is not well-defined and is a potential cause of long term morbidity, despite treatment with IVIG. We present a novel study at a US tertiary pediatric care center identifying risk factors for stenosis.

Methods:
We reviewed charts of all children that underwent cardiac catheterization for coronary artery abnormalities from 1998 to January 2014 at a tertiary pediatric care center. All demographic and diagnostic data was recorded including time intervals to echocardiographic changes and catheterization confirmed cases of stenosis. Multivariate survival analysis was used to identify risk factors with stenosis formation as the main outcome measure.

Results:
Fifty-two children met inclusion criteria and 18 (34.6%) developed stenosis. The highest risk group overall were children under the age of 6 months (HR 3.66, p=0.005) and those with giant coronary aneurysms (GCA). In a subset of only cases of GCA (33), children under the age of six months were at highest risk (HR 2.62, p=0.04). IVIG administration, gender, and ethnicity were statistically insignificant. The majority of individuals with GCA went on to develop stenosis (19/33). The presence of GCA was 100% sensitive for cases of stenosis.

Conclusions:
This is a novel study in an American population and demonstrates a relatively high incidence of stenosis in children with KD and coronary vascular abnormalities. Overall, a majority of GCA cases progressed into stenosis, with children under the age of 6 months being at highest risk.
Abstract O.72: The Spectrum Of Cardiovascular Lesions Requiring Intervention In Young Adults After Kawasaki Disease
Authors: Gordon John B , Daniels Lori B , Kahn Andrew M , Vejar Matthew , Shimizu Chisato , Burns Jane C
Published: July 2021

Background:
Coronary artery aneurysms resulting from vascular inflammation associated with Kawasaki disease (KD) in childhood may remain clinically silent until adulthood. Young adults presenting with large aneurysms, unstable angina, or myocardial infarction (MI) following KD in childhood present unique challenges to the interventional cardiologist and cardiothoracic surgeon. We present a range of management issues raised by this patient population.

Methods:
Participants who underwent cardiovascular interventions were identified from an observational cohort of 154 individuals with a history of KD enrolled in the San Diego Adult KD Collaborative. Of these 154 participants, 63 (40.9%) were originally diagnosed with KD and followed by one of the co-authors (JCB) and were designated as Cohort 1. The remaining 91 participants (Cohort 2) were referred by their physician or self-referred for participation in the study.

Results:
Of the 154 participants, 20 (12.9%; 2 from Cohort 1 and 18 from Cohort 2) underwent cardiovascular interventions: 9 had percutaneous interventions and 11 had surgery. Twelve participants had been diagnosed with KD in childhood, 7 had a history of a KD-compatible illness in childhood, and 1 had proximal coronary artery aneurysms compatible with KD. Fourteen participants were asymptomatic until experiencing a major cardiovascular event: 8 presented with an acute MI, 3 presented with angina, 1 presented with end-stage congestive heart failure requiring cardiac transplantation, and 2 presented with extremity claudication.

Conclusions:
Cardiovascular complications in individuals with a history of KD illustrate the following points: 1) Even small to moderate-sized aneurysms that “normalize” by echocardiography in childhood can lead to stenosis and thrombosis decades after the acute illness; 2) Coronary interventions without intravascular ultrasound may result in underestimation of vessel lumen diameter; 3) Failure to assess the extent of calcification may lead to suboptimal procedural outcomes, and 4) Patients with symptomatic peripheral aneurysms may benefit from endarterectomy or resection. Interventional cardiologists should be aware of the complications encountered in this growing population of young adults.
Abstract 10025: Human Umbilical Cord Stem Cells Increase Heart Contractility and Decrease Fibrosis in Congenital Cardiomyopathy
Authors: Henning Robert , Jimenez Ernesto
Published: July 2021

Introduction:
We have established that human umbilical cord blood stem cells (
hUCSC
) decrease inflammation and infarct size in acute myocardial infarctions in rats. We hypothesized that hUCSC can limit the progressive LV fibrosis and LV failure that occurs in TO2 hamsters, a model of congenital cardiomyopathy due to sarcoglycan deficiency.

Methods:
22 TO2 1 month old hamsters were treated with intramyocardial (
IM
) hUCBC, 4х 10
6
,in Isolyte®, and 23 TO2 1 month old hamsters were treated with IM Isolyte. 16 1 month old F1B hamsters served as controls and received IM Isolyte. No hamster was given immunosuppressive treatment. Echocardiograms were performed on all hamsters prior to and monthly after treatment for 6 months. Heart tissues were stained with hematoxylin and eosin, Masson’s Trichrome and human nuclear antibody.

Results:
In the F1B hamsters, LV fractional shortening (
FS
) and ejection fractions (
EF
) did not significantly decrease over 6 months. In contrast, in Isolyte treated TO2 hamsters, FS decreased from 56.2±1.0% to 19.7±3.2% and EF decreased from 89.5±1.4% to 41.9 ±5.9% at 6 months (both p < 0.001). The FS and EF in hUCSC treated TO2 hamsters also progressively decreased over 6 months but changes were more gradual, especially during first month after hUCSC when FS was 52.0±1.5% and EF was 89.5±1.4%, which was not significantly different from the F1B hamsters. In the hUCSC treated hamsters, the FS and EF were 20-30% greater than FS and EF in Isolyte TO2 hamsters at 3 and 5 months (p < 0.01). Injection of hUCBC in a subset of Isolyte treated TO2s at 4 months increased LV EF at age 5 months to 57.5±2.3% compared with a EF of 41.6±3.1% (p< 0.01) in Isolyte treated TO2s. In Isolyte treated TO2s at 6-7 months, fibrosis involved 30.0±5.0% of LV and 35.0±5.0% of LV septum. In contrast, in hUCSC treated hamsters, fibrosis involved only 16.5± 2.3% of LV and 16.3±1.8% of septum (p< 0.05). The average number of blood vessels per myocardial microscopic field in hUCSC treated hearts was 53.5 ± 0.8 versus 46.2 ± 3.0 in Isolyte treated TO2 hearts (p < 0.05).

Conclusion:
hUCSC, given as a single intramyocardial injection, can limit fibrosis and increase heart contractility over the short term in TO2 hamsters with congenital cardiomyopathy.
Abstract 10073: Characteristics of Very Late Stent Thrombosis Assessed by Coronary Angioscopy and Histopathology of Aspirated Thrombus
Authors: Fujita Kosuke , Ueno Masafumi , Ikuta Shinichiro , Kawamura Takayuki , Yasuda Masakazu , Ikeda Tomoyuki , Nakamura Takashi , Saratani Kazushi , Iwanaga Yoshitaka , Miyazaki Shunichi
Published: July 2021

Background:
The mechanisms of very late stent thrombosis (VLST) have not been fully elucidated and may involve multiple factors. The aim of this study was to evaluate characteristics of VLST based on angioscopy and histopathology of aspirated thrombus.

Methods:
Coronary angioscopy was performed in all stent thrombosis cases to evaluate the culprit lesion. The mechanisms of VLST were divided according to two factors by angioscopic findings such as uncovered struts and neoatherosclerosis. Uncovered struts were defined as stent struts uncovered by neointima. Neoatherosclerosis was defined as stent struts covered by yellow neointima. Furthermore, aspirated material was collected for assessment of atherothrombotic characteristics in all cases.

Results:
From February 2011 to April 2015, emergency PCI for acute myocardial infarction was performed in 336 patients, with 13 of these cases due to stent thrombosis. Clinical characteristics of VLST patients are shown in Figure. In uncovered struts, all 3 cases were not on any antiplatelet therapy prior to VLST, whereas patients with neoatherosclerosis were taking at least one antiplatelet agents except for one case. In the presence of neoatherosclerosis, thrombus with atheroma material was aspirated in 5 of 10 cases despite there was no atheroma material in patients with uncovered strut. The time period of occurrence of VLST was significantly shorter in patients with uncovered strut compared with neoatherosclerosis (48.6±12.5 month vs. 84.3±6.9 month, p=0.03) In 13 case of VLST, peri stent contrast staining (PSS) was found in 1 case of each neoatherosclerosis and uncovered strut at the time of follow-up angiography.

Conclusions:
Discontinuation of dual anti platelet therapy was an important predictor for VLST, especially in patients with uncovered struts. However, most VLST weredue to neoatherosclerotic plaque rupture assessed by coronary angioscopy, which were also confirmed by histopathology of aspirated thrombus.
Abstract 10210: Effects of Chronic Treatment With the Phosphodiesterase-5 Inhibitors Sildenafil and Tadalafil on Platelet Aggregation in Patients With Eisenmenger Syndrome
Authors: Maeda Nair Y , Clavé Mariana M , Mesquita Sonia M , Bydlowski Sergio P , Lopes Antonio A
Published: July 2021

Background:
Patients with pulmonary arterial hypertension (PAH) associated with the Eisenmeger syndrome (ES) frequently have decreased platelet counts and aggregation. This is probably due to chronic endogenous platelet activation and consumption associated with hypoxemia and blood hyperviscosity, with "exhausted" platelets present in circulation. When platelets are analyzed in vitro, decreased response to aggregation inducing agents is generally observed.

Purpose:
Since phosphodiesterase-5 inhibitors (PDE-5Is) are frequently used in the management of PAH, we investigated, the effects of sildenafil and tadalafil on in vitro platelet aggregation (PA) in adults with ES.

Methods:
Twenty-three naïve patients aged 28 (22-47) years (median and interquartile range) were randomly assigned to oral treatment with sildenafil (20mg t.i.d., N=11) or tadalafil (single daily dose of 40mg, N=12). Baseline spO
2
, Ht, Hb level and platelet count were 87% (80-92%), 52% (49-60%), 17 (16-20)g/dL and 205 (158-248) x 10
3
pl/μL, respectively. Data were collected at baseline, 90 and 180 days of treatment. Whole blood PA was analyzed by the impedance method. Results are expressed as percent normal.

Results:
Treatment with PDE-5Is resulted in decrease Ht and Hb level (p<0.001), but no change in platelet count. When patients analyzed as a whole (N=23), ADP-induced PA was 44% (23-91%), 54% (23-87%) and 71% (42-124%) respectively at baseline, 90 and 180 days (p=0.029). Collagen-induced PA was 55% (23-138%), 96% (67-162%) and 146% (62-187%), respectively (p=0.041). When treatment groups were investigated separately at 180 days, collagen-induced PA was 2.7 (1.1-11.1) times baseline in sildenafil-treated patients, and 1.8 (0.6-4.2) times baseline in the tadalafil group. ADP-induced PA was 2.2 (1.3-4.8) times baseline in the sildenafil , but 1.0 (0.7-3.6) time baseline for tadalafil.

Conclusion:
In ES patients, PDE-5Is therapy is associated with improvement of PA. This may be due to decelerated endogenous platelet activation associated with hemodynamic improvement. However, particularly for sildenafil, some patients may become transiently at a higher risk of thrombotic events, as PA increases far above normal levels.
Abstract 10260: Thrombin is a Novel Target of the Treatment of Dilated Cardiomyopathy
Authors: Ito Keiichi , Hongo Kenichi , Date Taro , Kashiwagi Yusuke , Yoshino Takuya , Nagoshi Tomohisa , Minamisawa Susumu , Yoshimura Michihiro
Published: July 2021

Introduction:
A state of hypercoagulability has been observed in patients with dilated cardiomyopathy (DCM) compared to healthy subjects. In addition to being found in blood, thrombin is also expressed in the heart. Hypothesis: We hypothesize that thrombin in the heart tissue may contribute to the pathology of DCM and thrombin inhibition may be beneficial for the development of DCM.

Methods:
We evaluated the expression of thrombin by immunohistochemical analysis in the left ventricle of 5 patients with DCM undergoing Batista operation and that of 4 patients without heart disease serving as controls. The immunohistochemical staining was scored subjectively on a semi-quantitative scale of 0-4. We investigated the effects of the direct thrombin inhibitor, dabigatran, in the development of DCM in a mouse model carrying a deletion mutant of cardiac troponin T (DCM mouse) which causes human DCM, by using echocardiography and Kaplan-Meier method. We also estimated the apoptotic index using the terminal dUTP nick-end labeling (TUNEL) assay using the heart tissue from DCM mouse.

Results:
Immunohistochemical analysis showed strong thrombin expression in DCM patients compared to patients without heart disease [3.60 in DCM (n=5), 1.25 in control (n=4), p<0.001]. Dabigatran significantly improved impaired left ventricular function of DCM mouse by echocardiographic examination; fractional shortening was 15.6±5.7 % in DCM mouse and was 42.7±7.3 % in DCM with dabigatran (p=0.03, n=4). Dabigatran also significantly improved the poor outcome of DCM mouse (p=0.02, n=7) (Figure1). Although there were no significant differences, dabigatran tended to reduce the apoptotic index; the percentage of TUNEL-positive nuclei was 0.20±0.04 % in DCM mouse and was 0.08±0.05 % in DCM with dabigatran (p=0.11, n=4).

Conclusion:
Upregulation of tissue thrombin may be involved in the pathogenesis of DCM. The direct thrombin inhibitor, dabigatran, may be a possible treatment option against DCM.