bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract O.07: The Clinical Risk Factors of Intravenous Immunoglobulin Resistance and Coronary Artery Lesion of Kawasaki Disease: Retrospective Analysis of 602 Cases
Authors: xie lijian , Zhou Cuizhen , Wang Renjian , Xiao Tingting , Shen Jie , Huang Min
Published: July 2021

Introduction:
The incidence of Kawasaki disease (KD) in China is increasing for years. The current coronary artery lesion (CAL) incidence is 5-10% in KD with intravenous immunoglobulin (IVIG) treatment. And the 10-20% KD patients still exhibit IVIG resistance. However, little clinical evidence on the occurrence of either CAL or IVIG resistance for big KD sample study in China during the past decade.

Objective:
In order to find clinical risk factors of CAL and IVIG resistance of KD in China.

Methods:
We retrospectively analyzed the clinical manifestations, laboratory results, treatment and complications of cardiac vascular of 602 KD cases from 2007 to 2012 admitted at Shanghai Children’s Hospital. The SAS 9.2 edition was used for statistical analysis. The mean ± standard deviation or the median were used for measurements. Case numbers and percentages were used for the count number. The t-test and the Mann-Whitney test were both used for mean comparisons. Single factor and multi-factor logistic regression analyses were used to analyze the risk factors.

Results:
1. The KD gender male to female ratio was 1.85: 1. The KD median age was 2.0 years old (one month to 11.7 years old). 20.1% cases (121 of 602) exhibited CAL. There was no difference of CAL incidence between the gender (p=0.09). 2. The incidence of bright red cracked lips (p=0.001), peeling of the skin of the toes (p=0.021) and perianal skin peeling (p=0.031) are less in group with CAL. 3. Among the 602 cases, there were 525 cases that were sensitive to IVIG therapy. 100 of those cases had CAL with an incidence of 19.1%. Among the 26 IVIG resistance cases, there were 9 cases with CAL with an incidence of 34.6%, which was higher than the IVIG sensitive group (p=0.05). 4. ESR (p=0.014), CRP (p=0.017), PLT (p=0.003) and Hb (p=0.032) were much higher in the IVIG resistance group than the IVIG sensitive group, even though the IVIG resistance group started the IVIG treatment earlier (p=0.003). 5. Logistic regression analysis was conducted to show that GPT≥80IU/L was the independent risk factor of IVIG resistance, risk ratio was 2.945 (p=0.012) .

Conclusion:
This research suggests that risk factors of clinical evidence for IVIG resistance and CAL in KD.
Abstract O.21: Inositol 1,4,5 triphosphate 3- kinase C regulates NLRP3 Inflammasome activation in Kawasaki disease
Authors: Alphonse Martin P , Duong Trang T , Shimizu Chisato , Hoang Long T , McCrindle Brian W , Franco Alessandra , Schurmans Stephane , Philpott Dana J , Hibberd Martin L , Burns Jane C , Kuijpers Taco W , Yeung Rae S
Published: July 2021

Background:
ITPKC controls calcium homeostasis and was identified in genome-wide studies to be associated with susceptibility and severity of KD. NLRP3 is activated by danger signals, leading to inflammasome activation and release of IL-1beta and IL-18. Ca
2+
mobilization mediates NLRP3 activation. We studied the contribution of ITPKC and NLRP3 inflammasome activation in KD.

Methods:
Cytokine levels were measured using ELISA. Gene expression was assayed using Illumina HumanHT-12v4. EBV-transformed B-cell lines from KD patients with different ITPKC genotypes were used to study the gene and protein expression and Ca
2+
flux using qRT-PCR, Western blot analysis, and FACS respectively.
In vivo
and
in vitro
analyses from ITPKC-deficient and wildtype mice were performed using ELISA, spinning disc confocal and Westerns, to determine cytokine release, Ca
2+
flux and protein expression responses respectively.

Results:
Children with KD show increased circulating IL-1beta, IL-18, IL-1RA and IL18BP protein during acute phase of KD (KD n=48, febrile controls n=41 p<0.001). NLRP3 and its associated inflammasome complex, and the IL-1[[Unsupported Character - Symbol Font ]] and IL18 receptor genes were up-regulated nearly two fold during the acute KD compared to matched convalescent controls (n=171, p<0.001). Pathway analysis showed specific up-regulation of NLRP3 related genes. The KD-associated genetic polymorphism in ITPKC (rs28493229) is functional, directly modulating [Ca
2+
]
i
mobilization resulting in NLRP3 activation and increased production of IL-1beta and IL-18, as demonstrated by gene expression, circulating protein levels and functional assays of PBMCs and immortalized cell lines from affected children. These biologic data are partnered with evidence showing resistance to IVIG therapy in those with the ITPKC polymorphism associated with the highest basal and stimulated [Ca
2+
]
i
levels. Studies using ITPKC-deficient mice in an animal model of KD support the molecular, cellular and clinical findings in affected children.

Significance:
ITPKC regulates NLRP3 activation via control of [Ca
2+
]
i
mobilization, directing production of IL-1beta and IL-18, pointing to the key role of calcium mobilization in the immunopathogenesis of KD.
Abstract O.29: Transcriptional Profiling Discriminates Complete and Incomplete KD from Human Adenovirus
Authors: Jaggi Preeti , Mejias Asuncion , Tremoulet Adriana , Burns Jane , Wang Wei , Ramilo Octavio
Published: July 2021

Background:
The diagnosis of Kawasaki disease (KD) is often difficult to distinguish from HAdV. Objective: 1) To characterize the specific transcriptional profiles of KD patients versus acute HAdV infection 2) To determine whether the molecular distance to health (MDTH) score (a molecular score that reflects the perturbation derived from whole genome transcriptional analysis) correlates with response to therapy.

Methods:
Whole blood RNA samples collected in Tempus tubes were analyzed using Illumina chips and GeneSpring software 7.4 from 76 pediatric patients with complete KD, 13 with incomplete KD, and 19 patients with HadV, and 20 age- and sex-matched healthy controls (HC). We used class comparison algorithms (Mann-Whitney p< 0.01, Benjamini-Hochberg, and 1.25- fold change filter) and modular analysis to define the KD profiles; class prediction algorithm was used to identify genes that best differentiate KD and HAdV.

Results:
Statistical group comparisons identified 7,899 genes differentially expressed in 39 complete KD patients versus HC (KD biosignature). This signature was validated in another 37 patients with complete KD and in 13 patients with incomplete KD. Modular analysis in children with complete KD demonstrated overexpression of inflammation, neutrophils, myeloid cell, coagulation cascade, and cell cycle genes. The class prediction algorithm identified 25-classifier genes that differentiated children with KD vs HAdV infection in two independent cohorts of patients with 92% (95% CI [73%-99%]) sensitivity and 90% [67%-98%] specificity. MDTH scores in KD patients significantly correlated with the baseline c-reactive protein (R=0.29, p=0.008) and was four fold higher than in children with HAdV (p<0.01). In addition, KD patients that remained febrile 36 hours after treatment with IVIG (non-responders) demonstrated higher baseline, pre-treatment MDTH values compared with responders [12,290 vs. 5572 respectively; p=0.009].

Conclusion:
Transcriptional signatures can be used as a tool to discriminate between KD and HAdV infection, and may also provide prognostic information.
Abstract O.39: The Incidence Of Abnormal Electroencephalographic Findings And Mild Encephalitis/encephalopathy With A Reversible Splenial Lesion In Kawasaki Disease
Authors: Nakagawa Naomi , Kamada Masahiro , Ishiguchi Yukiko , Moritoh Yuji , Okamoto Kengo
Published: July 2021

Background:
Central nervous system inflammation sometimes occurs in Kawasaki disease (KD). In 2012, we reported the first case of KD complicated with mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in a 14-year-old. Since then, similar cases have been reported. We studied the incidence of KD complicated with encephalitis/encephalopathy and MERS. Methods: We selected 36 patients (22 boys and 14 girls; age: range, 5-80 months; mean, 22 months) from 42 patients who had undergone electroencephalography (EEG) before intravenous immunoglobulin (IVIG) therapy between May 2013 and August 2014. Patients with and without abnormal EEG findings were assigned to groups A and B, respectively. Age; sex; time of diagnosis; neurological symptoms; N-terminal pro-brain natriuretic peptide, serum procalcitonin, serum sodium, serum albumin, and C-reactive protein (CRP) levels; liver disorder, coronary artery lesion, and IVIG therapy response were examined. Results: Group A comprised 6 patients (17%); and group B, 30 patients (83%). Consciousness disturbance was noted in 5 of 6 patients with abnormal EEG findings, without sequelae. Patients in group A were significantly older (56.5±16.8 vs 25.0±19.9 months ) and had higher CRP levels than those in group B (12.3±5.62 vs 6.56±3.47 mg/dL ). No other parameters showed significant differences. Magnetic resonance imaging revealed edema in 2 of 5 patients and MERS in the remaining patient in group A. Pleocytosis was noted in 1 of 4 patients in group A. Cytokine Il-6 and INF-γ levels were very high in the patient with MERS. Conclusion: EEG findings indicating central nerve disorders were noted in 17% patients, a lower incidence than that reported by Mitudome et al . We performed EEG early before IVIG therapy; thus, central nerve symptoms encountered may have occurred in the early stages of the disorders. MERS was noted in 1 of 6 patients with abnormal EEG findings, or 2 of 9 patients if past cases with neurological symptoms were included, suggesting that central nerve complications occur in a certain group of KD patients.
Abstract O.44: Infliximab For Kawasaki Disease Patients Who Did Not Respond To The Initial Therapy : A Japanese Nationwide Surveillance
Authors: Kobayashi Tohru , Takatsuki Shinichi , Saji Tsutomu , Sonobe Tomoyoshi , Ogawa Shunichi , Ogino Hirotaro , Nakamura Yosikazu , Hamaoka Kenji
Published: July 2021

Backgrounds:
In Japan, infliximab (IFX) has been used in patients with Kawasaki disease (KD) who did not respond to initial treatment. However, nationwide surveillance of the IFX for KD patients has not been reported. The objective of the present study is to reveal epidemiological and clinical features of KD patients treated with IFX.

Method:
This retrospective observational study was conducted from 2007 to 2013. We sent a questionnaire to members of Japanese Society of Kawasaki disease annually and collected demographic data and clinical outcomes of KD patients treated with IFX. A total of 315 patients (208 boys and 107 girls, age at onset 37±25 months, illness days of initial treatment 4.3±1.2) from 46 hospitals were identified and analyzed in the present study.

Results:
No patients received IFX as initial treatment. Over 60% of the patients were treated with IFX as first or second line additional rescue treatment. After the IFX administration, 237 patients (75.7%) became afebrile within 24 hours and 82 patients (26.0%) treated additional rescue treatments subsequently. Before IFX administration, 55 patients already had coronary artery aneurysm exceeding 4mm and 69 patients were finally affected coronary artery aneurysm exceeding 4mm. Serum level of C reactive protein were significantly decreased after IFX administration (10.6±7.2 to 4.9±4.7, P<0.001). Patients who required additional treatment after IFX showed significantly higher CRP levels before IFX compared to patients without additional treatment after IFX (12.3±8.3 vs. 10.0±6.7, P=0.049). Adverse events were observed in 50 patients (15.9%) which recovered spontaneously or after interventions.

Conclusions:
IFX therapy for Kawasaki disease patients who did not respond to the initial treatment would be well tolerated and play a certain role to improve clinical course.
Abstract O.49: Factors Associated with Development of Coronary Artery Aneurysms after Kawasaki Disease are Generally Similar for Those Treated Promptly Versus Those with Delayed or No Treatment
Authors: Downie Mallory L , Manlhiot Cedric , Collins Tanveer H , Chahal Nita , Yeung Rae S , McCrindle Brian W
Published: July 2021

Introduction:
While the risk is reduced, patients may develop coronary artery aneurysms (CAA) after Kawasaki disease (KD) despite receiving intravenous immunoglobulin (IVIG) within 10 days of onset of symptoms. Risk factors for CAA may differ compared to those patients with delayed or no treatment.

Methods:
Patients diagnosed with KD between 1990 and 2013 were included. Patients with maximum coronary artery z-scores >5 were classified as having CAA. Separate multivariable regression models were used to determine factors associated with CAA for those with vs. without prompt treatment.

Results:
Of 1,358 patients included, 83% were treated with IVIG within 10 days and 5.4% developed CAA. Patients who had delayed (>10 days) or no IVIG treatment were at increased odds of developing CAA (OR: 3.1, p<0.001). From 1990-2013, the proportion of patients treated promptly increased (OR: 1.05/year, p=0.006) while the total duration of fever decreased (EST: -0.10 (0.03) days/year, p=0.001). These trends were associated with a shift such that a greater proportion of the patients who developed CAA actually had been treated promptly (from <25% in 1990 to >70% in 2013, OR: 1.1/year, p=0.01). For patients with prompt treatment with IVIG, factors associated with increased odds of CAA were: longer duration of fever prior to treatment (OR: 1.2/day, p=0.04), age <1 year old (OR 3.9, p=0.001), higher pre-IVIG white blood cell count (OR: 1.05/x10
9
/L, p=0.007), lower hemoglobin (OR: 1.4/g/L, p=0.004) and non-response to the initial IVIG treatment (OR: 2.5, p<0.001). For patients with delayed or no treatment, factors associated with increased odds of CAA were: males (OR: 5.4, p=0.009), age <1 year old (OR: 29.9, p<0.001), lower red blood cell count (OR: 2.5/-0.5 x10
12
/L, p=0.01) and higher platelet count at diagnosis (OR: 1.4/100x10
12
/L, p=0.001). Additionally, delayed treatment with IVIG did not reduce the risk of CAA (OR: 1.9, p=0.28), and total duration of fever was not associated with CAA for this group (OR: 1.04/day, p=0.16). .

Conclusions:
Factors associated with the development of CAA are generally similar for those treated promptly vs. those with delayed or no treatment. For those with delayed diagnosis, treatment with IVIG does not appear to be effective to prevent CAA.
Abstract O.50: Favorable Outcome Of Patients With Kawasaki Disease Treated With Unified Protocol With Cyclosporine A As The Third Line Therapy
Authors: Hamada Hiromichi , Honda Takafumi , Yasukawa Kumi , Matsui Takuya , Terai Masaru
Published: July 2021

Background:
Cyclosporin A (CsA), which potently suppresses inflammatory cytokines by negative regulation of nuclear factor of activated T cells pathway, may be a promising option for the treatment of Kawasaki disease (KD), especially in patients resistant to intravenous immunoglobulin (IVIG). We treat KD patients with the unified protocol using CsA after 2nd IVIG. Here we report 6 years-outcome of this treatment. Patients and Methods: From 2008 to 2014, 441 patients were treated. At the persistence or recurrence of fever at the end of the 2nd IVIG (2 g/kg for 24 hours), patients were treated with CsA (4-5mg/kg/day) through oral administration except for infants younger than 4 months old. If patients failed to become afebrile after CsA treatment, they received 3rd IVIG. All patients received aspirin 50mg/kg/day at febrile stage. Results: 419 patients became afebrile after 1st or 2nd IVIG. At this point, 2 patients had mild CALs (max 4.7 mm, 2.5mm in 2month-old infant). Among the other 22 patients (5.0%) who failed to become afebrile, one infant aged 1 month-old received 3rd IVIG. Among a total of 21 patients treated with CsA, 10 patients responded promptly to be afebrile within 5 days. The other 11 patients failed to become afebrile and received 3rd IVIG. Eight out of the 11 patients became afebrile after 3rd IVIG. Three patients developed mild CALs (max 3.1mm, 3.7mm, 5.5mm). There were no serious adverse effects in CsA treatment. A total number of patients with CAL was 5 (1.1%). The maximum CAL diameter was 5.5 mm. Conclusions: The outcome of KD patients treated with CsA and 3rd IVIG as a third line therapy is safe and favorable. CsA could be a candidate drug of the first line therapy.
Abstract O.60: Kawasaki Disease Complicated by Coronary Artery Aneurysms: Mortality and 40-year Outcomes
Authors: Manlhiot Cedric , Crean Andrew M , Fernandopulle Nigel , Lew Brendan , Collins Tanveer H , Chahal Nita , McCrindle Brian W
Published: July 2021

Background:
Long-term outcomes and life expectancy for children with a previous history of Kawasaki disease (KD), particularly those with coronary artery aneurysms (CAA), remain to be determined.

Methods:
An inception cohort of all patients with KD assessed at The Hospital for Sick Children in Toronto between 1978 and 2013 was assembled. Patient outcomes were obtained throughout their pediatric and adult clinical follow-up as long as available. Prevalence of outcomes over time was modelled with Kaplan-Meier survival curves. Life tables from Statistics Canada were used to obtain age/gender specific cumulative mortality for the general population.

Results:
The cohort included 2,623 KD patients, of whom 410 (16%) had coronary artery involvement (215 dilatation, 57 non-giant CAA and 138 giant CAA). Average follow-up for patients with coronary artery involvement was 6.7 years (13.3 years for giant CAA); 57 and 34 patients had at least 15 and 25 years of follow-up, respectively. No patients with coronary artery dilatation or non-giant CAA had revascularization or a myocardial infarct. Freedom from revascularization (14 events) for patients with giant CAA was 90±6%, 87±7% and 80±13% at 10, 20 and 40 years of follow-up. Freedom from myocardial infarct (11 events) was 94±4%, 92±5% and 89±7% at 5, 20 and 40 years. For patients without coronary artery involvement, 3 (0.1%) deaths were recorded, one secondary to complications of macrophage activation syndrome during the acute phase of KD and 2 from cancer. No deaths were noted for patients with coronary artery dilatation or non-giant CAA, although clinical follow-up was more limited. For patients with giant CAA, 3 deaths (2.2%) were noted, 2 related to CAA complications and 1 from non-medical cause. Cumulative mortality for patients with giant CAA was 1.5% at 10 years of age (expected mortality 0.7%, HR: 2.2 (0.3-11.5), p=0.08) and 3.1% at 40 years of age (expected 2.3%, HR: 1.3 (0.4-4.0), p=0.37).

Conclusions:
Despite risks of myocardial infarction and revascularization, patients with giant CAA had life-expectancy similar to that of the general population up to the fourth decade of life. Additional follow-up will be necessary to determine if these trends continue into later decades.
Abstract O.62: Estimation Of The Severity Of Coronary Artery Aneurysm By Z-score Of The Internal Diameter In Kawasaki Disease.
Authors: Fukushima Naoya , Miura Masaru , Kobayashi Toru , Fuse Shigeto , Saji Tsutomu , Yamagishi Hiroyuki , Kato Taichi , Hamaoka Kenji , Nomura Yuichi , Fukazawa Ryuji , Kato Hitoshi , Hirono Keiichi , Suda Kenji
Published: July 2021

Background:
The standard values of normal coronary artery internal diameters in Japanese children have been recently established, making it possible to calculate Z-scores based on body surface area. The aim of this study was to clarify the appropriate cut-off points of coronary artery aneurysm (CAA) Z-scores to predict coronary events such as stenosis, obstruction, and thrombosis in patients with Kawasaki disease (KD).

Methods:
In this multicenter retrospective study, we investigated height, weight, CAA diameters measured by echocardiography in acute phase KD, and coronary events in CAA patients with KD (age 18 years or younger) who had coronary angiography from 1992 to 2011.

Results:
Interim analysis was performed on data of the 928 patients recruited from 45 institutions. Body surface area (calculated from height and weight) and CAA diameters were available in 702, 680, and 539 cases of right coronary artery (RCA), left main trunk (LMT), left anterior descending artery (LAD), respectively. Coronary events occurred in 62 RCA cases (8.8%), 8 LMT cases (1.2%), and 45 LAD cases (8.3%) . Areas under the ROC curves to predict coronary events were similar for actual diameter, Z-score, and the ratio of actual diameter to that showing a Z-score of zero in each segment. The cut-off points for the actual diameter, Z-score, and ratio which yielding the highest sensitivity plus specificity were 6.3 mm, 9.6, and 3.9 times for RCA; 7.4 mm, 11.1, and 2.8 times for LMT; and 5.3 mm, 8.9, and 3.5 times for LAD.

Conclusions:
We identified cut-off Z-scores for CAA diameters useful for coronary events prediction. Attention should be paid to coronary events when the Z-score for CAA diameter is over 10.
Abstract O.66: Exercise Response in Children and Adolescents Late After Kawasaki Disease According to Early Coronary Status
Authors: Dahdah Nagib , Gravel Hugo , Curnier Daniel , Dallaire Frédéric , Fournier Anne , Portman Michael
Published: July 2021

Background:
Cardiovascular sequelae after Kawasaki disease (KD) are typically linked to coronary artery aneurysms. This post-hoc analysis describes response to exercise challenge late after KD to determine response according to coronary artery status.

Methods:
Bruce treadmill testing was performed under an international trail in 117 KD without coronary complications (NS-KD) and 133 with coronary artery aneurysm (CAA-KD). Endurance time, heart rate, systolic and diastolic blood pressure were assessed at rest, at each treadmill stage, peak exercise and recovery. The presence of myocardial perfusion defects was assessed by Tc-99m sestamibi SPECT imaging.

Results:
Endurance time was similar between groups (11.3 ± 2.6 min vs11.0 ± 2.6 min, NS-KD vs CAA-KD; p=0.343). There were similar responses in all investigated parameters as well (table 1) (p=0.075-0.942). The prevalence of myocardial perfusion defects was comparable in both groups (22.2% in NS-KD and 16.5% in CAA-KD; p=0.255), but predicted lower heart rate at 1-min recovery as well as lower diastolic blood pressure at 1-min and 5-min recovery in patients with abnormal Summed Stress Score > 3 (p = 0.017-0.042).; reversible defects in 12.8% of NS-KD and 11.3% of CAA-KD (p=0.708).

Conclusion:
Compared to KD patients without CA involvement, the presence of coronary aneurysms at the sub-acute phase does not induce a differential effect on exercise parameters. In contrast, exercise induced myocardial perfusion defect late after the onset of KD correlates with abnormal recovery parameters. These data suggest that the exercise performance alone is unlikely to discriminate patients with or without coronary artery sequelae.
Abstract O.74: Statin Alleviates Persistent Coronary Arterial Inflammation Long After Kawasaki Disease - A Serial Fluorodeoxyglucose Positron Emission Tomography Study -
Authors: Suda Kenji , Tahara Nobuhiro , Honda Akihiro , Yoshimoto Hironaga , Kishimoto Shintaro , Kudo Yoshiyuki , Kaida Hayato , Abe Toshi , Ueno Takafumi , Fukumoto Yoshihiro
Published: July 2021

The patient, 42-year-old male, was suffered from Kawasaki disease (KD) at 4 month of age and left with giant left coronary artery aneurysm (CAA) and occluded giant right CAA. When he visited us at 40 years of age after long interval, a multi-detector X-ray computed tomography revealed persistent giant CAA with 12 mm in diameter at segment 6 with low density area inside of it, stenosis distal to this CAA, persistent giant CAA with 12 mm in diameter at segment 11, and total occlusion of right coronary artery orifice with recanalization. Positron emission tomography using fluorodexoy glucose (FDG-PET) with co-registration of x-ray computed tomography showed significant FDG uptake around the left coronary orifice of the aortic wall and extending to the proximal left CAA wall with 1.48 of target-to-background ratio, indicating persistent inflammation. He has 2 risk factors of atherosclerosis, dyslipidemia and a history of smoking and, since then he has been placed on 2 mg of oral pitavastatin. With the treatment, his LDL-cholesterol has decreased (105 at baseline vs. 74 mg/dL on treatment) though HDL-cholesterol did not change significantly (31 at baseline vs. 30 mg/dl on treatment). FDG-PET after 2 years of treatment indeed showed alleviation of coronary inflammation with significantly smaller area and lower uptake of FDG on the coronary wall with 1.28 of target-to-background ratio. This case indicates that statin can alleviate persistent coronary artery inflammation long after KD and FDG-PET can be a useful monitoring tool of this process.
Abstract 10041: Increased Triglyceride Levels are Associated With Endothelial Dysfunction: FMD-Japan Registry
Authors: Kajikawa Masato , Higashi Yukihito , Maruhashi Tatsuya , Iwamoto Yumiko , Iwamoto Akimichi , Oda Nozomu , Kishimoto Shinji , Hidaka Takayuki , Noma Kensuke , Tomiyama Hirofumi , Takase Bonpei , Yamashina Akira , Kihara Yasuki
Published: July 2021

Objective:
In contrast to low-density lipoprotein cholesterol, and high density lipoprotein cholesterol, which are well-established independent risk factors for cardiovascular disease, the importance of triglycerides remains controversial. In this study, we evaluated the associations between triglycerides and endothelial function in the general population.

Methods and Results:
We enrolled 4,908 subjects (3842 men and 1066 women; mean age, 48±12 years) who were enrolled in FMD-Japan registry. And, we investigated cross-sectional associations between triglycerides and endothelial function by measurement of flow-mediated vasodilation (FMD). The triglycerides levels were negatively associated with FMD (r=-0.10, P<0.001). Subjects were divided into six groups on the basis of the triglycerides level. FMD was significantly decreased with an increase in the triglycerides level (≤63 mg/dL, 7.0±3.5%; 64 to 83 mg/dL, 6.3±3.5%; 84 to 105 mg/dL, 6.0±3.1%; 106 to 131 mg/dL, 5.8±3.2%; 132 to 179 mg/dL, 5.7±3.1%; ≥180 mg/dL, 5.5±3.0%; P for trend<0.001). After adjustment for age, sex, cardiovascular risk factors including high density lipoprotein cholesterol, high triglycerides level groups independently remained associated with low quartile of FMD using the triglycerides ≤63 mg/dL group as the reference (Table).

Conclusions:
These findings supported an independent association between triglycerides and cardiovascular disease.
Abstract 10068: Cardiorespiratory Fitness Modifies the Association Between Leisure-Time Physical Activity and the Risk of Sudden Cardiac Death Among Middle-Aged Men
Authors: Hagnäs Magnus J , Lakka Timo A , Kurl Sudhir , Mäkikallio Timo H , Savonen Kai , Rauramaa Rainer , Laukkanen Jari A
Published: July 2021

Aim:
We investigated whether cardiorespiratory fitness (CRF) modifies the association between leisure-time physical activity (LTPA) and the risk of sudden cardiac death (SCD) among middle-aged men.

Methods:
The participants were a population sample of 2656 Finnish men aged 42-60 years at baseline. The mean follow-up time was 21 years. LTPA was assessed with a questionnaire and was expressed in kilocalories per day (kcal/d). CRF was measured directly using respiratory gas analysis during maximal exercise test and was expressed in metabolic equivalents (METs). The participants were divided into following 4 groups using the lowest tertiles of CRF (7.9 METs) and LTPA (< 191 kcal/d) as cut-offs: high CRF and LTPA, high CRF and low LTPA, low CRF and high LTPA and low CRF and LTPA. The risk of SCD was analysed using Cox regression models adjusted for age, smoking, alcohol consumption, body mass index, systolic blood pressure, low density lipoprotein cholesterol, C-reactive protein, prevalent type 2 diabetes and prevalent coronary heart disease.

Results:
Men with low CRF and low LTPA had a 1.8 (95% confidence interval 1.3-2.6, p=0.001) times higher risk of SCD than men with high CRF and high LTPA. The amount of LTPA did not significantly alter the risk of SCD among men with high CRF. Figure 1 shows the cumulative survival from SCD in the 4 groups.

Conclusions:
Our study shows that men with low CRF and low LTPA have increased risk of SCD. This finding emphasizes increasing LTPA to prevent SCD among men and particularly among those with low CRF.
Abstract 10229: Increase the Predictive Capacity of Coronary Risk With a Genetic Score
Authors: Pereira Andreia , Mendonca Isabel , Gomes Susana , Rodrigues Ricardo , Neto Micaela , Sousa Ana C , Ferreira Rui , Freitas Ana I , Freitas Sonia , Palma dos Reis Roberto
Published: July 2021

Introduction:
Genes associated with coronary artery disease (CAD) and traditional cardiovascular risk factors (TCRF) present a limited individual predictive value. It is expected that the inclusion in global scores may increase the predictive ability. In genetic terms, there are no validated risk scores to predict the occurrence of cardiovascular disease or its complications.

Hypothesis:
Evaluate the ability of a multifactorial genetic risk score (GRS) be able to add predictive power, for the development of CAD, to the model developed only with TCRF.

Methods:
A case-control study was performed with 1321 consecutive coronary patients (mean age 53.4±8.1 years, 78.8% male) and 1148 controls selected to be similar to cases in terms of gender and age. TCRF were evaluated according to the International criteria. The genetic variants were analyzed with specific primers and the GRS was determined in the entire population, based on 29 genetic polymorphisms previously associated with atherosclerotic disease in general and, in particular, with CAD. A multiplicative model was then used based on risk multiplication (odds ratio - OR) of each genotype of the 29 studied genes. Subsequently, a multivariate analysis was done with the TCRF only or the TCRF with the GRS and a ROC curve was constructed for both situations. Pairwise comparison of the two ROC Curve was done by the DeLong test.

Results:
After multivariate analysis, the GRS was found to be an independent predictor for CAD (OR=2.1; CI: 1.7-2.5; p<0.0001). The AUC increased from 0.71 to 0.74 after the inclusion of GRS to the TCRF in the multivariate analysis and this increase was highly significant (p<0.0001) (Fig.).

Conclusions:
In our population, the multiplicative GRS was an independent predictor for CAD. When analyzed together with TCRF, it adds predictive value. Its usefulness, in clinical practice, may be directed to the intermediate risk group, in which a possible risk reclassification can have different therapeutic measures.
Abstract 10865: Online Multielectrode Catheter-enabled Temporal Tctivation Electrogram Enalysis for Localization of Atrial Fibrillation Rotor Regions: Substrate HD Study
Authors: Bars Clément , Seitz Julien , Theodore Guillaume , Beurtheret Sylvain , Marijon Eloi , Ferracci Ange , Bremondy Michel , Faure Jacques , Curel Laurence , Penaranda Guillaume , Berenfeld Omer , Kalifa Jérôme , Pisapia André
Published: July 2021

Introduction:
Multi-electrode electrogram temporal activation and fractionation have been used to localize atrial fibrillation (AF) drivers. Yet, the feasibility of a simplified “online” analysis and its usefulness to ablate AF remain to be investigated.

Hypothesis:
Evaluating a simplified “online” electrogram analysis approach designed to localize and ablate AF drivers.

Methods:
105 patients undergoing AF ablation (77% with persistent AF, 3 centres) were prospectively enrolled. AF was first mapped in both atria with the 20-pole contact electrode catheter PentaRay® (Biosense Webster, Inc.) in order to identify regions with a temporal activation pattern compatible with the presence of rapidly rotating rotors. Specifically, regions with consecutive activations spanning the majority of the AF cycle length (including examples of rapid and continuously fractionated electrograms) were visually selected (“hot zone”).The endpoints were AF termination acutely, and freedom from long-term AF (single procedure). Off-line, electrogram cycle length values were compared between “hot” and “non-hot” regions and a numerical simulation of PentaRay-enabled unipolar recordings of a stable rotor driving AF was conducted

Results:
Visually selected “hot” regions located mostly in the left atrium (6.5 ±4.2/patient; ~70% of ”hot” regions). “Hot” regions were activated at a significantly shorter cycle length than “non-hot” regions (171.8 ± 4.8 vs. 193.0 ± 6.3 ms, p=0.01, N=20). 95.6% of the “hot regions” were automatically labelled CFAEs (automated analysis, Carto). However, 4.5±3.4 distinct CFAEs regions/patient were also labelled in “non-hot” regions. Ablation at “hot” regions terminated AF in 99/104 patients (95.2%), 46 [21-72] min after the 1st radiofrequency application within 20 [10-37] min of RF. Also, numerical simulations show that a simplified PentaRay®-enabled activation analysis is sufficient to distinguish rotor and non-rotor regions. After 9+3 [6-11], months of median [Q1-Q3] follow-up, 87 % were free from AF after 1 procedure and 53 % still under antiarrhythmic drugs.

Conclusions:
With this simplified “online” analysis, we could successfully localize rotor regions and perform efficient AF ablation. Clinical trial.gov: NCT02093949
Abstract 10937: Coronary Characteristic in Patients With Impaired Glucose Tolerance
Authors: Suzuki Keishi , Takano Hitoshi , Tanita Atsushi , Sangen Hideto , Nakamura Yuuki , Inui Keisuke , Kubota Yoshiaki , Aoyama Rie , Nakamura Shunichi , Tara Shuhei , Murai Koji , Tokita Yuukichi , Asai Kuniya , Shimizu Wataru
Published: July 2021

Background:
Impaired glucose tolerance (IGT) patients are known to have a higher risk of cardiovascular events and their prognosis is reported to be poor. We, therefore, aimed to compare the complexity and vulnerability of coronary artery disease (CAD) among normal glucose tolerance (NGT), IGT and diabetes mellitus (DM).

Methods:
232 patients (66.4 ± 12.6 years, 201 male) who received percutaneous coronary intervention for coronary artery disease were enrolled in the present study. All of the patients except those already given the diagnosis of DM underwent 75g oral glucose tolerance test (OGTT). The study cohorts were divided into 3 groups; DM (n=118), IGT (n=67), and NGT (n=47). IGT was defined as 2 hour post-load plasma glucose ≥140mg/dl during the OGTT. The lesion complexity was expressed as SYNTAX score. The vulnerability of coronary plaque was determined by optical coherence tomography (OCT).

Results:
Glycated hemoglobin (HbA1c) level was significantly higher in DM group (6.7±1.3%) than IGT (5.8±0.3%, P<0.01) or NGT group (5.6±0.3%, P<0.01). The SYNTAX score in IGT group was equivalent to that in DM group (12.7±8.1 vs.11.8±7.8, P = 0.61), and significantly greater than NGT group (10.2±5.8, P<0.05). OCT identified 137 non-target residual plaques in 101 patients. Out of those plaques, 72 plaques contain lipid core (16, 29, and 27 in NGT, IGT and DM groups, respectively). The size of lipid core expressed as mean angles of lipid arc was significantly greater in IGT and DM groups than NGT group (162.0±58.7°, 171.4±59.3° and 130.9±37.7°, respectively, P<0.05). Fibrous cap covering the lipid core in IGT group was equivalent to that in DM group (0.08±0.03mm vs. 0.09±0.03mm, P=0.10), and significantly thinner than NGT group (0.11±0.05mm, P<0.05).

Conclusions:
The lesion complexity and plaque vulnerability of IGT patients are not inferior to those of DM patients and significantly greater than NTG patients.
Abstract 10947: Longer and Faster Non-sustained Ventricular Tachycardia in Hypertrophic Cardiomyopathy Patients Predicts for Implantable Cardioverter Defibrillator Shocks and Sudden Cardiac Death
Authors: Wang Weijia , Lian Zhesi , Rowin Ethan , Maron Martin , Link Mark
Published: July 2021

Introduction:
Non-sustained ventricular tachycardia (NSVT) may be underestimated in patients with hypertrophic cardiomyopathy (HCM). Its impact on the risk of sudden cardiac death (SCD) in HCM is controversial. There is no distinction made in the guidelines as to the length or rate of NSVT as a risk marker for SCD.

Hypothesis:
NSVT may be nearly universal in HCM patients with high risk of SCD and not found because of the limited time frame of monitoring. NSVT may be associated with appropriate Implantable Cardioverter Defibrillator (ICD) shocks and SCD.

Methods:
A retrospective study of 181 HCM patients who had an ICD and were followed for at least 6 months from 2000 to 2013 at Tufts Medical Center was performed. The pre-operative evaluations as well as routine ICD follow up notes were reviewed.

Results:
ICD was implanted in 175 (96.7%) patients as primary prevention and in 6 (3.3%) patients as secondary prevention for SCD. Ninety six (53.0%) patients total had NSVT, including 48 (26.5%) before and 77 (42.5%) after ICD implantation. The agreement for detecting NSVT between Holter monitoring and ICD interrogation was poor (Kappa=0.18, p=0.054). Eighteen (18.75%) patients with NSVT and 6 (7.06%) patients without NSVT had appropriate ICD shocks or SCD (Figure 1). In multivariable analysis, NSVT was independently associated with appropriate ICD shocks and SCD (OR 3.69, 95%CI: 1.31 - 10.43) and remained significant in the 175 patients who had ICD implanted as primary prevention (OR 3.86, 95%CI: 1.13 - 13.18). More rapid NSVT (Cl < 310ms) predicted appropriate ICD shocks and SCD (OR 7.7, 95%CI: 1.6, 36.8), and longer NSVT (> 18beats) also predicted appropriate ICD shocks and SCD (OR=23.7, 95%CI: 2.7, 204.9).

Conclusion:
The agreement for detecting NSVT between Holter and ICD interrogation is poor. NSVT is significantly associated with appropriate ICD shocks and SCD. Faster and longer NSVT are even more predictive. Extending rhythm monitor time merits consideration in HCM patients.
Abstract 10954: Clinical and Angiographic Predictors of Adverse Outcomes After Percutaneous Coronary Intervention in Patients With Radiation Associated Coronary Artery Disease
Authors: Reed Grant W , Masri Ahmad , Griffin Brian P , Kapadia Samir R , Ellis Stephen G , Desai Milind Y
Published: July 2021

Background:
The clinical and angiographic predictors of outcomes after percutaneous coronary intervention (PCI) in patients with cancer and radiation associated coronary artery disease (CAD) are not well established.

Methods:
In this retrospective cohort study, 157 patients with thoracic malignancy and external beam radiation therapy (XRT) prior to PCI were identified. The rates of major adverse cardiovascular and cerebrovascular events (MACCE; all-cause mortality, myocardial infarction, repeat revascularization, or stroke) were compared across patient characteristics.

Results:
During follow-up of 5.4±4.5 years, 91 (58%) patients had MACCE; 59 (38%) died, of which 23 (39%) were cardiac deaths, 23 (39%) due to cancer or other causes, and 13 (22%) unknown. By Kaplan-Meier analysis, MACCE were more frequent with coronary artery calcification (p=0.023), ostial stenosis (p=0.049), target vessel diameter ≥ 3.0 mm (p=0.018), a SYNTAX score ≥ the median of 11 (p=0.014), or bare metal stenting (BMS) compared to drug-eluting stenting (DES) (p=0.006) (Figure). Cardiac death was more frequent in patients with SYNTAX score ≥ 11 (p=0.028) or BMS (p=0.043). After multivariable adjustment, independent predictors of MACCE were chronic kidney disease (CKD) (p=0.006), New York Heart Association (NYHA) class ≥ 3 (p=0.024), and BMS (p=0.008) (Table).

Conclusions:
In patients with radiation associated CAD treated with PCI, MACCE is more frequent in those with target vessel calcification, ostial stenosis, large vessel diameter, or SYNTAX score ≥ 11. BMS placement is independently associated with greater MACCE than DES, and other risk factors for MACCE include CKD and NYHA class ≥ 3.
Abstract 10960: Red Cell Distribution Width and Mortality in Cardiorenal Anemia Syndrome
Authors: Cheng Yu Lun
Published: July 2021

Introduction:
The interaction between heart failure, renal insufficiency and anemia has been termed as cardiorenal anemia (CRA) syndrome. Red cell distribution width (RDW) hasn’t been clarified of the prognostic impacts in acute heart failure (HF) with cardiorenal anemia syndrome.

Hypothesis:
RDW remained its prognostic predictive power in patient with cardiorenal anemia syndrome

Methods:
A total of 978 patients (age 75±14 years, 70% men) hospitalized for AHF were enrolled. National Death Registry was linked for the clinical outcomes of all-cause mortality. We collected data of past medical history, biochemistry profiles, and echocardiographic on admission.

Results:
Among the study population, 419 (43%) subjects had cardiorenal anemia syndrome. Across the tertiles of RDW distribution, high RDW was associated with lower left ventricular ejection fraction (LVEF) and hemoglobin levels, and higher serum creatinine levels. During a median follow-up duration of 31 months, 472 subjects (43%) died. The post-discharge mortality increased along with the tertiles of RDW(Figure). After accounting for age, gender, co-morbidities, hemoglobin, renal function, and sodium level, RDW remained an independent predictor of mortality (HR and 95% CI for 1% increase of RDW: 1.11; 1.07-1.15). With further adjustment of NT-proBNP, RDW still was an independent prognostic factor. With adjustments for age, sex and hemoglobin in subgroup analysis, RDW was associated with mortality in patients with chronic kidney disease stage I/II (1.09; 1.03-1.15), III (1.12; 1.06-1.19), and IV/V (1.07; 1.00-1.14). Furthermore, in patients with CRA syndrome, RDW was still related to mortality (1.07; 1.02-1.12).

Conclusions:
Elevated RDW is independently associated with mortality in patients hospitalized for acute HF, despite anemia status, renal function, or CRA syndrome status. Giving RDW an easily accessible marker, the study results may support RDW to improve the risk stratification of acute HF.
Abstract 10971: Myocardial Edema in Acute Myocarditis Detected by Echocardiographic 2D Myocardial Deformation Analysis
Authors: Løgstrup Brian B , Nielsen Jan M , Kim Wong Y , Poulsen Steen H
Published: July 2021

Introduction:
The diagnosis of acute myocarditis is in daily practice based on symptoms, electrocardiography, elevated myocardial necrosis biomarkers, echocardiography and in selected cases supported by myocardial edema and fibrosis demonstrated by cardiovascular magnetic resonance (CMR). Often conventional echocardiography reveals no obvious changes in global function despite and therefore provides limited diagnostic value. Myocardial deformation imaging by echocardiography is an evolving method to quantitatively characterize myocardial function that may be influenced in acute myocarditis.

Hypothesis:
The aim of our study was to assess deformation imaging of the left ventricle in patients with CMR verified acute myocarditis.

Methods:
We included 28 consecutive patients (mean age 32±13 years) with CMR verified diagnosis of acute myocarditis by Lake Louise criteria. The cardiac function was evaluated by a comprehensive assessment of left ventricular (LV) function including 2D speckle tracking echocardiography.

Results:
We found no correlation between LV function assessed by echocardiographic ejection fraction and the amount of edema. However, we found wall motion score index to be significantly correlated to the amount of myocardial edema, however only observed, in patients with >11% edema of the LV. Global longitudinal systolic strain correlated significantly to the amount of edema (r= 0.65; p<0.001). We found that both the epicardial longitudinal- and endocardial longitudinal systolic strain significantly correlated to edema (r=0.55; p=0.003 and r=0.54; p=0.004). No significant correlation was observed analyzing circumferential strain (global: r=0.3; p=0.13; epicardial: r=0.26; p=0.19 and endocardial: r=0.32; p=0.1). However, we found the circumferential strain to be decreased in the infero-postero-lateral region.

Conclusions:
In patients with acute myocarditis we found 2D speckle tracking echocardiography to be a useful tools in the diagnostic process of acute myocarditis. Myocardial deformation imaging improved the diagnostic accuracy in acute myocarditis patients, especially when conventional echocardiographic parameters of LV are normal.
Abstract 10989: Diagnostic Impact Of Electrocardiogram And Emergency Coronary Angiography In Patients With Out-of-hospital-cardiac-arrest
Authors: Tateishi Kazuya , Abe Daisuke , Iwama Toru , Sassa Tatsuro , Oohashi Kouichi , Miyazaki Kazuki , Kaneko Masakazu , Harunari Tomohiko , Yui Yashiaki , Kuroki Norihiro , Yuba Takao , Suzuki Ko , Hamabe Yuuichi
Published: July 2021

Objective:
The guideline suggests that coronary angiography (CAG) should be performed for the patients with out-of-hospital-cardiac-arrest (OHCA) and return of spontaneous cardiac arrest (ROSC). We investigated the association between initial ST-segment change after ROSC and incidence of acute coronary lesion in patients with OHCA. We also researched the number of patients with OHCA caused by vasospastic angina pectoris (VSA).

Methods:
From April 2011 to March 2015, there were 2,779 OHCA patients in our institution. We underwent CAG for all patients with ROSC, except for obvious extra-cardiac cause of OHCA. Initial ST-segment change after ROSC of serial 155 patients(61±14.5years old,83.9% male) was reviewed.

Results:
The 34% of patients had ST-segment elevation and the 66% had other electrocardiogram (ECG) pattern. Significant coronary lesion which needs percutaneous coronary intervention (PCI) was shown in the 81% of patients with ST-segment elevation and in 33% with other ECG (P<0.001). ST-segment analysis had a good positive predictive value (81%) but a low negative value (68%) in diagnosing the presence of acute coronary lesions. The patients who were diagnosed vasospastic angina were found in the 10% of patients with ST-segment elevation and in the 12% with other ECG.

Conclusion:
Even in the absence of ST-segment elevation, acute culprit coronary lesion may be present, and there is significant value to perform emergency CAG for ROSC patients. Furthermore, vasospastic angina pectoris may be present and considered the trigger of cardiac arrest. Emergency CAG could remove the coronary artery spasm by directly NO injection.