bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P352: Racial/Ethnic Differences in Cardiovascular Disease Outcomes among Patients with Hypertension or Type 2 Diabetes
Authors: Pu Jia , Chung Sukyung , Zhao Beinan , Nimbal Vani , Wang Elsie J , Fortmann Stephen P , Palaniappan Latha P
Published: July 2021

Background:
This study assesses racial/ethnic differences in CVD outcomes among patients with hypertension (HTN) or type 2 diabetes (T2DM) across Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese), Mexican, non-Hispanic black (NHB), and non-Hispanic White (NHW) in a large, mixed payer ambulatory care setting in northern California.

Study Design: We estimated the rate of CVD incidence among adult patients with HTN (N=171,864) or T2DM (N=10,570), or both (N=36,589) using electronic health records between 2000-2013. Average follow-up was 4.5 years. CVD, including CHD (410-414), PVD (415, 440.2, 440.3, 443.9, 451, 453), and stroke (430-434), was defined by ICD-9 codes; HTN and T2DM were defined by ICD-9 codes, medication history, or two or more elevated blood pressure measures/abnormal glucose lab test results. Cox proportional hazard models were used to estimate hazard ratios for CHD, PVD, and stroke across race/ethnicity.

Results:
Among these patients, 10.5% developed CVD by the end of year 2013 (5.4% CHD, 3.4%PVD, 3.6% stroke).

There was a gender difference in the risk of incident CHD. Among males, the age-adjusted hazard ratios for CHD were significantly higher for Asian Indians (HR: 1.3, 95% CI: 1.2-1.5) and significantly lower for Chinese (HR: 0.6, CI: 0.5-0.7) and Japanese (HR: 0.8, CI: 0.6-0.9) compared to NHWs. Among females, the age-adjusted hazard ratios for CHD were significantly higher for Mexican (HR: 1.3, CI: 1.1-1.5) and NHBs (HR: 1.7, CI: 1.4-2.0) and significantly lower for Chinese (HR: 0.6, CI: 0.5-0.7) and Japanese (HR: 0.5, CI: 0.4-0.7). NHB men and women also had significantly higher age-adjusted hazard ratios for PVD (men: HR: 1.5, CI: 1.2-1.9; women: HR: 1.6, CI: 1.3-1.9) and stroke (men: HR: 1.3, CI: 1.1-1.7; women: HR: 1.3, CI: 1.1-1.6) compared to NHWs. The age-adjusted hazard ratios for PVD and stroke were lower or equivalent to NHWs for all Asian subgroups and Mexican men and women. Patients with both HTN and T2DM were at elevated risk to develop CVD compared to patients with only one of the two conditions, regardless of their race/ethnicity.

Conclusions:
Compared to previous studies, we found less racial/ethnic variation in CVD outcomes, in particular stroke, among patients with HTN or T2DM. Our finding suggests the higher stroke incidence rates in several races/ethnicities are likely to be explained by the higher prevalence of HTN and T2DM among these groups. However, Asian Indian men and NHB and Mexican women with HTN or T2DM were at elevated risk for CHD compared to NHWs. Since the majority of patients in the study cohort had health insurance, further studies are needed to better understand the reasons for the observed racial/ethnic differences beyond disparities in access to health care. Special attention needs to be paid to patients with multiple conditions.
Abstract P358: Discovery Loci and Generalization of Platelet Count Associations in the Hispanic Community Health Study: Study of Latinos (HCHS/SoL)
Authors: Hodonsky Chani J , Schick Ursula , Morrison Jean , Laurie Cathy , Eckfeldt John H , Thornton Timothy , North Kari E , Reiner Alex P
Published: July 2021

Background:
The biology of platelets_anuclear megakaryocyte fragments required for clotting_is well defined, with abnormalities resulting in clotting disorders ranging from asymptomatic to severe. Although platelet count (PLT) is highly heritable (h
2
=0.57 in NHANES), genetic regulation of this trait remains incompletely characterized. In particular, Hispanic Latinos are a diverse population in which the genetic variability of PLT has not been analyzed. We aimed to 1) identify novel loci associated with PLT in participants of HCHS/SoL; and 2) determine if previously identified PLT loci generalize to the Hispanic Latino population.

Methods:
We performed a genome-wide association study of PLT in 12,491 participants of HCHS/SoL, which includes individuals with Dominican, Puerto Rican, Mexican, Cuban, South American, and Central American ancestral origins residing in the United States. Participants were genotyped on the Illumina SoL Omni2.5M array and imputed to the 1000 Genomes Phase I Reference panel. We implemented linear mixed-model regression assuming an additive genetic model, adjusting for sex, age, study center, ancestry and sample weights, and including random effects for individual relatedness, household, and block group.

Results:
Ten independent loci were significantly (α = 5x10
-8
) associated with PLT in HCHS/SoL and 13 of 57 previously identified platelet-count GWAS loci generalized to HCHS/SoL (+/-500kb, α = 8.78x10
-4
). Discovery loci included a significant association near
GABBR1
(rs3131857, MAF = 40%, β = -0.16) and a suggestive association near
ETV7
(rs9470264, MAF = 20%, β = -0.19). Furthermore, a noncoding variant in
ACTN1
was associated with increased PLT (rs117672662, MAF = 6%, β = 0.61);
ACTN1
codes for alpha-actinin, a multi-isoform actin-binding protein involved in cytoskeleton organization and platelet/megakaryocyte structural integrity. Missense mutations in
ACTN1
were recently implicated in congenital thrombocytopenia; exome sequencing also associated this locus with PLT, which supports a potential functional role in PLT for this gene. Conditional regression analyses to assess secondary association signals are in progress.

Conclusions:
Genetic associations in two discovery loci (
ETV7
and
GABBR1
) underscore the benefit of using diverse populations in GWAS. Expanding the number of loci associated with platelet count will help elucidate disease mechanisms and develop approaches to treat platelet disorders in populations of all ancestries.
Abstract P359: A Sickle Cell Variant Associates With Urine Albumin Excretion in Genome Wide Association Study of Hispanics: The HCHS/SOL Study
Authors: Franceschini Nora , Stilp Adrienne , Wassel Christina L , Mattix-Kramer Holly J , Flessner Michael F , Rasooly Rebekah S , Cai Jianwen , Laurie Cathy C
Published: July 2021

Introduction:
Genome wide association studies have identified genetic variants in the
Cubillin
gene (
CUBN
) that explain inter-individual variation in urine albumin-to-creatinine excretion (UACR) in populations. These studies have not included Hispanics/Latinos, the fast growing minority population in the U.S., who has also high prevalence of chronic kidney disease and its risk factors.

Hypothesis:
By leveraging on population admixture of Hispanics and using a genome wide association approach, we hypothesized that novel loci associated with UACR would be identified.

Methods:
We used data from 12,212 self-identified Hispanic individuals recruited in a community-based study, aged 18-74 years at screening (2008-2011), and randomly selected from households in four U.S. field centers (Chicago, IL; Miami, FL; Bronx, NY; San Diego, CA). Urine albumin (mg/dl) and creatinine (g/dl) were measured at the baseline exam. UACR was log-transformed for analysis. Individuals were excluded if reporting to have end-stage renal disease. Genotyping was performed using a custom Illumina Omni2.5M array. Imputation of variants was performed using 1000 Genome Project data from cosmopolitan HapMap samples. After quality control of imputed data, we performed mixed linear regression analyses that accounted for the sampling strategy and family relatedness, for variants with minor allele frequency (MAF) > 0.01 and imputation quality > 0.3. We used additive genetic models and adjusted for age, sex, and principal components which were estimated from the data. In a secondary analysis, we also examine the association of significant variants with kidney function using estimated glomerular filtration rate (eGFR) equations.

Results:
Among 12,212 participants, 41% were men, and mean age was 46 (SD =13). There was little evidence for genome wide inflation (lambda =1.024). We identified significant associations of single nucleotide polymorphisms (SNPs) with UACR at two loci:
CUBN
and
HBB
. The
CUBN
SNP (chr10:16966414, p=2.1x10-8) is an indel variant with MAF of 0.14, which was not in linkage disequilibrium with previously reported SNP rs1801239 (rsq=0.38, p=1.3x10-4) identified in individuals of European ancestry. The
HBB
SNP is a missense variant which results in an E [Glu] ⇒ A [Ala] substitution in the beta-globin chain of hemoglobin and a cause of the Mendelian disorder sickle cell anemia (rs334, T allele frequency =0.01, beta=0.44, SE=0.06, p=7.6x10-12). rs344 was not associated with eGFR in our data (p>0.05).

Conclusion:
This study identified a novel association of a sickle cell missense variant with UACR in Hispanics, and provided evidence for allelic heterogeneity at the
CUBN
locus. Our findings suggest a role for Mendelian gene variants in increased albuminuria in Hispanic populations with admixture.
Abstract P380: Coronary Artery Disease Extent is Predictive of Heart Failure Incidence After Myocardial Infarction
Authors: Gerber Yariv , Weston Susan A , Sarano Maurice E , Manemann Sheila M , Chamberlain Alanna M , Jiang Ruoxiang , Roger Veronique L
Published: July 2021

Background:
Little is known about the association between coronary artery disease (CAD) and the risk of heart failure (HF) after myocardial infarction (MI), and whether it differs by reduced (HFrEF) or preserved (HFpEF) ejection fraction (EF) has yet to be determined.

Subjects and Methods:
Olmsted County, Minnesota residents (n=1,924; mean age, 64 years; 66% male) with first MI diagnosed in 1990-2010 and no prior HF were followed through 2013. Framingham Heart Study criteria were used to define HF, which was further classified according to EF (applying a 50% cutoff). The extent of angiographic CAD was defined at index MI according to the number of major epicardial coronary arteries with ≥50% lumen diameter obstruction. Fine & Gray and Cox proportional hazards regression models were used to assess the association of CAD categories with incidence of HF, and multiple imputation methodology was applied to account for the 19% with missing EF data.

Results:
During a mean (SD) follow-up of 6.7 (5.9) years, 594 patients developed HF. Adjusted for age and sex, with death considered a competing risk, the cumulative incidence rates of HF among patients with 1- (n=581), 2- (n=622), and 3-vessel disease (n=721) were 11.2%, 14.6% and 20.5% at 30 days; and 18.1%, 22.3% and 29.4% at 5 years after MI, respectively. The increased risk of HF with greater number of occluded vessels was only modestly attenuated after further adjustment for patient and MI characteristics, and did not differ materially by EF (Table).

Conclusions:
The extent of angiographic CAD expressed by the number of diseased vessels is independently associated with HF incidence after MI. The association is evident promptly after MI and applies to both HFrEF and HFpEF.
Abstract P391: Metabolic Syndrome Does Not Associate with an Increase Mortality in End Stage Renal Disease Patients: a Systematic Review and Meta-Analysis
Authors: Upala Sikarin , Sanguankeo Anawin
Published: July 2021

Background:
Metabolic syndrome (Mets) is documented to increase mortality in the general population. However, there are reports of lower mortality in end stage renal disease (ESRD) patients with obesity. We conducted a meta-analysis to determine the association of all-cause and cardiovascular disease (CVD) mortality, and residual renal function with Mets in ESRD subjects.

Objectives:
PubMed/MEDLINE, EMBASE, and CENTRAL from their inception to September 2014 were comprehensively searched for eligible studies assessing the effects of the metabolic syndrome in ESRD subjects. Inclusion criterion was ESRD participants who had hemodialysis (HD or peritoneal dialysis (PD). Renal transplant subjects were excluded. Two authors independently assessed article quality and extracted the data. The primary outcome was all-cause mortality and secondary outcomes were CVD death and residual renal function.

Results:
From 23 full-text articles, 7 studies involving 613 (all-cause mortality), 284 (CVD death) and 383 (residual renal function) participants were included in the meta-analysis that was based on the random effects model. Compared with the non-Mets, ESRD subjects with Mets had no significant difference in risk of all-cause mortality (pooled odds ratio= 1.65; 95% CI, 0.86, 3.17) (figure 1) or CVD death (pooled odds ratio= 1.67; 95% CI, 0.75, 3.69). There was also no difference in residual renal function between the two groups with pooled standard mean difference of -0.26 ml/min/1.73 m2 (95% CI: -0.62, 0.10).

Conclusion:
Metabolic syndrome is not associated with an increased risk of all-cause or CVD mortality in ESRD patients who underwent HD or PD.
Abstract P392: Exome Sequencing From Extreme Responders to Aspirin Identifies a Novel Variant Associated With Platelet Aggregation
Authors: Backman Joshua , Ning Baitang , Lou Wensheng , Perry James , Shi Leming , Shuldiner Alan , Yerges-Armstrong Laura
Published: July 2021

Platelet dysregulation is integral in the formation of thrombi, and abnormal thrombus formation may ultimately lead to myocardial infarctions or stroke. Thus platelets, and more specifically platelet activation and aggregation pathways, are prime targets for intervention. Aspirin or Dual Anti-Platelet Therapy with Aspirin and Clopidogrel (DAPT) is often prescribed for primary and secondary prevention of cardiovascular events, however, these treatments often fail to significantly reduce thrombi formation in a large percentage of patients. Recent studies indicate that platelet aggregation response is highly heritable. To identify novel variants that may have a significant impact on platelet aggregation, we conducted whole exome sequencing and follow-up DNA genotyping on a cohort of Old Order Amish subjects with well tracked family histories and platelet response phenotypes. 30 individuals from the extremes of collagen-mediated platelet aggregation response to aspirin were analyzed to identify variants enriched in the high or low responders. One of the top hits in this analysis was rs17834991, a synonymous variant in the SVIL gene enriched in the high aspirin response group that has not previously been associated with platelet aggregation. The SVIL gene encodes two proteins: a muscle-specific isoform, Archvillin, as well as a ubiquitous form, Supervillin, that is expressed in platelets. In a previous study, mutations in SVIL were found to be associated with inhibition of platelet aggregation under shear stress conditions.

To follow up our initial findings, we genotyped rs17834991 in 851 healthy Amish individuals with platelet aggregation measured before and after a two-week 81mg/day Aspirin intervention from our HAPI dataset. An additional 661 Amish subjects with platelet aggregation measured before and after 1 week of Clopidogrel treatment, and following one 81mg dose of Aspirin plus Clopidogrel from our PAPI cohort were genotyped. We then conducted a multivariable linear regression controlling for age, sex, BMI, and two known effectors of platelet aggregation: CYP2C19*2 and rs12041331. Our findings indicate that rs17834991 is significantly associated with change in collagen-mediated aggregation with aspirin in whole blood (p=4.8x10-4), as well as lag time until maximum aggregation with collagen post aspirin (1.6x10-3) in whole blood. Additional associations were identified with collagen mediated aggregation in PRP, the strongest being change in lag time in post DAPT vs post Clopidogrel-alone samples (6.59x10-5). These findings suggest that SVIL variant rs17834991 significantly alters platelet response following Aspirin and DAPT treatment. Taken with previous findings, SVIL may not only play a role in platelet function but may also impact anti-platelet intervention. Further studies are warranted to elucidate its potential impact on cardiovascular disease.
Abstract P395: Statin Use in Late Life Does Not Impact Risk of Dementia or Cognitive Change in the Next Few Years: Results of a Systematic Review and Methodological Commentary
Authors: Power Melinda C , Weuve Jennifer , Sharrett A. R , Blacker Deborah , Gottesman Rebecca F
Published: July 2021

Introduction:
The recently published American College of Cardiology and American Heart Association guidelines on the management of cholesterol expanded the population recommended to receive statins by approximately 13 million United States adults. Statins are hypothesized to reduce risk of dementia through treatment of hyperlipidemia, through anti-oxidant and anti-inflammatory effects, or through influence on brain amyloid-beta or tau metabolism. However, firm conclusions about whether statin use impacts cognitive decline and dementia remain elusive. Existing reviews have focused solely on trials, did not systematically discuss study quality, or discussed and meta-analyzed all observational studies as a group, which may be inappropriate when differences in study design or analyses yield non-comparable effect estimates.

Hypothesis:
The purpose of this systematic review is to summarize findings from randomized controlled trials and observational cohort studies, study designs that are most useful for evaluating the putative causal effect of statin use on cognition. We hypothesized that the literature would support a protective effect of statin use on cognitive decline and dementia.

METHODS:
Following a systematic literature search, we grouped eligible reports by study design and statistical approach, and provide specific commentary on findings, as well as the potential for and direction of bias.

RESULTS AND CONCLUSIONS:
While observational studies of statin use at or near the time of dementia diagnosis suggest a protective effect, these findings may be attributable to reverse causation. Randomized controlled trials and well-conducted observational studies of baseline statin use and subsequent cognition do not support a causal preventive effect of statin use in late-life on cognitive decline or dementia. This of course does not undermine existing recommendations regarding statin use for preventing cardiovascular disease. Important questions remain unanswered, including questions about the impact of midlife or long-term statin use. Much future human research on statins and cognition will be observational; careful study design and analysis will be required to avoid common sources of bias. We advocate continuing systematic review with attention to study quality and the likelihood of bias; the AlzRisk database entry on this topic, which is currently limited to studies reporting on Alzheimer’s disease, will be available shortly and will be updated over time (see www.alzrisk.org for reviews of 11 other potential non-genetic risk factors for Alzheimer’s disease).
Abstract 158: Central arterial elasticity in patients post Kawasaki Disease - a Cardiac Magnetic Resonance Imaging (CMR) study
Authors: Christelle Tan X , Lynette Teo L , Lieng Hsi Ling , Cindy Hia P , Swee Chye Quek , Jie Ying Lee , Peng Guan Ong , Andrew Ng W , Terence Lim C
Published: July 2021

Background:
Measures of central arterial elasticity such as aortic pulse wave velocity (APWV) have been shown to correlate with development of atherosclerosis. Endothelial dysfunction after Kawasaki disease has been shown to persist despite resolution of anatomically demonstrable coronary anomalies and this may be reflected in abnormal central arterial elasticity. Measurement of APWV by CMR is most robust but has seldom been reported in KD patients.

Aim:
In a novel pilot study, we measured the APWV using CMR in patients with no coronary complications post KD. We compared this to age and gender matched published controls and APWV values measured on ultrasound.

Methods:
10 KD patients (with no coronary involvement) in our hospital database, at least 12 years post KD diagnosis, with no known personal cardiovascular risk factors or family history of premature cardiovascular disease, were recruited.

Each subject underwent both MRI and ultrasound investigations to determine the APWV. The results were compared using standard (z) scores calculated from published norms.

Results:
3 of the 10 KD subjects had significant z scores using CMR measurements of APWV ranging from +2.07 to +3.35. However, no significant difference was found on overall non parametric comparisons of measurements.

The US measurements of APWV all did not yield significant z scores. Z scores obtained from US and CMR measurements for the same subject showed no concordance.

Conclusion:
Central arterial stiffness tends to be higher in KD patients many years following the acute illness when assessed by CMR methods. CMR may be a more sensitive method than ultrasound for assessing central arterial stiffness post KD. The clinical implication of these findings require longitudinal follow up.
Abstract 171: A Mitral Regurgitation May be an Early Diagnostic Clue to Kawasaki Disease in Young Infants with Atypical Presentations
Authors: Oh Jin-Hee , Kim Ji Hoon , Lee Ji Eun , Kwon Hyo Jin , Lee Jae Young , Lee Soon Ju , Han Ji Whan , Lee Kyung Yil , Koh Dae Kyun
Published: July 2021

Background:
Very young infants with Kawasaki disease (KD) often present with atypical features that render diagnosis difficult and the incidence of coronary complications high. Picking up clues at early phase of KD can be critical. Herein we present 3 cases of KD in very young infants who showed mitral regurgitation (MR) around the 7th day from the onset of fever. They received IVIG around 7th fever day. However, the advice for short-term follow up echocardiography (ECHO) was neglected as clinical course thereafter were so unusual. Giant coronary aneurysms developed in all the patients later.

Case 1: A 31-day-old infant got admission care for sepsis. ECHO at the 7th day from the onset of fever showed trivial MR and the patient received IVIG. Follow up ECHO was recommended, but was not conducted as clinical course was ambiguous for KD thereafter. Being treated with steroids due to skin rash and eosinophilia that masked patient’s fever, the infant reappeared to hospital with cardiogenic shock 10 days later. ECHO revealed giant aneurysms in the right coronary artery (RCA) and CT angiography for pulsating axillary masses revealed axillary aneurysms.

Case 2; A 67-day-old infant was admitted with fever and persistent thrombodytopenia. ECHO done at the 5th day from the onset of fever due to red lips showed non-specific findings. Follow up ECHO at the 7th fever day showed newly developed MR. IVIG and steroids was added on for persistent fever, but severe leukocytosis ensued and clinical course was also ambiguous for KD. Defervescence was achieved with infliximab. The infant showed coronary aneurysms.

Case 3; A 80-day-old infant was admitted with fever and seizure, and treated for sepsis. On the 6th day from the onset of fever, MR was shown on ECHO and the patient received IVIG and steroids. However, fever and severe anemia, left shift of leukocytes, and severe thrombocytopenia persisted for two weeks. Giant coronary aneurysms, as large as the ascending aorta, developed in the RCA. Pulsatile masses identified in the axilla were found to be large aneurysms on CT angiography.

Conclusion:
A newly developed MR, even trivial, around the 7th day from the onset of fever may be a clue to the diagnosis of KD and short term follow up ECHO is recommended for ongoing febrile infants younger than 3 months.
Abstract 180: Coronary Artery Aneurysms Identified At School Cardiac Screening
Authors: Yoshimoto Hironaga , Suda Kenji , Kishimoto Shintaro , Kudo Yoshiyuki , Matsuishi Toyojiro , Yatsunami Koichi
Published: July 2021

Because most significant complication of Kawasaki disease (KD) is coronary aneurysms, echocardiography is an indispensable part of clinical practice and quality control of echocardiography is mandatory. On the other hand, Japanese government has enforced a law of regular school cardiac screening (SCS) at 1st, 7th, and 10th grader in 1995 and all patients with a history of KD were screened for coronary artery lesion. In this study we report 2 patients with coronary aneurysms picked up by SCS.

Case1: A 6-year-old boy was diagnosed with KD at 3 year old and received immunoglobulin (2g/kg/day). His condition improved within 8 days of illness and echocardiographic finding of coronary artery was “normal” in acute phase and at 1and 3 months after the onset of KD. Since then he did not visit clinic for follow-up. At 1st grader SCS, he was diagnosed as having giant coronary artery aneurysms by echocardiography. Indeed coronary angiography revealed sequential coronary aneurysms of 10.8 mm and 12.3 mm in diameter at segment 6 and 5 with a 99% stenosis in between them. Because of signs of coronary ischemia on myocardial perfusion scan, he underwent percutaneous coronary interventions and coronary artery bypass graft surgery later.

Case2: A 9-year-old boy was diagnosed with juvenile idiopathic arthritis and his fever continued 10 days. He underwent echocardiography at 9 days of illness but coronary artery lesions were not found. At 7th grader SCS, he was diagnosed as having coronary artery aneurysms by echocardiography. Coronary angiography revealed coronary artery aneurysms of 6.1mm and 6.1 mm in diameter at segment 1 and segment 6. Since then he has been placed on oral aspirin.

These 2 cases highlight the issue concerning timing and quality of echocardiography and importance of SCS in detecting patients with coronary undiagnosed aneurysms.
Abstract 65: T cell Differentiation in Human Kawasaki Disease and a Murine Model of Coronary Arteritis
Authors: Lin I-Chun , Kuo Hsuan-Chang , Lin Ying-Jui , Chien Shao-Ju , Huang Chien-Fu , Lo Mao-Hung , Lin Kuan-Miao , Hsien Kai-Sheng
Published: July 2021

The role of T cell differentiation in the immunopathogenesis of Kawasaki disease (KD) remains unclear. The aim of this study is to elucidate the role of T cell subsets in coronary artery lesion (CAL) of KD. Peripheral blood was obtained in 10 patients with acute KD before and 1 week after intravenous gamma-immunoglobulin (IVIG) treatment and in 20 patients with past history of KD for more than 5~20 years. Meanwhile, induction of coronary arteritis was performed on wild type BALB/c mice by
Lactobacillus casei
cell wall extract (LCWE). Human peripheral blood leukocytes were analyzed by using flow cytometric analysis and murine hearts were examined for immunofluorescence study and for RNA expression levels.

Results:
Compared to the febrile controls, KD patients prior to IVIG treatment had increased percentage of CD3
+
/CD4
+
/interferon-γ
+
(T helper 1, Th1) cells and CD3
+
/CD4
+
/interleukin-17A
+
(Th17) cells (mean ± SD, 1.36% ± 1.39% and 0.51% ± 0.25%, respectively) among Th cells (CD3
+
/CD4
+
). Both increases declined after IVIG treatment (0.71% ± 0.74% and 0.33% ± 0.18%) despite no statistically difference by Mann-Whitney test. None of these 10 acute KD patients developed CAL after IVIG treatment. However, patients with previous KD and definite CALs (n= 11) seemed to have higher percentage of Th17 cells (0.50% ± .025%
versus
0.35% ± 0.23%) but similar level of Th1 cells (0.93% ± 0.51%
versus
1.05% ± 0.64%) when compared to those without CAL (n= 9). Murine cardiac tissues displayed the presence of Th1 (double-stained with CD3 and T-bet) and Th17 cells (double-stained with CD3 and RORγt) during days 7 and 14 after LCWE treatment but not in PBS-treated mice. Compatible with these, cardiac mRNA levels showed both increased levels of IFN-γ and IL17A mRNA in LCWE-treated mice.

Conclusions:
Our initial data suggests that specific T cell differentiation into Th1 and Th17 cells occurred in both human KD and mice stimulated with LCWE. IVIG treatment was associated with the recovery of such T cell differentiation. However, the clinical application to predict IVIG responsiveness and future CAL development by such increase in the peripheral Th17 remains unclear. Further studies to elucidate the detailed immune regulation of these T subsets on CAL are warrant by using this LCWE murine model.
Abstract 70: Trial of Ulinastatin treatment for murine model of Kawasaki Desease
Authors: Tsujita Yuki , Kawamura Yoichi , Kanai Takashi , Takeshita Seiichiro , Nonoyama Shigeaki
Published: July 2021

Recently, we reported that the initial Ulinastatin (UTI) therapy combined with intravenous immunoglobulin (IVIG) reduced the proportion of patients with Kawasaki disease requiring additional rescue treatment and the occurrence of coronary artery lesions as compared with IVIG alone (Circulation. 2011;124(25):2822-2828.). However, there have been no reports that histologically examined the therapeutic effects of UTI., In the present study, to investigate the histological efficacy of UTI, we administered UTI in a vasculitis murine model, resembling Kawasaki disease

Four-week-old male mice DBA/2 were intraperitoneally administered Candida albicans water soluble extract (CAWS) for 5 days and were treated either with UTI, IVIG, or a combination of UTI and IVIG. Further, we examined the plasma levels of neutrophil elastase andcytokinesandevaluated histopathological features..

Neutrophil elastase, TNF-α, IL-6, IP-10, and MIG significantly increased in the CAWS-treated mice. Large amount of elastase-positive neutrophils infiltrated in the coronary tissue. In addition, the infiltration of elastase-positive neutrophils was reduced in the pathological tissue of the UTI treatment group.

Neutrophil elastase is strongly involved in the destruction of the elastic plate and smooth muscle layer. There is a possibility that destruction of the vascular structures can be suppressed by decreasing the elastase-positive neutrophils infiltration in the UTI treatment group.
Abstract O.13: Kawasaki disease in the Maghreb community in Quebec
Authors: Gorrab Arbia A , Abed Bouaziz Asma , Spigelblatt Linda , Fournier Anne , Dahdah Nagib
Published: July 2021

Background:
The real incidence of Kawasaki disease (KD) in the Maghreb countries (Morocco, Algeria, and Tunisia) is unknown. It is estimated low according to the literature. However, the number of Maghrebi children living in Quebec (Qc) affected by KD seems important. We sought to determine the incidence of KD among Maghrebi children in Qc, Canada, and to study its epidemiological and clinical features and to clarify possible risk factors related or superimposed to their immigration.

Methods:
A retrospective study of KD in Maghrebi children living in Qc (n=24) (1996-2013), compared to reports from Fes, Morocco (n=23) a doctoral thesis published in 2010 (2001-2009) and from Tunisia (n=31) collected in five university hospitals with four from the Great Tunis and one from Nabeul city (1996-2013). There are no reports available from Algeria. The “country of origin” specific population in the Province of Qc was obtained from Statistics Canada.

Results:
The annualized incidence rate (AIR) of KD among Maghrebi children in Qc was 9.58/100,000 children under 5 years(Standard-Denominator (SD)).This is 6 times higher in Qc (5.57/SD and 19.02/SD among Tunisian and Moroccan descents) vs Tunisia (Nabeul Governorate) and Morocco (Fes) (0.95/SD and 3.15/SD). Personal and family history of allergy were significantly higher in Qc 42% (10/24) and 75% (18/24), respectively, whereas these features were reported near 0% in both reports from Morocco and Tunisia. The prevalence of incomplete KD criteria was relatively high in the 3 series 46% (11/24) in Qc vs 43% (10/23) and 35% (11/31); (p=NS). Diagnosis was late (gt day 10 of fever) in 1/24(4%) in Qc vs 7/23 (30%) in Morocco and 11/31 (35%) in Tunisia; (p 0.01). IVIG were administered in the acute phase to all patients in Qc, 5/23 in Morocco and 28/31 in Tunisia. However coronary complications were more common in Qc 42% (10/24) vs 22% (5/23) vs 19% (6/31) (p=0.02). Aneurysms were significantly associated with the incomplete form in the 3 groups (p=0.01).

Conclusions:
The observed AIR of KD in the Maghreb community in Qc is higher than the countries of origin where underdiagnosis is possible. Atopy may still be a risk factor in Qc. The coronary artery disease seems linked not only to therapeutic delay but also to the underlying terrain.
Abstract 10018: High on Aspirin Platelet Reactivity in Children Undergoing the Fontan Procedure
Authors: Patregnani Jason T , Diab Yaser , Klugman Darren , Spaeder Michael , Freishtat Robert , Sinha Pranav , Berger John
Published: July 2021

Introduction:
Despite routine thromboprophylaxis with aspirin, thromboembolism (TE) continues to be a significant complication after the Fontan procedure. Data suggest that suboptimal ex-vivo aspirin-induced platelet inhibition-known as High on-Aspirin Platelet Reactivity (HAPR) is an independent risk factor for breakthrough TE. The occurrence of HAPR may potentially increase the risk of aspirin prophylaxis failure in children who underwent Fontan procedure. However, HAPR has not been adequately studied in this patient population.

Hypothesis:
There is a high incidence of HAPR in children after the Fontan procedure.

Methods:
We conducted a single-center, prospective, observational pilot study of children requiring Fontan procedure. Thromboelastography with platelet mapping (TEG-PM), platelet CD62P expression by flow-cytometry and urinary 11-dehydro-thromboxane B2 (11-dhTxB2) were measured at baseline prior to starting aspirin at 5 mg/kg/day and after at least 5 days of continuous therapy. HAPR was defined as less than 30% Arachidonic Acid (AA)-induced platelet aggregation inhibition as measured by TEG-PM.

Results:
17 patients (11 males and 6 females, median age 3 years) were enrolled. HAPR was identified in 9/17 (53%) with 3/9 (33%) patients exhibiting no detectable AA-induced platelet aggregation inhibition. There was no significant effect of aspirin on percentage of activated platelets (i.e.: platelets expressing CD62P marker) in children with or without HAPR. In contrast to children with HAPR, aspirin therapy in children without HAPR led to significant reduction in urinary 11-dhTxB2 levels (Table 1).

Conclusions:
A significant proportion of children with single ventricle physiology exhibited HAPR in the immediate post-operative period after Fontan procedure. Further studies are needed to examine association of HAPR with increased risk of TE in this patient population.
Abstract 10020: Impact of Race on Temporal Trends in Hospitalizations and Outcomes in New York State Among Patients With Valvular Heart Diseases
Authors: Supino Phyllis G , Hai Ofek Y , Govindarajulu Usha S , Borer Jeffrey S
Published: July 2021

Introduction:
Valvular heart diseases (VHD) are a growing public health problem but effect of race on temporal changes in VHD hospitalizations, valve surgeries and hospital mortality rates is undefined.

Hypothesis:
Non-White patients (pts) with VHD are at higher risk of hospital mortality vs White pts.

Methods:
We retrospectively analyzed all inpatient hospital records obtained between 1983-2012 from the New York State Statewide Planning and Research Cooperative System database with a primary or secondary ICD-9 code for VHD and racial self-classification (n=2,443,056). Linear regression was used to evaluate temporal changes in numbers of valve hospitalizations and valve surgeries performed among racial groups; ANOVA, χ
2
and t-tests were used, as appropriate, to compare subgroup differences on baseline clinical characteristics and lengths of stay; logistic regression (age, gender-adjusted) compared risk of hospital mortality by race.

Results:
During the 30-yr interval, proportions of non-White (predominantly Black) to White VHD pts increased by 65.9% (all VHD) and 72.1% (valve surgery). Though 12±1 yrs younger than White pts (p<.001), Black pts had more concomitant hypertension, diabetes, heart failure and/or kidney disease and longer lengths of stay (p<.001, all) vs White pts. Across all racial groups, hospital death risk was highest among Black pts (Figure), with men at greatest risk among all VHD cases (OR= 1.27, 95% CI=1.22-1.31, p<.001) and women at highest risk after valve surgery (OR= 1.32, 95% CI=1.18-1.48, p<.001).

Conclusions:
Pt demographics in New York hospitals are changing: pts from minority racial groups are proportionally increasing. The higher hospital mortality rates among Black pts with VHD is unexplained, though racial disparities in access to care and health risk factors may be involved. These disparities require evaluation as they will increasingly impact the health care system as the numbers of affected individuals continue to grow.
Abstract 10199: Right Atrial Fibrillation in Humans -
Evidence for A Right Atrial Driver Activated by Right Atrial Ectopies
Authors: Hasebe Hideyuki , Yoshida Kentaro , Iida Masataka , Hatano Naoki , Muramatsu Toshiro , Aonuma Kazutaka
Published: July 2021

Background:
A left-to-right dominant frequency (DF) gradient exists in acute atrial fibrillation (AF) in animals and in paroxysmal AF (PAF) in humans. PAF initiated by right atrial ectopy (PAF-RAE) is rare. Adenosine triphosphate (ATP) can be effective to unmask such a rare non-pulmonary vein (PV) ectopy and accelerate the frequency of a reentrant source of AF (driver).

Objective:
This study aimed to investigate characteristics of patients with PAF-RAE using pharmacological maneuvers and spectral analysis.

Methods:
Enrolled were 111 consecutive patients referred for catheter ablation of lone PAF. Infusions of isoproterenol and ATP were used to induce AF. Patients with PAF initiated only by PV ectopies and with PAF-RAE were classified into the PV-ectopy group (N=32) and RA-ectopy group (N=6), respectively. ATP was also injected during ongoing AF to unmask the AF driver. High RA, coronary sinus (CS), and PV-left atrial junction (PV-LAJ) electrograms underwent spectral analyses.

Results:
RA-ectopy group patients were younger (49±13 vs. 63±7 years, p<0.001), more commonly had a family history of AF (67% vs. 9%, p<0.001), and had a higher RA appendage/RA volume ratio (0.22±0.022 vs. 0.15±0.055, p=0.002) than PV-ectopygroup patients. The most common origin of RA ectopy was the base of the RA appendage (67%). There was a baseline right-to-left DF gradient in the RA-ectopy group (PV-LAJ: 6.0±0.4, CS: 5.7±0.7, RA: 7.4±0.8 Hz, p<0.05), in contrast to a left-to-right DF gradient in the PV-ectopy group (PV-LAJ: 5.9±0.8, CS: 5.3±0.7, RA: 5.2±0.8 Hz, p<0.01). ATP injection mainly increased the DF of the high RA, augmenting a right-to-left DF gradient in the RA ectopy group (PV-LAJ: 8.0±2.0, CS: 7.8±1.0, RA: 10.7±0.7 Hz, p<0.05), whereas it augmented a left-to-right DF gradient in the PV-ectopy group (PV-LAJ: 7.9±1.0, CS: 6.4±0.5, RA: 6.6±1.2 Hz, p<0.05).

Conclusions:
PAF-RAE may be maintained by a reentrant driver localized in the RA (so-called right atrial fibrillation).
Abstract 10257: Vascular Expansion During Worsening of Heart Failure: Effects on Clinical Features and Its Determinants
Authors: Kataoka Hajime
Published: July 2021

Introduction:
During worsening heart failure (HF), it is unknown whether clinical features differ according to the level of vascular expansion, and how changes in serum substance(s) are associated with volume changes.

Hypothesis:
Changes in serum solutes/albumin are associated with vascular expansion and induce different clinical features during HF worsening.

Methods:
Data from 47 HF patients that experienced a worsening HF episode were analyzed. Each patient had at least 2 of the following HF signs: S3, rales, leg edema, body weight (BW) gain (≥1.5 kg), and ultrasound pleural effusion. Blood tests included hemoglobin (Hb), hematocrit (Ht), albumin, solutes [sodium (Na), potassium, chlorine (Cl), blood urea nitrogen, creatinine (Cr), and uric acid], and b-type natriuretic peptide (BNP). The relative change in the vascular expansion from stable to worsening HF was estimated based on changes in the plasma volume (%PV) as follows: 100 x {Hb (stable) x [1-Ht (worse)]}/ {Hb (worse) x [1-Ht (stable)]}-100.

Results:
When divided into two groups by the median %PV, the clinical features of the expansion group [11≤%PV (range 11 to 36%); n=24] had a lower incidence of rales (13 vs 52%, p=0.005) and a tendency toward preserved renal function defined by a decrease in serum Cr (83 vs 57%, p=0.06) as compared with the non-expansion group [%PV (range -19 to 10.8%)<11;n= 23], though the increase in BW and log BNP did not differ between groups. The expansion group had a greater increase in serum Na (3.58±4.43 vs -0.11±3.31mEq, p=0.0016) and Cl (5.54±6.24 vs -0.03±4.18, p=0.0006), and a greater decrease in albumin (-0.37±0.3 vs -0.16±0.3, p=0.04) from stability to worsening HF. Logistic regression analysis revealed an independent association between the increase in %PV and the increase in the serum Cl concentration from stability to HF worsening (OR:12.5, 95%CI: 1.89-82, P=0.009).

Conclusions:
Vascular expansion during worsening HF is associated with changes in the serum Cl concentration. As a key osmolyte, greater accumulation of this solute in the blood vessels might act to increase or maintain intravascular volume, which induces different clinical features of HF, such as a lower incidence of rales and preserved renal function due to maintenance of the blood supply to the kidney.
Abstract 10261: Musculoskeletal Pain in Cardiac Sonographers: A Multisite Case Control Study
Authors: Orme Nicholas M , Geske Jeffrey B , Pislaru Sorin V , Askew John W , Lennon Ryan J , Lewis Bradley R , Rihal Charanjit S , Singh Mandeep , Pellikka Patricia A
Published: July 2021

Background:
Transthoracic echocardiography is the mainstay of cardiac imaging and is highly dependent upon cardiac sonographers for whom image acquisition can be physically demanding and associated with musculoskeletal pain. Prior studies are limited by the absence of adequate control groups and a lack of adjustment for potential confounders.

Objectives:
The purpose of this study was to determine the prevalence and impact of work-related musculoskeletal pain in cardiac sonographers as compared to a large control group of non-invasive healthcare professionals with similar demographics.

Methods:
An electronic survey was administered to Mayo Clinic employees identified by human resources at six major patient care facilities in four different states.

Results:
There were 2682 employees within the departments of cardiology and radiology who were contacted and 1532 (57%) completed the survey. After exclusion of those who wear protective lead aprons, 517 employees comprised the control group and 66 cardiac sonographers made up the study group. Cardiac sonographers and the control group were similar in age, sex, BMI, length of employment and history of prior musculoskeletal pain. Cardiac sonographers reported work-related musculoskeletal pain more frequently than the control group (88% vs 40%; p<0.001). This association persisted after multivariable adjustment for age, sex, body mass index, length of current employment and history of pre-existing musculoskeletal pain (OR 11.6; (95% CI 5.32, 25.5); p<0.001). Cardiac sonographers were more likely to seek medical care for their work-related pain (55% vs 21%; p<0.001) and to have missed work due to pain (35% vs 12%, p<0.001).

Conclusions:
In this multi-site case control study, cardiac sonographers experienced significantly more work-related pain and missed more work due to pain than a large control group of non-invasive healthcare professionals with similar demographics.
Abstract 10404: Incidence and Predictors of Asymptomatic Pericardial Effusion After Transcatheter Closure of Atrial Septal Defect
Authors: Wang Jingjin , Patel Mehul , Xiao Minghu , Xu Zhongying , Jiang Shiliang , Wang Hao
Published: July 2021

Introduction:
Pericardial effusion (PE) without obvious periprocedural complications (e.g., cardiac perforation, device erosion) may occur after transcatheter closure of secundum atrial septal defects (ASD).It has only been described in case reports, and has not been the subject of systematic study.

Hypothesis:
The aim of the study is to investigate the incidence and predictors of PE unrelated to procedural complications, thus providing interventional cardiologists with a novel way to approach new-onset PE after ASD closure.

Methods:
We included all patients who had undergone successful percutaneous ASD closure from June 2009 to April 2014 (n=2652) with no preexisting PE or cardiac perforation or erosion. Transthoracic echocardiography (TTE) was performed during the procedure and 1, 3, and 6 months postoperatively.

Results:
After device implantation, fifty patients (1.9 %) developed new-onset PE (37 immediately, 13 during follow-up). These patients were asymptomatic, stable hemodynamically, and had no new arrhythmias. PE appeared mild (5.1±1.9 mm) and homogeneously echo-lucent by TTE (Figure). PE diminished spontaneously. Compared with 2602 patients without PE, factors independently predicting asymptomatic PE were the device touching the atrial free wall, device size, patient age, and total defect size (Table). Areas under the receiver operating characteristic curves were 0.78 (p<0.001), 0.66 (p<0.001) and 0.77 (p<0.001) for device size, patient age, and total defect size, respectively.

Conclusion:
A new type of PE is firstly reported systematically. Our data provide new insights into new-onset PE after percutaneous ASD closure.
Abstract 10459: Acute Hemodynamic Effects of Adaptive Servoventilation in Patients With Pre-Capillary and Post-Capillary Pulmonary Hypertension
Authors: Bitter Thomas , Frank Anika , Fuge Jan , Welte Tobias , Hoeper Marius M , Olsson Karen M
Published: July 2021

Introduction:
Since recent data suggest an increased cardiovascular mortality associated with adaptive servoventilation therapy (ASV) in patients with heart failure with reduced ejection fraction and central sleep apnea there is major concern of whether to use this therapy in other diseases such as heart failure with preserved ejection fraction (HFpEF) or precapillary pulmonary Hypertension (PH).

Hypothesis:
This study therefore aimed to clarify acute hemodynamic effects of ASV in patients with HFpEF or PH.

Methods:
A series of clinically stable patients with pre- or post-capillary PH underwent ASV therapy (maximum pressure support 25 mmHg, minimum pressure support 15 mmHg) during right heart catheterization. Hemodynamics were measured at rest, at the end of a 15-minute episode of ASV therapy, and 15 minutes after ASV completion. Hemodynamic variables included heart rate, systemic blood pressure, right atrial pressure (RAP), mean pulmonary artery pressure (PAPm), pulmonary arterial wedge pressure (PAWP), cardiac output measured by thermodilution, and pulmonary vascular resistance (PVR).

Results:
The study enrolled 33 patients; 12 patients with post-capillary PH due to HFpEF, and 21 patients with pre-capillary PH due to pulmonary arterial hypertension (n=8) or chronic thromboembolic pulmonary hypertension (n=13). ASV was well tolerated by all patients and resulted in reductions in blood pressure, heart rate, PAPm (-5 mmHg, p <0.001) and PVR (-10%, p=0.01). Right and left filling pressure increased, while the cardiac output decreased (-0.4 L/min; p<0.001). The hemodynamic effects of ASV were almost identical in both patient populations.

Conclusions:
ASV has moderate hemodynamic effects in patients with HFpEF or PH of various origins, most importantly a consistent decline in PAPm and cardiac output. ASV was safe and well tolerated during this short-term study, but the observed drop in cardiac output may be of concern if this treatment is applied in patients with advanced HFpEF or PH with severely impaired right ventricular function.