bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11827: Endothelial Microparticles Modulate Vasculitis During the Acute Phase of Kawasaki Disease
Authors: Nakaoka Hideyuki , Hirono Keiichi , Okabe Mako , Miyao Nariaki , Saito Kazuyoshi , Ibuki Keijiro , Ozawa Sayaka , Takahashi Kei , Ichida Fukiko
Published: April 2024

Introduction:
Kawasaki Disease (KD) is an acute inflammatory disease that takes the form of systemic vasculitis. Endothelial microparticles (EMPs) are vesicles formed by cell membranes after endothelial activation, which contain microRNAs (miRs) recognized as an important transcellular delivery system in the exchange of biological signals. The purpose of this study was to elucidate whether EMPs are involved in vasculitis in acute KD.

Methods:
We enrolled 50 KD patients (aged 4 months to 14 years), 50 controls (25 non-KD febrile and 25 healthy children). KD patients were divided into two subgroups: those with coronary artery lesions (CAL, Z-socre>2.5, n=4) and those without coronary artery lesions (NCAL, Z-score≦2.5, n=46). Blood samples were collected three times; first, at the time of diagnosis before the initiation of IVIG treatment; second, immediately after the first IVIG infusion; finally, at 2-4 weeks after the onset of the disease. EMPs were measured using flow cytometry and miR expression profiling was performed using microarrays (Affymetrix
®
GeneChip
®
miRNA 4.0). We also performed miRCURY LNA™ microRNA in situ hybridization using 2 miRs in CAL patients and analyzed THP-1 monocyte stimulation using 2 miRs.

Results:
The percentage of EMPs was 1.27±0.16% in all of the small vesicles in KD patients prior to treatment, which was significantly higher than in controls (0.09±0.03%:
P
<0.0001). Furthermore the percentage of EMPs in patients with CAL rapidly increased after the initial treatment, and was significantly higher than those without CAL (p<0.001). We identified two miRs (hsa-miR-145-5p and hsa-miR-320a) out of 2578 miRs (0.08%) specific to the patients with CAL and these two miRs are predicted to affect the monocyte system using
in silico
analysis. We also detected these two miRs in CAL patients’ endothelial cells, using in situ hybridization, and showed these two miRs suppressed gene expression of the two inflammatory cytokines (IL-6 and TNF-α).

Conclusions:
EMPs could serve as a sensitive marker of the severity of endothelial dysfunction and vasculitis in acute KD. Moreover, hsa-miR-145-5p and hsa-miR-320a may contribute to regulation of gene expression of cytokines and pathogenesis of KD.
Abstract 11828: Follow-up of Genetically Confirmed Adult Long QT Syndrome Type 1 and 2 Patients: Clinical Course and Tools for Mutation-specific Risk Stratification
Authors: Koponen Mikael , Marjamaa Annukka , Viitasalo Matti , Toivonen Lauri , Swan Heikki
Published: April 2024

Introduction:
Long QT syndrome (LQTS) is an inherited cardiac disorder predisposing to sudden cardiac death (SCD). Research has been scarce on its clinical course in genetically confirmed patients not receiving β-blocker therapy. Also, applicability of specific mutations as a part of risk stratification calls for further investigation.

Methods:
The study population was drawn from the Finnish Inherited Cardiac Disorder Research Registry comprising 4000 molecularly tested subjects. The inclusion criteria were 1) genetically confirmed
KCNQ1
or
KCNH2
mutation, or non-carrier status of the family-specific LQTS mutation, and 2) the age of 18-40 years during the follow-up. A questionnaire was sent to the study subjects. Data of all deaths were obtained from Statistics Finland, and data of ICD and pacemaker implantations were acquired from Hospital discharge register (HDR).

Results:
A total of 2723 subjects fulfilled the inclusion criteria. Of them 14 died during the follow-up, 1495 (55%) responded to the inquiry, and additional 12 subjects with device therapy were drawn from the HDR. The final study population (n=1521) consisted of 867 LQTS mutation carriers (617 with
KCNQ1
, 242 with
KCNH2
, and seven with ≥1 mutation), and 654 non-carrier relatives. The total follow-up time including retrospectively collected data was 18.3±6.3 years. In mutation carriers, risk factors for cardiac events before initiation of β-blocker included LQT2 genotype (hazard ratio [HR]=2.1, p=0.002), female gender (HR=3.2, p<0.001), a cardiac event before the age of 18 years (HR=5.9, p<0.001), and QTc ≥500 ms (vs <470 ms, HR=2.7, p=0.01). LQT1 patients carrying the
KCNQ1
D317N mutation were at higher risk (HR=3.0-3.9, p<0.001-0.03) compared to G589D, c.1129-2A>G and other
KCNQ1
mutation carriers after adjusting for gender and QTc duration.
KCNH2
c.453delC, L552S and R176W mutations associated with lower risk (HR=0.12-0.24, p<0.001) than other
KCNH2
mutations. Of the seven SCDs four, and of the 14 aborted cardiac arrests three involved QT-prolonging drug.

Conclusions:
Specific mutations modulate the risk independently of gender and QTc duration. The avoidance of QT-prolonging drugs is fundamental in the prevention of potentially life-threatening cardiac events.
Abstract 11874: Sympathetic Control of Reflex Cutaneous Vasoconstriction in Human Hypertension
Authors: Greaney Jody L , Kenney W. L , Alexander Lacy M
Published: April 2024

Introduction:
Cardiovascular-related morbidity and mortality during environmental cold exposures increase disproportionally in hypertensive (HTN) adults. Although alterations in central control of sympathetic outflow and peripheral regulation of vascular function are evident in hypertension and contribute to increased cardiovascular risk, no studies have examined sympathetic control of reflex cutaneous vasoconstriction during cold stress in humans with hypertension. We hypothesized that 1) whole-body cold stress would elicit exaggerated increases in skin sympathetic nervous system activity (SSNA) and greater reductions in skin blood flow in HTN [n=10; 56±3 yrs; resting blood pressure (BP) 145±7/84±3 mmHg] compared to normotensive adults (NTN; n=12, 55±3 yrs; resting BP 126±4/79±3 mmHg) and 2) cutaneous adrenergic sensitivity would be increased in HTN adults.

Methods:
In Protocol 1, reflex vasoconstriction was induced by gradual whole-body cooling (to a mean skin temperature of 30.5°C) using a water-perfused suit. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry; dorsum of foot) were measured continuously. SSNA was expressed as a percent change from baseline. In Protocol 2, an intradermal microdialysis fiber was placed in the skin of the lateral calf to measure red cell flux in response to graded intradermal infusions of norepinephrine (NE; 10
-12
to 10
-2
M). In each study, cutaneous vascular conductance (CVC=flux/mean arterial pressure) was expressed as a change from baseline.

Results:
During cooling, HTN exhibited greater increases in SSNA compared to NTN adults (Δ = 194±26% HTN vs. 51±12% NTN; P<0.01) but cutaneous vasoconstriction was not different between groups (ΔCVC
base
= -0.03±0.003 ητν vs. -0.02±0.01 flux units mmHg
-1
NTN; P=0.97). The slope of the relation between ΔSSNA and ΔCVC
base
during cold stress was blunted in HTN adults (P<0.01). There was no group difference in cutaneous adrenergic responsiveness to exogenous NE (dose-response logEC
50
; -7.2±0.2 HTN vs. -7.5±0.4 NTN; P=0.75).

Conclusion:
Although cutaneous microvascular adrenergic responsiveness to NE is preserved, the sensitivity of the sympathetic reflex response to whole-body cold stress is diminished in human hypertension.
Abstract 11902: Mitochondria-targeted Antioxidant Therapy Improves Age-related Collateral Development With Ischemia Through p53 and Peroxisome Proliferator-activated Receptor γ Coactivator-1α (PGC-1α)
Authors: Miura Shunsuke , Kokubun Tomoki , Saitoh Shu-ichi , Takeishi Yasuchika
Published: April 2024

Background:
Aging is a major factor to decline collateral growth with ischemia, however, the underlying mechanism remains unclear.

Methods and Results:
We investigated the pathophysiological role of mitochondrial oxidative stress (MOS) in hindlimb ischemia with femoral artery ligation in young mice [8 weeks old (W)] and old mice (80 W) with or without treatment of a mitochondria-targeted antioxidant, MitoTEMPO [180 μg/kg/day, from before operative day 7 to post operative day (POD) 21] infusion using a subcutaneously implanted mini-pump. The recoveries of cutaneous blood flow in hindlimb and capillary density on POD 21 were lower in old mice than in young mice, that were improved in MitoTEMPO-treated old mice. Mitochondrial DNA damage was appeared in ischemic skeletal muscles of old mice, that was eliminated by MitoTEMPO treatment. On POD 2, treatment of MitoTEMPO suppressed the level of p53, the ratio of Bax/Bcl-2 and upregulated the levels of HIF-1α and VEGF in ischemic skeletal muscles of old mice. On POD 21, treatment of MitoTEMPO preserved the level of PGC-1α and its transcriptional factor, estrogen-related receptor α, in ischemic skeletal muscles of old mice. Ischemic soleus of old mice showed lower mitochondrial respiratory control ratio (state 3 respiration/state 4 respiration) on POD 21 than that of young mice, that was recovered in MitoTEMPO-treated old mice (young mice: 3.36±0.08, Old mice: 2.15±0.24 vs. MitoTEMPO-treated old mice: 3.37±0.03, P<0.01).

Conclusion:
These data suggest that scavenging of MOS recovers collateral growth with ischemia through suppression of p53 and preservation of PGC-1α.
Abstract 11919: A Potent and Selective Covalent Inhibitor of JNK Protects Heart From Both Ischemia/Reperfusion- and Hypertension-induced Heart Failure
Authors: Chen Xu , Quan Nanhu , Wang Lin , Chu Dongyang , Zhao Peng , Xue Mei , Bi Yanping , Cates Courtney , Li Ji
Published: April 2024

Introduction:
c-Jun NH
2
-terminal kinases (JNKs) are critical mediators of a variety of detrimental stimuli including ischemia-reperfusion (I/R) and mechanical stress induced by pressure overload. A novel synthesized highly selective JNK inhibitor, JNK-IN-8, can form an ATP site-directed covalent bond with a conserved cysteine residual in all JNKs, therefore, it may be broadly useful as a pharmacological tool for inhibiting JNK-dependent signal transduction that is involved in various pathological conditions.

Hypothesis:
The potent JNK inhibitor, JNK-IN-8, could act as a cardioprotectant against ischemia/reperfusion (I/R)- or hypertension-induced heart failure.

Methods:
The effects of JNK-IN-8 were monitored in a mouse I/R models with the left anterior descending coronary artery occluded and subsequently released, and a mouse model of transverse aortic constriction (TAC), in which pressure overload hypertrophy was induced in 4 weeks.

Results:
JNK-IN-8 treatment significantly reduced myocardial infarct area by 40% in mouse ischemia and reperfusion (I/R) model as compared to the vehicle groups (p<0.01). Interestingly, the immunohistochemistry data showed that JNK-IN-8 treatment attenuated the macrophage infiltration and caspase-3 executed apoptosis signaling in TAC-induced heart failure mice (p<0.01
vs.
vehicle groups). Moreover, the staining of wheat germ agglutinin (WGA) and Masson trichrome staining revealed that there are significant decreases in hypertrophy and fibrosis in the hearts of JNK-IN-8 treated TAC-induced heart failure mice. Furthermore, the immunoblotting data demonstrated that JNK-IN-8 treatment selectively attenuated both I/R- and pressure overload-induced JNK and downstream oxidative stress p-SHC (p66), inflammatory NF-kappaB signaling pathways, while the levels of other mitogen protein kinase family signals (p-p38 and p-ERK) remained unchanged, indicating the specificity of JNK-IN-8 on JNK signaling in the heart.

Conclusions:
JNK-IN-8 reduces myocardial infarction caused by ischemia and reperfusion, and attenuates pressure overload-induced inflammation, apoptosis, hypertrophy and fibrosis. Thus JNK-IN-8 is a potential therapeutic drug for I/R- and pressure overload-induced heart failure.
Abstract 12017: New-Onset Diabetes After Heart Transplantation is associated With Worse Long-term Survival: A Propensity Matched Analysis of a National Registry.
Authors: Deo Salil V , Sarabu Nagaraju , Kumar Sachin , Altarabsheh Salah , Dunlay Shannon M , Kilic Ahmet , Oliveira Guilherme H , Fonarow Gregg C
Published: April 2024

Introduction:
Limited data is available regarding the incidence of new-onset diabetes mellitus (NODM) after heart transplantation and it`s impact on patient survival.

Hypothesis:

Methods:
From the United Network of Organ Sharing database (January 2004 to September 2014), we identified 13,353 patients without pre-operative diabetes mellitus undergoing heart transplantation. Multivariable Cox regression was implemented to determine predictors for the development of NODM. A matched cohort of New-onset Diabetes mellitus (NODM (+)) and NODM (-) was generated by 1:1 nearest neighbor propensity-matching. The association of NODM with long-term survival was then estimated with robust Cox regression. Results are presented at the 95% Confidence level; all tests are two-tailed.

Results:
During the study period, 1,921 of 13,353 (14%) developed NODM. Estimated freedom from NODM was 97% (96-98%) & 77% (76 - 78%) at the end of 1 and 5 years respectively. Predictors for the development of NODM were recipient age > 50 years (HR 1.2 95% CI1.05, 1.3; p < 0.01), recipient BMI > 30 (HR 1.4 95% CI1.2, 1.6; p < 0.01) and race (African American vs Caucasian (HR 1.3 95% CI1.2, 1.5; p < 0.01)). Cox-regression of a propensity-matched cohort of 1921 NODM+ve and NODM-ve recipient-pairs demonstrates that NODM is associated with poorer survival (HR for mortality: 1.3 95% CI 1.1, 1.5; p < 0.001).

Conclusions:
More than one in ten heart transplant recipients develop NODM post heart transplantation. Obesity, older age, and African American race patients to be at higher risk for NODM. New onset diabetes was independently associated with an almost 30% reduced long-term survival. More than one in ten heart transplant recipients develop NODM post heart transplantation. Obesity, older age, and African American race patients to be at higher risk for NODM. New onset diabetes was independently associated with an almost 30% reduced long-term survival.
Abstract 12077: Stroke as the First Manifestation of Atrial Fibrillation
Authors: Jaakkola Jussi , Mustonen Pirjo , Kiviniemi Tuomas , Hartikainen Juha E , Palomäki Antti , Hartikainen Päivi , Nuotio Ilpo , Ylitalo Antti , Airaksinen K.E. J
Published: April 2024

Introduction:
Atrial fibrillation (AF) may remain undiagnosed until an ischemic stroke occurs. In this retrospective cohort study we assessed the prevalence of ischemic stroke or transient ischemic attack (TIA) as the first manifestation of AF in a cohort of patients with AF-associated stroke or TIA.

Methods:
Altogether 3,623 patients treated for their first ever ischemic stroke or TIA during 2003-2012 were identified from the electronic patient records of four clinical centers. Two groups were formed: patients with a history of AF and patients with new AF diagnosed during hospitalization for stroke or TIA. A control group of 781 patients with intracranial hemorrhage was compiled similarly to explore the direction of causality between new AF and stroke.

Results:
The median age of the patients was 78.3 [13.0] years and 2,009 (55.5%) were women. New AF was diagnosed in 753 (20.8%) patients with stroke or TIA, compared to 15 (1.9%) with intracranial hemorrhage. Younger age (odds ratio [OR]: 1.01; 95% confidence interval [CI]: 1.00-1.02; p=0.014) and no history of coronary artery disease (OR: 1.45; 95% CI: 1.16-1.82; p=0.001) or other vascular diseases (OR: 1.75, 95% CI: 1.09-2.79. p=0.020), heart failure (OR: 2.62; 95% CI: 1.94-3.54, p<0.001), or hypertension (OR: 1.22; 95% CI:1.01-1.47; p=0.041) were the independent predictors of new AF detected concomitantly with an ischemic event. Thus, ischemic stroke was the first clinical manifestation of AF in 37% of younger (<75 years) patients with no history of cardiovascular diseases (Figure).

Conclusions:
In conclusion, AF is too often diagnosed only after an ischemic stroke has occurred, especially in middle-aged healthy individuals. New AF seems to be predominantly the cause of the ischemic stroke and not triggered by the acute cerebrovascular event.
Abstract 12089: The Association Between Post-Operative Pulmonary Hypertension and Survival After Mitral Valve Surgery
Authors: Kiefer Todd L , Samad Zainab , Pomann Gina-Marie , Poon Victor , Shatila Wassim , Lokhnygina Yuliya , Velazquez Eric J , Wang Andrew
Published: April 2024

Introduction:
Pulmonary hypertension (PH) is a common complication of mitral valve disease, but the prognostic significance of PH after mitral valve surgery (MVS) is unclear.

Hypothesis:
Post-operative PH after mitral valve repair or replacement is associated with worse survival.

Methods:
Retrospective study at a single, tertiary medical center (1995-2015) using echo database. Patients with moderate-severe or severe regurgitation and/or stenosis who had 1) preoperative transthoracic echocardiogram (TTE) within 6 months of MVS; 2) post-operative TTE at least 30 days after MVS; 3) right ventricular systolic pressure (RVSP) measurement on both TTEs. The primary endpoint of the study was survival after post-op TTE. Non-parametric Kaplan-Meier method was used to estimate distribution of time to death related to severity of pre-op and post-op RVSP. Cox proportional hazards modeling was used to evaluate the relationship between post-op RVSP and survival with adjustment for co-variates including pre-op RVSP.

Results:
259 patients met inclusion criteria. Median time to post-operative TTE from MVS was 244 (IQR 86, 421) days. The mean RVSP was 47.2 (16) mm Hg. Following MVS, a statistically significant decrease in the post-operative compared with pre-operative RVSP was observed for the overall cohort (mean RVSP 39.1 [14.0] mm Hg), specifically in patients with baseline RVSP ≥35 mm Hg, but 53 (20.5%) patients had post-op RVSP >50 mm Hg. PH after MVS was significantly associated with lower survival in follow-up in the unadjusted log-rank test for trend (Figure). Post-op RVSP, but not pre-op RVSP, was significantly associated with mortality in the Cox proportional hazards model with adjustment for age, race, comorbidities, mitral stenosis, and if performed, mitral replacement size (RVSP >50mm Hg vs. RVSP ≥35 mm Hg: HR 2.214, 95% CI 1.316, 3.724, p=0.0027).

Conclusion:
Post-operative PH is significantly associated with lower survival after mitral valve surgery.
Abstract 12107: Worsening of Mitral Regurgitation During Off-pump Coronary Artery Bypass Grafting Causes Hemodynamics Deterioration by Dislocation of Beating Heart in Patients With Ischemic Heart Disease
Authors: Iwai-Takano Masumi , Fujimiya Tsuyoshi , Igarashi Takashi , Takase Shinya , Yokoyama Hitoshi
Published: April 2024

Introduction:
Worsening of mitral regurgitation (MR) during off-pump coronary artery bypass grafting (OPCAB) is one of the predictors, which is often observed during elevation and dislocation of the beating heart in patients with ischemic heart disease (IHD). It is considered that morphological changes of mitral valve complex and worsening of MR cause the hemodynamic deterioration during OPCAB. However, it remains unclear whether the worsening of MR causes the hemodynamic deterioration during OPCAB.

Hypothesis:
The dislocation of the beating heart during OPCAB leads to exacerbation of ischemic MR, and the worsening of MR relates with hemodynamics deterioration.

Methods:
We enrolled 19 patients with IHD, who did not show significant MR in pre-operative period. All patients undertook OPCAB. During OPCAB, we positioned the beating heart in 4 positions for CABG, i.e., control, LAD-, RCA-, and LCX- positions, using Starfish heart positioner
TM
and Octopus 2
TM
(Medtronic). In each position, we assessed the MR jet area by 2D-TEE and the hemodynamic parameters. We evaluated the relationship the worsening of MR and the hemodynamics deterioration.

Results:
Among the 4 positions, there was a significantly different in central venous pressure (CVP, Control: 9.6±2.7, LAD: 9.5±2.3, LCX: 10.9±2.4, RCA: 10.2±2.6 mmHg, P<0.01) and stroke volume (SV, Control: 69.1±23.3, LAD: 67.9±19.4, LCX: 52.3±14.4, RCA: 51.7±16.1 ml, P<0.01), but not in mean systemic pressure and mean pulmonary arterial pressure (mPA). The MR jet area was significantly increased in LCX and RCA positions compered to control position (control: 0.8±0.7 to LCX: 2.6±2.7, RCA: 2.0±2.2 cm
2
, each P<0.05). In LCX position, the MR jet area has the relationship with mPA (R=0.51, P<0.05) and SV (R=–0.71, P<0.01). On the other hand, the worsening of MR did not show the relationship with the wall motion score index, the location of asynergy and the hemodynamics before OPCAB.

Conclusion:
The dislocation of the beating heart during OPCAB (especially LCX and RCA positions) leads to the worsening of MR that relates with hemodynamics deterioration.
Abstract 12117: Global Real-World Data on the Use of Lomitapide in Treating Homozygous Familial Hypercholesterolemia: The Lomitapide Observational Worldwide Evaluation Registry (LOWER), Two-Year Data
Authors: Underberg James , Cannon Christopher , Larrey Dominique , Makris Lukas , Schwamlein Charles , Phillips Helen , Bloeden LeAnne , Blom Dirk
Published: April 2024

Introduction:
Lomitapide is a microsomal triglyceride transfer protein inhibitor indicated as adjunctive therapy for adults with homozygous familial hypercholesterolemia (HoFH). LOWER is a global observational registry to prospectively assess long-term, safety and effectiveness of lomitapide in clinical practice. Adult HoFH patients treated with lomitapide in clinical practice are eligible.

Results:
As of March 1, 2016, 143 patients had been enrolled in the USA, Canada, EU and Taiwan (Table); 139 patients had lomitapide exposure data (median 17.7 months, range 0.3-35.9 months). Globally, median lomitapide dose was 10 mg QD (range 5 mg QOD-40 mg QD, 6-33 months). A ≥ 50% reduction in LDL-C at any time post-baseline was measured in 58% of patients; 62% of patients achieved LDL-C < 100 mg/dL and 37% achieved LDL-C < 70 mg/dL. AEs were experienced by 73% of patients; GI disorders were the most common (45%). Serious AEs occurred in 21 (15%) patients. Thirty-three (24%) patients discontinued lomitapide because of an AE. Events of special interest comprised: major adverse cardiovascular events (11 patients, resulting in 2 deaths); hepatic events (19 patients, 6 discontinuations); GI events (20 patients, 16 discontinuations); oncologic events (2 patients: 1 pancreatic mass [diagnosis unconfirmed], 1 mediastinal B-cell lymphoma); 1 pregnancy; no coagulopathy events. Liver function tests were always performed per the label in 48% of patients. Peak ALT and AST was normal in 35% of patients and ≥ 3x ULN in 21% (among which 5% had ≥ 5x - <10x ULN). No cases of Hy’s Law were recorded.

Conclusions:
The LOWER registry demonstrated safety and efficacy consistent with product labeling in patients treated with lomitapide for up to 3 years, but efforts are needed to improve prescriber adherence to recommended hepatic safety monitoring. There were no new safety signals and LDL-C reduction was consistent and robust, with 62% of patients achieving LDL-C < 100 mg/dL.
Abstract 12142: Are Outcomes After Cardiac Arrest Influenced by the Quality of ICU Care?
Authors: Pitcher Joseph H , Dziodzio John T , Keller Joshua A , Riker Richard R , Seder David B
Published: April 2024

Objective:
To determine the association of modifiable hemodynamic and biochemical factors with outcome after cardiac arrest.

Hypothesis:
Optimal control of modifiable post-arrest factors for secondary injury improves outcome after cardiac arrest.

Methods:
We identified 222 consecutive cardiac arrest patients who received targeted temperature management in the Maine Medical Center registry from 1/2013 to 8/2015. We abstracted demographics, intra-arrest factors, and modifiable post-arrest factors [e.g. the absence of hypotension (MAP<60mm Hg in the first 6 hours), normoglycemia (median glucose 80-180mg/dl), normoxemia (no PaO2>300 or <60mm Hg), and normocapnia (median PCO2 30-50mm Hg)] during the first 24 hours after return of spontaneous circulation. Primary outcome was cerebral performance category (CPC) at discharge. We compared pre-arrest, intra-arrest, and modifiable post-arrest factors in patients with good and poor outcomes using the Wilcoxon or Fischer-exact test, as appropriate. We also constructed logistic regression models to determine the independent effects of these factors on outcome (SAS 9.3, Cary, NC).

Results:
Thirty percent of patients had a CPC 1-2 at discharge. In univariate analysis, pre-arrest factors associated with poor outcome were history of COPD, cardiovascular disease, hypertension. A shockable rhythm was associated with good outcome. Of the studied modifiable post-arrest factors, normoglycemia was significantly associated with good outcome (p=0.002). In multivariate analysis that included pre-arrest and intra-arrest variables, optimal control of two or more post-arrest factors was associated with improved outcome (OR 7.2, p=0.0007, AUC for model 0.842).

Conclusions:
Optimal control of blood glucose, oxygen, carbon dioxide and blood pressure in the post-arrest period is associated with improved outcome after cardiac arrest. The combined endpoint of 2 or more post-arrest modifiable targets controlled was the strongest post-arrest predictor of good outcome in our model. While previous studies have reported these factors to be individually associated with poor outcome, further studies evaluating how the combination of these factors contribute to outcome is warranted.
Abstract 12159: Metabolite Profiles Are Associated With Metabolically Unhealthy Obesity in Children and Adolescents
Authors: Spahillari Aferdita , de Ferranti Sarah , Osganian Stavroula , Pacold Michael E , Shah Ravi V , Murthy Venkatesh L
Published: April 2024

Background:
Metabolite profiling has been used to identify mechanisms of cardiometabolic disease (CMD). Whether metabolites can identify metabolic healthy obesity (MHO) versus unhealthy obesity (MUO) remains unclear.

Hypothesis:
We hypothesized that specific metabolite profiles would be associated with adverse cardiometabolic phenotypes in non-diabetic overweight/obese youth.

Methods:
We performed untargeted metabolomics (81 polar metabolites) in 90 overweight/obese youth (age 15.5±4.8 years, 54% female, BMI 33.8±10.0 kg/m
2
), and used principal components analysis to identify metabolite clusters. Metabolically unhealthy obesity (MUO) was defined as one of the following: homeostatic model of insulin resistance (HOMA-IR) ≥ 3.16, hypertension (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg), triglycerides ≥ 150 mg/dl, HDL <40 mg/dl or glucose ≥100. We used logistic regression to estimate the association between metabolite clusters and MUO.

Results:
Five principal components (PC) accounted for 61.9% variance in polar metabolites. Polar PC2 contained aromatic amino acids (phenylalanine, tyrosine), branched-chain amino acids (e.g., leucine, valine, isoleucine), and their downstream metabolites (e.g., glutamine) and was associated with MUO (odds ratio OR=1.92, 95% confidence interval CI 1.06-3.48, P=0.03).

Conclusions:
We identified patterns of metabolites previously implicated in diabetes risk in adults (e.g., branched chain and aromatic amino acids) associated with CMD phenotypes in overweight/obese youth. Common metabolic pathways contribute to heterogeneity in cardiometabolic health in pediatric obesity as in adults.
Abstract 12183:
SLCO1B1
Genotype-Guided Statin Therapy Lowers LDL Cholesterol in Patients With Statin-Intolerance- A Randomized Controlled Trial
Authors: Voora Deepak , Perry Emily , Singh Kavisha , Trujillo Gloria , Milazzo Nicholas , Savard Dillon , Haga Susanne , Musty Michael D , Li Yi-Ju , Peyser Bruce
Published: April 2024

Introduction:
Statin-intolerance is a barrier to reducing cardiovascular disease risk. A genetic variant (*5, rs4149056) in the
SLCO1B1
statin hepatic transporter gene is well characterized and linked to higher statin concentrations, statin-intolerance, and statin non-adherence.
SLCO1B1*5
has a high negative predictive value for severe simvastatin myopathy; Pravastatin[P]/ fluvastatin[F]/ rosuvastatin[R] are preferred statins in *5 carriers to minimize side effects. The effects of
SLCO1B1
genotype-guided statin therapy or delivery of
SLCO1B1
genetic risk information are unknown.

Hypothesis:
Genotype-guided statin therapy (GGST) is superior to usual care in patients with statin-intolerance for statin-related outcomes.

Methods:
We randomly assigned 159 primary care patients with statin intolerance not prescribed statins to either GGST vs. usual care. GGST patients and their providers received
*5
genetic risk information about statin side effects and genotype-specific statin prescription recommendations. Patients in the usual care arm received general information regarding statin risk and prescriptions. The outcomes measured at 3 and 8 months were statin re-initiation, LDL cholesterol (LDLc), and statin adherence using the validated Morisky Medication Adherence Survey.

Results:
The median age was 64.0 years, 57% were female, 41% reported intolerance to > 1 statin, 75% reported myalgia with statins, and 25% were *5 carriers. Follow up was complete for 144 patients (91%) at 3-months and 118 (74%) at 8-months. At 3-months, GGST was associated with a higher proportion of patients who restarted statin therapy (55.4% vs. 38.0%, p=0.037), and lower LDLc (131.9±42.0 vs. 144.4±43.0, p=0.041), but similar statin adherence scores (p=0.96). Effects at 8-months were consistent with 3-month results for statin prescriptions (54% vs. 37%, p=0.07) and LDLc (128.6±37.9 vs. 141.0±44.4, p=0.07). Use of P/F/R was higher in
*5
carriers assigned to GGST versus usual care (92% vs. 67%, p=0.24).

Conclusion:
In primary care patients with statin-intolerance,
SLCO1B1
genotype guided statin therapy is effective in lowering LDLc compared to usual care. GGST, however, did not improve statin adherence in those who re-initiated statin therapy.
Abstract 12222: Patient-Reported Health and its Correlates in Adults With Congenital Heart Disease From 15 Countries
Authors: Moons Philip , Kovacs Adrienne H , Luyckx Koen , Apers Silke
Published: April 2024

Objectives:
The importance of patient-reported health assessment as a critical measure of cardiovascular health has been emphasized. In adults with congenital heart disease (ConHD), geographic differences in patient-reported health are assumed, but international studies using a uniform methodology are non-existent. We sought (1) to explore patient-reported health in an international sample of adults with ConHD, and (2) to investigate the association between patient characteristics and patient-reported health.

Methods:
In a cross-sectional study, 4,028 patients (median age=32 y; 53% women; 26% mild, 48% moderate, 26% complex defects) from 15 countries worldwide were included. Patient-reported health was assessed using the SF-12, yielding a Physical Component Summary (PCS) and a Mental Component Summary (MCS). Patient characteristics included sex, age, marital status, educational level, employment status, ConHD complexity, and patient-reported New York Heart Association (NYHA) class. Multivariable linear regression analysis was performed.

Results:
Mean PCS was 77.2 ±20.9 and mean MCS was 72.1 ±19.0, on a scale 0-100. Fig 1 shows the PCS and MCS per country (flags) and per disease complexity (lines). Malta and Sweden have the highest scores; and France, Taiwan and India have the lowest scores. Lower PCS (worse physical health) was significantly associated with female sex; older age; lack of employment; being divorced or widowed; less education; greater disease complexity; and worse NYHA class (adj. R
2
=0.512). Lower MCS (worse mental health) was significantly related to female sex; lack of employment; being divorced or widowed; having complex ConHD; and worse NYHA class (adj. R
2
=0.234).

Conclusions:
International variation in patient-reported health is confirmed. The detection of both medical and sociodemographic correlates of perceived health status allow clinicians to identify patients at risk for poor health and to target resources accordingly.
Abstract 12471: CHA
2
DS
2
VASc Score Predicts Future Development of Atrial Fibrillation After Successful Catheter Ablation of Typical Atrial–Flutter
Authors: Bhan Adarsh , Dunskis Paula , Neiger Jeffrey S , Blair Christopher , Duggal Manoj
Published: April 2024

Introduction:
After successful catheter ablation (CA) for typical atrial flutter (AFL), long term development of atrial fibrillation (AF) is common. No definitive predictive models currently exist to identify patients who are likely to develop AF. The aim of this study was to evaluate whether CHA
2
DS
2
VASc score can predict future occurrence of AF after successful CA of AFL.

Methods:
We conducted a retrospective chart review of 171 consecutive patients with isolated AFL who underwent successful CA between years 2007-2014 at a teaching community hospital. Patients with at least 2 years of follow-up were included for analysis. 40 patients were lost to follow-up. CHA
2
DS
2
VASc scores were calculated at the time of CA. Follow up consisted of in-office electrocardiograms, and (when available) in-office and remote device interrogation. Patients were anticoagulated at the discretion of their treating physician. The endpoint was time to first occurrence of AF. Data was analyzed using appropriate descriptive and univariate statistics to describe, compare and contrast based upon AF occurrence groups. A cox regression was performed to examine CHA
2
DS
2
VASc score as a predictor of AF occurrence during CA follow-up.

Results:
131 patients were included in the study. Average age was 66 ±11.5 years and follow-up duration was 26.6±1.5 months. AF occurred in 52 patients (39.7%) by 2 years. Patients who developed AF had a CHA
2
DS
2
VASc score of 3.4±1.4, compared to 2.6±1.3 for patients who did not (p < 0.003). Patients who developed AF were also older (70.2±10.3 vs. 63.7±11.6 years, p<.001,), and had a higher rate of Hypertension (3.40±1.35 vs. 2.6±1.3, p=.037,). CHA
2
DS
2
VASc score was found to be significantly associated with AF onset during the 2 year follow-up (p<.007, Hazard Ratio 1.36, 95%CI 1.09-1.70).

Conclusion:
The incidence of AF following CA of AFL is common. CHA
2
DS
2
VASc score may be a useful tool and predictor of AF after typical AFL ablation. This needs to be evaluated further in larger randomized trials which may help in guiding long term anticoagulation therapy.
Abstract 12511: Left Ventricular Hypertrophy by Electrocardiogram versus Cardiac Magnetic Resonance Imaging as a Predictor for Stroke: The MESA Study
Authors: Oseni Abdullahi O , Effoe Valery S , Kamel Hooman , Sandfort Veit , Gottesman Rebecca F , Lima Joao A , Bluemke David A , Soliman Elsayed Z
Published: April 2024

Background:
Left ventricular hypertrophy (LVH) is an established risk factor for stroke and is a component of the Framingham Stroke Risk Score (FSRS). It is unknown, however, if LVH detected by the electrocardiogram (ECG-LVH) is equally predictive of stroke as LVH detected by cardiac magnetic resonance imaging (MRI-LVH).

Methods:
We analyzed 4716 participants (mean age 61±10 years, 53.4% women, 38.2% whites) from the Multi-Ethnic Study of Atherosclerosis (MESA) who were free of cardiovascular disease at baseline (2000-2002). ECG-LVH was defined as values > 95
th
percentile of left ventricular mass (LVM) derived from an established race- and sex-specific ECG model for estimating LVM indexed to weight. MRI-LVH was obtained from LVM by cardiac MRI using the 95th percentile cut-off value of observed LVM/predicted LVM calculated as 1.31. Multivariable Cox regression was used to examine the association between 1-standard deviation (SD) increase in estimated ECG-LVM and MRI-LVM as well as ECG-LVH and MRI-LVH, separately, with incident ischemic stroke. Harrell’s C-index was used to estimate the predictive ability of the FSRS model when either ECG-LVH or MRI-LVH was included.

Results:
Over a median follow-up of 11.2 years, 119 participants developed stroke. In a model adjusted for demographics and components of the FSRS, ECG-LVM and MRI-LVM as well as ECG-LVH and MRI-LVH were all predictive of stroke with ECG-LVM and MRI-LVH showing stronger associations with stroke in terms of hazard ratios but with wider confidence intervals (Table). However, the ability of FSRS model to predict stroke was slightly better when MRI-LVH (C-index 0.748, 95% CI: 0.514-0.829) was used as one of the FSRS components instead of ECG-LVH (C-index 0.739, 95% CI: 0.503-0.823), likelihood ratio test p 0.008.

Conclusion:
In asymptomatic cardiovascular disease-free individuals, both ECG-LVH and MRI-LVH are predictive of stroke. Using MRI-LVH slightly improves the predictive ability of the FSRS model.
Abstract 12522: Downregulation of Aryl-hydrocarbon Receptor Nuclear Translocator (ARNT) Exacerbates Cardiac Insulin Resistance After High Fat Diet
Authors: Chang Hsiang-Chun , Sato Tatsuya , Wu Rongxue , Shang Meng , Chen Chunlei , Ardehali Hossein
Published: April 2024

Introduction:
Altered cardiac insulin sensitivity, substrate utilization, and energetics have been reported in diabetic cardiomyopathy. However, the mechanism behind insulin resistance in the heart in diabetes remain poorly understood. Hypoxia inducible factors (HIFs) have been linked to cellular metabolism, and their deletion in the heart resulted in metabolic changes. We have previously demonstrated that cardiac-specific knockout of ARNT, the obligatory binding partner of HIFs, causes spontaneous cardiomyopathy bearing similarity to diabetic cardiomyopathy, and its levels are reduced in genetic- and diet-induced obesity models. Here, we hypothesize that downregulation of ARNT
in vivo
exacerbates cardiac insulin resistance after high fat diet (HFD).

Results:
Mice with cardiac-specific heterozygous deletion of ARNT (cs-ARNT
+/-
) had normal cardiac function at baseline, and had comparable food intake and weight gain during HFD treatment. We then evaluated cardiac substrate utilization using an
ex vivo
heart perfusion system. When perfused with a buffer without insulin, hearts from wild type (WT) and cs-ARNT
+/-
mice displayed comparable substrate utilization both after normal chow and after HFD. Addition of insulin to the perfusion system led to comparable increase in glucose utilization in hearts from normal chow-fed WT and ARNT
+/-
mice. However, the increased glucose utilization in response to insulin was attenuated in hearts from WT mice after HFD, while hearts from cs-ARNT
+/-
after HFD demonstrated virtually no increase in glucose utilization in response to insulin. This difference was not due to cardiac function as the cardiac work (assessed by heart rate and developing pressure) is comparable among all groups. Using neonatal rat cardiomyocytes, we also demonstrated that ARNT knockdown decreased glucose uptake and AKT phosphorylation in response to insulin, consistent with a blunted insulin-signaling pathway.

Conclusion:
Cardiac-specific ARNT heterozygote deletion exacerbates insulin resistance in a diet-induced obesity model, and the reduction of ARNT levels in various mouse models of diabetes is likely be a maladaptive response. Therefore, increasing ARNT signaling can be a potential therapy for diabetic cardiomyopathy.
Abstract 12524: Changes in Pulmonary Autograft Wall Stresses Immediately After the Ross Operation: First Steps Towards Understanding Aneurysmal Remodeling
Authors: Wisneski Andrew D , Xuan Yue , Guccione Julius M , Ge Liang , Tseng Elaine E
Published: April 2024

Introduction:
Pulmonary autograft dilatation is the Achilles heel of the Ross operation, often necessitating reoperation. To understand normal and abnormal autograft remodeling, first biomechanical understanding of human autografts after exposure to systemic pressure is required. Our aim was to quantify biomechanical wall stresses on normal autografts after Ross operation prior to remodeling and dilatation.

Hypothesis:
Elevated pressure of systemic circulation results in increased autograft wall stress to drive biomechanical remodeling.

Methods:
We previously developed a normal human autograft model using micro-computed tomography to obtain zero-pressure luminal geometry. Material properties of normal human autografts (n=9) was obtained by bi-axial stretching. Patient-specific zero-pressure wall thickness was incorporated. Autograft diameter and wall stress were determined at pulmonic and systemic pressures using finite element analyses.

Results:
At systemic systole, mean autograft diameter was 35.0±1.7mm at sinuses and 33.4±1.3mm at sinotubular junction (STJ); while at pulmonary systole, they were 32.5±1.9mm and 30.5±1.4mm, respectively. Distensibility, percent change in diameter from diastole to systole, was 1.4% at systemic pressures versus 3.0% at pulmonary pressures. Peak von Mises wall stress was 581±449kPa at systemic systole compared to 89.7±65.3kPa at pulmonic systole. Average wall stress at systemic systole was 223±88.3kPa and at pulmonic systole was 37.4±16.8kPa (Fig 1).

Conclusions:
Normal human pulmonary autograft biomechanical responses to systemic pressure were quantified. Nearly 6 fold increase in peak and average wall stress was observed at systemic pressures. Regions of peak stresses were observed in the sinuses. This data will serve as a necessary control for future comparison to aneurysmal pulmonary autografts, and will enable better understanding of patient-specific risk for autograft dilatation.
Abstract 12560: Effect of Somah Solution on Hypoxia/Reoxygenation Induced Coronary Artery Endothelial Injury: A Comparison to Current Ex-Vivo Heart Perfusates
Authors: Ribeiro Roberto V , Kawajiri Hiroyuki , Ghashghai Arash , Banner David , Badiwala Mitesh V , Rao Vivek
Published: April 2024

Introduction:
Ex-Vivo Heart Perfusion (EVHP) has been proposed to expand cardiac donation by enabling resuscitation and preservation of hearts donated after circulatory death. Hypoxia/reoxygenation endothelial injury affects organ viability and patient’s outcomes. STEEN Solution is accepted as the primary component for perfusion of other solid organs. However, there is lack of evidence to determine the optimal perfusate composition to maintain cardiac viability during longer periods of perfusion. Somah solution has been proposed as a novel cardioprotective solution optimized to meet cardiac metabolism and confer enhanced protective effects against reperfusion injury. Our aim was to compare the effects of STEEN and Somah on endothelial reoxygenation injury in vitro.

Methods:
Human coronary artery endothelial cells were exposed to 16 hours of hypoxia in culture medium followed by 16 hours of reoxygenation treated with Celsior, STEEN or Somah to simulate the EVHP setting. Endothelial activation markers’ gene expression was assessed through qRT-PCR; supernatant was collected to quantify endothelin-1 (ET-1) with ELISA; and quantitative neutrophil adhesion assay was performed to evaluate endothelial function.

Results:
Treatment with Somah demonstrated decreased expression of cell surface adhesion molecules E-Selectin (Me 0.133±0.12, So -0.073±0.34, ST 1.624±0.46, Ce 0.999±0.45 fold-change from hypoxia; p=0.002) and VCAM-1 (Me -0.004±0.20, So -0.363±0.43, ST 0.428±0.39, Ce 0.597±0.13 fold-change from hypoxia; p=0.023), and vasoactive molecule MCP-1 (Me 0.225±0.72, So -0.510±0.70, ST 1.500±0.49, Ce 0.829±0.28 fold-change from hypoxia; p=0.015). Celsior and Somah reduced cell secretion of ET-1 (Me 395 pg/ml, So 20 pg/ml, ST 448 pg/ml, Ce 16 pg/ml; n=4, p<0.05). Reoxygenation injury increased neutrophil adhesion to endothelial cells; there was a non-statistically significant trend towards protection against this injury with Somah.

Conclusions:
Somah exerts protective effect against reoxygenation injury when compared to STEEN in vitro. It may have utility in enhancing cardiac organ preservation during EVHP. Future studies in a pre-clinical setting should be conducted to address this question.
Abstract 12608: Coronary Artery Plaque Burden Characterization in Psoriasis Reveals Increase in High Risk Plaque
Authors: Lerman Joseph B , Chaturvedi Abhishek , Dey Amit K , Aberra Tsion M , Joshi Aditya A , Kabbany Mohammad T , Salahuddin Taufiq , Yunus Raza , Silverman Joanna I , Rodante Justin A , Playford Martin P , Chen Marcus Y , Sandfort Veit , Bluemke David A , Mehta Nehal N
Published: April 2024

Introduction:
Psoriasis (PSO), a chronic inflammatory skin disease associated with increased risk of MI, provides an ideal translational human model to study inflammatory atherogenesis. The presence of high-risk plaque (HRP) by coronary-computed tomography angiography (CCTA) is associated with prospective CV events. To date, however, no study has characterized HRP morphology in PSO.

Hypothesis:
We hypothesized that PSO would associate with an increased prevalence of HRP, as compared to controls (HC).

Methods:
PSO (n=107), HC (n=25), and hyperlipidemic patients (HLD) (n=30) who were candidates for statin therapy under NCEP ATP III guidelines, underwent CCTA (Toshiba, 320-detector row) for coronary plaque characterization. Total and non-calcified plaque burden were quantified using QAngio (Medis). To characterize HRP, a single reviewer evaluated for positive remodeling index (> 1.1), low-attenuation (< 30 HU), and spotty calcification. Statistical analysis included multivariable regression.

Results:
PSO patients were middle-aged, male-predominant, and at low Framingham risk (Table). Non-calcified plaque burden was higher in PSO than in HC (p =0.05) and in HLD (p = 0.02). The prevalence of HRP was greater in PSO than in HC (34% vs. 8%, p=0.01), and was comparable to that seen in HLD (34% vs. 37%, p=0.78). Logistic regression revealed a significant association between PSO and the presence of HRP, beyond Framingham risk, BMI, glucose, and statins (OR 5.8, p= 0.03). This association, however, attenuated in HLD after adjustment (OR 2.6, p = 0.3).

Conclusions:
PSO associated with a higher prevalence of HRP, independent of traditional CV risk, and similar to that observed in HLD. These findings are consistent with the known association between PSO and MI, and may lend insight to the residual CV risk not captured by traditional methods in PSO. Larger studies are needed to confirm these results.