bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17204: Nucleostemin and Nucleophosmin Express with Up-regulating Telomere Reverse Transcriptase in the Arteriosclerotic Lesions
Authors: Iwai Kunimitsu , Okuno Tazuo , Morita Takurou , Iritani Osamu , Okuro Masasi , Morimoto Shigeto
Published: July 2021

Introduction:
Nucleostemin (NS) and nucleophosmin (NPM) are the nucleolar proteins which not only regulate the proliferation of stem cells, but also protect myocardial cells from oxidative stress.

Hypothesis:
We hypothesize that NS and NPM regulate the proliferation of the arterial smooth muscle cell (SMC) and contribute to their survival in the process of arteriosclerosis. This study investigated for the first time the expression pattern of them and consider their roles in arteriosclerosis.

Methods and Results:
Immunohistochemical examination revealed the expression of NS and NPM in the nuclei of SMCs and endothelial cells (ECs) both in the media and the intima of the human autopsy coronary arteries and the aorta of the apo E-deficient mice. Immunoreactivity was especially strong in the SMCs and ECs constructing the fibrous cap covering the plaques. The immunoreactivity of telomere reverse transcriptase (TERT) was at once observed in these NS- and NPM-positive nuclei, indicating of the strong proliferating activities. In the fibro-muscular proliferating intima after denudation of the endothelium of rat abdominal aorta confirmed the same localization of NS and NPM with TERT. In order to investigate the roles of NS in the SMC, mRNA of NS was knocked down with siRNA in cultured human arterial SMC. The 47S ribosomal RNA reduced to 35%, without reducing 18S ribosomal RNA (real-time PCR), indicating the promoting effect of NS on the pre-ribosomal RNA processing necessary for total protein synthesis. Knocking down of NS mRNA also reduced the expression of TERT to 65% and on the contrary up-regulated p21 mRNA to 150%, indicating anti-senescence activity of NS. Subculture of human SMCs ultimately to the replicative senescence gradually reduced the number of NS positive nucleoli from four to only one per cell, maybe reflecting the reduced activity of NS in the senescence process.

Conclusion:
These results indicate that NS and NPM promote the proliferation of arterial SMCs and ECs in the arteriosclerotic lesions, collaborating with TERT.
Abstract 17218: Reduced Left Atrial Compliance in Heart Failure With Preserved Ejection Fraction: New Insights Into Pathophysiology
Authors: Zakeri Rosita , Chai Qiang , Moulay Gilles , Ogut Ozgur , Hussain Saad , Takahama Hiroyuki , Lu Tong , Wang Xiao-Li , Linke Wolfgang A , Lee Hon-Chi , Redfield Margaret M
Published: July 2021

Background:
Reduced left atrial (LA) compliance (LAC) contributes to pulmonary venous hypertension in heart failure with preserved ejection fraction (HFpEF); however the underlying mechanisms are poorly defined. We hypothesized that microvascular inflammation with rarefaction and impaired nitric oxide (NO) signaling, LA titin hypophosphorylation and fibrosis may each contribute to reduced LAC in HFpEF.

Methods:
Invasive LA pressure-volume (PV) analyses (open-chest; pericardiotomy; admittance catheter) were performed in 9 aged dogs with experimental hypertension (bilateral renal wrap + DOCA; HFpEF) compared to 13 sham-operated young adult dogs (control). LAC was measured at end-LA reservoir during acute preload reduction (cava occlusion). LA tissue and LA microvascular function were analyzed.

Results:
Compared to controls, the curvilinear end-LA reservoir PV relationship (
Fig A
) was shifted upward/leftward in HFpEF (LA diastolic stiffness constant 0.08 vs 0.16 mmHg/mL in controls, p=0.005). LA microvascular density (MVD; CD31 stain) tended to be lower in HFpEF than controls (2154±578 vs 2650±523 vessels/mm
2
, p=0.07) and LA MVD negatively correlated with the LA diastolic stiffness constant (r=-0.66, p=0.006). LA microvessels from HFpEF dogs showed impaired endothelium-dependent shear stress-mediated dilation compared to controls, consistent with impaired NO signaling (
Fig B
). Titin isoform expression was similar between groups, but isoform N2B (stiffer) was (p=0.03) and N2BA (compliant) tended to be (p=0.09) hypophosphorylated in HFpEF LA appendage (LAA) tissue. Fibrosis (Picrosirius Red) was similar between groups in the LA free wall and LAA, but increased in areas adjacent to the pulmonary veins in HFpEF (27±12% vs controls 15±8%, p=0.01).

Conclusion:
In experimental HFpEF, LAC was reduced in association with evidence of LA microvascular rarefaction and impaired NO signaling, titin hypophosphorylation and regional increases in LA fibrosis.
Abstract 17220: Effects of the Oral Adsorbent of AST-120 in Patients with both Chronic Heart Failure and Chronic Kidney Disease
Authors: Imazu Miki , Asakura Masanori , Hasegawa Takuya , Asanuma Hiroshi , Ito Shin , Nakano Atsushi , Funada Akira , Sugano Yasuo , Ohara Takahiro , Kanzaki Hideaki , Takahama Hiroyuki , Morita Toshisuke , Anzai Toshihisa , Kitakaze Masafumi
Published: July 2021

Background:
One of uremic toxins, indoxyl sulfate (IS) is related to the progression of chronic kidney disease (CKD) and the worse cardiovascular outcomes. We have previously reported the relationship between IS levels and the severity of chronic heart failure (CHF), but the question arises as to whether the treatment of uremic toxin is beneficial in patients with CHF. This study aimed to elucidate whether the treatment with the oral adsorbent which reduces uremic toxin improved the cardiac function of the patients with CHF.

Methods:
First of all, we retrospectively enrolled 49 patients with both CHF and stage ≤3 CKD in our institute compared with the healthy subjects without CHF or CKD in the resident cohort study of Arita. Secondly, we retrospectively enrolled 16 CHF outpatients with stage 3-5 CKD. They were treated with and without the oral adsorbent of AST-120 for one year termed as the treatment and control groups, respectively. We underwent both blood test and echocardiography before and after the treatment.

Results:
First of all, among 49 patients in CHF patients, plasma IS levels increased to 1.38 ± 0.84 μg/ml from the value of 0.08 ± 0.06 μg/ml in Arita-cho as a community-living matched with gender and eGFR of CHF patients. We found both fractional shortening (FS) and E/e’, an index of diastolic function were decreased (25.0 ± 12.7%) and increased (13.7 ± 7.5), respectively in CHF patients compared with the value of FS and E/e’ in Arita-cho (FS: 41.8 ± 8.3%, E/e’: 8.8 ± 2.1). Secondly, in the treatment group, the plasma IS levels and the serum creatinine and brain natriuretic peptide levels decreased (1.40 ± 0.17 to 0.92 ± 0.15 μg/ml; p<0.05, 1.91 ± 0.16 to 1.67 ± 0.12 mg/dl; p<0.05, 352 ± 57 to 244 ± 49 pg/ml; p<0.05, respectively) and both FS and E/e’ were improved following the treatment with AST-120 (28.8 ± 2.8 to 32.9 ± 2.6%; p<0.05, 18.0 ± 2.0 to 11.8 ± 1.0; p<0.05). However, these parameters did not change in the control group.

Conclusions:
The treatment to decrease the blood levels of uremic toxins improved not only renal dysfunction but cardiac systolic and diastolic dysfunction in patients with chronic heart failure. Oral adsorbents might be a new treatment of heart failure especially with diastolic dysfunction.
Abstract 17229: Survival after Veno-arterial Extracorporeal Membrane Oxygenation Support is Dependent on Underlying Etiology of Cardiogenic Shock
Authors: Carroll Brett J , McCullough Stephen A , Shah Ravi V , Lewis Gregory D , Camuso Janice M , Carlson William D , Parks Kimberly A , Moore Stephanie A , Newton-Cheh Christopher H , Sarswat Nitasha , Song Tae H , Macgillivray Thomas E , Melnitchouk Serguei , Sundt Thoralf M , Semigran Marc J , Baker Joshua N , Garcia Jose P
Published: July 2021

Introduction:
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an emerging therapy for refractory cardiogenic shock (CS); however, characteristics of patients most likely to benefit from this therapy remain to be determined. We hypothesized that the underlying etiology of CS and patient specific characteristics predict survival to discharge.

Methods:
We compared outcomes in patients supported with VA-ECMO for refractory CS resulting from (1) acute myocardial infarction (AMI; with or without revascularization); (2) acute pulmonary embolism (PE); (3) acute cardiomyopathy; (4) chronic cardiomyopathy; (5) post-cardiotomy; and (6) other etiologies of shock. Chi-square analysis was used to identify predictors of survival to discharge after VA-ECMO.

Results:
From 2009-2013, 102 patients were initiated on VA-ECMO for refractory CS. The average age was 52 ±15 (mean ± SD) years old with 71 (70%) males. Overall, 39 (38%) patients survived to discharge. In the cohort, 22 patients were post-cardiotomy and 5 (23%) of those survived to discharge. Of the 80 patients without prior cardiotomy, survival to discharge was 27% (8/30) after AMI, 64% (9/14) after PE, 75% (6/8) with acute cardiomyopathy, 50% (5/10) with chronic cardiomyopathy, and 39% (7/18) with other CS etiologies. Survivors were younger (45 ±13 vs 56 ±14, p = 0.0002) and none of the 24 patients over the age of 64 years old survived to discharge. There was a significant difference in survival when comparing etiologies of shock (p = 0.012 by Chi-square comparison among etiologies). There was no significant difference in survival by gender.

Conclusions:
Survival in patients with refractory CS requiring VA-ECMO may depend on age and underlying etiology of shock. Further research into predictors of survival after institution of VA-ECMO is warranted.
Abstract 17231: Loss of Zfp148 Reduces Atherosclerosis in Mice by Activating P53
Authors: Sayin Volkan I
Published: July 2021

Rationale:
Cell proliferation and cell cycle control mechanisms are believed to play central roles in the pathogenesis of atherosclerosis. The transcription factor Zinc finger protein 148 (Zfp148) was recently shown to maintain cell proliferation under oxidative conditions by suppressing p53, a checkpoint protein that arrests proliferation in response to various stressors. It is established that inactivation of p53 accelerates atherosclerosis, but whether increased p53 activation confers protection against the disease remains to be determined.

Objective:
We aimed to test the hypothesis that Zfp148 deficiency reduces atherosclerosis by unleashing p53 activity.

Methods and Results:
Mice harbouring a gene-trap mutation in the Zfp148 locus (Zfp148gt/+) were bred onto the Apoe-/- genetic background and fed a high-fat or chow diet. Loss of one copy of Zfp148 markedly reduced atherosclerosis without affecting lipid metabolism. Bone marrow transplantation experiments revealed that the effector cell is of hematopoietic origin. We next investigated whether p53 is part of the underlying mechanism. Peritoneal macrophages from Zfp148gt/+Apoe-/- mice showed increased levels of phosphorylated p53 compared to controls, and atherosclerotic lesions from Zfp148gt/+Apoe-/- mice contained fewer proliferating cells and more apoptotic cells. Zfp148gt/+Apoe-/- mice were further crossed with p53-null mice (Trp53-/-). There was no difference in atherosclerosis between Zfp148gt/+Apoe-/- mice and controls on a Trp53+/- genetic background.

Conclusions:
Zfp148 deficiency increases p53 activity and protects against atherosclerosis without affecting lipid metabolism. The protective effect is entirely dependent on p53 and suggests that drugs that increase p53 activity may be useful in the treatment of atherosclerosis.
Abstract 17245: The Effect on Vitamin D Levels of Long-term High-dose Treatment With a Concentrated Omega-3 Compound (Omacor®/Lovaza®) in Patients Hospitalized With a Myocardial Infarction
Authors: Naesgaard Patrycja A , Grundt Heidi , Brede Cato , Nilsen Dennis W
Published: July 2021

Background:
Several studies have demonstrated an inverse relationship between cardiovascular risk and levels of vitamin D and omega-3.

Objectives:
To assess the impact of high-dose treatment of concentrated omega-3 (ethylester form) on serum vitamin D measured as 25-hydroxyvitamin D [25(OH)D] in 288 patients hospitalized with a myocardial infarction who were randomly assigned into a daily dose of either 4 g highly concentrated omega-3 fatty acids (114 patients) or corn oil (114 patients), administered in a double-blind manner over 12 months. Four mg of alfa-tocopherol was added to each capsule to protect against fatty acid oxidation. Supplementation with other fish-oil products was discontinued. 25(OH)D was measured at baseline, at 6 weeks and 12 months follow-up. Changes in 25(OH)D were compared statistically.

Results:
Median 25(OH)D levels in the two groups are shown in Table 1. The increase in 25(OH)D was statistically significant in both treatment groups at 12 months; p < 0.001 for n-3 polyunsaturated fatty acids (PUFAs) and p = 0.011 for corn oil. A statistical significant rise in 25(OH)D was already apparent in the n-3 PUFA patients at 6 weeks follow-up (p < 0.001). There was no significant difference between intergroup changes after 6 weeks intervention (p = 0.867) or after 12 months intervention (p = 0.267) (Mann-Whitney Rank Sum Test).

Conclusion:
A statistical significant early rise in vitamin D at 6 weeks follow-up was noted in the omega-3 group of patients, persisting at 12 months, but these changes were not reflected as compared to corn oil, probably due to the fact that both compounds are biologically active.
Abstract 17246: Predictors for Listing for Transplant in Infants with Hypoplastic Left Heart Syndrome : an analysis of the Single Ventricle Reconstruction Trial
Authors: Kulkarni Aparna , Neugebauer Richard , Lamour Jacqueline M , Hsu Daphne T
Published: July 2021

Background:
Infants with Hypoplastic Left Heart Syndrome (HLHS) following the Norwood procedure have the worst survival among infant heart transplant (HT) recipients. The Single Ventricle Reconstruction (SVR) trial collected vital status and HT data in 920 eligible patients (pts) and prospective preoperative, operative and post-operative data in 554 randomized pts. This trial provides a unique opportunity to evaluate predictors of the need for HT in HLHS infants.

Methods:
The public use SVR database was used to analyze factors associated with listing for HT and mortality on the wait list and in HT pts. Pts listed for HT were compared with those who survived without listing.

Results:
Among 920 eligible pts, 41 were listed for HT and follow up data was available in 33/554 pts. 25 pts underwent HT. The median age at listing was 135 days (6 [[Unable to Display Character: –]] 713 days). All pts listed were status 1A, except for 2 at status 7 and 1 at status 2. Mean RV fractional area change at birth was significantly lower in the listed group (29±8% vs.35±9, p<0.05). ECMO/ CPR, and need for pacemaker were also more common in listed pts compared to the unlisted group. Gestational age, anatomic diagnosis of aortic atresia, AV valve insufficiency and the number of catheterization interventions were not risk factors for HT listing. The median time from listing to HT was 47 days (2 - 340 days). ECMO or VAD support was used in 10 pts prior to HT. Wait list mortality was 29% with a median time to death of 134 days (10 [[Unable to Display Character: –]] 707 days). Causes of death on the wait list included cardiac (8 pts), renal (1 pt), surgical (1 pt) and other (2pts). Mortality after HT was 36% with a median time to death of 197 days (48-658 days). Overall mortality after listing, including after HT, was 51%; younger age at listing was associated with increased mortality (292 vs 149 days, p<0.04).

Conclusion:
HT as a rescue procedure for HLHS in the first year of life carries a significant risk of mortality.
Abstract 17254: Adenosine A2A Receptor Polymorphisms and Response to Regadenoson
Authors: Kreutz Rolf P , Mastouri Ronald , Saab Rayan , Philips Santosh , Skaar Todd
Published: July 2021

Introduction:
Activation of adenosine A2A receptors induces coronary vasodilation and sympathetic activation. Regadenoson is an A2A agonist used in pharmacologic cardiac nuclear stress testing, and exhibits large variability in hemodynamic response and incidence of side effects. Common genetic variants of A2A have been associated with functional differences in neurological phenotypes.

Hypothesis:
We hypothesized that common polymorphisms of A2A may influence response to regadenoson during cardiac stress testing.

Methods:
We prospectively enrolled 268 patients undergoing resting regadenoson stress testing. Five common A2A receptor variants were analyzed by Taqman genotyping assay. SPECT technetium nuclear stress tests were performed and analyzed using the 17-segment model. Blood pressure and heart rate changes were recorded prospectively after administration of regadenoson.

Results:
Variants of A2A were associated with significant differences in heart rate (HR), peak systolic blood pressure (SBP), and summed stress score (Table). The association of rs2298383 (minor allele frequency (MAF)=0.49), rs5751876 (MAF=0.39), and rs3761422 (MAF=0.4) with heart rate and blood pressure at rest and peak remained significant after multivariate adjustment for demographics, race, and clinical variables. Similarly, carrier status of rs2298383, rs5751876, rs3761422, and rs2267076 (MAF=0.37) remained significantly associated with summed stress score (SSS) after multivariate adjustment.

Conclusion:
Common genetic variants of A2A may be associated with variability in heart rate and blood pressure response to regadenoson

and extent of ischemia on nuclear myocardial perfusion imaging. Further studies are necessary to examine the influence of A2A receptor variants on diagnostic sensitivity of regadenoson nuclear stress testing.
Abstract 17269: Extracelllular Protein Disulfide Isomerase Reshapes Vascular Architecture Against Constrictive Remodeling
Authors: Araujo Haniel A , Tanaka Leonardo Y , Hironaka Gustavo K , Araujo Thais L , Takimura Celso K , Rodriguez Andres I , Lemos-Neto Pedro A , Gutierrez Paulo S , Laurindo Francisco R
Published: July 2021

INTRODUCTION:
Vascular remodeling orchestrates a complex network of signaling pathways responsible for pathological changes in many vascular diseases such as atherosclerosis. We investigated the role of endoplasmic reticulum chaperone Protein Disulfide Isomerase (PDI) and the extracellular PDI (ecPDI) pool in vascular caliber and architecture during vascular repair and remodeling after injury (AI).

METHODS AND RESULTS:
After rabbit iliac artery balloon injury, PDI is markedly increased at mRNA and protein levels (25-fold vs. basal 14 days AI), with increase in both intracellular and ecPDI. Silencing PDI by siRNA in vitro induced ER stress markers upregulation and apoptosis (assessed by TUNEL assay). PDI knockdown also upregulated proliferation marker PCNA and decreased differentiation marker calponin-C. Furthermore, ecPDI inhibition prevents injury-increased hydrogen peroxide generation and decreases arterial nitrate (NO3-) level. EcPDI neutralization in vivo with PDIAb-containing perivascular gel from days 12-14AI promoted 25% decrease in vascular caliber at arteriography and similar decreases in total vessel circumference at optical coherence tomography, without changing neointima, indicating increased constrictive remodeling. EcPDI neutralization promoted striking changes in collagen, with switch from circumferential to radial fiber orientation towards a more rigid fiber type. Collagen type I and III were decreased after ecPDI inhibition in arteries 14 days AI. Cytoskeleton architecture was also disrupted, with loss of stress fiber coherent organization and switch from thin to medium-thickness actin fibers. In human coronary atheromas, PDI expression inversely correlated with constrictive remodeling. There was decreased PDI expression in media and intima from plaques exhibiting constrictive remodeling and, conversely, enhanced PDI expression in media of plaques depicting outward remodeling.

CONCLUSIONS:
Thus, PDI is highly upregulated after injury and reshapes matrix and cytoskeleton architecture to support an anticonstrictive remodeling effect. Such findings suggest an important role for PDI in lumen maintenance during vascular remodeling.
Abstract 17272: Ionic Current Remodeling Delays the Electrical Recovery of the Senescent Heart
Authors: Signore Sergio , Borghetti Giulia , Kannappan Ramaswamy , Sorrentino Andrea , Cannata Antonio , Meo Marianna , Zhou Yu , Mangiaracina Chiara , Alesi Nicola , Sena Brena F , Nahrendorf Matthias , Goichberg Polina , Leri Annarosa , Anversa Piero , Rota Marcello
Published: July 2021

Cardiac aging is associated with lengthening of the QT interval, a condition that enhances malignant ventricular arrhythmias and sudden death. The aim of this study was to establish whether ionic currents are altered in old myocytes contributing to the protracted electrical recovery of the senescent heart. Thus, mice at 3-30 months of age were studied by ECG and patch-clamp; these physiological determinations were complemented with molecular assays for the analysis of ion channel proteins. By surface ECG and telemetry system, PR, QRS and QT intervals were prolonged in mice at 25 months or older. These delays were maintained in ex-vivo Langendorff preparations. In comparison to young, epicardial monophasic action potential (AP) duration at 50% and 90% repolarization were 1.6- and 1.2-fold larger in old LV, respectively. Moreover, senescent hearts presented a 60% higher incidence of arrhythmias. In isolated myocytes, prolongation of the early (+47%), intermediate (+117%) and late (+75%) repolarization phases of the AP were identified in cells from old animals, whereas resting membrane potential, upstroke amplitude and +dV/dt were preserved. Voltage-clamp experiments were then performed to measure ionic current properties. The rapidly activating K+ current, which consists of the transient outward and ultrarapid delayed rectifier (Ito+Kur), is responsible for the early repolarization of the AP, and was significantly reduced in old myocytes. Molecular studies revealed low levels of transcripts and proteins for K+ channel subunits Kv1.4, Kv1.5 and KChiP2 in senescent cells. Also, the late Na+ current INaL, which presents slow inactivation kinetics and is operative during AP repolarization, was 1.5-fold larger in old cells. These changes were associated with alterations in gene and protein expression of Na+ channel subunits. Inhibition of INaL with mexiletine significantly shortened the intermediate and late repolarization phases of the AP in both myocytes and perfused myocardium from old mice. Importantly, INaL inhibition in vivo shortened the QT interval of senescent mice by 12%. Thus, defects in ionic current occur with aging resulting in prolongation of the AP and delays in electrical recovery which may lead to malignant ventricular arrhythmias.
Abstract 17289: A Baffling Heart: a 30 Year-old Man with Biventricular Heart Failure and Severe Pulmonary Hypertension
Authors: Zier Lucas S , Barnett Christopher , Foster Elyse
Published: July 2021

A thirty year-old man with an unknown surgery for congenital heart disease presented with intermittent chest pain and progressive decline in his exercise tolerance. Cardiovascular examination revealed a soft S1, loud S2 without splitting, right ventricular heave, a sustained and laterally displaced apical impulse and clubbing of his fingers. An echocardiogram showed d-transposition of the great arteries (d-TGA), a dilated, sub-pulmonic left ventricle (LV) with reduced function, smaller than expected sub-aortic right ventricle with reduced function, and elevated sub-pulmonic left ventricular systolic pressure without LV outflow tract obstruction. Cardiac MRI revealed d-TGA status post Senning repair, biventricular dysfunction without baffle obstruction, no evidence of repaired atrial or ventricular septal defect or delayed gadolinium enhancement. Cardiac catheterization showed a suprasystemic pulmonary artery pressure, a pulmonary vascular resistance of 18.4 Wood units and a small right to left shunt due to a baffle leak. No coronary disease was found on angiography. The patient was diagnosed with severe pulmonary arterial hypertension and biventricular dysfunction. This pattern of heart failure was discordant from the expected sequelae of palliated congenital heart defects as pulmonary arterial hypertension and LV dysfunction are both uncommon long-term complications after atrial switch. Systematic evaluation for a unifying cause of the patient’s pattern of heart failure was unrevealing until the patient presented with decompensated heart failure and evidence of stimulant withdrawal. Urine toxicology was positive for methamphetamine and the patient was diagnosed with methamphetamine induced pulmonary arterial hypertension and subpulmonic LV dysfunction. This case demonstrates the importance of understanding the common, long-term patterns of heart failure in repaired congenital heart disease and the need to search for alternative etiologies when the pattern is inconsistent. This case further shows the toxic effects of methamphetamine on the pulmonary vasculature and myocardium, which in our patient resulted in a highly unique pattern of sub-pulmonic LV dysfunction and pulmonary arterial hypertension.
Abstract 17314: Impact of Mild Therapeutic Hypothermia on Platelet Inhibition in Acute Coronary Syndrome
Authors: Kaufmann Jan , Stockmann Helena , Stawowy Philipp , Graf Kristof , Fleck Eckart , Schroeder Tim , Storm Christian
Published: July 2021

Background:
Mild therapeutic hypothermia (MTH) improves outcome for patients with acute coronary syndrome (ACS) after cardiac arrest (CA). Previous data point to an interaction between hypothermia and drug metabolism, thus potentially impacting on platelet function under antiplatelet therapy.

Purpose:
The aim of the study is to determine clopidogrel metabolism and platelet function in clopidogrel naïve ACS patients treated with mild hypothermia (33°C, n=12) compared with ACS patients (troponin positive) with normal body temperature (n=14).

Methods:
Platelet function was measured by light transmittance aggregometry (LTA), multiple electrode platelet aggregometry (MEA) and VASP phosphorylation analysis before, 2h, 4h and 24h after administration of a 600 mg clopidogrel loading dose. Furthermore, plasma concentrations of clopidogrel, the active thiol metabolite and the inactive carboxyl metabolite were determined. All patients were screened for CYP2C19*2 polymorphism and scheduled for PCI. Mild hypothermia was carried out according to current guidelines for 24 hours at a target temperature of 33°C.

Results:
Plasma concentration of clopidogrel and metabolites were lower in the MTH group after 2h and 4h, respectively (all p<0.005). All platelet function tests showed an attenuated response to clopidogrel with respect to baseline platelet activity in the MTH group. This was significant for VASP analysis and LTA (p<0.05). Moreover, there was no difference in genotype and platelet function determined
ex vivo
with 33°C and 37°C, respectively.

Conclusion:
Inhibition of platelet function is decreased under MTH, presumably due to a diminished clopidogrel absorption and metabolization. Thus, these patients might have a higher risk for cardiovascular events despite antiplatelet therapy.
Abstract 17315: Low Occurrence of Left Ventricular Reverse Remodeling and Poor Long-term Prognosis in Dilated Cardiomyopathy with Higher Immunohistological Expression of Myocardial Tenascin-C
Authors: Yokokawa Tetsuro , Sugano Yasuo , Nakayama Takafumi , Takigami Masao , Nagai Toshiyuki , Kanzaki Hideaki , Matsuyama Taka-aki , Ohta-Ogo Keiko , Ikeda Yoshihiko , Ishibashi-Ueda Hatsue , Nakatani Takeshi , Ogawa Hisao , Yasuda Satoshi , Anzai Toshihisa
Published: July 2021

Background:
Tenascin-C (TN-C) is an extracellular matrix protein, and may regulate matrix organization during tissue remodeling. Although serum TN-C is reported as a prognostic biomarker in patients with dilated cardiomyopathy (DCM), the clinical significance of myocardial expression of TN-C remains undetermined. The objective of this study is to clarify the significance of myocardial TN-C expression on left ventricular (LV) remodeling and long-term prognosis in patients with DCM.

Methods:
Eighty consecutive patients in 2005 and 2006, who were diagnosed with DCM by excluding ischemic cardiomyopathy and secondary cardiomyopathy by coronary angiography and right ventricular endomyocardial biopsy, were analyzed. Those patients were followed up to 73±34 months, and their clinical data were obtained. Immunohistochemistry for TN-C was performed on stored biopsy specimens to examine the association of TN-C deposition with the occurrence of LV reverse remodeling as well as long-term mortality. Immunostained area of myocardial TN-C was measured densitometrically and calculated in percent by the fraction of TN-C stained area to the whole myocardium (TN-C area). LV reverse remodeling was defined as LV end-diastolic dimension ≤55 mm and fractional shortening ≥25% by 60 months after diagnosis.

Results:
TN-C area was 1.2±1.6% on average. Twenty-two patients (28%) underwent LV reverse remodeling. Patients with LV reverse remodeling showed less TN-C area at diagnosis than those without (TN-C area; 0.6±0.5 vs. 1.5±1.8%, p=0.021). Patients were divided into two groups according to the extent of TN-C area; high TN-C group (TN-C area≥1.5%, n=19) and low TN-C group (TN-C area<1.5%, n=61). LV reverse remodeling occurred less frequently in high TN-C group compared with low TN-C group (5% vs 33%, p=0.01). Eleven patients (14%) died during the observation period. Kaplan-Meier analysis revealed high TN-C group had worse prognosis than low TN-C group (p=0.009).

Conclusions:
Patients with higher immunohistological expression of myocardial TN-C in DCM were characterized with lower occurrence of later LV reverse remodeling and poorer long-term prognosis. Myocardial TN-C may have some crucial role in LV remodeling process in patients with DCM.
Abstract 17352: Differences in Clinical Characteristics, Risk Factors, Rate of Recurrence and 1-year Outcome Between Acute Heart Failure Patients With Stroke or TIA and Those Without This Co-morbidity. Results From the Gulf aCute heArt failuRe rEgistry (gulf Care)
Authors: Al Hashemi Mohammed A , Sulaiman Kadhim , Al-Suwaidi Jassim , AlHabib Khalid F , AlFaleh Husam , Elasfar Abdelfatah , Al-Motarreb Ahmed , Panduranga Prashanth , Nidal Asaad Nidal Asaad , Almahmeed Wael , Alsheikh-Ali Alawi , Bazargani Nooshin , Ridha Mustafa , Bulbanat Bassam , Al-Jarallah Mohammed , Amin Haitham , Bollensdorff Christian , Yacoub Magdi
Published: July 2021

Background:
Chronic heart failure (CHF) is a known risk for stroke and morbidities and mortalities are known to be higher in CHF patients compared to stroke patients without CHF we here study the prevalence and the clinical significance in a group of patient with stroke or transient ischemic attack (TIA) who were admitted to hospital with acute heart failure (AHF) compared to those without stroke and are admitted with acute heart failure

Methods:
Data were derived from a prospective, multicenter, multinational study of 5005 patients hospitalized with AHF from February 2013 to November 2012. Data were analyzed according to the presence or absence of Stroke or bronchial TIA. Demographic, management, in-hospital and 1-year outcomes were compared

Results:
Stroke patients were likely to have a decompensation of chronic failure rather than De-Novo AHF when compared to those without Stroke/TIA (see table). Stroke patients were older; more likely to be female, have history of DM, HTN, dyslipidemia and CKD. Stroke patients were likely to have Atrial fibrillation, PVD, systolic LV dysfunction as well as CAD when compared to those without Stroke, they were also more likely receive NIV, IV inotropes and likely to have had cardiac PCI prior to this admission with AHF. Stroke patients had higher recurrence of stroke and one-year mortality rates.

Conclusion:
Patients who presented with AHF and history of stroke/TIA were having different clinical characteristics as well as comorbidities as compared to those without Stroke, with worse in-hospital and one-year outcome. The current study underlies the need to aggressively manage these high-risk patients.
Abstract 17399: Glutathione-S-Transferase P Regulates Neovascularization in the Remodeling Heart via Effects on Endothelial Progenitor Cells and Reparative Monocytes
Authors: Zhou Guihua , Zhong Hai , Wu Yixin , Sun Chiao-Wang , Townes Timothy M , Prabhu Sumanth D
Published: July 2021

Glutathione-
S
-transferase P (GSTP) modulates c-Jun N-terminal kinase (JNK) activation and the proliferation of bone marrow (BM) myeloid progenitors; however, its effects on endothelial progenitor cells (EPCs) and neovascularization are unknown.

Hypothesis:
GSTP promotes EPC function in a JNK-dependent manner, thereby supporting neovascularization in heart failure (HF). GSTP-/- mice exhibited significantly (p<0.01 vs. wild type [WT]) reduced circulating and BM EPCs, increased pro-inflammatory F4/80
+
CD11b
+
Gr-1
hi
monocytes, diminished BM EPC function (proliferation, migration, and vascular tube formation), and increased BM JNK phosphorylation. These effects were reversed upon treatment with the JNK inhibitor SP600125. HF was induced by left coronary ligation in WT and GSTP-/- mice (sham control). GSTP-/- HF mice exhibited (p<0.05 vs. WT HF): 1) fewer circulating and BM EPCs and increased pro-inflammatory monocytes; 2) exaggerated left ventricular (LV) remodeling and inflammation; and 3) reduced myocardial capillary density. Next, chimeric mice were generated via BM ablation in WT mice and reconstitution with either GSTP-/- (GSTP-/-c) or WT (WTc) BM. GSTP-/-c and WTc mice underwent coronary ligation or sham operation (n = 8-15/group). As compared with WTc HF, GSTP-/-c HF hearts had significant (p < 0.01): 1) exaggeration of LV remodeling and dysfunction; 2) increases in remote zone fibrosis; 3) reductions in capillary density and VEGF-A, -B, and -C gene expression; and 4) augmentation of interleukin (IL)-1β and IL-6 expression. GSTP-/-c mice also exhibited (p < 0.01 vs. WTc mice) increased BM JNK activation, reduced circulating EPCs, increased pro-inflammatory CD11b
+
Ly6C
hi
monocytes, but comparable Ly6C
low
monocytes at baseline. Moreover, at 3 and 7 d post-ligation, GSTP-/-c HF mice had fewer circulating EPCs and reparative Ly6C
low
monocytes, but significantly higher Ly6C
hi
monocytes.

Conclusion:
GSTP promotes EPC function and reparative monocyte mobilization, and suppresses inflammation, thereby improving angiogenic gene expression, neovascularization and LV remodeling after infarction. Hence, human GSTP polymorphisms, which are frequent, may impact cardiac reparative capacity in patients with myocardial infarction.
Abstract 17409: Comparison of Post-procedural Echocardiographic Valvular Performance after Transcatheter Aoritc Valve Implantation using Edwards SAPIEN valve versus Medtronic CoreValve for Severe Aortic Stenosis: a Meta-Analysis
Authors: Bhatheja Samit , Panchal Hemang B , Barry Neil , Patel Parthavkumar , Albalbissi Kais , Paul Timir
Published: July 2021

Background:
In patients with severe aortic stenosis (AS) who are at high risk for surgical aortic valve replacement, transcatheter aortic valve implantation (TAVI) is an emerged alternative procedure. TAVI can be performed using a balloon-expandable Edwards SAPIEN valve (EV) or self-expandable Medtronic CoreValve (CV). The objective of this meta-analysis is to compare post-procedural left ventricular ejection fraction and other echocardiographic valvular performance in patients who underwent TAVI using EV and CV.

Methods:
PubMed and the Cochrane Center Register of Controlled Trials were searched through May 2014. Eleven studies (n=1513) comparing TAVI procedures that used EV (n=774) and CV (n=739) were included. End points were left ventricular ejection fraction, aortic valve effective orifice area, and mean and peak trans-aortic pressure gradients. The mean difference (MD) with 95% confidence interval (CI) was computed and p<0.05 was considered as a level of significance.

Results:
There was no significant difference in left ventricular ejection fraction (MD: 1.02, CI: -1.25 to 3.28, p=0.38) and aortic valve effective orifice area (MD: -0.06, CI: -0.17 to 0.06, p=0.04) between EV and CV groups. Mean and peak trans-aortic pressure gradient were significantly higher in CV group compared to EV group (MD: 1.42, CI: 0.4-2.44, p=0.007) (Figure) and (MD: 4.21, CI: 2.33-6.09, p<0.0001) respectively.

Conclusion:
The results of our meta-analysis suggest that TAVI procedures using CV and EV provide clinically similar valvular performance with possibly clinically insignificant subtle differences in mean and peak trans-aortic pressure gradients in patients with severe aortic stenosis. Further randomized studies are needed for long term echocardiographic outcomes to evaluate valvular performance.
Abstract 17423: Unique Features of Cortical Bone Stem Cells Associated With Enhanced Cardiac Repair
Authors: Mohsin Sadia , Sharp Thomas E , Smith Shavonn , Kubo Hajime , Berretta Remus M , Hare Joshua M , Houser Steven R
Published: July 2021

Rationale:
Adoptive transfer of bone marrow and cardiac derived stem cells (CDCs) into failing human hearts has been shown to be safe, yet these cells have induced modest improvements in myocardial function. Recently we have shown in a mouse model that cortical bone derived stem cells (CBSCs) induced a greater enhancement of cardiac function after myocardial infarction than CDCs, possibly through enhanced paracrine signaling and transdifferentiation of the transplanted cells. However, the relative reparative potential of CBSCs relative to other known stem cell types including bone marrow derived mesenchymal stem cells (MSCs) and cardiac derived stem cells (CDCs) is not known.

Objective:
To characterize surface marker expression, proliferation, survival and differentiation capacity of swine CBSCs relative to MSCs and CDCs.

Methods and Results:
CBSCs, MSCs and CDCs were isolated from cortical bone, bone marrow and heart (left ventricle) of Gottingen miniswine. CBSCs were morphologically distinct from MSCs and CDCs, with differences in length to width ratio and overall cell surface area. Cell surface marker profiling using RT-PCR analysis revealed that CBSCs express some of the classical MSC markers such as CD106, CD271, CD105, CD90, CD44 and CD29 and are negative for CD45 and CD11-b. CBSCs had an enhanced proliferation capacity versus CPCs and MSCs, measured by CyQuant assay. Concurrently CBSCs had significantly a decreased population doubling time (3.57 and 1.26 fold decrease) as compared to MSC and CDCs respectively. CBSCs were also more hydrogen peroxide stress tolerant than CSCs and MSCs as measured by Annexin-V and propidium iodide (PI) labeling using flow cytometery. A significantly greater % of CBSCs expressed markers of cardiac lineage commitment when exposed to dexamethasone than did CSCs or MSCs. Markers of cardiac lineages including GATA-4, α SMA, Troponin T, Nkx2.5, sm22 were measured with RT-PCR and immunocytochemistry.

Conclusion:
CBSCs have enhanced proliferative capacity, survival in oxidative stress conditions and cardiac lineage commitment versus CSCs and MSCs. These features make them a promising cell source for cardiac regeneration after myocardial infarction.
Abstract 17425: Curcumin Ameliorates Experimental Autoimmune Myocarditis by Inducing M2 Macrophage Polarization
Authors: Gao Shanshan , Liu Na , Wang Lijun , Chen Fangyuan , You Hongjun , Liu Yang , Zhou Juan , Yuan Zuyi
Published: July 2021

AIMS:
Our previous study showed that curcumin, the main active ingredient in turmeric, induces the polarization of macrophages to anti-inflammatory M2 phenotype. In this study, we addressed the underlying mechanisms and observed whether curcumin exerts its protective effects on experimental autoimmune myocarditis (EAM) by facilitating the M2 phenotype polarization of macrophages.

METHODS AND RESULTS:
The mRNA and protein expression of M2 markers, including MMR, Arg-1, KLF-4 and PPAR-γ, were obviously up-regulated in curcumin-treated RAW264.7 macrophages. Curcumin increased not only IL-4 and IL-13 mRNA expression, but also protein content of these two cytokines in supernatant. The STAT6 inhibitor leflunomide antagonized the induction of MMR, Arg-1, KLF-4 and PPAR-γ by curcumin in RAW264.7 cells, which is suggested that curcumin induces macrophages M2 polarization through secretion of IL-4 and IL-13 in an autocrine manner. In vivo, 6-week-old male Lewis rats were immunized with myosin to induce EAM and orally administrated with curcumin (50mg/kg/day) or corn oil for 3 weeks after myosin injection. Cardiac functional parameters, including LVFS, EF, LVESD and HR, were significantly improved by curcumin treatment. Curcumin also reduced the heart weight-to-body weight ratio, inflammatory cell infiltration and the myocardial mRNA level of IL-1β and iNOS. Meanwhile, the myocardial mRNA level of KLF4, MMR and Arg-1 were markedly up-regulated by curcumin. Immunofluorescence assay showed that the number of CD68+MMR+ and CD68+Arg-1+ double positive macrophages in curcumin-treated myocardial tissue was obviously more than vehicle-treated ones.

CONCLUSIONS:
Taken together, these results show that curcumin ameliorates EAM by attenuating inflammation and by inducing macrophage M2 polarization.
Abstract 17428: Inpatient Mortality, Rates of Cardiac Catheterizations, Revascularization and National Trends after Acute Myocardial Infarction in Patients with Schizophrenia and Bipolar Disorders
Authors: Pilla Trinadha , Pilla Malathi , Pendyala Venkata , Dababneh Ehab , Scaife Steven , Aguirre Frank , Nallamothu Nasaraiah , Bottum Kathleen , Bennett Jeffrey
Published: July 2021

Objective:
To investigate inpatient mortality, cardiac catheterizations, revascularization and national trends after acute myocardial infarction (AMI) in schizophrenia and bipolar disorder patients compared with the general population.

Methods:
Nationwide Inpatient Sample database is a stratified inpatient discharges database in the United States. Data from 2002 to 2011 was used for this study. Patients with schizophrenia and bipolar disorders who had AMI were compared with a random sample of all other adults with AMI who had no mental illness. Inpatient mortality, rates of cardiac catheterization, PCI and CABG were compared in logistic regression models after adjusting for demographic, medical risk factors, hospital properties and AMI complications.

Results:
From the year 2002 to 2011 a total of 1,778,915 adult patients were identified who had AMI without any psychiatric disorders. Schizophrenia (n=6212) and bipolar disorders (n=9202) patients who had AMI were identified after exclusion of other coexisting psychiatry disorders. There has been approximately a 50% decrease in STEMI and a 5% increase in NSTEMI in the general population and an approximately 50% decrease and a 30% increase in STEMI and a 10% and 200% increase in NSTEMI in schizophrenia and bipolar disorders patients respectively over the last 10 years. Patients with schizophrenia and bipolar disorders were less likely to receive catheterization, PCI and CABG (60%, 60% and 45% respectively) vs. (40%, 45% and 45% respectively) after AMI compared with controls. Inpatient mortality in schizophrenia, bipolar disorders and general population above age 76 yr was 18.54%, 12.48%, 15.24%; in between 66 yr to 75 yr it was 13.98%, 7.63% and 9.59%; in between 56 yr to 65 yr it was 10.33%, 5.09%, 6.25% and in between 46 yr to 55 yr it was 5.70%, 2.82%, 3.36% respectively.

Conclusions:
Schizophrenia patients with AMI had significantly higher inpatient mortality and bipolar disorders with AMI had significantly lower inpatient mortality compared with the general population. Even after adjusting for potential confounders there were significant decrease in the rates of catheterizations, PCI and CABG in patients with anxiety and depressive disorders compared with the general population.
Abstract 17436: STAT3 Inhibition Protects Against Cardiomyocyte Hypertrophy Through a Novel NF-kB p65/Nrf2/HO-1 Pathway
Authors: Chen Lei , Zhao Lin , Samanta Anweshan , Choksi Kashyap , Cheng Guangming , Davani Arash , Girgis Magdy , Dawn Buddhadeb
Published: July 2021

Introduction:
Left ventricular hypertrophy is the end-result of diverse cardiovascular pathologies. STAT3 signaling has been implicated in cardiomyocyte hypertrophy, although the precise mechanism remains incompletely understood.

Hypothesis:
We hypothesized that STAT3 induces myocyte hypertrophy via NF-kB/Nrf2 pathway.

Methods and Results:
Treatment of H9c2 cells with 1 μM Angiotensin II for 48 h induced a 2.4-fold increase in cell size compared with controls. This cellular hypertrophy was significantly inhibited in the presence of STAT3 inhibitor WP1066 (Figure). The levels of heme oxygenase-1 (HO-1), a key molecule in cardioprotective signaling, were increased by WP1066 treatment and decreased by STAT3 overexpression. Further investigation of the underlying mechanism revealed that WP1066 blocks the inhibitory effect of NF-kB p65 on Nrf2, leading to an upregulation of HO-1 (Figure). By using chromosome-IP and bioinformatics analysis, we identified that p65 suppresses Nrf2 expression by directly binding to the promoter region of Nrf2. The p65/Nrf2/HO-1 signaling pathway was further confirmed by using both p65 transient overexpression and NF-kB inhibitor pyrrolidine dithiocarbamate (PDTC).

Conclusions:
We conclude that angiotensin II-induced cardiomyocyte hypertrophy involves STAT3 signaling and downstream components include p65, Nrf2, and HO-1. These novel molecular insights may lead to development of new therapy to prevent and treat cardiac hypertrophy.
Abstract 17460: Initial Clinical Experience with the Medtronic LinQ Loop Recorder: Concerns about Data Deluge
Authors: Kushner BA Geordan S , Ferrara CNP Martha , Nwokike BS Obiananma , Arshad MD Aysha , Musat MD Dan , Preminger MD Mark , Sichrovsky MD Tina , Steinberg MD Jonathan S , Mittal MD Suneet
Published: July 2021

Introduction:
Long-term ECG monitoring is often necessary in patients (pts) with unexplained syncope and suspected or known atrial fibrillation (AF). The recently released Medtronic LinQ loop recorder (ILR) accrues ECG data daily; “alert” conditions are wirelessly transmitted to providers. To date, the frequency and characteristics of these alerts are unknown.

Hypothesis:
We hypothesized that alerts would occur infrequently, thus allowing for remote management of large numbers of pts.

Methods:
Consecutive pts implanted with the LinQ were assessed. All alerts were collected and analyzed. Alerts ideally reflect a change within the past 24 hours of monitoring. However, some alerts (once triggered) perpetuate daily until cleared by a patient initiating a manual transmission.

Results:
Our first 100 LinQ pts (mean age 67.5 years; 51% male) implanted within the first 3 months of market release were assessed. The indications for monitoring included suspected AF (cryptogenic stroke, n=10; history of atrial flutter, n=1), known AF (n=61), and unexplained syncope (n=25). During follow-up, an alert occurred in 63 pts; a similar frequency of alerts occurred in AF and syncope pts (Figure). Once present, 29 (46%) alerts perpetuated daily and required manual transmission to clear.

Conclusion:
We report the initial clinical experience with the LinQ ILR. We found that alerts occurred frequently, irrespective of indication for monitoring. Once present, alerts were frequently perpetuated due to a major design limitation. A more robust system is needed to triage the data being accrued to prevent unnecessary data deluge.