bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18089: Functional Mitral Regurgitation in Patients With Ischemic Cardiomyopathy Undergoing Surgical Ventricular Restoration for Anterior Aneurysm: Echocardiographic Findings and Clinical Impact
Authors: Garatti Andrea , Castelvecchio Serenella , Bandera Francesco , Guazzi Marco , Menicanti Lorenzo
Published: April 2024

Objective:
to evaluate clinical impact of severe functional mitral regurgitation(MR) in patients with dilatative post-ischemic CMP submitted to Surgical Ventricular Restoration(SVR).

Methods:
Among 445 consecutive patients operated of SVR for anterior aneurysm at our Institution between July 2001 and December 2011, 337(76%) patients presented with MR<2+(Group A,mean age 65±10yrs) while moderate to severe MR(3-4+) was evident in 108(24%) patients(Group B,mean age 64±9yrs;). LV volumes(p=.019), LV sfericity index(p=.004) and mitral tenting area(p=.005) resulted independent predictor of severe MR at presentation(Figure 1).

Results:
All patients underwent standard SVR with exclusion of antero-septal akinetic area. CABG was concomitantly performed in 414 patients(93%; mean number of graft=2.7±1.5). All patients in Group B underwent mitral annuloplasty; on the opposite, mitral repair was performed in 18 patients(5%) of GroupA, who presented with annular enlargement > 40mm.

Thirty-days mortality was significantly higher in Group B(15%vs6%; p=.006). Seventy-five patients(22%) in Group A and 46 patients(43%) in Group B died at follow-up(p=.001). Kaplan-Meyer 5 and 10 years cumulative survival were significantly higher in group A(p=.008). Despite identical early mitral repair success rate, 15(7%) and 22(35%) patients in group A and B respectively(p=.001) showed long-term recurrence of severe MR. At Cox regression analysis preoperative mitral annulus dimension and postoperative systolic conicity index were the only independent predictors of late MR recurrence. Long-term 5 and 10 years survival(p=.037) as well as 5 and 10 years freedom from HF readmission(p=.001) were significantly affected by MR recurrence at FU.

Conclusion:
Severe preoperative MR significantly impacts surgical risk of SVR as early and long-term mortality. Furthermore, despite early succesfull surgical repair, severe MR recurrs in nearly a third of the discharged patients.
Abstract 18109: β-Arrestins Regulate Collagen Synthesis in Human Cardiac Fibroblasts via GPCR-Dependent and Independent Signaling
Authors: Li Jinju , L. Philip Jennifer , Theccanat Tiju , Akhter Shahab
Published: April 2024

End-stage heart failure (HF) is characterized by high levels of circulating catecholamines to increase cardiac output and uncoupling of cardiac β-adrenergic receptors (β-ARs). β-arrestins are scaffold signaling molecules that also play a key role in G protein-coupled receptor (GPCR) desensitization, but also have other G protein independent functions including activation of MAPK signaling. This study investigates a potential novel role of β-arrestins in regulating cardiac fibroblasts (CF) biology and myocardial fibrosis which can lead to HF. Both isoforms of β-arrestins expressed in the heart, β-arrestin1 and 2 are upregulated in failing CF versus normal controls. This is a primary mechanism for impaired β-AR signaling as basal and β-agonist-stimulated cAMP production is much lower in the failing CF and there is loss of the β-agonist-mediated inhibition of collagen synthesis in the failing cells. siRNA-mediated knockdown of β-arrestins in failing CF led to decreased α-SMA and fibronectin expression indicative of a reversal from the activated myofibroblast phenotype to the normal quiescent state. β-arrestin knockdown also restored CF β-AR signaling as measured by β-agonist-stimulated cAMP production as well as β-agonist-stimulated inhibition of collagen synthesis. Overexpression of either β-arrestin1 or 2 in normal control CF uncoupled β-AR signaling and blunted the inhibition of collagen synthesis by β-agonist stimulation. To investigate potential non-GPCR effects of β-arrestins in CF, cells were treated with TGF-β. Knockdown of β-arrestin1 or 2 in failing CF significantly inhibited TGF-β-stimulated collagen synthesis and expression of collagen I and III were decreased under both basal conditions and with TGF-β. Pre-treatment of these CF with the pharmacological ERK inhibitor, UO126, abolished Smad phosphorylation in the setting of β-arrestin overexpression and inhibited TGF-β-stimulated collagen synthesis. Both of these isoforms of β-arrestin play a significant role in CF transformation and regulating collagen synthesis via GPCR-dependent and independent signaling pathways. Targeted inhibition of β-arrestins in CF may represent a novel therapeutic strategy to prevent pathological myocardial fibrosis and progression to HF.
Abstract 18118: Overexpression of Angiotensin-Converting Enzyme 2 in the Rostral Ventrolateral Medulla Inhibits the Neuroinflammation in Hypertensive Rats
Authors: Wang Weizhong , Wang Yang-Kai , Deng Yu
Published: April 2024

Neuroinflammation has been reported to contribute to cardiovascular dysfunction in hypertension. Gene transfer of angiotensin-converting enzyme 2 (ACE2) into the rostral ventrolateral medulla, a key region for controlling the sympathetic outflow, leads to a significant reduction in blood pressure and sympathetic activity in hypertension. The goal of the present work is to determine the effect of ACE2 overexpression in the RVLM on neuroinflammation in spontaneously hypertensive rats (SHRs). SHRs was received lentiviral-mediated overexpression of ACE2 (lenti-ACE2) or lenti-enhanced green fluorescent protein (lenti-GFP) control. It was found that a significant reduction in blood pressure and heart rate in the SHRs 3 weeks after lenti-ACE2 injected into the RVLM. Activation of microglia in the RVLM was confirmed in the SHR-GFP, but it was significantly reduced in SHR-ACE2. Content and mRNA expression of the proinflammatory cytokine interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha in the RVLM was significantly (P<0.05) decreased in the SHRs that treated with injection of lenti-ACE2 compared with lenti-GFP. In normotensive WKY rats, we also found that overexpression of ACE2 in the RVLM significantly (P<0.05) reduced the increases in mRNA expression of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha evoked by intracerebraventricular infusion of lipopolysaccharides (4 weeks). Based on the present data, it is suggested that ACE2 gene transfer into the RVLM inhibits neuroinflammation in hypertensive rats, which may be responsible for the beneficial effects of central ACE2 on hypertension. (This work is supported by NSCF 81070214 and 81170240).
Abstract 18121: Extracranial Systemic Embolic Events in Patients With Atrial Fibrillation: Incidence and Outcomes
Authors: Bekwelem Wobo , Adabag Selcuk , Duval Sue , Chrolavicius Susan , Halperin Jonathan L , Connolly Stuart J , Hirsch Alan T
Published: April 2024

Background:
Nonvalvular atrial fibrillation (AF) is associated with thromboembolic events, including stroke, but the impact of extracranial systemic embolic events (SEE) remains undefined. No prior study has accumulated a sufficient number of SEE to comprehensively evaluate their incidence, clinical characteristics and outcomes.

Methods:
All suspected SEE reported among participants in recent large randomized trials were independently re-adjudicated by three clinicians for this analysis. Verification of SEE required clinical and objective evidence of sudden loss of perfusion of a limb or organ. The anatomic distribution, method of detection, severity and outcomes of events were abstracted from case report forms and source documents. The risk of SEE-related death was compared to stroke fatality by Cox proportional hazards regression analysis.

Results:
Over 91,746 patient-years, 223 SEE occurred in 219 subjects, an incidence of 0.24/100 patient-years; the stroke rate during the same period was 1.92/100 patient-years. Patients with SEE were likely to be female (57%), mean age (SD) 73.4 (8.6) years, and mean CHADS
2
score 2.4 (1.3), compared with 55.9%, 73.5 (8.9) years, CHADS
2
score 2.5 (1.2) for patients with stroke. SEE most often involved lower extremity (61%), visceral-mesenteric arterial (28%), and upper extremity (11%) arterial beds. Severity ranged from clinic assessment alone (5%), to hospitalization (30%), surgical intervention (60%), and amputation (5%). Within 3 days of event, outcomes included full recovery in 55%, survival with deficit in 20%, and death in 24%. Mortality was greater after visceral-mesenteric than lower or upper extremity SEE (48, 16 and 9%, respectively, p=0.00001). The relative risk of death during long term follow-up of patients surviving until 3 days compared to those without event was 1.7 (95% CI 1.4, 2.1) after SEE and 1.8 (95% CI 1.7, 1.9) after stroke.

Conclusion:
SEE constituted 11.5% of clinically manifest thromboembolic events in patients with AF. SEE are associated with considerable morbidity and mortality, depending upon the anatomical site. The risk of mortality associated with SEE is comparable to that of ischemic stroke. Improved surveillance for and earlier detection of SEE might improve outcomes.
Abstract 18189: Focal Fibrosis and Diffuse Fibrosis Are Predictors of Positive Left Ventricular Remodeling in Patients With Non-Ischemic Cardiomyopathy
Authors: Yingchoncharoen Teerapat , Negishi Tomoko , Negishi Kazuaki , Popovic Zoran B , Gai Neville , Tang W.h, , Flamm Scott D , Kwon Deborah H
Published: April 2024

Background:

Prognostic value of myocardial fibrosis in patients with non-ischemic idiopathic cardiomyopathy (NICM) is not well-defined. We sought to assess the association of focal and diffuse myocardial fibrosis to left ventricular reversed remodeling.

Methods:

Patients with NICM who underwent cardiac MRI and baseline and subsequent follow-up echocardiographic were included in the study. Post-contrast T1 times were measured using Look-Locker gradient echo, and was adjusted for renal function, body size, gadolinium dose and delayed time after Gadolinium injection. Patients were followed over a median time of 29 months (20,37) to evaluate changes of left ventricular end-systolic volume index (LVESVi) over time. Linear Mixed Model was used to assess the relationship between the LVESVi during follow-up,T1 value, and delayed hyperenhancement (DHE).

Results:
A total of 103 patients (mean age 51±15 years, 62% male) were included in the analysis. Mean LVEF 32±10%, LVESVi 62±39 ml/m2, and T1 time 415+98. DHE was identified in 45 patients (44%). Age, LVEF and LVESVi in patients with DHE are not statistically different compared to patients without DHE. Patient with DHE were more likely to be male (32 vs 11, p=0.024) and had lower T1 time (381±104 Vs 440±87, p=0.003). Patients with focal DHE (n=45) had higher LVESVi at baseline and during follow-up, compared to the patients with no DHE (Δ= 11.3 ml/m2 SE 8.8 ml/2, p= 0.024) (Figure A). However, post T1 values of the myocardium without DHE were not associated with differences in LVESVi. In patients without DHE (n=58), T1 value > 450 was associated with further reduction in LVESVi at the follow-up (Δ= 24.6 ml/m2 SE 14.6 ml/2, p= 0.048)(Figure B.)

Conclusion:
Presence of myocardial DHE, but not T1 value, is a marker of LV reversed remodeling in NICM patients. However, diffuse fibrosis predicts LV reversed remodling in patients without DHE.
Abstract 18196: Sh2 Domain-Containing 5-Inositol Phosphatase 2 (SHIP2) is an Effector of Lymphatic Dysfunction
Authors: Agollah Germaine D , Sevick-Muraca Eva M ,   Cntr for Molecular Imaging
Published: April 2024

Background:
Discovery of variants responsible for familial lymphatic abnormalities have been limited by candidate gene searches and inaccurate phenotyping that is restricted to overt symptomatic presentation. As a result, the majority of patients do not harbor any of the known genes associated with inherited lymphatic abnormalities.

Methods:
We employed near-infrared fluorescence lymphatic imaging (NIRFLI) to identify asymptomatic, but abnormal lymphatic phenotypes in a nucleus family with two daughters who were previously diagnosed with congenital and praecox lymphedema. Following DNA collection and whole exome sequencing, we first sought to identify causal variants known to be associated with lymphatic abnormalities and then secondly, to discover new gene variants, through unbiased analysis of rare, damaging SNPs with co-segregation analysis that was based upon NIRFLI phenotyping. Relevancy of variants was tested through functional cell culture studies following siRNA candidate gene knock down in lymphatic endothelial cells (LECs), and following overexpression of WT and mutant candidate gene variants.

Results:
A damaging mutation in hepatic growth factor (HGF), expressed by blood and lymphatic endothelial cells and ligand to its ubiquitously expressed receptor tyrosine kinase (RTK) cMET was passed to both daughters from the asymptomatic father who showed no abnormal NIRFLI phenotype. Yet the mother, who at time of study was found to have abnormal lymphatics through NIRFLI and minor swelling attributed to minor trauma several years prior, had passed a mutation in SHIP2, encoded by
INPPL1
, to her daughters. Extended, asymptomatic family members, who agreed to the NIRFLI procedure and harbored the SHIP2 mutation, also possessed an abnormal lymphatic phenotype. Migration and tubulogenesis in LECs was arrested by SHIP2 knock down, and when compared to WT overexpression, was attenuated following HGF and VEGF-C stimulation with mutant SHIP2. Proximity ligation assay showed intracellular association of SHIP2 with cMET and with VEGFR3 upon HGF and VEGF-C stimulation respectively, consistent with SHIP2 functionality as an RTK adaptor protein.

Conclusions:
SHIP2 may be an effector of lymphatic dysfunction.
Abstract 18250: Tafazzin-Knockdown Mice: Heart Mitochondrial Structure and Function
Authors: Kim Junhwas , Fujioka Hisashi , Tandler Bernard , Hoppel Charles
Published: April 2024

Barth syndrome is a genetic disorder with mutations in the tafazzin gene resulting in cardiomyopathy, hypotonia, growth delays, and cyclic neutropenia. Mitochondria have been examined for functional defects in Barth syndrome and defects found in oxidative phosphorylation, a decreased content and abnormal composition of cardiolipin, and an increased content of monolysocardiolipin. Consequently, mitochondrial dysfunction resulting from the cardiolipin abnormality has been posited as the primary cause for pathology in Barth syndrome. However, the mechanisms that link cardiolipin abnormality, mitochondrial dysfunction, and the various pathological conditions in Barth syndrome are still unknown. We studied isolated heart subsarcolemmal and interfibrillar mitochondria from tafazzin knockdown mice to examine the role of cardiolipin in mitochondrial dysfunction. In the knockdown mice, the cristae assume the shape of Florence flasks, so we designate them as “florentine”. They have a narrow tubular neck connected directly to the boundary membrane_these are the crista junctions, which in these organelles are of exaggerated length. In mitochondria from tafazzin knockdown mice, the yield of mitochondrial protein is similar to wild type, but the content of cardiolipin decreased by 50 %, monolysocardiolipin increased 25-fold, and unsaturated acyl chains increased. In both mitochondrial populations, state-3 respiration using glutamate plus malate, succinate (+rotenone), and acetylcarnitine plus malate was similar to wild type mice. However, state-3 respiration was decreased with palmitoylcarnitine plus malate (both @-25%;p<0.05) and pyruvate plus malate (subsarcolemmal -25%, p<0.05; interfibrillar -14%, p NS), localizing defects to these separate processes, not the oxidative side of oxidative phosphorylation. Mitochondria from knockdown mice did not generate increased reactive oxygen species. Despite a 50 % decrease in cardiolipin content there is only a mild selective defect in mitochondrial function in this mouse model. However, this change in cardiolipin might be involved in the morphological and perhaps physiological alteration of crista junctions.
Abstract 18257: Use of the TIMI Risk Score in the Emergency Department Discriminates Acute Coronary Syndrome Among Chest Pain Patients With Known Coronary Artery Disease
Authors: Crim Matthew T , Korley Frederick K , Berkowitz Scott A , Saheed Mustapha , Miller Jason , Deutschendorf Amy , Gerstenblith Gary , Hill Peter
Published: April 2024

Background:
Patients with known coronary artery disease (CAD) presenting to the Emergency Department (ED) with chest pain thought to be of ischemic origin are often admitted to the hospital, yet half or fewer are eventually diagnosed with acute coronary syndrome (ACS). We assessed whether the use of the TIMI risk score, developed for UA/NSTEMI prognostication, applied in the ED and modified to eliminate the “known CAD” variable, could discriminate which of these high-risk patients actually do and do not have ACS.

Methods and Results:
Chart review was performed on a prospectively defined cohort of 111 patients with known CAD (73% prior PCI, 42% prior CABG) presenting to the ED with chest pain thought to be of ischemic origin, all of whom were admitted to the hospital from December 2012 to April 2013. The composite TIMI risk score and its individual variables were assessed with logistic regression models for their association with ACS as determined by the inpatient attending physician at hospital discharge. ACS was eventually diagnosed in 36 (32.4%) of the patients. Non-ACS patients had a 2.8 day average length of stay and $9,290 average inpatient (post-ED) hospital charges, which is $696,773 for the 75 (67.6%) non-ACS patients. The odds of having ACS increased by 207% (p <0.001) per 1 point increase in TIMI score. TIMI score discriminates ACS and non-ACS with an area under ROC curve (AUC) of 0.794. In a multi-variable model with the individual TIMI variables, elevated troponin (OR 8.00, p 0.002) and ST deviation (OR 8.38, p 0.007) in the ED, and 2 or more prior chest pain episodes (OR 3.89, p 0.061), were most predictive; AUC 0.834. In a multi-variable model with the TIMI variables and each of the CAD risk factors, elevated troponin (OR 6.95, p 0.008) and ST deviation (OR 9.54, p 0.007) in the ED, and 2 or more prior chest pain episodes (OR 3.90, p 0.067) remained most predictive, and diabetes was the most predictive risk factor (OR 2.03, p 0.282); AUC 0.850.

Conclusions:
A modified TIMI risk score is a valuable tool for discriminating between ACS and non-ACS among patients with known CAD presenting to the ED with chest pain. Application of this risk score, along with other clinical factors, may help avoid short, though potentially unnecessary admissions, and reduce associated costs.
Abstract 18264: High Prevalence of Arterial Hypertension in Adults With Repaired Coarctation of the Aorta
Authors: Rinnström Daniel , Dellborg Mikael , Thilén Ulf , Johansson Bengt
Published: April 2024

Aim:
Arterial hypertension is a long-term complication in adults with coarctation of the aorta (CoA) and may potentially affect prognosis. Here we have investigated the prevalence of hypertension, analysed associated factors, and evaluated blood pressure at the latest clinical visit.

Methods:
The national registry of congenital heart disease was searched for adults with previous surgery for CoA. The diagnosis of hypertension was defined as either registry diagnosis of hypertension and/or medical treatment consistent with this diagnosis.

Results:
527 adult patients with CoA (mean age 38.5±14.5 years) and previous surgery were identified of whom 39.5 % had arterial hypertension. The prevalence of arterial hypertension increased with age and was more common among men (44.1 % vs. 32.0 %, p=0.006). Age, body mass index and peak systolic velocity in the descending aorta were independently associated with hypertension (Nagelkerke R2=0.222, p<0.001). At the latest clinical visit, blood pressure was over 140/90 - a usually referred target value for treatment - in 53.0 % patients with the diagnosis of hypertension. Among these, men were more likely than women to have blood pressure over 140/90.

Conclusion:
Arterial hypertension is common in CoA and increases with age. In this registry study, blood pressure was above recommended levels in approximately half of the patients with CoA and hypertension, and more commonly among men.
Abstract 18282: Association Between Cardiac Computed Tomography Perfusion Imaging and Electronatomic Mapping to Evaluate Left Atrial Fibrosis in Patients With Atrial Fibrillation
Authors: Ling Zhiyu , McManigle John , Khurram Irfan , Zimmerman Stefan , Marine Joseph , Spragg David , Ashikaga Hiroshi , Calkins Hugh , Nazarian Saman
Published: April 2024

Background:
Prior studies have shown that contrast enhanced multislice computed tomography (ceMSCT) can visualize ventricular scar. The purpose of this manuscript is to assess the ability of ceMDCT to detect left atrial (LA) fibrosis in patients undergoing repeat ablation for atrial fibrillation (AF).

Methods and Results:
We enrolled 10 patients prior to repeat ablation. All patients underwent pre-procedural ceMSCT of the LA followed by voltage mapping of the LA during the ablation procedure. The ceMSCT images were processed off-line using Seg3D software (University of Utah, Salt Lake City, USA). Epicardial and endocardial contours were manually drawn around LA myocardium on multi-planar axial images. Electroanatomic mapping points were retrospectively registered to the corresponding ceMSCT images. LA Scar identified by an image intensity range between 0-30 Hounsfeld units (HU) on ceMSCT correlated qualitatively with scar identified by low-voltage (bipolar voltage <0.1 mV). Qualitative agreement in the posterior wall and the left pulmonary vein antrum was excellent. In a linear regression model of a subset of 4 patients, the local CT image intensity was associated with local bipolar voltage (+0.1 mV +/- 0.06 / 100 HU,P=0.019)

Conclutions:
We demonstrate that ceMSCT can provide valuable information about LA myocardial fibrosis with excellent electro-anatomic concordance.

Electroanatomic voltage map of a redo PVI patient showing LA fibrosis in red corresponding to Low voltage (<0.1 mV). Figure 1-B. Contrast enhanced multislice computed tomography imaging derived scar map of the same patient showing the same projection of the left atrium. Image intensity of LA between 0 to 30 is shown in red and blood pool of left atrium is shown in light blue.
Abstract 18289: Cardiac Macrophages Adopt Profibrotic/M2 Phenotype in Ischemic Hearts
Authors: Carlson Signe , Helterline Deri , Dupras Sarah , Minami Elina , Stempien-Otero April
Published: April 2024

Background:
Macrophages (macs) that over express urokinase plasminogen activator(uPA) adapt a profibrotic M2 phenotype in the heart in association with cardiac fibrosis. We tested the hypothesis that cardiac macs are M2 polarized in ischemic mouse and human hearts and that polarization is dependent on mac derived uPA.

Methods:
Mouse cardiac macs were isolated from hearts of infarcted (MI) and uninjured(UI) wild-type (WT) , uPA overexpressing (SR-uPA), or uPA null mice. RNA was extracted after isolation or culture with vehicle, IL-4 or plasmin. M2 markers Arg1, YM1, and Fizz1 measured with qrtPCR. Human cardiac macs were isolated from tissue at time of LVAD placement or transplantation. Peripheral blood was collected at the same time and monocyte-derived macs (PMDM) generated. Expression of CD206 was measured in isolated and IL-4 treated macs. All values were normalized to GAPDH. Values are meanSEM

Results:
Macs from WT mice had increased expression of Arg1 and Ym1 following MI (41.36.5 and 70.336, fold change vs UI, n=8, p < 0.007). ANOVA analysis of UI vs MI in WT, SR-uPA, and uPA null showed significant upregulation of Arg1 and Ym1 with MI in all genotypes (n=4-9 per genotype and condition). There was no increase in Fizz1 in any group. Treatment with IL-4 increased expression of Arg1 and YM1, to a greater degree in cardiac macs from SR-uPA versus WT mice. Human cardiac macs expressed increased levels of CD206 in comparison to PMDM (4.91.3).

Conclusions:
Cardiac macs in mouse and human hearts adapt a M2 phenotype in association with cardiac fibrosis. uPA is not necessary for M2 phenotype development. Altering mac phenotype in the heart is a potential target to modify cardiac fibrosis.
Abstract 18344: Smoking Worsens the Risk of Oxidative Stress in Individuals With Hepatic Steatosis
Authors: Oni Ebenezer T , Singha Pragya , Ali Shozab S , Aboagye Jonathan , Muzaik Wasim , Blaha Michael J , Agatston Arthur A , Blumenthal Roger S , Conceicao Raquel D , Meneghelo Romeu S , Carvalho Jose A , Santos Raul D , Nasir Khurram
Published: April 2024

BACKGROUND:
Serum gamma-Glutamyl Transferase (GGT) is a marker of increased oxidative stress and also associated with an increased cardiovascular (CV) risks. The oxidative stress effect of smoking may be aggravated individuals with hepatic steatosis (HS). We aimed to ascertain the effect of smoking on GGT levels in the presence or absence of HS.

METHODS:
We evaluated 6,373 healthy Brazilian subjects (43±10 years, 79% males) without clinical coronary heart disease between November 2008 and July 2010. HS was ultrasound diagnosed and smoking was categorized as current smokers or none smokers.

RESULTS:
The prevalence of NAFLD was 36% (n=2,075) and 564 (9%) were smokers. There was an increasing prevalence of smokers in higher GGT quartiles (q1-19%, q2-24%, q3-25%, q4-32%, p<0.001). As shown in figure below, smoking was associated significantly with higher GGT levels in smokers with HS (p<0.001), whereas no such association was noted among those without HS. In multivariate adjusted model, mean GGT was 11.08 mg/dl higher as compared to non-smoker among those with HS, whereas no such relationship was observed in those without HS. Overall the interaction of HS and smoking for prediction of GGT levels as marker of oxidative stress was statistically significant

Conclusions:
In this cohort of asymptomatic individuals, smoking significantly raised oxidative stress as measured by GGT level among persons with hepatic steatosis. This suggests smoking worsens the CV risk in individuals with HS. Future studies to ascertain this association is imperative, and may provide a much needed boast to emphasize lifestyle modification among HS individuals.
Abstract 18354: Chronic Pressure-Dependent Cardiac Unloading With a Novel Intra-Atrial Shunt (V-Wave Device) in an Ovine Model of Ischemic Heart Failure: Evidence for Shunt-mediated Improvements in Function and Survivability
Authors: del Rio Carlos L , McConnell Patrick I , Nitzan Yaacov , Ueyama Yukie , Kloepfer Pamela , Youngblood Bradley L , George Robert , Jacoby Meni , Hamlin Robert L , Oz Orna , Keren Gad , Verheye Stefan , Abraham William T
Published: April 2024

Introduction:
Progressive elevations in left-ventricular (LV) filling pressures, as occurring during heart failure (HF), increase myocardial energy demand and facilitate maladaptive remodeling. We hypothesized that chronic selective left-atrial unloading can mitigate LV remodeling and functional deterioration in HF. Hence, we studied a novel intra-atrial device designed to act as a selective/pressure-dependent one-way (left-to-right) shunt, implanted in sheep with chronic ischemic HF.

Methods:
Sheep (45 ± 2 Kg) underwent serial/selective coronary embolizations resulting in chronic left HF (EF: 65±1 to 36±1%, LVIDd: 3.5±0.1 to 4.9±0.1 cm; P<0.05). Subsequently, sheep were instrumented via a thoracotomy with indwelling catheters into the pulmonary artery, the left atrium, and the right atrium/superior vena cava in order to monitor pressures and oxygen saturations. The animals were assigned either to serve as controls (CTRL, n = 7) or had the V-Wave device (n = 14) deployed into the fossa ovalis. After recovery, valved-shunt patency (via Fick’s method), mean atrial/pulmonary pressures, and LV function (echocardiography) were evaluated weekly for up to 12 weeks.

Results:
The deployed shunts acutely lowered left-atrial pressures (LAP, 17±1 to 14±1 mmHg, P<0.05) without increasing right-atrial/pulmonary-artery pressures. Implanted shunts were patent for the duration of the study (mean Qp/Qs: 1.17±0.03 vs 0.76±0.03 in CTRL, P<0.05). Chronically, shunt-treated sheep had improved LV loading/function when compared to controls, which progressively deteriorated; over the 12-week study, treated sheep had lower filling pressures (LAP: 14±1 vs. 22±2 mmHg in CTRL, P<0.05) and preserved LV function (EF: 42±3 vs. 25±2% in CTRL, P<0.05) . Notably, the 12-week survival in treated animals was 93%, while only 57% of the untreated controls survived the monitoring period.

Conclusion:
The V-Wave device, a novel intra-atrial shunt designed to selectively unload the left-heart in a pressure-dependent manner, lead to chronically reduced filling pressures, preserved right-sided pressures, and improved LV function in a clinically-relevant chronic model of ischemic heart failure.
Abstract 18357: Vulnerable Carotid Plaque is Characterized by a Difference in Mobility Between Plaque Core and Cap
Authors: Kerbikov Oleg , Voynov Sergey A , Borskaya Ekaterina N , Shakhnovich Elena B , Yaroshchuk Nataliya A , Krutova Tamara V , Averyanov Alexander V
Published: April 2024

Vulnerable carotid plaque can cause an ischemic stroke, but its detection is elusive. The aim was to study the mechanical properties of carotid plaques using ultrasound speckle tracking.

Methods:
Study population consisted of 61 (aged 53-89, median 68) patients with carotid atherosclerosis: 21 with acute atherothrombotic stroke (7 day after stroke onset) and 40 without symptoms. The stroke subtype was classified according to TOAST criteria. In total, 21 symptomatic and 47 asymptomatic plaques were analyzed. For plaque-free area (PFA) and for each plaque, maximum circumferential and longitudinal strains (S[[Unable to Display Character: с]], Sl) and strain rates (SRc SRl) were measured (with separate measurements for plaque cap, core and base). Plaque characteristics (echogenicity, length, degree of stenosis) were also assessed.

Results:
plaque and PFA differed in Sl and SRl values, whereas no difference was observed for Sc and SRc (Table 1). Sc and SRc for cap and core of echolucent plaques were higher as compared with hyperechogenic ones (Table 1). For echolucent plaques a significant difference in Sc and SRc was also detected between segments, and the highest values were observed in cap (Table 1).

However, for symptomatic plaques, Sc and SRc of plaque core were significantly higher than values for cap (Table 1). Plaque internal motion coefficient Pim=(core SRc - cap SRc)/base SRc was developed to quantify the relative motion of different plaque segments against each other. According to ROC curve analysis, plaques with Pim>0.09 are associated with ischemic event (sensitivity 76%, specificity 65%, AUC=0.76, p<0.001). Logistic regression confirmed that Pim>0,09 is an independent predictor of plaque vulnerability, OR=5.26, 95% CI 1.4-19.3 controlling for age, gender, plaque length, degree of stenosis and echogenicity.

Conclusions:
Echolucent plaques are more mobile than hyperechogenic ones. In symptomatic plaques, the increased deformation of inner core may be linked with plaque vulnerability.
Abstract 18402: Outcomes of Pacing in Patients With Cardiac Amyloidosis - A Single Center Experience
Authors: Hai Jo Jo , Webster Tracy L , Lin Grace , Dispenzieri Angela , Grogan Martha , Brady Peter A
Published: April 2024

Background:
Cardiac amyloidosis (CA) is associated with sinus node dysfunction (SND) and conduction system disease (CSD) yet data on pacing indications and outcomes is scarce.

Methods:
Retrospective review of patients (pts) with CA who had device implantation due to pacing indication at our institution.

Results:
At total of 51 (mean age 67.2±9.2 years, 90.2% male) pts with immunoglobulin light chain (n=27, 52.9%), hereditary transthyretin (n=7, 13.7%) and wild-type transthyretin (n=17, 33.3%) CA were included. Indication for pacing was exercise intolerance (n=16, 31.4%), syncope (n=16, 31.4%), congestive heart failure (n=5, 9.8%) and palpitation (n=2, 3.9%) with SND (n=23, 45.1%), CSD (17=33.3%) and uncontrolled atrial fibrillation (n=11, 21.6%). 16 (31.4%) pts received defibrillators (ICD) for primary prevention, of whom 8 (15.7%) had left ventricular ejection fraction (LVEF) ≤35%. Atrial (P wave: 1.7±1.2mV, threshold: 1.1±0.5mV/0.5±0.2ms) and right ventricular (RV) (R wave: 7.9±3.8mV, threshold: 0.8±0.4mV/0.4±0.1ms) lead parameters were satisfactory at implantation. During follow-up (mean 36.6±33.6 months), 26 (51%) pts reported symptomatic improvement (SI). Syncope was the only predictor of SI (OR 16.4, 95%CI 1.8-145.2, p=0.01) while exercise intolerance was not (OR 0.09, 95%CI 0.02-0.44, p=0.003). First-time life-threatening ventricular arrhythmias (VA) occurred in 6 (11.8%) pts, 3 (5.9%) had ICD implanted for LVEF ≤35%, 3 (5.9%) without ICD and LVEF ≥35%. Syncope was not predictive of first-time VA. RV lead noise led to inappropriate ICD shocks in 1 patient. Atrial lead sensing failure occurred in 6 (11.8%) and loss of capture in 5 (9.8%).

Conclusion:
Device implantation in patients with cardiac amyloidosis is safe but atrial lead failure is common. Syncope usually improves with pacing whereas other factors should be considered in those presented with exercise intolerance. Selection of pts who need pacing for prophylactic ICD implantation is challenging as neither left ventricular ejection fraction nor syncope are predictive of arrhythmic events.
Abstract 18446: Receipt of Implantable Cardioverter-Defibrillator Among HIV+ and HIV- Veterans With Cardiomyopathy
Authors: Fatemi Omid , Karasik Pamela , Singh Steven , Chang Chung-Chou , Tate Janet P , Gibert Cynthia , Benator Debra , Amdur Richard , Rimland David , Gottlieb Stephen , Budoff Matthew , McGinnis Kathleen , Freiberg Matthew
Published: April 2024

Introduction:
Those with HIV infection (HIV+) are at increased risk for AMI, CHF, and sudden cardiac death compared to uninfected individuals (HIV-). HIV+ people also receive fewer cardiac procedures for AMI than HIV- people. Whether those with HIV with cardiomyopathy (CM) and low ejection fraction (EF) receive fewer implantable cardioverter defibrillators (ICD) compared to HIV- people with CM is not known.

Hypothesis:
We hypothesized (1) that HIV+ veterans with CM who qualify for an ICD (EF≤ 35%, NYHA II-III) will receive proportionally fewer ICDs than uninfected people with CM and (2) among those not receiving an ICD, mortality rates will be the highest for those with HIV infection.

Methods:
We analyzed data on 626 participants (44% HIV+) from the Veterans Aging Cohort Study Virtual Cohort, a prospective longitudinal of HIV+ and 1:2 matched HIV- Veterans, who were free of prevalent cardiovascular disease at study enrollment (n=97,685) and experienced an incident CM event with an associated EF ≤35% and/or left ventricular EF described as moderately to severely reduced between 2003-2009. Chi square testing was used to determine difference in the proportion of receipt of an ICD by HIV status. We calculated age and race adjusted mortality rates by HIV and ICD status.

Results:
Of the 626 participants with CM and low EF, 8.7% of HIV+ and 14.3% of HIV- patients received an ICD (p=0.04). Mortality rates (per 1000 person years) were: HIV+ no ICD (134, 95% CI=101-183), HIV+ with ICD (100, 95% CI=59-171), HIV- no ICD (73, 95% CI=53-103), HIV- with ICD (55, 95% CI=32-95). Among HIV+ and HIV-, there was no difference in mortality by ICD placement, p=0.66 and p=0.27, respectively. Mortality rates by HIV and ICD status over time are presented in Figure 1.

Conclusions:
Among Veterans with cardiomyopathy and low EF, receipt of ICD was lower among HIV+ compared to HIV- Veterans. Although not statistically significant, mortality rates were higher among those not receiving ICD, regardless of HIV status.
Abstract 18469: Syncope in the Pediatric Emergency Department - Can We Predict Cardiac Disease Based on History Alone?
Authors: Hurst David M , Hirsh Daniel , Oster Matthew , Ehrlich Alex , Campbell Robert , Mahle William , Mallory Michael , Phelps Heather
Published: April 2024

Objective:
The AHA published a statement on the evaluation of syncope in 2006 which stated that a "meticulous history" is of paramount importance when evaluating patients with an initial episode of syncope. However, little is known about which features of the history are most helpful in identifying children with undiagnosed cardiac syncope. Our objective was 1) to describe in a pediatric ED the burden of syncope due to cardiac disease and 2) to identify the historical features which are associated with an underlying cardiac diagnosis. We hypothesized that patients with cardiac syncope would present with at least two of the following four historical features: syncope with exercise, syncope preceded by palpitations, syncope without prodrome, or syncope with exercise preceded by chest pain.

Methods:
Using a cohort of patients who presented with syncope to our pediatric ED between May 1, 2009 and February 28, 2013, we 1) performed a cross-sectional study to describe the burden of cardiac syncope and 2) determined the sensitivity and specificity of our identified historical features with regard to identifying patients with cardiac syncope.

Results:
Of 3624 patients, 43.3% were male presenting at a mean age of 12.7 +/- 7.3 years. Of 67 (1.8%) with a cardiac diagnosis, 52 were previously known. Of the 15 new cardiac diagnoses, 12 were considered incidental. Three patients (0.11%) had a newly confirmed cardiac cause of syncope; two with supraventricular tachycardia and one with myocarditis. Among the three cases of cardiac syncope and 50 randomly selected cases of non-cardiac syncope, the respective sensitivity and specificity of the historical features were 67% and 100% for syncope with exercise, 100% and 98% for syncope preceded by palpitations, 67% and 70% for syncope without prodrome, and 67% and 100% for chest pain preceding syncope. Using the presence of at least 2 of the features as a marker for cardiac syncope yielded a sensitivity of 100% and specificity of 100%.

Conclusions:
Our study represents the largest series of pediatric patients presenting with syncope to an ED and our data confirms that newly diagnosed cardiac causes of syncope are rare. Furthermore, use of a few specific historical features on initial interview can help guide further workup more precisely.
Abstract 18495: Lung Inflammation Impairs Hypoxic Pulmonary Vasoconstriction Through Activation of Nuclear Factor of Activated T-Cells
Authors: Fraidenburg Dustin R , Voiriot Guillaume , Pohl Nicole M , Smith Kimberly A , Yuan Jason X
Published: April 2024

Hypoxic pulmonary vasoconstriction (HPV) is an important physiologic mechanism that directs blood flow away from poorly ventilated regions of the lung toward well-ventilated regions in order to maintain optimal ventilation (V) and perfusion (Q) matching which supports adequate gas exchange and oxygenation. Impaired HPV has been implicated in multiple disease processes that are associated with both hypoxemia and inflammation. Nuclear factor of activated T-cells (NFAT) is a calcium-dependent transcription factor with emerging evidence to suggest an important role in inflammatory as well as cardiovascular disorders. We hypothesize that lipopolysaccharide (LPS)-induced lung inflammation leads to impaired HPV as a result of NFAT activation. In the current study we have utilized the isolated perfused mouse lung (IPL) preparation to test acute hypoxic pulmonary vasoconstriction. Murine lung inflammation is induced by intratracheal instillation of LPS (1 mcg/gm body weight) and acute hypoxic pulmonary vasoconstriction is elicited by five minute challenges of 1% inspired oxygen tension. LPS-induced lung inflammation significantly impairs HPV at 24 hours compared to sham (saline) treatment. In protein isolates from whole mouse lung lysates, LPS-induced lung inflammation is associated with significant increases in both calcineurin and NFATc3 protein expression at 24 hours. Finally, pretreatment with a calcineurin inhibitor, cyclosporin A, one hour prior to LPS treatment prevents the impaired HPV seen in LPS-induced lung inflammation in a dose dependent manner at 30 and 100 mg/kg. We conclude that LPS-induced lung inflammation impairs hypoxic pulmonary vasoconstriction in mice. This effect is mediated by NFAT activation and we show that inhibition of calcineurin, leading to decreased NFAT activation, can attenuate the impaired HPV seen in murine lung inflammation. Impaired HPV results in V/Q mismatching and worsening hypoxemia, a detrimental effect in both acute and chronic cardiopulmonary disease. These results implicate NFAT as a potential novel therapeutic target in diseases characterized by hypoxemia and impaired HPV. We plan to continue this work to determine the downstream effects of NFAT activation that lead to impaired HPV.
Abstract 18497: Attenuated Endothelial Cd39 Activity Mediates Vascular Remodeling in Pulmonary Arterial Hypertension
Authors: Helenius Mikko , Vattulainen Sanna , Komulainen Anne , Taimen Pekka , Koskenvuo Juha , Alastalo Tero-Pekka
Published: April 2024

Occlusive intimal hyperplasia in pulmonary arterial hypertension (PAH) leads to devastating consequences in pulmonary circulation and increased mortality. A phenotypic switch in endothelial cells (EC) has been suggested to play a role in the pathobiology of occlusive vasculopathy. We hypothesized that alterations in extracellular purinergic signaling could play a role in regulating EC fate during PAH progression. Purine signaling is regulated by cell surface ecto-enzymes such as CD39 and CD73. These enzymes are powerful mediators of cellular signaling since their activity adjusts the level of extracellular purine nucleotides that are potent cell signaling molecules.

By using our unique magnet bead-based ex vivo EC profiling strategy in the rat monocrotaline model of PAH we identified a major ~50% decrease (p<0.001) in adenosinetriphosphate (ATP) -hydrolyzing CD39 activity at early stages of the disease. The activity of AMP-hydrolyzing CD73 was not changed during the disease course. Similar ~50% (p<0.05) decrease in specific CD39 activity, leading to accumulation of ATP niche, was observed in cultured pulmonary ECs from end-stage human idiopathic PAH patients. This attenuated enzyme activity was, at least partly, mediated through down-regulation of CD39 expression on RNA (~70%, p<0.05) and protein level. Immunohistochemistry on human iPAH patient lung revealed that CD39 was significantly down-regulated in arteries with intimal disease compared to arteries with normal appearance. We then showed that suppression of CD39 through RNAi or excess 2 μM ATP niche initiates an EC phenotypic switch with apoptosis resistant and hyperproliferative phenotype, identical to iPAH ECs. We also show that increased ATP niche stimulates synthesis of extracellular matrix components associated with intimal disease, such as versican. In addition, increased 2 μM ATP concentration and co culture with CD39-deficient ECs induce pulmonary artery smooth muscle cell (PASMC) proliferation (~50%, p<0.005) and migration (~50%, p<0.05) and, thus, could contribute to SMC pathology in PAH. We show evidence, both in rat and human, that attenuation of CD39 activity is tightly linked to vascular remodeling, EC phenotypic switch and could represent a novel target for PAH therapy.
Abstract 185: Additional Benefit of Cyclosporine-Assisted Adipose-Derived Mesenchymal Stem Cell Therapy for Against Acute Kidney Ischemia-Reperfusion Injury
Authors: Tsai Tzu -Hsien , Chua Sarah , Sheu Jiunn-Jye , Yip Hon-Kan
Published: April 2024

Objectives:
This study tested the hypothesis that cyclsporine (CsA)-supported adipose-derived mesenchymal stem cell (ADMSC) therapy offered superior attenuation of acute ischemia-reperfusion (IR) kidney injury than either therapy alone.

Methods:
Adult SD-rats (n=40) were equally divided into group 1 (sham controls), group 2 (IR injury), group 3 [IR + CsA (20 mg/kg at 1 and 24 hr after procedure)], group 4 [ADMSC (1.2x106) at 1, 6 and 24 h after procedure], and group 5 (IR + CsA-ADMSC).

Results:
By 72 h after IR procedure, creatinine level and the ratio of urine protein to creatinine were highest in group 2 and lowest in group 1, significantly higher in groups 3 and 4 than in group 5, but they showed no differences between groups 3 and 4 (all p<0.0001). The inflammatory biomarkers at mRNA (MMP-9, RANTES, TNF-α), protein (TNF-α, NF-κB, ICAM-1, PDGF), and cellular (CD68+) levels of IR kidney showed an identical pattern to creatinine level in all groups (all p<0.0001). The protein expressions of oxidative stress (oxidized protein), ROS (NOX-1, NOX-2), apoptosis (Bax, caspase-3 and PARP) and DNA damage markers (γH2AX+, PNCA+ cells) exhibited a similar pattern to inflammatory mediators (all p<0.0001) amongst all groups (all p<0.0001). Anti-oxidant biomarkers at cellular (GPx, GR, HO-1) and protein (NQO-1, HO-1, eNOS) levels, and endothelial progenitor cell markers (CXCR4+, SDF-1α+) were lowest in groups 1 and 2, higher in groups 3 and 4 and highest in group 5 (all p<0.0001).

Conclusions:
Combination therapy using cyclosporine-plus-ADMSCs offers improved protection against acute IR kidney injury.

Key words:
cyclosporine, adipose-derived mesenchymal stem cell, acute kidney ischemia-reperfusion injury, combination therapy, inflammation, oxidative stress, apoptosis
Abstract 18511: Early Re-Implantation After Infected Device Extraction is Safe, Reduces Length of Stay and is Not Associated With a Higher Rate of Reinfection
Authors: Sparano Dina M , Ericson Kyle J , Broman Michael T , Mehrotra Amit K , Sheth Harshal , Shin John H , Burke Martin C , Moss Joshua D , Nayak Hemal M
Published: April 2024

Introduction:
Cardiac implantable electronic device (CIED) infection often necessitates complete system removal (CSR) and eventual reimplantation. Concern for reinfection and other complication can delay reimplantation. We evaluated whether early reimplantation is safer, reduces length of stay (LOS) and predisposes to a higher reinfection rate than late reimplantation in patients undergoing CSR for CIED infection.

Methods:
We retrospectively reviewed data in 220 patients with CIED infection requiring CSR from 1995-2013 at a single academic medical center. We compared the incidence of major complications, wound dehiscence, and reinfection in patients undergoing early (≤ 48 hours) versus delayed (> 48 hours) reimplantation. A subgroup analysis in multi-drug resistant organism (MDRO) infections was performed.

Results:
A total of 97 patients were included. There were 43 patients reimplanted within 48 hours (88.4% men, mean age 69.0 yrs) and 54 patients reimplanted after 48 hours (77.8% men, mean age 65.1 yrs). There were more patients with initial systemic versus local infection in the delayed group (58.6% vs. 18.6%, p=0.0002). Reinfection after early reimplantation was not associated with a systemic presentation (40% vs. 50%, p=0.81). Early reimplantation did not portend a higher risk of major complications (4 vs. 1, p=0.10), wound dehiscence (1 vs. 0, p=0.26) or reinfection (5 vs.2, p=0.13). The findings were similar in early (n=18) versus delayed (n=19) reimplantation in patients with MDRO-positive infections (major complications: 2 vs.1, p=0.52, dehiscence: 0 vs.0, reinfection: 1 vs.1, p=0.97). Early reimplantation was associated with shorter hospital stay than delayed reimplantation (9.3 vs. 16.3 days, p=0.0005).

Conclusions:
In patients with CIED infection who have undergone CSR, including those with MDRO infections, early device reimplantation within 48 hours is safe, is not associated with a higher reinfection rate and reduces hospital LOS.