bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19231: Chemotactic Properties of Perivascular Adipose Tissue in Angiotensin Ii Dependent Hypertension
Authors: Nosalski Ryszard , Mikolajczyk Tomasz , Korbut Ryszard , Harrison David , Guzik Tomasz
Published: April 2024

Introduction.
Recent studies show that immune system is involved in hypertension (HT). Angiotensin II (AngII) causes accumulation of T cells in perivascular adipose tissue (pvAT) but precise mechanisms of their infiltration remain unclear.

Hypothesis.
RANTES and it’s receptors recruit T cells towards pvAT.

Methods.
Expression of chemokine receptors on peripheral blood T cells and chemokine ligands in pvAT was studied by flow cytometry and quantitative RT-PCR respectively. Chemotaxis of T cells towards pvAT, vAT (epidydymal AT) or RANTES was studied in Boyden chambers.

Results.
14 day infusion of AngII (490mg/d/kg) was associated with significant increase in T cell content in pvAT with concomitant increase of RANTES mRNA expression (p<0.001). Expression of other CCR5 ligands MCP-1, MIP-1α and MIP-1β was significantly decreased. AngII significantly increased total content of T cells in pvAT expressing receptors for RANTES: CCR1 (27.9±4.6% vs.15.7±1%), CCR3 (17.1±1.4% vs.10.5±1.4%), CCR5 (23.6±0.9% vs.17±0.9%), while having no effect in vAT. T cells showed increased chemotaxis towards pvAT obtained from AngII infused mice when compared to sham animals (4.4±0.7 vs.0.17±0.17; p<0.01). Moreover pvAT attracted higher amount of T cells as compare to vAT (4.4±0.7% vs.0.8±0.1%; p<0.05); there was minimal migration toward subcutaneous fat. Moreover RANTES (10ng/ml) recruited T cells, but not B cells, from blood. Ang II infusion increased chemotaxis of blood derived T cells towards RANTES by 2-fold (p<0.01). However the most prominent chemotaxis potential was observed in pvAT isolated T cells from AngII treated mice (2.4±0.3% vs.0.8±0.2% in sham, p<0.01). CD4-CD8- T cells were characterized by the highest rate of migration towards RANTES. In contrast, migration capability of T cells resident in vAT was of minimal rate.

Conclusions.
Ang II enhances T cell migration into pvAT but not vAT by increasing local RANTES expression. All known RANTES receptors are involved. And in particular CCR1 and CCR5 on CD3+CD4-CD8- cells.
Abstract 19253: Acute Inflammation Following Dental Treatment Alters Endothelial Effects, but not Cholesterol Efflux Capacity of HDL
Authors: O'Neill Francis P , Besler Christian , Colin Sophie , Riwanto Meliana , Manz Jasmin , Madden-Raja Kate , Chinetti Giulia , Staels Bart , D'Auito Francesco , Landmesser Ulf , Deanfield John E
Published: April 2024

Background:
HDL elevating therapies have thus far failed to improve CV outcome and the loss of anti-atherosclerotic properties of HDL has recently been reported in CAD. This suggests specific biological activities of HDL, rather than its cholesterol content, may be crucial in mediating the anti-atherogenic effects of HDL.

Aim:
To determine the impact of acute systemic inflammation on various measures of HDL function.

Methods:
50 subjects with periodontitis (PD) (Age 49.8 [6.5]) underwent dental treatment. In vivo changes in endothelial function were determined using Flow Mediated Dilatation (FMD). HDL function was assayed at baseline, at the peak of the inflammatory response (24 hours after PD treatment) and following resolution (6 months post PD treatment). HDL-mediated cholesterol efflux was measured in J774 macrophage cells, pre-treated with cAMP. Impact of HDL on cultured endothelial aortic cells was assayed by measuring HDL-dependent Nitric Oxide bioavailibility (NO) and superoxide (SO) production using ESR Spectroscopy. HDL-associated Paraoxonasae-1 (PON1) activity was measured by spectrophotometry.

Results and Discussion:
24 hours after dental treatment HDL became dysfunctional, as shown by reduced NO and increased SO production by cultured endothelial cells (P<0.01 for both). In addition, PON1 activity was reduced (P=<0.05), but no difference was found in cholesterol efflux capacity. At 6 months, these changes in HDL function returned to baseline levels, whereas cholesterol efflux capacity remained unchanged. Endothelial effects of HDL tracked with changes in inflammatory markers and FMD.

Conclusion:
HDL becomes dysfunctional during acute inflammation resulting in abnormal endothelial responses, in the absence of any change in efflux capacity. Furthermore, the acute impairment of HDL function is reversible upon resolution of inflammation and tracks changes in FMD. These results suggest HDL function may contribute to the vascular alterations observed during an inflammatory response and may represent a novel mechanism whereby inflammation may promote atherosclerosis, i.e. by altering the endothelial effects of HDL.
Abstract 19254: Engineering a Bioactive Pulmonary Valve using Patient-Specific Valvular Cells
Authors: Simpson David , Galat Vasil , Galat Yekaterina , Kaushal Sunjay
Published: April 2024

Background:
Valvular heart disease is an unfortunate part of the natural history of many congenital heart patients. Even with surgical interventions that use valvular replacements, pediatric patients with valvular dysfunction will likely require reoperations due to a progressive deterioration of graft durability and limited repair/growth potential. In order to address these concerns we sought to generate a biologically active pulmonary valve using patient-specific valvular cells and decellularized human pulmonary grafts.

Methods and Results:
Mesenchymal stem cells (MSCs) were generated from patient derived induced pluripotent stem (iPS) cells using culture conditions that favored an epithelial to mesenchymal transition. iPS-MSCs displayed CD105 and CD90 expression > 90% after four passages and could differentiate into osteocytes, chondrocytes and adipocytes (N=4). iPS-MSCs lacked expression of CD45 and CD34. Additionally, compared to bone marrow MSCs, iPS-MSC proliferated more readily (43 ± 1 vs 87 ± 1, p < 0.001) but maintained a gene expression profile >80% identical to bone marrow MSCs. Next, decellularized human pulmonary heart valves (provided by CryoLife®, Inc.) were seeded with iPS-MSCs using a combination of static and dynamic culture conditions. Repopulated pulmonary grafts were cultured up to 30 days. Immunohistochemistry demonstrated increased cellularity and presence of extracellular matrix components such as vimentin, proteoglycans and glycosaminoglycans in repopulated pulmonary valves compared to decellularized pulmonary valves, suggesting sustained cell function and maturation.

Conclusions:
Our results demonstrate the feasibility of constructing a biologically active human pulmonary valve using a sustainable and potent cell source. It is expected that once implanted, the bioactive pulmonary valve will have advantages over existing valvular replacements by its ability to remodel and grow in the repair of congenital defects.
Abstract 19265: Adipose Tissue Overexpression of a Constitutively Active Isoform of Chrebp Protects Against Obesity and Insulin Resistance in Mice
Authors: Nuotio-Antar Alli , Poungvarin Naravat , Li Ming , Chan Lawrence
Published: April 2024

Obesity is associated with increased risk for T2DM and CVD in humans, and nutrients typically consumed in excess in the Western diet, such as various saturated fats, cholesterol, and simple sugars, are thought to regulate the activity of metabolic genes that modulate risk for obesity and insulin resistance. The glucose-sensing transcription factor carbohydrate response element binding protein (ChREBP) has been shown to regulate hepatic intracellular glucose and lipid homeostasis independent of the effects of insulin. Recent publications have reported that white adipose tissue (WAT) and brown adipose tissue (BAT) depots also highly express ChREBP, that ChREBP expression is upregulated during adipocyte differentiation, and that increased ChREBP activation in adipocytes is associated with obesity, but not insulin resistance, in the context of adipose tissue-specific GLUT4 overexpression in mice. However, independent modulation of ChREBP expression in adipose tissue has not yet been achieved. To better understand the impact of adipocyte-specific ChREBP activity on intracellular and whole-body metabolism, we have generated a novel transgenic mouse model that overexpresses a constitutively active ChREBP (caChREBP) isoform in adipose tissue (ap2-Cre;eGFPflox-caChREBP mice). When fed either standard chow diet or Western-type diet (WD) for 10 weeks, total fat mass, but not lean mass, was significantly decreased in male ap2-Cre;eGFPflox-caChREBP mice versus ap2-Cre littermate controls. Both glucose tolerance testing and insulin tolerance testing revealed no differences between groups of chow-fed mice, but significantly improved insulin sensitivity in WD-fed male ap2-Cre;eGFPflox-caChREBP mice. RER during the daily active cycle was increased in WD-fed ap2-Cre;eGFPflox-caChREBP mice, implying greater utilization of carbohydrate for energy expenditure. Transgenic overexpression of caChREBP resulted in increased expression of lipogenic genes, but not genes involved in adipocyte differentiation, in gonadal fat. Taken together, these data indicate that upregulation of ChREBP activity in adipose tissue may defend against WD-induced obesity and insulin resistance, despite increased adipocyte expression of lipogenic genes.
Abstract 19284: Clinical Determinants of Global and Regional Left Ventricular Systolic Function by Cardiac Magnetic Resonance Imaging: The Jackson Heart Study
Authors: Balfour Pelbreton C , Musani Solomon K , Williams Renaldo , Samdarshi Tandaw S , Carr Jeffrey , Hundley William G , Terry Greg , Taylor Herman A , Ramachandran Vasan S , Fox Ervin
Published: April 2024

Introduction:
Cardiac MRI (CMRI) provides high-resolution images, along with accurate and reproducible measurements of global and regional left ventricular (LV) systolic function (including LV ejection fraction, stroke volume, global and regional systolic strain). We examined the cross-sectional association of traditional cardiovascular (CV) risk factors with CMRI determined systolic function in a community-based cohort of African Americans (AAs).

Methods:
We evaluated 1,322 Jackson Heart Study participants (63% women, mean age 57 years) who had MRI exams performed at Examination 2. Measures of LV systolic function included ejection fraction, stroke volume, global strain (considered the mean peak systolic midwall Eularian strain -averaged for the base, mid-ventricle and apex in all segments) and regional strain (averaged for the mid-ventricle or apex only). Clinical covariates included age, sex, systolic and diastolic BP, BMI, fasting glucose (FG), diabetes status (DM), lipids, smoking, alcohol use, hypertension (HTN) medication, lipid lowering medication, education and income. Multiple stepwise linear regression analysis was used to model the association of clinical covariates (independent variables) with global and regional measures of LV systolic function.

Results:
Regression analysis demonstrated that LV ejection fraction was independently and positively associated with systolic BP (p= 0.0002) but inversely associated with male sex and FG (p < 0.0001 and p = 0.011 respectively). Stroke volume was independently and positively associated with male sex, systolic BP, and BMI (p < 0.001 for all) but inversely related to age, diastolic BP, and smoking (p= <0.01 for all). More optimal (more negative) global and mid wall systolic strain were inversely associated with older age, male sex, BMI, and smoking (all p <0.002). Lower (more optimal) apical strain was inversely associated with older age, male sex, HTN status, higher BMI, and smoking (p <0.02 for all) but was positively associated with DM (p= 0.049).

Conclusions:
In our cross-sectional study of a large AA community-based cohort, we identified several modifiable CV risk factors (BP, BMI, FG, smoking) associated with global and regional measures of LV systolic function as assessed by CMRI.
Abstract 19337: Cathepsin L is Required to Modulate Cardiac Hypertrophy through Activation of the Autophagy-Lysosomal Dependent Protein Processing Pathway
Authors: Moon Mark , Sun Mei , Ouzounian Maral , Li Guohua , Liu Youan , Gramolini Anthony , Liu Peter P
Published: April 2024

Background_Autophagy is critical in the maintenance of cellular protein quality control involved in the cell growth, survival and death. Cathepsin L (CTSL) is a key member of the lysosomal protease family that is expressed in the murine and human heart, and may play an important role in dynamic protein control. We hypothesized that CTSL is important in regulating protein processing in the heart, particularly under pathological stress.

Methods and Results_Phenylephrine-induced cardiac hypertrophy in vitro was significantly more pronounced in CTSL deficient neonatal cardiomyocytes compared to controls. This was accompanied by a significantly increased accumulation of autophagosomes, increased levels of ubiquitin-conjugated protein, impaired protein degradation and increased cell death. These phenomena were rescued with Ctsl1 replacement via adeno-associated virus mediated gene transfer. In the in vivo murine model of aortic banding (AB), CTSL deficiency (Ctsl-/-) markedly exacerbated cardiac hypertrophy, worsened cardiac function, and increased mortality. Ctsl-/- AB mice demonstrated significantly decreased lysosomal activity, and increased sarcomere-associated protein aggregation. Homeostasis of the endoplasmic reticulum was also altered with increased Bip and GRP94 proteins in Ctsl-/- AB mice, accompanied by increased ubiquitin-proteasome system activity and higher levels of ubiquitinated proteins in response to AB. These changes ultimately led to a decrease in cellular ATP production, enhanced oxidative stress, and increased cellular apoptosis.

Conclusions_Lysosomal CTSL is a key contributor to modulate the cardiac response to hypertrophic stress through regulation of protein processing and quality control.
Abstract 19344: Evaluation of the Effects of Diabetes, Insulin Resistance, and Inflammation on Coronary Endothelial Function Assessed by Cardiac Perfusion MRI with Cold Pressor Test
Authors: Marfori Wanda , Hollada Jacqueline L , Tognolini Alessia , Sayre James W , Yang Eric H , Ruehm Stefan
Published: April 2024

OBJECTIVE:
To evaluate the effects of diabetes, insulin resistance (IR) and inflammation on coronary endothelial function assessed by cardiac stress perfusion MRI (CMRI) w/ cold pressor test (CPT).

METHODS:
20 subjects (14 men, 6 women; mean age: 53.5 - Range: 39-62) w/ T2DM (5-15 years) and 20 healthy controls (age/sex matched) were enrolled in a prospective IRB-approved HIPAA compliant study. Medical history for risk factors was obtained. Subjects w/ known CAD were excluded. Fasting plasma glucose (FPG), insulin, C-peptide, HbA1c, eGFR, lipids and UA/Cr ratio; inflammatory markers: IL-6, TNF-α, hs-CRP and PAI-1 were obtained. 2-hour OGTT was performed on healthy subjects to confirm absence of pre-DM/T2DM. BMI, W/H ratio and HOMA-IR were calculated. To assess vascular tone and myocardial blood flow (MBF) responses to CPT, CMRI w/ CPT was performed w/ gadolinium (Multihance, Bracco) on a 3.0T scanner. Signal slope,
myocardial perfusion reserve index (MPRI
), and RPP were calculated.

RESULTS:
Comparison of MPRI between T2DM (
1.39 ± 0.10)
vs. healthy
(2.52 ± 0.36)
showed significantly decreased endothelium-dependent change in MBF to CPT in diabetics (p=0.003). Univariate analysis showed that age (p=0.001); HbA1c (p=0.001); FPG (p=0.005); HOMA-IR (p=0.04); IL-6 (p=0.05) and TNF-α (p=0.004) showed significant association w/ MPRI in T2DM. Multivariate analysis, age (p=0.017); FPG (p=0.05); UA/Cr ratio (p=0.001); insulin (p=0.046) and C-peptide (p=0.036) remain statistically significant independent predictors of changes in MBF. Correlative studies showed an inverse relationship w/ MPRI and the following: BMI, W/H ratio, FPG, HOMA-IR, LDL, Triglycerides, PAI-1, IL-6, TNF-α and Hs-CRP as well as a direct relationship w/ HDL and eGFR.

CONCLUSIONS:
Our results demonstrate that the diabetic state characterized by IR and chronic inflammation is significantly associated w/ low or decreased MPRI that reflects impaired endothelium-related coronary vasomotion, CMRI w/ CPT provides a non-invasive, analytical tool for early detection of endothelial dysfunction. Large scale clinical trials using CMRI w/ CPT for detection of endothelial dysfunction in at-risk populations w/ long term follow-ups, after therapeutic and lifestyle intervention, is warranted.
Abstract 19348: The Impact of Hypothyroidism on Platelet-Fibrin Clot Characteristics in Patients Undergoing Cardiac Catheterization
Authors: Singla Anand , Bliden Kevin , Tantry Udaya , Jeong Young-Hoon , Gurbel Paul A
Published: April 2024

Hypothyroidism and accompanying hypercholesterolemia are associated with accelerated atherosclerosis. Hypothyroidism has been associated with inﬂammation, endothelial dysfunction, and platelet function abnormalities. However, impact of hypothyroidism on the physical characteristics of the platelet-fibrin clot is unknown. We sought to determine the impact of hypothyroidism on platelet-fibrin clot characteristics in patients undergoing cardiac catheterization.

Methods:
Patients on 325 mg daily aspirin with (n=41) and without (n=286) a history of hypothyroidism undergoing cardiac catheterization were studied. Hypothyroidism was defined as treatment with thyroid hormone replacement. Blood samples were collected immediately prior to coronary angiography to determine clotting characteristics by thrombelastography (TEG). Urinary 11-dehydrothromboxane B
2
was performed by immunoassay method.

Results:
Baseline demographics and cardiac risk factors were similar between groups. Thyroid stimulating hormone levels were within the normal range with no significant difference between groups. Patients with a history of hypothyroidism had significantly higher thrombin-induced platelet fibrin clot strength(67.9±5.3 mm vs.66.1±5.8 mm, p=0.04) , faster time to initial thrombin formation (6.9±1.9 vs. 7.8±2.1, p=0.02) , and higher clotting index(0.7±2.4 vs. -0.4±2.0, p=0.005). There were no differences in urinary 11-dehydrothromboxane B
2
between groups.

Conclusion:
This is the first report that a history of hypothyroidism is associated with altered physical characteristics of the platelet-fibrin clot; an increase in the tensile strength of the clot. Further studies are needed to confirm this association and its relation to ischemic outcomes.
Abstract 19351: Reduced Proteasome Heterogeneity Augments Cardiac Remodeling
Authors: Liem David , Koser Franziska , Tsukamoto Osamu , Wang Yibin , Hecker Markus , Ping Peipei , Drews Oliver
Published: April 2024

The ubiquitin proteasome system regulates cellular function through targeted degradation of signaling and structural proteins. In the mammalian heart, there exist proteasome subpopulations with distinct functionality, conferring the capacity to adjust proteolytic function under physiological and pathological conditions. In fact, the composition of proteasome subpopulations seems to be highly dynamic during cardiac remodeling. However, whether proteasome composition in turn affects myocardial remodeling is not known. Therefore, aim of the study was to determine whether specific proteasome subpopulations impact cardiac remodeling. Analyses of cardiac proteasome assembly during seven day catecholamine treatment of mice demonstrated that the inducible proteasome subunits β1i and β5i were increasingly incorporated in proteasome complexes (up to 50%), whereas the incorporation of constitutive subunits remained unchanged. During the treatment, heart weight to body weight ratio (HW/BW) increased by approx. 50% (6.1 vs 4.1), documenting that the mice developed cardiac hypertrophy. Functional assays of proteasome activities in hypertrophic hearts showed heterogeneous regulation of substrate specificity and turn-over, further indicating a shift in the composition of proteasome subpopulations. Unchallenged mice lacking the subunit β1i and the corresponding proteasome subpopulation are visually indistinguishable from wild-type mice and have a HW/BW ratio of approx. 4.4. Remarkably, catecholamine challenge for seven days induced a more severe cardiac phenotype in those mice with increased HW/BW of approx. 70% (7.6 vs. 4.4). In conclusion, this study demonstrates for the first time that the ubiquitin proteasome system has the capacity to modulate cardiac tissue mass in response to a hypertrophic stimulus via specific proteasome subpopulations, providing a novel mechanism to regulate cardiac remodeling.
Abstract 19381: Imatinib Mesylate Modifies Induced Pathological Hypertrophy by Altering Myocyte Calcium
Authors: Barr Larry , Kubo Haji , Gao Hui , Makarewich Catherine , Berretta Remus , Force Thomas , Houser Steven R
Published: April 2024

Background —

 Imatinib mesylate (IM) is a small molecule inhibitor of the fusion protein Bcr-Abl, which causes chronic myelogenous leukemia. There is some concern that IM can induce cardiac dysfunction in cancer patients. A previous study showed that chronic treatment of adult mice with IM for 3-4 weeks leads to deterioration in contractile function and LV mass decrease. We investigated the effects of IM on neonatal rat ventricular myocytes (NRVMs). The hypothesis is that calcium regulatory mechanisms are altered to induce pathological hypertrophy.

Methods and Results —

 NRVMs were treated with a clinical dosage (2 µM) of IM.  Western analysis showed a significant increase in phospholamban phosphorylation at T-17, signifying activation of CaMKII. The rate of decay of the systolic Ca
2+
transient was increased, consistent with an increase in rate of Ca
2+
resequestration into the SR. Coulter counter analysis was used to determine cell size and showed that average NRVM volume increased significantly (Con-102 pl; IM-133 pl. p<0.05). Myocyte surface area also increased with IM treatment (Con-6277 μm
2
; imatinib-10259 μm
2
p<0.05). Western analysis showed significant increases in ANP abundance, a pathological hypertrophy marker, after IM administration. NRVMs were infected with AdNFATc3-GFP and NFAT nuclear translocation was analyzed as nuclear/cytoplasmic GFP. Nuclear translocation was significantly increased with IM treatment. The calcineurin inhibitor FK506 inhibited IM induced NFAT nuclear translocation (Con-0.8162 ± 0.032; imatinib-2.233 ± 0.13; imatinib+FK506-0.6277 ± 0.037. p<0.05).

Conclusions —

 These data show that clinical doses of IM activate pathological hypertrophy signaling pathways by enhancing SR function. This could be a mechanism for adverse cardiac effects of IM.
Abstract 19383: Reduced Longitudinal and Circumferential Strains with Radial Compensation in End Stage Renal Disease Patients Despite Normal Ejection Fraction
Authors: Varadarajan Padmini , Rasool Shuja , Aftab Waqas , Pai Ramdas G
Published: April 2024

Background:
Patients with end stage renal disease (ESRD) have high prevalence of heart failure despite normal left ventricular (LV) ejection fraction (EF) leading to adverse outcomes and higher mortality. Hence, we prospectively assessed LV strain patterns in ESRD patients with normal EF.

Methods:
We prospectively evaluated 100 ESRD patients with normal EF and wall motion and compared them to 22 age and gender matched controls. Complete demographic, clinical and echocardiographic data were collected. LV longitudinal, circumferential and radial strains were computed using speckle tracking echocardiography and corresponding end systolic wall stresses were calculated using Mirsky’s formulae.

Results:
The mean age was 54 years, 41% men, 53% had diabetes, mean EF was 65% and 15% had heart failure. The global longitudinal and mid LV circumferential strains were significantly lower in patients with ESRD with normal EF compared to the age and gender matched controls (-15.7+7.9% vs -20.4+4.1%, p=0.02 and 19.8+6.2% vs 25.2+3.8%, p=0.01 respectively). However, the radial strain was marginally higher compared to the controls (26.2+15.4% vs. 17.4+9.6%, p=0.07). Normalized for the corresponding wall stresses, only the circumferential strain was lower in ESRD patients and longitudinal and radial stresses were similar between the groups.

Conclusions:
1) Global longitudinal and circumferential strains are reduced accompanied by an increase in radial strain in ESRD patients with normal EF. 2) This may only partly be explained by changes in wall stress and reflects incipient LV myocardial dysfunction. 3) Evaluation and targeting of abnormalities of LV wall stress and strain in this high risk population may help obviate heart failure and its deleterious consequences.
Abstract 19385: Comparison between Oral Rapamycin Plus Bare Metal Stent versus Drug Eluting Stent for the Prevention of Restenosis in the Treatment of Coronary Disease with Percutaneous Coronary Interventions. Four Years Results from the ORAR III Trial
Authors: Rodriguez Alfredo E , Rodriguez-Granillo Alfredo M , Fernandez-Pereira Carlos , Mieres Juan , Risau Gustavo , Rubilar Bibiana , Antoniucci David , Palacios Igor F , Serruys Patrick W
Published: April 2024

Background.
One and three years results of ORAR III trial previously published showed a significant reduction in costs with oral rapamycin plus bare metal stent (OR) compared with drug eluting stents (DES) without significant differences in death, myocardial infarction (MI) and stroke for the prevention of restenosis. (
NCT00552669
)

Methods:
From January 2006 to September 2007 in 3 hospitals in Buenos Aires, Argentina, 200 patients (pts) were randomized either to OR (n=100) or DES (n=100). Primary endpoint compared clinical efficacy and safety of OR vs DES treatment for denovo coronary lesions evaluated by the composite of death, MI and stroke (D,MI,S); Target Vessel Failure (TVF) defined as cardiac death, MI and Target Vessel Revascularization (TVR) and TVR alone at 4 years of follow up. A sub-analysis of pts over and under 65 years old was also done (40 pts in OR and 48 pts in DES ≥ 65 years). OR was given as a bolus of 10 mg the day before PCI followed by 3 mg/daily during the following 13 days. DES group received clopidogrel for at least one year and OR group for a month. Exclusion criteria were MI in the last 24 hours, in stent restenosis and previous PCI in the last six months.

Results:
Baseline demographic, clinical and angiographic characteristics were similar. 1.6 +/- 0.7 vs 1.7 +/- 0.8 (p=0.3) lesions per pt were treated in OR vs DES respectively, and 171 stents in OR vs 176 in DES groups were deployed (p=0.9). 4 years clinical follow up was accomplished in 99% of pts. In DES group 45.9% of pts were still receiving thyenopiridines vs. 18.9% of OR (<0.001). D,MI,S was 11.0% in OR group vs. 23.0% in DES, p=0.02; TVF was 25.0% in OR vs 37.0% in DES, p=0.06 and TVR was 14.5 % in OR group vs 20.8% in DES group, p=0.17. When analyzing pts ≥ 65 years dyslipemia was the only significantly different baseline characteristic. At 4 years D,MI,S was 7.5% (OR) vs. 25.0% (DES), p=0.03, TVF 22.5% (OR) vs 45.8% (DES); p=0.02 and TVR was 14.0% in OR vs 21.9% in DES groups (p=0.26); there were no differences in outcomes of pts < 65 years old.

Conclusions:
Four years follow up of this randomized trial revealed significant differences in the composite of death, MI and stroke in favor of OR therapy in overall population and in pts > 65 years old without differences in TVR. No differences were seen between groups under 65 years.
Abstract 19389: The Net Clinical Benefit of Left Atrial Appendage Closure in the Continued Access Protocol (CAP) Registry
Authors: Gangireddy Sandeep R , Halperin Jonathan L , Fuster Valentin , Reddy Vivek Y
Published: April 2024

Introduction:
PROTECT AF revealed LA appendage closure (LAAC) to be an effective alternative to warfarin in nonvalvular AF patients. The non-randomized CAP registry demonstrated that with increased operator experience, there were fewer procedure-related complications with LAAC. Our objective was to estimate the net clinical benefit (NCB) of percutaneous LAAC in the CAP registry.

Methods:
Post hoc analysis of outcomes in both the randomized PROTECT AF trial (n=707) and the non-randomized CAP registry (n=566). Based on the relative clinical impact, outcomes were weighted using death as the index parameter (ie, =1): ischemic stroke = 0.2, intracranial hemorrhage = 0.6, major bleeding = 0.1, tamponade =0.1. NCB was calculated as the sum of annualized rates of these outcomes after LAAC in the CAP registry minus rates on warfarin in the PROTECT AF control group.

Results:
The NCB of LAAC during 962 person-years of follow-up in the CAP registry was 3.87%/year (95% CI 1.90-6.11%/year), compared with 1.62%/year (95% CI -0.25-3.72%/year) in PROTECT-AF trial. Among patients with a history of ischemic stroke, NCB was greater in CAP (7.34%/year, CI 1.97-14.85%/year) than PROTECT AF (3.62%/year, CI -1.50-9.23%/year). In the registry, the NCB of LAAC increased from 1.64 %/year (95% CI -0.3-5.16%/year) in patients with CHADS2 scores=1 to 4.99%/year (95% CI 1.3-9.07%/year) in those with scores >2.

Conclusion:
With increased operator experience, the net clinical benefit of LAA closure exceeds Warfarin therapy.
Abstract 19397: Poor Appetite or Overeating Predict Shorter Survival in Chronic Systolic Heart Failure
Authors: Warrings Bodo , Störk Stefan , Gelbrich Götz , Frantz Stefan , Jahns Roland , Piepenburg Sven , Saglam Ilknur , Ertl Georg , Angermann Christiane , Faller Hermann
Published: April 2024

Introduction:
Chronic systolic heart failure (CHF) is a major cause of death and hospitalization. There is growing interest in psychosomatic factors impacting on outcome in CHF. Both obesity and cachexia were shown to influence the outcome of CHF patients. We investigated the prevalence and prognostic impact of eating disorders (reduced appetite or overeating) on mortality risk in CHF.

Hypothesis:
Reduced appetite or overeating predict reduced survival in CHF.

Methods:
864 patients hospitalized for cardiac decompensation with left ventricular ejection fraction <40% (mean age 67 years, 72% male,) were examined after best possible recompensation prior to discharge using the Patient Health Questionnaire (PHQ-9). The PHQ-9 is a 9-item self-administered questionnaire for identification and semi-quantitative assessment of suspected depression. Question #5 addresses poor appetite or overeating. The survival status was reassessed after a median follow-up of 18 months. Cox proportional hazards regression was used to determine the relationship between reported poor appetite or overeating and survival.

Results:
At baseline, poor appetite or overeating were reported “not at all” by 403 patients (figure, line 1), “on several days” by 272 patients (line 2), “more than half of all days” by 81 patients and (line 3), “nearly every day” by 101 patients (line 4). At follow-up, 156 patients (18%) had died. All-cause mortality risk was increased in all patient groups with eating disorders: hazard ratio(line 4) 2.7 (95%CI 1.7-4.2; p<0.001), HR(line 3) 2.6 (95%CI 1.6-41.2; p<0.001), HR(line 2) 1.5 (95%CI 1.0-2.3; p=0.03). These results remained significant also in multivariable analysis adjusting for the other 8 PHQ-9 items.

Conclusion:
Eating disorders with reduced or absent appetite or overeating represent powerful prognostic indicators regarding all-cause mortalityrisk in patients with CHF hospitalized for cardiac decompensation.
Abstract 19465: Cardiac Gene Knockdown Using Small Inhibitory RNA-Loaded Microbubbles and Ultrasound
Authors: Carson Andrew R , McTiernan Charles F , Chen Xucai , Villanueva Flordeliza S
Published: April 2024

Background
RNA interference (RNAi) is a cellular process that regulates gene expression via sequence-specific mRNA degradation and translational blockage. The potent gene knockdown effects of RNAi could have broad therapeutic applications in cardiovascular disease, but is currently limited by inefficient delivery strategies, off-target effects, and nuclease activity which degrades RNAi molecules such as small inhibitory RNA (siRNA). We hypothesized that cardiac ultrasound (US)-targeted destruction of microbubbles (MB) bearing siRNA would selectively knock down target cardiac genes.

Methods
A transgenic mouse model of cardiac restricted luciferase expression was used. RNA binding-MBs were prepared by amalgamation of cationic and neutral lipids in the presence of siRNA specific to luciferase or negative control siRNA. RNA binding was confirmed by serial washing of loaded MBs followed by electrophoresis. RNAse resistance was determined by exposure of siRNA-loaded MBs to RNAseA, followed by electrophoresis. siRNA-loaded MBs (5 µg per 7x10
8
MBs) were infused through the internal jugular of transgenic mice over 15 min during concurrent MB-destructive transthoracic US (1.3 MHz, MI 1.6). The US pulse sequence was designed to allow complete myocardial MB replenishment between each destruction sequence, as confirmed by contrast-specific US imaging. Luciferase expression was determined 3 days later by luciferase assay and RT PCR.

Results
MBs bound ∼7 µg siRNA per 10
9
MBs and protected siRNA from RNAseA digestion at concentrations sufficient for digestion of siRNA in the absence of MBs. US-targeted cardiac delivery of MBs bearing luciferase siRNA resulted in significant knockdown of luciferase expression in transgenic mice 3 days after treatment compared to controls (53% knockdown vs. no treatment, p=0.03; 65% knockdown vs. control siRNA+MBs+US, p=0.02) and by RT PCR (68% knockdown vs. no treatment, p=0.05).

Conclusion
siRNA delivery using custom MBs and US silences cardiac reporter gene expression. These data establish general principles that can be extended to US-MB theranostic platforms for image-guided targeted gene knockdown in cardiovascular diseases for which specific gene silencing represents a therapeutic approach.
Abstract 19470: Presence of Anemia at Induction of Therapeutic Hypothermia as a Predictor of Neurological Outcome in Cardiac Arrest Survivors
Authors: Patel Nishant , Nair Sanjeev U , Manandhi Raghu , Ganga Harsha V , Lundbye Justin B
Published: April 2024

Introduction:
Therapeutic hypothermia (TH) has become an accepted practice to improve neurological outcome in survivors of cardiac arrest. Co-morbid factors that may impact neurological outcome in such patients are not well understood. Anemia has been shown to have a prognostic value in a wide variety of diseases. We investigated the effect of hematocrit on neurological outcome in cardiac arrest survivors undergoing TH.

Methods:
A retrospective analysis was performed on 196 consecutive cardiac arrest survivors who underwent TH with endovascular cooling in the cardiac intensive care unit at a tertiary care center between January 2007 and April 2012. Patients were divided into two groups based on anemia as per their hematocrit (Hct) value at induction of TH (Hct≤36 and Hct>36). The primary endpoint was measured using the Pittsburgh cerebral performance category (CPC) scale and patients were assessed for a good (CPC 1 and 2) or poor (CPC 3-5) neurological outcome prior to discharge from hospital.

Results:
Of the 196 patients, 130 patients (66 %) had a Hct ≤ 36 and 66 patients (34 %) had a Hct > 36. Forty two (32%) patients with Hct ≤ 36 and 25 patients (38%) with Hct>36 had a good neurologic outcome (P=0.50)
(Figure 1)
. On multivariable analysis, initial/presenting rhythm (OR: 8.752; 95 % CI 2.60-29.40, P< 0.001) and time to return of spontaneous circulation (OR: 0.942; 95 % CI 0.90-0.99, P=0.02) were independent predictors of neurologic outcome.

Conclusion:
Presence of anemia at induction of TH is not associated with neurological outcome in cardiac arrest survivors.
Abstract 19480: Non-Calcified Coronary Plaque (NCCP) Burden & its Correlation with Left Ventricular Mass (LVM) in Diabetic vs Non-Diabetic Patients
Authors: Khan Atif N , Khosa Faisal , kang Jian , Malik Zehra , Jon Ali F , Niazi Faraze , Clouse Melvin E
Published: April 2024

Determine Non-Calcified Coronary Plaque (NCCP) burden & its correlation with Left Ventricular Mass (LVM) in Diabetic vs Non-diabetic patients.

Methods
: IRB approved, retrospective review of 190 patients imaged with 320-row MDCTA [89 Diabetics (mean age 62.5 ± 8.73 Yrs & BMI 31.49 ± 5.13) & 101 Non-diabetic (mean age 61.15±14.6 Yrs & BMI 27.47 ± 5.47)]. Measurements were taken for plaque subtypes and total plaque burden (TPB) using Vitrea 5.2. RCA, LM, LAD and LCX were analyzed to quantify fatty, fibrous and calcified plaque in mm
3
. LVM was calculated from left ventricular inner diameter (LVID), posterior wall thickness (PWD) and Septal wall thickness (SWT) measured in diastolic phase from 4 and 2 chamber views using ASE formula. STATA was used for analyses.

Results:
TPB & LVM for diabetic vs. non-diabetic were: RCA: 10.00±3.80 mm
3
vs 8.69±4.2 mm
3
, p = 0.029; LM 16.66±5.24 mm
3
vs 13.74±4.58 mm
3
,p = <0.001, LAD: 7.41±2.67 mm
3
vs 6.55±2.72 mm
3
, p = 0.034; LCX: 9.69±2.93 mm
3
vs 8.30±2.76 mm
3
,p = 0.002 & LVM: 175.29 ± 53.8 vs 173.92 ± 71.6 gm, p = 0.0881 respectively Diabetic had significantly ↑ TPB in all arteries compared to non-diabetics. Diabetics had significantly ↑ fibrous and fatty plaque in LM, LAD & LCX and fatty plaque only in RCA. Calcified plaque volume and LVM were same in both groups (Table 1). Adjusting for demographic and clinical variables, linear regression showed no difference in TPB in all vessels. In sub analyses LAD had significantly ↑ fibrous (p = 0.050), fatty (p =0.042) and calcified plaque (p = 0.031) whereas LM had ↑ fibrous (p =0.039) and LCX had ↑ calcified plaque (p =0.039) in diabetics. Linear regression showed significantly ↑ PWT (p =0.017), LVID (p =<0.001) and LVM (p =<0.001) in diabetics.

Conclusion:
Diabetes is associated with higher non-calcified plaque burden with increase in LVM which may provide a reason for increased risk of adverse cardiac events in diabetics. Timely screening and appropriate medical therapy may reduce coronary events in this specific group.
Abstract 19498: Abnormal Left ventricular Volumes Identified by Computed Tomography Improves Risk Stratification and Discrimination of Patients At Risk of Increased Mortality: Results from 3706 Patients in the Prospective Multicenter International CONFIRM Study
Authors: Arsanjani Reza , Labounty Troy , Cheng Victor Y , Lin Fay Y , Achenbach Stephen , Al-Mallah Mouaz , Budoff Matthew J , Cademartiri Filippo , Callister Tracy Q , Chinnaiyan Kavitha , Chow Benjamin J , Delago Augustin , Hadamitzky Martin , Hausleiter Joerg , Kaufmann Philipp , Shaw Leslee J , Villines Todd C , Berman Daniel S , Min James K
Published: April 2024

Background:
Prior studies have evaluated the prognostic value of abnormal left ventricular end-systolic (LVESV) and end-diastolic (LVEDV) volumes by cardiac CT angiography. These studies were limited to smaller studies and single centers. We evaluated whether left ventricular volumes improves risk stratification and discrimination for mortality prediction in a large prospective study.

Methods:
From 27125 subjects in the CONFIRM registry, we identified subjects without prior known coronary artery disease (CAD) who underwent CCTA with quantitative LVESV and LVEDV assessment. LVESV and LVEDV were categorized as normal (< 90ml and 90ml and > 200ml, respectively). CAD extent and severity was categorized as none (0%), non-obstructive ( 50%) 1-, 2- and 3-vessel disease. LVESV, LVEDV, and CAD were examined in relation to risk prediction and discrimination for future mortality employing Cox proportional hazards models and area under the receiver operating characteristics curve (AUC), respectively.

Results:
In a follow-up of 2.2+0.9 years, 3706 patients (59.1 + 12.6 years, 54.2% male) were studied with 207 (5.6%) with abnormal LVESV and 190 (5.1%) with abnormal LVEDV. Abnormal volumes were associated with male gender, hypertension, smoking and younger age (p<0.05 for all). In multivariable analyses, increased volumes was independently associated with mortality for abnormal LVESV (hazards ratio (HR) 6.56, 95% confidence interval (CI) 3.75-11.46, p<0.001) and abnormal LVEDV (HR 4.00, 95% confidence interval 1.98-8.08, p<0.001). Abnormal LVEDV (AUC 0.8178) and LVESV (0.8335) improved discrimination for identification of individuals at risk of death, when compared to CAD risk factors alone (0.7745) or CAD extent and severity and risk factors (0.7819) [p<0.001].

Conclusions:
Incremental to clinical variables and CAD extent and severity, abnormal left ventricular volumes by CCTA offers improved risk prediction and discrimination for future mortality.
Abstract 19508: Remote Supervised Reinforcement of Cardiopulmonary Resuscitation Skills by Telephone Improves One-Year Retention: A Randomized-Controlled Trial
Authors: LI Jia , Xu Yimin , Yue Peng , Wang Yanling , Wu Fangqin , Zhou Lin , Yu Meng , Wang Ling , Xing Lijuan , Zhang Shu , Wu Ying
Published: April 2024

Objective:
Bystander CPR is an effective way of improving the outcome of out of hospital cardiac arrest (OHCA). However, the survival rate of OHCA remains < 10% due to rapid skill deterioration following CPR training. We explored the effect of two remote supervised review models (audio-visual [AV] and audio-visual-practice [AVP]) on CPR skill retention.

Method:
Family members of patients at high risk of sudden cardiac arrest (SCA) were recruited from communities in Beijing, China. All subjects received a 90-min CPR course, and a CPR instruction booklet for review at home as needed. At the end of the course, if the subjects passed the skill test, they were randomized into one of the 3 groups (AV, AVP, and control) using sealed envelopes. The AV group was provided with a CPR instruction video (CPR-V) and asked to watch it every 3 months. The AVP group was provided with a practice dummy (designed for the project) as well as a CPR-V, and asked to practice their skills on the dummy while watching the CPR-V every 3 months. Both groups were given telephone follow up every 3 months to encourage compliance. The controls were given a placebo video without follow up. CPR skills were re-assessed after 12 months using Resusci Anne recording manikins. The subjects, the instructors, and the evaluators were blinded to the group assignment.

Results:
Of the 262 family members who finished the study, the retention rates of overall, and key elements of CPR skills were significantly higher in the AVP and AV groups, compared to the control group. Skill retention was higher in the AVP group compared to the AV group.

Conclusion:
Both review models improved long-term CPR skill retention for family members of high-risk patients with SCA. The AVP model was more effective than the AV model especially for skills related to performing high quality chest compression.
Abstract 19528: Parent of Origin Effect in Lipid Profiles
Authors: Predazzi Irene , Lilley Jessica , Bush William , Linton Macrae , Fazio Sergio , Williams Scott
Published: April 2024

Even though heritability estimates for lipid traits are high (40-60% for HDL and 40-50% for LDL), genetic contributions to lipid expression are complex and are not fully understood. Part of this variability may be due to epigenetic influences such as genomic imprinting; maternal hypercholesterolemia is thought to influence in offspring cardiovascular outcomes even in adult life. Such epigenetic factors can be observed as parent of origin effects within families. To explore this mechanism in lipid traits, we examined natural lipid variation that can be explained by parent of origin effects in the general population. We performed linear regressions in the second and third generations from the Framingham Cohort (n= 9,219 participants) to compare lipid trait correlations between mothers and daughter, mothers and sons, fathers and daughters, and fathers and sons with the goal of identifying sex-specific transmission effects. Models were adjusted for BMI, age, smoking status, treatment, and menopausal status of both parent and offspring. We performed a likelihood ratio test to compare a reduced model (containing offspring and parent covariates only) to a full model that includes parent lipid values as a risk factor. As anticipated, we observe that a significant amount of offspring HDL and LDL is explained by parent HDL/LDL levels. However, we also note that maternal HDL and LDL levels explain significantly more variance in daughter HDL and LDL compared to other models of other parent/offspring pairs, with the full model showing R2=0.19 versus a reduced model with R2=0.12 (chi2 = 104.9 and p=1.285e-24) for HDL a full model showing R2=0.17 versus a reduced model with R2=0.11 (chi2 = 84.0 and p=4.948e-20) for LDL. By contrast, the relationship between maternal HDL explains only 2% of the son’s HDL (LR=19.74, p<8.872e-6) and the relationship between maternal LDL explains only 3% of the son’s LDL.
Abstract 19536: Primary and Secondary Prevention of Athletic Sudden Cardiac Death in Suffolk County Public High Schools, New York
Authors: Htin Thanda W , Moulinie Nicole , JUng Kim , Maccaro Katherine , Maccaro Paul , Stephenson Kent
Published: April 2024

Optimal strategies to prevent and treat SCD (Sudden Cardiac Death) in student athletes remain debatable. To identify students at risk of SCD, American Heart Association (AHA) has recommended a 12-point pre-participation evaluation (PPE) tool. NY State laws require the presence of Automated External Defibrillators (AEDs) during high school sports activities.

Aim:
To examine (1) adherence to AHA’s 12 element PPE (2) presence, training and implementation of AEDs in Suffolk County public schools.

Methods:
In 2010, voluntary surveys were sent out to 53 public school districts in Suffolk County. Each district’s PPE forms were requested to evaluate adherence to AHA recommendations. AED survey included its presence, training and use.

Results:
A total of 52 districts responded to PPE request (response rate 98.1%). No districts used all 12 elements in their forms; 11 districts (21.5%) used no elements; majority (35 districts, 67.31%) used ≤ 4 elements. Maximum number of elements used was 8 in 19 districts (15.38%). Most frequently used element was syncope (57.9%). Each elements frequency is tabulated. 27 districts completed AED survey (response rate 50.9%). Each school had at least 2 AEDs (range 2-34, mean 19.2); students per AED was 70.9. Coaches (92.6%) were mostly to be trained in AED formally followed by 85.2% of school nurses, 51.9% of security staff, 32.14% of teachers, and 17.85% of students. A total 25 districts (89.29%) had emergency response plan, 26 (92.85%) had access to early defibrillation, 21 (75%) had practiced emergency response plan. There was no significant correlation between number of AEDs in a school and number of AHA elements used in PPE forms (ρ = -0.3251, P < 0.2567).

CONCLUSION:
In the absence of legislation mandating implementation of the AHA PPE tool, suboptimal adherence persists. In contrast, implementation of AEDs appears more promising. Future management guidelines should focus on broader AED training of students and teachers.