bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18702: Obesity Paradox in Women Undergoing Percutaneous Coronary Intervention With Drug-eluting Stents: Results From a Patient-level Pooled Analysis of Randomized Controlled Trials
Authors: Ehteshami Afshar Arash , Giustino Gennaro , Dianai-Maleki Neda , Baber Usman , Sartori Samantha , Aquino Melissa , Saporito Robert , Steg Philippe G , Windecker Stephan , Leon Martin B , Stone Gregg W , Dangas George D , Jeger Raban V , Morice Marie-Claude , Kimura Takeshi , Kim Hyo-Soo , Mehran Roxana
Published: March 2022

Background:
Obesity is associated with increased cardiovascular risk. Paradoxically, however, patients with higher body mass index (BMI) might have better outcomes after acute coronary syndrome treated with percutaneous coronary intervention (PCI). The effect of different BMI categories on long-term cardiac outcomes in women receiving drug-eluting stents (DES) has not been well characterized.

Methods:
We pooled patient-level data for female participants from 26 randomized trials of DES in patients with coronary artery disease. Patients were stratified according to BMI category in BMI < 25 (normal weight), 25 to 30 (overweight), > 30 to 35 (obese) or > 35 (Morbidly obese). Primary endpoint was major adverse cardiac events (MACE), defined as the composite of death, myocardial infarction or target lesion revascularization. Secondary endpoint was all-cause mortality.

Results:
From 11,557 women included in the pooled database, 9,420 had received DES and had BMI data available. Patients with higher BMI were significantly younger and more likely to have hypertension, hyperlipidemia and diabetes mellitus. However, they exhibited lower anatomical and procedural complexity. There were no differences in crude 3-year MACE rates across the 4 groups (14.6% vs. 12.9% vs. 14% vs. 13.2%; p = 0.34) but normal BMI group was associated with increased all-cause mortality (5.9% vs. 4.0% vs. 4.2% vs. 4.5%; p = 0.01). Following multivariable adjustment the 3-year risk of MACE progressively decreased with increase in BMI category (HR: 0.76, 95% CI: 0.61 - 0.94; HR: 0.71, 95% CI: 0.54 - 0.92; HR: 0.52, 95% CI: 0.38 - 0.73; p < 0.001; for overweight, obese and severely obese, respectively). Similarly, risk of 3-year mortality independently decreased in all BMI categories compared with normal BMI (HR: 0.41, 95% CI: 0.28 - 0.61; HR: 0.51, 95% CI: 0.32 - 0.80; HR: 0.48, 95% CI: 0.28 - 0.81; for overweight, obese and severely obese, respectively, p < 0.001).

Conclusion:
Following PCI with DES, lower rather than higher BMI appears to be associated with higher risk of cardiac events and mortality. The reason for this paradoxical effect of obesity is not clear but may include unknown or unmeasured confounding variables or more aggressive therapies.
Abstract 18767: Race-related Disparities in Ventricular-arterial Coupling in Elderly Individuals: The Atherosclerosis Risk in Communities Study
Authors: Fernandes-Silva Miguel M , Shah Amil M , Hegde Sheila M , Goncalves Alexandra , Claggett Brian , Cheng Susan , Nadruz Wilson , Lam Carolyn S , Borlaug Barry A , Solomon Scott D
Published: March 2022

Introduction:
The incidence of heart failure (HF) is higher in black than in white Americans, but the causes are unclear. We proposed that ethnic differences in ventricular-arterial interaction may contribute to this differential HF risk.

Methods:
We studied measures of arterial elastance (Ea) and left ventricle (LV) end-systolic elastance (Ees) in 5767 community-based elderly participants (76±5 years, 41% male, 22% black) who underwent echocardiography in the Atherosclerosis Risk in Community (ARIC) Study.

Results:
Black participants were more frequently women (66 vs 57%) and had a higher prevalence of obesity (46 vs 31%), hypertension (94 vs 80%), and diabetes mellitus (47 vs 34%). Adjusting for these baseline differences, the prevalence of LV hypertrophy was similar, but Ea, Ees and Ea/Ees ratio were higher in blacks than whites, particularly in black women (Figure). Ea was positively associated with LV mass index and E/e’ ratio in blacks, but not in whites (p for interaction < 0.001).

Conclusion:
These community-based data demonstrate that ventricular-arterial stiffening is greater in black than white Americans, coupled with more ventricular remodeling and dysfunction. The heightened afterload dependence in blacks suggests greater potential for risk reduction with anti-hypertensive therapy.
Abstract 18791: Immune Cell Derived Nerve Growth Factor Initiates Neurogenic Hypertension in Obesity
Authors: Drummond Grant R , Matthai Klaus I , Morton Susan K , Vinh Antony , Ferens Dorota M , Ellyard Juila I , Vinuesa Carola G , Hill Caryl E , Haddock Rebecca E
Published: March 2022

Introduction:
Hypertension in the obese is a rapidly increasing problem. It has both neurological and immunological antecedents, however the relationship between these is unclear.

Methods and Results:
Here we used a mouse model of diet-induced obesity, pressure myography, immunohistochemistry, flow cytometry and radiotelemtry to demonstrate that immune cells, located within the vascular adventitia of arteries important for controlling blood pressure, produce nerve growth factor (NGF) and rapidly initiate growth of the perivascular sympathetic nerve plexus; which increases vascular tone and thereby elevates blood pressure. We also show that Rag1-/- mice lacking T and B cells do not develop hypertension when obesity is induced with a high fat diet (HFD) and show that their sympathetic innervation and vascular tone remains normal, suggesting that neurogenic hypertension in the obese likely occurs independently of weight gain. Furthermore, we show that the adoptive transfer of wildtype CD3+ T cells restores the sympathetic hyperinnervation and associated hypertension whereas the transfer of CD3+ T cells deficient in NGF had no effect on sympathetic innervation or blood pressure.

Conclusion:
These results not only demonstrate the role of T cells in the genesis of obesity-related hypertension but also demonstrate the pivotal role of NGF in linking dysfunction of the immune and sympathetic nervous systems that characterize hypertension in the obese. a, Change in body weight b, nerve-mediated contraction amplitude recorded from pressurized small mesenteric arteries (1Hz, 30s) and c, systolic BP in mice in RAG-1-/- mice, which lack B and T cells, fed NCD or HFD. RAG-1-/-Tcell mice are recipients of CD3+ T cells via adoptive transfer. d, Perivascular nerve density (synaptophysin) over wholemount small mesenteric arteries from RAG-1-/- mice. Scale, 50μm.
Abstract 18828: Association Between Serum Uric Acid Level and Metabolic Syndrome in a Rural Japanese Population
Authors: Nakao Yuki , Mikami Shinske , Takemoto Hajime , Susawa Hitoshi , Kobayashi Kengo , Tanaka Haruki , Tanaka Kouichi , Kihara Yasuki
Published: March 2022

Objective:
Several reports have showed associations between serum uric acid (UA) levels and metabolic syndrome (MetS). Limited information, however, is available concerning the prospective relation between UA and the risk of developing MetS. Hypothesis: The aim of this study was to evaluate whether hyperuricemia or their combination predicts MetS.

Methods:
We evaluated 1468 subjects (783 male subjects, 685 female subjects; mean age 48.3 years) who underwent health examination programs in 2008 and 2013, who were free of MetS.

Results:
At baseline, hyperuricemia was detected in 86 male subjects (11%) and 14 female subjects (2%). Male subjects with baseline hyperuricemia had significantly higher MetS prevalence in 2013 than those without (male subjects: 17.9 vs. 8.4%, P<0.0001; female subjects: 6.1 vs. 1.8%, P=0.143). Compared with subjects in the first quintile of uric acid levels at baseline, the age-adjusted odds ratios (ORs) for MetS cumulative incidence among subjects in the second, third, and fourth quintiles were, 1.2 (95% confidence interval (CI): 0.4-2.8: P=0.07), 2.1 (95% CI: 0.9-4.7: P=0.81) and 1.2 (95% CI: 0.3-4.8: P=0.81), for male subjects. Multivariable logistic analysis revealed that hyperuricemia was significantly associated with MetS cumulative incidence in male subjects (OR 1.9: 95% CI: 1.1-3.1, P=0.013) and not in female (OR 3.8: 95% CI: 0.2-18, P=0.1).

Conclusion:
Hyperuricemia is a significant predictor of MetS in rural Japanese male subjects.
Abstract 18863: Poorer Attention in Heart Failure is Related to Increased Attentional Demands and Oxygen Saturation
Authors: Jung Miyeon , Jonides John , Northouse Laurel , Berman Marc G , Koelling Todd M , Larson Janet L , Pressler Susan J
Published: March 2022

Introduction:
Attention is critical to performing self-care and is impaired in 25% of patients with heart failure (HF). Although HF patients may have greater attentional demands from their chronic condition, reasons for their impaired attention have included altered oxygenation to the brain, but not mental effort.

Purpose:
To compare attention between HF patients and age-matched healthy adults and examine relationships between attention and mental effort, blood pressure (BP), and oxygen saturation (SpO2).

Methods:
Baseline data were included from 40 participants (20 HF, 20 healthy) enrolled in a cognitive intervention study. Attention was measured using 4 neuropsychological tests (Multi-Source Inference Task (MSIT), Stroop, Trail Making (TMT), Digit Span Tests) and perceived attention by Attentional Function Index (AFI). Mental effort for chronic disease was measured by a self-report questionnaire. BP and SpO2 were measured during testing.

Descriptive statistics, t-tests, X2 tests, and Pearson correlations were conducted. Significance level was .05.

Results:
Demographics were similar for HF and healthy groups (age = 60 vs 59 yrs, education = 15 yrs for both). Mean LVEF was 37% and NYHA class was 2.5 in HF patients. Compared with healthy adults, HF patients performed poorer on 3 tests of attention. On TMT, HF patients took 40% longer to complete test A (41 vs 27, p = .001) and B (100 vs 60 sec, p = .002). Similarly, HF patients had slower responses and more errors on MSIT and Stroop test (p = .007 - .045). Patients with HF scored lower in AFI than healthy adults (p < .001).

Compared with healthy adults, HF patients had greater mental effort (p = .014), lower BP (110/66 vs 124/74mmHg) and SpO2 (96.6 vs 97.6%). Greater mental effort was related to slower responses on TMT-A and MSIT, more errors on MSIT and Stroop test, and poorer AFI (p = <.001 - .048). Lower SpO2 was related to poorer attention on TMT-B and AFI. More time with SpO2 < 95% was related to poorer attention on TMT-B, MSIT, and AFI.

Conclusions:
Patients with HF had poorer attention than healthy adults. Poorer attention was associated with increased mental effort and lower oxygen saturation. Future studies are needed to improve attention and to evaluate if improving oxygen and mental effort improve attention in larger samples.
Abstract 18877: An Accurate Method for Automated Rhythm Classification During CPR
Authors: Kwok Heemun , Coult Jason , Blackwood Jennifer , Kudenchuk Peter , Sherman Lawrence , Rea Thomas
Published: March 2022

Introduction:
Accurate identification of the cardiac rhythm during CPR could facilitate appropriate defibrillation and guide medication treatments without interrupting chest compressions for rhythm analysis.

Hypothesis:
A rhythm classification method which “reads-through” CPR artifact would identify shockable rhythms with high sensitivity and non-shockable rhythms with high specificity during CPR.

Methods:
Two physicians annotated rhythms as shockable (VF or other shockable), non-shockable (asystole or organized) or indeterminate, throughout defibrillator recordings from a convenience sample of 185 treated OHCA cases. CPR was determined from impedance and/or accelerometer signals. Each ECG tracing was divided into consecutive 4-second frames, and only frames during CPR were included. The “read-through” method was derived from a development set (N=95 cases) and uses features generated by cross-correlation with a series of QRS-like wavelets and a hidden Markov model to integrate sequential data. In the validation set (N=90 cases), frame-by-frame classifications (shockable vs. non-shockable) were compared to the gold standard of physician assessment. Sensitivity and specificity were estimated using a multilevel model to account for clustering of frames within cases.

Results:
The validation set included a median 456 (IQR 179, 756) seconds of ECG data from each case. Overall, there were 13,851 4-second frames: 10% shockable, 88% non-shockable and 2% indeterminate. Mean sensitivity for VF was 0.97 (95% CI 0.84, 0.99), and specificities for an organized rhythm and asystole were 0.99 (95% CI 0.99, 1.0) and 0.99 (95% CI 0.97, 1.0), respectively. There was moderate variability in VF sensitivity across cases (IQR 0.77, 1.0).

Conclusion:
A “read-through” CPR method classified the shockable versus non-shockable rhythms with high overall sensitivity and specificity, though with some variability across individual patients.
Abstract 18880: Inflammation Imaged With [18F]-FDG PET/CTA is Related to 3D Ultrasound Phenotypes of High-risk Carotid Plaque: Sub-study of the Canadian Atherosclerosis Imaging Network (CAIN-2)
Authors: Cocker Myra S , Fenster Aaron , Hammond Robert R , Lim Siok P , deKemp Robert A , Lum Cheemun , Hill Andrew , Nagpal Sudhir , Stotts Grant , Warren Brittany , Garrard Linda , DaSilva Jean , Tardif Jean-Claude , Beanlands Rob S , Spence J. David
Published: March 2022

Background:
Inflammation may contribute to plaque instability. [18F]-fluorodeoxyglucose (FDG) uptake imaged with positron emission tomography (PET) and computed tomography (CT) may serve as a biomarker of plaque inflammation.

3-dimensional ultrasound (U/S)-derived total plaque volume (TPV) and vessel wall volume (VWV) are measures of plaque volume and vessel wall thickness that are used for monitoring progression and regression of carotid atherosclerosis. Progression of TPV has been related to cardiovascular events.

The volumetric phenotype (TPV and VWV) and extent of the inflammatory burden (FDG uptake) may independently predict carotid plaque vulnerability. However, the interrelationship between FDG uptake and measures of TPV and VWV remains poorly understood.

Methods:
Thirty-seven patients (67±9 years, 9 female) scheduled for carotid endarterectomy were prospectively recruited for 3D U/S and FDG PET/CT imaging of the left and right internal carotid arteries.

Maximum FDG uptake normalized to blood (tissue to blood ratio - TBR) was measured for bilateral carotid plaque.

Manual planimetry was used to measure bilateral TPV and VWV. Each 3-D image were evaluated from the bifurcation to the common carotid, and then to the internal and external carotid arteries.

Results:
Maximum FDG uptake correlated with TPV (r=0.42, p<0.001) and VWV (r=0.30, p=0.015) (Figure 1). FDG uptake was greater in plaque scheduled for endarterectomy (TBR=3.6±1.3 endarterectomy vs. 3.0±1.2 contralateral, p=0.049). There was also a trend for greater TPV at the side of endarterectomy: 799±390mm
3
endarterectomy vs. 672±150mm
3
contralateral (p=0.088).

Conclusion:
FDG uptake in high-risk carotid plaque is related to TPV and VWV. The inflammatory burden and the volumetric phenotype of plaque may synergistically provide a more robust evaluation of plaque vulnerability. Longitudinal follow-up for the assessment of plaque progression in this study cohort is currently underway.
Abstract 18886: Predictors for Long-term Clinical Outcomes After Endovascular Treatment in Patients With Critical Limb Ischemia
Authors: Jujo Kentaro , Nakao Masashi , Yamaguchi Junichi , Otsuki Hisao , Shimazaki Kensuke , Kamishima Kazuho , Arashi Hiroyuki , Hagiwara Nobuhisa
Published: March 2022

Backgrounds:
Critical limb ischemia (CLI) is a severe clinical presentation of patients with peripheral artery disease, and their limb salvage and survival rates are extremely poor. However, there is still only limited evidence from observational studies for contemporary outcomes in CLI patients who underwent endovascular treatment (EVT) including both above and below the knee lesion. Therefore, this study aimed to evaluate the prognostic and predictive factors for patients with CLI who underwent EVT.

Methods:
Cumulative total number of 192 patients with CLI who underwent EVT between March 2009 and April 2014 was prospectively enrolled. After the exclusion of patients who were lost to follow-up within 6 months, 175 patients were retrospectively analyzed for clinical and angiographic parameters. The primary endpoints of this study were all-cause death and major amputation above the ankle joint.

Results:
The study population was typically elderly (average age: 68 year-old) and 76% male with a normal body mass index (BMI: 23 kg/m2) and diverse comorbidities, including 34% diabetes and 72% maintenance hemodialysis. Target lesions consisted of 23% aortoiliac, 56% femoropopliteal and 67% below-the-knee arteries, including 37% isolated below-the-knee lesion. Median follow-up period was 23.9 months. Survival rate and major amputation free rate at 1-year were 87% and 95%, respectively (Figure). Multivariate analysis elucidated that low BMI and cerebrovascular disease were independent predictors for all-cause mortality (Table 1). Interestingly, infection was the leading cause of death (23 patients (46%), and main focus of infection was lower extremities (15 patients (30%)). As for major limb amputation, current smoking was the only independent predictor (Table 2).

Conclusion:
This study demonstrates that low BMI and cerebrovascular disease predict all-cause mortality, and current smoking does major amputation after EVT in patients with CLI.
Abstract 18896: The Clinical Course of the Rare Disorder of Segmental Arterial Mediolysis Through Retrospective Review
Authors: Makar Gerges , Patel Salma , Hines Robert , Temkit M'hamed , Wysokinski Waldemar E , Greene Eddie L , Menias Christine , Naidu Sailendra , McBane Robert D , Shamoun Fadi
Published: March 2022

Introduction:
Segmental arterial mediolysis (SAM) is nonatherosclerotic and noninflammatory arteriopathy. It commonly affects the abdominal vasculature. There is uncertainty about its presentation, radiological findings, prognosis and management.

Hypothesis:
The goal of this study is to describe the clinical course and evaluate risk factors for disease progression.

Method:
Retrospective review of all cases diagnosed with SAM at the Mayo clinic between 2001 and 2014. Medical records were reviewed for demographics, risk factors, laboratory, imaging findings and treatment options at presentation and during follow-up visits. A non-parametric Wilcoxon-rank-sum test and the Chi-Square test were used.

Results:
Out of 247 reviewed cases, 114 patients were confirmed with SAM and included in the analysis. (69%) were male and a majority (84%) had no other connective tissue disorder. Mean age was (52) years old. Pre-existing hypertension was identified in (48%), hyperlipidemia (31%), migraine (11%) and smoking (32%). The most common symptoms at presentation were abdominal pain (70%), flank pain (21%), back pain (8%) and chest pain (5%). Only (30%) of patients had recurrent symptoms and most (89%) had negative inflammatory markers. On angiography the following arteries were commonly affected: renal (51%), celiac (43%), superior mesenteric (49%), and iliac (18%). At presentation (85%) of patients were found to have mesenteric arterial dissection; (45%) aneurysms; (14%) wind or wall thickening; (21%) occlusion; and (38%) with evidence of end organ ischemia or infarct. 82 patients were followed up with a CT angiogram for an average of 19 months, 17 (20.73%) had evidence of disease progression. (22%) required revascularization. Aspirin (47%) was the most common treatment used followed by anticoagulation (38%), beta blocker (35%) and ACEI/ARB (29%). Risk factors for disease progression are being male (P<0.0173), Hypertension (P<0.0128), hyperlipidemia (P<= 0.0044). The use of antiplatelets and ACEI/ARB was not associated with disease stability.

Conclusion:
SAM is an arteriopathy that affects the mesenteric arteries in middle age men. Conservative management with control of risk factors and close follow up are preferred approach.
Abstract 18909: Interaction Between a Novel Protein Glycan Derived Inflammation Biomarker (GlycA) and HDL Particle Subclasses on Mortality in a Cardiac Catheterization Cohort
Authors: McGarrah Robert W , Craig Damian , Haynes Carol , Dowdy Z. Elaine , Shah Svati H , Kraus William E
Published: March 2022

Background:
GlycA, a novel serum inflammatory biomarker composed of enzymatically glycosylated acute phase proteins, is associated with cardiovascular events in a primary prevention population. Emerging data suggest that inflammation may adversely impact HDL function. We sought to define the role of GlycA as a biomarker of adverse events in a secondary prevention population and to understand potential interactions between GlycA and HDL subclasses.

Methods:
GlycA and medium and small HDL particles (MS-HDL) were measured with NMR spectroscopy in 7,617 individuals in the CATHGEN biorepository. Cox proportional hazards modeling was used to test the relationship of GlycA, MS-HDL and the GlycA*MS-HDL interaction term with time-to-death in multivariable models adjusted for 11 CV risk factors and stratified by diabetes status. We then assessed the ability of GlycA, MS-HDL, and GlycA*MS-HDL to improve risk discrimination in clinical models.

Results:
Over a mean time-to-event of 2547 days, 2318 individuals died. Higher GlycA levels were associated with increased risk of death (HR 1.34 [1.29-1.39], p<0.0001). In diabetes-stratified models, the greatest quartile of GlycA in patients without diabetes conferred greater risk of mortality than the lowest quartile of GlycA in patients with diabetes. In models containing MS-HDL (main effect HR 0.69 [0.66-0.72], p<0.0001), addition of GlycA (HR 1.28 [1.24-1.32], p<0.0001) and GlycA*MS-HDL (p<0.0001) demonstrated independent associations of these variables with mortality. MS-HDL levels were associated with lower mortality risk at lower GlycA levels but with increased mortality risk at greater GlycA levels. There was an increasing improvement of model fit characteristics with incremental addition of GlycA, MS-HDL and GlycA*MS-HDL to robust clinical models.

Conclusion:
GlycA is associated with an increased risk of mortality in a secondary prevention population. The interaction of GlycA with MS-HDL suggests that greater systemic inflammation can modify the association of HDL subclasses with clinical outcomes and at the highest levels of GlycA, may reverse the protective effect of HDL. These findings have implications for the interpretation of diagnostic and therapeutic tools involving HDL measurements.
Abstract 18950: Changes in Vasodilator Reactivity and Vasoconstrictor Tone in Metabolically Healthy Obesity and the Metabolic Syndrome
Authors: Iantorno Micaela , Schinzari Francesca , Mores Nadia , Tesauro Manfredi , Di Daniele Nicola , Campia Umberto , Cardillo Carmine
Published: March 2022

Background:
Patients with obesity-related metabolic syndrome (MetS) have endothelial dysfunction due to decrease nitric oxide (NO) availability and increased endothelin (ET)-1-mediated vasoconstrictor tone. Given the prognostic significance of endothelial dysfunction, these abnormalities may be involved in the increased risk of cardiovascular mortality of these patients. Whether patients with metabolically healthy obesity (MHO), in whom those metabolic abnormalities that define the MetS are not present, have similar impairment of endothelial function is unknown.

Methods:
Forearm blood flow (FBF) responses were measured by strain-gauge plethysmography during intra-arterial infusion of graded-doses of acetylcholine (ACh; an endothelial-dependent vasodilator) and sodium nitroprusside (SNP; an endothelium-independent vasodilator), and/or during selective antagonism of ETA receptors by BQ-123 (10 nmol/min for 60 minutes) in lean subjects (n=56) and in obese patients (n=119), with either MHO (n=34) or the MetS (n=85).

Results:
ACh and SNP caused vasodilation in both obese and lean participants (all P<0.001 vs. baseline). The response, however, to both agents was significantly lower in the obese than in the control group (both P<0.001). Among the obese participants, the reactivity to ACh was higher in MHO than in the MetS (P<0.001), whereas the responsiveness to SNP was equally impaired in both groups (P=0.45); this suggests higher degree of endothelial dysfunction in the MetS, but similar impairment of smooth muscle reactivity in MHO and the MetS. As expected, BQ-123 increased FBF in obese (P<0001 vs. baseline), but not in lean participants, hence the FBF response to ETA receptor blockade was higher in both obese groups than in controls (both P<0.001). In keeping with the ACh results, the FBF response to BQ-123 was significantly higher in patients with the MetS than in those with MHO (P=0.007).

Conclusions:
Patients with MHO have abnormal vascular reactivity, albeit their endothelial dysfunction is less pronounced than in patients with the MetS. These findings indicate that obesity per se is associated with some degree of vascular damage independently of those metabolic abnormalities underlying the MetS.
Abstract 18963: Over-expression of Angiopoietin-2 in Human Patients With Continuous-flow Left Ventricular Assist Devices Induces Abnormal Angiogenesis and Predicts Gastrointestinal Bleeding Events
Authors: Tabit Corey E , Kim Gene H , Fedson Savitri E , Sayer Gabriel , Jeevanandam Valluvan , Uriel Nir , Liao James K
Published: March 2022

Arteriovenous malformations are common in patients with Continuous-Flow Left Ventricular Assist Devices (LVAD) and may reflect deregulation of angiogenesis. Angiopoietin-2 (Ang-2) is a stimulator of angiogenesis produced by endothelial cells in response to thrombin. In this study, we evaluate Ang-2 expression in patients with LVAD compared with stable heart failure (HF) or orthotopic heart transplant (OHT) and test the hypothesis that elevated Ang-2 in patients with LVAD leads to increased angiogenesis. Blood samples were taken from 79 patients (n= 21 HF, 41 LVAD, 17 OHT) during routine heart catheterization. Ang-2 was measured by ELISA and thrombin was measured by Western Blot. Cultured human umbilical vein endothelial cells (HUVECs) were incubated with plasma from each patient and Ang-2 expression was measured by RT-PCR. HUVECs were then incubated on Matrigel with serum from each patient in the presence or absence of an Ang-2 blocking antibody and tube formation was measured by microscopy. Also, vena caval endothelial cells were isolated from discarded guide wires used during catheterization and Ang-2 expression was measured by quantitative immunofluorescence. In patients with LVAD vs. HF or OHT, Ang-2 was elevated in both serum (12.3±9.6, 4.5±2.1, and 4.9±2.0 ng/mL respectively, p<0.01) and endothelial cells (56.3±14.1, 31.3±4.2, 35.0±11.2 AU respectively, p<0.05). On Matrigel, serum from patients with LVAD vs. HF or OHT induced increased tube formation (57.1±3.2, 39.2±7.1, 34.7±5.1 tubes per low power field respectively, p<0.05) and this elevation normalized with Ang-2 blocking antibody. Plasma from patients with LVAD vs. HF or OHT induced Ang-2 gene over-expression in HUVECs (1.6±0.4, 1.0±0.3, 0.6±0.2 RQ respectively, p<0.01) and was associated with higher plasma thrombin. In patients with LVAD, serum Ang-2 >10 ng/mL was associated with a higher 3 month risk of GI bleeding vs. Ang-2 <10 ng/mL (30% vs. 0%, p<0.01). Therefore, we conclude that over-expression of Ang-2 in patients with LVAD induces increased angiogenesis and predicts GI bleeding events. Thrombin is increased in patients with LVAD and their plasma induces Ang-2 over-expression
in vitro
. Therefore, Ang-2 overexpression may contribute to AVM formation in patients with LVAD.
Abstract 18976: Progenitor Cell Ploidy: The Regulator of Regenerative Fate
Authors: BROUGHTON KATHLEEN , Quijada Pearl , Wang Jessica , Monsanto Megan , Gude Natalie , Sussman Mark
Published: March 2022

Cellular therapy is an emerging interventional strategy to treat heart failure and has demonstrated tremendous potential in recent years. Use of endogenous stem cells found within the heart, cardiac progenitor cells (CPC), has prompted intense basic research in multiple experimental animal models as well as clinical trials in heart failure patients. Scientifically, the field continues to unravel mechanisms of CPC involvement in remodeling and repair of the heart under both normal and pathologic conditions. Research has been primarily performed in mouse models, which represent the fundamental experimental platform for a vast array of regenerative medicine research. Given the importance of mouse models for stem cell research, understanding fundamental differences between mouse and human stem cell biology are essential. Our findings show that adult murine CPCs contain tetraploid (4n) chromosome content in contrast to the normally expected diploid (2n) chromosome content as found in human CPCs by karyotype analyses. To expand the significance of this finding, CPCs were isolated from standard lab mice (FVB and C57), human telomere-length equivalent mice (CAST and SPRET) and an early onset senescence mouse (SAMP6), which revealed mononuclear tetraploid content as characterized through a combination of flow cytometry and confocal microscopy analysis using antibodies and fluorescence in situ hybridization (FISH) techniques. In comparison, isolated murine ckit+ bone marrow stem cells possess mononuclear diploid content through similar analysis. The ploidy content of endogenous murine and human CPCs was investigated in situ with heart tissue sections with comparable ploidy determinations to that of cultured CPCs. Furthermore, the unique tetraploid content of CPCs within the murine heart is reinforced by comparison with ckit+ progenitor cells of secondary tissues (intestine and bone) that exhibit diploid chromosome content. These studies reveal a fundamental difference between human and murine CPCs that is essential for functional regenerative potential since regenerative tissues commonly are polyploid. Future directions will focus on defining the advantage of polyploidy in mediating regeneration.
Abstract 18980: Improving Anticoagulation Knowledge and Quality of Life in Older Adults Using Tablet Mobile Applications
Authors: Lee Jung-Ah , Amin Alpesh N
Published: March 2022

Background:
Older adults with cardiovascular diseases who require oral anticoagulation therapy (AT) report difficulty managing medications and diet, which affects therapeutic benefit and quality of life (QOL). Mobile health (mHealth) tools such as health applications (app) via smartphones or tablets can assist in managing AT but such tools have not been tested among older adults including Spanish speaking elders.

Objective:
The objective of the study was to test the feasibility of an mHealth intervention composed of culturally appropriate and age-sensitive components to improve QOL in older adults on AT.

Methods:
The pilot study used a single-arm, experimental, pre-post design to assess the feasibility of a 12-week mHealth-based intervention in older adults with AT by examining changes in outcomes (ie, knowledge, adherence, QOL, perception, depression) and usability of the warfarin app on a 10-inch tablet computer after 3-month use.

Results:
Twenty older patients from two anticoagulation clinics have enrolled in the study - average age 67.7 ± 9.8 years; predominantly male (14/20, 70%); Caucasians (9/20, 45%), Hispanics (8/20, 40%); high school completion (13/20, 65%); living with family (16/20, 80%); average number of comorbidity 3.4 (±1.4). Fifteen participants completed 3-month follow-ups; two dropped due to inability to use the app; one died; two are currently on use of the app. Outcomes were improved from baseline to 3 months (see Table). The mean satisfaction with and mean usefulness of the app were 5.4 of 7 (±1.5) and 5.4 of 7 (±1.4) in usability survey after 3 months.

Conclusions:
Our findings suggest that on-going mHealth intervention for older adults with chronic diseases show promise in being able to enhance anticoagulation knowledge and QOL with the treatment. The satisfaction of mHealth intervention using the health app was moderate to high in this sample. The findings can be used to modify the health app to make the mHealth intervention more elder-friendly.
Abstract 18984: Impact of Functional vs. Organic Baseline Mitral Regurgitation on Short- and Long-Term Outcomes Following Transcatheter Aortic Valve Replacement
Authors: Kiramijyan Sarkis , Koifman Edward , Asch Federico M , Magalhaes Marco A , Escarcega Ricardo O , Baker Nevin C , Didier Romain , Negi Smita I , Minha Sa'ar , Jerusalem Zachary D , Kang Won Yu , Lipinski Michael J , Torguson Rebecca , Gai Jiaxiang , Okubagzi Petros , Wang Zuyue , Ben-Dor Itsik , Satler Lowell F , Pichard Augusto D , Waksman Ron
Published: March 2022

Introduction:
The impact of the specific etiology of mitral regurgitation (MR) on outcomes in the TAVR population has not been previously studied.

Hypothesis:
Functional MR improves to a greater degree than organic MR after relief of the aortic gradient.

Methods:
The complete TAVR population from May 2007 through May 2015, who had TTE assessments of MR at baseline, was retrospectively analyzed. The TTEs were rigorously evaluated on a de-novo basis in regard to the left-ventricular function, MR etiology, severity, and mitral valve anatomy at multiple intervals including: pre- & post-procedure, 30-days, 6-months, 1-, 2-, and 3-years follow-up. Only patients with baseline ≥moderate MR were selected for this study and further divided into two groups; functional vs. organic etiology. Longitudinal, mixed-model statistical analyses were performed to assess the differences in the degree of longitudinal changes.

Results:
A total of N=70 patients (44% male, mean 82 years) with ≥moderate MR at baseline including n=30 functional vs. n=40 organic MR. There were no significant differences in the baseline, procedural or in-hospital parameters. The primary outcome of mortality were similar at 30-days (10% vs. 17.5%, p=0.498) and 1-year (26.7% vs. 22.5%, p=0.687) in the functional vs. organic groups, respectively. The secondary outcomes demonstrated significant differences in the longitudinal changes including: greater degrees of improvement in MR severity, LVEF, and NYHA class in the functional vs. the organic MR groups at up to 3-years follow-up (figure).

Conclusions:
Although the etiology of significant baseline MR in patients undergoing TAVR does not have an impact on 30-days or 1-year mortality, in patients with functional MR, there are greater degrees of short- and long-term improvement of MR severity, LV positive remodeling and functional class. These findings may help strategize therapies for MR in patients with aortic and mitral disease who are undergoing TAVR.
Abstract 18992: Kappa Opioid Receptor Improves Postresuscitation Myocardial Dysfunction via Activation of Grk3 and Phosphorylation of Erk
Authors: Shan Yi , Wan Jian , Lin Zhaofen , Zheng Jinhao , Huang Zhigang
Published: March 2022

Objective:
To investigate the signaling pathway of kappa opioid receptor (κ-OR) on postresuscitation myocardial protection.

Method:
A total of 120 male SD rats were randomized into control group (n=40), κ-OR agonist group (n=40) and κ-OR inhibitor group (n=40). Asphyxia-induced cardiac arrest was performed by turning-off the ventilator and clamping the endotracheal tube. Cardiac arrest was started when systolic blood pressure dropped below 25mmHg. CPR with chest compression and mechanical ventilation were started 6mins after cardiac arrest. Normal saline (1ml/kg), U50488H (ΚOR agonist, 1mg/kg) or GNTI(ΚOR inhibitor, 0.5mg/kg) was injected from on set of CPR in each group. The baseline blood gas, HR, SBP, DBP, MAP, dP/dtmax and -dP/dtmax were measured. The rat hearts were harvested at 1h, 2h, 6h, 12h and 24h post resuscitation (PR). The expression of both total κ-OR and phosphorylated κ-OR in myocaridum were determined, the likely signaling pathway molecules of G protein receptor kinase 3(GRK3) and ERK1/2 were detected.

Results:
The postresuscitation myocardial function, include HR, SAP, MAP, dP/dtmax and -dP/dtmax were improved in κ-OR agonist group compared to κ-OR inhibitor and control group, specifically after PR2h(p<0.01).Both phosphorylated κ-OR and GRK3 protein impression were significantly increased in κ-OR agonist group, in comparison to κ-OR inhibitor group and control group (p<0.01). Positive linear correlation was observed between κ-OR and GRK3. The ERK1/2 mRNA and protein expression were significantly increased in κ-OR agonist group and significantly decreased in κ-OR inhibitor group, in comparison to control group(p<0.05).

Conclusion:
The activation of κ-OR improves postresuscitation myocardial dysfunction. The protective effects of κ-OR may via activation of GRK3 and ERK1/2 signaling pathway.
Abstract 19002: Predictive Value of the Intraoperative Pulmonary Artery Flow Study for Early and Late Outcome After Surgical Treatment of Pulmonary Atresia With Ventricular Septal Defect and Major Aortopulmonary Collateral Arteries (MAPCAs)
Authors: Trezzi Matteo , Albano Antonio , Albanese Sonia B , Cetrano Enrico , Carotti Adriano
Published: March 2022

Introduction & Hypothesis:
1. To evaluate the accuracy of the intraoperative pulmonary artery (PA) flow study in determining the feasibility of concomitant VSD closure after complete one-stage unifocalization in patients with pulmonary atresia with VSD and MAPCAs. 2. To determine the ability of the PA flow study to predict long-term outcomes.

Methods:
Between October 1996 and May 2015, a PA flow study was obtained in 92 patients undergoing complete one-stage unifocalization. The study was performed by cannulating the unifocalized central PA. With the heart beating, incremental volumes of blood were pumped through the PAs. The ability to achieve 100% flow (2.5 l/min/m
2
) into the pulmonary bed at a mean pressure (mPAP) ≤ 30 mmHg was used as an indicator for acceptability of VSD closure.

Results:
Among the 92 patients who had a PA flow study, 23 had a mPAP > 30 mmHg and the VSD was left open. VSD closure was performed in 69 patients (mPAP 24 ± 5 mmHg, range 11-34 mmHg). However, four (5.8%) required patch fenestration due to suprasystemic RV pressure. The recorded mPAPs of these 4 patients were 29, 24, 22 and 28 mmHg, respectively. In the whole cohort, median weight at operation was 7.9 kg (range, 2.5-54 kg). The PA flow study accurately predicted successful VSD closure (area under the curve 0.852, Figure 1A). VSD closure at the time of unifocalization resulted in a clear survival advantage (p = 0.0363). mPAP correlated with RVP to LVP ratio (rho 0.460, p = 0.0001) and better long-term results were observed with intraoperative mPAP ≤ 30 mmHg (p = 0.24, Figure 1B).

Conclusions:
Successful VSD closure in patients with MAPCAs can be reliably defined by an intraoperative PA flow study with a cut-off of 30 mmHg. The PA flow study predictive value is particularly useful to select patients in which the VSD should be left open. mPAP strongly correlates with the intraoperative RVP/LVP ratio and lower values of mPAP at the time of the unifocalization are associated with improved long-term outcomes.
Abstract 19018: Histone 3 Lysine 4 Tri-Methylation is Necessary for Epicardial Epithelial-to-mesenchymal Transformation
Authors: Krainock Michael R , Toubat Omar , Danopoulos Soula , Keho Kaho , Al Alam Denise , Starnes Vaughn A , Kim Richard W
Published: March 2022

Introduction:
Recent whole exome sequencing carried out in patients with congenital heart disease revealed an over-representation of mutations in members of the Histone 3 Lysine 4 Methyltransferase Complex, indicating that the methylation of Histone 3 Lysine 4 (H3K4) is of particular importance during heart development. In the tri-methylated state (H3K4me3) this signature actively promotes gene transcription through the recruitment of the Pre-Initiation Complex to the promoter. There are currently no data regarding the role of the H3K4me3 modification in cardiogenesis. We investigated the hypothesis that the acquisition of H3K4me3 is necessary for Epicardial Epithelial-to-Mesenchymal Transformation (EMT).

Methods:
Global patterns of H3K4 tri-methylation were investigated in epicardial cells undergoing EMT in the embryonic quail heart in-vivo, via co-staining of H3K4me3 with the epicardial marker pan-cytokeratin, and the mesenchymal marker alpha-Smooth Muscle Actin. For the in-vitro investigation of H3K4me3 during Epicardial EMT, quail epicardial explants were induced to undergo mesenchymal transformation via treatment with Fetal Bovine Serum alone, and in the presence of an H3K4 methyltransferase inhibitor. Epicardial EMT was characterized by the induction of Snail expression, a loss of E-cadherin, the expression of alpha-Smooth Muscle Actin, and an increase in nuclear area. The acquisition of new H3K4me3 was investigated via Immunohistochemistry.

Results:
There is a global acquisiton of H3K4me3 in quail epicardial cells undergoing EMT in-vivo and in-vitro. Inhibition of H3K4 methyltransferase activity impaired Snail gene expression, rescued E-cadherin, prevented the expression of alpha-Smooth Muscle Actin, and prevented nuclear enlargement in epicardial cells in-vitro, while having no effect on cell proliferation.

Conclusions:
We conclude that the acquisition of tri-methylated H3K4 is featured in Epicardial EMT both in-vivo and in-vitro in embryonic quail epicardium. This acquisition is necessary for Epicardial Epithelial-to-Mesenchymal Transformation in-vitro. These data represent the first potential explanation as to how mutations in the H3K4 Methyltransferase Complex impair heart development.
Abstract 19027: Glycation of ApoA-IV is Associated With the Severity of Coronary Artery Disease in Diabetic Patients and Glycated ApoA-IV Protein Promotes Atherogenesis Through Nuclear Receptor NR4A3 Mediation
Authors: Lu Lin , Dai Yang , Shen Ying , Sun Jia Teng , Wang Xiao Qun , Yan Xiao Xiang , Zhang Rui Yan , Shen Wei Feng
Published: March 2022

Background:
ApoA-IV is associated with HDL in plasma but a large portion circulates lipid free. It has been shown to possess anti-inflammatory and anti-atherosclerotic effects.

Methods and Results:
We isolated HDL from plasma of type 2 diabetic patients and healthy controls, and found that apoA-IV of HDL from diabetic patients was significantly glycated by using Western blot and mass spectrometry. The glycation levels of apoA-IV were higher in diabetic patients than in controls, and were associated with the severity of coronary artery disease. Immunohistochemically, glycation sites co-localized with apoA-IV in atherosclerotic plaques from diabetic patients.

In cell and animal studies, in vitro glycated apoA-IV protein promoted inflammatory reactions in human aortic endothelial cells and atherogenesis in apoE-KO mice as compared with control, whereas apoA-IV exhibited anti-inflammatory and anti-atherogenic effects. The pro-inflammatory action of glycated apoA-IV was mediated by receptor for glycation end products in endothelial cells. In microarray analysis and verification in endothelial cells, glycated apoA-IV but not apoA-IV, enhanced the expression of nuclear receptor NR4A3 greatly. Glycated apoA-IV-induced inflammatory reaction and atherogenic effect was significantly attenuated in endothelial cell with siRNA-NR4A3, native endothelial cells and macrophages from NR4A3-KO mice and in NR4A3-KO mice. Co-localization of NR4A3 with CD31 was observed in atherosclerotic plaque from diabetic patients. Moreover, glycated apoA-IV but not apoA-IV induced trans-activation of NR4A3 to the promoter of adhesion molecules (VCAM-1, ICAM-1 and E-selectin).

ESI-Q-TOF-MS identified several glycation sites including K78, K189 and K328 in apoA-IV from diabetic patients, but not in controls. Mutated apoA-IV proteins (m-apoA-IV-K78A/K189A/K328A) were made. In vitro glycated m-apoA-IV displayed significantly attenuated activation of NR4A3 in endothelial cells and atherogenesis in apoE-KO mice, as compared with glycated apoA-IV.

Conclusion:
Glycation of apoA-IV is associated with the severity of coronary artery disease in diabetic patients and glycated apoA-IV protein promotes atherogenesis through nuclear receptor NR4A3 mediation.
Abstract 19035: Cardiovascular QTc Interval-Prolonging Medications and the Risk of Death, Stroke and Incident Atrial Fibrillation in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Alburikan Khalid A , Savitz Samuel T , Tisdale James E , Soliman Elsayed Z , Sueta Carla A , Stearns Sally C , Rodgers Jo E
Published: March 2022

Objective:
Prolongation of corrected QT interval (QTc) has been linked with increased risk of stroke, atrial fibrillation (AF) and mortality. We examined the associations between cardiovascular QTc prolonging medications (QTPMs) and these outcomes in a longitudinal study of a population-based cohort.

Methods:
We assessed 7,183 ARIC participants with a resting, standard 12-lead electrocardiogram and ≥ 1 measure of cardiovascular medication over up to four triennial examinations between 1987 and 1998. Participants with QRS ≥ 120 ms, atrial fibrillation and stroke were excluded. We identified participants using QTPMs classified as known, possible or conditional by CredibleMed®. Participants were followed on average for 3.2 visits, resulting in 18,287 person-visit observations for all users and 5, 178 for new users, no prior exposure). In all users and new users, we used generalized estimating equation logistic regression with inverse propensity score weighting to examine the association between cardiovascular QTPMs, in comparison to cardiovascular non-QTPMs, and the composite end point of death, stroke or incident AF within 3 years of each visit. The regressions controlled for person characteristics and whether QTPM were for cardiovascular conditions.

Results:
The participants’ mean age was 60 +4 years; 70% were females. The composite outcome occurred in 956 visits (5.2%) during the 3-year follow-up periods. Known cardiovascular QTPMs increased the risk of composite outcome threefold, due to significant increase for all components of the endpoint. In contrast, conditional cardiovascular QTPMs were associated with reduction in the composite end point.(Table). No participants were taking Possible QTPMs.

Conclusions:
Known cardiovascular QTPMs were associated with an increased risk of composite outcome of death, stroke and incident atrial fibrillation compared to cardiovascular non-QTPMs.