bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12493: Comparison of Coronary Plaque Progression by Coronary Computed Tomography Angiography in Systemic Lupus Erythematosus and Rheumatoid Arthritis
Authors: Moore Jeff , Lakshmanan Suvasini , Kinninger April , Budoff Matthew , Karpouzas George
Published: April 2024

Introduction:
Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are autoimmune diseases associated with high incidence of cardiovascular disease (CVD), likely related to common underlying pathways of inflammation. Characterization of coronary atherosclerosis, particularly total plaque (TP) and total non-calcified plaque (TNCP), on Coronary Computed Tomography Angiography (CCTA) has been correlated with adverse CV events. We compared rates of coronary plaque progression by serial CCTA in SLE and RA patients.

Methods:
Semi-automated plaque software (Qangio, Medis) was used for quantitative coronary assessment. Analysis included 22 SLE [48.5 (13.0) years; 19 females; 64% White] and 22 age and sex- matched RA patients [49.1 (11.2) years; 19 females; 95% Hispanic]. Linear regression was used to compare log adjusted total atheroma volume ((TAV
norm
) = (Plaque volume)/Vessel length * mean cohort vessel length)) for TP and TNCP between SLE and RA patients.

Results:
Baseline mean levels of TAV
norm
for TP and TNCP in RA patients vs SLE patients were 0 (0 - 7.3) mm
3
vs 21.2 (1.1 - 64.1) mm
3
(p <.0001) and 0 (0 - 5.8) mm
3
vs 19.5 (1.1 - 62.2) mm
3
(p<.0001), respectively. After adjustment for baseline plaque and CV risk factors, progression of TAV
norm
was higher in SLE than RA patients (log TAV TP volume (β: 2.271 (.530), p=.0001) and log TNCP volume (β: 2.384 (.502), p<.0001) (Table 1). Patients with RA had 87% less TP and 89% less TNCP progression than those with SLE.

Conclusions:
These results suggest that coronary plaque progression is greater in young, adult SLE patients, compared to RA patients. These results improve the mechanistic understanding of increased CV risk in these patients. Further research to evaluate screening and targeted management strategies for CVD in this high risk cohort, especially SLE is warranted.
Abstract 12496: Plasma Growth Factors and Hormones Drive Constitutive Translation of a Broad-Spectrum Proteome in Circulating Platelets via Stimulation of Translation Initiation Signal Pathways, Necessary for Rapid Hemostasis
Authors: Goldfinger Lawrence , Wurtzel Jeremy G , Lazar Sophia
Published: April 2024

Introduction:
The ability of anucleate platelets to translate nascent protein from their inherited mRNAs was first demonstrated in 1967. Later studies supported these findings, but translation quickly ceased in washed
ex vivo
platelets, leading to a general presumption that platelet translation is not robust, and thus of limited biological significance. Agonist stimulation promotes platelet protein translation, and recent profiling studies confirmed >6000 inherited mRNAs in polysomes, associated with inducible translation of cognate protein products in thrombin-stimulated human platelets. However, relevance of post-activation translation - a slow, rate-limiting step in cell response - to rapid hemostasis is not clear. Platelets express the requisite components and show broad ribosome occupancy of mRNAs under resting conditions.

Hypothesis:
Plasma-borne growth factors/hormones (GFH) drive constitutive translation in circulating platelets to modulate reactivity.

Methods:
We employed metabolic labeling of newly synthesized proteins by bio-orthogonal non-canonical amino acid tagging in plasma-starved human platelets fed back with autologous plasma or isolated GFH (VEGF, IGF-1, insulin, EGF, HMGB1), coupled with translation initiation signaling and functional tests.

Results:
We found that platelets undergo constitutive translation of a broad-spectrum translatome dependent on plasma or GFH exposure. Platelets freshly isolated from platelet-rich plasma showed homeostatic activation of translation initiation signaling, evidenced by phosphorylation of p38/ERK upstream kinases, essential intermediate MNK1/2, and downstream effectors eIF4E/4E-BP1. Plasma starvation led to a steady loss of phosphorylation of this pathway, which was fully restored within 5 min stimulation by either plasma or most GFH. Inhibition of translation with puromycin or cycloheximide suppressed thrombin-induced integrin GPIIb/IIIa activation, P-selectin exposure, and platelet aggregation
in vitro
, and delayed platelet clot retraction. Transfusion of puromycin or MNK inhibitor eFT-508 resulted in delayed hemostasis in a tail bleed assay in mice.

Conclusions:
Constitutive plasma GFH-driven translation supports hemostatic platelet function.
Abstract 12527: Acceleration Time and Doppler Velocity Index Are Flow Dependent in Patients With Severe Bioprosthetic Aortic Valve Dysfunction
Authors: Roslan Aslannif , Naser Jwan , Pislaru Cristina , Nkomo Vuyisile T , Fletcher Miller , Thaden Jeremy J , Pislaru Sorin
Published: April 2024

Introduction:
Acceleration time (AT) and Doppler Velocity Index (DVI) are critical parameters in assessment of bioprosthetic aortic valve dysfunction (BAVD). AT>100ms and DVI < 0.25 are highly suggestive of prosthetic obstruction and are incorporated in all triage algorithms. Little is known about their relationship with flow.

Hypothesis:
AT and DVI may be affected by transprosthetic flow in patients with significant bioprosthetic aortic valve dysfunction (BAVD).

Methods:
Single center, retrospective analysis of patients with severe BAVD (confirmed at surgical re-replacement, transcatheter valve-in-valve implantation, or successfully treated bioprosthetic valve thrombosis). Standard prosthetic parameters (AT, DVI, effective orifice area (EOA), mean gradient, presence and degree of regurgitation), flow (stroke volume index, Svi; transprosthetic flow rate, FR) were measured on the transthoracic echocardiogram at the time of diagnosis with severe BAVD.

Results:
A total of 266 patients with severe BAVD underwent treatment between 2008-2020. BAVD mechanism was obstruction (N=192, 72%), regurgitation (n=48, 18%) mixed stenosis and regurgitation (n=15, 6%) and patient-prosthetic mismatch (n=12, 5%). DVI was moderately correlated with FR (r=0.50, p<0.001); AT had a weak but significant inverse correlation with FR (r=0.24, p<0.001). SVi had a weaker influence on DVI (r=0.35, p<0.001) and no correlation with AT.

Conclusions:
AT and DVI are influenced by transprosthetic flow rate. This flow-dependency should be considered when assessing the mechanism of BAVD.
Abstract 12560: The Association of Social Risk Factors With Hypertrophic Cardiomyopathy Treatments and Mortality: US National Inpatient Sample, 2012-2018
Authors: Johnson Daniel Y , Waken RJ , Fox Daniel K , Hammond Gmerice , Joynt Maddox Karen E , Cresci Sharon
Published: April 2024

Introduction:
Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiac disease. In small studies race has been associated with disparities in septal reduction therapy (SRT) but little is known about the association of social risk factors with HCM treatments and outcomes.

Methods:
A retrospective cohort of admissions for HCM in the National Inpatient Sample from 2012-2018 was identified using ICD-9-CM and ICD-10-CM diagnosis codes. SRT and implantable cardioverter-defibrillator (ICD) procedures were identified using ICD-9-CM and ICD-10-CM procedure codes. Logistic regression controlling for social risk factors, Elixhauser comorbidities, pre-existing ICD, and clustering by hospital-year was used to determine the association of social risk factors with HCM procedures and in-hospital mortality.

Results:
We identified 60,227 patients with HCM; 45.82% with obstructive HCM (oHCM). Among them, 57.25% were female, 18.65% were Black, 26.75% were in the lowest ZIP income quartile, and 14.89% lived in rural areas. ICD procedures were done on 3.07% of patients with HCM. Septal myectomy and alcohol septal ablation were received by 6.89% and 2.21% of patients with oHCM, respectively. The in-hospital mortality rate was 3.32% for HCM admissions. Compared to White patients, Black patients were less likely to receive septal myectomy (odds ratio [OR] 0.56, 95% confidence interval [0.45-0.70], p<0.001) and more likely to receive ICD procedures (OR 1.17 [1.01-1.36], p=0.03). Patients in the lowest income quartile were less likely to receive septal myectomy (OR 0.81 [0.68-0.98], p=0.03) and ICD procedures (OR 0.83 [0.71-0.98], p=0.02). Rural patients were more likely than urban patients to receive septal myectomy (OR 1.39 [1.17-1.64], p<0.001) and to die during hospitalization (OR 1.38 [1.19-1.59], p<0.001). Female patients were less likely to receive ICD procedures (OR 0.69 [0.62-0.76], p<0.001) but more likely to die during hospitalization (OR 1.19 [1.07-1.31], p<0.001).

Conclusions:
Among 60,227 patients with HCM, social risk factors were associated with significant disparities in in-hospital mortality and in receiving septal myectomy and ICD treatment. Further research is required to identify and address the sources of these disparities.
Abstract 12568: Angptl2 is Essential for Aortic Valve Development in Mice
Authors: Labbe Pauline , Munoz Goyette Victoria , Villeneuve Louis , Desanlis Ines , Alikashani Azadeh , delwarde constance , Thorin-Trescases Nathalie , Kmita Marie , Thorin Eric
Published: April 2024

Introduction:
Angiopoietin-like 2 (Angptl2) is a pro-inflammatory anti-apoptotic protein, secreted by senescent cells. Angptl2 also contributes to maintain tissue homeostasis, and we previously reported that adult Angptl2-knockdown (KD) mice exhibit spontaneous Aortic Valve (AoV) stenosis with thickened leaflets compared to wild-type (WT) littermates. It is unknown whether and how Angptl2 contributes to AoV development.

Hypothesis:
Angptl2 is expressed in the AoV at the embryonic stage and is essential for its development, by contributing to programmed apoptosis/senescence and proliferation occurring during organogenesis.

Methods:
Embryonic hearts aged 14.5 (E14.5) and 18 days (E18) of
Angptl2
-KD and WT mice were dissected. Protein expression (immunofluorescence) and leaflets/hinges thickness of AoV (hematoxylin & eosin) were quantified in histological sections. Data are mean±SEM of
n
embryos.

Results:
Compared to WT mice, in AoV leaflets from
Angptl2
-KD mice at E14.5, we observed a decrease in apoptotic cells (determined by TUNEL;-47%, p<0.05, n=4), mostly in Valve Interstitial Cells (VICs), a decreased number of Valve Endothelial Cells (VECs) expressing the senescence marker p21 (-48%, p<0.05, n=4), together with a trend towards an increased cell proliferation (Ki67; +396%, p=0.13, n≥6). In turn, a premature thickening of both the leaflets (from 73±18 to 91±33μm, p<0.05, n≥8) and the hinges (from 38±10 to 49±20μm, p<0.01, n≥8) of the valves was measured in
Angptl2
-KD mice at E18. Concomitantly, Angptl2 is dynamically expressed during AoV development in WT mice: at E14.5, Angptl2 is expressed in all cell types, suggesting that it could effectively contribute to regulate apoptosis/senescence in both VICs and VECs. At E18, Angptl2 expression in WT mice is restricted to VICs at the border of the leaflet, where the mechanical stress is high, a pattern also observed in adult WT mice.

Conclusions:
Knockdown of Angptl2 is deleterious to AoV development by disturbing the fine balance between embryonic cell apoptosis/senescence and proliferation, which is essential to adequate AoV maturation; this unbalance progresses to severe AoV stenosis in adult mice.
Angptl2
-KD is a new mouse model of spontaneous AoV stenosis, a disease in high medical needs.
Abstract 12571: Predictors of Successful Ablation of Premature Ventricular Contractions in Structurally Normal Heart
Authors: Mahmoodi Javid , Bernstein Hannah , Khatiwala Roshni , Potter Laura , Srivatsa Uma N
Published: April 2024

Background:
Long term exposure of premature ventricular contractions (PVCs) may lead to development of cardiomyopathy. Catheter ablation has been reported to effectively reduce PVC burden.

Objective:
To determine factors that may predict acute and long-term success with catheter ablation in the following locations: left ventricular outflow tract (LVOT), right ventricular outflow tract (RVOT), left ventricular summit (LVS), and papillary muscle (PM).

Methods:
All PVC ablations in structurally normal hearts from 6/2010 to 6/2017 were included. Acute and long-term success was assessed. Long-term success was defined as >80% PVC reduction.

Results:
A total of 149 patients were included. Mean age of subjects was 57.7 ± 13.1, 55.0% were female. Mean PVC per hour prior to procedure was 900.5 ± 716.8. Distribution of PVC location was: 46.3% RVOT, 21.5% LVOT, 20.1% LVS, 20.5% PM. 8.2% of patients had more than one location of ablation. Acute success was 93.3%. Mean PVC/hour reduction for all locations was 79.5%, RVOT 77.3%, LVOT 89.5%, LVS 77.2%, PM 82.6%, and 67.8% for multiple locations. There was statistically significant reduction in mean PVC/hour when comparing baseline and follow-up PVC burden for each anatomic location except when multiple locations were ablated (Paired t test, p = values shown in Graph 1). Long-term success was 70.5%, measured by rhythm monitor with median follow up of 69 days (IQR 20-323). To assess predictors for ablation failure, logistic regression was performed for the following variables: age, sex, ethnicity, method (robotic magnetic navigation (RMN) vs manual), location, and reduced EF. The only statistically significant predictor of long-term failure was reduced EF (OR = 2.67, p = .048).

Conclusion:
Acute success was high with PVC ablation regardless of location of origin. Deep sites requiring ablation at multiple locations were less effective.
Abstract 12602: Local NET Burden is Associated With Biomarkers of Thrombosis and Cardiac Damage in Left Atrial Cardiopathy
Authors: Martinod Kimberly , Claessen Annika , Martens Caroline P , Krauel Krystin , Pereira Velàsquez Leydi Carolina , Witsch Thilo
Published: April 2024

Atrial cardiopathy results in disturbed blood flow, providing an ideal thrombogenic environment. Neutrophils promote large vessel occlusions and microthrombosis via release of neutrophil extracellular traps (NETs) and thus lie at the interface of (sterile) inflammation, thrombosis, and fibrosis. We profiled NETs, cytokines, thrombotic factors, and cardiac damage markers in left atrial (LA) cardiopathies together with LA structural analysis. A total of 71 patients (median age 66, 46.5% male) undergoing catheterization procedures with atrial transseptal access at the Freiburg Heart Center were enrolled in this prospective study. Paired samples were collected from peripheral blood draws or from within the left atrium (LA). NET biomarkers, sP-selectin, PAD4, proinflammatory cytokines, thrombotic factors (D-dimers, VWF, ADAMTS13), and cardiac damage markers (TropT, proBNP, ICTP) were measured in plasma or serum as appropriate. Echocardiography was performed to assess LA structure and left ventricular function. Data were analyzed by the type of procedure (MitraClip (MC), left atrial appendage closure (LAAC), pulmonary vein ablation (PVA), or patent foramen ovale closure (PFOC), and by atrial fibrillation (Afib) status at time of procedure. NETs, but not other markers, were elevated in local LA samples as compared to peripheral blood. Conversely, most thrombotic, inflammatory, and cardiac damage markers, but not NETs, were elevated in MC or LAAC as compared to PFOC or PVA patients. Across all patients, NET biomarkers positively correlated with IL-6/TNF-α, VWF, and cardiac damage biomarkers. PAD4/NETs negatively correlated with ADAMTS13 activity, indicating that citrullination may contribute to the prothrombotic phenotype of these patients. Afib was not key to these observations. NETs are locally elevated within the left atrium, with elevation of thrombosis markers including VWF in patients with a diseased left atrium. These elevations partly correlate with structural changes of the left atrium and, therefore, may point toward a disturbed local blood flow. This may provide insight on mechanisms that drive detrimental left atrial remodeling as well as clues regarding thromboembolic risks that are rooted in LA changes rather than Afib.
Abstract 12614: Impact of Hospital Invasive Procedure Capability on Pulmonary Embolism Mortality
Authors: Chan Kevin , Lu Daniel , Kim Luke K
Published: April 2024

Objective:
This study aimed to evaluate the impact of hospital invasive procedure capability and inpatient mortality of patients with pulmonary embolism (PE).

Background:
PE is associated with significant mortality. Catheter-directed thrombolysis and surgical embolectomy are the interventional methods accessible to hospitals with specialized procedural resources. Limited data exist comparing outcomes of patients who are admitted to hospitals with these capabilities versus those that do not.

Methods:
PE hospitalizations were obtained from the National Inpatient Sample for the years 2012-2014. Hospitals equipped to perform either catheter-directed thrombolysis or surgical embolectomy were classified as specialized hospitals (SH). Those without such capabilities were classified as non-specialized hospitals (NSH). In-hospital mortality of patients with PE was compared among these two cohorts.

Results:
Among hospitals treating patients with PE, 333 (9.1%)were classified as SH and 3337 (91.0%) were classified as NSH. There were 43,461(21.9%) admissions with PE to SH and 154,731 (78.1%) to NSH. Mortality was 6.1% at SH and 7.6% at NSH (p<0.01). Of patients admitted to SH, 3.6% underwent invasive procedures. Hospitalizations at SH were associated with higher hospitalization cost and longer lengths of stays. On multivariable analysis, there was no difference in mortality among patients admitted to SH versus NSH (OR 0.99, CI 0.93-1.04, p=0.61)

Conclusions:
Patients with pulmonary embolism being treated at specialized hospitals have a similar mortality rate to those being treated at non-specialized hospitals. Further investigation into the factors contributing to this similar rate is warranted.
Abstract 12615: Slow and Oscillatory Blood-Flow in the Left Atrial Appendage is Associated With Stroke Risk in Atrial Fibrillation Patients
Authors: Paliwal Nikhil , Mao Yuncong , Spragg David D , Calkins Hugh G , Park Hwan-Cheol , Trayanova Natalia
Published: April 2024

Introduction:
Atrial fibrillation (AF) patients are at high risk of stroke with ~90% clots originating from the left atrial appendage (LAA). Studies correlating left atrial (LA) and LAA geometrical parameters with stroke exhibit conflicting results. Also, blood-flow based parameters and their association with stroke for AF patients remains unexplored.

Hypothesis:
Low blood-flow in the LA/LAA is associated with stroke for AF patients.

Methods:
We retrospectively collected CT images of 53 AF patients and dichotomized them based on clinical event into stroke and non-stroke groups. After image segmentation to obtain 3D LA geometry, personalized blood-flow analysis was performed to model LA hemodynamics. For geometry, we calculated area of 4 pulmonary veins (PVs) and area and volume of LA/LAA. For hemodynamics, we quantified blood flow velocity, wall shear stress (WSS, blood-friction on LA wall), oscillatory shear index (OSI, directional change of WSS) and endothelial cell activation potential (ECAP, ratio of OSI and WSS quantifying slow and oscillatory flow) in LA/LAA. All parameters were compared between the groups.

Results:
Twenty-seven patients were included in the stroke and 26 in the non-stroke group. Geometrically, there was non-significant difference between the LA/LAA area and volume, and area of PVs between the groups (Figure A). In terms of blood-flow (Figure B), velocity, WSS, OSI and ECAP in the LA had non-significant differences between the groups. However, stroke group had significantly lower velocity, WSS and higher ECAP in LAA as compared to non-stroke group. This suggests that stroke patients had slow and oscillatory circulating blood-flow in the LAA, exposing it to thrombogenesis, potentially causing stroke.

Conclusion:
Slow and oscillatory flow in the LAA alone is associated with stroke in this AF cohort. Personalized blood-flow analysis can identify such hemodynamic conditions, aiding in clinical stroke risk stratification of AF patients.
Abstract 12620: Myeloid Cell-Specific Arginase-1 is Essential for Cardiosphere-Derived Cell Extracellular Vesicle Mediated Angiogenesis Following Acute MI
Authors: Mentkowski Kyle I , Manzanero Cody A , Eagler Lisa A , Lang Jennifer K
Published: April 2024

Introduction:
Following a myocardial infarction (MI), macrophages play a pivotal role in initiating and resolving inflammation. Extracellular vesicles (EVs) released by cardiosphere-derived cells (CDCs) have been shown to improve cardiac function in animal models of ischemia in part via effects on immunomodulation. We have recently shown that CDC-EVs polarize macrophages toward a unique pro-angiogenic phenotype, characterized by increased expression of Arginase-1 (Arg1) and enhanced release of pro-angiogenic factors. We hypothesized that CDC-EV dependent activation of Arg1 could underlie their therapeutic benefit
in vivo
.

Methods:
LysMCre mice were crossed with Arg1 fl/fl mice to generate a myeloid cell-specific Arg1 knockout model (Arg1-KO) according to institutional approved protocols. To assess the importance of myeloid-specific Arg1 in the therapeutic efficacy of CDC-EVs
in vivo
, Arg1-KO mice and their fl/fl littermates (wt) were subjected to permanent LAD ligation and randomized to receive 1) CDC-EVs or 2) vehicle control. Prior to euthanasia, mice were injected with BSL-1 Lectin to measure capillary density. Ejection fraction was measured by echocardiography at 5 days post-MI and tissue samples processed for western blot, PCR, flow cytometry, and histological analyses.

Results:
Arg1 protein expression was significantly repressed in splenic monocytes isolated from Arg1-KO mice compared with WT mice (fold change: 0.3 ± 0.1, p<0.05, t-test, n=3). CDC-EV therapy enhanced ejection fraction in both Arg1-KO mice and WT mice following MI (Arg1-KO: 49.0 ± 3.2% vs. 40.3 ± 1.9%, WT: 51.2 ± 2.9% vs. 39.0 ± 3.8%, p<0.05, t-test, n=6-7 mice/group). CDC-EV therapy significantly increased capillary density in WT mice compared with PBS control (3642 ± 632 vs. 2125 ± 290 capillaries/mm
2
, p<0.05, t-test, n=4-5), but was unable to increase capillary density in Arg1-KO mice above the level seen with PBS treatment (2979 ± 341 vs. 3033 ± 469 capillaries/mm
2
, ns, t-test, n=4-5).

Conclusions:
Myeloid-specific Arg1 expression is required for CDC-EV mediated angiogenesis but occurs independently of CDC-EV beneficial effects on LVEF following acute MI.
Abstract 12625: Troponin I3 A157V Homozygous Mutation Induces Diastolic Dysfunction
Authors: Duran Jason M , Bushway Paul , Manso Maria , Gu Yusu , Cho Yoshitake , Fong Joshua , Ross Robert S , Adler Eric D
Published: April 2024

Introduction:
Previous studies describe a morbid restrictive cardiomyopathy in patients with substitution of alanine with valine at amino acid 157 (A157V) within the calcium-binding domain of the inhibitory subunit of cardiac troponin (TNNI3); yet the precise mechanism of disease remains unknown.

Hypothesis:
A murine model of A157V TNNI3 would recapitulate key features of disease and serve as a model of cardiac restriction.

Methods:
TNNI3
A157V mice were generated using a cloning-free CRISPR/Cas-9 system to introduce a point mutation (c.470c>T) resulting in missense substitution of valine for alanine at amino acid 157 in Exon 7 of
TNNI3
. Heterozygous and homozygous mice were generated in a C57BL/6 background. At one year of age animals had echocardiography and electrocardiogram (ECG) performed, followed by invasive hemodynamics. Mice were then sacrificed for cardiac morphometry and hearts were fixed and embedded for histology.
TNNI3
A157V adeno-associated virus-9 (AAV-9) construct was generated and injected retro-orbitally into 8-12 week old wild-type mice.

Results:
Serial echocardiography at 2, 4, 6 and 12 months of age demonstrated normal wall thickness, ejection fraction and strain. No differences were noted in cardiac arrhythmias assessed using ECG. Hemodynamics performed at 15 months of age demonstrated significantly reduced minimum derivative of pressure/time (dP/dT) and Tau in response to dobutamine in
TNNI3
A157V mice v. controls. No significant differences between genotypes were detected in cardiac morphometry (heart weight and heart weight normalized to body weight or tibia length), myocyte cross sectional area measured on trichrome-stained heart sections, or myocardial oxygen consumption rate measured by oroboros. Mice injected with
TNNI3
A157V AAV-9 demonstrated expression of the mutant TNNI3 construct on western analysis and immunohistochemistry.

Conclusions:
We have developed a novel mouse model in which substitution of valine for alanine at amino acid 157 in
TNNI3
induces diastolic dysfunction despite the absence of cardiac hypertrophy that recapitulates key features of human disease and can serve as a platform for further mechanistic and translational studies.
Abstract 12641: Performance of Mortality Prediction Models in Dilated Cardiomyopathy Patients and the Incremental Value of Late Gadolinium Enhancement
Authors: Tang Siqi , Chen Yucheng , Zhang Qing
Published: April 2024

Introduction:
Mortality prediction models assist decision-making for patients with dilated cardiomyopathy (DCM). Published heart failure (HF) models have not been validated in large DCM cohorts; whether late gadolinium enhancement (LGE) provides incremental predictive power remains unclear.

Hypothesis:
Incorporating LGE location improves the performance of existing HF mortality prediction models.

Methods:
We used data from a prospective registry enrolling DCM patient who underwent clinical CMR examination between June 2012 and May 2020. Five recent or classic models estimating the risk of all-cause death or heart transplantation in chronic HF patients were examined: SHFM, GISSI-HF, MAGGIC, BIOSTAT-CHF, and PARADIGM-HF score. We added LGE location to the risk scores generated by the original models.

Results:
Of 524 DCM patients with available data required for all five models (age 48.7 ± 15.1, 71% male), 100 patients (19.1%) died or underwent heart transplantation (median follow-up of 26.3 months). PARADIGM-HF showed the best overall discrimination [Harrell’s C index and 95% CI: 0.75, 0.70-0.80], similar to SHFM and MAGGIC [0.72, 0.67-0.77 and 0.71, 0.66-0.76, respectively; all comparisons
P
>0.05], and better than GISSI-HF and BIOSTAT-CHF [0.66, 0.60-0.71 and 0.66, 0.60-0.72, respectively]. PARADIGM-HF exhibited decreased discrimination for 2-year and 3-year mortality/heart transplantation risk. The net reclassification by adding LGE location to the models improved the 2-year and 3-year risk prediction in 25-29% of patients, except for MAGGIC; however, 1-year risk prediction remained unaltered.

Conclusions:
Existing HF mortality prediction models made moderately accurate risk estimates. LGE assisted long-term risk stratification but may have less additive value for the short-term risk prediction.
Abstract 12660: Novel Model of Oxalate Diet Induced Chronic Kidney Disease in Dahl-Salt-Sensitive Rats
Authors: Dube Prabhatchandra , Aradhyula Vaishnavi , Connolly Jacob , Khalaf Fatimah , Soehnlen Sophia , DeRiso Armelle , Cash Ayla , Kleinhenz Andrew , Domenig Oliver , Malhotra Deepak , Dworkin Lance D , Haller Steven T , Kennedy David J
Published: April 2024

Background:
Diet induced models of chronic kidney disease (CKD) may offer several advantages vs surgical models in terms of clinical relevance and animal welfare. Oxalate is a plant-based, terminal toxic metabolite that is eliminated by the kidneys through glomerular filtration and tubular secretion. Increased load of dietary oxalate leads to supersaturation, calcium oxalate crystal formation, renal tubular obstruction and eventually CKD. Dahl-salt-sensitive rats (Dahl-S) are a common strain used to study for hypertensive renal disease however characterization of other diet induced models on this background would allow for comparative studies of CKD within the same strain. We hypothesized that Dahl-S rats on a low-salt, oxalate rich diet would have increased renal injury and will serve as a novel rat model to study CKD.

Methods/Results:
Ten week-old male Dahl-S rats were fed either 0.2% salt normal chow (SS-NC) or a 0.2% salt diet containing 0.67% sodium oxalate (SS-OX) for five weeks (n=6-8/group). Real-time PCR demonstrated increased expression of inflammatory marker IL-6 (235% vs SS-NC, p<0.0001) and fibrotic marker Timp-1 metalloproteinase (142% vs SS-NC, p<0.0001) in the renal cortex of SS-OX rat kidneys compared to SS-NC. Immunohistochemistry of kidney tissue demonstrated increase in CD-68 levels, a marker of macrophage infiltration in SS-OX rats (275% vs SS-NC, p<0.001). In addition, SS-OX rats displayed increased 24-hour urinary protein excretion (UPE) (97% vs SS-NC, p<0.01) as well as significant elevations of plasma Cystatin C (135% vs SS-NC, p<0.01). Furthermore, oxalate diet induced hypertension (23% increase in systolic blood pressure vs. SS-NC, p<0.05) and renin-angiotensin-aldosterone system (RAAS) profiling (via LC-MS/MS) in the SS-OX plasma showed significant (p<0.05) increases in angiotensin [1-5] (128% vs SS-NC) and angiotensin I (56% vs SS-NC) as well as suppression of the steroid aldosterone (-54% vs SS-NC).

Conclusion:
Oxalate diet induces significant renal inflammation, fibrosis, renal dysfunction, decreased aldosterone secretion as well as RAAS activation and hypertension in Dahl-S rats and provides a novel diet-induced model to study hypertension and CKD.
Abstract 12685: Feasibility and Safety of Vascular Closure Devices After Undergoing Leadless Pacemaker Implantation
Authors: mendoza ivan , Penalver Jorge , Aranguibel Ninoska N , Chamorro Jose , zambrano Juan , Mendoza Cesar , Braghiroli joao , Ramalho Isabella A , Castiblanco Daisy A , Mendoza Ivan
Published: April 2024

Introduction:
Transcatheter pacing systems have recently emerged as a safe and effective alternative in treating patients who require right ventricular pacing therapy. Traditionally, the right femoral venous was the preferred insertion site for the 23 French Micra introducer catheter due to the manufactured design of the delivery system. Vascular closure of the venous access has been performed with figure 8 closure technique and manual pressure . There is no data supporting the use of closure devices in this specific procedure. The purpose of this study was to assess the feasibility and safety of vascular closure devices after undergoing implantation of the leadless pacemaker device.

Methods:
One hundred and eighty ( 180 ) consecutive patients who had undergone implantation of a Micra transcatheter pacing were evaluated. One hundred and sixty eight ( 168 ) patients had traditional vascular closure after implantation and twelve ( 12 ) received the Perclose vascular closure device for the femoral venous access . A t-test analysis was used to compare patient demographics total procedure times and complications rates

Results:
None of the 180 patients suffered complications during the procedure. The mean procedure time using the traditional figure eight technique was 21.24 min versus 30.67 min (P = 0.01) by the closure device . The mean number of recaptures required for the patients undergoing the traditional venous closure was 0.48 vs. 0.67 (P = 0.70) by the closure device

Conclusions:
The Perclose device appears safe and feasible alternative for the vascular closure after implantation of the Micra transcatheter leadless pacemaker system. This approach tends to have longer procedure times
Abstract 12754: Is an Induction Test Necessary While Catheter Ablation of Atrial Fibrillation
Authors: Sato Tetsuro , Oikawa Jun , Fukaya Hidehira , Kishihara Jun , Ishizue Naruya , Saito Daiki , Matsuura Gen , Murayama Yusuke , mitani yutaro , Niwano Shinichi , Ako Junya
Published: April 2024

Introduction:
In general, several reports have been that it is beneficial to confirm the induction test of atrial arrhythmias by burst and provide additional procedures after catheter ablation (CA) for atrial fibrillation (AF). However, few reports on whether the presence or absence of an induction test of arrhythmia affects long-term recurrence.

Hypothesis:
In this study, we sought to elucidate the relationship between induction test and recurrence of atrial arrhythmias in patients who underwent CA for AF.

Methods:
We enrolled 678 consecutive patients who underwent the first CA for AF from 2014 to 2020. Of all patients, 573 patients (85%) were performed induction test during CA. After propensity score matching with factors that may affect recurrence i.e., age, left atrial diameter, gender, disease type, and history of coronary artery disease, we divided into induction group (n = 104) and non-induction group (n = 104). The primary endpoint was the recurrence of AF and the occurrence of other atrial tachy-arrhythmias after the 90-day blanking period. The observational period was set at one year after the index.

Results:
The median age was 67 (59 - 73) years old with 22% of female. During the periods, the recurrence occurred in 46 (22%) patients. In the log-rank test, there was no significant difference in the recurrence rate between the two groups (P = 0.74).

Conclusions:
The induction test might not be required for atrial fibrillation ablation; however, we will need a prospective study in the future.
Abstract 12759: Iron Deficiency in Heart Failure is Associated With Upregulation of Pathways Also Related to Cancer Development
Authors: Grote Beverborg Niels , van der Wal Haye , Lang Chim C , Dickstein Kenneth , Filippatos Gerasimos , Cleland John , Anker Stefan D , Metra Marco , van Veldhuisen Dirk , Voors Adriaan A , De Boer Rudolf A , van der meer peter
Published: April 2024

Introduction:
Iron deficiency is common in patients with heart failure (HF) and associated with a poorer prognosis. Mechanisms underlying these associations in HF are currently mostly unknown.

Hypothesis:
We aimed to identify pathophysiological pathways which are altered in HF patients with iron deficiency versus those without.

Methods:
We studied 1,933 subjects with worsening HF from the BIOSTAT-CHF cohort. Patients were classified by iron deficiency (transferrin saturation<20%). Biological processes were identified using the differential expression of 368 plasma proteins and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database using STRING v11.0. Analyses were adjusted for 13 potential confounders including hemoglobin concentration. Sensitivity analyses were performed on matched populations.

Results:
Patients were mainly men (74%) with a mean age of 69 (±12) years and a left ventricular ejection fraction of 31% (±11). Iron deficiency was identified in 1,219 (63%) patients. Plasma concentrations of 27 proteins were higher and three proteins lower in patients with iron deficiency compared to those without (false discovery rate<0.05). The most strongly up-regulated proteins included the transferrin receptor, IL-6, fibroblast growth factor-23, (N-terminal pro-)B-type Natriuretic Peptide and mucin-16 (cancer antigen-125). KEGG analyses identified cytokine-cytokine receptor interaction and cancer-related pathways as enriched, including PI3K-Akt, MAPK, Rap1 and Ras signaling, and “gastric cancer” and “pathways in cancer”. Downregulated proteins were chemokine ligand-17, paraoxonase-3 and platelet derived growth factor subunit B, which resembled no networks.

Conclusion:
Our post-hoc analyses of the proteome shows that in patients with HF, those with iron deficiency have higher plasma concentrations of proteins involved in cancer related pathways.
Abstract 13007: Change in QRS 3D Voltage Time Integral (3D QRS Area) Predicts Left Ventricular Reverse Remodeling in Sacubitril-Valsartan Treated Patients With Left Bundle Branch Block
Authors: Parimi Nikhil K , Mahmood Uzair , Abudan Anas , Sami Farhad , Lacy Sean , Harvey Christopher J , Reddy Madhu , Sheldon Seth H , Noheria Amit
Published: April 2024

Introduction:
The instantaneous absolute 3D ECG voltage integrated over the duration of QRS (VTI
QRS-3D
) is an improved marker of left ventricular (LV) electrical dyssynchrony compared to QRS duration (QRSd). Among patients with left bundle branch block (LBBB) receiving heart failure medical therapy, the relationship between electrical remodeling assessed by VTI
QRS-3D
and structural LV remodeling is unclear.

Hypothesis:
Reduction in VTI
QRS-3D
is correlated with left ventricular reverse remodeling.

Methods:
We retrospectively studied heart failure patients with underlying LBBB who were treated with sacubitril-valsartan for ≥3 months between January 2014 - June 2019. Echocardiograms and 12-lead ECGs were collected pre and post sacubitril-valsartan treatment. ECGs were converted to orthogonal X, Y, Z leads using Kors matrix, to then obtain VTI
QRS-3D
. Echocardiographic LV measures included end-diastolic volume (LVEDV), end-systolic volume (LVESV) and ejection fraction (LVEF). We calculated the Pearson correlations between electrical variables and changes in echocardiographic measures pre to post treatment.

Results:
We included 56 patients (mean age 64.0±13.5 years, men 53.6%, baseline LVEF 25.2±9.1%). ΔVTI
QRS-3D
was strongly correlated with improvement in all 3 echocardiographic measures (all p ≤0.01). ΔVTI
QRS-3D
outperformed ΔQRSd in predicting echocardiographic response (Table).

Conclusions:
In heart failure patients with LBBB on medical therapy, electrical remodeling assessed as reduction in VTI
QRS-3D
is strongly predictive of LV structural and functional reverse remodeling.
Abstract 13008: Patients Are Often Unaware Of Their Heart Failure Diagnosis, Even After A Heart Failure Hospitalization
Authors: Zhu Aowen , Levitan Emily B , Clarkson Stephen , Brown Todd , Durant Raegan W , Kingery Justin , Shen Megan J , Khodneva Yulia , Jackson Elizabeth A , Safford Monika M , Goyal Parag
Published: April 2024

Introduction:
Self-reported heart failure (HF) is an important data source for epidemiologic studies of HF for clinicians caring for HF patients. We sought to understand the prevalence, predictors, and outcomes of patients who did not self-report a diagnosis of HF despite a history of a HF-hospitalization.

Methods:
We studied participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, who experienced an adjudicated hospitalization for HF and completed a computer-assisted telephone interview approximately 10 years following initial recruitment. We compared characteristics and mortality for participants who self-reported a HF history (aware) to those who did
not
self-report a HF history (unaware). To understand correlates of being aware vs. unaware of a HF diagnosis, we constructed a logistic regression model including demographics, social determinants of health, HF characteristics, comorbid conditions, cognitive status, and health literacy.

Results:
Among 15,560 eligible participants, 362 participants experienced an adjudicated HF-hospitalization over the 10-year study period, of which 114 (31%) did not self-report a HF diagnosis (unaware). Mortality after the 10-year follow-up was higher among participants who were unaware of their HF diagnosis (Figure). Participants with HFrEF trended toward higher odds of being aware of their HF diagnosis (OR 1.20 95%CI[0.73-1.98]) while less than high school education (OR 0.79 95%CI[0.39-1.61]) and living in a high poverty zip code (OR 0.57 95%CI[0.31-1.04]) were associated with a trend toward lower odds of being aware of a HF diagnosis, though these associations did not reach statistical significance.

Conclusions:
Nearly one-third of participants with an adjudicated HF-hospitalization may not be aware of their diagnosis of HF. This may result in inaccurate estimates of HF prevalence and may contribute to worse outcomes such as mortality.
Abstract 13010: Aquaporin 4 Alleviates Myocardial Ischemia-reperfusion Injury By Inhibiting Cardiomyocyte Apoptosis
Authors: Jiang Qiong , Ye Mingfang , Yan Yuanming , Fang Jun , Luo Yukun
Published: April 2024

Introduction:
Myocardial injury caused by ischemia-reperfusion is the main pathological manifestation of coronary artery disease (CAD), which is characterized by high mortality and morbidity. Thus, there’s an urgent need to develop efficacious strategies and elucidate the underlying mechanisms to prevent or alleviate myocardial ischemia-reperfusion injury to improve the clinical outcomes.

Hypothesis:
Aquaporin 4 may alleviates myocardial ischemia-reperfusion injury by inhibiting cardiomyocyte apoptosis.

Methods:
In this study, we took advantage of a typical myocardial cell line of mice (HL-1) and cultured with or without an aquaporin 4 inhibitor (TGN-20 denoted as AQP4i) under normal conditions (NC), ischemia (IS) and ischemia reperfusion (IR), respectively. The cytomorphology, ultrastructure, cell vitality and expression pattern of apoptotic proteins were verified with scanning electron microscope (SEM), immunofluorescence staining, flow cytometry, quantitative real-time PCR and western-blotting analysis, respectively.

Results:
HL-1 under IS or IR condition revealed higher expression of Aquaporin 4 (Aqp4) compared to the NC group, whereas showed similarity in cytomorphology and ultrastructure. Aqp4 inhibition was sufficient to improve the apoptotic cells in HL-1 while showed minimal effects to the other cellular vitality. Furthermore, the expression pattern of apoptotic proteins and anti-apoptotic proteins together with proinflammatory factors in HL-1 was effectively rescued by Aqp4i treatment both at the mRNA level and protein level.

Conclusions:
Ischemia and ischemia reperfusion caused higher expression of Aqp4 and resultant increase of cardiomyocyte apoptosis. Myocardial ischemia-reperfusion injury of HL-1 was effectively alleviated by Aqp4 and apoptosis inhibition. Our findings provided new references for myocardial ischemia-reperfusion injury management via targeting Aqp4-mediated apoptosis of cardiomyocyte.
Abstract 13014: Sex-Differences in Nonagenarians With ST Elevation Myocardial Infarction
Authors: Lantz Rebekah , Shukla Janki , Larson David , Yildiz Mehmet , Schmidt Christian , Mattingly Georgia , Sharkey Scott W , Coulson Teresa , Chambers Jenny , Henry Timothy D , Quesada Odayme
Published: April 2024

Introduction:
Longevity of the population continues to increase but frequently elderly patients are excluded from clinical trials. Women with STEMI have been reported to have higher mortality, delay to treatment, and suboptimal prescription of goal directed medical therapy compared to men. We recently demonstrated higher utilization of PCI with improved outcomes in elderly patients treated in regional STEMI systems with standardized protocols. We evaluated sex-differences in nonagenarians with STEMI.

Methods:
The Midwest STEMI Consortium (MSC) consists of four regional STEMI centers includes 15,039 consecutive STEMI activations between March 2003 and December 2020. Sex differences were assessed in the subgroup of patients ≥ 90 years old (n=303, 2%), including baseline demographic, intervention, mortality outcomes, and pre/post hospitalization residence status.

Results:
Of 303 nonagenarians, women (N=194, 64%) were less likely to have a smoking history, family history of coronary artery disease (CAD), and personal history of CAD (including MI, PCI or CABG). Surprisingly, there were no sex differences in time to treatment, use of PCI (84 vs 78%), adjunctive medical therapy or clinical outcomes including in-hospital and 1-year mortality (Table).

Conclusions:
In 4 established regional STEMI systems, in elderly patients ≥ 90 years old women were more common (64%) and although the risk profiles were different, there were no sex differences in reperfusion strategy, time to treatment, or adjunctive therapy. Importantly, there were no differences in clinical outcomes including mortality. The high rate of PCI, excellent treatment times and clinical outcomes compared to historical data likely reflect the benefit of regional STEMI programs using standardized protocols.
Abstract 13019: Association of Histopathologic Phenotypes With Demographics and Cardiovascular Risks in People With Clinically Diagnosed Heart Failure
Authors: Kim Sarah , Gaddam Meghna , Sunderraj Ashwin , Sinha Arjun , Shah Sanjiv J , Lloyd-jones Don , Thorp Edward B , Lomasney Jon W , Feinstein Matthew J
Published: April 2024

Introduction:
Heart failure phenotypes are often defined based on imaging diagnoses and clinical risk factors without corroborative tissue-level investigation. Defining clinical factors associated with specific tissue phenotypes among people with HF may yield important insights.

Methods:
We analyzed cardiac autopsies performed on people with clinical diagnoses of HF (N=526) at a large urban medical center between 4/6/2002 and 04/01/2021. We determined whether or not patients had histopathologic evidence of the following: (1) cardiomegaly; (2) atherosclerosis (any); (3) severe/obstructive coronary atherosclerosis; (4) remote MI; (5) acute/recent MI (<14 days old pathologically); (6) myocardial fibrosis; and/or (7) myocardial inflammation. We determined associations of demographics and clinical factors with histopathologic phenotypes among people with a clinical diagnosis of HF using Chi-square and ANOVA. A Bonferroni-corrected p-value of <0.00102 was considered statistically significant to correct for multiple comparisons.

Results:
We observed significant differences by sex and several clinical factors in cardiac histopathology among patients with clinical diagnoses of HF (Table). Men were significantly more likely than women to have histopathologically-defined fibrosis (73% vs. 59%; p=0.0008) and cardiomegaly (76% vs. 60%; p=0.0002). HF patients with atrial fibrillation were significantly more likely to have cardiac fibrosis than those without atrial fibrillation (73% vs. 58%; p=0.0005). HF patients with LVEF >=50% were significantly less likely to have pathologic evidence of prior MI than patients with LVEF 40 to <50% and LVEF <40% (respectively, 24%, 50%, and 48% of patients in these groups; p<0.00001).

Conclusions:
Among patients with HF, sex, atrial fibrillation, and LVEF were associated with distinct cardiac histopathology at autopsy. Future tissue-level analyses in humans to define underlying mechanisms are needed.
Abstract 13052: Antiarrhythmic Effect of Artemisinin in Canine Experimental Model of Brugada Syndrome
Authors: Jeong Hyung Ki , Yoon Namsik , Lee Ki Hong , Park Hyung Wook , Cho Jeong gwan
Published: April 2024

Introduction:
Brugada syndrome is an inherited arrhythmia syndrome which presents sudden cardiac death (SCD) without structural heart diseases. One of the mechanisms of SCD has been suggested that uneven dispersion of Ito channel between epicardium and endocardium induces ventricular arrhythmia.

Hypothesis:
Artemisinin is used as antimalarial drug widely. Its antiarrhythmic effect which included suppression of Ito channel was reported previously. We investigated the effect of Artemisinin for suppression of Brugada syndrome in canine experimental model

Methods:
Transmural pseudo-ECG and epicardial/endocardial action potentials were recorded from coronary-perfused canine right ventricular wedge preparation (N=7). To mimic the Brugada syndrome model, acetylcholine (3 μM), calcium channel blocker verapamil (1 μM), Ito agonist NS5806 (7-10 μM) were used and waited until ventricular arrhythmia induction. Then, Artemisinin 100-150 μM was perfused to ameliorate the ventricular arrhythmia. Action potential duration, J wave area, notch index and T wave dispersion were measured.

Results:
In 5 sample models, ventricular arrhythmia was induced. The Artemisinin suppressed ventricular arrhythmia (n=5) and recovering the action potential dome of RV epicardium after provocation of ventricular arrhythmia in all preparations (n=7). J wave area and epicardial notch index were also decreased after Artemisinin perfusion. Action potential duration prolonged as the ventricular arrhythmia provocation and recovered after Artemisinin perfusion.

Conclusions:
Our findings suggest that Artemisinin alleviate the Brugada syndrome in the wedge preparation model by inhibition of Ito channel and it suppressed the development of phase 2 reentry and ventricular tachycardia/ventricular fibrillation.