bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11962: Applying a Deep-Learning Approach for Automated Quantification of Epicardial Adipose Tissue on Coronary Computed Tomography Angiography in Challenging Clinical Populations
Authors: West Henry W , Siddique Muhammad , Volpe Lucrezia , Desai Ria , Lyasheva Maria , Dangas Katerina , Shirodaria Cheerag , Neubauer Stefan , Channon Keith M , Desai Milind Y , Williams Michelle C , Rodrigues Jonathan C , Adlam David , Ed Nicol D , Antoniades Charalambos
Published: April 2024

Introduction:
Epicardial adipose tissue (EAT) is a visceral fat deposit within the pericardial sac. The automated quantification of EAT volume is possible from routine CCTA scans via a deep-learning approach.

Purpose:
To apply a deep-learning approach for automated segmentation of EAT from CCTA scans in challenging clinical populations to assess the real-world viability of automated segmentation.

Methods:
A deep-learning automated EAT segmentation tool using a 3D Residual-U-Net neural network architecture for 3D volumetric segmentation of CCTA data was created and trained on over 2500 consecutive CCTA scans performed as part of clinical care in patients with stable chest pain from 2015 onwards within the European arm of the Oxford Risk Factors And Non Invasive Imaging (ORFAN) Study. External validation was performed in 817 scans from USA ORFAN sites (Figure 1A demonstrates human vs machine segmented EAT volume for a single case). The network was then applied to sets of unseen CCTAs from the AdipoRedOx Study (UK, n=253) and the SCOTHEART trial (UK, n=1558) to test its ability to perform EAT segmentations in challenging but common patient populations: 1) recent cardiac surgery (<6 weeks post operation), 2) BMI ≥ 40, 3) CAC ≥ 400, 4) significant metallic artefact within the pericardium, and 5) a combined group of recent open-heart surgery, BMI ≥ 30 & CAC ≥ 400.

Results:
There was excellent correlation between machine and human expert in the within-ORFAN validation cohort (Lin's concordance correlation coefficient (CCC) = 0.972, for both whole pericardial volume and EAT volume). CCC for machine vs human experts for all five challenging but common patient groups were also excellent (range 0.955-0.962) and are presented in Figure 1B-F.

Conclusions:
A new deep learning network achieves excellent automated segmentation of EAT and can be used to provide this information in a highly accurate and reproducible way, even in challenging common clinical populations.
Abstract 11967: Benefit of Implantable Cardioverter Defibrillator Therapy in Patients With Advanced Renal Impairment: A Competing Risk Analysis From the MADIT Trials
Authors: Goldenberg Ido , Aktas Mehmet , Kutyifa Valentina , Zareba Wojciech , Younis Arwa , Rao Mohan
Published: April 2024

Introduction:
The life-saving benefit of the implantable cardioverter defibrillator (ICD) in patients with advanced chronic kidney disease (A-CKD) is still controversial. This is possibly due to a higher risk of dying from non-arrhythmic causes in A-CKD patients, and thereby die prior to receiving therapy from the ICD. We aimed to evaluate the competing risk for ventricular tachycardia/fibrillation (VT/VF) vs. death without prior VT/VF in ICD recipients by renal function.

Methods:
The study population comprised 3953 patients with an ICD enrolled in the landmark MADIT trials, categorized by renal function into: A-CKD (estimated Glomerular Filtration Rate [eGFR] ≤40 ml/min/1.73 m
2
[N=403]; Moderate CKD (eGFR 41-60 ml/min/1.73 m
2
[N=995]); and No-CKD (eGFR >60 ml/min/1.73 m
2
[N=2555)). Cumulative incidence function curves were used to display the rate of fast VT/VF (>200 bpm) and the competing risk of death without experiencing prior fast VT/VF using the Fine and Gray method.

Results:
At 4-years of follow-up, patients in the A-CKD group had a significantly lower cumulative incidence of VT/VF compared to patients with Moderate-CKD and No-CKD (13%, 17%, and 20%, respectively; p=0.006 for the overall difference [Figure: left panel]). In contrast, the corresponding 4-year rates of death without experiencing prior fast VT/VF were significantly highest among patients with A-CKD and attenuated among those with Moderate- and No-CKD (28%, 17%, and 9%, respectively; p<0.001 for the overall difference [Figure: right panel]).

Conclusion:
Our data from 4 landmark primary prevention ICD trials show significant differences in the risk of VT/VF vs the competing risk of death without experiencing prior VT/VF by renal function. This suggests an attenuated benefit of ICD therapy with declining renal function.
Abstract 11978: Increased Early Prothrombotic Potential of Transcatheter Aortic Valve Implantation Compared With Percutaneous Coronary Intervention Identified With Viscoelastic Hemostatic Assessment of Coagulation
Authors: Fanning Jonathon P , Roberts Shaun , Natani Sarvesh , Poon Karl , Incani Alexander , Anstey Christopher , Fraser John F
Published: April 2024

Introduction:
Antithrombotic guidelines for transcatheter aortic valve implantation (TAVI) are extrapolated from percutaneous coronary intervention (PCI). Comparison of the thrombotic profiles of the procedures is necessary to determine the validity of this supposition.

Hypothesis:
TAVI has higher thrombogenic potential than PCI due to greater endothelial damage, artificial surface exposure and altered rheology.

Methods:
Patients undergoing transfemoral TAVI with Edwards SAPIEN-3 (n=16) or elective PCI (n=12), were prospectively recruited. Blood was sampled at 4 timepoints, following: T1-sedation/anesthesia; T2-heparin (100 IU/kg) and TAVI/PCI deployment; T3-protamine (1mg/100IU heparin); and, T4-6h post procedure. Analysis included: 1) viscoelastic hemostatic profiling with thromboelastometry (ROTEM
Sigma
), thromboelastography (TEG6s) and activated clotting time; 2) platelet function (Multiplate analyzer); and, 3) routine coagulation panel (PT/INR, aPTT, thrombin clotting time, anti-Xa, platelet count and direct/Claus fibrinogen).

Results:
There were no difference in baseline characteristics except for older age in the TAVI cohort (83±2 vs 73±4; p=0.028). A relative prothrombotic effect was demonstrated early post TAVI for all components of the coagulation pathway measured by rotational thromboelastometry (Figure), including: intrinsic (INTEM), extrinsic (EXTEM), fibrinogen (FIBTEM) and despite heparin neutralisation (HEPTEM). Heparin effect limited thromboelastography analysis and resulted in significant rises between T1 and T2 for all variables in the routine laboratory coagulation panel (except direct fibrinogen), which normalised by T4.

Conclusions:
Coagulation profiles differ between the two procedures with TAVI relatively more prothrombotic than PCI. While the clinical significance of this is unclear further investigation to determine optimal periprocedural antithrombotic prophylaxis is mandated.
Abstract 11989: Cardiac Muscle-Specific Disruption of the Exocyst Trafficking Complex Results in Heart Failure
Authors: Ha Herena Y , Shimada Briana K , Nakamura Nicole K , Carter Lamar T , Luo Emi Lin , Tokunaga Darcy S , Zoll Janna , Polgar Noemi
Published: April 2024

Increased myocardial glycolysis is protective against ischemic injury. Glucose uptake via glucose transporter GLUT4 is the rate-limiting step of glycolysis in cardiomyocytes. GLUT4 delivery to the cardiomyocyte membrane can be triggered by insulin or by increased ATP-demand (i.e. during ischemia) via the AMP-activated protein kinase (AMPK). Previous studies of adipocytes and our recent study in skeletal muscle demonstrated that the exocyst trafficking complex is critical for GLUT4 exocytosis in response to insulin. But it is not known if the insulin-insulin receptor-exocyst-GLUT4 signaling axis is conserved in the cardiomyocytes, or if the exocyst also regulates cardiac glucose uptake via AMPK-induced GLUT4 translocation. Investigating glucose transporter trafficking in cardiomyocytes will be key to better understanding the mechanism of cardiac glucose metabolism under normal and disease conditions.

We hypothesized that the exocyst is necessary for myocardial glucose uptake and metabolism and its activity protects the heart from ischemic injury.

We have generated tamoxifen-inducible cardiac muscle-specific knockout mice of the central exocyst subunit Exoc5 (Exoc5-CMKO) to evaluate the role of the exocyst in cardiac fuel metabolism
in vivo
.

Unexpectedly we found that cardiac muscle-specific Exoc5 knockout shortened the lifespan of Exoc5-CMKO mice (median survival after tamoxifen treatment was 60.5 days). Echocardiography showed cardiac dysfunction in Exoc5-CMKO mice, with reduced ejection fraction (Ctrl: 0.77; CMKO: 0.43; p<0.0001) and fractional shortening (Ctrl: 45.57; CMKO:21.62; p<0.0001), and increased systolic and diastolic LV diameters (LVID
s
(mm): Ctrl: 1.81; CMKO: 3.32; LVID
d
(mm): Ctrl: 3.47; CMKO:4.2; p<0.0001) compared to controls. Histological analysis revealed increased fibrosis in Exoc5-CMKO hearts, while isolated knockout primary cardiomyocytes showed decreased contractility and altered calcium handling.

Our findings suggest that the exocyst is necessary for proper cardiac muscle function. Future studies will investigate how impaired exocyst-mediated membrane trafficking leads to heart failure in our Exoc5-CMKO mice.
Abstract 12360: A Pilot Study of Remote Patient Monitoring for Hypertension in Primary Care
Authors: Persell Stephen D , Anthony Lauren , Peprah Yaw , Petito Lucia , Lee Ji Young , Li Jim , Sato Hironori
Published: April 2024

Introduction:
Out-of-office BP should guide hypertension care. CMS now covers remote patient monitoring (RPM). We assessed uptake and initial effects of introducing RPM.

Hypothesis:
At 6-months, hypertensive Medicare patients in RPM clinics would have greater antihypertensive medication intensification, better blood pressure control (NQF 0018), and lower SBP at last office visit.

Methods:
This was a pragmatic observational study in primary care in a single health system. We integrated Omron VitalSight
TM
RPM into the system’s EHR to enable transmission of BP and pulse from a BP monitor into the EHR without manual entry. We oriented two clinics [17 primary care physicians (PCPs)] using meetings and written material, leaving the decision to order RPM to PCPs. We compared their patients to controls from other clinics matched by age, sex, BP, and number of office visits in the prior year. We examined outcomes in: (P1) those with poor BP control at baseline—last two office BP ≥140/90, and (P2) all hypertensive patients (diagnosed hypertension or last office BP ≥140/90). Additional criteria included: age 65-85 years; ≥1 office visit in past year; and absence of persistent atrial fibrillation, CKD stage IV or V, or dementia.

Results:
RPM implementation was feasible. In P1, 207 intervention patients had mean (SD) baseline BP 151.7 (10.1) / 79.7 (8.1) mmHg, and 828 controls had BP 151.4 (10.6) / 79.5 (8.9) mmHg. In P2, 2356 intervention patients and 4712 controls had corresponding mean baseline BPs of 131.3 (14.7) / 74.9 (8.3) and 131.3 (14.7) / 74.8 (8.8) mmHg. During 6 months, PCPs ordered RPM for 14 (6.8%) P1 patients and 78 (3.3%) P2 patients. In both P1 and P2, NQF 0018 satisfaction was higher at RPM-eligible clinics (p = 0.044, 0.020 respectively) (Table). Medication intensification did not differ in P1 or P2.

Conclusions:
RPM uptake was modest. Controlling High Blood Pressure at 6 months favored the RPM intervention and was likely due to factors other than medication intensification.
Abstract 12364: Dysfunction of N-terminal Acetylation Causes Multiple Electrical Abnormalities Leading to Long QT Syndrome and Dilated Cardiomyopathy
Authors: Yoshinaga Daisuke , Feng Rui , Feng Jasmine , Walker David , de la Serna Buzon Sofia , Boss Bridget , Upton Sheila , Ward Tarsha , Seidman Jonathan , Bezzerides Vassilios J
Published: April 2024

Introduction:
NAA10-related syndrome, also known as Ogden syndrome, is characterized by long QT syndrome (LQTS), cardiomyopathy, hypotonia, and neurodevelopmental delay. NAA10 complexes with the regulatory subunit NAA15 to make the post-translationally modifying N-terminal acetyltransferase, NatA. Despite the association of LQTS and NAA10 mutations, the mechanism is unknown.

Hypothesis:
NAA10 dysfunction affects the function of cardiac ion channels or related proteins causing LQTS.

Methods:
Target sequencing of large kindred with multiple family members who had LQTS and sudden death revealed a segregating mutation in NAA10 (c.10C>A; p.R4S). Somatic cell reprogramming was used to create an induced pluripotent stem cell (iPSC) line from a gene-positive male patient with LQTS and dilated cardiomyopathy, (pNAA10
R4S
). We also genome-edited the mutation into a control iPSC line (eNAA10
R4S
). The iPSC lines were differentiated into cardiomyocytes (iPSC-CMs) for electrophysiologic characterization.

Results:
Action potential duration (APD) of wild-type (WT) and mutant iPSC-CMs was evaluated using patch-clamp and dynamic-clamp electrophysiology. There was significant APD prolongation in NAA10
R4S
-iPSC-CMs and eNAA10
R4S
-iPSC-CMs as compared to WT iPSC-CMs (448.1 ± 102.2 ms and 392.3 ± 20.8 ms, vs 73.1 ± 12.1 ms; p<0.05). We then investigated potential derangements in the underlying sodium (I
Na
), potassium (I
K
) and calcium (I
CaL
) currents. Voltage-clamp measurements demonstrated increased peak I
Na
in mutant iPSC-CMs lines (pNAA10
R4S
: -72.2 ± 11.1 pA/pF and eNAA10
R4S
: -77.4 ± 15.3 pA/pF vs. WT: -44.4 ± 7.9 pA/pF, N>12, p<0.05) However, there were no changes in voltage-dependent activation or inactivation. Similarly peak I
CaL
was also increased (-10.2 ± 1.7 pA/pF, vs -7.0 ± 1.2 pA/pF (N= 5 and 3, respectively)) compared to control iPSC-CMs without any changes in Ca
2+
channel biophysics. There were no significant differences in measured I
K
.

Conclusion:
We demonstrate that the NAA10 mutation cause APD prolongation by increasing I
Na
and I
CaL
current densities leading to QT prolongation and arrhythmia. This data indicated a novel role for N-terminal acetylation in cardiac ion channel regulation leading to cardiovascular disorders.
Abstract 12371: Genetic Deletion of Cystathionine Gamma Lyase in Endothelial Cells Exacerbates Cardiovascular Dysfunction in Heart Failure With Preserved Ejection Fraction
Authors: Xia Huijing , Li Zhen , Lapenna Kyle B , Sharp Thomas E , Moles Karl H , Pfeilschifter Josef , Beck Karl-Friedrich , Goodchild Traci T , Lefer David J
Published: April 2024

Background:
Endothelial dysfunction has been suggested as a central pathophysiological mechanism in heart failure with preserved ejection fraction (HFpEF). We reported that Cystathionine Gamma Lyase (CSE), one of the 3 hydrogen sulfide producing enzymes, expressed in endothelial cells is critical for maintaining normal endothelial function and protecting against myocardial ischemia/reperfusion injury. However, the role of endothelial CSE in HFpEF remains unknown.

Method:
Endothelial specific CSE knockout mice (EC-CSE KO, n=15) and CSE
flox/flox
control animals (n=6) were fed a high-fat diet (60% kcal from fat) and administered L-NAME (0.5 g/L in drinking water) for 18 weeks to induce HFpEF. Body weight and cardiac function (echocardiography and doppler imaging) were monitored every 4 weeks. Invasive left ventricular hemodynamic procedures were performed and vascular reactivity was measured in isolated thoracic aorta at 18 weeks.

Results:
Baseline body weight, ejection fraction (EF), the ratios of E/A and E/E’ were not different between EC-CSE KO and controls. At 12 & 16 weeks following HFD and L-NAME, E/E’ ratios were significantly higher in EC-CSE KO compared to controls (p < 0.05), with normal EF in both groups. At 18 weeks of HFpEF, a 33.3% of mortality was observed in the EC-CSE KO group while no mortality was shown in control. In addition, left ventricular end-diastolic pressure (LVEDP) was higher (p < 0.01) and aortic vasorelaxation maximal response to acetylcholine was lower (p < 0.01) in EC-CSE KO compared to controls.

Conclusion:
Genetic deletion of CSE in vascular endothelial cells exacerbates cardiac diastolic dysfunction, promotes vascular dysfunction, and increases mortality in HFpEF. Studies are currently underway to define the protective role of endothelial CSE in HFpEF.
Abstract 12382: Evaluation of Tissue Engineered Human Acellular Vessels as a Blalock-Taussig-Thomas Shunt in a Juvenile Primate Model
Authors: Nash Kevin M , Boe Brian A , Carrillo Sergio A , Harrison Andrew , Iwaki Ryuma , Kelly John , Kirkton Robert D , Krishnamurthy Ramkumar , Niklason Laura E , Matsuzaki Yuichi , Prichard Heather L , Shah Kejal , Shinoka Toshiharu , breuer christopher K , Lawson Jeffrey H
Published: April 2024

Cyanotic congenital heart disease (CCHD) due to one or more structural abnormalities causes insufficient blood oxygenation. Approximately 2 out of every 1000 infants are born with CCHD and palliative treatment for many patients involves shunting blood from the systemic to the pulmonary circuits, often through a modified Blalock-Taussig-Thomas shunt (BTTs). Synthetic vascular grafts typically used for BTTs have associated risks for intimal hyperplasia, thrombosis, and infection. Humacyte, Inc. has developed a 6mm diameter tissue-engineered blood vessel, the Human Acellular Vessel (HAV), currently being studied in adults suffering from vascular trauma, peripheral arterial disease, and renal failure requiring hemodialysis. In addition to restoring blood flow and providing arteriovenous access in these patients, the HAV has demonstrated the capacity for host cellular remodeling that transformed it into a native-like living tissue. Here the HAV production platform was modified to generate small diameter (3.5mm) vessels for preclinical evaluation. BTTs were placed from the right subclavian artery to the pulmonary artery in juvenile rhesus macaques. Post-operative imaging from 1 week to 6 months using angiography and MRI was used to confirm HAV patency, structure, and quantify blood flow. At explantation, the HAV and surrounding tissues were collected and processed for histological analyses. Results confirmed the feasibility of using the HAV BTTs, but also showed that all macaques had some immunological reactivity to the HAV human extracellular matrix in this xenogeneic animal model. Nonetheless, the HAV BTTs remained patent and performed well for up to six months in animals that had only mild host reactivity. HAV repopulation by host cells expressing smooth muscle and endothelial markers as well as the formation of neoadventitial tissue was also observed. These findings may support use of the HAV as a BTTs in CCHD and potentially other pediatric indications.
Abstract 12420: Interleukin-38 Inhibits Nod-Like Receptor Protein 3 Inflammasomes to Suppress Aortic Valve Calcification
Authors: The Erlinda , Graaf Dennis M de , Zhai Yufeng , Yao Qingzhou , Luo Zichao , Ao Lihua , Fullerton David A. , Dinarello Charles A. , Meng Xianzhong
Published: April 2024

Calcific aortic valve disease (CAVD) is common in the elderly. Progressive valvular calcification is a characteristic pathobiology in CAVD, and chronic valvular inflammation is known to promote CAVD progression. Matrilin-2 is an extracellular matrix (ECM) protein. Soluble matrilin-2 can function as a damage
-
associated molecular pattern to induce the inflammatory and osteogenic responses in aortic valve interstitial cells (AVICs). Interleukin-38 (IL-38) is a novel anti-inflammatory cytokine. Lower IL-38 levels are associated with several chronic inflammatory diseases. Recent studies found that IL-38 limits skin inflammation and nephritis by reducing the inflammatory activity of immune cells. We
hypothesized
that IL-38 is capable of suppressing AVIC osteogenic activity.

Methods and Results:
We performed immunoblotting and ELISA to assess IL-38 protein levels in AVICs isolated from normal human aortic valves (normal AVICs) and diseased human aortic valves (diseased AVICs). Diseased AVICs had lower levels of IL-38 compared to normal AVICs. Interestingly, recombinant IL-38 inhibited spontaneous deposition of calcium in diseased AVICs. To determine the effect of recombinant IL-38 on AVIC osteogenic response to soluble matrilin-2, we treated normal AVICs with recombinant IL-38 (0, 1, 5 and 10 ng/ml) prior to an exposure to matrilin-2 for 24-72 hour. IL-38 at 10 ng/ml markedly reduced the expression of RUNX-2 and ALP in normal AVICs exposed to matrilin-2. Further, IL-38 suppressed calcium deposition in normal AVICs exposed to matrilin-2 for a prolonged period. Knockdown of IL-38 by shRNA enhanced the osteogenic responses and exaggerated the calcification deposit formation in normal AVICs exposed to matrilin-2. The anti-osteogenic effect of IL-38 is associated with down-regulation of Nod-like receptor protein 3 (NLRP3) inflammasomes, and inhibition of the NLRP3 inflammasomes also suppresses the osteogenic activity in normal AVICs exposed to matrilin-2.

Conclusions:
IL-38 suppresses the osteogenic activity in human AVICs by inhibiting NLRP3 inflammasomes. The novel findings of this study suggest that IL-38 may have therapeutic potential for prevention of CAVD progression.
Abstract 12488: Serum Cystatin C is an Early Predictor of Acute Renal Injury in Infants After Cardiac Surgery With Cardiopulmonary Bypass
Authors: Abadeer Maher , Kent Alison L , SCHWARTZ George J , Martin Susan , Swartz Michael F , brophy patrick , Alfieris George , Cholette Jill M
Published: April 2024

Introduction:
Acute kidney injury (AKI) following infant cardiac surgery is common, with increased morbidity and mortality. Changes in urine output and/or serum creatinine (SCr) are unreliable in the detection of AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines, and lag behind onset of renal injury. Serum Cystatin C (SCC) has been used as a biomarker of AKI in adults and older children. If SCC predicts AKI in infants following cardiopulmonary bypass (CPB) is unknown.

Hypothesis:
SCC is an early biomarker of AKI following infant cardiac surgery requiring CPB.

Methods:
42 infants (< 1 year of age) were prospectively enrolled when presenting for cardiac surgery requiring CPB. SCC and SCr were measured at baseline (pre-operatively), and at 12, 24, and 48 hours following CPB initiation, and changes in SCC and SCr compared to baseline (ΔSCC and ΔSCr, respectively) were calculated. AKI was defined using KDIGO guidelines, as an increase in SCr ≥ 50% and/or a urine output < 0.5mL/kg/hr for ≥ 6-12 consecutive hours in the first 3 post-operative days. Subjects were divided in 2 groups: AKI and non-AKI. Receiver Operating Characteristic (ROC) curves were utilized to predict AKI based on ΔSCC and ΔSCr, and the area under the curve (AUC) was quantified.

Results:
AKI occurred in 17 (40.4%) subjects. Baseline SCC and SCr measurements were similar between groups, as were age, gender, weight, and CPB time. Post-operative SCC values decreased from baseline, suggesting volume overload. While SCC concentrations did not differ significantly between the 2 groups, ΔSCC measurements were significantly different in those with AKI at 12 hours (0.2 ± 0.3 vs 0.4 ± 0.2; p < 0.01) and remained different at 24 hours (0.1 ± 0.3 vs 0.3 ± 0.2; p = 0.02). ΔSCr measurements were significantly greater in the AKI group at 24 hours (0.1 ± 0.1 vs 0.0 ± 0.1; p < 0.01) and 48 hours (0.1 ± 0.1 vs. 0.0 ± 0.1; p < 0.01) but not at 12 hours. ROC curves demonstrated that both the ΔSCC at 12 hours (AUC = 0.72; p = 0.02) and the ΔSCr at 24 hours (AUC= 0.78; p < 0.01) predicted AKI.

Conclusions:
The 12 hour ΔSCC predicts AKI in infants after cardiac surgery, and correlated with a rise in ΔSCr the following day. Earlier detection of AKI would allow earlier post-operative intervention to mitigate renal injury in infants.
Abstract 12495: Differentiating Slow- And Rapid-growing Abdominal Aortic Aneurysms Using Computational Modeling
Authors: Sunderland Kevin , Johnson Tonie , Liedl David , Hofer Jan J , Zhang Xiaoming , McBane Robert D , Jiang JingFeng
Published: April 2024

Introduction:
Abdominal aortic aneurysms (AAA) are common among individuals over age 65 with a prevalence of 9%. Most AAAs are small and require surveillance imaging to monitor size and growth rates. Tools capable of predicting growth rates would be clinically useful.

Hypothesis:
We investigated how computational hemodynamics derived from CT angiography (CTA) differentiated slow and rapid-growing AAAs.

Methods:
Using readily available computing power in the clinical workflow, 3D models were generated for 25 subjects with AAA from available 3D CTA data. AAA growth rates were categorized as slow ( less than 5 mm/year) or rapid (greater than 5 mm/year) based on serial imaging. A geometrical analysis was performed using 7 indices (Volume, Surface Area, Length, Max/Min radius, Expansion Ratio [Mean radius/vessel radius], Proximal vessel area, Voronoi diagram-based metrics) for each AAA. Computational hemodynamics were performed using commercial software (ANSYS-Fluent). Computational hemodynamics were completed for all cases (see Fig. 1). In-house software assessed wall shear stress-(WSS) and vortex-based hemodynamics. Support vector machine (SVM) was run with cross-validation (50 iterations) to assess predictive strength using these 16 parameters.

Results:
Among 25 AAAs studied, 7 were rapid and 18 were slow-growing. The combination of proximal vessel area, spatiotemporally averaged WSS, and spatially averaged OSI provided the best accuracy for growth differentiation. The area under receiving operating curve (AUROC) and total accuracy are 0.770 and 0.765, respectively, with 48% and 86% of rapid and slow-growing AAAs correctly identified, respectively.

Conclusions:
Computational hemodynamics appears feasible with reasonable growth rate prediction. With optimization, this tool may enable resource utilization refinement for imaging surveillance strategies by distinguishing rapid from slow-growing AAAs.
Abstract 12526: T Cell Response to Influenza Vaccination Remains Intact in Adults With Congenital Heart Disease Who Underwent Early Thymectomy
Authors: Leone David M , Park Hong-Jai , Unlu Serhan , Gurvitz Michelle Z , Kang Insoo , Elder Robert W
Published: April 2024

Introduction:
Thymectomy is routine during surgery for congenital heart defects to access to the heart. T cells developed in the thymus play a key role in immunity. Individuals with thymectomy in infancy have altered T cell populations suggesting early immunosenescence.

Hypothesis:
Adults with Congenital Heart Disease (ACHD) who underwent thymectomy in the first year of life have an altered response to influenza vaccination due to T cell immunosenescence.

Methods:
We recruited ACHD with early thymectomy ≤ 1 year of age (ACHD-ET;
n
= 12), ACHD and no thymectomy (ACHD-NT;
n
= 8), and healthy controls (HC;
n
= 14). Peripheral blood was collected prior to influenza vaccine and 4 weeks following administration. Flow cytometry of T cell subsets and intracellular cytokine staining of CD4
+
T cells was done following
in vitro
stimulation with influenza viral antigen.

Results:
Subject's mean age was 34 ± 10.6 years with no difference between the groups. At baseline, the median (IQR) frequency of naïve CD4
+
T cells was 24.7% (15.9) in ACHD-ET vs. 43.6% (16.9) in HC (
P
=0.01). Similarly, naïve CD8
+
T cells were lower with 37.5% (25.7) in ACHD-ET vs 62.8% (22.9) in HC (
P
=0.02). This also resulted in a reciprocal increase in memory CD4
+
and CD8
+
T Cells in the ACHD-ET group. The ACHD-NT was not significantly different than the other groups. The frequencies of influenza antigen-specific memory CD4
+
T cells expressing IFN-γ and TNF-α were significantly increased in post-vaccine blood samples compared to pre-vaccine samples across all 3 groups (
P
<0.05).

Conclusions:
ACHD-ET have a smaller population of naïve T cells, suggestive of immunosenescence. Despite this they have an equivalent cytokine response suggesting that early thymectomy does not inhibit the response to vaccination in young adulthood. Our findings support the recommendation that preventative vaccination against pathogens including influenza virus and the newly emerging SARS-CoV-2 should continue to be routinely performed in ACHD.
Abstract 12529: Sex-Specific Mortality Associated With High Left Ventricular Ejection Fraction After ST-segment Elevation Myocardial Infarction
Authors: Nikolakopoulos Ilias , Garcia Santiago , Henry Timothy D , Sharkey Scott W , Schmidt Christian , Okeson Brynn , Quesada Odayme , Goessl Mario , Baechler Courtney , Karacsonyi Judit , Kostantinis Spyridon , Vemmou Evangelia , Rangan Bavana V , Brilakis Emmanouil S
Published: April 2024

Introduction:
Using sex-specific cutoffs, high left ventricular ejection fraction (LVEF) is associated with increased mortality in women but not in men with chronic coronary syndromes.

Purpose:
To explore the association between LVEF and mortality after an acute coronary syndrome in women and men.

Methods:
Using population-derived sex-specific LVEF cutoffs, we compared characteristics and outcomes of 1,953 ST-segment Elevation Myocardial Infarction (STEMI) patients (1,399 men and 554 women) presenting at Minneapolis Heart Institute between 2003 and 2020. Patients who had a follow-up LVEF measurement available within 2 months of the index hospitalization were included in the analysis. Sex specific cutoffs for post STEMI LVEF were a) for men, >70% (high), 47-70% (normal), <47% (low); b) for women, >72% (high), 50-72% (normal), <50% (low). Standard cutoffs were: >65% (high), 55-65% (normal), <55% (low).

Results:
When comparing high vs normal vs low LVEF, 1-year mortality was 0% vs 0.8% vs 4.4% in men (
P
log-rank
<0.001) and 13.3% vs 2.2% vs 3.4% in women (
P
log-rank
=0.03) (Figure). Five-year mortality was 0% vs 5.1% vs 12% in men (
P
log-rank
<.001) and 13.3% vs 11.4% vs 19.9% in women (
P
log-rank
=0.18). The findings were not replicated when standard LVEF cutoffs were used (1-year mortality in women was 6.1% vs 2.5% vs 2.5%,
P
log-rank
=0.33). After adjustment for baseline variables and comorbidities (age, diabetes, dyslipidemia, hypertension, history of MI, door-to-balloon time less than 90 minutes, and the presence of congestive heart failure), high LVEF was associated with 1-year mortality when compared with normal LVEF in women (HR, 10.83; 95% CI, 1.94-60.57,
P
=0.007). Landmark analysis showed that among women alive beyond 1 year, 5-year mortality was 0% vs 9.4% vs 16.1%,
P
log-rank
=0.31.

Conclusion:
High LVEF after STEMI using sex-specific cutoffs is associated with lower 1-year survival in women but not in men.
Abstract 13012: A Novel Risk Score For Predicting Atrial Fibrillation Ablation Outcomes
Authors: Wagle Anjali A , Isakadze Nino , Daimee Usama , Spragg David D , Calkins Hugh G , Martin Seth S
Published: April 2024

Introduction:
Pre-procedural predictors of atrial fibrillation (AF) ablation have focused largely on non-modifiable risk factors. This study aimed to identify a risk score derived entirely from modifiable risk factors. Such a predictive model can permit optimization of these risk factors prior to ablation procedures.

Methods:
We evaluated 160 patients who underwent their first AF ablation from 2014 through 2018. We derived a novel ABCs (
A
lcohol use,
B
MI,
B
lood pressure,
b
lood glucose,
C
igarette smoking,
c
holesterol,
s
leep apnea) model consisting of modifiable AF risk factors by receiver operating characteristic curve analysis to predict AF recurrence at 1 year after AF ablation (Table 1). Each risk factor was assigned a score of 0-2, and the total ABC score ranged from 0-14, with 0-4 indicating poor, 5-9 intermediate and 10-14 being ideal.

Results:
Among 160 study participants, the mean age was 63.1
+
9.6 years, and 33% were women. There were 55 (41%) patients with AF recurrence. Mean ABCs score was 9.2
+
1.9 among those without AF recurrence and 7.9
+
1.5 among those with recurrence (p < 0.01). The ABCs AUC was 0.70 and the CHA
2
DS
2
-VASc was 0.61 (Figure 1). A cut-off value of
>
9 displayed the highest discrimination for AF recurrence (sensitivity = 64.8%, specificity 61.8%).

Conclusions:
The novel ABCs risk score consisting of modifiable AF risk factors has superior predictive capacity for AF recurrence compared with CHA
2
DS
2
-VASC score. This may allow for risk factor optimization prior to ablation. External validation of ABCs score is needed to further evaluate its predictive capability.
Abstract 13045: Metformin in Management of Diabetic Patients With Advanced Heart Failure (HFrEFf): A Propensity Score-Matched Analysis
Authors: Benes Jan , Kotrc Martin , Kroupova Katerina , Wohlfahrt Peter , Kovar Jan , Franekova Janka , Hegarova Marketa , Hoskova Lenka , Hoskova Eva , Pelikanova Terezie , Jarolim Petr , Kautzner Josef , Melenovsky Vojtech
Published: April 2024

Introduction:
The role of metformin (MET) in the treatment of patients with advanced heart failure with reduced ejection fraction (HFrEF) and type 2 diabetes mellitus (DM) is not firmly established.

Hypothesis:
Meformin treatment will be associated with better outcome even in DM patients with advanced HFrEF.

Methods:
A total of 847 stable patients with advanced HFrEF (57.4± 11.3 years, 67.7% NYHA III/IV, LVEF 23.6± 5.8%) underwent clinical and laboratory evaluation and were prospectively followed for a median of 1126 (IQRs 410; 1781) days for occurrence of death, urgent heart transplantation or mechanical circulatory support implantation. A subgroup of 380 patients (44.9%) had DM, 87 of DM patients (22.9%) were treated with MET.

Results:
Compared with MET-free diabetic patients, MET-treated individuals had similar fasting glucose, but worse DM control (Hb1Ac 60 mmol/mol, IQRs 50-73 vs. 52 IQRs 48-62, p=0.002), higher insulin, glucagon, β-hydroxybutyrate levels and increased insulin resistance (all p< 0.05), but better quality of life (MLHFQ-score: 36 vs. 48 points, p= 0.002). Compared to diabetics treated with any other glucose-lowering agent, MET-treated patients had better event-free survival (p=0.0005, Fig. 1), which remained significant (p= 0.035) even after adjustment for BNP, BMI and eGFR. Propensity score-matched analysis with 17 covariates yielded 81 pairs of patients and showed a significantly better survival for MET-treated subgroup (p= 0.01).

Conclusions:
MET treatment in patients with advanced HFrEF and DM is associated with better quality of life and improved outcome, by mechanisms beyond the improvement of blood glucose control. MET should stay among frontline drugs for treatment of HFrEF patients with DM.

Supported by a grant no. NV19-02-00130 by Czech Health Research Council.
Abstract 13058: Outcomes With Venoarterial Extracorporeal Membrane Oxygenation for Acute Myocarditis: A 20-year Experience From the ELSO Registry
Authors: Nunez Jose I , Reyes-Castro Tiago , kennedy kevin , Rycus Peter , Tonna Joseph , Sabe Marwa A , Fleming Lisa M , Sriwattanakomen Roy , Quintero Pinzon Pablo A , Motiwala Shweta R , Grandin Edward , Garan Arthur Reshad
Published: April 2024

Introduction:
Acute myocarditis can result in severe hemodynamic compromise requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO). Outcomes with VA-ECMO and factors associated with mortality are not well described and mostly confined to small cohorts in this population.

Methods:
We queried the ELSO registry from 2000-2020 for adults with acute myocarditis undergoing VA-ECMO support, excluding patients with non-cardiac support, central cannulation, and multiple ECMO runs. The primary outcome was in-hospital mortality, and secondary outcomes were the incidence of major adverse events during ECMO. We used multivariable logistic regression modeling to examine factors associated with in-hospital mortality.

Results:
Among 956 patients with acute myocarditis supported with VA-ECMO, 338 (36.2%) died before hospital discharge. The patients had a mean age of 40.7 years, 51.0% were male, 42.5% of Asian race, mean weight was 73.7 kg, and 31.6% suffered a cardiac arrest before support. Prior to ECMO initiation the mean arterial pressure was 63.5 mmHg, pH 7.28, and 26.1% required >2 vasopressors. After multivariable modeling, risk factors for mortality were earlier year of support, older age, higher weight, extracorporeal cardiopulmonary resuscitation modality, lower blood pressure, lower pH, and need for >2 vasopressors prior to VA-ECMO initiation (
Figure: Panel A
). Major complications during VA-ECMO support were more common among non-survivors (
Figure: Panel B
).

Conclusions:
For patients with myocarditis, outcomes with VA-ECMO are favorable with nearly 2/3 of patients surviving to discharge. Predisposing factors for inpatient mortality include markers of illness severity, including lower blood pressure, lower pH, need for multiple vasopressors, and ongoing cardiopulmonary resuscitation. Use of VA-ECMO prior to severe hemodynamic collapse and minimizing complications during ECMO support could improve outcomes in this population.
Abstract 13154: Association of Serial Health Status Measurements With Clinical Events: Insights From the ISCHEMIA Trial
Authors: Saxon John , Spertus John , Jones Philip , Mark Daniel B , Bangalore Sripal , Stone Gregg W , Reynolds Harmony R , Hochman Judith S , Maron David J
Published: April 2024

Introduction:
The Seattle Angina Questionnaire (SAQ), a disease-specific health status measure, has been shown to predict future clinical outcomes in patients with chronic coronary disease (CCD) at a single point in time. The prognostic value of serial SAQ scores in patients with CCD is unknown.

Methods:
Serial assessments of the 7-item SAQ were obtained in the ISCHEMIA trial of patients with CCD and moderate/severe ischemia. Using Cox regression, we examined the association of baseline and 3-month SAQ-7 Summary Scores (SAQ7-SS) with CV death, MI or unstable angina hospitalization over a 12 month period (between 3 and 15 months after randomization) in patients randomized to conservative treatment. We fit several models including: (a) baseline score only; (b) 3-month score only; (c) 3-month change only; (d) baseline and 3-month score; (e) 3-month change and score.

Results:
The mean age was 64.3 years in 2095 patients randomized to conservative care with SAQ scores at 1 and 3 months; 78% were men. Twelve-month event rates were 3.3% overall; 2.9% with a 3-month SAQ7-SS ≥75, and 6.9% in those with 3-month scores <50. In unadjusted analyses, higher scores at baseline, 3 months, and greater 3-month improvement were associated with fewer clinical events (Figure 1a). In landmark analyses combining serial scores, neither baseline nor change were significant after adjustment for 3-month score (Figures 1b and 1c).

Conclusions:
We found that the most recent SAQ score was more predictive of subsequent clinical events than prior scores or changes. Following patients’ health status not only provides an assessment of their current angina control, but also a continuously updatable insight into their risk for subsequent cardiac events.
Abstract 13171: The Role of Novel Brugada Syndrome Gene
MAPRE2
in Maintaining Normal Cardiac Electrophysiology
Authors: Chiang David Y , Verkerk Arie , van der Vaart Babet , Narendran Nakul , Victorio Rachelle , KC Ashmita , Wang Jianing , Sampognaro James , Buys Eva P , Kiviniemi Tuomas O , Akhmanova Anna , Bezzina Connie R , Macrae Calum
Published: April 2024

Introduction:
Brugada syndrome (BrS) is a significant cause of sudden cardiac death yet only ~20% of patients are found with a loss-of-function variant in
SCN5A
encoding the cardiac Na
+
channel, leaving ~80% genetically undiagnosed. A recent genome-wide association study found 12 loci associated with BrS, including one in
MAPRE2
encoding microtubule end-binding protein 2 (EB2).

Hypothesis:
MAPRE2
loss-of-function contributes to BrS and is necessary in maintaining normal cardiac electrophysiology (EP).

Methods:
Using CRISPR/Cas9, we generated two
mapre2
loss-of-function mutants in zebrafish: a full knock-out and a mutant lacking the unique N-terminus of EB2 (delN). Cardiac EP was assessed using optical mapping in larvae, surface ECG in adults, and patch clamping in ventricular myocytes. Cardiac structure was assessed using videomicroscopy, histology, and confocal microscopy. Transcriptional changes were assessed using RNA-seq.

Results:
No gross changes in cardiac structure were observed with
mapre2
loss-of-function. However, in both mutants, voltage mapping showed decreased ventricular conduction velocity and action potential upstroke velocity (V
max
) and ECGs showed prolonged QRS, P wave, and corrected QT. Patch clamp of delN ventricular myocytes revealed reduced Na
+
current density without changes in gating properties consistent with the reduced V
max
. RNA-seq of larvel hearts suggested disruption of cell adhesion, confirmed by confocal microscopy, whereas Ca
2+
imaging found an increase in Ca
2+
transient amplitude. RNA-seq of adult hearts showed disruption in the Wnt signaling pathway and treatment with GSK3β inhibitor SB217673 rescued mutant ECG abnormalities.

Conclusions:
Our study supports
MAPRE2
as a novel contributing gene in BrS pathogenesis and conduction slowing in general. Beyond its effect on Na
+
channel function,
mapre2
and in particularly its unique N-terminal segment may play a broader role in cellular organization via the microtubule network affecting cellular EP in multiple ways. Our study also implicates for the first time the Wnt signaling pathway in BrS, suggesting not only shared biology with arrhythmogenic cardiomyopathies, but also the possibility of GSK3β modulation as a novel therapeutic approach.
Abstract 13174: Female Sex is Not Associated With Subsequent Heart Failure in Adult Patients Treated With Anthracyclines
Authors: Pajares Hurtado Gabriel , Rosas Diaz Andrea Nathalie , Turissini Cole , Dommaraju Sujithraj , Warack Sarah , Keyes Michelle J , Strom Jordan B , Asnani Aarti
Published: April 2024

Introduction and Hypothesis:
Female sex has long been considered a risk factor for anthracycline-associated cardiotoxicity, based largely on data in childhood cancer survivors. However, preclinical experiments suggest that female sex hormones present in adulthood may protect against doxorubicin cardiotoxicity. We therefore hypothesized that female sex would be associated with a decreased odds of heart failure in adult patients treated with anthracyclines.

Methods:
We conducted a retrospective cohort study of 871 adult patients (44% women and 56% men) at our medical center with no prior history of heart failure who were treated with anthracyclines for non-hormone-dependent malignancies including lymphoma, leukemia, and sarcoma. Patients who expired during the study period were excluded. The presence or absence of heart failure within five years of initiation of anthracyclines was assessed using ICD-9/10 codes. Logistic regression models were used to assess odds ratios based on self-reported sex and other covariates, adjusting for age.

Results:
Baseline characteristics were similar in men and women, including age, total cumulative anthracycline dose, and prevalence of cardiovascular comorbidities such as hypertension, diabetes, and coronary artery disease. The odds of heart failure increased modestly with age (OR: 1.02; 95% CI: 1.01 to 1.03, p = 0.001). In an age-adjusted model, female sex was not associated with subsequent heart failure (OR: 1.03, 95% CI 0.72 to 1.47, p = 0.88), including after stratification by age ≤ 50 years or > 50 years as a surrogate for menopausal status.

Conclusions:
In this retrospective cohort study, female sex was not associated with heart failure in adult patients treated with anthracyclines for non-hormone-dependent tumors. These findings diverge from prior reports suggesting an increased risk of cardiotoxicity in women. Future studies will assess the competing risks of cancer and cardiovascular disease/death in men versus women treated with anthracyclines.
Abstract 13655: DUSP-1 May Be a Key Regulator of NK Cell Function in Obesity Potentially Accelerating Cardiovascular Disease in African American Women
Authors: Baumer Yvonne , Komudi Singh , Gutierrez Huerta Cristhian A , Gray Veronica , Briana Turner S , Mitchell Valerie , Collins Billy , Pirooznia Mehdi , Schwartz Daniella M , Powell-wiley Tiffany
Published: April 2024

Background:
Obesity disproportionately affects African American (AA) women and contributes to disparate cardiovascular disease (CVD) outcomes. Natural killer cells have been shown to be functionally impaired by obesity. However, underlying mechanisms regulating NK cell function in obesity are largely unknown. Therefore, we sought to elucidate potential signaling pathways involved in obesity-related NK cell function loss in AA women.

Methods:
All experiments were performed with freshly isolated naïve NK cells. NK cells were isolated from AA women (n=29; 15 BMI<25, 14 BMI>30). NK cell function was measured by flow cytometry by determining the ability of NK cells to degranulate towards K562 cells. NK cell gene expression profile was determined by RNA sequencing to identify important signaling pathways, which were verified using chemical pathway inhibitors. Publicly available datasets were analyzed to determine the importance of identified target genes.

Results:
NK cells isolated from AA women with obesity displayed diminished capacity to induce K562 cell death as determined by decreased degranulation (decreased surface CD107a expression and decreased intracellular IFNγ and TNFα expression). RNA sequencing analysis of NK cells isolated from lean vs AA women with obesity revealed 1645 significantly regulated genes with DUSP-1 being in the top 50 and displaying a 2.8-fold upregulation in AA women with obesity (p=0.0009). Furthermore, DUSP-1 gene expression was significantly correlated with BMI (R
2
=0.72, p=0.02).
In vitro
experiments revealed a DUSP-1 inhibitor to enhance NK cell function. Additionally, analysis of publicly available RNA sequencing dataset (GSE20129) in women revealed an increase of DUSP-1 mRNA expression in Black and Latinx women with CVD when compared to women without CVD group; this difference was not observed in White women.

Conclusion:
Our data demonstrate that NK cells are functionally impaired in NK cells isolated from AA women with obesity. We identified DUSP-1 as a crucial regulator of the observed NK cell dysfunction in obesity, which may be of particular importance in CVD development and progression in AA women, a population disproportionally affected by obesity and CVD.