bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11489: Pregnancy Increases Cardiac Vulnerability to Post-Partum Pathological Stimuli
Authors: Yang Yijun , Kurian Justin , Johnson Jaslyn , KUBO Hajime , Berretta Remus M , Khan Mohsin , Mohsin Sadia , Houser Steven R
Published: June 2023

Introduction:
The hemodynamic demands on the heart during normal pregnancy induce physiological cardiac hypertrophy. Together with exercise induced cardiac hypertrophy and cardiac enlargement during post-natal growth, these physiological cardiac adaptations are distinct from pathological hypertrophy caused by heart diseases including volume/pressure overload. Exercise-induced cardiac hypertrophy can induce a protective phenotype that leads to resistance from ischemic injury or pressure overload induced pathological remodeling. Whether pregnancy induced cardiac hypertrophy can also protect the heart from post-partum (PP) pathological stimuli remains unknown and is the focus of this study.

Methods:
We challenged both post-partum and age matched non-pregnant female C57BL/6 mice with 7-day osmotic minipump infusion of Angiotensin II/phenylephrine (AngII/PE) and determined the cardiac alterations.

Results:
PP mice had more severe cardiac pathological remodeling after AngII/PE infusion compared with non-pregnant counterparts, with greater increases in heart weight, cardiomyocyte hypertrophy and fibrosis. Echocardiography showed both left and right ventricular hypertrophy without overt systolic dysfunction. PP mice had greater elevations in expression levels of fetal genes and fibrotic genes compared with non-pregnant mice after AngII/PE infusion. RNA-sequencing analysis suggested a more robust change in gene expression level in PP mice after AngII/PE treatment compared to non-pregnant counterparts, with a substantial role for extracellular matrix organization genes. We also found a significant alteration of gene expression levels for enriched extracellular structural organization at 1-day PP, which underlies ongoing structural re-organization in the myocardium shortly after deliver. These PP changes may predispose the heart to adverse remodeling when simultaneously challenged with pathological stimuli.

Conclusions:
Pregnancy induced cardiac remodeling does not protect the heart against PP pathological stimuli. In fact, the rapid remodeling in the PP heart may predispose it to exacerbation of pathological remodeling.
Abstract 11505: Predicting In-Hospital All-Cause Mortality in Chronic Total Occlusion Percutaneous Coronary Intervention: PROGRESS-CTO Mortality Score
Authors: Simsek Bahadir , Kostantinis Spyridon , Karacsonyi Judit , Alaswad Khaldoon , Krestyaninov Oleg , Khelimskii Dmitrii , Davies Rhian , GOKTEKIN OMER , Gorgulu Sevket , El Guindy Ahmed , Chandwaney Raj , PATEL MITUL P , Karmpaliotis Dimitrios , Khatri Jaikirshan , Jaffer Farouc A , Rangan Bavana V , Sandoval Yader , Choi James , Nicholson William , Jaber Wissam , Rinfret Stephane , KUTUZIS MICHAEL , Tsiafoutis Ioannis , Yeh Robert W , Burke M Nicholas , Allana Salman S , Mastrodemos Olga , Brilakis Emmanouil S
Published: June 2023

Introduction:
Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is associated with increased risk of periprocedural complications. Estimating the risk of complications facilitates risk-benefit assessment and procedural planning.

Methods:
We analyzed the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO, NCT02061436) and created a risk score for in-hospital all-cause mortality. Logistic regression prediction modeling was used to identify independently associated variables and the model was internally validated with bootstrapping.

Results:
Of the 10,480 CTO PCI cases performed between 2012-2022 at 40 US and non-US centers, in-hospital mortality occurred in 47 (0.45%). The final prediction model identified 4 independent predictors of mortality: Age ≥65 years, Odds Ratio [OR]: 2.83 (95% confidence interval [CI], 1.30-6.16), 1-point; Left ventricular ejection fraction ≤45%, OR: 2.13 (95% CI, 1.14-3.98), 1-point; Moderate-severe calcification, OR: 2.45 (95% CI, 1.18-5.08), 1-point; and Antegrade dissection re-entry, OR: 2.81 (95% CI, 1.06-7.43), 1-point; or Retrograde strategy, OR: 3.51 (95% CI, 1.67-7.37), 1-point; with a bootstrap corrected c-statistics of 0.71 (95% confidence interval: 0.63-0.81). The calculated risk percentages for mortality based on the PROGRESS-CTO mortality score ranged from 0.05-2.42% for mortality, and 63% of patients in the PROGRESS-CTO cohort had PROGRESS-CTO mortality score of 1 or 2, corresponding to a mortality risk of 0.1-0.5% (Figure 1).

Conclusions:
The PROGRESS-CTO in-hospital mortality risk score can facilitate risk-benefit assessment and procedural planning in patients undergoing CTO PCI.
Abstract 11524: Maternal Vaping Impacts on Cerebrovascular Function in Offspring
Authors: Mills Amber , Nassabeh Sydney , Frazier James , Maloney Derek , Chantler Paul D , Olfert Ivan M
Published: June 2023

Electronic cigarettes (E-cigs) are marketed as a safer alternative to smoking even during pregnancy, but health effects of vaping are still largely unknown and under investigation. Emerging studies find cerebrovascular dysfunction in offspring with in-utero E-cig exposure, but little is known what the effect of E-cig device wattage has. We hypothesize maternal vaping at 30 watts will have a greater effect (compared to 5-watts) on cerebrovascular dysfunction in offspring. Female Sprague Dawley rats were time-mated, and the dams were randomly assigned to the following groups 1) 5-watts (N=5), 2) 30-watts (N=5), 3) and ambient air (control, N=5). Exposure was 60-puffs/day (5 days/week) beginning on gestational day (GD) 2-3 until GD21 using whole-body chambers. E-liquid was 50% vegetable glycerin, and 50% propylene glycol containing no nicotine and no flavor. One male & female offspring per dam are reported at 1- and 6-months of age, where the middle cerebral artery (MCA) was isolated and reactivity assessed using dose-response (10
-9
M to 10
-4
M) to acetylcholine (ACh), serotonin (5-HT), and sodium nitroprusside (SNP) via pressure myography. 1-month offspring, maximal MCA dilation to ACh was impaired in both 5- and 30-watts compared to air (33±3%, 50±3%, respectively, p<0.05). SNP-induced dilation (20±6%, 39±4%, respectively, p<0.05) and 5-HT vasoconstriction (37±3%, 47±3%, respectively, p<0.05) were blunted in both groups compared to controls. Compared to air, the 6-month offspring showed similar impairments in 5- and 30-watt groups (27±3% and 45±2%, respectively, p<0.05). Likewise, SNP dilation (12±3% and 23±6%, p<0.05) and 5-HT constriction (21±3% and 36±3%, p<0.05) were impaired in 5- and 30-watt groups, respectively, compared to controls. For all conditions, 30-watt MCA impairment was significantly greater than 5-watts in 1 and 6-month offspring (p<0.05). These data show (regardless of the E-cig device wattage used) that maternal vaping during pregnancy results in cerebrovascular impairment involving endothelial-dependent and -independent pathways in adolescent and adult offspring, but also shows that the magnitude of impairment is greater with maternal vaping at higher compared to lower wattage.
Abstract 11531: Neurodevelopmental Outcomes After Neonatal Tetralogy of Fallot Repair or Palliation: Scope of The Problem and Does Treatment Strategy Matter
Authors: Zampi Jeffrey D , Ilardi Dawn L , McCracken Courtney E , Glatz Andrew C , Beshish Asaad , Goldstein Bryan H , Petit Christopher J , Qureshi Athar M , Goldberg Caren S , Law Mark A , Meadows Jeffery J , Shahanavaz Shabana , Batlivala Sarosh P , Maskatia Shiraz A , Pettus Joelle A , Romano Jennifer C , Stack Kathryn O , Khan Hala Q , Parekh Shalin , Nicholson George T
Published: June 2023

Introduction:
Neonates with symptomatic tetralogy of Fallot (sTOF) require early intervention with either staged repair (SR; initial palliation with subsequent complete repair) or primary repair (PR). Implications of these neonatal management strategies on late outcomes are not well understood. Thus, we aimed to assess neurodevelopmental (ND) outcomes and identify risk factors for ND concerns.

Methods:
From 2005-2017, sTOF patients who underwent neonatal intervention across 9 centers were identified. To assess ND, all living patients were sent age-appropriate parent-rating scales of executive function (Behavior Rating Inventory of Executive Function - BRIEF) and psychosocial symptoms (The Behavior Assessment System for Children, 3rd Edition - BASC-3). The results were compared by primary treatment strategy (SR vs. PR) using multivariable models. Patient and clinical factors were compared between those with normal and clinically significant abnormal results (T-score ≥60).

Results:
Of 572 patients in the initial cohort, surveys were sent to 511 survivors and returned from 144 (28%, 53% male, age 3.2-15.9 years). Up to 37% of respondents had a clinically concerning score on ≥ 1 scales, including 36% with ≥1 abnormal scale present on the BRIEF and 30% with an abnormal scale on the BASC. Across SR and PR strategies, there was no difference in ND outcomes (BRIEF adjusted odds ratio (AOR) 1.55 (0.57, 4.21, p=0.39); BASC AOR 1.13 (0.43, 2.99, p=0.81)). Factors associated with clinically significant executive dysfunction included genetic syndrome (p=0.001), need for invasive ventilatory support (p=0.003) and inotropic support (p=0.01) prior to the index procedure. Only genetic syndrome (p=0.026) was associated with clinically significant psychosocial problems.

Conclusions:
Late ND abnormalities, specifically executive dysfunction and psychosocial concerns, are common in sTOF patients. While initial treatment strategy does not appear to have impact, intrinsic patient characteristics and pre-procedure measures of clinical severity may predict late ND outcomes and help target increased surveillance for ND complications. Forthcoming analyses will explore existing ND service utilization and parental concerns in the context of these findings.
Abstract 11538: The Impacts of the Patient Voice in Continuing Medical Education (CME) to Enhance Homozygous Hypercholesterolemia (HoFH) Diagnosis and Management
Authors: Drexel Carole , Bixler Emily , Gulati Martha , Bhatt Deepak L , Toth Peter P
Published: June 2023

Introduction:
Early diagnosis and management of HoFH are key to achieving CV risk reduction. However, barriers to identifying probable cases, low awareness of current guidelines, and a lack of knowledge of treatment options continue to present challenges to HCPs.

Hypothesis:
CME with the patient voice can enhance HCP's competence in diagnosing and managing HoFH and adopting newest treatment options.

Methods:
A 60-minute CME activity that incorporated the patient voice was launched live-online 7/20/21 and was available on-demand for 1 year. Test questions were administered before and immediately after the activity. A follow-up survey on HCP behavior was sent to post-test respondents 2 months after activity completion. Responses were analyzed for engagement, lessons learned, and continuing gaps. Chi-square tests compared paired responses (P less than 0.05; pre/post).

Results:
As of 6/6/22, 1,806 HCPs had engaged (14% cardiologists and 57% PCPs managing an average of 50.2 patients per year with very high lipid levels). At entry, 68% of HCPs were at least “somewhat confident” in managing HoFH, while 48% did not know about newly approved agents for HoFH. Outcomes showed significant increases (pre vs post) in ability to recognize manifestations of HoFH (47% vs 87%), apply guidelines to reduce high LDL-C levels despite statin therapy (38% vs 92%), and recognize mechanism of action of evinacumab (43% vs 88%). On follow up, HCPs reported positive impacts on practice related to diagnosing HoFH, applying guideline-driven care to lower LDL-C, identifying high-risk patients, and referring appropriately.

Conclusions:
Live and on-demand CME including the voice of the patient successfully highlighted HoFH patient’s expectations of care and enhanced HCPs’ ability to adapt to the changing HoFH landscape. Additional education on this evolving landscape and associated guidelines can further enhance quality of care for HoFH patients.
Abstract 11546: Racial Disparities in Zip-Code Level Social Determinants of Health and Cardiovascular Outcomes in Females With Breast Cancer
Authors: Stabellini Nickolas , Dmukauskas Mantas , Cullen Jennifer , Barda Amie J , Cao Lifen , Moore Justin , Dent Susan F , Shanahan John , Hamerschlak Nelson , Barnholtz-Sloan Jill , Waite Kristin , Montero Alberto , Guha Avirup
Published: June 2023

Introduction:
Cardiovascular disease (CVD) prevalence and cancer mortality are higher in non-Hispanic Blacks (NHB) relative to other racial subpopulations.

Hypothesis:
Among females with BC (≥18 years), there are racial differences in cardiac events (CEV) which can be explained by adverse social determinants of health (SDOH).

Methods:
Data were obtained from a Cleveland area integrated health care systems informatics platform. (2005-2019). Zip-code level demographic features were extracted using the SDOH Database from the Agency for Healthcare Research and Quality. The CEVs included were heart failure (HF), acute coronary syndrome (ACS), and ischemic stroke (IS). Multivariable Cox proportional hazards regression models were used to examine racial disparities in CEVs. Race-stratified (NHB and non-Hispanic Whites [NHW]) multivariable logistic regression was performed to assess the role of each SDOH in association with CEV.

Results:
This study included 9,022 females with breast cancer (BC) of which 18.8% were NHB, and 48.7% had a CEV. The racial differences in CEV and the role of zip-code level SDOH are presented in
Table 1.
These racial differences were not explained by the proportion of people unemployed in the zip code (p=0.42, race*unemployment % [cross-product]), proportional of people in the zip code with only a high school diploma (p=0.66, race*education % [cross-product]), and proportion of people in the zip code who use public transport (p=0.24, race * transport % [cross-product]).

Conclusion:
There are racial differences in the risk of ACS and IS after a BC diagnosis, but this does not seem to be explained by the 3 adverse zip-code level SDOH included in this study. Therefore, studies with individual-level SDOH and including other domains are necessary to better understand their relationship with CEVs.
Abstract 11554: Biochemical and Molecular Newborn Screening for Familial Hypercholesterolemia
Authors: Peterson Amy L , Held Patrice K , Shao Xiangqiang , Lasarev Michael , Zhang Xiao , Wiberley-Bradford Amy , Campbell Kristin , Benoy Megan , Dodge Ann M , Horner Vanessa
Published: June 2023

Introduction:
Familial Hypercholesterolemia (FH) is a common genetic disorder resulting in elevated low-density lipoprotein cholesterol (LDL-C) causing premature atherosclerosis. Despite guidelines, universal screening rates remain low. Newborn screening could increase FH diagnostic rates.

Hypothesis:
Biochemical newborn screening for LDL-C, total cholesterol (TC), and apolipoprotein B (apoB) followed by selective molecular testing identifies pathogenic and likely pathogenic variants causing FH.

Methods:
De-identified, residual newborn screening bloodspots collected for routine screening at 24-48 hours of life were analyzed for LDL-C, TC, and apoB. Values are expressed as multiples of median (MoM). Mahalanobis distance, measuring how far MoM values differed positively from 1, was computed. Samples with the most extreme Mahalanobis distance were selected for molecular testing (panel includes
LDLR
,
APOB
,
PCSK9
,
LDLRAP1
,
APOE
,
STAP1
,
LIPA
,
ABCG5
, and
ABCG8
).

Results:
Distributions of apoB, TC, and LDL-C from 5,248 samples are shown below (figure). ApoB followed a Gamma distribution; TC and LDL-C followed non-normal but symmetric distributions. ApoB and LDL-C accounted for 93% of variance among biomarkers. Of the first 2500 samples, 192 samples were selected for molecular testing; a pathogenic variant for monogenic FH was detected in 1 sample and risk factors for polygenic FH in 4 samples (table below).

Conclusions:
Pathogenic or likely pathogenic variants for FH were identified with an incidence of 1 in 500 in the first 2500 newborn specimens tested. Further study will determine if this two-tiered screening strategy adequately detects FH in newborns.
Abstract 11595: Applying Machine Learning on Myocardial Deformation Parameters for Identifying Subjects in High Risk of Heart Failure: The Copenhagen City Heart Study
Authors: Højlund Rune , Simonsen Jakob Oeystein , Modin Daniel , Skaarup Kristoffer G , Lassen Mats , Johansen Niklas D , Sanchez Sergio , Claggett Brian , Marott Jacob , Thorsten Magnus , Jensen Gorm , Schnohr Peter , Mogelvang Rasmus , Biering-Srensen Tor
Published: June 2023

Background
Recently, speckle tracking echocardiography (STE) and tissue doppler imaging (TDI) has gained increasing traction as a non-invasive tissue characterisation method within cardiology. But until now many patterns from the strain and TDI curves remain uninvestigated. In this work we applied supervised machine learning (ML) to identify unknown pathophysiological drivers of heart failure (HF) in the general population.

Methods
A total of 2383 subjects from the general population (Mean age 55.9 years ± 17.3, male 42%) underwent STE, TDI, and clinical examination. We applied an ensemble decision tree and a logistic regression model to investigate unknown speckle tracking parameters and to predict the endpoint: Occurrence of HF within five years. The ML models were evaluated with 20-fold cross-validation to provide a clear split between training and validation data.

Results
The median follow up-time was 5.41 years (ICR 4.49 - 6.28). 88 subjects (3.7%) developed HF within 5 years.We identified 4 new echocardiographic characteristics that improved the prediction of HF: 1. Peak systolic strain rate (SRs), 2. Strain at AVC, 3. Accumulated systolic strain/HR, 4. TDI Peak LV Diastolic Acceleration(Figure 1 and Figure 2). The model combining both novel strain- and TDI parameters as well as conventional echo parameters and clinical features performed significantly better than a model based on clinical features alone (AUC echocardiographic and clinical parameters vs. clinical parameters = 0.88/0.84, p = 0.04). An ensemble decision tree model predicted the outcome reasonably well with a precision of 24% at a sensitivity of 50%.

Conclusion
Adding novel echocardiographic parameters to a clinical ML model for prediction of HF improved the prognostic performance significantly. We identified 4 new parameters relevant for prediction of HF and found that peak systolic strain rate (SRs) was the most important predictor.
Abstract 116: Regulation Of Nampt Secretion From Human Neutrophils By The Trpv2 Channel
Authors: Zhu Xiangdong , Li Jing , Lin Shaoxia , JUSTICE CODY , Vanden Hoek Terry L
Published: June 2023

Introduction:
Nampt functions both as an intracellular enzyme critical for NAD
+
salvage and a novel extracellular damage-associated molecular pattern. In a mouse model of cardiac arrest, increased plasma Nampt correlates with inflammation, cardiovascular dysfunction and death. The mechanism that regulates Nampt secretion during cardiac arrest is not known.

Hypothesis:
We hypothesize that Nampt secretion is regulated by a non-selective cation channel TRPV2.

Methods:
Extracellular Nampt (eNampt) concentration was measured by ELISA. Neutrophils were isolated from human peripheral blood.

Results:
In non-stimulated human neutrophils incubated at 37
o
C, eNampt was observed in cell supernatants at 10 min and plateaued after 30 min. eNampt is not released by the ER-Golgi classical pathway. Brefeldin A, an inhibitor of protein transport from ER to Golgi had no effect on eNampt release. Similarly, nocodazole, which disrupts microtubule assembly, had no effect on eNampt release either. eNampt release was markedly reduced at 4
o
C, suggesting that the release is active. eNampt release was regulated by extracellular pH. The decline in pH from 7.4 to 6.5 suppressed the secretion of eNampt, while the increase of pH from 7.4 to 7.8 enhanced the amounts of eNampt release. We therefore reasoned that ion channels sensitive to pH and/or involved in intracellular pH homeostasis might play a role in Nampt secretion. 10 μM 5-(N,N-Hexamethylene) amiloride had no effect on eNampt release, which indicates that Na
+
/H
+
exchanger is not involved in eNampt release. In contrast, eNampt release was upregulated by the TRPV2 agonists 200 μM H
2
O
2
, 1 mM 2-aminoethoxydiphenyl borate and10 μM anandamide, and downregulated byTRPV2 inhibitors 0.5 mM EGTA, 5 mM NAM, 100 μM tranilast and 100 μM piperlongumine.

Conclusion:
Nampt is secreted from neutrophils via a non-classical pathway and its secretion is regulated by the pH sensitive TRPV2 channel.
Abstract 11605: Association of Patient Characteristics and Center on Age of Fontan Completion: A Retrospective Cohort Study Using the Pediatric Health Information Systems Database
Authors: Lemley Bethan , Shinohara Russell , Okunowo Oluwatimilehin , Ampah Steve , Goldberg David , Rychik Jack , Glatz Andrew C , Amaral Sandra , O'Byrne Michael
Published: June 2023

Introduction:
Little is known regarding optimal timing of the Fontan operation and whether timing affects outcomes in patients with single-ventricle heart disease. The association of patient-level factors with age at the Fontan operation and the degree of practice variation among surgical centers have not been quantified in large studies.

Methods:
A retrospective cohort study of patients who underwent a Fontan operation between 1/1/2007 and 12/31/2017 at Pediatric Health Information Systems Database centers was performed to evaluate associations between patient characteristics and center on timing of Fontan operation. Mixed-effects multivariable linear regression was used to adjust for patient characteristics and center-level covariance.

Results:
In all, 7,840 patients (41% male, 57% white) at 46 centers were included. Median age at Fontan was 3.3 years (IQR 2.5-4.3). In an adjusted model hypoplastic left heart syndrome (-16 months, 95% CI -18 to -13), heterotaxy (-9 months, 95% CI -13 to -5), and ECMO history (-11 months, 95% CI -17 to -5) were associated with younger age at Fontan. Non-cardiac diagnoses (+4 months, 95% CI 0.1-9) and technology-dependence (+21 months, 95% CI 16-25) were associated with older age at Fontan (
Figure 1A
). There was no evidence of racial differences in Fontan timing. Children with Medicaid insurance were significantly younger at Fontan than counterparts with other insurance. We observed center effects on age at Fontan (p<0.001, ICC 0.03 95% CI 0.02-0.05) with youngest median age of 0.9 years (IQR 0.6-2.8) at one center and oldest median age of 5.0 years (IQR 4.6-5.9) at another center (
Figure 1B
).

Conclusion:
In this study, age at Fontan was significantly associated with cardiac anatomy, non-cardiac diagnoses, ECMO history, and insurance but not race. There was practice variation between centers in Fontan timing. Future studies will examine associations between timing of Fontan and patient outcomes.
Abstract 11606: The Association Between Sarcoidosis and In-Hospital Outcomes Among African Americans With Acute Myocardial Infarction
Authors: Soji-Ayoade Demilade A , Weze Kelechi O , Bolaji Olayiwola A , Echols Melvin
Published: June 2023

Introduction:
Sarcoidosis (SD) has a higher prevalence among African Americans (AA). It is also associated with an increased risk of ischemic heart disease (IHD); however little is known of its effect on in-hospital outcomes after an acute myocardial infarction (AMI). Therefore, we sought to evaluate the association between SD and in-hospital outcomes among AA patients (pts).

Methods:
Using the National Inpatient Sample between 2005-2014, we evaluated admissions of AA presenting with AMI and a concurrent diagnosis of SD. We used propensity score matching in 1:3 fashion to create a comparison group of patients without SD based on age and comorbidities. Our primary outcome of interest was in-hospital mortality. Secondary outcomes were length of hospital stay and total cost of hospitalization.

Results:
We evaluated 416, 209 representative admissions of AA with AMI. Of these, we compared 2,647 had a concurrent diagnosis of SD to 7,942 pts without SD. The pt group with SD had mean age 58.1 years and were 61.5% female. When compared with the pts without SD, the pts with sarcoid were more likely to smoke (21.5% vs 19.5%, p=0.028), have liver failure (4.5% vs. 3.4%, p=0.007) and have a cancer diagnosis (2.8% vs. 2.1%, p=0.37), but less likely to have renal failure (25.0% vs 29.1%, p<0.001). When compared with the pts without SD, pts with SD had a significantly lower in-hospital mortality and cost of hospitalization ($46,593±69,981 vs $51,941±80,624, p=0.023).

Conclusion:
Although sarcoidosis is associated with increased risk of IHD, SD is associated with lower in-hospital mortality and lower cost of care in AA pts presenting with AMI. Further investigations are warranted to understand these outcomes.

Table 1:
Baseline characteristics of AA patients with AMI and sarcoidosis compared with a propensity-score matched cohort without sarcoidosis.
Abstract 11622: A Case of Successful Malignant Lymphoma Treatment Following Transcatheter Aortic Valve Replacement
Authors: Osawa Takumi , Tajiri Kazuko , Ieda Masaki
Published: June 2023

Doxorubicin, an anthracycline drug, is a key drug in the treatment for diffuse large B-cell lymphoma (DLBCL). It is contraindicated in patients with serious heart diseases due to the cardiotoxicity. Transcatheter aortic valve replacement (TAVR) has been an established treatment for patients with severe aortic stenosis (AS) at high or prohibitive risk for surgical aortic valve replacement (SAVR). A 67-year-old woman was referred to our department with severe AS. Two months ago, the patient presented with bilateral cervical and inguinal lymphadenopathy. A biopsy of the lymph nodes revealed the primary diffuse large B-cell lymphoma (DLBCL). The patient had been diagnosed with stage IVA non-Hodgkin lymphoma according to the Ann Arbor staging system. The echocardiogram demonstrated a left ventricular ejection fraction of 67% and severe bicuspid AS with a peak velocity of 4.1 m/sec, mean pressure gradient of 44.1 mmHg, and aortic valve area of 0.58 cm
2
. She was initially treated with chemotherapy without anthracycline due to the high risk of anthracycline cardiotoxicity. However, anthracyclines were thought to be essential for controlling DLBCL. She was referred to our department and evaluated from the heart-team, which considered the following characteristics: severe impairment of mobility and frailty with a Society of Thoracic Surgeons (STS) score of 5.99%. Due to the high surgical risk for SAVR, we decided to perform TAVR. The procedure was completed without complications during the perioperative period. Ten days after TAVR, the patient received the therapy of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), which resulted in complete remission without cardiac symptoms. Before the advent of TAVR, it was difficult for patients with both severe AS and cancer to receive surgery and/or cardiotoxic treatment. In patients with cancer, AS may interfere with optimal antineoplastic therapy (ie, high-risk oncological surgery and/or cardiotoxic anticancer drugs). TAVR does not need cardiac arrest, extracorporeal circulation, and thoracotomy. TAVR could increase therapeutic options in cancer patients with severe AS who are at high surgical risk.
Abstract 11644: The Role of Neutrophil Extracellular Traps in Models of Diabetic Vascular Dysfunction
Authors: Liu Chao , Atkins Kevin B , Yalavarthi Srilakshmi , zeng lixia , Rysenga Christine E , Alizadeh Nikoo , PENNATHUR Subramaniam , Knight Jason S
Published: June 2023

Aim:
NETosis is a type of neutrophil cell death that results in the release of pro-inflammatory neutrophil extracellular traps (NETs). While NETs contribute to some diabetes-associated complications such as dysfunctional wound healing, their potential role in diabetic vascular dysfunction has not been studied. To investigate this possibility, we utilized knockout mice (

Elane
-/-

and

Pad4
-/-

) deficient in NETosis through loss of neutrophil elastase and peptidylarginine deiminase 4, respectively.

Methods and Results:
Akita mice develop hypoinsulinemia and hyperglycemia by 4 weeks of age. Akita mice were crossed separately with

Elane
-/-

and

Pad4
-/-

mice to generate NETosis-deficient diabetic mice. Endothelium-dependent vasodilation was assessed in the aortae of the following strains by wire myography (n=10-15/group): wild-type (WT), Akita, Akita-

Elane
-/-

, and Akita-

Pad4
-/-

. By 24 weeks of age, Akita mice demonstrated consistent impairment of acetylcholine-mediated relaxation (Akita E
max
=54.1% ± 1.8 and WT=80.6% ± 1.8; p<0.0001). As compared with Akita mice, both Akita-

Elane
-/-

mice (E
max
=75.1% ± 1.7; p<0.0001) and Akita-

Pad4
-/-

mice (E
max
=70.2% ± 1.5; p<0.0001) demonstrated superior relaxation. Furthermore, transfer of neutrophils from aged Akita mice into young WT mice rapidly triggered impaired acetylcholine-mediated relaxation (p<0.0001). Prostanoid metabolites were measured in aortae of 24-week-old mice. TXB
2
(a surrogate for TXA
2
) was 5-fold higher in both intact and denuded aortae of Akita mice as compared with WT mice (p<0.01); Akita-

Elane
-/-

and Akita-

Pad4
-/-

mice had TXB
2
levels near WT. Interestingly, 15-deoxy-Δ12,14-PGJ
2
(a dehydration product of PGD
2
and potent PPARγ agonist) was upregulated 10-fold (p<0.001) in Akita endothelium, suggesting an attempted compensatory mechanism.

Conclusion:
Inhibition of NETosis largely prevented the development of vascular dysfunction in diabetic mice. Thromboxane was strongly upregulated in the vessel walls of NETosis-competent diabetic mice suggesting a role for neutrophils in driving the production of this vasoconstrictive and atherogenic prostanoid. NETosis may represent a novel target for prevention of diabetic complications including vascular dysfunction.
Abstract 11651: Machine Learning of Action Potential Shape to Define Refractory Periods in Ischemiccardiomyopathy
Authors: Ruiperez-Campillo Samuel , Deb Brototo , Selvalingam Anojan , Feng Ruibin , Ganesan Prasanth , Tjong Fleur V , Chang Hui Ju , Kowalewski Christopher , Kolk Maarten Z. H. , Clopton Paul L , Vasireddi Sunil K , Rogers Albert J , Narayan Sanjiv M
Published: June 2023

Introduction:
The effective refractory period (ERP) can characterize arrhythmic risk. To measure it clinically, a pacing protocol with 8-10 beats is required, preventing beat to beat analysis. Monophasic action potentials (MAP) can indicate ERP on every single beat (Fig A), but are often difficult to annotate due to a wandering baseline (Fig B).

Hypothesis:
We hypothesized that machine learning of ventricular MAPs could help identify instantaneous repolarization, without requiring manual measurement and without measuring time to drop to a specific repolarization voltage.

Methods:
We analyzed 5706 MAPs from 42 patients (age 65±13 Y) with ischemic cardiomyopathy in pacing. A multilayer perceptron (MLP) was developed to input MAP shapes and output action potential duration at 30, 60, 90% (MAPD 30,60,90) repolarization, indicating ERP. We used 60% of data in training, 20% in validation, 20% in testing. Results were compared to manual measurement. To identify which MAP regions were key to machine learning, we systematically perturbed MAP regions with white noise and assessed the drop in performance.

Results:
Errors between APD 30,60 and 90 from MLP and manual marking were 9.3(2.0), 5.8 (1.1) and 5.8 (0.7) ms respectively (fig. C). Fig D shows that MAP phases 0 and 3 were used by MLP to predict APD, as seen in the significant increase in error with perturbations in those MAP regions (
P
<0.05).

Conclusions:
Machine learning can directly indicate effective refractory periods by learning the electrogram shape of single beats, without extrastimuli or manual measurement. Explainability studies confirm that machines learn physiological data. This approach can be used to assess beat-to-beat characterization of atrial fibrillation patients.
Abstract 11655: Direct Oral Anticoagulants Compared With Low Molecular Weight Heparin and Vitamin K Antagonists in the Management of Cancer-Associated Thrombosis: A Systematic Review and Network Meta-Analysis
Authors: Mir Ali , Rahman Mohammed F , Ragab Khaled M , Elsayed Sarah M , Fathallah Ahmed H , Hagrass Abdulrahman I , Kamal Ibrahim , Farooq Waseem , Bahuva Ronak , Page Brian
Published: June 2023

Objective:
Low molecular weight heparin (LMWH) has been established for the treatment of cancer-associated thromboembolism (CAT). Recent guidelines suggest Direct Oral Anti-Coagulants (DOACs) may have a role in the management of CAT, however these recommendations were conditional. This study aims to compare DOACs with LMWH and Vitamin K Antagonists (VKAs) in CAT.

Methods:
We conducted a meta-analysis of studies through a systematic search of four electronic databases (PubMed, Scopus, Web of Science, and Cochrane) published before January 25, 2022. Our criteria included studies in patients with all cancer types who received DOACs, VKAs, or LMWH for prevention or treatment of CAT. We analyzed outcomes including recurrent venous thromboembolism, major bleeding, clinically relevant non-major bleeding (CRNMB), and all-cause mortality. The quality assessment of the included RCTs was conducted through Cochrane Tool, while the quality of the included cohort studies was assessed by the NIH tool. The network meta-analysis was performed using the netmeta package in R software.

Results:
A total of 55 studies were included; 18 RCTs, and 37 cohort studies. DOACs (RR= 0.72, 95% CI [0.63; 0.83]) and LMWH (RR= 0.78, 95% CI [0.64; 0.94]) had a significantly lower risk of major bleeding than VKAs. There was also a significantly decreased risk of clinically relevant non-major bleeding (CRNMB) with LMWH than DOACs (RR= 0.63, 95% CI [0.55; 0.73]) and DOACs compared to VKA (RR= 0.83, 95% CI [0.72; 0.95]). With regards to recurrent venous thromboembolism risk (VTE), DOACs showed a significantly lower risk compared with either LMWH (RR=0.70, 95% CI [0.59; 0.83]) or VKA (RR=0.66, 95% CI [0.54; 0.80]).

Conclusion:
We conclude that DOACs are more effective in the management of CAT when compared to LMWH and VKA. DOACs and LMWH have significantly lower risk of major bleeding when compared to VKA. More research is needed to determine the best anticoagulation strategy for distinct types of cancers.
Abstract 11682: Spiked Helmet Sign - Poor Prognostic Sign or Artifact?
Authors: Al-Saiegh Yousif , Spears Jenna , Liskov Steven , Yan Gan-Xin
Published: June 2023

81 year old female with lung cancer suffered a PEA cardiac arrest while receiving chemotherapy. She received 20 minutes of CPR. Upon arrival to the ICU, she was afebrile, BP 85/55 mmHg on mechanical ventilation. Labs were unrevealing. ECG showed sinus tachycardia with normal intervals and ST segments. Pulmonary embolism and aortic pathology were ruled out. A TTE showed normal biventricular size and function without significant valvular abnormalities. An anaphylactic reaction to the chemotherapy was hypothesized as etiology of her arrest. After initiation of norepinephrine, dynamic oscillatory changes were noted on telemetry and confirmed on 12 lead ECG with a sharp R wave, convex ST changes and QT prolongation, resembling the spiked helmet sign (Fig. 1). Prompt work up showed no abnormal labs and a hyperdynamic left ventricle on TTE. The patient recovered well and was discharged to a nursing facility. The spiked helmet sign was first described in 2011 and defined as an upward shift of the isoelectric baseline followed by a sharp R wave and a convex ST segment elevation; commonly seen in inferior leads. It was exclusively observed in critically ill patients and associated with a high mortality. The mechanism has not been established yet. Proposed mechanisms include possible activation of the diaphragm by the inferior wall of the left ventricle or increased intrathoracic pressure during ventilation. We propose referred aortic pulsation as the mechanism. Specifically, when the left leg (LL) lead - as seen in this patient and frequently done in clinical practice- is placed on the abdomen. This explains the synchronicity of the upsloping with the QRS complex, and why it affects the inferior leads (Fig. 1c). We were able to reproduce the pattern by manually tapping on the LL lead in the same patient (Fig. 1b). The spiked helmet sign is associated with a poor prognosis despite poorly understood mechanism. Further studies are required to prove a cardiac mechanism as opposed to an artifact.
Abstract 11703: A Rare Case of Redo MitraClip Failure Requiring Salvage Mitral Valve Replacement
Authors: Dasari Mahati , Arun Kumar Pramukh , Arun Kumar Sumukh , Titus Anoop , Sherif Akil A , Kranis Mark
Published: June 2023

Presentation:
A 74-year-old lady with history of hypertension, COPD, severe pulmonary hypertension, HFpEF, redo MitraClip placement for severe mitral regurgitation (MR) secondary to mitral valve (MV) prolapse presented with four months of progressive dyspnea and bilateral lower extremity swelling. Vitals were significant for hypotension and tachycardia. Examination revealed a holosystolic murmur at the apex, crackles in bibasilar lung fields, and 3+ bilateral pitting pedal edema.

Work-up:
TTE revealed EF of 65%, enlarged right ventricle, flattened interventricular septum, multiple mitral clips attached to the MV leaflets, and an eccentric MR jet. TEE revealed severe left atrial dilation, severe MR with eccentric and posteriorly directed regurgitant jet and mal-coaptation of MV leaflets with three MitraClips attached (Figure 1-3).

Management:
For recurrent severe mitral regurgitation resulting in decompensated heart failure, options included another redo MitraClip procedure versus surgical MV replacement. After extensive discussion with the multidisciplinary team and the patient, a decision was made to proceed with surgical MV replacement accepting a high operative risk with STS risk score of >8%. Intraoperative findings revealed one inverted MitraClip with posterior leaflet detachment and two other clips that had densely scarred into the posterior leaflet leaving an unrecognizable MV (Figure 4). A 29 mm Epic Plus bioprosthetic MV was placed successfully. After a prolonged postoperative course, her clinical status improved.

Conclusion:
In patients who have failed the MitraClip procedure, significant destruction and fibrosis of the leaflets leaves surgical MV replacement being the only reasonable option. Surgical risk must be determined in conjunction with a multidisciplinary team as MV repair is performed at advanced centers in high-risk patients with good results. This can reduce the number of redo MitraClip and salvage MV surgery.
Abstract 11710: Sex Differences in Right Ventricular Flow Dynamics and Kinetic Energy in Healthy Volunteers
Authors: ZHAO XIAODAN , Leng Shuang , Tan Ru-San , Chai Ping , Bryant Jennifer A , Teo Lynette , Fortier Marielle V , Ong Ching Ching , Low Ting Ting , Koh Angela , Zhang Shuo , van der Geest Rob J , Tan Teng Hong , Yip James Wei Luen , Tan Ju Le , Zhong Liang
Published: June 2023

Introduction:
Accurate right ventricular (RV) flow and function is crucial for optimal cardiovascular health. However, research on RV flow and function has lagged behind that for the left ventricle. Whole-heart 4D flow cardiovascular magnetic resonance (CMR) uniquely quantifies simultaneous multi-directional phasic blood flow and kinetic energy (KE). Gender differences in these parameters have not been well studied and may contribute to the predilection for developing certain cardiovascular diseases among females. This study aims to compare RV flow and KE parameters in healthy female and male subjects.

Methods:
Healthy subjects from 2 centers (n=163) were prospectively recruited to undergo 4D flow CMR. RV flow components —direct flow, retained inflow, delayed ejection flow and residual volume —and KE (KE=1/2·ρ
blood
·
V
voxel
·
v
2
where ρ
blood
is blood density 1.06 g/cm
3
;
V
voxel
, voxel volume; and
v
, velocity) were calculated. All KE parameters were indexed to RV end-diastolic volume (KEi
EDV
) and expressed in μJ/ml. KEi
EDV
parameters at physiologically relevant epochs (global [entire cycle], systole, diastole) and cardiac cycle time points (peak systole, peak E-wave, peak A-wave) were extracted from a time-resolved KEi
EDV
curve.

Results:
Compared to males (n=95, mean age 44 years old), females (n=68, mean age 42 years old) had higher RV ejection fraction but smaller RV volumes; higher RV direct flow (38 vs 34%, P=0.007) and delayed ejection flow (17 vs 15%, P=0.043) and lower RV residual volume (27 vs 33%, P=0.001). Females had higher global KEi
EDV
(8.9 vs 7.5μJ/ml, P=0.005), diastolic KEi
EDV
(6.7 vs 5.6μJ/ml, P<0.001), peak E-wave KEi
EDV
(14.4 vs 11.9μJ/ml, P<0.001) and E-wave/A-wave ratio (1.68 vs 1.30, P=0.028) than males. No differences were observed for RV retained inflow, RV peak systolic, average systolic and peak A-wave KEi
EDV
between gender.

Conclusion:
Females have higher RV direct flow and lower RV residual volume, higher preload-adjusted RV global, average diastolic, peak E-wave and E-wave/A-wave ratio KEi
EDV
, compared to males by 4D flow cardiovascular magnetic resonance imaging. These parameters that related to right heart efficiency may lead to further understanding of the sex-based predispositions to right heart disease.
Abstract 11758: Sex Differences in the Associations Between Uric Acid and Incidence of Hypertension, Diabetes, and Chronic Kidney Disease in a Healthy Japanese Population
Authors: SALIM ANWAR A , Kawasoe Shin , Kubozono Takuro , Ojima Satoko , Kawabata Takeko , Ikeda Yoshiyuki , Miyahara Hironori , Tokushige Koichi , Ohishi Mitsuru
Published: June 2023

Introduction:
Uric acid (UA) has been linked to the development of cardiometabolic diseases. However, the effects of UA levels by sex have not been reported.

Hypothesis:
We hypothesized that UA plays a critical role in the development of hypertension, diabetes, and chronic kidney disease (CKD) in Japanese men and women who are apparently healthy at baseline.

Methods:
This retrospective cohort study included individuals who participated in a health checkup at the Kagoshima Kouseiren Hospital from October 2008 to April 2019 who had a 5-year follow-up. We excluded participants with hypertension, diabetes, dyslipidemia, obesity, estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2, history of gout, hyperuricemia medication, and missing data at baseline. Uric acid levels were divided into quartiles as follows: men: 1st quartile UA
<
4.8 mg/dL, 2nd quartile 4.9-5.6 mg/dL, 3rd quartile 5.7-6.4 mg/dL, and 4th quartile UA
>
6.5 mg/dL; women: 1st quartile UA
<
3.4 mg/dL, 2nd quartile 3.5-4.0 mg/dL, 3rd quartile 4.1-4.7 mg/dL, and 4th quartile UA
>
4.8 mg/dL. To assess the association between baseline UA levels and the development of hypertension, diabetes, and CKD, we performed a multivariable logistic regression analysis adjusted for age, body mass index, systolic blood pressure, diastolic blood pressure, current smoking, alcohol consumption, exercise habit, serum triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, and eGFR by sex.

Results:
In total, 21,514 participants (age, 52.9±10.9 years; men, 39.8%), were enrolled. In men, the OR and 95% CI for the fourth to first quartile was associated with increased risk for hypertension (OR, 1.35; 95% CI, 1.13-1.62, P=0.0011), and CKD (OR, 1.42; 95% CI, 1.04-1.95, P=0.0287), and inversely related with diabetes (OR, 0.60; 95% CI, 0.39-0.93, P=0.0221). In women, the OR and 95% CI for the fourth to first quartile showed no association with neither hypertension (OR, 1.14; 95% CI, 0.95-1.36, P=0.1541), diabetes (OR, 0.97; 95% CI, 0.53-1.77, P=0.9271), nor CKD (OR, 1.26; 95% CI, 0.97-1.65, P=0.0828).

Conclusion:
Elevated serum UA indicates the risk of future hypertension and CKD, and an inverse relation with diabetes in apparently healthy Japanese men.
Abstract 11795: Sex Modifies Compositional Plaque Progression in Non-Obstructive Coronary Artery Disease
Authors: Berge Caroline A , Solvik Margrete , Khan Ingela , Pedersen Eva R , Larsen Terje Hjalmar , Hovland Siren , Lonnebakken Mai Tone
Published: June 2023

Introduction:
Coronary artery disease (CAD) is a progressive disease where plaque composition is associated with cardiovascular events. Whether sex modifies compositional plaque progression in non-obstructive CAD is less explored.

Methods:
We identified 34 patients with non-obstructive CAD (<50% stenosis) undergoing clinically indicated serial coronary computed tomography angiography (CCTA) with >1 year interscan interval from the Norwegian Registry of Invasive Cardiology. All coronary segments were analyzed at baseline and follow-up using a semi-automated analysis software. We assessed the annual progression rate in total and compositional plaque volumes among women and men.

Results:
In the total study population (mean age 59.9 ± 11.3 years, median interscan interval 1.9 years [interquartile range (IQR): 1.6-2.3 years]), 41% were women. Women were older (64.9 ± 8.0 years vs. 56.3 ± 12.0 years, p=0.025), while there was no significant difference in the prevalence of hypertension, diabetes, statin treatment or smoking between groups (all p>0.05). Women had a higher total plaque burden at baseline and follow-up compared to men (p=0.017 and p=0.026, respectively), and their plaque composition remained unaltered (Figure 1). To the contrary, men had a higher progression rate of hypodense plaque proportions, comprising necrotic core (-30 - 30 HU) and fibrous fatty (31 - 130 HU) plaque (p=0.046 and p=0.019, respectively), with an associated increase in diseased segments at follow-up (p=0.003).

Conclusions:
In non-obstructive CAD, women had a higher plaque burden and an unaltered plaque composition, while men had faster progression of hypodense plaque proportions in serial CCTA. Whether sex differences in compositional plaque progression is associated with prognosis in non-obstructive CAD needs further investigation.