bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18313: Sex Disparities in Optimal Medical Therapy for Ischemic Heart Disease
Authors: Alhassan Hassan A , Mann Harnoor , Chiu Leonard , Countouris Malamo , Johnson Amber E
Published: December 2023

Background:
Despite secondary prevention guidelines recommending optimal medical therapy (OMT) forischemic heart disease (IHD), which includes antiplatelets, statins, renal-angiotensin aldosterone inhibitors (RAASi), and β-blockers, significant sex disparities in OMT utilization have been observed. However, theimpact of national efforts on narrowing this gap in contemporary cohorts remains uncertain.

Methods:
Using data from the National Health and Nutrition Examination Survey cycles 2011-2020, we examined the distribution and trends of OMT medication classes and combinations used in the preceding 30 days (verified through containers in most cases) among adult men and women with self-reported IHD (myocardial infarction or coronary artery disease).

Results:
Among 1905 adults included (40.6% women, mean age 65.4years), women had significantlylower proportions of OMT use across all medication classes- antiplatelets (68% vs. 77.7%), statins (57.2% vs. 73.9%), RAASi (45.6% vs. 59.0%), and β-blockers (51.2% vs. 61.1%); as well as combinations such as aspirin+statins (47.4% vs. 64.1%) and all four medications (17.5% vs. 32.5%). After adjusting forsociodemographic and clinical factors, the odds of using antiplatelets (OR 0.71 95%CI 0.52-0.94), statins (OR 0.62, 0.40-0.96), and RAASi (OR 0.56, 0.38-0.84) were significantly lower among women than men,whereas β-blocker use was comparable. Moreover, between 2011 to 2020, fewer women consistentlyreported using statins, RAASi, β-blockers, antiplatelets+statins, and all four medications in each survey cycle.

Conclusion:
This nationally representative study reveals persistent sex disparities in OMT utilization forIHD, with women receiving suboptimal treatment compared to men. These findings emphasize the urgentneed for novel targeted interventions to address and mitigate the sex disparities in OMT utilization foreffective IHD prevention.
Abstract 18317: Implications of Noise on Deep Learning Models for 12-Lead ECG Construction
Authors: Jain Utkars , Leasure Michael , Butchy Adam , Covalesky Veronica A , Mintz Gary S
Published: December 2023

Introduction:
ECG construction with deep learning can help standardize ECGs and remove noise and artifacts, transforming potentially unusable ECGs into clinically useful ones. However, noise levels, often unpredictable in clinical settings, may impact model performance.

Hypothesis:
This study explores the relationship between ECG noise levels and deep learning model performance in constructing noise-free ECGs. We hypothesize that beyond a certain noise threshold, the model's output ceases to be clinically usable.

Aims:
Our study aims to determine noise effects on the performance of deep learning models in constructing 12-Lead ECGs, providing insights into the model's robustness and the optimal conditions for its application.

Methods:
Using 250 digital 12-Lead ECGs from the PTB database, we injected Gaussian noise (mean 0.0, standard deviations between 0.0 and 1.0) into these ECGs, all processed and scaled to unitless values (-1 to +1) and resampled at 100Hz. A model was asked to construct a noise-free ECG from a full 12-lead ECG with noise injection, which was compared to the original noise-free ECG.

Results:
The findings reveal two distinct linear phases in the relationship between noise and model performance (measured by mean absolute error, MAE). Between standard deviations of 0.0 and 0.03, the MAE increased marginally, while a sharp increase occurred between 0.03 and 1.0. Importantly, critical features of the original ECG were retained for noise levels up to 0.08, implying a noise threshold for clinical usability.

Conclusions:
Deep learning models, though not entirely resistant to noise, demonstrate efficacy in constructing ECGs up to certain noise levels (standard deviation 0.03). Beyond this, performance declines markedly. These findings outline the limits and potential of deep learning models like ECGio in clinical practice. Future research should focus on resilience to higher noise levels or noise-reduction preprocessing strategies.
Abstract 18324: Artificial Intelligence ECG as a Novel Method to Detect Cardiotoxicity After Anthracyclines
Authors: Jacobs Johanna E , Greason Grace , Wildiers Hans , Willems Rik , Janssens Stefan P , Noseworthy Peter A , Lopez-Jimenez Francisco , Voigt Jens-Uwe , Friedman Paul , Van Aelst Lucas , Vandenberk Bert , Attia Zachi , Herrmann Joerg
Published: December 2023

Introduction:
Cardiotoxicity is a serious side effect of anthracycline treatment, most commonly manifesting as a reduction in left ventricular ejection fraction (LVEF) on cardiac imaging. Cost-effective alternatives to cardiac imaging are currently not available. Artificial intelligence (AI) models have been developed to detect a reduced LVEF from 12-lead electrocardiograms (ECGs) in the general population.

Hypothesis:
AI-ECG model can detect a reduced LVEF after anthracycline therapy (i.e. cardiotoxicity).

Methods:
We included an unbiased oncological population of 989 female breast cancer patients receiving (neo)adjuvant anthracycline chemotherapy. Average follow-up time was 9.83±4.2 years. Patients with incomplete transthoracic echocardiography (TTE) data, HER-2-directed therapy, significant comorbidities, upfront metastatic disease, second primary malignancy or pre-existing cardiovascular disease were excluded from the analyses. Patients with LVEF decline for reasons other than anthracycline-induced cardiotoxicity were also excluded. Primary readout was the diagnostic performance of AI-ECG by area under the curve (AUC) for various levels of LVEF <50%.

Results:
Using 1,877 ECGs from 703 unique patients, the AI-ECG model detected an LVEF <50% and ≤35% after anthracycline therapy with an AUC of 0.93 and 0.94, respectively.

Conclusions:
These data support the use of AI-ECG for cardiomyopathy (cardiotoxicity) screening after anthracycline-based chemotherapy. This technology could serve as a gatekeeper to more costly testing and could enable patients to monitor themselves over long periods of time.
Abstract 18352: Impact of Approach Site on Conduction Defect in Right Ventricular Biopsy
Authors: Yoshida Shohei , Tada Hayato , Nomura Akihiro , Takashima Shinichiro , Usui Soichiro , Sakata Kenji , Hayashi Kenshi , Fujino Noboru , Takamura Masayuki
Published: December 2023

Introduction:
Myocardial biopsy is a fundamental procedure for diagnosing myocarditis and cardiomyopathy. Complete right bundle branch block (CRBBB) is a potential complication of right ventricular biopsy (RV-EMB) that occurs at a certain rate. Consequently, patients with complete left bundle branch block (CLBBB) often exhibit reluctance to undergo RV-EMB due to the risk of complete atrioventricular block. However, it is precisely in such cases that the diagnosis of CLBBB through myocardial biopsy becomes crucial and concerns clinicians.Although there are two approaches to RV-EMB, namely the transfemoral vein and transjuglar vein approaches, and each institution has its preferred method, no study has investigated the variation in complication rates, particularly the occurrence of CRBBB, based on the different approach sites for RV-EMB. AIMS:This study aims to analyze the disparity in complication rates, primarily CRBBB, attributable to differences in the approach site during the RV-EMB procedure.

METHODS/RESULTS:
Over all 266 cases who underwent RV-EMB at Kanazawa University between January 2017 and December 2022 including 87 cases with transfemoral venous approach (Group TF) and 179 cases with transjugular venous approach (Group TJ) were enrolled in this retrospective single-center study. Group TF exhibited a higher usage of warfarin (15.1% vs. 3.4%, p=0.001) and obtained fewer specimens compared to Group TJ (2.97±0.98 vs. 3.90±0.65 pieces, p<0.001).Transient CRBBB was observed in 26 (29.9%) patients in Group TF and 13 (7.3%) patients in Group TJ (p<0.001); CRBBB persisted beyond 24 hours in 8 (9.1%) and 2 (1.1%) patients(p=0.004), respectively. One case of cardiac tamponade occurred in Group TF, and two cases of VF were reported in Group TJ, with no instances of stroke, permanent pacemaker implantation, or mortality.Multivariate logistic regression analysis identified approach cite (Group TF/TJ) as an independent predictor of CRBBB (p<0.001, odds ratio 0.43).

CONCLUSIONS:
The transjugular venous approach in RV-EMB demonstrates potential in reducing the occurrence of CRBBB as a complication. In cases where complete atrioventricular block is a concern, such as those with CLBBB, the transjugular vein approach may be preferable.
Abstract 18365: Elevated Biomarkers of Subclinical Myocardial Injury and Inflammation Among Community-Dwelling Adults With Covid-19
Authors: Ogungbe Oluwabunmi V , deCardi Hladek Melissa , Sokoll Lori , Mohr Phaedre , Dennison Himmelfarb Cheryl R , Davidson Patricia , Post Wendy S , Farley Jason , Commodore-Mensah Yvonne
Published: December 2023

Background:
Subclinical cardiovascular impact of SARS-CoV-2 infection in mild-moderate cases is unclear.
Hypothesis
We hypothesized that positive anti-nucleocapsid/spike SARS-CoV-2 antibodies will be associated with elevated subclinical cardiac and inflammatory biomarkers.

Methods:
This study was nested within a randomized controlled trial among community-dwelling adults. We used logistic regression to estimate adjusted odds of positive anti-nucleocapsid/ spike protein antibodies and elevated cardiac and inflammatory biomarkers (high-sensitivity cardiac troponin [hs-TnI], N-terminal pro-B-type natriuretic peptide [NT-proBNP], Galectin-3 [Gal-3], and C-reactive protein, [CRP]).

Results:
Among 231 adults, mean (±SD) age was 50 (±17.6) years, 63% were female, 57% were Black persons. Overall, 11% had detectable hs-cTnI (≥6 ng/L), 21% had elevated NT-proBNP (≥125pg/dL), 42% had elevated Gal-3 (≥18.5 ng/mL), 70% had elevated CRP (≥0.9 mg/dL). CRP levels were significantly higher among persons with positive spike protein antibodies [positive: median, 1.9 (Interquartile range IQR, 4.1) vs. negative: median, 0.7 (IQR, 2.1); p=0.014]. Those with positive spike protein antibodies were 3.49 (95% CI, 1.33-9.15) times more likely to have elevated CRP than those who were negative. Cardiac/inflammatory biomarkers were slightly higher in persons with positive SARS-CoV-2 IgG antibody detecting nucleocapsid protein (virus-specific antibody) versus negative (
Figure
).

Conclusions:
In this sample, we observed elevated cardiac and inflammatory biomarkers indicative of myocardial injury. Further research on the durability of elevated cardiac biomarkers and their contributions to post-acute sequela of COVID-19 is needed.
Abstract 18368: Management of Incident AF in Hospitalized Patients - Deficient, Delayed, Detrimental
Authors: Prinz Nick , Soto Daniel , Monfredi Oliver , Moorman Randall ,   Cntr for Advanced Med Analytics
Published: December 2023

Introduction:
Atrial fibrillation (AF) is potentially associated with significant complications including stroke and cardiac decompensation. Early appropriate AF management mitigates this risk. However, intervention is frequently delayed - a median of 1.5 days from AF onset in the ICU to clinical response. We sought to better understand delays in detection and management of AF in patients admitted to a cardiology bed and the consequences of delays.

Methods:
We undertook a retrospective review of 498 patients admitted to cardiology beds at the University of Virginia Medical Center who had automated algorithmic detection of AF episodes lasting ≥6 min. Time from algorithmic detection to clinical identification, AF burden, AF interventions and complications, medical history, and demographics were identified in each patient’s chart.

Results:
Of the 498 patients, 171 had an algorithmically detected episode of AF that was not acknowledged medically. These undetected episodes were generally shorter relative to episodes that were acknowledged (median 8 min vs. 52 min). 96 of the 498 patients had initial clinical detection of AF following algorithm detection; of the 96, 21 received early intervention (within 60 min), 51 received late intervention (after 60 min), and 24 received no intervention at all. Patients with early intervention experienced less AF burden compared to late and no intervention groups (median 8.6 hrs vs 21.75 hrs vs 29.35 hrs). Late intervention patients had more AF related complications compared to early intervention patients (9.8% vs. 4.8%). 20.8% of patients with clinical acknowledgement of AF but no intervention suffered a complication. Patients with a history of AF were more likely to have delays in intervention and over twice as likely to suffer an AF complication compared to those with no history (15.6% vs. 7.4%). Patients of lower socioeconomic status (SES) were also more likely to experience a complication.

Conclusions:
In summary, cardiology inpatients at our hospital commonly experience delays in management of AF that are considerable in duration, resulting in greater AF burden and higher complication rates. Differences in management, and subsequent outcomes, following AF appear to be impacted by prior history of AF and patient SES.
Abstract 18378: Ischemic Heart Diseases Mortality is Decreasing in Older Women: A Population-Based Time-Trend Analysis Using the Global Burden of Diseases Database, 1990-2019
Authors: Abughazaleh Saeed , Mkhaimer Yaman , Alsakarneh Saqr , Al Nawaiseh Ahmad , Hamarsha Qais , Rawabdeh leen
Published: December 2023

Introduction:
Ischemic heart diseases (IHD) are a major cause of mortality in the US despite that there is limited data on recent age and sex-specific mortality rates.

Aim:
This study aimed to conduct a time-trend analysis of mortality rates of IHD in the US using the global burden of disease (GBD) database.

Methods:
Mortality data was obtained from the GBD database. Age-adjusted mortality rates were stratified by gender and age-specific groups: younger adults (≤55 years) and older adults (>55 years). Annual percentage change (APC) and average APC (AAPC) were estimated using Joinpoint Regression Software (v.4.9.0.1, NCI).

Results:
959,513 patients were diagnosed with IHD in the US in 2019. Overall, mortality rates have decreased in older adults but remained stable in younger adults (AAPC = -2.9 vs -1.0, AAPC difference = 1.9, P < 0.001). Similar trends were observed in men, with an AAPC difference between older and younger adult men (0.9, P < 0.001). In women, while similar results were seen, there was a greater AAPC difference between younger and older adult women (2.6, P < 0.001), suggesting that the disparity in IHD mortality rates between age-specific groups arises from women.

Conclusions:
Our study showed decreasing IHD mortality rates among older adults and women over the past three decades. Further research is warranted to understand the factors behind the decreasing mortality rate in older adults, particularly older women.
Abstract 18410: Correlation Between Body Mass Index and NT-proBNP Levels in Heart Failure With Preserved Ejection Fraction: Implications for Clinical Outcomes
Authors: Vungarala Soumya , Jani Vivek , Vaishnav Joban , Hahn Virginia S , Kass David A , Sharma Kavita
Published: December 2023

Introduction:
N-terminal pro B type natriuretic peptide (NT-proBNP) is associated with increased cardiovascular events in heart failure with preserved ejection fraction (HFpEF). Adiposity is inversely correlated with NT-proBNP. It remains unclear whether obese HFpEF patients exhibit disproportionate outcomes with lower NT-proBNP.

Hypothesis:
We aimed to study the relationship between NT-proBNP and BMI in the Johns Hopkins University (JHU) HFpEF cohort to identify patient characteristics with increased NT-proBNP in obese HFpEF patients, adjusting for the inverse relation between NT-proBNP and BMI.

Methods:
We identified 338 individuals from June 2013 to November 2022. Univariate linear regression was performed between NT-proBNP and BMI. The cohort was split based on the median BMI and studentized residuals from NT-proBNP-BMI relationship (low BMI high BNP [Group 1] high BMI high BNP [Group 2] low BMI low BNP [Group 3] high BMI low BNP [Group 4]). Kruskal-Wallis test or Chi-square test was used to compare groups.

Results:
The median BMI of the cohort was 37kg/m
2
, and with every 1kg/m
2
increase in the BMI, the cut-off for elevated NT-proBNP reduced by 4 pg/ml. High BMI HFpEF patients were younger, predominantly female, and on diuretics (p<0.05 for all), independent of their NT-proBNP levels. Group 4 patients performed better on the 6-minute walk test (240±136 m), had better renal function (eGFR: 68.7±27.3), and less left ventricular (LV) hypertrophy and only mild diastolic dysfunction on echocardiography. Surprisingly, Group 2 resembled Group 1 despite having 70% reduced median NT-proBNP (1898[1047,4409] vs 574[207,1322], p<0.0001). Both “high BNP” groups exhibited lower event free survival for all -cause mortality(p=0.0001) and HF-hospitalization(p<0.05).

Conclusions:
NT-proBNP is predictive of clinical outcomes in HFpEF even in the presence of obesity. BMI adjusted NT-proBNP may be useful in the diagnosis and prognosis of HFpEF.
Abstract 18413: Therapeutic Genome Editing of Endothelial FABP4 by Endothelium-Targeted Nanoparticle Delivery of the CRISPR/Cas9 System Inhibits Pulmonary Arterial Hypertension in Mice and Rats
Authors: Dai Jingbo , Peng Yi , Zhao Youyang
Published: December 2023

Introduction:
Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive vasoconstriction and obliterative vascular remodeling. The molecular mechanisms of obliterative pulmonary vascular remodeling remain elusive.

Hypothesis:
Therapeutic genome editing of endothelial Fabp4 will knockout FABP4 expression selectively in endothelial cells and inhibit PAH in mice and rats.

Methods:
Employing the newly developed endothelial cell (EC)-targeted nanoparticle delivery technology, plasmid DNA expressing CRISPR/Cas9 controlled by
Cdh5
promoter and
Fabp4
-specific guide RNAs driven by
U6
promoter was administered i.v. to adult SD rats and

Egln1
Tie2Cre

mice which exhibit severe PAH and obliterative pulmonary vascular remodeling. One week after nanoparticle administration, the rats were injected with a single dose of monocrotaline (MCT) to induce PAH. At 4 weeks post-MCT, right ventricular systolic pressure (RVSP), ratio of right ventricular versus left ventricular plus septum (RV/LV+S) and pulmonary vascular remodeling were determined. Pharmacological FABP4 inhibitor was also employed to treat MCT rats as a comparison. Similarly, the pulmonary hypertensive phenotype in genome-edited

Egln1
Tie2Cre

mice was also characterized.

Results:

Nanoparticle delivery of the all-in-one CRISPR

rCdh5

plasmid DNA knockout Fabp4 selectively in endothelial cells in adult rats and

Egln1
Tie2Cre

mice leading to reduced RVSP, RV hypertrophy and pulmonary vascular remodeling in MCT rats and also in

Egln1
Tie2Cre

mice. Obliterative pulmonary vascular remodeling seen in

Egln1
Tie2Cre

mice was inhibited and the mortality rate in endothelial Fabp4-deficient

Egln1
Tie2Cre

mice was reduced. Treatment of FABP4 inhibitor also inhibits PAH in MCT rats. We also observed a marked increase of FABP4 expression in endothelial cells of lung samples of IPAH patients. Overexpression of FABP4 in primary cultures of human lung microvascular endothelial cells resulted in a 70% increase of cell proliferation.

Conclusions:
These findings demonstrate endothelial FABP4 is a promising target for PAH therapy.
EC-targeted nanoparticle delivery of the genome editing system may represent an effective and safer gene therapy approach for PAH treatment.
Abstract 18420: Appropriateness and Cost Analysis of Adult Inpatient Transthoracic Echocardiograms in a Community Hospital
Authors: Goel Swecha , Bliden Kevin , Singh Sahib , Dilli Babu Aravind , Kharkongor Chengappa Nivedita , Sainatham Chiranjeevi , Raghavakurup Lekshminarayan , Sidorski Damian , Gurbel Paul
Published: December 2023

Introduction:
Although inpatient transthoracic echocardiograms (TTEs) are important for guiding patient management, their overuse could be a concern leading to delayed discharges, unnecessary burden on hospital staff, and increased hospital costs. We analyzed the appropriateness, benefits, cost expenditure and unnecessary burden of TTE testing.

Methods:
A retrospective cohort analysis of a subset of patients undergoing TTEs in 2022 from a community hospital was performed. Appropriateness of use criteria (AUC) in accordance with American Society of Echocardiography and alteration in medical management was evaluated by 3 independent reviewers. Hospital cost analysis was performed based on median TTE cost ($682), yearly total adult TTEs performed (n=4,636), AUC criteria, and alteration in management under Maryland all-payer insurance model.

Results:
In 234 TTEs matched by age, gender, and race, AUC was not met in 32.5% of patients. Most TTEs were indicated for LV function assessment and ACS (Figure). Change in management was significantly higher in patients who met vs. not meeting AUC (54 vs. 11%, p<0.001). In patients meeting AUC, men had a higher change in management compared to women (61 vs. 46%, p = 0.05). No significant differences were found in the percentage of patients who benefitted from inpatient TTE by subgroups based on indications, except for cardiac trauma. Inappropriate TTE testing led to a yearly loss of approximately $313,000 in hospital revenue and an additional loss of $150,000/year for every 5% of patients who meet AUC with no alteration in medical management.

Conclusion:
In this community hospital analysis, nearly one-third of adult inpatient TTEs were obtained outside the recommendations of established guidelines. Strategies to improve adherence to ASE guidelines and patient selection for TTE testing are warranted to reduce unnecessary resource utilization and healthcare costs.
Abstract 18441: Long-Term Outcomes of Total Arch Replacement With Frozen Elephant Trunk Procedure for Patients With Acute Type A Aortic Dissection: A Single-Center Experience
Authors: wei jinhua
Published: December 2023

Introduction:
Total arch replacement (TAR) with frozen elephant trunk (FET) is an extensive surgical procedure for patients with acute type A aortic dissection (ATAAD). This study aimed to investigate the long-term outcomes of TAR with FET procedure for patients with ATAAD.

Methods:
A total of 670 patients with ATAAD who underwent TAR with FET procedure between January 2013 and December 2018 were included in this study. The patients were divided into two groups: the early group (n=245, 2013-2015) and the modern group (n=425, 2016-2018). In-hospital and long-term outcomes were compared between the two groups.

Results:
The average age and gender distribution were similar between the two groups (P>0.05). The modern group had a higher prevalence of preoperative coma (P<0.001). Patients in the modern group had a shorter mean duration of surgical procedure, including cardiopulmonary bypass time (189.8 ± 53.0 vs 176.0 ± 53.0 min, P=0.001) and hypothetical cardiac arrest time (22.8 ± 5.2 vs 15.1 ± 6.2 min, P<0.001). Although the in-hospital mortality was lower in the modern group, the difference was not statistically significant (6.1% vs 3.3%, P=0.064). The modern group had a significantly lower incidence of postoperative major adverse outcomes compared to the early group (33.9% vs 20.2%, P<0.001). The mean follow-up period was similar between the two groups. The overall long-term survival rate of patients undergoing TAR with FET procedure in this cohort was 92.7%. Patients in the modern group had a significantly lower cumulative incidence of all-cause mortality compared to those in the early group (P<0.001). Cox regression analysis showed that the modern year was an independent protective factor for the long-term survival of ATAAD patients undergoing TAR with FET procedure (HR=0.336, 95% CI: 0.193-0.585, P<0.001).

Conclusions:
The in-hospital and long-term outcomes of TAR with FET procedure for patients with ATAAD are promising and have improved over time.
Abstract 18445: Rigorous Mechanics in Engineered Heart Tissues
Authors: Lee Benjamin W , Moni Jamie , BOUHRIRA NESRINE , DeGrave Alisa N , Boone Noah R , Corbin Elise A , Margulies Kenneth B
Published: December 2023

Introduction:
Heart failure can develop or be exacerbated by mechanical stressors, including increased diastolic strain (preload) and increased systolic impedance (afterload). Recent advances in human induced pluripotent stem cell (iPSC) technology and tissue engineering have enabled long term culture and maturation of engineered heart tissues (EHTs). Most current platforms do not allow for mechanical assessment under a range of loading conditions. Here, we develop a technique to engineer cardiac tissues that allow for non-destructive rigorous phenotyping of tissue mechanics.

Methods:
Custom tissue anchors were 3D printed using Boston Micro Fabrication HTL Resin and placed within polydimethylsiloxane tissue casting molds. iPS cardiomyocytes and ventricular fibroblasts were mixed 5:1 in 2 mg/mL collagen and cast in rectangular molds. Tissues were compacted around custom tissue anchors over 14 days. Tissues were dismounted from the molds and fixed for immunostaining or hooked onto a force transducer for length-tension, force-frequency, and work-loop analysis.

Results:
3D printed tissue anchors accommodated EHT molding and compaction. EHTs spontaneously contracted after 3 days in culture, and compacted to 15.9±0.8% their initial tissue area by 14 days of culture. Engineered tissues were cell dense and mature, with bands of aligned sarcomeres. During isometric testing, tissues display a physiologic length-tension relationship, with linear increases in force with stretch between L
0
(slack length) and L
max
(length at maximum active force generation, 4.3±0.7 mN/mm
2
; r
2
=0.96). These are coupled with increases in contraction and relaxation velocities. EHTs were capable of mimicking physiologic work loops.

Conclusions:
In summary, we have shown the ability to grow and mature three-dimensional human engineered heart tissues capable of rigorous mechanical assessment, enabling future studies on load-dependent cardiac remodeling.
Abstract 18449: Myocarditis in Patients With Cancer Undergoing Combination Checkpoint Inhibitor Therapy
Authors: Lindsay Alistair C , Walker Alexander N , Schneeweiss Sebastian
Published: December 2023

Introduction:
Immune checkpoint inhibitors (ICI) have improved the clinical outcomes of several cancers but have also been associated with a greater risk of cardiovascular adverse effects.

Hypothesis:
The use of combination ICI therapy is associated with an increased risk of myocarditis, compared to use of a single ICI.

Methods:
A cohort study was conducted using medical and pharmacy claims data (2011 to 2022) in the Optum Clinformatics database. Cox regression models quantified the comparative risk of myocarditis between cancer patients receiving combination therapy (nivolumab and ipilimumab) and those taking a single ICI.

Results:
Among 53,018 patients to whom ICI were dispensed there were 148 cases of myocarditis (0.3%): 33 (0.7%) in patients on combination therapy and 115 (0.2%) in patients on monotherapy. The crude risk of myocarditis per 1,000 patients was 7.40 in the combination therapy group and 2.37 in the monotherapy group (risk ratio= 3.12; 95% CI: 2.12 to 4.60) over an average follow-up period of 226 days (IQR 93-495 days). After propensity score-matching the hazard ratio comparing myocarditis in the combination therapy versus monotherapy groups was 3.67 (1.76 to 7.67; p<0.01). 76% of all myocarditis events in both groups occurred within six months of commencing treatment (figure).

Conclusions:
Simultaneous combination therapy with nivolumab and ipilimumab was associated with an increased risk of myocarditis compared to the use of single agents. Myocarditis was infrequent and occurred most often within six months of treatment start.
Abstract 18452: Microtubule Motors Coordinate mRNA Export and Transport to Direct Local Translation in the Cardiomyocyte
Authors: Scarborough Emily A , Randell Rani M , Vogel Maria C , Prosser Benjamin L
Published: December 2023

Introduction:
The post-mitotic cardiomyocyte (CM) must maintain proteostasis while also preserving the ability to remodel, particularly during times of cardiac growth. How the CM couples transcription and translation in space and time for normal maintenance of the cell is understudied, and thus it is also unclear how these programs are co-opted to enable hypertrophy. Our lab’s previous work has indicated the necessity of microtubules (MTs) and kinesin-1 in proper localization of transcripts, translation and growth of the CM, yet the molecular mechanisms that direct specific mRNAs to subcellular regions for local translation remain opaque.

Research Questions:
We hypothesize that changes to MT PTMs are sufficient to alter the subcellular localization of motors, mRNA and translation. We additionally postulate that changes to the MT network during initial cardiac growth facilitate mRNA transport and translation.

Methods/Approach:
To visualize mRNA and protein localization in CMs, we couple immunofluorescence (IF) and smFISH. To measure translation, we methionine-deplete and use methionine-analogues and click chemistry. To measure cell size, we use live cell imaging of a membrane dye.

Results:
We find that the CM contains at least three subdomains for mRNA localization and local translation, and that some transcripts require proper localization for translation. Nearly any change to the MT detyrosination or tyrosination status is sufficient to mislocalize motors and mRNA. We observe mRNA accumulation at the nuclear short axis when detyrosinated tubulin is increased at the nuclear poles using taxol. This mRNA accumulation is accompanied by dynactin1 and kinesin-1 accumulation as well as nucleoporin relocalization. Taxol treatment in neonatal rat CMs results in a similarly asymmetric mRNA and nucleoporin localization, concomitant with an increase in width along this mRNA axis.

Conclusions:
A precise balance of dynein/dynactin1 and kinesin-1 in the CM is necessary for mRNA localization, which is at least partly established by MT PTMs. Stabilizing the MT network reveals a role for dynein/dynactin1 and nucleoporins in mRNA export and transport. We propose that perturbed mRNA export/localization may alter downstream translation to direct the growth of the CM.
Abstract 18480: Type 2 Diabetic Patients Have Increased Coronary Plaque Burden and Plaque Progression During 10-Year Serial Coronary CT Angiography Follow-Up
Authors: Gaillard Emilie L , Nurmohamed Nick S , Bom Michiel J , de Groot Robin J , Ibrahim Shirin , Min James K , Earls James , Planken R. Nils , Boekholdt S. Matthijs , Choi Andrew D , Stroes Erik S , Knaapen Paul
Published: December 2023

Background
Individuals diagnosed with type 2 diabetes are at high risk for coronary artery disease, however, data on long-term progression of coronary artery plaque burden is lacking. This study investigated atherosclerotic plaque characteristics and long-term plaque progression in patients with and without type 2 diabetes mellitus (T2DM).

Methods:
Per-protocol, patients from a coronary CT angiography (CCTA) cohort were invited for repeat CCTA imaging, regardless of symptoms. A total of 299 patients underwent follow-up CCTA imaging with a median scan interval of 10.2 [IQR 8.7-11.2] years. Patients who underwent coronary artery bypass grafting and vessels revascularized by percutaneous coronary intervention were excluded. Scans were analyzed using atherosclerosis imaging-quantitative CCTA (AI-QCT; Cleerly Inc.). The associations between diabetic status, baseline and follow-up plaque burden and characteristics were evaluated using multivariable regression adjusted for clinical risk factors, statin use and scanner settings.

Results:
In total, 274 patients were included, 43 (15.7%) had T2DM at baseline. The mean age was 57±7 years, 42% were women. At baseline, patients with T2DM had a median percent atheroma volume (PAV) of 6.80 (2.80, 17.70) at baseline; patients without T2DM had a median PAV of 3.20 (0.80, 9.55). Adjusted for clinical risk factors, patients with T2DM had a higher rate of plaque progression (Figure 1). The difference in PAV caused by T2DM was similar to the effect of a 13-year age difference. At baseline patients with T2DM had a higher prevalence of high-risk plaque (OR 2.11; p=0.025). After 10 years of follow-up, patients with T2DM had a higher prevalence of both high-risk plaque (OR 3.49; p<0.001) and low-density plaque (OR 3.74; p<0.001).

Conclusion
Patients with T2DM had a more than twofold higher coronary plaque burden, increased plaque progression during 10-year follow-up and had an increased prevalence of high-risk and low-density plaque.
Abstract 18486: Recurrent Pericarditis Following Atrial Fibrillation Ablation: Unmasking Latent Tuberculosis Infection
Authors: Yadav Ritu , Sinha Sunil K
Published: December 2023

Background:
Tuberculous pericarditis is rare in the United States but can lead to serious sequelae in the absence of diagnosis and treatment. We report a case of recurrent pericarditis following catheter ablation of atrial fibrillation (AF) due to reactivation of latent TB infection.

Case Summary:
A 52-year-old male with no past medical history underwent a difficult trans-septal puncture & cryo-balloon PV isolation, complicated by acute pericarditis and pericardial effusion with cardiac tamponade. He underwent pericardiocentesis with removal of 260cc bloody fluid. He had resolution of chest pain with ibuprofen, but experienced recurrence after 3 months and was given a longer NSAID course. Two months later, he presented with chest pain along with night sweats & low-grade fever. He had an elevated C-reactive protein, and echocardiography revealed thickened pericardium & constrictive physiology. He received high-dose aspirin, prednisone, and colchicine for recurrent pericarditis. Extensive Infectious Disease & Rheumatology work-up ruled out autoimmune & viral etiologies but his T-Spot TB test was positive. He denied personal or contact history of TB except travel to Asia 20 years ago. CT scan ruled out pulmonary TB infection. A 6-month course of Rifampin was prescribed. He experienced a 4th episode of pericarditis while tapering off prednisone, and restarted prednisone, Ibuprofen, and colchicine. Additionally, Rilonacept was prescribed. After completing 6-months of Rifampin and Rilonacept, he had significant improvement and no further recurrences on 1 year follow up.

Discussion:
Pericarditis is a common complication of catheter ablation, often resulting from direct injury. We report a case of recurrent pericarditis, initially believed to be a traumatic complication of AF ablation. However, investigation revealed underlying latent pericardial TB infection. Appropriate treatment led to complete resolution without sequelae.
Abstract 18492: Cross-Sectional Analysis of Demographic and Clinical Characteristics of Patients Using Icosapent Ethyl, With a Focus on Patients With Diabetes
Authors: Ganda Om P , Toth Peter P , Soran Handrean , Nelson John R , Wong Nathan D , Abrahamson David , Hannachi Hakima , Hartman Josh , Philip Sephy
Published: December 2023

Background:
Icosapent ethyl was approved in Dec 2019 to reduce CV event risk in statin-treated adults with elevated TG (≥150 mg/dL) and established CVD or diabetes with other risk factors of CVD.

Hypothesis:
Patients who take icosapent ethyl have demographic/clinical characteristics consistent with its indication.

Aims:
This study describes demographic/clinical characteristics of US patients taking icosapent ethyl, focusing on those with diabetes.

Methods:
A database of >89 million US electronic medical records identified patients taking icosapent ethyl (ie, ≥2 prescriptions on 2 separate days). Patient demographic/clinical baseline data were retrieved.

Results:
As of Jan 19, 2023, 40,408 patients taking icosapent ethyl were identified, with a mean (SD) age of 60.3 (12.9) y, BMI of 31.9 (6.07) kg/m
2
, HbA1c of 7.24% (1.88), and glucose level of 143 (67.8) mg/dL. Most were men (60.5%), White (75.2%), and taking statins (71.8%). Mean (SD; median) TG in the 3 mo before icosapent ethyl initiation was 422 (506; 300) mg/dL; 8.1% of patients had TG ≥500 mg/dL. In line with the indication of icosapent ethyl, 65.3% had prior atherosclerotic CVD or diabetes and ≥1 risk factor. Among 16,564 patients with diabetes (
Figure
), 13.0% had a history of myocardial infarction, 12.5% had stroke, and 10.4% had revascularization. Overall, 14.2% had chronic kidney disease and 5.5% had type 2 diabetes mellitus with diabetic kidney disease. Common risk factors for CVD were hypertension (68.4%), obesity (40.9%), and history of cigarette smoking (21.6%). Common antidiabetic medications were metformin (37.4%), insulin (27.9%), and sulfonylurea (15.1%).

Conclusions:
Patients using icosapent ethyl often had diabetes and/or CVD, took statins, and had elevated TG, meeting indications for its use. However, the high median TG before therapy suggests that many physicians reserve icosapent ethyl for more severe TG; thus many patients with more moderate levels (>150 mg/dL) could potentially benefit.
Abstract 18495: Right and Left Ventricular Starling Function in Heart Failure With Preserved Ejection Fraction
Authors: Bagga Joetsaroop , Wakeham Denis J , Hughes Seamus , Howrey Matthew , Brazile Tiffany , Balmain Bryce , Tomlinson Andrew R , Hearon Christopher , Macnamara James P , Babb Tony , Levine Benjamin D , Sarma Satyam
Published: December 2023

Background:
Efficient conversion of cardiac filling pressure to stroke volume (SV) is described by the Frank-Starling mechanism. Our group has previously characterized dynamic Starling mechanisms (DSM) in the frequency domain using respiratory mediated changes in beat-by-beat SV as a function of changes in pulmonary artery diastolic pressures (PAD) and shown this to be impaired in heart failure with preserved ejection fraction (HFpEF). Right ventricular (RV) dysfunction is common in HFpEF but efficiency of the RV Starling mechanism is unknown. The goal of this study was to characterize RV and LV DSM in patients with HFpEF.

Methods:
We studied 16 HFpEF patients (10 females; age: 68 ± 6 years) at seated rest following the placement of a radial arterial and right heart catheter. DSM was quantified by transfer function (input/output frequency) analyses of beat-by-beat changes in PAD (for LV) and A wave right atrial pressures (for RV) as input variables. Output variable was SV (Modelflow from radial arterial line waveform) and normalized for LV DSM using direct-Fick derived SV and for RV DSM using acetylene rebreathing derived SV as a measure of pulmonary blood flow.

Results:
The power spectral density (PSD) was higher for LV compared to RV filling pressure (521 ± 446 vs 125 ± 111 mmHg
2
,
P
= 0.001); there was no difference for adjusted SV PSD (819 ± 764 vs 808 ± 765 ml
2
,
P
= 0.232). DSM gain was higher for LV compared to RV for all but 1 subject (0.58 ± 0.29 vs 0.30 ± 0.16 ml/mmHg,
P
= 0.002; Figure).

Conclusions:
RV DSM gain was significantly worse than LV DSM gain suggesting decreased RV contractile and/or compliance reserve in patients with HFpEF. These results highlight the utility of RV DSM gain to characterize RV dysfunction in patients with HFpEF.
Abstract 185: Regional Oxygen Saturation and Capnography Monitoring During Resuscitation After Cardiac Arrest in a Swine Pediatric ARDS Model
Authors: Al-subu Awni , Braun Rudolf K , Staehler Ava , Stolen Kaisa Q , Rodgers Allison , Hacker Timothy A , Eickhoff Jens , Nadkarni Vinay M , Eldridge Marlowe
Published: December 2023

Introduction:
Survival and outcomes after cardiac arrest (CA) depend largely on the effectiveness of cardiopulmonary resuscitation (CPR). Traditional invasive methods of monitoring CPR can be challenging out-of-hospital and are lacking in more than 50% of in-hospital pediatric CA. Regional oxygen saturation (rSO
2
) monitoring with Near Infrared Spectroscopy (NIRS) and volumetric capnography offers a noninvasive approach that could potentially overcome these challenges.

Aim:
To determine the feasibility and effectiveness of NIRS and volumetric capnography monitoring in a swine model of pediatric hypoxia induced CA.

Approach:
Juvenile pigs were sedated and mechanically ventilated. Mild to moderate Acute Respiratory Distress Syndrome (ARDS) was induced by continuous oleic acid infusion. Respiratory and hemodynamic variables were monitored using invasive and noninvasive (NIRS and capnography) monitoring to assess efficacy of CPR. Animals were randomized into one of the two groups: High-quality CPR (hqCPR) to achieve coronary perfusion pressure of 25-30 mmHg and low-quality CPR (lqCPR) to achieve coronary perfusion pressure of 10-15 mmHg. Trajectories over time were analyzed using regression analyses. The discriminatory ability to distinguish between groups based on trajectories were analyzed using receiver operating characteristics curve (ROC) analysis.

Results:
39 animals (23±3 kg) were included in our study. In the hqCPR group, there are generally higher values for cerebral and renal rSO
2
, ETCO
2
, volume of CO
2
elimination (VCO
2
), and carotid blood flow, compared to the lqCPR group (p<0.0001). Cerebral and renal rSO
2
values increase over time, while ETCO
2
, VCO
2
, and carotid flow values decrease in the hqCPR group. Cerebral rSO2 had a ROC AUC of 0.76 (95% CI: 0.58-0.94), whereas renal rSO2 had a ROC AUC of 0.54 (95% CI: 0.22-0.87) representing nearly no discrimination ability. ETCO
2
had a ROC AUC of 0.66 (95% CI: 0.49-0.84), whereas VCO
2
had a ROC AUC of 0.62 (95% CI: 0.38-0.85).

Conclusions:
Higher mean cerebral rSO2 values during CPR might be used to assess quality of CPR effectiveness and provide real-time adjustments as needed. This could guide healthcare providers in optimizing CPR quality and improving outcomes for cardiac arrest patients.
Abstract 18505: Cancer Therapy Induced Cardiotoxicity - A Look at Frailty
Authors: Hanlon Emma , Rosas Andrea , Strom Jordan B , Asnani Aarti
Published: December 2023

Background:
Malignancy and cardiovascular disease are leading causes of death in elderly adults. While assessments of functional status have long been used for decision-making regarding initiation of chemotherapy, less is known about the association between frailty and cardiotoxicity outcomes.

Aims:
To evaluate the association between claims-based frailty (using the Fried phenotypic definition) and heart failure and all-cause death in patients treated with anthracyclines.

Hypothesis:
An increased probability of frailty will be associated with an increased risk of heart failure after treatment with anthracyclines.

Methods:
We performed a single center retrospective analysis of Medicare Fee-for-Service beneficiaries (≥65 years) who received anthracycline chemotherapy. The Johns-Hopkins claims-based frailty index, based on the Fried frailty definition, was generated for all participants and divided into quartiles. Cox models, adjusted for the competing risk of death, were used to model time to heart failure hospitalization or death within 5 years of anthracycline receipt (both adjudicated on chart review).

Results:
A total of 312 patients (mean age 74 with range 65-94, 50% female) were included of which 35 (11.2%) individuals developed heart failure and 167 (54%) died over a median 476 (IQR 149.3-2074.5) days of follow-up. Increasing quartiles of frailty were not associated with heart failure (HR 1.77, 95% CI 0.51-6.21, p = 0.4 for highest frailty quartile), but were associated with death (HR 2.04, 95% CI 1.30-3.20, p = 0.002 for highest frailty quartile). However, the association with death was mitigated by adjustment for age, gender, coronary artery disease, hematopoietic stem cell transplant and leukemia (HR 1.91, 95% CI 0.93-3.97, p = 0.08 for highest frailty quartile).

Conclusions:
In this single center study at a large academic center, frailty was not associated with anthracycline-associated heart failure but identified individuals at higher risk of death. Future studies are needed to investigate frailty as a risk stratification tool.
Abstract 18513: Causes and Predictors of 30-day Readmissions Following Covid-19 Hospitalizations and Co-Existing Acute Heart Failure: Insights From National Readmission Database 2020
Authors: Gajjar Rohan , Bobba Aniesh , Vardar Ufuk , Teaima Taha , Karki Sadichhya , Gangu Karthik , Vummaneni Siri , Yadav Neha
Published: December 2023

Introduction:
COVID-19 infection notably impacts the cardiovascular system, with evidence of higher in-hospital mortality in patients with acute heart failure (AHF) and COVID-19 infection. However, less is known about short-term outcomes following discharge. Therefore, we sought to analyze readmission data in COVID-19 hospitalizations with AHF from the National Readmission Database (NRD).

Methods:
NRD (2020) was queried to identify all COVID-19 hospitalizations and co-existing AHF using ICD-10 CM codes. The group was then stratified into heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). The outcomes were 30-day readmission rate, length of stay (LOS), total hospital charge (THC), and predictors of readmission. Multivariate/univariate logistic and linear regression analyses were used to analyze the outcomes and adjust for possible confounders.

Results:
A total of 53,337 COVID-19 admissions with co-existing AHF were identified, of which 38,401 were discharged alive. Within 30 days from discharge, 8,159 (21.26%) were readmitted. Upon stratification, 51% belonged to the HFrEF group and were found to have scarcely higher 30 days readmission rates than encounters with HFpEF (21.46% vs. 21.14%). Readmissions lead to an additional mean THC of $85,687 and a mean LOS of 7.8 days. The top five all-causes of readmissions were COVID-19 infection (24.8%), heart failure (16.2%), sepsis (15.4%), acute kidney injury (2.2%), and pneumonia (1.2%). Figure-1 shows a multivariate analysis of independent factors associated with readmissions.

Conclusions:
Our analysis showed a 21.26% 30-days readmission rate following acute heart failure during COVID-19 infection. Cirrhosis, anemia, diabetes mellitus, chronic lung diseases, and discharge against medical advice were significant readmission predictors. Optimizing these co-morbidities during index admission may reduce readmissions and overall financial burden.
Abstract 18519: Inhibition of G Protein-Coupled Receptor 35 Accelerates Wound Healing Through Augmenting Endothelial Function
Authors: Li Hainan , Xu Liping , Wang Jie-Mei
Published: December 2023

Introduction:
G protein-coupled receptor 35 (GPR35) is associated with various pathologies, including diabetes, but the precise function and underlying mechanisms are less understood. Oxidative stress responsive 1 (OXSR1) is a serine/ threonine protein kinase participating in cell cytoskeleton morphology in response to environmental stress. We hypothesized that GPR35 inhibition pace wound healing by augmenting endothelial function by targeting OXSR1.

Methods and Results:
Human dermal microvascular endothelial cells (HDMVECs) from healthy subjects and type 2 diabetic (T2D) patients at passages 5-7 were cultured
in vitro
. The transfection of an adenovirus carrying the GPR35 gene (Ad-GPR35) resulted in impaired migration of T2D HDMVECs (n = 3) or healthy HDMVECs exposed to high glucose (25mM, n =5). Meanwhile, Ad-GPR35 diminished OXSR1 protein expression (Western Blot, n=5). Fluorescent staining suggested that the decreased OXSR1 in HDMVECs exposed to high glucose was reversed by GPR35 siRNA (n=5, p<0.05). The GPR35 siRNA in HDMVECs improved cell migration, and this was reversed by simultaneously knocking down OXSR1 (Modified Boyden Chamber assay, n=5, p<0.05). In type 2 diabetic db/db mice, systemic delivery of adeno-associated virus carrying shRNA against GPR35
via
tail-vein injection accelerated wound closure (7-mm full-thickness excisional wound, n=4, p< 0.05).

Conclusions:
Our data suggested that the inhibition of GPR35 can accelerate wound closure, possibly through boosting OXSR1 signaling in endothelial cells. This study provided novel evidence for a potential therapeutic target in tissue repair in hyperglycemia.