bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15176: Development of Femoral Artery Denervation Models for Vascular Remodeling
Authors: Brown Taylor K , Xiong Liqun , Alharbi Sara , Ho Karen , Jiang Bin
Published: June 2023

Introduction:
Restenosis is a common cause of vascular device failure. An important contributor is the transdifferentiation of vascular smooth muscle cells (VSMCs) from a contractile to synthetic phenotype. Healthy arteries are innervated by sympathetic nerves to regulate VSMC contractility and phenotype, yet this interaction has been overlooked in pathological vascular remodeling such as restenosis.

Hypothesis:
Sympathetic denervation of the femoral artery will lead to transdifferentiation of arterial VSMC and pathological remodeling of the arterial structure.

Methods:
The femoral arteries of male BALB/c mice were surgically exposed and treated with specific dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) or vehicle for 5 minutes. In the model of long-term denervation, the mice were subcutaneously injected with 6-OHDA or vehicle weekly for 4 weeks. Femoral arteries and peri-adventitial tissue were harvested for histology. Innervation density was calculated as the number of sympathetic nerve fibers (tyrosine hydroxylase-positive) normalized to the medial layer area (α-smooth muscle actin-positive). Extracellular matrix (ECM) composition was visualized with Masson’s trichrome and Verhoeff's elastic staining.

Results:
One week after surgery, 6-OHDA-treated arteries had a notable reduction in sympathetic nerve density compared to controls (2.9 vs. 11.7 fibers/10,000 μm
2
[P=.22, n=2]). This difference decreased at 2 weeks (6.8 vs. 8.0 fibers/10,000 μm
2
[P=0.50, n=3]) and at 4 weeks (4.4 vs. 5.0 fibers/10,000 μm
2
[P=0.83, n=3]), suggesting nerve recovery. No difference was observed in ECM composition. Tissues harvested at 1 and 4 weeks in the 6-OHDA injection model demonstrate qualitative denervation of the treated limb compared to control.

Conclusions:
Sympathetic denervation of murine femoral arteries can be achieved by direct surgical application or subcutaneous injection of 6-OHDA. Future work will characterize vascular remodeling after long-term denervation and combine denervation with vascular injury. If a causal relationship can be identified between sympathetic denervation and VSMC pathology, engineering reinnervation could be a viable approach for future graft design.
Abstract 15177: Speckle-Tracking Echocardiography Improves Risk Stratification in Patients With Chagas Cardiomyopathy
Authors: Maia Marcelo A , Sabino Ester Cerdeira , da Silva José Luiz Padilha , Oliveira-da Silva Lea , Santos-Junior Omar R , Nobre Maia Ana Isabel , Versiani Fellipe , Ferreira Ariela , Ribeiro Antonio Luiz , Nunes Maria C
Published: June 2023

Introduction:
Chagas cardiomyopathy is an important cause of death in endemic areas. Speckle-tracking echocardiography (STE)-derived strain is a sensitive tool for evaluating myocardial function which may be helpful to improve risk stratification of Chagas cardiomyopathy patients. This study evaluated whether STE has incremental value for prognosis over traditional clinical and echocardiographic parameters in patients with Chagas cardiomyopathy.

Methods:
Patients with Chagas disease who had evidence of heart failure were selected for the study. Clinical evaluation, electrocardiogram (ECG), and echocardiogram were performed at the time of enrollment. STE-derived global longitudinal strain (GLS) was analyzed offline. The outcome was all-cause mortality.

Results:
A total of 317 patients were enrolled, mean age was 66 ± 13 years and 184 (58%) were women. During a mean follow-up of 2.6 years, 114 patients died (36%) with overall mortality incidence rate of 14.0 deaths per 100 patient-years (95% CI 11.6-16.8). GLS was an important predictor of death (HR 0.90; 95% CI 0.86 to 0.95; P<0.001), adding incremental prognostic value to standard echocardiographic parameters including right ventricular (RV) end-diastolic area, E/e’ ratio, left atrial (LA) volume, and left ventricular ejection fraction (LVEF). In overall population, the model including GLS had better accuracy in predicting mortality than the model including only conventional echocardiographic variables (P = 0.015). When the patients were stratified according to LVEF, GLS provided incremental prognostic information in patients with preserved (n=84; HR 0.80; 95% CI 0.64 to 0.98) or with mild to moderate reduced LVEF (n=166; HR 0.92; 95% CI 0.85 to 0.98), whereas in those who had severe LV dysfunction (n=67), GLS was no longer associated with mortality.

Conclusions:
In a cohort of patients with Chagas cardiomyopathy living in remote areas, GLS was a strong predictor of death, improving risk stratification beyond that provided by standard echocardiographic measurements, especially in patients with non-severe LV dysfunction. STE assessment may be used in a clinical setting to improve the risk prediction model for mortality in patients with Chagas cardiomyopathy.
Abstract 15178: Impact of Anemia on Mortality Among Patients With Type 2 Myocardial Infarction
Authors: Kiradoh Suud , Russell Greg , Greenberg Steven , Schuchardt Brett , Chevli Parag A , Thazhathuveetil Kunahamed Luqman Arafath
Published: June 2023

Introduction:
Anemia, a common precipitant of Type 2 Myocardial Infarction (T2MI), is well studied in Acute Coronary Syndrome (ACS), but its impact on mortality in T2MI population is lacking. We evaluated the association of hemoglobin (Hgb) levels on all-cause mortality within 60 days in patients with T2MI.

Methods:
In this single-center retrospective study, we evaluated 812 patients with Hgb > 7g/dl and troponin >0.04 ng/L (>99
th
percentile) presenting to a tertiary ED from 08/2016-08/2018. Exclusion criteria included patients with ischemic EKG changes, ACS treatment, cardiac catheterization showing intervenable lesions. Adjusted confounding variables are included in the figure. Iterative code was created to test each possible Hgb cut-off, from 7.1 to 15.2, to maximize the area under the curve while also looking for the smallest p-value and largest odds ratio. Five Hgb categories were then created, and mortality was calculated across groups. A multivariate-adjusted logistic regression model was used to predict mortality using Hgb category 13+ as the reference group.

Results:
Cut-off analysis showed Hgb of 9.9 as an inflection point of maximal mortality benefit (p<0.0001). Thus, our Hgb categories were 7-9.9, 10-10.9, 11-11.9, 12-12.9, and 13+. 60-day mortality rate for the above respective groups were 45.4% (n=216), 40.0% (n=135), 36.5% (n=104), 34.8% (n=115), and 26.9% (n=242) respectively. The overall 60-day mortality was 36.3% (295/812). In comparison with the reference group, multivariate analysis showing ORs for 60-day mortality for the above Hgb categories were 1.92 (95% CI: 1.28-2.96, p-0.003), 1.42 (0.87-2.32, p-0.16), 1.46 (0.86-2.49, p0.16), and 1.46 (0.88-2.42, p-0.15) respectively.

Conclusions:
Hospitalized patients with T2MI have an exceptionally high mortality rate that independently correlate with anemia severity. Those with Hgb < 9.9 had significantly higher mortality compared to Hgb > 9.9.
Abstract 15187: Comparison of Resting and Hyperemic Coronary Physiological Indices to Evaluate Myocardial Bridging in Patients With Angina and No Obstructive Coronary Arteries
Authors: Pargaonkar Vedant S , Schnittger Ingela , Tremmel Jennifer A
Published: June 2023

Introduction:
A hemodynamically significant myocardial bridge (MB) is an important diagnosis in patients with angina and no obstructive coronary arteries (ANOCA). The most appropriate intracoronary functional assessment to distinguish an incidental vs. hemodynamically significant MB remains unclear. We compared the ability of several resting and hyperemic physiological indices to identify a hemodynamically significant MB.

Methods:
We prospectively studied 11 patients with ANOCA and an MB confirmed by intravascular ultrasound (IVUS). All patients had intracoronary functional testing at rest, including instantaneous wave-free ratio (iFR), resting full-cycle ratio (RFR), and the ratio of distal coronary pressure (Pd)/aortic pressure (Pa). These measurements were repeated at hyperemia, including adenosine fractional flow reserve (FFR), dobutamine diastolic FFR (dFFR), iFR, and RFR. Resting iFR and RFR ≤ 0.89; resting Pd/Pa ≤ 0.91; hyperemic FFR, iFR, and RFR ≤ 0.8; and dFFR ≤ 0.76 were considered indicative of hemodynamic significance of an MB. Dobutamine dFFR was considered as reference standard.

Results:
At rest, iFR and RFR were significant in 6 and 7 patients respectively, while Pd/Pa was significant in 6. Adenosine FFR was significant in only 4 patients. With dobutamine, iFR and RFR were significant in 8 and 9 patients, respectively, and dFFR was significant in 9. Resting Pd/Pa and hyperemic iFR had a strong positive Spearman's rank correlation coefficient with dFFR (Figure). By kappa statistics, dobutamine iFR and RFR had almost perfect agreement with dobutamine dFFR.

Conclusion:
In patients with ANOCA who have an MB by IVUS, intracoronary physiology assessment is necessary to determine if the MB is hemodynamic significant. While adenosine FFR is an insufficient measure, diastolic indices such as dobutamine dFFR, iFR, or RFR may

identify hemodynamic significance, although whether one diastolic index outperforms another requires further evaluation.
Abstract 15189: The
‘July Effect’
in the Management and Outcomes of Acute Myocardial Infarction: An 18-Year United States National Study
Authors: Patlolla Sri H , Vallabhajosyula Saraschandra
Published: June 2023

Introduction:
Limited clinical experience of new trainees has been associated with poor outcomes in the first month of training (July) in teaching hospitals. It remains unclear if this ‘July effect’ continues to be present in contemporary era in patients with acute myocardial infarction (AMI).

Methods:
Adult hospitalizations for AMI in May and July in urban teaching and non-teaching hospitals in the United States were identified from the HCUP-NIS database (2000-2017). Admissions to rural hospitals, and those without in-hospital mortality data were excluded. In-hospital mortality was compared between those admitted in May and July. A difference-in-difference analysis comparing a change in outcome from May to July in teaching hospitals to a change in outcome from May to July in non-teaching hospitals was also performed to evaluate the July effect.

Results:
During the study period, there were a total of 1,312,006 hospitalizations for AMI admitted in urban teaching (54.2%) or non-teaching (45.8%) hospitals in the months of May and July. Demographic characteristics were comparable between those admitted in May and July, however, May admissions had greater comorbidity and higher rates of acute multiorgan failure when compared to July admissions in teaching and non-teaching hospitals. Additionally, May AMI admissions to non-teaching hospitals had higher rates of cardiogenic shock (4.6% vs 4.3%) and cardiac arrest (5.2% vs 5.0%) compared to July admissions (
all
p<0.001). July AMI admissions had lower in-hospital mortality compared to May admissions in both teaching (5.6% vs 5.8%; adjusted OR (aOR) 0.94 [95% confidence interval {CI} 0.92-0.97]; p<0.001) and non-teaching (5.9% vs 6.3%, p<0.001; aOR 0.97 [95% CI 0.95-0.99]; p=0.02) hospitals. When we analyzed the July effect using the difference-in-difference model for in-hospital mortality, we did not identify a July effect for in-hospital mortality in AMI admissions (p=0.14).

Conclusions:
Unlike prior reports, we did not identify a July effect for in-hospital mortality in this large contemporary AMI population in the United States. Greater care and support for new incoming trainees and/or awareness of a potential July effect among hospitals may have resulted in improved outcomes in July when compared to May.
Abstract 15192: Neighborhood Social Vulnerability Predicts Cardiovascular Disease Outcomes Through Pro-Inflammatory Risk Factors
Authors: Almuwaqqat Zakaria , Nayak Aditi , Martini Mohamed Afif , Islam Shabatun , Ejaz Kiran , Alras Zahran , Alkhoder Ayman A , Mehta Anurag , Ko Yi-An , Sperling Laurence , Quyyumi Arshed A
Published: June 2023

Introduction:
Emerging evidence suggests that neighborhood adverse characteristics are linked to nationwide disparities in cardiovascular disease (CVD) incidence and mortality. However, it is unclear if this association is linked to disease progression and outcomes in people with established CVD.

Hypothesis:
We hypothesized that in patients with CVD, neighborhood social adversity, measured as social vulnerability index (SVI) predicts incident cardiovascular events at least partly through pro-inflammatory.

Methods:
A total of 4150 participants enrolled in the Emory Cardiovascular Biobank, residential addresses were geocoded according to the census tract and SVI was determined using the Center for Disease Control data. Serum hs-C-reactive protein (hsCRP) levels were measured during enrollment and participants were followed up for incident myocardial infarction (MI) and cardiovascular death. Subdistribution hazard models were used to investigate the association between SVI and the study endpoint. A mediation analysis was performed to evaluate whether hsCRP levels underly this association.

Results:
Mean age was 63 years, 24% Black, and 64% were women. During a median 5 year follow-up, there were 904 (22%) adverse events. SVI and hsCRP were correlated (r=0.12, P<0.001). After adjustment for age, race, sex,hypertension, diabetes mellitus, body mass index, prior MI, prior heart failure, renal function, smoking, statin and aspirin use, participants in the highest SVI quartile (most socially vulnerable), had a 31% (95%CI, 4%,64%) higher risk of CV death/MI compared to those in the lowest quartile. The risk was attenuated and became insignificant after adjusting for the hsCRP 23% (CI -3%, 54%). Serum hsCRP levels mediated 61% of the association between SVI and adverse events.

Conclusions:
Neighborhood social vulnerability is an independent risk factor for adverse outcomes in CVD, that is at least in part mediated through increased systemic inflammation. Neighborhood social vulnerability may explain some of the residual risk observed in patients with CVD.
Abstract 15193: Coronary Ectasia in Patients With Thoracic Aortic Aneurysm
Authors: Tripathi Rishi , Zafar Mohammad , Ziganshin Bulat A , Elefteriades John A , Altin Elissa
Published: June 2023

Introduction:
Coronary ectasia is identified on coronary angiography in 1-5% of cases; however, its etiology, associations, and prognostic significance are poorly characterized

Methods:
In a large retrospective cohort of thoracic aortic aneurysm (TAA) patients, we identified rates of coronary ectasia and the presence of aortic aneurysm and bicuspid aortic valve. Two reviewers independently assessed coronary angiograms for the presence of coronary ectasia, defined as a diameter 1.5 times larger than the adjacent healthy reference segment or an absolute diameter > 4.5 mm.

Results:
Of the 474 TAA patients assessed, coronary ectasia was identified in 87 (18.4%). Amongst patients with coronary ectasia, 59 (67.8%) had isolated thoracic aortic aneurysms [11 (18.6%) had aortic root involvement, 46 (78.0%) had ascending aortic involvement, and 2 (3.4%) had descending aortic involvement]. Further, 28 patients had aneurysms across vascular beds [5 (17.9%) had root and ascending aortic involvement; 11 (39.3%) had combined ascending and descending aortic involvement; 9 (32.1%) had both thoracic and abdominal aortic aneurysms and 3 (10.8%) had diffuse aneurysmal disease involving other beds including intracranial, iliac and distal aortic aneurysms]. Additionally, 16 (18.39%) patients with coronary ectasia were found to have a bicuspid aortic valve where fused right and left coronary cusps were the most common anatomic variant [7 (43.75%) patients]. Of the 87 ectasia patients, there were no major adverse cardiac events including rupture of the ectatic coronary segments or related thrombosis or myocardial infarction during the mean follow-up period of 5 years.

Conclusion:
This study identifies that coronary ectasia occurs in TAA patients at a rate higher than expected for the general population, demonstrating a potential association between these conditions. At 5-year follow up, the presence of coronary ectasia is not associated with any major adverse cardiac events.
Abstract 15199: Automated Machine Learning (AutoML) Algorithms to Predict Post-Operative Venous Thromboembolism (VTE) Using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Database
Authors: Thangirala Avinash , Aphinyanaphongs Yindalon , Chen Ji , Martin Jacob A , Alam Usman , Dhaduk Nehal , Kelleher Andrew C , Oeding Jake F , Hu Eric , Ostberg Nicolai , Katz Gregory , Brejt Shelly , Kan Karen C
Published: June 2023

Introduction:
Post-operative patients are at increased risk for venous thromboembolism (VTE). Given the morbidity and mortality associated with VTE, risk stratification calculators have been developed based on pre-operative patient characteristics. Most risk calculators rely on logistic regression (LR) analysis. However, automated machine learning (AutoML) programs consistently outperform standard LR models in non-medical contexts. This study aims to investigate the utility of novel methods in developing a model for post-operative VTE after non-cardiac and cardiac surgeries.

Hypothesis:
We hypothesized that AutoML models would be superior to logistic regression models in predicting post-operative VTE.

Methods:
We used an AutoML system developed and released by Amazon in 2020, AutoGluon v0.3.1, to predict post-operative VTE using the 2016-2018 ACS NSQIP database. A total of 3,049,617 patients and 79 pre-operative variables were included. Post-operative VTE was defined as a deep venous thrombosis (DVT) or a pulmonary embolism (PE) within 30 days of the surgery. Models were trained for four hours to optimize performance on the Brier score, with lower being better. Validation of all performance metrics was done using the 2019 ACS NSQIP database.

Results:
0.79% of the patients (n = 23,974) developed post-operative VTE. Brier scores were calculated for each model with the top performing model being an ensembled neural net model having a Brier score of 0.00758 on the validation set. The corresponding AUROC and AUC-PR was 0.784 and 0.035 respectively (Figure).

Conclusions:
The models generated via AutoML to predict post-operative VTE had similar discriminatory characteristics to those reported in the literature. Future post-operative VTE models may benefit from AutoML analysis.
Abstract 15201: Empagliflozin Improves Baroreflex Sensitivity and Heart Function in Infarcted Rats
Authors: da Silva Bruno Durante , de Souza Leandro E , da Silva Maikon B , do Nascimento-Carvalho Bruno , Marques Juliana Romeu , Dourado Paulo M , Columbo Fernanda , Irigoyen Maria C
Published: June 2023

Introduction:
Several experimental studies have shown improvement in cardiac function of infarcted animals (diabetic or not) when treated with empagliflozin. Likewise, several clinical studies have shown improved outcomes in patients with heart failure with reduced ejection fraction or preserved ejection fraction in patients using empagliflozin.

Methods:
Wistar rats were divided into 2 groups: AMI - acute myocardial infarction (n=8) and EMPA - acute myocardial infarction + Empagliflozin (n=9).The animals of both groups were anesthetized and submitted to thoracotomy and ligature of the left coronary artery. The animals in the EMPA group received 10 mg/kg of empagliflozin daily through oral gavage for 14 days. After this period, an echocardiographic examination was performed, followed by cannulation of the femoral vein and artery, to evaluate hemodynamic parameters and baroreflex activity. Data were compared using unpaired t test or Mann-Whitney test and considered significant when p<0,05.

Results:
In the echocardiographic evaluation, an improvement in the systolic function indices was observed in the EMPA group in comparison to the AMI group: SF (27.42% ± 3.117 vs 19.17% ± 0.857), EF (50.69% ± 4.848 vs 37.95% ± 1.528), FAC (38.46% ± 2.382 vs 23.65 ± 1.415), as well as diastolic function indices: E'/A' ratio (1.571 ± 0.156 vs 0.574 ± 0.040) E/E' ratio: (16.24 ± 2.461 vs 28.27 ± 2.788).A reduction in mean arterial pressure was observed in the EMPA group (85.96 mmHg ± 1.437) in comparison to the AMI group (92.21 mmHg ± 2.345).In addition, there was an improvement in the baroreflex mediated tachy and bradycardic responses in the treated animals: tachycardic response (4.957 bpm/mmHg ± 0.125 vs 3.243 bpm/mmHg ± 0.157) and bradycardic response (1.532 bpm/mmHg ± 0.058 vs 0.710 bpm/ mmHg ± 0.017).

Conclusions:
Empagliflozin treatment in infarcted rats improved left ventricular systolic and diastolic function and improved baroreflex sensitivity.
Abstract 15206: Significance of Electrocardiogram Changes With Exercise in Pediatric Pectus Excavatum
Authors: Guerrier Karine , Bejnood Aram , Chang James , Wetzel Glenn , Hyde Ann , Hendrickson Benjamin , Philip Ranjit
Published: June 2023

Introduction:
The change in cardiac position caused by the thoracic deformity in patients with pectus excavatum (PEX) produces characteristic electrocardiogram (ECG) findings. However, the significance of ECG changes during exercise is unknown.

Hypothesis:
The ECG changes with exercise in PEX are related to worsening severity of PEX and location of PEX in relation to the heart.

Methods:
This was a retrospective review of patients ≤19 years old that underwent an institution-based protocol for preoperative PEX evaluation with ECG, echocardiogram (TTE), chest computerized tomography (CT) and cardiopulmonary exercise test (CPET) between January 2015 and December 2021. ECG changes with exercise were compared to the severity of PEX as defined by the Haller index (HI; mild = 2-3.2, moderate = 3.2-3.5, severe > 3.5) and location of the PEX as determined by right ventricular compression on CT. ECG changes were also compared to tricuspid valve annulus size (TVAS) on TTE and resting heart rate (HR) and HR reserve on CPET. Pearson's χ2 was used to compare categorical variables. Two-sample T-test was used to compare categorical with continuous variables.

Results:
There were 124 patients (85% male; median age 15 years [10-19 years]) with median HI 3.7 (2.4-20). Abnormal ECG changes with exercise were seen in 33 % of patients. Premature ventricular complexes (PVC) were the most frequently encountered (n=30; 73%). There was no significant difference in severity of PEX in patients with PVCs [χ2 =0.93, p 0.33; median HI of 3.9 (IQR 1.6) vs 3.7 (IQR 1.4)]. The majority of patients (96%) with PVCs had evident right ventricular compression on CT (χ2 = 5.20, p 0.02). Similarly, those with abnormal ECG changes with exercise were more likely to have a lower TVAS in comparison to those without [χ2 = 4.17, p 0.04; median TVAS z score -2.06 (IQR 1.22) vs -2.32 (IQR 0.75)]. The CPET indices were not significantly different between the two groups.

Conclusions:
The most frequent ECG abnormality seen with exercise in PEX in this cohort is PVCs. Lower TVAS and right ventricular compression on CT were significantly correlated with the development of PVCs with exercise. Follow-up evaluation of ECG during CPET after PEX repair may help affirm resolution of ectopy.
Abstract 15208: Association Between Electrocardiographic St-t Wave Abnormalities and Stroke Risk in the Allhat Trial
Authors: Basyal Binaya , Dey Amit K , Sajja Aparna , Joshi Aditya A , Ashish Kumar , Taylor Allen J
Published: June 2023

Background:
The presence of electrocardiographic (ECG) ST-T wave abnormalities has previously been shown to be associated with increased risk of coronary artery disease but their association with stroke incidence is unclear.Objective: We sought to investigate the relationship between ST-T wave abnormalities and stroke incidence in the ALLHAT trial.

Methods:
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized double-blinded clinical trial (n=33,357) conducted from 1994 through 2002, examining whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers incidence of CHD or CVD events compared to treatment with a diuretic. Major ST depression or T wave inversion on any ECG in the past 2 years were included in the study. One of the secondary outcomes included in the study was incident stroke. Hazard ratios (relative risks [RRs]) and 95% confidence intervals (CIs) were obtained using Cox proportional hazards regression model. All statistical analyses were performed using STATA 12 (Stata Corp., College Station, TX, USA).

Results:
Study participants were predominantly middle-aged, male, white, with prevalence of ST-T wave abnormality being 10.35% (N=3,420). Presence of ST-T wave abnormalities were not associated with a higher risk of stroke [hazard ratio 0.47 (95% CI, 0.91-1.22)] in unadjusted analyses. This relationship was not significant even after adjustment for prevalent cardiovascular disease (CABG, ASCVD) [0.51(95% CI, 0.91- 1.22)], cardiovascular risk factors (age, sex, diabetes, systolic blood pressure, diastolic blood pressure, cholesterol, BMI) [0.15 (95% CI, 0.96-1.31)] as well as randomized treatment groups in ALLHAT [0.15 (95% CI, 0.96-1.31)].

Conclusion:
Presence of major ST-T wave abnormality does not predict incident stroke in the the ALLHAT trial, more observations from contemporary studies need to be elucidated.
Abstract 15217: Intrahepatic Gene Expression Profile Differences in Patients With Fontan Associated Liver Disease
Authors: Bravo Jaimes Katia M , Wu Xiuju , Reardon Leigh C , Lluri Gentian , Naini Bita , Bostrom Kristina I , Aboulhosn Jamil A , Kaldas Fady
Published: June 2023

Introduction:
Fontan associated liver disease (FALD) develops shortly after the Fontan palliation as the long-term consequence of chronically elevated central venous pressures. The molecular pathways underlying FALD remain largely unknown. We aimed to assess intrahepatic gene expression profile differences among these patients with advanced vs early fibrosis.

Hypothesis:
Advanced fibrosis in patients with Fontan circulation shows a specific gene expression profile with specific enriched pathways.

Methods:
This retrospective cohort study included adults with the Fontan circulation who had tissue available from at least one liver biopsy at the UCLA Adult Congenital Heart Disease Center. Clinical, laboratory, imaging and hemodynamic data prior to the liver biopsy were extracted from medical records. Patients were classified into early (F1-F2) or advanced fibrosis (F3-F4). RNA was isolated from formalin-fixed paraffin embedded liver tissue, RNA libraries were constructed using ribosomal RNA depletion method and sequencing was performed on Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were carried out using DESeq2 and Metascape.

Results:
Seventy-seven patients were included, 53% women, 50% White and 20% Hispanic. Most patients had either a lateral tunnel (40%) or atriopulmonary (24%) Fontan. Four patients had 2 liver biopsies and 1 had hepatocellular carcinoma. Early and advanced fibrosis were present in 43 (54%) and 37 (46%) samples, respectively. Both groups had similar age, comorbidities, NYHA class, liver function tests and liver ultrasound features. Patients with advanced fibrosis had higher BNP, Fontan, mean pulmonary artery and capillary wedge pressures. Samples with advanced fibrosis had 921 up-regulated genes compared to the ones with early fibrosis. The up-regulated genes were enriched in extracellular matrix organization, regulation of cell adhesion, response to wounding, TGF-beta signaling pathway and blood vessel morphogenesis.

Conclusions:
Advanced fibrosis in patients with Fontan circulation exhibits up-regulated genes compared to early fibrosis, including pathways related to inflammation, congestion and angiogenesis, adding further insight into FALD pathophysiology.
Abstract 15227: Decreased Left Atrial Emptying Fraction is Associated With Increased Odds of Diagnosing Atrial Fibrillation Within 1 Year of ESUS
Authors: Shah Ravi S , Raco Joseph , Williams Ryan , McConkey Nathaniel , Foley David , Mills Kevin , Hegwood Emma , Jia Kelly , Maheshwari Ankit
Published: June 2023

Introduction:
A significant proportion of patients with embolic stroke of unknown source (ESUS) are subsequently diagnosed with atrial fibrillation (AF). Left atrial myopathy characterized by mechanical left atrial dysfunction has been associated with development of AF.

Hypothesis:
Decreased left atrial emptying fraction (LAEF) is independently associated with AF in patients with ESUS.

Methods:
Patients admitted at a tertiary care medical center for ESUS treated with implantable loop recorders from 2015-2022 were included. Patients were excluded for lack of an interpretable transthoracic echocardiogram during sinus rhythm and electrocardiogram with 6 months of ESUS. Patients were also excluded for lack of clinical follow-up. Co-variates (table) were ascertained from chart review. LAEF was calculated by Simpson’s method of discs.

Results:
153 patients were included. The mean(standard deviation) LAEF of patients who developed and did not develop AF within 1 year post ESUS was 48.0%(17.0%) and 57.6%(13.1%), respectively (P<0.001). The odds of diagnosing atrial fibrillation within 1 year post ESUS were 7.18-fold greater in patients with LAEF<40%.

Conclusions:
LAEF is independently associated with increased odds of AF within 1 year post ESUS. Future research is needed to validate these findings.
Abstract 15236: A Systematic Review of the Quality of Life (QOL) Assessment Tools Used in Aortic Dissection in the Context of Survivorship
Authors: hanna lydia , Jha Rama , Sounderajah Viknesh , Markar Sheraz , Gibbs Richard
Published: June 2023

Introduction:
The term 'survivorship' describes the therapeutic, functional, psychosocial, and financial experience of living with a chronic condition.This term acknowledges the fact that a patient’s life can be radically altered overnight because of their disease and treatment, but also designates patients as ‘survivors’, having overcome the acute phase (‘acute survivorship’) and now needing to live with, through and beyond their condition (‘extended survivorship’ and ‘permanent survivorship’). The aim of this systematic review was to identify the most frequently used quality of life (QOL) assessment tools and to determine how closely these align to the concept of 'survivorship'.

Methods:
A systematic literature review was conducted according to PRISMA guidelines. Embase, Medline and the Cochrane Library were electronically searched till January 2022 for studies reporting on QOL in aortic dissection patients. Observational studies and case series studies were included. Due to the degree of heterogeneity existing between the studies, a meta-analysis was not conduced. Study quality was assessed using the Agency for Healthcare Research and Quality (ARHQ) methodology checklist.

Results:
A total of 27 studies were included, encompassing 32 QOL tools. The most common QOL tool utilised was the SF-36, across 11 studies. Only one qualitative study investigated patient perspectives of living with aortic dissection. Overall, QOL was found to be poor in aortic dissection survivors. All identified QOL tools demonstrated a poor alignment with the survivorship domains. Included studies displayed a moderate to high risk of bias, having small sample sizes and an insufficient follow-up period.

Conclusion:
This review highlights the absence of an aortic dissection specific QOL tool. All QOL tools identified failed to encompass the breadth of survivorship domains, with a lack of studies focusing on the patients’ perspective. Further research is urgently required to gain an insight into the quality of life of patients who have survived an aortic dissection, and to develop an aortic dissection specific QOL tool, underpinned by the survivorship domains.
Abstract 15275: Dysregulated Micro-RNA Expression in Fat Tissue Linked to Angiogenesis Response in Patients in Peripheral Artery Disease
Authors: Rizvi Syed H , Breton-Romero Rosa , Weisbrod Robert M , Hamburg Naomi M
Published: June 2023

Microvascular dysfunction contributes to adverse clinical outcomes in patients with peripheral artery disease (PAD). Compromised angiogenesis may be a treatment target for limb ischemia but is challenging to assess in patients. Selected circulating miRNAs have been implicated in the pathogenesis of PAD, thus, we seek to identify and find correlation between altered miRNA signatures and angiogenesis potential in patients with PAD. We collected adipose tissue from ischemic limbs of patients with PAD (n=15, age=64±11, 33% women, 66% T2DM, 61% current smoking) at the time of revascularization surgery. Control adipose tissue was procured from patients without PAD undergoing joint replacement surgery (n=6, age=58±6, 50% women, 17% T2DM, 33% current smoking). Endothelial cell sprouting assay demonstrated lower angiogenesis response over 8 days in adipose tissue samples from PAD patients compared to controls (p=0.008). We performed miRNA profiling using NextSeq (Illumina Inc.) sequencer. miRNA NGS libraries were prepared using QIAseq miRNA Library Kit. Quality controlled NGS libraries were sequenced according to the manufacturer protocol. Our results demonstrated 40 upregulated and 11 downregulated miRNAs (FDR q<0.01, log2 fold change>2) in PAD fat tissue compared to controls. Using bioinformatics approaches to prioritize differentially expressed miRNA predicted to impact pathways relevant to cardiovascular disease, we identified miR205-5p and miR182-5p as top candidate. There were higher levels of miR205-5p (4.8-fold, FDRq=1.5e-10) and miR182-5p (4.1-fold, FDRq=5.4e-16) in adipose tissue from PAD patients compared to controls. We confirmed the differentially expressed levels using qPCR in selected samples. Ingenuity pathway analysis indicates that miR205-5p inhibits VEGF-A, a key regulator of angiogenesis. We observed a trend toward an association of miR205-5p (r=-0.58, p=0.1) and miR182-5p (r=-0.67, p=0.06) and lower angiogenesis response. Taken together our findings demonstrate impaired microvascular angiogenesis response in patients with PAD along with upregulation of selected miRNA predicted to impair angiogenesis pathways.
Abstract 15279: Ablation or Antiarrhythmic Drugs Alone in the Treatment of Ventricular Storm
Authors: Zhong Qiaonan , Deshmukh Abhishek , Bennett Courtney
Published: June 2023

Introduction:
Ventricular storms are managed with a combination of antiarrhythmic drugs (AAD) and ablation therapy. This study examines outcomes in patients who required cardiac intensive care unit (CICU) admission for ventricular storms.

Methods:
A retrospective cohort study was conducted of 200 random adult patients who admitted to the CICU at Mayo Clinic Rochester in 2016-2017 for ventricular storm. Continuous variables were analyzed with the Mann-Whitney U test. Categorical variables were analyzed with Fisher's exact test.

Results:
Of the 200 patients, 33 (16.5%) patients underwent ablation and AAD therapy for ventricular arrhythmias; 167 underwent AAD therapy alone. The patients in the ablation group were significantly younger (median of 60.3 vs. 72.7, U=1570, p<.001), had a lower Charlson Comorbidity Index (3.56 vs. 5.21, U=1916, p=.005), and a higher BMI (31.6 vs. 28.2, U=2028, p=.032). There was no difference in sex and race (white vs. non-white) between the two groups. The patients in the ablation groups had a significantly lower in-hospital mortality (0% vs. 20%, p=.001) and higher 1-year survival (91% vs. 63%, p=.001). There was no difference in length of stay in the CICU, length of stay in the hospital, or rate of hospital readmission within one year of discharge.

Conclusions:
Our study indicates that critically ill patients who undergo ablation and AAD for ventricular arrhythmias have decreased mortality compared to patients who underwent AAD therapy alone. More research is needed to elucidate whether this survival benefit is secondary to differences in treatment or baseline comorbidities in the two groups.

Table 1: Characteristics and outcomes of patients undergoing ventricular storm treatment. Data is reported either as median or number of occurrences (%). Antiarrhythmic drug (AAD), Charlson Comorbidity Index (CCI), Body Mass Index (BMI), Cardiac Intensive Care Unit (CICU), Length of Stay in days (LOS). * Significance with p values < .05
Abstract 15281: Patient and System-Related Delays in Presentation and Invasive Coronary Angiography in Patients Presenting With Acute Myocardial Infarction Secondary to Spontaneous Coronary Artery Dissection: A Report of the ISCAD Registry
Authors: Kumbhani Dharam J , Kim Esther S , Wood Malissa , Leon Katherine , Chi Gerald C , Grodzinsky Anna , Gornik Heather L , Wells Bryan , Lewey Jennifer , Taylor Angela , Kadian Dodov Daniella , Hess Connie N , Henkin Stanislav , Lindley Kathryn , Morris Gretchen , Orford James L , Tam Lori , Norris Samuel , Reyes Cassandra , Alkhalfan Fahad , Vitarello Clara , Femnou Mbuntum Laurette , naderi sahar
Published: June 2023

Introduction:
Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome especially in young patients. Factors associated with delays in presentation and care delivery are not well understood.

Methods:
We used data from the iSCAD Registry which is a prospective multicenter US registry of patients with SCAD. Early vs. delayed hospital presentation (< 24 vs. ≥ 24 hours), and early vs. delayed coronary angiography (time from hospital presentation to coronary angiography < 24 vs. ≥ 24 hours) for SCAD patients with AMI were assessed. Patient characteristics, and in-hospital events were compared between the two groups. Factors associated with delayed presentation and angiography were explored using multivariable logistic regression.

Results:
A total of 346 SCAD (294 white, 52 non-white) patients presented with STEMI (34%) or NSTEMI; 57 had a delayed presentation to the hospital after symptoms onset. No significant factors were identified for delays in seeking care. However, white race was less likely to have delayed invasive coronary angiography (multivariable OR=0.38; 95% CI 0.19 to 0.76; p=0.0059). Patients undergoing delayed angiography were also more likely to be medically managed (91.7% vs. 69.8%, p=0.0008), but less likely to receive dual antiplatelet therapy (57.0% vs. 73.1%, p=0.007). In-hospital outcomes were similar between the two groups.

Conclusion:
In this study, no patient-related variables were identified that predicted a delay in presentation with AMI secondary to SCAD. On the other hand, non-white race was associated with delays in performing invasive coronary angiography. Further investigation is required to determine the factors contributing to this potential disparity.
Abstract 15306: Nocturnal Hypertension is Associated With Hypertension Mediated Organ Damage Independent of Twenty-Four Blood Pressure in Hypertension
Authors: Mahmud Azra , Allhadaib Ruba , Alhabdan Nawaf A , Alkhidri Mohammad H , Silke Bernard
Published: June 2023

Introduction:
The new 2017 American College of Cardiology/American Heart Association guidelines propose that blood pressure (BP) measured during the awake period (clinic BP and ambulatory BP) should be controlled to <130/80 mm Hg as a universal BP goal. However, even after controlling daytime BPs, there is still a residual risk in hypertension, i.e., nocturnal hypertension. It has been well-established that night-time BP during sleep is closely associated with cardiovascular events in both community-dwelling subjects and hypertensive patients.

Hypothesis:
We hypothesized that nocturnal hypertension is associated is associated with hypertension-mediated organ damage (HMOD) in hypertensive patients.

Methods:
All subjects underwent the following procedures: 2-D and Doppler echocardiography, spot urine microalbuminuria (MA), arterial stiffness using pulse wave velocity (PWV) and ambulatory BP monitoring over 24-h periods. Nocturnal hypertension was defined according to current guidelines (i.e., nighttime systolic BP (SBP) ≥110 and/or diastolic BP ≥70 mm Hg).

Results:
Among 2375 subjects, (mean age 55±12 years, 45% female), nocturnal hypertension was evident in more than half of the study population with some 43% being masked uncontrolled nocturnal hypertension. Compared to the patients without nocturnal hypertension, the prevalence of left ventricular hypertrophy, increased relative wall thickness, MA and PWV>12m/s in patients with nocturnal hypertension was significantly higher at 25%, 64%, 56%, and 55%, respectively. In multivariate logistic regression analyses, after adjusting for other risk factors, nocturnal BP was associated with HMOD, independent of daytime BP.

Conclusions:
Nocturnal hypertension is a strong independent risk factor for HMOD, highlighting the importance of early detection and control of this particular BP phenotype in hypertensive patients.
Abstract 15312: Automatic Left Atrial Volume and Sphericity Index Calculation From Cardiac CT Using Computer Graphics Imaging and Deep Learning
Authors: Feng Ruibin , Deb Brototo , Ganesan Prasanth , Tjong Fleur V , Rogers Albert J , Ruiperez-Campillo Samuel , Somani Sulaiman , Rodrigo Miguel , Clopton Paul L , Zou James , Zaharia Matei , Narayan Sanjiv M
Published: June 2023

Introduction:
Left atrial (LA) volume and sphericity index are important for atrial fibrillation (AF) recurrence prediction after ablation and AF-associated atrial remodeling analysis. However, calculating these indexes from computed tomography (CT) requires manual outlining, which is subjective and difficult to scale.

Hypothesis:
We hypothesized LA body can be "virtually" dissected from electroanatomic shells using computer graphics imaging (CGI). We further hypothesized that the results of virtual dissection can be used to train a deep learning (DL) model for automatic LA volume and sphericity index calculation.

Methods:
First, by encoding the anatomic knowledge with geometric modeling, we developed a mathematical method (termed "virtual dissection") based on CGI techniques to isolate the LA body from electroanatomic shells (Fig A). Second, we used virtual dissection to train a DL model to segment CTs in N=20 patient atria (Fig B-C). Finally, we used this pipeline to segment raw CTs in a test cohort of N=100 patients (30.0% women, 66.0±10.3Y; Fig D).

Results:
In the independent test cohort (N=100), the LA volume and sphericity index were automatically calculated from DL-based segmentation, with the agreement within 4.04 ml (95% CI: -11.48 to 19.55; r=0.98; p < 0.0001; Fig E-F) and 2.75% (95% CI: -5.71 to 11.22; r=0.88; p < 0.0001; Fig G-H), compared to expert annotation.

Conclusions:
Encoded anatomical knowledge combined with deep learning in small datasets can accurately extract 3D cardiac models from raw CT scans in large populations, yielding automatic calculation of indexes such as volume and sphericity. This computational pipeline may simplify the outcome analysis and prediction using geometric indexes as predictors.
Abstract 15325: Dynamic Change From Mitochondrial Compensation to Mitochondrial Failure During Aortic Disease Progression and Dissection Formation
Authors: Li Yanming , Zhou Zhen , Zhang Chen , Vasquez Hernan , Li Yang , Chakraborty Abhijit , Rebello Kimberly , Zhang Lin , Ren Pingping , Azares Alon R , Chen Rui , li yumei , Lu Hong S , Cassis Lisa A , Coselli Joseph S , Daugherty Alan , LeMaire Scott A , Milewicz Dianna M , Shen Ying H
Published: June 2023

Introduction:
Ascending thoracic aortic aneurysm (ATAA) progression to dissection (ATAD) is associated with a high risk of mortality. Since the specific molecular and cellular changes leading to dissection are poorly understood, we compared transcriptome profiles of aortic smooth muscle cells (SMCs) between ATAD, ATAA, and controls.

Methods:
We performed single-cell RNA sequencing (scRNA-seq) of ascending aorta tissues from patients with acute ATAD (dissected and non-dissected areas were collected separately, 3 women, 5 men) and ATAA without dissection (3 women, 4 men), and from control subjects without aortic diseases (transplant donors, 3 women, 5 men). SMCs clusters were analyzed and immunofluorescence staining was performed to confirm expression of key genes. Mice exposed to β-aminopropionitrile monofumarate (BAPN) starting at P21 were used to investigate the changes of mitochondria-related genes during disease progression in undissected mice.

Results:
Compared with controls, SMCs in ATAA exhibited an adaptive response characterized by upregulation of a subset of focal adhesion and contractile genes and a pro-fibroblast phenotype. These expression changes were decreased in SMCs in ATAD, which instead exhibited significant increases in genes for inflammatory response, glycolysis, senescence and cell death. Additionally, mitochondrial genes including tricarboxylic acid (TCA) cycle genes (e.g.
SDHB
,
FH
, and
MDH2
) and mitochondria genome genes (e.g.
MT-ND4
,
MT-CO2
, and
MT-CYB
), exhibited increased expression in ATAAs, and downregulated in ATADs. Immunofluorescence staining of corresponding proteins confirmed some key findings. Consistent with human data, scRNA-seq showed increased mitochondria-related genes in SMCs in BAPN mouse model at P35 when aneurysms form, which were decreased in the proximal aortic tissues after the onset of dissection deaths in surviving mice at P42.

Conclusions:
Our data suggest a dynamic change from mitochondrial compensation to failure with progression from normal to aortic aneurysms to dissections, which ultimately increases cell death pathways.
Abstract 15353: Identifying Different Clinical Phenotypes in Peripartum Cardiomyopathy by Latent Class Analysis
Authors: Oyenubi Olamide , Benjamin Patrick , Chan Marvyn Allen G , Teweldemedhin Bisrat , Gruen David , Pomerantz Daniel , Jesmajian Stephen
Published: June 2023

Introduction:
Peripartum cardiomyopathy (PPCM) is a heterogeneous disorder whose pathophysiology remains poorly understood. To better understand the heterogeneity of PPCM, we used latent class analysis (LCA) to explore the different clinical phenotypes in a large sample of PPCM patients.

Methods:
Using the National Inpatient Sample (NIS) database, we identified 917 patients admitted to hospitals in 2017-2019 with a primary diagnosis of PPCM. We performed LCA based on 8 risk factors: age (< 30 vs > 30), race (African American (AA) vs non-AA), hypertension in pregnancy (HIP) (preeclampsia, gestational hypertension, or chronic hypertension), diabetes mellitus (DM), obesity, tobacco use, cannabis use, and psychiatric disorders (anxiety, depressive, bipolar, or schizophrenia spectrum disorders). We then compared in-hospital outcomes among the different clusters identified by LCA. Data were analyzed using Stata version 17 for descriptive analysis and Mplus version 8.8 for LCA.

Results:
Four patient clusters were identified. C1 (n=471, 51.4%) had no AA or cannabis users and members had the lowest probability of having HIP (0.387), DM (0.27), and obesity (0.17). C2 (n=328, 35.8%) were all AA who did not use cannabis and had the lowest probability of using tobacco (0.076), and having psychiatric disorders (0.084). C3 (n=31, 3.4%) was the youngest group all of whom used tobacco and cannabis and had the largest probability of having psychiatric disorders (0.484). On the other hand, C4 (n=87, 9.5%) was the oldest group none of whom used cannabis but members had the highest probability being obese (0.664), having HIP (0.825), and DM (0.642). Among all clusters, C3 had the lowest in-hospital mortality (0.0%) and hospital charges ($57,357). C4 had the highest in-hospital mortality 1.1% and longest hospital length of stay (5.4 ± 7.0 days).

Conclusions:
Using LCA, we identified four clinically distinct classes PPCM with varying in-hospital outcomes. These may reflect different additional underlying mechanisms in PPCM. Our findings may help identify treatment targets and patient selection for future clinical trials.