bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16842: Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy
Authors: Nakamori Shiro , Rowin Ethan J , Jaafar Narjes , Rodriguez Jennifer , Ngo Long H , Manning Warren J , Maron Martin , Nezafat Reza
Published: December 2023

Background:
There is limited data on the progression of the scar on LGE in patients with hypertrophic cardiomyopathy (HCM) stratified by age and its relationship with sudden cardiac death (SCD).
Objectives:
We compared LGE progression as stratified by age and examined the relationship of this risk to SCD.

Methods:
A total of 102 HCM patients (age <60 years; n=75, age ≥60 years; n=27) undergoing two consecutive cardiovascular magnetic resonance (CMR) at an interval of 4.3 ± 3.3 years from two medical centers were evaluated. LGE was quantified semi-automatically using a 6-SD threshold followed by manual adjustment. Median follow-up from study entry to the most recent evaluation was 7.3 years. The primary endpoint was the composite of resuscitated cardiac arrest and SCD.

Results:
At the first CMR, LGE was detected in 61 (60%) patients. At the follow-up, 25 patients developed a new LGE; thus, 86 (84%) patients had LGE by the follow-up CMR. Overall, the progression rate was 0.7 ± 1.0%/year, including 21 patients (21%) with LGE progression ≥1% /year and 5 (5%) with LGE >15% at follow-up. The risk of LGE progression ≥1%/year was significantly higher in patients <60 years (25% vs. 7%, p=0.02). There was a trend for the highest risk of LGE progression ≥1%/year in patients <60 years with LGE >10% at baseline scan. LGE progression ≥1%/year was a strong predictor of the primary outcomes (HR 1.88 [95% CI; 1.08-3.26], p=0.03). LGE progression moderately correlated with changes in LV mass, indexed LV mass index, and maximal LV end-diastolic wall thickness (p<0.001 for all).

Conclusions:
Progressive fibrosis occurs more frequently in young to middle-aged HCM patients and identifies a cohort at high risk of SCD. One-quarter of young to middle-aged patients exhibit LGE progression ≥1%/year, underscoring the importance of repeating CMR to re-evaluate for potential LGE progression in this age group.
Abstract 16845: Heart Failure Hospitalist Service Line Have Decrease All Cause Readmission, Length of Stay and Cost at 3 UPMC Hospitals in Central Pennsylvania in 2022
Authors: Vargas Jesus
Published: December 2023

Introduction:
Heart Failure (HF) is an important health care issue given its high prevalence, mortality, and cost of care. Despite numerous evidence-based strategies in the literature aiming at reducing HF readmissions, patients with HF remain at high risk for subsequent hospitalization with 20 to 25% readmitted within 30 days.

Methods:
Patients with both primary diagnosis HF at UPMC Harrisburg/West Shore/Community General totaled to 1574 in 2022. Hospitalist, Cardiologist, teaching service N= 547 (36%); CHF hospitalist Team N=1027 (64%). Heart failure order set usage, length of stay, all-cause 30-day readmission rates, readmission with HF, cost per case were assessed between these two groups for 2022.

Results:
All-cause 30-day HF readmission rates at UPMC (Harrisburg, West Shore, Community General Hospitals) for all other providers (Hospitalist, Cardiologist, teaching service) is 32%. HF Hospitalist team at 3 UPMC hospitals had lower 30 day all cause readmission rates: 8.46%. All other providers length of stay was 7.7 days while length of stay while on HF hospitalist service was 6.3 days. Potential cost savings to UPMC hospitals greater than $2.3 million dollars since start of HF Hospitalist service line.

Conclusions:
HF patients rarely have a consistent provider when readmitted. To address this health care priority at a system level, UPMC Central Pennsylvania’s strategy of creating a HF hospitalist service line has shown to be a unique method to not only develop trusting relationships with our patients but also attain impressive results. The HF Hospitalist service line was created to support an environment of patient-centered care by providing continuity of care for HF admissions and HF patients admitted for non-HF medical issues. At this community-based healthcare system, HF Hospitalist outcomes include decreased 30 day all-cause readmission to an impressive 8.2%, and reduced 30 day HF readmissions 4.12%. This was done while reducing healthcare costs during the 5yrs of the HF Hospitalist service line now at 3 hospitals at UPMC.
Abstract 16852: Pathological ECG Findings in 24-h-Holter-ECGs in Patients With Ischemic Stroke
Authors: Uhe Tobias , Wasser Katrin , Schaebitz Wolf , Koehrmann Martin , Brachmann Johannes , Laufs Ulrich , Dichgans Martin , Gelbrich Götz , Petroff David , Groeschel Klaus , Wachter Rolf ,   Find-AF 2 study group
Published: December 2023

Introduction:
ECG-monitoring covering several days is recommended by current guidelines to detect atrial fibrillation (AF) and other arrhythmias in stroke patients. In practice, the extent of rhythm monitoring varies. Here, we use data from the 24-hour screening-Holter-ECGs of the ongoing randomized multicenter trial Find-AF 2 to assess the rate of AF and other arrhythmias.

Methods and Results:
Find-AF 2 (NCT04371055) is a randomized and controlled open-label parallel multicenter trial with central AF adjudication (intervention arm) and blinded endpoint assessment. Patients ≥60 years with recent (≤30 days) ischemic strokes according to the AHA/ASA definition of any etiology are screened for eligibility. All eligible patients receive a 24-hour Holter-ECG prior to randomization. Holter ECG data are analyzed by the core laboratory using dedicated analysis software and following a predefined standard operation procedure. In this analysis, we included all 24-hour Holter-ECGs up to June 1, 2023.

We analyzed 3742 24-hour-Holter-ECGs from 51 different centers and found new arrhythmias in 120 patients (3.2%). AF was detected in 61 patients (1.6%) with a median duration of the longest episode of 730 minutes [interquartile range (IQR) 220;1180] (see Figure 1). This led to the initiation of anticoagulation in all 61 patients (100%). In 47 patients (1.3%), pauses >2.5 s (mean 3.1s±0.5s; longest pause 4.8s) or relevant bradycardias <40 bpm were diagnosed. This resulted in the implantation of pacemakers in six patients. Finally, we found regular supraventricular tachycardias in 25 patients (0.7%; median duration 7.0 min [IQR 1.0;21.3]) - 24 of them had focal atrial tachycardias and one an AVNRT.

Conclusion:
Overall, 3.2% of ischemic stroke patients had pathological ECG findings, leading to a therapeutic change in 56%, most commonly anticoagulation for AF detection The number needed to screen for a change in medical management was 56.
Abstract 16856: The Upside Down: A Case of Reverse McConnell’s Sign in Mixed Shock and ARDS
Authors: Curtis Brett , Ha Albert , Xie Jeffrey , Helms Adam S , Howe John , Hyzy Robert
Published: December 2023

Introduction:
We present a case of reverse McConnell’s sign in shock and respiratory failure.

Hospital Course:
A 48-year-old woman with cirrhosis presented to the emergency department with hypoxia, hypotension, and tachycardia. She endorsed lower extremity edema and orthopnea.

Labs noted elevated BNP, procalcitonin, troponin, and lactate. Urinalysis showed signs of infection. EKG did not reveal ischemic changes. CT pulmonary embolism (PE) protocol was negative for PE but showed pulmonary edema. Parasternal short axis views on bedside ultrasound revealed interventricular septal flattening during systole consistent with right ventricular pressure overload ("D sign").

She received broad-spectrum antibiotics for E. coli bacteremia. Trans-thoracic echocardiogram showed a hyperdynamic LV and decreased RV function with a "reverse McConnell sign (rMS)" (figure 1).

Providers initiated diuresis once her vasopressor requirement stabilized. She was soon extubated and her oxygen requirement continued to improve with diuresis. Vasopressors weaned in several days.

Prior to discharge, trans-thoracic echocardiogram echo showed recovery of RV function.

Discussion:
This case of respiratory failure and shock highlights the value of prompt echocardiography. Her rMS was likely caused by increased pulmonary arterial pressure from hypoxic vasoconstriction and V/Q mismatch from ARDS. Other heart failure processes seem unlikely.

rMS refers to right apical hypokinesis and basal hyperkinesis, inverted compared to its counterpart. Cases are associated with PE and Takotsubo cardiomyopathy, but rMS likely more generally indicates right heart strain.

Evidence suggests that rMS may be associated with higher rates of comorbidities and adverse events. Finally, it may represent the RV’s protective mechanism for abruptly increased afterload.

Conclusion:
Providers should consider rMS as a sign of RV strain to assist diagnosis and management of undifferentiated shock.
Abstract 16858: QRS/T Ratio With Progression of Left Bundle Branch Block From New to Old: Is Voltage-Time-Integral Better Than Amplitude in Discriminating of Chronicity of Block?
Authors: Kettelkamp Nicholas , Kircher Charles , Harvey Christopher , Sheldon Seth , Reddy Madhu , Pimentel Rhea C , Noheria Amit
Published: December 2023

Introduction:
Discriminating acute versus chronic left bundle branch block (LBBB) has well known and important clinical implications. QRS/T vector magnitude ratio, and ratio of deepest S to tallest T in precordial leads, have been shown to discriminate new vs old LBBB. We sought to evaluate how QRS/T voltage-time-integral (VTI) ratio, as opposed to QRS/T amplitude ratio changes with progression of LBBB from new to old.

Hypothesis:
We proposed that QRS/T VTI ratio would be equivalent to QRS/T amplitude ratio in distinguishing new from old LBBB.

Methods:
We analyzed ECGs of patients with known chronic LBBB (n=385, 53.5% female, age 70.6±12) against ECGs of patients with acute LBBB (n=79, 53.6% female, age 77.7±9.5) one day post transcatheter aortic valve replacement (TAVR) and at 1 month post TAVR utilizing VTI of 3D QRS and 3D T-wave ratio. Orthogonal X, Y, Z leads were reconstructed from 12-lead ECG using Kors’s matrix. VTI
X, Y ,Z
and VTI
3D
were obtained from temporal integration of voltage in X, Y, Z and root-mean-squared (3D) ECGs respectively. We compared changes in QRS/T amplitude, VTI ratios, and maximum precordial S/T magnitude ratio 1 month after versus day 1 of new LBBB using pairwise t-tests.

Results:
We found acute post-TAVR LBBB was best distinguished utilizing VTI of 3D QRS (3.37±1.27,
p
<0.0005) compared to 3D T-wave ratio (2.90±1.00,
p
<0.003). We also found LBBB post TAVR at one month is best distinguished by the 3D QRS/T-wave VTI ratio (1.53±0.32,
p
< 0.0001) and less so by the 3D amplitude ratio (3.27±1.37,
p
0.003) Acute max precordial S/T magnitude was not able to differentiate chronic from acute LBBB (
p
0.1). At one month follow up, acute LBBB TAVR QRS-T amplitude ratios were found to return to their baseline values (3.37±1.27 for acute and 3.27±1.37 with
p
0.5).

Conclusions:
Between VTI of 3D QRS and 3D T wave ratio, VTI 3D QRS proved to be more reliable for distinguishing acute versus chronic LBBB. Chronicity of LBBB was not predicted by maximum precordial S/T magnitude.
Abstract 16865: Epicardial Adipose Tissue Density Predicts the Presence of Atrial Fibrillation and Its Recurrence After Catheter Ablation: Three-Dimensional Reconstructed Image Analysis
Authors: Nodera Minoru , Kakehashi Shota , Mukai Moe , Aoyama Daisetsu , Hasegawa Kanae , Uzui Hiroyasu , Tada Hiroshi
Published: December 2023

Introduction:
Epicardial adipose tissue (EAT) induces inflammation in the atria and is associated with atrial fibrillation (AF). Several studies have examined the relationship between EAT volume (EAT-V) and density (EAT-D) and the recurrence of AF after catheter ablation. However, the conclusions of these studies have not always been consistent, which might be due to the differences in the location and method of EAT measurement.

Methods:
This study included 43 consecutive patients who underwent catheter ablation for AF and 30 control patients with no documented history of AF who were matched for baseline characteristics. EAT-V and EAT-D around the entire heart, both atria, left atrium (LA), and right atrium (RA) were measured in detail using reconstructed three-dimensional (3D) EAT images from dual-source computed tomography before ablation.

Results:
None of the measurements of EAT-V differed significantly between patients with AF and controls or between patients with recurrent AF and those without. On the other hand, all measurements of EAT-D were higher in patients with AF than in controls (both atria, p<0.001; RA, p<0.001; LA, p=0.002). All EAT-D measurements were associated with the presence of AF. Among patients with AF who underwent ablation, all EAT-D measurements were higher in patients with recurrent AF than in those without. The difference was significant for EATRA-D (p=0.032). All atrial EAT-D values predicted recurrent AF (EATRA-D: hazard ratio [HR], 1.208; 95% confidence interval [95%CI], 1.053-1.387; p=0.007; EATLA-D: HR, 1.108; 95% CI,1.001-1.225; p=0.047; EATatrial-D: HR, 1.174; 95% CI,1.040-1.325; p=0.010). According to the ROC curve analysis, EATatrial-D> –80.9 HU is associated with AF recurrence with 100% sensitivity and 58% specificity (AUC, 0.75; p<0.05), and EATRA-D > –80.9 HU could distinguish patients with AF recurrence with 86% sensitivity and 61% specificity (AUC, 0.76; p<0.01). However, EATLA-D > –85.3 HU had low accuracy (sensitivity, 100%; specificity, 33%; AUC, 0.65; p=0.209).

Conclusion:
For predicting the presence of AF, 3D analysis of EAT-D, rather than EAT-V, is useful. Peri-atrial EAT-D is responsible for recurrent AF after ablation and useful for predicting recurrent AF after catheter ablation.
Abstract 16884: CircNPHP1 Regulates Endothelial Function in Ischemic Heart Disease
Authors: Emanueli Costanza , Sarkar Moumita , Anwar Maryam , Chamorro-Jorganes Aranzazu , Ford Kerrie , Laftah Abas , angelini gianni , Punjabi Prakash
Published: December 2023

Background:
Ischemic heart disease (IHD), which is characterized by reduced myocardial blood flow, is aggravated by diabetes mellitus (DM). Non-coding RNAs, including microRNAs (miRs) and circular RNAs (circRNAs), regulate gene expression and impact angiogenesis. Canonically, miRs bind to the 3’UTR region of their target messenger RNAs (mRNA) to mediate post-transcriptional gene inhibition. CircRNAs can “sponge” and sequestrate miRs, thus preventing the repression of their mRNA targets.

Hypothesis:
The circRNAs/miR/mRNA interactions are deregulated in the diabetic heart, contributing to IHD.

Aims:
To identify and mechanistically investigate the circRNA-miRNA-mRNA networks deregulated in IHD and diabetes.

Methods:
We generated bulk RNA-seq data on whole transcriptome (for mRNAs and circRNAs) and small RNA (for miRs) using heart left ventricle biopsies of 3 groups of cardiac surgery patients (n=12/group) from the ARCADIA cohort (13/LO/ 1687): 1) and 2) suffering from IHD with/out type-2 DM and 3) non-ischemic non-diabetic controls. Customized bioinformatics approaches identified differentially expressed (DE) circRNAs, mRNAs and miR in IHD and IHD+T2DM patients (vs. Controls). Prediction tools and databases (CircInteractome, miRWalk) identified “sponging associations” between circRNAs and miRs and the targets of sponged miRs, producing the circRNA-miR-mRNA networks. The network’s individual components were filtered for endothelial cell (EC) expression using GEO datasets and for involvement in angiogenesis using KEGG, Wiki and Panther pathways and Gene Ontology. The endogenous role of the circRNAs in the top emerging network was tested in cultured ECs using siRNA-mediated silencing, while the circRNA-miRNA sponging interaction were confirmed determined after using circRNA pulldown with divergent primers.

Results:
A putative proangiogenic subnetwork commanded by circNPHP1 is DE in IHD+DM. circNPHP1 silencing in the ECs reduced angiogenesis and downregulated 2 validated target genes of miR-221-3p, namely VEGF and BCL2. The pull-down assay confirmed circNPHP1 binding to miR-221-3p.

Conclusions:
circNPHP1 supports vascular repair and holds potential as novel therapeutic target in IHD and DM.
Abstract 16892: Statin Utilization and Recurrent Cardiovascular Disease Events in a Secondary Prevention Cohort of Older Adults
Authors: Acharya Deeksha , Walker Aaron , Zhu Jianhui , Thoma Floyd W , Koczo Agnes , Mulukutla Suresh R , Saeed Anum
Published: December 2023

Introduction:
The ACC/AHA guidelines recommend that patients with established ASCVD should be on high intensity statins for secondary prevention. Prior data suggests that older adults (>75 years) are sub-optimally treated for both primary and secondary prevention of ASCVD events. We investigated guideline directed statin intensity (GDSI) use, associated LDL cholesterol levels and ASCVD outcomes in a cohort of older adults in a large healthcare network.

Methods:
EMR data was abstracted to assess statin prescriptions between 2010-2020 amongst adults with known ASCVD (CAD, ischemic stroke/TIA or PAD). Prescriptions of statins as GDSI (high intensity), <GDSI (low/moderate intensity), and no statin were assessed and stratified by age groups. LDL-C levels across the follow up time were calculated. Cox regression models were used to assess HRs (Hazard Ratios) for repeat ASCVD event (MI and stroke/TIA) and all cause death, stratified by age and GDSI treatment.

Results:
Over ~5y follow up, amongst adults aged>75 years (n=11,596), less than half (49.6%) were on GDSI and only ~54% older adults achieved LDL-c<70mg/dL. Compared to GDSI use, older adults on 75y 1.59; 95% CI (1.30-1.95)], stroke [HR>75 1.659; 95% CI (1.21-2.24)] and mortality [HR>75 1.88; 95% CI (1.57-2.25)]; all p<0.01 in <GDSI group vs GDSI group. GDSI use had a greater reduction of MI and mortality in older adults than younger counterparts [Table 1].

Conclusions:
In this contemporary healthcare network, GDSI use for secondary prevention and LDL-C<70 mg/dL was suboptimal amongst all age groups. Any statin use conferred a greater reduction in MI and mortality amongst older adults >75y. Systemic interventions for guideline implementation and optimal statin use in older adults with ASCVD should be explored further.
Abstract 16950: The Genetic Basis of Atrial Fibrillation in a Large-Scale Multi-Ancestry Sample
Authors: Weng Lu-Chen , Roselli Carolina , Rämö Joel , Treu Timothy M , Gunn Sophia , Wang Xin , Sun Yan , Pirruccello James , Nauffal Victor , Bapat Aneesh , Choi Seung H , Jurgens Sean J ,   AFGen consortium,   Million Veteran Program, Gudbjartsson Daniel , Holm Hilma , Stefánsson Kári , Surakka Ida , Willer Cristen , Lunetta Kathryn , Gaziano Michael , Cho Kelly , Wilson Peter , Ellinor Patrick T , Lubitz Steven A
Published: December 2023

Introduction:
Atrial fibrillation (AF) is a heritable arrhythmia and associated with substantial morbidity.

Hypothesis/Aims:
We sought to expand our understanding of the genetic basis of AF by examining a large and ancestrally diverse sample.

Methods:
We performed a meta-analysis of ancestry-specific GWAS results from 600K unrelated individuals (85K with AF) in the Million Veteran Program (MVP) with GWAS results from nearly 2.25 million individuals (267K with AF) in the Atrial Fibrillation Consortium (AFGen). We estimated genetic correlations across ancestry groups and traits in MVP. To evaluate GWAS loci, we examined possible gene functions, prioritized relevant genes and pathways, and explored potential drug targets. We derived a multi-ancestry polygenic risk score (PRS) and independently evaluated associations with AF in the All of Us cohort (nearly 100K individuals; 3K with AF).

Results:
We identified 376 loci associated with AF, including 63 that have not been reported. We observed closer genetic correlation of AF between individuals of European and Hispanic (r2=1.0) than with African ancestry (r2=0.6). AF is highly correlated genetically with multiple cardiovascular traits, especially coronary artery disease, heart failure, and hypertension. GWAS loci implicate 15 genetic regulators of the cardiac action potential, including targets of commonly used AF drugs and 2 potential therapeutic targets whose predicted cardiac expression is positively associated with AF risk (KCNJ5 and KCND3). A PRS derived from the meta-analysis outperforms all previously reported PRSs in European, African and Hispanic ancestry participants and is strongly associated with multiple cardiovascular outcomes.

Conclusions:
In the largest genetic study of AF to date, we identify disease-relevant pathways and improve polygenic prediction for AF. We demonstrate the importance of ancestry-specific analyses in assessing AF risk and suggest that further inclusion of participants from more diverse ancestries is likely to accelerate genetic discoveries.
Abstract 16954: Sex Differences in Cardiac and Vascular Function With Healthy Aging: Implications for Greater Risk of HFpEF in Women
Authors: Brazile Tiffany L , Wakeham Denis J , De Oliveira Gomes Diana , Hearon Christopher , Macnamara James P , Levine Benjamin D , Sarma Satyam
Published: December 2023

Introduction:
Mechanisms mediating the disproportionate risk for heart failure with preserved ejection fraction (HFpEF) in women are poorly understood. Impaired stroke volume (SV) reserve, increased afterload, arterial and left ventricular (LV) stiffness contribute to exercise intolerance in HFpEF. It is unknown whether subclinical changes in these measures predispose women to HFpEF; therefore, we compared resting and exercise cardiovascular structure and function across age in healthy men and women.

Methods:
We studied 192 sedentary normotensive, non-obese adults (53% female; age: 58 ± 13 [20-90] years) at rest, during sub- and maximal exercise. We measured systolic blood pressure (SBP; electrosphygmomanometry) and aortic stiffness (carotid-femoral pulse wave velocity; aPWV). Myocardial stiffness was assessed as the slope of individual pressure-volume (right heart catheterization-echocardiography) curves generated by graded LV loading and unloading. SV was calculated from cardiac output (Q˙c; C
2
H
2
rebreathe)/heart rate to assess afterload (Ea; SBP/SV) and SV reserve (% change from rest) during exercise. Data were compared via two-way ANOVA (age*sex).

Results:
There was no significant age*sex interaction for aPWV, SV reserve, resting or maximal SBP, or myocardial stiffness; however, there was a main effect for sex with higher myocardial stiffness in women (Figure). aPWV and SV reserve were not different between sexes (p=0.349, p=0.940). Maximal exercise SBP was lower in women, but a similar proportion of each sex had an exaggerated maximal exercise SBP (Men: >210; Women: >190 mmHg; 28% vs 35%, χ
2
=0.290). Peak exercise afterload was higher in women (Figure) due to lower SV.

Conclusions:
Increased risk for HFpEF in women may be driven in part by greater myocardial stiffness throughout the aging process. Sex related abnormalities in afterload were most prominent with exercise in women, which may predispose to LV hypertrophy and increased stiffness.
Abstract 16961: Characterization of Extracellular Vesicles and RNA Content and Its Relevance to Thrombo-Inflammatory Biomarkers in Patients With Acute Pulmonary Embolism
Authors: Siddiqui Fakiha , Zhang Chongyu , Nikolovski Srdjan , Kantarcioglu Bulent , Darki Amir , Hoppensteadt Debra , Saetern Lonnie , Tafur Alfonso J , Monreal Manuel , Jones Keith , Fareed Jawed
Published: December 2023

Introduction:
Pulmonary embolism (PE) is a complex disease with significant morbidity and mortality rates globally. Previous studies have shown that extracellular vesicles (EV) carrying disease specific ribonucleic acids (RNA’s) may contribute to pro-inflammatory and pro-coagulant state in VTE. This study aimed on profiling EV related parameters, RNA content, and thrombo-inflammatory markers in patients with acute PE compared to healthy individuals.

Materials & Methods:
Prospective cohort of patients with PE (n=72) were compared with normal healthy individuals (n=19) and further stratified by PE severity. Blood samples were collected under an IRB-approved project from Loyola University Chicago. Plasma samples were analyzed for the EV parameters, RNA parameters, and thrombo-inflammatory markers (D-Dimer, PAI-1, and CRP) respectively.

Results:
PE cohort includes 72 patients (41 male, and 31 female) with a median age of 67-years (interquartile range; IQR= 53-76), and a median body mass index (BMI) of 27.5-kg/m
2
(IQR= 24.7-35.7). Compared to controls, EV concentration, and EV/ng RNA were significantly (p= <0.05) lower, while D-Dimer, CRP and PAI-1 were significantly (p= <0.05) higher in patients with PE. In correlation analysis, varying levels of positive and negative correlations between the EV, and RNA parameters, and thrombo-inflammatory markers were noted (Figure 1). Upon stratification on PE severity, D-dimer was higher in massive PE compared to low-risk (p= 0.012), and sub-massive PE (p=0.036) respectively.

Conclusion:
These studies demonstrate significant changes in extracellular vesicles, RNA content and thrombo-inflammatory markers in acute PE patients compared to healthy controls. These changes may be due to the drivers of VTE pathogenesis or the result of a consumption process in acute PE. Further large scales studies on disease specific exosomes and RNA signatures are warranted to understand their relevance.
Abstract 16966: Temporal Trends and Race Differences in Catheter Ablation for Atrial Fibrillation Among Patients With Heart Failure With Reduced Ejection Fraction Before and After CASTLE-AF
Authors: Rosenblatt Anna , Segar Matthew W , Keshvani Neil , Link Mark S , Joglar Jose A , Fonarow Gregg C , Piccini Jonathan P , Pandey Ambarish
Published: December 2023

Background:
Catheter ablation (CA) for atrial fibrillation (AF) reduced the risk of all-cause death or heart failure (HF) hospitalization among patients with HF with reduced ejection fraction (HFrEF) in the CASTLE-AF randomized trial. The trends in utilization of CA for AF in the setting of HFrEF before and after CASTLE-AF and whether disparities in CA by race have changed over time have not been well studied.

Methods:
Patients with AF and HFrEF from the GWTG-AF registry from 1/2016-6/2022 were included. Temporal trends in AF ablation in the overall cohort and across self-reported race-ethnicity groups (Black, White, and other) were examined using linear regression models with generalized estimating equations accounting for within-hospital clustering. Change in ablation rates following the CASTLE-AF publication (2/1/2018) were assessed using interrupted time-series analysis with linear splines with knots at the time of publication.

Results:
Overall, 26,678 patients (71.3±12.6 years, 45.4% Female, CHADS-VASc 1.3±0.6, 80.4% White) were included in the cohort. In the pre-Castle-AF period ablation rates were 5.2% with significantly lower rates of ablation in Black and other race patients compared with White patients (2.6% vs. 3.0% vs. 5.8%, respectively). The rates of CA increased post-CASTLE-AF (overall: 21.8%) and for each race group (Black: 20.3%, White: 22.6%, Other: 16.8%;
Figure
) without significant difference in rate of increase across race groups (P-interaction for time*race = 0.82). Older age, female sex, non-White race, higher CHADS-VASc, and bleeding history were associated with less CA, while history of hypertension, obstructive sleep apnea, and the post-CASTLE-AF time period were associated with more CA.

Conclusion:
CA rates significantly increased post-CASTLE-AF among the entire cohort and across all race-ethnicity groups, however, non-White race was associated with lower utilization of CA over the entire period.
Abstract 16995: Distensibility and Aortic Growth Rate Predict Type B Aortic Dissection in Marfan Syndrome
Authors: Campello Jorge Carlos Alberto , Marway Prabhvir , Tjahjadi Nic , Knauer Heather , Patel Himanshu J , Figueroa C A , Burris Nicholas S
Published: December 2023

Introduction:
Marfan syndrome (MFS) is associated with high aortic growth rate (GR) and incidence of aortic dissection (AD), including delayed type B AD (TBAD) after prophylactic root repair. Elevated aortic stiffness has been investigated as a biomarker in MFS, but it remains uncertain how stiffness relates to GR and risk of AD. Vascular deformation mapping (VDM) is a technique that uses clinical CT angiography (CTA) to yield accurate, 3D maps of aortic growth over surveillance (VDM-G). This technique can also be used to assess aortic stiffness via quantification of cyclic wall stretch between systole and diastole (VDM-D) using multi-phasic dynamic CTA.

Research Question:
Is distensibility of the descending thoracic aorta associated with aortic GR or development of TBAD in MFS patients?

Goal:
The aim of this study was to analyze stiffness of the descending thoracic aorta in MFS and its association with aortic GR and occurrence of TBAD.

Methods:
We identified 36 adult MFS patients with dynamic CTA studies (>1 year interval) between 2004-2020. Growth was quantified by VDM-G, and linearized descending aortic stiffness by VDM-D - via calculation of distensibility - as the ratio of cyclic aortic surface area change (AR) over pulse pressure [(AR-1)/PP].

Results:
Patients were 38.9 ± 12.1 years old, 58% were male and 25 (69%) had prior ascending repair. Mean CT follow-up interval was 5.7 ± 3.4 years and 8 developed TBAD during follow-up with pre-dissection diameter of 31.12 ± 6.01 mm at tear location. Age (β -0.4, 95%CI: -0.07, -0.01, p=0.015) and baseline diameter (β 0.10, 95%CI: 0.02, 0.18, p=0.017 ) independently predicted GR on multivariable analysis, but distensibility did not (p=0.38). Both distensibility (OR 0.02, 95% CI: 0.00, 0.68, p=0.03) and GR (OR 8687.05, 95% CI: 1.43, 5x10^7, p=0.04) were independent predictors of TBAD during follow-up, but diameter was not (p=0.49).

Conclusion:
Aortic stiffness and growth rate are likely predictors of type B aortic dissection in MFS.
Abstract 17006: Clinical Characteristics and All-Cause Mortality After Non-Major Bleeding in Patients With Atrial Fibrillation Taking or Not Oral-Anticoagulant: The Fushimi AF Registry
Authors: Ishigami Kenjiro , Nakanishi Yumiko , Ikeda Syuhei , DOI KOSUKE , Yoshizawa Takashi , Hamatani Yasuhiro , Ide Yuya , Fujino Akiko , Ishii Mitsuru , Iguchi Moritake , Masunaga Nobutoyo , Esato Masahiro , Wada Hiromichi , Hasegawa Koji , Abe Mitsuru , Akao Masaharu
Published: December 2023

Background:
The use of oral anticoagulants (OAC) in atrial fibrillation (AF) patients increases the risk of bleeding. However, the relationship between OAC use before and after non-major bleeding and all-cause mortality remains unknown.

Purpose:
We aimed to investigate the association between OAC prescription before and after non-major bleeding and all-cause mortality in AF patients.

Method:
In the Fushimi AF Registry, follow-up data were available in 4,496 patients by the end of February 2022. Patients were divided into four groups based on OAC prescription before and after non-major bleeding: G1 (OAC prescribed both before and after), G2 (OAC prescribed before but not after), G3 (OAC not prescribed before but prescribed after), and G4 (OAC neither prescribed before nor after). Non-major bleeding was defined as all bleeding except for major bleeding according to the criteria of the International Society on Thrombosis and Haemostasis.

Result:
During the median follow-up of 1,448 days, 733 patients experienced non-major bleeding. G1 had 452 patients, G2 had 54, G3 had 63, and G4 had 164. G1 and G2 were more often non-paroxysmal AF and had significantly higher prevalence of previous stroke or systemic embolism, heart failure and dyslipidemia and had higher CHADS2 scores than G3 and G4. All-cause mortality after non-major bleeding occurred in 91 patients in G1, 54 in G2, 63 in G3, and 164 in G4. (G1: 5.1%, G2: 13.0%, G3: 7.1%, and G4: 6.8% per patient-year, p=0.0004). Multivariate analysis showed that the G2 group had a higher incidence of all-cause mortality as compared with G1 (HR 2.49, 95%CI 1.58-3.93; p<0.0001), G3 (HR 2.44, 95%CI 1.23-4.84; p=0.011), and G4 (HR 1.71, 95%CI 1.00-2.93; p=0.0502) [Figure].

Conclusion:
Discontinuation of OAC therapy after non-major bleeding in Japanese AF patients was associated with increased all-cause mortality.
Abstract 17015: Mitophagy Facilitates Cytosolic Proteostasis to Preserve Cardiac Function
Authors: Rawnsley David R , Islam Moydul , Ma Xiucui , Zhao Chen , Mendoza Adelita , Kumari Minu , Diao Jiajie , Kovacs Attila , Nigro Jess , Diwan Abhinav
Published: December 2023

Introduction:
Protein quality control (PQC) is critical for maintaining sarcomere structure and function in cardiac myocytes. Mutations in PQC pathway proteins, such as CRYAB (arginine to glycine at position 120, R120G) and BAG3 (proline to lysine at position 209, P209L), induce protein aggregates with cardiomyopathy in humans. Novel observations in yeast and mammalian cells demonstrate mitochondrial uptake of cytosolic protein aggregates. The functional relevance of this pathway in myocardial proteostasis is unknown.

Hypothesis:
We hypothesize that mitophagy removes cytosolic protein aggregates in cardiac myocytes.

Methods:
Mice with inducible cardiac myocyte specific ablation of TRAF2 (TRAF2icKO), which impairs mitophagy, were assayed for protein aggregates with biochemical fractionation and super-resolution imaging in comparison to floxed controls. Transgenic mice expressing R120G CRYAB (R120G TG) were subjected to both TRAF2 gain-of-function (with AAV9-cardiac Troponin T promoter-driven TRAF2 transduction) and TRAF2 loss-of-function (with tamoxifen-inducible ablation of one
Traf2
allele) in cardiac myocytes to determine the effect of mitophagy modulation on cardiac structure, function, and protein aggregate pathology.

Results:
Poly-ubiquitinated protein-rich aggregates accumulate in the cytosol and within mitochondria with desmin mislocalization in TRAF2icKO myocardium. CRYAB R120G and BAG3 P209L mutant proteins are taken up by isolated mitochondria. CRYAB R120G protein aggregates co-localize with damaged mitochondria and lysosomes by Coupa imaging, and accumulate in the mitochondrial fraction in R120G TG myocardium with upregulation of TRAF2 and induction of mitophagy. Adult-onset haplo-insufficiency of
Traf2
accelerated mortality (P=0.003), impaired left ventricular (LV) fractional shortening (P<0.001) and worsened mitochondrial morphology in R120G TG mice. AAV9-cTnT-TRAF2 transduction delayed mortality (P=0.027), rescued LV fractional shortening (P=0.039), reduced mitochondrial protein aggregates and improved desmin localization in R120G TG mice.

Conclusions:
Mitophagy facilitates removal of cytosolic protein aggregates and can be stimulated to ameliorate proteotoxic cardiomyopathy.
Abstract 17016: Mitral Valve Prolapse Induces Localized Left Ventricular Fibrosis in a Novel Large Animal Model
Authors: van Kampen Antonia , Morningstar Jordan , Nagata Yasufumi , GOUDOT Guillaume , Izquierdo-Garcia David , Caravan Peter , Guerrero Luis , Yaghoubian Koushiar , Woodcock Rebecca , Borger Michael A , Melnitchouk Serguei , Norris Russell A , Levine Robert A
Published: December 2023

Background:
Mitral valve prolapse (MVP) has recently been associated with localized left ventricular (LV) fibrosis linked to malignant arrhythmia and sudden cardiac death. However, fibrosis mechanisms remain unknown, with no large animal model to distinguish mechanical and genetic influences.
Goals:
We tested the hypothesis that surgically induced MVP leads to localized myocardial fibrosis in LV regions mechanically linked to the mitral valve, aiming to establish a reproducible large animal model of MVP as a platform for mechanistic studies.

Methods:
In 6 adolescent sheep, MVP was created surgically by replacing primary chordae tendineae to P2 with longer artificial chords. Intraoperative echocardiography and LV pressure-volume loops were obtained. After 7 months recovery, cardiac MRI with gadolinium and T1-mapping were done before end-of-study surgery with repeat echo and pressure-volume loops. Three sham surgery sheep were similarly studied. Myocardial samples from valve-linked papillary muscle and inferobasal LV and control septal regions were analyzed by histology. Bulk RNA was sequenced on samples from 3 MVP and 3 sham sheep.

Results:
All 6 MVP sheep showed pronounced localized LV fibrosis in valve-linked regions but not control regions on MRI, with replacement fibrosis by Masson’s trichrome stain. Sham sheep had no fibrosis, with similar LV function and contractility at end-of-study. RNA sequencing revealed gene expression differences between the two LV regions in MVP sheep and the valve-linked regions of MVP vs sham sheep.

Conclusions:
In a novel surgically created large animal model of MVP, localized fibrosis is induced in formerly healthy LV myocardium. This suggests a mechanical mechanism is sufficient to create the localized LV fibrosis associated with arrhythmia in MVP patients. This model provides a platform to study fibrosis mechanisms and investigate therapeutic approaches to avoid catastrophic events in MVP patients.
Abstract 17026: Predictors of Exercise Performance in Pediatric Heart Transplant Recipients
Authors: Curran Tracy , Pymm Jennifer , Yin Suellen M , Huang Yisong , Singh Tajinder P , Gauthier Naomi
Published: December 2023

Introduction:
Previous studies have shown that peak oxygen consumption (VO
2
) is impaired in pediatric heart transplant (HT) recipients compared to healthy controls. This impairment in exercise performance is variable among patients, however.

Research Question:
What are the predictors of exercise performance in pediatric HT recipients?

Aim:
To assess the association of demographic (age at HT, sex, BMI, diagnosis, duration since HT), echocardiographic (LV volume z-scores, ejection fraction), hemodynamic (cardiac index, filling pressures), hematologic (hematocrit) and pulmonary (FEV1, FVC) factors with percent predicted peak (ppp) VO
2
in pediatric HT recipients.
Methods
:
The first cardiopulmonary exercise test (CPET) performed in each HT recipient at our institution from 2003-2021 was assessed. Imaging, catheterization, and laboratory data closest in time to CPET were used. A multivariable linear regression model was developed to assess independent predictors of pppVO
2
.

Results:
Of 154 patients studied, 46% were female, age at HT was 9.6 ± 6 years, age at CPET was 15.4 ± 4.9 years, and time since HT was 5.8 ± 4.4 years. LV ejection fraction was 60 ±10%, pulmonary capillary wedge pressure was 12 ±4mmHg, FVC was 81 ±20% predicted, and mean pppVO
2
was 70 ± 18%. Multivariable analysis showed the age at transplant (β=-3.02/year, p<0.001) and duration since HT (β=-2.4/year, p=0.02) were significantly associated with pppVO
2.
No other clinical factors were significantly associated with pppVO
2
. Variability in pppVO2 among patients was mostly explained by the variability in ppp O2 pulse (Pearson correlation coefficient, r=0.88) and surprisingly, much less by variation in ppp heart rate (r=0.3).

Conclusions:
Older age at HT and longer duration since HT are both independently associated with lower pppVO
2
among pediatric HT recipients whereas all other clinical factors were not. Further research is warranted to explore changes in exercise performance in this patient population longitudinally. The stronger mechanistic correlate with ppp O2 pulse (surrogate for stroke volume) rather than with ppp heart rate suggests that interventions such as rehabilitation/exercise training may improve exercise performance in pediatric HT recipients.
Abstract 17029: Prospective Comparisons and Reference Ranges of Left Ventricular Global Longitudinal Strain by Contemporary Vendor-Neutral Echocardiography Software in Healthy Subjects
Authors: Arockiam Aro Daniela , Dong Tiffany , Agrawal Ankit , El Dahdah Joseph , Majid Muhammad , Rodriguez L L , Grimm Richard A , Popovic Zoran B , Griffin Brian P , Wang Tom Kai Ming
Published: December 2023

Background:
Left ventricular global longitudinal strain (LVGLS) by speckle-tracking is an established measure of left ventricular systolic function with many clinical applications. Most strain software traditionally can only analyze strain on scans of the same vendor, however recent advances have allowed them to analyze all scans, although external validation studies are lacking. We aimed to determine the normal ranges and compare two-dimensional LVGLS measurements by contemporary strain software in a healthy prospective cohort.

Methods:
One-hundred healthy subjects undergoing transthoracic echocardiography during January-April 2023 at our institution were prospectively recruited, 20 per age-group, 50% were female, and 50%GE and 50% Philips scans. TomTec version 51.02 (Autostrain LV), EchoPAC version 206 (AFI) and VVI software were utilized to quantify two-dimensional LVGLS in all patients for comparative and regression analyses.

Results:
Means (and lower limits of normal)±standard errors LVGLS were -17.1±0.2% (-13.2±0.3%) by TomTec, -17.8±0.3% (-12.7±0.4%) by EchoPAC and -16.3±0.3% (-11.0±0.5%) by VVI, with significant differences on all pairwise T-tests of means (P<0.001-0.017). Means±standard errors LVGLS by strain software for each subgroup are listed in the Table. In multivariable linear regression analyses, factors significantly associated with LVGLS measurements with their beta-coefficients (95%CI) were heart rate (per 1 bpm) 0.05 (0.01-0.07) for TomTec; male sex 1.19 (0.13-2.26) and diastolic blood pressure (per mmHg) 0.06 (0.00-0.12) for EchoPAC; and body mass index (per kg/m
2
) 0.12 (0.01-0.22) with VVI.

Conclusion:
All three contemporary strain software demonstrated vendor-neutral properties to measure LVGLS on both GE and Philips scans, with means and lower limits of normal determined, and notably, factors affecting LVGLS values differed by software vendor.
Abstract 17032: Association of Blood Pressure Patterns During Pregnancy With Incident Hypertension and Cardiovascular Disease Risk at 2-7 Years After Delivery: The nuMoM2b Heart Health Study
Authors: Cameron Natalie A , Huang Xiaoning , Petito Lucia C , McNeil Rebecca B , Varagic Jasmina , Catov Janet M , Bairey Merz MD, FACC, FAHA, FESC C Noel , Chung Judith , Haas David , Levine Lisa , Saade George , Silver Robert , Reddy Uma , Mercer Brian , Yee Lynn , Greenland Philip , Grobman William , Khan Sadiya S
Published: December 2023

Introduction:
Hypertensive disorders of pregnancy (HDP) are risk factors for cardiovascular disease (CVD). However, associations between subclinical blood pressure (BP) elevations in pregnancy and CVD risk are unknown.

Aims:
To identify BP patterns during pregnancy among individuals without HDP and determine their association with long-term CVD risk and hypertension (HTN) 2-7 years after delivery.

Methods:
We included nulliparous individuals from the prospective, multicenter nuMoM2b Study Heart Health Study (nuMoM2b-HHS) who had
>
1 BP from each trimester, and excluded those with chronic HTN or HDP. We modeled patterns using group-based trajectory analysis of the mid-BP (average of systolic and diastolic BP) during pregnancy. We selected the final number of groups based on the Bayesian Information Criteria. At 2-7 years after delivery, 30-year predicted CVD risk was estimated using the Framingham risk score; incident HTN was defined as BP
>
130/80. Generalized linear models estimated associations between mid-BP trajectory group and CVD risk, adjusting for sociodemographics, adverse pregnancy outcomes, and first-trimester mid-BP.

Results:
Of 3309 participants, mean age was 27.1 (SD 5.5) years. Five mid-BP groups were identified (
FIGURE
). Incident HTN at mean follow-up of 3.7 years after delivery was 4.2% in low-stable, 11.1% moderate-stable, 21.4% moderate-decreasing, 21.8% moderate increasing, and 44.2% in elevated-stable groups. Compared with the moderate-stable group, adjusted 30-year predicted CVD risk was significantly higher by 0.8% (0.4, 1.1), 1.6% (0.9, 2.3) and 2.6% (2.1, 3.1) in the moderate-decreasing, moderate-increasing and elevated-stable groups, respectively.

Conclusions:
Among people not meeting HDP criteria, but with elevated mid-BP during pregnancy, nearly half had HTN within 5 years after delivery, and long-term CVD risk was higher. Mid-BP elevations during pregnancy may inform long-term CVD risk even in the absence of HDP.
Abstract 17035: Relationship Between Neighborhood Level Deprivation and Blood Pressure Among 122,177 Adolescents, Analysis of PEDSnet Data
Authors: Baker-Smith Carissa M , Zhang Zugui , Eckrich Dan , Prospero Carol , Zadokar Varsha , Falkner Bonita E , Akins Robert E
Published: December 2023

Introduction:
Hypertension (HTN) begins in youth and accounts for ~80% of the cardiovascular disease burden in the US. Socio/environmental factors are critical, and greater knowledge of the relationship between neighborhood level deprivation and blood pressure (BP) in youth is needed.

Hypothesis:
We hypothesized that greater neighborhood deprivation is associated with intermediate/poor BP status in adolescents even after adjusting for other factors.

Methods:
Data from 2009 to 2019 were extracted from PEDSnet (a PCORI-funded aggregate of pediatric health data). We modeled the relationship between BP and neighborhood deprivation based on national Area Deprivation index (ADI; scaled 1-100) tertiles (ADI<25=best/low, 25-52,
>
52=worst/high). The BP status of each youth was coded as good (BP score: 80-100) or intermediate/poor (BP score: 0-80) where BP score=100 if median BP <120/80mmHg and score=75 if median BP 120-129/<80mmHg. Analyses were carried out using SAS 9.4 with
p<0.05
considered significant. The outcome of interest was poor/intermediate BP score.

Results:
Data from 122,177 youth, 13-17 years of age were analyzed. 51% were female, 58% were non-Hispanic white, and 22% non-Hispanic Black. 24% lived in neighborhoods with ADI <25; 35% lived in neighborhoods with ADI
>
52. In a multivariate logistic model, ADI
>
52 was associated with a 49% greater odds of intermediate/poor BP score. Due to significant interactions between ethnicity-race and ADI, compared to non-Hispanic Black youth, non-Hispanic White and Other youth had lower odds of intermediate/poor BP score by univariate analysis, but greater odds in the full model (Table). Female sex was associated with lower odds of HTN. The model’s goodness of fit was strong with a ROC, AUC of 0.73 (Figure).

Conclusions:
Higher neighborhood deprivation is associated with greater odds of hypertension in adolescents. Greater emphasis on measures to mitigate this risk are needed.