bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10314: Post-GWAS Functional Genomics Analysis of CBLN2 Locus to Define the Pathogenic Role of CUX1 in Pulmonary Arterial Hypertension
Authors: Sun Wei , Jiang Danli , Wu Ting , Zou Meijuan , Li Gang , Chan Stephen Y
Published: March 2022

Introduction:
Pulmonary arterial hypertension (PAH) is a rare but morbid disease and highly relevant to genetic susceptibility. Genome-wide Association Studies (GWAS) have identified 12 SNPs on 9 PAH- associated loci. However, GWAS is unable to identify the causative functional SNPs (fSNP) or define the mechanisms by which a fSNP regulates the risk gene expression.

Methods:
We developed a novel functional genomics analysis to identify PAH-associated fSNPs. It includes Reel-seq (Regulatory element-sequencing), an EMSA-based high-throughput technique, to identify fSNPs in a synthetic DNA library containing PAH-associated SNPs; SDCP-MS (SNP-specific DNA competition pulldown-mass spectrometry) to identify proteins that specifically bind to fSNPs; and AIDP-Wb (allele-imbalanced DNA pulldown-Western blot) to show allele-imbalanced binding of these proteins to fSNPs. The regulation of risk gene expression by these fSNP-binding proteins was determined in PAECs and confirmed in PAH patients.

Results:
By Reel-seq, rs11151770 is identified a fSNP in the CBLN2 locus, and its risk allele A is associated with a 1.97-fold increase in PAH susceptibility. By using SDCP-MS and AIDP-Wb, transcription factor CUX1 was found to specifically bind to this fSNP, with higher affinity to the risk allele A than non-risk allele G, thus controlling the expression of CBLN2. CUX1 knockdown prevented, but CUX1 overexpression induced, the pathophenotypes in PAECs that are associated with PAH. CUX1-CBLN2 was upregulated by the acquired PAH trigger IL-1β, and was also increased in PAH lungs. Genotyping of this fSNP showed a 2.1-fold risk allele A enrichment in PAH patients associated with connective tissue disorders, supporting a pathogenic mechanism of an inflammation-sensitive pathway (CUX1-CBLN2) combined with a PAH susceptible genotype (risk allele A) for the manifestation of clinical PAH.

Conclusion:
We demonstrate that CUX1 regulates the expression of target gene CBLN2 via binding to fSNP rs11151770. Alteration of CBLN2 expression, in turn, controls crucial endothelial function relevant to PAH. These results identify a novel role of CUX1 in PAH, clarifying the pathogenic function of this PAH-associated locus and providing a potential target for PAH intervention.
Abstract 10322: Mental Health Conditions Are Associated with Underuse of Rhythm Control Therapies in Patients with Atrial Fibrillation: The FinACAF Study
Authors: Teppo Konsta , Jaakkola Jussi , Airaksinen Juhani , Biancari Fausto , Halminen Olli , Putaala Jukka , Mustonen Pirjo , Haukka Jari , Hartikainen Juha , Kinnunen Janne , Tiili Paula , Linna Miika , Lehto Mika
Published: March 2022

Introduction:
Mental health conditions (MHCs) have been associated with undertreatment of unrelated medical conditions, but whether patients with MHCs face disparities in receiving antiarrhythmic therapies (AATs) for atrial fibrillation (AF) is currently unknown. We assessed the hypothesis that MHCs are associated with decreased use of AATs.

Methods:
The FinACAF cohort included records on all AF patients in Finland during 2007-2018 identified from nationwide registries covering all levels of care as well as their drug purchases. The main exposure was any MHC (previous diagnosis of depression, bipolar disorder, anxiety disorder or schizophrenia or fulfilled prescription of psychiatric medication within preceding year from first AF diagnosis) and the main outcome was use of any AAT, including cardioversion, catheter ablation, and fulfilled antiarrhythmic drug (AAD) prescription.

Results:
We identified 239 222 patients with incident AF and the prevalence of any MHC was 19.9%. Mean age was 72.6 years (SD 13.2). Lower overall rate of any AAT use was observed in patients with any MHC than in those without MHC (16.9% vs. 22.9%, p<0.001). Cumulative five-year incidence curve of any AAT is presented in Figure 1. Any MHC was associated with decreased use of any AAT, AADs, cardioversion and catheter ablation (adjusted hazard ratios (aHR) 95% CI 0.804 (0.784-0.823), 0.870 (0.839-0.902), 0.784 (0.762-0.806) and 0.832 (0.771-0.899), respectively). Depression, bipolar disorder, anxiety disorder and schizophrenia were individually associated with decreased use of any AAT (aHR 95% CI 0.879 (0.837-0.922), 0.871 (0.760-0.998), 0.786 (0.731-0.845), and 0.423 (0.358-0.500), respectively). A lower rate of AAT use was observed in patients with MHC across the study period and no meaningful temporal change was noted in the MHC related deficit.

Conclusions:
MHCs are associated with decreased use of rhythm control therapies in patients with AF.
Abstract 10326: Do Veterans Having Superficial Femoral Artery Revascularization Have Worse Disease and Poorer Long-Term Outcomes Than Non-Veterans?
Authors: Kinlay Scott , Todoran Thomas , Ostrowski Simon , Sherrod Rebecca , Andrew Eisenhauer , Sobieszczyk Piotr
Published: March 2022

Introduction:
Veteran Affairs (VA) patients may have higher risk factors and worse outcomes after peripheral revascularization compared to patients treated in non-VA facilities.

Hypothesis:
Compared to non-VA patients, VA patients have higher rates of risk factors and poorer outcomes after superficial femoral artery (SFA) endovascular revascularization.

Methods:
We assessed long-term outcomes in all patients having SFA endovascular revascularization between 2003-2010 in 2 regional referral institutions in Boston, one a VA hospital (VA Boston) and the other a non-VA hospital (Brigham and Women’s Hospital). Atherosclerosis risk factors, lesion characteristics, and outcomes of death, repeat revascularization, and limb amputation were assessed by review of the chart and national death indices. The hazard ratio and 95% confidence interval (HR, 95%CI) of death and adverse limb events for VA versus non-VA patients were assessed by Cox proportional hazard models.

Results:
Of the 203 subjects, 88 were VA patients and 115 were non-VA patients and 254 limbs were revascularized. VA and non-VA patients had a similar mean age (68 vs 68 years, p=0.74), and aspirin and statin use were over 90% in both groups. VA patients had a higher prevalence of diabetes (59% vs 41%, p=0.011) and current smoking (36% vs 18%, p=0.006). The prevalence of limbs with critical limb ischemia was similar (VA: 20% vs Non-VA: 17%, p=0.51), but limbs in VA patients were more likely to have TASC C or D lesions (57% vs 43%, p=0.028), and lesions > 200mm in length (44% vs 31%, p=0.044). Over an average 5.1 years follow-up, 96 patients died and 82 limbs required repeat revascularization. Compared to non-VA patients, VA patients had similar risks of death (HR=0.91, 95%CI=0.55, 1.49) and repeat revascularization (HR=1.1, 95%CI=0.67, 1.75). 17 limbs required subsequent surgical revascularization and 16 limbs had minor or major amputation with similar rates in both groups. Multivariable models showed similar results.

Conclusion:
In this comparison, VA patients having SFA endovascular revascularization had a higher prevalence of some atherosclerosis risk factors and more complex lesion characteristics, but similar long-term outcomes over an average 5 years.
Abstract 10328: Eicosapentaenoic Acid versus Mixed Eicosapentaenoic/Docosahexaenoic Acid Added to Statin Therapy for Reducing Plaque Volume in Coronary Atherosclerosis: A Systematic Review and Meta-Analysis of Prospective Randomized Trials
Authors: Sheppard John P , Lakshmanan Suvasini , Dahal Suraj , Kinninger April , Roy Sion K , Bhatt Deepak L , Budoff Matthew J , Nelson John R
Published: March 2022

Introduction:
Multiple trials demonstrate efficacy of eicosapentaenoic acid (EPA) for lowering cardiovascular risk. Imaging studies suggest this benefit may relate to measurable effects on coronary plaque. Interestingly, EPA mixed with docosahexaenoic acid (DHA) has largely failed to show clinical benefit. The differential effects of EPA and EPA/DHA on coronary plaque burden and characteristics, including prognostically significant features such as lipid volume, remain unclear.

Methods:
We performed a systematic review of clinical trials that longitudinally measured coronary plaque volume in patients randomized to statin+EPA or statin+EPA/DHA versus statin alone, and performed network meta-analysis to estimate the standardized mean difference (SMD) of these treatments in percent change of total plaque volume and plaque lipid volume.

Results:
Ten trials comprising 860 patients met inclusion criteria among 535 articles. Four studies used intravascular ultrasound, three used coronary CTA, and three used optical coherence tomography. Among statin, statin+EPA, and statin+EPA/DHA treatments, random effects analysis yielded changes of +1.7% [-2.8%, +6.3%], -11.0% [-20.7%, -1.3%], and -3.4% [-14.5%, +7.8%] in total plaque volume and +3.1% [-1.6%, +7.8%], -19.8% [-27.5%, -12.1%], and -6.4% [-20.3%, +7.5%] in plaque lipid volume. Compared with statin, statin+EPA achieved greater percent reduction in coronary plaque volume (total volume: SMD = 0.92,
P =
0.002; lipid volume: SMD = 1.04,
P
= 0.003) but statin+EPA/DHA showed no difference (total volume: SMD = 0.19,
P
= 0.58; lipid volume: SMD = 0.42,
P =
0.38).

Conclusions:
In this most up-to-date meta-analysis, EPA as an adjunct to statins is associated with significant reductions in coronary plaque burden, including plaque lipid volume - unlike EPA/DHA combinations. These differential effects on coronary atherosclerosis offer mechanistic insights to observed clinical benefits of statin+EPA therapy.
Abstract 10331: Caring for Heart Failure with Confidence: Better Preparation and Training Determine Home Health Aide Self-Efficacy
Authors: Stawnychy Michael A , Ringel joanna , Riegel Barbara , Sterling Madeline R
Published: March 2022

Background:
Over 3 million home health and personal care aides (HHA) provide essential support for adults with chronic illness, including the complex self-care needs of adults with HF. Self-efficacy has been shown to mediate HHAs’ preparedness for caregiving and contribution to HF self-care. The determinants of HHA self-efficacy are unknown.

Aim:
Identify the determinants of HHAs’ self-efficacy in contributing to HF self-care.

Methods:
Secondary analysis of a cross-sectional survey (n=328) that examined the influence of HHA characteristics on contributions to HF self-care. Self-efficacy in contributing to patient HF self-care was assessed using the 10-item Caregiver Self-Efficacy in Contributing to Self-Care Scale. Standardized scores range 0-100; scores ≥ 70 pts indicate adequate self-efficacy. Preparedness was assessed with the 8-item Caregiver Preparedness scale. Additional predictors included job satisfaction, HHA experience, prior HF training, and agency size. Participants were divided into two groups based on a self-efficacy cutoff score of 70 points: low self-efficacy (< 70 pts) vs adequate self-efficacy (≥ 70 pts). Poisson regression with robust standard errors, adjusted for sociodemographic variables, was used to estimate prevalence ratios with 95% confidence intervals (PR [95% CI]) to identify determinants of adequate self-efficacy.

Results:
HHAs with adequate self-efficacy came from smaller and medium sized agencies (92% vs 84%,
p
=.049), and cared for either fewer than 6 (78% vs 68%,
p=.002
) or > 10 HF patients (11% vs 8%,
p=.002
). They had at least some prior HF training (55% vs 17%,
p
<.001), felt better prepared for caregiving (4.55±0.50 vs 3.39±0.85,
p
<.001), and were more satisfied with their jobs (90% vs 77%,
p
=.003). In a fully adjusted model, significant determinants for adequate self-efficacy were length of employment (1.02 [1.00-1.03],
p
=.027), better preparation for caregiving (3.10 [2.42-3.96],
p
<.001), and more HF training (1.48 [1.20-1.84],
p
<.001).

Conclusion:
Preparation for caregiving and HF training were the strongest determinants of HHAs’ caregiving self-efficacy. Home care agencies and policy-makers can target these modifiable determinants to improve this workforces’ ability to care for HF patients.
Abstract 10334: The Association of Trimethylamine N-oxide (TMAO) with Findings of Vascular Brain Injury on Magnetic Resonance Imaging in the Cardiovascular Health Study (CHS)
Authors: Dahal Suraj , Shi Peilin , Wang Meng , Longstreth Will , Lai Heidi , Lemaitre Rozenn , Siscovick David S , McKnight Barbara , Fretts Amanda M , Otto Marcia D , Sotoodehnia Nona , Tang W. H. Wilson , Hazen Stanley L , Mozaffarian Dariush , Budoff Matthew J
Published: March 2022

Introduction:
Findings on MRI of vascular brain injury, such as brain infarcts and white matter hyperintensities, are chronic manifestation of atherosclerosis. A gut-microbiome-generated metabolite, trimethylamine N-oxide (TMAO), is an independent predictor of clinical cardiovascular events. However, no study has examined associations between TMAO and subclinical vascular brain injury in the general population.

Hypothesis:
TMAO levels are positively associated with evidence of progressive subclinical vascular brain injury on serial MRI scans with incident brain infarcts and white matter worsening.

Methods:
The Cardiovascular Health Study (CHS) is a community-based prospective cohort study in adults aged >65 years. Plasma TMAO was measured using mass spectrometry from samples collected in 1992-1993 and 1996-1997. Brain MRI was performed at 1991-1994 and again at 1997-1999. White matter was graded on a 10-point scale, higher being worse, and white matter worsening (WMW) was defined by an increase of least one point comparing initial and follow up scans. In these analyses, participants with prior TIA or stroke were excluded. Those with serum TMAO and both MRI scans were included: n=1196 for incident brain infarct and n=1553 for white matter worsening. Logistic regression was used for the association of baseline TMAO levels and incident brain infarcts, and Poisson regression, for the change in TMAO levels and WMW. Models were adjusted for age, sex, race, alcohol use, intake of meat and vegetable, and vascular risk factors.

Results:
Between the two MRI scans, 191(15.9%) participants had subclinical incident brain infarcts, and 423 (27.2%) participants had WMW. Comparing the highest vs. lowest quartile, the first TMAO were not significantly associated with incident brain infarcts: odds ratio 0.78 (95% CI: 0.49 to 1.25). Again comparing the highest vs. lowest quartile, changes in TMAO were not associated with WMW: 1.08 (0.77 to 1.51).

Conclusions:
Baseline and changes in plasma TMAO levels were not associated with findings of subclinical vascular brain injury on MRI in older US adults. The associations of TMAO with the adverse clinical events seen in prior clinical samples of patients were not seen at the subclinical level in our population-based study.
Abstract 10335: Increased Left Atrial Minimum Volume Index is Associated with Low Left Atrial Appendage Emptying Velocity
Authors: Jia Kelly , Shah Ravi , Park Robert , Mcconkey Nathaniel , Malamas Peter , Plamenac Jovan , Gonzalez Mario D , Naccarelli Gerald , Maheshwari Ankit
Published: March 2022

Background:
Increased left atrial minimum volume indexed by body surface area (LAVImin) is a risk factor for ischemic stroke. The mechanism underlying this association is not well defined.

Hypothesis:
We hypothesized that increased LAVImin is associated with low left atrial appendage emptying velocity (LAAV).

Methods:
We reviewed medical records of 167 patients who underwent transesophageal echocardiography (TEE) within twelve months of transthoracic echocardiography (TTE), which was obtained during sinus rhythm, in a tertiary care medical center from 2017 to 2020. We used the student’s T-test to compare the means of continuous variables. We used logistic regression analysis to estimate the odds ratio of LAVImin (per unit increase) for low LAAV (≤40 cm/s) adjusting for CHA
2
DS
2
VASc variables and heart rate during TEE. We also stratified our analysis by rhythm during TEE.

Results:
In our final cohort, patients with LAAV≤40 cm/s and LAAV>40 cm/s had a mean (SD) LAVImin of 27.6 (16.6) ml/m
2
and 20.3 (12.0) ml/m
2
, respectively (P=0.003). In our subgroup of sinus rhythm TEEs, patients with LAAV≤40 cm/s and LAAV>40 cm/s had a mean (SD) LAVImin of 22.5 (12.8) ml/m
2
and 20.0 (12.4) ml/m
2
, respectively (P=0.30). In our subgroup of atrial fibrillation TEEs, patients with LAAV≤40 cm/s and LAAV>40 cm/s had a mean (SD) LAVImin of 39.0 (19.7) ml/m
2
and 23.7 (10.6) ml/m
2
, respectively (P=0.01). LAVImin was independently associated with low LAA emptying velocity. When stratified by rhythm during TEE, this association was only significant for patients in atrial fibrillation (OR 1.17 [1.06-1.39], p<0.01), and not in sinus rhythm (OR 0.99 [0.96-1.03], p= 0.75).

Conclusion:
The association between increased LAVImin and low LAAV is dependent on heart rhythm.
Abstract 10338: A Junctophilin-2-Mitofusin-2 Interaction Links T-Tubule Remodeling to Mitochondrial Dysfunction in Pulmonary Arterial Hypertension-Mediated Right Ventricular Failure
Authors: Prisco Sasha Z , Eklund Megan , Hartweck Lynn , QUICK Ann , Lahiri Satadru K , Wehrens Xander H , Prins Kurt W
Published: March 2022

Introduction:
Junctophilin-2 (JPH2) plays a crucial role in t-tubule structure/function and gene regulation in cardiomyocytes. In addition, JPH2 downregulation causes mitochondrial dysfunction and mitofusin-2 (MFN2) dysregulation, but the link between JPH2 and mitochondria is undetermined. Here, we investigated the hypothesis that a direct JPH2-MFN2 interaction is important for mitochondrial regulation and subsequent right ventricular (RV) function in pulmonary arterial hypertension (PAH).

Methods and Results:
Confocal microscopy revealed JPH2 and MFN2 colocalized at t-tubules in isolated cardiomyocytes. Immunoprecipitation demonstrated JPH2 and MFN2 interacted in RV extracts. Pulldown experiments showed JPH2 directly bound MFN2, and that the MFN2 binding domain was localized to the N-terminal third of JPH2. To probe the importance of the JPH2-MFN2 interaction for RV function, we compared the effects of treatment with AAV9-JPH2 to AAV9-GFP in monocrotaline-induced PAH. Consistent with its known role in t-tubule homeostasis, AAV9-JPH2 normalized RV t-tubule architecture. Interestingly, transmission electron microscopy showed AAV9-JPH2 corrected RV mitochondrial morphology. Immunoblots of RV extracts demonstrated AAV9-JPH2 increased JPH2 and MFN2 expression, which may underlie the restoration of mitochondrial morphology. At the organ level, AAV9-JPH2 reduced RV cardiomyocyte hypertrophy and RV fibrosis. AAV9-JPH2 increased tricuspid annular plane systolic excursion and RV free wall thickening as quantified by echocardiography. Pressure-volume loop analysis showed AAV9-JPH2 augmented RV ejection fraction and right ventricular-pulmonary arterial coupling and lowered RV end diastolic pressure and tau. Importantly, the improvements in RV systolic and diastolic function were independent of altering PAH severity as RV systolic pressure, effective arterial elastance, and pulmonary arterial small vessel remodeling were not altered with AAV9-JPH2.

Conclusions:
Disruption of the JPH2-MFN2 interaction may link altered t-tubule structure to mitochondrial dysfunction in the compromised RV. Strategies to increase JPH2 expression could have therapeutic value for RV failure.
Abstract 10345: Video-Based Deep Learning Model for Automated Assessment of Ejection Fraction in Pediatric Patients
Authors: He Bryan , Ouyang David , Lopez Leo , Zou James , Reddy Charitha D
Published: March 2022

Introduction:
Echocardiographic assessment of left ventricular (LV) systolic function by ejection fraction (EF) is crucial for diagnosis and monitoring in pediatric patients. EF requires manual tracing of the LV but measurement reproducibility is affected by diverse phenotypes, image quality, and operator skill. We sought to train a deep learning model (EchoNet-Peds) on a pediatric-specific video dataset to automatically segment the LV and estimate EF by 5/6 Area Length (AL) using two common views, the apical 4 chamber (A4C) and parasternal short axis (PSAX).

Methods:
EchoNet-Peds evaluated raw A4C and PSAX videos to segment the LV and predict the EF from the A4C and PSAX views. Eighty percent of the dataset was used for algorithm training, 10% for validation, and 10% for testing. We used the training set to predict the EF by AL, determined hyperparameters from the validation set, and reported results using 10-fold cross-validation on the test set.

Results:
The dataset included 1923 children (43% female) with 4400 echocardiogram studies. EFs ranged from 10% to 81% (61% ± 10.1) and ages from 0 to 18 years (10 ± 5.4 years). EchoNet-Peds achieved Dice Similarity Coefficients of 0.901 (0.895 - 0.907) and 0.887 (0.879 - 0.895) for segmenting the LV in A4C and PSAX views respectively. The A4C view predicts an EF by AL with an R2 of 0.73 (0.67 - 0.77) and the PSAX view predicts an R2 of 0.74 (0.70 - 0.77). Combining both predictions results in an overall R2 of 0.78 (0.74 - 0.81). The model performs well when stratified by sex, age, and body surface area (BSA), and improves in younger patients and lower BSA (Figure 1 b-d).

Conclusions:
EchoNet-Peds is the first demonstration that AI trained on a pediatric-specific dataset utilizing multiple views can accurately segment the LV and predict EF. The automated functionality of EchoNet-Peds can be used for real-time assessment of cardiac function despite pediatric heterogeneity.
Abstract 10361: Cardiovascular Risk Factor Control and Treatment Across the Spectrum of Patients with Atherosclerotic Cardiovascular Disease: The Precision Medicine Initiative - All of Us Study
Authors: Gong Yufan , Wong Nathan D
Published: March 2022

Objective:
The 2018 Multisociety Cholesterol Guideline categorized patients with atherosclerotic cardiovascular disease (ASCVD) according to very high risk status, but there are few reports of recent medication use and risk factor control by risk group. We examined in a current cohort of US adults the extent of ASCVD risk factor control and treatment by these ASCVD groups.

Methods:
The NIH Precision Medicine Initiative (All of Us Study) is an ongoing program aiming to enroll
>
1 million adults across the US. Since May 2018, >315,000 participants have been recruited from >340 sites nationwide, oversampling underrepresented groups. We studied adults age
>
18 years with prior ASCVD, classified based on the 2018 guideline as 1) very high risk with
>
2 major ASCVD events, 2) very high risk with 1 major event and
>
2 major ASCVD conditions, or 3) ASCVD not at very high risk. We examined proportions at recommended therapies (high intensity statin, blood pressure [BP] and diabetes [DM] medication, and aspirin) and desired levels of risk factors (LDL-C, BP, HbA1c, and non-smoking status) across ASCVD risk categories.

Results:
Our 34,195 participants with ASCVD included 49% female, 20.5% non-Hispanic Black and 12.9% Hispanic or Latino adults, with an overall age of 66.0
+
12.4 years. 44.6% were classified as very high risk, of which 10.8% had
>
2 prior ASCVD evets. The table shows the proportion of each risk group on recommended therapies and risk factor targets. Across ASCVD risk groups use of high intensity statins (10-14%) and attainment of acceptable LDL-C levels (17-27%) and BP levels (42-47%) are markedly suboptimal. Across risk groups only 3-8% were on all 4 recommended therapies and <5% were at all desired levels of all 4 risk factors.

Conclusions:
Improved efforts are needed to communicate the importance of multiple risk factor control and recommended therapies across the spectrum of ASCVD patients, and especially those at very high risk.
Abstract 10362: Association of Sex and Age with Mortality in Stemi Patients Without Standard Modifiable Risk Factors: Analysis from Nationwide Readmission Database
Authors: Jang Sun-joo , Yeo Ilhwan , Goyal Parag , Cheung Jim W. , Feldman Dmitriy N. , McCullough Stephen , Krishnan Udhay , Narotsky David , Singh Harsimran S , Minutello Robert M , Bergman Geoffrey , WONG Shing-chiu , Kim Luke K.
Published: March 2022

Introduction:
The proportion of STEMI patients without standard modifiable cardiovascular risk factors (SMuRFs: hypertension, diabetes mellitus, hypercholesterolemia and smoking) has increased over time. However, outcomes of STEMI patients without SMuRFs are not well known.

Hypothesis:
To test the hypothesis that age and sex would have a significant impact on mortality after STEMI in the absence of SMURFs.

Methods:
Patients who underwent primary PCI after STEMI were identified from the Nationwide Readmission Database. Clinical characteristics, in-hospital and 30-day mortality in STEMI patients with or without SMuRFs were compared in men and women stratified into 5 age groups (<50, 50 to 59, 60 to 69, 70 to 79 and ≥80 years of age).

Results:
Between January 2010 and November 2014, 54,665 (11.3%) of 482,947 patients, who underwent primary PCI for STEMI, did not have pre-existing SMuRFs. Absence of SMuRFs was more common in men than women (11.4% vs 9.8%, p<0.001) across all age groups, and patients without SMuRFs had higher in-hospital mortality rates than those with SMuRFs . Among those without SMuRFs, in-hospital mortality rate was significantly higher in women than men (13.5% vs 9.3%, p<0.001) accross all age groups and was increased with advanced age groups. In addition, absence of SMuRFs was associated with higher 30-day mortality rates than those with SMuRFs (0.5% vs 0.3%, p<0.001). Among patients without SMuRFs, women had higher 30-day mortality than men (0.7% vs 0.5%, p<0.001). The increased risk of in-hospital (Odds Ratio [OR] 2.02, 95% CI 1.87 to 2.20) and 30-day mortality (OR 1.40, 95% CI 1.11 to 1.78) in patients without SMuRFs remained significant after multivariate adjustment.

Conclusions:
Patients presenting with STEMI without SMuRFs have a significantly higher risk of in-hospital mortality and 30-day mortality compared with those with SMuRFs. Women and older age group without SMuRFs experienced more frequent in-hospital mortality and 30-day mortality.
Abstract 10366: Comparative Evaluations of Six Risk Scores Proposed for Baseline Prediction of Atrial Fibrillation Recurrence Post Catheter Ablation
Authors: Tang Lisa Y , Hawkins Nathaniel , Macle Laurent , Ho Kendall , Tam Roger , Deyell Marc , Lim Michael , Khairy Paul , Andrade Jason
Published: March 2022

Background:
Being able to identify patients who are at risk of arrhythmia recurrence following catheter ablation is important for prognostication, shared-decision making, etc. While numerous predictive models for atrial fibrillation recurrence (AFR) have been proposed, few models have underwent external validation, and few studies compared multiple models using the same patient cohort.

Aims:
To evaluate six prediction models using an external dataset.

Methods:
Data from 632 patients was pooled from two independent clinical trials that enrolled patients with anti-arrhythmic drug refractory atrial fibrillation who underwent catheter ablation. Primary outcome for both trials was documented atrial tachyarrhythmia (atrial fibrillation/flutter/tachycardia as adjudicated by a clinical committee blinded to treatment strategy). We compared 6 models for predicting AFR recorded between days 91-365 post ablation using standard metrics and ranked them according to the positive and negative clinical utility indices.

Results:
As the figure shows, the top performing model was CHA2DS2-VASc, followed by DR-FLASH, albeit both achieved positive and negative predictive values lower than 65%. Many models achieved high specificity but low sensitivity, except for CAAP-AF, which achieved high sensitivity but low specificity. In summary, all achieved area under receiver operating characteristic curve lower than 56% and were deemed to have poor clinical utility (less than 0.5 out of 1) when evaluated on our dataset.

Conclusion:
All models performed poorly and had objectively limited clinical utility. There remains a need to develop generalizable tools for predicting post ablation AFR.
Abstract 10367: An Unusual Vasodilator Response: Recognizing a Rare Subtype of Pulmonary Arterial Hypertension
Authors: Hyland Patrick M , Diamond Jamie , Theodore Miranda , Garan Arthur Reshad , Schoenberg Noah
Published: March 2022

Introduction:
Pulmonary veno-occlusive disease (PVOD) is a rare subtype of pulmonary arterial hypertension (PAH) caused by intimal fibrosis of the pulmonary venules and septal veins. While the hemodynamic profile is suggestive of pre-capillary pulmonary hypertension, vascular obstruction distal to the pulmonary capillary beds distinguishes PVOD from other forms of PAH.

Case:
A 29-year-old woman presented with progressive dyspnea and fatigue. She was tachycardic, hypotensive, and volume overloaded on exam. ECG was notable for right-axis deviation. TTE showed a dilated, hypokinetic RV and small LV with mild global hypokinesis and septal flattening throughout the cardiac cycle. A CTA chest excluded pulmonary embolism but showed diffuse centrilobular ground-glass opacities and lymphadenopathy which raised suspicion for PVOD. She underwent right heart catheterization with the following measurements (mmHg): RA 14, PA 99/56 (mean 71), PCWP 12, and CI 1.1 L/min/m
2
with PVR 28.1 WU. Following initiation of an epoprostenol infusion, she became increasingly hypoxemic with repeat CT chest demonstrating dramatic worsening of ground-glass opacities and vascular congestion. This response to a vasodilator challenge led to a clinical diagnosis of PVOD. She was urgently listed for and underwent bilateral lung transplantation. Explanted lung tissue subsequently confirmed the diagnosis.

Conclusion:
In most forms of PAH, vasodilators mitigate arteriolar narrowing and improve pulmonary blood flow, while in PVOD they exacerbate pulmonary capillary congestion due to increased arteriolar blood flow relative to the venous outflow due to fixed narrowing of the pulmonary venule network. Because lung biopsy is contraindicated in severe pulmonary hypertension, the clinician must recognize that worsening pulmonary edema in response to vasodilator challenge with normal PCWP is a critical clue pointing towards PVOD. Timely diagnosis is essential given the poor prognosis for this condition for which lung transplantation is the definitive treatment.
Abstract 10374: Ankle and Toe-Brachial Index for Peripheral Artery Disease Identification: Unlocking Clinical Data Through Novel Methods
Authors: Friberg Julia , Qazi Abdul H , BOYLE BRENDEN , Franciscus Carrie , Vaughan-Sarrazin Mary , Westerman Dax , Patterson Olga V , Parr Sharidan K , Matheny Michael E , ARYA Shipra , Smolderen Kim G , LUND BRIAN , Gobbel Glenn T , Girotra Saket
Published: March 2022

Objectives:
Develop a natural language processing (NLP) system for identification of patients with peripheral artery disease (PAD).

Background:
Despite its high prevalence and clinical impact, research on PAD remains limited due to poor accuracy of billing codes. Ankle and toe-brachial index (ABI, TBI) can be used to identify PAD patients with high accuracy using electronic health record (EHR) data.

Methods:
A random sample of 800 ABI test reports from 94 Veterans Affairs (VA) facilities during 2015-2017 were selected and annotated by clinical experts. We trained the NLP system using random forest models and optimized it through sequential iterations of 10-fold cross validation and error-analysis on 600 test reports and evaluated its final performance on a separate set of 200 reports. We also assessed the accuracy of NLP-extracted ABI and TBI values for identifying patients with PAD in a separate cohort undergoing ABI testing.

Results:
The NLP system had an overall precision (positive predictive value) of 0.85, recall (sensitivity) of 0.93 and F1-measure (overall accuracy) of 0.89 to correctly identify ABI/TBI values and laterality. Among 261 patients with ABI testing (49% PAD), the NLP system achieved a positive predictive value of 92.3%, sensitivity of 83.1% and specificity of 93.1% to identify PAD when compared to a structured chart review (Table). The above findings were consistent in a range of sensitivity analysis (Table).

Conclusion:
We successfully developed and validated an NLP system for identifying patients with PAD within the VA’s EHR. Our findings have broad implications for PAD research and quality improvement efforts.
Abstract 10380: Differences in Cardiac Magnetic Resonance Native T1 Values Demonstrate Utility in Identifying Acute Cellular Rejection and Assessing Graft Health
Authors: Patel Devika , Gurijala Nyshidha , Mandell Jason , Hamann Karin , Rossi Christopher , Cross Russell , Kanter Joshua , Berger John T , Olivieri Laura
Published: March 2022

Introduction:
Cardiac Magnetic Resonance (CMR) is an emerging tool for cardiac graft assessment in heart transplant recipients, with native T1 mapping directed at identifying both rejection and graft fibrosis to predict and guide management of graft dysfunction.

Hypothesis:
CMR native T1 values may identify acute rejection, predict graft dysfunction, and in secondary analysis, correlate with fibrosis percentage from right ventricle (RV) endomyocardial biopsy (EMB).

Methods:
Pediatric subjects (n=34, age 12.4±4.9 y, graft age 5.4±4.3 y, LVEF 62.9±5.6%) underwent simultaneous EMB and 1.5T CMR with breath-held T1 mapping via Modified Look-Locker Inversion recovery in 8 short-axis slices, from which global mean and peak native T1 values were quantified. EMB analyzed for histopathological fibrosis% using digital analysis of Maisson’s trichrome stained slides. Patients were stratified into three groups by decision to treat: acute rejection with new treatment initiated, ongoing treatment modified, or no change in treatment. In patients without acute rejection, linear regression was used to compare T1 values with clinical markers of right atrial (RA) mean pressure and brain natriuretic peptide (BNP).

Results:
Mean T1 values were higher in patients with acute rejection compared to those without, with stratified groups demonstrating a monotonic trend; peak T1 values trended towards significance. In patients without acute rejection, peak T1 values correlated with BNP (r=0.53, p=0.004) and RA mean pressure (r=0.39, p=0.046). Fibrosis% from random RV EMB did not correlate with native T1 values or clinical markers of graft dysfunction.

Conclusion:
In pediatric heart transplant patients, T1 values from comprehensive CMR identified acute rejection requiring initiation of treatment and graft dysfunction, with regional analysis key to capturing correlation with clinical markers. CMR shows promise as an important tool for evaluation of graft health in children.
Abstract 10382: Large Lipid-Rich Plaque Predicts Intra-Stent Thrombus Formation After Primary Pci in Patients with Acute Coronary Syndrome: Insights from Near-infrared Spectroscopy and Optical Coherence Tomography Imaging Analysis
Authors: Kitahara Satoshi , Kataoka Yu , Murai Kota , Iwai Takamasa , Sawada Kenichiro , Matama Hideo , Honda Satoshi , Fujino Masashi , Yoneda Shuichi , Takagi Kensuke , Otsuka Fumiyuki , Asaumi Yasuhide , Tsujita Kenichi , Noguchi Teruo
Published: March 2022

Backgrounds:
The formation of intrastent thrombus is a PCI-related complication in subjects with ACS, which infrequently causes acute stent thrombosis. Given that lipid-rich plaque, a substrate for ACS, activates inflammation inducing prothrombotic state, the degree of lipidic plaque materials may associate with intrastent thrombus formation.

Methods:
Culprit lesions in 70 ACS subjects (=STEMI/NSTEMI/uAP=28/27/15) receiving newer-generation DES implantation were evaluated by both near-infrared spectroscopy (NIRS) and optical coherence tomography (OCT) imaging. NIRS-derived 4-mm maximum lipid-core-burden index (maxLCBI
4mm
) at culprit lesion was measured prior to PCI. OCT-derived intrastent thrombus-burden index (ITBI) after stent implantation were calculated as follows: [Σ(every 1-mm cross sectional thrombus-arc score: 1=1-90°,2=91-180°,3=181-270°,4=271-360°)/analyzed length]x(averaged longitudinal length). ITBI was compared between subjects with maxLCBI
4mm
<400 and ≥400.

Result:
The averaged maxLCBI
4mm
was 525±236, and dual-antiplatelet therapy with aspirin and clopidogrel, and aspirin and prasugrel was used in 43 and 56%, respectively. On OCT imaging analysis, maxLCBI
4mm
was significantly associated with ITBI (r=0.55,
p
<0.001, Figure), whereas there were no significant relationships of minimum stent area (MSA) (r=0.18, p=0.13) and stent malapposition diameter with ITBI (r=0.00. p=0.97). Multivariate analysis demonstrated maxLCBI
4mm
as an independent predictor of higher ITBI even after adjusting MSA, stent malapposition and other clinical characteristics (Table).

Conclusions:
The presence of lipid-rich plaque was associated with intrastent thrombus formation in the setting of ACS. Our findings suggest the potential importance to modulate activated prothrombotic cascade by using more potent antiplatelet agent in ACS patients exhibiting lipid-rich plaques.
Abstract 10387: Utility of Esophageal Image Segmentation for Guidance of Posterior Wall Lesions During Atrial Fibrillation Ablation
Authors: Pourmousavi Khoshknab MirMilad , Zghaib Tarek , Xu Lingyu , Arkles Jeffrey , Santangeli Pasquale , Marchlinski Francis , Han Yuchi , Desjardins Benoit , Nazarian Saman
Published: March 2022

Introduction:
Despite luminal esophageal temperature (LET) monitoring, esophageal injury remains a risk which impacts decision making during atrial fibrillation (AF) ablation. We sought to compare procedural characteristics including radiofrequency (RF) power, duration, and LET, among ablation procedures with and without visualization of esophageal segmentations relative to the left atrial dome.

Hypothesis:
We sought to test the hypothesis that esophageal image registration and visualization during AF ablation would improve operator efficiency and reduce esophageal temperature changes during the procedure.

Methods:
The retrospective cohort included 63 patients (mean age 65.5 ± 8.8 years, 33% female, 54% paroxysmal AF) that underwent pre-procedural cardiac magnetic resonance (CMR) and LET monitoring. Of all patients, 35 underwent standard AF ablation without esophageal image segmentation, and 28 underwent AF ablation with registration of esophageal image segmentation.

Results:
Total RF time was shorter with esophageal visualization (28.6 ± 11.8 min versus 39.1 ± 22.5 min, P<0.05). The distribution of ablation power delivery was skewed toward higher power with esophageal visualization (P<0.001), while the mean LET was identical among patient groups and the standard deviation of LET was lower in those with esophageal visualization (35.9 ± 0.5 °C versus 35.9 ± 0.7 °C, P=NS). The within patient standard deviation for LET change during posterior wall ablation was 0.3 ± 0.1 °C and 0.4 ± 0.2 °C for patients with and without esophageal visualization respectively (P=0.017).

Conclusions:
Esophageal visualization was associated with improved efficiency of AF ablation using higher power and resulting in shorter RF time, while reducing the variation in esophageal temperature.
Abstract 10388: The Role of Patient, Community and Healthcare System Factors in the Variability of Cardiovascular Hospital Readmissions
Authors: Saef Joshua , Kochar Arshneel S , Riggs Jennifer , Reed Grant W , Cremer Paul , Kim Yuli Y , Tang W. H. Wilson , Menon Venu
Published: March 2022

Introduction:
The Hospital Readmissions Reduction Program (HRRP) penalizes hospitals by reducing Medicare (CMS) reimbursement for institutions with higher rates of readmissions following hospitalizations for myocardial infarction (MI), coronary artery bypass grafting (CABG) and heart failure (HF). Understanding the contributors to these readmissions can identify meaningful areas for intervention. We examine whether community and patient or healthcare system factors contribute more to variability in cardiac readmissions.

Methods:
We compiled CMS hospital data on MI, CABG and HF readmissions, CMS physician reimbursement data, and 2020-21 County Health Rankings (Credit: University of Wisconsin). The outcome was the ratio of a hospital’s composite readmissions for MI, CABG and HF to discharges for the same conditions. Physician/healthcare system factors included total cardiac subspecialists, presence of all subspecialties, and the mean proportion of reimbursed charges. Patient and community factors included mean Hierarchical Condition Category (HCC) risk score, median household income, proportion of residents reporting no physical activity, and access to food stores. Linear regression models were compared using R
2
, AIC, BIC in model training data and mean absolute prediction error (MAPE) and root mean square prediction error (RMSE) in test data.

Results:
The linear regression model incorporating community and patient factors explained greater variability in readmission rates in training data and performed with greater accuracy in the test data (R
2
0.35; AIC -1839; BIC -1811; MAPE 0.017; RMSE 0.022) than the model incorporating physician/healthcare system factors (R
2
0.04; AIC - 1685; BIC - 1664; MAPE 0.022; RMSE 0.027). HCC score, level of physical activity, and number of cardiac specialists were associated with the largest effect sizes on the outcome.

Conclusions:
At a county level, community and patient factors appear to contribute more to variability in hospitals’ MI, CABG and and HF readmission rates. Further analyses should explore other community, patient, and provider factors that may contribute. The HRRP does not account for community/patient factors, indicating its limitations.
Abstract 10392: Association of Frailty with Incident Heart Failure with Preserved and Reduced Ejection Fraction in Late Life: The Aric Study
Authors: Ramonfaur Diego , Skali Hicham , Kitzman Dalane W , Palta Priya , Ndumele Chiadi E , Claggett Brian , Konety Suma H , Shah Amil M
Published: March 2022

Introduction:
The incidence and prevalence of both frailty and heart failure (HF) are greatest in late life, and both have been associated with inflammation and markers of myocardial injury. While frailty is cross-sectionally associated with HF, the association of frailty with incident HF, and HF with preserved (HFpEF) or reduced ejection fraction (HFrEF) is unclear.

Methods:
Among 5,517 participants in the Atherosclerosis Risk in Communities study with frailty assessment and free of HF at Visit 5 (2011-2013), frailty was ascertained using information on weight loss, low grip strength, exhaustion, low energy expenditure and slow gait. Frail was defined as the presence of
>
3 frailty components, pre-frail as 1-2 components, and robust as 0 components. HF was ascertained through adjudication of hospitalizations with related ICD codes. Multivariable Cox proportional hazard models were used to evaluate the association of frailty status at Visit 5 with incident HF overall, HFpEF (LVEF ≥50%), and HFrEF (LVEF <50%). Models were adjusted for age, race, gender, BMI, GFR, and history of stroke, MI, atrial fibrillation, hypertension and diabetes mellitus.

Results:
Mean age was 75 +/- 5 years, 58% were female, and 22% were Black. Forty-six percent were classified as robust, 48% as pre-frail, and 6% frail. Frail participants were older and had a higher prevalence of cardiovascular co-morbidities. Over a median follow-up of 7.1 (IQR 5.5-7.8) years, 525 participants developed incident HF (249 HFpEF, 209 HFrEF, 67 HF with unknown LVEF). Both pre-frailty and frailty were associated with heightened risk of incident HF compared to robust participants (Figure). The magnitude of risk associated with frailty status was similar for both HFpEF and HFrEF.

Conclusions:
Pre-frailty and frailty are both associated with heightened risk of incident HF in late life, independent of traditional cardiovascular risk factors. These associations are similar in magnitude for HFpEF and HFrEF.
Abstract 10398: Clot or Not? A Meta-Analysis of Autopsy Findings in Spontaneous Coronary Artery Dissection
Authors: Jaspan Vita , Rapkiewicz Amy , Reynolds Harmony
Published: March 2022

Introduction:
Spontaneous coronary artery dissection (SCAD) is an uncommon but likely underdiagnosed cause of acute coronary syndrome. Current treatment of SCAD commonly includes antiplatelet agents, though pathogenesis relates to intramural hematoma, rather than atherothrombosis as in typical myocardial infarction. Our goal was to determine whether thrombus in the true lumen is part of the pathophysiology of fatal cases of SCAD, which could help guide treatment decisions.

Methods:
A review of electronic databases including PubMed and EMBASE was conducted from inception through June 2021. Citations were included that provided pathology images of dissected coronary arteries acquired from autopsies of patients who died of SCAD. Images were independently reviewed by a pathologist who described the presence or absence of thrombus and inflammatory cells.

Results:
A total of 35 citations containing autopsy images were identified. These included 42 cases of which 88% were female, with an average age of 44 years. The most common vessel involved was the left anterior descending (74%), with 40% involving multiple vessels. Most decedents had no medical history, though 5% had systemic vasculitis and 17% were pregnant or peri-partum. On independent review of the pathology images, all had intramural hematoma, none had evidence of thrombus in the true lumen, and 16% had evidence of thrombus in the false lumen. There was eosinophilic inflammation of the affected artery in 64% of cases.

Conclusions:
There was no evidence of thrombus in the true lumen in any of 42 cases of fatal SCAD for whom autopsy images were available. This suggests that the use of antiplatelet agents in the treatment of SCAD should be re-evaluated. Clinical trials are necessary to determine whether antiplatelet agents are beneficial for patients with SCAD. Additionally, further research is necessary to better understand the role of eosinophils in the pathophysiology of SCAD.