bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13256: Factors Determining Mitral Valve Dysfunction in Patients Who Underwent Surgical Mitral Valve Replacement With Bio-Prosthetic Valves
Authors: Gwak Seo-yeon
Published: April 2022

Introduction:
There is increasing interest in bio-prosthetic MVD as recent advances in transcatheter MV interventions, but there is limited data. We sought to identify the factors determining mitral valve (MV) dysfunction (MVD) in patients who underwent MV replacement with bio-prosthetic valves and sought to clinical outcomes in patients with bio-prosthetic MVD.

Hypothesis:
MVD was related to younger age, renal dysfunction, postoperative elevated mean diastolic pressure gradient across the bio-prosthetic MV and anemia.

Methods:
A total of 233 patients underwent surgical bio-prosthetic MV replacement between June 1996 and May 2015. Finally, 226 patients (mean age 66.9±11.5 years, 74.3% of women) were analyzed. MVD was defined as an increase in mean gradient ≥ 5 mmHg with leaflet motion limitation and/or newly developed MV regurgitation during follow-up. Clinical outcome was defined as a composite of CV death, redo MV surgery or intervention, and hospitalization for heart failure.

Results:
During a median of 102 months (IQR 72 to 132 months), 65 patients (28.8%) revealed MVD. Factors associated with bio-prosthetic MVD were young age at operation (HR 0.97, 95% CI 0.95-0.99, p=0.001), end-stage renal disease (HR 4.29, 95% CI 1.45-12.71, p=0.007), elevated MDPG >5.5 mmHg early after operation (HR 1.86, 95% CI 0.97-3.74, p=0.063) and anemia after operation (HR 0.84, 95% CI 0.74-0.95, p=0.007). Kaplan-Meier curves revealed significant differences in event-free survivals for the occurrence of bio-prosthetic MVD according to each factor (
Figure 1
). Patients with bio-prosthetic MVD showed significantly poor clinical outcomes compared with those without bio-prosthetic MVD (EFS 43.1% vs. 91.9%, log-rank p<0.001) during the follow-up.

Conclusions:
Young age at operation, ESRD, elevated MDPG and anemia after operation were associated with bio-prosthetic MVD in patients who underwent bio-prosthetic MV replacement.
Abstract 13260: Relationship Between Localization of Myocardial Asynergy and Presence of Pathological Q Wave in Synthetic Posterior Lead Electrocardiogram
Authors: Kikuchi Takashi , Kodama Takahide , Ota Mitsuhiko , Koike Yukako
Published: April 2022

Background:
Synthesized posterior lead derived from 12-lead ECG can represent ST elevation in posterior acute myocardial infarction with high accuracy. However, the validity of pathological Q wave (Q) in synthesized lead ECG remained unclear.

Objective:
To investigate the relationship between localization of ventricular wall motion abnormality (Asynergy) and presence of Q in synthetic V7-V9 lead (synV7-V9).

Subjects:
Consecutive 1319 walk-in patients (68±13y, Male 67.5%, LVEF 64.0±10.4%) who underwent ECG and transthoracic echocardiography (TTE) were extracted from our database.

Method:
(1) Posterior lead: synV7-V9 was obtained from synECi18 system (Nihon Kohden) and V2-V5, II•aVF, and I•aVL•V6 leads were obtained from 12-lead ECG. (2) Asynergy was detected as increased wall motion score on 16-segments from TTE and classified into coronary perfusion regions. We analyzed the relationship between Q in synV7-V9 and patient characteristics, ECG parameters, or TTE parameters.

Results:
Wall motion abnormality was observed in 217 cases (16.5%). Q in synV7-V9 was detected in 79 cases (6.0%), and 38 cases out of them showed asynergy in any coronary perfusion site (Figure. A). In order to clarify relationship between Q in synV7-V9 and asynergy, wall motion score of 16-segments were compared in Presence of Q in synV7-V9 limited group and Non Q in all lead group (Figure. B). As a result, in the former, the scores in basal to mid on inferior to infero-lateral wall were found to be significantly higher. Logistic regression analysis for presence of Q in synV7-V9 limited showed asynergy in RCA to LCx region (OR 4.5, 95%CI 1.6-13.0), in RCA region (OR 4.0, 95%CI 1.4-11.0), in LCx region (OR 5.8, 95%CI 1.2-27.7), male (OR 2.6, 95%CI 1.2-6.0), right bundle brunch block (OR 3.2, 95%CI 1.4-7.3) remained as significant factors.

Conclusion:
Present study suggests Q in posterior lead using synthesized ECG can help diagnose myocardial scarring in RCA to LCx region including posterior wall.
Abstract 13261: Utility of a Novel Ensemble Based Deep Learning Network for the Automatic Detection of Pulmonary Hypertension and Right Ventricular Dilatation: A Study Based on Data From 783 Individuals From Two Tertiary Centres
Authors: Benesch Vidal Maria Luisa , Kempny Aleksander , Li Wei , Dimopoulos Konstantinos , Wort John , Fischer Alicia , Orwat Stefan , Baumgartner Helmut , Gatzoulis Michael A , Diller Gerhard
Published: April 2022

Background:
Pulmonary arterial hypertension (PAH) is associated with high morbidity and mortality. Echocardiography represents the main screening tool but requires specific expertise and diagnosis is often delayed. We hypothesized that an ensemble of deep learning (EDL) networks could reliably detect PAH in routine echocardiograms and improve patient management.

Methods:
Consecutive patients with PAH, Tetralogy of Fallot (TOF) or atrial septal defects (ASD) and right ventricular (RV) dilation, as well as normal controls were included. An ensemble of deep convolutional networks incorporating apical and parasternal views as well as tricuspid regurgitation gradients (TRG) into one unified network was trained to classify patients by presence of (invasively confirmed) PAH.

Results:
Overall, 408 PAH patients (median age 59 years, 74% female; 34% idiopathic, 66% associated PAH, RV inflow diameter 4.7±0.9 cm), 308 patients with RV dilatation (201 TOF and 107 ASD patients (med. age 41 years, 81% female, RV-inflow diameter 4.6±1.0 cm) and 67 normal controls (med. age 49 years, RV-inflow 3.4±0.6 cm) were included. Overall, 84% of PAH patients had usable TRGs and the sensitivity of detecting PAH by conventional RV diameters and TRG (estimated RV systolic pressure >40 mmHg) was 68.6% (81.7% in patients with adequate TRGs). In contrast, only 35% of normal controls and 64% of RV dilatation patients had interrogable TRGs. The EDL algorithm trained on 53,832 frames and validated on 26,474 frames not used for training achieved an on-frame accuracy of 95.0% in the validation set. On a per patient basis all normal controls and PAH patients were correctly classified, while two patients with RV-dilatation, elevated RV pressure and poor image quality were assigned to the PAH group, yielding an overall accuracy of 97.6% and a sensitivity of detecting PAH of 100%.

Conclusions:
The study is the first to demonstrate the utility of ensemble based deep learning algorithms, trained on routine echocardiograms, to detect PAH based on large tertiary center data. These algorithms outperform by far conventional echocardiographic evaluation for detecting PAH. Due to the automated process involved, they could be deployed to the community and contribute to the earlier diagnosis of PAH.
Abstract 13267: The Shifted Balance of Arginine Metabolites in Patients With Acute Myocardial Infarction and Its Association With the Composition of the Infarct-Related Culprit Lesion
Authors: Molek Patrycja , Wlodarczyk Aleksandra , Zmudzki Pawel , Rychlak Radoslaw , Wnuk Mateusz , Nessler Jadwiga , Zalewski Jaroslaw
Published: April 2022

Introduction:
We hypothesize that acute phase of myocardial infarction (MI) is associated with suppression of nitric oxide synthase (NOS) and enhanced arginase activity. Moreover, this altered metabolic balance might correlate with the composition of vulnerable culprit lesion in the infarct-related coronary artery (IRA).

Methods:
Arginine metabolites (μM) including ornithine, citrulline, proline, spermine, spermidine, agmatine, homoarginine, creatine, asymmetric dimethylarginine (ADMA) and monomethyl-L-arginine acetate were measured using liquid chromatography and tandem mass spectrometry in 85 consecutive MI patients upon admission and at 6-month follow-up and were compared with the composition of the IRA culprit lesion assessed with optical coherence tomography (OCT).

Results:
The concentration of ornithine in acute phase of MI was higher by 44% and homoarginine by 62% whereas level of arginine was lower by 39% and citrulline by 64% (P<0.001 for all), when compared to 6-month stable conditions. Following ischemia, the ratios of citrulline/arginine (0.10 [0.08; 0.14] vs 0.22 [0.18; 0.28]) and citrulline/ornithine (0.09 [0.07; 0.12] vs 0.47 [0.36; 0.55]) were decreased while the indices of ornithine/arginine (1.48 [1.08, 2.39] vs 0.50 [0.41, 0.60]) and homoarginine/arginine (0.17 [0.12; 0.22] vs 0.04 [0.03; 0.05]) were higher as compared with 6-month results (P<0.001 for all). Both, concentrations of arginine metabolites and their ratios were not associated with the mechanism of IRA occlusion, the amount of calcium or lipids and the presence of intramural hematoma. However, in patients with (n=67) versus without (n=18) thin-cap fibroatheroma (TCFA) in OCT the higher median concentrations of ornithine (10.24 [7.86; 12.52] vs 7.82 [4.38; 9.57]), ADMA (0.40 [0.29; 0.49] vs 0.29 [0.23; 0.42]), homoarginine (1.02 [0.81; 1.27] vs 0.74 [0.62; 1.00]) and a higher ornithine/arginine ratio (1.73 [1.29; 2.54] vs 1.18 [1.01; 2.07]) with a lower citrulline/ornithine ratio (0.07 [0.09; 0.11] vs 0.13 [0.09; 0.15]) were found (P<0.05 for all).

Conclusions:
During acute phase of MI the altered balance of arginine metabolites indicates NOS suppression and enhanced arginase activation and is associated with the presence of TCFA in IRA culprit lesion.
Abstract 13271: Combined Assessments of Monogenic and Polygenic Risk for Dilated Cardiomyopathy
Authors: Aragam Krishna G , Biddinger Kiran , Jurgens Sean J , Wang Minxian , Pirruccello James , Maamari Dimitri , Chaffin Mark , Choi Seung H , Morrill Valerie , Newton-cheh Christopher , Khera Amit V , Lubitz Steven A , Ellinor Patrick T
Published: April 2022

Introduction:
Genetic testing for non-ischemic dilated cardiomyopathy (DCM) currently comprises assessment of rare (monogenic) mutations in DCM-relevant genes. The role of a common-variant (polygenic) predictor for DCM has yet to be evaluated.

Methods:
Leveraging genotyping array and exome-sequencing data from UK Biobank, we curated monogenic, predicted loss-of-function (LOF) mutations in 91 genes on clinical genetic testing panels for DCM, and tested their prevalence and penetrance. Next, we constructed and evaluated a polygenic score for DCM from measures of left ventricular structure and function by cardiac magnetic resonance imaging. Finally, we combined monogenic carrier status with the polygenic score to estimate aggregate genetic risk for DCM.

Results:
Among study participants (N= 166,690), mean age was 57 (SD, 8.1) years, 75,154 (41%) were male, and 336 (0.21%) had DCM. 14.4% of DCM cases harbored a disease-relevant LOF mutation, including 8.8% within cardiac exons of the sarcomeric gene
TTN
. LOF mutations in
TTN
(OR, 25.36),
DSP
(OR, 17.55), and
RBM20
(OR, 12.85) were the most strongly associated with dilated cardiomyopathy (all
P
< 0.001). 0.7% of all LOF carriers - and 4.0% of LOF carriers in
TTN
- developed DCM. A polygenic score comprising 2.3 million common genetic variants was strongly associated with DCM in all participants (OR per SD=1.62, p=8.61E-39), and in non-carriers (OR per SD=1.60, p=6.28E-15; N=159,811) and carriers (OR per SD=1.79, p=4.76E-05; N=6,879) of LOF mutations. Comparing the top and bottom 20% of the polygenic score, a >3-fold risk difference was observed among non-carriers of
TTN
LOF, and a >10-fold risk difference among
TTN
LOF carriers.
TTN
LOF carriers with high polygenic risk were at 46-fold odds of developing DCM as compared to non-carriers with intermediate polygenic risk (p=4.16E-29).

Conclusions:
Combining monogenic and polygenic risk expands the scope and improves the precision of clinical genetic testing for DCM.
Abstract 13283: Mitochondrial DNA Damage and Remodelling of Nucleoid Bodies in Pulmonary Artery Smooth Muscle Cells From Human Patients With Pulmonary Arterial Hypertension
Authors: Rossi Jenna A , Dunham-Snary Kimberly J , Mewburn Jeffrey D , Archer Stephen L
Published: April 2022

Introduction:
Pulmonary arterial hypertension (PAH) is an obstructive pulmonary vasculopathy characterized by pulmonary artery smooth muscle cell (PASMC) hyperproliferation. PAH-PASMC have mitochondrial defects, including increased fragmentation, and increased production of reactive oxygen species (ROS). Mitochondrial-derived ROS can cause DNA damage. Mitochondrial DNA (mtDNA) is surrounded by replication proteins which form nucleoid bodies (NB).

Hypothesis:
We hypothesize that mtDNA damage is increased and NB structure altered in human PAH PASMC.

Methods & Results:
We profiled mtDNA and NB composition and integrity in control and PAH PASMC (n = 5/group). mtDNA content was assessed via confocal immunofluorescence of discrete extranuclear double-stranded DNA colocalized with mitochondria. Lower mtDNA content was observed in PAH PASMC vs control (1.8±0.2 vs 3.5±0.2 mtDNAs/μm
3
mitochondria, p<0.0001). Reduced mtDNA in PAH vs control was validated by qPCR (0.69±0.07 vs 1.00±0.07 ng mtDNA/μg cellular protein, n=4-5, p=0.0182). siRNA targeting of Mitofusin2 (Mfn2) in normal PASMC to mimic the mitochondrial fragmentation of PAH, reduced total mtDNA compared to control (1.05±0.06 vs 3.5±0.2 mtDNA/μm
3
mitochondria, n=9, p<0.0001), suggesting increased fission reduces mtDNA expression. Amplification of an 8.8kb mtDNA fragment, a measure of mtDNA damage, revealed increased damage in PAH vs control (14.3±3.9 vs 28.7±2.4 pg mtDNA, n=4, p=0.02). PAH PASMC exhibited higher expression of NB proteins vs control (n=5/measurement): TFAM (+96.7±23.3%, p=0.0032), SSBP (+63.4±14.4%, p=0.0023), and POLG (+59.0±24.0%, p=0.0397). These results were confirmed via immunoblotting for TFAM (+161.9±39.3%, n=4-5, p=0.0045) . Immunofluorescence verified increased TFAM in PAH PASMC vs control.

Conclusions:
We report a paradoxical upregulation of NB proteins despite reduced mtDNA content and elevated mtDNA damage in PAH. We speculate there is an unsuccessful compensatory attempt to restore mtDNA levels by increasing the expression of mtDNA’s replication apparatus in PAH PASMC.
Abstract 13290: Childhood-Onset Arrhythmogenic Cardiomyopathy Associated With Genetic Variants in Desmoplakin
Authors: Hylind Robyn J , Roston Thomas M , Austin Karyn M , Bezzerides Vassilios J , DeWitt Elizabeth S , Abrams Dominic J
Published: April 2022

Introduction:
Arrhythmogenic cardiomyopathy (ACM) resulting from variants in the desmosomal gene desmoplakin (DSP) is typically an adult onset disorder. Here, we describe penetrance, expression and outcomes of DSP-associated ACM in children.

Methods:
Patients aged ≤21 years with pathogenic/likely pathogenic variants in DSP were included. Penetrance was defined by:(i) ECG: T-wave inversion V4-V6; mean QRS amplitude <0.5mV in limb leads.(ii) Arrhythmia: >500 VPBs/24 hours, non-sustained or sustained ventricular arrhythmia (VA)(iii) LV dysfunction (EF<50%)(iv) Sub-epicardial late gadolinium enhancement (LGE). The cardiac phenotype was defined as primarily RV, isolated LV (left dominant) or biventricular. Myocardial inflammation was defined as chest pain with elevated troponin ± ST segment changes. A composite primary outcome was sustained VA, death or transplant.

Results:
We identified 24 patients (67% female) inclusive of 8 probands and 16 family members. Variants were truncating in 22 and missense in 2; a second variant occurred in 4. Presenting symptoms were cardiac arrest (1); myocardial inflammation (3) with cardiac arrest (1), sustained VA (1), dyspnea (2), syncope (1), palpitations (1).

ACM was penetrant in 17 (71%), with expression first evident at 15.2±3.3 years. The cardiac phenotype was left dominant (12) and biventricular (5). Isolated RV disease was not seen. Penetrant features were:(i) ECG: transient T-wave inversion in 1 (6%) and QRS amplitude <0.5mV in 6 (35%). (ii) Arrhythmia in 14 (82%) evident at presentation in 13 (92%) and an isolated finding in 2. (iii) LV dysfunction in 10 (59%; EF 35 ± 12%) evident at presentation in 9. (iv) Sub-epicardial LGE in 13 (76%) evident at presentation in 12 (92%) and an isolated finding in 2. Over 3.4±3.2 years, 6 (35%; 4 probands and 2 family members) reached the primary outcome; sustained VA at presentation (3), sustained VA (2), transplant (1). Myocardial inflammation occurred in 5 (21%), 2 of whom reached the primary outcome but this was not significant (p=0.79).

Conclusions:
DSP-mediated ACM may be fully penetrant in children affecting both probands and family members. VA and subepicardial LGE are prominent early features of disease and pediatric surveillance should reflect these findings.
Abstract 13291: Assessing Organ Procurement Organization Performance Across the Different Routes to Deceased Organ Donation
Authors: Valikodath Nishma G , Lambert Andrea N , Butler Alison , Lebovitz Daniel J , Chapman Gretchen , Karp Seth , Godown Justin
Published: April 2022

Introduction:
Organ procurement organizations (OPOs) are responsible for organ donor recruitment which can occur via donor registries or next-of-kin consent. Donor conversion rate is a metric used to assess OPO performance, reflecting the number of donors per eligible death. However, OPOs are not directly responsible for the success of donor registration. This study aims to describe the trends in donor recruitment via registries and next-of-kin consent, report the relationship between consent mechanisms, and assess the variability across OPOs.

Methods:
The SRTR database was queried for all eligible deaths (2008-2019), stratified by consent mechanism (Fig A). Trends were assessed over time. Multivariable logistic regression models adjusted for population demographic differences. Linear regression assessed the association between donor registration and next-of-kin consent at the OPO level. The probability of next-of-kin consent was assessed across OPOs after adjusting for population differences.

Results:
Donor registration has increased over time with a concurrent decrease in next-of-kin consent (Fig B & C). At the OPO level, an increase in donor registration is associated with lower next-of-kin consent rates. However, there are OPOs that demonstrate a high probability of next-of-kin consent in the face of highly successful donor registration (Fig D). The success of next-of-kin consent is highly variable across OPOs, even after adjusting for population demographic differences (Fig E).

Conclusions:
Utilization of registries for donor recruitment has increased over time while next-of-kin consent has declined. Donor conversion rate provides an incomplete assessment of OPO performance and may artificially favor OPOs in regions with highly successful donor registration practices. There is significant variability across OPOs in next-of-kin consent. Knowledge of detailed donor recruitment data may allow OPOs to better target areas for improvement.
Abstract 13296: Bivalirudin versus Unfractioned Heparin in Patients With Diabetes Mellitus Undergoing Elective Percutaneous Coronary Intervention: Results at One Year
Authors: Li Yulong , Li Jiawen , Yang Yuejin , Yuan Jinqing , Zhao Xueyan
Published: April 2022

Introduction:
Patients with Diabetes Mellitus (DM) and coronary heart disease have high risk in bleeding and thrombotic events. However, data on safety and effectiveness of bivalirudin in patients with DM undergoing elective percutaneous coronary intervention (PCI) are lacking which needs further scientific research.

Methods:
1152 patients undergoing elective PCI anticoagulated with bivalirudin and 10250 patients anticoagulated with unfractioned heparin (UFH) were performed propensity score matching at 1:4 ratio. Finally, 376 (bivalirudin group) and 878 (UFH with or without glycoprotein IIb/IIIa inhibitors [GPI] group)patients with DM were enrolled respectively. The safe endpoints were according to the Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding and BARC 3 or 5 bleeding. The effective endpoint was major adverse cardiac and cerebrovascular events (MACCE), including death, MI, revascularization, stent thrombosis and stroke.

Results:
During one-year follow-up, multivariate Cox analysis showed there was no significant difference in the risk of BARC 2,3 or 5 bleeding (P=0.451) and BARC 3 or 5 bleeding (P=0.124) between bivalirudin group and UFH with or without GPI group. As for MACCE, there was no significant difference between bivalirudin group and UFH with or without GPI group (P=0.153). Moreover, there was a reduction in the risk of MI between bivalirudin group and UFH with or without GPI group (HR:0.199, 95%CI: 0.047-0.845, P=0.029) but no significant difference in the risk of death, revascularization, stent thrombosis or stroke (all P>0.05).

Conclusions:
Although DM is considered a high risk factor for bleeding and thrombotic events, compared with UFH with or without GPI, bivalirudin reduced the risk of MI in patients with DM undergoing elective PCI and did not increase the risk of MACCE, while the risk of bleeding was similar in two groups.
Abstract 13315: Feasibility and Effectiveness of Using a Modified Microvascular Plug to Reduce Pulmonary Blood Flow for Various Congenital Heart Diseases
Authors: Kiene Ashley , Harvey Evan , Johnson Jason , Waller Benjamin , Knott-Craig Chris , Sathanandam Shyam
Published: April 2022

Background:
Neonates with certain congenital heart diseases (CHD) experience pulmonary overcirculation requiring a sternotomy for either pulmonary artery banding or neonatal corrective surgery. We present an alternative, percutaneous technique of utilizing custom fenestrated microvascular plug (MVP) as pulmonary flow reducers (PFR) for five different CHDs complicated by pulmonary overcirculation in the newborn.

Methods:
Fourteen PFRs were implanted percutaneously via a femoral venous only approach under fluoroscopic and echocardiographic guidance in nine neonates for five different CHDs. The success rates, complications, effectiveness and follow-up details are described.

Results:
All 14 PFRs were successfully implanted in the desired locations in with no procedural failures or complications. Bilateral PFRs were implanted within the branch pulmonary arteries in two patients to balance pulmonary and systemic circulations in single ventricle physiology and in three patients to reduce left-to-right shunt physiology. Single PFRs were placed within the patent ductus arteriosus (PDA) in one patient with a PDA stent who developed pulmonary overcirculation and three patients with large PDAs and pulmonary hypertension. Effectiveness was assessed either by a 10% drop in systemic oxygen saturation,
>
35 mmHg Doppler gradient, or weaning off diuretics depending on the indication. On latest follow-up, there were no PFR related mortality or re-interventions.

Conclusion:
It is feasible to modify and implant the MVP to function as an effective PFR for various congenital heart lesions in neonates. Outcomes following explanation such as, pulmonary artery growth, re-interventions rates are unknown. Once the learning experiences are overcome, longer term comparison studies are necessary to demonstrate benefits over existing therapies.
Abstract 13321: Identifying Mitral Valve Prolapse at Risk for Ventricular Arrhythmias and Myocardial Fibrosis From 12-lead ECGs Using Deep Learning
Authors: Tison Geoffrey H , Abreau Sean , Lim Lisa , Barrios Joshua , Hu Gene , Nguyen Thuy , Dixit Shalini , nah gregory , Lee Yoo Jin , Delling Francesca N
Published: April 2022

Background:
Inferior biphasic or inverted T waves have been described on a standard 12-lead ECG in some, but not all patients with malignant mitral valve prolapse (MVP). In contrast, complex ventricular ectopy (ComVE) is associated with myocardial fibrosis and increased mortality in MVP and may represent a better marker of arrhythmic risk. We hypothesize that an ECG-based machine-learning model can identify MVP with ComVE and/or myocardial fibrosis on cardiac magnetic resonance (CMR) imaging within a large ECG database beyond traditional ECG criteria.

Methods:
A deep convolutional neural network (DNN) was trained to detect ComVE using 12 leads in 6,916 ECGs from 569 MVP patients evaluated at the University of California San Francisco (UCSF) between 2012 and 2020. A DNN was also trained using 87 UCSF MVP patients with available contrast CMR to detect late gadolinium enhancement (LGE).

Results:
The prevalence of ComVE was 160/569 or 28% (20 or 3% with cardiac arrest or sudden arrhythmic death). The area under the curve (AUC) of the DNN to detect ComVE was 0.81 (95% CI, 0.78-0.84) (Figure). AUC remained high even after excluding patients with moderate-severe mitral regurgitation (MR) [0.80 (95% CI, 0.77-0.83)], or with bileaflet MVP [0.81 (95% CI, 0.76-0.85)]. The top ECG segments able to discriminate ComVE vs no ComVE were related to ventricular depolarization and repolarization (early-mid ST and QRS fromV1, V3, and III). LGE in the papillary muscles or basal inferolateral wall was present in 22 of 87 (25%) with available CMR. The AUC for detection of LGE was 0.75 (95% CI, 0.68-0.82).

Conclusions:
A deep-learning model can detect MVP at risk for ventricular arrhythmias and fibrosis from standard 12-lead ECGs, and can identify novel ECG correlates of arrhythmic risk regardless of leaflet involvement or mitral regurgitation severity. ECG-based deep-learning may help select, within a large echocardiographic database, those MVP patients requiring closer follow-up and/or a CMR.
Abstract 13330: Deep Learning Algorithm Predicts Angiographic Diameter Stenosis in Stable Patients Using Only a Standard 12-lead Electrocardiogram
Authors: Leasure Michael , Leasure Michael , Jain Utkars , Covalesky Veronica A , McCormick Daniel J , Mintz Gary S
Published: April 2022

Introduction:
Current standard electrocardiogram analysis algorithms cannot predict the presence and extent of coronary artery disease (CAD), especially in stable patients.

Hypothesis:
A novel artificial intelligence algorithm (ECGio) is able to predict the presence, location, and severity of coronary artery lesions in a minimally selected stable patient population as verified by coronary angiography.

Methods:
A cohort of 1659 stable outpatients were randomly divided into training (86%) and validation (14%) subsets, maintaining population characteristics. ECGio was trained and then validated using electrocardiograms paired with angiograms collected from electronic medical records. Coronary artery lesions were evaluated by a continuous measure of stenosis ranging from 0% - 100%. The prediction was then compared to the angiogram result (worst diameter stenosis in each vessel) with the error calculated per patient and per vessel.

Results:
In the primary analysis of the validation cohort, 22 had no angiographic CAD and were grouped with 56 patients with mild CAD (DS ≤30%), 31 had moderate CAD (DS 30-70%), and 113 had severe CAD (DS ≥70%). On a vessel level ECGio was able to predict stenosis severity with an overall average error of 16% as well as vessel specific errors of 18% in the LAD, 19% in the LCX, 18% in the RCA, and 8% in the Left Main. Absolute Error and Left Main error can be seen in the Figure.

Conclusion:
This validation study strongly suggests that it is possible to utilize an artificial intelligence algorithm to determine the presence and severity of CAD in stable patients using data from a standard 12- lead electrocardiogram.
Abstract 13333: Systolic Blood Pressure Is An Independent Risk Factor For Diabetic Retinopathy In Both Hypertensive And Normotensive Patients
Authors: Li Yu-Ting , Wang Yi , Hu Xiu-Jing , Mohammed Bedru H. , Liang Xiao-Ling , Hernandez Jose , Huang Wen-Yong , Wang Harry H.X.
Published: April 2022

Introduction:
Treatments with targets of systolic blood pressure (BP) <140 mmHg reduce the onset, or decrease the progression of diabetic retinopathy (DR) - a most common microvascular complication in type 2 diabetic patients with established hypertension. However, the debate on further intensive vs. standard BP control targets in limiting the onset and progression of diabetic microvascular complications remains to be an area of controversy. We aimed to explore whether the extent to which systolic BP levels were associated with the presence of DR in type 2 diabetic patients with normal BP were similar to that in patients with coexisting hypertension.

Hypothesis:
We assessed the hypothesis that systolic BP levels were not associated with DR in normotensive patients.

Methods:
This was a baseline analysis of a cohort of adult Chinese patients diagnosed with type 2 diabetes who attended ophthalmoscopic exam with primary care referral in the context of a Specialist-Generalist Working Alliance in Guangzhou, China. A hospital-based, standardised investigation included a dilated, comprehensive eye examination, a measurement of BP values and anthropometric parameters, and a clinical laboratory test for haemoglobin A1c and lipid profiles. A binary logistic regression analysis was conducted to examine patient-level risk factors associated with DR.

Results:
The mean age of all study participants (N=2,510) was 64.8 years, and more than half were females. More than one in three patients (40.4%) were normotensive. The average duration of diabetes was 8.6 years, and one in five patients were clinically diagnosed with DR. A higher systolic BP level was significantly associated with DR (adjusted odds ratio [aOR]=1.019, 95%CI: 1.012-1.027; p<0.001 for hypertensives, and aOR=1.020, 95%CI: 1.005-1.036; p=0.009 for normotensives), after adjusting for diabetes duration, sex, lifestyle behaviours, and HbA1c levels.

Conclusions:
In conclusion, we found that increased systolic BP level was an independent, significant risk factor associated with DR in both hypertensive and normotensive diabetic patients. Physicians, patients and caregivers are recommended to maintain regular monitoring of BP in all diabetic patients irrespective of the coexistence of hypertension.
Abstract 13338: Sociodemographic Differences in the Associations Between Omega-3 Polyunsaturated Fatty Acid Levels and Lipid Profiles in the United States
Authors: Riggs Daniel W , Bhatnagar Aruni , Hellmann Jason
Published: April 2022

Introduction:
Omega-3 (n-3) fatty acids have been shown to improve cardiovascular disease related lipid profiles, however, it is unclear whether these benefits vary by sociodemographic status. Therefore, we conducted a cross-sectional study to examine sociodemographic differences in n-3 fatty acids and their associations with lipid profiles in the general US population.

Methods:
Data from 2,444 participants in the 2011-2012 National Health and Nutrition Examination Survey were used in the study. Omega-3 fatty acids eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were measured in serum and analyzed as a percentage of total fatty acids. The primary outcomes included LDL/HDL ratio, total cholesterol/HDL ratio, and log of triglycerides/HDL ratio. Survey weighted regression with domain analysis were used to test for sociodemographic differences in associations.

Results:
We found that males had significantly lower levels of total n-3 fatty acids than females. Compared with Non-Hispanic Whites, Mexican Americans had lower levels of n-3 fatty acids, while Non-Hispanic Asians had higher levels. Omega-3 levels were also highest in college graduates and participants with a household income greater than $65,000. After adjusting for relevant confounders, we found an inverse association between DHA and LDL/HDL (-0.14 per 1% higher relative DHA; 95% CI:-0.25,-0.02), total cholesterol/HDL (-0.31; 95% CI: -0.45,-0.17), and triglyceride/HDL (-0.26; -0.34,-0.17). We also found an inverse association between EPA and triglyceride/HDL (-0.15; 95% CI: -0.26, -0.5). No associations were found with DPA. Subgroup analysis revealed that the association between DHA and LDL/HDL ratio was only significant in females, Non-Hispanic Whites, those with an annual household income greater than $65,000, and college graduates. Subgroup analysis of total cholesterol/HDL revealed an inverse association with EPA in females, Non-Hispanic Blacks, and college graduates.

Conclusions:
In the United States, the beneficial effects of n-3 fatty acids on lipid profiles vary by sociodemographics. These results may be due to sociodemographic inequalities in n-3 fatty acid consumption.
Abstract 13342: Transcriptional Profiling of Surgical Myectomy Tissue in Patients With Hypertrophic Cardiomyopathy Reveals Genotype Independent Counterregulatory Alterations in Hypertrophy Pathways
Authors: Garmany Ramin , Bos Johan , Tester David J , Dos Remedios Cristobal , Maleszewski Joseph J , Dearani Joseph A , Ackerman Michael J
Published: April 2022

Introduction:
Hypertrophic cardiomyopathy (HCM) is one of the most common genetic heart diseases characterized by asymmetric left ventricular hypertrophy (LVH) and vast clinical and genetic heterogeneity. Several transcriptional studies in HCM heart tissues have shown severe alterations in gene expression. However, these earlier studies relied on microarray technology or were limited by small sample size or lack of genotype-specific analyses.

Methods:
We obtained flash-frozen cardiac tissue from patients with HCM undergoing surgical myectomy/septal reduction therapy for relief of left ventricular outflow tract obstruction. RNA-sequencing (RNAseq) was performed using paired-end index reading on 97 myectomy tissues (44 female [45%]; mean age at surgery of 47 ± 18 years) and 23 control tissues (10 female [43%]; mean age at death of 43 ± 12 years) to identify differentially expressed genes (DEGs) using edgeR and pathways in HCM using Ingenuity Pathway Analysis. Additionally, genome sequencing (GS) was performed and HCM patients were divided into genotype-based subgroups to compare the transcriptional profile across different genotypes.

Results:
Overall, 43% had a pathogenic, HCM-associated variant including 23% with MYBPC3-HCM and 15% with MYH7-HCM. Among the 15,634 genes expressed in the cardiac tissue,1,246 genes (8%) were upregulated and 738 genes (3%) were downregulated significantly in HCM vs. controls. Pathway analysis showed alterations in 126 pathways with downregulation of 44 pathways and upregulation of 1 pathway. There were notable transcriptional alterations of most canonical, pro-hypertrophic pathways, including statistically and biologically significant downregulation of five pathways [-log (BH p-value)≥ 1.3; Z-score≤ -2]: ERK/MAPK, p38 MAPK, ERK5, IL6, and NF-κB signaling. Far less DEGs were observed between genotypic subgroups, with only 37 DEGSs identified between sarcomere positive- and genotype negative-HCM.

Conclusions:
At the time of surgical myectomy, the ventricular myocardium’s transcriptome, independent of genotype, reveals widespread downregulation of pro-hypertrophic pathways. Whether these counter regulatory measures can be targeted therapeutically warrants further investigation.
Abstract 13343: Cognitive Impairment in Older Adults With Peripheral Arterial Disease
Authors: Iannuzzi James C , Gan Siqi , Smith Eric , Gasper Warren J , Finlayson Emily , Walter Louise , Conte Michael S , covinsky kenneth
Published: April 2022

Introduction:
Peripheral arterial disease (PAD) is common among older adults and shares a pathophysiologic mechanism with vascular dementia, yet there remains a paucity of data about the prevalence of cognitive impairment (CI) in this population. The aim of this study was to estimate CI prevalence in a nationally representative sample of adults with PAD and identify independent risk factors for CI.

Hypothesis:
We hypothesized CI would be common and that risk factors would include advancing age.

Methods:
The U.S. Health and Retirement Study with Medicare Linkage and CI assessment was utilized for years 2000-2016. PAD was identified using ICD-9/10 and CPT codes. CI was defined using the Langa-Weir classification based on CI assessment within 2.5 years prior to first documented PAD diagnosis in the Medicare. Bivariate analysis for association with CI was performed appropriate to the data followed by multivariable logistic regression for the primary endpoint of CI.

Results:
Overall, 4,383 PAD individuals aged 65 and over at time of PAD diagnosis were included. Overall, 39% had CI. CI was associated with increasing age (p<0.01) female gender (42% females vs. 35% males, p<0.01) Race (60% Black, 66% Hispanics, 31% white, p<0.01) and Charlson score>2 (p<0.01). Geriatric syndromes were common with mean 1.7 (SD 1.5, p<0.01) and were associated with CI (2.7 in CI vs. 1.0 in no CI, p<0.01). On multivariable analysis risk factors included age, education, Race, vision impairment, depression, falls within the past year, and any dependency in activities of daily living (Table 1).

Conclusions:
Cognitive impairment is common in adults living with PAD and is associated with age, race/ethnicity, education, depression, geriatric syndromes and functional status, similar to those without PAD. Given CI’s prevalence in individuals with PAD, future study is imperative to understand how CI impacts PAD related health. These findings can be used to risk stratify patients for CI screening.
Abstract 13348: Single Nuclear RNA-seq of Human Thoracic Aortic Dissection Identifies Expansion of Vascular Smooth Muscle Cells With a Distinct Transcriptional Phenotype
Authors: Vellarikkal Shamsudheen , Atri Deepak , Lee-Kim Vivian , Reddy Ankith , Kaneko Tsuyoshi , MALLIDI Hari R , Rehman Rakhshinda , Shekar Prem S , Fredenburgh Laura E , Sias-Garcia Oscar , Muehlschlegel J Daniel D , Gupta Rajat
Published: April 2022

Introduction:
Phenotypic switching of vascular cells is a complex process associated with vascular disorders, including thoracic aortic aneurysm (TAA). Vascular smooth muscle cells (VSMCs) appear to switch from a contractile to synthetic phenotype in TAA. Single nuclear RNA-seq (snRNA-seq) of normal human and TAA aortas may be used to characterize cell heterogeneity of normal aortas, population shifts in disease, and the transcriptional profile of VSMC phenotypic switching.

Hypothesis:
snRNA-seq of normal and TAA aortas will identify the cell heterogeneity and transcriptional profiles of TAA.

Methods:
We performed snRNA-seq of 5 aortas from 2 normal and 3 TAA patients. We used a 10X-CellBender pipeline for profiling and analysis.

Results:
snRNA-seq identified 6 major cell types. The majority were VSMCs, exhibiting 4 sub-populations in all specimens (a). Cell distribution comparisons showed VSMC1 (ELN, PKD1, FLNA high) and VSMC2 (PRKG1, PDE3A, PCDH7 high) to be differentially-enriched in controls and TAA samples, respectively (b,c). Gene set and trajectory analyses confirmed prior observations of phenotypic switching (d,e). Genes associated with switching in VSMCs included TAA genes (PRKG1, PKD1, FLNA) with concordance of expression and putative function of Mendelian variants (i-k). Cell junction and regulation of muscle contraction pathways drove trajectory. We further assessed cell-type heritability of vascular GWAS variants (h). These gene sets were differentially-regulated between control and TAA. The strongest association was between VSMC2 and ascending aortic size (h).

Conclusions:
In this study, we demonstrated a dissociation bias-free method for snRNA-Seq of human vasculature. We confirmed enrichment of synthetic VSMCs in TAA and implicate phenotypic switching as a pathologic mechanism. Our study identifies a cell type-specific transcriptional profile of aortopathy genes, which may drive TAA and represent therapeutic targets.
Abstract 13351: New York Heart Association Functional Class Guide Assists With Providers Assessment of Functional Class in Patients With Heart Failure
Authors: Prasun Marilyn A , McCoy Thomas P , Rathman Lisa , Stamp Kelly D
Published: April 2022

Background:
Correct assignment of New York Heart Association Functional Classification (NYHA-FC) I-IV in patients with heart failure (HF) helps to promote evidence-based guideline directed care. Past research has shown difficulty with providers making consistent decisions about NYHA-FC due to its subjective nature. Therefore, we developed a NYHA-FC Guide to assist with promoting a more accurate NYHA-FC assignment by providers.

Objective:
Examine the validity, reliability, and accuracy of HF and primary care providers’ assignment of NYHA-FC in patients with HF using the NYHA-FC Guide.

Methods:
A cross-sectional design was used with validated vignettes after expert review. Advanced practice providers (
n
=75) in HF and primary care (PC) utilized a newly developed NYHA-FC Guide to assist in the assignment of NYHA-FC. Known-group validity comparisons, interrater reliability and internal consistency were used to evaluate the validity and reliability of the NYHA-FC Guide.

Results:
Heart failure providers’ accuracy total mean scores were significantly higher compared to PC providers (
M
= 6.0 vs. 5.4,
p
= 0.020). Primary care providers’ accuracy was higher than anticipated with no significant difference in accuracy of assignment for NYHA-FC II, III and IV relative to HF providers. A majority of HF providers (62%) and primary care providers (80%) reported that the NYHA-FC Guide assisted them with deciding NYHA-FC.

Conclusion:
Correct assignment of NYHA-FC can promote more objective decision-making regarding prescribing evidence-based treatment to patients with HF. The newly developed NYHA-FC Guide shows promise for facilitating accuracy of NYHA-FC assignment. Further research is warranted to evaluate the accuracy of using the NYHA-FC Guide compared to the gold standard 6 minute walk test and the applicability for use the NYHA-FC Guide in a busy clinical practice.
Abstract 13360: Racial Differences in Hospitalization Rates of Patients Who Receive a Diagnosis of Acute Coronary Syndrome in the Emergency Department
Authors: Islek Duygu , Ali Mohammed K. , Manatunga Amita , Alonso Alvaro , Vaccarino Viola
Published: April 2022

Introduction:
Although there is literature on missed diagnoses of acute coronary syndrome (ACS) in the Emergency Department (ED), and on avoidable admissions to hospitals, no previous studies have examined racial disparities in hospitalization rates among patients who received a discharge code of ACS in the ED.

Hypothesis:
We hypothesized that Non-White patients are more likely to be discharged home with a diagnosis of ACS than White individuals, and that health insurance, as a mediator, drives racial disparities in these hospitalization rates.

Methods:
We examined 51,022,910 discharge records of ED visits in Florida, New York, and Utah in years 2008, 2011, 2014, 2016/7, using state-specific data from the Healthcare Cost and Utilization Project. We identified ED admissions for acute myocardial infarction (AMI) or unstable angina using the International Classification of Disease ninth or tenth revision diagnosis codes, excluding those with chronic coronary heart disease to examine incident events only. We used generalized estimating equation models to compare risks of being sent home across race/ethnic groups including White, Black, Hispanic, and Asian/Pacific Islander patients. We used inverse probability weighting to estimate the mediating role of health insurance status on the associations.

Results:
Among 235,936 patients who visited the ED and received a discharge code of ACS in the study period, the proportion discharged home was 12 % among Black patients, 6 % among White patients, 9 % among Hispanic patients, and 9 % among Asian or Pacific islander patients. In age and sex-adjusted models the incidence risk ratio (IRR) for being discharged home was 1.3 (95% CI, 1.2 - 1.3) in Black patients 1.2 (95 % CI, 1.1 - 1.3) in Hispanic patients and 1.1 (95% CI, 0.9 -1.3) in Asian or Pacific Islander patients compared with White patients. Health insurance status did not play any role as a mediator. In patients below 55 years of age, differences were magnified for all racial groups compared to White patients.

Conclusions:
Racial disparities exist in hospitalization of AMI at the ED, which are especially marked among younger patients. Health insurance does not explain these racial differences; other possible causes need to be investigated.
Abstract 13391: Increased LV Afterload Improves Rv Function in a Longitudinal Study of RV-Pressure Overloaded Mice
Authors: Dufva Melanie J , Ichimura Kenzo , Ivy Dunbar D , Spiekerkoetter Edda F , Kheyfets Vitaly O
Published: April 2022

Introduction:
The left ventricle (LV) is known to transfer kinetic mechanical energy to the right ventricle (RV) during systole. Normally, the RV relies on this mechanical assistance for up to 70% of its pressure generation. However, this biventricular relationship and its effect on RV function has not been explored in the progression in the pressure overloaded RV. In this study, we developed a longitudinal mouse model of pulmonary arterial (PA)-banding concomitant with transverse aortic constriction (TAC) to initiate an adaptive LV remodeling response. We hypothesized that adaptive LV remodeling would improve RV systolic function in an RV pressure overloaded setting.

Methods:
Surgical PAB was performed on mice to induce RV pressure overload and myocardial remodeling. Mild surgical TAC was performed on these mice 2-weeks (w) post-PAB. Steady-state free precession (SSFP) cardiac magnetic resonance (CMR) imaging (SSFP-CMR) was performed at 1w post-PAB, 1 w post-TAC (PAB-TAC) and 4 w and 7 w post-surgery (n=7). As controls we used Sham (n=5), TAC-only (n=4, TAC) as well as PAB-only (n=4, PAB) mice at 1, 4, and 7 w after surgery. These images were analyzed using feature-tracking (FT) software to compute measurements of ventricular volumes.

Results:
RV ejection fraction (RVEF) was reduced in PAB mice compared to Sham at 1w (p=0.02, 0.38±0.06 versus 0.52±0.08, respectively). After TAC, PAB-TAC mice showed an increase in RVEF compared to PAB-only mice at 4 w (p=0.03, 0.49±0.04 versus 0.39±0.08, respectively), and at 7 w (p=0.001, 0.50±0.06 versus 0.37±0.1, respectively). Similarly, tricuspid annular plane systolic excursion (TAPSE) showed a decrease in PAB mice compared to sham (p=0.002, 0.85±0.15mm versus 1.73±0.33mm, respectively) and an increase after TAC at 2 w (p=0.001, 1.55±0.29mm versus 0.85±0.15mm, respectively), 4 w (p=0.002, 1.75±0.32mm versus 0.93±0.21mm, respectively), and at 7 w post-surgery (p=0.001, 1.70±0.33mm versus 0.91±0.14mm, respectively).

Conclusions:
Even though LV-to-RV mechanical energy transfer is well established in normotensive animals, our data supports a mechanistic link between RV systolic function and LV pressure in remodeled and pressure-overloaded RVs.