bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11576: Demand Ischemia in Patients with Diabetic Ketoacidosis : A Retrospective Analysis
Authors: Amin Saad M , Mehta Harsh , Shah Dr. Shyam
Published: March 2022

Introduction:
Demand ischemia (DI) or type 2 myocardial infarction refers to a mismatch between supply and demand of oxygen to myocardium leading to ischemia. Volume depletion is a cardinal feature of Diabetic Ketoacidosis (DKA) that can lead to decrease flow to myocardium. The purpose of this study is to document the incidence of demand ischemia in patients admitted with DKA.

Methods:
Using the Nationwide Inpatient Sample (NIS) for 2018, we performed a retrospective analysis of adults older than 18 years who were admitted to the hospital with a diagnosis of DKA. They were further divided in 2 groups. One group developed demand ischemia and the other group did not. Patients who suffered acute myocardial infarction were excluded from the study.

Results:
We had a total population of 202,505 that were admitted with the diagnosis of DKA, out of which 1685 (0.83%) patients suffered from demand ischemia. Comorbidities like prior diagnosis of DM, dyslipidemia, obesity, CKD, atrial fibrillation, chronic lung and liver disease were more prevalent in patients within the DI group (table 1). Complications like Acute kidney Injury (77.45% vs 39.77% p0.0001), Acute Respiratory Failure (15.43% vs 2.86% <0.0001), Ventricular arrhythmias (2.37% vs 0.43%) and Sudden cardiac arrest (1.48% vs 0.25% p<0.0001) occurred more frequently in DI subpopulation. Patients with DI underwent more procedures like angiography (12.46% vs 0.47% p<0.0001) and angioplasty (0.89% vs 0.08% p<0.0001). Overall, patients with DI had higher inpatient mortality (1.78% vs 0.42% p<0.0001) and longer length of stay (table 1).

Conclusions:
With wider availability of high sensitivity Troponin early recognition of myocardial ischemia has become possible. Demand Ischemia in DKA patients carried a higher burden of comorbidities, had more complications, underwent a higher number of procedures and had significantly higher number of deaths. Closer monitoring and precise management are prudent to avoid poor outcomes.
Abstract 11578: Genome-Wide Pleiotropy Analysis of Coronary Artery Disease and Pneumonia
Authors: Yu Zhi , Zekavat Seyedeh , Haidermota Sara , Bernardo Rachel , Libby Peter , Finucane Hilary , Natarajan Pradeep
Published: March 2022

Introduction:
Pneumonia correlates strongly with coronary artery disease (CAD) risk, and influenza vaccination reduces CAD risk in trials. Elucidating shared pathways may elucidate novel insights regarding residual CAD risk.

Hypothesis:
Genetic alleles exhibit pleiotropy for pneumonia and CAD, and may be leveraged for causal inference.

Methods:
We performed genome-wide pleiotropy analyses CAD and pneumonia with the PLACO method using summary statistics from CARDIoGRAMplusC4D (CAD) and FinnGen v4 (pneumonia). For genes near independently replicated SNPs (in UK and Mass General Brigham Biobanks) and expressed in GTEx v8 tissues, we examined the causal effects of index and interacting (by STRING) gene expression with CAD and pneumonia through Mendelian randomization (MR). Lastly, we examined for interactions between prioritized SNPs and smoking status on incident CAD and pneumonia risks.

Results:
Among 115 SNPs with significant genetic pleiotropy between CAD and pneumonia, 90 of them were replicated, and nearby genes (
ADAMTS7
,
IL6R
) showed heritable gene expression. Across tissues, increased
ADAMTS7
expression consistently showed decreased risk for CAD and increased risk for pneumonia, and increased
IL6R
expression showed increased risk for CAD and decreased risk for pneumonia. Among genes that interacted closely with
ADAMTS7
and
IL6R
,
NLRP3
similarly demonstrated significant causal effects on CAD and pneumonia in the same directions as that of
ADAMTS7
. Sensitivity analysis using multiple MR methods yielded consistent results. The presence of
ADAMTS7
p.Ser214Pro conferred a significantly reduced risk of CAD among non-smokers but not those who ever smoked (
P
interaction
0.01) and a significantly increased risk of pneumonia only among those who ever smoked (
P
interaction
0.0003).

Conclusions:
Genetic immune-inflammatory axes of CAD linked to respiratory infections implicate
ADAMTS7
and
IL6R
, and related genes.
Abstract 11580: Platelet Activity and Cardiovascular Events in Patients with Diabetes and Peripheral Artery Disease: Findings from the American Heart Association Cardiometabolic Health Strategically Focused Research Network
Authors: Jindal Manila , Cofer Lucas , Xia Yuhe , Luttrell-Williams Elliot , Myndzar Khrystyna , Giannarelli Chiara , A Fisher Edward A , Newman Jonathan D , Goldberg Ira J , Berger Jeffrey S
Published: March 2022

Introduction:
Peripheral artery disease (PAD) and diabetes mellitus (DM) are significant risk factors for atherothrombosis. Platelets mediate atherothrombosis and are therapeutic targets in PAD and DM. We investigated the relationships between PAD, DM, platelet activity, and cardiovascular risk.

Methods:
The Platelet Activity and Cardiovascular Events (PACE) study enrolled 289 PAD patients undergoing lower extremity revascularization (LER). Prior to LER, platelet activity was measured via light transmission aggregometry in response to submaximal ADP, collagen (coll), serotonin (ser), epinephrine (epi), and arachidonic acid (AA). Patients were followed for a median of 18 months for the composite of major adverse cardiac or limb events (MACLE; MI, stroke, death, major amputation, and limb revascularization).

Results:
There were 93 (32%) patients with insulin-dependent DM (IDDM), 60 (21%) with non-insulin dependent DM (NIDDM), and 136 (47%) without-DM. Patients with IDDM were more likely than those without DM to be female, non-white, and Hispanic, and to have history of coronary artery disease, heart failure, and critical limb ischemia (P<0.05 for all). Use of antiplatelet therapy was similar across groups. Maximum platelet aggregation was highest in the IDDM group in response to multiple agonists (
Figure)
. MACLE occurred in 51%, 57%, and 69% of the without-DM, NIDDM, and IDDM groups, respectively (P=0.02). Compared to subjects without DM, only those with IDDM were at increased risk of MACLE after multivariable adjustment (aHR 1.6 [95% CI 1.02-2.4]; P=0.04) (
Figure
). After further adjustment for platelet aggregation, the association between IDDM and MACLE was no longer statistically significant (1.4 [0.9-2.3]; P=0.17); platelet aggregation mediated 24% of the excess MACLE risk in individuals with IDDM.

Conclusions:
In patients with PAD, IDDM is associated with increased platelet activity that mediates, in part, the risk for incident cardiac and limb events.
Abstract 11585: Determination of Aortic and Mitral Valve Opening and Closing Times Using Only LV Pressure Data
Authors: Aufan M. Rifqi , Miller Neal J , Jost Zachary T , Sharifov Oleg F , Gupta Himanshu , Denney Thomas S , Lloyd Steven G
Published: March 2022

Background:
Identification of aortic and mitral valve opening and closure timing is crucial for assessment of left ventricle (LV) function, e.g. pressure-volume loops. This is particularly problematic when simultaneous imaging (e.g. echocardiography) is not available. We hypothesize that LV pressure and its time derivatives can detect valve opening and closure times. Our aim was to determine the aortic and mitral valve opening and closures using properties of the LV pressure waveform.

Methods:
For this pilot study, in 3 human participants in sinus rhythm, LV pressures were recorded with a high-fidelity catheter. Echocardiographic 2D-guided M-mode images were obtained across the aortic and mitral valves in the parasternal long axis view. The timing of aortic and mitral valve events was linked to the ECG tracing, using the peak of the ECG R wave as the reference point. For each participant, two consecutive heartbeats were selected and the first (dP/dt), second (d
2
P/dt
2
), and third derivatives (d
3
P/dt
3
) of LV pressure calculated. Local maxima and minima from these were compared with the valve timing from M-mode.

Results:
The maximum of dP/dt at the beginning of the systolic phase occurred consistently with the opening of the aortic valve. Local minimum and maximum d
2
P/dt
2
occurred at the closure of the aortic valve and pre-atrial contraction timing, respectively. The early diastolic minimum of d
3
P/dt
3
and early systolic maximum of d
3
P/dt
3
coincided with M-mode mitral valve opening and closure timing, respectively. There was a strong correlation between the valve events timing that was measured using these two methods (R
2
=0.98, p<0.001).

Conclusion:
Aortic and mitral valve timing defined using LV pressure waveform agrees with valve opening/closure timing determined using echo M-mode as the gold standard. Determination of these valve timings is helpful for advanced analysis of LV mechanics when simultaneous echocardiography is not available.
Abstract 11587: Absent Ductus Arteriosus is Relatively Common in Neonates with Symptomatic Tetralogy of Fallot, and Rarely Associated with Critically Deficient Pulmonary Blood Flow at Birth
Authors: Maskatia Shiraz A , Glatz Andrew C , Goldstein Bryan H , Qureshi Athar M , Zampi Jeffrey , McCracken Courtney , Kelleman Michael , Nicholson George , Meadows Jeffery J , Shahanavaz Shabana , Law Mark A , Batlivala Sarosh P , Pettus Joelle , Mascio Christopher , Chai Paul , Romano Jennifer , Asztalos Ivor , Pajk Amy , Beshish Asaad , Petit Christopher J
Published: March 2022

Introduction:
Absent ductus arteriosus (ADA) is a poorly described feature associated with tetralogy of Fallot (TOF). We compare characteristics and outcomes of neonates with symptomatic TOF (sTOF) with ADA to those with a ductus arteriosus (DA).

Hypothesis:
We hypothesized: neonates with sTOF and ADA would have similar outcomes to those born with a DA, and a small portion of the ADA cohort would have critically-deficient pulmonary blood flow (CDPBF).

Methods:
Consecutive neonates with sTOF who underwent intervention during the neonatal period from 2005—2017 were identified from the Congenital Cardiac Research Collaborative. Those with DA on echocardiogram performed on the first day of life or on fetal echocardiogram were identified and compared to those with ADA. ADA neonates who required ECMO or intervention to augment PBF on the first day of life were defined as having CDPBF. Patient characteristics and outcomes were compared between DA and ADA groups.

Results:
Among 519 neonates, 460 (89%) had a DA and 59 (11%) had ADA. ADA neonates were more likely to carry a genetic or syndromic diagnosis, had smaller branch PA sizes, and were more likely to receive a transannular patch compared to those with a DA. Despite this, reintervention rates were similar (data not shown), and there was only a small difference in mortality that did not reach statistical significance. Of ADA neonates, 7/59 (12%) had CDPBF. Compared to ADA neonates without CDPBF, those with CDPBF had lower baseline oxygen saturation (58 vs 87%, p=0.031) and smaller pulmonary valve (PV) annular z-score (-2.9 vs -2.5, p=0.015) with similar reintervention rates and mortality.

Conclusion:
ADA is relatively common in sTOF. Despite higher rates of comorbidities, mid-term reintervention rates and mortality are similar to those with DA. CDPBF is a rare, high-risk feature of infants with sTOF and ADA. Smaller PV size may be a marker of CDPBF. Future work should focus on prenatal factors to identify fetuses with TOF, ADA and CDPBF.
Abstract 11593: Survival from Sudden Cardiac Arrest Depends on Type of Diabetes
Authors: Norby Faye L , Chugh Sumeet S , Uy-Evanado Audrey , Jui Jonathan , Reinier Kyndaron
Published: March 2022

Introduction:
A diagnosis of diabetes prior to sudden cardiac arrest (SCA) is associated with decreased survival following resuscitation. Patients with Type 1 diabetes mellitus (T1D) vs Type 2 diabetes mellitus (T2D) can be quite different and potential differences in survival outcomes have not been evaluated. Our aim was to compare the SCA resuscitation profile between individuals with T1D, T2D, and no diabetes.

Methods:
Using data collected from 2002-19, we performed a case-case study of 2771 SCA (age ≥18 years) from the Oregon Sudden Unexpected Death Study. We used medical records to determine diabetes status and the resuscitation profile was based on EMS reports, time of 911 call, and medical records. We used logistic regression to evaluate the independent association between diabetes and resuscitation profile.

Results:
SCA cases had a mean age of 65 ± 16 years, were 33% female and 24% non-White race. In total, 37% (n=1016) of cases had diabetes, of which 6% (n=66) were T1D. Those with T1D were 2 times more likely (p=0.008) to have an unwitnessed SCA compared to those without diabetes, and 1.7 times more likely (p=0.04) compared to those with T2D. (Figure, panel A). T1D were half as likely (p=0.04) to have resuscitation attempted compared to both T2D and no diabetes. There were no significant differences in initial rhythm. Individuals with T1D or T2D had a higher risk of death (vs. survival to hospital discharge) compared to those without diabetes, and in diabetics, those with T1D had 1.9 times higher odds of death compared to T2D (p=0.19). Descriptively, those with T1D tended to have SCA between the hours of 6am-10am compared to those with T2D and no diabetes (Figure, Panel B).

Conclusions:
Diabetes reduces the chances of survival from SCA, and individuals with T1D have worse outcomes than T2D. Given the global epidemic of diabetes, these findings have important implications for sudden death prevention and should be investigated further.
Abstract 11595: The Influence of Social Determinants on Heart Failure Outcomes: A Systematic Review
Authors: Coleman Alyssa , Enard Kimberly R , Yakubu R. Aver , Butcher Briona , Hauptman Paul J
Published: March 2022

Introduction:
Heart failure (HF) is an ongoing health concern that is expected to affect 9 million Americans by 2030. Growing research shows the association between non-clinical, social determinants of health (SDoH) and adverse outcomes (hospitalizations, high costs, and premature mortality). Providers must be able to identify SDoH risk factors to improve care delivery and patient outcomes.

Aim:
To summarize how SDoH risk factors have been included, defined, measured, and assessed in studies that examine outcomes in the HF care continuum.

Methods:
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a search of five databases was conducted for observational or interventional studies published between 2009 and 2021 that assessed the influence of SDoH risk factors on outcomes among subjects with HF. Study quality was assessed using NIH’s quality assessment tools.

Results:
The search identified 1,209 unique records; 108 were selected for full-text review. In total, 59 articles including retrospective and prospective cohort, cross-sectional, and intervention studies met criteria for inclusion. The majority of studies examined readmissions and hospitalizations (k=36); mortality or survival (k=32); and success of medical devices and transplantation (k=8). SDoH risk factors most commonly evaluated were race/ethnicity; age; gender; SES; social support; and education or health literacy. Studies used a range of 1-9 SDoH (M = 3.6, SD = 2.2) as primary independent variables and 0-7 SDoH as controls (M = 2.4, SD = 2.1). The studies used multiple data sources, frequently EMR linked with national surveys, disease registries, and/or data from large national studies. Overall, the effects of the SDoH risk factors on HF outcomes were mixed, and these differences appeared to be related to heterogeneity of data sources and SDoH constructs employed across studies.

Conclusions:
Our systematic review suggests that the influence of SDoH on HF outcomes remains incompletely assessed in part due to both inconsistent measurement and absence of potentially relevant variables. More expansive, real-time SDoH data collection is required if HF interventions are to meaningfully impact value-based and patient-centered models of care.
Abstract 11598: Post-Developmental Deletion of Cardiomyocytes PR Domain Containing 16 (prdm16) Causes Pathological Hypertrophy
Authors: Ghosh Rajeshwary , Fatahian Amir N , Vinod Vishaka , Mimche Patrice , Warren Junco S , Campbell Kenneth S , Drakos Stavros G , Boudina Sihem
Published: March 2022

Despite recent medical advances, heart failure (HF) remains to be the leading cause of mortality worldwide. Delineating the underlying molecular mechanisms involved in the pathogenesis of HF is critical for the development of new therapies. The transcription factor PRDM16 is involved in cell fate determination and differentiation. We previously showed that PRDM16 variants/deletion resulted in left ventricular non-compaction cardiomyopathy in humans and mice indicating its involvement in cardiac development. Here, we investigated the role of PRDM16 in adult cardiac physiology. We showed that patients with HF exhibited a significant reduction in cardiac
PRDM16
mRNA expression compared to control individuals. These results were substantiated by the significant attenuation of
Prdm16
mRNA 2 weeks post- transverse aortic constriction (TAC) in mice when compared to age matched sham controls. Additionally, cultured neonatal rat ventricular cardiomyocytes treated with the hypertrophy inducing agent, phenylephrine, demonstrated a suppression of
Prdm16
gene expression while fibrotic gene expression was elevated. To directly assess the contribution of PRDM16 to cardiac hypertrophy and HF, we generated mice with tamoxifen-inducible cardiomyocyte-specific
Prdm16
deletion (CiPrdm16). CiPrdm16 KO mice developed concentric hypertrophy as evidenced by enhanced heart weight/tibia length, elevated left ventricular mass and increased cardiomyocyte hypertrophy. Initially, ciPrdm16 KO mice exhibited enhanced contractility but progressively developed contractile dysfunction and impaired diastolic function. Consistent with these findings, transcriptomic analysis revealed an increase in protein synthesis pathways in ciPrdm16 KO hearts compared to wild-type controls. Collectively, these data show for the first time that PRDM16 transcriptionally regulates pro-hypertrophic signaling in the adult mouse heart and may contribute to the progression of HF in humans.
Abstract 11603: Pulmonary Artery Dilation in Submassive Acute Pulmonary Embolus and Chronic Thromboembolic Pulmonary Hypertension
Authors: Dandawate Nupur , Minhas Jasleen , Nardelli Pietro , San Jose Estepar Ruben , Piazza Gregory , Washko George , San Jose Estepar Raul , Rahaghi Farbod
Published: March 2022

Introduction:
CT imaging is the primary mode of diagnosis of acute pulmonary embolus. At initial presentation, both patients with acute PE and undiagnosed decompensated CTEPH may present with similar clinical findings of presence of clot and RV dysfunction. Extraction of markers of disease from CT scans at the point of diagnosis may help with clinical decision making. In this study we compare two CT markers of disease severity in patients with submassive PE and CTEPH. We hypothesized that higher pressures and thus increased dilation of the pulmonary artery would be hemodynamically tolerated in the chronic disease.

Methods:
We conducted a retrospective chart review study at Brigham and Women’s Hospital for patients with acute submassive PE between 2009-2017. Patients with adequate imaging and at least one positive right ventricular echocardiogram findings were included. The CTEPH cohort consisted of patients with CT imaging within one year of RHC proven CTEPH and patients from the submassive PE cohort found to have subsequently been diagnosed with CTEPH. The ratio of the main pulmonary artery (PA) to aorta (A) and RV to LV diameter ratio were measured by multiple operators to confirm reproducibility. All data collection was approved by the IRB at Mass General Brigham. Data was analyzed using R version 4.0.1 and Wilcoxon Rank-sum test with two-sided p-values for differences. Medians and interquartile ranges are reported.

Results:
355 patients with the diagnosis of acute submassive PE and positive echo findings and 31 patients with CTEPH were included. Patients with acute PE were older (63 [53-73] vs 48 [41-67] p= 0.003) and had a similar fraction of females (190/355 vs 17/31). PAA was significantly higher in the CTEPH cohort (1.16 [0.97-1.32] vs 0.94 [0.85-1.04] p < 0.0001) as was the RV/LV ratio (1.44 [1.34-1.57] vs 1.31 [1.16-1.46]; p = 0.0005).

Conclusions:
Patients with CTEPH have a higher PA/A ratio than patients with submassive PE and echocardiographic signs of RV dysfunction. This study is limited in part because of the time between imaging and diagnosis of CTEPH, and lack of definitive follow-up for all acute PE cases. Prospective data collection would help evaluate clinical utility of CT markers in identifying chronic disease.
Abstract 11604: The Cincinnati Atrial Fibrillation Score (CAFS): Multi-Center Derivation of the First Polysomnography-Based Risk Scoring System for Predicting Incident Atrial Fibrillation in Asymptomatic Community Adults
Authors: Thirumal Rithika , Vaughan Benjamin , Dey Swati , Vogel Anna , Limpitikul Worawan B , Dorante Miguel , Guallar Eliseo , Punjabi Naresh M , Jones Steven R , Demazumder Deeptankar
Published: March 2022

Introduction:
Early diagnosis of atrial fibrillation (AF) leading to early therapy can improve clinical outcomes (e.g., stroke). Current approaches for AF risk stratification are limited. Dynamic ECG analysis during sleep is an alternate, underexplored approach for AF risk stratification.

Hypothesis:
Dynamic ECG analysis during sleep predicts AF incidence in community adults, and adds major independent prognostic value to conventional AF risk factors and scores.

Methods:
In the multi-center prospective Sleep Heart Health Study, we studied consecutive, asymptomatic, ostensibly healthy, middle-aged and older community adults without a history of AF who were in sinus rhythm during home polysomnography. We performed comprehensive and systematic univariate and multivariate analyses of all available clinical, ECG and polysomnography parameters for association with AF incidence over follow-up.

Results:
Over 5.3±0.29 years, 315 (11.2%) of 2,807 people had new onset AF. We identified the major independent significant AF predictors, including established risk factors and ECG dynamics, and derived a multivariate prediction model entitled, the Cincinnati AF score (CAFS) (
FIGURE 1
). Addition of CAFS to a multivariate model with (1) CHA
2
DS
2
-VASc score increased ROC curve area by 9% and yielded net reclassification improvement (NRI) of 90% [43+47% for cases and non-cases, respectively]; or with (2) CHARGE-AF score increased ROC curve area by 3.5% and yielded NRI of 54% [23+31%]. These improvements were driven primarily by the ECG dynamics, independent of sleep apnea and other risk factors.

Conclusion:
Dynamic ECG analysis during sleep adds major independent prognostic value to established AF risk factors and scores. The ability to better identify individuals who will and will not develop AF has potential for broad clinical impact. We are currently validating CAFS in another multi-center cohort of asymptomatic ambulatory adults with a diverse demographic profile.
Abstract 11605: Analysis of 10-yr MACE Risk of LDL-C ≥160-189 Mg/dL Compared to <160 Mg/dL in Young Adults (ages 20-39) in an Integrated Healthcare System
Authors: Le Viet T , Anderson Jeffrey L , Calderone Peter , Perez Ana C , Knight Stacey , May Heidi T , Horne Benjamin D , Muhlestein Joseph B , Knowlton Kirk U
Published: March 2022

Introduction:
Adults <40-yrs (20-39) may have elevated cardiovascular risk based on higher LDL-C (e.g., ≥160 mg/dL). We sought to compare the risk of MACE (all-cause death, MI, ischemic stroke, heart failure hospitalization, and peripheral vascular disease [PVD]) in adults <40-yrs and LDL-C ≥160 to 189 compared with LDL-C <160 mg/dL.

Hypothesis:
Adults <40-yrs with LDL-C ≥160-189 mg/dL are minimally addressed in the current cholesterol management guidelines but may have a higher risk of MACE compared to other healthy controls.

Methods:
Patients (pts) from 20- 39 yrs of age with at least three lipid labs and outpatient primary care encounters at Intermountain Healthcare, a large integrated healthcare system, prior to January 2010 and an LDL-C measurement between January and December of 2020 (n=14,570) were included and followed for MACE until June 2021. Pts with LDL-C >190 or <160 on statin in 2010 but previously ≥160 were excluded. Pts were identified using MDClone (ADAMS self-service analytics platform). Outcome of interest was MACE during 10-yr follow-up, LDL-C was stratified as ≥160-189 vs <160 mg/dL. Baseline characteristics were compared by either a chi-squared or t-test, as appropriate. Multivariate logistic regression was used to identify the role of LDL-C as a predictor of outcome. A p-value of <0.05 was considered statistically significant.

Results:
Baseline characteristics are presented in the Table. MACE for LDL-C ≥160-189 mg/dL was not statistically significant compared to LDL-C <160 (OR 1.28, 95% CI 0.94 - 1.74, p<0.115).

Conclusions:
The risk of 10-yr MACE in adults <40 yrs of age with LDL-C ≥160-189 mg/dL did not confer a statistically significant elevated risk. Our findings are consistent with current guidelines that statin therapy is not mandated in these individuals.
Abstract 11606: Mature Ipsc-Derived Atrial Cardiomyocytes Show That Saturated Fatty Acids Differentially Modulate Ion Channel and Structural Remodeling in Obesity-Induced Atrial Fibrillation
Authors: Sridhar Arvind , Ly Olivia T , Arif Pavel Mahmud , Chen Hanna , Gonzalez Francisco , Perike Srikanth , HONG Liang , McCauley Mark , Rehman Jalees , Darbar Dawood
Published: March 2022

Background:
Obesity-induced atrial fibrillation (AF) is modulated in part by increased serum free fatty acids (FFA) and FA infiltration of the heart. Mass spectrometry data on obese mice have shown increased saturated FAs (SFA), monounsaturated FAs (MUFA), and polyunsaturated FAs (PUFA) compared to lean controls with the largest increase in the PUFA, linoleic acid (LA). Although reports suggest that some FAs induce ventricular arrhythmias in mice, the differential electrophysiological (EP) effects of SFAs, MUFAs, and PUFAs on the atria remain unclear.

Objective:
To determine if SFAs, MUFAs, and PUFAs differentially modulate atrial remodeling using mature human induced pluripotent stem-derived atrial cardiomyocytes (iPSC-aCMs) and HL1 cells. .

Methods:
We compared iPSC-aCMs and HL-1 cells treated with bovine serum albumin (BSA) with palmitic acid (PA), oleic acid (OA) and LA (600 uM each) for 1 week. Ion channel function was assessed using whole-cell patch clamping and we assessed β-oxidation and atrial remodeling with using ELISA, qPCR, and Western blotting.

Results:
iPSC-aCMs treated with PA, OA, and LA displayed higher expression of
FABP3
,
ANGPTL4
, and
CPT1A
suggesting increased FA metabolism and β-oxidation (Figure A-C). In HL1 cells, protein expression of Cpt1a was increased in all groups after FA treatment (Figure D). PA differentially modulated expression of Kv7.1 and NCX1 in HL1 cells (Figure E-F) and ion channel mRNA expression in iPSC-aCMs (Figure G-L). After 1 week PA and LA treatment β-adrenergic signaling was significantly increased in iPSC-aCMs while OA decreased it compared to controls (Figure M-O).

Conclusions:
Using mature iPSC-aCMs, we showed for the first time that SFA, MUFA, and PUFA not only increased FA metabolism but also differentially modulated ion channel and structural remodeling and β-adrenergic signaling in the atria. Our findings may have important implications for the management of obesity-induced AF in patients.
Abstract 11608: DOAC Effect on Cardiovascular Outcomes in Patients with Peripheral Arterial Disease
Authors: Matti Lana , Firth Christine , Girardo Marlene , Rayfield Corbin , Fatunde Olubadewa , Apolinario Michael , Liedl David , Wennberg Paul W , Shamoun Fadi
Published: March 2022

Introduction:
Peripheral arterial disease (PAD) increases cardiovascular (CV) morbidity and mortality, but remains underdiagnosed and undertreated. Several trials support low-dose rivaroxaban in PAD treatment, although this has yet to be widely adopted in clinical practice. The effect of warfarin and direct oral anticoagulants (DOACs) on comprehensive PAD outcomes warrants further study.

Hypothesis:
Anticoagulant therapy, particularly DOACs, improves CV outcomes in PAD.

Methods:
We conducted a retrospective study of patients who underwent ankle-brachial index testing (ABI) from 1996 – 2020 at Mayo Clinic. We included patients with PAD defined by abnormal ABI (<1.0 or >/=1.4). Prolonged (>6 months) DOAC or warfarin use was compared to no anticoagulant therapy. Multivariable (MV) regression, controlling for baseline CV risk factors, was used.

Results:
21,891 patients had abnormal ABI readings; 3,093 were on warfarin and 267 were on DOAC for any indication. Anticoagulation improved mortality, with DOACs superior to warfarin. DOACs improved critical limb ischemia (CLI)/amputation in univariate analysis, although this was not significant in MV. Patients with poorly compressible vessels (ABI >/=1.4) had increased limb outcomes compared to reduced ABI (<1.0). Ischemic stroke and myocardial infarction occurred more frequently in those on anticoagulation, but the risk was less for DOACs vs. warfarin. Notably, both anticoagulant groups had greater baseline comorbidity than the non-anticoagulant group; the DOAC and warfarin groups were similar. Major bleeding (6.7%) was increased in both anticoagulant groups, but less so with DOACs and this was similar to the bleeding risk seen with aspirin (HR 1.20).

Conclusion:
Anticoagulant therapy improved mortality in a large cohort of PAD patients. The risk of limb events appears improved in those on DOACs. DOACs showed improved risk profiles compared to warfarin regarding CV and bleeding outcomes.
Abstract 11610: Characteristics and Predictors of Effective Height of the Aortic Valve Assessed by Electrocardiography-Gated Cardiac Computed Tomography
Authors: Ishida Keiichi , Igarashi Takashi , Yokoyama Hitoshi
Published: March 2022

Introduction:
Effective height of the aortic valve has been used as an index for durable aortic valve repair. This study aimed to analyze the relationship between effective height and the other morphological parameters of aortic valve complex when aortic valve is closed.

Methods:
We retrospectively analyzed 100 patients (70.7±10.2 years) without diseased aortic valve, root or ascending aorta, who had electrocardiography-gated cardiac computed tomography as a screening test of coronary artery, from August 2014 to December 2018. Parameters of the configuration of aortic valve complex (effective height ; geometric height ; aortic annular diameter ; sinus of Valsalva diameter ; sinotubular junction diameter ; commissure height) in diastole were measured using the software Ziostation2 (Ziosoft, Tokyo, Japan). Pearson correlation was used to evaluate the association between effective height and the other parameters. In addition, multiple regression analysis was performed to determine which variables predict effective height.

Results:
Significant correlations were shown between effective height and geometric height (r = 0.704 ; P < 0.001), sinus of Valsalva diameter (r = 0.433 ; P < 0.001), sinotubular junction diameter (r = 0.547 ; P < 0.001) and commissure height (r = 0.396 ; P < 0.001). There was no significant correlation between effective height and aortic annular diameter (r = 0.111 ; P = 0.27). Multivariable analysis showed that geometric height (regression coefficients β = 0.853 ; 95% confidence intervals, CI, 0.647 to 0.923 ; P < 0.001), aortic annular diameter (β = -0.574 ; 95% CI, -0.467 to -0.284 ; P < 0.001) and sinotubular junction diameter (β = 0.327 ; 95% CI, 0.085 to 0.211 ; p < 0.001) were significant predictors of effective height. The overall model fit was R
2
= 0.716.

Conclusions:
This study demonstrated that effective height was strongly correlated with geometric height, and predicted by geometric height, aortic annular diameter and sinotubular junction diameter. These findings may help heart surgeon to decide an appropriate effective height for individual aortic valve complex during aortic valve repair surgery.
Abstract 11611: The Wnt Inhibitor Secreted Frizzled-Related Protein 3 Protects Mitral Valve Endothelium from Mi-Induced Endothelial to Mesenchymal Transition
Authors: Alvandi Zahra
Published: March 2022

Introduction:
There are changes in the mitral valve (MV) leaflets seen within 2-6 months post-myocardial infarction (MI) that include endothelial to mesenchymal transition (EndMT) and fibrosis. Early modulation of EndMT and fibrosis in MV leaflets may limit ischemic mitral regurgitation and heart failure. The onset of EndMT and fibrosis in MV leaflets and the mechanism of their instigation are not known.

Hypothesis:
We hypothesized that circulating molecules present in plasma within days after MI incite EndMT and fibrotic processes in MV leaflets.

Methods:
Using flow cytometric analysis and immunofluorescence staining, we examined the onset of EndMT in 20 adult sheep: 8 sheep with IMI, 8 with sham surgery, and 4 naïve controls with immediate excision of hearts under general anesthesia. The effect of plasma on EndMT induction in primary MV endothelial cells (VECs) was assessed by qPCR, migration assays, and immunofluorescence staining. Plasma cytokine levels were assessed using a cytokine array. Immunoblotting, immunofluorescence staining, RNA sequencing and bioinformatic analysis were used to identify biochemical changes by post-MI plasma.

Results:
Ovine MVs harvested 8-10 days after inferior MI revealed an onset of EndMT, shown by increased CD31/α-SMA-positive cells in post-MI MV leaflets. In contract to sham plasma, post-MI plasma induced EndMT and pro-fibrotic markers and enhanced migration of primary mitral VECs. Analysis of sham versus post-MI plasma revealed a significant drop in the Wnt antagonist sFRP3 in post-MI plasma. Addition of recombinant sFRP3 to post-MI plasma reversed its EndMT-inducing effect on mitral VECs, measured by restored VE-cadherin, reduced α-SMA, and reduced TGFβ1-3 expression. RNA-seq analysis of mitral VECs exposed to post-MI showed upregulated FOXM1. Blocking FOXM1 with Siomycin A reduced EndMT and pro-fibrotic transcripts in mitral VECs treated with post-MI plasma. Finally, FOXM1 induced by post-MI plasma was downregulated by sFRP3.

Conclusions:
Reduced sFRP3 in post-MI plasma facilitates EndMT and fibrosis in mitral VECs by increasing the transcription factor FOXM1. Restoring sFRP3 levels and/or inhibiting FOXM1 may provide new strategies to minimize MI-induced maladaptive changes that occur in the MV.
Abstract 11612: The Different Impact of Disproportionately Low B-Type Natriuretic Peptide Levels on Outcome in Patients of Acute Decompensated Heart Failure Between Sinus Rhythm and Atrial Fibrillation
Authors: Sakane Kazushi , Kanzaki Yumiko , Tsuda Kosuke , Hoshiga Masaaki
Published: March 2022

Introduction:
B-type natriuretic peptide (BNP) has been widely used for the diagnosis of heart failure. Previous data suggest a lower diagnostic accuracy of BNP in HF patients with atrial fibrillation (AF). However, little is known about disproportionately low BNP levels in AF patients even during acute heart failure conditions.

Hypothesis:
The factors related to disproportionately low BNP might be different between AF and sinus rhythm (SR) in patients with acute decompensated heart failure (ADHF).

Methods:
Among 424 patients hospitalized for ADHF between January 2015 and December 2017, we divided into two groups based on the rhythm at hospital admission (AF group, n=201 and SR group, n=223) and subdivided them into four groups (Q1-Q4) according to each quartile of BNP levels at hospital admission (BNP lowest quartile (Q1) group (LB): < 320 pg/mL in SR; Q1 < 240 pg/mL in AF).

Results:
The proportion of patients with unexpectedly low BNP (BNP < 200 pg/mL) was higher in AF group (19.9%) than in SR group (12.1%, p=0.03). BNP was correlated with left ventricular end-diastolic volume index (LVEDVi), left ventricular ejection fraction (LVEF) in both groups (AF: r=0.28, p<0.01; r=-0.43, p<0.01, SR: r=0.41, p<0.01; r=-0.39, p<0.01, respectively) . On the other hand, BNP was positively correlated with left atrial diameter in SR group but negatively correlated in AF group (r=0.14, p=0.039 vs. r=-0.21, p<0.01, respectively, Figure). Furthermore, survival rates significantly increased along BNP tertiles in SR group. On the contrary, in AF group, Q1 (LB) did not show the highest survival rates (p=0.02, Figure).

Conclusions:
A higher proportion of ADHF with disproportionately low BNP was seen in AF than in SR group. In ADHF patients with AF, LB may be reflected by LA structural remodeling. Furthermore, LB was related to good prognosis in SR group, but not in AF group.
Abstract 11619: Cost of Treatment is a Barrier to Hypertension Control in Puerto Rican Adults in Massachusetts
Authors: Kankam Lawreta
Published: March 2022

Introduction:
Little is known about hypertension (HTN) control among Puerto Ricans living on the U.S mainland. We examined awareness, treatment and control of HTN among Puerto Rican adults living in the Boston area to determine whether cost of treatment is a barrier to control.

Methods:
We used baseline data (2004-2009) from the Boston Puerto Rican Health Study, a longitudinal study of approximately 1500 Puerto Rican adults. Blood pressure was based on the mean of up to 4 determinations. Awareness, treatment and control among all participants, and those being treated, were defined as in the National Health and Nutrition Examination Survey (NHANES). Perceived cost as a barrier to treatment was based on response to a single item. The association of cost with HTN control was tested in multivariable logistic models, adjusting for covariates suggested in the literature, including BMI, serum, creatinine, diabetes, age, alcohol use, and nonsteroidal anti-inflammatory drugs (NSAIDs) use.

Results:
Participants with HTN (n= 941) had mean age 58.6
+
7.6 years, and 70% were female. Among these, 83.6%, were aware of their HTN, 77.8% were treated, and 37.0% were controlled. Among those being treated, 47.5% were controlled. Seventeen percent of those with HTN reported cost as barrier to treatment. Among those reporting cost as barrier, 27.6% were controlled compared to 38.9% of those with no cost barrier (p<0.01). Among treated HTN patients, 36.4% of those reporting cost as a barrier to treatment were controlled compared to 49.5% of those with no cost barrier (p<0.01). The odds ratio (95%Cl) for control was 0.63 (0.43, 0.93) for cost as a barrier among all participants with HTN, and 0.60 (0.39, 0.91) among those treated.

Conclusion:
HTN control in Boston-area Puerto Ricans is lower than reported in NHANES for the general US population. Cost of treatment appears to be an important barrier to achieving control.
Abstract 11622: Resolution of Inflammation via Rvd1/fpr2 Signaling in Abdominal Aortic Aneurysms
Authors: Filiberto Amanda , Leroy Victoria , Ladd Zachary , Su Gang , Elder Craig , Pruitt Eric , Hensley Sara , Lu Guanyi , Zarrinpar Ali , Sharma Ashish , Upchurch Gilbert R R
Published: March 2022

Introduction:
Resolvin D1 (RvD1) is derived from a ω-3 polyunsaturated fatty acid and is involved in the resolution phase of inflammation during abdominal aortic aneurysm (AAA) formation.

Hypothesis:
The aim of this study was to decipher the protective role of RvD1 via formyl peptide receptor 2 (FPR2) receptor signaling in attenuating AAA formation.

Methods:
C57BL/6 (WT) and FPR2
-/-
mice (8-12 week old) underwent treatment with topical elastase or heat-inactivated elastase (control). Separate groups of mice were administered RvD1 (100ng/kg) or saline i.p. daily from day(d)1 to d13 and aortic diameter was measured by video micrometry on d14. mRNA quantification of FPR2 expression in aortic tissue was performed by RT-PCR on d7, 14 and 21. Human aortic tissue from AAA patients and controls (organ transplant donors) were analyzed for quantification of FPR2 expression. Data is presented as mean ± SEM and statistical analysis was performed by using Mann-Whitney test for phenotype or Wilcoxon Signed Rank Test for gene expression data.

Results:
Elastase-treated WT mice had significantly increased aortic diameter compared to controls (127±8% vs. 1± 0.6%; p<0.0001). Importantly, elastase-treated FPR2
-/-
had a significant increase in aortic diameter compared to elastase-treated WT mice (165±16% vs. 127± 8%; p=0.03). RvD1 treatment attenuated AAA formation in WT mice, but not FPR2
-/-
mice, on d14 (56± 10% vs.121± 8%; p<0.0001). Immunohistology documented decreased elastin and smooth muscle cell α-actin expression, as well as increased neutrophil and macrophage infiltration in FPR2
-/-
mice compared to WT mice, after respective treatments with RvD1. Elastase-treated WT mice had significantly increased FPR2 receptor mRNA expression compared to respective controls on d7, d14, and d21. Human AAA tissue demonstrated significantly decreased FPR2 mRNA expression compared to controls (p=0.02).

Conclusions:
This data identifies the role of FPR2 in dysregulation of inflammation-resolution during AAA pathogenesis. Immunomodulation of FPR2 signaling by exogenous RvD1 identifies a novel mechanism in resolution of aortic inflammation and vascular remodeling during AAA pathogenesis.
Abstract 11627: Effectiveness of Statin Therapy in an Urban Metropolitan Patient Population
Authors: Ambalavanan Manoj , Gokhale Sanket , Seok Minji , Nazir Noreen T
Published: March 2022

Introduction:
Severely elevated serum LDL (>190 mg/dL) is an independent risk factor in the development of ASCVD complications. Despite current guidelines recommending the immediate initiation of high dose statin therapy in high-risk patients, limitations in care continue to exist, especially amongst different genders, races and populations with a higher burden of health disparities.

Hypothesis:
We assessed the hypothesis of whether or not race and gender affected the timeliness and appropriateness of initiating statin therapy in a patient population that has a higher burden of health disparities.

Methods:
We performed a single centered, retrospective observational study where 499 patients with an initial LDL level greater than 190 mg/dL were identified. These patients were then stratified according to race and gender and evaluated for intensity and timing of statin therapy for 12 months after their initial lipid profile.

Institutional survey data was acquired to quantify health disparities of our patient population in comparison to US census and Chicago Public Health data.

Results:
All 499 patients were included in the study. The mean LDL was 224.72 mg/dL and the SEM was 1.775 mg/dL. When compared to state and national averages, respectively, patients from our geographic region were found to have a higher percentage of unemployment (11% vs 7% vs 7%), uninsured status (13% vs 9% vs 10%) and inadequate access to transportation (25% vs 11% vs 9%). There was no significant difference between race or gender regarding the timing of statin initiation or degree of statin intensity. Of all patients, 38.2% were not started on any statin while 29.8% were immediately started on statin therapy (p=0.04). Of those patients started on statin therapy, only 11.4% were started on a high intensity statin (p=0.039).

Conclusions:
In conclusion, we found that, regarding race or gender, there was no significant difference in initiation of statin or strength of statin started. However, the overall percentage of patients that were started on a timely and appropriate dosage was significantly lower, especially in comparison to national averages. This may be due to the high degree of health disparities that are prevalent amongst our patient population.
Abstract 11629: Contributions of Socio-Economic Status, Lifestyle, and Biological Risk Factors to Ethnic Differences in Type 2 Diabetes Risk in a Multi-Ethnic Asian Population
Authors: Seah Jowy Yi Hoong , Sim Xueling , Seow Wei Jie , Tai E Shyong , van Dam Rob M.
Published: March 2022

Introduction:
There is no study that identified contributions of socio-economic status (SES), lifestyle, and biological risk factors to ethnic differences in T2D risk in Asia’s populous ethnic groups - Chinese, Malays and Indians.

Methods:
We used data of 7,427 participants from the Multiethnic Cohort, a population-based study of subjects aged ≥21 y. Information on SES and lifestyle were collected using standardized questionnaires. Biological risk factors were measured using validated methods. T2D cases were based on self-reported physician-diagnosed diabetes or a national medical registry, or fasting plasma glucose ≥7.0 mmol/L or HbA1c ≥6.5 %, after an average of 7.2 y (SD: 2.2 y). Multivariable logistic and linear regression models were used in association and mediation analyses.

Results:
In Model 1, Malays and Indians had a twofold higher risk of developing T2D compared with Chinese (
Table 2
). In Model 2, only the association between Indians and Chinese remained. The higher T2D risk in Malays and Indians was largely mediated by BMI and HDL cholesterol (
Table 3
). Adjusting for adiponectin concentrations widened the differences in T2D risk. We observed a larger mediation effect by HOMA-IR for Indians than Malays.

Conclusion:
The excess risk in Malays was completely explained by higher BMI. In contrast, neither adiposity nor SES and lifestyle could fully explain the higher T2D risk in Indians.
Abstract 11631: A Critical Role of Parathyroid Hormone in the Development of Pulmonary Hypertension
Authors: Joki Yusuke , Konishi Hakuoh , Takasu Kiyoshi , Minamino Tohru
Published: March 2022

Background:
Pulmonary hypertension (PH) is characterized by increased pulmonary artery pressure and develops right heart failure. Parathyroid hormone (PTH) is secreted from parathyroid gland and play a critical role in calcium homeostasis. Recent studies have suggested that PTH also acts on the cardiovascular system and affects cardiovascular prognosis. We hypothesized that PTH would play a role in the pathogenesis of PH.

Object:
This study aimed to investigate the effect of PTH on pulmonary hemodynamics.

Method:
We measured serum PTH levels in patients who were suspected of PH and underwent right heart catheter examination. We used two types of PH animal models, hypoxia (Hx)-induced PH mouse model and Sugen/hypoxia (SuHx)-induced PH rat model. Hx mice were administered PTH daily for 3 weeks. SuHx rats underwent parathyroidectomy, after which they received SuHx treatment for 10weeks. We measured physical data and right ventricular systolic pressure (RVSP) in these models. We cultured pulmonary artery smooth muscle cell (PASMC) treated with PTH to analyze cell signaling, proliferation and migration.

Result:
We enrolled 20 participants. PTH concentration was significantly correlated with mean pulmonary artery pressure and pulmonary vascular resistance. PTH treatment exacerbated right ventricular hypertrophy and increased RVSP (33.6mmHg vs. 48.2mmHg) in Hx mice compared with non-treated Hx mice(Figure). Conversely, parathyroidectomy significantly attenuated right ventricular hypertrophy and reduced RVSP (54.2mmHg vs. 29.3mmHg) in SuHx rats compared with sham-operated SuHx rats. PTH promoted migration and proliferation through ERK signaling in PASMC.

Conclusion:
Our clinical and experimental data demonstrated a critical role of PTH in the development of PH and suggested that PTH would be a novel therapeutic target for PH treatment.