bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16852: The Role of Repeat Stress Radionuclide Myocardial Perfusion Imaging for New or Progressive Cardiovascular Symptoms
Authors: Fernandes Marcelo , Rivera-Maza Manuel , Grevious Salih , Vincent Louis , Marzouka George , Chakko Simon
Published: April 2024

Background:
The appropriateness use criteria (AUC) offers guidance to assist with the appropriate use of cardiac imaging. The recent AUC consensus is that follow-up radionuclide myocardial perfusion imaging (MPI) within 2-years of a normal MPI is rarely appropriate in asymptomatic patients or in those with stable symptoms. The utility of repeat testing in a patient with new or progressive symptoms has not been studied.

Methods:
After IRB approval, records from veterans who underwent multiple MPI stress testing within 2-years of a negative MPI, between 2013 and 2016, at our VA Medical Center were accessed and variables of interest collected. Descriptive analysis as well as direct comparison by means of χ2 for dichotomous variables was conducted.

Results:
A total of 318 male veterans underwent repeat MPI within 2-years of a normal MPI. The median age was 65 [IQR, 59-70]. Among this group, repeat testing for new or progressive symptoms was done in 206 veterans (65%), compared to 112 (35%) veterans without symptoms. 50 cases had reversible ischemia on repeat MPI. Of these, 37 (18%) were symptomatic. Among asymptomatic veterans with a positive repeat MPI, 3 out of the 11 (27%) were noted to have obstructive coronary artery disease (CAD) on coronary angiogram. In contrast, 24 out of 37 veterans with symptoms underwent coronary angiogram, with 15 (40.6%) found to have obstructive CAD. Overall, 2.6% of asymptomatic veterans who underwent repeat MPI had obstructive CAD on coronary angiogram, compared to 7.2% of veterans who had repeat testing for new or progressive symptoms. Comparison of angiogram findings for abnormal MPIs based on the presence of symptoms on presentation did not reach statistical significance (p=0.053).

Conclusion:
Among asymptomatic veterans who underwent repeat MPI, < 3% of veterans had obstructive CAD. These findings support the AUC’s position that for asymptomatic patients, repeat MPI within 2-years of a normal study is rarely appropriate. However, among veterans with symptoms, 7 % were found to have obstructive CAD, but the difference between asymptomatic and symptomatic patients did not reach statistical significance. In the setting of symptoms, a negative MPI within 2-years is possibly a marker of low risk for obstructive CAD.
Abstract 16874: Ablation of Ventricular Tachycardia is Associated With Improved Arrhythmia-Free Survival Among Patients With Severe Heart Failure
Authors: Beck Natalie M , Sauer Peter J , Tumolo Alexis Z , Sandhu Amneet , Zipse Matthew M , Borne Ryan T , Nguyen Duy T , Schuller Joseph L , Aleong Ryan G , Tompkins Christine , Varosy Paul D , Rosenberg Michael , Khazanie Prateeti , Altman Natasha , Brieke Andreas , Cornwell William , Wolfel Eugene , Ambardekar Amrut , Allen Larry , Tzou Wendy S
Published: April 2024

Background:
Ventricular tachycardia (VT) ablation is often avoided in patients with advanced heart failure (HF) and this group of patients is often excluded from research trials.

Objective:
To evaluate VT recurrence rates among patients with severe HF and VT treated with ablation (Abl) versus medications (Med) alone.

Methods:
We performed a retrospective analysis of patients presenting to a tertiary referral hospital between 2006 and 2017 with ventricular tachycardia and severe heart failure (New York Heart Association functional Class IV or any Interagency Registry for Mechanically Assisted Circulatory Support score) for whom electrophysiology consult was requested. Baseline characteristics and VT recurrence were compared based on method of arrhythmia treatment.

Results:
Of 129 patients, 47% underwent ablation while 53% were managed medically. In this cohort, mean age was 60 ± 12 years, 84% were males, ischemic cardiomyopathy was present in 55%, mean LVEF was 24±12%, and 77% had a preexisting ICD.One-year mortality was 23%, 40% of whom were treated with Abl versus 60% with Med, p=0.196. Abl patients were more likely to have an ICD prior to presentation (85% vs 69%, p=0.037) and had shorter length of hospital stay (14±16 vs 21±16 days, p=0.021) compared to Med patients. Other baseline characteristics were not significantly different between groups. Abl patients overall had better VT-free survival compared to those treated with medications alone (OR 0.36, 95% CI [0.18, 0.80], Figure).

Conclusions:
Ablation of ventricular arrhythmia even in patients with severe heart failure is associated with decreased length of hospitalization and improved VT-free survival compared to medical therapy alone. These findings warrant additional, prospective study to verify and possibly improve management of this high-risk group of patients.
Abstract 16878: Preoperative Risk Factors for Delayed Discharge Post Carotid End Arterectomy and Carotid Artery Stenting: Is There Variability Among Centers?
Authors: Vasudevan Anupama , Nodine Rosha , Mannoia Kristyn , Shutze William P
Published: April 2024

Introduction:
Patient and procedure related factors contribute to prolonged post-procedural length of stay (PLOS) in patients undergoing Carotid End Arterectomy (CEA) or Carotid Artery Stenting (CAS).

Objective:
Identify pre-procedural risk factors for a discharge later than the day following the procedure. We also explored if there was variability in the patient population and PLOS between the centers.

Methods:
Regional VQI data (SoVONet) from the Society for Vascular Surgery Patient Safety Organization was obtained; outlier centers were those with higher median PLOS than the rest. The independent risk factors were identified by logistic regression analysis.

Results:
A total of 4867 CEA subjects (14 centers, 2012-2017) were included. Median age was 71 (22-90), 59.6% were male, median PLOS (days) was 1 (0-38) for 12 centers and 2 (1-94) for centers 5 &14 (outlier centers). Including all centers, 72.0% of subjects were discharged within one day while 28% stayed longer than a day post procedure. Differences in the independent risk factors were noted with and without including outlier centers (Table 1). Patients who underwent CEA at outlier centers were younger with higher proportion of non-whites and transferred from other hospitals. Burden of pre procedural dialysis and prior neuro events was higher, while COPD was lower among outlier centers. A total of 801 CAS patients (11 centers, 2012-2016) were included. Median age was 70 (22-90), 61.3% were male, median PLOS was 1 (0-16) day. Preop ambulation, hemoglobin levels prior CEA/CAS, transfer from another hospital were independent risk factors. However, “transfer from another hospital” was marginally significant when adjusted for centers, indicating a center influence.

Conclusion:
The risk factors for a delayed discharge were different for CEA and CAS. In addition, the patient population differed between the centers for CEA and this is to be taken into consideration when exploring for risk factors for delayed discharge.
Abstract 16885: Exposure to Heavy Metals Increases Cardiovascular Risk by Elevation of Serum Lipid Levels- a National Health and Nutrition Examination Survey Based Study
Authors: Buhari Olajide A , Atanda Adebayo C , Medhane Fitsumberhan , Faillace Robert T
Published: April 2024

Introduction:
Heavy metals, defined as metals with densities higher than 5g/cm3, can interact with various physiological processes in the body with cardiovascular consequences. We sought to gain a better understanding of the relationship between serum levels of heavy metals and serum total and LDL-cholesterol.

Hypothesis:
Serum total and LDL-cholesterol may be related to serum levels of heavy metals.

Methods:
a Cross-sectional survey using the NHANES 2009-2012 database. Age, Gender, were considered as covariates. Serum total cholesterol (TC; normal <200 mg/dl) and LDL cholesterol (LDL-C; normal < 100 mg/dl) were related to levels of lead, cadmium, and mercury.

Results:
We divided subjects into three tertiles, T1, T2 and T3 based on levels of heavy metals. The exposure for heavy metals was significantly different across all age groups and gender (P<0.0001) therefore we adjusted for these variables. There was a significant difference in the level of LDL-C and TC from the first to the third tertile for lead with progressively increasing values (P <0.0001). After adjusting for age and sex, the odds of having a higher TC was higher in T3 for lead when compared with T1 (OR 1.567,95CI1.376-1.786), the odds were also higher in T3 for mercury (OR 1.730,95CI 1.512-1.981) and cadmium (OR 1.412, 95CI1.184-1.700). Concerning LDL-C, the odds of having a higher LDL was more in T3 for lead when compared to T1( OR 1.225, 95CI 0.835-1.739), also the odds of having a higher LDL-C was higher in T2 for mercury (OR 1.233, 95CI 1.004-1.515). Compared to the reference group, the odds of having a higher TC level was statistically significant (p < 0.01) in T3 for all the metals studied, and the odds of having a higher LDL cholesterol was more in the second tertile for mercury (p < 0.01).

Conclusions:
Our study demonstrates increasing serum levels of heavy metals are significantly associated with increasing TC and LDL-C. This, in turn, may be associated with cardiovascular consequences in populations exposed to heavy metals such as areas with natural disaster water crises raising the consideration of screening for heavy metals as a risk for hyperlipidemia and cardiovascular disease.
Abstract 16901: Utilizing In Silico Pathogenicity Prediction Tools and Heterologous Expression Patch Clamp Studies to Identify Bona Fide Pathogenic
KCNH2
Variants Among Publically Available Exomes Derived From Subjects Without Evidence for Either Type 2 Long QT Syndrome or Type 1 Short QT Syndrome
Authors: Mattivi Connor L , Ye Dan , Tester David J , Clemens Daniel J , Zhou Wei , Giudicessi John R , Ackerman Michael J
Published: April 2024

Introduction:
Loss-of-function (LOF) and gain-of-function (GOF) pathogenic variants in the
KCNH2
-encoded Kv11.1 potassium channel cause type 2 long QT syndrome(LQT2) and type 1 short QT syndrome (SQT1), respectively. Given the prevalence of
KCNH2-
mediated heart disease (1 in 8000 for LQT2,1 in 100,000 for SQT1) and the reduced penetrance/variable expressivity seen in LQTS and SQTS, large databases such as the Genome Aggregation Database (gnomAD, n=141,352 individuals) might harbor subjects with unidentified LQT2/SQT1-causative mutations.

Objective:
To determine which “ultra-rare”
KCNH2
missense variants (MVs) in gnomAD are most likely to be LQT2- or SQT1-causative.

Methods:
A list of gnomAD-derived MVs in
KCNH2
was compiled. The frequency of each MV in gnomAD was assessed. Each MV was analyzed by 8
in silico
pathogenicity prediction tools. MVs that were seen once in gnomAD and predicted damaging by all 8 tools were considered possible LQT2/SQT1-causative MVs worthy of functional validation via whole-cell patch clamp.

Results:
Overall, 233/474 (49%) of gnomAD
KCNH2
MVs were seen in just 1 of >140,000 subjects. Of these, 2 (0.4%) MVs (S320W, S379Y) were predicted damaging by 8
in silico
tools. Both S320W and S379Y localize to the N-terminus of the Kv11.1 potassium channel. There was no significant change in peak or tail current density between heterozygously expressed KCNH2-S320W (n=13, p=NS) and KCNH2-WT (n=13). However, heterozygous KCNH2-S379Y (n=12) produced a marked increase in peak current density across the range -30 mV to +20 mV and shifted the V
1/2
of activation by -17 mV (p < 0.001). Also, tail current density of S379Y channels significantly increased across the range -20 mV to +20 mV and the V
1/2
of deactivation shifted by -26 mV (p < 0.001).

Conclusion:
With this stringent requirement of ultra-rarity, universal prediction of damaging impact, and functionally abnormal electrophysiological properties, one SQT1-causative pathogenic variant in gnomAD was identified consistent with the predicted frequency of SQTS. The search continues among the remaining 32 ultra-rare MVs in
KCNH2
where at least 75% of the
in silico
tools predicted deleterious impact of the MV to find the 15-20 subjects in gnomAD’s population who ought to have an LQT2-causative MV.
Abstract 16907: Natural Killer T (NKT) Cells Are Protective in Cardiac Arrest and Resuscitation
Authors: Kim Edy Y , Hayashida Kei , Ikeda Kohei , Choi Ji Young , Guo Jing Yu , Cullen Aidan M , Ngoy Soeun , Olenchock Benjamin , Ichinose Fumito , Brenner Michael B
Published: April 2024

(Submitted for Cournand and Comroe Award)
.

Introduction:
After out-of-hospital cardiac arrest and cardiopulmonary resuscitation (CA/CPR), mortality rates are 90%, primarily because of neurological dysfunction. However, there are no pharmacological treatments to help neurological function after sudden CA/CPR. The role of the immune system after CA/CPR is unclear and has not been tested as a therapeutic target. Innate T cells are a subset of T cells. We explored the role of innate T cells in CA/CPR because innate T cells are potent master regulators of the early inflammatory response in other diseases, such as infections.

Hypothesis:
Innate T cells and their antigens are novel therapeutic targets to treat neurological dysfunction after CA/CPR.

Methods:
Mice were mechanically ventilated and underwent 8 min. of normothermic asystolic cardiac arrest with potassium chloride i.v. Mice were resuscitated with chest compressions and epinephrine i.v.

Results:
The two major types of innate T cells in mice are Natural Killer T (NKT) cells and gamma-delta T cells. Here, we show that NKT cells improved neurological function and survival after experimental CA/CPR. First, we found that, after CA/CPR, NKT cells recognized the lipid antigen sulfatide, which is abundant in brain myelin. These sulfatide-specific NKT cells trafficked to the brain after CA/CPR. Mice deficient in NKT cells had worsened neuro-inflammation, with increased IFNγ and infiltration of Ly6c+CCR2+ macrophages and neutrophils in the brain after CA/CPR. Deficiency in IFNγ or CCR2 improved neurological function and survival after cardiac arrest. Treatment with the lipid antigen sulfatide after cardiac arrest improved neurological outcomes.

Conclusions:
This study identifies NKT cells as a key regulator of neuro-inflammation, neurological function and survival after cardiac arrest. We introduce immunomodulatory lipids, such as sulfatide, as a novel treatment class for cardiac arrest.
Abstract 16918: Non-Invasive Diagnosis of Pulmonary Vascular Disease Using Inhaled 129-XenonMRI
Authors: Swaminathan Aparna , Bier Elianna , Nouls John , Kennedy Karla , Womack Samantha , Almeida-Peters Susana , Driehuys Bastiaan , Rajagopal Sudarshan
Published: April 2024

Introduction:
Pulmonary arterial hypertension (PAH) carries significant morbidity and mortality. Its diagnosis requires meeting specific hemodynamic and clinical criteria and can be particularly challenging in patients with concomitant heart or lung disease. Hyperpolarized
129
Xenon (
129
Xe) magnetic resonance imaging and dynamic spectroscopy may overcome these challenges, providing a non-invasive new tool to diagnose and monitor PAH. This is based on its unique cardiogenic oscillations reflected in the
129
Xe spectrum as it transfers to red blood cells (RBCs, Figure).

Hypothesis:
We hypothesized that changes in the RBC
129
Xe spectroscopic parameters will discriminate PAH from healthy volunteers, patients with left heart failure, idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD).

Methods:
129
Xe spectra were dynamically acquired every 20 milliseconds in all subjects. At each time point, the amplitude, chemical shift, linewidth, and phase of the
129
Xe-RBC resonance was calculated. Cardiogenic oscillations in these spectral parameters were compared using the Kruskal-Wallis test, followed by pairwise comparisons with the Wilcoxon rank sum test.

Results:
A total of 14 healthy volunteers, 10 subjects with PAH, 5 subjects with left heart failure, 9 subjects with IPF, and 7 subjects with COPD underwent
129
Xe spectroscopy. In patients with PAH, RBC amplitude oscillations were significantly reduced compared to those with IPF (p < 0.001) or healthy subjects (p = 0.0064, Figure). Oscillations in chemical shift and phase were only observed in IPF patients.

Conclusions:
129
Xenon dynamic spectroscopy produces different RBC signatures in patients with PAH, IPF, and healthy volunteers.
129
Xe uniquely probes the alveolar-capillary interface and can thus detect the effect of arterial lesions on capillary blood volume oscillations.
Abstract 16930: Outcomes of Transcatheter and Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis and Pulmonary Hypertension: A Nationwide Inpatient Sample Matched Analysis
Authors: Fugar Setri , Kolkailah Ahmed A , Okoh Alexis K , Mattumpuram Jishanth , Siddamsetti Sisir , Al-Ogaili Ahmed , Ayoub Ali , Ranka Sagar , Sleiman Jose , Russo Mark J , Campagnoli Tania , Doukky Rami
Published: April 2024

Background:
Transcatheter aortic valve replacement (TAVR) has been established as a viable alternative to surgical aortic valve replacement (SAVR) in select patients with severe aortic stenosis (AS). Patients with pulmonary hypertension (PH) are at increased perioperative morbidity and mortality and thus were excluded from the major TAVR trials. We sought to compare the in-hospital outcomes after SAVR and TAVR in patients with severe AS and PH.

Methods:
We identified patients from the Nationwide Inpatient Sample (NIS) between 2012 and 2015 who underwent SAVR or TAVR using the ICD-9-CM procedure codes 35.21, 35.22 and 35.05, 35.06, respectively. We identified PH with codes 416.0, 416.8, and 416.9. A 1:1 propensity-matched cohort was created to examine the outcomes. Primary endpoint was in-hospital mortality. Secondary endpoints included hospital length of stay (LOS), cost, and post-procedural complications.

Results:
A matched pair of 670 TAVR and 670 SAVR patients were identified. The respiratory complications were less frequent with TAVR as opposed to SAVR. These included non-invasive ventilation requirement (3.3% vs. 5.8%, OR 0.55, p=0.028), pneumonia (1.5% vs. 4.3% vs. OR 0.33, p=0.003), acute respiratory failure (17.6% vs. 34.0%, OR 0.41), re-intubation (7.5% vs. 14.8%, OR 0.47), and tracheostomy (1.5% vs. 5.7%, OR 0.25), all p<0.001. The non-respiratory complications were also significantly less frequent in the TAVR group, including acute myocardial infarction (3.9% vs. 11.5%, OR 0.31), bleeding requiring blood transfusion (17.0% vs. 41.3%, OR 0.29), and acute kidney injury (11.5% vs. 22.4%, OR 0.45), all p<0.001. Permanent pacemaker (PPM) implantation was the only complication which was significantly higher in the TAVR group (24.6% vs. 11.8%, OR 2.43, p<0.001). Lastly, TAVR was associated with a significantly reduced risk of in-hospital mortality, total median cost, and shorter LOS (4.0% vs. 6.9%, OR 0.57, p=0.024, $171,496.0 vs. $218,625.4, p<0.001, and 5 vs. 12 days <0.001, respectively).

Conclusions:
Patients with PH undergoing TAVR had lower risk of in-hospital mortality, post-operative complications, shorter LOS and reduced overall cost compared to patients undergoing SAVR. Aside from higher risk of PPM implantation, TAVR may be the preferred option in this patient population.
Abstract 16962: The Genetic Basis of Hypercholesterolemia in a Community-Based Cohort
Authors: Jose Merin , Kochan David C , Kullo Iftikhar J
Published: April 2024

Introduction:
Prior reports of the genetic etiology of hypercholesterolemia are affected by referral bias, inclusion of individuals with secondary hypercholesterolemia and variability in identifying pathogenic variants. We sought to assess the prevalence of monogenic and polygenic etiologies in a community based cohort of adults with primary hypercholesterolemia (LDL-C ≥155 mg/dL after excluding secondary causes).

Methods:
We identified 1719 individuals aged 18-70 years with primary hypercholesterolemia from SE Minnesota. The Dutch Lipid Clinic Network (DLCN) score was ascertained by an electronic health record (EHR) based algorithm followed by manual review. Familial hypercholesterolemia (FH) was considered present with a DLCN score ≥6 whereas a DLCN score of 3-5 was considered possible FH. Participants underwent sequencing of FH genes (
LDLR, APOB, PCSK9
) and genotyping of 12 SNPs known to be associated with LDL-C. Rare (frequency <0.1%) and putatively functional variants were identified and pathogenicity was assigned based on the ACMG guidelines using relevant database, literature and EHR review. A polygenic score (PGS) for LDL-C (derived from 12 SNPs) >90
th
percentile was considered an indicator of polygenic etiology.

Results:
A pathogenic/likely pathogenic variant (16 in
LDLR
, 1in
APOB
and 2 in
PCSK9
) was present in 24 (1.3%) individuals, a PGS >90
th
percentile was present in 265 (15.4%) and 4 (0.2%) had both a monogenic and polygenic etiology. The overall prevalence of an identifiable genetic etiology was 17%. Based on clinical criteria the overall prevalence of FH (DLCN ≥6) was 7.0% (6.1% probable and 0.9% definite) and that of possible FH was 30.0%. In the possible, probable and definite FH categories, a monogenic etiology was present in 2.4%, 9.5% and 26.7% and a polygenic etiology in 19.1%, 21.0% and 13.3% respectively. 52.0% of those with a monogenic etiology and 9.7% of those with a polygenic etiology met the DLCN criteria for FH.

Conclusions:
This study provides for the first time estimates of monogenic and polygenic etiology of hypercholesterolemia in adults from the community, excluding cases of secondary hypercholesterolemia and using standardized methods of variant annotation.
Abstract 16997: Polymorphic Ventricular Tachycardia: Torsade De Pointes or Purkinje Fiber Triggered Polymorphic Ventricular Tachycardia?
Authors: Coromilas James , Saluja Amardeep , Kostis William J , Kassotis John
Published: April 2024

Introduction:
Purkinje Fiber triggered polymorphic ventricular tachycardia (Purkinje VT) is often misidentified as torsade de pointes ventricular tachycardia (TdP), While TdP is almost always responsive to IV magnesium, correcting electrolytes and removing offending QT prolonging drugs, Purkinje VT is not amenable to this treatment, is usually refractory to anti-arrhythmic drug treatment and is best managed by ablation of Purkinje fiber triggers.

Methods:
We compared the clinical and electrocardiographic features of Purkinje VT to TdP to determine distinguishing features.

Results:
Since June 2015, we identified 11 patients (pts) with Purkinje VT and compared them to 11 patients with TdP. Ten of the 11 Purkinje VT pts were male vs 1 of 11 TdP pts (p < 0.005). The LVEF was 22.4 ± 7.2 % in the Purkinje VT pts vs.39.8 ±10.4 % in the TdP pts (p <0.005). Both the QTc (0.46 ± 0.05 vs. 0.62 ± 0.09 sec) and the coupling interval from the last normal complex to the first VT complex (0.35 ± 0.06 vs. 0.53 ± 0.08 sec) were shorter in the Purkinje VT pts than in the TdP pts (p <0.0001 for both). Although the QTc was significantly longer in the TdP pts, 4 of the 11 Purkinje VT patients had QTc intervals ≥ 500 msec. All the Purkinje VT pts had frequent PVCs triggering the PMVT vs 5 of 11 pts with TdP who had PVC of the same morphology as the first complex of torsade preceding the TdP (p <0.05). Patients with Purkinje VT were more likely to be in cardiogenic shock (6 of 11 vs 0 of 11) and to present with VT storm (7 of 11 vs 1 of 11) than pts with TdP (p <0.05 for both). In addition, Pts with Purkinje VT were more likely to have associated episodes of rapid monomorphic VT (9 of 11 vs 2 of 11) than those with TdP (p <0.01)

Conclusions:
Purkinje VT is distinguished from TdP by a short coupling interval, a relatively shorter QTc and the obligatory presence of triggering. PVCs. Pts with Purkinje VT are more likely to present with VT storm, cardiogenic shock and to have associated episodes of monomorphic VT/VFlutter than pts with TdP.
Abstract 12325: Psychosocial Correlates of Hypertension Among Filipinos Living in Primarily Rural Areas of the Philippines
Authors: Lorenzo Elizabeth , Evangelista Lorraine S
Published: April 2024

Introduction:
Self-reported depression, anxiety, stress, and poor health-related quality of life (HRQoL) have all been linked to an elevated risk of hypertension (HTN), although indicators of psychosocial burden among Filipinos residing in rural parts of the Philippines are poorly defined.

Methods:
This cross-sectional study was conducted in the Philippines in 2017 and included a large representative sample of 1203 Filipinos (64.6 % female; 49.5 ± 17.7 years old; 16% widowed) seeking care from their barangay health clinics. Sociodemographic characteristics, health history, and psychosocial factors (depression, anxiety, stress, HRQoL) were assessed through a structured survey. In addition, height, weight, blood pressure, and waist circumference were measured. Multivariable-adjusted binary logistic regression was used to assess the independent predictors of hypertension.

Results:
HTN was observed in 42.5%, while depression, anxiety, stress, and overweight/obesity were noted in 20.6%, 39.0%, 82.1% and 29.4%, respectively. Women were more likely to be widowed and men married. No gender differences were noted in HTN, depression, or physical HRQoL, but women were more likely to be stressed and had higher anxiety and lower mental HRQoL than men. HTN was associated with higher depression and lower physical HRQoL. Significant positive correlates of HTN were being widowed and lower physical and mental HRQoL. Stress was the only correlate of HTN for men and lower physical and mental HRQoL for women.

Conclusions:
The results of this study are broadly consistent with prior studies from other East Asian countries. The study stresses the significance of reconsidering methods to assess both demographic and contextual characteristics in terms of psychological comorbidities in Filipinos, which could aid in identifying those at high risk for HTN. Future research should concentrate on raising knowledge of psychosocial factors and HTN in rural communities and designing interventions that target self-management of concomitant disorders. Decision-makers and policymakers must be aware of the rising trend and the socioeconomic and psychosocial drivers of HTN to limit its influence on cardiovascular disease morbidity and mortality.
Abstract 12344: Impact of Age on Hospital Outcomes Associated With Percutaneous Left Atrial Appendage Occlusion: Insights From a Nationwide Cohort Sample
Authors: Shatla Islam , Elkaryoni Ahmed , Abumoawad Abdelrhman , El Iskandarani Mahmoud , kennedy kevin , Wimmer Alan P
Published: April 2024

Introduction:
Percutaneous left atrial appendage occlusion (LAAO) has emerged as a proven alternative for thromboembolism prevention in patients with atrial fibrillation (AF) who cannot tolerate long term anticoagulation. The mean age in clinical trials has been less than 75 years. There are limited data on LAAO safety in older patients.

Methods:
We used the National Inpatient Sample and ICD-10 codes to identify AF patients who underwent LAAO during the years 2016-2018. Patients were grouped by age <75 and ≥ 75 years. We studied baseline characteristics, length of stay, cost, hospital mortality, and other adverse events, including, hematoma, vascular complications, and perforation/tamponade, and stroke/transient ischemic attack in the two groups.

Results:
Our search criteria identified a total of 6877 patients, of whom 4160 (60.4%) were ≥ 75 years. LAAO increased similarly among patients in both groups (figure1). The average length of stay after LAAO was 1.5 ± 1.9 days for the entire cohort and did not differ for the two groups (p=0.603). Hospitalization costs were $25635.6 ± 12041.5 among patients ≥ 75 years and $26175.6 ± 11768.0 in those < 75 years (P=0.067). There were 10 deaths in patients ≥75 years and 1 death among patients <75 years (p=0.059). Perforation/tamponade was 1.3% among patients ≥75 years vs 0.6% for those <75 years (p=0.008). This difference persisted on multivariate analysis (OR 1.82; 95% CI 1.04-3.17; p=0.036). There was a trend towards higher combined procedure related adverse events (OR 1.46; 95% CI 0.99-2.15; p= 0.059) among patients ≥75 years. There was no difference in the individual components of hematoma, vascular complication, and stroke/TIA between both groups.

Conclusions:
Percutaneous LAAO was associated with a higher incidence of perforation and tamponade and a concerning trend towards higher in-hospital mortality among older patients. Further clinical investigations are warranted to explore the risk in this vulnerable group.
Abstract 12358: Oral Iron Supplementation is Associated With Lower Pulmonary Vascular Resistance in Patients With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction
Authors: Tang Yicheng , Patel Ashish B , Rahman Haris , Jang Sae K , Handen Adam , Hickey Gavin W , Kelly Neil , Chan Stephen Y
Published: April 2024

Introduction:
Pulmonary hypertension (PH) associated with left heart disease can be stratified as isolated post-capillary (IpcPH) or combined pre and postcapillary (CpcPH) on the basis of a normal or elevated pulmonary vascular resistance (PVR). While CpcPH carries a poor prognosis, the mechanistic determinants of PVR in this population remain undefined. We hypothesize that discrepant medication usage between hemodynamic extremes of IpcPH and CpcPH may underlie this phenotypic divergence.

Methods:
Invasive hemodynamics were obtained at UPMC between 2008 and 2018. 4,567 patients met diagnostic criteria for Group 2 PH (mean pulmonary artery pressure [mPAP] ≥ 25mmHg, pulmonary artery wedge pressure [PAWP] > 15mmHg) based on the 2013 definition. Patients were classified as having extreme IpcPH (PVR<2WU, N=414) or CpcPH (PVR>4WU, N=172). Patients with overlapping PH diagnoses were excluded. Preserved ejection fraction was defined as a left ventricular EF >40%. Follow-up analyses were conducted on an independent set of PH-HFpEF patients with two RHCs more than 90 days apart inclusive of all PVRs (N=46).

Results:
Compared to IpcPH (N=127), patients with CpcPH (N=47) were prescribed anticoagulants (53.19 vs. 19.69%, p<0.001) more frequently and oral iron supplements less frequently (4.26 vs. 20.47%, p=0.010). Red cell distribution width (RDW), a marker of iron deficiency, was significantly higher in CpcPH (16.57 vs. 15.24%, p=0.007). In PH-HFpEF patients with successive RHCs, change in PVR correlated positively with change in RDW (p=0.002). Compared to iron naïve patients (N=30), iron initiation (N=7) between RHCs was associated with a lower change in PVR (-1.05 vs. +0.66WU, p=0.008).

Conclusions:
In a PH-HFpEF cohort, iron supplementation was associated with lower PVR, suggesting that iron deficiency may contribute to vascular remodeling in PH-HFpEF.
Abstract 12385: TBX5-Based Lineage Tracing Identifies a Propensity for Left Ventricular Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells Using Biphasic Modulation of WNT Signaling
Authors: Galdos Francisco X , Lee Soah , Goodyer William R , Paige Sharon , Lee Carissa , Xu Sidra , Escobar Gabriela V , Bak Rasmus O , Porteus Matthew , Wu Sean M
Published: April 2024

Introduction:
Patient-derived induced pluripotent stem cells (iPSCs) present an exciting avenue for the modeling of adult and congenital heart diseases. While hiPSC cardiac differentiations generate various cell types, the presence of mixed cell populations can confound interpretation of study results. During cardiac development, progenitors from the first (FHF) and second heart fields (SHF) give rise to cells in the left (LV) and right ventricles (RV), respectively. The availability of a lineage tracing tool to identify these progenitors and their descendants during differentiation would enhance our understanding of the mechanisms that regulate heart development.

Hypothesis:
Heart field lineage tracing in human iPSCs will reveal the stepwise emergence of FHF and SHF progenitor cells and address whether 3D differentiation format provides greater capacity than 2D for generating cells in the SHF lineage.

Methods/Results:
Using CRISPR/Cas9, we introduced gene targeting constructs into two healthy human iPSCs lines to permanently label all TBX5 expressing FHF cells and their descendants with GFP. Standard small molecule biphasic WNT modulation protocols in both 2D and 3D differentiation formats were used to generate ventricular cardiomyocytes. At days 11-30 of differentiation, cells were analyzed by FACS for the percentage that express GFP and TNNT2. Analysis of GFP+ cells out of TNNT2+ CMs showed an increase in GFP expression on days 11 (55.8% ± 3.6%), 15 (67.0% ± 3.0%), 20 (89.2% ± 1.7%), and 30 (99.4% ± 0.4%) in 2D differentiations. Single-cell RNA-seq analysis of day 15 CMs confirmed the co-expression of GFP and HAND1 (a LV marker) in >80% of total cells and showed absent expression of SHF-specific markers, TBX1 and FGF8. In 3D differentiations, we also observed GFP expression in greater than 95% of TNNT2+ CMs, confirming the FHF propensity of this differentiation protocol.

Conclusions:
We generated two FHF lineage tracing hiPSC lines and showed that the WNT modulation differentiation protocol gives rise to predominantly FHF (LV) but not SHF (RV) CMs in both 2D and 3D formats. Ongoing studies will clarify the mechanism for this increased propensity as well as the developmental signaling pathways that drive the differentiation of the FHF and SHF.
Abstract 12403: Type 1 Diabetes Alters Estrogen-Stimulated microRNA Expression and Impairs Nitric Oxide Production in Human Coronary Artery Endothelial Cells
Authors: Wang Jingli , Hofeld Benjamin , Puppala Venkata K , Ying Rong , Harris Ryan A , Widlansky Michael E
Published: April 2024

Introduction:
Women developed CAD about 1 decade after men. This advantage is erased in T1DM women, and the mechanisms remain unclear. Estrogen (E2) stimulates endothelial NO production via estrogen receptors, and microRNA (miR) have emerged as critical regulators of endothelial function. Whether E2 stimulation of NO production is impaired in T1DM and whether E2 stimulates different miR expression patterns are unknown.

Hypothesis:
E2-stimulated NO production will be impaired in T1DM endothelial cells which will also express differences in miR expression with E2 exposure.

Methods:
All experiments were done with and without incubation with 1 nM 17β-estradiol for 24 hours. MicroRNA was isolated from culture human coronary artery endothelial cells (HCAECs) from a woman with and a woman without T1DM. MicroRNA was isolated from HCAECs with four different exposure conditions (T1DM ± 1 nM 17β-estradiol for 24 hr and non-T1DM± 1 nM 17β-estradiol for 24 hr, N=4 biological replicates for all exposures). Fold changes in expression comparing T1DM and non-T1DM cells with and without estradiol stimulation were generated at significance testing performed using DESeq2 with FDR set at 5%. NO production was measured in HCAECs under the same 4 conditions using DAF2-DA and HPLC.

Results:
249 miRs were differentially expressed inT1DM HCAECs compared to non-T1DM HCAECs in non-E2 stimulated samples. In E2-stimulated samples, 201 miRs were differentially expressed. Cross-referencing these comparisons showed 16 miRs differentially expressed in T1DM HCAECs relative to non-T1DM HCAECs both with and without E2 stimulation. 4 of these (miRs 548-ar-3p, 625-3p, 369-3p, and 376a-5p) were significantly changed in the opposite direction with estrogen stimulation compared to unstimulated HCAECs, suggesting changes in the expression were due to changes in E2 signaling in T1DM HCAECs. Further, estradiol stimulation of T1DM HCAECS demonstrates a significantly blunted NO production compared to non-T1DM HCAECs (N=6, P<0.05).

Conclusions:
E2-stimulated NO production is impaired and E2-stimulated changes in miR expression differ in the T1DM endothelium. Further work is necessary to determine whether these differences in miR expression impact E2-stimulated NO production in T1DM.
Abstract 12418: History of Physical or Sexual Abuse in Early Life and Risk of Preeclampsia
Authors: Stuart Jennifer J , Mason Susan M , Becene Iris A , Koenen Karestan C , Rexrode Kathryn M , Rich-edwards Janet W
Published: April 2024

Introduction:
Women with a history of abuse are more likely to develop chronic hypertension later in life. However, it is unknown whether early life abuse is associated with the risk of developing preeclampsia, a hypertensive disorder that complicates 5-7% of pregnancies.

Hypothesis:
We hypothesized that women with a history of physical or sexual abuse during early life would have a higher risk of developing preeclampsia during their first pregnancy.

Methods:
Nurses’ Health Study II participants reported on their histories of physical and sexual abuse in early life (childhood [0-10 years] or adolescence [11-17 years]) in 2001 and pregnancy complications (including preeclampsia) in 2009. Parous women with available information on early life abuse and pregnancy history comprised the study sample (n=46,212). Modified Poisson regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) for the associations between physical and sexual abuse in early life and preeclampsia. Models were adjusted for maternal age at pregnancy, year of birth, race/ethnicity, body size (somatogram) at age five, and childhood socioeconomic status.

Results:
More than half of women (53%; n=24,212) reported a history of physical abuse in early life, with 9% reporting severe abuse. A history of sexual abuse in early life was reported among 33% of women (n=15,389); 22% reported touch only sexual abuse while 11% reported a history of forced sexual activity. History of severe physical abuse in early life was associated with a 37% increased risk of preeclampsia in first pregnancy (CI: 1.19-1.57) compared to no early life physical abuse. History of forced sexual activity in early life was associated with a 33% increased risk of preeclampsia in first pregnancy (CI: 1.19-1.48) compared to no early life sexual abuse. Histories of less severe physical abuse or touch only sexual abuse were not associated with preeclampsia risk.

Conclusion:
Women with a history of severe physical or sexual abuse in childhood or adolescence appear to have an increased risk of developing preeclampsia during pregnancy.
Abstract 12421: Clinical Evidence, Electric and Fluid Dynamics Reveal Systolic Volume as the Direct Effector of RV Systolic Impedance Variations: Innovations on CLS Algorithm in Pacing
Authors: Sabatini Antonella , Tomaino Marco
Published: April 2024

Background:
Dual chamber PM-CLS algorithm, originally conceived as Rate Responsive (RR) algorithm in cardiac pacing, has been recently clinically used beyond RR, by being activated in a selected group of patients (pts) affected by severe recurrent reflex syncope and tilt-induced asystole. PM-CLS is highly effective in reducing recurrences (BIOSync CLS Trial, 2021).

Methods:
After Biosync Trial, PM-CLS has experienced increasing importance in the scientific community. CLS exhibits peculiar features in the context of a selected group of Neurally Mediated reflex Syncope (NMS) due to different triggers: central or orthostatic. The mechanism of PM-CLS in intrinsic disturbances and extrinsic central and orthostatic triggered NMS are depicted in Fig.1.

Discussion:
NMS prevalence (# of events ≥ 1, gen. population) is 50%. Only pts with severe clinical presentation may benefit from pacing. CLS functioning as RR provides compensative pacing in pts affected by intrinsic electric disturbance (sinus node disease). In NMS (normal electric conduction system but extrinsic disturbance) CLS can anticipate pacing at appropriate heart rate (HR) at reflex triggering, avoiding abrupt HR drop and preventing asystolic syncope.CLS measures intracardiac systolic Right Ventricle (RV) impedance (Z), after PM pacing/sensing, via subthreshold high-freq. current pulses.

Clinical evidence (BIOSync CLS Trial), electric circuits and fluid dynamics reveal systolic volume as the direct effector of RV Systolic Z, bound by inverse proportionality (Fig.1): • Hypovolemia = High Z • Hypervolemia = Low Z Systolic Z variations activate CLS.

Conclusions:
Cardiac pacing with CLS is also highly effective in reducing recurring syncope. CLS highlights the importance of volemia being the direct effector of RV systolic impedance. Innovative use of PM-CLS could be exploited in other NMS conditions, dysautonomia and heart failure follow-up.
Abstract 12446: Lipocalin10 Deficiency Exacerbates Myocardial Ischemia/Reperfusion Injury via Impairing Macrophage Efferocytosis
Authors: Li Yutian , Wang Xiaohong , Huang Wei , Li Qianqian , Wang Yi-gang , Chen Jing , Fan Guo-chang
Published: April 2024

Introduction:
Efficient clearance of dead cells by macrophages (termed as efferocytosis) is critical for timely repairing the injured heart after ischemia/reperfusion (I/R), as defective removal of dying cells could cause secondary necrosis and infarct expansion. Recent studies have shown that lipocalin 10 (Lcn10) is significantly downregulated in cardiac tissue from patients with heart failure. However, the role of Lcn10 is virtually unknown during cardiac I/R, and its function in macrophage efferocytosis has never been explored.

Hypothesis:
Our initial data showed that Lcn10 expression was upregulated in bone marrow-derived macrophages (BMDMs) during efferocytosis. Thus, we hypothesize that knockout (KO) of Lcn10 would diminish macrophage efferocytosis, leading to exacerbated cardiac I/R injury.

Methods/Results:
Since Lcn10 is a secreted protein, we generated a global Lcn10-KO mouse model. After co-culturing BMDMs with GFP-labeled dead myocytes for 2h, we observed a 25% reduction on efferocytosis by KO-BMDMs, compared to wild-type (WT) controls. Using Lcn10-KO
mCherry
mouse model (cardiac-specific overexpression of mCherry in Lcn10-KO mice), we detected that KO cardiac macrophages ingested fewer dead myocytes at 3 days post-I/R, compared to WT-mCherry controls. Accordingly, cardiac contractile function, measured by echocardiography at the same time, was significantly declined in KO-mice, together with increased accumulation of apoptotic cells and higher serum levels of troponin I, a marker of cardiac damage, compared with WTs (n=7-10,
p
<0.05). In addition, pre-treatment of KO-BMDMs with recombinant Lcn10 protein could rescue the impaired efferocytosis. Mechanistically, RNA-seq analysis showed that many downregulated genes (i.e., ItgaV, Itga6, Cx3cr1, and Msr) in KO-macrophages are associated with efferocytosis. Interestingly, we identified that Lcn10 contains a potential phosphatidylserine (PS)-binding motif (RxKRK), located at a helix-turn-helix structure, which is the primary “find-me” signal for efferocytosis.

Conclusions:
Our data indicate that Lcn10 is pivotal for macrophage efferocytosis to remove cardiac dead cells during I/R. Thus, Lcn10 could be used as a new mediator for the treatment of cardiac I/R injury.
Abstract 12447: Early-Stage, Community-Based Design Process to Understand User Needs for Hypertension Management mHealth Intervention: The WIRED-L Study
Authors: Robles Maria Cielito , Huang Linde , Merid Beza , Doshi Aalap , Choi Soo Ji , Kurien Chris , Newman Mark , Dorsch Michael , Nallamothu Brahmajee K , Skolarus Lesli E
Published: April 2024

Background:
Black Americans and older adults have high rates of hypertension and face unique barriers to managing their blood pressure. Using a community-based participatory design approach, we sought out to understand such barriers and determinants for engaging in a healthy lifestyle to inform the development of a wearables-based mHealth intervention.

Methods:
As part of the Wearables In Reducing risk and Enhancing Daily Life-style (WIRED-L) study, we performed semi-structured discovery interviews of hypertensive adults in Flint and Ann Arbor, MI that relied on the capability, opportunity and motivation behavior (COM-B) framework focusing on 2 behaviors: 1) increase physical activity and 2) decrease salt intake. A rapid analysis approach was used to analyze interview data. Transcripts were used as artifacts for the subsequent empathy mapping session, attended by academic partners and community participants, to contextualize the discovery interviews. Results were compared across study sites.

Results:
We conducted 9 discovery interviews (Flint = 4 Black people; Ann Arbor = 3 White and 2 Asian people). Physical capability (i.e. pain and disability) and automatic motivation (i.e. habits and drive) were barriers for physical activity, while psychological capability (i.e. understanding), automatic and reflective motivations (i.e. plans and evaluations) were barriers for healthy eating. From empathy mapping that included 12 stakeholders, the primary insight for the Flint user group was a desire to decrease salt intake, but practical constraints exist (e.g., unhealthy foods are the cheaper option, and price is an important factor in health decisions). In the Ann Arbor user group, participants were comfortable with navigating technology and had environments more conducive for physical activity.

Conclusion:
User groups faced different challenges to maintaining a healthy lifestyle. To reduce hypertension disparities, our design will focus on the barriers that were more prevalent among the Flint population. Our results suggest reducing racial disparities in hypertension will require addressing all phases of mHealth intervention development.
Abstract 12451: Monocytes Enhance Inflammatory Responses to Soluble Matrilin-2 in Human Aortic Valve Interstitial Cells via the Interaction of β
2
-integrin With ICAM-1
Authors: Luo Zichao , The Erlinda , Zhang Peijian , Yao Qingzhou , Zhai Yufeng , Ao Lihua , Zeng Qingchun , Fullerton David , Meng Xianzhong
Published: April 2024

Calcific aortic valve disease (CAVD) is a slow progressive disease. Chronic inflammation plays a crucial role in CAVD progression. Monocyte infiltration and macrophage accumulation are found in calcified aortic valves. Soluble extracellular matrix proteins can act as damage-associated molecular patterns to induce the pathobiology associated with CAVD in aortic valve interstitial cells (AVICs). While human AVICs exhibit inflammatory response to soluble matrilin-2, the impact of monocytes on this response is unknown. We hypothesized that monocytes enhance AVIC inflammatory response to soluble matrilin-2 by a mechanism involving cell-cell interaction.

Methods and Results:
Human AVICs isolated from normal aortic valves were cultured alone or cocultured with monocytes in the absence or presence of recombinant matrilin-2 (1, 2 or 4 μg/ml). AVIC expression of ICAM-1 and IL-6 following an exposure to any dose of matrilin-2 was markedly enhanced by the presence of monocytes although matrilin-2 in the tested dose range had no effect on monocyte production of ICAM-1 or IL-6. Monocytes adhered to AVICs following matrilin-2 stimulation. Interestingly, matrilin-2 up-regulated the expression of β
2
-integrin in monocytes and ICAM-1 in AVICs. Neutralization of β
2
-integrin or ICAM-1 in coculture with specific antibody reduced the number of monocytes adhering to AVICs and suppressed the expression of ICAM-1 and IL-6
.
Conversely, addition of β
2
-integrin CD18 enhanced the expression of ICAM-1 and IL-6 in AVICs exposed to matrilin-2. Further, stimulation of coculture with matrilin-2 induced greater YAP and NF-κB phosphorylation compared to AVIC monoculture. Inhibition of either YAP or NF-κB markedly suppressed the inflammatory response to matrilin-2 in coculture.

Conclusions:
Monocyte β
2
-integrin interacts with AVIC ICAM-1 to augment AVIC inflammatory response to soluble matrilin-2 through enhancing the activation of YAP and NF-κB signaling pathways. Infiltrated monocytes may promote valvular inflammation through cell-cell interaction with AVICs to enhance their sensitivity to damage
-
associated molecular patterns.