bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10159: Underuse of Evidence-based Therapies for Patients with Type 2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease: Insights from Clinical Research Networks in the United States
Authors: Nelson Adam J , O'Brien Emily , Kaltenbach Lisa A , Green Jennifer , Lopes Renato D , Morse Caryn G , Al-khalidi Hussein , Aroda Vanita , Cavender Matthew A , Gaynor Tanya , Kirk Julienne , Lingvay Ildiko , magwire melissa , McGuire Darren K , Pak Jonathan , Pop-Busui Rodica , Richardson Caroline , Senyucel Cagri , Kelsey Michelle , Pagidipati Neha J , Granger Christopher B
Published: March 2022

Background:
Evidence-based therapies for cardiovascular risk reduction are generally underused in patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). While patterns of preventive care have been documented in selected populations, insight into the contemporary use of these evidence-based therapies in broader US populations is lacking.

Methods:
Data were obtained from 12 health systems with data marts linked to the National Patient-Centered Clinical Research Network. Patients with T2DM and established ASCVD (coronary artery disease, cerebrovascular disease and peripheral artery disease) with a healthcare encounter in 2018 were identified and their lipid, blood pressure and glucose-lowering therapies evaluated. Descriptive analyses were performed on patient characteristics by prescription of any of the following key evidence-based therapies: high-intensity statin, angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB), and sodium glucose co-transporter-2 inhibitors (SGLT-2i) or glucagon-like peptide-1 receptor agonist (GLP-1RA).

Results:
The overall cohort comprised 324,706 patients with mean age 68.2 years, 44.4% were female, 36.0% non-white and 12.8% Latinx. In the prior year, 8.7% visited an endocrinologist, while 26.4% visited a cardiologist and 74.8% visited a primary care physician. Overall, 58.6% were prescribed a statin (26.8% were on a high-intensity formulation), 45.5% were prescribed an ACEi or ARB, and 3.9% were prescribed a GLP-1RA and 2.8% an SGLT-2i. Overall, 4.6% were prescribed all three therapies and 42.5% were prescribed none. Those prescribed either an SGLT-2i or a GLP-1RA were younger, more likely to be privately insured, have fewer comorbidities, more complex T2DM and have seen an endocrinologist.

Conclusions:
In this large, US national cohort of patients with T2DM and ASCVD, fewer than 1 in 20 patients were prescribed all 3 of a high intensity statin, either an ACEi or ARB and either an SGLT-2i or a GLP-1RA. Multifaceted interventions are needed to overcome barriers to the implementation of evidence-based therapies and their suboptimal use, as confirmed in this large, representative cohort of patients in the United States.
Abstract 10163: Ca
2+
Within the Mitochondria Can Affect the Occurrence of Triggered Arrhythmias in Rats with Right Ventricular Hypertrophy
Authors: Kumasaka Kazunori , Sato Haruka , Satoh Wakako , Shindoh Chiyohiko , Miura Masahito
Published: March 2022

Background:
Ca
2+
within the sarcoplasmic reticulum affects the propagation of intracellular Ca
2+
(Ca
i
) waves, and the velocity of Ca
i
waves play important roles in the occurrence of triggered arrhythmias. It is still unknown, however, whether Ca
2+
within the mitochondria (Ca
m
) affects the velocity of Ca
i
wave and the occurrence of arrhythmias in right ventricular (RV) hypertrophy.

Objective:
To know the roles of Ca
m
in the velocity of Ca
i
waves and the occurrence of triggered arrhythmias in rats with RV hypertrophy.

Methods:
Rats were subcutaneously injected with 60 mg/kg monocrotaline (MCT-rats) or solvent (Ctr-rats). Four weeks after the injection, trabeculae were dissected from the RVs. The force was measured using a silicon strain gauge, Ca
m
using rhod-2, Ca
i
using microinjected fura-2 and a CCD camera, and production of reactive oxygen species (ROS) from the slope DCF fluorescence during electrical stimulation. Ca
2+
waves and arrhythmias were induced by electrical stimulation (24°C).

Results:
MCT-rats showed a higher RV pressure, a larger weight ratio of RV free wall to left ventricle (RV/LV), and faster and larger Ca
i
waves than Ctr-rats (p<0.01). Among MCT-rats, Ru360 (10 μM), a mitochondrial calcium uniporter (MCU) inhibitor, decreased the occurrence of arrhythmias in trabeculae from rats with a higher RV pressure and a larger RV/LV (n=19). Ru360 decreased rhod-2 signal within trabeculae depending on the RV/LV (r=-0.85, p<0.01, n=10) without changes in Ca
i
transients, suggesting that inhibition of MCU decreases Ca
m
in MCT-rats with more severe RV hypertrophy. In addition, Ru360 decreased the velocity of Ca
i
waves depending on systolic RV pressure (r=-0.60, n=6) and the RV/LV (r=-0.64, n= 7), suggesting that inhibition of MCU decreased the velocity of Ca
i
waves in MCT-rats with higher RV pressure and more severe RV hypertrophy. Ru360 decreased the slope of DCF fluorescence (p<0.01, n=13).

Conclusions:
In the hearts with severe RV hypertrophy, inhibition of MCU can cause larger reduction of Ca
m
, decrease ROS production, and decrease the velocity of Ca
i
waves and arrhythmias. Thus, in the hearts with severe RV hypertrophy, more Ca
2+
may enter the mitochondria through the MCU, and higher Ca
m
may be involved in the occurrence of arrhythmias.
Abstract 10167: Coronavirus Disease 2019 Pandemic and Incidence of Takotsubo Syndrome: A Retrospective Study
Authors: Trivedi Dyuti , Black Emma , Khatri Surya , Tripolone Janice , Gathright Emily , Salmoirago-blotcher Elena
Published: March 2022

Introduction:
During the Coronavirus Disease 2019 (COVID-19) pandemic individuals have been exposed to unprecedented levels of psychological, social, and financial stress. Given the association between Takotsubo Syndrome (TS) and stress exposure, we hypothesized that the incidence of TS would increase during the Covid-19 pandemic.

Methods:
We performed a retrospective review of electronic medical records of patients admitted to three large hospitals in RI, United States. The proportion of TS admission (based on Mayo Clinic criteria)/all-cause admissions during the first pandemic year (3/1/2020-2/28/2021) was compared with that of the previous, non-pandemic, year (3/1/2019-2/28/2020). We collected information on demographics, medical history, and length of hospitalization. T-test and chi-square were used to compare continuous and categorical variables, respectively. A p value (2-sided) < .05 was considered significant.

Results:
The number of all-cause admissions was lower during the pandemic vs. the pre-pandemic year (229,906 vs. 316,299), p < .001. During the pandemic year, 39/229,906 patients were admitted with TS, compared to 35/316,299 in the pre-pandemic period. Characteristics of TS patients were similar except for the duration of hospital stay (Table 1). TS incidence proportion was 0.017% during the pandemic period vs. 0.011% (p .07, Fig. 1), and the rate ratio was 1.53 (95% CI: 0.97, 2.42).

Conclusions:
Despite the limitations of this study (small sample size; retrospective design), findings suggest the incidence of TS was higher during the pandemic year. These findings need to be confirmed in a larger and more diverse population.
Abstract 10170: Mode of Death After Heart Failure Hospitalization in Elderly Patients
Authors: Nakamaru Ryo , Shiraishi Yasuyuki , Kohsaka Shun , Kohno Takashi , Goda Ayumi , Takei Makoto , Nagatomo Yuji , Tanaka Toshikazu D , Nakano Shintaro , Fukuda Keiichi , Yoshikawa Tsutomu
Published: March 2022

Introduction:
Mode of death in heart failure (HF) patients varies by age. This study aimed to assess associations between cardiovascular (CV) and non-CV mortality with age among patients discharged after HF hospitalization using the competing risk analysis.

Methods:
From 2006 to 2017, 3558 consecutive patients enrolled in a prospective multicenter registry in Japan (the West Tokyo Heart Failure registry) were analyzed. The patients were categorized based on age and LVEF as follows: 1) <65 years (younger; LVEF ≥50% [n=182] and LVEF<50% [n=575]); 2) 65-84 years (elderly; LVEF ≥50% [n=894] and LVEF<50% [n=1159]); and 3) ≥85 years (very elderly; LVEF ≥50% [n=429] and LVEF<50% [n=319]). We evaluated the cumulative incidence of all-cause death and each mode of death after discharge. A Cox proportional hazards modeling was used with the Fine-Gray competing method.

Results:
During the median follow-up of 2.0 years, the incidence of all-cause death increased in parallel with increasing age categories. The Fine-Gray model demonstrated that LVEF was independently associated with risk of CV death (CVD) (adjusted subdistribution hazards ratio, 1.03; 95% confidence interval, 1.03-1.04, p<0.01). An enrichment in the proportional risk of CVD vs. non-CVD was also observed in patients with LVEF <50% even with increasing age categories: LVEF<50% (younger: 65.0%, elderly: 64.2%, very elderly: 55.6%) and LVEF ≥50% (younger: 50.0%, elderly: 41.2%, very elderly: 38.2%) (Figure).

Conclusions:
Mortality after HF hospitalization remains substantial in the contemporary era, particularly among elderly patients. Of note, the proportion of non-CVD increased with age, albeit CVDs still accounted for over half of deaths in patients with LVEF <50% in the patients within the oldest category.
Abstract 10171: Higher Rates of Major Adverse Cardiac and Cerebrovascular Events in Non-White Patients Among Nationwide Hospitalizations of Young Adults: A Race and Sex-Stratified Analysis
Authors: Sachdeva Sonali , Binkam Mounika , Yar Khan Nibras , Jabar Ali Jamila Begum , Bhatt Nilay R , Tzorin Pablo , Asfeen Ummul , Vyas Ankit , Desai Rupak
Published: March 2022

Introduction:
Cardiovascular disease rates among young adults have been increasingly affected by racial and gender disparities and detailed evidence regarding these differences and their impact on cardiovascular events in young adults hospitalizations remain unknown.

Methods:
The National Inpatient Sample (Oct2015-2017) was queried to identify young adult hospitalizations (18-44 years). Socio-demographics, comorbidities, and rates of major adverse cardiac and cerebrovascular events (MACCE: all-cause mortality, AMI, cardiac arrest, and stroke) were retrieved for males and females and with a more granular comparative analysis for different racial subgroups. A p<0.05 was considered statistically significant.

Results:
Of 19,448,301 (median age 31 years [25-37], 69.1% non-elective) young adult hospitalizations, 315,290 (1.6%) were identified with MACCE. Black patients followed by Hispanics were most likely hospitalized non-electively. Overall, the MACCE rate was higher in males than in females. Among males, MACCE were higher (5.3%) in Asian or Pacific Islanders (API), whereas in females, black patients were affected the most (1.3%) (Fig. 1). Traditional cardiovascular comorbidities were more prevalent in black and Native American patients (among both male/females) followed by Hispanic/API whereas Caucasians had higher rates of drug abuse including smoking and depression (p<0.001) (Table 1).

Conclusions:
Among young hospitalizations, non-white, male patients were more frequently admitted non-electively and had higher rates of cardiovascular comorbidities that could have translated into higher MACCE. Special emphasis needs to be laid on gender and racial differences for CVD disease prevention and risk factor modification in young adults.
Abstract 10172: Mitochondrial Connexin43 Can be Involved in the Occurrence of Arrhythmias
Authors: Satoh Wakako , Kumasaka Kazunori , Shindoh Chiyohiko , Sato Haruka , Miura Masahito
Published: March 2022

Background:
Connexin43 (Cx43) forms gap junctions in cardiac ventricles and exits as hemichannels in the inner mitochondrial membrane (mCx43).

Objective:
To examine whether mCx43 is involved in the occurrence of arrhythmias with modulation of mitochondrial K
ATP
channels (mK
ATP
).

Methods:
To generate cardiac-specific Cx43-deficient (
Cx43
-/-
) mice,

Cx43
flox/flox

mice were crossed with α-myosin heavy chain

-cre
+/-

mice. The resulting offspring,
Cx43
-/-
-mice and their littermates (

Cx43
+/+

-mice) were used. Trabeculae were obtained from right ventricles. Force was measured with a strain gauge, Ca
2+
within the mitochondria (Ca
m
) with rhod-2, intracellular Ca
2+
(Ca
i
) with microinjected fura-2 (22°C). The minimal extracellular Ca
2+
concentration (Cao
min
), at which arrhythmias were induced by electrical stimulation, was determined. Using isolated single ventricular myocytes, mitochondrial membrane potential (ΔΨ
m
) was estimated with tetramethylrhodamine methylester (TMRM), ROS production with 2’,7’-dichlorofluorescein (DCF), and Ca
2+
spark frequency with fluo-4 and confocal microscopy.

Results:
Cx43
-/-
-mice showed sudden death within 8 weeks (p<0.01). Cx43 was present in the inner mitochondrial membrane in

Cx43
+/+

-mice but not in
Cx43
-/-
-mice. Developed force and Ca
i
transients by 0.5 Hz electrical stimulation showed no difference between
Cx43
-/-
- and

Cx43
+/+

-mice (n=7). The Cao
min
in
Cx43
-/-
-mice was lower than that in

Cx43
+/+

-mice (n=5, p<0.01) and was increased by diazoxide (DZX, n=4, p<0.05), suggesting that arrhythmia susceptibility is increased in
Cx43
-/-
-mice and is suppressed by DZX. Ca
2+
spark frequency and DCF oxidation rate in
Cx43
-/-
-mice were higher (p<0.01) and were decreased by DZX (p<0.01). TMRM fluorescence was decreased in
Cx43
-/-
-mice, and it was increased by DZX (p<0.01) and was decreased by 5-hydroxydecanoic acid (p<0.01). Rhod-2 signal was increased at 4 - 6 mM extracellular Ca
2+
in
Cx43
-/-
-mice but not in

Cx43
+/+

-mice.

Conclusions:
Cx43 deficiency depolarizes ΔΨ
m
and increases Ca
m
at higher Ca
o
, ROS production, Ca
2+
spark frequency, and arrhythmia susceptibility. These changes in
Cx43
-/-
-mice are suppressed by DZX. Thus, mCx43 can be involved in the occurrence of arrhythmias with modulation of mK
ATP
.
Abstract 10183: Augmentation of Cardiac Micrornas Enhanced Cardiac Mesenchymal Cell Differentiation Into Cardiomyocyte Like Cells
Authors: Muthusamy Senthilkumar , V. NATH ASHA V , Ajit Shilpa , KUMAR ANIL K
Published: March 2022

Introduction:
Infusion of cardiac mesenchymal cells (CMCs) showed improved cardiac function in myocardial infarction models. Cell based therapy to treat cardiac injuries have shown modest success due to limitations, including poor retention and differentiation. Current studies are focused to improve engraftment and differentiation potential of the therapeutic cells. Here, we used cardiac miRNAs in CMCs to increase their differentiation potential towards cardiac lineage.

Hypothesis:
Increased expression of cardiac miRNAs in CMCs could allow them to differentiate into cardiomyocyte like cells.

Methods:
Mouse CMCs were isolated from the adult mouse heart and analyzed for the expression of cardiac miRNAs. The CMCs were transiently transfected with cardiac miRNAs cocktail (miR-1, miR-133, miR-208 and miR-499) and cultured for 48h. (n=3) The potential miRNAs targets such as HDAC4 (miR-1), Snail-1 (miR-133), myostatin (miR-208) and Sox6 (miR-499) were analyzed using western blot and immunostaining. The miRNAs cocktail transfected CMCs were cultured for 7 days and analyzed for the expression of cardiac specific genes with RT-PCR. (n=3)

Results:
Quantitative PCR analysis showed that the cardiac miRNAs were either less or not expressed in CMCs, whereas transient transfection significantly elevated them. Western blot analysis showed significant downregulation of cardiac miRNAs targets HDAC4 (0.62±0.06), Snail1 (0.61±0.03), Sox6 (0.75±0.01) and Myostatin (0.3±0.04). Immunostaining confirmed significant reduction of these target proteins. Cardiac miRNAs cocktail transfected CMCs showed significantly increased expression of cardiac specific genes such as mef2c (3.87±1.54), Gata4 (3.73±1.07), Tnni3 (3.31±1.01), Nkx2.5 (3.89±0.37) Actc1 (4.27±1.57), Tnnt2 (2.49±1.12) and Cx40 (2.37±0.61). The expression of fibroblast markers such as Col1a and Thy1 were reduced upon enriching the cardiac miRNAs in the CMCs.

Conclusions:
Our results demonstrate that enrichment of cardiac miRNAs in CMCs increase their differentiation into cardiomyocyte lineage, which could improve their therapeutic efficacy. Further in vivo experiments would reveal functional benefits from these improved CMCs for clinical use.
Abstract 10193: Association of Inflammation with Decreased Myocardial Function in Covid Patients with Shock
Authors: Hollenberg Steven M , Fata Matthew , Klinkhammer Brent , Gayed Noha , Glotzer Taya , Go Ronaldo , Gourna-Paleoudis Elli , Landers David , Jamal Sameer , Safi Lucy , Shah Neel , Shah Roshan , Tancredi Jana , Turi Zoltan , Parrillo Joseph E
Published: March 2022

Introduction:
The response to COVID infection has been associated with intense inflammation, and some patients have cardiac involvement. In a group of patients with COVID infection and shock whose ventricular function was characterized by echocardiography, we examined the relationship between levels of ferritin, an inflammatory marker that is elevated in COVID, and LV ejection fraction (EF).

Methods:
Of 1275 patients hospitalized with COVID pneumonia, 215 had shock requiring vasopressors. 162 had echocardiography to assess ventricular function and stroke volume. EF was measured using Simpson’s rule and stroke volume (SV) by Doppler. Patients were divided into groups with low or preserved EF (

EF
L

or

EF
P

, cutoff <e45%), and low or normal cardiac index, (CI,

CI
L

or

CI
N

, cutoff ≤<e2.2 L/min/m
2
). Ferritin within 7 days of the echo was available in 147/162 patients. We examined the association between ferritin levels and ejection fraction.

Results:
Mean age was 66.7, EF 58.7±13.9; CI 2.41±0.89 L/min/m
2
, ferritin 3036±2318 ng/mL (normal <336). Five patients had obstructive shock from pulmonary embolism (normal LVEF, low SV, RV dysfunction) and were excluded. The other 157 patients were divided into groups based on EF and CI (
Figure
). High ferritin levels correlated with low EF (r=-0.18, p=0.02), and ferritin levels were greatly increased in patients with a hemodynamic profile of cardiogenic shock. (

EF
L
CI
L
, Figure,

p=0.017 by ANOVA)

Conclusion:
COVID-induced shock had a cardiogenic profile (EF
L
CI
L
) in 10% of patients, and another 5% had low EF but normal CI. Ferritin correlated with low EF and was increased in patients with a profile of cardiogenic shock. This suggests that marked inflammation may depress myocardial function in COVID patients with shock - analogous to a similar myocardial depression seen with bacterial-associated septic shock.
Abstract 10194: Pacing Site- and Rate-Dependent Shortening of Retrograde Conduction Time Over the Slow Pathway After Atrial Entrainment of Fast-Slow Atrioventricular Nodal Reentrant Tachycardia
Authors: Kaneko Yoshiaki , Nakajima Tadashi , Tamura Shuntaro , Hasegawa Hiroshi , Hiroshi Hasegawa
Published: March 2022

Introduction:
The entrainment rule by which the site of entrainment has no effect on the orthodromic conduction time across the reentry circuit immediately after cessation of pacing has not been unequivocally verified in atypical atrioventricular nodal reentrant tachycardia (AVNRT). We have recently observed a unique electrophysiological response upon atrial induction of fast-slow (F/S-) AVNRT, characterized by a shortening of the retrograde conduction time across the slow pathway (SP) (retro-SP-time).

Hypothesis:
Atrial entrainment pacing (EP) of a) the common-type (com-) F/S-AVNRT using a typical SP, or b) the superior-type (sup-) F/S-AVNRT using a superior SP, both might modify the retro-SP-time immediately after termination of EP.

Methods:
In 16 patients of com-F/S-AVNRT and 11 patients of sup-F/S-AVNRT in whom successful EP from the high right atrium (EP-HRA) and the proximal coronary sinus (EP-CS) was obtained at 2±2 rates, we evaluated the difference in the His-atrial (HA) interval measured immediately after cessation of each EP attempt (HA difference) between EP-HRA and EP-CS (HA[1]-HRA and HA[1]-CS, respectively) and also measured atrial-His and HA intervals in the 1st and 2nd cycles immediately after the EP, and during tachycardia stabilized.

Results:
>20 ms HA difference, defined as an atypical difference, at ≥1 rates of EP was observed in 16 patients (56%), including 7 with com- and 9 with sup-F/S-AVNRT. Irrespective of the EP rate, the atypical response of com-F/S-AVNRT was always due to a shorter HA[1]-CS than HA[1]-HRA, with a 39±22 ms HA difference, whereas the atypical response of sup-F/S-AVNRT was always due to a longer HA[1]-CS than HA[1]-HRA, with a 51±26 ms HA difference. Moreover, the atypical response disappeared within 2 cycles after the cessation of EP. The atypical difference, although its exact mechanism remains unclear, might attribute to a shortening of the retro-SP-time according to decremental properties of the SP with deeper antidromic penetration during EP provoked depending on the site and rate of pacing.

Conclusions:
We have identified a little-known pacing site- and pacing rate-dependent shortening of the retro-SP-time. This phenomenon may affect an interpretation of post-pacing interval after EP of F/S-AVNRT.
Abstract 10198: Association Between Admission Low-Density Lipoprotein Cholesterol and In-Hospital Mortality Among Inpatients with Acute Myocardial Infarction in China: Findings from CCC-ACS Project
Authors: Liu Tianxiao , Liu Jing , Hao Yongchen , Liu Jun , Yang Na , Huo Yong , Smith Sidney C , Ge Junbo , Fonarow Gregg C , Morgan Louise , Ma Chang-Sheng , Yaling Han , Zhao Dong , Qi Yue ,   CCC-ACS Investigators
Published: March 2022

Introduction:
Lowering low-density lipoprotein cholesterol (LDL-C) to <1.4 mmol/L is an important strategy for most patients with acute myocardial infarction (AMI) in secondary prevention of cardiovascular diseases. The association between admission LDL-C levels and all-cause mortality during acute period of AMI is not well established. This study aims to examine the relation between admission LDL-C levels and the risk of in-hospital all-cause mortality among patients with AMI.

Methods:
The Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project is a nationwide registry study. Admission LDL-C level associated with in-hospital all-cause mortality were evaluated on a continuous scale with restricted cubic splines and by categories with multivariate Cox regression models among 94623 inpatients with AMI in 159 tertiary hospitals and 82 secondary hospitals in 30 provinces from November 2014 to December 2019.

Results:
Among total inpatients, 1852 cases (2.0%) died, 5434 patients (5.7%) have LDL-C level<1.4 mmol/L. The association between LDL-C levels and the risk of all-cause mortality was U shaped, with low and high LDL-C levels associated with an increased risk. Compared with inpatients with LDL-C level of 1.4-1.8 mmol/L, the adjusted hazard ratio was 1.48 (95% confidence interval: 1.18 to 1.87) for patients with LDL-C< 1.4 mmol/L, and 1.50 (95%CI: 1.19 to 1.90) for patients with LDL-C≥ 4.1 mmol/L. Propensity score matched analysis confirmed these associations. Similar results were seen in both gender, in patients with and without diabetes, across age groups and triglycerides groups, across ST-segment elevation AMI and non-ST-segment elevation AMI patients, and after excluding patients who died within 24 hours after admission. However, such association was not observed in patients received lipid-lowering treatment before hospitalization and those treated with percutaneous coronary intervention during hospitalization.

Conclusions:
Lower LDL-C is associated with increased risk of in hospital all-cause mortality among patients hospitalized for AMI. Lower LDL-C levels may help identify patients at higher risk for in-hospital mortality, who could potentially benefit from intensification of treatment strategies.
Abstract 10200: Enhanced Human VIC Calcification and Altered RNA Expression in Dynamic Culture with Induction Media in Microphysiological Systems
Authors: Dittfeld Claudia , Winkelkotte Maximilian , Schmieder Florian , Behrens Stephan , Jannasch Anett , Matschke Klaus , Tugtekin Sems-Malte , Sonntag Frank
Published: March 2022

Introduction:
Aortic valve (AV) calcification is the main characteristic in AV stenosis affected by fibrosis, endothelial cell layer damage and altered shear stress. Osteogenic differentiation of valvular interstitial cells (VIC) is research focus. VIC culturing in micro-physiological systems (MPS) that allows the adjustment of flow rate/shear force and oxygen concentration are new approaches to evaluate AV disease processes. Culture media inducing VIC calcification were applied in dynamic MPS VIC culture to investigate the impact on calcification and gene expression.

Methods:
A MPS able to modulate fluidic conditions (pulsatile flow of 2.7 μl/s resulting in average shear forces of 0.04 dyn/cm
2
) was applied for human VICs. ADGMedium (50 μM ascorbic acid phosphate, 100 nM dexamethasone,10 mM β-glycerophosphate) was compared with PMedium (2 mmol/L NaH
2
PO
4
, 0.3 mM ascorbic acid) and standard DMEM (72 h). VIC viability was proven using a lactate dehydrogenase assay. Calcium accumulation was quantified in dynamic vs. static culture and mRNA expression of ACTA2, FN1, COL1A1, COL3A1, RUNX2 and SOX9 was quantified via qRT-PCR.

Results:
Viability of MPS VIC cultures was confirmed. ADGM induced calcium accumulation was significantly enhanced to 5.1 ± 1.4 Ca
2+
mol/kg protein in dynamic but not static culture compared to static DMEM control (0.1 ± 0.2 Ca
2+
mol/kg protein; n=4). PM resulted in a significantly higher calcium level compared to static DMEM control in static and dynamic chip culture (7.8 ± 5.2 and 9.2 ± 1.6 Ca
2+
mol/kg protein). Myofibroblastic ACTA2, Fibronectin and osteogenic factor RUNX2 were significantly induced but SOX9 (prevents AV calcification) was downregulated in ADGM but not in PM and independent from culture dynamics. Collagen COL1A1 mRNA level was significantly enhanced two-fold in ADGM and PM but exclusively in dynamic culture. An induction of COL3A1 was detected in ADGM dynamic but not static culture vs. DMEM counterparts.

Conclusion:
Dynamic culture significantly enhances calcium content in ADGM induced VIC cultures accompanied with enhanced collagen expression. MPS culture allows the investigation of VIC pathogenesis at defined shear forces and seeking the combined adjustment of oxygen supply. SMT and FSo contributed equally
Abstract 10203: Effect of Hydroxychloroquine on Endothelial Function in Older Adults with Moderate-Severe Sleep Apnea: A Randomized Clinical Trial
Authors: Tedesco Silva Leticia Maria , Waclawovsky Gustavo , Boll Liliana , Caye Rossi Beatriz Juliana , Eibel Bruna , Cadaval Gonçalves Sandro , Irigoyen Maria , Martinez Denis
Published: March 2022

Introduction:
Obstructive sleep apnea (OSA) is considered a low-grade chronic inflammatory disease. OSA impairs endothelial function and increases cardiovascular mortality. Hydroxychloroquine (HCQ), an anti-inflammatory drug, seems to reduce cardiovascular mortality. In animal and
in vitro
models, HCQ improved endothelial function. Its effects on endothelial function of patients with OSA is unknown.

Hypothesis:
Hydroxychloroquine can improve endothelial function in patients with OSA.

Methods:
Adults older than 65 years with an apnea-hypopnea index (AHI) greater than 15 events/hour were allocated to receive either 400mg of HCQ or placebo daily for eight-weeks. The randomization was computer-generated and pharmacy-controlled. Participants and outcome evaluators were blinded to the group allocation. Home sleep apnea test and measurements of flow-mediated dilation of brachial artery (FMD) and peripheral artery tonometry (PAT) were performed at baseline and follow-up in a research facility. The primary outcomes were the change in FMD (Δ%FMD) and change in PAT reactive-hyperemia index (ΔRHI). Change in AHI (ΔAHI) was a secondary outcome. Generalized estimating equations were used to verify time*group interaction.

Results:
Fourteen patients were assigned to the HCQ group and fifteen patients to the placebo group between April 2019 and May 2020 with no losses to follow-up. The recruitment was interrupted due to COVID-19 pandemic. Mean Δ%FMD was 0.35 (95% CI –4.26 to 4.97) in placebo group and 0.48 (95% CI –4.08 to 5.04) in HCQ group. Mean ΔRHI was 0.02 (95% CI -0.11 to 0.07) in placebo group and 0.05 (95% CI -0.24 to 0.13) in HCQ group. Mean ΔAHI was 7 (95% CI -1 to 15) in placebo group and -4 (95% CI -11 to 2) in HCQ group. P values for time*group interaction were 0.97, 0.74 and 0.04, respectively. No important adverse events have occurred.

Conclusions:
In this trial, HCQ did not improve endothelial function measured by FMD and PAT in older adults with OSA. A slight but significant reduction in AHI was observed in HCQ group, suggesting that some specific inflammatory mechanisms participate in OSA causation that could become a future therapeutic approach.
Abstract 10212: Exposure to Volatile Organic Compounds - Acrolein, Crotonaldehyde, and Styrene - is Associated with Blood Pressure in the Jackson Heart Study
Authors: McGraw Katlyn E , Konkle Stacey L , Riggs Daniel W , Rai Shesh N , DeJarnett Natasha K , Xie Zhengzhi , Oshunbade Adebamike A , Keith Rachel J , Hall Michael E , Bhatnagar Aruni
Published: March 2022

Introduction:
Cardiovascular disease (CVD) is the leading cause of death from environmental exposures. Although exposure to particulate matter ≤2.5μm (PM
2.5
) is an established risk factor for CVD, the contribution of other hazardous pollutant exposure to CVD risk is less clear.

Hypothesis:
We assessed the hypothesis that volatile organic compounds (VOCs) are associated with blood pressure in 778 nonsmokers from the Jackson Heart Study (JHS), a large, community based observational study of CVD in African Americans from the tri-county Jackson, MS area.

Methods:
We measured urinary metabolites of 17 parent VOCs in spot urine samples collected at baseline using UPLC/MS. We tested the association between VOC metabolites and blood pressure in nonsmokers using generalized linear models adjusted for age, sex, body mass index (BMI), estimated glomerular filtration rate, cholesterol to high-density lipoprotein ratio, triglycerides, blood pressure medications, diabetes, and PM
2.5
. Two measurements of systolic and diastolic blood pressure (SBP, DBP) in the resting state were averaged using a Hawksley random zero sphygmomanometer.

Results:
Included participants had a BMI of 31.3 ± 7.1 kg/m
2
(mean ± SD), had triglycerides of 99.9 ± 57.9 mg/dL, and a less than 10% prevalence of CVD events. More than one-third were affluent (37.8%) and almost half used blood pressure medications (46%). We found that metabolites of acrolein (CEMA) and crotonaldehyde (HPMMA) were associated with a 1.5mmHg (CI: 0.5, 2.7; p=0.01), and a 1.1mmHg higher (CI: 0.1, 2.0; p=0.02) SBP per interquartile range (IQR) of VOC metabolite, respectively. Additionally, we found a 0.5mmHg higher (CI: 0.1, 0.8; p= 0.01) DBP per IQR of styrene metabolite, MA. In subgroup analysis, the association between CEMA and MA and blood pressure persisted only in men.

Conclusions:
In conclusion, these findings suggest that exposure to VOCs (acrolein, crotonaldehyde, and styrene) may be a significant contributor to risk of hypertension among African American nonsmokers.
Abstract 10233: Interruption of Perirenal Adipose Tissue Thromboinflammation Reverses Prediabetic Kidney Impairment
Authors: Al-Saidi Aya M , Abdallah Samaya , Hammoud Safaa , Mougharbil Nahed , El-Yazbi Ahmed
Published: March 2022

Introduction:
Mounting evidence suggests that micro- and macrovascular complications typically seen in diabetic patients commence in prediabetes. In absence of protracted hyperglycemia and its downstream pathological pathways, alternative mechanisms contribute to the observed cardiorenal involvement. Recent work from our laboratory implicated localized adipose inflammation in the detrimental phenotype in early metabolic deterioration, where inflammatory changes in perirenal adipose tissue triggered kidney functional and vascular deterioration. Significantly, thromboinflammatory processes involving increased factor Xa activity contribute to the low-grade adipose tissue inflammation resulting in vascular remodeling, vascular injury, atherosclerosis and organ damage, acting in a positive feedback loop further exacerbating tissue damage.

Hypothesis:
As such, we hypothesize factor Xa inhibition in a non-obese prediabetic rat model of localized perirenal adipose inflammation will mitigate the functional and renovascular derangements associated with metabolic dysfunction.

Methods:
Our rat model is induced by twelve weeks of high-caloric diet feeding to evoke a non-obese normoglycemic prediabetic phenotype. Prediabetic rats received daily oral rivaroxaban (20 mg/Kg) for the last two weeks of feeding. Renal function was assessed by measuring urinary protein excretion and glomerular filtration rate. Renovascular reactivity was examined in isolated perfused kidney preparations. Markers of inflammation, oxidative stress, and structural damage were studied in perirenal adipose and renal cortices.

Results:
High-calorie diet induced local adipose tissue inflammation and subsequent renovascular deterioration evident by an impaired renovasular endothelial feedback. This was associated with augmented oxidative stress and interstitial fibrosis. Rivaroxaban treatment decreased markers of perirenal adipose inflammation, oxidative stress and improved kidney structure and function.

Conclusion:
Our results highlight a pleotropic effect of the factor Xa inhibitor, rivaroxaban, in decreasing perirenal adipose tissue inflammation and subsequent amelioration of the deteriorated kidney function in prediabetes.
Abstract 10236: Prospective Assessment of ECG-Image-based Real-Time Individual Virtual-Heart Automatic Localization (RIVAL) for Scar-Related Ventricular Tachycardia (VT)
Authors: Zhou Shijie , Sung Eric , AbdelWahab Amir , Sapp John L , Aronis Konstantinos , Horacek B. M , Berger Ronald D , Tandri Harikrishna S , Chrispin Jonathan , Trayanova Natalia
Published: March 2022

Background:
We developed a novel RIVAL system that consists of a CT-based computational simulation to identify VT circuits and an ECG-based automated approach to localize VT exit sites.

Objective:
Prospectively assess the ability of the RIVAL system to localize VT circuits and exits.

Methods:
Patients presenting for VT ablation were enrolled into the study. Pre-procedural cardiac CT was performed and used to conduct heart simulations for predicting VT circuits. The patient’s CT geometry with the predicted VT circuits was registered to the electroanatomic shell created during the procedure and imported into the RIVAL program. During the procedure, exit sites of induced VTs are localized in real-time using the 12-lead ECG onto the patient-specific CT surface. Predicted ablation regions obtained by combining RIVAL-predicted VT circuits with exit sites were analyzed offline to assess localization accuracy to the invasive VT ablation procedure.

Results:
Four patients with ischemic cardiomyopathy undergoing VT ablation had preprocedural cardiac CT. In P1, two VTs were induced during the procedure. The RIVAL predicted 2 VT circuits and achieved a mean localization error of 7.0mm for VT exit site prediction (Fig1). There was a spatial concordance between the predicted ablation areas and the clinical ablation regions. For P2, three VTs were induced during the VT ablation. A large area of scar was associated with 6 RIVAL-predicted VT circuits. The exit site localization accuracy could not be precisely quantitated because the VTs terminated with ablation at a mid-diastolic site. For P3, no VTs were inducible, however substrate modification (SM) was performed in the anterior-apical LV. The RIVAL predicted only one VT circuit located in the area where SM was performed. No VT was induced for P4 and the RIVAL did not predict any VT circuits.

Conclusions:
The RIVAL predicts the VT circuit and exit accurately, which may improve the precision of ablation therapies and procedure outcomes.
Abstract 10238: Quantification of Myocardial Ischemia and Subtended Myocardial Mass at Adenosine Stress Cardiac Computed Tomography. A Feasibility Study
Authors: van Driest Finn , van der Geest Rob , Broersen Alexander , Dijkstra Jouke , El Mahdiui Mohammed , Jukema J Wouter , Scholte Arthur
Published: March 2022

Introduction:
Combination of computed tomography angiography (CTA) and adenosine stress CT myocardial perfusion (CTP) allows for coronary artery lesion assessment as well as myocardial ischemia. Nowadays, ischemia on CTP is assessed semi-quantitatively by visual analysis. The aim of this study was to fully quantify myocardial ischemia and the subtended myocardial mass on CTP.

Methods:
We included 33 patients referred for a combined CTA and adenosine stress CTP with good or excellent imaging quality on CTP. Firstly, the coronary artery tree was automatically extracted from CTA and the relevant coronary artery lesions (≥ 50%) were manually defined (fig 1A). Secondly, epi- and endocardial contours along with CTP deficits were manually defined in short-axis images (fig 1D, 1E). Thirdly, a Voronoi-based algorithm was used to quantify the subtended myocardial mass (fig 1B). Fourthly, the perfusion defect and subtended myocardial mass were spatially registered to the CTA and measured in grams (fig 1F, 1C). Finally, this can be used to quantitatively correlate the perfusion defect to the subtended myocardial mass. To assess reproducibility, left ventricular epicardial and endocardial contours along with perfusion defects were re-drawn.

Results:
Voronoi-based segmentation was successful in all cases. We assessed a total of 64 relevant coronary artery lesions. Average values for left ventricular mass, total subtended mass and perfusion defect mass were 118, 69 and 7 grams respectively. In 19/33 patients (58%) the total perfusion defect mass could be distributed over the relevant coronary artery lesion(s). Results were highly reproducible (r≥0.822, p<0.01).

Conclusions:
Quantification of myocardial ischemia and subtended myocardial mass using a Voronoi-based segmentation algorithm seem feasible at adenosine stress CTP and allows for quantitative correlation of coronary artery lesions to corresponding areas of myocardial hypoperfusion.
Abstract 10242: Single versus Dual Antiplatelet Post Transcatheter Aortic Valve Replacement: An Updated Meta-Analysis
Authors: Khalid Muhammad , El Iskandarani Mahmoud , Yar Allah , Tahir Amina , Tahir Sidra , HELTON THOMAS
Published: March 2022

Introduction:
Perioperative use of dual antiplatelet therapy (DAPT) after transcatheter aortic valve replacement (TAVR) remains controversial. This meta-analysis compares the safety and efficacy of single anti-antiplatelet therapy (SAPT) versus DAPT after TAVR in patients with no indications for long-term anticoagulation.

Hypothesis:
The use of SAPT is safe and efficacious in TAVR patients.

Methods:
Electronic databases were queried for randomized controlled trials (RCTs) and observational studies matching the inclusion criteria. The safety endpoints included bleeding and major vascular complications. The efficacy outcomes included myocardial infarction (MI), stroke, short and long-term all-cause mortality. The ratio risk ratio (RR) with 95% confidence interval (CI) was computed using a random-effect model.

Results:
A total of 4 RCTs and 2 observational studies (n=1,417) were included in the final analysis. There were decreased rates of bleeding (life-threatening or major) (RR: 0.44; CI: 0.31-0.63) with aspirin only therapy. However, there was no difference of MI (RR: 0.73; CI: 0.28-1.87), stroke (RR: 0.92; CI: 0.55-1.54), major vascular complications (RR: 0.61; CI: 0.35-1.07), short-term mortality (>30 days) (RR: 0.82; CI: 0.45-1.49), and long-term mortality (>30 days) (RR: 1.13; CI: 0.73-1.76).

Conclusions:
This analysis showed lower rates of bleeding and composite of bleeding/thromboembolic events with aspirin only compared to dual antiplatelet amongst patients that underwent TAVR for aortic stenosis.
Abstract 10243: Meta-Analysis of Direct Oral Anticoagulants versus Vitamin K Antagonists in Patients with Atrial Fibrillation and Bioprosthetic Valves
Authors: Yokoyama Yujiro , Briasoulis Alexandros , Ueyama Hiroki , Mori Makoto , Iwagami Masao , Misumida Naoki , Takagi Hisato , Kuno Toshiki
Published: March 2022

Objective:
The optimal anticoagulation strategy for patients with bioprosthetic valves and atrial fibrillation remain uncertain. Thus, we conducted a meta-analysis using updated evidence comparing direct anticoagulants (DOAC) and vitamin K antagonist (VKA) in patients with bioprosthetic valves and atrial fibrillation.

Methods:
MEDLINE and EMBASE were searched through March, 2021 to identify randomized control trials (RCT) and observational studies that investigated the outcomes of DOAC and VKA in patients with bioprosthetic valves and atrial fibrillation. The outcomes of interest were all-cause death, major bleeding, and stroke or systemic embolism.

Results:
Our analysis included 4 RCTs and 6 observational studies which enrolled a total of 6,405 patients with bioprosthetic valves and atrial fibrillation assigned to the DOAC group (n =2,142) and VKA (n =4,263). Pooled analysis demonstrated the similar rates of all-cause death (HR [95% confidence interval [CI]] =0.90 [0.77-1.05];
P
=0.18;
I
2
=0%)between the DOAC and VKA groups. However, the rates of major bleeding were significantly lower in the DOAC group compared to the VKA group (HR [95% CI] =0.66 [0.48-0.89];
P
=0.006;
I
2
=0%) (Figure), while the rates of stroke or systemic embolism were similar (HR [95% CI] =0.72 [0.44-1.17];
P
=0.18;
I
2
=39%).

Conclusion:
DOAC was associated with lower rates of major bleeding without increasing the risk of stroke or systemic embolism or all-cause death compared to VKA in patients with bioprosthetic valves and atrial fibrillation.
Abstract 10245: Egfr Calculation Without the Race Coefficient Obscures Obesity Related Glomerulopathy in Female Adolescents
Authors: Bielopolski Dana , Bentur Ohad S , Singh Neha , Vaughan Roger D , Charytan David M , Kost Rhonda G , Tobin Jonathan N
Published: March 2022

Introduction:
Obesity is more prevalent among minorities, increasing the risk for cardio-renal morbidity.

Hypothesis:
We explored interactions between race, body mass index (BMI), and the risk of hyperfiltration associated with Obesity Related Glomerulopathy (ORG).

Methods:
We created a cohort of women and girls ages 12-21 from the New York Metropolitan area using their longitudinal electronic health records (EHR). Glomerular filtration rate (GFR) was estimated in two ways: I) using the standard age recommended formulae, and II) eGFRr -without a race-specific coefficient. Multivariate logistic regression was used to analyze the relative contribution of risk factors for ORG associated hyperfiltration, defined by a threshold of ≥135ml/min/1.73m
2
.

Results:
7315 Black and 15,102 non-Black women and girls were evaluated for kidney function in parallel to body measures. Hyperfiltration was more frequent in Black compared to non-Black individuals when using standard eGFR but was lower after eliminating the race-specific coefficient. Black race was independently associated with hyperfiltration with standard eGFR calculation (OR=3.43, 95% CI 2.95-3.99) but the association was reversed when estimated by eGFRr (OR=0.56, 95% CI 0.45-0.70). Risk of hyperfiltration was higher for Black individuals across all BMI strata with standard eGFR estimates, but when estimated as eGFRr hyperfiltration risk was reduced for overweight (OR =0.70 95% CI 0.54-0.89) and obese (OR=0.47, 95% CI 0.37-0.60) black participants. Simultaneous removal of the race coefficient and adjustment to individual BSA provided the most accurate estimation of GFR compared to creatinine clearance.

Conclusions:
Estimated CKD prevalence among Black adolescents and young adults increases following removal of the race coefficient while fewer have evidence of ORG. Removing the race coefficient should be accompanied by adjustment to individual BSA in order to estimate more realistically GFR.
Abstract 10253: Sin3a Gene Delivery Restores Bmpr2 Expression Through Foxk2 in Pulmonary Arterial Endothelial Cells and Inhibits Sugen/Hypoxia-Induced Pah
Authors: Bisserier Malik , zhang shihong , Dorfmuller Peter , Humbert Marc , Weber Thomas , Perros Frederic , Sassi Yassine , Bonnet Sebastien , Hadri Lahouaria
Published: March 2022

Background:
Pulmonary arterial hypertension (PAH) is a fatal lung disease of multifactorial etiology, with no curative treatment. Several studies have previously suggested that the loss of BMPR2 expression is associated with a severe hemodynamic profile and poor outcomes in PAH patients. Furthermore, preclinical studies showed that the loss of BMPR2 function is sufficient to induce a PAH-like phenotype. Recently, our group showed that SIN3a (Switch-Independent 3) plays a critical role in the epigenetic regulation of BMPR2 expression in human pulmonary arterial smooth muscle cells (hPASMC). However, our preliminary data suggested that SIN3a regulates BMPR2 expression through a different pathway independently of DNA-methylation in human pulmonary arterial endothelial cells (hPAEC).

Methods/Results:
We found a significant downregulation of SIN3a expression in the PAEC isolated from PAH patients. In hPAEC, our results showed that SIN3a inhibits cell proliferation, migration and upregulates BMPR2 independently of the methylation status by upregulating the FOXK2 transcription factor. Using a loss-of-function approach using a specific shRNA against FOXK2, we found that the loss of FOXK2 expression using a specific shRNA decreased the expression of BMPR2 in hPAECs. Interestingly, we found that SIN3a overexpression in FOXK2-depleted hPAEC restored the expression of BMPR2. Our results also showed that SIN3a regulates hPAEC proliferation in a FOXK2-dependant manner. Mechanistically, we found that SIN3a interacts physically with FOXK2 to promote its nuclear localization. As a result, we also found enrichment in FOXK2 abundance within the BMPR2 promoter by ChIP-qPCR in PAEC.
In vivo
, our results showed that restoring SIN3a expression by lentivirus-mediated gene transfer significantly decreased SuHx-induced PAH in mice, as illustrated by decreased vascular remodeling, RV hypertrophy (Fulton index, hypertrophic markers, cardiomyocyte size), and RV systolic pressure.

Conclusions:
Altogether, our study revealed that SIN3a plays a critical role in the regulation of BMPR2 expression through FOXK2. Additionally, our study identifies lung-targeted SIN3a gene therapy as a new promising therapeutic strategy for treating PAH patients.