bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17188: Cryoem Analysis in Cardiac Isolated Mitochondria Reveals New Insights for CsA and mPTP Activation
Authors: Strubbe Jasiel O , Schrad Jason , Conway James F , Parent Kristin N , Bazil Jason N
Published: July 2021

Excessive Ca
2+
accumulation is the main source of cardiac tissue and cell death during myocardial ischemia-reperfusion injury (IR injury) and myocardial infarction. Calcium dysregulation and overload leads to mitochondrial dysfunction, excessive reactive oxygen species (ROS) production, catastrophic energy failure, and opening of the cyclosporine A-sensitive mitochondrial permeability transition pore (mPTP). Mitochondrial Ca
2+
accumulation also results in the formation of amorphous Ca
2+
-phosphate granules localized in the mitochondrial matrix. These amorphous electron-dense granules are main components of the mitochondrial Ca
2+
sequestration and buffering system by mechanisms not yet well understood. The two aims of the present study are to test the relationship of Ca
2+
-phosphate granule size and number in cardiac mitochondria 1) exposed to a bolus calcium sufficient to elicit permeabilization and 2) whether CsA-treated mitochondria alters granule formation and size. A time course series of CryoEM images was analyzed to follow the permeabilization process. CryoEM results showed that mitochondrial incubated for longer time-courses have increased number of small granules (40 - 110 nm), swelling, membrane rupture and induction of mPTP opening. Conversely, shorter incubation time resulted in less granules per mitochondrion yet of similar size (35 - 90 nm). CsA- treated mitochondria, on the other hand, showed bigger phosphate granules (120 - 160 nm), and both lower granules per mitochondria and mPTP opening susceptibility. These results suggest a novel mechanism for CsA in which Ca
2+
-phosphate granule sizes are enhanced while maintaining fewer per mitochondrion. This effect may explain why CsA-treated mitochondria have higher calcium tolerance, delayed Ca
2+
-dependent opening of the mPTP, and protects against reperfusion-induced myocardial necrosis.
Abstract 17212: Whole Exome Sequencing Identifies Novel Genetic Variants in Left Ventricular Noncompaction Cardiomyopathy
Authors: Collyer John , Xu Fuyi , Munkhsaikhan Undral , Zhang Wenying , Lu Lu , Towbin Jeffrey A , Purevjav Enkhsaikhan
Published: July 2021

Introduction:
Causal and modifier genes associated with left ventricular noncompaction (LVNC) often occurring in conjunction with other familial cardiomyopathies remain elusive.

Hypothesis:
The LVNC-associated di- and multigenic abnormalities can be identified by whole exome sequencing (WES).

Methods:
Five families with a history of LVNC, including five affected probands, three affected family members, and twelve unaffected relatives, were studied. Genomic DNA was extracted from whole blood samples followed by WES and Sanger sequencing to confirm possibly pathogenic variants predicted by
in-silico
analysis. Phenotype-genotype correlation and quantitative co-segregation studies are performed.

Results:
We identified nine missense possibly pathogenic variants, a 2-bp frameshift insertion, and a 9-bp in-frame insertion in the five families. Two affected siblings in Family 1 were found carrying digenic heterozygous variants: c.4048G>A (p.E1350K) in
MYH7
and c.827C>T (p.A276V) in
ANKRD1.
Unaffected parents were carriers for each of the two variants. Three affected members, father and two daughters, of Family 2 carried c.550A>C (p.K184Q) variant in
MYH7
in contrast to two unaffected members, mother and another daughter. In Family 3, multigenic heterozygosity (c.673G>T (p.D225Y) in
CACNA2D1
; c.440T>A (p.V147E) in
COQ4
and c.3700C>A (p.H1234N) in
MYH7)
was identified in the proband. These variants were found in none of three unaffected relatives. The proband of Family 4 was positive for heterozygous variants: c.2684_2685insAG (p.A897Kfs*3) in
DSC2
, c.8633T>C (p.V2878A) in
OBSCN
, and c.11717C >T (p.T3906I) in
PLEC.
The T3906I PLEC variant was identified in his unaffected half-sibling and his father, but not in his mother. In Family 5, c. 2591A>T (p.D864V) in
HDAC9
, c.9616C>T (p.R3206W) in
PLEC
and c.954_955insT (p.L319Sfs*74) in
MYH14
were identified in the proband. None of those variants were identified in his unaffected sibling.

Conclusions:
We report several potential pathogenic LVNC-associated variants in novel genes (ANKRD1, DSC2,
OBSCN
,
PLEC, HDAC9, MYH14, COQ4, CACNA2D1)
and known genes (
MYH7
and
MYH7B).
The diverse profile of inheritance (digenic and multigenic heterogeneity) that may cause and modify the heterogeneous LVNC phenotypes.
Abstract 17215: Pacing Burden in Those Undergoing Permanent Pacemaker Implantation After TAVR With Latest Generation Valves
Authors: Sandhu Amneet , Ream Karen , Tzou Wendy , Tumolo Alexis , Fleeman Blake , Mantini Nicholas , Nguyen Duy T , Sauer William H , Aleong Ryan G
Published: July 2021

Background:
Risk factors leading to heart block (HB) and need for permanent pacemaker (PPM) implantation post-TAVR using latest generation heart valves have been described. Yet, little is known regarding pacing burden following PPM implantation among such patients.

Objective:
We sought to determine follow-up RV pacing burden among those undergoing PPM for HB following TAVR.

Methods:
From July 2016 to July 2017, we reviewed procedural and 3-month follow-up data (including PPM interrogation data) from all patients undergoing implantation of Edwards Sapien 3® and Medtronic Evolut-R® valves at our institution and requiring implantation of a PPM due to HB secondary to the TAVR procedure.

Results:
Of 132 included patients who underwent TAVR with new generation valves, 25 (19%) required post-TAVR PPM implantation. Of 25 patients, 18 had available follow-up pacemaker data [Table]. Pacing burden post-PPM implantation of 29mm valves was significantly greater compared to non-29mm valves (40.2% vs. 5.4%, p = 0.02). Those with baseline conduction system disease (RBBB or LBBB) had greater pacing burdens, in particular when 29mm Evolut-R® self-expanding valves were deployed (n=3, RV pacing burden 63.3%). Extension of programmed AV delays produced significant reduction in RV pacing burden.

Conclusion:
In those undergoing TAVR with latest generation valves complicated by HB requiring PPM use, implantation of larger-sized valves (29 mm Evolut-R® in the present series), as well as baseline RBBB or LBBB results in increased follow-up RV pacing burden. This may be mitigated by adjustment of pacing parameters. Further work investigating long-term pacing burden and its consequences is needed to provide additional insight.

Table:
Demographics, baseline ECG characteristics, procedural characteristics, pacing mode, pacing parameters and follow-up RV pacing burden.
Abstract 17237: Physical Inactivity, Mortality and Incident Coronary Heart Disease in Blacks: The Jackson Heart Study
Authors: Kamimura Daisuke , Cain Loretta , Clark Donald T , Guild Cameron S , Loprinzi Paul D , Newton Robert , Suzuki Takeki , Hall John E , Correa Adolfo , Butler Javed , Hall Michael E
Published: July 2021

Introduction:
Despite reductions in overall mortality in recent decades, blacks continue to have higher death rates compared to whites. According to a recent CDC report, blacks were more likely to have a higher prevalence of unhealthy behaviors such as physical inactivity/sedentariness compared to whites. We assessed the associations between physical activity (PA) and incident coronary heart disease (CHD) and overall mortality in blacks in the Jackson Heart Study (JHS).

Methods:
Among the 5306 participants enrolled in JHS at baseline (2000-2004), we examined overall mortality through 2016, and among 3507 participants without prevalent CHD at baseline, clinically adjudicated incident CHD events (CHD hospitalizations and fatal myocardial infarction). Based on participant responses and the American Heart Association’s Life’s Simple 7 metrics, participants were classified as having poor (0 minutes/week), intermediate (&rt;0 and <75 minutes/week) or ideal (<=150 minutes/week) PA based on number of minutes of moderate of vigorous PA per week. Cox proportional hazard ratios (HR) were used to assess the relationships between PA categories and incident CHD and overall mortality.

Results:
Through 2016, there were 992 deaths (18.7% mortality rate) with higher rates in men (21.5%) compared with women (17.1%, p<0.0001). After adjustment for age, sex, education, systolic blood pressure, hypertension medications, diabetes, cholesterol, alcohol use and current smoking at baseline, poor PA was associated with increased mortality (HR 1.53, 95% CI 1.18, 1.98) compared to those with ideal PA. However, there was no significant difference in incident CHD events between those with ideal and poor PA (HR 1.05, 95% CI 0.66, 1.67). Compared with ideal PA, there was no significant difference in mortality in those with intermediate PA (HR 1.23, 95% CI 0.93, 1.62).

Conclusions:
In a large community-based cohort of blacks, lower PA was associated with higher overall mortality but was not associated with increased risk of incident CHD events.
Abstract 17238: Global Burden of Calcific Aortic and Degenerative Mitral Valve Diseases: Analysis From the Global Burden of Disease 2017 Study
Authors: Yadgir Simon R , Alam Tahiya , Johnson Catherine , Naghavi Mohsen , Roth Greg
Published: July 2021

Introduction:
Although non-rheumatic valvular heart diseases (NRVD) are common, there have been no studies to estimate their global burden. As part of the Global Burden of Disease (GBD) 2017 Study, we estimated the age and sex-specific number of deaths, prevalent cases, and disability-adjusted life years (DALYs) for calcific aortic valve disease (CAVD) and degenerative mitral valve disease (DMVD) for every country from 1990 to 2017.

Methods:
We used vital registration data, epidemiological survey data, and hospital claims data to estimate the cause-specific mortality rate, prevalence, and incidence of CAVD and DMVD using the GBD modelling framework. Results accounted for level of disease severity as well as the availability of valve repair or replacement procedures. Burden estimates for CAVD and DMVD were generated for each sex, 5-year age group, country, and year from 1990 to 2017.

Results:
We estimated 1.5M DALYs (1.3M to 1.7M) lost due to CAVD and 1.1M DALYs (0.8M to 1.4M) due to DMVD, globally, representing 0.12% (0.1% to 0.14%) of total lost health from all diseases in 2017. CAVD and DMVD caused 97.8K (75.0K to 104.8K) and 32.7K (28.5K to 38.2K) deaths, and 12.9M (11.5M to 14.2M) and 27.1M (26M to 27.1M) cases, respectively. The number of DALYs increased for both CAVD and DMVD between 1990 and 2017, by 123% (101% to 137%) and 64% (50% to 75%), respectively. There is large national and regional variation in the prevalence, mortality rate, and overall burden of these diseases, with the highest age-standardized rates estimated for high income countries.

Conclusions:
CAVD and DMVD are common diseases among the elderly. Health systems will need to consider improving prevention of CAVD and access to effective valve diagnostics and procedures if progress is to be made in addressing these treatable conditions.
Abstract 17241: National Trends in Systolic and Diastolic Heart Failure From 2004 to 2014
Authors: Afzal Aasim , Nisar Tariq , Kluger Aaron , Jamil Aayla , Felius Joost , Hall Shelley A , Kale Parag
Published: July 2021

Introduction:
Heart Failure (HF) affects 6 million people in the US and costs $30.7B/year. Prior studies have shown declines in hospitalization rates, length of stay (LOS), and mortality for HF patients, but it is unclear if these trends hold true for both systolic HF (SHF) and diastolic HF (DHF). To better assess the epidemiological and economic burden of HF, we assessed the trends in LOS, mortality, and cost for both SHF and DHF.

Methods:
We identified hospitalizations for SHF (primary diagnosis ICD-9 codes 428.1, 428.2x, 428.4x or 428.9) and DHF (code 428.3x) from 2004 to 2014 in the National Inpatient Sample (NIS). National estimates were calculated using the NIS sampling weights. LOS, in-patient mortality, charges, demographics, and co-morbidities were abstracted.

Results:
We found an overall decreasing trend in LOS for HF, with LOS declining more sharply for DHF than for SHF hospitalizations (Cuzick test; Table 1 and Fig. 1). In 2014, LOS for DHF was on average 4.1 hours shorter than for SHF (95% confidence interval [CI] 3.5 - 4.6h). Inpatient mortality decreased despite an increase in number of co-morbidities for both groups, but in 2014 the odds of a patient dying with SHF were higher than for DHF (odds ratio 1.16, CI (1.14, 1.17). Total charges increased for SHF but remained relatively unchanged for DHF. In 2014, a hospitalization for SHF cost on average $10,349 more than for DHF (p<0.001).

Conclusion:
While DHF costs have remained relatively unchanged, SHF costs have risen between 2004 and 2014 despite an overall decrease in LOS and concurrent decline in inpatient mortality. This cost increase may have resulted, in part, from increased use of advanced support devices in these patients. Further studies will be needed to identify the reasons for increased cost of care such as use of percutaneous mechanical circulatory support devices.
Abstract 17260: Body Mass Index, Waist Circumference and the 6-Year Risk of Coronary Heart Disease in 708,544 Thai Men and Women: HCUR Study
Authors: Chamnan Parinya , Mahawanakul Weera , Aekplakorn Wichai , Nitiyanant Wannee , Boongird Prasert ,   HCUR Investigators
Published: July 2021

Introduction:
Body mass index (BMI) and waist circumference has been reported to have a positive association with risk of coronary heart disease (CHD) and their optimal levels have been proposed. However, the association was less well described in Asian population.

Hypothesis:
This study aimed to examine the risk of developing CHD across different levels of BMI and waist circumference in a large retrospective cohort of Thai general population.

Methods:
This retrospective cohort was derived from the linkage of 2006 health checks data with diagnostic information from electronic health records of 708,544 men and women aged 20 years and above residing in Ubon Ratchathani. We examined the incidence of CHD over 6 years of follow-up in individuals with different levels of BMI defined by the WHO Asia-Pacific cut-offs and central obesity defined as waist circumference higher than half of each individual’s height. Corresponding hazard ratios were computed using Cox proportional hazards regression.

Results:
Over 3,514,681 person-years, 2,562 CHD cases developed, an overall incidence of 0.73 (95%CI 0.70-0.76) per 1,000 person-years. BMI had a J-shape association with CHD risk, with those with a BMI of 20-22.4 kg/m2 showing the lowest CHD incidence. Waist circumference had a curvilinear relationship with CHD risk, with CHD risk starting to increase after waist circumference of 80 and 85 cm in women and men respectively. CHD risk increased with higher levels of BMI and waist circumference (Table 1). Compared to those with BMI of 20.0-22.9 kg/m
2
and without central obesity, those with BMI higher than 30 kg/m
2
and with and without central obesity had a 1.8 and 2.4 fold increased risk of CHD (Adjusted hazards ratio 1.80 (1.46-2.24) and 2.39 (1.38-4.13) respectively).

Conclusions:
Different levels of BMI and waist circumference conferred different CHD risk. Change in optimal cut-off of BMI and waist circumference for the Thai population should be considered.
Abstract 17262: Recent Trends in Incidence of Pregnancy Related Acute Myocardial Infarction and Associated Outcomes
Authors: Tripathi Byomesh , Sharma Purnima , Kumar Varun , Arora Shilpkumar , Atti Varunsiri , Lahewala sopan , Mishra Abhishek , Malhotra Shikha , Gopalan Radha , Deshmukh Abhishek
Published: July 2021

Introduction:
Acute myocardial infarction (AMI) during pregnancy is a rare but fatal complication. Recent trends in incidence of pregnancy-related AMI and associated outcomes are unclear.

Methods:
Nationwide inpatient sample (NIS) database was utilized for years 2005-2014. International classification of disease-Ninth revision (ICD-9) was used to identify pregnancy-related (antepartum as well as postpartum) admissions and acute myocardial infarction (AMI). The primary outcome was incidence and trend of AMI related to pregnancy during the study period. Secondary outcomes were trends in mortality and resource utilization. P-values for trends were generated by Cochrane-Armitage test for categorical variables and simple linear regression for continuous variables.

Results:
We identified a total of 43,437,621 pregnancy-related hospitalization and 3,786 cases of AMI (86% antepartum and 14% post-partum) were noted during the study period. The incidence of AMI during the study period was 8.7 per 100,000 pregnancies with an overall increase in incidence during study period (relative increase of 18.9%, p <0.001) and concomitant decrease in mortality (relative decrease of 40.05%, p <0.001), cost of care (relative decrease of 8.70%, p<0.001) and length of stay (relative decrease of 13.53%, p<0.001).

Conclusions:
Incidence of AMI during the period is on the rise in recent years with concomitant improvement in mortality and resource utilization. This reflects improved diagnostic capability and a better understanding of non-atherosclerotic mechanisms of AMI during pregnancy such as spontaneous coronary artery dissection, coronary spasm, and coronary thrombus.
Abstract 17274: Timed up and Go Test Predicts One-Year Mortality Among Patients Cardiovascular Events After Percutaneous Coronary Intervention
Authors: Khan Nadeem , Singh Mandeep
Published: July 2021

Timed Up and Go test predicts one-year mortality among patients cardiovascular events after percutaneous coronary intervention

Nadeem A. Khan, R. Jay Widmer, Amrit Kanwar, Mohammed A. Al-Hijji, Abdallah El Sabbagh, Ryan J. Lennon, Rajiv Gulati, Amir Lerman, Arashk Motiei, Mandeep Singh

Background:
Frailty is frequently seen in older adults and among patients with cardiovascular disease (CVD). Timed Up and Go Test (TUG) is a reliable and validated measure of frailty. We aim to assess 1-year mortality and stratify patients based on the performance on the test.

Methods:
Patients ≥55 years and referred to the cardiac catheterization laboratory underwent the TUG, a simple test to measure static and dynamic balance. We timed the patients while they were instructed to rise from the chair, walk 3 meters (or 10 feet), turn around, and walk back to the chair and sit down. Timing was divided in four categories [<7 sec (controls), 8-10 sec, 11-14 sec, and > 15 sec]. Mortality at one year was evaluated using a Cox proportional hazards model.

Results:
Those with TUG >15s were older (75.8 ±9.1years vs. 71.2±9.2 years in controls; P<0.001) and more women (42% vs. 29%) had TUG >15s, P=0.002. Patients with TUG >15 s had a significantly increased risk of mortality on follow-up (HR 3.88, 95% CI 1.97-7.66; P<0.001, Figure) which remained significant after adjusting for age and sex (HR 1.86, 95% CI 1.05, 3.30).

Conclusions:
The TUG test predicts one year mortality among patients referred to the cardiac catheterization laboratory. These data underscore the importance of frailty assessment in patients with CVD.
Abstract 17307: TGR5 Contributes to Improved Perivascular Adipose Tissue Function (PVAT) After Vertical Sleeve Gastrectomy in Mice
Authors: Zaborska Karolina E , Cha Eumee K , Garibay Darline , Sethupathy Praveen K , Cummings Bethany P
Published: July 2021

PVAT is a critical regulator of vascular contractility and its dysfunction contributes to obesity-induced hypertension (HTN). Bariatric surgery, such as vertical sleeve gastrectomy (VSG), causes high rates of HTN remission prior to weight loss, and rescues PVAT function by increasing nitric oxide (NO) production. We have previously validated a VSG mouse model that recapitulates the body weight-independent lowering of blood pressure. VSG increases bile acid (BA) signaling through the BA receptor, TGR5. TGR5 stimulates NO production from endothelial cells (ECs) but the role of TGR5 signaling in adipocyte NO production is unknown. We hypothesized that VSG increases NO bioavailability within PVAT in a TGR5-dependent manner. High fat diet (HFD)-fed male C57BLmice underwent VSG or sham surgery (
n
=4-6) Sham (S) mice were food restricted to match body weight to VSG mice. Vascular contractility was reduced in VSG mice (Max contraction (%): S: 30±2, VSG: 23±3;
P
<0.05). To assess the role of TGR5 on NO production within PVAT, we performed western blotting on mesenteric PVAT from VSG or sham-operated HFD-fed TGR5 WT and KO mice. eNOS phosphorylation was increased in PVAT in VSG WT, but not VSG KO (western blot quantification (AU): S WT: 1.0±0.1, VSG WT: 1.3±0.1, S KO: 1.1±0, VSG KO: 1.0±0.1;
P
<0.05). To determine how TGR5 regulates PVAT NO production, we assessed the impact of TGR5 on microRNA-21 (miR-21) expression. MiR-21 stimulates NO production in ECs but its role in adipocytes in unknown. Thus, we hypothesized that TGR5 regulates NO production within PVAT by upregulating miR-21. MiR-21 expression was increased in PVAT from VSG-operated TGR5 WT mice but not KO compared to sham controls (western blot quantification (AU): S WT: 0.9±0.1, VSG WT: 2.1±0.5, S KO: 0.7±0.6, VSG KO: 0.6±0.1;
P
<0.05). We further investigated whether TGR5 activation and miR-21 overexpression stimulate NO production in adipocytes. Mature 3T3-L1 adipocytes were treated with INT-777 or transfected with miR-21 mimic. TGR5 activation and miR-21 overexpression increased eNOS phosphorylation (
P
<0.05). In conclusion, our data suggest that VSG increases NO bioavailability in PVAT by activating adipocyte TGR5 signaling and upregulating miR-21 expression.
Abstract 17310: Outcome of Octogenarians Undergoing High Risk Percutaneous Coronary Intervention With Percutaneous Mechanical Circulatory Support
Authors: Alraies M Chadi , Kaki Amir , Blank Nimrod C , Hasan Reema , Mohamad Tamam , Elder Mahir , Schreiber Theodore C
Published: July 2021

Introduction:
The procedural risks of high risk percutaneous coronary intervention (HRPCI) using mechanical circulatory support (MCS) for octogenarians have not been well established.

Hypothesis:
We sought to study the outcome of octogenarians (≥80 years) undergoing HRPCI with MCS compared with those who are <80 years old

Methods:
Using the cVAD Registry, we identified a total of 1,273 complex high-risk indicated patients who underwent PCI with MCS using Impella 2.5 or Impella CP. Patients without cardiogenic shock who underwent elective or urgent intervention were included. A total of
259
(20.2%) were octogenarians and (79.6%) were < 80 years old

Results:
octogenarians were older (84±3 vs. 65±8, p<0.001), had less diabetes (39% vs. 55%, p<0.001), higher STS score (9.1±8 vs. 4.6±6, P<0.001) and higher baseline ejection fraction (35±116 vs. 27±15, P<0.001). Despite higher STS score, octogenarians had no difference in in-hospital mortality, stroke, myocardial infarction or need for recurrent revascularization compared with non-octogenarians (p value insignificant for all comparisons). Ejection fraction improved in both octogenarians and younger patients at the time of discharge (28% to 32% and 31% to 38%, respectively, p<0.0001) as well as NYHA class post PCI (NYHA Class III/IV 73% to 50% in octogenarians and younger patients, p<0.001). Freedom from death and MACE 30 days follow up, was similar as well in octogenarians and younger patients (figure)

Conclusions:
the use of percutaneous circulatory support for HRPCI is reasonable and feasible in a selected octogenarian population with similar outcomes as those of younger selected patients. Irrespective of age, the use of Impella 2.5 was an independent predictor of favorable outcomes.
Abstract 17312: Hand1 Impairs Angiogenesis in Heart and Placenta
Authors: Courtney Jennifer A , Jones Helen N
Published: July 2021

Introduction:
Congenital heart defects affect approximately 1% of live births, often requiring complex surgeries at birth. The most significant risk factor for surgery survival is birthweight. Proper placental development and function is vital for normal fetal growth. We have previously demonstrated abnormal placental development and vascularization in human CHD placentas. Hand1 has roles in heart and placental development and has been implicated in multiple types of CHD including double right outlet, hypoplastic left heart syndrome, and septal defects. We utilized the Hand1
A126fs/+
mouse to investigate the role of Hand1 in placentation and vascularization.

Methods:
Hand1
A126fs/+
female mice were time-mated with Nkx2.5cre or Cdh5cre males. Feto-placental units were harvested at E10.5 and E12.5 for histological analysis, vascular assessment by IHC for CD-31, and RNA expression by qPCR.

Results:
Nkx2.5cre/Hand1
a126fs/+
fetuses demonstrated embryonic lethality by E10.5 due to lack of placental labyrinth formation and vascularization (Figure 1). In contrast, ablation of Hand1 in vascular endothelium (Cdh5cre) did not disrupt placental labyrinth or heart at E12.5. Expression of VegFb, Ang1, Ang2, Flt1, Flk was reduced in Hand1
A126fs/+
; Nkx2.5cre placentas compared to control littermates, but VegFa expression was increased.

Conclusion:
Our data demonstrate that Hand1 expression in placental trophoblast, but not endothelium, is necessary for vascularization of the labyrinth and may disrupt multiple angiogenic factors known to be expressed in trophoblast. Alterations in Hand1 may represent a mechanism for abnormal placentation in cases of CHD.

Figure 1. H/E (A-C) and CD31 (D-F) images of Hand1
+/+
(A, D), Hand1
A126fs/+
; Nkx2.5cre (B, E), and Hand1
A126fs/+
; Cdh5cre (C, F) placentas at day E12.5. Hand1A
126fs/+
; Nkx2.5cre placentas fail to form labyrinth and fetal vasculature, while Hand1
A126fs/+
; Cdh5cre placentas develop normally at this timepoint.
Abstract 17349: The Biomimetic Cardiac Tissue Model (BCTM) Reproduces the Pathological Remodeling Seen in Hypertrophic and Dilated Cardiomyopathy
Authors: Rogers Aaron J , Miller Jessica M , Kannappan Ram , Sethu Palaniappan
Published: July 2021

Introduction:
Cardiovascular research and regenerative strategies have been significantly limited by the lack of relevant cell culture systems that can recreate complex hemodynamic stresses associated with pressure-volume changes in the heart. To address this issue, we designed a Biomimetic Cardiac Tissue Model (BCTM) where encapsulated cardiac cells can be cultured in 3D fibers and subjected to hemodynamic loading to mimic pressure-volume changes seen in the left ventricle.

Hypothesis:
We tested the hypothesis that stimulation under hemodynamic loads as seen in pressure and volume overload is capable of reproducing the pathological remodeling seen
in vivo.

Methods:
The 3D fibers are suspended between two posts within a pumping chamber that is integrated within a flow loop. Various parameters associated with heart function like heart rate, peak-systolic pressure, end-diastolic pressure and volume, end-systolic pressure and volume, and duration ratio between systolic and diastolic can all be precisely manipulated allowing culture of various cardiac cell types under developmental, normal, and disease states. Using the BCTM we reproduced the pathophysiological mechanical stresses of pressure overload and volume overload.

Results:
Using H9c2 cells, a cardiomyogenic cell line, our results clearly show that culture within the BCTM under pathological hemodynamic loads accurately induces morphological and gene expression changes similar to those seen in both hypertrophic and dilated cardiomyopathies
in vivo
. Cells within the BCTM under pressure overload see increased hypertrophic remodeling and fibrosis whereas cells subject to prolonged volume overload experience significant changes to cellular aspect ratio through thinning and elongation of the engineered tissue.

Conclusions:
These results clearly demonstrate that the BCTM can accurately reproduce pathological remodeling and create highly relevant models for cardiovascular disease modeling.
Abstract 17350: Comparison of Radiological Risk Between Transfemoral and Transradial Approach: An Updated Meta-Analysis
Authors: Siddamsetti Sisir , Joshi Udit , Yandrapalli Srikanth , Pallath Harshakumar Sreedevi , Vij Aviral , Kodumuri Vamsi
Published: July 2021

Background:
Studies have shown that transradial approach (TR) is associated with increased radiation exposure compared to transfemoral (TF) approach. However, it is believed that the difference in radiation exposure may not be significant between the two approaches when performed by experienced operators, as TR approach has a challenging learning curve. Newer studies have shown conflicting results in radiation exposure between the two treatment strategies. Hence, we sought to perform a meta-analysis comparing the radiation exposure between TR and TF approach during coronary angiography (CA) and percutaneous coronary intervention (PCI).

Methods:
We searched PubMed, EMBASE and SCOPUS for eligible studies. 27 randomized controlled trials (RCTs) were included in our analysis. Outcomes analyzed were Fluoroscopy time (FT) in minutes and dose-area product (DAP) in Gy/cm2. We used Inverse variance random effects model to calculate the mean difference (MD) and 95% confidence interval (CI). We performed a subgroup analysis of trials that compared the two approaches for CA and PCI separately. We also performed a subgroup analysis of trials that only included self-identified experienced operators.

Results:
FT was reported by 26 trials and was significantly higher with TR approach for both CA (MD=1.28, 95% CI 0.78 to 1.77, P <0.00001) and PCI (MD=0.96, 95% CI 0.59 to 1.33, P<0.00001). FT was still higher (MD=0.95, 95% CI 0.63 to 1.27, P<0.00001) in subgroup analysis of trials that only included experienced operators. DAP was only reported in 10 trials and there was no significant difference between TR and TF approach for both CA (MD=1.44, 95% CI -0.52 to 3.41, P=0.15) and PCI (MD=0.54, 95% CI -4.45 to 5.53, P=0.83). There was also no significant difference in DAP (MD=0.81, 95% CI -3.68 to 5.29, P=0.79) between the two approaches in trials that only included experienced operators.

Conclusions:
TR approach is associated with higher radiation exposure than TF approach even with experienced operators. However, the clinical significance of this finding has to be evaluated in larger RCTs.
Abstract 17352: Hand Grip Strength as a Predictor of Exercise Capacity in Coronary Heart Disease
Authors: Choi Cheol Ung , Kim Woohyeun , Park Se-Hyun , Kim Woo-Sub , Jang Won Young , Park Yoonjee , Seo Hong Seog , Park Chang Gyu , Rha Seung-Woon , Kim Eung Ju , Na Jin Oh , Kim Jin Won , Park Eun Jin , Kang Dong Oh
Published: July 2021

Introduction:
Exercise capacity is related to the prognosis of coronary heart disease (CHD). Recent study have shown that quadriceps strength can be used to predict exercise capacity levels in patients with CHD.

Hypothesis:
The aim of this study is to determine whether this relationship between muscular strength and exercise capacity is maintained in hand grip strength (HGS).

Methods:
We studied 310 participants (Age; 62.1 ± 11.5, Men; 77.4 %) who underwent coronary intervention and participated cardiac rehabilitation. Maximal HGS was expressed as absolute value (kg), and relative to bodyweight (%bodyweight). Logistic regression was used to assess the relationship of maximal HGS, age, sex, type of CHD, diabetes, hypertension, renal insufficiency, ejection fraction, body mass index, body weight, waist to hip ratio, and basal metabolic rate with distance walked on 6-minuite walk test (6MWT) and estimated metabolic equivalents (eMETs).

Results:
Maximal HGS was significantly related to distance walked on 6 MWT (r = 0.40 for %bodyweight, p < 0.001) and eMETs (r = 0.43 for %bodyweight, p < 0.001). Maximal HGS was the strongest predictor of exercise capacity in each distance walked on 6 MWT category. Receiver operating characteristics curves identified maximal HGS of 35.7, 42.0% bodyweight as the best predictive cut offs for 200, and 400 meters, respectively with positive predictive values of 0.64. They also identified HGS of 38.3, and 44.6% bodyweight as the best predictive cut offs for 6 and 8 eMETs, respectively with positive predictive values of 0.70.

Conclusions:
Maximal HGS is related with distance on 6 MWT and eMETs levels at exercise test in CHD patients. This result suggests that maximal HGS can be used to predict exercise capacity levels. Based on this result, prospective study investigating the association between HGS and clinical outcome of CHD is needed.
Abstract 17361: Phenotype of the Aortic Valve in Patients With Filamin-A Mutations: Echocardiographic Features and Clinical Outcomes
Authors: Capoulade Romain , Cueff Caroline , Piriou Nicolas , Toquet Claire , Blandin Stéphanie , Guimbretiere Guillaume , Omen Toon , Aalberts Jan J , Berstein Daniel , Berstein Jonathan A , Trochu Jean-Noel , Le Marec Herve , Merot Jean , Schott Jean-Jacques , Le Tourneau Thierry
Published: July 2021

Background:
Filamin-A (
FLNA
) mutations have been associated with the development of mitral valve prolapse and a unique mitral valve features described as a paradoxical restrictive leaflets motion in diastole has been recently described using a comprehensive echocardiographic screening. Polyvalvular diseases have also been reported in these patients, especially affecting the aortic valve.

Objectifs:
The objective of this study was to perform a comprehensive echocardiographic analysis of the aortic valve (AV) and the proximal aortic root of patients with
FLNA
mutations, and assess the impact of the aortic disease on outcomes.

Methods:
We included in this analysis 256 subjects (42±22 years, 136 men, 76 mutated: FLNA+) with confirmed genetic status, from 5
FLNA
families. Comprehensive echocardiographic characterization of the aortic valve and the proximal aortic root, including the measurement of the aortic annulus, sinuses of Valsalva, sinotubular junction and ascending aorta, was performed in FLNA+ patients vs control relatives.

Results:
Overall, 47 subjects (18%) presented an aortic valve alteration: 40 (53%) of FLNA+ compared to 7 (4%) FLNA- subjects (p<0.001). Among the 76 FLNA+ patients, 7 (9%) had a bicuspid aortic valve phenotype as opposed to 2 (1%) in control relatives (p=0.02). The underlying disease affecting the aortic valve was AV sclerosis, stenosis and AV regurgitation with either prolapse or restricted cusps motion. A restrictive opening of the AV was also reported in some patients. Aortic valve mean gradient was slightly increased in FLNA+ compared with FLNA- subjects (5.7±5.1 vs 4.2±1.8 mmHg, P= 0.02). In adults, left ventricular outflow tract diameter (12.5±1.4 vs 12.0±1.0 mm/m
2
; p=0.02), sinuses of Valsalva (17.8±2.5 vs 16.2±1.9 mm/m
2
; p<0.001) and sinotubular junction (15.0±2.0 vs 13.7±1.6 mm/m
2
; p<0.001) were larger in FLNA+ subjects as compared to control relatives. 8 FLNA+ subjects (11%; 6 males) underwent aortic valve-related surgery versus 0 in controls (p<0.001). Survival was also impaired in FLNA+ male subjects (70 year old: 72% vs 64%, p=0.03).

Conclusion:
The
FLNA
-mutated patients presented aortic valve disease more frequently, including a higher prevalence of bicuspid valve, stenosis, and regurgitation owing to either cusp prolapsed or restrictive motion. This unique features described in this population was associated with worse clinical outcomes, especially in FLNA+ males. Management and decision making should be done according to the features of these patients with polyvalvular diseases
Abstract 17374: Trends in Prevalence and Percutaneous Coronary Intervention Utilization Among Patients With Anomalous Coronary Artery
Authors: Tripathi Byomesh , Arora Shilpkumar , Kumar Varun , Atti Varunsiri , Nalluri Nikhil , Sharma Purnima , Malhotra Shikha , Patel Nileshkumar J
Published: July 2021

Introduction:
Previous studies on anomalous coronary artery suggested its association with significant stenosis and worse in-hospital outcomes. Limited information is available about the prevalence of anomalous coronary artery and utilization of Percutaneous coronary intervention(PCI) in this population.

Methods:
We derived our study cohort from HCUP’s Nationwide Inpatient Sample (NIS) database (2004-2014). Anomalous coronary artery and PCI related hospitalizations were recognized using ICD-9-CM diagnostic code 746.85 and procedural code 36.06,36.07 and 00.66 respectively in either primary or secondary fields, Cochran-Armitage trend test was used to generate p-value.

Results:
We identified 59,819 patients with anomalous coronary artery in our study cohort (83.6% age ≥50 years, 69.5% male, 65.2% white), exhibiting significant increase from 4,187 in 2004 to 5940 in 2014 (relative increase of 45.3 %). Utilization of PCI in this population has increased from 14% in 2004 to 17.3 % in 2014 (ptrend <.0001). The most common comorbid conditions coexisting with PCI admissions were dyslipidemia (68.5%), Hypertension (66%), Coronary artery disease (54.2%) and Smoking (41.3%), STEMI (27.3%); All exhibit increasing prevalence from 2004-2014 (ptrend <.0001). (Fig 1B). Weekend admission has increased from 16.2 % to 23% (ptrend <.0001) and maximum PCI (40.6%) were performed in the southern region of United States.

Conclusions:
Prevalence of anomalous coronary artery has significantly increased in united states with a concomitant increase in PCI utilization in this population. We also noted a concurrent increase in the prevalence of comorbidities such as smoking, dyslipidemia, coronary artery disease, hypertension, STEMI and weekend admission over the study period in these patients.
Abstract 17387: Time Difference Between Mitral and Tricuspid Opening Has a Prognostic Value in Patients With Heart Failure
Authors: Sugahara Masataka , Asakura Masanori , Goda Akiko , Masai Kumiko , Masuyama Tohru
Published: July 2021

Introduction:
It is certain that comprehensive noninvasive assessment of LV and RV hemodynamics is valuable in the management of patients with heart failure (HF); however, the value of the noninvasive bi-ventricular hemodynamic assessment has been hampered by methodological limitations. Dual Doppler echocardiography was used to overcome the limitations by measuring a time difference between the mitral and tricuspid valve opening (MO-TO time) in a real-time fashion.

Hypothesis:
We hypothesized that MO-TO time was of additive prognostic value in patients with HF.

Methods:
We prospectively enrolled 60 patients with sinus rhythm who were admitted because of worsening of HF and underwent an invasive hemodynamic study after stabilization of the acute phase of HF. MO-TO time was measured in addition to routine echo parameters, invasive hemodynamic parameters and plasma BNP level in all patients. Patients were divided into either of two groups based on the MO-TO time: MOP (MO precedes to TO), and TOP (TO precedes to MO) groups. We followed up the predefined adverse outcome, cardiovascular death, and hospitalization due to worsening HF in all patients for a year.

Results:
The pulmonary artery wedge pressure (PAWP) and mean pulmonary artery pressure (mPAP) were higher in the MOP group than in the TOP group (21 ± 8.5 vs. 11 ± 4.5 mmHg, p < 0.001; 32 ± 8.8 vs. 21 ± 5.5, p < 0.001), respectively. PAWP and mPAP correlated with the MO-TO time (r = -0.74, p < 0.001; r = -0.70, p < 0.001). MOP had a high probability of adverse cardiovascular outcome (Log-rank test; p = 0.002). In univariate Cox analysis, mitral E/A ratio, BNP, and MO-TO time were significant predictors (p = 0.044, p = 0.019, and p = 0.012), respectively. An addition of MOP improved the predictive power of univariate predictors (mitral E/A ratio, BNP) in the bivariate Cox analysis.

Conclusions:
The MO-TO time may be a useful marker to detect the elevation of PAWP and mPAP. MOP reflects pulmonary hypertension due to left heart disease and has a prognostic value in predicting adverse cardiovascular events in patients with HF.
Abstract 17396: RV Remodeling in Two Animal Models of Pulmonary Arterial Hypertension
Authors: Zhang Xiaoyan , Velez-Rendon Daniela , Valdez-Jasso Daniela
Published: July 2021

Introduction:
Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis. By relating ventricular hemodynamics to wall mechanics, we aimed to discriminate the contributions of ventricular geometric remodeling and intrinsic changes in myocardial mechanical properties in two commonly used PAH animal models at end-systole (ES) and end-diastole (ED) to the maintenance of cardiac output during the early compensated phase.

Methods:
PAH was induced in 13 male Sprague-Dawley rats. The MCT group (N=4) was injected with a single dose of 60mg/kg of monoctroaline and kept in normoxia for 4 weeks. The SuHx group (N=9) was injected with a single dose of 20mg/kg of sugen, a VEGF inhibitor, and was placed on a hypoxia chamber for 3 weeks followed by 3 weeks of normoxia. 7 animals were used as a control group.
In-vivo
measurements of RV pressure and volume with preload changes were acquired. To relate ventricular pressure-volume relations to sarcomere mechanics, a computational model of the RV was developed. Using ventricular morphology and volume measurements from PAH groups, sarcomere material mechanics were adjusted to evaluate ES and ED functions in the treated animals.

Results:
ED pressures rose significantly in the treated groups (31.7 vs. 70.5 and 71.1 mmHg). ED and ES volumes remained the same in SuHx and CTL group, but increased significantly in the MCT group. RV hypertrophy increased in both PAH animal models, but it was significantly higher in the SuHx group. Even though differences in pressure, volume and morphology exist between the PAH groups, SV and CO were preserved in all treated animals. Model material parameters of increased in PAH, significantly in MCT maximal isometric tension.

Conclusions:
The model analysis suggests compensation to ESP rises was only possible due to a significant increase in the contractility of RV myocardium in the MCT and SuHx animals. No changes in diastolic function were found in the MCT animals, but there was an increase stiffness in the SuHx animals.
Abstract 17401: Diesel Exhaust Induces Mitochondrial Dysfunction, Hyperlipidemia and Liver Steatosis
Authors: Yin Fen , Driscoll Will , Sulaiman Dawoud , Vergnes Laurent , Ricks Jerry , Ramanathan Gajalakshmi , Stewart James , Mehrabian Margarete , Beaven Simon W , Reue Karen , Lusis Aldons J , Rosenfeld Michael E , Araujo Jesus A
Published: July 2021

Introduction:
Air pollution associates with increased cardiovascular morbidity and mortality, partly due to induction of dyslipidemia and metabolic syndrome. Our goal was to dissect mechanisms involved.

Hypothesis:
Diesel exhaust exposure induces hyperlipidemia and liver steatosis by dysregulating lipid metabolism, and altering gut microbiota composition.

Methods:
We assessed the effects of exposure to air pollution on lipid metabolism in mice through assessment of plasma lipids and lipoproteins, oxidized fatty acids 9-HODE and 13-HODE, lipid and carbohydrate metabolism, and gut microbiota composition. Findings were corroborated and mechanisms further assessed in culture of HepG2 hepatocytes.

Results:
ApoE KO mice exposed to inhaled diesel exhaust (DE, 6 hours/day, 5 days/week for 16 weeks) exhibited significantly (p< 0.05) elevated plasma cholesterol and triglyceride levels, increased hepatic triglyceride content, and increased hepatic levels of 9-HODE and 13-HODE (oxidative products of linoleic acid) indicative of increased oxidative stress, as compared with control mice treated with filtered air (FA). DE also led to downregulation of
Acad9
, which suggested decreased β-oxidation of fatty acids and decreased lipid catabolism. A direct effect of DEP exposure on hepatocytes was demonstrated by treatment of HepG2 cells with a methanol extract of DE particles followed by loading with oleic acid. As observed
in vivo
, this led to decreased
ACAD9
expression, increased triglyceride content, and altered total, mitochondrial and ATP-linked respiration assessed by a Seahorse metabolic flux analyzer, indicative of mitochondrial dysfunction. Direct treatment of mitochondrias with DE particles affected mitochondrial complexes I and IV.

Conclusions:
Diesel exhaust exposure leads to dyslipidemia and liver steatosis in ApoE KO mice, likely due to mitochondrial dysfunction and decreased lipid catabolism.
Abstract 17402: Increased Epicardial Adipose Tissue Volume is Associated With Left Ventricular Diastolic Function in Patients With Zero Coronary Artery Calcium Score
Authors: Utsunomiya Hiroto , Yamamoto Hideya , Shimada Atsushi , Kitagawa Toshiro , Hidaka Takayuki , Kihara Yasuki
Published: July 2021

Background:
Recent publications suggested that epicardial adipose tissue (EAT) contributes to the pathogenesis of coronary atherosclerosis. Although some studies showed the association between EAT accumulation and left ventricular (LV) diastolic dysfunction, these associations are not fully understood.

Methods:
We evaluated 153 patients without coronary artery disease who underwent coronary computed tomography (CT) angiography and Doppler echocardiography. We evaluated 153 patients (mean age of 60 years and 54% men) with zero coronary artery calcium score in coronary CT. Visceral adipose tissue (VAT) area was simultaneously measured by abdominal scans, and EAT volume was also calculated. These measurements were corrected by body surface area; VAT area index (VATAI), and EAT volume index (EATVI). The early diastolic mitral annular velocity at the septal (septal E’) and lateral (lateral E’) were measured using tissue Doppler echocardiography.

Results:
The mean values of BMI, VATAI, EATVI, and LVMI were 23.7 ± 3.8 kg/m
2
, 52.6 ± 26.4 cm
2
/m
2
, 71.3 ± 29.8 cm
3
/m
2
, and 83.3 ± 17.7 g/m
2
, respectively. The mean septal E’ and lateral E’ velocities were 7.2 ± 2.2 cm/s and 9.8 ± 2.9 cm/s, respectively. Each E’ velocity was negatively correlated with EATVI (septal, R = 0.276, p < 0.001; lateral, R = 0.342, p < 0.001) and VATAI (septal, R = 0.241, p = 0.03; lateral, R = 0.255, p = 0.002; Figure). In contrast, each E’ velocity was not correlated with LVMI (septal, R = 0.161, p = 0.03; lateral, R = 0.118, p = 0.14) and BMI (septal, R = 0.182, p = 0.03; lateral, R = 0.152, p = 0.06). To determine each E’ velocity, we performed stepwise multiple regression analyses where all clinical parameters were entered. Diastolic blood pressure (p = 0.014), statin use (p = 0.011), LVMI (p = 0.003), and EATVI (p = 0.004) were independently correlated with septal E’ velocity, and statin use (p = 0.024), LVMI (p = 0.011), and EATVI (p < 0.001) were independently correlated with lateral E’ velocity.

Conclusion:
An increase in EATVI was associated with the decrease of early diastolic mitral annular velocity along each side of the left ventricle in patients with coronary calcium score of zero. These findings indicate that EAT accumulation may cause LV diastolic dysfunction in the early phase of coronary artery disease.