bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11515: Noninvasive Quantitation of Coronary Collateral Flow Capacity in Patients with Chronic Total Occlusion Treated with External Counter Pulsation: Dobutamine Compared with Vasodilator Stress Pet Identifies Collaterogenesis
Authors: Merhige Michael E , Davis Cory , Keppler Julia , Knapp Connor , Wilson Kevin
Published: March 2022

Introduction:
FDA approved external counterpulsation (ECP) improves coronary collateral flow index measured invasively, using intracoronary wedge pressure beyond a severe stenosis. However, there is presently no noninvasive method to measure coronary collateral flow capacity (CCFC), in patients with total coronary occlusion (CTO).

Hypothesis:
CCFC can be measured noninvasively by comparing the improvement in flow in the ischemic bed beyond CTO, using dobutamine stress (DBT), which supports supply side pressure, compared with vasodilator stress (DIP), which lowers supply side pressure, causing coronary steal.

Methods:
Seven patients with CTO were treated with 35 sessions of ECP, and studied with both DIP and DOB stress PET myocardial perfusion imaging. Coronary flow capacity (CFC), which integrates absolute rest and stress flow with coronary flow reserve on a per pixel basis, was measured objectively with FDA approved HeartSee software.

Results:
As shown in the Table, all patients demonstrated a decrease in the size of the ischemic zone at risk, defined as moderate or severely reduced CFC, when CFC with DIP was compared with DOB: 28% LV mass vs. 5%; p < 0.01. Five of 7 patients also demonstrated significant improvement in global CFC by Kolmogorov-Smirnoff analysis. Absolute stress flow into the ischemic zone improved significantly in all ECP treated patients during demand ischemia compared with vasodilator stress (1.9 vs. 1 ml/min/g; p < 0.01). One of the two patients who did not improve global CFC, despite ECP treatment, underwent coronary arteriography demonstrating a new flow limiting stenosis in the supply side vessel, which was successfully stented.

Conclusion:
ECP treatment is associated with improved coronary collateralization in patients with CTO, which can be identified noninvasively with quantitative PET myocardial perfusion imaging.
Abstract 11516: Quantification of Regurgitation Through Dual Orifices: Pulsatile
in Vitro
Analysis with Echocardiography and MRI Assessment
Authors: Wu Erik , Lee Jeesoo , Mason Oneil R , Markl Michael , Thomas James D
Published: March 2022

Introduction:
Proximal Isovelocity Surface Area (PISA) measurement is widely accepted to quantify mitral regurgitant volume (RVol), but flow convergence (FC) zones are complicated with dual orifices, seen with mitral clipping. This study seeks to investigate how flow through one orifice affects PISA measurement across the other to better quantify RVol in dual orifice conditions.

Methods:
3D-printed dual circular orifice models with varying relative areas were integrated into a pulsatile flow phantom simulating left heart flow. One orifice (A) was standardized at 19.6 mm
2
while the other (B) was 1X, 2X, and 3X the area of A in three models. Inter-orifice distance was 5 mm to emulate mitral clipping. Continuous wave doppler echocardiography measured peak velocity and velocity time integral. PISA was performed at four aliasing velocities normalized to peak velocity (V
a
/V
peak
) (10%, 8%, 4%, 2%) to compute RVol with 2D phase contrast MRI as reference. In each model, PISA RVol and percent error was calculated to see how varying the area of B impacts PISA accuracy of A. 4D flow MRI FC data was also collected to visualize the 3D formation of FC zones.

Results:
Using a high V
a
/V
peak
to create distinct FC zones provides a better RVol estimation with PISA, as low V
a
/V
peak
will merge the FC zones, overestimating flow across individual orifices. Single factor analysis of variance (ANOVA) of percent error of A across the three models showed no significant difference at high V
a
/V
peak
(8%: p=0.80, 10%: p=0.23), but significant difference at low V
a
/V
peak
(2%: p=0.010, 4%: p=0.005). High V
a
/V
peak
FC zones of orifices are independent from each other; PISA can be measured with standard practices and added together for an accurate total RVol. At low V
a
/V
peak
, FC orifice zones overlap with overestimation error increasing with larger B area. This finding suggests that resolving two separate FC zones to minimize flow interference is important for accurate RVol estimate in a dual orifice setting.
Abstract 11518: Association of Individual- and Neighborhood-Level Determinants Across Young Adulthood with Racial Disparity in Premature Cardiovascular Disease: The Coronary Artery Risk Development in Young Adults Study
Authors: Shah Nilay S , Ning Hongyan , Petito Lucia , Kershaw Kiarri N , Bancks Michael , Jared Reis P , Sidney Stephen , Rana Jamal S , Jacobs David R , KIEFE Catarina I , Carnethon Mercedes , Lloyd-jones Don , Allen Norrina , Khan Sadiya
Published: March 2022

Introduction:
Black adults experience higher rates of cardiovascular disease (CVD) compared with White adults, particularly across young adulthood. To identify intervention targets to reduce disparities, we quantified the contribution of individual- and neighborhood-level determinants across young adulthood to Black-White differences in incidence of premature CVD.

Methods:
In Black and White adults (baseline age 18-30 years) in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, the associations of clinical, lifestyle, psychosocial, socioeconomic, and neighborhood determinants with racial disparities in incident CVD were evaluated with sex-stratified Cox proportional hazards models adjusted for time-updated risk factors. Percent reduction in the ß estimate (log-hazard ratio [HR]) for race quantified the contribution of each risk factor group, individually and combined, to incident CVD racial disparities.

Results:
In 1707 Black and 2001 White young adults followed for median 33.9 (IQR 33.7-34.0) years, Black adults had higher risk of incident CVD than White adults (Figure). The fully adjusted model yielded significant attenuation of the disparity: HR 1.22 (0.68-2.21) for Black vs. White women, HR 1.42 (0.91-2.23) for Black vs. White men. In women, clinical risk factors were associated with the largest percent reduction in the ß estimate (83%) for race. In men, socioeconomic, lifestyle and clinical risk factors were each associated with significant percent reductions in ß estimates (45%, 37%, and 28%, respectively).

Conclusions:
In CARDIA, risk for premature CVD was no longer significantly higher in Black vs. White adults after adjustment for upstream determinants across multiple domains. The largest contribution to racial disparities was from clinical factors in women and socioeconomic factors in men. These findings may inform earlier-life interventions to reduce disparities in premature CVD.
Abstract 11519: CHA
2
DS
2
VASc Score as a Predictor of Ablation Success Defined by Continuous Long-Term Monitoring
Authors: Liu Albert Y , Lohrmann Graham , Ziegler Paul D , Monteiro Joao V , Varberg Nathan V , Passman Rod S
Published: March 2022

Introduction:
There are few readily available and effective risk stratification tools for successful catheter ablation (CA) of atrial fibrillation (AF). CHA
2
DS
2
VASc score is a marker for vascular disease and has been shown to be mildly predictive of CA success, although prior studies have used short-term external monitors to define success.

Hypothesis:
Lower CHA
2
DS
2
VASc score correlates with CA success as measured by continuous monitoring via cardiac implantable electronic devices (CIED).

Methods:
Using the Optum® de-identified Electronic Health Record dataset (01/2007 to 06/2019) linked with the Medtronic CareLink device database, we identified patients who underwent a 1
st
CA procedure for AF following CIED implantation. CA success was defined as absence of ≥1 hour of AF on any day following a 3-month blanking period. A proportional hazard model was used to estimate hazard ratios (HR) between CHA
2
DS
2
VASc subgroups (0-2, 3-4, ≥5).

Results:
A total of 665 patients (age 66.9±9.1 years, 73.4% male, CHA
2
DS
2
VASc 3.5±1.8, 37.3% paroxysmal AF, 62.7% persistent AF) were analyzed and included 36.2% insertable cardiac monitor, 28.0% PPM, 21.4% ICD, 13.2% CRT-D, and 1.2% CRT-P. CA success at 24 months post blanking period was 39.8% (95% CI 32.4%-48.9%), 36.9% (95% CI 29.7%-45.8%), and 20.9% (95% CI 13.9%-31.4%) for CHA
2
DS
2
VASc subgroups of 0-2, 3-4, and ≥5, respectively. Kaplan-Meier curves demonstrate a difference in survival free from AF between the three CHA
2
DS
2
VASc subgroups (p=0.007, Figure), with CHA
2
DS
2
VASc score being a significant predictor of CA ablation success (c-statistic 0.533). After controlling for AF type, patients with a score ≥5 remained at higher risk for AF recurrence compared to patients with a score of 0-2 (HR 1.28, 95% CI 1.001-1.63).

Conclusions:
In this real-world dataset of AF patients with continuous monitoring undergoing CA, CHA
2
DS
2
VASc score is a modest predictor of CA success.
Abstract 11520: Cost-Related Medication Nonadherence in Adults with Diabetes Mellitus in the United States
Authors: Taha Mohamad , Valero Elizondo Javier , Caraballo Cesar , Yahya Tamer , Khera Rohan , Satish Priyanka , Acquah Isaac , Hagan Kobina , Patel Kershaw , Mossialos Elias , Cainzos Achirica Miguel , Nasir Khurram
Published: March 2022

Background:
Health-related expenditures due to diabetes mellitus (DM) are rising in the US. Medication nonadherence is associated with worse health outcomes, particularly among individuals with DM who require uninterrupted treatment. We sought to determine whether patients with DM in the US report cost-related nonadherence (CRN), a potential consequence of rising drug costs.

Methods:
We used the National Health Interview Survey (2013-18), a nationally representative study, to identify participants with and without self-reported DM. Participants were considered to have experienced CRN if during the preceding year they reported skipping doses, taking less medication, or delaying filling a prescription to save money.

Results:
Of the 20,326 participants with DM, a weighted 14% (or 3 million annually) experienced CRN, including 9.5% skipping doses, 9.9% taking less medicine, and 11.8% delaying prescription filling to save money. Compared to those without DM (N=145,186), participants with DM reported a higher prevalence of CRN, with the largest differences being observed among non-elderly adults (Figure). Among non-elderly adults with DM, a weighted 19.4% (or 2.3 million annually) reported CRN. In multivariable logistic regression models, the main drivers of CRN among participants with DM were lack of insurance (OR 4.34, 95% CI 3.49, 5.39), younger age (OR 3.43, 95% CI 2.65, 4.44), low income (OR 1.82, 95% CI 1.58, 2.09), use of insulin (OR 1.19, 95% CI 1.04, 1.35), and unfavorable risk factor profile (OR 1.53, 95% CI 1.21, 1.93) (Table).

Conclusion:
In the US, 1 in 7 adults with DM reported CRN, and the burden was highest among non-elderly adults. Cost represents a serious barrier for therapy adherence among individuals with DM in the US, particularly among the most vulnerable. Removing financial barriers to accessing medications may improve adherence to essential therapies among individuals with DM, and ultimately improving outcomes.
Abstract 11521: Mitochondrial Metabolism is Regulated by the Type III Transforming Growth Factor Beta Receptor
Authors: Trykall David , Agrawal Vineet , West James , Barnett Joey V
Published: March 2022

Introduction:
In adults myocardial injury activates an epicardial process initiating epicardial cell epithelial-mesenchymal transformation (EMT) contributing epicardial-derived cells that become vascular smooth muscle, cardiac fibroblasts, or produce factors that support myocardial repair. The Type III Transforming Growth Factor Beta Receptor (TGFβR3) is an important mediator of EMT; a process influenced by metabolism. Here we probed wild type and TGFβR3-deficient metabolism in murine epicardial cells to determine if TGFβR3 regulates mitochondrial function.

Hypothesis:
Does TGFβR3 regulate mitochondrial metabolism in epicardial cells?

Methods:
Cultured murine epicardial cells were analyzed. Gene constructs were transduced by adenovirus. Mitochondrial function was assessed by Seahorse XFe96 and immunostaining or electron microscopy.

Results:
Loss of a single allele of
Tgfbr3
significantly decreased the oxygen consumption rate; an effect enhanced by loss of both alleles. Decreased mitochondrial function is associated with reduced mitochondrial number and abnormal morphology. These alterations coincide with dysregulated expression of genes involved with mitochondrial biogenesis:
Ppargc1a
,
Ppargc1b
,
Erra
,
Errb
, and
Errg
. Addition of TGFβR3 and TGFβ2 or BMP2, but not TGFβ1, to
Tgfbr3
null cells partially restored mitochondrial function and morphology. Expression of a constitutively active receptor rescues mitochondrial function, while expression of TGFβR3 lacking either the cytoplasmic domain or the three C-terminal amino acids that bind the scaffolding protein GIPC failed to rescue. Further, rescue of
Tgfb
r3 null cells by TGFβR3 and BMP2 was blocked by GIPC targeted siRNAs.

Conclusions:
These results demonstrate that the loss of a single allele of
Tgfbr3
significantly alters mitochondrial function. Both the cytoplasmic domain of TGFβR3 and GIPC are required for the regulation of mitochondrial function.
Abstract 11530: Cardiovascular Risk Profile and Preterm Birth by Maternal Nativity in Racially Diverse, Urban, Low Income Women in the United States
Authors: Boakye Ellen , Kwapong Yaa A , Obisesan Olufunmilayo H , Shah Lochan M , Ogunwole S. Michelle , Vaught Arthur J , Nasir Khurram , Bennett Wendy , Creanga Andreea , Blumenthal Roger S , Blaha Michael J , Wang Xiaobin , Sharma Garima
Published: March 2022

Introduction:
Preterm Birth (PTB) is an independent risk factor for future cardiovascular disease (CVD). Nativity-related disparities in CVD risk profile and risk of PTB have been shown among non-Hispanic Black (NHB) women; however, studies exploring these disparities among women of other races are limited. We hypothesized that foreign-born NHB, White, and Hispanic women will have better CVD risk profile and lower risk of PTB compared to their US-born counterparts.

Methods:
We utilized data from 6096 women with mean age 27.5(±6.3) years in the Boston Birth Cohort who self-identified as NHB (2699), White (997), or Hispanic (2400). We examined differences in sociodemographic characteristics and CVD risk factors such as smoking, obesity, and hypertension by nativity status. Using multivariable logistic regression models, we examined the association of nativity and length of U.S. residence with PTB by race.

Results:
Of the total sample, 27.2% delivered preterm (29.1%, 29.8%, and 24.1% among NHB, White, and Hispanic women, respectively). Compared to foreign-born women, US-born women in each of the three racial groups were younger and more likely to be obese, single, smoke in pregnancy, and report severe stress. After adjusting for sociodemographic characteristics and CVD risk factors, foreign-born NHB women had lower odds of PTB compared to U.S-born NHB women (adjusted odds ratio, aOR: 0.79; 95%CI: 0.65-0.97). Similarly, foreign-born Hispanic women had lower odds of PTB compared to U.S-born Hispanic women (aOR: 0.72; 95%CI: 0.56-0.93). In all 3 racial groups, shorter (<10 years), but not longer (≥10 years) length of U.S. residence was associated with lower odds of PTB.
(Figure)

Conclusions:
US-born women in all three racial groups had a higher prevalence of CVD risk factors including smoking, obesity, and stress, compared to foreign-born women. The “foreign-born advantage” which is protective of PTB was not observed among foreign-born women with ≥10 years of U.S. stay.
Abstract 11551: Using the UK Biobank to Identify Novel Genetic Risk Factors Associated with Renal Artery Atherosclerosis
Authors: Alkhalfan Fahad , Gyftopoulos Alex , Chen Yi-Ju , Williams Charles H , Perry James A , Hong Charles C
Published: March 2022

Introduction:
Atherosclerotic renal artery stenosis (ARAS) is one of the most common pathologies affecting the renal vessels and accounts for 90% of all renovascular lesions. ARAS is associated with renovascular hypertension and nephropathy. ARAS tends to be a progressive disease that has a significant impact on a patient’s overall prognosis. ARAS is likely to occur because of a complex interaction between environmental and genetic factors. We aim to utilize the UK Biobank to identify novel genetic markers associated with renal artery atherosclerosis.

Methods:
The UK Biobank is a prospective cohort containing clinical and genetic data gathered from over 500,000 individuals. We used Plink’s GLM options for analyzing associations between genotypes and phenotypic manifestations of the disease. We defined renal artery atherosclerosis by selecting ICD-10 code I70.1 and compared cases to age- and gender-matched controls with a case-to-control ratio of 20:1. Related individuals and those with confounding diagnoses such as coronary artery disease, ischemic cerebrovascular disease, and peripheral artery disease were excluded from the controls.

Results:
There are 80 and 131 instances of I70.1 as a primary or secondary diagnosis, respectively. We identified 32 variants in 22 different genes with p ≤ 1 x 10
-6
. Identified genes have a minor allele frequency ≥ 0.5%. Variants achieving genome-wide significance (p < 5 x 10
-8
) tightly linked, representing a single haplotype on chromosome 22 near the
L3MBTL2
(L3MBTL histone methyl-lysine binding protein 2; p = 3.2 x 10
-8
, OR = 8.0) and
EP300-AS1
(EP300 antisense RNA 1; p = 3.5 x 10
-8
, OR = 7.9) genes.

Conclusions:
Genome wide analysis using ICD-10 codes as a phenotype has the potential to identify previously unknown gene loci that may contribute to an increased risk of ARAS. Future studies are warranted to confirm the association of the chromosome 22 loci to ARAS.
Abstract 11554: Measures of High-Density Lipoprotein Function and Composition in Men and Women with Severe Aortic Valve Stenosis
Authors: Hafiane Anouar , Favari Elda , Bortnick Anna E
Published: March 2022

Introduction and Hypothesis:
Aortic valve calcification (AVC), is the intrinsic mechanism of valvular obstruction in severe aortic stenosis (AS), sharing similarities with atherosclerosis. There are differences in AVC by sex, with women having a lower burden of calcification than men, but the mechanism for this is unclear. Improved HDL functionality has been associated with protection against coronary artery calcification, but its relationship to AVC is less studied.

Methods:
We evaluated measures of high-density lipoprotein (HDL) functionality in 46 patients with severe AS, n= 30 men, n=16 women. ATP-Binding Cassette A1 (ABCA1) mediated cholesterol efflux capacity (CEC) was measured from human cultured Tamm-Horsfall protein 1 (THP-1) macrophages to apoB-depleted patient plasma samples. Lipid profile, lecithin-cholesterol acyltransferase activity (LCAT), fast protein liquid chromatography (FPLC), HDL size, and small pre-β1 and α-HDL particles, were measured in apolipoprotein B-depleted patient plasma. Proteomic analysis was used to explore sex-based differences in the HDL proteome.

Results:
Women with severe AS had higher ABCA1-mediated CEC, as compared to men (n=46, p=0.04). We found differences in FPLC profiles between sexes in severe AS along with a reduction in preβ and α-particles in men vs women by spectral counts, (preβ-HDL, 15661.74±789.00 vs 20298.29±1076.15, p=0.002), and (α-HDL, 50447.00± 546.52 vs 63006.35±756.81, p=0.03). Conversion of free cholesterol into cholesteryl esters by LCAT was decreased in men vs. women (12.00±8.07 %/h vs 16.44±9.11 %/h, p=0.03). We identified 108 HDL-associated proteins in a representative man and woman, of which, 15 were found only in the female sample

Conclusions:
Sex-specific differences in measures of HDL functionality were found in patients with severe AS. Future studies should consider whether sex-based differences in HDL functionality might account for the decreased burden of calcification in women vs. men with severe AS.
Abstract 11557: Rates of Early Target Vessel Revascularization and Target Lesion Revascularization Amongst Third Generation Drug-Eluting Stents
Authors: Chew Christopher , Hendrickson Michael , Yang Hannan , Stouffer George A , Rossi Joseph
Published: March 2022

Background:
While the benefits of drug-eluting stents (DES) during percutaneous coronary intervention (PCI) are well established, the frequency and timing of repeat revascularization events, particularly early events, is not well described in contemporary clinical practice.

Methods:
Patients undergoing PCI at two large tertiary centers in a single health system from April 2014 to December 2019 were prospectively enrolled into the NCDR CathPCI Registry. Target vessel revascularization (TVR) and target lesion revascularization (TLR) were defined as a repeat intervention to the index vessel or lesion respectively and determined by linking to subsequent PCI events and CABG admissions in the EMR. Early TVR and TLR rates were identified at 30 days, 90 days, six months, and one year. Logistic regression was used to estimate the association between stent type and TVR/TLR at the pre-specified time points. Generalized estimating equations with nested modeling were used to account for patients with multiple vessels and lesions.

Results:
Overall, 8,221 PCI procedures were identified in 7,128 patients with 9,558 vessel interventions and 12,019 lesion interventions. There were similar rates of TVR for Zotarolimus eluting durable polymer stents (ZES-DP), Everolimus eluting bioabsorbable polymer stents (EES-BAP), and Everolimus eluting durable polymer stents (EES-DP) at 30 days (p=0.61), 90 days (p=0.79), six months (p=0.58), and one year (p= 0.35). There were similarly no differences in TLR between stent types at each time point (p= 0.57, 0.79, 0.16, 0.13 respectively). The total rates of TLR and TVR progressed linearly throughout the year following PCI with nearly half of all repeat revascularization events occurring within 6 months.
Table 1.

Conclusions:
Within a single health system from 2014 to 2019, ZES-DP, EES-BAP, and EES-DP were associated with similar rates of TVR and TLR. These events appear to occur earlier than typically reported in clinical trials.
Abstract 11559: Acute and Chronic Effect of Heme on Vascular Function and Pulmonary Hypertension
Authors: Valuparampil Varghes Mathews , James Joel , Rafikova Olga , Rafikov Ruslan
Published: March 2022

Introduction:
Patients with hemolytic anemia are at high risk of developing lung disease. We recently reported that free heme in circulation causes acute lung endothelial barrier dysfunction via activation of MKK3/p38 signaling. However, we did not evaluate the effects of chronic heme infusion in the lungs.

Hypothesis:
Chronic free heme infusion will cause sustained activation of the MKK3/p38 pathway leading to inflammation and vascular remodeling in the lungs.

Methods:
Mitogen-activated protein kinase kinase-3 knockout (MKK3-KO) mice were used for this study. Acute group mice received heme 250μM for 24-hours by i.v injection as a single dose, and the chronic group mice received 2-weeks of continuous heme i.v injection using an osmotic minipump. Human pulmonary artery endothelial cells (HPAEC) were studied in endothelial cell dysfunction experiments.

Results:
Heme treatment (50μM) disrupts HPAEC endothelial barrier, tube formation and decreases HPAEC migration capacity suggesting direct heme involvement in the endothelial dysfunction. Chronic heme exposure of WT mice (250uM, 2wks) increased right ventricular (RV) systolic pressure (SP) (31.89±0.88mmHg), RV-hypertrophy (0.38±0.02), and pulmonary vascular remodeling (18.47±1.15 μm) compared to the MKK3-KO group (RVSP-29.33±0.69mmHg, Fulton index-0.33±0.01, and wall thickness-13.69±1.13μm, p<0.05). Loss of tight junction proteins and activation of MKK3/p38/HSP27 axis was noticed in heme-treated WT. MKK3-KO significantly attenuated downstream targets of p38 such as Akt, STAT3, and ERK1/2. Furthermore, the MKK3-KO attenuated endothelial barrier dysfunction by maintaining the tight-junction protein, zona occludens-1 and reducing lung inflammatory cell infiltration. Cytokine multiplex analysis of plasma exhibited an inflammatory cytokine storm with a surge of 21-cytokines in WT mice, but the MKK3-KO mice were substantially protected. This includes IFN-g (1502 vs. 113 Fold Control (FC)), IL-1b (6.8 vs. 2.2 FC), IL-6 (221 vs. 6.9 FC), etc.

Conclusion:
Our findings suggest that free-heme triggers MKK3/p38 cascade activation resulting in the cytokines storm, endothelial barrier dysfunction, and proliferative signaling activation, all contributing to PH manifestation.
Abstract 11562: Contrast Minimization Devices in the Cath Lab: Real-World Outcomes Within a VA Hospital
Authors: Suffredini John M , Daher Marilyne , Jneid Hani , Denktas Ali E , Khalid Mirza , PANIAGUA DAVID
Published: March 2022

Introduction:
Contrast-induced acute kidney injury (CI-AKI) remains one of the leading causes of hospital acquired AKI. Patients with baseline chronic kidney disease (CKD) and/or elevated risk scores are at increased risk of developing CI-AKI. Contrast minimization devices have been proposed as a mechanism for contrast usage reduction in the cath lab. Since May 2017, the cardiac catheterization lab at the Michael E DeBakey VA Medical Center has used the Osprey Medical DyeVert contrast minimization device.

Methods:
We retrospectively evaluated the outcomes of 120 patients with known CKD who underwent cardiac catheterization with the DyeVert Contrast Reduction System for contrast monitoring and minimization.

Results:
The results of 120 DyeVert cases from Q2 2019 through Q4 2020 were analyzed. The mean baseline eGFR of the evaluated patients was 50. Mean overall contrast media volume (CMV) savings were 37 +/- 21 mL per procedure or 36%. 90% of DyeVert cases achieved a procedure CMV/eGFR ratio
<
3. Mean attempted CMV/eGFR ratio was 2.5 versus actual ratio of 1.6 after device contrast diversion.

Conclusions:
Our results suggest that contrast minimization devices in the cath lab can reduce the overall contrast media volume usage and result in improved CMV/eGFR ratios for at-risk patients undergoing coronary angiography.
Abstract 11568: The Role of the Microbiome in the Improved Exercise Performance in the Regulator of G Protein Signaling 14 (rgs14) Knock Out (KO) Mice
Authors: Campbell Sara C , Oydanich Marko , Zhang Jie , Longoria Candace R , Ibironke Olufunmilola , Vatner Dorothy E , Siderovski David P , Vatner Stephen F
Published: March 2022

The Regulator of G Protein Signaling 14 knockout (RGS14 KO) mouse strain has a unique brown adipose tissue (BAT) mechanism mediating its phenotype of healthful longevity and improved exercise performance. RGS14 KO mice demonstrated a 51 ± 8% increase in treadmill running distance before exhaustion and a 44 ± 7% increase in work to exhaustion compared to their wild type littermates (WTLs). Three days after BAT transplantation from RGS14 KO mice to WTL mice, the RGS14 KO BAT donor mice lost their enhanced exercise capacity, whereas it was gained in the WTL BAT recipients: their running distance and work to exhaustion rose by 46 ± 5% and 52 ± 7%, respectively. In contrast, when BAT was transplanted to WTL mice from other WTL mice, exercise capacity did not increase at 3 days after transplantation, but was only seen after 2 months post-transplantation. Based on these observations, our hypothesis was that the unique characteristics of RGS14 KO BAT, in inducing enhanced exercise capacity upon transplantation, are mediated by novel gene upregulation within the BAT, as well as potential interactions between the BAT and the microbiome. We found that RGS14 KO mice harbor two unique, health-beneficial strains of
Akkermansia muciniphilia
(
A. muciniphilia
BIOML-A22 and
A. muciniphilia
AN78) in their gut and their BAT has a number of novel genes upregulated, including
Lnpep
(leucyl/cystinyl aminopeptidase),
TFAM
(transcription factor A, mitochondrial), and
Lncbate10,
the latter being a critical regulator of BAT differentiation. To address directly the role of the microbiome, the mice were treated with antibiotics for 1 week. Although WTL exercise capacity was not significantly different before and after antibiotic-induced microbiota clearance, the RGS14 KO mice lost their enhanced exercise capacity after antibiotic treatment: RGS14 KO running distance fell by 35 ± 7%, and work to exhaustion fell by 41 ± 7%. Thus, RGS14 KO BAT engages changes to resident commensal microbiota that are beneficial to exercise capacity and therefore represents a potential (and novel) therapeutic modality for improving exercise performance and for creating healthful longevity.
Abstract 11575: The Effects of Tlr4 Deletion on Aortic Stiffness and Gut Microbiota Composition in High Fat Diet-Fed Mice
Authors: Gentile Chris E , Trikha Satya Raj J , Stark Grace , Brown Gabriele , Weir Tiffany L , Gentile Chris L
Published: March 2022

Introduction:
We have previously shown that alterations to the gut microbiota are an important mediator of diet-induced cardiometabolic dysfunction. One potential mechanism by which these microbial alterations may affect cardiometabolic function is via lipopolysaccharide (LPS), a component of gram-negative bacteria that can enter circulation following dysbiosis-related intestinal permeability. Once in circulation, LPS binds to toll-like receptor 4 (TLR4) in various tissues and induces a robust inflammatory response. TLR4 null mice are partially protected from obesity-related metabolic dysfunction, but it’s unclear if this mutation offers protection from vascular dysfunction.

Methods:
24 male mice lacking the TLR4 receptor (KO) and 24 C57BL/6 wild type male mice (WT) were fed either a control diet (CON) containing 4% fat or a high fat diet containing 60% fat (HFD) for 6 months, yielding the following four experimental group: WT+CON; WT+HFD; KO+CON; KO+HFD. After 6 months, mice underwent measurement arterial stiffness (via pulse wave velocity), and glucose tolerance (via ip glucose tolerance test). The gut microbiota was analyzed by 16S gene sequencing.

Results:
Mice fed a high fat diet increased body weight, although the magnitude of weight gain was attenuated in KO+HFD vs WT+HFD (p<0.05). Oral administration of FITC-dextran was used to determine intestinal permeability, HFD fed mice exhibited an increase intestinal permeability, compared to their respective control groups (p<0.05). Circulating LPS binding protein was increased in both HFD groups compared to WT. Aortic pulse wave velocity was increased in WT+HFD but not KO+HFD. Glucose tolerance was higher in WT+CON compared to the other three experimental groups. Microbiota shifts occurred between groups, and surprisingly, genotype was the main driver of these shifts, followed by diet (explaining 27% and 22% respectively).

Conclusions:
These data indicate that deletion of TLR4 in male mice partially protects from arterial stiffness. These data support the supposition that LPS signaling downstream of gut dysbiosis may be an important factor in diet-induced vascular dysfunction.
Abstract 11577: Clinical Presentation and Medium-Term Outcomes in Anomalous Aortic Origin of a Coronary Artery with High Take-Off
Authors: Chang Jack Y , Reaves-O'neal Dana , Bonilla-Ramirez Carlos , Doan Tam , Sachdeva Shagun , masand prakash , Qureshi Athar M , HEINLE Jeffrey S , Caldarone Christopher , Mery Carlos M , Molossi Silvana
Published: March 2022

Introduction:
Anomalous aortic origin of a coronary artery (AAOCA) confers risk of sudden death in the young. Paucity of data exists in AAOCA with high take-off (ht-AAOCA) from the aorta.

Hypothesis:
Patients with ht-AAOCA may be at risk of inducible myocardial ischemia and surgery might be indicated in a small subset with good medium-term outcomes.

Methods:
Patients with ht-AAOCA, defined as origin at the sinotubular junction and above by CTA, <25 years old were prospectively enrolled. Myocardial functional studies were obtained under provocative stress: exercise stress test, stress nuclear perfusion imaging, dobutamine stress cardiac MRI, or cardiac catherization (in select patients). These studies were repeated 3 months post-operatively (post-op) in surgical patients.

Results:
A total of 71 patients (45 male, 63%) with ht-AAOCA were enrolled, median age 15 [IQR 12; 19] years. ht-AAOCA of the right (ht-AAORCA) was seen in 66/71 patients (93%): 15 (23%) had exertional symptoms, 13 (20%) had nonexertional symptoms, 14 (21%) had both, 24 (37%) were asymptomatic. Ht-AAOCA of the left (ht-AAOLCA) was seen in 5/71 patients (7%), only 1 (20%) had exertional symptoms. In ht-AAORCA patients, 50/66 (76%) had abnormal ostia and 6/66 (9%) juxtacommissural origin, as compared to 3/5 (60%) and 2/5 (40%), respectively, in ht-AAOLCA patients. Average intramural course in ht-AAORCA was 4.46 mm and 2.36 mm in ht-AAOLCA. Abnormal functional testing corresponding to the affected territory was seen in 11/71 (15%) ht-AAOCA patients. Surgery was recommended for 18/71 (25%) patients due to concerning symptoms, coronary anatomy, or abnormal functional testing. Of these, 13/18 (72%) underwent coronary artery unroofing (in 12) or reimplantation (in 1), 3 declined surgery, 2 pending decision. All surgical patients have returned to unrestricted exercise after reassuring post-op studies, but 1/18 (6%) awaits completion. At median follow up of 1.8 years (range 0.1-8.9), all patients are alive and well, 93% are exercising with no restrictions.

Conclusion:
Although ht-AAOCA appears benign in most patients, 15% shows inducible myocardial ischemia. Surgery may be indicated in a subset of patients, with overall excellent medium-term outcomes and freedom from exercise restrictions.
Abstract 11582: Prognostic Implications of Anatomical Aortic Valve Area in Patients with Bicuspid Aortic Stenosis by Three-Dimensional Transesophageal Echocardiography
Authors: Maeda Mika , Taku Omori , Kagawa Shunsuke , Uno Goki , Shiota Takahiro
Published: March 2022

Background:
Three-dimensional (3D) transesophageal echocardiography (TEE) provides high-resolution images of aortic valve area (AVA) in patients with bicuspid aortic stenosis (AS). However, the correlation with pressure gradient compared with conventional echocardiographic indices and prognostic implications of 3D TEE derived valve area (AVA
3DTEE
) has not been evaluated. Therefore, we assessed the disease severity and the prognostic value of AVA
3DTEE
in patients with bicuspid AS.

Methods:
We retrospectively analyzed 105 patients with at least mild bicuspid AS (peak aortic velocity >2.5m/sec) and LVEF ≥50% (mean transaortic pressure gradient 46±17 mm Hg) underwent transthoracic echocardiography, two-dimensional (2D) and 3D TEE between 2012 and 2019. AVA was measured using (i) the continuity equation (CE) obtained with transthoracic echocardiography, (ii) planimetric 2D TEE, and (iii) volumetric 3D TEE. Cardiac events were defined as surgical or transcatheter aortic valve replacement and/or aortic replacement, heart failure admission, or cardiac death.

Results:
AVA
3DTEE
was larger than AVA
CE
(mean difference 0.21±0.03,
P
<0.001), and smaller than AVA
2DTEE
(mean difference 0.11±0.02,
P
<0.001). AVA
3DTEE
had an excellent correlation with mean transaortic pressure gradient (r=0.91,
P
<0.001), whereas AVA
2DTEE
and AVA
CE
showed lower correlations (r=0.81 and r=0.59, both
P
<0.001). AVA
3DTEE
significantly reduced the proportion of inconsistent AS grading, compared with AVA
CE
(6% versus 17%,
P
<0.001). During a follow-up period (median, 853 days; range 513 to 1287 days), 101 surgical or transcatheter aortic valve replacement and/or aortic replacement, 6 heart failure admission, or 1 cardiac death occurred. AVA
3DTEE
≤1cm
2
was an independent predictor of cardiac events (adjusted hazard ratio (HR) 2.40, (1.41 to 4.09),
P
=0.001) and AVA
3DTEE
of 1 cm
2
was the optimal cutoff value for predicting cardiovascular events with sensitivity of 71% and specificity of 100%.

Conclusions:
AVA measured by 3D TEE has a good correlation with mean transaortic pressure gradient and improved the hitherto inconsistent AS grading. AVA
3DTEE
≤1cm
2
is an important predictor for cardiac events of patients with bicuspid AS.
Abstract 11584: Prevalence of Isolated Nocturnal Hypertension in Adolescents with Use of Adult Hypertension Criteria
Authors: Lyon Shannon M , Hartz Jacob , Chen Ming Hui , De Ferranti Sarah D
Published: March 2022

Introduction:
The 2017 Blood Pressure Guidelines aligned clinic hypertensive thresholds for children ≥13 years of age with adult BP criteria, increasing the predictive value for adverse cardiovascular outcomes. However, thresholds for adolescents have not been updated for ambulatory blood pressure monitoring (ABPM), a confirmatory test in the diagnosis of hypertension. We examined the impact of using adult ABPM criteria in adolescents, including the contribution of daytime (DH) and isolated nocturnal hypertension (INH), and associations with left ventricular hypertrophy (LVH).

Methods:
This retrospective study included all ABPMs obtained in 13–16-year-olds at Boston Children’s Hospital (2015-2020). ABPMs were interpreted using both pediatric and adult thresholds. For studies newly classified as hypertensive using adult criteria, available echocardiograms were reviewed for LVH. Independent T-test and Chi-square were used to compare age, gender, BMI, left ventricular mass (LVM), indexed LVM >95
th
percentile, and LVM z-score >2 in individuals with INH vs. DH.

Results:
347 ABPMs were included in this study; 92 studies (87 unique patients) were reclassified as hypertensive using adult thresholds; 96.7% of these studies were obtained in males. Of the 92 studies, 31 (33.7%) studies had INH and 58 (63.0%) had DH (54/58 had day & night hypertension). There was no difference in age or BMI between INH and DH groups; more studies in the INH group were from females (p=0.05). We reviewed 14 and 42 echocardiograms for the INH and DH groups, respectively. There were no differences in indexed LVM or LVM z-score between the 2 groups. Though a small sample size, we found that 3/14 (21.4%) and 12/42 (28.6%) in the INH and DH groups respectively had an indexed LVM >95
th
percentile; there was no significant difference between groups (p=0.601). An LV mass z-score > 2 was not seen in the INH group and was in 4/42 (9.5%) of the DH group.

Conclusions:
With use of adult ABPM criteria, INH significantly contributed to ABPMs reclassified as hypertensive. Prevalence of LVH was similar in INH and DH groups. Further study is needed to investigate the appropriateness of using adult thresholds for nocturnal hypertension in adolescents, whose sleep patterns may differ from adult counterparts.
Abstract 11588: Variation in Reader-Reported Severity of Paradoxical Low-Flow Low Gradient Aortic Stenosis: Observations from AaLarge Academic Health System
Authors: Shah Nimish N , Sugeng Lissa , Wang Kangxin , McNamara Robert L , Agarwal Vratika , Hur David , Lombo Bernardo , Bellumkonda Lavanya , Forrest John K , Krumholz Harlan M , Velazquez Eric J , Faridi Kamil
Published: March 2022

Introduction:
Paradoxical low-flow low-gradient (PLFLG) aortic stenosis (AS) is frequently reported as non-severe AS on transthoracic echocardiogram (TTE) in clinical practice. It is uncertain how reader characteristics are associated with reporting of AS severity in patients with PLFLG AS.

Methods:
We identified all adults ≥ 18 years old from 9/2015-11/2019 with PLFLG AS on TTE within a large academic health system, and included only readers with ≥10 TTEs in this cohort. We determined the proportion of TTEs reported as either severe or moderate-severe and non-severe, and evaluated differences in reporting based on years of experience, volume of PLFLG AS studies interpreted per year, and quaternary vs. non-quaternary care site. We performed unadjusted and adjusted analyses using multivariable logistic regression.

Results:
Among 1329 patients meeting TTE criteria for PLFLG AS, only 37.3% were reported as severe/moderate-severe AS. Among 53 readers, the median proportion of patients reported as having severe/moderate-severe AS was 31.6% (25
th
-75
th
percentile 20.0%-50.0%, range 0.0-91.7%). There were differences in reporting between quartiles based on reader years of experience (33.3-40.9% across Q1-Q4 for proportion of patients reported with severe/moderate-severe AS; p = 0.01) but not volume (34.3-43.1% across Q1-Q4; p = 0.10). Quaternary care readers reported severe/moderate-severe AS for a much higher proportion of patients than non-quaternary care readers (64.3% [reader median 55.2%] vs. 30.9% [reader median 27.3%]; p < 0.001) (Figure), and this was the strongest reader-associated predictor of reporting severe-range AS (adjusted OR 7.6, 95% CI 5.1-11.5).

Conclusions:
Among patients with PLFLG AS, quaternary care TTE readers report severe AS much more commonly than non-quaternary care readers. Greater focus on TTE reporting of PLFLG AS at non-quaternary sites is likely needed to address underreporting of severe AS in this population.
Abstract 11589: Hemodynamic Assessment of Inhalational Epoprostenol for Post-Operative Right Ventricular Dysfunction in Cardiac Surgery Patients
Authors: shah harsh , Papolos Alexander I , Kenigsberg Benjamin
Published: March 2022

Introduction:
Right ventricular (RV) dysfunction after cardiac surgery presents a significant challenge. Epoprostenol (EPO) is a pulmonary vasodilator that can be administered via inhalation and is often used in patients with post-operative RV dysfunction. However, the effects of EPO on RV performance have not been well studied. Furthermore, EPO is generally contraindicated in WHO Group 2 pulmonary hypertension. The purpose of this study is to describe the hemodynamic consequences of weaning inhaled epoprostenol (iEPO) in post-operative RV dysfunction and potentially identify any predictive markers for successful weaning.

Methods:
This is a single-center case series of patients receiving iEPO after cardiac surgery identified by convenience sampling. Inclusion criteria included post-cardiac surgery patients, >18 years, and receiving iEPO for RV dysfunction. Exclusion criteria included pregnancy, open chest, SARS-COV-2 pneumonia, left ventricular assist device use, extracorporeal membrane oxygenation use, heart transplantation, or receiving iEPO for refractory hypoxia. A paired two sample t-test compared the hemodynamic parameters collected pre and post iEPO weaning.

Results:
EPO weaning was associated with a decrease in mean pulmonary artery pulsatility index (PAPi) (pre-wean 1.81 vs post-wean 1.57, p=0.04) and increase in pulmonary artery systolic pressure (PASP) (46.5mmHg vs 55.1mmHg, p=0.01). Cardiac index and right atrial pressure were not significantly different (p=0.35 and p=0.26 respectively). Case 5 had EPO weaning failure and had the lowest baseline PAPi in the cohort.

Conclusion:
iEPO weaning is associated with dynamic changes in PASP and PAPI in post-operative cardiac surgery patients. This finding supports the conceptual role of iEPO in improving post-operative RV-PA coupling and RV performance. Baseline PAPi may be a predictive marker to guide the weaning process. However, larger cohorts are needed to confirm these findings.
Abstract 11592: Glycogen Synthase Kinase 3β Localizes to the Z-Disc to Maintain Length Dependent Activation
Authors: Stachowski Marisa , Papadaki Maria , Martin Thomas , Ma Weikang , Gong Henry , Aima Muntu Nitha , Kumar Mohit , Martin Jody , Moravec Christine S , Sadayappan Sakthivel , Irving Thomas , Kirk Jonathan A
Published: March 2022

Glycogen Synthase Kinase 3β (GSK-3β) can modulate myofilament function
in vitro
. However, it’s
in vivo
role, mechanism, and translational relevance are unknown, which we investigated here using inducible cardiomyocyte specific GSK-3β KO mice. Compared to tamoxifen-treated GSK-3β
fl/fl
Cre- mice (Con), skinned myocytes from KO mice had reduced calcium sensitivity at long sarcomere lengths (SL = 2.2 μm), but there were no differences at short SL (~1.9 μm). Thus, myocytes from KO mice did not sensitize to calcium with stretch, a mechanism called length dependent activation (LDA) that underlies the organ-level Frank-Starling law. LDA has been attributed to (1) phosphorylation of myofilament proteins, (2) altered lattice-spacing, and (3) changes to titin’s elastic properties. Using mass spectrometry and small energy x-ray diffraction we ruled out the first two mechanisms, however we did find that GSK-3β KO myocytes had decreased passive tension – indicating the loss of LDA was due to loss of titin as a length sensor. Interestingly, immunofluorescence showed that GSK-3β localized to the z-disc when phosphorylated at Y216 and, via mass spectrometry, phosphorylated primarily z-disc proteins including several sites on the structural protein Ablim-1, which we showed also localizes to the z-disc. These data suggested that GSK-3β’s effect on titin is likely through altering its ability to anchor to the z-disc through targeting of these z-disc proteins. To provide further evidence that GSK-3β is specifically altering LDA, we genetically removed a downstream effecter of LDA, cardiac myosin binding protein-C (cMyBP-C). In vitro treatment with exogenous GSK-3β was able to increase calcium sensitivity at long SLs in both KO and WT mice but had no effect on cMyBPC KO mice or mice lacking the c-terminal domains of cMyBPC that are known to be important for LDA. Lastly, we found that human heart failure patients had less myofilament GSK-3β compared to non-failing patients, and that these same samples had a depressed LDA. This work has identified a novel mechanism by which GSK-3β localizes to the myofilament to modulate LDA and indicates that z-disc localized GSK-3β may be a possible therapeutic target to restore the Frank-Starling mechanism in heart failure patients.
Abstract 11594: Deep Learning of the Retina Enables Phenome- and Genome- Wide Analyses of the Microvasculature
Authors: Zekavat Seyedeh M , Raghu Vineet , Trinder Mark , Ye Yixuan , Pampana Akhil , Urbut Sarah , O'Regan Declan , Zhao Hongyu , Ellinor Patrick T , Segre Ayellet , Elze Tobias , Wiggs Janey , Martone James , Adelman Ron A , Zebardast Nazlee , Del Priore Lucian , Wang Jay C , Natarajan Pradeep
Published: March 2022

Introduction:
The retinal fundus is a window for non-invasive assessment of the microvasculature. However, the range of phenotypes and inherited genetic variants associated with the retinal microvasculature remain unknown.

Hypothesis:
Deep learning of retinal fundus images enables large-scale quantification of vascular indices and an unbiased assessment of phenotypes and genetic variants linked to the microvasculature.

Methods:
We utilized 97,895 retinal fundus images from 54,813 UK Biobank participants (ages 40-70y, 55% female). Using convolutional neural networks to segment vessels, we calculated vascular branching complexity using fractal dimension (FD), and vascular density, and associated these indices with 1,100 incident ICD-based conditions (median 10y follow-up) and 88 quantitative traits, adjusting for age, sex, smoking status, and ethnicity. Genome-wide association study (GWAS) among 38,932 unrelated individuals was performed.

Results:
Low retinal vascular FD and density were significantly associated with increased risk of incident hypertension, congestive heart failure, renal failure, type 2 diabetes, sleep apnea, anemia, and multiple ocular conditions. Low retinal vascular FD and density were also linked to quantitative traits including elevated blood pressure, anemia indices, abnormal pulmonary function tests, measures of metabolic disease (high HbA1c, % body fat, BMI), and ocular traits (decreased visual acuity and increased intraocular pressure). GWAS of vascular FD and density identified loci enriched among pathways linked to angiogenesis (VEGF, PDGFR, angiopoietin, and WNT signaling pathways), and inflammation (interleukin, cytokine signaling).

Conclusions:
Through phenotypic and genotypic analyses, our study showed that the retinal vasculature may serve as a biomarker for future cardiometabolic and ocular disease, and provided insights on genes and biological pathways influencing microvascular indices.