bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16008: Association Between Statin Exposure and Diabetes Incidence in a Nationwide Claims Database
Authors: Ahmad Tariq Ali , Liu Guodong , Alagona Jr Peter , Chuang Cynthia H , Foy Andrew J , Bokhari Syeda M , Leslie Douglas
Published: March 2022

Background:
Statins reduce risk for cardiovascular events; however, concerns have been raised about their association with diabetes mellitus (DM). We used a national health insurance claims database, which captures the health care experiences of >50 million privately insured individuals, to determine if there was a significant association between statin exposure and incidence of DM when controlling for multiple covariates not accounted for in prior analyses.

Method:
A cohort of non-diabetic patients who initiated treatment with a statin was matched with a control group of patients who did not receive a statin based on age, gender and geographic location. Patients were then followed for a minimum of 2 years to determine whether they developed DM (i.e. ≥2 ICD-9 code for DM and/or pharmacy claim for DM medications). In addition to Pearson chi-square tests for unadjusted comparisons, Cox proportional hazard models were used to examine the relationship between statin exposed and unexposed groups adjusting for HTN, CAD, PAD, CVA, CHF, hyperlipidemia and healthcare costs in the prior year. Predefined subgroup analyses were performed based on age, gender, obesity status and statin type.

Results:
The study population included 231,478 matched pairs of exposed and unexposed subjects (age 51.3 ±7.5 years; follow up duration of 1140 ±212.77 days). Statin exposure was associated with an increased DM incidence [adjusted HR 2.236 (2.182, 2.291)]. However, the effect was significant only after the age of ≥50 years [for age groups 30-39, 1.0 (0.86, 1.163); 40-49, 1.053 (0.91, 1.22); 50-59, 1.19 (1.028, 1.374); 60-69, 1.276 (1.101, 1.478) with age group 20-29 as reference]. Compared to males, statin-exposed females had an increased incidence of DM [HR 1.08 (1.06, 1.10)]. In obese individuals DM incidence was 1.820 (1.610, 2.057) in statin exposed versus unexposed. All statin types were associated with increased DM incidence without any statistically significant differences between them.

Conclusion:
In this large study, there was an association between statin exposure and diabetes incidence. These findings are consistent with other data reported in literature and strengthen the causal link between statin exposure and diabetes.
Abstract 16024: High Frequency Driving Sites are Anchored by Fibrotic Regions in Chronic Atrial Fibrillation
Authors: Angel Nathan A , Kholmovski Eugene , Dosdall Derek J , MacLeod Rob S , Marrouche Nassir , Ranjan Ravi
Published: March 2022

Introduction:
Stable high frequency sources and rotors have been described to drive episodes of atrial fibrillation (AF) but the mechanism for their stability is unknown. We used a chronic animal model of AF to test the hypothesis that fibrosis anchors sites of high frequency activation during AF, which may drive the arrhythmia..

Methods:
Endocardial electrograms were measured with a Constellation catheter (Boston Scientific) placed in the left atrium (LA) of chronic AF dogs (n=6) (AF > 12 months). An EnSite (St. Jude) geometric shell was then fused with a LA wall created by segmenting a high resolution T1 Mapping MRI. Regions with the lowest 10% T1 in the LA wall, used as a surrogate measure of fibrosis, were included on the LA wall segmentation. Fibrosis densities were calculated from histology and correlated with T1 Mapping MRI. Electrograms recorded during AF were processed to determine the dominant frequency (DFs) at each recording site. A probability map with the highest 10% DF value for each minute of AF at each of the sites was created to determine the stability of the DF during the 30 min AF episode.

Results:
Each AF animal had at least one site of high DF which was stable for at least 22.5 (75%) of a 30-minute AF episode and 82% of the high DF sites stabilized within 2 mm of a region of fibrosis (chi square test, p < 0.05). The mean DF was 8.5±1.2 Hz and the highest DF sites showed an average DF of 10.3±1.1 Hz. The region of T1 Mapping MRI detected fibrosis of the LA wall had an average value of 283±32 ms whereas the rest of the LA had an average value of 463±79 ms. Histology confirmed that that T1 Mapping MRI detected fibrosis had more fibrosis than other LA regions. (25±1% vs. 13±2%).

Conclusions:
Fibrosis developed during chronic AF may provide a substrate that anchors sites of high DF. Cardiac T1 Mapping MRI provides a means to determine such fibrotic sites noninvasively. Ablating these sites may reduce the stability of these high frequency sources and eliminate the drivers of persistent AF.
Abstract 16027: Low-dose Clofibrate Protects the Heart and Kidney in the 5/6 NX Model of Chronic Kidney Disease
Authors: Chuppa Sandra L , Kriegel Alison J
Published: March 2022

Cardiovascular related disease and/or events are the leading single cause of death in patients with chronic kidney disease (CKD), yet the pathological mechanisms involved are not well understood. We have previously reported that the 5/6 nephrectomy (5/6 NX) rat model of CKD exhibits left ventricle (LV) dilation, reduced function, and increased miR-21 levels 7 weeks post-surgery. Suppression of miR-21 prevented LV dilation and improved cardiac function, at least in part, by upregulation of target peroxisome proliferator-activated receptor alpha (PPARα). The focus of this study was to evaluate the therapeutic potential of clofibrate (CLO), a PPARα agonist, in the 5/6 NX model. We hypothesized that low-dose CLO treatment would reduce cardiac dysfunction in 5/6 NX rats. To test this, we performed 5/6 NX or sham surgery on 10 week old male Sprague Dawley rats. Left ventricular remodeling and function was evaluated by echocardiography prior to surgery and bi-weekly thereafter, throughout the 10 week study. Renal function was monitored by 24 hour urine and plasma creatinine measurements at those time points. We administered CLO (25 mg/kg/day i.p., roughly 1/10 the dose commonly used in rats) to a subset of animals (n=4-6/group) beginning 5 weeks post-5/6 NX. We found that 5/6 NX rats developed progressive LV dilation and impaired function over the 10 week study. Treatment with CLO completely prevented LV dilation and normalized wall thickness. Further, CLO treatment significantly increased % fractional shortening (47.9±6.0 CLO vs. 32.6±1.7 5/6 NX control, p<0.05, ANOVA). With 10 weeks of 5/6 NX proximal convoluted tubules exhibited a loss of brush border, severe dilation of the tubules, and extensive epithelial shedding. Treatment of 5/6 NX rats with CLO largely prevented these changes. Despite this improvement in tubular morphology, plasma creatinine levels were not different than 5/6 NX controls. In conclusion, we find that low-dose CLO treatment initiated during progressive kidney disease is both cardio- and reno-protective. Our data suggest that PPARα agonists may be an effective therapeutic intervention in established CKD.
Abstract 16029: Increased Brain Injury After Asphyxial Cardiac Arrest vs. Ventricular Fibrillation is Associated With Greater Brain Antioxidant Depletion
Authors: Lamade Andrew M , Uray Thomas , Kenny Elizabeth , Misse Amalea , Stezoski Jason , Drabek Tomas , Kochanek Patrick , Dezfulian Cameron
Published: March 2022

Background:
Cardiac arrest may present as ventricular fibrillation (VF) or asphyxia (ACA). Differences in outcomes between VF and ACA are recognized but treatment remains static. ACA has been linked with poor neurological outcomes though the mechanisms for these differences are unknown.

Hypothesis:
ACA results in greater reactive oxygen species (ROS) generation on reperfusion accounting for increased brain injury compared to VF.

Methods:
Isoflurane-anesthetized male Sprague-Dawley rats (n=24, 3 shams) were subjected to 5 minute no flow VF or ACA. Resuscitation was attempted using CPR, epinephrine, bicarbonate, and defibrillation (VF only). At 15 minutes post-ROSC, brain ascorbate was assessed fluorometrically with 4-((9-acridinecarbonyl)-amino)-2,2,6,6-tetramethylpiperidine-1-oxyl radical (Ac-TEMPO).Total antioxidant reserve of the samples was assessed with 2,2'-azobis-2-methyl-propanimidamide, dihydrochloride (AAPH) and luminol. Hippocampal neuronal loss and recall of cue conditioned fear (measured as freezing %) were assessed at day 7. Comparisons were made to sham and data were analyzed using ANOVA or Kruskal-Wallis test.

Results:
Ascorbate concentrations (mean [nmol/mg protein]; 95% CI) in the rat brain was significantly different between groups (p=0.0004). Non-arrested shams had higher levels (39.1; 37.0-41.3) followed by VF (31.7; 29.6-33.8), then ACA (28.4; 25.6-31.3). ACA brain ascorbate was significantly reduced compared to VF brain ascorbate. Total antioxidant reserve of the same brain samples were congruous (p=0.0001): There was a significant decrease in recall of cued conditioned fear in ACA vs. VF (p<0.05) and significantly greater hippocampal neuronal loss (p<0.001, live cells/mm CA1) in ACA (3.99; 2.4-5.6) vs. VF (10.35; 7.2-13.5).

Conclusions:
ACA results in greater ROS generation as marked by antioxidant depletion which may explain worsened outcomes despite similar no flow ischemic durations.
Abstract 16031: The Apolipoprotein A1 Mimetic 4F Attenuates Cardiac Remodeling After Reperfused Infarction by Modulating Monocyte Polarity and Attenuating Immune Cell Activation
Authors: Hamid Tariq , Ismahil Mohammad A , Bansal Shyam S , Patel Bindiya , Goel Mehak , Michaud Amy M , White C R , Anantharamaiah G M , Prabhu Sumanth D
Published: March 2022

Heart failure (HF) is characterized by exaggerated systemic and myocardial pro-inflammatory responses, which impede myocardial healing and promote pathological remodeling and dysfunction. Currently, there are no strategies available to restrain and/or modulate immune cell responses triggered by myocardial injury. 4F, an apolipoprotein A-I mimetic, exhibits anti-inflammatory properties and influences macrophage polarity. We hypothesized that 4F treatment following reperfused myocardial infarction (MI) in mice would attenuate post-MI cardiac remodeling by inducing an anti-inflammatory and tissue healing monocyte polarity. C57BL/6 mice (6-8/group) were intravenously injected with either PBS or L-4F (100 μg/day) for 5 d starting at day 3 after reperfused MI (60 min ischemia). Flow cytometry revealed that compared to PBS injected MI mice, 4F significantly (p < 0.05) decreased levels of pro-inflammatory monocytes (CD45+Cd11b+Ly6Chigh) in blood (20.4 ± 4.6 vs 9.4 ± 1.7%), spleen (25.5 ± 7.4 vs 8.0 ± 6.0%), and heart (0.9 ± 0.4 vs 0.2 ± 0.1%); and decreased myocardial macrophage (CD45+CD11b+F4/80+) infiltration (1.6 ± 0.8 vs 0.28 ± 0.2%). The levels of anti-inflammatory monocytes, however, were unchanged. Echocardiography revealed that these changes in immune cell profiles in 4F-injected mice were also accompanied by improvements in cardiac function. Compared to PBS injected MI mice, 4F treatment attenuated post-MI LV chamber dilatation (84.1 ± 16 vs 65.0 ± 8.5 uL and 59.15 ± 16.6 vs 38.4 ± 11.8 uL; end-diastolic and systolic volumes, respectively), and improved LV ejection fraction (28.4 ± 10.8 vs 41.7 ± 12.8%). In addition, in vitro studies using mouse peritoneal macrophages indicated that 4F promotes an anti-inflammatory macrophage phenotype potentially by inhibiting the glycolytic metabolic profile typical of pro-inflammatory macrophages. These effects on macrophage polarity by 4F were associated with parallel alterations in the expression of hypoxia inducible factor isoforms 1 and 2α, known markers of macrophage polarity. We conclude that 4F could be used therapeutically after MI to augment reparative immune responses and thereby limit the long-term maladaptive effects of exaggerated inflammation on adverse post-MI cardiac remodeling.
Abstract 16040: Corin Reduces Myocardial Infarction and Protects Against Cardiomyocyte Apoptosis
Authors: Wang Dong , Sullivan Ryan D , Gladysheva Inna P , Houng Aiilyan , Tripathi Ranjana , Fan Tai-Hwang M , Reed Guy L
Published: March 2022

Corin is a cardiac-selective membrane protease that activates pro-ANP and pro-BNP. Emerging evidence suggests that corin may be a key biomarker and modulator of heart failure in dilated cardiomyopathy, but there is little known about the role of corin in myocardial infarction (MI). In acute MI in mice, we found that corin transcript and protein levels were significantly decreased when compared to non-MI controls 24 hrs post MI (1.0±0.1 vs 0.6±0.1, p=0.01; 1.0±0.04 vs 0.5±0.1, p<0.01). To examine the functional role of corin, we studied effect of transgenic overexpression of corin (corin-Tg) on cardiomyocyte survival in acute MI and we explored the effects of corin on cardiomyocyte survival in vitro. Compared to control, wild-type mice, there was a significant decrease in infarct size in corin-Tg mice (infarct area:left ventricle area, 44±3 % vs 25±3%, p=0.01) and in the ratio of infarct area:area at risk (102±8% vs 63±4%, p<0.001) 24 hrs post MI. Apoptosis was also significantly reduced in the infarcted left ventricle of corin-Tg mice vs. control (TUNEL-positive cells/myocardium mm
2
, 261±13 vs 106±16, p<0.0001). In the HL-1 mouse cardiomyocyte cell line, overexpression of corin protected HL-1 cells from staurosporine -induced apoptosis by blocking cytochrome c release and caspase 3 cleavage; whereas siRNA knock down of corin in HL-1 cells promoted caspase 3 activation, as evaluated by immunofluorescence staining and Western-blotting. We conclude that experimental myocardial infarction is associated with marked reductions of corin transcript and protein levels in the heart. Overexpression of corin significantly reduces infarct size and protects against cardiomyocyte apoptosis, both in vivo and in vitro. Taken together these data suggest that corin promotes cardiomyocyte survival after MI. Corin appears to mediate its protective role in part by blocking the cytochrome c-caspase 3 mediated apoptotic pathway.
Abstract 16043: Pulmonary Artery Proportional Pulse Pressure Predicts Adverse Clinical Outcomes in Advanced Heart Failure
Authors: Mazimba Sula , Kennedy Jaime L , Bergin James , Tallaj Jose A , Abuannadi Mohammad , Bilchick Kenneth C
Published: March 2022

Introduction:

There is increasing interest in ventriculo-arterial hemodynamics in heart failure (HF).

Hypothesis:

Based on the normal physiological distribution of Pulmonary artery (PA) systolic pressure (PASP) being more than twice the PA diastolic pressure (PADP), we hypothesized that PA proportional pressure (PAPP), defined as (PASP-PADP)/PASP, would be associated with clinical outcomes using data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial.

Methods:

Multivariable Cox proportional hazards and logistic regression was performed using independent covariates of creatinine at discharge, PAPP, and pulmonary capillary wedge pressure (PCWP) (based on final hemodynamic measurement) for the 6-month outcome of death, transplant, left ventricular assist device (LVAD), or rehospitalization (DTxLVADHF), as well as secondary outcomes of death alone and death, transplant, or LVAD (DTxLVAD).

Results:

Among n=175 patients, there were 110 (62.9 %) and 65 (37.1%), respectively, with optimal PAPP (> 0.50) and non-optimal PAPP (<=0.50). During 6 months of follow-up, 15.5% and 33.9%, respectively, died in these 2 groups (p=0.008). In Cox models adjusted for final PCWP and creatinine at discharge, an increase of 0.10 in the final PAPP (continuous variable, range 0-1) was associated with a 26.4% reduction in DTxLVADHF (HR 0.736, 95% CI = 0.592-0.913). Furthermore, non-optimal PAPP status was associated with increased risk for the outcomes of DTxLVADHF, DTxLVAD, and death alone with hazard ratios of 1.82 (95% CI 1.22-2.73), 2.09 (95% CI 1.09-4.02), and 2.72 (95% CI 1.29-5.72), respectively. The AUC obtained with multivariable logistic regression for the outcome of death with the model containing final PAPP, final PCWP, and creatinine at discharge was 0.804 (p<0.0001), with p< 0.05 for the odds ratios of each covariate in the model.

Conclusions:

PAPP at final hemodynamic measurement in patients undergoing hemodynamically guided therapy for ADHF is strongly associated with adverse clinical outcomes even after adjustment for final PCWP and creatinine at discharge. These results have important clinical implications for hemodynamic targets in patients treated for ADHF.
Abstract 16047: Novel Association of Polymorphic Genetic Variants With Baseline PR Interval in Patients With Atrial Fibrillation: New Directions From a Prospective Study (DECAF)
Authors: Mohanty Sanghamitra , Hall Amelia W , Mohanty Prasant , Trivedi Chintan , Di Biase Luigi , Bai Rong , Al-Ahmad Amin , Horton Rodney , Burkhardt John David , Sanchez Javier , Zagrodzky Jason , Bailey Shane , Gallinghouse G. J , Hranitzky Patrick , Iyer Vishwanath R , Natale Andrea
Published: March 2022

Background:
Prolongation of the PR interval in the electrocardiogram (ECG) is known to be associated with increased risk of atrial fibrillation (AF). We examined the association of selected single nucleotide polymorphisms (SNPs) with PR interval in AF patients.

Methods:
Four hundred AF patients undergoing catheter ablation were prospectively enrolled at our center. DNA extraction and genotyping for 16 AF-related SNPS from blood samples were performed using Qiagen QiaAMP kit and TaqMan assay respectively. A total of 371 DNA samples were available for genotyping. Multivariate linear regression analyses (after adjusting for age, gender, BMI, AF type) were applied to test allelic association (for minor allelic frequency) with baseline PR interval. PR interval duration in millisecond (ms) was derived from 12-lead ECGs recorded at the time of patient enrollment.

Results:
Three hundred seventy-one AF patients (67% male, 62±12 year, left atrial size 45.3±7 mm, 64% non-paroxysmal) undergoing catheter ablation were included in the analysis. Two SNPs, rs3807989 and rs7193343 were identified to have significant association with baseline PR interval.

For rs3807989 (7q31), median [interquartile range] of PR interval durations were 174 (149-202), 169 (145-194), 162 (137-184) ms for AA, AG, GG (risk allele: A) respectively. The regression analysis for rs3807989 in a dominant model, showed significant allelic association (regression coefficient (beta) 9.8 [95% CI 1.58 to 18.02], p=0.019) with prolonged PR interval.

For rs7193343, median [interquartile range] of PR interval durations were 169 (144-194), 162 (142-184), 154 (128-186) ms for CC, CT, TT (risk allele: T) respectively. When considering the effect of rs7193343 fitted with an additive model, significant inverse association with PR interval was observed (beta -7.4 [95% CI -14.23 to -2.63], p=0.032).

Conclusion:
We identified two novel genetic markers located near developmental genes CAV1 and ZFHX3 to be associated with PR interval; rs3807989 correlated directly with prolonged PR duration while rs7193343 demonstrated inverse correlation with the phenotype. Defining the etiology of this differential association will provide important insight into underlying AF mechanisms.
Abstract 16061: Effects of UNOS Policy Changes on Market Competition and Heart Transplant Outcomes
Authors: Givens Raymond C , Lewey Jennifer , Mancini Donna M , Schulze Paul C
Published: March 2022

Introduction:
Higher competition among transplant centers is associated with improved access of higher-risk patients to extrathoracic organ transplantation but worse outcomes. The effects of major United Network for Organ Sharing (UNOS) policies on competition for hearts are unknown. We studied associations of listing priority (1999) and organ allocation policy revisions (2006) with local organ procurement organization (OPO) competition and heart transplant (HT) outcomes.

Methods:
In the UNOS database we found 80 OPOs providing hearts to 45,727 adults from 1988-2013. We calculated for each OPO yearly a Herfindahl-Herschmann Index (HHI) that varies inversely with competition and used segmented regression analysis to assess trends.

Results:
Aggregate local competition was stable in era 1 (1988-2000) then increased until 2006 (era 2), after which there was an increase in competition but subsequent reversal of the previous trend (era 3; Figure). Across all eras, increasing competition was associated with higher proportions of recipients who were nonwhite, status 1 or 1A, and received IABP or LVAD bridging (all p <0.0001 for era, competition and era*competition). Despite a progressive increase in center volume with level of competition (p <0.0001), patients served by higher-competition OPOs in era 3 had higher post-HT death and graft failure rates (p <0.0001).

Conclusions:
Policy revisions regarding listing criteria and organ allocation have been associated with specific changes in local competition. The most competitive OPOs appear to serve sicker patients but have lower post-HT survival. Understanding effects of market competition may inform future policy decisions.
Abstract 16197: Pedicled Vein Grafts in Coronary Surgery Exhibit Reduced Intimal Hyperplasia at 6 Months
Authors: Pettersen Øystein , Wiseth Rune , Hegbom Knut , Nordhaug Dag O
Published: March 2022

Introduction:
Less-than-optimal long-term patency of the saphenous vein is one of the main obstacles for the success of CABG. Harvesting saphenous veins including a pedicle of perivascular tissue has been proposed to improve graft patency rates and endothelial function.

Hypothesis:
We hypothesized that pedicled vein grafts would show less intimal hyperplasia at 6-month angiographic follow-up.

Method:
Sixty patients scheduled for first time elective on-pump CABG were randomized to conventional or pedicled vein harvesting. Exclusion criteria were insulin dependent diabetes mellitus, recent smoking or renal failure. Pedicled veins were harvested with perivascular tissue and conventional veins were skeletonized. All veins were distended manually to check for leakage and stored in heparinized blood and saline. At 6 months vein grafts were examined with Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT). Imaging analysis was performed by an external blinded Core-lab.

Results:
Fifty-four patients were available for follow-up. There were no significant differences in occlusion rates between the two groups. IVUS showed no significant difference in intima-media complex thickness (pedicled: n=28, mean 0.229 mm, SEM 0.011; conventional: n = 26, mean 0.235 mm, SEM 0.017). However, using OCT pedicled veins showed significantly less intimal thickness than conventional veins (pedicled: mean 0.270 mm, SEM 0.012; conventional: mean 0.358 mm, SEM 0.021; p<0.001). In conventional veins higher perioperative flow was positively correlated to increased intimal thickness. Such a correlation was not found in pedicled grafts. The difference in response to flow was significant using a general linear model including an interaction term (adjusted R squared = 0.254, p<0.018).

Conclusion:
Performing CABG using saphenous vein grafts harvested with a pedicle of perivascular tissue provides significantly less vein graft intimal hyperplasia at 6 months.
Abstract 16214: Percutaneous Intra-myocardial Injection of Exosomes From Cardiosphere-derived Cells (CDCs) Halts Adverse Remodeling and Decreases Scar Size in Porcine Ischemic Cardiomyopathy
Authors: Gallet Romain , Dawkins James , Simsolo Eli , Valle Jackelyn , Kreke Michel , Smith Rachel , Marbán Linda , Marbán Eduardo
Published: March 2022

Background:
Multiple lines of evidence indicate that the beneficial effects of CDCs in heart disease are mediated by exosomes. So far, no study has assessed the benefit of CDC-derived exosomes in a translationally-realistic large-animal model.

Objective:
Exosomes are nanoscale particles, few of which may linger in the heart after routine intracoronary delivery. Previous work in rodents shows efficacy in myocardial infarction (MI) with intramyocardial injection. We therefore sought to evaluate the efficacy of trans-endocardial delivery of CDC-secreted exosomes using the NOGA MYOSTAR injection catheter in a porcine model of post-MI cardiomyopathy.

Methods:
MI was induced in 7 mini-pigs by balloon occlusion of the mid-LAD for 2.5h, then the MI was allowed to heal for 4 weeks. At that point, and at the end of the study one month later, MRI was performed to measure LV volumes and ejection fraction (EF), scar mass and viable mass. Just after the first MRI, the left ventricle (LV) was mapped using a NOGA catheter to delineate infarcted, border and remote areas. After mapping, human CDC-secreted exosomes (7.5mg of exosome protein divided into 10-15 injections, n=4) or vehicle (n=3) were injected in the border zone (4-7 mV tip potentials).

Results:
EF was identical in the two groups at baseline (38±4%). All pigs were successfully injected with exosomes or vehicle after comprehensive LV mapping. One month post-injection, EF was preserved in exosome-treated pigs but dramatically decreased in placebo-treated animals (ΔEF=-1.2±2.2% vs. -7.6±2.8%, p<0.02). LV adverse remodeling was attenuated in CDC-injected pigs (less increase in end-systolic and end-diastolic volumes, P=0.08 and P=0.03 respectively). Additionally, exosomes reduced scar mass (-1.6±0.6g vs. +1.2±0.5g, P=0.001) and scar size (P<0.05).

Conclusions:
CDC-secreted exosomes halt adverse remodeling and decrease scar size when injected in the border zone using an injection catheter. This demonstration of safety and efficacy motivates testing of exosomes as cell-free therapeutic agents in humans.
Abstract 16229: The Performance of Dispatcher Assisted Cardiopulmonary Resuscitation Among Elderly Laypersons is Inferior Compared to Young Laypersons: A Simulation Study
Authors: Nebsbjerg Mette A , Rasmussen Stinne E , Bjørnshave Katrine , Krogh Lise Q , Krogh Kristian , Povlsen Jonas A , Riddervold Ingunn S , Grøfte Thorbjørn , Kirkegaard Hans , Løfgren Bo
Published: March 2022

Introduction:
Standardized instructions in dispatcher assisted CPR (DA-CPR) increase the rate and quality of bystander CPR. Most cardiac arrests occur in private homes and the most likely bystander to initiate CPR is an elderly layperson. Studies on elderly performing DA-CPR are sparse. The aim of this study was to compare the performance of DA-CPR between elderly and young laypersons.

Hypothesis:
DA-CPR performance is inferior among elderly laypersons compared to young laypersons.

Methods:
The study was performed in two substudies. Substudy 1 compared the performance of DA-CPR between elderly (>65 years) and young (18 - 40 years) laypersons. Substudy 2 evaluated the attainable level of CPR skills after attending a standardized CPR course. CPR was performed in a mock cardiac arrest scenario in both substudies. CPR quality data was obtained from the manikin and video recordings. CPR performance was evaluated by two assessors. The primary endpoint was chest compression depth during DA-CPR. Secondary endpoints included chest compression rate, time to first compression and hands-off time.

Results:
In total, 120 laypersons were included. Substudy 1 (DA-CPR): Elderly laypersons performed significantly shallower (mean (SD): 39 (19) mm vs. 56 (14) mm, p<0.001) and slower (median (IQR): 84 (74 - 107) min-1 vs. 107 (97 - 112) min-1, p<0.001) chest compressions compared to young laypersons. Elderly laypersons had significantly longer time to first compression (mean (SD): 104 (38) sec vs. 71 (11) sec, p<0.001) and significantly more hands-off time pr. minute (median (IQR): 5 (2 - 10) sec vs. 0 (0 - 1) sec, p<0.001) than young laypersons. Substudy 2 (End-of-course assessment): Elderly laypersons performed significantly shallower (mean (SD): 50 (14) mm vs. 64 (8) mm, p<0.001) and slower (mean (SD): 93 (18) min-1 vs. 111 (11) min-1, p<0.001) chest compressions compared to young laypersons.

Conclusions:
Performance of DA-CPR is inferior among elderly laypersons compared to young laypersons. The study found an acceptable quality of CPR skills among both elderly and young laypersons after CPR-training.
Abstract 16245: The Impact of Delirium After Trans-catheter Aortic Valve Replacement
Authors: Huded Chetan P , Huded Jill M , Sweis Ranya N , Ricciardi Mark J , Russell Hyde M , Malaisrie Sukit C , Davidson Charles J , Flaherty James D
Published: March 2022

Introduction:
Delirium is associated with increased healthcare utilization, morbidity, and mortality. We assessed the impact of delirium on outcomes after trans-catheter aortic valve replacement (TAVR).

Methods:
We reviewed 294 consecutive cases of TAVR at a tertiary care academic medical center from June, 2008 to February, 2015. Delirium was identified by prospective confusion assessment method screening and retrospective chart review. The primary outcome was overall survival. Secondary outcomes included length of hospital stay, discharge destination, hospital re-admission within 30 days, and 30 day mortality.

Results:
Delirium was identified in 61 patients after TAVR (21%). Non-femoral access for TAVR was more common in delirious than non-delirious patients (41% vs 28%, P=0.04). There was no difference in the post-operative stroke rate between delirious and non-delirious patients (8% vs 6%, P=0.45). Post-TAVR respiratory failure was more common in delirious patients (21% vs 3%, P<0.001). Of 13 delirious patients who developed respiratory failure, delirium preceded respiratory failure in 8 (62%). Median follow-up was 8.2 months. Delirious patients had decreased overall survival compared to non-delirious patients (figure, log-rank P<0.01). After adjusting for Society of Thoracic Surgeons risk score and TAVR access type, delirium remained an independent predictor of overall survival (hazard ratio 1.97, 95% confidence interval 1.18 to 3.23, P<0.01). Delirium was associated with longer mean length of hospital stay (13.3 +/- 9.5 days vs 6.7 +/- 3.8 days, P<0.001) and higher rates of discharge to a rehabilitation facility (61% vs 27%, P<0.001). There was no difference in 30 day hospital re-admission rates or 30 day mortality between groups.

Conclusions:
Delirium, a common syndrome after TAVR, is associated with decreased survival and increased healthcare utilization. Early detection of delirium after TAVR may help identify a high risk subset of patients.
Abstract 16255: Left Cervical Vagal Nerve Stimulation Suppresses Cardiac Sympathetic Tone
Authors: Yuan Yuan , Hassel Jonathan , Doytchinova Anisiia , Adams David , Wright Keith , Salanova Vicenta , Meshberger Chad , Chen Lan S , Lin Shien-Fong , Everett Thomas , Chen Peng-Sheng
Published: March 2022

Background:
In ambulatory dogs, the left cervical vagal nerve stimulation (VNS) reduces stellate ganglion nerve activity (SGNA) and heart rate, while upper thoracic skin sympathetic nerve activity (SKNA) has been shown to be a surrogate of SGNA to measure sympathetic tone.

Objective:
To test the hypothesis that VNS suppresses SKNA in human.

Methods:
We used conventional electrocardiogram (ECG) patches to continuously record SKNA in 12 patients who were admitted for video electroencephalographic monitoring. The ECG patches were placed under the right subclavian and left subclavian areas to form Lead I. The signals were band pass filtered between 200 to 1000 Hz to reveal SKNA. All antiepileptic medications were withdrawn. No patients had known organic heart diseases. No seizures occurred during the recording period. Nerve activity was quantified by integrating (iSKNA) the absolute value of the filtered signal over a 1 min window at intervals of 2 min, 20 min, and 40 min past each hour between 6 AM and 1 PM. Heart rate was determined by calculating the R-R intervals.

Results:
Six patients (2 men, age 40±5 years ) received chronic left cervical VNS (VNS group) and 6 (1 man, age 44±7 years) had no VNS pacing (control group). The admission diagnoses were generalized seizure (N=1) and partial seizure (N=5) in VNS group; generalized seizure (N=2) and partial seizure (N=4) in control group. The VNS pacing was continuous with an ON-time of 30 s and OFF-time of 158±72 s. The output was 1.92±0.42 mA with a frequency of 24.17±2.01 Hz. Fast Fourier Transform of the signals showed only physiologic activity between 200-1000 Hz. The iSKNA during VNS OFF-time was 13.77 mV-s [95% confidence interval, CI, 11.09 to 16.45], which was significantly lower than 20.75 mV-s [95% CI, 16.34 to 25.16, p=0.006] of the control Group. The heart rate was 67 bpm [95% CI, 60 to 74] in VNS group, significantly lower than 73 bpm [95% CI, 63 to 84] in control group.

Conclusion:
Patients with left cervical VNS had lower heart rate and iSKNA than patients without VNS. These findings are consistent with those observed in ambulatory canines, and suggest that chronic intermittent VNS can suppress cardiac sympathetic tone in human.
Abstract 16280: Intramyocardial Delivery of Extracellular Vesicles Released From Induced Pluripotent Stem Cells Induces Cardiac Repair After Myocardial Infarction
Authors: Cheng Guangming , Adamiak Marta , Xuan Yu-Ting , Samanta Anweshan , Bobis-Wozowicz Sylwia , Girgis Magdy , Wang Ou-Li , Karnas Elzbieta , Davani Arash , Kedracka-Krok Sylwia , Sarna Michal , Vincent Robert J , Yang Yanjuan , Madeja Zbigniew , Zuba-Surma Ewa , Dawn Buddhadeb
Published: March 2022

Introduction:
Induced pluripotent stem cells (iPSCs) have recently emerged as a promising therapy for cardiac repair. Whether extracellular vesicles (EVs) derived from iPSCs can confer similar benefits remains unclear.

Hypothesis:
We hypothesized that injection of iPSC-derived EVs would produce at least similar improvement in cardiac structure and function compared with iPSCs.

Methods:
Murine iPSCs were generated using standard protocol and iPSC-EVs were harvested from culture supernatants by sequential centrifugation. Wild-type (C57BL/6) mice underwent a 30-min coronary occlusion followed by reperfusion, and 48 h later received intramyocardial injection of vehicle (PBS, n=14), iPSCs (n=15) or iPSC-EVs (n=13). Echocardiography was performed 4 d prior to coronary occlusion/reperfusion (BSL) and at 48 h and 30 d after injection. Mice were sacrificed at 30 d.

Results:
At 48 h after injection, LVEF was significantly and similarly reduced in all groups (Fig). At 30 d after MI, mice injected with iPSC-EVs exhibited significantly greater EF (Fig) compared with vehicle-treated mice. iPSC-EV-injected hearts also showed significantly smaller LVEDV compared with vehicle-treated mice, indicating improved remodeling. Although iPSCs-injected hearts also showed somewhat improved function and structure, several mice in this group grew tumors at myocardial injection sites.

Conclusions:
We conclude that intramyocardial injection of iPSC-EVs after a reperfused MI improves LV function and remodeling. The use of iPSC-EVs also averts cardiac tumor formation that was noted in mice after iPSC whole cell injection. These findings support therapeutic potential of iPSC-EVs in patients after MI.
Abstract 16282: Coronary Fibromuscular Dysplasia Angiographic Manifestations
Authors: Saw Jacqueline , Bezerra Hiram , Gornik Heather , Machan Lindsay , Mancini GB John
Published: March 2022

Background:
We previously described a strong association between fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection (SCAD). Angiographic manifestation of coronary FMD aside from dissection was reported to be rare. However, we observed several non-dissection coronary angiographic abnormalities in patients with multifocal FMD.

Methods:
Baseline demographics and imaging of patients with suspected non-dissection coronary FMD at Vancouver General Hospital were retrospectively reviewed. Presence of multifocal FMD in non-coronary territories was confirmed by 3 specialists. Coronary angiograms with suspected coronary FMD changes (excluding dissected segments) were reviewed and classified by 2 experienced angiographers for: (1) irregular stenosis (beading) - multiple areas of stenosis in a focal or diffuse pattern and with/without systolic accentuation, (2) smooth stenosis - diffuse or focal, (3) segmental dilatation/ectasia, and (4) tortuosity. Optical coherence tomography (OCT), if performed, were reviewed by 2 specialists.

Results:
Of 28 patients with multifocal FMD and suspected coronary involvement on angiography, 23 were women (82.1%), mean age was 58.6 ± 9.5, and mean BMI was 24.6. Sixteen presented with myocardial infarction (10 due to SCAD), 12 underwent angiography for stable or atypical angina. The observed coronary angiographic abnormalities were: irregular stenosis (beading) in 14 (12 diffuse, 2 focal, 3 with systolic accentuation), smooth stenosis in 6 (4 diffuse, 2 focal), segmental dilatation/ectasia in 14 (majority with multi-segmental, diffuse enlargement in an entire vessel), and tortuosity in 25 cases. Fourteen patients had OCT of the abnormal segments showing abnormalities distinct from atherosclerosis. These included multiple areas of patchy or diffuse intimal, medial or adventitial abnormalities with disorganized fibrotic thickening, proteoglycan accumulation, macrophage infiltration, loss of elastic membranes, and cavitation.

Conclusions:
This is the first case series describing angiographic manifestations of coronary FMD, which can be categorized into irregular stenosis, smooth stenosis, dilatation and tortuosity, representing features that are additional to dissection.
Abstract 16294: A Theory Based Pedometer App Intervention to Promote Physical Activity Among African American Women: The ChangeMySteps Project
Authors: Nkonde-Price Chileshe , Shea Judy , Rosin Roy , Merchant Raina
Published: March 2022

Background:
Improving physical activity (PA) levels among all Americans is a national priority. National surveys indicate that African American (AA) women have low levels of PA. Smartphone applications (apps) that promote PA offer an innovation solution. Little is known about their feasibility and acceptability among AA women.

Methods:
A 2-phase mixed methods study design was used. First, in-depth interviews about barriers and facilitators of PA were conducted in AA women recruited from the hair salon setting. Second, themes from interviews were incorporated into the design of a theory-based smartphone pedometer app (Moves App) intervention. The intervention, The ChangeMySteps Project, was piloted in the target population (n=24) in a 1 month, single arm pre and post study design. We measured participant demographics, feasibility (retention rate) and acceptability (ability to incorporate into everyday life, impact on participant hair maintenance and participant satisfaction). In addition, as a secondary outcome we measured daily step count.

Results:
Themes from interviews (n=32; median age= 34) revealed that lack of time (competing responsibilities) and hair maintenance (negative effect of moisture on hair) were the most commonly cite barriers. Social support (exercise partners and online social network support) were the most commonly cited facilitators. The Smartphone Pedometer App intervention successfully engaged 6 teams (n=24; median age = 36). Retention rates were high (83%).The majority of participants (83%) reported that they were “able” or “very able” to incorporate the intervention into everyday life. The majority (90%) denied any negative effect on hair maintenance. Participant satisfaction rates were high including (100%) likelihood to recommend. Additionally, participants demonstrated an increase in mean daily step count from 5661 (SD 3652) steps /day at baseline to 8071 (SD 3804) steps/day step per day at 1 month (p = 0.03).

Conclusion:
The ChangeMySteps Project successfully engaged community dwelling AA women to participate in a theory based smartphone pedometer app intervention tailored to the needs of AA women. Findings suggest the intervention was feasible and well accepted among AA women.
Abstract 16301: Oxidative Mitochondrial DNA Damage Affects Mitochondrial Respiration and Cardiac Development in Mice With Altered DNA Repair
Authors: McLendon Jared M , Alvarez Diego F , Gorodnya Olena M , Sukhanov Sergiy , Rachek Lyudmila I , Gillespie Mark N , Ruchko Mykhaylo V
Published: March 2022

Impaired mitochondrial proliferation and function may lead to heart failure. Mitochondrial biogenesis during postnatal cardiac development in rodents is accompanied by oxidative mitochondrial (mt) DNA damage and repair. How mtDNA damage is linked to mitochondrial biogenesis is unknown, but our previous data suggest that site-specific mtDNA oxidation is involved in regulation of mtDNA replication. Here we tested the hypothesis that modulation of Ogg1, a DNA glycosylase mediating the first step in the base excision repair of oxidative mtDNA damage, coordinately affects mitochondrial function and cardiac development. Wild type (WT) mice, Ogg1 knock-out (KO) mice and KO mice transgenically overexpressing mitochondria-targeted Ogg1 (KOTG) were analyzed for mtDNA damage and replication using Southern and slot-blot analyses; mitochondrial respiration using oxygraph; and cardiac function using echocardiography. Compared to WT, KO mice showed increased oxidative mtDNA damage in cardiac tissue, (0.18 ± 0.04 vs. 0.35 ± 0.04 lesions/104 bp respectively, p<0.05), 2-fold decrease in mtDNA copy number (p<0.05) and increased heart:body mass ratio (4.96 ± 0.11 vs. 5.70 ± 0.10 mg/g respectively, p<0.05). Conversely, KOTG mice showed decreased mtDNA oxidation, restored mtDNA copy number and blunted elevation in cardiac mass. Echocardiography confirmed increased cardiac mass in KO mice with a trend towards decrease of cardiac contractility. Compared to hearts from WT mice, KO animals displayed significant increase in mitochondrial oxygen flux at state III (54.0 ± 8.1 vs. 93.9 ± 9.2 pmol/sec/ml/10 mg respectively, p<0.05) with concurrent decrease in respiratory ratio (2.56 ± 0.42 vs. 1.46 ± 0.27 respectively), indicating constitutive uncoupling in the cardiac tissue. Mitochondrial bioenergetics of KOTG mice did not differ from WT animals. In summary, Ogg1 deficiency in mice leads to elevated oxidative mtDNA damage; decreased mtDNA copy number and respiration; and cardiac hypertrophy. Restored mtDNA repair completely eliminated these effects on mitochondrial function and cardiac development. These results suggest that abnormalities in mitochondrial function and cardiac development can be manipulated by altering mtDNA damage and repair.
Abstract 16323: Hyperhomocysteinemia Potentiates Type 2 Diabetes-induced Inflammatory Monocyte Differentiation and Vascular Dysfunction
Authors: Fang Pu , Pansuria Meghana , Jiang Xiaohua , Yang Xiao-Feng , Wang Hong
Published: March 2022

Hyperhomocysteinemia (HHcy) is associated with increased diabetic cardiovascular diseases. Soinio M et al. showed that coronary heart disease death was increased from 13.5% to 26.1% in type 2 diabetes mellitus (T2DM) subjects with HHcy. However, the role and underlying mechanism of HHcy in T2DM associated atherosclerosis remains unknown. To examine this, we established a mouse model with both HHcy and T2DM by feeding db/db mice (blood glucose level 493 mg/dL) a high fat+high methionine (HF+HM) diet (methionine is homocysteine (Hcy) precursor). The HF+HM diet induced severe HHcy in the control (CT) mice (129 μM) and T2DM mice (180 μM), which was lowered by vitamin supplement therapy via feeding the mice a HF+HM+high vitamin (HF+HM+HV) diet to 42 μM and 87 μM in CT and T2DM mice, respectively. We found HHcy and T2DM individually impaired endothelial-dependent vessel relaxation. HHcy worsened T2DM-impaired endothelial-dependent vessel relaxation in the aorta. More, HHcy and T2DM individually increased circulating mononuclear cell (MNC), CD11b
+
MNC (monocyte, MC), CD11b
+
Ly6C
middle+high
inflammatory MC, and M1 macrophage (MØ). HHcy potentiated T2DM-increased circulation MNC, MC, inflammatory MC, and M1 MØ. Similar cellular changes were observed in the bone marrow and spleen. It is evident that HHcy induced system inflammation as HHcy increased the levels of inflammatory cytokines in the CT and T2DM mice. Importantly, we found HHcy increased CD11b
+
Ly6C
middle+high
inflammatory MC infiltration in the aortas from mice with/out T2DM. Hcy-lowering therapy reversed HHcy-related MNC, MC, inflammatory MC and MØ induction in the system and reversed inflammatory MC infiltration in the vessel in mice with/out T2DM. In addition, peripheral and vessel wall inflammatory MC were positively correlated with plasma Hcy levels and negatively correlated with plasma s-adenosylmethionine/s-adenosylhomocysteine ratio, which is a methylation indicator. In conclusion, our study suggested that HHcy and T2DM induces systemic inflammation and promotes MC-derived vascular inflammation, which may contribute to vascular dysfunction. This HHcy-induced inflammatory MC differentiation, at least in part, via hypomethylation-related mechanisms.
Abstract 16326: Safety and Efficacy of Novel Oral Anticoagulants in Subjects With Atrial Fibrillation in Relation to Renal Function: Meta-analysis of Randomized Clinical Trials
Authors: Del Carpio Freddy , Gharacholou Shahyar M , Branson Andrea M , Paletta Dawn M , Brose Pamela K , Asirvatham Samuel J
Published: March 2022

Introduction:
The efficacy and safety of novel oral anticoagulants (NOACs) has not been assessed in subjects with renal impairment.

Methods:
We performed a meta-analysis of RCTs comparing NOACs with warfarin in patients with atrial fibrillation (AF), in relation to renal function estimated by glomerular filtration rate (GFR): normal (GFR>80 ml/min/1.73m2), mild (50-80 mL/min/1.73m2), and moderate (<50 mL/min/1.73m2) impairment. MEDLINE, Embase, Web of Science and the Cochrane Library were searched to identify articles published up to the third week of January 2015. Data were supplemented with FDA data. Data on stroke or systemic embolism (S/SE) and major bleeding according to renal function were collected and extracted. We estimated the pooled relative risk (RR) of S/SE and major bleeding, for NOACs compared to warfarin.

Results:
We retrieved four randomized clinical trials (each randomizing dabigatran, rivaroxaban, apixaban, or endoxaban versus warfarin) enrolling a total of 58338 subjects, 29123 randomized to NOACs and 29123 randomized to warfarin; 21132 had normal renal function, 13126 had mild and 11027 had moderate renal impairment. In subjects with moderate renal impairment, compared to warfarin, NOACs reduced the risk of S/SE (RR 0.8; 95% CI 0.68-0.94) and major bleeding (RR 0.80; 95% CI 0.71-0.91). In subjects with mild renal impairment NOACs were associated with a reduced risk of S/SE (RR 0.75; 95% CI 0.66-0.85) and major bleeding (RR 0.87; 95% CI 0.79-0.95). In subjects with normal renal function no difference in the risk of S/SE was observed, while the risk of major bleeding was slightly less for subjects taking NOACs (RR 0.87; 95% CI 0.76-0.99). The test for interaction among groups of renal function was borderline significant for S/SE, but not for major bleeding.

Conclusions:
The use of NOACs was associated with a reduced risk of S/SE in subjects with mild or moderate renal impairment; while the risk of bleeding was reduced by NOACs compared to warfarin.