bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16712: Premedical Students are an Effective and Cost Efficient Way to Teach Large Numbers of People Hands Only CPR in a Community Based Approach
Authors: Oliver Alexandria , King Kayla , Scalzo Anna , Dillon William C
Published: July 2021

Introduction:
There are approximately 750 cases of cardiac arrest in Jefferson Co, KY each year and only an estimated 6-14% of these individuals survive. The overwhelming death rate can in part be attributed to the low amount of by-stander CPR being performed. A citywide CPR initiative was started to increase the amount of by-stander CPR and ultimately increase the cardiac arrest survival rate.

Hypothesis:
Premedical students can be trained as hands only CPR instructors and can teach large numbers of people hands only CPR in a community based approach cost effectively.

Methods:
The program officially launched in the summer of 2014. Over a 12 month period, 12 premedical students were taught to become hands only CPR instructors.

These instructors went into high schools, community based organizations and churches to educate individuals on cardiac arrest, hands only CPR, and preventative health measures. Demographic data was collected as well as a pre and post test was performed by each student to gauge the efficacy of the teaching program.

Results:
During the study period, 7554 people in Louisville, KY participated in the hands only CPR classes. We taught classes in 30 high schools and reached over 90% of all freshmen high school students in Louisville. We taught people in each zip code in Louisville and taught greater than 75 people in 25 of the 35 (70%) zip codes in Louisville. The cost for this program was $3.40/person taught hands only CPR.

Conclusions:
Using premedical students as hands only CPR instructors is an effective way of teaching large numbers of people hands only CPR in a cost effective manner. This program could be reproduced in other communities.
Abstract 16775: Efficacy and Safety of a Thinner-strut Silicon Carbide-coated Cobalt Chromium Bare-metal Stent Compared to a Thin-strut Uncoated Cobalt Chromium Bare-metal Stent in Large Vessel Stenting: Insights From Two Prospective Randomised All-comers Trials
Authors: Hansen Kim W , Sørensen Rikke , Jeger Raban , Kaiser Christoph , Pfisterer Matthias , Galatius Søren
Published: July 2021

Introduction:
The new generation thinner-strut silicon carbide (SiC) coated cobalt chromium (CoCr) bare-metal stents (BMS) are designed to accelerate rapid endothelialisation and reduce thrombogenicity when implanted in coronary arteries. However, smaller studies suggest reduced efficacy with higher rates of symptomatic restenosis in patients receiving the newer generation BMS.

Objective:
We investigated the efficacy and safety of a new generation thinner-strut SiC coated CoCr BMS (SCC-BMS) as compared to an older thin-strut uncoated CoCr BMS (UC-BMS) in patients presenting with coronary artery disease requiring stenting of large vessels (≥3.0mm) and thus at low risk of restenosis.

Methods:
We included all patients randomized to SCC- (n=761) or UC-BMS (n=765) in the BASKET-PROVE II and I trials, respectively. Design, patients, interventions and follow-up were similar between trials except differing regimens of dual antiplatelet therapy. The primary endpoint was clinically driven target-vessel revascularization within 24 months. Safety endpoints of cardiac death, non-fatal myocardial infarction (MI), and definite/probable stent thrombosis were also assessed. We used Cox proportional hazards regressions to estimate relative hazards adjusting for known confounders.

Results:
Demographics, clinical presentation, and risk factors were comparable between the groups, but patients receiving SCC-BMS underwent less complex procedures. Rates of the primary endpoint were 10.4% in the SCC-BMS group and 8.4% among patients receiving UC-BMS yielding an adjusted relative hazard (HR) of 1.46 ([1.03-2.07], p=0.032). Estimates for the safety endpoints were: cardiac death (1.8% vs. 2.4% ; HR 0.77 [0.36-1.59], p=0.46), non-fatal MI (3.2% vs. 2.5% ; HR 1.68 [0.88-3.21], p=0.11), and definite/probable stent thrombosis (0.8% vs. 1.0% ; HR 0.97 [0.32-3.00], p=0.96). We detected no particular subgroups driving the increased risk of target-vessel revascularization in the SCC-BMS group.

Conclusions:
In patients requiring stenting of large coronary arteries, use of the newer generation SCC-BMS was associated with a higher risk of symptomatic restenosis despite less complex procedures compared to the UC-BMS with no signs of an offsetting safety benefit.
Abstract 16852: Left Ventricular Hypertrophy and Cognitive Decline in Dementia-free Older Subjects at Risk of Cardiovascular Disease
Authors: Sabayan Behnam ,   PROSPER study group
Published: July 2021

Background:
Impaired cardiac function in patients with heart failure has been linked with structural and functional alterations in the brain. Left ventricular hypertrophy (LVH) is associated with lower cardiac output which can jeopardize cerebral perfusion. In this study, we investigated whether LVH is related with accelerated cognitive decline in dementia-free older subjects at risk of cardiovascular disease.

Methods:
We studied 4240 men and women dementia-free subjects, mean age 75.1 years, who were enrolled in PROSPER (PROspective Study of Pravastatin in the Elderly at Risk). From baseline electrocardiograms Sokolow-Lyon Product, a measure of LVH, was calculated. Four domains of cognitive functional testing reaction time, processing speed and immediate and delayed memory were assessed at baseline and repeated during a mean follow-up of 3.2 years. The association between Sokolow-Lyon Product and annual decline in various cognitive domains were evaluated using linear regression models adjusted for socio-demographic and cardiovascular factors.

Results:
At baseline higher Sokolow-Lyon Product, indicating higher degrees of LVH, was associated lower cognitive scores in reaction time (p<0.001) and processing speed (p<0.001). However, the associations attenuated after adjustments for demographic and cardiovascular factors. In the longitudinal analyses, higher Sokolow-Lyon Product was associated with steeper decline in processing speed (p=0.001), immediate (p=0.001) and delayed (p=0.003) memory function. All these associations were independent of cardiovascular factors and events during follow up.

Conclusion:
Higher degrees of LVH are independently associated with steeper cognitive decline, in particular in processing speed and memory domains. Older subjects with LVH need to be recognized as high risk groups for cognitive impairment.
Abstract 16853: Dietary Improvements and the Preventable Cost of Cardiovascular Disease: Evidence From the Literature
Authors: Zhang Donglan , Cogswell Mary E , Wang Guijing
Published: July 2021

Introduction:
Cardiovascular diseases (CVD) risk has been linked to dietary components in many studies, but the associated reduction in CVD healthcare costs with dietary improvements has not been systematically evaluated.

Hypothesis:
CVD healthcare cost savings associated with an improvement in dietary metrics are substantial.

Methods:
We searched PubMed, Embase, CINAHL and ABI/Inform to identify population-based studies published between January 1990 and December 2014 on CVD healthcare costs related to a dietary component. The selected dietary components, in accordance with those identified by the American Heart Association in their 2010 Strategic Impact goals, included salt/sodium, sugar-sweetened beverages, fruits and vegetables, fish/omega-3 fatty acids, whole grains/fiber. Other selected dietary components, based on AHA’s secondary dietary metrics, were nuts, processed meat and saturated fat. For each dietary component, we evaluated the CVD healthcare cost savings if the current consumption level were to be changed.

Results:
In 329 articles obtained, 15 studies evaluated the healthcare costs associated with one or more of dietary components: salt/sodium (n=12); fruit and vegetables (n=1); meat (n=1); saturated fat (n=3). The majority of studies (n=11) used an incidence-based approach, and the remaining were prevalence-based analyses. Adjusting the costs to 2013 US dollar values using consumer price index and purchasing power parity exchange rate, reducing average sodium intake by 1.2 g/day could save $1794 per person per year in the United Kingdom. Reducing individual sodium intake to 2.3 g/day could save $1955 per person in the United States. Increasing consumption of fruits and vegetables from <0.5 cup / day to more than 1.5 cups / day could save $1481 per person in the United States.

Conclusions:
In conclusion, reducing sodium intake and increasing consumption of fruits and vegetables could substantially reduce CVD costs. Few studies were available on the cost savings associated with dietary components for cardiovascular health. These results suggest a need for economic studies using high-quality cost information and the most recent evidence to predict long-term cost savings.
Abstract 16894: The Effect of Cangrelor on Cardiovascular and Bleeding Events in Patients With Peripheral Artery Disease - Insights From CHAMPION PHOENIX
Authors: Gutierrez Antonio , Harrington Robert A , Stone Gregg W , Steg Ph. G , Gibson Michael C , Hamm Christian W , Price Matthew J , Prats Jayne , Deliargyris Efthymios N , Mahaffey Kenneth , White Harvey D , Bhatt Deepak L
Published: July 2021

Background:
Patients with peripheral artery disease (PAD) are high risk for adverse cardiovascular and bleeding events. In CHAMPION-PHOENIX, cangrelor, an intravenous P2Y12 inhibitor, reduced rates of ischemic events in patients undergoing PCI.

Hypothesis:
We hypothesize that cangrelor will safely reduce ischemic events in patients with PAD undergoing PCI.

Methods:
A total of 11,145 patients were randomly assigned in a double-dummy, double-blind manner to either cangrelor followed by clopidogrel 600 mg or to clopidogrel loading at PCI. The primary endpoint was a composite of death, MI, ischemia-driven revascularization (IDR), or stent thrombosis (ST) at 48 hours.

Results:
837 (8%) patients with PAD and 9,994 (90%) patients with no prior history of PAD underwent PCI. Among the PAD cohort the primary endpoint occurred in 20 (4.5%) cangrelor vs. 44 (11.4%) clopidogrel patients (OR [95% CI] = 0.36 [0.21, 0.63]), and 235 (4.7%) cangrelor vs. 276 (5.5%) clopidogrel patients (OR [95%CI] = 0.86 [0.72, 1.03]) without PAD (p for interaction = 0.003). Among the PAD cohort the rate of GUSTO severe/life-threatening bleeding was 0.4% cangrelor vs. 0% clopidogrel (p = 0.19), and 0.1% cangrelor vs. 0.1% clopidogrel patients (OR [95%CI] = 1.78 [0.52, 6.07], p = 0.35) without PAD (p for interaction = 0.34). The rate of blood transfusion in the PAD cohort was 0.9% cangrelor vs. 0% clopidogrel (p = 0.06), and 0.4% cangrelor vs. 0.3% clopidogrel patients (OR [95%CI] = 1.42 [0.73, 2.76], p = 0.30) without PAD (p for interaction = 0.13).

Conclusion:
In CHAMPION-PHOENIX, cangrelor significantly reduced ischemic events with no significant increase in severe bleeding or transfusions in patients with PAD.
Abstract 16913: Greater Coronary Atheroma Regression in Women Compared With Men: A Pooled Analysis of Serial Intravascular Ultrasonography Trials Utilizing High-intensity Statin Therapy
Authors: Stegman Brian , Shao Mingyuan , Nichols Stephen , Elshazly Mohamed , Kapadia Samir , Tuzcu E. Marat , Nissen Steven , Puri Rishi
Published: July 2021

Introduction:
High-intensity statin therapy (HIST) reduces cardiovascular events, however sex-related differences in treatment effects are not well characterized, possibly contributing to gender disparities in HIST use.

Hypothesis:
Sex-related differences in coronary atheroma regression exist following HIST.

Methods:
We undertook a patient-level post-hoc pooled analysis of 3 randomized trials utilizing serial coronary IVUS to test the anti-atherosclerotic effects of HIST in patients with coronary disease. Sex-related differences in changes (Δ) in coronary percent atheroma volume (PAV) were ascertained following 18-24 months of either atorvastatin 80 mg or rosuvastatin 40 mg.

Results:
In women (n=451) compared with men (n=1190), levels of on-treatment LDL-C (68±24 vs. 68±22mg/dl, p=0.62) were similar, however HDL-C (53±12 vs. 47±11 mg/dl, p<0.01) and CRP [1.7 (0.9, 3.8) vs. 1.1 (0.6, 2.7) mg/l, p<0.01] were higher. Compared with men, women harbored lower baseline PAV (34.8±8.7 vs. 38.3±8.8%, p<0.001), yet demonstrated greater PAV regression (ΔPAV -1.07±0.26 vs. -0.66±0.23%, p=0.02). When achieved on-treatment LDL-C levels were <70mg/dl, women demonstrated greater PAV regression than men (-1.49±0.21 vs. -0.97±0.13%, p=0.035), however had similar rates of PAV regression with on-treatment LDL-C levels ≥70 mg/dl (-0.63±0.25 vs. -0.42±0.16%, p=0.47). Sex-related differences in atheroma regression did not differ according to achieved levels of HDL-C, non-HDL-C or CRP (Figure). Multivariable analysis revealed female sex to independently associate with PAV regression (coefficient -0.66, p=0.017).

Conclusion:
Women systematically demonstrate greater degrees of coronary plaque regression compared with men following long-term HIST, especially in the setting of lower achieved LDL-C levels. Further research is required for elucidating mechanisms underpinning sex-related variations in plaque progression-regression.
Abstract 16970: Statin Reduce Mortality and Major Cardiovascular Events in End-stage Renal Disease Patient, a Taiwan Cohort Study
Authors: Cheng Kai-Hung , Chu Chih-Sheng , Chang Yu-Han , Lu Tzongshi , Lai Wen-Ter
Published: July 2021

Introduction and Hypothesis:
Coronary artery disease (CAD) is the leading cause of mortality in end-stage renal disease (ESRD) patients. Vitamin D deficiency is common in patients with ESRD, and therapeutic use of Calcitriol may improve cardiovascular outcomes. Studies indicate that Statin can reduce incidences of major adverse cardiac events (MACE), and mortality in CAD. However, both 4D and AURORA studies report Statin cannot reduce MACE and mortality in ESRD patients. The goal of our study is to assess the effects of Statin and Calcitriol administration in ESRD.

Methods:
A total of 837 subjects selected from 12342 ESRD patients from Taiwan’s National Health Insurance Research Database were stratified into four groups (Control (n=498), S: Statin (n=131), C: Calcitriol (n=130), SC: Statin and Calcitriol (n=78)). We analyze their mediation history for twelve years since their ESRD diagnosed. One way ANOVA with Bonferroni correction, chi-square test, fisher's exact and Cox proportional hazard regression were used for statistics. Statistical significances were set at a P< 0.05.

Results:
Our data (Adjusted Hazard Ratio (HR), 95% Confidence Interval (CI)) showed that mortality was significant reduced when treated with Statin (0.6, 0.43-0.84), Calcitriol, (0.5, 0.35-0.72), Statin and Calcitriol (0.51, 0.31-0.82) in comparison with control group, respectively. Interestingly, these significant changes were first observed at 10th-year in S and SC groups, but at 12th-year in C group. In addition, Statin reduced MACE (0.55, 0.37-0.81) and heart failure (0.51, 0.27-0.95) incidences. Furthermore, Calcitriol also reduced MACE (0.37, 0.23-0.59), stroke (0.34, 0.16-0.72) and heart failure (0.46, 0.25-0.86) incidences as well as SC treatment decreased MACE (0.38, 0.22-0.68), stroke (0.45, 0.21-0.97), and heart failure (0.26, 0.09-0.73) incidences.

Conclusions:
Our data show for the first time that Statin alone can reduce incidences of mortality, MACE and heart failure but not stroke in ESRD. And, combination of Statin and Calcitriol provides best outcomes in ESRD patients with heart failure among these groups. This finding may provide important information in developing therapeutic strategies for the roles of Statin and Calcitriol in ESRD.
Abstract 17022: The Gap Between Indicated and Prescribed Stroke Prevention Therapies in A High-risk Geriatric Population in Ontario
Authors: Shurrab Mohammed , Crystal Eugene , O'Donnell Denis , Navare Hrishikesh , Neves Paula , Lashevsky Ilan , Newman David
Published: July 2021

Introduction:
Atrial fibrillation (AF) is the most common cardiac dysrhythmia, with estimated risk of about 25% by 80 years of age. The use of oral anticoagulation (OAC) in the elderly population treated in long term care (LTC) facilities is inconsistent and poorly studied. Hypothesis: We performed a retrospective analysis to assess the magnitude and sources of the gap between indicated and prescribed use of OAC in the elderly with AF along with the prevalence of different therapies.

Methods:
We retrospectively scanned 25 LTC facilities in Ontario, Canada. The diagnosis of AF was drawn from electronic medical records. This was merged with a pharmacy database, which was the sole provider of all medications for each resident. Attributable risk factors for possible failure to prescribe use of OAC were: Advanced directives for no hospitalization, Do-Not-Resuscitate order, Dementia, Cognitive Performance Scale, Activities of Daily Living Self Performance Hierarchy scale and Changes in Health, End-Stage Disease, Signs, and Symptoms Scale.

Results:
In total 3378 active residents were examined in 25 LTC facilities. All patients were ≥ 65 years old with mean age 85 ± 8 years and 2449 (72%) were female. We identified 433 (13%) AF patients with mean age 87 ± 7 years and mean CHADS2 score 3 ± 1; all qualify for OAC therapy. Out of all AF patients, 273 (63%) patients were on OAC therapy. Patients were mostly treated with Vitamin K antagonists (N= 114 (42%)), rivaroxaban (N= 71 (26%)) or apixaban (N= 62 (23%)) followed by dabigatran (N= 26 (10%)). Antiplatelet drugs as the only stroke prevention therapy were used in 88 (20%) patients and 28 (6%) patients were on dual therapy (anticoagulation and antiplatelet drugs). Seventy-two (17%) patients were not on any antiplatelet or antithrombotic therapy. None of the attributable risks identified consistently correlated with the failure to prescribe indicated therapy. Conclusions: This real world data set suggests that 37% of eligible elderly LTC patients fail to receive recommended stroke prevention therapies. Vitamin K antagonists are the most common OAC therapy used in elderly patients in LTC facilities. Lack of use of indicated therapy appears to be idiosyncratic.
Abstract 17027: Expression Quantitative Trait Locus (eQTL) Map for Genetic Variants Associated With Cardiovascular Traits in Human Heart
Authors: Wheeler Nicole E , Cameron Vicky A , Pearson John F , Gardener Paul P , Moravec Christine S , Sweet Wendy E , Tang WH W , Troughton Richard W , Richards A M , Pilbrow Anna P
Published: July 2021

Introduction:
To identify genetic variants that may influence disease susceptibility by modulating gene expression, this study investigated associations between genetic variants associated with cardiovascular traits and gene expression in heart tissue.

Methods:
In left ventricle from 102 heart donors with no diagnosed heart disease and 100 heart transplant patients (explanted failed hearts), genotyping was performed with Illumina CardioMetabo Chips (covering ~200,000 variants associated with cardiovascular and metabolic traits). Gene expression profiles for each tissue sample were generated with Affymetrix Human Gene ST 1.0 microarrays. Associations between genotype and gene expression (expression quantitative trait loci, eQTLs) were tested with an additive genetic model, adjusted for multiple comparisons. For each gene, proximal (cis) and distal (trans) eQTL effects were tested by analyzing variants <1Mb and >1Mb from the transcription start site, respectively.

Results:
After quality control filtering, 30,412 genes were tested for association with 54,908 variants in donors and 56,976 variants in transplant patients. In donors, 275 genes with cis-eQTL effects and 100 genes with trans-eQTL effects were identified (adjusted p<0.05, effect size: 0.1-1.8). In patients, 244 genes with cis-eQTL effects and 101 genes with trans-eQTL effects were identified (adjusted p<0.05, effect size: 0.1-1.3). Fewer than half the genes with cis-eQTL effects (n=115) were shared by donors and transplant patients.

Conclusions:
This study provides the first eQTL map of disease-associated variants in established heart disease. These data may help identify functional non-coding variants that contribute to susceptibility to disease.

Figure:
Upper panel, Manhattan plot of genes with cis-eQTL (dark blue) and trans-eQTL (light blue) effects in heart donors (top) and transplant patients (bottom). Lower panel, example cis-eQTL shared by donors and transplant patients.
Abstract 17048: Prognostic Implication of Enlarged Left Ventricle in Patients Who Underwent Valve Surgery due to Mitral Valve Prolapse or Flail Mitral Valve: Volume versus Dimension
Authors: Jang Jeong Yoon , Kang Se Hun , Bae Jae Seok , Lee Cheol Hyun , Kim Yu Na , Cho Min Soo , Kim Dae-Hee , Song Jong-Min , Kang Duk-Hyun , Song Jae-Kwan
Published: July 2021

Introduction:
Left ventricular end-systolic dimension (LVESD) has been being used to guide the optimal timing of surgery in patients with mitral valve prolapse (MVP) or flail mitral valve (FMV). We sought to evaluate whether LVES volume (LVESV) measured by echocardiography can provide additive prognostic information.

Methods:
Of patients who underwent MV surgery due to MVP or FMV from 2000 to 2014, after exclusion of patients whose rhythm was atrial fibrillation or who needed concomitant maze procedure, aortic valve or coronary bypass surgery, a total of 648 patients (age 51±14 years; ejection fraction 64±7%; LVESD 38±6 mm; LVESV 60±26 mL; repair/replacement = 612/36) was selected. Clinical outcomes included cardiovascular (CV) death, admission due to heart failure (HF) and development of LV dysfunction (EF <45% at the last follow-up).

Results:
During median follow up of 4.2 years (interquartile range, 1.8-6.6 years), 5 patients died of CV death, 36 admitted for HF, and 38 developed LV dysfunction. Increased LVESD (≥45mm) could not predict CV death. But patients with enlarged LVESV index (LVESV/ body surface area ≥50 ml/m
2
, n=64, 10%) showed higher rate of CV death (p=0.04), HF admission (p=0.04) and composite clinical events (p<0.001). In multivariate regression analysis, enlarged LVESV index was the only independent variable associated with composite clinical events (hazard ratio 2.67, 95% confidence interval 1.39-5.13, p=0.003).

Conclusions:
In the modern era of MV repair surgery for MVP and FMV, LV volume provides more robust prognostic information than LV dimension.
Abstract 17065: Cardiac Progenitor Cell-mediated Cardiac Regeneration in the Poastnatal Mammalian Heart
Authors: Liu Yuan-Hung , Lai Ling-Ping , Huang Shih-Yun , Lin Yi-Shuan , Huang Hsing-Yu , Lin Jiunn-Lee
Published: July 2021

The massive loss of cardiomyocytes after myocardial infarction often results in cardiac fibrosis, chamber dilatation and heart failure. Several studies have shown that inflammation contributes to adverse left ventricular remodeling, however, anti-inflammatory therapy with NSAID during the acute phase of myocardial infarction augments the adverse cardiac remodeling and increases mortality. We hypothesized that inflammation in the acute phase of myocardial infarction might trigger the activation of cardiac progenitors and that anti-inflammatory therapy might attenuate the repair by the cardiac progenitors.

We confirmed that Nkx2.5 enhancer-expressing cells existed in the postnatal mouse heart and could differentiate into striated cardiomyocytes in vitro. Using the Nkx2.5 enhancer-eGFP transgenic mice, we found the number of eGFP+ cells and inflammatory cells (marked by Gr1. Mac1, B220, CD45) increased remarkably and significantly after coronary artery ligation. The activated Nkx2.5 enhancer expressing cells expressed up-regulated cardiogenesis genes and could differentiate into cardiomyocytes in vivo by lineage tracing.

To prove that anti-inflammatory therapy might attenuate the repair by the cardiac progenitors, we added NSAID (ibuprofen) to the feeding water after coronary ligation on the Nkx2.5-eGFP transgenic mice and found the activated level of progenitor cells was decreased by 73% after the mice were treated with ibuprofen. We further lineage-traced the post-inury inducible Nkx2.5-Cre; ROSA26-LacZ double transgenic mice with ibuprofen or water and found the LacZ+ positive area was decreased by 80% in the heart sections of ibuprofen-treated mice.

We concluded that the inflammatory signaling enhances the cardiac progenitor cells to proliferate and differentiate into cardiomyocytes. Understanding the factors regulating cardiac regeneration helps us treat the patients with myocardial infarction or heart failure.
Abstract 17124: Sex Differences in the Incidence of Peripheral Artery Disease (PAD) in the Chronic Renal Insufficiency Cohort (CRIC)
Authors: Wang Grace J , Shaw Pamela A , Townsend Raymond R , Anderson Amanda H , Xie Dawei , Nessel Lisa C , Mohler Emile R , Sozio Stephen M , Jaar Bernard G , Chen Jing , Wright Jackson , Taliercio Jonathan J , Ojo Akinlolu , Ricardo Ana C , Lustigiva Eva , Fairman Ronald M , Feldman Harold I , Ky Bonnie ,   CRIC Study Investigators
Published: July 2021

Introduction:
Chronic kidney disease (CKD) results in an increased risk of peripheral artery disease (PAD). However, the epidemiology of PAD in CKD, and particularly how the incidence differs according to sex remains incompletely defined. We sought to define how the epidemiology of peripheral arterial disease (PAD) in chronic kidney disease (CKD) differs according to sex and age.

Methods:
The Chronic Renal Insufficiency Cohort (CRIC) is a multi-center, prospective cohort study of CKD participants. Fine and Gray methods were used to determine the cumulative incidence of PAD, defined by an ankle brachial index (ABI) < 0.90 or a confirmed PAD event, with death as a competing event. Adjusted subdistribution hazard ratios from the Fine and Gray model determined the risk of PAD according to sex. A priori, we hypothesized that the relationship between sex and cumulative incidence of PAD differed according to age.

Results:
The mean age of the 3,174 participants in this study was 56.6 years and consisted of 55% males. Over a median follow-up of 5.9 years, 17.8% developed PAD and 11.1% died. Females had a 1.72-fold greater adjusted PAD risk compared to men (95% CI 1.44-2.06, p<0.001). These sex-related differences in PAD risk also differed by age (p<0.001, Figure). Women, compared to men, were at a markedly increased risk for PAD at younger ages; however, at ages greater than 70 years, the risk was similar across both sexes. Older men had a substantially greater PAD risk compared to younger men. In women, PAD risk did not vary with age.

Conclusions:
Females with CKD have a higher PAD risk compared to males at younger ages. There is an important need to improve our understanding of the biological and clinical basis for these differences.
Abstract 17126: Efficacy and Safety of Dabigatran Compared With Warfarin in Patients With Atrial Fibrillation and Normal Renal Function Over Time: Insights From the RE-LY Trial
Authors: Hijazi Ziad , Hohnloser Stefan H , Oldgren Jonas , Andersson Ulrika , Connolly Stuart J , Eikelboom John W , Ezekowitz Michael D , Reilly Paul A , Yusuf Salim , Wallentin Lars
Published: July 2021

Background:
In patients with atrial fibrillation (AF) and normal renal function it has been reported that one oral factor-Xa inhibitor is associated with decreased efficacy compared to warfarin. In the RE-LY trial of patients with AF dabigatran, with approximately 80% renal elimination, was superior to warfarin for prevention of stroke and systemic embolism (SEE) with the 150 mg dose and non-inferior with the 110 mg dose and associated with significantly less major bleeding with the 110 mg dose. This is a post hoc analysis of the efficacy and safety of dabigatran vs. warfarin treatment in patients with normal renal function during the study.

Methods:
In the RE-LY trial among patients who received at least one dose of study medication, 17882 had creatinine measurements available at baseline, out of which 91% also had measurements after randomization. There were a total of 382 stroke/SEE, 280 ischemic strokes, and 1018 major bleed events during median follow-up of 1.8 years. The relations between outcomes, treatment, and renal function (Cockcroft-Gault estimated glomerular filtration rate (eGFR)) during follow-up were evaluated using Cox regression including treatment, eGFR as a continuous time dependent covariate, fitted using restricted cubic splines, and interaction. Hazard ratios (95% CI) comparing treatment effects were analyzed according to eGFR level.

Results:
In patients with normal renal function the relative risk of stroke/SEE was consistently lower in those treated with dabigatran as compared with warfarin. The patterns were similar for major bleeding with a trend of greater relative risk reduction with dabigatran as compared to warfarin at normal renal function.

Conclusions:
In patients with AF and normal renal function during treatment the efficacy of dabigatran compared to warfarin was consistent with the overall result of the RELY study. Both dabigatran doses were associated with lower risk of major bleeding in patients with normal renal function.
Abstract 17152: Frequency and Management of Major Bleeding in Atrial Fibrillation Patients Treated With Warfarin and Non-vitamin K Oral Anticoagulants in Community Practice: Results From the ORBIT-AF II Registry
Authors: Steinberg Benjamin A , Simon DaJuanicia N , Thomas Laine , Ansell Jack , Fonarow Gregg C , Gersh Bernard J , Kowey Peter R , Mahaffey Kenneth W , Peterson Eric D , Piccini Jonathan P
Published: July 2021

Background:
Non-vitamin K oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the frequency of major bleeds on NOACs and how these events are managed in clinical practice.

Methods:
We assessed the rates, management, and outcomes of ISTH major bleeding events among AF patients in the ORBIT-AF II registry (mean follow-up 213 days).

Results:
Overall, 103 patients experienced 110 major bleeding events during follow-up n=90/4986 (1.8%) on NOAC, and n=20/1320 (1.5%) on warfarin. Patients with bleeding events on NOAC were slightly younger than those on warfarin (median age 76 vs. 80; p=0.2). Among mutually-exclusive bleeding types, intracranial bleeding was more common in warfarin treated patients than NOAC-treated (15% vs 6.7%), whereas GI bleeding was more common on NOACs (56% vs. 40%, overall p=0.1 for bleeding type). Management of bleeding differed by anticoagulation type: blood products and reversal agents were more commonly used in patients on warfarin (Table). No patient received prothrombin complexes, recombinant factor VIIa, aminocaproic acid, tranexamic acid, aprotinin, or desmopressin. Out of 90 major bleeding events in NOAC patients, only 1 was fatal (1%). Within 30 days following bleeding, there were no strokes and 1 TIA (NOAC). Following a major bleed, the recurrent bleeding rate in NOAC patients in the next 30-days was 4% and the death rate was 4%.

Conclusions:
Rates of major bleeding with NOACs in clinical practice are comparable to those reported in clinical trials. Compared with warfarin, bleeding among NOAC users was less likely intracranial and more likely to be GI. Management of bleeding in the setting of NOAC rarely includes reversal agents.
Abstract 17203: Postnatal Management of Fetuses With Ebstein Anomaly or Tricuspid Valve Dysplasia in the Current Era: A Multi-center Study
Authors: Freud Lindsay R , Kalish Brian T , Escobar-Diaz Maria C , Komarlu Rukmini , Puchalski Michael D , Jaeggi Edgar T , Szwast Anita L , Freire Grace , Levasseur Stephanie M , Kavanaugh-McHugh Ann , Michelfelder Erik C , Moon-Grady Anita J , Donofrio Mary T , Howley Lisa W , Selamet Tierney Elif Seda , Cuneo Bettina F , Morris Shaine A , Pruetz Jay D , van der Velde Mary E , Kovalchin John P , Ikemba Catherine M , Vernon Margaret M , Samai Cyrus , Satou Gary M , Gotteiner Nina L , Phoon Colin K , Silverman Norman H , McElhinney Doff B , Tworetzky Wayne
Published: July 2021

Background:
A recent multi-center study of perinatal outcome in fetuses with Ebstein anomaly or tricuspid valve dysplasia (EA/TVD) found that 1/3rd of live-born patients (pts) died prior to hospital discharge. The purpose of this study was to explore differences in postnatal management and the relationship to outcome.

Methods:
This 23-center, retrospective study included 243 fetuses with EA/TVD from 2005 to 2011. Neonatal procedure (NP) was defined as surgery or interventional catheterization (cath) prior to discharge. Associations between postnatal management and outcome at discharge were explored.

Results:
Of 176 live-born pts, 7 received comfort care only, 11 died <24 hrs of life, and 4 had insufficient data. Among 154 remaining pts, 38 (25%) did not survive to discharge. Pts who required ECMO at any point (n=18) had 83% mortality. More than half of pts (54%) did not have an NP, 34% had surgery, 8% had interventional cath, and 4% had both. The median age at 1st NP was 6 days (quartiles: 1-11). Survival did not differ between pts who had an NP and those who did not (70% vs. 80%; p=0.19) or between pts who had surgery and those who did not (68% vs. 80%; p=0.09). However, mortality differed by NP performed and whether pulmonary regurgitation, an indicator of high risk, was present prenatally (Figure). No pts with a right ventricular exclusion (RVE) died. Of 49 surviving neonates with ≥1 procedure, 28 (57%) were palliated with a shunt or RVE and 21 (43%) had a biventricular circulation. Thus, in total, 86 of 154 live-born pts (56%) survived with a biventricular circulation: 65 with medical management only and 21 with ≥1 NP.

Conclusion:
Among live-born pts diagnosed with EA/TVD in utero, a variety of postnatal management strategies were employed with overall poor outcomes. If surgery beyond PDA ligation is necessary, then RVE or other palliative procedure may need to be considered. A prospective, multi-center study utilizing a management algorithm would help elucidate the optimal strategy.
Abstract 17217: Serum Paraoxonase 1 (PON1) Activity is Associated With Indices of Hypertensive Heart Disease and Cardiac Remodeling in the Dallas Heart Study Population
Authors: Teiber John F , Kramer Gerald L , de Lemos James A , Drazner Mark H , Haley Robert W
Published: July 2021

Introduction:
A recent study in clinic patients found serum activity of the anti-oxidative, anti-inflammatory HDL-associated enzyme paraoxonase 1 (PON1) inversely associated with plasma brain natriuretic peptide (BNP), a marker of heart failure, and predictive of cardiovascular events. We tested whether PON1 protects from hypertensive heart disease in a population sample.

Methods:
The Dallas Heart Study measured blood biomarkers at baseline in a population sample of 3480 subjects. Left ventricular mass and ejection fraction were measured by cardiac MRI. Serum PON1 activity was measured by the standard arylesterase enzymatic assay. Incident deaths and causes of death were ascertained for 9 years from baseline through the National Death Index where ICD-9 codes I10 –I13.1 indicated hypertensive heart disease. Multivariable models controlled for age, sex, race, cystatin-C, LDL, HDL, high sensitivity C-reactive protein and uncontrolled hypertension. Preliminary mechanistic studies explored effect modification of 34 biomarkers by PON1.

Results:
In a general linear model PON1 activity was independently associated inversely with log Pro-BNP (standardized r = -0.11, s.e. 0.015, P<0.001) and log BNP (std r = -0.07, s.e. 0.017, P<0.001). It was also inversely associated with left ventricular mass (std r = -0.05, s.e. 0.012, P<0.001) but not with ejection fraction (std r = -0.02, s.e. 0.018, P=0.19). In multivariable logistic regression low PON1 activity predicted the 28 incident deaths from hypertensive heart disease (odds ratio for PON1 activity below the median = 3.58, 95% CI 1.42 – 9.05, P=0.007). Significant interactions indicated that high PON1 activity mitigates the strong association of log Pro-BNP with periostin, a matricellular protein associated with cardiac fibrotic remodeling (P
interaction
< 0.001, Fig.).

Conclusions:
The findings suggest that PON1, a component of HDL, may protect from hypertensive heart disease by mitigating cardiac remodeling.
Abstract 17272: Regionalization of Pediatric Cardiac Surgery Lowers Mortality, Re-operation, and Healthcare Costs
Authors: Swartz Michael F , Orie Joseph , Egan Matthew , Gensini Francisco , Alfieris George M
Published: July 2021

Introduction:
The mortality of infants requiring cardiac surgery is related to center and surgeon case volume. One solution for increasing case volume is to regionalize pediatric cardiac surgical care.

Hypothesis:
We hypothesized that the regionalization of pediatric cardiac surgical care from two medical centers would lower mortality, rate of re-operation, and subsequent health care costs.

Methods:
Infants undergoing a biventricular repair were divided into two groups: pre-regionalization when operations were performed in two separate hospitals (1991-2000) and post-regionalization when all operations were performed in one regional hospital (2001-2010). Operative survival, midterm mortality, need for re-operation, and subsequent healthcare costs were compared between the groups.

Results:
There were 508 infants in the pre-regionalization group, and 479 infants in the post-regionalization group. There were no significant differences in pre-operative age, weight, or gender between groups. Pre-regionalization operative survival was significantly lower than the state average. Post-regionalization operative survival was significantly greater than pre-regionalization and was similar to the state average (Figure 1). Five and 10 year survival remained significantly greater in the post-regionalization group (5 year: 96.8% vs 90.6%, 10 year: 96.8% vs. 89.9%, p<0.01). Five and ten year freedom from re-operation was significantly higher in the post-regionalization group (5 year: 88.8 vs 79.5 %, 10 year: 82.7 vs 73.3%, p=0.001). Subsequent health care costs were significantly lower in the post-regionalization group ($20,233 ± 53596 vs. 37,516 ± 82,947, p<0.001).Conclusions: Regionalization of pediatric cardiac surgical care lowered operative and 10 year mortality, rate of re-operation, and subsequent costs of health care.
Abstract 17291: Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis: CREST-2 update
Authors: Meschia James , Lal Brajesh K , Howard George , Roubin Gary , Brown Robert D , Barrett Kevin M , Chaturvedi Seemant , Chimowitz Marc I , Demaerschalk Bart M , Howard Virginia , Huston John , Lazar Ronald M , Moore Wesley S , Moy Claudia S , Turan Tanya N , Voeks Jenifer , Brott Thomas G
Published: July 2021

Purpose:
The safety of revascularization for asymptomatic carotid stenosis, and the efficacy of medical therapy for stroke prevention have improved. Therefore, results of prior randomized trials may not apply to current treatment decisions. The NINDS-funded CREST-2 will compare carotid endarterectomy and intensive medical therapy (IMT) versus IMT alone (n=1240), and carotid stenting and IMT versus IMT alone (n=1240) in asymptomatic patients with≥70% stenosis.

Materials & Methods:
CREST-2 consists of two parallel randomized clinical trials to be conducted at a target of ≈120 centers, including within NINDS StrokeNet. The composite primary outcome is stroke or death during the peri-procedural period or ipsilateral ischemic stroke thereafter up to 4 years. Blinded assessment of cognition will be done periodically. Centrally directed IMT includes tight control of blood pressure (systolic target <140 mm Hg) and cholesterol (LDL target <70 mg/dl) as well as lifestyle coaching.

Results:
As of June 12, 2015, 94 centers have been approved by the Site Selection Committee. Credentialing is ongoing, with 198 approved surgeons and 64 approved interventionists; 124 additional conditionally approved interventionists will be able to submit additional cases for review under the

CREST-2 Registry. The Centers for Medicare and Medicaid will offer CAS reimbursement for Registry enrollees. As of June 12, 2015, there are 39 actively enrolling centers, and 37 patients have been randomized.

Conclusion:
CREST-2 is designed to identify the best approach for asymptomatic carotid stenosis. The first patient was randomized in December, 2014. An update will be provided regarding the numbers of patients randomized, centers certified, as well as surgeons and interventionists fully approved.

Registration:
ClinicalTrials.gov Identifier: NCT02089217
Abstract 17426: Pulmonary Vein Isolation ‘Rewires’ Electrical Communications to Enhance Small-world Network Topology During Atrial Fibrillation
Authors: Ashikaga Hiroshi , Chrispin Jonathan , Wu Degang , Garland Joshua
Published: July 2021

Recent evidence suggests that pulmonary vein isolation (PVI) may perturb the electrophysiological substrate for maintenance of atrial fibrillation (AF). Our previous work indicates that information theory metrics can quantify electrical communications during arrhythmia. We hypothesized that PVI ‘rewires’ the electrical communication network during AF such that the topology exhibits higher levels of small-world network properties, with higher clustering coefficient and lower path length, than would be expected by chance. Thirteen consecutive patients (n=6 with prior PVI and n=7 without) underwent AF ablation using a 64-electrode basket catheter in the left atrium. Multielectrode recording was performed during AF for 60 seconds, followed by PVI. Mutual information was calculated from the time series between each pair of electrodes using the Kraskov-Stögbauer-Grassberger estimator. The all-to-all mutual information matrix (64x64; Figure, upper panels) was thresholded by the median and standard deviations of mutual information to build a binary adjacency matrix for electrical communication networks. The properties of small-world network (
swn
; ‘small-world-ness’) were quantified by the ratio of the observed average clustering coefficient to that of a random network over the ratio of the observed average path length to that of a random network.
swn
was expressed in normal Z standard deviation units. As the binarizing threshold increased, the Z-score of
swn
decreased (Figure, lower panel). However, the Z-score at each threshold value was consistently higher with prior PVI than those without (p<0.05). In conclusion, electrical communication network during AF with prior PVI is associated with higher levels of small-world network properties than those without. This finding supports the concept that PVI perturbs the underlying substrate. In addition,
swn
of electrical communication network may be a promising metric to quantify substrate modification.
Abstract 17472: Association of Recurrence During Blanking Period With Poor Left Atrial Reverse Remodeling After Initial Catheter Ablation of Non-paroxysmal Atrial Fibrillation: Their Impact on the Clinical Outcome
Authors: Oka Takafumi , Inoue Koichi , Tanaka Koji , Toyoshima Yuko , Tanaka Nobuaki , Okada Masato , Koyama Yasushi , Okamura Atsunori , Iwakura Katsuomi , Fujii Kenshi
Published: July 2021

Background:
Left atrial reverse remodeling (LARR) after catheter ablation (CA) to atrial fibrillation (AF) indicates reduction of AF substrates in left atrium (LA). In this study, we investigated the impact of LARR on the outcome after CA of non-paroxysmal AF (non-PAF; persistent AF and long-standing persistent AF) and determined the predictor of LARR.

Methods and Results:
Consecutive 303 patients who underwent initial CA of non-PAF in our institute were retrospectively analyzed. We performed multi-detector computed tomography (MDCT) to evaluate LA end-systolic volume (LAESV) before and 90 days after CA. We determined LARR using %LA reduction [defined as (pre LAESV - post LAESV) / pre LAESV x100]. The average %LA reduction was 20.2±16.8% (median 22.2%). Then we divided them into LARR group (%LA reduction >20%, N=167) and non-LARR group (%LA reduction<20%, N=136). We followed them for 630±153 days to observe their recurrence rate after 90 days blanking period (BP). The recurrence was less frequently observed in LARR group than non-LARR (31.1% vs 56.4%, p<0.01, log-rank test). Next, we examined the predictor of LARR. In univariate analysis, there were no significant differences in age, sex, CHADS2 score, AF duration before CA, anti-arrhythmic drug administration after CA, CA procedure, echocardiographic data and MDCT parameters. Only the recurrence rate during BP was significantly smaller in LARR than non-LARR (43% vs 61%, p=0.002). Then, we divided BP into three parts, early BP, mid BP and late BP (within 7 days, 8 to 30 days, and 31 to 90 days after CA, respectively). The recurrence rate in LARR group was lower than in non-LARR during early BP (27.5% vs 36.8%, p=0.09), mid BP (30.5% vs 42.6%, p=0.03), and late BP (9.0% vs 31.6%, p<0.01). In multivariable analysis, recurrence in late BP revealed to be the predictor of LARR (odds ratio 0.19, [95% confidence interval: 0.10-0.37]).

Conclusions:
The LARR was associated with better clinical outcome. The absence of recurrence during late BP (31-90 days after CA) was the strong predictor of LARR. These parameters can be acquired at the time point of 3 months after CA and they may be useful for predicting the CA results. Recurrence during late BP might be one of the causes of the poor LARR after CA for non-PAF.
Abstract 17497: Management of Acute Type A Aortic Dissection in an Hybrid Operating Room: - Feasibility and Added Value of Preoperative Angiography and Intravascular Ultrasound
Authors: Janosi Rolf A , Tsagakis Konstantinos , Kahlert Philipp , Kottenberg Eva , Gorla Riccardo , Dohle Daniel S , Frey Ulrich H , Eggebrecht Holger , Mehta Rajendra , Bossone Eduardo , Peters Jürgen , Jakob Heinz , Erbel Raimund
Published: July 2021

Introduction:
Acute type A aortic dissection (ATAAD) is rapidly lethal and requires comprehensive tactics and decision making. To refine our respective approach we retrospectively analyzed our patients undergoing urgent surgery in our hybrid operating room over a 10 year period for the impact of immediate preoperative coronary angiography (CA), aortography, and/or intravascular ultrasound (IVUS) for the detection of coronary artery disease (CAD) and/or arterial malperfusion.

Methods:
136 patients (mean age: 60.6 y ± 13; 63% male, March 2004-February 2014) underwent preoperative CA with or without IVUS. We assessed the time interval from preoperative CA to surgery and the impact for concomitant coronary artery bypass grafting (CABG) or endovascular interventions.

Results:
The delay to proceed with surgery due to preoperative catheterization averaged 32 min ± 26 (Fig. 1) in the setting of the hybrid OR. CA revealed CAD in 47/136 (35%) patients, with CABG consequently performed in 38 (28%). In 12 (9%) patients, CABG was necessary due to ostium obstruction by the dissection. 30-day mortality more than doubled in patients with concomitant CAD (27.7% vs. 11.2%, respectively, p<0.01). However in patients with confirmed CAD, mortality was less 19% (6/31), in those undergoing CABG, compared to 44% (7/16) for isolated aortic repair (p=0.08).

Conclusions:
In a hybrid operating room setting, preoperative coronary and aortic angiography do not unduly delay surgery, facilitate diagnosis of coronary malperfusion, and allowing concomitant CABG in as much as 28% of patients.