bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15628: Prevalence of Non-Pulmonary Vein Triggers in Patients With Previous History Of Coronary Artery Bypass Grafting Undergoing Catheter Ablation for Atrial Fibrillation
Authors: Mohanty Sanghamitra , Trivedi Chintan , Di Biase Luigi , Gunes Mahmut F , Gokoglan Yalcin , Bai Rong , Burkhardt John David , Sanchez Javier , Hranitzky Patrick , Gallinghouse G. J , Al-Ahmad Amin , Horton Rodney , Hongo Richard , Hao Steven , Beheiry Salwa , Natale Andrea
Published: July 2021

Introduction:
Post-operative atrial fibrillation (AF) is reported in up to 5-40% of patients following coronary artery bypass graft (CABG) surgery. Age-related atrial dilatation and fibrosis, electrical remodeling, autonomic imbalance and post-operative inflammation are few of the many pathophysiological factors that play an important role in the genesis and persistence of post-CABG AF. Recent data on fibroblast-myocyte interaction indicates the central role of cardiac fibrosis in the origin of non-pulmonary vein (non-PV) drivers that serve as a source for maintenance of AF. Therefore, we sought to examine the prevalence of non-PV triggers and their impact on ablation outcome in post-CABG AF patients.

Methods:
Two-hundred sixty seven patients with history of CABG undergoing catheter ablation for atrial fibrillation were included in this analysis (61±11 years, 69% male, LVEF 50±10%, LA size 41.0±6.8mm, non-PAF 72%). All patients underwent pulmonary vein antrum (PVAI) and posterior wall isolation. Non-PV triggers were defined as ectopic triggers originating from sites other than pulmonary veins such as interatrial septum, superior vena cava, left atrial appendage, coronary sinus, ligament of Marshall, crista terminalis. Those were identified by isoproterenol challenge and were ablated based on operator choice.

Results:
During ablation, non-PV triggers were detected in 243 (91%) patients. The triggers were most commonly mapped to CS (62%) and LAA (70%). Additional sites of non-PV triggers were LA septum, superior vena cave, crista terminalis and mitral valve annulus. Based on operator choice, non-PV triggers were ablated in 118 of the 243 patients and not targeted in 125 patients. At the end of 32±7 month follow-up after a single procedure, overall success rate was 130 (53.5%). Of the 118 patients undergoing non-PV trigger ablation, 81(68.6%) patients remained arrhythmia-free off anti-arrhythmic drugs compared to 49 of 125 (39.2%) where non-PV ablation was not performed (log rank p <0.001, hazard ratio 3.76 [95% CI 2-6.43]).

Conclusion:
Our results for the first time demonstrate that non-PV foci are highly prevalent in post-CABG AF patients and ablation of those triggers results in significantly better long-term outcome.
Abstract 15675: Variability in Post-Arrest Targeted Temperature Management Practice in the US: 33°C vs. 36°C
Authors: Leary Marion , Delfin Gail , Grossestreuer Anne , Bobrow Bentley , Santos Jillianne , Buckler David , Abella Benjamin S , Blewer Audrey
Published: July 2021

Background:
A recent study examining 33C vs 36C use in Targeted Temperature Management (TTM) after cardiac arrest showed equivalent outcomes. However, it is unclear whether providers are changing goal target temperature based on these findings.

Objectives:
To characterize the state of TTM practice in US hospitals and to assess whether institutions are using a goal temperature of 33C or 36C.

Methods:
A 10-question internet-based survey was sent to a convenience sample of healthcare providers throughout the US. Providers associated with the Penn Alliance for Therapeutic Hypothermia database, Hypothermia and Resuscitation Training Institute, and other resuscitation specific email lists were included. Participants were queried regarding their institution’s TTM protocol. Descriptive analyses were performed.

Results:
Between 12/2014-05/2015, 219 healthcare providers responded from 112 institutions in 35 states. Respondents were staff nurses (39%), advanced practice nurses (28%), physicians (22%) and other providers (11%). Respondents represented medical ICU (25%), cardiac ICU (21%), ED (15%), and other ICUs (39%).

When asked about their institution’s TTM protocol, of those who responded (204/219), 65% reported a goal temperature of 33C, 8% reported 36C, 25% reported either 33C or 36C, and 3% were unknown. When asked how the target temperature was selected, 30% stated there were only adequate data to support 33C, 3% stated there were only adequate data supporting 36C, 42% stated they were reevaluating 33C v 36C, and 25% stated unknown.

A median of 2 (IQR 2-3.5) clinicians from the same institution completed the survey. Of those, 5/39 (13%) of the respondents from the same institution did not agree on or were unsure whether their institution had a TTM protocol; 33% did not agree on the target temperature within their hospital; 64% did not agree or did not know if data supported the instruction’s choice of target temperature.

Conclusions:
Across hospitals in the US, and even within the same institution, the target temperature for post-arrest patients varies widely. More research is required to understand the choice of TTM target temperature for specific patient indications to improve outcomes.
Abstract 15737: Passive Range of Motion Exercise to Enhance Growth in Infants Following the Norwood Procedure: A Pilot Study
Authors: Lambert Linda M , Dagincourt Nicholas , Pemberton Victoria , Trachtenberg Felicia L , Andreas Shelley , Schlosser Robin R , Barnard Teresa , Wood Janine , Daniels Kaitlyn , Harrington Ann T , Miller Thomas A
Published: July 2021

Background:
Growth impairment is common in infants with single ventricle (SV) physiology, especially after the Norwood operation. Passive range of motion (ROM) exercise increases somatic growth in preterm infants without adverse effects but has not been studied in infants with SV.

Objective:
To evaluate the safety and feasibility of a passive ROM exercise program in infants with SV physiology.

Methods:
Passive ROM exercise was administered to all extremities daily according to a standardized protocol, by a trained physical therapist, during post-Norwood hospitalization for up to 21 days or until discharge. Vital signs were measured pre-, intra- and post-procedure and height and weight were measured at baseline, 14 and 21 days, and 3 months of age or at the time of their pre-Glenn visit. Feasibility was determined by percent of days that medium (50-75%) or high (>75%) completion of the ROM exercise was performed. Adverse events (AE) were collected up to 3 months of age or pre-Glenn visit; all were adjudicated by the medical monitor.

Results:
Of 20 infants enrolled at 3 institutions, 70% were male. Parents voluntarily withdrew 1 subject on day 3. Median age at enrollment was 8 days (5-23), with the first ROM exercise started on a median post op day 4 (2-12). Median hospital length of stay following surgery was 15 days (9-131), allowing for an average of 13.4 in-hospital days/patient (3-21) for attempted ROM exercise. High completion of the exercise protocol across all subjects was achieved on 88% of eligible days and medium completion was achieved on an additional 2% of the days. Of 11 AE’s reported in 6 subjects; all were expected and one was determined to be possibly related to the study intervention (midsternal wound dehiscence). There were no clinically significant changes in vital signs. At 3 months, weight for age z-score (-0.84 ±1.2) and length for age z-score (-0.83 ±1.31) were higher than previous reports in SV populations.

Conclusion:
A passive ROM exercise program is safe and feasible in infants with SV physiology and may improve growth following Norwood operation. Larger studies are required to explore the optimal duration of passive ROM exercise and its effect on growth.
Abstract 15738: New Left Bundle Branch Block (LBBB) as a Predictor of Coronary Occlusion After Out-of-Hospital Cardiac Arrest (OHCA)
Authors: Kowalski Lindsey , Jentzer Jacob , Fitzgibbon James , Scutella Michael , Callaway Clifton , Dezfulian Cameron ,   Cardiac Arrest Team
Published: July 2021

Introduction:
In the setting of recent cardiac arrest, it is controversial whether new LBBB with or without Sgarbossa Criteria is an ST elevation (STE) equivalent for predicting acute coronary occlusions. The 2010 AHA guidelines recommend urgent coronary angiography after OHCA when either STE or new LBBB is present. These guidelines are extrapolated from the non-arrest population with few data from OHCA patients.

Hypothesis:
New LBBB on EKG early after OHCA will have a weaker association with acute coronary occlusion than STE.

Methods:
This was a retrospective 2 center study of 284 OHCA subjects who underwent early coronary angiography (within 24 hours of resuscitation). The post-resuscitation EKG was reviewed by a study investigator (LK) with cardiology over reading (JJ). Subjects with either STE or new LBBB were identified. Cardiologists performed percutaneous intervention (PCI) at their discretion when a culprit lesion or acute thrombus was found. We calculated the sensitivity and specificity for STE, LBBB, and STE + LBBB (current standard) for predicting PCI and the odds ratio (OR) and 95% confidence intervals (CI) for the association between these EKG findings and PCI. OR were calculated relative to subjects with no STE or LBBB.

Results:
Of the 284 patients, 125 presented with STE and 19 presented with new LBBB resulting in 144 patients meeting AHA criteria for angiography. None of the LBBB met Sgarbossa Criteria. PCI was performed in 95/125 (76%) of those with STE, 4/19 (21%) of those with LBBB and 99/144 (69%) with either finding. The sensitivity and specificity of STE for PCI were 62% and 77% and the unadjusted OR was 5.82 (95% CI: 3.45, 9.83; p < 0.001). The sensitivity and specificity of ST elevation or new LBBB for PCI was 65% and 66% (OR =3.72 [95% CI: 2.28, 6.09; p < 0.001]). New LBBB was inversely associated with PCI (OR = 0.21 [95% CI: 0.07, 0.66; p = 0.0075]. Survival was higher in those who underwent PCI with STE (OR 8.23 [95% CI: 3.31, 20.48; p <0.0001]) but not in those with LBBB (OR of 0.60 [95% CI: 0.09, 4.01; p=0.5950]).

Conclusions:
Our findings confirm STE after OHCA is strongly associated with coronary occlusion amenable to PCI, but cast doubt on using new LBBB as an STE equivalent. These findings mirror recent reports about LBBB in non-OHCA patients.
Abstract 15783: Reduction in Hepatic Tristetraprolin Increases Oxidative Metabolism and Protects Against High-Fat Diet Induced Diabetes
Authors: Shapiro Jason S , Sawicki Konrad T , Yar Sumeyye , Chen Chunlei , Ardehali Hossein
Published: July 2021

Introduction:
Type II diabetes mellitus (T2DM) is a growing health problem affecting over 29 million Americans and individuals with T2DM have increased mortality after myocardial infarction and stroke. Thus, it is imperative to find novel treatments for diabetes to offset the increased risk of cardiovascular disease (CVD) related mortality. Tristetraprolin (TTP) is an mRNA binding protein first identified as an insulin responsive gene. It binds to AU-rich elements (AREs) in the 3’ untranslated region (UTR) of certain transcripts and promotes their degradation. Reduced TTP expression has been observed in human patients with obesity and insulin resistance, and computational analysis suggests that TTP may bind to and degrade the mRNA of key enzymes involved in glucose oxidation.
Thus, we hypothesized that downregulation of TTP would increase glucose oxidation and protect against T2DM.

Results:
We found hepatic expression of TTP to be decreased in diabetic mice. Using an
in silico
analysis to identify mRNAs that are targeted by TTP and play a role in glucose metabolism, we identified the pyruvate dehydrogenase-E2 subunit (PDH-E2) to contain several conserved TTP binding sites in its 3’ UTR. PDH-E2 expression was significantly increased (mRNA > 1.4-fold; protein > 2-fold) in hepatocytes isolated from liver-specific TTP knockout (KO) mice. Furthermore, measurement of PDH-E2 mRNA stability showed that PDH-E2 mRNA is significantly stabilized with TTP deletion, indicating that TTP regulates PDH-E2 mRNA. We then assessed whether the regulation of PDH-E2 by TTP alters glucose metabolism. Using Seahorse, we found a 1.7-fold increase in oxidative metabolism in TTP KO cells fed with glucose and pyruvate. This increase was reversed with siRNA mediated downregulation of PDH-E2. Systemically, liver-specific TTP KO mice fed a high-fat diet had significantly lower blood glucose levels after glucose tolerance tests and insulin tolerance tests.

Conclusion:
Our results suggest that a decrease in TTP protects against the development of T2DM by increasing PDH-E2 expression and subsequent glucose oxidation in the liver. Together, these data provide a novel, potential therapeutic target for T2DM, a significant modifiable risk factor contributing to CVD mortality.
Abstract 15796: Increased Cardiac Heme Levels Through Cardiac Overexpression of Delta-aminolevulinic Acid Synthase 2 (ALAS2) Lead to Exacerbated Ischemic Injury
Authors: Sawicki Konrad T , Shang Meng , Wu Rongxue , Chang Hsiang-Chun , Khechaduri Arineh , Sato Tatsuya , Kamide Christine , Liu Ting , Prasad Sathyamangla N , Ardehali Hossein
Published: July 2021

Introduction:
Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes.

Hypothesis:
We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart.

Results:
We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of ALAS2. While ALAS2 transgenic mice have normal cardiac function at baseline, their hearts display increased heme content, higher oxidative stress, exacerbated cell death, and worsened cardiac function after coronary ligation compared to non-transgenic littermates. We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death by ALAS2 overexpression is mediated by increased heme accumulation. Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death. Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress. The clinical relevance of these findings was supported by the finding of increased ALAS2 induction and heme accumulation in failing human hearts from patients with ischemic cardiomyopathy compared to non-ischemic cardiomyopathy.

Conclusions:
Heme accumulation is detrimental to cardiac function under ischemic conditions, and reducing heme in the heart may be a novel approach for protection against the development of heart failure.
Abstract 15799: Body Mass Index Modulates Symptomatic Atrial Fibrillation Burden
Authors: Dickerman Deanna , Chalazan Brandon , Shoemaker Ben , Darbar Dawood
Published: July 2021

Introduction:
Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity and increased mortality. Approximately fifty percent of patients have AF-related symptoms and require rhythm control therapy with antiarrhythmic drugs (AADs) or cathether ablation. Obesity is increasingly recognized as an important risk factor for the development of AF.

Hypothesis:
We assessed the hypothesis that body mass index (BMI) modulates AF symptom severity.

Methods:
Cross-sectional data was collected from 1429 patients in the Vanderbilt AF Registry. AF burden was assessed using the Toronto Atrial Fibrillation Severity Scale (AFSS), a validated survey tool measuring the frequency, duration and severity of AF episodes. BMI was categorized according to WHO guidelines, with BMIs of 18.5 kg/m
2
-25 kg/m
2
considered normal, 25 kg/m
2
-30 kg/m
2
overweight, 30 kg/m
2
-35 kg/m
2
obese and >35 kg/m
2
morbidly obese. Patients were grouped according to their current AF treatment regimen; no treatment (n=195), rate control with AV-nodal blocking agents (n=388), rhythm control with AADs (n=678) and prior AF ablation (n=220).

Results:
Morbidly obese patients had higher AFSS scores than normal and overweight patients in the rate control (43.57 vs 38.21: P=0.0057), AAD (46.61 vs. 41.08: P=0.00016) and ablation (44.01 vs. 39.02: P=0.047) groups. In univariate linear models, BMI was associated with an increase in the AFSS score in the rate control (0.27, 95% CI 0.05-0.5, P=0.0181), AAD (0.38, 95% CI 0.21-0.56, P=2.49 x 10
-5
) and ablation (0.38, 95% CI 0.03-0.73, P=0.033) groups. The association remained significant in the AAD group after adjusting for age, gender, race, and comorbidities (0.29, 95% CI 0.11-0.49, P=0.0024).

Conclusion:
In conclusion, our results showed that obesity and increasing BMI were associated with a significant increase in patient-reported measures of AF symptom severity and frequency of AF episodes. The association was most significant in patients on rhythm control therapy with AADs. Further research is needed to determine whether this finding is due to an overlap between subjective obesity-related and AF-related symptoms, or whether obesity may modulate response to rhythm control therapies.
Abstract 15871: Trends in Myocardial Infarction as a Secondary Discharge Diagnosis
Authors: Levitan Emily B , Muntner Paul , Chen Ligong , Howard George , Kilgore Meredith L , Brown Todd M , Safford Monika M
Published: July 2021

Background:
Little research has focused on myocardial infarctions (MIs) that are not the primary illness, and thus MI is listed as a secondary hospital discharge diagnosis.

Objective:
We examined secular trends in the proportion of MI hospitalizations where MI was a secondary diagnosis and changes in the primary reasons for hospitalization associated with secondary diagnosis of MI.

Methods:
Using data from the Medicare national 5% sample for 1999-2011, we identified MI hospitalizations as inpatient claims with primary or secondary discharge diagnoses of International Classification of Diseases, Ninth Revision, Clinical Modification, 410.xx, excluding 410.x2 which represents subsequent episodes of care. This approach has previously been validated. For each year, we calculated the proportion of MI hospitalizations where the MI diagnosis appeared in a secondary position. For hospitalizations with MI as a secondary diagnosis, we examined the trends in the most common primary diagnoses.

Results:
The number of MI hospitalizations ranged from 20,821 in 2003 to 17,640 in 2011 among Medicare beneficiaries in the 5% sample. In 1999, 21% of MI diagnoses were secondary diagnoses, and by 2011, this proportion had risen to 36% (Figure). Over this time period, the proportion of MI hospitalizations with congestive heart failure and coronary atherosclerosis as primary diagnoses declined (16% to 9%, and 11% to 3%, respectively) and the proportion with septicemia as the primary diagnosis increased (3% to 17%).

Conclusions:
Our results suggest that a growing number and percentage of MI diagnoses are occurring among patients hospitalized for other reasons. The causes of this increase require further investigation. Because individuals whose primary illness is not MI are underrepresented in research studies, the appropriateness and effectiveness of secondary prevention of cardiovascular disease in this patient population are not well described.
Abstract 15888: N-3 Polyunsaturated Fatty Acids in Erythrocyte Membranes and Risk of Sudden Cardiac Death in Primary and Secondary Prevention
Authors: Chiuve Stephanie E , Cook Nancy R , Vandenburgh Martin J , Rimm Eric B , Manson JoAnn E , Albert Christine M
Published: July 2021

Introduction:
Long-chain n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-arrhythmic effects in experimental studies and blood levels of EPA + DHA, an objective marker of intake, have been associated with lower risk of sudden cardiac death (SCD) in healthy populations. However, data from observational studies and clinical trials of n-3 PUFAs in secondary prevention have been mixed.

Methods:
We conducted a nested, case-control study among individuals from 6 prospective cohort studies. RBC levels of α-linolenic acid (ALA), EPA, docosapentaenoic acid (DPA), and DHA were measured in 442 cases of SCD and 852 controls matched on age, sex, race, smoking status, fasting status and prevalent and incident CVD using risk-set sampling. The Omega-3 Index was estimated as EPA + DHA. Multivariable conditional logistic regression was used to estimate the relative risk (RR) separately in each cohort. The RRs were combined using random effect meta-analyses and stratified by presence of absence of known CVD prior to SCD.

Results:
In this population, the mean age was 64 years, 51% were women and 41% had prior CVD. Higher EPA and DHA levels, as summarized by the Omega-3 Index, were associated with lower risk of SCD in the entire population (Table). Compared to the lowest quintile, the RR in the highest quintile of the Omega-3 Index was 0.40 (95%CI, 0.21-0.77; P, trend= 0.04). When stratified by history of prior CVD, this association was restricted to individuals without prior CVD (Table, P, trend = 0.03). Neither DPA nor ALA was associated with risk of SCD in those with or without CVD.

Conclusions:
In this prospective nested, case-control study, the inverse association between long-chain n-3 PUFAs and SCD was limited to individuals without prior CVD. These data suggest that the utility of n-3 PUFAs as markers of SCD and/or as preventative dietary supplements may be greater in a primary prevention population.
Abstract 15928: A Mobile Health Driven Walking Program Improves Quality of Life but not Fitness or Fatness in Obese Sedentary Women
Authors: Stewart Kerry J , Katz Jonathan , Dobrosielski Meredith , Ouyang Pamela
Published: July 2021

Background:
Many mHealth programs exist for increasing physical activity (PA) yet few have been tested for their effects on fitness, fatness, and health related quality of life (HRQOL).

Methods:
We conducted a 3-month randomized trial that examined 2 message formats that promoted the 10,000 steps/day walking program. Women (n=70), aged 48±12 years, BMI 35.0 ±3.8, with self-report of no regular (PA), were given a FitBit and smartphone, which automatically sent daily step data to us daily. Daily messages with feedback about meeting step goals and motivation to add 500 more daily steps/week were sent to the subject’s smartphone. We compared the Multimedia Messaging Service (MMS) consisting of audio, video and graphs versus the Short Message Service (SMS), or plain text messages. Message content was the same for both groups. Outcomes included the 6-minute walk test, weight, waist and hip circumferences, BMI, SF-36, and Profile of Mood States (POMS). We hypothesized that MMS subjects would be more engaged, walk more, and attain greater gains in study outcomes.

Results:
We delayed messaging for the first 2 weeks to establish a daily step baseline, which was 6665 ±2270. There were no group differences in daily steps at baseline or at any time point in the study. Daily steps in Month 1 was 6926±2465; Month 2, 7327± 3310; and Month 3, 6642±2914. The increases from baseline to the full Month 1 (p=0.004) and Month 1 to 2 (p=0.025) were significant but not the decrease from Month 2 to 3. The FitBit was worn 91% of study days in both groups. There were no changes or group differences in any fitness or fatness measure. Both groups similarly improved SF-36 General Health (p=0.02) and Vitality (p=0.01); and POMS Fatigue (p=0.01), Vigor (p=0.001), Tension-Anxiety (p=0.03), and Total Mood Score, (p=0.02). Conclusions: Baseline steps were about 2-3 times more than expected for sedentary women. It seems that the novelty of using a tracking device accelerated the planned progression for walking, with a much higher than expected step count initially and then a slight drop over time. An average of 10,000 steps/day was not met. There were no changes in physical measures though indicators of HRQOL improved. Contrary to our hypothesis, the different messaging formats did not affect outcomes.
Abstract 15931: Risk of Post Procedural Atrial Fibrillation in Patients Undergoing Transcatheter Aortic Valvular Replacement - A Meta-Analysis
Authors: Qureshi Waqas , Nasir Usama b , Soliman Elsayed Z , Belford Peter M , Gandhi Sanjay K , Applegate Robert J , Zhao David X
Published: July 2021

Introduction:
Atrial fibrillation is a common postoperative complication of surgical aortic valve replacement (SAVR). However, it is not known if the incidence of post procedure AF is impacted by performing Transcatheter Aortic Valvular Replacement (TAVR) instead of SAVR.

Hypothesis:
There is no difference in risk of post procedure incident AF in patients undergoing TAVR vs. SAVR.

Methods:
We systematically reviewed studies evaluating TAVR vs. SAVR and risk of post procedure AF. We searched MEDLINE, EMBASE, CINAHL, Web of Science, meeting abstracts, presentations and Cochrane central databases from inception through May 2015. For a study to be selected, it had to report the rates of incident AF in individuals undergoing TAVR. Data were extracted by 2 independent authors (WTQ and UBN). Forrest plot was created to show the effect sizes (Figure 1).

Results:
A total of 8 studies including 2483 patients (mean age 81.4 years, 70.3% male) were analyzed. There were 1293 patients that underwent TAVR and 1190 patients that underwent SAVR. The 1- year incidence of AF was 231 (17.9%) in TAVR group vs. 377 (31.6%) in SAVR group. In a random effects model, patients treated with TAVR had a 48% decreased risk of post procedural 1 year risk of AF [pooled Risk Ratio (95% confidence interval) 0.52 (0.37-0.73), p <0.001]. There was moderate heterogeneity in the results (I2 = 80%). The risk of AF was higher in studies with older patients and was lower in studies with higher proportion of patients that underwent transfemoral TAVR vs. transapical TAVR.

Conclusions:
In this meta-analysis, the post procedure risk of AF was lower in TAVR group as compared to SAVR group. The risk of post procedure AF should be considered while making decision for TAVR vs. SAVR.
Abstract 15973: The Association Between Blood Pressure Control and Outcomes Among Black Participants in the Jackson Heart Study
Authors: Randolph Tiffany C , Greiner Melissa A , Egwim Chidiebube , Hernandez Adrian F , Thomas Kevin L , Curtis Lesley H , Muntner Paul , Wang Wei , Mentz Robert J , O'Brien Emily C
Published: July 2021

Introduction:
The 2014 hypertension (HTN) guidelines liberalized blood pressure (BP) goals for people ≥60 years.

Hypothesis:
Increased systolic and diastolic blood pressure (SBP/DBP) will be associated with a higher risk of mortality and heart failure hospitalization (HFH) across all age groups.

Methods:
We used age-adjusted Kaplan-Meier estimates to calculate the cumulative incidence of mortality and HFH across SBP/DBP categories (Figure) among 5280 participants of the Jackson Heart Study (JHS), an exclusively black population. We used Cox proportional hazards models to investigate associations between baseline visit SBP/DBP and both mortality and HFH. Linearity of associations and differential effects by age were assessed.

Results:
Median age was 56 years (IQR: 46-65); 63% were female; median SBP was 125 mmHg (IQR: 114-137); and median DBP was 79 mmHg (IQR: 72-86). There were 520 deaths over 9 years and 340 HFHs over 7 years. The age-adjusted cumulative incidence of both mortality and HFH increased with SBP, while rates of both outcomes were similar by DBP (Figure). After multivariable adjustment, every 10 mmHg increase in SBP was associated with increased mortality (HR 1.12 95% CI [1.06, 1.17]; p<.001) and HFH (HR 1.07 95% CI [1.00, 1.14]; p=0.05). The mortality risk per 10mmHg increase in SBP was greater in participants <60 years (HR 1.26 95% CI [1.13, 1.42]; p<.001) than ≥ 60 years (HR 1.09 95% CI [1.03, 1.15]; p=.004). DBP was inversely associated with risk of mortality (HR 0.85 95% CI [0.77, 0.94]; p= .002) and not associated with HFH (p=.20).

Conclusions:
In this JHS cohort, SBP was associated with both mortality and HFH, while DBP was inversely associated with mortality. Adults across all age groups were at increased risk of mortality as SBP increased. In the context of new HTN guidelines, these findings have important implications and should be considered when determining BP treatment goals in Black patients.
Abstract 15999: Beyond Morbidity and Mortality: Academic Outcomes in Children With Congenital Heart Disease
Authors: Oster Matthew , Watkins Stephanie , Hill Kevin , Meyer Robert
Published: July 2021

Introduction:
While children with congenital heart disease (CHD) are known to have neurodevelopmental challenges, how these challenges translate to school performance is unknown. The purpose of our study was to compare the academic achievement of children with CHD to that of children without known birth defects.

Hypothesis:
Children with CHD would have lower standardized test performance scores and greater need for grade retention than their peers without birth defects.

Methods:
We performed a retrospective cohort study comparing educational outcomes for children born 1998-2003 with CHD, identified from the North Carolina (NC) Birth Defects Registry, vs. those without a known birth defect, randomly sampled from NC birth certificates. All children were linked to 3rd grade public school records from the NC Department of Public Instruction through 2012. We performed logistic regression to compare our outcomes of interest: a) meeting standards on the reading and math portions of 3rd grade End of Grade Testing, and b) 3rd grade retention. Models were adjusted for maternal education, public pre-K enrollment, and race/ethnicity.

Results:
Of the 5624 subjects with CHD and 10,832 with no birth defect, 51% and 60% were linked, respectively, to 3rd grade standard End of Grade testing records. Compared to children without a birth defect, those with CHD were more likely not to meet proficiency standards in reading (OR 1.4, 95% CI 1.3-1.6), math (OR 1.2, 95% CI 1.1-1.4), or both (OR 1.5, 95% CI 1.3-1.7). (Figure) Similarly, children with CHD were more likely to be retained in 3rd grade (2.8% vs. 1.9%, OR 1.4, 95% CI 1.1-1.9).

Conclusions:
Children with CHD have poorer educational achievement as compared to their peers without birth defects. History of CHD should be considered an important factor in determining a student’s need for specialized education services.
Abstract 16016: Role For Macitentan in Angiogenesis of Right Ventricle, Peripheral Muscle and Lungs in Pulmonary Arterial Hypertension
Authors: Nadeau Valerie , Bonnet Sebastien , Paradis Renée , Tremblay Eve , Potus Francois , Lambert Caroline , Iglarz Marc , Provencher Steeve
Published: July 2021

Background:
Pulmonary arterial hypertension (PAH) is a vascular disease characterized by remodeling of distal pulmonary arteries (PA) leading to increased mean PA pressure, subsequent right ventricular (RV) failure and ultimately death of patients. Impaired angiogenesis is now recognized as a major factor in PAH etiology. It contributes not only to the decrease in lung perfusion but also to a rarefaction of the capillary network within the skeletal muscle and RV leading to exercise intolerance and RV failure. Several studies have suggested that endothelin-1 (ET-1) contributes to decrease angiogenesis in PAH. In light of these observations, we hypothesized that macitentan, an ET-1 receptors blocker, improves PAH by promoting angiogenesis in lungs, RV and skeletal muscles.

Methods/Results:
In the Sugen/hypoxia rat model of PAH, we demonstrated by right catheterization in closed chest rats that compared to vehicle treated animals, daily treatment during two weeks with macitentan (30 mg/kg) decreases significantly mean PA pressure (n=8-20; p<0.01) and total pulmonary resistance (n=8-20; p<0.05) and improves cardiac output, stroke volume (n=7-17; p<0.05) and RV hypertrophy measured by echo (n=6-10; p<0.05). These effects were associated with an increase of 2.9 fold in lung blood perfusion (n=6), 4.1 fold in quadriceps perfusion (n=5-7) and 1.5 fold in right ventricle perfusion (n=5-6) measured in vivo by micro CT angiogram (p<0.05). Both in vivo lectin perfusion (n=4-10; p<0.05) and immunologic CD31 staining (n=4-5; p<0.05) confirmed these findings. In the lungs, the hemodynamic and perfusion improvements were associated with decreased vascular remodeling (H&E) (n=6-17; p<0.01). In vitro, using primary cultured human endothelial cells isolated from distal PA (PAEC) and RV (RVEC), we showed that macitentan decreases PAH-PAEC proliferation (Ki67 assay) and resistance to apoptosis (TUNEL assay), while increasing angiogenesis capacity of healthy PAEC and RVEC (matrigel assay).

Conclusion:
Our data provide structural and functional evidence that ET-1 receptor inhibition with macitentan may improve PAH by promoting angiogenesis.
Abstract 16067: Phosphorylation of Lamin-A/C Modulates Peak Sodium Current in a Patient With Cardiac Conduction Disease
Authors: Olaopa Michael , Spoonamore Katherine , Chen Peng-Sheng , Ai Tomohiko , Vatta Matteo
Published: July 2021

Introduction:
Deleterious variants in the
LMNA
gene, which encodes for Lamin-A/C, have been shown to be associated with cardiac conduction diseases (CCDs) and cardiomyopathy. We previously reported that two
LMNA
variants found in patients presenting with CCDs can prevent the
LMNA
-mediated activation of peak sodium current (I
Na
). In addition, western blot analyses showed phosphorylation of Lamin at serine 22 (S22) was reduced in HEK293 cells expressing either variant. Thus, we sought to investigate what potential role S22 plays on modulating Nav1.5 function. In this study, we focused our analyses on one of the two variants, which is c.1634G>A (p.R545H) in
LMNA
. We tested the hypothesis that S22 affects peak I
Na
.

Methods and Results:
We generated two plasmids that mimic unphosphorylated wild type
LMNA
(
p.S22A
) and constitutively phosphorylated mutant
LMNA
(
p.S22D-p.R545H
). We measured and compared peak I
Na
using patch clamp techniques in HEK293 cells transfected with each
LMNA
and
SCN5A
plasmids. Our study showed that
p.S22A
significantly prevented the
LMNA
-mediated activation of peak I
Na
by 63% compared to wild type (
p.S22A
: -121 ±11 pA/pF, N =10 vs. wild type
LMNA
: -340 ±45 pA/pF, N=10, Mann-Whitney
U
=2, p<0.0005 one-tailed). On the contrary,
p.S22D-p.R545H
partially restored the reduced peak I
Na
by 44% (
p.S22D-p.R545H
: -137 ±43 pA/pF, N=7 vs.
p.R545H
: -95 ±15 pA/pF, N=10, Mann-Whitney
U
=27, p<0.1 one-tailed).

Conclusions:
Our data indicate the loss of phosphorylation at S22 significantly reduces the
LMNA
-mediated activation of peak I
Na
. In the disease state, constitutive phosphorylation partially restores, yet fails to normalize peak I
Na
. Our observation suggests that S22 could represent a potential therapeutic target in patients with
LMNA
-mediated CCD. To our knowledge, this is the first study to functionally link phosphorylation of Lamin-A/C at S22 to peak I
Na
levels and Nav1.5 function.
Abstract 16121: The Decade of Change: Survival Following Out-of-hospital Cardiac Arrest in Teaching versus Nonteaching Hospitals in the United States: 2000-2012
Authors: Eid Shaker M , Albaeni Aiham , Akinyele Bolanle , Raghavakurup Lekshmi N , Chandra-Strobos Nisha
Published: July 2021

Background:
All hospitals, regardless of teaching status, need to provide care for OHCA patients. Whether outcomes differ in teaching vs nonteaching hospitals is unknown and was examined in this study.

Methods:
Using the National Inpatient Sample database, we selected adults ≥18 years old admitted with a principle diagnosis of non-traumatic OHCA (ICD-9 CM codes 427.5 & 427.41) between 2000 and 2012. Patients were stratified to teaching (THs) or nonteaching hospitals (NTHs). The association of hospital teaching status with length of stay, total charges/case, survival to discharge, and survival with good neurologic outcome was assessed by multivariate logistic regression or generalized linear regression models, adjusting for patient and hospital-level characteristics.

Results:
Of 186,483 admitted patients, 86,053 (46.15%) were treated at teaching hospitals during the study period. Overall OHCA incidence in the United States was 3.86 per 10,000 hospital admissions. Patients at teaching hospitals were more often younger, more likely to have VF, and less likely to be Caucasian [all p < 0.001] but with a similar comorbidity burden. Mean length of stay and total charges were higher in teaching hospitals (5 vs. 4 days, p<0.01 & $72,436 vs. $52,917, p<0.01). Risk-adjusted survival and survival with good neurologic outcome were significantly better in THs as compared to NTHs (odds ratio,
1.06
; 95% CI 1.02 – 1.14 &
1.19
; 95% CI 1.09 – 1.29 respectively). Despite a significant increase in OHCA survival at NTHs between 2000 and 2012 (
P
trend
<0.01), OHCA survival rate at THs remained higher without any change in trend (
P
trend
=0.07) during the study period.

Conclusion:
For OHCA patients in the US, survival has been consistently higher in teaching hospitals. However, a dramatic improvement in survival has been realized in nonteaching hospitals over the last 12 years with lesser healthcare expenditure when compared to teaching hospitals; this phenomenon is worthy of further study.
Abstract 16161: GSK-3β Activates Autophagy and Protects Against Cardiac Aging Through Ulk1
Authors: Zhai Peiyong , Shirakabe Akihiro , Yamamoto Takanobu , Ikeda Yoshiyuki , Magrys Bonaventure , Maejima Yasuhiro , Sadoshima Junichi
Published: July 2021

Accumulating lines of evidence suggest that glycogen synthase kinase-3β (GSK-3β) is involved in aging. However, the effects of GSK-3β on cardiac aging and the underlying mechanisms remain to be elucidated. Autophagy, a protective mechanism in aging, decreases with age. We hypothesized that GSK-3β attenuates cardiac aging via Ulk1, a regulator of autophagy, and studied constitutively active GSK-3βS9A knock-in mice (βKI), GSK-3βS9A/Ulk1+/- bigenic mice (Bigenic), and GSK-3β+/- mice (βKO) up to 24 months (M) of age. Left ventricular (LV) weight/body weight (LVW/BW, mg/g) was not significantly different among wild-type mice (WT), βKI and βKO at 6M. It was lower in βKI (2.4±0.1, p<0.005) and higher in βKO (4.8±0.8, p<0.05) than in WT (3.8±0.2) at 24M. Cardiomyocyte cross-sectional area (CSA, μm2) was smaller in βKI (360±9, p<0.001) but bigger in βKO (540±11, p<0.01) than in WT (502±5) at 24M. The LVW/BW was greater (3.5±0.2, p<0.001) and the CSA was bigger (527±4, p<0.001) in Bigenic than in βKI at 24M. These data demonstrate that GSK-3β inhibits age-dependent cardiac hypertrophy via Ulk1. Cardiac fibrosis (%) was more in βKO (5.4±0.1, p<0.001) and less in βKI (2.4±0.1, p<0.001) than in WT (4.0±0.3) at 24M. There was much more fibrosis in Bigenic (5.5±0.6, p<0.001) than in βKI at 24M. These data show that GSK-3β reduces age-related cardiac fibrosis via Ulk1. LV end-systolic elastance (Ees, mmHg/μl) and chamber stiffness constant (CSC, μl-1) were not significantly different among WT, βKI, and βKO at 6M. At 24M, the Ees was lower in βKO (4±1, p<0.05) and higher in βKI (12±3, p<0.05) than in WT (7±0), and the CSC was higher in βKO (0.19±0.01, p<0.001) and lower in βKI (0.06±0.01, p<0.001) than in WT (0.14±0.01). The beneficial effects of GSK-3β on cardiac function were abolished in the Bigenic, indicating that GSK-3β prevents age-specific cardiac dysfunction via Ulk1. The level of p62, a protein degraded by autophagy, was lower in βKI and higher in βKO than in WT. The numbers of autophagosomes and autolysosomes were significantly greater in βKI/tfLC3 (tandem fluorescent mRFP-GFP-LC3) mice than in tfLC3 or βKI/tfLC3/Ulk1+/- mice. These data suggest that GSK-3β activates autophagy via Ulk1. In conclusion, GSK-3β attenuates cardiac aging by activating Ulk1-dependent autophagy.
Abstract 16342: Feasibility and Safety of Intra-operative Mapping for Diagnosis of the Substrate of Atrial Fibrillation
Authors: van der Does Lisette , Yaksh Ameetha , Kik Charles , Knops Paul , Oei Frans , van de Woestijne Pieter , Lanters Eva , Teuwen Christophe , Bogers Ad , Allessie Maurits , de Groot Natasja
Published: July 2021

Introduction:
Multi-site, high-resolution mapping can be used to identify either the trigger or substrate perpetuating atrial fibrillation (AF). The goal of this study was to assess the feasibility and safety of a new high-resolution epicardial mapping approach.

Hypothesis:
Epicardial atrial mapping of the entire atria can be safely performed as a routine procedure during cardiac surgery.

Methods:
Epicardial mapping of the entire right atrium, left atrium and Bachmann’s Bundle was performed in 291 patients (218 male, age:66±11yrs) undergoing elective surgery during sinus rhythm (SR) and (induced) AF using high-resolution mapping arrays with inter-electrode distances of 1-2mm. Electrophysiological parameters were quantified and designated to anatomical quadrants of 1cm2.

Results:
AF was non-inducible in 36 patients. Hemodynamic parameters (mean arterial pressure, right atrial pressure, BIS score, ST-T segment alterations) before and during SR mapping were comparable (P<0.22). During AF, only mean arterial pressure (71±11 versus 67±10mmHg (P<0.004)) and right atrial pressure (10±4 versus 11±4mmHg (P<0.0001)) decreased. Total mapping time during SR or AF was respectively 3±1min. and 4±2min. Beat-to-beat variation of SR cycle length and peak-to-peak amplitude of unipolar potentials were respectively 0.04±14.42ms and -0.01±0.53mV, reflecting stability of the mapping array. Complications were not observed.

Conclusions:
Our novel intra-operative epicardial atrial mapping approach can be safely applied during both SR and AF. This mapping approach is the first technique allowing quantification of the arrhythmogenic substrate in the individual patient thereby taking the first step towards personalizing treatment of AF.
Abstract 16415: Switching of ADP Receptor Inhibitor After Hospital Discharge Among Myocardial Infarction Patients: Insights From the TRANSLATE-ACS Observational Study
Authors: Zettler Marjorie E , Peterson Eric D , McCoy Lisa A , Effron Mark B , Anstrom Kevin J , Henry Timothy D , Baker Brian A , Messenger John C , Cohen David J , Wang Tracy Y
Published: July 2021

Background:
With the availability of several ADP receptor inhibitors (ADPri), switching between agents is known to occur. However, among myocardial infarction (MI) patients treated with percutaneous coronary intervention (PCI), the incidence and patterns of post-discharge ADPri switching are unknown.

Methods:
Using data from the TRANSLATE-ACS study (2010-2012), we assessed the incidence of post-discharge ADPri switching among 8672 MI patients who were discharged after PCI and remained on ADPri therapy through 1 year post-MI. We examined bleeding and major adverse cardiovascular events (MACE: MI, stroke, unplanned revascularization) within 7 days before and after switching.

Results:
During the first year after index MI discharge, 663 patients (7.6%) had a switch in ADPri; switching occurred at a median of 50 days (IQR 7-154) post-discharge. Switching occurred most frequently in patients discharged on ticagrelor (64/226, 28.3%), then prasugrel (383/2489, 15.4%), and clopidogrel (216/5957, 3.6%, p<0.001). Among patients discharged on prasugrel, 97.3% of switches were to clopidogrel; 87.5% of ticagrelor switches were to clopidogrel. Among clopidogrel patients who switched, 55 (25.5%) had a MACE event in the 7 days preceding switch. Among prasugrel and ticagrelor patients who switched, a GUSTO moderate/severe bleeding event occurred in 5 (1.3%) and 1 (1.5%) patients, respectively, in the 7 days preceding switch. Patients switched from prasugrel or ticagrelor most often cited cost as a reason for the switch (43.6% and 39.1%, respectively), while 60.7% of patients switched from clopidogrel attributed the switch to a physician decision. In the week following a switch, both MACE and major bleeding events were infrequent (table).

Conclusions:
ADPri switching occurred infrequently within the first year post-MI. Switching occurred more commonly among patients discharged on higher potency ADPri, but only a minority of these switches were triggered by bleeding.
Abstract 16433: Protection Conferred by Y-chromosome Against Hypoxia-induced Pulmonary Hypertension is Not Due to Ddx3y Gene
Authors: Umar Soban , Barseghyan Mariam , Centala Alex , Itoh Yuichiro , Mackie Ryan , Arnold Arthur P , Eghbali Mansoureh
Published: July 2021

Introduction:
Pulmonary hypertension (PH) is a chronic pulmonary vascular disease characterized by elevated pulmonary arterial pressures and vascular remodelling leading to right ventricular failure. It is 4 times more likely to occur in females than males. The reasons for the female predominance or male protection are still not fully elucidated. Our previous work showed that in gonadectomized (GDX) Four Core Genotypes (FCG) mice (XX and XY males, XX and XY females, C57BL6/J), XY mice having a Y-chromosome (XYM, XYF) develop less severe PH than the XX mice lacking a Y-chromosome (XXM, XXF).

Hypothesis:
Protection against hypoxia-induced PH in gonadectomized mice is due to the presence of Y-chromosome and not due to the number of X-chromosomes. We also examined the role of a Y-chromosome gene Ddx3y, a cellular growth suppressor expressed consistently in the lungs and heart in protection against PH.

Methods:
Here we used GDX XY* C57BL/6J mouse model which allows us to have male mice with XY or XXY and female mice with XX or XO genotypes (n=5/group). In addition we also used XX female mice with and without a transgenic copy of Y-chromosome gene Ddx3y (n=10/group). Mice were gonadectomized at day-75 and 4-weeks after gonadectomy, were exposed to hypoxia (10% O2) for 3-weeks. RVSP was measured through direct catheterization.

Results:
In the GDX XY* model, right ventricular systolic pressure (RVSP) in mice with Y-chromosome (XY=33.5±0.6, XXY=32±2mmHg) was significantly lower than that of mice without a Y-chromosome (XO=38.7±2, XX=41.5±3.8, P<0.05). We concluded that presence of Y-chromosome confers protection against PH in GDX mice. Four Y-chromosome genes are expressed consistently in the lungs and heart (Ddx3y, Kdm5d, Uty, Eif2x3y) and are thus candidate protective genes. We did not find a significant difference between the RVSP of XX mice with or without a transgenic copy of Ddx3y.

Conclusions:
We conclude that Y-chromosome confers protection against hypoxia-induced PH in GDX mice which is not due to Ddx3y gene. Next we plan to investigate effects of the other Y-chromosome candidate genes Kdm5d, Uty, and Eif2x3y.