bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16788: Delivery of Pluripotent Stem Cell Specific Microrna-294 Induces Cardiomyocyte Proliferation Augmenting Cardiac Function After Myocardial Infarction
Authors: Khan Mohsin , Verma Suresh K , Garikipati Venkata N , Zhou Jibin , Benedict Cynthia , Nickoloff Emily , Johnson Jennifer , Koch Walter J , Kishore Raj
Published: July 2021

Rationale:
Embryonic heart is characteristic of rapidly dividing cardiomyocytes that give rise to sufficient numbers required to build a working myocardium. In contrast, cardiomyocytes retain some proliferative capacity in the neonates but lose most of it in adulthood. Embryonic stem cell cycle (ESCC) miRs are a class of microRNAs regulating the unique cell cycle of ESCs and their characteristic pluripotency. Nevertheless, expression of miR-294, a member of the ESCC miRs is lost during developmental transitions from the ESCs to mature cells. Effect of miR-294 to induce cardiac proliferation and heart function has not been previously studied.

Objective:
To determine whether miR-294 drives cardiomyocyte cell cycle reentry leading to augmentation of cardiac function after myocardial infarction.

Methods and Results:
miR expression analysis was carried out in the heart during development to determine levels of miR-294. Elevated level of miR-294 was observed in the prenatal heart confirmed by qRT-PCR. In contrast, miR-294 expression is lost in the neonates and adult mice. To further assess the effect of miR-294, neonatal ventricular cardiomyocytes (NRVMs) were treated with miR-294 mimic to determine the effect on proliferation and cell cycle. Elevated mRNA levels of cyclins A2 and E1 together with CDK2 was observed in NRVMs treated with 25nM mimic for miR-294. Increased expression of p-histone 3, PCNA (S-phase), Aurora B kinase (G2/M) and Ki67 was confirmed by immunocytochemistry in NRVMs after miR-294 treatment compared to control cells. Intramyocardial administration of miR-294 was carried out in mice at the time of myocardial infarction to determine whether miR-294 delivery increases cardiomyocyte proliferation and survival in response to injury. Enhance cardiac function was observed in mice receiving miR-294 3 weeks after myocardial infarction. Concurrently, increase myocyte proliferation was observed in the heart after miR-294 treatment as analyzed by BrdU uptake, PCNA and Aurora B expression by immunostaining.

Conclusion:
Ectopic expression of miR-294 recapitulates embryonic signaling and enhances cardiomyocyte ability to proliferate and reenter the cell cycle leading to augmented cardiac function in mice after myocardial infarction.
Abstract 16807: Burden and Timing of Hospitalizations in Heart Failure: A Community Study
Authors: Chamberlain Alanna M , Gerber Yariv , Dunlay Shannon M , Manemann Sheila M , Weston Susan A , Roger Veronique L
Published: July 2021

Background:
Heart failure (HF) patients are experiencing an epidemic of hospitalizations. Nevertheless, data on the frequency and distribution of hospitalizations over the course of the disease are lacking.

Methods:
We determined the rates of hospitalizations during periods of follow-up in Olmsted County, MN residents with incident HF from 2000-2010. HF was identified using ICD-9 code 428 and validated by the Framingham criteria. All hospitalizations were obtained for the 2 years following incident HF and each was categorized as due to HF, other cardiovascular (ICD-9 codes 390-427, 429-459), or non-cardiovascular causes. Follow-up was divided into discrete time periods (epochs): 0-30, 31-182, 183-365, and 366-730 days. Negative binomial regression examined associations between epochs of follow-up time and hospitalizations.

Results:
Among 1702 incident HF patients (mean age 76, 44% male), 1143 (67%) were hospitalized at index. Over the 2 year follow-up, 3008 hospitalizations were observed among 1136 patients, and 351 patients were hospitalized within 30 days of incident HF (median time from HF to hospitalization: 11 days). The majority of hospitalizations were due to non-cardiovascular causes (63% vs. 14% HF, 23% other cardiovascular); however, a larger proportion of HF and other cardiovascular hospitalizations were observed within the first 30 days (52% non-cardiovascular, 18% HF, 30% other cardiovascular) compared to the other time periods. The rate of hospitalization was highest within the first 30 days and was similar across sex, presentation of incident HF (inpatient, outpatient), and type of HF (preserved (≥50%), reduced (<50%) ejection fraction) (Table).

Conclusions:
HF patients experience high rates of hospitalizations, particularly within the first 30 days, and the majority of hospitalizations are for non-cardiovascular causes. Continued efforts to manage comorbid conditions and reduce hospitalizations in HF patients are needed.
Abstract 16848: Evolving Standards for Athlete ECG Interpretation Result in Declining Abnormal Rates
Authors: Marek Joseph C , Marek Kathleen A , Davis Johneen , Sinno Ziad , Zimmerman Frank
Published: July 2021

Introduction:
ECG screening of athletes is believed to be effective in addressing the issue of sudden cardiac death (SCD) in young athletes. One criticism against screening has been the concern for a high percentage of abnormal ECG findings recently reported to be as high as 21.8%. The prevalence of conditions believed to be responsible for SCD is 0.3-0.7%. Since 2007 there have been several modifications of interpretation standards.

Hypothesis:
We hypothesized that these changing standards in addition to increased experience reading screening ECGs would reduce the abnormal ECG rate in our screening program and bring it closer to the expected prevalence of SCD causing conditions.

Methods:
The Young Hearts for Life (YH4L) ECG screening program has been performing ECGs on young athletes in the Chicago region since 2006. Interpretation was limited to six cardiologists experienced in the interpretation of adolescent ECGs and possessing knowledge of the ECG changes that occur in conditions associated with SCD. Two of these cardiologists read 90% of the total ECGs during the study. As new standards and research for interpretation were published, they were incorporated into the YH4L screening protocol. The annual abnormal rate for screening ECGs was compiled from 2006-2014.

Results:
A total of 108,057 ECGs were performed from 2006-2014 on young athletes age 14-19. The abnormal ECG rate gradually declined as the new interpretation standards were employed (see graph). The highest abnormal ECG rate of 2.43% was seen in the early period of the screening program (2007) compared to the rate of 1.00% seen during the most recent ECG screening (2014). The abnormal ECG rate was reduced by 59% over the 8 year time period (p<0.001).

Conclusions:
Greater experience and evolving standards for interpretation of screening ECGs in young athletes have resulted in a 59% reduction in abnormal rates found in the YH4L screening program. This rate is closer to expected prevalence of SCD causing conditions.
Abstract 16851: ST Segment Variability as a Predictor of Clinical Deterioration in Hypoplastic Left Heart Syndrome
Authors: Vu Eric L , Rusin Craig G , Penny Dan J , Kibler Kathy K , Easley Ronald B , Andropoulos Dean , Brady Ken
Published: July 2021

Introduction:
The interstage mortality rate for hypoplastic left heart syndrome (HLHS) is high at 12%. Modalities to predict clinical decline would be useful in this high risk population. Due to cardiac conduction system anomalies in HLHS, electrocardiogram (ECG) monitoring of the ST segment is confounded. Our aim is to develop a monitor of ST variability that predicts deterioration despite the presence of an abnormal ST segment baseline.

Hypothesis:
Increased ST variability is associated with clinical deterioration in HLHS.

Methods:
A prospective, observational study was conducted at Texas Children’s Hospital using interstage recordings of 5 lead ECG. From January 2013 to January 2014, 25 subjects were admitted with HLHS; 21 had requisite ECG data for inclusion. In 11 subjects, there were 17 deterioration events, defined as rapid response team (RRT) activation. Events included 13 instances of respiratory failure with intubation and 4 instances of chest compressions. The control group included 10 subjects with no deterioration. An approach to quantify variability was developed where the ST segment vector was resolved using 3 orthogonal leads (II, V5, and aVF) and variability quantified with two metrics: 1) Displacement: distance between ST vector tips at 30 s intervals and 2) Component range: sum of ST vector tip movement in 3 dimensions over 10 min intervals. Comparison was made with the four hour window prior to RRT activation in the deterioration group against the four hour window prior to ICU discharge in the control group.

Results:
Four hours prior to clinical deterioration, increased ST variability was noted in both methods. For the 30 s displacement method, subjects with deterioration had a median value of 0.059 mm [IQR: 0.039 - 0.075] compared with 0.037 mm [IQR: 0.025 - 0.053] in the control group (p = 0.023). For the 10 min component range method, subjects with deterioration had a median value of 3.0 mm [IQR: 1.8 - 4.5] compared with 1.9 mm [IQR: 1.0 - 2.8] in the control group (p = 0.031).

Conclusions:
ST variability is increased in HLHS subjects prior to deterioration. Although conduction abnormalities limit the utility of ST monitoring in this population, quantification of ST variability may have a role in advanced systems to monitor clinical deterioration.
Abstract 16853: Going Beyond Patient Satisfaction: Unmet Psychosocial Needs Following Coronary Revascularization
Authors: Manierre Matthew , Elliott Daniel J , Jurkovitz Claudine T , Weintraub William S , Martin Steven S
Published: July 2021

Background:
Hospitals routinely employ measures of patient satisfaction to understand if patient needs are being met, but they rarely look beyond patient discharge and general satisfaction. This study’s objective was to assess both satisfaction and problems that may be faced by patients after discharge from a large east coast hospital following percutaneous coronary intervention or coronary artery bypass graft.

Methods:
Permission was gained from almost all patients to be contacted by phone after discharge. University researchers called them 90 days after discharge to gauge both their satisfaction with post-discharge care and any problems they may have experienced.

Results:
A total of 365 patients accepted to participate for a response rate of 42.1%. Surveys were administered on average 134 days after discharge (SD=22.7). While the three measures of patient satisfaction used found that 95% of the patients were satisfied or very satisfied with post discharge care, many patients still reported substantial difficulties since they were discharged. In particular, 28% had problems feeling depressed or stressed, 21% reported having difficulty paying for healthcare related expenses, and 32% had difficulty keeping up with diet or exercise plans.

Open ended probes expanded on the first two problems. In the case of depression and stress, many respondents struggled to acclimate to reduced autonomy and mobility. Some of these patients described substantial social strain induced by feelings of isolation and inability to meet caregiving duties for other ill family members. Financial strains were often serious, sometimes resulting in struggles with the stress of debt collectors, being unable to afford medications, and missing bills. Even more important is the finding that, in spite of the widespread prevalence of these three problems, only 53% of respondents with these problems ever reported them to someone at the hospital or the post discharge care team, and only 58% of those reported being helped.

Conclusion:
These results suggest that a high number of potentially fixable issues may be going unassisted. Even patients expressing high satisfaction are still frequently subject to a wide array of psychosocial stressors that can influence the recovery process.
Abstract 16887: Impact of Variability in Echocardiographic Interpretation on Assessment of Repair Following Congenital Heart Surgery
Authors: Parthiban Anitha , Levine Jami C , Nathan Meena , Marshall Jennifer A , Shirali Girish S , Simon Steve D , Colan Steven D , Newburger Jane W , Raghuveer Geetha
Published: July 2021

Background:
Technical Performance Score (TPS), a tool based largely on the presence and magnitude of residua on postoperative echocardiograms (echo), has been used for assessing surgical repair and correlates with outcomes. The reproducibility of the echo measures that drive TPS classification has not been tested. We evaluated reader variability for echo components of TPS for tetralogy of Fallot (TOF) repair and arterial switch operation (ASO) in 2 centers and measured its effect on TPS.

Hypothesis:
Inter-reader echo measurement variability will not substantially impact TPS classification.

Methods:
Postoperative echos were evaluated in 67 subjects (39 TOF and 28 ASO). Two readers (1 per center) read each echo, blinded to center of origin. To assess intra-reader variability, 25% of echoes were re-reviewed by each reader. Measurements between readers were compared with Intra-class correlation (ICC). TPS Class (1 Optimal
no residua
, 2 Adequate
minor residua
, 3 Inadequate
major residua
) was assigned for each echo review by an independent investigator. The impact of measurement variability on overall TPS variability was compared using weighted Kappa (K) and % raw agreement.

Results:
ICC was highest for Doppler velocity data and lower for measurements of small linear structures such as septal defects and vena contracta
Figure.
Overall TPS demonstrated good agreement (between reader TOF K = 0.82 and ASO K = 0.81). The 2 readers were concordant for TPS Class for 53 subjects (79%) and discordant for Classes 2 vs. 3 in 6 (9%); no readings were discordant between Classes 1 and 3
Table
.

Conclusions:
Although overall TPS demonstrated good agreement, inter-reader variation for echo measurements had a small, but important effect on TPS for ASO and TOF, particularly for the distinction between minor and major residua. Future studies of generalizability and reproducibility of TPS across centers and lesions are needed before TPS could be adopted as a national quality measure.
Abstract 16930: Inhibition of Glutamine Synthase Causes Glucose Intolerance in Mice
Authors: Dejam Andre , Alborghetti Marcos , O’Sullivan John , Gerszten Robert E
Published: July 2021

Background:
We recently performed metabolite profiling in 2,346 non-diabetic participants in the Framingham Offspring cohort. The glutamine/glutamate ratio was among the strongest predictors of the development of type II diabetes mellitus (DMII) during a 12-year follow-up period. Glutamate and glutamine are in a precursor-product relationship via the enzyme glutamine synthase (GS).

Hypothesis:
We hypothesized that inhibition of systemic GS activity would decrease the circulating glutamine/glutamate ratio and worsen glucose homeostasis in vivo.

Methods:
We administered 20 mg/kg of methionine sulfoximine (MSO), an irreversible inhibitor of GS, to 12 - 16 week old C57Bl6 mice intraperitoneally (i.p.) over 14 days (every other day for 7 injections). We then performed an intraperitoneal glucose tolerance test (IPGTT) with glucose measurements at 0, 30, 60, 90, 120 min from the tail vein. In a separate cohort of mice, we administered a single dose of 300 mg/kg of glutamine to both MSO-treated and control mice to assess reversibility of MSO effects.

Results:
Administration of MSO decreased circulating glutamine levels (n = 18, -64 ± 19% from baseline, p < 0.01), whereas glutamate levels increased significantly (n = 18, +25 ± 8, p = 0.03). The glutamine/glutamate ratio decreased from 2.16 ± 0.16 to 0.44 ± 0.03 (n = 12, p < 0.001). In the MSO-treated mice, the area under the curve of glucose excursion during the IPGTT increased markedly (n = 24, 12,098 ± 452 vs. 8,158 ± 368 AU, p < 0.001). In livers isolated from MSO-treated animals, we documented reduced liver GS activity by 94 ± 3% (n = 24, p < 0.001). Further, glutamine treatment of the MSO-treated animals at a dose of 300 mg/kg i.p. reversed the diabetogenic effects of MSO treatment (n = 12, 12,687 ± 568 vs 9,235 ± 399 AU, p < 0.01).

Conclusion:
Inhibition of systemic GS causes a reversal of the plasma glutamine/glutamate ratio and worsening of glucose tolerance. Glutamine administration rescues MSO-induced glucose intolerance. These studies implicate glutamine/glutamate metabolism in the control of glucose homeostasis. Further studies will focus on the mechanism of MSO-induced glucose intolerance and relate the murine findings to human pathology.
Abstract 16947: A Meta-Synthesis on Usefulness of Stress Reduction with Meditation in the Prevention and Treatment of Cardiovascular Disease
Authors: Aquino-Russell Catherine , Ruff Amy , Schneider Robert H
Published: July 2021

Introduction:
Epidemiological research has documented that psychosocial stress is a major risk factor for atherosclerotic cardiovascular disease (CVD). In providing effective health education to patients with CVD, nurses and other health professionals require evidence-based information on behavioral methods to reduce stress for primary and secondary prevention of CVD. Previously published trials suggest that selected stress reduction methods, including meditation may modify CVD risk factors, quality of life, morbidity and mortality.

Hypothesis:
Stress reduction with meditation may contribute to the management of psychosocial stress, hypertension, metabolic syndrome, chronic CVD, nonfatal/fatal CVD clinical events and associated health care costs.

Methods:
We performed a meta-synthesis (qualitative review) of published biomedical literature for randomized controlled trials, meta-analyses and professional guidelines on the effects of meditation on CVD and its risk factors.

Results:
The two most widely studied stress reduction - meditation approaches in CVD were the Transcendental Meditation (TM) technique and mindfulness meditation

There were 11 RCTs, two meta-analyses and one American Heart Association scientific statement on TM and blood pressure that suggest TM is clinically useful in lowering high BP, short and long-term, in diverse populations. Other risk factors showing beneficial responses to TM were anxiety, insulin resistance, smoking and surrogate markers for CVD. RCTs and meta-analyses report significant risk reductions for myocardial infarction, stroke and mortality over 5-8 years. In patients with CVD, mindfulness meditation was associated with beneficial psychological effects; however, in meta-analyses of physical parameters of CVD, effects were not yet well-established.

Conclusion:
Available evidence suggests that meditation may be useful in the behavioral interventions for cardiovascular health and quality of life. Both Transcendental Meditation and mindfulness meditation practices show beneficial effects on psychosocial stress factors. Substantial evidence indicates that TM practice is associated with reductions in hypertension, other CVD risk factors, and rates of CVD morbidity and mortality.
Abstract 16955: Effects of Evolocumab (AMG 145) as a Monotherapy or in Combination with Statins on Lipoprotein Particles and Subclasses
Authors: Xu Ren , Peach Matt , Tracy Michael , Hamilton Lisa , Djedjos Stephen , Dent Ricardo , Fitzpatrick Dan , Scott Rob , Wasserman Scott M
Published: July 2021

Background:
Evolocumab (AMG 145) reduces LDL-C alone or in combination with statins. We evaluated the effect of evolocumab on lipoprotein particles from subjects receiving evolocumab as monotherapy or combined with statins using biomarker samples collected from 2 clinical studies.

Methods:
Exploratory biomarker samples, taken before and after evolocumab treatment from a phase 1b study evaluating evolocumab combined with statins in hypercholesterolemic (HCL) subjects and from a phase 2 study evaluating evolocumab as a monotherapy in HCL subjects, were analyzed by NMR at LipoScience, Inc. Lipoprotein particle concentrations and size were determined using the LP-3 module.

Results:
Evolocumab alone or in combination with statins significantly reduced total, small, and large LDL-P in a dose-dependent manner. As shown in the table, evolocumab monotherapy reduced total LDL-P by 45% and 54%, small LDL-P by 36% and 35%, and large LDL-P by 68% and 84%, after 140 mg and 420 mg doses, respectively. LDL-P values were reduced slightly less than LDL-C (52% at 140 mg and 62% at 420 mg), but LDL-P reductions were similar to those seen for ApoB. IDL-P, total VLDL-P, and small VLDL-P were also reduced. Total HDL-P increased, primarily due to increases in large HDL-P. Similar results were obtained when evolocumab was given combined with statins, but with greater reductions in total, small, and large LDL-P. Notably, greater reductions in LDL-P or LDL-C were correlated with higher concentrations of total LDL-P, small LDL-P, triglycerides, smaller LDL size, and lower HDL-C at baseline.

Conclusion:
Evolocumab either alone or in combination with statins affected lipoprotein particles similarly. In both treatment regimens, LDL-C and total LDL-P were significantly reduced and large LDL-P were reduced, on average, to a greater extent than small LDL-P. Total LDL-P was reduced to a lesser extent than LDL-C. Additionally, reductions in VLDL-P and IDL-P were observed along with increases in HDL-P.
Abstract 16964: Triplane Measurement of Fractional Area Change to Assess Single Right Ventricular Function
Authors: Qureshi Muhammad Y , Reece Chelsea L , Miller Angela R , Lindquist Rebecca K , O’Leary Patrick W
Published: July 2021

Background:
Echocardiographic (echo) functional assessment of single systemic right ventricle (RV) lacks a reliable parameter and does not provide a substitute of volumetric ejection fraction (EF). RV volumes by 3D-echo are challenging and not widely used. Apical RV fractional area change (FAC) has shown some relation to CMR EF, but the strength of correlation has been suboptimal. Adding additional planes to apical FAC may improve this correlation. Our objective was to assess correlation of triplane FAC (apical, short-axis, and inflow-outflow) with CMR EF and to compare the tri- and single plane methods of measuring FAC to each other.

Methods:
Subjects with hypoplastic left heart syndrome (after superior or total cavopulmonary anastomosis) were prospectively recruited. CMR was performed and right ventricular ejection fraction was calculated. Transthoracic echo studies were performed close to the time of the CMR scan (median interval: 1 d). FAC was measured in apical 4-chamber view, parasternal short axis view at the mid ventricular level, and para-apical right ventricular inflow-outflow view. Triplane FAC was calculated by the average of the three FAC. Comparison was made between FAC and CMR-derived ejection fraction.

Results:
A total of 25 subjects underwent testing. Triplane FAC could not be assessed in 5, due to lack of optimal acoustic windows. Mean age was 10 ± 8 y (range 9 m to 24 y). Out of the uniplanar methods, apical FAC had the closest relationship to CMR EF. Triplane FAC showed even better correlation coefficient and R
2
values; although in this small group the difference did not reach significance. Results are summarized in the Table.

Conclusion:
In patients with single systemic RV, triplane FAC offers improved correlation with CMR EF relative to single plane evaluations. This approach may be useful if 3D echo is unavailable or of suboptimal quality and warrants further study.
Abstract 17058: Does Intensive Glucose Control Prevent Cognitive Decline in Diabetes? a Meta-analysis
Authors: Peñaherrera Oviedo Carlos A , Duarte Martinez María C , Moreno Zambrano Daniel A , Palacios Mendoza Michael , Jurado María B , Tamariz Leonardo , Santibañez Vasquez Rocío A
Published: July 2021

Background:
Long term diabetes is associated with cognitive decline. Blood glucose control improves outcomes in patients with diabetes, it is unclear if intensive glucose control prevents cognitive decline. The aim of this study is to conduct a meta-analysis to determine the effects of intensive glucose control on cognitive decline in patients with diabetes.

Methods:
We searched the MEDLINE database (1966 to December 2013) and supplemented the search with manual searches of bibliographies of key relevant articles. Keywords used for the search were: diabetes mellitus, cognitive decline, cognitive function, cognitive impairment, and glucose control. We selected all randomized studies where a measurement of cognitive decline and the level of glucose control were reported in patients with diabetes. We calculated the weighted standardized mean difference (SMD) of the measurement of cognitive decline between the intensive and standard glucose control arm. We also conducted meta-regression to evaluate the effect of the type of diabetes had on the results and stratified the analysis by type of diabetes.

Results:
The search strategy yielded 260 studies, of which only 7 met our eligibility criteria. Only three studies included subjects with type 2 diabetes, patients with type 2 diabetes had a median age of 62(59-63), 48(42-60) were female, the median HbA1c was 8% and the median duration of diabetes was 9 years. We included four studies with type 1 diabetes with a median age of 27(16-29) years, 49(49-50) % were female, the median Hba1c was 9% and the median duration of diabetes was 6(5-18) years. The weighted SMD of each cognitive test is shown in Table 1.

Conclusions:
Intensive glucose control prevents cognitive decline. The largest improvements were seen in the memory and speed processing domains. This was seen mostly in middle-aged type 2 diabetics with diabetes for 9 years and slightly out of control HbA1c.
Abstract 17063: Enhanced Prediction of Heart Failure 30-Day Readmission Risk With Four Readily-Available Clinical Variables
Authors: Wettersten Nicholas , Wilson Machelle , Tong Kathleen , López Javier E
Published: July 2021

Introduction:
Heart failure (HF) readmissions, with ~25% within 30 days of discharge, can be reduced with costly post-hospitalization interventions. Determining which patients will benefit from these interventions remains a critical challenge.

Hypothesis:
We aimed to devise a simple model to predict 30-day HF readmission risk.

Methods:
Patients ≥21 years of age admitted for HF to a single academic center from July 1st, 2008 to December 31st, 2009 were identified by billing codes for HF. Patients were excluded if they died within 90 days, were transferred, discharged to hospice or prison, or later admitted electively or for a surgical emergency not related to HF. Demographics, co-morbidities, laboratories, vitals, and discharge medications (27 variables) were tested as predictors for risk of 30 day readmission. First, independent univariate testing of categorical variables was performed utilizing a retention p-value of < 0.2. Next, continuous variables and retained categorical variables were tested in a multivariable model with retention of variables with p-value < 0.1. False discovery rate was controlled by the method of Benjamini and Hochberg. Statistical analyses were performed using SAS® software version 9.3.

Results:
Of 1253 HF admissions, 657 (55.8% men, age 60.9 ± 13.8 men, 66.8 ± 14.5 women) met criteria with complete data. Twenty percent were readmitted within 30 days. Odds for readmission increased 1.6% for every 100 pg/ml increase in BNP (p=0.082), 5.6% for each additional discharge medication (p=0.003), 200% if not discharged on an ACE-I/ARB (p=0.001), and 7% for every 10 mmHg increase in systolic blood pressure at discharge compared to admission (p=0.078).

Conclusion:
One laboratory value and 3 clinical variables were predictive of 30-day HF readmission risk in a multivariate prediction model. The 3 clinical predictors provoke the idea that “in hospital” care is a predictor and potential target for intervention to reduce 30-day readmission risk. Future validation studies should help define standard-of-care interventions that could still be improved to reduce readmission rates in HF patients as well as address the relative cost of more intense hospital interventions over outpatient interventions.
Abstract 17106: Transition From Adipose to Fibrotic Tissue in the Atrial Subepicardium in Humans and in a Sheep Model of Atrial Fibrillation
Authors: Haemers Peter , Hamdi Hadhami , Claus Piet , Farahmand Patrick , Bruneval Patrick , Lendeckel Uwe , Jalife José , Jaïs Pierre , Willems Rik , Hatem Stéphane
Published: July 2021

Epicardial adipose tissue (EAT) is recognized as potentially involved in the pathophysiology of atrial fibrillation (AF). In addition to EAT fatty infiltration commonly observed in myocardium might be also associated with the substrate for AF. We conducted a histological study in 93 human right atrial samples obtained during cardiac surgery and in a sheep model of long-term persistent AF (PAF) induced by atrial tachypacing (24±8 weeks) (15 PAF, 11 SR). Upon Sirius Red and Harris Haematoxylin staining, human atria showed various degree of fatty infiltration starting from the epicardium (rarely from vessels), which could be associated with various degree of subepicardial fibrosis realizing in some cases a true fibro-fatty infiltration. The extent of remodeled epicardium was assessed as % of infiltrating and fibrotic epicardium±adipose tissue to total epicardial length; 44±26 % of the epicardium was remodeled. A multiple regression model (including history of AF, % adipose tissue, age, BodyMassIndex, coronary artery bypass, ejection fraction) significantly predicted the percentage of epicardial remodeling (R=0.501, p=0.003). Only AF and the % adipose tissue were significant predictors (respectively β=0.27;p=0.016 and β=-0.267;p=0.016). To further analyze the relationship between fibro-fatty infiltration and AF, a histological study was performed in LA specimen of a sheep PAF model which revealed 4 grades of subepicardial infiltrates from pure fatty to dense fibro-fatty infiltration (fig A). EAT infiltrates (316) were graded, demonstrating a shift towards more severe grades in the AF group p<0.0001) (fig B). Inflammatory cells were detected in 14 fatty infiltrations (grade 2 and 3) of 6 AF sheep (and only in 1 fatty infiltration of SR sheep).

Conclusion:
, AF is associated with the transformation of fat into fibro-fatty infiltrations suggesting that the subepicardial adipose tissue plays a role in the atrial fibrotic remodeling.
Abstract 17127: Sports-Related Sudden Cardiac Arrest: Comparison of Survival Outcomes in Europe versus the United States
Authors: Marijon Eloi , Uy-Evanado Audrey , Dumas Florence , Teodeorescu Carmen , Reinier Kyndaron , Narayanan Kumar , Bougouin Wulfran , Lamhaut Lionel , Jost Daniel , Pochmalicki Gilbert , Gunson Karen , Jui Jonathan , Celermajer David S , Jouven Xavier , Chugh Sumeet S
Published: July 2021

Background:
Sports-related sudden cardiac arrest (sport SCA) has always attracted attention and the United States and European Union have developed divergent strategies for prevention over the last decade; notably regarding screening of younger athletes but also for SCA prevention in middle-aged and senior individuals. In this context, the extent to which outcomes of sports SCA differ between Europe and the USA have not been characterized.

Methods:
SCA cases aged 15-75 years were identified in two large prospective, population-based SCA programs, one in the Paris region (Paris-SDEC) and the other in a Northwestern US metro region (Oregon-SUDS) between 2002 and 2012. Cases of SCA, occurring during sports activity were compared between the two regions.

Results:
Of the 7,357 cases studied, 290 (4%) occurred during sports, with very similar proportions in both regions: 86 out of 1,894 (4.5%) in Oregon and 204 out of 5,463 (3.8%) in Paris. Subjects’ characteristics of cases in both programs were very similar (Paris vs. Oregon, respectively, for all results following), regarding age (50.7±14 vs. 50.4±13 years, P=0.55), male proportion (94%vs. 92%, P=0.53), past medical history of ≥2 cardiovascular risk factors (16% vs. 23%, P=0.16) and/or heart disease (10% vs. 8%, P=0.55). There was a high proportion of witnessed events in both populations (89% vs. 90%, P=0.94). However, we observed significant differences with more bystander cardiopulmonary resuscitation in Paris (63% vs. 48%, P=0.02), faster response time in Oregon (8.3±6 vs. 6.9±4 min, P=0.05), and more initially shockable rhythms in Oregon (52% vs. 70%, P=0.006). Overall, resuscitation outcomes were very similar for return of spontaneous circulation (26% vs. 33%, P=0.21) and survival to hospital discharge (27% vs. 26%, P=0.80).

Conclusions:
On either side of the Atlantic, burden and characteristics of sports-related SCA are very similar. Survival rates are approximately one in four cases. Optimizing bystander cardiopulmonary resuscitation rates and emergency response times could further improve outcomes. Deployment of uniform, effective strategies for screening and prevention are likely to make the greatest impact on sports SCA.
Abstract 17143: Obstructive and Central Sleep Apnea and Risk of Incident Atrial Fibrillation
Authors: Tung Patricia , Levitzky Yamini S , Wang Rui , Quan Stuart F , Gottlieb Daniel J , Reuschman Michael , Punjabi Naresh M , Bertisch Suzie , Benjamin Emelia J , Redline Susan
Published: July 2021

INTRODUCTION:
Prior studies have documented a higher prevalence of atrial fibrillation (AF) in those with obstructive sleep apnea (OSA). OSA has been associated with AF recurrence following cardioversion and ablation, and with prevalent and incident AF in cross-sectional and retrospective studies. Central sleep apnea (CSA) also has been associated with AF in patients with heart failure. However, data from prospective cohorts are sparse and few studies have evaluated the association of CSA with AF in population studies.

METHODS:
We assessed the association of OSA and CSA with incident AF among 3,420 subjects without a history of AF in the Sleep Heart Health Study (SHHS), a prospective, community-based study designed to evaluate the cardiovascular consequences of sleep disordered breathing. Subjects underwent overnight polysomnography at baseline and were

followed over time for the development of incident AF, documented at any time after baseline polysomnogram until the end of follow-up. OSA was defined as an obstructive apnea-hypopnea index ≥ 5 and CSA was defined as a central apnea index ≥ 5.

RESULTS:
At baseline, the sample include 1499 men (44.4%) with a mean age of 62.4 (±10.9); 1569 (45.9%) subjects met criteria for mild to severe OSA and 54 (1.6%) for CSA. Over a mean follow-up of 8.2 years, 382 cases of incident AF were identified. The prevalence of both OSA and CSA was higher among those who developed AF compared to those who did not (OSA 49% vs 44%, p=0.001 and CSA 5% vs 1.2%, p=0.001). After adjustment for multiple AF risk factors, CSA was associated with an approximately 2-fold increased odds of incident AF (RR=2.38, 95% CI, 1.15-4.94; p = 0.02). The association persisted after exclusion of 258 subjects with a history of heart failure (RR=2.78, 95% CI, 1.28-6.04; p = 0.01). We did not find a significant association of OSA with incident AF (Table).

CONCLUSION:
In our prospective, community-based cohort baseline CSA was associated with incident AF.
Abstract 17155: Complications with Cardiac Perforation and Lead Dislodgement of the 5086 MRI Pacing Lead
Authors: Choi Jin Hee , Kim Jun , Jo Uk , Kwon Chang Hee , Lee Woo Seok , Kim Yoo Ri , Nam Gi-Byoung , Choi Kee-Joon , Kim You-Ho
Published: July 2021

As the MR-conditional Medtronic 5086 lead has been implanted, there were some reports that the 5086 lead demonstrated higher lead dislodgement and cardiac perforation compared with the 5076 lead. However, little is known regarding the rates of complications between the 5086 lead and the 5076 lead especially in asian populations.

The purpose of this study was to describe the incidence of lead-related complications including cardiac perforation and lead dislodgement of the 5086 lead compared to the 5076 lead and to investigate the clinical factors associated with development of cardiac perforation or lead dislodgement.

This study was a retrospective single center study. Consecutive 292 patients who underwent dual chamber pacemaker implantation using either 5076 (N=121) or 5086 lead (N=171) between January 2008 and March 2014 were enrolled in this study. Primary endpoint was incidence of cardiac perforation with pericardial effusion or cardiac tamponade within 30 days of implant. Secondary endpoint was combined incidence of cardiac perforation or lead dislodgement.

Primary outcome occurred in 3 patients with the 5806 lead (1.8%) and no patient with the 5076 lead (0.0%) (p=0.269). Lead dislodgement occurred in 9 patients with the 5806 lead (5.3%) and 5 patient with the 5076 lead (4.1%) (p=0.784) (Table1). There was no difference in the incidence of secondary endpoint between groups (7.0 vs 4.1%, p=0.447). On logistic regression analysis after multivariate adjustment, factors associated with an increased risk for dislodgement and cardiac perforation included heart failure, taking a rivaroxaban, and location of atrial lead other than right atrial appendage (Table2).

Compared with the 5076 lead, the rate of cardiac perforation and lead dislodgement was not significantly higher with the 5086 MRI lead in asian population. Cardiac perforation and lead dislodgements occured more often in patient with heart failure, taking a rivaroxaban, and unusual location of atrial lead.
Abstract 17179: Uremic Toxins Contribute to Cardiac Fibrosis after Myocardial Infarction: Role of MicroRNAs
Authors: Rana Indrajeet , Kompa Andrew , Skommer Joanna , Lekawanvijit Suree , Kelly Darren J , Krum Henry , Charchar Fadi J
Published: July 2021

Introduction:
A decline in renal function is a common consequence of myocardial infarction (MI) resulting in increased cardiovascular events, known as cardiorenal syndrome (CRS). Although molecular mechanisms contributing to CRS are not well understood, a role for elevated plasma levels of the uremic toxin indoxyl sulphate (IS) and increased fibrosis have been described. MicroRNAs are small endogenously transcribed regulatory RNAs that modulate gene expression and regulate many cardiac processes involved in cardiac dysfunction.

Aim:
Using a rat model we investigated whether MI leads to changes in expression of cardiac microRNA-21 and microRNA-29, both known to contribute to fibrosis. We also investigated the effect of lowering plasma uremic toxins on cardiac expression of these microRNAs.

Methods:
MI was induced by coronary artery ligation in male Sprague-Dawley rats. At 16 weeks cardiac function was measured prior to sacrifice. Cardiac tissues were assessed for molecular changes using real-time PCR, western blot analysis and histological methods.

Results:
MI significantly increased cardiac microRNA-21, collagen1A1, fibronectin-1 and TGFβ1 mRNA expression, as well as cardiac fibrosis and collagen 1 protein expression. Conversely, microRNA-29 expression was reduced in the heart (Table). Treatment with the AST-120 significantly reversed all these changes (Table). MicroRNA-21 levels significantly correlated with mRNA for TGF-β1 (P=0.049; r2=0.17) and its target genes collagen1A1 (P=0.004; r2=0.35) and fibronectin-1 (P=0.003; r2=0.52). MicroRNA-29b levels negatively and significantly correlated with TGF-β1 (P=0.017; r2=0.26) and collagen1A1 (P=0.048; r2=0.18) and fibronectin-1 (P=0.013; r2=0.29).

Conclusions:
We report a link between the beneficial effects of lowering circulating uremic toxins and microRNAs changes in the heart. Targeting microRNA’s may provide a therapeutic target for the treatment of CRS.
Abstract 17191: Fragmentation Assessed by Magnetocardiography but not Electrocardiogram Can Predict Future Cardiac Events in Patients with Non-ischemic Dilated Cardiomyopathy and Narrow QRS
Authors: Kawakami Shoji , Takaki Hiroshi , Hashimoto Shuji , Wada Mitsuru , Ishibashi Kohei , Nakajima Ikutaro , Miyamoto Koji , Okamura Hideo , Noda Takashi , Aiba Takeshi , Kusano Kengo , Yasuda Satoshi , Ogawa Hisao , Kamakura Shiro , Sugimachi Masaru
Published: July 2021

Background:
Fragmented QRS (fQRS) in 12-lead ECG, ascribed to myocardial scar, has been shown to predict future cardiac events in patients with both ischemic and non-ischemic dilated cardiomyopathy (NIDCM). Various definitions and low specificity of fQRS, however, limited its use. We hypothesized that the advantage of 64-channel magnetocardiography (MCG), i.e., high spatio-temporal resolution, enables more accurate detection of fragmented LV conduction (fLV), that would lead to accurate prediction of future events.

Methods:
In 51 patients with NIDCM and narrow QRS (LVEF, 22±7%; QRS duration, 99±11 ms), we recorded MCG. We defined, in MCG superimposed vector magnitude waveforms, fLV as distinct abnormal components (>20% of maximal amplitude). In current arrow map, fLV corresponded to heterogeneous QRS currents (Figure). We predicted major adverse cardiac events (MACE), including sudden cardiac death (SCD), sustained ventricular tachyarrhythmias (VF/VT), appropriate defibrillator discharge (Def) and left ventricular assist device implantation (LVAD).

Results:
fLV was present in 27 (Group-F) and not in 24 (Group-N). Age, gender, ECG and echocardiographic findings, laboratory data and medications were similar irrespective of fLV. During a mean follow-up of 2.2 years, MACE occurred in 19 (4 SCD, 9 VF/VT, 2 Def, and 4 LVAD). MACE more frequently occurred with fLV (63%, 17/27) than without (8%, 2/24, Kaplan-Meier analysis, p<0.001). Multivariate analysis revealed fLV as the only independent predictor of MACE (HR 4.82, p=0.015).

Conclusion:
MCG analysis is a promising noninvasive tool to accurately detect fragmentation and predict MACE in patients with NIDCM and normal QRS.
Abstract 172: Thrombopoietin Receptor Agonists Protect Human Cardiac Myocytes from Injury by Activation of Cell Survival Pathways
Authors: Baker John E , Su Jidong , Koprowski Stacy , Dhanasekaran Anuradha , Aufderheide Tom P , Gross Garrett J
Published: July 2021

Thrombopoietin confers immediate protection against injury caused by ischemia/reperfusion in the rat heart at a dose that does not increase platelet levels. Eltrombopag is a small molecule agonist of the thrombopoietin receptor; the physiological target of thrombopoietin. Administration of thrombopoietin and eltrombopag result in a dose- and time-dependent increase in platelet counts in patients with thrombocytopenia. However, the ability of eltrombopag and thrombopoietin to immediately protect human cardiac myocytes against injury and the mechanisms underlying myocyte protection are not known. Human cardiac myocytes (7500 cells, n=10/group) were treated with eltrombopag (0.1- 30.0 μM) or thrombopoietin ( 0.1 - 30.0 ng/ml) and then subjected to 5 hours of hypoxia (95% N
2
/5%CO
2
) and 16 hours of reoxygenation to determine their ability to confer resistance to necrotic and apoptotic myocardial injury
.
The thrombopoietin receptor (c-Mpl) was detected in unstimulated human cardiac myocytes by western blotting. Eltrombopag and thrombopoietin confer immediate protection to human cardiac myocytes against injury from hypoxia/reoxygenation by decreasing necrotic and apoptotic cell death in a concentration-dependent manner with an optimal concentration of 3 μM for eltrombopag and 1.0 ng/ml for thrombopoietin. The extent of protection conferred to cardiac myocytes with eltrombopag is equivalent to that of thrombopoietin. Eltrombopag and thrombopoietin activate multiple pro-survival pathways; inhibition of JAK-2 (AG-490, 10 μM), p38 MAPK (SB203580, 10 μM), p44/42 MAPK (PD98059, 10 μM), Akt/PI
3
kinase (Wortmannin, 100 nM), and src kinase (PP1, 20 μM) prior to and during hypoxia abolished cardiac myocyte protection by eltrombopag and thrombopoietin. These inhibitors had no effect on hypoxia/reoxygenation injury in myocytes when used alone. Eltrombopag and thrombopoietin may represent important and potent agents for immediately and substantially increasing protection of human cardiac myocytes, and may offer long-lasting benefit through activation of pro-survival pathways during ischemia.
Abstract 17202: Synthetic Modified RNA Driven Delivery of Insulin-Like Growth Factor-1 Promotes Early Cardiomyocyte Survival Post-Acute Myocardial Infarction
Authors: Huang Chien-Ling , Leblond Anne-Laure , Turner Elizebeth C , Kumar Arun H , O’Sullivan Donnchadh M , Martin Kenneth , Whelan Derek , Caplice Noel M
Published: July 2021

To extend the temporal window for cytoprotection in cardiomyocytes undergoing apoptosis after hypoxia and myocardial infarction (MI), a synthetic modified RNA (modRNA) was used to drive delivery of insulin-like growth factor-1 (IGF1) within the area at risk in a murine model of MI. Transient transfection of synthetic GFP modRNA as an tracking indicator, with polyethylenimine (PEI)-based nanoparticle, showed efficient delivery of modRNA derived protein and minimum cytotoxicity in HL-1 cardiomyocytes (CM; 44±5%). ModRNA-IGF1 protein expression and secreted levels increased 3.5 fold (
p
<0.05) at 24 hours and peaked at 48 hours post-transfection. The expression efficiency of modRNA was further enhanced (~2 fold at 24 hours post-transfection;
p
<0.05) under hypoxia-induced apoptosis conditions. ModRNA augmented secreted and cell associated IGF1 promoting CM survival and abrogating cell apoptosis (71±5% in controls to 37±7%,
p
<0.05). Translation of modRNA-IGF1 was sufficient to induce downstream increases in Akt and Erk phosphorylation (3 fold and 2 fold, respectively;
p
<0.01). Downregulation of IGF1 specific miRNA-1 and -133 (52% and 56%, respectively;
p
<0.01) but not miR-145 expression, was also confirmed. As proof of concept, intramyocardial delivery of modRNA-IGF1 but not control modRNA-GFP significantly decreased in TUNEL-positive cells within the infarct border zone (BZ) at 24

hours (22±3% versus 53±8% in controls,
p
<0.01). Akt phosphorylation was augmented while caspase-9 activity and cleavage was downregulated in the infarct BZ compared to controls (
p
<0.05). These findings demonstrate extended
in vivo
cytoprotective effect of IGF1 24 hours post-MI driven by synthetic modRNA delivery. This provides a novel strategy to reduce ischemic injury by controlled release of IGF1 using a controllable bioactive nanoparticle for ‘short burst’ IGF1 cytoprotective therapy.