bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18331: Endothelial Microrna-155 Promotes Myocardial Microvascular Permeability and Inflammatory Cell Adhesion in Experimental Septic Cardiomyopathy
Authors: Vasques-Nóvoa Francisco , Quina-Rodrigues Catarina , Cerqueira Rui , Baganha Fabiana , Laundos Tiago L , Nascimento Diana S , Ribeiro Sara , Pinto-do-Ó Perpétua , Leite-Moreira Adelino F , Roncon-Albuquerque Jr. Roberto
Published: July 2021

Introduction:
Septic cardiomyopathy remains a leading cause of death in critically ill patients. Myocardial edema and inflammatory cell recruitment to cardiac interstitial space are proposed mechanisms underlying sepsis-induced contractile dysfunction.

Hypothesis:
Evaluate the role of endothelial microRNA-155 (miR-155) in experimental septic cardiomyopathy.

Methods:
Experimental sepsis was induced using LPS injection in WT (n=20) and miR-155-/- (KO; n=20) male mice. Cardiac function was evaluated through echocardiography. Expression of NOS2, NOS3, VASP phosphorylation and myocardial nitrite/nitrate content was evaluated. Cardiac microvascular (MV) permeability was assessed with evans blue-albumin conjugate leaking to extravascular space and myocardial water content. Mouse cardiac MV endothelial cells (MCMVEC; CD31+Sca-1+CD45-) were isolated with FACS. Quantification of miR-155, cytokine mRNA profile and adhesion molecules (ICAM1, VCAM1 and E-selectin) was performed. Human cardiac MV endothelial cells (HCMVEC) were transfected with anti-miR-155 or scramble LNA probe and incubated with LPS (100ng/mL) or vehicle for 24h. Evaluation of cytokine mRNA profile, NOS isoforms, VASP phosphorylation and adhesion molecules was performed. Monocyte adhesion assay was performed using Dil-stained THP1 monocytic cells.

Results:
LPS exposure increased miR-155 expression in the myocardium, MCMVEC and HCMVEC. KO mice presented with attenuated LPS-induced cardiac dysfunction, MV permeability, NOS2 expression and VASP phosphorylation, compared with WT. KO MCMVEC presented with attenuated LPS-induced cytokine expression and adhesion molecules, compared with WT cells. Mir-155 inhibition in HCMVEC prevented LPS-induced overexpression of cytokines and adhesion molecules, nitric oxide production and monocyte adhesion, through SOCS1-mediated inhibition of STAT3 and NF-kB signaling pathways.

Conclusions:
Endothelial miR-155 is upregulated in experimental septic cardiomyopathy. MiR-155 knockout attenuates LPS-induced myocardial dysfunction, edema and MV permeability. In MCMVEC and HCMVEC, miR-155 inhibition blunted LPS-induced nitric oxide production, cytokine and cell adhesion molecules overexpression.
Abstract 18338: Genomics-metabolomics Integrative Approach Reveals Novel Biomarkers In DPYS Associated With Higher Glucose Change After Treatment With Atenolol
Authors: de Oliveira Felipe A , Shahin Mohamed H , Gong Yan , McDonough Catrin W , Beitelshees Amber L , Gums John G , Chapman Arlene B , Boerwinkle Eric , Turner Stephen T , Frye Reginald F , Fiehn Oliver , Kaddurah-Daouk Rima , Johnson Julie A , Cooper-DeHoff Rhonda M
Published: July 2021

Introduction:
β-blockers, including atenolol, are among the most widely prescribed antihypertensive drug classes. However, their use has been associated with hyperglycemia and incident diabetes, which poses concern for prescribers and patients. The Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study is a multicenter clinical trial with one of its objectives to identify genetic influences on adverse metabolic events in patients treated with atenolol. Here we report a genomics-metabolomics integrative approach to identify biomarkers associated with atenolol-induced glucose change.

Methods:
PEAR participants were genotyped using the Illumina Omni 1M-Quad Chip. Metabolite profiles were acquired through GC-TOF-MS. Association between baseline levels of metabolites and glucose change was conducted using a multivariate linear regression model adjusted for age, gender and baseline fasting glucose. Genomics-metabolomics integration included selecting SNPs within genes involved in the synthesis and degradation of top metabolites and testing their effect on glucose change in 234 atenolol-treated Caucasians in PEAR, adjusting for age, gender, baseline glucose and principal components 1 and 2. A false discovery rate (FDR) of .05 was used to adjust for multiple comparisons. Replication of significant SNPs was conducted in an additional 228 participants treated with atenolol in PEAR.

Results:
Metabolomics analysis revealed 3 metabolites associated with glucose change that passed FDR adjustment. The top metabolite signal was beta-alanine. Increasing levels of baseline beta-alanine was significantly correlated with greater glucose increases after atenolol treatment (p=.0003). A total of 79 SNPs in 12 genes in the beta-alanine pathway were explored. SNP rs2669429 in DPYS was significantly associated with glucose change, after FDR adjustment. We found that G allele carriers had significantly greater glucose change compared with non-carriers (p=.0006; β=+2.76 mg/dL). This finding was successfully replicated in the other 228 patients who received atenolol (p=.04; β=+1.86 mg/dL).

Conclusions:
These results suggest that beta alanine and DPYS rs2669429 SNP might be an important predictor of atenolol-induced dysglycemia.
Abstract 18340: Alternatively Spliced Tissue Factor Promotes Atherosclerosis by Increasing Foam Cell Formation via LOX-1 and SR-A1 up-regulation
Authors: Alicea Daniel , Hekmaty Saboor , Rodriguez David T , Bhandari Peter , Yang Dong Kwong , Jeong Dongtak , Kovacic Jason C , Bjorkegren Johan L , Badimon Juan J , Weber Thomas , Hajjar Roger J , Fuster Valentin , Giannarelli Chiara
Published: July 2021

Introduction:
Alternatively Spliced Tissue Factor (asTF) is an isoform of tissue factor that is expressed in human atherosclerotic plaques and promotes plaque progression in experimental atherosclerosis (Giannarelli C, Circulation 2014).

Hypothesis:
asTF is the isoform of tissue factor that most strongly promotes atherosclerosis by increasing foam cell formation.

Methods:
ApoE-/- mice (8 weeks old) were fed a Western-type diet starting 2 weeks before surgery. Immediately after transluminal wire injury of the left common carotid artery (LCCA), LCCA was incubated with lentivirus encoding asTF-GFP (asTF+;n=10), fl-TF-GFP (fl-TF+, n=10) or GFP (controls; n=5). Four weeks after, LCCA was removed and processed for the quantification of plaque size (H&E) and lipid accumulation (Oil-Red O). The effect of asTF on foam cell formation was tested in vitro by treating THP-1 derived macrophages with oxLDL (75μg/ml), with asTF (10nM) or vehicle. Total cholesterol (TC) and cholesterol esters (CE) were measured in lipid cell extracts. The mRNA levels of the oxLDL scavenger receptors LOX-1, SR-A1 and CD36 in macrophages and foam cells were assessed using qRT-PCR.

Results:
Plaque size and lipid accumulation were significantly greater in asTF+ vs. fl-TF+ and control mice (Fig.1, A-D). In vitro results showed that asTF promotes TC and CE accumulation in foam cells (Fig.1, E,F). Gene expression studies showed that asTF significantly increased the mRNA expression of scavenger receptors LOX-1, SR-A1 in both macrophages and foam cells (Fig.1, G-I). An increase in mRNA levels of CD36 (1.4-fold) was only detected in asTF-treated foam cells.

Conclusions:
In vivo results suggest that asTF promote plaque progression and lipid accumulation. In vitro studies imply that asTF promotes foam cell formation by increasing the expression of oxLDL scavenger receptors implicated in lipoprotein uptake by macrophages. These studies suggest a functional role for asTF in atherosclerotic plaque progression.
Abstract 18362: Cardiac-targeted Therapy With Cardiotrophin-1 Rescues Defective Right Ventricular Adaptation in Severe Pulmonary Arterial Hypertension in Fischer Rats
Authors: Suen Colin , Abdul-Ghani Mohammad , Deng Yupu , Megeney Lynn , Stewart Duncan J
Published: July 2021

Introduction:
In patients with pulmonary arterial hypertension (PAH), right ventricular (RV) dysfunction is one of the strongest predictors of poor prognosis. Therapies targeting RV failure could lead to significant improvement in exercise tolerance and survival in patients with severe PAH. Cardiotrophin-1 (CT-1) is a member of the IL-6 cytokine family that promotes physiological cardiac hypertrophy and cardiomyocyte survival.

Hypothesis:
We hypothesized that RV-specific therapy using CT-1 therapy will improve RV adaptation to PAH.

Methods:
PAH was induced by a single subcutaneous injection of SU5416 (SU; 20 mg/kg) followed by exposure to chronic hypoxia (CH; 10% O2) for 3 weeks. On day 22 post SU, human recombinant cardiotrophin-1 (CT-1, Fate Therapeutics) (6 ug/kg/hr) or vehicle (PBS) was administered via subcutaneously implanted mini-osmotic pumps until end-study at 7 weeks. Echocardiography (Vevo 2100, VisualSonics) was performed weekly starting at baseline (day 21).

Results:
We observed a ~5-fold reduction in expression of endogenous CT-1 mRNA in the RV of rats treated with SU5416+hypoxia compared to healthy controls. Administration of CT-1 to Fischer rats with PAH had no significant effect on pulmonary hemodynamics (pulmonary acceleration time, RVSP), nor RV/LV+S. At 6 weeks post SU, CT-1 significantly reduced RV dilatation (end diastolic RV/LV internal diameter) (p<0.001), improved RV function (cardiac output, RV fractional area change, p<0.05) (Figure 1), which was associated with an increase in RV capillary density (p<0.05) and a 2-fold improvement in survival (31 vs 12%).

Conclusions:
Targeted cardiac therapy with CT-1 therapy improved RV adaptation in the SU/CH model of severe PAH without altering pulmonary hemodynamics, which in part was mediated by enhancing RV myocardial angiogenesis. These findings support the development of RV-targeted therapeutics for patients with severe PAH and RV failure.
Abstract 18416: Discordance Between nonHDLc and Lipoprotein Particle Concentration (apoB and LDLp) in Relation to Future Coronary Events in Women
Authors: Lawler Patrick R , Akinkuolie Akintunde O , Ridker Paul M , Sniderman Allan D , Glynn Robert J , Buring Julie , Mora Samia
Published: July 2021

Background:
There remains equipoise as to which plasma lipid/lipoprotein marker most accurately reflects longitudinal risk of coronary heart disease (CHD) events. To compare differences in risk related to nonHDLc (atherogenic particle cholesterol) and LDL particle number (LDLp) or apoB (atherogenic particle number), we examined risk when these markers were discordant.

Methods and Results:
We divided 27,533 initially-healthy women in the Women’s Health Study (NCT00000479) into concordant/discordant groups based on median nonHDLc (154 mg/dL) and apoB (100 mg/dL) or
1
H NMR-measured LDLp (1,216 nmol/L). Discordance was defined as nonHDLc < median and the alternative measure ≥ median, or vice versa. We compared risks between concordant and discordant groups (using the concordant group as reference) with Cox proportional hazard models adjusted incrementally for: age; and randomization arm, hormone use, postmenopausal status, smoking, and hypertension (“minimally adjusted”); and diabetes, BMI, hsCRP, HDLc, triglycerides, and family history of CHD (“fully adjusted”). Although all 3 biomarkers were strongly correlated - nonHDLc and apoB (Spearman r=0.86, P<0.0001), nonHDLc and LDLp (r=0.77, P<0.0001), and apoB and LDLp (r=0.85, P<0.0001) - discordance between nonHDLc and apoB or LDLp occurred in 13.9% and 20.2% of women, respectively. A total of 1,246 CHD events occurred over median (max) 20.4 (21.7) years of follow-up (514,725 person-years). With nonHDLc < median (Fig. a), CHD risk was underestimated among women with discordant high apoB or LDLp: fully adjusted HR (95% CI) high apoB = 1.33 (1.04, 1.71); high LDLp = 1.27 (1.01, 1.61). Alternately, with nonHDLc ≥ median (Fig. b), CHD risk was overestimated among women with discordant low apoB or LDLp: fully adjusted HR [95% CI] low apoB = 0.74 (0.57, 0.96); low LDLp = 0.93 (0.76, 1.14).

Conclusions:
For women with discordant levels of nonHDLc with apoB or LDLp, CHD risk may be underestimated or overestimated with nonHDLc.
Abstract 18435: ETCO2 Alone is Inadequate to Verify CPR Quality
Authors: Hu Chengcheng , Spaite Dan , Vadeboncoeur Tyler , Hypes Cameron , Murphy Ryan A , Silver Annemarie , Bobrow Bentley
Published: July 2021

Background:
Previous studies have described modest correlation between end-tidal CO
2
(ETCO
2
) and CPR quality during resuscitation of cardiac arrest patients, but it is unclear whether ETCO
2
alone can indicate CPR quality. The present study investigated whether ETCO
2
adequately identifies the quality of CPR provided during out-of-hospital cardiac resuscitation.

Methods:
ETCO
2
was monitored with side-stream CO
2
(Philips/Respironics) and CPR quality measured with an accelerometer-based system (E Series, ZOLL Medical) during the treatment of consecutive adult OHCA patients with presumed cardiac etiology by 2 EMS agencies in the Arizona SHARE QI Program between 10/08-06/13. Minute-by-minute ETCO
2
and CPR quality were extracted. ETCO
2
values were log transformation to achieve approximate normality. Linear mixed effect models were fitted to use (transformed) ETCO
2
level to predict four CPR variables: chest compression (CC) depth, CC rate, CC release velocity (CCRV), and ventilation rate (VR). A random intercept for each case was included and a spatial power covariance structure assumed for measurements over time.

Results:
230 subjects (median age 69 yrs, 69% male) with 1581 minutes of data were studied. Transformed ETCO
2
was significant for CC depth (p< 0.0001), CCRV (p=0.003) and VR (p<0.0001), but only explained 3.7%, 2.7%, and 10.0% of the total variance for these variables, respectively. Transformed ETCO
2
was not a significant predictor for CC rate (p=0.89). The Figure illustrates the overlap in CC depth over quartiles of ETCO
2
, demonstrating that any specific ETCO
2
level could be found over a wide range of CC depths.

Conclusion:
In this secondary analysis, ETCO
2
was not an independent indicator of CC rate but was a weak predictor for CC depth, CCRV and VR. These findings suggest that ETCO
2
may be not be an adequate substitute for CPR quality monitoring. Future studies should investigate how ETCO
2
and CPR quality monitoring can be used in conjunction to optimize CPR.
Abstract 18446: Treatment With Tetrahydrobiopterin Decreases White Matter Injury in a Mouse Model for In Utero Hypoxia in Congenital Heart Disease
Authors: Romanowicz Jennifer , Korotcova Ludmila , Morton Paul , Cheema Amrita , Gallo Vittorio , Jonas Richard A , Ishibashi Nobuyuki
Published: July 2021

Introduction:
Reduced oxygen delivery in complex congenital heart disease (CHD) can lead to brain white matter (WM) injury in utero. Currently, no treatment exists. Tetrahydrobiopterin (BH4) is a cofactor for neuronal nitric oxide synthase, and in its absence, toxic peroxynitrite production is favored. Hypoxia activates nitric oxide synthase, which reduces BH4 availability.

Hypothesis:
Decreased BH4 levels underlie WM injury in the fetus with CHD, and treatment with BH4 will reduce this injury.

Methods:
Mice were divided into three groups: normoxic controls (Nx), hypoxic (Hx), and hypoxic with BH4 treatment (Hx-BH4). Hx and Hx-BH4 mice were kept at 10.5% FiO2 from postnatal day 3 to 11--a period of WM development equivalent to the 3rd trimester in humans. Brain BH4 levels were quantified and compared between Nx (n=11) and Hx (n=12). Densities of cells expressing CNP (marker of oligodendrocytes--cells responsible for myelination) and Caspase3 (apoptosis marker) were quantified in three WM regions and compared between groups (n=3-6 each). Western blot detected myelin basic protein (myelin marker).

Results:
Brain BH4 levels were depleted in Hx compared to Nx (-38.4%, p=0.02). CNP+ oligodendrocytes increased after Hx compared to Nx (Fig.1a), consistent with hypoxia-induced proliferation seen previously. BH4 treatment did not limit this proliferation (Fig.1a). Hx had increased WM apoptosis (Fig.1b), which decreased with BH4 treatment (Fig.1b). Remarkably, there was no difference in WM caspase3+ cells between Nx and Hx-BH4 (Fig.1b). There was no difference in effect across WM region. Finally, loss of myelin with hypoxia was mitigated by BH4 treatment (Fig.1c).

Conclusions:
Our results show that suboptimal BH4 levels influence hypoxic WM injury. BH4 treatment of phenylketonuria is safe during pregnancy, thus maternal BH4 therapy is feasible. Our data demonstrate that repurposing BH4 for use during fetal brain development has potential to limit WM injury in CHD.
Abstract 18447: Peri-operative Atrial Fibrillation (POAF) Complicating Non-cardiothoracic Surgery: A Systematic Review
Authors: Wenner Joshua , Bami Karan , Samardhi Himabindu , Nery Pablo , Birnie David , Nair Girish , Redpath Calum
Published: July 2021

Introduction:
More than 37 million non cardiothoracic operations are performed in the USA per annum. Single studies have reported that peri-operative atrial fibrillation (POAF) complicates non-cardiac surgery in ≤12% of patients. It is not clear if POAF is associated with adverse outcomes. Purpose: We conducted a systematic review to determine the frequency and implications of POAF.

Methods:
We conducted a literature search of MEDLINE, Embase, HTA, Cochrane, and Pubmed databases. We defined POAF as a single episode of AF confirmed by ECG within 30 days of non cardiothoracic surgery. Inclusion criteria were published manuscripts and abstracts containing patient level information. We excluded studies which were not published in English, described cardiothoracic surgery, were missing patient-level AF data or included patients aged <18 years.

Results:
Our search produced 4445 publications, from which 716 abstracts and 534 manuscripts were identified for review. After applying inclusion/exclusion criteria, 225 manuscripts were analysed. Combining all studies, POAF occurred in 18789/650120 patients (2.9%, n=172, median [IQR] 2.2% [0.9-5.8]). Among 37 prospective studies, POAF occurred in 517/10990 patients (4.7%, n=37, 3.23% [1.0-8.8]). AF was prospectively identified pre-op in 875/26596 (3.3%, n=18, 9.0% [5.5-13.1]) and post-op in 472/14719 (3.2%, n=18, 8.8% [5.5-13.0]). In 135 retrospective studies, POAF occurred in 18272/639130 patients (2.9% n=135, 2.13 [0.8-4.4]). In retrospective analyses, AF was pre-existent in 49756/2440489, (2.0%, n=44, 6.7% [4.3-13.1]) and de novo in 12043/1641875, (0.7%, n=23, 6.0% [1.6-12.3]). Stratifying by surgery type, POAF was most common in vascular (104/1380, 7.5%), followed by orthopaedic (128/2384, 5.4%), and neurosurgical (197/4390, 4.5%) patients. Patient outcomes were not systematically reported: at 1 year, mortality occurred in 927/4136 (22.4%) POAF patients, compared to 8498/63746 (13.3%) non-POAF patients (n=7). Conclusions: POAF occurred in 2.9% of 650120 patients and was associated with a 68% increase in mortality. Prospective research is required to determine whether any specific intervention(s) in POAF patients will improve outcomes.
Abstract 18468: The Healthy Weights Initiative
Authors: Lemstra Mark
Published: July 2021

Few community-based obesity reduction programs have been evaluated. After 153 community consultations, the city of Moose Jaw, Saskatchewan, Canada decided to initiate a free comprehensive program. The initiative included 71 letters of support from the Mayor, every family physician, cardiologist and internist in the city and every relevant community group including the Heart and Stroke Foundation, the Canadian Cancer Society and the Public Health Agency of Canada.

The objective was to promote strong adherence while positively influencing a wide range of physical and mental health variables measured through objective assessment or validated surveys. The only inclusion criteria was that the individuals must be obese adults (BMI >30).

Participants were requested to sign-up with a “buddy” who was also obese and identify three family members or friends to sign a social support contract.

During the initial 12 weeks, each individual received 60 group exercise sessions, 12 group cognitive behaviour therapy sessions and 12 group dietary sessions with licensed professionals. During the second 12 week period, maintenance therapy included 12 group exercise sessions.

To date, 243 people have been referred with 229 starting. Among those who started, 183 completed the program (79.9%) while 15 quit for medical reasons and 31 quit for personal reasons.

Mean objective reductions included 31.0 pounds of body fat, 3.9 percent body fat, 2.9 inches from the waist, 2.3 inches from the hip, blood cholesterol by 0.5 mmol/L, systolic blood pressure by 5.9 mmHg and diastolic blood pressure by 3.2 mmHg (all p<.000). There were no changes in blood sugar levels. There was also statistically significant differences in aerobic fitness, self-report health, quality of life measured by SF-36 and depressed mood measured by CES-D (all p<.000).

An independent risk factor for not completing the program was not having a family member or friend sign a social support contract (OR 2.91; 95% CI 1.01-8.34, p=.047). Education level was a confounder.

Comprehensive obesity reduction programs can be effective when there is extensive consultation at the community level and social support at the individual level.
Abstract 18472: Electrocardiographic and Imaging Predictors for Permanent Pacemaker (PPM) Implantation Following Transcatheter Aortic Valve Replacement (TAVR)
Authors: Routh Jared M , Joseph Lee , Marthaler Brodie R , Bhave Prashant
Published: July 2021

Hypothesis:
The purpose of this study was to identify predictors of permanent pacemaker (PPM) placement post-TAVR.

Introduction:
Cardiac conduction abnormalities requiring PPM are well-recognized complications of TAVR. Reliable predictors of post-TAVR PPM placement, however, remain elusive.

Methods:
A total of 114 patients who underwent trans-apical or trans-femoral TAVR using the balloon-expandable Edwards SAPIEN valve at the University of Iowa Hospitals and Clinics were identified. We then excluded patients with a pre-existing pacemaker and who required conversion to an open/salvage procedure. We performed a retrospective chart review aimed at abstracting raw data related to patient characteristics, EKG variables, imaging, procedural variables, outcomes, and follow-up data. Univariate and multivariate logistic regression was performed, with post-TAVR PPM implantation as the outcome.

Results:
A total of 100 patients were included in the study and PPM was placed in 9 patients (9%). AV block was the indication for all PPM. In univariate analysis, the ratio of valve size to diameter of Sinus of Valsalva was a significant predictor of PPM (84.1±9.3 vs 76.8±7.1, p=0.009) (Table 1). In multivariate analysis, using right bundle branch block (RBBB), sex and the ratio of valve size to diameter of Sinus of Valsalva as predictors, pre-existing (RBBB) (OR: 6.5, 95% CI: 1.1-37.1, p=0.035) was identified as a predictor of PPM and the ratio of valve size to diameter of Sinus of Valsalva (OR: 1.2, 95% CI: 1.03-1.3, p=0.012) was identified as a novel predictor of PPM.

Conclusions:
PPM placement was required in 9% of patients without pre-existing PPM who underwent TAVR. In addition to pre-existing RBBB, the ratio of valve size to diameter of Sinus of Valsalva was identified as a novel predictor of PPM after TAVR. Our findings differ from prior published manuscripts which reported valve size to LV outflow tract diameter ratio as a significant predictor of post-TAVR PPM implantation.
Abstract 18484: An App-based Discrete Choice Survey Tool for Assessing Patient Treatment Preferences in Critical Limb Ischemia
Authors: Corriere Matthew A , Barnard Ryan T , Saldana Santiago , Boone Derrick S , Easterlin g Douglas , Hyde Adam , Burke Gregory L , Guzman Raul J , Duwayri Yazan , ip Edward
Published: July 2021

Introduction:
Patient centered care has potential to improve PAD treatment but providers need structured approaches to understand patients' values and apply them to individualized treatment. We used focus groups to identify factors patients with critical limb ischemia (CLI) consider important for treatment choices and developed an app to assess their treatment preferences during clinical encounters.

Methods:
Focus groups were used to identify factors patients with CLI consider important and relevant for treatment decisions. Treatment attributes and levels derived from qualitative data were then used to design an app for assessing treatment preferences through a discrete choice survey. Treatment options were presented pair-wise in patients' own terms using an orthogonal array design, and choice set order was individually randomized. The app also collected demographic and educational information, vascular specific health related quality of life, and user satisfaction. Aggregate responses were evaluated using conjoint analysis, and relative attribute importance was defined based on a ratio-based share of overall utility.

Results:
26 patients with CLI participated in focus groups used to identify important attributes, levels, and terminology. A patient friendly app was developed and subsequently pilot tested in 20 additional patients. Mean participant age was 63.4 ± 11.2 years; 25% were women, 30% were African American, and 40% had a college education. Mean app completion time was 20.4 ± 6.6 minutes. Aggregate attribute importances in decreasing utility order were: type of treatment (45.9), chance of successful treatment outcome (22.9), treatment risk (15.8), symptomatic response (13.5), and treatment durability (1.9). 90% of participants indicated that they believed the app will help patients contribute to better treatment choices, and 90% believed it would help providers understand what patients consider most important.

Conclusion:
CLI treatment preference assessment is feasible during clinical encounters and may facilitate patient contributions to choices. Structured decision tools have potential to increase patient engagement and improve both satisfaction and outcomes.
Abstract 18497: Hospital-based Exercise Training Program Post Coronary Artery Bypass Graft Surgery: Impact of Once and Twice Daily Exercise Program on Cardiac Autonomic Modulation
Authors: Mendes Renata , Pantoni Camila B , Simões Rodrigo P , Di Thommazo-Luporini Luciana , Caruso Flávia C , Kabbach Erika Z , Borghi-Silva Audrey
Published: July 2021

Introduction:
Coronary artery bypass surgery (CABG) patients with postoperative decreased cardiac autonomic modulation (CAM) have a higher mortality rate and although cardiovascular rehabilitation and exercises have substantial benefits in CAM, there is a paucity of information about its effects considering a possible "dose-dependent” autonomic adaptation in a hospital-based exercise program. The aim was to evaluate the impact of once daily versus twice daily dosing regimens of hospital-based exercise training on CAM in post CABG patients. Hypothesis: We hypothesized that there is a dose-dependent exercise adaptation on CAM and greater benefit to twice daily exercise group.

Methods:
Thirty-seven patients post-CABG were divided into: GEX1 (n = 12) and GEX2 (n = 11), composed of patients who underwent exercises one and two daily sessions, respectively; and of a control group (CG, n = 14) who received usual care (respiratory therapy). GEX patients initiated the exercises on post-operative day 1 (PO1), following a whole progressive program until discharge. CAM was assessed by indices of heart rate variability (HRV) analyzed from heart rate and R-R intervals signals recording at rest during 10 minutes on PO1 (baseline) and discharge time.

Results:
At the time of discharge after the hospital rehabilitation conclusion, GEX2 presented higher values of rMSSD index, representative of parasympathetic modulation, and also higher values of RRtri, TINN and STDRR indices, representative of overall variability of RRi compared to GC, respectively (rMSSD: 7.5±1.9 vs 5.2±1.8 ms; RRtri: 3.2±1.4 vs 2.0±0.7ms; TINN: 46.0±30.5 vs 25.7±11.0 ms and STDRR: 10.0±6.3 vs 5.4±3.3 ms), while GEX1 presented only higher values of rMSSD compared to CG (rMSSD: 7.8±2.5 vs 5.2±1.8 ms). However, no differences were observed between groups on HRV baseline and at discharge time between groups GEX1 and GEX2.

Conclusion:
Our results suggested that twice daily hospital-based exercise program stimulated more favorably the cardiac autonomic nervous system adaptations in patients post-CABG. Although a daily exercise session promotes beneficial adaptations, two sessions should be encouraged to additional benefits in the cardiac autonomic modulation FAPESP 2015/2015 / 16730-3.
Abstract 18513: School-based Rheumatic Heart Disease Education Results in Improved Knowledge - Data From the PROVAR Study
Authors: Nascimento Bruno R , Beaton Andrea Z , Chequer Graziela , Bruno Kaciane K , Miri Cassio O , Lopes Eduardo L , Castro Iara M , Nunes Maria do Carmo P , Santos Julia P , Ribeiro Antonio Luiz P , Sable Craig
Published: July 2021

Introduction:
Rheumatic Heart Disease (RHD) remains an important cause of morbidity and mortality in Brazil and other low- and middle-income countries (LMIC). Lack of public awareness of the causes and prevention of RHD limit the efficacy of primary and secondary prevention programs.

Objectives:
To evaluate the efficacy of knowledge transfer that results from a structured public-school educational program on RHD.

Methods:
A prospective, cohort study was conducted over 7 months (9/2014-3/2015) in 5 randomly selected low-income public schools in Belo Horizonte, Brazil. All enrolled and present students received education. A nurse and an imaging technician utilized two custom structured educational curriculums, targeting children in grades 6 - 11 (aged 11-17). Pre-tests, taken immediately prior to educational curriculum queried students’ knowledge of the causes, prevention, diagnosis, and treatment of RHD. Post-tests, 1-3 weeks following education assessed the efficacy of knowledge transfer and retention.

Results:
The educational curriculum was delivered to 3200 students. One-third of these (1025) were randomly selected to participate in pre- and post-testing including 403 (39%) in 6th/7th grades (G1), 360 (35%) in 8th/9th (G2), and 261 (26%) of in 10th/11th grades (G3). The mean interval between pre-test and post-test was 10±10 days. Prior to the intervention, general knowledge regarding RHD was universally low (median score 46.7%, 40.0-60.0). Children in higher grades (G3) knew more about RHD than those in lower grades (60% vs. 40.0% G1/46.7% G2), p<0.001. Children showed significant gains in the post-test, raising the median score by 20 percent (60%, 40.0-73.3). Again, children in the higher grades showed higher overall scores (73%, 60.0-80.0 G3; 56.7%, 40.0-73.3 G2; 53.3%, 33.3-66.7 G1), p<0.001. However, the percent increase was similar between groups (6.8% G1, 6.8% G2, 8.5% G3), p=0.47.

Conclusions:
School-based RHD education resulted in consistent but modest gains in knowledge. Novel educational techniques and use of technology to engage young learners may lead to improved knowledge gains and retention. Further studies are needed to determine if increased knowledge leads to behavioral changes that could decrease the burden of RHD in LMIC.
Abstract 18533: Walking on Eggshells: Patient Narratives of Recovery After Atrial Fibrillation Ablation
Authors: Wood Kathryn , Barnes Angel , Hines Kristina
Published: July 2021

Introduction:
Atrial Fibrillation (AF), the most common irregular heart rhythm worldwide, is now considered an epidemic. Ablation is a highly successful, curative procedure in most arrhythmias except AF. The first six months after an AF ablation can be wrought with more arrhythmias and symptoms than before the procedure. This study explored the patient’s perspective of the challenges faced during the first six months following an AF ablation.

Methods:
Our longitudinal mixed methods study used interviews and questionnaires at baseline and at 1, 3, and 6 months following AF ablation treatment in 20 AF patients. Subjects were recruited from an online AF patient website to obtain geographic diversity. Subjects also wore a Zio®Patch monitor at each of the measurement points to correlate symptoms with underlying cardiac rhythm. Grounded theory analysis was used for the qualitative data. A repeated measure ANOVA was used to compare changes in quantitative scores over time.

Results:
Mean age = 64 ± 14 years and the sample was 55% female. Qualitative analysis themes included: (1) seeking reassurance and meaning of symptoms were constant throughout the six months; (2) struggling with feelings of isolation, fatigue, and anxiety were common yet varied across the six months; (3) patient expectations of treatment outcome varied greatly from provider expectations; (4) managing symptoms and drug changes was very challenging work for patients. Patterns of fatigue and anxiety expressed during the interviews correlated with the quantitative scores. Patients felt that standard educational preparation was inadequate in both content and timing. Many patients were using smart phone apps and websites for information and reassurance that the providers were not aware of.

Conclusions:
Despite the AF epidemic, patients struggled in perceived isolation with little direction from providers. Quicker recognition by health care providers of the most common challenges patients face in following AF ablation could lead to earlier diagnosis and more targeted interventions based on their needs. By obtaining these insights into patients’ perspectives on AF and treatment, providers learn to develop interventions specifically aimed at the challenges patients feel are most difficult.
Abstract 18550: Association Between a Healthy Cardiovascular Risk Factors Profile and Coronary Artery Calcium Score: Results From the Brazilian Longitudinal Study of Adults Health (ELSA-Brasil)
Authors: Bensenor Isabela M , Goulart Alessandra C , Santos Itamar S , Chor Dora , Pereira Alexandre C , Bittencourt Marcio S , Nasir Khurran , Blankstein Ron , Lotufo Paulo A
Published: July 2021

Introduction:
Few studies evaluated the relationship between a favorable lifestyle a healthy profile of cardiovascular risk factors and subclinical atherosclerosis measured by Coronary Artery Calcium Score (CAC).

Hypothesis:
to identify the association between lifestyle profile and CAC among mid-elderly men and women.

Methods:
We included 4058 participants of the Brazilian Longitudinal Study of Health aged 35-74 years who underwent CAC measurement. The 2010 Task Force of the American Heart Association cut-offs were used to define the ideal profile and included smoking, physical activity, diet, blood pressure, glucose/cholesterol levels, and body-mass index. Only 21 participants had at least 6 ideal metrics. Participants were categorized according the number of ideal risk factors (IRF): 0-1 (n=1152, 28.4%), 2 (n=1234, 30.4%), 3-4 (n=1489, 36.7%), or 5-7 (n=183, 4.5%).

(Figure 1).

Results:
Compared to individuals with 0-1 IRF, the odds ratio (OR) of participants with 2 IRF presenting with CAC of 0 (compared to >0), <100 (compared to ≥100), and <400 (compared to ≥400) was 0.65 (95% confidence interval [CI]: 0.54-0.79), 0.59 (95%CI: 0.45-0.77), and 0.61 (95%CI: 0.39-0.94), respectively. Similarly, the ORs of CACs of 0, <100, and <400 in individuals with 3-4 IRF were 0.54 (95%CI: 0.44-0.66), 0.42 (95%CI: 0.31-0.57), and 0.56 (95%CI: 0.34-0.92), respectively. The ORs of CACs of 0, <100, and <400 in individuals with 5-7 IRF were 0.33 (95%CI: 018-0.58), 0.17 (95%CI: 0.04-0.72), and zero, respectively.

Conclusion:
Subjects with more IRF had lower CAC compared to subjects with lower ICH metrics, but CAC >0 was found even in these individuals.
Abstract 18572: Limitations of Endocardial Unipolar Voltage Mapping in Predicting the Epicardial Substrate
Authors: Gökoglan Yalçin , Günes Mahmut F , Di Biase Luigi , Gianni Carola , Mohanty Sanghamitra , Trivedi Chintan , Bai Rong , Al-Ahmad Amin , Burkhardt J D , Gallinghouse Joseph G , Horton Rodney , Hranitzky Patrick M , Sanchez Javier E , Natale Andrea
Published: July 2021

Introduction:
Bipolar voltage mapping detects areas of scar and guides ablation of VT. The role of endocardial unipolar voltage mapping is not well defined. We examined the endo-epicardial substrate in a mixed cohort of patients with structural heard disease (SHD) to determine whether an endocardial unipolar low voltage area predicts the presence and location of an epicardial scar.

Results:
Data from 24 consecutive patients with SHD (11 ICM, 6 NICM, 3 HCM, 2 ARVC, 1 myocarditis, 1 Brugada) with a detailed (mean points per map 200) combined endocardial-epicardial substrate mapping were retrospectively reviewed. Maps were obtained using a 3D mapping system (CARTO 3) and normal thresholds used were ≤1.5 mV for bipolar voltage, and ≤5.5 (RV) or ≤8.3 mV (LV) for unipolar voltage. Mapping was performed in the LV in 17 patients, in the RV in 6 patients, in both in 1 patient.

An endocardial unipolar low voltage area was found in 21/25 maps. In 12/21 maps there was no corresponding epicardial scar, while in 3/4 cases an epicardial scar was detected despite a negative unipolar map (PPV=43%, NPV=25%, P=NS; Fig. 1). In the 9 cases with both positive endocardial unipolar and epicardial bipolar maps, the epicardial scar was found in the corresponding ventricular region of the endocardial low-voltage area, although unipolar area had a tendency to overestimate the area of the scar (115 vs 95 cm
2
).

Conclusion:
In this series of patients with SHD, analysis of unipolar voltage maps could not reliably predict the epicardial arrhythmogenic substrate. There is a modest correlation between areas of endocardial unipolar low voltage and epicardial scars (57% of patients with an abnormal unipolar map had a normal epicardial substrate). Moreover, an epicardial substrate cannot be safely excluded based on a normal unipolar endocardial map.

Fig. 1
Abnormal bipolar epicardial map (left) with corresponding normal unipolar endocardial map (right) in a patient with ARVC. Pink dots represent area of defragmentation.
Abstract 18584: Decoding the Regulatory LncRNAs in Neonatal Heart During Perinatal Circulatory Transition
Authors: Touma Marlin , Cass Ashley , Kang Xuedong , Zhao Yan , Biniwale Reshma , Reemtsen Brian , Xiao, Xinshu , Wang Yibin
Published: July 2021

Background:
Fetal to neonatal transition of heart is an elaborate process, during which, neonatal cardiomyocytes undergo functional maturation and terminal exit from the cell cycle. However, transcriptome programming in neonatal cardiac chambers during perinatal stages is understudied. In particular, the changes in long non-coding RNAs (lncRNAs) in neonatal heart have not been explored.

Objective:
To achieve transcriptome-wide analysis of lncRNAs in neonatal left ventricle (LV) and right ventricle (RV) during maturation stages using deep RNA-Sequencing

Methods:
Deep RNA-sequencing was performed on male newborn mouse (C57 BL) LV and RV at 3 time points of perinatal circulatory transition: P0, P3 and P7. Reads were mapped to mouse genome (mm10). The lncRNAs annotated in NONCODE database were identified. Differentially expressed lncRNAs were defined as those with coefficient of variation ≥0.2, at a false discovery rate ≤0.05, and expressed at ≥3 RPKM in at least one sample. Correlated lncRNAs/ gene pairs were identified using Pearson’s (r2≥0.8, P≤0.05). A subset of LncRNAs/gene expression was validated using qRT-PCR.

Results:
Out of the 70, 983 observed unique lncRNAs, approximately 7000 were identified exhibiting significant variation during maturation windows with highly spatial-temporal dependent expression patterns, including approximately 5000 known and 2000 novel lncRNAs. Notably, 20% of these lncRNAs were located within 50 KB of a protein coding gene. Out of a total of 2400 lncRNAs/gene pairs, 10 % exhibited significantly concordant (lncRNA/gene) expression patterns. These correlated genes were significantly enriched in metabolism, cell cycle and contractility functional ontology. Interestingly, some of these lncRNAs exhibited concordance with their neighboring gene in human tissues with congenital heart defects, suggesting conserved, potentially significant, regulatory function.

Conclusions:
Transcriptome programming during neonatal heart maturation involves global changes in lncRNAs. Their expression concordance with neighboring protein coding genes implicates potential important regulatory role of lncRNAs in neonatal heart chamber specification and congenital diseases.
Abstract 18632: Variation in Patient Profiles and Outcomes in US and non-US Subgroups of the Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) PHOENIX Trial
Authors: Vaduganathan Muthiah , Harrington Robert A , Stone Gregg W , Steg Ph. Gabriel , Gibson C. Michael , Hamm Christian W , Price Matthew J , Prats Jayne , Deliargyris Efthymios N , Mahaffey Kenneth W , White Harvey D , Bhatt Deepak L
Published: July 2021

Objectives:
To describe the clinical profiles, safety and efficacy endpoints, and response to cangrelor in US and non-US subgroups.

Background:
CHAMPION PHOENIX demonstrated superiority of cangrelor in reducing ischemic events at 48 hours in patients undergoing percutaneous coronary intervention (PCI) compared with clopidogrel.

Methods:
We analyzed all patients included in the modified intention-to-treat analysis in US (n=4,097; 37.4%) and non-US subgroups (n=6,845; 62.6%).

Results:
The US cohort was older and had higher rates of cardiovascular risk factors and prior cardiovascular procedures. US patients more frequently underwent PCI for stable angina (72.4% vs. 46.4%). Utilization of clopidogrel loading doses of 600mg and bivalirudin was also higher in US vs. non-US participants. At 48 hours, rates of the primary composite endpoint were lower in the cangrelor arm compared with the clopidogrel arm in US (4.5% vs. 6.4%; OR 0.71 [0.54-0.92]) and in non-US patients (4.8% vs. 5.6%; OR 0.85 [0.69-1.05]); interaction P=0.26 (
Table
). Similarly, rates of the key secondary endpoint, stent thrombosis, were reduced by cangrelor in both regions. Rates of GUSTO (Global Use of Strategies to Open Occluded Arteries)-defined severe bleeding were low and not significantly increased by cangrelor in either region.

Conclusions:
Despite broad differences in clinical profiles and indications for PCI by region in a large global cardiovascular clinical trial, cangrelor consistently reduced rates of ischemic endpoints compared with clopidogrel without an excess in severe bleeding in both US and non-US subgroups.
Abstract 18639: Implantable Cardioverter-defibrillator Use is Associated With Improved Survival on the Waitlist for Heart Transplantation: A UNOS/ OPTN Registry Analysis of 36,397 Patients
Authors: Vakil Kairav , Cogswell Rebecca , Duval Sue , Levy Wayne , Eckman Peter , Anand Inder , Dardas Todd , Adabag Selcuk
Published: July 2021

Background:
Current guidelines do not support routine use of implantable cardioverter-defibrillators (ICDs) in patients (pts) with end-stage heart failure (HF), unless these pts are awaiting advanced HF therapies such as left ventricular assist devices (LVADs) or a heart transplantation (HT). Whether ICDs improve survival in end-stage HF pts awaiting HT has not been previously examined in a large, multicenter cohort.

Hypothesis:
Presence of ICDs at time of listing for HT is associated with lower waitlist mortality.

Methods:
The United Network for Organ Sharing registry was used to identify adults (≥18 years) listed for HT between January 4, 1999 & September 30, 2014. Pts with congenital heart disease, total artificial heart, restrictive cardiomyopathy, prior HT, or missing covariates were excluded. Cox regression analysis was used to assess the impact of an ICD at the time of listing on waitlist mortality.

Results:
The analysis included 36,397 pts (mean age 53±12; 77% males) listed for HT. The prevalence of ICDs at listing has steadily increased over time before reaching a plateau in 2006 (27% in 1999, and range 76-82% between 2006-2014). In the unadjusted model, ICD use was associated with a 36% reduction in waitlist mortality (HR 0.64, 95% CI 0.60-0.68, p<0.001). After adjustment for covariates such as age, sex, race, creatinine, ischemic cardiomyopathy, and listing status, this association was nearly unchanged (HR 0.67, 95% CI 0.62-0.72, p<0.001). Test for interaction by listing era (pre- and post-2006) was non-significant (p=0.28). In the final adjusted model, that included listing era and LVAD status in addition to the above listed covariates, ICD use continued to remain associated with a mortality benefit on the waitlist for HT (HR 0.84, 95% CI 0.78-0.91, p<0.001).

Conclusion:
ICDs are increasingly prevalent in pts listed for HT; however many pts are still listed for HT without these devices. The presence of an ICD at the time of listing is associated with lower mortality on the waitlist. Although the magnitude of ICD efficacy diminishes slightly, its benefit continues to remain significant even after adjustment for listing era and LVAD use. Further analyses are required to identify specific sub-groups of pts where ICD use is most beneficial and appropriate.
Abstract 18650: Activation Mapping of Ventricular Ectopy: Characterization of a Threshold Value Predicting Successful Catheter Ablation
Authors: Camnitz Will , Bilchick Kenneth , Dimarco John , Driver Kevin , Ferguson John , Mangrum James M , Mason Pamela , Malhotra Rohit , Darby Andrew
Published: July 2021

Background:
Catheter ablation of ventricular ectopy is performed with increasing frequency. Activation mapping to determine the site with the earliest presystolic electrogram (EGM) is the most accurate method to locate the optimal ablation site. Despite this, activation mapping of ventricular ectopy has not been systematically reviewed in a large series, and the optimal activation time predicting successful ablation has not previously been determined. The goal of this study is to determine the local presystolic activation time most predictive of successful ablation.

Methods and Results:
We retrospectively reviewed 100 consecutive successful endocardial PVC ablations and analyzed the local activation time at each successful and unsuccessful ablation site. A total of 561 ablation lesions were reviewed. Activation time was calculated as the difference between the peak of the local bipolar EGM and the onset of the reference surface QRS complex. Acute success was defined as complete elimination of the target PVC during the procedure with no recurrence at 30 days by ECG and follow-up Holter. A local activation time 27 msec presystolic best predicted success with a sensitivity of 88%, specificity 85%, and an area under the ROC curve of 0.936 (95% CI 0.91 - 0.95; figure 1). The 27 msec presystolic activation time remained most predictive of success after sub-stratifying activation times by location (RVOT v LVOT, outflow v intracavitary). The odds ratio for success with each 1 msec increase in activation time (becomes more negative by 1 msec) is 1.24 (95% CI 1.19 - 1.29).

Conclusion:
In our experience, a local presystolic activation time of 27 msec is the threshold value most predictive of successful PVC ablation. Our review is the first to systematically characterize an activation time predicting success with PVC ablation in a large cohort.

Figure 1