bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19742: Effects of a "Health Partner" Intervention on the Metabolic Syndrome
Authors: Wilson Natalee K , Al Mheid Ibhar , Cunningham Lynn , Brigham Kenneth , Martin Greg S. , Gibbons Gary , Jones Dean P. , Vaccarino Viola , Quyyumi Arshed A.
Published: July 2021

Introduction:
The Metabolic Syndrome (MetS) is highly prevalent, afflicting a third of U.S. adults, and confers higher cardiovascular morbidity and mortality. Features of MetS include abdominal obesity, elevated blood pressure, dysglycemia and atherogenic dyslipidemia. While lifestyle modifications are the first-line of MetS treatment, sustained adherence is achieved by a minority of patients. We investigated the effects of a Health Partner (HP) intervention on MetS.

Methods and Results:
A total of 119 university employees with MetS (51±9 years, 59% women, 26% African Americans) were enrolled in an academic program that promotes clinical self-knowledge and healthier lifestyles at the Center for Health Discovery and Well Being at Emory University in Atlanta, GA. Baseline anthropometric, laboratory and vascular function measurements were used by the HP to generate an action plan with detailed strategies to improve dietary and exercise habits, and subjects returned for follow up at 6 months and annually thereafter for 2 years. Repeated measures ANOVA showed statistically significant changes in waist circumference (p=0.007; baseline vs. 2 years: 103.1 vs. 98.2 cm), weight (p=0.004; 216.1±35 vs. 204.9±37 lbs), body fat percent (p=0.042; 39.6±7.4 vs. 38.1±7.9), fasting insulin levels (p=0.034; 11.4±8.3 vs. 7.9±9.9 μIU/ml), low density lipoprotein (p=0.005; 114.7±31.2 vs. 104.9±28.9 mg/dl), as well as a reduction in carotid-femoral pulse wave velocity (p=0.016; 7.4±2.2 vs. 6.7±1.1 m/s), systolic (p=0.001; 131.6±17.5 vs. 125.7±14.2 mmHg) and diastolic blood pressure (p=006; 84.7±11.1 vs. 80.1±10). There were no significant changes in glucose, triglyceride levels or brachial-artery flow mediated dilation.

Conclusion:
A personalized, goal directed HP intervention improves abnormalities associated with MetS, including body habitus, lipid and insulin secretion abnormalities, and resulted in significant blood pressure improvements that accompanied decreased central arterial stiffness. These improvements were sustained after two years of follow-up. Whether HP intervention improves long-term outcomes and whether it is cost-effective needs further investigation.
Abstract 19766: Prediction of Clinical Atrial Fibrillation induced during Typical Atrial Flutter Ablation
Authors: Romero Jorge , Estrada Rodolfo , Holmes Anthony , Goodman David , Roth Norman , Golive Anjani , Doshi Jay , Manheimer Eric , Fisher John D , Gross Jay , Krumerman Andrew , Ferrick Kevin , Kim Soo , Di Biase Luigi
Published: July 2021

Background:
Atrial fibrillation (AF) and isthmus dependent atrial flutter (AFL) are two separate entities that in many patients coexist. We sought to investigate whether AF inducibility (spontaneous or drug induced) during isthmus AFL ablation predicted the occurrence of AF at follow up after successful AFL ablation.

Methods:
Two hundred seventy three consecutive patients with isthmus dependent AFL undergoing ablation of AFL at our institution were enrolled in this study. 119 (43%) patients were excluded since they had evidence of AF prior to AFL ablation. Univariate and multivariate analyses were performed.

Results:
A total of 154 patients (male: 72%, age: 61 ±13) with AFL and without history of AF composed our patient population. All patients underwent successful AFL ablation. During ablation, AF was induced in 28 (18%) patients. After a mean follow up of 34 ± 23.5 months a total of 50 (32%) experienced AF. Univariate and multivariate analyses showed that only age and AF inducibility during AFL ablation were predictors of AF. Univariate analysis (age: p=0.038 and inducible AF p=0.032 and multivariate analysis (age: p=0.011 inducible AF: p=0.016) ) with and adjusted odds ratio of 3.3 [95% CI (1.250-8.676)] (Table 1). A total of 169 (62%) patients experienced AF before or after AFL ablation.

Conclusion:
AF inducibility in patients undergoing isthmus dependent AFL without history of AF is a strong predictor of AF recurrence. This has an important clinical relevance on anticoagulation management of these patients.
Abstract 19787: Transcatheter Aortic Valve Implantation in Patients With Bicuspid Aortic Valve: a Patient Level Multi-center Analysis
Authors: Yousef Altayyeb , Simard Trevor , Webb John , Rodés-Cabau Josep , Costopoulos Charis , Kochman Janusz , Hernández-Garcia José M , Chiam Paul T , Welsh Robert C. , Wijeysundera Harindra C. , García Eulogio , Ribeiro Henrique B. , Latib Azeem , Huczek Zenon , Shanks Miriam , Testa Luca , Farkouh Michael E. , Dvir Danny , Velianou James L , Lam Buu-Khanh , Pourdjabbar Ali , Glover Christopher , Hibbert Benjamin , Labinaz Marino
Published: July 2021

Objective:
The purpose of the study was to determine the safety and efficacy of TAVI in patients with stenotic bicuspid aortic valve (BAV).

Background:
To date, patients with BAV have been excluded from major TAVI studies due to a theoretical increased risk of paravalvular leak (PVL). Data on the clinical performance of TAVI in these patients is limited.

Methodology:
We conducted a retrospective international multicenter cohort study of patients with BAV undergoing TAVI. The primary outcome of the study was the combined early safety endpoint - a composite of 30 day mortality, stroke, life-threatening bleeding, acute kidney injury, coronary artery obstruction, major vascular complication and valve related dysfunction. Secondary endpoints included the individual components of the primary endpoint as well as post TAVI paravalvular leak (PVL), rehospitalization, new pacemaker insertion and device success rates at 30 days and 1 year.

Results:
A total of 107 patients with BAV were identified in 21 centers in Canada, Spain, Italy, Poland and Singapore who underwent TAVI between January 2005 and March 2014. The composite primary outcome occurred in one third of patients (28.6%) - mainly driven by re-intervention for valve malposition (12.3%). The 30-day and 1 year mortality rate was 9.7% and 17.2% respectively with AR ≥ 3+ occurring in 8.8% of patients. Device success was achieved in 85% of cases with pacemaker insertion in 17.9%. While PVL was not associated with an increased risk of 30 day or 1 year mortality - Type I

BAV anatomy with left and right cusp fusion had significantly better outcomes than other variants.

Conclusion:
In selected patients with BAV and severe aortic stenosis TAVI appears both safe and feasible with acceptable clinical outcomes. A randomized comparison of TAVI versus surgical aortic valve replacement in this patient population is warranted.
Abstract 19792: Prediction of Right Ventricular Failure After Cardiac Transplantation : A Recipient Transcriptomic Study
Authors: Guijarro Damien , Gueffet Jean-Pierre , Steenman Marja , Roussel Jean-Christian , Trochu Jean-Noel , Lamirault Guillaume
Published: July 2021

Introduction:
Right ventricle failure (RVF) is a frequent and severe complication after cardiac transplantation. However, risk stratification for RVF is poorly achieved. Development of transcriptomic biomarkers for outcome prediction in cardio-vascular diseases is promising.

Hypothesis:
Our aim was to identify right ventricular gene expression signature associated to RVF and to define a transcriptomic biomarker that could predict post-transplantation RVF.

Methods:
Recipient RV myocardial samples of 44 patients transplanted from February 1998 to November 2002 in our center were collected. We retrospectively identified patients with (RVF group) and without (CTL group) post-transplantation RVF.

A 4035-gene expression profile was obtained for all patients. Differentially expressed genes between RVF and CTL groups were identified and a molecular RVF predictor was used to determine for each patient a RVF prediction score (RVFs).

Results:
9 (20%) and 18 (41%) patients were classified in RVF and CTL groups respectively. As compared to CTL group, RVF patients showed higher pre-operative bilirubin level and higher post-operative death rate.

Molecular RVF predictor included 75 differentially expressed genes. Using this predictor, risk for post-transplantation RVF was 2.8-fold greater if RVFs was >0.5 (CI 95%: 1.243-6.305). Sensitivity and specificity of RVFs were 0.778 and 0.889, respectively. Using receiver operating characteristic analysis, RVFs area under curve (AUC) was significantly greater than AUC of commonly used RVF predictors (pulmonary vascular resistance, trans-pulmonary gradient).

Conclusions:
Gene expression profiling of recipient right ventricle could be used to predict post-transplantation RVF. Transcriptomic biomarkers should be further investigated as a new tool for selection of cardiac transplant candidates.
Abstract 19820: Heterogeneity of Disease Progression Rates in Patients With Bicuspid Aortic Valve: Is There a Suitable Bio-marker?
Authors: Nguyen Thanh H , Shah Ranjit , Chapman Matthew , Ali Onn A , Horowitz John D
Published: July 2021

Introduction:
Bicuspid aortic valve (BAV) is associated with inflammatory activation and endothelial dysfunction. Worsening of aortic valve stenosis/regurgitation represents the most common complication of BAV, but clinical and biochemical markers of disease progression are not currently available.

Objective:
The objective of the current study was to (1) evaluate rates of progression of aortopathy and valve dysfunction, and (2) identify correlates of accelerated progression among BAV patients.

Methods:
43 BAV patients aged 45 ± 16 (SD) years were evaluated clinically and with echo/MRI. Inflammatory activation was assessed via hs-CRP and myeloperoxidase (MPO) levels, endothelial function/NO responsiveness via flow-mediated dilatation (FMD), plasma asymmetric dimethylarginine (ADMA) levels, inhibition of platelet aggregation by SNP, and endothelial progenitor cell counts. Follow-up was undertaken after 47 ±16 months to determine rate of progression and of need for valve replacement; some patients did not undergo repeat echo (Figure). Biochemical/physiological correlates of valve dysfunction and aortic dimensions were sought via univariate and multiple linear regression analyses.

Results:
AV max increased from 2.1 ± 0.6 to 2.5 ± 1.1(m/s), p < 0.05, while ascending aorta (Asc Ao) dimensions increased from 18.2 ± 6.1 to 21.2 ± 4.9 (mm/m
2
), p < 0.05 over the monitoring period. Although there was a direct correlation (p < 0.01) between baseline AV max and MPO levels on multivariate analysis, this correlation did not extend to progression rates. Indeed neither clinical nor biochemical parameters predicted accelerated progression.

Conclusions:
(1) Progression of valve disease and aortopathy in BAV is often rapid, with annual mean rate of 0.1 m/s for AV max and 0.4 mm/m
2
for Asc Ao. (2) Despite physiological evidence linking BAV with inflammation and endothelial dysfunction, these biochemical factors did not appear to predict rapid disease progression.
Abstract 19822: Arterial Calcification Can Be Inhibited via Stress Protein Induction Through a PPAR-dependent Pathway
Authors: Lim Kenneth , Xu Jen , Kao E-Jay , Kong Tianqing , Lu Tzongshi
Published: July 2021

Introduction:
Cardiovascular disease occurs prematurely in chronic inflammatory conditions such as Chronic Kidney Disease (CKD) and unfortunately, remains the leading cause of death in these patients. Vascular calcification (VC) is a significant contributor to cardiovascular mortality in CKD patients with the sequela of arterial hardening, congestive heart failure and sudden cardiac death. We recently reported that heat shock protein 72 (HSP72) when inducted, can inhibit the development of VC.

Hypothesis:
We hypothesize that HSP72 exerts its vasculo-protective effects by functioning as a molecular chaperon for peroxisome proliferator-activated receptor γ (PPARγ).

Methods:
We developed an in vitro long-term calcification model using HA-SMCs treated with calcification medium (CM) containing 5mM CaCl2 and 5mM β-glycerophosphate for 21 days. Cells were subjected to heat shock treatment at 43°C for 30 minutes daily to induce HSP72. Calcification was assessed qualitatively by alizarin red staining and quantitatively by the arsenazo III method.

Results:
Our results show that inducible HSP72 is significantly expressed following heat shock treatment in HA-SMCs. Induction of HSP72 inhibited the development of VC in our long-term calcification model and these effects were abolished by HSP72 siRNA, in vitro. We next showed that HSP72 formed a protein-protein complex with PPARγ by co-immunoprecipitation. Expression of both these proteins was down-regulated in calcific HA-SMCs and their gene expression was down regulated in atherosclerotic human arteries. Furthermore, we found that the PPARγ inhibitor, FABP4 (fatty acid binding protein-4) which function as an atherosclerosis promoter was up-regulated in calcified human arteries. Lastly, induction of HSP72 restored expression of the HSP72-PPARγ complex and inhibited upregulation of FABP4 with reduction in calcification in our in vitro calcification model. These vasculo-protective effects were abolished by HSP72 siRNA.

Conclusion:
HSP72 is a powerful inhibitor of VC and exerts its vasculo-protective effects by functioning as a molecular chaperon to stabilize PPARγ and regulate the PPARγ-FABP4 pathway. We suggest treatment strategies involving induction of HSP72 as a new approach to inhibit VC.
Abstract 19824: Percutaneous Mitral Balloon Comissurotomy versus Surgical Comissurotomy in the Treatment of Severe Symptomatic Mitral Stenosis
Authors: Cardoso Rhanderson N , Ansari Mohammad , Garcia Daniel , De Marchena Eduardo , Mendoza Cesar E
Published: July 2021

Introduction:
Percutaneous mitral balloon comissurotomy (PMBC) and surgical comissurotomy can be used for treatment of stage D mitral stenosis. Randomized controlled trials (RCTs) comparing PMBC and surgery have shown inconsistent results.

Hypothesis:
PMBC is associated with better hemodynamic and clinical results for the treatment of stage D mitral stenosis.

Methods:
Databases were searched for RCTs that compared double-balloon PMBC to surgical comissurotomy. Inclusion criteria were no left atrial clot, a favorable valve morphology and absence of significant mitral regurgitation. Clinical and hemodynamic outcomes were evaluated within short-term (less than 6 months) and long-term (over 6 months) follow up. Random-effects model was used due to anticipated heterogeneity.

Results:
A total of 6 RCTs with 474 patients were included, of whom 222 (46.8%) underwent PBMC. In short-term follow up, PMBC was associated with a larger mitral valve area (MVA) compared to surgical comissurotomy (mean difference 0.41 cm2; 95% CI 0.16-0.67; p=0.002; figure 1A), but also a higher incidence of moderate to severe mitral regurgitation (MR; OR 2.63; 95% CI 1.04-6.70; p=0.04; figure 1B). Short-term symptomatic (NYHA II-IV) heart failure (p=0.40) and new MR (p=0.32), as well as long-term MVA (p=0.23), restenosis (p=0.39), symptomatic heart failure (p=0.11), new MR (p=0.64) and need for reintervention (p=0.21) were not significantly different between groups.

Conclusions:
Our meta-analysis of RCTs suggests that PMBC is associated with an increased MVA as well as a higher incidence of moderate to severe MR when compared to surgery in the treatment of stage D MS. Therefore, the decision to proceed with PMBC or surgery in patients suitable for both procedures must rely on patient preferences, physician experience and risk of procedure-specific complications, such as left-to-right shunt with PMBC and wound infection/dehiscence with surgical comissurotomy.
Abstract 19854: A National Perspective of Weekend- Effect on Mortality and Adverse Outcomes in Patients with Intracerebral Hemorrhage
Authors: Patel Achint , Nadkarni Girish , Patel Neil , Lahewala Sopan , Busani Sudharani , Solanki Shantanu , Dhaduk Grishma , Bambhroliya Chirag , Mahajan Abhimanyu , Simoes Priya , Konstantinidis Ioannis , Gujarati Yogesh , Benjo Alexandre M , Jani Vishal , Badheka Apurva , Hussain Syed I
Published: July 2021

Introduction:
Management of intracerebral hemorrhage (ICH) requires urgent diagnostic and therapeutic procedures, which may not be uniformly available throughout the week. We attempt to define a "weekend effect" for ICH, which has not yet been fully established in this patient population.

Hypothesis:
We aimed to evaluate whether outcomes differ with respect to the day of admission in patients admitted with ICH.

Methods:
We reviewed the Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample (NIS) database from 2000 to 2011 for ICH using ICD 9-CM codes. NIS represents 20% of all US hospital pts and weighted numbers represent national estimates.We defined primary outcome as mortality and adverse outcome(composite of in-hospital mortality & discharge other than home). We utilized chi-square test for univariable analysis for categorical variables and generated hierarchical multilevel regression models to determine independent predictors of mortality and adverse outcome.

Results:
We included 161017 patients (weighted n=788641) with ICH, out of which 42996(weighted n= 210592) were admitted on weekend. After adjusting for confounders (demographics, Deyo’s modification of charlson’s co-morbidity index, admission type (elective or emergent), hospital region, hospital teaching status, hospital ICH volume and primary payer), the weekend admissions were still associated with 10 % higher mortality (OR 1.10, 95% CI 1.07-1.16, P=0.001) and 20% higher adverse outcome (OR 1.12, 95% CI 1.09-1.16, p=0.001).

Conclusions:
Thus, admission for ICH on the weekend was a significant and independent predictor of increased in hospital mortality and adverse outcomes as compared to weekday admission. The reasons for this are likely manifold and warrant further investigation both from a quantitative and qualitative standpoint.
Abstract 19907: Clinical Prediction Risk Scores Systematically Underestimate the Presence and Extent of Subclinical Atherosclerosis in Brazilian Women: The Brazilian Study of Longitudinal Health (ELSA-Brasil)
Authors: Bittencourt Marcio S , Pereira Alexandre C , Staniak Henrique L , Sharovsky Rodolfo , Gomez Luz Marina , Mendes Vytor Hugo , Blankstein Ron , Nasir Khurram , Bensenor Isabela , Lotufo Paulo A
Published: July 2021

Introduction:
Different scores were developed to predict cardiovascular events in different populations. Due to genetic, social and economical differences, their performances vary according to the population to which they are applied. While there is concern that some scores may underestimate risk in women, few data exist for the Brazilian population.

Hypothesis:
Clinical risk scores will underestimate the coronary artery calcium (CAC) in Brazilian women.

Methods:
In a substudy from the ELSA-Brasil, a multicenter prospective study that enrolled civil servants in Brazil, 4546 participants underwent a CAC score. We calculated the Framingham risk score, Reynolds score, ASSIGN, PROCAM and both the low and the high European SCORE. To test the ability of each score to predict CAC values, we used a zero inflated model, which accommodates better CAC distribution. This is a two part model; the discrete part evaluates the association of the predictor with the probability of a CAC=0, and the continuous part of the model evaluates the association of the score with the CAC value.

Results:
The population included 1868 (55%) women with a mean age of 48±8 years. The median CAC was 0 (range 0 - 5363). In figure 1 we present the association of each score with the CAC values stratified by gender. All score are significantly associated with the discrete part of the model (probability of a CAC=0) (p>0.001). However, while all scores were associated with the continuous part of the model for men (p<0.0001); only the Reynolds (p=0.035) and the high SCORE (p<0.0001) were associated with the continuous part of the model in women, whereas the Framingham score (p=0.96), ASSIGN (p=0.33) and PROCAM (p=0.78) were not. Figure 1 shows the association of each score with the CAC results stratified by gender.

Conclusions:
In a large Brazilian cohort, all clinical risk scores were significantly associated with the presence of CAC in men, whereas only the SCORE and Reynolds were associated with CAC values in women.
Abstract 19932: A Neuroimmune Drive Activates Plgf to Control an Epigenetic Mechanism in the Spleen That Allows T Cells Activation in Hypertension
Authors: Carnevale Daniela , Iacobucci Roberta , Pallante Fabio , Fardella Valentina , Fardella Stefania , De Lucia Massimiliano , Lembo Giuseppe
Published: July 2021

Introduction and Hypothesis:
In the past several years, there has been mounting interest in the roles played by immunity in hypertension. However, where and how the immune system gets activated under hypertensive stimuli to contribute to hypertension, is still enigmatic. The activation of effector T cells in hypertension suggests that antigen presentation by a specialized subset of innate cells represents an important component that participates in this process. In particular, it has been recently shown that T cell costimulation by B7 ligands is an important mechanism in the development of hypertension.

Methods and Results:
Here we demonstrate a novel splenic mechanism driven by Placental Growth Factor (PlGF) and regulating T cells costimulation in AngII-induced hypertension. We have found that PlGF is necessary to allow CD86 expression, crucial in AngII hypertension. Moreover, we show that this effect is exerted by a Sirt1-dependent epigenetic modulation of Timp3 expression in splenic macrophages, obtained by controlling p53 repressor activity on its promoter. Since the brain plays a pivotal role in AngII-induced hypertension and it is known that a selective removal of sympathetic innervation to the splanchnic district, obtained by celiac ganglionectomy (CGX), markedly attenuated hypertension, we looked whether the early induction of splenic PlGF upon AngII could be mediated by a nervous drive. Indeed, when we performed CGX in WT mice, splenic PlGF was markedly reduced, thus demonstrating that is is activated by Ang-II induced SNS overactivity. Importantly, we show that this neuroimmune mechanism driven by PlGF is crucial for the onset of hypertension, since PlGF KO mice display a clear-cut protection from the typical AngII-hypertensive response and from T cells infiltration in vessels and kidneys. Finally, chimeric mice generated by spleen transplantation (PlGF KO spleen in WT background and vice versa), allowed us to finally demonstrate that PlGF is indispensable in the spleen for the onset of hypertension.

Conclusions:
Summarizing, our study brought to light both how important the neuroimmune drive in the spleen is in the genesis of hypertension and, at same time, unveil that PlGF is the molecular pathway recruited in the spleen to control BP raising.
Abstract 19944: A PDE5A Gene Mutation Affecting Risk of Myocardial Infarction
Authors: Dang Tan An , Braenne Ingrid , Aherrahrou Redouane , Tennstedt Stephanie , Kessler Thorsten , Hengstenberg Christian , Erdmann Jeanette , Schunkert Heribert
Published: July 2021

INTRODUCTION:
Multiple frequent genetic variants were shown to affect myocardial infarction (MI) risk. Genetic causes for familial clustering of MI are less clear. We aimed to identify and characterize the molecular underpinnings of premature MI in a family with 9 affected individuals.

METHODS AND RESULTS:
Employing cosegregation analysis and exome sequencing we identified a mutation in the phosphodiesterase 5A (
PDE5A
) gene in all affected individuals (LOD score 3.16). It is located in an alternative promoter site of
PDE5A
and leads to a premature stop codon in one of the
PDE5A
isoforms (p.Lys7Ter).
PDE5A
encodes for three isoforms catalyzing cGMP, a second messenger mediating vasodilation and platelet passivation. Effects of the stop codon were investigated by western blot analysis after
in vitro
mutagenesis. Overexpression in HEK cells did not reveal a loss of transcript but the expression of a N-terminally truncated protein. Deeper analyses of translation initiation by deletion of possible transcription starts via
in vitro
mutagenesis uncovered a protein lacking 91 amino acids compared to the full-length isoform. Activity of the truncated PDE5A was measured using PDEGlo (Promega). Moreover, the effect of the variant on the alternative promoter site was analyzed by luciferase assays. Therefore, a 600 bp fragment containing either the mutated or WT allele was cloned into a pGL4.10 vector (Promega). Overexpression in HEK cells showed 40% increase of promoter activity with the mutated allele (p<0.05). Similar results could be shown in other cell lines.

CONCLUSION:
We identified a mutation in the
PDE5A
gene associated with premature MI. While a gain of function of
PDE5A
makes sense from a pathophysiological stance, the particular variant seemed to result in a premature stop codon. However, we could demonstrate that the variant might lead to increased promoter activity and that the presumable stop codon does not result into a loss of transcript but rather a truncated, potentially more active PDE5A isoform. Along with our homology modeling results and x-ray crystallographic and biochemical studies of Wang
et al.
(2010), these data support the idea of overexpression of a truncated though functional PDE5A in mutation carriers, possibly resulting in a gain function.
Abstract 19973: Dynamic Thallium-201 SPECT/CT Provides Quantitative Index of Myocardial Flow and Viability: Validation in Porcine Post-Myocardial Infarction Model
Authors: Thorn Stephanie L , Stacy Mitchel R , Bregasi Alda , Paeng Jin C , Tavakoli Vahid A , Winters James O , Hawley Chris , Tang Yangfeng , Bennett James , Wells R. G , Liu Chi , Klein Ran , Sinusas Albert J
Published: July 2021

Introduction:
Thallium-201 (Tl-201) SPECT imaging is routinely used to evaluate relative myocardial perfusion and/or viability. In this study, we have evaluated Tl-201 kinetics in a porcine model of myocardial infarction (MI) with dynamic imaging on a hybrid SPECT/CT system.

Methods:
Tl-201 SPECT and contrast CT imaging were performed on hybrid SPECT/64-slice CT (GE Discovery NM/CT 570c) in Yorkshire pigs (n=5) one week following a 90 min balloon occlusion of the LAD below the first diagonal branch. Tl-201 (83-158 MBq) was injected after the initiation of a 900s list-mode acquisition. The list-mode data was reconstructed with MLEM using 30 iterations creating 23 frames (12 x 10s; 6 x 30s; 5 x 120s). Reconstructed dynamic SPECT data was analyzed using FlowquantTM semi-automated analysis software with a 1-compartment model. K1 (index of flow) and k2 (index of viability) were assessed within a 17-segment model of the left ventricle. Four segments within the central infarcted LAD territory were compared to six segments of the contralateral inferolateral wall. The same segments were analyzed for wall thickening from ECG-gated contrast CT scans using centerline approach (GE AW Cardiac Function Xpress).

Results:
K1 was significantly decreased in the MI vs contralateral normal regions (0.52 ± 0.17 vs 0.61 ± 0.16 ml/min/g, p<0.02). K2 an index of tissue viability was significantly increased in the MI region (0.42 ± 0.19 vs 0.32 ± 0.12 /min, p<0.04), reflecting accelerated Tl-201 washout in MI. Wall thickening in the same MI region was significantly decreased (0.33 ± 1.5 mm vs 3.3 ± 1.9 mm, p<0.005).

Conclusions:
Dynamic Tl-201 SPECT/CT imaging provides a quantitative index of both myocardial flow and viability using a 1-compartment model. This preliminary pre-clinical demonstrates the potential for dynamic Tl-201 SPECT imaging to quantify myocardial viability early post-MI.
Abstract 19986: Cyclic Stretch-induced CRP3/MLP Sensitizes Vascular Smooth Muscle Cells to Apoptosis During Vein Remodeling in Response to Arterialization
Authors: Campos Luciana C , Menegon Alessandra S , Barauna Valerio , Mautan Pamela R , Miyakawa Ayumi A , Krieger Jose
Published: July 2021

Introduction:
We have demonstrated stretch-induced up-regulation of cysteine- and glycine-rich protein 3/muscle LIM-domain protein (CRP3/MLP) rat and human saphenous veins in response to arterialization.

Hypothesis:
We developed a KO rat to test the hypothesis that CRP3/MLP is a key modifier of vein remodeling during arterialization.

Methods/Results:
Under basal conditions, we found no micro-macroscopic gross abnormalities in conduit arterial/vein vessels in KO rats. Upon arterialization of jugular vein for 28 days, CRP3 KO compared to WT rats showed a 3-fold increase of intima layer (Area 103 μm2 - CRP3 KO: 250.9 ± 80.0, WT: 79.7 ± 32.3) and inhibition of early apoptotic event (TUNEL positive cells - CRP3 KO: 0.4 ± 0.7, WT: 30.6 ± 6.8). To gain insight on the increased remodeling response, we investigated CRP3 role on apoptosis. Interestingly, ceramide-induced apoptosis was restricted to the presence of basal CRP3 expression. Aortic SMCs, with endogenous CRP3 expression, displayed increased apoptosis compared to cells from KO rats (% of dead cells - CTRL - CRP3 KO: 1.8 ± 0.3, WT: 8.3 ± 1.7; Ceramide 100μm- CRP3 KO: 12.4 ± 7.3, WT: 54.8 ± 8.3). Ceramide failed to induce apoptosis in the absence of CRP3 expression in both jugular vein SMC KO and WT under basal conditions. Upon stretch, WT vein SMC displayed increased CRP3 expression (CRP3/GAPDH gene expression -Static: 0; Stretched: 0.4 ± 0.05) that was accompanied by ceramide-induced apoptosis (% of dead cells - Static control: 0.5 ± 0.1; Static ceramide: 0.8 ± 0.1; Stretched control: 0.7 ± 0.6; Stretched ceramide: 11.4 ± 0.1). Similarly, ceramide-induced apoptosis decreased in stretched CRP3-KO jugular (% of dead cells - Static control: 0.4 ± 0.06; Static ceramide: 0.8 ± 0.07; Stretched control: 0.4 ± 0.2; Stretched ceramide: 0.9 ± 0.06). Western blot analysis showed that ceramide stretch-induced apoptosis in SMC is accompanied by decreased pFAK and pAKT, which may lead Bax to translocate to mitochondria, resulting in caspase 3 activation.

Conclusion:
Taken together, we provide evidence that CRP3/MLP influences vein remodeling in response to arterialization by sensitizing cells to stretch-induced apoptosis.
Abstract 2: Sodium Nitroprusside--Enhanced Cardiopulmonary Resuscitation Facilitates Intra-arrest Cerebral Therapeutic Hypothermia in a Porcine Model of Prolonged Ventricular Fibrillation
Authors: Debaty Guillaume , Matsuura Timothy , Bartos Jason , Rees Jennifer , McKnite Scott , Lurie Keith , Yannopoulos Demetris
Published: July 2021

Introduction:
Intra-arrest cooling has been shown to improve survival and neurologic outcome in animal models. The aim of this study was to assess the effect of Sodium Nitroprusside enhanced Cardiopulmonary Resuscitation (SNPeCPR) on heat exchange during surface cooling. We hypothesized that SNPeCPR would decrease the time to reach brain temperature to <35°C compared to Active Compression Decompression plus Impedance Threshold Device (ACD+ITD) CPR alone, when surface cooling starts during CPR. Further, addition of epinephrine during SNPeCPR would mitigate heat exchange.

Methods:
After 10 minutes of untreated ventricular fibrillation, 26 animals were randomized to 3 different protocols: SNPeCPR (n=6), SNPeCPR plus epinephrine (SNP+EPI, n=10) and ACD+ITD alone (Control, n=10). All animals received surface cooling with ice bags at the initiation of CPR. SNPeCPR included ACD+ITD plus abdominal binding, 2mg of SNP every 4min, and no epinephrine during CPR. Control and SNP+EPI groups included 0.5mg of epinephrine every 4min during CPR. Defibrillation occurred after 10 minutes of CPR. After ROSC, an Arctic Sun® at maximum cooling was used on all animals. The primary endpoint was the time to reach brain temperature <35°C. Hemodynamic parameters were recorded continuously. Data are presented as mean ± SEM. ANOVA or Kruskal Wallis test were used to compare continuous variables.

Results:
Time to reach brain temperature of 35°C was decreased with SNPeCPR vs. Control or SNP+EPI (18 ± 6 min, 53 ± 8 min and 40 ± 9 min, respectively, p=0.03). All animals survived 2h in the SNPeCPR group and 9/10 in the two other groups. Carotid blood flow was higher during CPR in the SNPeCPR group (96 ± 16 ml/min versus 26 ± 7 and 35 ± 5 in the Control and SNP+EPI group, respectively p=0.04). There were no other differences in hemodynamic parameters.

Conclusion:
This study demonstrates that SNPeCPR facilitates intra-CPR hypothermia, with the brain reaching target temperature (35°C) in less than half of the time of controls without impairing hemodynamics. The addition of epinephrine to SNPeCPR during CPR attenuated its effect on heat exchange.
Abstract 20015: Value of Quantitative Atherosclerotic Plaque Assessment Using CCTA to Predict Lesion-specific Ischemia, Data from 407 Coronary Lesions
Authors: Heo Ran , Park Hyung-Bok , Ryo Nakazato , Cho Iksung , Gransar Heidi , Chang Hyuk-Jae , Min James K
Published: July 2021

Introduction:
While coronary computed tomographic angiography (CCTA) demonstrates high diagnostic performance for identification and exclusion of high-grade anatomic stenosis, it is unable to effectively discriminate coronary lesions that causes ischemia.

Hypothesis:
To study whether quantitative assessment of CCTA offer incremental information for discrimination of lesion ischemia beyond stenosis measures.

Methods:
252 consecutive patients with suspected or known coronary artery disease (CAD) from 17 centers in 5 countries were enrolled (mean age 63±9 years, 71% male). Patients underwent CCTA and invasive coronary angiography (ICA), with 407 coronary lesions interrogated by invasive fractional flow reserve (FFR) at the time of maximum hyperemia. For these coronary lesions, we evaluated % diameter stenosis (%DS), % area stenosis (%AS), minimal luminal diameter (MLD, mm), minimal luminal area (MLA, mm
2
), and plaque burden at MLA by CCTA. Plaque burden (PB, %) was defined as (vessel area–lumen area)/vessel areaх100. Lesion-specific ischemia by FFR was defined as a value ≤0.8.

Results:
In quantitative analysis area under the receiver operating characteristic curves (AUC) value of %DS, %AS, MLD, MLA, and PB for prediction of ischemia were 0.72 (95% confidence interval (CI) 0.68-0.77, p<0.001), 0.73 (95% CI 0.68-0.77, p<0.001), 0.75 (95% CI 0.70-0.79, p<0.001), 0.75 (95% CI 0.70-0.79, p<0.001), and 0.77 (95% CI 0.73-0.81, p<0.001), respectively. PB showed significantly improved AUC when compared to % area stenosis (p=0.002). However, PB didn’t show incremental power over MLA (p=0.213). There also was no significant difference in AUC between MLA and % area stenosis (p=0.330)

Conclusions:
Quantitative plaque assessment using CCTA could predict lesion-specific ischemia with good discrimination. Plaque burden showed incremental value over % area stenosis for ischemia prediction.
Abstract 20042: Comparison Between Alcohol Septal Ablation and Myomectomy for Hypertrophic Obstructive Cardiomyopahty: A Meta-Analysis
Authors: Garcia Daniel , Mehdi Ansari Mohammad , Nascimento Rhanderson , Alfonso Carlos , Heldman Alan
Published: July 2021

Introduction:
Both myomectomy and alcohol septal ablation (ASA) are used to treat patients with symptomatic hypertrophic obstructive cardiolmyopathy (HOCM). There is limited evidence to guide decision making between the two. Our aim was to compare the clinical and procedural outcomes among septal ablation and surgical myomectomy in patients with HOCM.

Methods:
We systematically searched PubMed, EMBASE, and Cochrane for studies comparing septal ablation to surgical myomectomy between January 1966 and June 2014. Primary end-point was 30 day mortality. Secondary end-points were long-term mortality (>12 months), and peak LVOT gradient reduction. We used RevMan 5.1.7 software. Heterogeneity was defined as I2 values > 25%.

Results:
A total of 11 observational and case-control studies were included and provided a total of 1155 patients. Myomectomy group was younger than septal ablation (9.37± 4 years; p<0.01).There was no difference in 30 day mortality between septal ablation and surgical myomectomy 1.7% vs. 1.4% (95% CI: 0.39-2.57;p=0.99) (Figure A). There was no difference on long term mortality among groups (5.9% vs. 5.3%; 95% CI: 0.47-1.98; p=0.92) (Figure B). There was a significant 64.43% reduction of LVOT gradient in SA group and 71.03% in the surgical groups (p<0.01) respectively (Figures C,D).

Conclusion:
Patients undergoing myomectomy are significantly younger than those having ASA. Short and long term mortality were similar. Clinical and anatomical features favoring one or the other strategy were not captured by our analysis. Further studies are required to resolve clinical equipoise.
Abstract 20047: Nasa Model of "Threat and Error" in Paediatric Cardiac Surgery: Death Typically Results From Cycles of Error That Originate in the Operating Room and Are Amplified by Additional Error in Intensive Care
Authors: Hickey Edward , Nosikova Yaroslavna , Pham-Hung Eric , Gritti Michael , Wilder Travis , Hussain Sara , Caldarone Christopher A , Schwartz Steven , Redington Andrew , Van Arsdell Glen S
Published: July 2021

Introduction:
We introduced the NASA “threat and error model” to our surgical unit; all admissions are considered “flights”, which should pass through stepwise de-escalations in risk.

Hypothesis:
Errors significantly influence risk de-escalation and contribute to poor outcomes.

Methods:
Patient flights (524) were tracked real-time for threats, errors and unintended states (figure). Expected risk de-escalation was: wean from mechanical support, sternal closure, extubation, ICU discharge and discharge home. Data were accrued via performance personnel, bedside data, reporting mechanisms and staff interviews. Infographics of flights were openly discussed weekly.

Results:
In 12% (64/524) of flights, the child failed to de-escalate sequentially through expected risk levels; unintended increments instead occurred. Failed de-escalations were highly associated with errors (426; 257 flights), however seemingly benign (P<.0001). Errors with clinical consequence (263; 173 flights) had 29% rate of failed de-escalations vs 4% (P<.0001).

The most dangerous errors were “apical” errors typically (84%) occurring in the OR which led to cycles of propagating unintended states (n=110): these had 43% (47/110) rate of failed de-escalation (vs 4%, P<.0001). Apical errors were triggered by identifiable threats in 25% (28/110) (usually - 75% - morphology/ comorbidities); 75% were instead “unforced” errors. Cycles of unintended state were often (46%) amplified by additional (up to 7) errors in ICU that would worsen clinical deviation. Overall, failed de-escalations in risk were extremely closely linked to brain injury (N=13; P<.0001), or death (N=7; P<.0001).

Conclusions:
Deaths and brain injury almost always occur from propagating error cycles that originate in the OR and are often amplified by additional ICU errors. Improvements in threat management, error detection/rescue and vigilance at times of failed de-escalation will translate into improved outcomes.
Abstract 20072: Incremental Prognostic Value of Left Ventricular Global Longitudinal Strain and Late Gadolinium Enhancement in Patients with Dilated Cardiomyopathy
Authors: Chimura Misato , Onishi Tetsuari , Kawai Hiroya , Yamada Shinishiro , Yasaka Yoshinori
Published: July 2021

Introduction:
Reduced left ventricular (LV) global longitudinal strain (GLS) by two-dimensional speckle-tracking (2DST) echocardiography and late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) have been reported to be associated with unfavorable outcome in patient with heart failure (HF). We investigated to assess these 2 markers as prognostic parameters over conventional HF markers in patients with dilated cardiomyopathy (DCM).

METHODS:
We studied consecutive 179 DCM patients (Age 61±15 years, 121 males, LV ejection fraction (LVEF) 33±9%, NYHA class I: n= 0; II: n=71; III: n=107; IV: n=1) who underwent CMR and echocardiography with conventional assessment including LV end-diastolic and end-systolic volume (LVEDV, LVESV), LVEF and mitral regurgitation grade (MR), and with 2DST analysis of GLS. Brain natriuretic peptide (BNP) was measured. Outcome was assessed according to death and hospitalization with heart failure in the follow-up period for 3.8±2.5 years.

RESULTS:
There were 7 cardiac deaths and 40 HF hospitalizations in the follow-up period. Univariate Cox proportional hazard regression analysis showed NYHA class, systolic blood pressure, diastolic blood pressure, BNP, LVEDV, LVESV, LVEF, MR, GLS and positive LGE were significantly associated with outcome. Multivariate Cox proportional hazards regression analysis revealed GLS and positive LGE (p<0.05 for both) were independent predictors of outcome. Dividing all 179 patients into 4 groups with the median of GLS (-8.3%) and the presence or absence of LGE, Kaplan-Meier analysis showed worse GLS predicted adverse events in patients with and without LGE (p<0.05 for both). GLS and LGE provide additional benefit over conventional parameters (Age, NYHA class, LVEF and BNP).

CONCLUSIONS:
Risk stratification with LGE and GLS is useful to predict long-term outcome in DCM patients. These 2 markers provide incremental prognostic value to conventional HF markers.
Abstract 20118: Defining the Sufficiency of Atg7 to Suppress Phenylephrine-induced Cardiac Hypertrophy
Authors: Tjeerdsma Marcus , Froke Levi , Freeling Jessica , Pattison Scott
Published: July 2021

Introduction:
Macroautophagy is a process of bulk protein degradation. Our prior work showed that Atg7 expression is sufficient to induce autophagic flux
in vitro
and in vivo
. When Atg7 was co-expressed with CryAB
R120G
in the heart, cardiac hypertrophy was blunted in heart weight/body weight ratios and fetal gene expression markers. To determine if Atg7 expression is sufficient to limit hypertrophic growth in another model, we tested the effects of Atg7 overexpression with phenylephrine-induced hypertrophy both
in vitro
and
in vivo
.

Hypothesis:
Atg7 will blunt the hypertrophic effects of phenylephrine.

Methods:
Rat neonatal cardiomyocytes were infected with adenoviruses expressing either LacZ or Atg7 and treated with phenylephrine to induce cardiomyocytes hypertrophy. Osmotic pumps were surgically implanted into control mice and mice with cardiac-specific expression of Atg7 to infuse phenylephrine (PE) or vehicle (saline) for four weeks.

Results:
PE treatment significantly increased neonatal cardiomyocyte areas in LacZ-expressing cells, while Atg7-expressing cardiomyocytes showed no growth. In mice, all genotypes responded to PE treatment with significantly increased heart weight/body weight ratios and increased fiber size. However, Atg7-expressing hearts differed significantly from control hearts in normalized heart mass following PE delivery. Vehicle treated Atg7-expressing hearts had 17% smaller myofiber cross-sectional areas than those from control genotypes and had a reduced hypertrophic response to PE, relative to controls. Echocardiography showed that Atg7-expressing hearts had significantly elevated cardiac function (% fractional shortening) prior to and throughout the experiment over control hearts (33% vs. 29%). PE significantly increased fractional shortening) from 29% to 36% in control hearts, but failed to significantly elevate cardiac function in Atg7-expressing hearts further (33% vs 35%). Additional assays are underway to understand the Atg7-dependent adaptations to PE.

Conclusion:
Atg7 expression yields modestly smaller hearts with enhanced cardiac function which may protect them from hypertrophic stresses like phenylephrine.
Abstract 20132: Quantification of Multiple Mitral Regurgitant Jets: An in vitro Assessment of Doppler Methods Pertaining to MitraClip
Authors: Maragiannis Dimitrios , Jackson Matthew S , Igo Stephen R , Zoghbi William A , Little Stephen H
Published: July 2021

Introduction:
Mitraclip deployment creates a double orifice valve with multiple regurgitant jets making quantification of mitral regurgitation (MR) difficult.

Hypothesis:
Our objective was to evaluate the accuracy of double jet MR quantification by summation of individual jet 3D echo-derived vena contracta area (VCA) or 2D proximal isovelocity surface area (PISA) estimation of regurgitant volume (RV).

Methods:
In a pulsatile flow loop model, six valve constructs were evaluated with RV of 25 ml, 45 ml, and 65ml/beat. Regurgitant orifices tested were: a single circular hole (n=6), two symmetric circular holes (n=6), and an asymmetric configuration with a circular hole and an elliptical hole (n=6). RV was compared with true flow measurements from in vitro flow transducers. RV was calculated as: 1) PISA-Effective regurgitant orifice area x Doppler time velocity interval (TVI) or 2) VCA x Doppler TVI.

Results:
RV derived by PISA method correlated well with reference standard flow measures for both single orifice and double orifice valve constructs (R=0.96 vs R=0.90, p<0.0001, respectively). PISA-RV also demonstrated a good correlation to true RV when tested through symmetric or asymmetric double orifice disks (R=0.96 vs R=0.87,p<0.0001). 3D-VCA derived RV showed a superior correlation using the symmetric vs asymmetric disks (R=0.946 vs R=0.63,p<0.001).

Conclusions:
In a pulsatile model of double orifice MR, total RV is accurately measured by summation of PISA-derived RV or VCA -derived RV from each orifice. These methods deserve further evaluation in the clinical setting.
Abstract 20134: Transcriptional Profiling Identifies Candidate Regulators of Neonatal Heart Regeneration
Authors: O’Meara Caitlin , Wamstad Joseph , Boyer Laurie , Lee Richard T
Published: July 2021

Some higher organisms, such as zebrafish and neonatal mice, are capable of complete and sufficient regeneration of the myocardium following injury, which is thought to occur primarily by proliferation of pre-existing cardiomyocytes. Although adult humans and adult mice lack this cardiac regeneration potential, there is great interest in understanding how regeneration can occur in the heart so that we can activate this process in humans suffering from heart failure. The aim of our study was to identify mechanisms by which mature, post-mitotic adult cardiomyocytes can re-enter the cell cycle to ultimately facilitate heart regeneration following injury. We derived a core transcriptional signature of injury-induced cardiomyocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiomyocyte differentiation and in an in vitro cardiomyocyte explant model, as well as a neonatal heart resection model. We identified a panel of transcription factors, growth factors, and cytokines, whose expression significantly correlated with the differentiated state of the cell in all datasets examined, suggesting that these factors play a role in regulating cardiomyocyte cell state. Furthermore, potential upstream regulators of core differentially expressed networks were identified using Ingenuity Pathway Analysis and we found that one predicted regulator, interleukin-13 (IL13), significantly induced cardiomyocyte cell cycle activity and STAT6/STAT3 signaling in vitro. siRNA knockdown experiments demonstrated that STAT3/periostin and STAT6 signaling are critical for cardiomyocyte cell cycle activity in response to IL13. These data reveal novel insights into the transcriptional regulation of mammalian heart regeneration and provide the founding circuitry for identifying potential regulators for stimulating cardiomyocyte cell cycle activity.