bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 127: Severity of Postresuscitation Myocardial Dysfunction Is Dependent on the Duration of Untreated Cardiac Arrest
Authors: Russo Ilaria , Affatato Roberta , Ceriani Sabina , Secomandi Alessandra , Fumagalli Francesca , Zani Davide D , Novelli Deborah , Letizia Teresa , Di Giancamillo Mauro , Masson Serge , Latini Roberto , Staszewsky Lidia , Ristagno Giuseppe
Published: July 2021

Introduction:
The duration of untreated ventricular fibrillation (VF) is one of the major determinant for outcome of cardiac arrest (CA). We investigated the relationship between different durations of untreated VF and post-resuscitation myocardial dysfunction and survival in a pig model.

Methods:
An established model of myocardial infarction followed by CA and CPR was used. Twenty pigs(35-43 Kg) were subjected to 3 different untreated VF intervals, prior to mechanical CPR and defibrillation: 8-10 min; 12-13 min; or 14-15 min. Arterial and central venous pressures were invasively monitored. Ejection fraction (EF) was echocardiographically assessed together with termodilution cardiac output (CO) and high sensitivity cardiac troponin T (hs-cTnT) assay. Ninety six hr survival was evaluated.

Results:
All the animals were resuscitated, except for 2 in the 14-15 min VF duration (Table). More than 80% of animals survived when the duration of VF was below 13 min, compared to only 17% after 14-15 min (Fig A). The duration of untreated VF correlated with the number of defibrillations required prior to resuscitation (r=0.60, p=0.01, Table). Longer durations of VF were characterized by higher post-resuscitation heart rate and right atrium pressure and by lower post-resuscitation CO and EF (p<0.01, Table). Ninety six hr EF recovered in all animals except in the pig that survived after 14-15 min VF. EF correlated with the number of defibrillation delivered (Fig B) and with hs-cTnT release (r=-0.84, p<0.0001).

Conclusions:
In this model, post-resuscitation myocardial dysfunction and survival were affected by the duration of untreated VF in a time-dependent manner.
Abstract 12717: Improvement of Longitudinal Function is Closely Related to Reverse Remodeling in Cardiac Resynchronization Therapy
Authors: Hasselberg Nina E , Haugaa Kristina H , Bernard-Brunet Anne , Kongsgård Erik , Donal Erwan , Edvardsen Thor
Published: July 2021

Introduction:
Response to cardiac resynchronization therapy (CRT) is often defined as reverse remodeling as a reduction in left ventricular (LV) end systolic volume (ESV). How myocardial mechanics are affected by biventricular pacing is not fully clarified. We tested the hypothesis that longitudinal and circumferential function are affected differently by biventricular pacing.

Methods:
Echocardiography (two dimensional) was performed before and 6 months after CRT implantation in heart failure patients with LV ejection fraction (EF) ≤ 35% and QRS ≥ 120 ms. LV function was assessed by EF and by global longitudinal (GLS) and global circumferential (GCS) strain from 16 LV segments by speckle tracking technique. CRT responders were defined as patients with reverse remodeling with a reduction in ESV ≥ 15% at 6 months.

Results:
We included 138 heart failure patients (65±10 years, 22% women, NYHA functional class 2.8±0.4, 48% ischemic cardiomyopathy). In the total population, GLS did not change (-8.5±3.9% to -8.9±4.7%, p=0.31) after 6 months with biventricular pacing, while GCS (-11.3±3.3% to -14.2±4.5%, p<0.001) and EF (27±9% to 36±12%, p<0.001) improved. Analyzing CRT responders (62%) and non-responders separately, GLS improved in responders (-8.4±3.8% to -9.5±3.8%, p=0.02) but not in non-responders (-8.7±4.1% to -7.9±4.5%, p=0.30) (Figure). GCS improved in both groups (-11.3±3.0% to -15.0±4.3%, p<0.001 and -11.4±3.8% to 13.0±4.7%, p=0.01). ΔGLS was a predictor of CRT response (OR 0.84 (0.75-0.95), p=0.009) and of ΔESV (1.62 (0.45-2.79), p=0.007) independently of ΔGCS.

Conclusions:
Biventricular pacing by CRT generally induced less changes in GLS than in GCS and EF. Importantly, GLS improved only in CRT responders with reverse remodeling. We suggest that reverse remodeling is more dependent on improved longitudinal function than circumferential function.
Abstract 12721: Compensatory Mechanism in HCM Patients With Preserved LV Ejection Fraction Determined by 2D Speckle Tracking Echocardiographic LV Myocardial Strain Gradient Using a Novel Multi-Layer Technique
Authors: Ozawa Koya , Funabashi Nobusada , Takaoka Hiroyuki , Kobayashi Yoshio
Published: July 2021

Introduction:
A novel multi-layer technique on speckle tracking transthoracic echocardiography (TTE) can achieve quantitative strain measurements of all, subendocardial, and subepicardial layer of left ventricle (LV), respectively.

Aim:
To evaluate compensatory mechanism in hypertrophic cardiomyopathy (HCM) subjects with preserved LV ejection fraction (EF), we measured myocardial strain gradient by 2D LV global longitudinal (GLS) and circumferential strain (GCS) using a multi-layer technique on speckle tracking TTE.

Methods:
60 subjects (40 HCM (30 male; age 62 ± 15 years, LV EF >50%, and 20 age matched controls (10 male; age 59 ± 10 years)) underwent TTE (Vivid E9, GE). Apical 4-, 2-, 3-chamber views for GLS and parasternal short-axis views at the level of mitral valve, papillary muscle, and apex for GCS were acquired. We defined myocardial strain gradient as the ratio of subendocardial strain to subepicardial strain.

Results:
GLS from each view were significantly smaller in HCM than controls in all, subendocardial, and subepicardial layers. GCS at all levels were significantly smaller in HCM than controls in all and subepicardial layer; however there were no significant differences in subendocardial GCS between both groups at mitral valve and papillary muscle levels. GLS gradient was significant greater in HCM than controls in GLS from 4 chamber views. GCS gradients were significantly greater in HCM than in controls at all levels. In HCM, subendocardial GCS at mitral valve and papillary muscle levels significantly positive correlated with LV EF (R=0.446, 0.34, respectively) and subendocardial GLS from 4-, and 2- chamber views, and subendocardial GCS at mitral valve and papillary muscles levels significantly negatively and GCS gradients at mitral valve and papillary muscle levels significantly positively correlated with interventricular septum thickness in end diastole (R=-0.44, -0.347, -0.335, -0.359, 0.363, and 0.373, respectively).

Conclusions:
In HCM subjects with preserved LV EF, GLS was significantly smaller than in controls, but GLS and GCS gradients tended to be greater than controls. We speculate that in HCM, subendocardial GCS was maintained in compensation for subendocardial GLS decrement; thus GCS gradient may increase.
Abstract 12762: Clinical Characteristics and Determinants of Non-Eligibility for Reperfusion in Patients With ST Segment Elevation Myocardial Infarction: Insights From the NCDR®
Authors: Dasari Tarun W , Hamilton Steve , Chen Anita Y , Wang Tracy Y , de Lemos James A , Peterson Eric , Saucedo Jorge F
Published: July 2021

Background:
There is little recent data describing the characteristics and outcomes of STEMI patients who do not undergo urgent reperfusion.

Methods:
Using the ACTION Registry®-GWTG™ database, we examined 232,208 STEMI patients presenting January 2007 through December 2013 at 793 U.S. centers. The cohort was divided into those who underwent reperfusion (n=194,916; 84%), had documented contraindication to reperfusion (n=31,518; 13.5%) and were eligible but not reperfused (n=5,774; 2.5%). Clinical characteristics and in-hospital outcomes were compared between these groups.

Results:
Compared with those reperfused, patients not reperfused were older, more often female and had higher rates of hypertension, diabetes, MI, stroke and atrial fibrillation. LBBB and CHF were more common in the non-reperfused groups upon presentation. The major documented contraindications to reperfusion were unsuitable anatomy for primary PCI (31%), symptoms onset > 12 hours (9%), patient/family refusal/DNR status (6%), resolved chest pain (6%) and ST elevation (5%) presentation to non-PCI centers (4%). Three-vessel disease and in-hospital CABG were more common in non-reperfused patients with and without contraindication compared with those receiving reperfusion (39 & 37% vs. 26%, p<0.001) and (17 & 17% vs. 3%, p<0.001 respectively). In-hospital outcomes are summarized in the table.

Conclusion:
Most STEMI patients who were not reperfused had a documented contraindication. Unsuitable anatomy for PCI was the major contributor to ineligibility. In hospital mortality, death/MI and cardiogenic shock were higher in the non-reperfused groups.
Abstract 12770: Left-Atrial Contractile Contribution to Left Ventricle Filling is Preserved in Moderate Chronic Heart Failure
Authors: Putko Brendan N , Paterson Ian , Thompson Richard B , Ezekowitz Justin A , Dyck Jason R , Anderson Todd , Oudit Gavin Y ,   Alberta HEART Investigators
Published: July 2021

Introduction:
The extent that left atrium (LA) functional remodeling is impacted by left ventricle (LV) systolic function or clinical history in patients with chronic heart failure (HF) is unresolved. Cardiac imaging and plasma biomarkers may provide valuable information in this regard.

Hypothesis:
Elastic and active contributions to LV stroke volume (LV SV) are variable, independent of LV systolic function and reflected in natriuretic peptide measurements.

Methods:
We recruited 27 controls without overt cardiovascular disease and 68 patients with moderate HF, including preserved and reduced LV ejection fraction (LVEF). Cardiac MRI was used to evaluate LV volumes at end diastole and end systole, and LA volumes at end diastole, diastasis and end systole to determine passive and active volume changes. Plasma mid-region pro-atrial and N-terminal pro-brain natriuretic peptides (MR-proANP and NT-proBNP, respectively) were measured.

Results:
Elastic LA contribution to LV SV was significantly lower in HF (median, IQR: 14%, 8-23%) than controls (24%, 17-30%; p=0.001), but active contribution was not (23%, 0-34% vs 24%, 21-31%; p=0.163). In patients with HF, active LA contribution to LV SV was negatively associated with history of hypertension (β=-0.41, p=0.007) and positively associated with aging (β=0.40, p=0.008) in a multiple linear regression model. Seven of nine subjects with HF and a history of atrial fibrillation (AF), but in sinus rhythm (SR) on the day of study, had active LA contributions to LV SV >15%. Increased LA volume at end diastole (β=0.51, p=0.001) and LVEF (β=-0.33, p=0.008) were independently associated with NT-proBNP (β=0.51, p=0.001) in a model that included age and history of AF. Similarly, LA volume at end diastole (β=0.48, p=0.001) was independently associated with MR-proANP in a model that included age and history of AF. Notably, natriuretic propeptides were not associated with elastic or active LA contributions to LV SV.

Conclusions:
Heart failure is characterized by preserved LA active contribution to LV SV, regardless of LVEF, which increases with age, and is modifiable by hypertension and AF. Imaging-based assessment can elucidate the contribution of LA function in HF and may provide insight into the impact of AF in patients with HF.
Abstract 12809: Pre-Procedural Aortic Valve Area Predicts Degree of Thrombocytopenia Following Trans-Catheter Aortic Valve Implantation
Authors: Retzer Elizabeth , Tabit Corey , Paul Jonathan , Nathan Sandeep , Friant Janet , Jeevanandam Valluvan , Balkhy Husam , Ota Takeyoshi , Lang Roberto , Dill Karin , Shah Atman
Published: July 2021

Introduction:
Thrombocytopenia (TP) has been described following percutaneous balloon aortic valvuloplasty (BAV) and surgical aortic valve replacement (SAVR), but only recently noted following trans-catheter aortic valve implantation (TAVI). While transient, the TP may be severe leading to increased bleeding.

Methods:
We conducted a retrospective analysis of all patients undergoing TAVI with either a 23mm or 26mm Edwards Sapien valve (Edward Lifesciences, Irvine, California) at our institution.. The effect of multiple independent variables on % platelet change after TAVI were analyzed using paired and unpaired T-tests, two-way ANOVA, and Chi-square tests as appropriate. Platelet % change was correlated with aortic valve area using Pearson correlation. A p-value of <0.05 was considered statistically significant.

Results:
A total of 33 patients (54.5% male, median age 79.3, mean valve area 0.76 cm2) were included in this analysis. The degree of aortic valve stenosis significantly correlated with post-procedural TP severity (Figure 1). The degree of TP post TAVI was found to be significantly lower in those patients who received BAV prior to their TAVI procedure (p < 0.01).

Conclusions:
Post-TAVI TP correlates with the degree of pre-procedure aortic stenosis. Given the need for peri-procedural anticoagulation and post-procedural dual antiplatelet therapy, this finding can help identify patients at risk for symptomatic TP and may help guide post procedure antiplatelet therapy. Further studies are needed to elucidate the underlying mechanism.
Abstract 12814: Incidence of Stroke or Systemic Embolism in Paroxysmal versus Sustained Atrial Fibrillation: From the Fushimi Af Registry
Authors: Takabayashi Kensuke , Hamatani Yasuhiro , Ishii Mitsuru , Ogawa Hisashi , Esato Masahiro , Chun Yeong-Hwa , Wada Hiromichi , Hasegawa Koji , Abe Mitsuru , Akao Masaharu
Published: July 2021

Background:
Atrial fibrillation (AF) increases the risks of stroke. Previous studies revealed patients with paroxysmal AF (PAF) have a risk of stroke similar to that in patients with sustained (persistent or permanent) AF (SAF).

Methods:
The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients in Fushimi-ku, Kyoto, Japan. At present, we have enrolled 3,985 patients from March 2011 to April 2014. One-year follow-up was completed in 3,189 patients as of April 2014. We compared the baseline clinical characteristics and one-year outcome between PAF (n=1,534, 48.1%) and SAF (n=1,655, 51.9%).

Results:
Patients with PAF were younger (PAF vs. SAF: 72.3±11.7 vs. 74.9±9.9 years; p<0.01), less likely to have a history of stroke (15.0% vs. 22.1%; p<0.01), heart failure (17.3% vs. 34.9%; p<0.01), and had lower CHADS2 score (1.82±1.29 vs. 2.22±1.35; p<0.01). During the one-year follow-up period, there was no significant difference in all-cause death (116 (7.6%) vs. 137 (8.3%); p=0.45) or major bleeding (25 (1.6%) vs. 29 (1.8%); p=0.78) between PAF and SAF. In patients with PAF, incidence of stroke or systemic embolism (SE) was less (29 (1.9%) vs. 52 (3.1%); p=0.02) and so was the hospitalization for heart failure (43 (2.8%) vs. 83 (5.0%); p<0.01). In subgroup of patients with CHADS2 score ≥2, there was no significant difference in the incidence of stroke or SE between PAF and SAF (p=0.58) (figure B). In contrast, PAF was associated with lower incidence of stroke or SE in patients with CHADS2 score 0 or 1 (p=0.02) (figure A). After the adjustment by gender and established risk factors (components of CHADS2 score) in multiple logistic regression models, PAF was independently associated with lower incidence of stroke or SE in CHADS2 score 0 or 1 (adjusted odds ratio, 0.22; 95% confidence interval, 0.05 to 0.72; p=0.01).

Conclusion:
PAF was independently associated with lower incidence of stroke or SE in low risk patients with CHADS2 score 0 or 1.
Abstract 12851: Clinical Significance of Myeloperoxidase, Neopterin, and High Sensitivity C-Reactive Protein as Independent Predictors of Cardiovascular Events
Authors: Yoshiyama Tomotaka , Yunoki Kei , Komatsu Ryushi , Haze Kazuo , Naruko Takahiko , Sugioka Kenichi , Nakagawa Masashi , Inaba Mayumi , Yoshiyama Minoru , Ueda Makiko
Published: July 2021

Background:
We previously demonstrated that inflammatory biomarkers such as myeloperoxidase (MPO), a member of the heme peroxidase superfamily, and neopterin (produced by activated macrophages after interferon-γ stimulation by T-lymphocytes) are important in the pathogenesis of coronary plaque instability. Additional evidence supports high sensitivity C-reactive protein (hs-CRP) as an independent predictor of increased coronary risk. We assessed the prognostic significance of plasma MPO and neopterin levels, and serum hs-CRP levels in patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP).

Methods:
Plasma MPO, neopterin, and serum hs-CRP levels were measured in 219 SAP patients and 144 UAP patients at admission. Cardiovascular (CV) events were defined as sudden cardiac death, fatal or non-fatal myocardial infarction and other non-fatal events including unstable angina pectoris or coronary revascularization.

Results:
Over a mean follow-up of 27±14 months, 56 SAP patients (26%) had CV events. When SAP patients were stratified based on the median neopterin level (15.0 nmol/L), Kaplan-Meier analysis showed that the high-neopterin group (>15.0 nmol/L) had significantly worse outcomes (P=0.015) than the low-neopterin group. Multivariate analysis showed that elevated neopterin was the only independent factor associated with CV events (OR, 2.19; 95% CI, 1.18-4.09; P=0.014). In contrast, over a mean follow-up of 30±24 months, 33 UAP patients (23%) had CV events. When UAP patients were divided based on the median MPO level (16.0 ng/mL), Kaplan-Meier analysis showed that the high-MPO group (>16.0 ng/mL) had significantly worse outcomes (P=0.012) than the low-MPO group. Multivariate analysis showed that elevated MPO was the only independent factor associated with CV events (OR, 2.58; 95% CI, 1.07-6.23; P=0.035). With regard to hs-CRP levels, there were no significant differences in CV events between the two groups according to the median hs-CRP in both SAP and UAP patients.

Conclusions:
The clinical significance of elevated MPO and neopterin levels as independent predictors of CV events differs depending on the clinical condition of SAP and UAP patients, because of different production mechanisms of these biomarkers.
Abstract 12930: Neutrophil Extracellular Traps Correlate With Impaired Myocardial Reperfusion in Patients With St Elevation Myocardial Infarction After Primary Percutaneous Coronary Intervention
Authors: Kurata Mie , Autar Anouchska S , Mensink Daniëlle , Duncker Dirk J , Cate Hugo t , Govers-Riemslag José , Reutelingsperger Chris , Regar Evelyn , Valgimigli Marco , Leebeek Frank W , Zijlstra Felix , de Maat Moniek P , van Beusekom Heleen M
Published: July 2021

Introduction:
Impaired myocardial reperfusion after successful percutaneous coronary intervention (PCI) is an important determinant of prognosis of patients with ST elevation myocardial infarction (STEMI). Neutrophil extracellular traps (NETs) are toxic DNA-protein complexes, upregulated in pro-thrombotic states and may induce endothelial injury.

Aim:
We aimed to assess in systemic and culprit coronary plasma, the level of NETs and their relationship with microvascular perfusion after PCI.

Methods:
Forty-nine STEMI patients treated with thrombectomy and PCI were enrolled. Patients with past history of coronary revascularization were excluded. Systemic blood was drawn at baseline and post PCI, and from the culprit lesion during thrombectomy. NETs and extracellular histone-DNA (E-DNA) were measured by capture ELISA (myeloperoxidase-DNA complex, histone-DNA complex, respectively). Corrected thrombolysis in MI (TIMI) frame count (cTFC) was calculated from coronary angiography.

Results:
The relation between NETs and cTFC is summarized in the figure. Both NETs and E-DNA were highest in culprit lesion plasma (p<0.05). Baseline and post-PCI levels of NETs were similar (p=0.56). Baseline, aspirate, and post-PCI NETs levels were inversely correlated with cTFC (ρ=-0.43, -0.31, -0.39, respectively, all p<0.05), and baseline NETs was an independent predictor of cTFC (β=-0.40, p=0.04), not age, gender, total ischemia time or troponin T level at admission. All E-DNA levels positively correlated with troponin T at admission (ρ=0.58, 0.47, 0.38, p<0.05, respectively), and were higher post PCI than at baseline (p<0.01), suggesting a reflection of myocardial damage. E-DNA showed no correlation with cTFC.

Conclusions:
Prior to PCI, baseline NETs level predict impaired reperfusion and may assist in tailored therapy and follow up.
Abstract 12935: Therapeutic Silencing of Leukocyte Adhesion Molecules in Atherosclerosis and Acute Myocardial Infarction
Authors: Sager Hendrik B , Dutta Partha , Dahlmann James , Borodovsky Anna , Fitzgerald Kevin , Heidt Timo , Courties Gabriel , Wojtkiewicz Gregory , Guiles Yoshiko , Khan Omar , Langer Robert , Swirski Filip , Weissleder Ralph , Anderson Daniel , Nahrendorf Matthias
Published: July 2021

INTRODUCTION/HYPOTHESIS:
Leukocytes are a major component of atherosclerotic plaques, drive plaque progression and are continuously recruited from the blood. The leukocyte adhesion molecules VCAM-1, ICAM-1/2 and E-/P-Selectin are expressed on plaque endothelial cells and are the key players in this recruitment process. We here present a novel therapeutic approach that targets leukocyte recruitment to plaques.

METHODS:
We tested a nanoparticle system that effectively delivered short interfering RNAs targeting VCAM-1, ICAM-1/2 and E-/P-Selectin simultaneously (siCAM5) to endothelial cells of atherosclerosis prone ApoE-/- mice and C57BL/6J mice after myocardial infarction (permanent coronary ligation) and assessed leukocyte recruitment/content and plaque phenotype by flow cytometry, histology, qPCR and fluorescence molecular tomography/computed tomography imaging.

RESULTS:
Efficient degradation of VCAM-1, ICAM-1/2 and E-/P-Selectin on endothelial cells attenuated neutrophil and monocyte numbers in infarcts and atherosclerotic plaques (neutrophil numbers, siControl 10,974±1,250 vs. siCAM5 6,963±1,077, p<0.05; Ly6Chigh monocyte numbers, siControl 6,044±1,212 vs. siCAM5 3,770±293, p<0.05), reduced levels of pro-inflammatory cytokines in plaques, decreased protease activity in plaques (protease activity in pmol, siControl 49.4±2.8 vs. siCAM5 35.9±3.0, p<0.01), and resulted in a less inflammatory plaque phenotype (necrotic core mm2/aortic root, siControl 0.09±0.01 vs. siCAM5 0.05±0.01, p<0.05; fibrous cap μm/aortic root, siControl 36.7±9.5 vs. siCAM5 63.1±5.4, p<0.05) and lower numbers of plaque macrophages (siControl 30,313±4,414 vs. siCAM5 17,198±2,070, p<0.01).

CONCLUSIONS:
Taken together, the described approach can successfully suppress leukocyte recruitment to atherosclerotic plaques and infarcted hearts. It may allow aggressive medical interventions in patients with inflammatory atherosclerosis.
Abstract 12983: Impact of Door to Balloon Time on Outcome of Patients Presenting With Different Symptom Onset to Door Time
Authors: Dadu Razvan T , Davis Ana , Bobek Jaromir , Alam Mahboob , Goswami Rajiv , Lakkis Nasser
Published: July 2021

Objective:
Delay in reperfusion > 4h in patients with ST elevation myocardial infarction (STEMI) is associated with negative outcomes. We sought out to examine the impact of DTBT on 30-day cardiovascular outcomes and persistent ST elevation (STE) on the post reperfusion EKG, in patients with different symptom onset to door time (SOTDT).

Methods:
122 consecutive patients undergoing primary percutaneous coronary intervention for STEMI in a tertiary care county hospital from 2011-2013 are included. All patients had DTBT ≤ 90min. Patients were divided into 3 groups according to their SOTDT: Group1 ≤ 90min, Group2 between 90min and 4h and Group3 >4h. Each group was further divided in 2 subgroups based on median DTBT of the entire population. The primary outcome was a composite endpoint of mortality, re-hospitalization for chest pain or heart failure, repeat revascularization and re-infarction at 30 days. A secondary outcome was persistence of > 50% STE on the post reperfusion EKG.

Results:
Median SOTDT was 129 min and the median DTBT was 47min for all included patients in the study. The 3 groups had comparable baseline characteristics. The mean DTBT was similar (49±20 min, 47±18 min and 50±16 min, p=0.7). In the 3 groups, the primary outcome was present in 16.7 %, 16.2 % and 35%, respectively (p=0.08) and there was a significant difference in STE resolution: 16.7%, 17.1% and 78.6%, respectively (p<0.001). Group 1 and 3 demonstrate that short DTBT (≤ 47 min) does not affect overall outcomes compared to those with longer DTBT (> 47 min). In group 2, patients with DTBT ≤ 47min had significantly lower persistent STE on EKG (0% vs 36.8%, p=0.002) and a trend to a favorable clinical outcome (table).

Conclusion:
Patients with intermediate SOTDT seem to benefit mostly from shorter DTBT compared to all other patient groups. Achieving shorter DTBT may have no impact on outcome in patients with very early or very late presentation. Larger studies are needed to further confirm these findings.
Abstract 130: Effect of Cardiopulmonary Bypass Resuscitation on Outcomes After Out-of-Hospital Cardiac Arrest: A Nationwide Observational and Propensity Score--Matched Analysis
Authors: Shin Sang Do , Song Kyoung Jun , Lee Eui Jung , Ro Young Sun , Lee Yu Jin
Published: July 2021

Objective:
This study aimed to determine whether cardiopulmonary bypass (CPB) resuscitation comparing with conventional cardiopulmonary resuscitation (C-CPR) is associated with improved OHCA outcomes in Korea.

Methods:
We used a Korean national OHCA cohort database composed of hospital and ambulance data. We included all EMS-treated OHCA with presumed cardiac etiology for the period Jan. 2009 to Dec. 2012 excluding cases without available hospital outcome data. The primary exposure was CPB resuscitation during CPR at emergency department (ED). The endpoints were survival to admission, hospital discharge with brain recovery (cerebral performance category 1 or 2). We compared outcomes between CPB versus non-CBP group using multivariable logistic regression for calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for individual, Utstein, post-resuscitation factors, and comorbidities. using original and propensity-score matched datasets.

Results:
Of 93,562 patients with OHCA, we included 55,255 excluding non-treated (n=14,733), non-cardiac (n=23,521), and unknown brain recovery at discharge (n=55). Overall survival to admission and to discharge with good brain recovery was 13.5% and 2.1%, respectively. CPB was performed in 207 (0.4%); 0.1% (2009), 0.2% (2010), 0.4% (2011), 0.7% (2012), respectively. Survival to admission was significantly higher in CPB group (78.3%) than non-CPB (13.3%) in original dataset (Adjusted OR=9.98, 95% CI 7.00-14.24). Discharge with good brain recovery was significantly higher in CPB (9.7%) than non-CPB (2.0%) but adjusted OR (95% CI) was not significant in original dataset; 1.15 (0.62-2.13). From propensity score matched dataset (N=414 from 207 CPB cases and 207 non-CPB cases), survival to admission was significantly higher in CPB group (78.3%) than non-CPB (56.0%) (Adjusted OR=5.37, 95% CI 2.82-10.21). Discharge with good brain recovery was significantly lower in CPB (9.7%) than non-CPB (15.9%) with adjusted OR (95% CI); 0.51 (0.24-1.11).

Conclusions:
The CPB resuscitation has been increased by year and was associated with higher survival to admission. But it is not associated with hospital discharge with brain recovery in nationwide observational study in Korea.
Abstract 13031: Real-Time Three-Dimensional Transesophageal Echocardiography for Diagnosis of Pannus Formation in Mechanical Aortic Valves: Comparison with Multi-detector Computed Tomography and Surgical Findings
Authors: Lee Sahmin , Lee Seung-Pyo , Park Eun-Ah , Hong Mi-Kyung , Kim Ji-Hyun , Yang Han Mo , Kim Hyung-Kwan , Lee Whal , Kim Yong-Jin , Sohn Dae-Won
Published: July 2021

Introduction:
Pannus formation is a rare but important complication that can be missed in patients with prosthetic valves. However, currently available methodologies are not sufficient to diagnose subvalvular pannus formation especially in mechanical aortic valves.

Hypothesis:
In this study, we explored a series of experiences with three-dimensional transesophageal echocardiography (3D-TEE) for the visualization and accurate assessment of subvalvular pannus in patients with mechanical aortic valve.

Methods:
We enrolled 11 patients (mean age 64±8.6 years, 10 patients with either double or triple valve replacement) who had previously implanted mechanical aortic valve, with transaortic mean pressure gradient >40mmHg or transaortic maximal velocity >4m/sec despite normal occluder motion. All patients underwent 3D-TEE examination to rule out pannus formation and these findings were compared with multi-detector computed tomography (MDCT) images and/or surgical findings.

Results:
In 10 patients, 3D-TEE allowed good visualization of subaortic pannus formation whereas there was no significant pannus ingrowth in one patient. Through cropping full-volume 3D-TEE images, subaortic pannus formation could be visualized well in en face view, which was confirmed by MDCT images. The 3D-TEE images of the pannus were also matched with intraoperative findings in 7 patients undergoing reoperation of the mechanical aortic valve (Figure). Quantitative measurement of geometric subvalvular area using 3D planimetry was feasible and correlated well with the area measured by MDCT and with transaortic mean pressure gradient on transthoracic echocardiography (Spearman’s ρ=0.761 and -0.726, all p-value<0.05).

Conclusions:
Real-time 3D-TEE is a useful diagnostic tool for the anatomical assessment of subvalvular pannus formation in mechanical aortic valves.
Abstract 13035: Overexpressing Superoxide Dismutase 2 Induces Super-normal Cardiac Function by Enhancing Mitochondrial Function and Metabolic Dilation
Authors: Kang Patrick T , Ohanyan Vahagn , Chilian William M , Chen Yeong-Renn
Published: July 2021

During heightened cardiac work, O
2
consumption by the heart increases. This increase benefits energy production via mitochondrial e
−
transport, but some e
−
“leak” from respiratory chain and yields O
2
[[Unable to Display Character: ˙]]
−
, which is rapidly metabolized into H
2
O
2
by SOD2. To understand the potential systemic effects of the metabolic dilator, H
2
O
2
, we studied mice with cardiac specific SOD2 overexpression, which would increase H
2
O
2
produced by the cardiac mitochondria (by 1.9 fold vs WT). To determine if this enhanced production of H
2
O
2
enhances metabolic dilation, we first evaluated the effectiveness of SOD2 overexpression to effectively enhance mitochondrial function. Mitochondria of SOD2 transgenic mice had a decreased state 3 oxygen consumption rate, but maintained the same level of ATP production; thus indicating a higher P/O ratio and bioenergetics efficiency induced by overexpressing SOD2. Mitochondria of SOD2-tg (compared to WT) produced less
•
O
2
−
, and had lower redox activity (by EPR) and lower GSSG concentration (decreased by 37.2±4.5%). EPR analysis of the isolated mitochondria showed significant decrease of semiquinone in the SOD2-tg at the Q
i
site (by 69.4±9.9%), and a diminished complex I-derived protein thiyl radical(s). These results support a more reductive physiological setting of the SOD2-tg heart. Cardiac mitochondria isolated from SOD2-tg exhibited no significant differences in the respiratory control index between WT and SOD2-tg. These results support that the SOD2

overexpression is effective and results in enhanced mitochondrial function. Contrast echocardiography was employed to evaluate hemodynamic effects. Mean arterial pressure (MAP) was lower in the SOD2-tg, but was normalized by intravenous injection of catalase suggesting “spill-over” of H
2
O
2
from the myocardium in sufficient amounts to produce a systemic effect. Increasing myocardial work (norepinephrine) caused a far greater increase myocardial blood flow (MBF) per level of work in SOD2-tg compared to WT. Echocardiography indicated SOD2-tg had a significant greater ejection fraction (90±1% vs 74±2%). In conclusion, SOD2 overexpression in myocytes enhances mitochondrial function and metabolic vasodilation, leading to phenotype of super-normal cardiac function.
Abstract 13037: Tenascin-c Modulates Inflammatory Response and Aggravate Ventricular Remodeling After Myocardial Infarction in Mice Model
Authors: Kimura Taizo , Sato Akira , Tajiri Kazuko , Zeng Wang , Sakai Satoshi , Yoshida Toshimichi , Hiroe Michiaki , Yoshida Kyoko I , Aonuma Kazutaka
Published: July 2021

Tenascin-C (TN-C), an extracellular matrix glycoprotein, transiently appeared in myocardial tissue after acute myocardial infarction (AMI). We have previously reported that AMI patients with higher serum TN-C levels had worse long-term prognosis, suggesting TN-C may play important roles during the development of ventricular remodeling. However, the biological function of TN-C in ventricular remodeling is not fully understood. In this study, using TN-C knock-out(KO) mice, we investigated the effects of TN-C on LV remodeling and the biological function of TN-C during the acute phase of inflammatory responses after myocardial infarction.

The 8 to 10 weeks old male wild type (WT) and TN-C knock-out (KO) mice were divided into 4 groups of WT+Sham, KO+Sham, WT+MI and KO+MI. Mice 12 weeks post-MI, the survival rate of both WT+MI (48.3%,14 of 29 mice) and KO+MI (55.6%,15 of 27 mice) groups had no significant difference. However, TN-C KO group had the better cardiac function than WT had (LVEF, 19.02±6.31% vs 10.63±4.43%; p<0.001). Interstitial fibrosis at border area was significantly increased in the WT +MI group to compare with that of KO+MI, whereas the extent of fibrosis in the remote area revealed no significant difference between the two groups. By RT-PCR analysis, WT+MI group showed significantly higher expression of atrial natriuretic peptide at the border including infarcted areas than that of KO+MI at chronic MI phase. At acute phase, fluorescence activated cell sorting analysis showed that ratio of CD45+, CD11b+, Ly6c high pro-inflammatory monocyte were significantly decreased, whereas CD45+, F4/80+, CD206+, anti-inflammatory M2 macrophage were significantly increased in KO+MI compared with WT+MI group 7 days after MI. RT-PCR analysis showed that the expression of IL-10, an anti-inflammatory cytokine, was significantly higher in KO+MI than WT+MI.

These findings suggest, TN-C aggravates the deterioration of LV function due to MI partly by modulating inflammation at acute phase.
Abstract 13051: A Lin28-let-7 Axis Modulates Adaptation of the Myocardium to Ischemia
Authors: Joshi Shaurya , Wei Jian Qin , Bishopric Nanette H
Published: July 2021

Background:
The RNA binding protein Lin28 and microRNA-let-7 each regulate glucose metabolism, tissue repair and pluripotency; however, their roles in cardiac adaptation to ischemia are unknown.

Methods and Results:
miR-let-7c was significantly downregulated in myocardium of mice following a 2 hour coronary occlusion, compared to sham-operated controls (0.69 fold, p<0.05). In parallel, Lin28 protein was induced in the ischemic myocardium compared to adjacent non-ischemic tissue (~2.0-fold, p<0.05). Consistent with this, mature but not precursor forms of miR-let-7c were downregulated (0.7 fold, p<0.05) in neonatal rat ventricular myocytes (NRVMs) during both hypoxia and hypoxia with glucose depletion, but not in similarly treated fibroblasts, together with a time-dependent 6-fold increase in Lin28 protein compared to normoxic controls. mRNA levels of Lin28 were also increased, but less strikingly (2.2 fold vs normoxia control, p<0.05). Ischemia induced acetylation of Lin28, both in vivo and in NRVMs that was potentiated by the non-selective histone deacetylase (HDAC) inhibitor, trichostatin A, suggesting that Lin28 is post-translationally stabilized. Mechanistically, transduction of NRVM with a let-7g lentiviral expression vector rescued let-7 levels, prevented ischemia-induced myocyte death and caspase activation, and promoted phosphorylation and activation of Stat3. Knockdown of the let-7 family in hypoxic NRVMs using a sponge vector containing 6 let-7 binding sites derepressed predicted target genes Bcl2l1, DUSP1, INSR, Ras at both mRNA and protein levels and depressed STAT3 phosphorylation. Using PAR-CLIP, in which the RISC complex is crosslinked to its target transcripts, we observed direct let-7 targeting of Lin28A in cardiac myocytes.

Conclusion:
During ischemic stress, let-7 is post-transcriptionally downregulated in a myocyte-specific manner through the ischemia-mediated induction of its repressor, Lin28. Induction of Lin28 occurs through transcriptional induction as well as post-translational acetylation and stabilization. This Lin28-let-7 axis constitutes a bidirectional feedback loop that directly and indirectly regulates signaling cascades of known importance to myocardial adaption to ischemic stress.
Abstract 13052: Stability of Hospital Rankings for Acute Myocardial Infarction
Authors: Girotra Saket , Rosenthal Gary , Lu Xin , Vaughan-Sarrazin Mary , Cram Peter
Published: July 2021

Background:
Although hospital mortality for acute myocardial infarction (AMI) varies widely, little is known regarding the trajectory of mortality over time at hospitals with high and low mortality at baseline.

Methods:
We studied 623,488 Medicare AMI patients at 1923 hospitals during 2007-2010. We used 30-day risk-standardized mortality rates (RSMR) to stratify hospitals as bottom 25% and top 25% in 2007 (baseline) and compared their performance on AMI mortality during next 3 years. We also ranked top 25% and bottom 25% hospitals into quartiles of RSMR, each year during 2008-2010 (0 = worst mortality quartile, to 3 = lowest mortality quartile), and summed quartile ranks for each year to yield a composite score (CS: range = 0 to 9). We examined which bottom 25% and top 25% hospitals achieved low (
<
1) and high CS (≤ 8).

Results:
Average RSMR in 2007 was 15.5% (range: 11.2%-21.6%). During 2008-2010, there was considerable overlap in AMI mortality at 481 hospitals that were top 25% (blue bars) and bottom 25% (red bars), respectively (Figure). Of bottom 25% hospitals, only 107 (22%) had persistently high mortality over next 3 years (CS
<
1) where as 37 (8%) hospitals had marked improvement in AMI mortality (CS ≤ 8). Similarly, only 127 (26%) of top 25% hospitals had persistently low mortality over next 3 years (CS ≤ 8) and 37 (8%) had marked worsening in AMI mortality (CS
<
1). Average RSMR at hospitals with persistently high mortality was 18.5% vs. 13.7% at hospitals with persistently low mortality, which led to an additional 834 Medicare deaths at high mortality hospitals. Patient and hospital characteristics were limited in differentiating hospitals with persistently high and persistently low mortality.

Conclusions:
Among hospitals with high and low mortality at baseline, performance on AMI mortality does not persist during subsequent years. Concentrating quality improvement efforts at a few hospitals with persistently high mortality could avoid a substantial number of AMI deaths.
Abstract 131: Cardiac Arrest Due to Cardiac Etiology: A Progress Report on the Past 20 Years in an Emergency Department in Vienna
Authors: Sulzgruber Patrick , Hubner Pia , Schober Andreas , Spiel Alexander , Uray Thomas , Van Tulder Raphael , Wallmüller Christian , El-Tattan Diana , Graf Nikolaus , Ruzicka Gerhard , Schrief Christoph , Laggner Anton N , Sterz Fritz
Published: July 2021

Background:
Based on demographic changes in the western world, the number of patients with cardiac arrest due to a cardiovascular event is continuously rising. A large variety of factors impacting on favorable neurological outcome (CPC 1-2) and the 6-month survival, are well established. The question whether the knowledge about these predictive factors result in improved outcome over the last 20 years, has not been proven within a long-term study so far.

Methods:
We prospectively identified 2670 patients (out-of hospital [OOH], n = 1822; in-hospital [IH], n = 848) with cardiac arrest of cardiac etiology and ventricular fibrillation as a first rhythm treated at our emergency department between January 1992 and December 2012. Chi-square test and Cochran-Mantel-Haenszel test have been used to assess differences in CPC and 6-month survival within the observation-period.

Results:
Within our total cohort, 2189 patients (82.0%) survived the initial event. After a follow-up period of 6 months, 1007 patients (46%) with ROSC deceased. A favorable CPC (1-2) after 6 months has been detected in 1197 patients (54.7%). Within the last 20 years there was an improvement of favorable neurological outcome (CPC 1-2) (p<0.001) and as well a reduction of 6-month mortality rates (p=0.004).

Independently in patients with IH cardiac arrest, 78.5% (n=666) survived the initial event, but the 6-month survival rate (n=381, 57.2%) and the favorable CPC outcome (n=443, 66.5%) were approximately higher. Independently within IH cardiac arrest patients a reduction of 6-month mortality rates (p=0.048) was found. Still there were constantly high rates of favorable neurological outcome (CPC 1-2) after 6 months, but there was no improvement within the past 20 years (p=0.665).

Conclusion:
We were able to demonstrate, that outcome of patients with cardiac arrest of a cardiac etiology has improved significantly within the last 20 years. This gives the impression, that critical care medicine on a high level for patients with cardiac arrest even in the emergency department could be important for outcome. If such specific cardiac arrest centers merged with emergency departments prove to be valuable for ideal patient care has to be further evaluated in detail.
Abstract 13248: DPP-4 Inhibition Reduces Atherosclerosis by Priming Monocytes into Alternative M2 Macrophages
Authors: Brenner Christoph , Franz Wolfgang M , Kuehlenthal Sarah , Kuschnerus Kira , Remm Friederike , Theiss Hans D , Landmesser Ulf , Krankel Nicolle
Published: July 2021

Introduction:
Major parts of the population in the western world are suffering from atherosclerotic diseases like coronary and peripheral artery disease or stroke. Interventional and pharmacological therapies at present focus on the treatment of vascular stenoses, secondary prophylaxis or reduction of cardiovascular risk factors.

Hypothesis:
In this project, we want to establish the pharmacological inhibition of DPP4 as a new therapeutic concept focussing on macrophage polarization during development of atherosclerosis.

Methods:
Non-diabetic ApoE-/- mice were treated with normal diet or high fat diet for three months to induce arterial atherosclerotic lesion formation. The descending aorta was stained using Oil-Red-O to quantify atherosclerotic lesions. In parallel mice were treated with Sitagliptin or placebo. Macrophage subtype content (M1, M2) in the aortic wall was quantified using FACS.

Results:
Mice on high fat diet treated with Sitagliptin showed a dramatic reduction in atherosclerotic lesion formation in contrast to placebo treated animals. Regarding total macrophage content in the vascular wall we could not detect a difference between the treatment groups. However, the number of protective M2 macrophages was more than tripled in the gliptin-treated animals. Moreover, the number of mural M2 macrophages inversely correlated with the aortic plaque burden. In further analyses we could demonstrate that Sitagliptin favoured macrophage polarization to alternatively activated M2 macrophages via the CXCR4-signaling pathway.

Conclusions:
We demonstrated that long-term Sitagliptin treatment in ApoE-/- animals on high fat diet can successfully inhibit atherosclerotic lesion formation via induction of macrophage polarization to the protective M2 phenotype. Due to the promising results of this study we are currently planning to transfer the underlying therapeutical concept into a randomized clinical trial.
Abstract 13261: Determining the Cost-Benefit Yields of Participating in a Cardiac Rehabilitation Program
Authors: Biswas Aviroop , Alter David
Published: July 2021

Background and Objective:
Regular participation in cardiac rehabilitation (CR) has been consistently shown to improve survival prognosis for patients suffering from a recent cardiovascular episode. No study has quantified the thresholds of baseline risk/behavioral attrition beyond which the cost-benefits of CR become economically unattractive. We aimed to determine how the cost-benefits associated with CR vary across baseline risk and behavioral attrition patterns amongst an actual population of patients participating in an outpatient CR program.

Methods:
Data was obtained from 11,998 consecutive patient referrals to Toronto Rehab Cardiac Rehabilitation and Secondary Prevention Program (1995 to 2010). Baseline risk was defined as the probability of death/hospitalization at 2 years following program termination and behavioral attrition as the probability of program drop-out. We assumed a fixed cost of $1500 per program and a fixed program efficacy of 20% reduction in death/hospitalization. Multiple logistic regression models were used to predict the number of deaths/hospitalizations avoided per 1000 patients treated.

Results:
Regression models for baseline risk and baseline behavioral attrition produced C-statistics of 0.66 and 0.85, respectively. Increasing age, type 2 diabetes were found to be concordant predictors of CR cost-benefit and higher baseline functional capacity as a discordant predictor. The correlation between program drop out risk and baseline risk was poor (r=0.22, p<0.001). There was a 13% increased risk of predicted dropout for each quartile of program cost to yield (RR 0.87, 95% CI: 0.87, 0.89), while for each 10% baseline risk increase, RR was found to be 1.36 (95% CI: 1.34, 1.37). For both risk factors as predictors of improved cost-benefit yield ($1000 cost per adverse-event avoided) there was a 21% higher likelihood of the program being economically attractive for each 10% increase in behavioral attrition risk (RR 1.21, 95% CI: 1.207, 1.213).

Conclusion:
Baseline risk and behavioral attrition are important determinants of CR effectiveness and underscores the potential utility of risk stratification and patient baseline/behavioral attrition risk thresholds to estimate the programmatic benefit of CR programs.