bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 317: Effect of Intra-arrest Induction of Therapeutic Hypothermia on Out-of-Hospital Cardiac Arrest
Authors:   NYC Project Hypothermia Working Group, Freese John , Rabrich Jeffrey , Menegus Mark , Slesinger Todd , Silverman Robert , Keller Norma , Dillworth Judy , Isaacs Doug , Ben-Eli David , Lai Pamela , Asaeda Glenn , Prezant David
Published: July 2021

Introduction:
The resuscitation literature has recently suggested that the prehospital initiation of therapeutic hypothermia following successful resuscitation does not alter outcomes among patients who suffer sudden out-of-hospital cardiac arrest (OOHCA). We sought to assess the impact of earlier, intra-arrest induction of therapeutic hypothermia on OOHCA survival.

Methodology:
Out-of-hospital cardiac arrest data from two consecutive twelve-month periods was analyzed: August 1, 2009 - July 31, 2010 (Phase I), August 1, 2010 - July 31, 2011 (Phase II). In Phase I, paramedics in this urban system transported OOHCA patient to participating Cardiac Arrest Centers where the use of therapeutic hypothermia had been incorporated to the standard post-resuscitation care pathway. In Phase II, paramedics initiated hypothermia during the initial resuscitation effort through the rapid infusion of large-volume, ice-cold saline. Consistent with the Utstein definitions, analyses utilized only those cases which were bystander witnessed and of cardiac etiology.

Results:
There were 1,487 and 850 bystander witnessed arrests of cardiac etiology in the two phases. Patient and arrest characteristics for the two groups did not differ with respect to age, gender, race, response time, bystander witnessed status, or the frequency of bystander CPR. Return of spontaneous circulation (ROSC), sustained ROSC, survival to hospital admission and survival to hospital discharge did not differ significantly from Phase I to Phase II: 40.82% vs 39.59% (p=.54), 31.10% vs 31.17% (p=0.58), 27.15% vs 24.88% (p=0.27), and 6.62% vs 6.19% (p=0.41). In addition, among those survivors for whom neurologic status is known, the intra-arrest initiation of therapeutic hypothermia did not significantly change the proportion of survivors considered neurologically intact (76.47% vs 70.37%, all p=0.59).

Conclusions:
The intra-arrest initiation of therapeutic hypothermia did not alter outcomes among OOHCA patients, demonstrating neither harm nor benefit. Whether this is due to a lack of continuation of hypothermia following hospital admission or a true lack of benefit requires further collaborative work between the prehospital and hospital communities.
Abstract 331: Activation of the Safe Pathway Against Cardiac Ischemia-Reperfusion Injury Goes Beyond the Risk Pathway in the Late Pregnancy
Authors: Li Jingyuan , Eghbali Mansoureh
Published: July 2021

Introduction:
We have recently shown that the heart of late pregnant (LP) rodent is more prone to ischemia/reperfusion (I/R) injury compared to non-pregnant. We also reported that post-ischemic adminstartion of (ITLD) protects the LP hearts against I/R injury. Here we investigated Survivor Activating Factor Enhancement (SAFE) pathway, which requires the activation of the signal transducer and activator of transcription 3 (STAT-3) and it can successfully lessen cardiomyocyte death at the time of reperfusion, independently of the activation of the already well-described Reperfusion Injury Salvage Kinase (RISK) pathway (which includes activation of phosphoinositide 3-kinase (PI3K) signaling pathways) in ITLD-induced cardioprotetion.

Methods:
Isolated LP mouse hearts were subjected to 20 min ischemia followed by 40 reperfusion with 1) Krebs Henseleit buffer (CTRL group), 2) 1% intralipid (ITLD group) or 3) ITLD+STAT3 inhibitor Stattic (20 μM, Stattic group), and 4) ITLD+PI3K inhibitor LY294002 (45 μM). Hemodynamics and myocardial infarction were measured. Two-way and one-way ANOVA was used for statistical analysis. The data are from four to six mice in each group. P<0.05 was considered statistically significant. Values are expressed as mean± SE.

Results:
The Intralipid-induced cardioprotection was only partially abolished by PI3K inhibitor, LY294002, whereas it was fully abolished when stattic was applied at the end of 40 min reperfusion. The RPP was significantly lower in LY294002 treated group compared to the group treated with Intralipid alone, but still significantly higher than ITLD+Stattic: RPP=8881±1331 mmHg*beats/min in ITLD vs. 5212±1955 mmHg*beats/min in ITLD+LY, p<0.05; 1186±563 mmHg*beats/min in ITLD+Stattic vs. 5212±1955 mmHg*beats/min in ITLD+LY, p<0.05. The infarct size was also larger in LY294002 treated group when compared to Intralipid alone (32.8±3.1% in ITLD+LY vs. 21.7±2.6% in ITLD, p<0.05), but lower than ITLD+Stattic group (32.8±3.1% in ITLD+LY vs 47.9±2.5% ITLD+Stattic, p<0.05).

Conclusion:
Intralipid protects the heart of late pregnant mice against I/R injury mainly through SAFE-STAT3 pathway.
Abstract 334: Serum MicroRNA-378 as a Novel Diagnostic Biomarker for Myocardial Infarction
Authors: Zhu Hua , Lagana Alessandro , Veneziano Dario , Adesanya Timothy , Mohler Peter , Nishi Miyuki , Takeshima Hiroshi , Kilic Ahmet
Published: July 2021

Purpose:
Chest pain represents one of the most common reasons for a visit to the emergency department accounting for ~10% of all visits. Of these only 45% represented true acute coronary syndromes (ACS) (stable angina, unstable angina or myocardial infarction (MI)). The current methods to detect a true ACS have a clinic delay of several hours and hence it is the focus of our experiments to explore a novel diagnostic biomarker that can detect myocardial infarction more rapidly and reliably.

Methods and Results:
In order to establish a library of potential diagnostic biomarkers, we developed a novel non-thoracotomy model of MI in the
Ovis aries
to minimize potential confounders of serum microRNA changes due to unrelated thoracotomy induced injuries. We obtained serum samples from different time points following MI and level of circulating microRNAs were detected by a microRNA array and compared to the concentration of Troponin I from the same sample. Among more than 300 identified microRNA in the array, 12 microRNA were tested with the highest fold expression change, and a single microRNA, miR-378, identified as a promising biomarker of MI. We used a mouse model of left coronary artery ligation induced MI to quantify the dynamics of miR-378 levels in response to MI injury (Figure) , we found miR-378 was non-detectable before MI, reached peak at 4 hours post MI; whereas Troponin I reached peak at 6 hours.

Conclusion:
In both a large and small animal models of MI, microRNA-378 showed a reproducible time frame of peak expression that may serve as a more efficient diagnostic biomarker for myocardial infarction.
Abstract 342: Differences in Inflammatory Dysregulation in TBI Versus Major Trauma
Authors: Hinson Holly E , Schreiber Martin , Morris Cynthia , Bourdette Dennis
Published: July 2021

Introduction:
Up-regulation of aseptic inflammation is a prominent feature of major trauma, with or without head injury. Observational studies in TBI often lack control groups with major trauma, obscuring the genesis of the reported biomarkers. We hypothesized that patients with TBI would display a unique inflammatory signature that would differ from patients with major trauma without brain injury, due to blood-brain-barrier compromise.

Methods:
We prospectively enrolled patients with major trauma with and without TBI from a busy level I trauma center ICU. TBI was defined as GCS<13 not related to intoxication, or the presence of intracranial hemorrhage on admission CT scan. Plasma samples were obtained on admission (<8 hours from the trauma), and banked at -80°C for subsequent analysis. Plasma was analyzed by the Stanford Human Immune Monitoring Center using a Luminex human 61-plex analyte platform that screens 61 secreted proteins using multiplex fluorescent immunoassay; samples were run in duplicate for confirmation, and the means reported. Measurements are reported in median [IQR] in pg/mL. P values of 0.05 or less were considered significant, though final data will be adjusted for multiple comparisons.

Results:
Forty patients were enrolled, 21 had TBI. Total injury severity scores (ISS) (26 [11-27 v. 14 [10-21] P=0.11) and APACHE (14 [12-24] v. 12 [10-14] P=0.07) scores were comparable between groups. Patients in the TBI group had a lower GCS on admission (15 [4-15] v. 15 [15-15]) P=0.04). While both groups had evidence of elevated cytokines, only TNF-alpha (72.23 [63.68-91.27] v. 63.52 [58.36-69.5], P=0.05) and interferon beta (19.31 [14.13-33.8] v. 14.79 [10.71-17.32], P=0.04) were statistically significantly different between the groups, both more elevated in the TBI group.

Conclusion:
Our data provides preliminary evidence of immunologic dissonance unique to TBI as compared to major trauma. Future studies using biomarkers in TBI must control for major trauma as a confounder.
Abstract 72: Addition of Real-Time CPR Feedback Improves Immediate Outcomes for Out-of-Hospital Cardiac Arrest
Authors:   NYC Project Hypothermia Working Group, Freese John , Menegus Mark , Rabrich Jeffrey , Slesinger Todd , Silverman Robert , Keller Norma , Dillworth Judy , Isaacs Doug , Ben-Eli David , Lai Pamela , Asaeda Glenn , Prezant David
Published: July 2021

Introduction:
The 2010 American Heart Association Guidelines stated that “cardiopulmonary resuscitation prompt and feedback devices may be useful for training rescuers and may be useful as part of an overall strategy to improve the quality of CPR for actual cardiac arrests.” We sought to assess the effect of one such device on OOHCA outcomes in a large, urban setting.

Methodology:
Out-of-hospital cardiac arrest data from two consecutive twelve-month periods was analyzed: August 1, 2010 - July 31, 2011 (control) and August 1, 2011 - July 31, 2012 (CPR feedback). During the CPR feedback period, defibrillators capable of providing real-time audible and visual CPR feedback were added to standard prehospital resuscitation care.

Results:
There were 850 and 748 bystander witnessed arrests of cardiac etiology in the two periods. Patient and arrest characteristics for the two groups did not differ with respect to age, gender, race, response time, bystander witnessed status, or the frequency of bystander CPR. As compared to the control period, the addition of real-time CPR feedback resulted in a significant improvement in immediate outcomes: return of spontaneous circulation, or ROSC (39.59% vs. 47.71%, p=0.001); sustained ROSC (31.17% vs. 36.14%, p= 0.037). However, there was no improvement in survival to hospital admission (24.88% vs. 25.32%, p=0.85) or survival to hospital discharge (5.63% vs. 6.72%, p=0.43). In addition, among those survivors for whom neurologic status is known, the addition of CPR feedback did not significantly change the proportion of survivors considered neurologically intact (70.37% vs 65.63%, all p=0.78).

Conclusions:
The addition of real-time CPR feedback to a large urban EMS system’s resuscitation care resulted in significant improvements in immediate survival but did not affect overall survival rates. It is also possible earlier introduction of these devices (through their use by first responder and/or earlier arriving basic life support units) may provide greater benefit. Further data analysis is required to determine the specific effect of CPR feedback devices on long-term survival and to optimize their use in resuscitation care.
Abstract 79: Restart a Heart Day: The Danish Way 2013 and Strategy for 2014
Authors: Thomas Grethe , Kabel Merete , Kjærgaard Jesper , Lippert Freddy
Published: July 2021

Purpose of the Study:
The first European Restart a Heart Day was held on October 16
th
2013, with the purpose of creating awareness of OHCA and the importance of bystander CPR.

Material and methods:
The goal was to provide Danes with knowledge of CPR, the use of AEDs and
www.hjertestarter.dk
. Additionally, Danes were encouraged to take an ERC-approved CPR-AED course. The combination of research presentation and citizen engagement provided the background for the strategic planning of the day.
www.hjertestarterdagen.dk
was created to enable Danes to view upcoming free events with CPR and AED demonstrations. Pamphlets and posters were made available free of charge for organizers to market the events. Furthermore, a nationwide competition encouraged Danes to locate AEDs not yet registered in the national network for public use. An updated publication of the Danish Cardiac Arrest Registry served as a communicative icebreaker toward the media. Figure 1. This astonishing development was highlighted to motivate more Danes to learn CPR. The media campaign included successfully resuscitated persons, bystanders and leading Danish resuscitation scientists. They stressed the importance of learning CPR and emphasized the lack of publicly accessible AEDs. Figure 2.

Conclusion:
Combining new scientific results with a well-planned media strategy and citizen engagement can motivate and encourage Danes to learn CPR and to register more AEDs available for public use

Strategy for 2014:
Focus on traffic hubs - e.g. ferries, train stations and airports. Why? Traffic hubs are the most likely places in public space for OHCA.
Abstract 83: Effect of Therapeutic Hypothermia on Oxygenation Index in Rat Model of Cardiac Arrest
Authors: Yu Haifang , Yin Lu , Gong Ping , Wang Jiangang , Yang Zhengfei , Zhao Shen , Qian Jie , Wu Xiaobo , Cahoon Jena , Tang Wanchun
Published: July 2021

Introduction:
Therapeutic hypothermia improves the outcomes of cerebral function after resuscitation from cardiac arrest (CA). The effect of therapeutic hypothermia on post resuscitation pulmonary function, however, is less known. In the present study, we investigated the effect of therapeutic hypothermia on oxygenation index, a sensitive index of pulmonary function,in a rat model of cardiac arrest and resuscitation.

Hypothesis:
We hypothesize that during therapeutic mild hypothermia in a rat model of cardiac arrest, the pulmonary function following resuscitation is less impaired when compare to normothermia.

Methods:
Twenty-one male Sprague-Dawley rats were randomized into three groups: 1) control group (control, n=5): the normothermic rats only received anesthesia and the surgical procedure as the other groups without ventricular fibrillation (VF); 2) normothermia group (NT, n=7): the normothermic rats were subjected to induced VF for 8 mins followed by 8 mins of cardiopulmonary resuscitation (CPR); 3) Mild hypothermia group (HT, n=9): the rats were subjected to induced VF for 8 mins followed by 8 mins of CPR. Mild hypothermia of 33±0.5°C was started 5 mins after return of spontaneous circulation (ROSC) and maintained for 8 hrs. The oxygenation indexes were measured at baseline, 2, 4 or 8 hours after ROSC with a conventional blood gas analyzer (PHOX plus L; Nova Biomedical Corporation, Waltham, MA, USA).

Results:
Compared to the control group, the oxygenation indexes of both the NT and HT groups were significantly decreased at 2 hrs after ROSC. However, more significant reduction in oxygenation index was observed in the NT group (Figure).

Conclusions:
There is an early pulmonary dysfunction after successful resuscitation from cardiac arrest. Hypothermia reduces the impairment of pulmonary function.
Abstract 86: Association Between Hospital Postresuscitative Performance and Clinical Outcomes in Patients with Out-of-Hospital Cardiac Arrest
Authors: Stub Dion , Schmicker Robert H , Anderson Monique L , Peterson Eric D , Callaway Clifton W , Daya Mohamud R , Sayre Michael R , Elmer Jonathan , Grunau Brian , Aufderheide Tom P , Lin Steve , Buick Jason , Zive Dana , Nichol Graham ,   ROC Investigators
Published: July 2021

Context: Whilst performance measures have been extensively evaluated in conditions such as myocardial infarction, it remains unclear if adherence to post-resuscitation guidelines is associated with better outcome in patients hospitalized after out-of-hospital cardiac arrest (OHCA).

Objectives:
To assess whether survival and good functional status at discharge are associated with post-resuscitation performance score based on treatment guidelines for patients with OHCA, comprised of a) initiation of temperature management; b) target temperature 32
0
-34
0
C achieved; c) temperature management continued for more than 12 hours; d) coronary angiography performed within 24 hrs; e) life sustaining treatment not withdrawn prior to day 3.

Methods:
An observational analysis of hospital care in 111 North American hospitals, including 3252 patients enrolled in the Resuscitation Outcomes Consortium (ROC-PRIMED) study, between 2007 and 2009, following OHCA. Performance scores were calculated, utilizing opportunity based scoring, with each factor weighted equally and scaled from 0-1. Scores for individual patients were grouped at the hospital level, with hospitals divided for descriptive purposes into quartiles based on their median opportunity composite score.

Results:
Performance score varied widely (median [IQR] scores from lowest to highest hospital quartiles, 21% [20%-25%] vs 59% [55%-64%]. Adjusted survival to discharge increased with each quartile of performance score (lowest to highest: 16.2%, 20.8%, 28.5%, 34.8%,
P
<0.01). Similarly adjusted rates of good functional outcome improved (lowest quartile to highest: 8.3%, 13.8%, 22.2%, 25.9%, P<0.01). Hospital performance score were significantly associated with outcome after risk adjustment for established prehospital resuscitative factors (Highest versus lowest adherence quartile: adjusted OR of survival 1.64; 95% CI 1.13, 2.38)

Conclusions:
Increased survival and improved functional status at discharge are associated with greater adherence to recommended hospital based post-resuscitative care guidelines. Measuring, reporting and improving hospital adherence to guideline-based performance metrics could improve outcomes following OHCA.
Abstract 9379: Higher Levels of Plasminogen-Activator Inhibitor 1 Are Associated with Progression of Coronary Artery Calcification in Middle-Aged Women: The Study of Women’s Health Across the Nation (SWAN) Heart Study
Authors: Wang Norman C , Matthews Karen A , Barinas-Mitchell Emma J , Chang Chung-Chou H , El Khoudary Samar R
Published: July 2021

Introduction:
Relationships of inflammatory and hemostatic biomarkers with progression of coronary artery calcification (CAC) in asymptomatic women are unknown.

Hypothesis:
We assessed the hypothesis that C-reactive protein (CRP), fibrinogen, plasminogen-activator inhibitor 1 (PAI-1), and tissue plasminogen activator antigen (tPA-ag) were associated with CAC progression in women free of known coronary heart disease (CHD) and stroke.

Methods:
CRP, fibrinogen, PAI-1, and tPA-ag were measured in SWAN Heart participants from the Pittsburgh and Chicago sites at baseline. CAC was obtained by CT scans and quantified by the Agatston score at baseline and after 2.3±0.5 years of follow-up. Significant CAC progression was defined as present if 1) CAC score was >0 at follow-up in subjects with CAC score = 0 at baseline, 2) annualized change in CAC score was ≥10 in subjects with 0<CAC score<100 at baseline, and 3) annualized percent change in CAC score was ≥10% in subjects with CAC score ≥100 at baseline. Univariable and multivariable logistic regression were used for statistical analyses. The novel biomarkers were log-transformed. Baseline CAC was transformed as log(CAC+1).

Results:
The study included 252 women (32.5% black, 67.5% white; 56.4% pre- and early perimenopausal, 30.6% late peri- and postmenopausal, and 13.1% hormone therapy users) with a mean age of 51.2±2.6 years at baseline. In unadjusted analyses, log(PAI-1) and log(tPA-ag) were positively and significantly associated with CAC progression (p<0.05), but log(CRP) and log(fibrinogen) were not. Adjusted analyses included the following covariates: baseline CAC, age, site, race, menopausal status, income, education, systolic blood pressure, body mass index, Homeostasis Model Assessment insulin resistance index, family history of cardiovascular (CV) disease, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, CV medication use, and current smoking. Only log(PAI-1) was significantly associated with CAC progression (OR: 1.91; 95% CI: 1.24-2.93; p=0.003).

Conclusions:
In conclusion, PAI-1 is associated with the presence of CAC progression in middle-aged women. Targeting PAI-1 may decrease atherogenesis beyond conventional CHD risk factors.
Abstract 9387: A Better Personalized Prediction for International Normalized Ratio Levels in Inpatients Receiving Warfarin
Authors: Zhao Yao , Liu Nan , Wang Yijun , Hickey Kathleen
Published: July 2021

Objectives:
The objectives of this study were: 1) to test the effectiveness of a novel prediction method for International Normalized Ratio (INR) levels in inpatients receiving warfarin therapy; 2) to compare the prediction accuracy between this method and existing methods.

Methods:
We developed a novel personalized pharmaco-kinetic and pharmaco-dynamic (PKPD) model to predict the trajectory of INRs over time. We tested this model on 60 inpatient cases in New York Presbyterian Hospital from 2012 to 2013 using two different methods. The first method (fixed horizon) predicts future INR levels by the initial five observed INRs; the second method (rolling horizon) makes predictions based on the latest five observed INRs on a rolling basis. Prediction accuracy is evaluated by the Absolute Percentage Prediction Error (PAPE), which is |Predicted INR - Actual INR|/Actual INR.

Results:
A personalized INR prediction example:

Summary statistics for prediction errors:

Conclusions:
The rolling horizon method continuously updates the PKPD model based on the individuals’ latest INR responses, and thus significantly improves the prediction accuracy as compared to the fixed horizon method (p<.001). The rolling horizon method provides accurate predictions for INR trajectory five days into the future, and can help clinicians improve warfarin dosing to reduce adverse outcomes due to INRs that are not within a therapeutic range.
Abstract 9411: Urine Aquaporin-2 Level is a Novel Marker for the Better Prognosis After Long-Term Tolvaptan Treatment in Patients With Advanced Heart Failure
Authors: Imamura Teruhiko , Kinugawa Koichiro , Fujino Takeo , Inaba Toshiro , Maki Hisataka , Hatano Maasaru , Yao Atsushi , Komuro Issei
Published: July 2021

Introduction:
Preserved function of collecting duct is essential for the response to tolvaptan (TLV), and urinary level of aquaporin 2 (U-AQP2) can be a marker for vasopressin-dependent activity of collecting duct.

Hypothesis:
Higher levels of U-AQP2 in proportion to plasma levels of vasopressin (P-AVP) may be associated with better initial responses to TLV and eventually result in the improved prognosis after long-term treatment of TLV.

Methods:
Consecutive 60 in-hospital patients with stage D heart failure (HF) who received TLV on a de novo basis were enrolled during 2011-2013. We also selected 60 HF patients by propensity score matching who were hospitalized during the same period but never treated with TLV. Events were defined as death and/or HF re-hospitalization.

Results:
TLV (3.75-15 mg/day) was continuously administered except death or ventricular assist device implantation occurred. There were 41 patients (group 1) who had increases in UV over the first 24 h after TLV initiation, and all of them had U-AQP2/P-AVP ≥0.5 х103 with higher U-AQP2 levels (5.42 ± 3.54 ng/mL) before TLV treatment. On the other hand, UV rather decreased even after TLV initiation in 19 patients over the first 24 h (group 2). Those in the group 2 universally had U-AQP2/P-AVP <0.5 х103, extremely low U-AQP2 levels (0.76 ± 0.59 ng/mL, p<0.001 vs. group 1), and similar P-AVP with the group 1 at baseline. The 41 and 19 patients without TLV treatment (group 3 and 4) were respectively matched to the group 1 and 2 by propensity scores. Interestingly, every patient in the group 3 had U-AQP2/P-AVP ≥0.5 х103, and vice versa in the group 4. Among the four groups, congestion-related symptoms were only improved in the group 1 after 1 month of enrollment. The patients in the group 1 had significantly better event-free survival over 2-year by TLV treatment compared with the group 3 (76% vs. 43%, p<0.014). In contrast, the patients in the group 2 and 4 had very poor prognoses regardless of TLV treatment (7% vs. 11%, p=0.823).

Conclusions:
U-AQP2/P-AVP is a novel predictor for the initial response to TLV in HF patients. Patients with higher U-AQP2/P-AVP may enjoy a better prognosis by long-term TLV treatment probably due to efficient resolution of congestion.
Abstract 9421: Additional Wiping of the Skin With 70% Isopropil Alcohol Just Before Routine Povidone-Iodine Antisepsis Reduces Cardiac Implantable Electronic Device Infections
Authors: Takahashi Takanori , Shimotakahara Junichi , Yagi Nobuhito , Nakazato Jun , Miyagi Tadayoshi , Wake Minoru , Hirata Kazuhito
Published: July 2021

Introduction:
Cardiovascular Implantable Electronic Device(CIED) Infections are one of the most serious complication after CIED implantation or replacement. To prevent infection, appropriate skin antisepsis and perioperative antibiotic prophylaxis at CIED implantation/replacement are important. But the most optimal antisepsis for CIED surgery is not well defined. Then we assessed whether additional wiping of the skin with 70% isopropyl alcohol just before routine skin antisepsis with povidone-iodine reduces the incidence of CIED infection.

Methods:
Consecutive 473 cases of CIED implantation or generator replacement from Jan.2008 to Dec.2013 at one community hospital were divided into two groups according to preoperative skin antisepsis with 70% isopropyl alcohol wipes lasting for at least 1 minute just before povidone-iodine scrub and paint(IPA group, n=183), or povidone-iodine only(No IPA group, n=290). All cases received perioperative antibiotic prophylaxis 30 minute before and 6 hours after procedure. Incidence of CIED infection requiring complete extraction of the leads and the generator within 1-year after implantation/replacement were compared between two groups by Kaplan-Meier analysis.

Results:
There were no significant difference in background CIED infection risk factors identified by past studies (diabetes, renal insufficiency, anticoagulant use, corticosteroid use, tempolary pacing, and generator replacement) between two groups. During the follow up period, 8 cases of confirmed CIED infection requiring complete extraction were identified, 6 pacemaker and 2 implantable cardioverter-defibrillator(ICD) or biventricular ICD. All infected cases belonged to No IPA group (p = 0.0235).

Conclusions:
In conclusion, wiping of the skin with 70% isopropyl alcohol just before routine antisepsis with povidone-iodine at CIED implantation/replacement significantly reduces the incidence of infection.
Abstract 9480: Persistent MR Reduction With Stabilization of LV Remodeling and Following Chronic Polymer-Mesh Device on Infarcted Myocardium in a Chronic Ischemic MR Model
Authors: Kataoka Akihisa , Zeng Xin , Garcia Michael , Seybolt Margo , Sullivan Suzanne , Guerrero J. Luis , Muriuki Maryanne , Kozak Adam , Braithwaite Gavin , Handschumacher Mark D , Levine Robert A , Hung Judy
Published: July 2021

Background:
Mitral valve repair with ring annuloplasty for ischemic mitral regurgitation (IMR) is associated with significant recurrent IMR due to continued left ventricular (LV) remodeling as it does not directly address LV and mitral valve tethering. We aimed to assess chronic implantation of novel polymer based mesh device to reduce IMR reduction and reverse LV remodeling.

Methods:
Five Dorset sheep underwent ligation of second and third circumflex obtuse marginal branches to produce chronic IMR after 8 weeks. Poly-mesh was attached to the infarcted myocardium underlying the papillary muscle with a further 8 weeks follow-up. In addition, chronic IMR was produced in 5 untreated control sheep. IMR severity was assessed by 2D vena contracta width (VCW) and 3D vena contracta area (VCA). LV end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF) by 2D echo and hemodynamic data were also obtained at each baseline, chronic MR, and chronic poly-mesh stages.

Results:
In all sheep, after poly-mesh attachment, IMR decreased and this reduction persisted over 8 weeks (VCW 0.42±0.09 to 0.08±0.12cm; VCA 0.13±0.08 to 0.05±0.08cmsq, p<0.01) with significant increase in Emax (1.1±0.5 to 2.9±0.7mmHg/ml, p<0.05). There were no significant changes in LVEF (45.4±6.7 vs 42.6±3.5%, p=NS). Importantly, LV EDV and ESV at chronic poly-mesh stage were reduced compared to the chronic MR stage (EDV 110±15 to 88±18ml, p<0.05; ESV 61±14 to 51±12ml, p=NS) and % increases of both EDV and ESV from chronic MR to chronic poly-mesh stage were significantly lower than those of untreated control sheep (%EDV change -22±11 vs 11±10%, p<0.01; %ESV change -10±14 vs 9±10%, p<0.05) (FIGURE).

Conclusions:
Chronic follow up after polymer-mesh device attachment shows the stabilization of mitral-LV complex in a chronic IMR model, causing persistent reduction of IMR and preventing continued LV remodeling.
Abstract 9576: Predictors of Silent Cerebral Events Detected on Magnetic Resonance Imaging in Patients After Atrial Fibrillation Ablation
Authors: Deneke Thomas , Nentwich Karin , Müller Patrick , Roos Markus , Krug Joachim , Mügge Andreas , Szöllösi Atilla , Schmitt Rainer , Schade Anja
Published: July 2021

Introduction:
Silent cerebral events (SCE) have been identified on magnetic resonance imaging (MRI) in asymptomatic patients after atrial fibrillation (AF) ablation. Silent cerebral lesions represent irreversible cerebral damage, comparative analysis using a consistent MRI definition is missing and factors influencing the risk of SCE are poorly understood.

Methods:
351 Patients undergoing AF ablation underwent post-ablation cerebral MRI. SCE were identified based on a sensitive definition using a 1.5Tesla MRI including DWI and ADC-map (but not including FLAIR). AF ablation was performed either using irrigated single-tip radiofrequency (RF) ablation (group 1, N=73), phased RF pulmonary vein isolation (PVI) (group 2, N=129), endoscopically-guided laser balloon (group 3, N=41), cryo-balloon PVI (group4, N=34) and irrigated RF multipolar catheters (nMARQ) (group 5, N=73). Differences in regard to SCE rates were analyzed.

Results:
In group 1 22%, in group 2 37%, in group 41%, in group 4 21% and in group 5 27% of patients had documented SCE. There was a significantly higher incidence of SCL in patients with compared to without exchanges of catheters over a single transseptal sheath (34% vs. 18%, p=0.007) and in patients with left atrial dilation (48% vs. 30%, p=0.01).

In a subgroup analysis incidence of SCE was lower when patients were ablated under continued oral anticoagulation (11%) compared to novel oral anticoagulants (33%) or without continuous appropriate anticoagulation bridged with low-molecular weight heparin (45%). Documented left atrial low-voltage areas were associated with a higher incidence of SCE (46% versus 24% in the control group).

Conclusions:
When using a sensitive MRI definition of SCE incidences are relevantly higher compared to using the “old” definition including the FLAIR-sequence. Technology-associated and procedural characteristics associated with a higher risk of SCE have been identified. Modification of procedural steps of the AF ablation procedure may further reduce the risk of SCE.
Abstract 9603: Extreme Hypercholesterolemia Exacerbated by Breast Feeding: Infantile Cases of Sitosterolemia With Novel Mutations in ABCG5 Gene
Authors: Tada Hayato , Kawashiri Masa-aki , Konno Tetsuo , Hayashi Kenshi , Nohara Atsushi , Inazu Akihiro , Mabuchi Hiroshi , Yamagishi Masakazu
Published: July 2021

Background:
Sitosterolemia is an extremely rare inherited disease characterized by increased levels of plant sterols such as sitosterol, the cause of which is ATP-binding cassette (ABC) sub-family G member 5 or member 8 (ABCG5 or ABCG8) gene mutations. It has been described that infantile sitosterolemic cases exhibit clinical manifestations resembling homozygous FH, including severe hypercholesterolemia, the mechanism of which still remains unclear. In the present study, we tried to determine the molecular diagnosis for 6 Japanese infantile cases with severe hypercholesterolemia and systemic xanthomas without any mutations in LDL receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDL receptor adaptor protein 1 (LDLRAP1) genes, then evaluated their clinical features, especially the responsiveness to variety of therapies, including statins, ezetimibe, colestimide, and weaning from breast feeding.

Methods and Results:
We performed genetic analysis for ABCG5, and ABCG8 genes for those 6 cases, and identified 2 pairs of mutations in ABCG5 gene in each case, including 2 novel mutations (c.130C>T and c.1813_1817delCTTTT) and 2 known mutations (c.1306G>A and c .1336C>T). During their clinical courses, significant reduction of their LDL cholesterol levels could be obtained through their weaning alone (from 540 ± 164 mg/dl to 147 ± 60 mg/dl, p < 0.05). Also, a substantial reduction of their sitosterol levels were observed (from 90 ± 69 μg/ml to 52 ± 38 μg/ml, p < 0.05) using ezetimibe without any apparent side effects, although statins and colestimide did not have any effects on their sitosterol levels. Interestingly, their cutaneous xanthomas completely disappeared associated with the reductions of their cholesterol levels rather than those of sitosterol levels.

Conclusion:
We have identified infantile Japanese sitosterolemic subjects with extreme hypercholesterolemia exacerbated by breast feeding. Their unique manner of responses to weaning as well as to ezetimibe could provide us novel insights into the metabolic basis for cholesterol and plant sterols in human.
Abstract 9613: Randomized Evaluation of Anacetrapib Lipid-Modifying Therapy in Patients With HeteroZygous Familial HypercholesterolEmia (REALIZE Study)
Authors: Kastelein John J , Besseling Joost , Shah Sukrut , Bergeron Jean , Langslet Gisle , Hovingh G Kees , Al-Saady Naab , Koeijvoets Michiel , Hunter John , Johnson-Levonas Amy O , Fable Jennifer , Sapre Aditi , Mitchel Yale
Published: July 2021

Introduction:
Anacetrapib, a cholesteryl ester transfer protein inhibitor, has been shown to robustly reduce atherogenic lipoproteins including low-density lipoprotein cholesterol (LDL-C), Apo B and raise high-density lipoprotein cholesterol (HDL-C) as well as ApoA1.

Hypothesis:
This 1-year, Phase 3, multicenter, randomized, double-blind, placebo-controlled study assessed the lipid-modifying efficacy and safety profile of anacetrapib added to optimized LDL-C lowering therapy in patients with heterozygous familial hypercholesterolemia (HeFH).

Methods:
Patients with a genotype-confirmed or clinical diagnosis of HeFH, treated with an optimal dose of statin ± other lipid-modifying medication(s) and having an LDL-C ≥100 mg/dL without history of cardiovascular disease or LDL-C ≥70 mg/dL with a history of CVD were randomized in a ratio of 2:1 to anacetrapib 100 mg (n=204) or placebo (n=102) for 52 weeks followed by a 12-week reversal phase. The primary end points were the percent change from baseline in LDL-C (beta-quantification method) and the safety profile of anacetrapib. This trial is registered in ClinicalTrials.gov, #NCT01524289.

Results:
A total of 306 patients were enrolled at 25 sites in 9 countries. At baseline, most patients were on high-dose statin therapy and >70% also were on ezetimibe. Baseline LDL-C and HDL-C were 129.4 and 53.3 mg/dL, respectively. At Week 52, anacetrapib vs. placebo significantly reduced LDL-C by 39.7% and increased HDL-C by 102.1% (p<0.001 for both). Significant placebo-adjusted reductions in Apo B (24.8%) and increases in Apo A-I (32.9%) also were observed. Significantly more patients in the anacetrapib vs. placebo group achieved LDL-C <100 (82% vs. 18%; p<0.001) and <70 mg/dL (44% vs. 5%; p<0.001). Sustained effects on LDL-C (21.9%; p<0.001) and HDL-C (53.0%; p<0.001) were seen 12-weeks after cessation of anacetrapib therapy. No clinically important between-group differences were seen in the proportions of patients with abnormalities in liver enzymes, CK, blood pressure, electrolytes, adverse experiences and adjudicated CV events.

Conclusion:
In patients with HeFH, treatment with anacetrapib for 1 year was generally well tolerated and resulted in substantial reductions in LDL-C and increases in HDL-C.
Abstract 9658: Generation Differences in Long-Term Clinical Outcomes in Diabetic Patients After PCI Across POBA-, BMS- and DES-Era
Authors: Naito Ryo , Miyauchi Katsumi , Konishi Hirokazu , Tsuboi Shuta , Ogita Manabu , Kasai Takatoshi , Tamura Hiroshi , Okazaki Shinya , Daida Hiroyuki
Published: July 2021

Introduction:
PCI has evolved with technological advance, improvement of operators’ techniques and medical therapy for secondary prevention. Despite these improvements, diabetes remains a negative predictor. To date, little is known regarding improvement of clinical outcomes in diabetic patients with PCI. We examined a temporal trend of long-term clinical outcomes in diabetic cohort across the different generations.

Hypothesis:
We hypothesized that clinical outcomes would improve with advances of PCI.

Methods:
We analyzed data of diabetic patients with PCI in Juntendo University from 1984 to 2010. The patients were divided into three groups according to the procedure data (POBA-era; January 1984 - December 1997, BMS-era; January 1998 - July 2004 and DES-era; August 2004 - February 2010). Primary endpoint was a composite of major adverse cardiovascular events including all-cause mortality, non-fatal myocardial infarction, non-fatal stroke and revascularization.

Results:
A total of 1544 patients were examined (POBA-era; 374, BMS-era; 494 and DES-era; 676). The mean age was higher in DES-era. A higher prevalence of hypertension and dyslipidemia was observed in DES-era. The success rate of PCI was lower among the patients in POBA-era. Kaplan-Meier estimation for 3-year MACE was significantly different among the eras (Figure 1). Multivariable Cox regression analysis showed that DES-era was a predictor for long-term MACE (DES- vs BMS era; HR 0.50, 95%, CI 0.38 - 0.66, P < 0.001, DES- vs POBA-era; HR 1.60, 95% CI 0.34-27.9, P = 0.6).

Conclusions:
Long-term clinical outcomes in diabetic patients who underwent PCI were more favorable in DES-era, despite the higher risk profiles.
Abstract 9923: The Ethics of Unilateral ICD and CRT-D Deactivation: Patient Perspectives
Authors: Daeschler Margaret G , Verdino Ralph J , Kirkpatrick James N
Published: July 2021

Background:
Decisions about deactivation of implantable cardioverter defibrillators (ICDs) are complicated. Unilateral Do-Not-Resuscitate (DNR) orders (against patient/family wishes) have been ethically justified in cases of medical futility. Unilateral deactivation of ICDs may be seen as a logical extension of a unilateral DNR order.

Methods:
60 respondents who had an ICD or cardiac resynchronization therapy ICD (CRT-D) were interviewed at a quaternary medical center outpatient electrophysiology practice. Survey questions addressed the inclusion of ICD deactivation in advanced directives, whether ICD deactivation constitutes physician-assisted suicide, and whether unilateral ICD deactivation can be ethically justified. The average age was 59 (range 23-89), and 70% were male. Of the respondents, 35% had ICDs, and 65% had CRT-Ds. Respondents had had their devices for an average of 6.74 years (range 0.11-25). 82% of respondents were Caucasian, 15% were African American and 3% were Hispanic.

Results:
Only 15% of patients had thought about device deactivation if they were to develop a serious illness from which they were not expected to recover, and single respondents were more likely to have considered this point (38%, p=0.03). A small majority (53%) had advance directives, and only one mentioned what to do with the device. Only 3% had discussed device management with clinicians. Most (55%) believed turning off a patient’s pacemaker was no different than not performing CPR or administering external defibrillation. A majority (77%) did not consider device deactivation in accordance with patient wishes to be physician-assisted suicide. A majority (78%) responded that it was not ethical/moral for doctors to deactivate ICDs against patients’ wishes.

Conclusion:
In an era of cost-consciousness and scrutiny of resources, management of ICDs and CRT-Ds as patients near the end of their lives create ethical dilemmas. Few patients consider device deactivation at end of life, though a large majority believes that unilateral deactivation is not ethical or moral, even in the setting of medical futility. Advance care planning for these patients should address device deactivation.
Abstract 16: A Pro-Vegetarian Food Pattern and Cardiovascular Mortality in the Epic Study
Authors: Lassale Camille , Beulens Joline , Van der Schouw Yvonne , Roswall Nina , Weiderpass Elizabete , Romaguera Dora , Riboli Elio , Tzoulaki Ioanna
Published: July 2021

Background:
Plant-based dietary pattern consumption, especially the Mediterranean Diet, have consistently shown inverse risk associations with mortality due to cardiovascular disease (CVD). In agreement, adherence to a vegetarian diet has been associated with reduced CVD risk compared to non-vegetarian; however, the proportion of vegetarians in the population is low. The Pro-vegetarian food pattern (PVEG) has recently been proposed as an intermediate dietary pattern towards vegetarianism which consists in favouring only plant-based foods while concomitantly reducing animal-derived foods.

Hypothesis:
We aimed to investigate the associations between the a priori defined PVEG score and CVD mortality across 10 different European countries.

Methods:
Included in the analysis were 451,256 participants (130,370 men and 320,886 women) between 35 and 70 years from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study. At recruitment, between 1992 and 2000, dietary, anthropometric and lifestyle data was collected. CVD mortality was defined as death from circulatory cause (I00–I99 according to the ICD 10th revision). An a priori PVEG dietary score was constructed comprising 12 components. The consumption of 7 plant-based food groups (vegetables, fruit, legumes, cereals, potatoes, nuts, olive oil) were categorized into quintiles, positively rated, and 5 animal-based food groups (meats/meat products, animal fats, eggs, fish and other seafood and dairy products) were inversely rated for a total score ranging from 12 to 60. Five categories of the total score were created: very low (<30), low (30-34), moderate (35-39), high (40-44), and very high (>45) adherence to a PVEG diet. Associations with the PVEG dietary score and CVD mortality were estimated using Cox regression analysis using age as the primary time metrics providing Hazard Ratios (HR) and 95% Confidence Intervals (95%CI). The fully adjusted models included total energy intake, body mass index, physical activity, educational level and stratified by centre, sex and age at baseline. Restricted cubic splines were used to assess the shape of the association in continuous.

Results:
Over follow-up (median: 12.8 years), 5083 CVD deaths occurred. Compared to very low adherence to a PVEG diet (reference category), the fully-adjusted HRs (95%CI) were: 0.92 (0.85-1.01) in the low, 0.88 (0.80-0.74) in the moderate, 0.81 (0.74-0.90) in the high and 0.80 (0.70-0.93) in the very high adherence categories. The suggested floor effect for a score >=40 was also seen by restricted cubic spline.

Conclusion:
Adherence to the plant-based PVEG food pattern was associated with overall decreased risks of CVD mortality up to 20% risk reduction, although no further risk reduction was obtained from a very strong compared to a strong adherence.
Abstract 29: Loss of Ideal Total Cholesterol Early in Life: The National Health and Nutrition Examination Survey (NHANES)
Authors: Engeda Joseph C , Holliday Katelyn M , Hardy Shakia T , Chakladar Sujatro , Heiss Gerardo , Lin Danyu , Zeng Donglin , Shay Christina M , Avery Christy L
Published: July 2021

Introduction:
Ideal total blood cholesterol (TC) levels are associated with lower cardiovascular disease (CVD) morbidity and mortality. In the U.S. TC increases up to middle age, but declines at older ages. Few studies have characterized the transition from ideal to intermediate and poor TC levels in different life epochs and in minorities.

Methods:
Cross-sectional 2007-2012 NHANES data (N = 11,140) were used to estimate the age-, race-, and sex- specific prevalence of ideal (≥20 years: <200 mg/dL untreated, 16-19 years: <170 mg/dL), intermediate (≥20 years: 200-239 mg/dL or treated to goal, 16-19 years: 170-199 mg/dL), and poor (≥20 years: ≥240 mg/dL, 16-19 years: ≥200 mg/dL) TC, defined per American Heart Association criteria. We then used these data and novel Markov-type models to estimate net transition probabilities between ideal, intermediate and poor TC.

Results:
Between the ages of 16 and 18, the prevalence of ideal TC among European American (EA) and African American (AA) men was approximately 68%, notably higher than the prevalence in EA women (63%) and AA women (61%). Variation in the loss of ideal TC was also observed by race and sex. Between 16-50 years of age, the proportion of AA men, EA men and EA women with ideal levels of TC declined approximately 2.0% (95% CI: 1.8%, 2.2%) per year. In AA women by contrast, the age-specific decline in ideal TC was not uniform between 16-50 years of age. The proportion of AA women with ideal levels of TC declined 0.7% (95% CI: 0.2%, 1.2%) per year from 16-20 years of age but increased to 2.8% (95% CI: 2.4%, 3.3%) per year by age 50. Among populations with intermediate TC levels, estimated 1-year net transitions to poor TC peaked at age 16, the earliest age under investigation, for EA men, EA women, and AA men but remained stable for AA women through 70 years of age, where a net 0.6% (95% CI: 0.1%, 1.3%) of the population with intermediate TC levels transitioned to poor TC levels one year later. In all demographic groups and life epochs, greater proportions of the population transitioned from intermediate to poor TC than from poor to intermediate TC.

Conclusions:
Loss of ideal TC begins early in life and shows divergent patters by gender and race. Difficulties re-attaining ideal TC once classified as intermediate or poor support interventions that promote ideal TC levels in younger ages, especially among AA women.