bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 40: Is Severe Post-shock Bradyarrhythmia In Patients Using Wearable Defibrillators Common or Serious?
Authors: Freeman Gary , Quan Weilun , Szymkiewicz Steven , Nichol Graham
Published: July 2021

Background
: Previous studies have shown a 40% to 60% incidence of asystole immediately after transthoracic defibrillation of pulseless ventricular tachycardia/ventricular fibrillation (VT/VF). Such post-shock asystole has very poor outcomes. Wearable cardioverter defibrillators (WCD, LifeVest, ZOLL Lifecor) automatically record and treat VT/VF by delivering transthoracic defibrillation without the need for a bystander. Post-shock bradyarrhythmia (PSB) is of clinical concern in patients (pts) using WCD.

Objective
: Determine the incidence and outcomes of PSB during WCD use.

Methods
: ECG recordings from consecutive pts who had VT/VF while using WCD between March 2005 and March 2007 were retrospectively analyzed. All VT/VF occurring within 24 hours from the initial shock for VT/VF were defined as a single sudden death event (SDE) while those beyond 24 hours as a SDE recurrence. ECGs contained 30 seconds prior to the VT/VF detection and > 15 seconds following VT/VF termination. Severe PSB was defined as a pause longer than 10 seconds. Survival was defined as conscious at emergency department (ED) arrival or not needing to go to the ED. Pt calls and medical orders were reviewed to determine the indications for WCD use and pt post-shock status.

Results
: Between March 2005 and March 2007, 3564 pts used WCD for an average of 51 days. 56 pts (51% ICD explants, 28% ischemic cardiomyopathy (ICM), 11% Non-ICM, 8% delayed ICD implant, 2% others) received 142 shocks for 79 SDE. 14 pts had > 1 SDE (max = 5). 15 SDE had >1 VT/VF (max = 47). 79/79 (100%) initial SDE shocks terminated VT/VF. 76/79 (96%) of treated SDE resulted in survival. Severe PSB was found in 4 ECGs from 4 pts. 3/4 (75%) occurred after the initial SDE shock, 1/4 (25%) after VT/VF recurrence; 2/4 (50%) developed ventricular complexes prior to the end of the recording, 2/4 (50%) did not; 3/4 (75%) pts survived, 1/4 (25%) did not. Median time from VT/VF onset to shock was 44 seconds.

Conclusions
: WCD is an efficacious therapy. The majority of pts with severe PSB after WCD survived. Severe PSB was less frequent and had a better prognosis than that observed in EMS studies. This may be attributed to faster WCD shock therapy (median 44 seconds) compared with EMS (>10 minutes).
Abstract 59: The Incidence Of Pulmonary Aspiration With Laryngeal Mask Airway Use During Cardiopulmonary Resuscitation And Positive Pressure Ventilation In Swine.
Authors: Suffoletto Brian , Menegazzi James , Logue Eric , Salcido David
Published: July 2021

Objective: Pulmonary aspiration of gastric contents occurs 20 –30% of the time during cardiopulmonary resuscitation (CPR) of cardiac arrest. This is due to loss of protective airway reflexes, pressure changes generated during CPR, and positive pressure ventilation (PPV). Even though the American Heart Association (AHA) has recommended the laryngeal mask airway (LMA) as an acceptable alternative airway for use by EMS personnel, concerns over the capacity of the device to protect from pulmonary aspiration remain. We sought to determine the incidence of aspiration after LMA placement, CPR and PPV.

Methods: We conducted a prospective study on 16 consecutive post-experimental mixed-breed domestic swine of either sex (mean mass 25.7 ±1.4 kgs). A standard size-4 LMA was modified so that a vacuum catheter could be advanced into and past the LMA diaphragm. The LMA was placed into the hypopharynx and its position confirmed using End-tidal CO
2
and direct visualization of lung expansion. Fifteen milliliters of heparinized blood were instilled into the pharynx. After 5 PPVs with a mechanical ventilator, chest compressions were performed for 60s with asynchronous ventilations continuing at a rate of 12 per minute. After chest compressions, a suction catheter was inserted through the cuff and suction applied for approximately 1 minute. The catheter was removed and inspected for signs of blood. The LMA cuff was deflated and the LMA removed. The intima of the LMA diaphragm was inspected for signs of blood. In a validation cohort of 4 animals, the LMA was reinserted, a cricothyrotomy performed and 5 mL of blood instilled directly into the trachea.

Results: There were 0/16 (95% CI=0 –17%) with a positive tests for the presence of blood in both the vacuum catheter and the intima of the LMA diaphragm. In the validation cohort, all four were positive for blood in both the vacuum catheter and the intima of the LMA diaphragm.

Conclusions: In this simple model of regurgitation of after LMA placement, there was no sign of pulmonary aspiration, and no evidence that blood had passed beyond the seal created by the LMA cuff. Concerns over aspiration with LMA use may be unfounded. Future studies should determine the frequency of pulmonary aspiration after LMA placement in the clinical setting.
Abstract 70: Improving the Prehospital Trauma Triage Guidelines for Physiologic Derangement: Can We Do Better?
Authors: Newgard Craig D , Rudser Kyle , Hedges Jerris R , Bulger Eileen , Stiell Ian G , Davis Daniel , Morrison Laurie J , Kerby Jeffrey , Terndrup Thomas E , Minei Joseph P , Emerson Scott
Published: July 2021

Introduction:
The American College of Surgeons (ACS) recommends immediate transport to a trauma center for all injured persons with field physiologic derangement (ACS Step 1 trauma triage criteria). However, it remains unclear whether these criteria could be refined to identify high-risk trauma patients with improved predictive value.

Hypothesis:
We assessed the hypothesis that an easily applied, prehospital, clinical decision rule could be developed to better identify high-risk injured persons meeting ACS Step 1 criteria.

Methods:
We conducted a prehospital prospective cohort study of injured adults > 15 years where field resuscitation was attempted and ACS physiologic criteria were present: SBP <<26>90, RR <10 or >29 breaths/minute, GCS <<26>12, or field intubation. Population-based data were collected from December 1, 2005 through November 30, 2006 by 268 EMS agencies transporting to 287 acute care hospitals (trauma and non-trauma centers) in 11 sites across the U.S. and Canada. Ten prehospital variables were assessed: SBP, RR, GCS, pulse, pulse oximetry, shock index (pulse/SBP), mechanism of injury, penetrating injury, age, and gender. High risk injured persons included: death (before or after admission) or hospital LOS >2 days. 60% of the sample was randomly selected for rule derivation and analyzed using classification and regression tree analysis. The remaining 40% were used for rule validation. The final rule was based on a targeted sensitivity of >90%.

Results:
Of 4,983 eligible patients, 4,326 injured persons had complete outcome information and were included in the analysis. The sample included 2,495 (58%) persons with death or LOS >2 days, as well as 1,061 (25%) patients that did not require admission. The final rule included the following variables (in order): field intubation, GCS < 8, shock index > 1.4, mechanism of injury, and age >=70 years. Rule validation demonstrated the following accuracy measures: sensitivity 94.9% (95% CI 93.5–96.3%), specificity 14.1% (95% CI 11.6 –16.6%).

Conclusions:
While we were able to generate a highly sensitive decision rule, the rule appears too complex for field application and is non-specific. Further refining ACS physiologic triage criteria to increase predictive value remains an ongoing challenge.
Abstract 89: The Prognostic Factor of Patients with Asystole on Arrival
Authors: Shokawa Tomoki , Tanigawa Koich , Yamamoto Hideya
Published: July 2021

Background: Patients with asystole on arrival (AOA) at hospital have a poor prognosis. However, little is known about the prognostic factor of patients with AOA.

Objective: The purpose of this study was to determine predictors for 24 hours survival in patients with AOA.

Methods and results: Consecutive patients with AOA admitted to the Hiroshima University Hospital (Hiroshima, Japan) from April 2002 to January 2007 were retrospectively analyzed. Patients were divided into two groups according to the outcomes, i.e. non-survivors vs. survivors at 24 hours after admission. Data including blood gas analysis, lactate levels, and levels of minerals on admission were obtained and analyzed. Of 102 (male; 60) patients with AOA, fourteen patients survived for 24 hours. Univariate analysis found that pH, PaO2, PaCO2, base excess, lactate, and serum potassium concentration were associated with survival (p< 0.05) (Table

). Multivariate analysis determined that serum potassium concentration independently affected 24 hours survival.

Conclusions: These results suggested that the serum potassium level on admission is a strong, independent predictor of survival of patients with AOA.

survivors vs. non-survivors
Abstract 92: Evaluation Of Knowledge And Practice Of Cardiopulmonary Resuscitation Of Children And Infants By An Out-of-hospital Emergency Care Team
Authors: Goddet Nathalie S , Dolveck François , Descatha Alexis , Lode Noella , Chabernaud Jean-Louis , Loeb Thomas , Farges Céline , Lagron Patrick , Stenger Laurent , Baer Gé raldine , Baer Michel , Fletcher Dominique
Published: July 2021

Introduction
The French emergency response system in life threatening situations is the deployment of fully equipped ambulances with paramedic, nurse and emergency physician. The 2005 ILCOR and ERC guidelines concerning cardiopulmonary resuscitation (CPR) have led to significant changes, especially in terms of basic life support (BLS). We aimed to review fundamental knowledge and practice by our personnel concerning CPR in children and infants to determine current training needs for our teams.

Materials and methods
Paper questionnaires were filled out by our personnel and immediately collected. Inclusion criteria: physicians, nurses, and paramedics (refusals to fill out questionnaire were not included). We recorded: profile of personnel, knowledge of 2005 guidelines, basic CPR and advanced CPR parameters. Majors results were compared based on job title.

Results
Sixty-one questionnaires were filled out (25 paramedics, 13 nurses, and 23 physicians). Personnel was mostly aged under 40 (70,5%, n=43), with over 2 years experience in prehospital emergency care(75,4%, n=46); 47,5% (n=\29) had no training in pediatrics; 68,9% (n=42) had BLS certification and 31,1% (n=19) reported regular participation in first aid training programs. A minority of subjects declared knowing the 2005 Guidelines (11,5%, n=7), even among physician (17,4%, n=4). Table 1

shows major results about CPR parameters according to job title.

Conclusion
This study emphasizes the lack of knowledge and the repeated changes witch require more frequent and more extensive training for entire personnel on the team, focusing on basic CPR for physicians and advanced CPR for paramedics and nurses.

Table 1:

Answers according to job title AED : Automatic External Defibrillator
Abstract 545: Polyethylene-glycol Coated Liposomal Adenosine Attenuates Hypotension and Bradycardia and Augments Cardioprotection Against Ischemia/reperfusion Injury in Rats - Nano-size Drug Delivery System Targeted to Infarcted Myocardium -
Authors: Takahama Hiroyuki , Minamino Tetsuo , Asanuma Hiroshi , Fujita Masashi , Wakeno Masakatsu , Asakura Masanori , Kim Jiyoong , Takashima Seiji , Komamura Kazuo , Hori Masatsugu , Mochizuki Naoki , Kitakaze Masafumi
Published: July 2021

Background
Liposome is a nano-size particle that can delay the drug degradation and induce the drug to the specific tissues including ischemia/reperfused myocardium. Coating liposome with polyethylene-glycol (PEG) prolongs the residence time in the blood stream. Although adenosine reduces myocardial infarct size in clinical trials, its half-time is extremely short and a high-dose of adenosine administration causes both hypotension and bradycardia. In this study, we investigated whether PEGylated liposomal adenosine minimizes systemic hemodynamic effects of adenosine and maximize cardioprotective effects against ischemia/reperfusion injury.

Methods and Results
We obtained PEGylated liposomal adenosine (average diameter: 126.2+/−42.9 nm) by the remote loading method. In rats, the intravenous administration of free adenosine (450 μg/kg/min for 10 minutes) decreased mean blood pressure and heart rate by 22.7% and 15.4% compared with the baseline, respectively. PEGylated liposomal adenosine at the same dose did not significantly change either mean blood pressure or heart rate compared with the baseline. Next, we produced myocardial infarction (MI) in male rats by 30-minutes of ligation of the left anterior descending coronary artery followed by reperfusion. We evaluated the accumulation of liposome in the hearts and infarct size 72 hours after the MI. Fluorescence microscopy revealed the accumulation of fluorescent-labeled PEGylated liposomes in ischemic, but not non-ischemic area. PEGylated liposomal adenosine (450 μg/kg/min), free adenosine (450 μg/kg/min) or free-PEGylated liposome was intravenously administered for 10 minutes starting 5 minutes before the onset of reperfusion. PEGylated liposomal adenosine significantly (p<0.05 each) reduced infarct size (11.4±3.1 %) compared with free adenosine (21.7±3.0%) or free PEGylated liposome (23.6±2.2%).

Conculusion
PEGylated liposomal adenosine attenuated the systemic hemodynamic effects of adenosine and augmented cardioprotection against ischemia/repefusion injury. Nano-size PEGylated liposomal adenosine is a promising candidate for the adjunctive therapy for AMI.
2007 Russell Ross Memorial Lectureship in Vascular Biology—Epigenetic Control of Vascular Smooth Muscle Differentiation in Development and Disease
Authors: Owens Gary K.
Published: July 2021

There is clear evidence that alterations in the differentiated state of the smooth muscle cell (SMC) play a key role in the pathogenesis of a number of major human diseases, including atherosclerosis and postan-gioplasty restenosis. This process is referred to as “phenotypic switching” and likely evolved to promote repair of vascular injury. However, the mechanisms controlling phenotypic switching as well as normal differentiation of SMCs in vivo are poorly understood. This talk will provide an overview of molecular mechanisms that control differentiation of SMCs during vascular development. A particular focus will be to consider the role of CArG elements found within the promoters of many SMC differentiation marker genes, as well as regulation of their activity by serum response factor and the potent SMC-selective serum response factor coactivator myocardin. In addition, I will summarize recent work in our laboratory showing that SMC- and gene-locus–selective changes in chromatin structure play a critical role both in normal control of SMC differentiation and in phenotypic switching in response to vascular injury. Finally, I will present evidence based on conditional knockout experiments in mice showing that krupple-like factor 4 is induced in SMCs after vascular injury and regulates SMC phenotypic switching and growth through:

binding to G/C repressor elements located in close proximity of CArG elements within the promoters of many SMC marker genes,

suppressing expression of myocardin, and

inducing epigenetic modifications of SMC marker gene loci associated with chromatin condensation and transcriptional silencing.

Supported by NIH grants P01 HL19242, R37 HL57353, and R01 HL 38854.
2008 Laennec Clinician/Educator Lecture—The Gene From Limone: Is It Golden or Not?
Authors: Shah Prediman Krishan (P.K.)
Published: July 2021

Valerio Dagnoli of the lake-side town of Limone sul Garda was noted to have a very low high-density lipoprotein cholesterol (HDL-C) level (12 mg/dL) in 1975 and was referred to Cesare Sirtori at the University of Milan. Cesare Sirtori, Guido Franceschini, and collaborators from the Gladstone Laboratories in San Francisco eventually discovered that Valerio’s HDL contained a mutant form of Apo A-I with an Arginine 173 to Cysteine 173 substitution. This mutant, labeled Apo A-I milano, was present in 40 of the approximately 1000 inhabitants of Limone sul Garda. Through birth records maintained at the local church, the carriers were traced back to a common ancestral couple (Rosa Giovaneli and Giovani Pomaroli) in the 18th century. The carriers have very low HDL-C and elevated triglycerides levels, with an unexpectedly low incidence of cardiovascular disease. This led to the suggestion that this mutation may be protective, perhaps by creating a “turbo-charged” form of Apo A-I that is more athero-protective than wild-type Apo A-I. Our laboratory first demonstrated marked and rapid athero-protective, athero-regressive, and vascular anti-inflammatory effects of rApo A-I Milano in hyperlipidemic rabbits and mice, later confirmed by Sirtori and others. These promising experimental results were supported later by the small phase II clinical trial led by Dr Steve Nissen, where rapid regression of coronary atheroma was shown after 5 weekly intravenous infusions of rApo A-I milano. Difficulties in large-scale production of rApo A-Imilano at a tolerable cost and without bacterial contaminants has been an impediment in further development of this novel therapeutic approach. However, recent progress in recombinant protein expression in safflower seeds using plant biotechnology and the potential for gene transfer promise to overcome these barriers; we are currently testing these strategies in our laboratory. These new developments may allow full validation of this promising strategy in humans. Stay tuned.
2008 Stroke Council Award and Lecture—Brain and Heart: The Good, the Bad, and the Different
Authors: Hachinski Vladimir
Published: July 2021

The brain and the heart are unique and essential organs, with autoregulated blood supplies and sophisticated electrical systems, functioning with harmonious complementarity in health; however, disease of one organ can threaten the other. Cardiac valvular disease, atrial fibrillation, and acute myocardial infarction carry a risk of stroke, and both ischemic and hemorrhagic strokes can lead to cardiac abnormalities and sudden death.

Heart disease and stroke share most of the same risk factors, but not to the same degree, nor necessarily with the same consequences. For example, hypertension represents the single most powerful risk factor for stroke and can result in a major intracerebral hemorrhage, a condition without equivalent in any other organ. Despite the superficial resemblance between angina and transient ischemic attack, the mechanisms differ. Angina can be brought on by exercise, but no amount of mental exercise will lead to “brain angina.” Most cardiac patients can maintain a reasonable quality of life on half of their cardiac output. No meaningful quality of life is likely with half of brain output. Stroke recovery is complex. The brain is the only organ with which one can communicate directly and whose feelings have to be considered in recovery. Although stroke and heart disease prevention have much in common, puzzling differences remain. In primary prevention, aspirin prevents heart attacks in men but not in women, and strokes in women but not in men.

Given the great commonalities and interrelationships between vascular brain and heart disease, it has been sensible and successful to have one organization encompassing cerebrovascular and cardiovascular health and diseases. To continue to progress at an accelerated pace, we need to become more familiar with the mutual relationship between cerebrovascular and cardiovascular disease, work together where we can, and separately where we must, but with the common aim of vanquishing both.
Early Detection of Cardiovascular Autonomic Neuropathy Using Exercise Testing in Patients With Type 2 Diabetes Mellitus
Authors: Banthia Smriti
Published: July 2021

Abstract 1132

Smriti Banthia, Jason Ng, Alexandru Chicos, Mark Molitch, Alan H Kadish, Jeffrey J Goldberger, Northwestern Univ, Chicago, IL

Smriti Banthia, 2008 Finalist and Presenting Author
Abstract 5842: Patients with an Elevated Proportion of Small, Dense LDL and a Lower Adiponectin Blood Level are at Higher Risk of Developing Early Bioprosthetic Valve Dysfunction
Authors: Shetty Rahul , Girerd Nicolas , Arsenault Benoit , Pibarot Phillipe , Fournier Dominique , Voisine Pierre , Charbonneau Eric , Després Jean P , Mathieu Patrick
Published: July 2021

Long-term durability of bioprosthetic heart valves (BPs) is limited by structural valve degeneration (SVD) leading to stenosis and/or regurgitation. We recently reported that patients having the metabolic syndrome (MetS) have higher incidence of SVD. In this study, we sought to determine the metabolic markers associated with SVD. In a cohort of 240 patients with an aortic BP and a mean follow-up of 2.5± 1.2 years, we compared the blood lipid profile and LDL size in individuals who developed echocardiographic evidence of early BP hemodynamic dysfunction versus those who did not. BP dysfunction was defined as a mean annualized transprosthetic gradient of ≥3mmHg/year and or worsening of the transprosthetic regurgitation during the echocardiographic follow-up after valve implantation. Patients developing BP dysfunction (n= 63; 26%) had higher triglyceride (TG) levels (1.53± 0.08 mmol/L vs 1.29± 0.08 mmol/L; p= 0.01), proportion of small, dense LDL (%LDL< 255Å) (46.87± 22.14 vs 40.29 ± 21.63; p= 0.08) and a tendency for having lower BP size (p= 0.05) as well as lower clearance of creatinine (p= 0.05) compared to those who had no evidence of BP dysfunction. On multivariate analysis, after adjustment for age, gender, BP size, and clearance of creatinine, the %LDL< 255Å (p=.04) were significantly associated with BP dysfunction. In addition, patients having an elevated level of %LDL< 255Å along with a decreased plasma Adiponectin level were at a very high risk of developing early BP hemodynamic dysfunction (O.R= 4.35; p= 0.01). BP dysfunction is significantly associated with the proportion of small, dense LDL. Patients having low Adiponectin levels and a high proportion of small, dense LDL are at very high risk of developing early signs of SVD. Interventions aiming at reducing the proportion of small, dense LDL particles and increasing plasma levels of Adiponectin may contribute to decrease incidence of SVD in BPs.
Abstract 5849: The Effects of Statins and Prenylation Inhibitors on Chronic Rejection in Heart Transplantation
Authors: Stein William , Itoh Satoshi , Bartos Jason , Schrepfer Sonja , Robbins Robert , Fischbein Michael
Published: July 2021

HMG-CoA Reductase Inhibitors (statins) increase patient survival and decrease Graft Coronary Artery Disease (GCAD) in heart transplants. Although the exact mechanism is unknown, the protective role of statins may be attributed to two factors:

modifications in cholesterol metabolism or small G protein prenylation, and/or

immunosuppression or changes on graft endothelial cell (EC) and smooth muscle cell (SMC) function. We hypothesized that statins attenuate GCAD development through alterations in G protein prenylation primarily in graft SMC and EC. Using a murine heterotopic heart transplant model (B6
BM12
to C57BL/6), animals received

no treatment (control);

HMG-CoA Reductase inhibitor (Atorvastatin, AT); or

drugs that selectively block the four major downstream branches of the mevalonate pathway (squalene synthase (ZA), farnesyl protein transferase (MA), geranylgeranyl protein transferase (GGPT-2) (NE), GGPT-1 and -2 (PA), and both FPT and GGPT-2 (NE+MA)).

Intimal proliferation was measured with morphometric analysis. In vitro assays were utilized to determine SMC activity, T-cell function, and EC MHC-2 expression. AT, MA, and NE significantly decreased GCAD development, while ZA and NE+MA had no effect (control 63.2± 38%, AT 29.3± 37.5%, MA 43.0± 39.3%, PA 47.5+/−42.5%, NE 24.7± 37.1%, ZA 65.4± 32.5%; p< 0.01). After 5 days of therapy, ELISPOT analysis revealed that all selective inhibitors decreased the Th2 response, and all except AT decreased the Th1 response, with NE levels equivalent to syngeneic controls (p< 0.001). In vitro, inhibition with AT, PA, or NE reduced SMC proliferation and migration compared to controls (p< 0.01). IFNγ-stimulated MHC-2 expression on EC decreased with AT, PA, or NE treatment in a dose dependent manner (p< 0.01). This is the first study to evaluate the effects of prenylation inhibitors on both recipient and graft responses to heart transplantation. Our data shows that inhibition of GGPT-2, and not cholesterol synthesis, is the molecular target of statins’ attenuation of GCAD. Our data suggests that the beneficial effects seen with statin therapy after heart transplant are due to decreased T-cell function and decreased graft SMC and EC function.
Abstract 5851: Activation of Inflammatory and Apoptotic Pathways in Human Donor Heart Dysfunction
Authors: Bulcao Christian F , D’Souza Karen M , Malhotra Ricky , Staron Michelle , Pandalai Prakash K , Duffy Jody Y , Akhter Shahab A
Published: July 2021

Donor heart dysfunction (DHD) precluding procurement for transplantation occurs in up to 25% of brain dead donors in the absence of structural heart disease. The molecular mechanisms of DHD remain unclear. We investigated the potential role of myocardial interleukin (IL)-6 signaling through the JAK2/STAT3 pathway which leads to the generation of nitric oxide (NO) and decreased cardiac myocyte contractility in vitro. NO can also lead to induction of the proapoptotic gene Bnip3 in vitro. Hearts were procured using standard technique with UW solution from 14 brain dead donors with a left ventricular ejection fraction of < 30% (DHD) in the absence of structural heart disease. Six hearts with normal function (NF) that were procured but not transplanted for non-cardiac reasons served as controls. Left ventricular (LV) IL-6 levels were quantitated by ELISA and signaling through the JAK2/STAT3 pathway via IL-6 and gp130 receptors was assessed by expression of activated, or phosphorylated STAT3. NO signaling was measured by myocardial expression of inducible NO synthase (iNOS) and protein immunoblotting for Bnip3 was performed. Myocardial IL-6 protein levels were 8-fold greater in the DHD group vs. NF controls (
P
< 0.02). Phosphorylated STAT3 expression was 5-fold higher in DHD vs. NF (
P
< 0.01) indicating increased JAK2/STAT3 signaling as there was no difference in total STAT3 expression between groups (
P
>0.05). LV expression of iNOS was 2-fold greater in DHD vs. NF (
P
< 0.03) consistent with increased iNOS activity. In addition, LV expression of the proapoptotic gene Bnip3 was 3-fold greater in the DHD group vs. NF (
P
< 0.04) suggesting that apoptosis may contribute to DHD. N= 14 for DHD and n= 6 for NF in all studies. Increased myocardial IL-6-mediated signaling through the JAK2/STAT3 pathway leading to upregulation of iNOS and NO production may be an important mechanism in human DHD. Increased myocardial NO also appears to lead to upregulation of proapoptotic Bnip3 in cardiac myocytes, and apoptotic cell death may also contribute to ventricular dysfunction following brain death. Inhibition of IL-6/JAK2/STAT3 signaling may represent a novel strategy to increase the severely limited number of cardiac donors.
Abstract 5857: Low Operative Mortality with implantation of a Continuous Flow LVAD and Impact of Concurrent Cardiac Procedures
Authors: Pal Jay D , Klodell Charles T , John Ranjit , Pagani Francis , Rogers Joseph G , Farrar David J , Milano Carmelo A
Published: July 2021

Objective: Our goal was to determine the operative mortality of isolated implantation of the HeartMate II continuous flow LVAD and the impact of additional concurrent cardiac procedures on patient outcomes.

Methods: In a multicenter trial, 279 patients at 33 clinical sites underwent implantation of the HeartMate II continuous flow LVAD as a bridge to transplantation from March 2005 to March 2007. HeartMate II implantation (HM II) was the only procedure required in 172 patients while 80 patients required concurrent cardiac procedures in conjunction with LVAD implantation (HM II+CCP).

Results: Preoperative characteristics were similar, but central venous pressure (14.5 vs 11.6 mmHg) was greater for patients requiring concurrent cardiac procedures, suggesting worse right heart dysfunction. Mean cardiopulmonary bypass times increased from 97 to 120 minutes when a concurrent cardiac procedure was performed (p<0.001). Length of stay slightly increased from 23 to 26 days (p=0.17). Overall 30- and 180-day mortality was 5.8% and 13.3% for the HM II group, and 11.3% and 20.0% for the HM II+CCP group. Concurrent valvular procedures increased the risk to 8.5% and 19.1%. Patients who underwent an aortic valve replacement with cardioplegic arrest had a 30-day mortality of 25%, higher than for isolated concurrent mitral (0%) or tricuspid repair (3.3%). Other cardiac procedures were associated with a 30-day mortality of 27.8%. Survival at 180 days was 87% for HMII alone and 80% for HMII+CCP.

Conclusion: There is a low 5.8% operative mortality for patients requiring uncomplicated HeartMate II implantation, with no apparent increased risk for concurrent PFO closure, mitral or tricuspid repair. However, concurrent aortic valve and other cardiac procedures are associated with a significantly decreased survival. The increased risk of these procedures must be balanced against the negative impact of uncorrected aortic insufficiency during VAD support.
Abstract 5893: Biventricular Versus Right Ventricular Delivered Anti-Tachicardia Pacing for the Termination Of Ventricular Tachyarrhythmias in Heart Failure Patients Receiving a Biventricular ICD: Results from the ADVANCE CRT-D Trial
Authors: Gasparini Maurizio , Anselme Frédéric , Clémenty Jacques , Santini Massimo , Martinez-Ferrer José , Mainardi Marc , De Santo Tiziana , Ligorio Giuseppe , Schwab Joerg O
Published: July 2021

Aim:
To investigate the efficacy and safety of anti-tachycardia pacing (ATP) simultaneously delivered from right and left ventricles (BIV) vs conventional right ventricular (RV) delivery in heart failure (HF) patients treated with a biventricular ICD (CRT-D).

Methods
: Multicenter, prospective, randomized, controlled trial of pts implanted with a Medtronic CRT-D device. Anti-tachycardia detections were programmed: VF detection set at NID 18/24 for ≥250 bpm; FVT (via VF) with NID 18/24 between 188–250 bpm; VT detected when 20 consecutive RR intervals ≥143 bpm. Randomization was 1:1 to either BiV or RV ATP (single burst 8 pulse, 88% coupling interval ). Pts were followed for 12 months. Stored EGM, used to classify all spontaneous episodes, as well as all adverse events (including death) were adjudicated by an independent committee adjusting for pts with multiple episodes. The primary end-point (PEP) compared the efficacy of first BiV vs RV to terminate any ventricular tachyarrhythmias (VTs). The secondary composite end-point (SEP) compared adverse events (accelerations+ syncope/pre-syncope) to assess safety.

Results
: In total, 526 patients were enrolled and randomized (BiV = 260, RV = 266). There were no baseline differences between groups. In total, 1077 detections in 178 patients were recorded: 634 were true VTs in 119 patients (69 VF [11%] in 18 pts, 202 FVT [32%] in 49 pts, and 363 VT [57%] in 92 pts). PEP: Efficacy of first ATP was comparable between BiV (65%) and RV (68%) (p=0.58). In VT zone, RV was better (62% vs 71%., p=0.24), while in FVT zone BIV proved better (71% vs. 61%, p=0.33). RV ATP was significantly less effective in ischemic (I) pts (81% vs 59%, p=0.005). SEP: BIV ATP was ineffective 20 times and 3 accelerations occurred, whereas RV ATP failed 41 times and 14 accelerations occurred (p=0.12). Syncope/pre-syncope events never occurred for BiV ATP, while 4 times (3%) in RV ATP(p=0.3). No difference in mortality was observed.

Conclusion
: This trial demonstrated that ATP is also effective in CRT-D recipients. No significant differences in overall ATP efficacy were found between BIV and RV, but RV was significantly less effective in I patients; BIV was effective across different etiologies and showed a trend for superior safety profile.
Abstract 5901: Cardiac Expression of CCN1, Capable of Promoting Adhesion of CD34+ Progenitor Cells, Is Strongly Induced in Parvovirus B19-Associated Cardiomyopathy
Authors: Wittchen Frank , Kuehl Uwe , Suckau Lennart , Wang Xiaomin , Schultheiss Heinz-Peter , Poller Wolfgang
Published: July 2021

The clinical phenotype of human dilated cardiomyopathy (DCM) encompasses a broad spectrum of etiologically distinct disorders. We obtained the cardiac expression profile of a DCM subtype (DCMi-B19) characterized by cardiac inflammation and parvovirus B19 (B19) persistence, to identify possible new therapeutic targets in humans. By microarray analysis and TaqMan PCR endomyocardial biopsies from DCMi-P19 patients (n=8) were compared to controls w/o cardiac disease. In DCMi-B19 an expression profile with dysbalance between several gene regulatory networks was observed. Tab. 1/2 classify deregulated genes in a group closely correlated (p<0.01) with left ventricular ejection fraction (EF) and another one w/o correlation to EF. CCN1 was the most strongly upregulated of the EF-independent genes which encompass further members of the CCN1 regulatory network including CCN2=CTGF. In contrast the genes in tab. 2 are closely EF-correlated. We have previously shown that CCN1 is induced in endothelial cells by pro-inflammatory cytokines in vitro, which may also be the mechanism of its induction in human DCMi-B19 hearts. Two recent studies described the potential of CCN1 to promote migration/adhesion of CD34+ stem cells, and of activated monocytes via alphaMbeta2 integrin. This suggests that the CCN1 induction in DCMi-B19 may influence the influx of CD34+ stem cells and activated monocytes to the inflamed heart, and obviously this may occur independent of hemodynamic impairment. B19 viruses infect cardiac microvascular endothelium, and endothelial CCN1 induction may therefore be involved in disease pathogenesis by altering circulating cell interactions with the inflamed heart.

Table 1:

EF-Independent Gene Deregulation

Table 2:

EF-Correlated Gene Deregulation
Abstract 5952: Fibrotic Atherosclerotic Lesion Exacerbates Large Arterial Stiffening Following Aortic Constriction In Apolipoprotein E Deficient Mice
Authors: Xu Qi , Gao Xiaoming , Ming Ziqiu , Kiriazis Helen , Du Xiao-Jun , Dart Anthony M
Published: July 2021

Hypertension, particularly systolic hypertension, is known to be a major risk factor for the development of atheroma. The effects of aortic atheroma on large arterial stiffness remain unclear. We introduced pressure overload in
apoE
−/−
mice by transverse (TAC) or abdominal aorta constriction (AAC) for a period of 12-weeks. TAC led to 107% and 119% increase of pulse pressure, and AAC led to 55% and 51% increase of pulse pressure in wild-type and
apoE
−/−
mice, respectively (all
P
<0.01), accompanied by a 3–4 fold increase of lesion area in
apoE
−/−
mice (19.2±3.9% in TAC and 15.9±4.0% in AAC vs. 5.2±0.9% in sham-operation, all
P
<0.05). The lesion area correlated significantly with pulse pressure, but not with mean blood pressure (Fig

). Interestingly, plaque in TAC mice was fibrotic, while plaque in mice subjected to AAC was lipid-rich with a histology associated with plaque instability (Fig

). Furthermore,
Apoe
−/−
mice post-TAC showed a more stiffened aorta than wild-type counterparts, evidenced by a greater degree of reduction in augmentation time (6.5±0.2 ms vs. 7.7±0.5 ms,
P
<0.05) and a greater degree of increment in augmentation index (77±2% vs. 71±2%,
P
<0.05). However, no such differences were observed between large artery stiffness in wild-type and
Apoe
−/−
mice post-AAC. Our results show that different features of plaques developed in TAC and AAC models differing in PP only, and fibrotic plaques in
Apoe
−/−
mice with TAC were associated with more pronounced large arterial stiffening. Plaque with thick layer of smooth muscle cells (SMC) in TAC vs lipid-rich plaque in AAC. Arrows indicate the organized blood clot in the expanded adventitial tissue due to plaque rupture.
Abstract 5956: Modulation of Urocortin 2 Contractile EFFects by Endocardial Endothelium
Authors: Bras-Silva Carmen , Fontes-Sousa Ana Patrícia , Almeida Mónica , Mendes Susana , Leite-Moreira Adelino F
Published: July 2021

Purpose: The urocortin (Ucn) peptides Ucn1, Ucn2, and Ucn3 are recently isolated members of the corticotropin-releasing factor family. Ucn2 promotes positive inotropic and lusitropic effects and both endothelium-dependent and -independent vasodilatation. In the current study, we investigated the modulation of Ucn2 contractile effects by endocardial endothelium (EE).

Methods: The effects of increasing concentrations of Ucn2 (10 –10 to 10 – 6M) were evaluated in isolated right papillary muscles (Krebs-Ringer: 1.8mM CaCl2, 35°C) with intact EE (n=11) and after damaging EE (0.5% Triton X-100, n=12). Reported parameters include: active tension (AT; mN/mm2) and maximum velocities of tension rise and tension decline (dT/dtmax and dT/dtmin, respectively; mN/mm2/s). Only significant results (mean±SEM, p<0.05) are given, expressed as % change from baseline.

Results: Ucn2 induced concentration-dependent positive inotropic and lusitropic effects in muscles with intact EE (at 10 – 6M it increased 65.6±5.2% AT, 196.9±16.7 dT/dtmax and 145.0±13.5% dT/dtmin). These effects were potentiated in papillary muscles with damaged EE. In this condition, the higher concentration of Ucn2 increased 169.1±39.2% AT, 412.5±43.9% dT/dtmax and 296.7±56.7%dT/dtmin.

Conclusions: This study shows that the positive inotropic and lusitropic effects induced by Ucn2 are enhanced in the presence of endocardial endothelial dysfunction. These findings reinforce the importance of Ucn2 in the regulation of myocardial function and provide new elements for the comprehension of the pathophysiology of HF, a condition where Ucn2 levels are increased and endothelial dysfunction might be present.
Abstract 5998: Final Results of the HEALING 2B Trial to Evaluate a Bioengineered CD34 Antibody Coated Stent (Genous
™
Stent) Designed to Promote Vascular Healing by Capture of Circulating Endothelial Progenitor Cells in CAD Patients
Authors: Duckers H , Onuma Yoshinobu , Benit Edouard , de Winter Robert J , Wijns William , Grisold Manfred , Verheye Stephan , Silber Sigmund , Teiger Emmanuel , Hill Jonathan , Serruys Patrick W
Published: July 2021

Background: In contrast to a cytotoxic or cytostatic pharmacotherapy, promoting the vascular healing response by capturing and sequestering circulating endothelial progenitor cells (EPC) to the stent surface by a CD34 antibody coating (Genous
™
stent) may accelerate stent reendo-thelialization and prevent restenosis formation, as well as stent thrombosis (ST)

Methods: The HEALING IIB study was a multi-center, prospective trial designed to assess the safety and efficacy of the Genous
™
bio-engineered stent in conjunction with HmG CoA reductase inhibitors (statins) to stimulate EPC recruitment, in the treatment of patients with de novo coronary artery lesions (n=100 pts). The primary safety endpoint was major adverse cardiac events (MACE) at 30 days, whereas the primary efficacy endpoint was late luminal loss by QCA at 6 months follow-up.

Results: At interim analysis of the first 45 patients that completed the 6-month angiographic follow-up, the composite MACE rate was 11.1%, whereas 6.6% clinically justified target lesion revascularizations were observed. 2 Patients died within the first 30 days after stent implantation due to angiographically verified stent thrombosis. Low circulating EPC titers were previously associated with a poor response to the EPC capture stent with TLR events and high late loss. Therefore, patients were pre-treated with Atorvastatin 80 mg qd prior to the PCI in order to augment EPC levels. Statin therapy stimulated the levels of committed EPCs by +294%, but failed to increase the titer of CD34+cells (+25%). Although statin pretreatment stimulated EPC levels, the angiographic outcome of the EPC capture stent was not improved in these patients: in-stent late luminal loss was 0.77±0.46 mm. We anticipate to complete analysis of the 6 month angiographic follow-up of all 100 patients by the time of the AHA2008.

Conclusions: The HEALING-IIB study suggests that the EPC capture coronary stent in combination with statin therapy does not sufficiently impede stent restenosis formation for the treatment of de novo coronary artery disease. Although concomitant statin therapy was able to stimulate EPC recruitment, it failed to stimulate CD34+ stem cell levels and did not improve the angiographic outcome of the bioengineered EPC capture stent.
Abstract 6031: Impact of Pre-procedural C-reactive Protein on Intravascular Ultrasound Parameters following Everolimus-eluting Stent Implantation: Results from the SPIRIT III Trial
Authors: Nakatani Daisaku , Ako Junya , Yamasaki Masao , Shimohama Takao , Otake Hiromasa , Tsujino Ichizo , Koo Bon-Kwon , Waseda Katsuhisa , Chang Hyeonsoo , Sakurai Ryota , Yock Paul G , Honda Yasuhiro , Pierson Wesley , Sudhir Krishnankutty , Fitzgerald Peter J
Published: July 2021

Background:
It has been reported that pre-procedual C-reactive protein (CRP) correlates with neointimal hyperplasia following bare-metal stent as well as a certain type of drug-eluting stent implantation. The aim of this study was to investigate potential impact of inflammation, as assessed by high sensitivity-CRP (hs-CRP) collected pre-procedure, on neointimal hyperplasia following everolimus-eluting stent (EES) implantation.

Methods:
Data were obtained from the SPIRIT III trial, a randomized controlled trial comparing an EES with a paclitaxel-eluting stent. Enrolled patients fulfilled the following criteria

patients treated with EES

stable angina; and

volumetric intravascular ultrasound (IVUS) analysis available at 8 months follow-up.

Volume index (volume/length) was calculated for vessel (VVI), plaque (PVI), neointima (NIV), and lumen (LVI). Percent neointimal volume (%NIV) was calculated as (NIV/SVI)× 100. Cross-sectional narrowing (CSN) was defined as neointimal area divided by stent area (%).

Results:
One-hundred thirty two patients met the inclusion criteria (mean age; 65±9 years, male; 75%). There was no significant correlation between hs-CRP and VVI, PVI, and LVI at either baseline or 8 months follow-up. Furthermore, hs-CRP did not correlate with %NIV (r=−0.071, P=0.416) and max CSN (r=−0.020, P=0.819) at follow-up (figure

).

Conclusion:
Pre-procedual inflammation assessed by hs-CRP did not affect the neointimal hyperplasia at 8 months following everolimus-eluting stent implantation.
Abstract 6119: Ultrasound 2D Speckle Tracking Differentiates Stunned from Scarred Myocardium after Acute MI
Authors: Prat-Gonzalez Susanna , Pizarro Gonzalo , Benson Babu A. , Ibanez Borja , Cimmino Giovanni , Giannarelli Chiara , Fuster Valentin , Badimon Juan , Sanz Javier , Garcia Mario J.
Published: July 2021

Background:
The aim of this study was to evaluate 2D Speckle Tracking radial strain by ultrasound in stunned and scarred myocardium as defined by cardiac magnetic resonance (CMR) in a porcine reperfusion model of acute MI.

Methods:
Seven pigs underwent MI induction by 90′ mid-LAD balloon occlusion. CMR was performed in a 1.5 T magnet 4 days post-MI. For edema imaging a T2-weighted sequence was employed. Delayed enhancement (DE) images were acquired 10–15 minutes after the administration of 0.2 mmol/kg of Gd-DTPA using an inversion recovery gradient-echo sequence. Before CMR, echocardiographic short axis images of the LV were obtained at the basal, mid and apical levels. Echo and CMR images were matched and divided into 6 segments per slice. DE and edema were defined as those regions with signal intensity >3 SD of the mean signal of remote normal myocardium, and quantified as % of the LV. Stunned myocardium was defined as edema- DE. Radial strain was compared in segments containing predominantly normal myocardium (<10% edema; n=70), stunned myocardium [>25% (edema - DE); n=12] or predominantly scar (>75 % DE; n=19).

Results:
A total of 126 segments were analyzed. Radial strain was negatively correlated with the amount of edema (r=−0.41) and scar (r=−0.39, p<0.0001 for both). Radial strain was significantly lower in necrotic than in normal segments (p<0.001). Stunned segments showed intermediate degrees of myocardial deformation. (Figure

)

Conclusions:
Our study suggests that 2D Speckle Tracking radial strain can be a simple tool to differentiate stunned from scarred segments. This could be particularly useful in unstable patients after acute MI.
Abstract 6138: Two-Dimensional Atrial Strain and Strain Rate Predict Maintenance of Sinus Rhythm After Pulmonary Vein Ablation in Patients with Atrial Fibrillation
Authors: Hwang Hye Jin , Kim Sung-Ai , Joung Boyoung , Choi Eui-Young , Kim Jin-Bae , Lee Moon-Hyoung , Jang Yangsoo , Chung Namsik , Kim Sung Soon
Published: July 2021

Introduction
A novel method to measure strain and strain rate from standard 2-dimensional(2D) has been developed. However, clinical usefulness of 2D atrial strain and strain rate has been not yet investigated.

Hypothesis
We assessed the hypothesis that 2D strain and strain rate might be reduced in patients with atrial fibrillation (AF) and predictive of maintenance of sinus rhythm after AF ablation.

Methods
Echocardiographic examinations were performed in 44 patients with lone AF before AF ablation. Using a dedicated software package, bidimensional acquisitions were analyzed to measure longitudinal strain and strain rate in apical 4- and 2-chamber views. Maintenance of sinus rhythm after AF ablation was assessed during a 9 months follow-up. 2D left atrial(LA) strain and strain rate values in AF patients were compared with those of age- and sex-matched referents(N=40). Moreover, clinical and echocardiographic parameters of patients with maintenance of sinus rhythm (n=30) over the follow-up period were compared with those from patients with AF recurrence (n=14).

Results
All components of strain and strain rate were significantly reduced in AF patients. Average LA longitudinal strain and strain rate in patients with AF and referents were 28.1 ± 8.7 % versus 40.5 ± 6.4 and 1.8 ± 0.5 versus 2.4 ± 0.9, respectively (all p < 0.001). The individual predictors of sinus rhythm maintenance after AF ablation were paroxysmal AF(80 vs. 35.7%, p = 0.007), duration of AF (3.5 ± 3.1 vs. 5.9 ± 3.4 years, p=0.037), LA volume index(29±8 vs. 36±14ml/m2, p=0.045), average LA longitudinal strain (30.9±7.9 vs. 21.9 ± 7.3, p=0.001) and strain rate (2.0 ± 0.4 vs.1.6±0.6, p=0.008) peak systolic values. Average LA longitudinal strain parameter (OR 0.85, 95% CI 0.74–0.97, p=0.016) was confirmed as independent predictor of sinus rhythm maintenance by multivariate analysis, with a contribution from paroxysmal AF (OR 8.17, 95% CI 1.03–64.85, p=0.047). Average interobserver and intraobserver variabilities for strain and strain rate were 9.2%, 10.3%, 13.2%, and 14.1%, respectively.

Conclusions
Patients with higher atrial strain appear to have a greater likelihood of maintenance of sinus rhythm after AF ablation. 2D strain of LA may be helpful to select candidates of AF ablation.