bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3774: Cost Effectiveness Of Enoxaparin In Patients With ST-elevation Myocardial Infarction: Results From EXTRACT-TIMI 25
Authors: Zhang Zefeng , Kolm Paul , Zhang Wei , Ewen Edward , Jurkovitz Claudine , Fidan Dogan , Weintraub William
Published: July 2021

Background:
The efficacy of enoxaparin versus unfractionated heparin in the setting of ST-elevation myocardial infarction (STEMI) has been demonstrated in EXTRACT-TIMI 25, with 17% reductions in relative risk in the primary endpoint of death or nonfatal recurrent myocardial infarction (MI) (p<0.0001). This study considers the cost effectiveness of enoxaparin versus unfractionated heparin with fibrinolysis based on EXTRACT-TIMI 25.

Methods: The ITT population of 20,479 patients from 48 countries were monitored for clinical and adverse events during the index hospitalization and through 30 days. Trial-wide resource utilization from all participating countries was used in the analysis while all costs were based on 2004 US costs. Medicare Fee Schedule was used for outpatient procedures and DRGs were applied for index and subsequent hospitalizations costs. Lost life years associated with 30-day in-trial events (death, MI and stroke) were estimated from published data from Framingham.

Results: Overall, costs of index hospitalizations and outpatient procedures were lower, while costs for the subsequent hospitalization were higher for the enoxaparin patients. Total 30 days’ costs remained lower for enoxaparin, although the difference did not reach significance. Life years lost were significantly less with enoxaparin. For lifetime, when costs beyond the trial period were considered, the costs of enoxaparin in patients with STEMI were $506 higher, and the incremental cost-effectiveness ratio of enoxaparin compared to UFH was $4,369 per life year gained, with 99.9% of estimates falling below the $50,000 per life year gained threshold.

Conclusions: Enoxaparin is effective in reducing mortality or nonfatal MI, and is highly cost-effective strategy in the US settings for the treatment of STEMI patients.
Abstract 3777: High Rates of Recidivism in Patients Presenting to a Chest Pain Unit: Incidence, Patient Profiles and Outcomes in a Total Cohort of Over 3,000 Patients
Authors: Kupersmith Adam , Diercks Deborah B , Madriago Erin , Baker Larry , Kirk J D , Amsterdam Ezra A
Published: July 2021

Background:
There are minimal data on the magnitude of recidivism and clinical course in patients (pts) with multiple negative evaluations (NE) for acute coronary syndrome (ACS) in a chest pain unit (CPU).

Methods:
We identified pts with multiple NE in our CPU to determine the incidence, clinical characteristics and ultimate outcomes of this group.

Results:
During a 7.5 year interval, 3,432 pts were admitted to our CPU of whom 2,249 (66%) had NE. Multiple (≥ 2) NE occurred in 13% (289/2,249) of these pts but they accounted for 26% (696/2656) of total NE. Of the multiple NE pts, 261 (90%) had 2–3 NE and 28 (10%) had ≥ 4 NE (mean 2.7). Characteristics of pts (n=289) with multiple NE: age 52 yr, 54% (156/289) women, 14% (40/289) known coronary artery disease (CAD), 59% (169/289) ≥ 2 risk factors, 65% (188/289) uninsured, 58% (169/289) non-White. During 11.5 yr follow-up, 25% (72/289) of multiple NE pts had a major clinical event (MCE) (2.2%/yr): all-cause mortality 11% (31/289), ACS 8% (24/289), revascularization 10% (28/289), cardiac failure 10% (29/289). Mean time to MCE was 5 yr. MCE was associated with age ≥ 65yrs (47% of 43 pts had MCE), positive insurance (52% of 101), and known CAD (53% of 40 pts) (all p <0.01).

Conclusions:
Our findings indicate that

pts with multiple NE in a CPU accounted for a disproportionate number of all NE

one-fourth developed a MCE during longterm follow-up, the majority of which were temporally remote from initial NE, and included 1% annual mortality

MCE were associated with older age, known CAD and positive insurance status.

NE pts with the latter characteristics may warrant earlier and more aggressive management.
Abstract 3781: A Reduction in Urinary Albumin Excretion is Associated with a Decrease in 10-year Cardiovascular Mortality in Hypertensive Type 2 Diabetic Patients
Authors: Estacio Raymond , Coll Joseph , Dale Rita , Bucher-Bartelson Becki , Krantz Mori J
Published: July 2021

Urinary albumin excretion (UAE) is one of the strongest predictors of both adverse renal and cardiovascular outcomes in patients with type 2 diabetes. Although measurement of UAE is widely recommended, there is little available data to suggest that reducing UAE translates into a reduction in cardiovascular mortality. We assessed whether an early reduction in UAE is associated with improved long-term cardiovascular mortality in hypertensive type 2 diabetic patients with normo, micro, or overt albuminuria at baseline. The study is a 10-year longitudinal analysis of a prospective, randomized study- the Appropriate Blood Pressure Control in Diabetes (ABCD) trial including 393 type 2 diabetic patients with hypertension. We evaluated the association between the change in UAE from baseline to 1-year with the incidence of all cause and cardiovascular mortality over a ten year period. Our results revealed that a reduction in log UAE achieved at one-year was one of the strongest predictors of reduced cardiovascular mortality in a multivariable model that adjusted for multiple cardiovascular risk factors (HR1.42, 95% CI 1.06 – 1.92). This association was at all levels of UAE, normo, micro and overt albuminuria. In conclusion, an early reduction in UAE even at the normoalbuminuria level is associated with improvements in long-term cardiovascular mortality. Our data support current guideline recommendations to screen for UAE in all type 2 diabetic patients, but also suggest that serial UAE measurements after initiation of therapy may have clinical value. Prospective studies addressing this approach to care are needed prior to widespread adoption in practice.
Abstract 3794: Long-term Effects Of An Aerobic Training Program On Exercise Tolerance And Quality Of Life In Patients With Chronic Heart Failure. A Randomised Controlled Trial
Authors: Nilsson Birgitta Blakstad , Westheim Arne , Risberg May Arna
Published: July 2021

Introduction
: Exercise training has been shown to improve exercise tolerance (ET) and quality of life (QoL) in patients with chronic heart failure (CHF). However, the long-term effects of training programs are very spare. We hypothesized that a 4 months group-based aerobic interval-training program would improve ET and QoL in patients with CHF, and after follow-up without supervised exercise training.

Methods
: Eighty consecutive patients with stable CHF (mean age 70 ± 7.9 years, 63 males), in New York Heart Association-class II-IIIB were randomized to training (n=40) and control (n=40). The ejection fraction was 30.2 % ± 7.6 in the training group and 30.8% ± 9.4 in the control group. All were on optimal medical treatment (93% on beta-blockers and 98% on ACEI inhibitors or A2 receptor blockers at baseline). The training group exercised in a group-based aerobic interval-training model for 50 min, two times a week for 16 weeks. For the next 8 months they only got individual advices to exercise on their own. During the exercise period the patients had 4 consultations with a CHF nurse, including diatory advices, medication adherences, symptom monitoring and social support. In the follow-up period, the patients had 2 consultations with a CHF nurse. The control group received standard medical treatment without additional exercise training. The effects were evaluated by: bicycle ergometer test; 6-minute walk test and Minnesota Living with Heart Failure Questionnaire.

Results:
After 4 months, both exercise time (+19.2%, p=0.001), workload (+14%, p=0.001) and walking distance (+18%, p<0.001) had increased significantly in the exercise group without any change in the control group. QoL showed a significant improvement (p<0.05), with a mean difference of -12.1 points in the exercise group and no difference in the control group. After 12 months the differences were still significant for all parameters (exercise time, +19.8%, p=0.003, work load; +16%, p=0.001, walking distance; +17%, p<0.001) and QoL with a mean difference of -11.7 points in the exercise group and +5.2 in the control group, p=0.002.

Conclusions:
Our results support the implementation of a group-based aerobic interval-training program, to improve both ET and QoL in patients with CHF.
Abstract 501: Function of Connexin30.2 and Connexin40 in AV-Nodal Conduction
Authors: Schrickel Jan W , Kreuzberg Maria , Ghanem Alexander , Troatz Clemens , Tiemann Klaus , Nickenig Georg , Willecke Klaus , Lewalter Thorsten
Published: July 2021

Objective: Connexin30.2 (Cx30.2) and Connexin40 (Cx40) have been shown to be major components of the gap-junctions murine AV-nodal tissue. Cx30.2 has been shown to contribute to physiological conduction slowing of the AV-node but functional interactions of Cx30.2 and fast conducting connexins like Cx40 in the AV-node remaines unclear.

Methods: 18 wildtype-(WT), 10 Cx30.2-deficient (Cx30.2−/−), 6 Cx40-deficient (Cx40−/−) and 10 Cx30.2/Cx40 double-deficient (Cx30.2/Cx40−/−) mice were in vivo electrophysiologically investigated using transvenous right cardiac catheterization.

Results: Independent from a tendency towards P-wave prolongation in Cx40−/− and Cx30.2/Cx40−/− mice, PQ was significantly shorter in Cx30.2 (35.7±3.4 ms) as compared to all other investigated groups (WT: 46.6±4.0 ms; Cx40−/−: 50.8±6.2 ms; Cx30.2/Cx40−/−: 51.6±5.1 ms; p<0.0001). Accelerated AV-conduction was attributable to a significant faster supra-Hisian conductivity with shortened AH-intervals in Cx30.2−/− (28.2±4.3 ms vs. WT: 35.9±4.4 ms; Cx40−/−: 35.8±1.9 ms; Cx30.2/Cx40−/−: 37.3±5.5 ms, p<0.0001). A significantly lower Wenckebach-periodicity was present in Cx30.2−/− (basal stimulation cycle-length S1S1: 79.7±7.2 ms), but not in Cx30.2/Cx40−/−(81.5±6.7 ms; p<0.001) compared to the other groups. The HV-Interval was prolonged in Cx40−/− compared to WT and Cx30.2−/− as an indicator for impaired infra-Hisian conductivity. As a result, QRS was prolonged in Cx40−/− (21.3±2.7 ms) and Cx30.2/Cx40−/−(19.9±2.4 ms) compared WT (12.9±1.9 ms) and Cx30.2−/− (14.2±2.0 ms; p<0.0001).

Conclusions: Thefact that no acceleration of AV-nodal conduction is present in Cx30.2/Cx40−/− compared to Cx30.2−/− implicates that the presence of fast conducting Cx40 is essential for faster impulse propagation in Cx30.2−/−. This study strongly points towards functional interactions of Cx40 and slow conducting Cx30.2 in the murine AV-node. The conductive properties of the AV-node under physiological conditions and in pathological states (such as hereditary AV-blocks and AV-nodal reentrant tachycardia) might therefore be mediated by a differential expression or activation of such interacting connexins.
Abstract 503: Paracrine Factors from Cardiac Fibroblasts Slow Conduction Velocity and Prolong the Action Potential Duration of Cardiomyocytes
Authors: Pedrotty Dawn , Klinger Rebecca , Bursac Nenad
Published: July 2021

By acting as passive current sinks or conduction obstacles, cardiac fibroblasts directly slow conduction and increase electrical anisotropy in fibrotic cardiac tissue, leading to increased arrhythmogenicity. We studied if indirect paracrine action by cardiac fibroblasts can alter electrical properties and related gene expression in cardiomyocytes. Confluent cardiomyocyte cultures were incubated for 24 h in serum-free defined media conditioned 24 h by cardiac fibroblasts. Age-matched unconditioned cultures served as controls. The cell membrane potentials were optically mapped at 504 sites using voltage sensitive dye, Di-4 ANEPPS. Remarkably, a two-fold decrease in conduction velocity and three-fold increase in action potential duration were measured. Observed changes in conditioned cultures were not caused by increased cell apoptosis or fibroblast proliferation. Fresh medium with concentrated fibroblast paracrine factors induced the same effect. Consistent with electrophysiological changes, conditioned cultures had decreased mRNA expression for fast sodium (SCN5A, 3.8 fold), inward rectifier potassium (Kir2.1, 6.6 fold) and transient outward potassium (Kv4.3, below detection limit) channels, but unchanged expression of Connexin 43 and 45. Expressions of myosin heavy chain-beta and alpha were respectively increased 17 fold and decreased 2.2 fold. Importantly, media conditioned by the same number of fibroblasts in the presence of cardiomyocytes had no effect on cardiac electrical properties, suggesting that under normal conditions, cardiomyocytes may secrete protective factors that inhibit the negative paracrine action of cardiac fibroblasts.

Isochrone maps and action potential traces of control (A1) and fibroblast conditioned cardiac cultures (A2). Pulse sign (Π) denotes pacing site and circles represent recording sites. Comparative conduction velocity (B1) and action potential duration (B2) values given. The gene expression of the conditioned cardiac cells reported relative to the gene expression of the control cultures (C). In conditioned cultures, expression of Kv4.3 was below the detectable level.
Abstract 509: Myocardial Fatty Acid Oxidation Rates Remain Elevated in ob/ob Mice Despite Reversal of Obesity and Diabetes by Caloric Restriction
Authors: Sloan Crystal , Tuinei Joseph , Abel E. Dale
Published: July 2021

Leptin deficient ob/ob mice are commonly used to study the effects of obesity and insulin resistance on myocardial substrate metabolism. However, it is difficult to discern the specific contribution of obesity, insulin resistance and diabetes versus leptin deficiency to the observed phenotypes. We therefore adopted a strategy using caloric restriction to normalize body weight and reverse insulin resistance to study the effect of leptin deficiency on myocardial metabolism in lean ob/ob mice. Male 4-week old ob/ob mice were “pair fed” to a leptin-treated group (3mg/kg/day by i.p. injection) for three weeks. Glucose tolerance, serum insulin, serum triglycerides and FA oxidation rates in hearts perfused with 0.4mM palmitate ± 1 nM insulin were determined. Leptin-treated ob/ob mice ate significantly less than non-treated ob/ob mice, and their weight returned to wild type levels. Hyperglycemia, hyperinsulinemia, hypertriglyceridemia and cardiac hypertrophy were also completely reversed in leptin-treated ob/ob mice. In contrast, cardiac hypertrophy persisted in pair fed ob/ob mice and despite normalization of glucose tolerance and insulin levels, serum triglyceride concentrations increased by 2 and 6 -fold in pair fed ob/ob mice relative to untreated ob/ob and wildtype mice respectively (p<0.05). As previously reported, palmitate oxidation rates were 2.1-fold increased in ob/ob hearts relative to controls (p<0.005) and were normalized with leptin treatment. In contrast, palmitate oxidation rates remained elevated in pair fed ob/ob mice relative to wildtype controls (1.9-fold, p<0.01). Insulin has a positive inotropic effect in perfused wildtype hearts, and this effect was absent in ob/ob hearts. The insulin-induced inotropic response was restored by leptin treatment in ob/ob mice but was not restored in pair fed ob/ob mice. These data support a direct antihypertrophic effect of leptin in the heart and suggest that leptin deficiency may directly contribute to myocardial insulin resistance and abnormal FA metabolism. Potential mechanisms include increased hepatic triglyceride production in leptin deficiency or direct effects of leptin signaling in the hypothalamus and/or the periphery on myocardial substrate utilization.
Abstract 1: Statewide Out-of-Hospital Cardiac Arrest Survival Improves after Widespread Implementation of Cardiocerebral Resuscitation
Authors: Bobrow Bentley J , Vadeboncoeur Tyler F , Clark Lani , Chikani Vatsal , Ewy Gordon , Sanders Arthur B
Published: July 2021

OBJECTIVE
: To evaluate the impact of cardiocerebral resuscitation (CCR), an alternative emergency medical services (EMS) protocol, on out-of-hospital cardiac arrest (OOHCA) survival in the state of Arizona. CCR, emphasizes 200 preshock chest compressions, a single defibrillator shock (when indicated) followed immediately by 200 postshock chest compressions, early intravenous epinephrine and delayed endotracheal intubation.

METHODS
: The Save Hearts in Arizona Registry and Education (SHARE) program collected Utstein style data from 38 different fire departments (FDs) servicing approximately 70% of Arizona’s population. 2671 consecutive OOHCAs, of which 1847 were adult and presumed cardiac etiology were enrolled between October, 2004 and December, 2006. The CCR protocol was implemented in 11/38 (29%) FDs and the remaining FDs 27/38 (72%) utilized standard ACLS. The primary end-point was survival to hospital discharge of all cardiac arrests and for the subgroup with witnessed arrest and ventricular fibrillation (VF) on EMS arrival. Outcomes were obtained from the Office of Vital Statistics as well as local hospitals and were compared using chi square testing; alpha = 0.05.

RESULTS:
457/1847 (24.7%) patients were treated by CCR FDs and 1390/1847 (75.3%) were treated by ACLS FDs. Overall survival in the CCR group was significantly better than in the ACLS group (9.2% (42/457) vs. 3.5% (49/1390), p < 0.001). Similarly, survival for witnessed VF arrests was significantly better in the CCR group than the ACLS group (29.3% (29/99) vs. 11.1% (30/271), p < 0.001). Odds ratios were adjusted for age, gender, location, bystander CPR performed, % witnessed, % VF and EMS dispatch to arrival time. The odds of overall survival was 2.7 times higher in the CCR group compared to the overall ACLS group (95% CI 1.7,4.4), and 3.0 times higher in the CCR subgroup of witnessed VF (95% CI 1.6,5.6).

CONCLUSION:
Survival of patients with OOHCA in Arizona was significantly better in fire departments utilizing the cardiocerebral resuscitation protocol than in fire departments utilizing ACLS. Implementing the cardiocerebral resuscitation protocol on a large scale is feasible and saves lives.
Abstract 4: Inducing Hypothermia During Resuscitation Improves Return Of Spontaneous Circulation In Prolonged Porcine Ventricular Fibrillation
Authors: Menegazzi James J , Rittenberger Jon C , Suffoletto Brian P , Logue Eric S , Salcido David D , Sherman Lawrence D
Published: July 2021

Introduction: Induced hypothermia has been shown to improve survival and neurologic outcomes for ventricular fibrillation (VF) cardiac arrest. Clinical studies have not begun inducing hypothermia until after return of spontaneous circulation (ROSC). The effects of cooling during the resuscitation are not well-studied.

Hypothesis: We hypothesized that inducing hypothermia at the start of resuscitation would increase the rates of ROSC and short-term survival (20 minutes) in an established porcine model of prolonged VF. We compared intra-resuscitation hypothermia (IRH) with a normothermic control group (CTL).

Methods: We anesthetized and instrumented 28 domestic swine (mean mass 26.5 ±2.4 kgs) with ECG, esophageal temperature, and micromanometer-tipped aortic and right atrial catheters. We then randomly assigned them to IRH and CTL groups (n= 14 each). VF was electrically induced and untreated for 8 minutes. Then resuscitation was begun with mechanical chest compression and ventilation. Hypothermia was induced by rapid IV infusion of ice-cold normal saline (30 mL/kg) at the beginning of resuscitation in the IRH group. The CTL group got 30 mL/kg of body-temperature saline at the start of resuscitation. After 8 minutes of VF, two minutes of CPR was followed by delivery of drugs (epinephrine 0.1 mg/kg, vasopressin 40 U, and propranolol 1.0 mg) and 3 more minutes of CPR (first rescue shock at 13 minutes of VF). ROSC (systolic BP above 80 mmHg for one minute continuously) and survival were recorded, as was total fluid given and hematocrits. Temperatures are reported in degrees C. Rates were compared with 2-tailed Fisher’s exact test, with alpha=0.05.

Results: Baseline temperatures at 8 minutes VF did not differ (IRH=37.9° and CTL=37.7°). Post-infusion temperatures at 13 minutes of VF were IRH=34.9° and CTL=37.9°. ROSC occurred in 12/14 (86%) IRH animals and in 6/14 (43%) CTL, with p=0.046. Survival occurred in 8/14 (57%) IRH animals and 4/14 (36%) CTL, with p=0.15. Total fluid volumes given and hematocrits did not differ between groups.

Conclusions: IRH doubled the rate of ROSC compared to CTL. There was a non-significant 58% relative improvement in short-term survival. In this porcine model, rapid infusion of ice-cold saline quickly cooled during resuscitation.
Abstract 10: Outcome Of Pediatric In-hospital Cardiac Arrest By Extracorporeal Membrane Oxygenation Implementation During Active Cardiopulmonary Resuscitation
Authors: Wu Enting , Huang Shuchien , Ko Wenje , Chen YihSharng
Published: July 2021

Background:
To achieve intact neurological survival is a challange for pediatric cardiac arrest. Here we describe the outcome and identify the factors associated with survival among pediatric patients following extracorporeal cardiopulmonary resuscitation (ECPR) for in-hospital pediatric cardiac arrest.

Method:
Retrospective study of 27 pediatric in-hospital cardiac arrest who received extracorporeal membrane oxygenation during active cardiopulmonary resuscitation-.The primary outcome was survival to hospital discharge. The secondary outcome was neurological status after ECPR at hospital discharge and late follow-up. Continuous variables were expressed as medians (inter-quartile range)

Results:
. We identified 27 ECPR events. The survival rate to hospital discharge was 41% (11/27). The non-survivors had higher serum lactate levels (14 [10.2–19.6] mmol/L vs 8.5 [4.4 –12.6] mmol/L, p < 0.01), longer durations of cardiopulmonary resuscitation (CPR) (60 [37– 81] minutes vs 45 [25–50] minutes, p < 0.05) with longer activating time for ECMO (12.5 [7.5–33.8] minutes vs 5 [0 –10] minutes, p<0.01),and more renal failure after ECPR (68%
11
/
16
vs 9%
1
/
11
, p < 0.01). By multivariate analysis, the earlier cohort and renal failure after ECPR were independent risk factors for mortality. Among the11 survivors, 10 of them had good neurological outcomes.

Conclusions:
ECPR successfully rescued some pediatric patients who failed rescue with conventional in-hospital CPR. Good neurological outcomes were achieved in the majority of the survivors. Early cohort and post-ECPR renal failure were associated with poor outcomes. Early activation of the ECMO team could possibly shorten the CPR duration and improve the ECPR results.
Abstract 17: Ambulance Paramedics Interrupt Chest Compressions And Delay Defibrillation After Taking Over From Lay Rescuers With An Automated External Defibrillator
Authors: Berdowski Jocelyn , Schulten Ron J , Koster Rudolph W
Published: July 2021

Introduction: There are no guidelines for transition of care from rescuers with AED to paramedics with ongoing CPR. After disconnection of the AED, clock time as running in the AED is not available for subsequent protocollized CPR duration, rhythm check and shock. We hypothesize that defibrillation shocks are delayed and CPR interrupted without reason after AED disconnection.

Methods: This was a prospective observational community study in an area of 2.6 million inhabitants. During 16 months, all available continuous ECG recordings of AEDs and associated manual defibrillator (mDFB) recordings of out-of-hospital cardiac arrests were collected. All clock times were synchronized. We observed CPR time through the impedance signal. For shockable rhythms, we measured the duration of CPR given between the connection time of the mDFB and expected time of defibrillation of the AED. For non shockable rhythms, the expected moment of AED rhythm analysis was the endpoint of the time interval. Time available for CPR given during that time interval was set at 100%. Delay in defibrillation was the difference between expected moment of the next shock as advised by the AED and the actual shock given by paramedics.

Results: Results are shown in table 1

. Of the 245 cases, 73 cases had a shockable rhythm during take over, 141 a non-shockable rhythm and 31 patients had Return of Spontaneous Circulation. A shock was delivered too early or too late in 68 of 73 patients. Four patients were never defibrillated.

Conclusion: Disconnection of the AED by professionals interrupts the treatment protocol of the AED, delaying time of defibrillation by almost two minutes. Premature defibrillation leads to decrease in CPR time. The optimal moment of disconnecting the AED should be described in new guidelines.

Table 1:

Shock delay and CPR interruption, devided in shockable and non shockable rhythms
Abstract 62: Resuscitation with Actual Performance Integrated Debriefing (RAPID) Improves CPR Quality and Initial Patient Survival
Authors: Edelson Dana P , Litzinger Barbara , Arora Vineet , Kim Salem , Lauderdale Diane S , Hoek Terry L Vanden , Becker Lance B , Abella Benjamin S
Published: July 2021

Introduction
Recent investigations have documented poor cardiopulmonary resuscitation (CPR) performance in clinical practice. We hypothesized that a debriefing intervention using CPR quality data from actual cardiac arrests (Resuscitation with Actual Performance Integrated Debriefing, or RAPID) would improve CPR performance and initial patient survival.

Methods
Rescuers at a university teaching hospital underwent weekly RAPID sessions between March, 2006 and February, 2007. During the intervention period, facilitators led debriefing discussions using actual performance data, obtained from a CPR-sensing defibrillator with audiovisual feedback capability, and highlighted deficiencies in CPR quality and defibrillation. These data were compared to an historical control in which a similar defibrillator was used. The main outcomes were objective metrics of CPR performance and initial return of spontaneous circulation (ROSC).

Results
CPR quality and outcome data from 123 patients resuscitated during the intervention period were compared to 101 patients in the baseline cohort. Compared to the control period, CPR quality parameters and defibrillation accuracy were improved (table

). These were associated with a significant improvement in the unadjusted rate of ROSC (table

). After adjusting for shockable vs. non-shockable rhythm, time and location of arrest, and patient demographics, the RAPID intervention was associated with a significant increase in the adjusted odds of ROSC (OR 1.84 [1.06 –3.20]; p=0.03).

Conclusions
The combination of RAPID and real-time audiovisual feedback improved CPR quality over the use of feedback alone, and was associated with an increased rate of ROSC. CPR sensing and recording devices allow for methods of debriefing that were previously available only for simulation based education; such methods have the potential to fundamentally alter resuscitation training and improve patient outcomes.

Resuscitation Performance and Patient Outcomes by Cohort
Abstract 64: A Tale of Seven EMS Systems: An Impedance Threshold Device and Improved CPR Techniques Double Survival Rates After Out-of-Hospital Cardiac Arrest
Authors: Aufderheide Tom P , Birnbaum Marvin , Lick Charles , Myers Brent , Romig Laurie , Stothert Joseph , Vartanian Levon
Published: July 2021

Introduction: Maximizing outcomes after cardiac arrest depends on optimizing a sequence of interventions from collapse to hospital discharge. The 2005 American Heart Association (AHA) Guidelines recommended many new interventions during CPR (‘New CPR’) including use of an Impedance Threshold Device (ITD).

Hypothesis: The combination of the ITD and ‘New CPR’ will increase return of spontaneous circulation (ROSC) and hospital discharge (HD) rates in patients with an out-of-hospital cardiac arrest.

Methods: Quality assurance data were pooled from 7 emergency medical services (EMS) systems (Anoka Co., MN; Harris Co., TX; Madison, WI; Milwaukee, WI; Omaha, NE; Pinellas Co., FL; and Wake Co., NC) where the ITD (ResQPOD®, Advanced Circulatory Systems; Minneapolis, MN) was deployed for >3 months. Historical or concurrent control data were used for comparison. The EMS systems simultaneously implemented ‘New CPR’ including compression/ventilation strategies to provide more compressions/min and continuous compressions during Advanced Life Support. All sites stressed the importance of full chest wall recoil. The sites have a combined population of ~ 3.2 M. ROSC data were available from all sites; HD data were available as of June 2007 from 5 sites (MN, TX, Milwaukee, NE, NC).

Results: A total of 893 patients treated with ‘New CPR’ + ITD were compared with 1424 control patients. The average age of both study populations was 64 years; 65% were male. Comparison of the ITD vs controls (all patients) for ROSC
and
HD [Odds ratios (OR), (95% confidence intervals), and Fisher’s Exact Test] were: 37.9% vs 33.8% [1.2, (1.02, 1.40), p=0.022]
and
15.7% vs 7.9% [2.2, (1.53, 3.07), p<0.001], respectively. Patients with ventricular fibrillation had the best outcomes in both groups. Neurological outcome data are pending. Therapeutic hypothermia was used in some patients (MN, NC) after ROSC.

Conclusion: Adoption of the ITD + ‘New CPR’ resulted in only a >10% increase in ROSC rates but a doubling of hospital discharge rates, from 7.9% to 15.7%, (p<0.001). These data represent a currently optimized sequence of therapeutic interventions during the performance of CPR for patients in cardiac arrest and support the widespread use of the 2005 AHA CPR Guidelines including use of the ITD.
Abstract 72: Muscle Metabolomic Changes in a Porcine Model of Hemorrhagic Shock and Resuscitation
Authors: Witowski Nancy , Beilman Greg
Published: July 2021

Introduction: Treatment of hemorrhage shock remains a clinical challenge despite decades of study. Investigation of metabolism during hemorrhagic shock and resuscitation may yield novel approaches for intervention strategies.

Methods: Pigs underwent a standardized hemorrhagic shock protocol after general anesthesia and instrumentation. Animals were hemorrhaged via IVC cannula, then resuscitated to a goal of 80 mm Hg systolic blood pressure after 45 minutes. Animals were fully resuscitated after 8 hours and weaned and extubated at 24 hours after beginning experiment. Survivors were sacrificed at 48 hours post-hemorrhage. Muscle samples were obtained at baseline (prior to hemorrhage), shock45 (after 45 min of shock), and 8, 23, and 48 h post resuscitation (PR). Muscle samples were processed using a dual-phase extraction process and the water-soluble metabolites examined by 1H and 31P NMR.

Results: The phosphocreatine:inorganic phosphate ratio decreases with shock and remains below baseline values at 48 h PR (A). Phosphoesters (glycolytic intermediates) increase during shock and return to levels below baseline at 48PR in successfully resuscitated pigs (B). Non-survivors exhibited higher levels of 1H NMR-visible lipids and of 31P NMR-visible ADP at baseline when compared to survivors (C).

Conclusions: Hemorrhage shock induces metabolic changes observable with NMR spectroscopy. Survivors exhibited persistent metabolic changes not resolved at 48 hours. Response to hemorrhage and risk of mortality may be dependent on initial metabolic state.
Abstract 75: Electronic Integrated Monitoring of Medical Emergency Team Calls to a Step Down Unit
Authors: Hravnak Marilyn , Edwards Leslie , Foster-Heasley Molly , Clontz Amy , Valenta Cynthia , DeVita Michael , Pinsky Michael
Published: July 2021

Purpose:
Early discharge from intensive care units (ICU) to lower acuity monitoring units (step-down units or SDU) is increasing to improve care throughput. However, the ability of minimally invasive monitoring via electronic integrated monitoring systems (IMS) in SDUs to identify cardiopulmonary deterioration in order to activate Medical Emergency Team (MET) response is unknown. We evaluated the ability of an IMS index value to detect clinically significant events which might trigger activation of the MET earlier than called.

Methods:
Patients were monitored on a 24 bed trauma SDU according to prevailing policy and bedside decision making. An IMS (BioSign
TM
) was inserted into the monitoring system and IMS data were collected in a blinded fashion for 8 weeks from all patients. The IMS uses 4 parameters (heart rate [HR], respiratory rate [RR], blood pressure [BP], peripheral oxygen saturation [SpO
2
]) to develop a single neural networked signal known as the BioSign Index (BSI). Data were analyzed for patient deterioration according to both BSI trigger value and local MET criteria (DeVita, Qual Safety Health Care 2004).

Results:
Data from 333 patient admissions were evaluated reflecting 18,692 hours of continuous monitoring. SpO
2
monitoring data were absent in 38.5% of monitored hours, despite being mandatory. Most patients were stable throughout their SDU stay. MET activation occurred on 10 occasions (4 respiratory cause [2 SpO
2
, 2 SpO
2
+RR], 2 cardiac (BP), 1 mixed respiratory + cardiac, and 3 other (1 chest pain, 2 acute mental status change). All 7 MET events of respiratory and/or cardiac cause were detected by BSI in advance (mean advanced detection time prior to MET activation was 6.33 hours). Cardiopulmonary deterioration was generally characterized by progressive increases in BSI over time, not step increases.

Conclusion
: In this population, cardiopulmonary deterioration requiring MET activation was uncommon but always preceded by IMS index elevations which would have alerted the nursing staff in advance. Continuous monitoring of physiological variables may be augmented by integrating information from multiple parameters to create a new variable. The new index parameter may detect patient deterioration earlier than single parameter monitoring.
Abstract 82: Awareness of Guidelines of Automated External Defibrillator Use in Children within Emergency Medical Services
Authors: Haskell Sarah E , Kenney Melanie A , Patel Sonali , Sanddal Teri L , Altenhofen Katrina L , Sanddal Nels D , Atkins Dianne L
Published: July 2021

BACKGROUND
. Ventricular fibrillation occurs in 10 –20% of pediatric cardiac arrests. Survival rates in children with ventricular fibrillation can be as high as 30% when the rhythm is identified and treated promptly. In the last five years, recommendations have been made for the use of automated external defibrillators(AED) in children 1– 8 years of age.

OBJECTIVE
. The goal of this study was to determine the awareness of American Heart Association (AHA) guidelines and statewide protocols concerning AED use in children ages 1– 8 among emergency medical providers after new guideline release. Availability of pediatric capable AED equipment was also assessed.

METHODS
. Surveys were distributed to EMS providers in Iowa and Montana within one year of the AHA advisory statement in 2003 recommending use of AEDs in children ages 1– 8, and again approximately one year after the 2005 AHA guidelines on cardiopulmonary resuscitation were published. In Iowa, there were concentrated efforts to disseminate information about AED use in children, while there were minimal efforts in Montana.

RESULTS
. Awareness of AHA guidelines for use of AEDs in children was low in both states in 2003 (29% in Iowa vs 9% in Montana, p< 0.001). After release of the 2005 guidelines, awareness improved significantly in both states but was still significantly greater in Iowa (83% vs. 60 %, p < 0.002). In 2003, less than 20% of respondents in both states reported access to pediatric capable AEDs. Availability of pediatric pads and cables increased significantly in 2006 but remained low in Montana (74% in Iowa vs 37% in Montana, p < 0.001).

CONCLUSIONS
. At the present time, publication of new or interim guidelines in the scientific literature alone is insufficient to ensure that awareness among providers and that new protocols are implemented. An effective and efficient method to disseminate new pediatric out-of-hospital protocols emergency care to become standard of care in a timely matter should be developed.
Abstract 93: The Potential Mechanisms of Reduced Incidence of VF as the Presenting Rhythm
Authors: Wang Hao , Tang Wanchun , Sun Shijie , Tsai Min-shan , Li Yongqin , Wang Tong , Weil Max H
Published: July 2021

Background. In our previous studies, we have demonstrated that the administration of both beta-adrenergic receptor blocker (βετα-blocker) and angiotensin converting enzyme (ACE) inhibitor significantly shortened the duration of ventricular fibrillation (VF). In the present study, we investigated the potential mechanisms of shortened VF durations by pre-treatment of βετα-blocker and ACE inhibitor.

Hypothesis. Both βετα-blocker and ACE inhibitor increase the duration of monophasic action potential (MAP) and ventricular fibrillation threshold (VFT) which accounted for the decreased duration of VF.

Methods and Results. Three groups from a total of 15 Sprague-Dawley rats weighing 450 –550 g were fed βετα-blocker propranolol (40 mg/kg/day), ACE inhibitor captopril (100 mg/kg/day), or diluent placebo continuously for 30 days prior to the experiment. MAP90 were measured by self-made contact electrophysiology catheter in an open chest rat model. VFT was determined as the lowest current intensity at which two consecutive stimuli precipitated VF using a previously reported method. Both propranolol and captopril significantly increased the VFT and MAP90 in comparison with placebo controls (Table

).

Conclusions. Increased VFT and MAP90 in a rat model pretreated with propranolol and captopril may be the potential mechanisms of reduced duration of VF.
Abstract 101: Gender Differences in the Timing of Access to the Prehospital Phase of STEMI Care
Authors: O’Connor Robert , Megargel Ross , DiSabatino Angela , Weintrub William , Reese Charles
Published: July 2021

Introduction
: The purpose of this study is to determine the degree of gender differences in lay person recognition, emergency medical services (EMS) activation, and the prehospital management of STEMI.

Methods
: Data were gathered prospectively from May 1999 to January 2007 on consecutive patients with STEMI who presented to a tertiary care hospital emergency department. Patients arriving by ambulance and private vehicle were included. Data collection included determining symptom duration, whether a prehospital ECG was obtained, whether the cardiac interventional lab was activated prior to patient arrival at the hospital, patient age, and hospital length of stay. Prehospital activation of the cath lab was done by emergency medicine based on paramedic ECG interpretation in consultation with cardiology. Statistical analysis was performed using the Mann-Whitney U test, the Yates-corrected chi-square test, and linear regression.

Results
: A total of 3260 cases were studied, of which, 3097 had complete data for analysis. Only EMS cases were included in the ECG analysis, and only patients having a prehospital ECG were included in the prehospital activation of cath lab analysis. Regression analysis showed that older age and female gender were significant predictors of access and arrival by EMS. The mean age in years was higher for EMS arrival (69 women; 59 men) than for private vehicle (62 women; 56 men).

Conclusion
: Women with STEMI tend to use EMS more frequently then men, but are older and wait longer before seeking treatment. Whether these factors contribute to the longer length of stay remains to be determined.
Abstract 535: Proteomics Analysis Identifies Positive Transcription Elongation Factor b as a Novel GATA-4-binding Partner Involved in Hypertrophic Responses in Cardiomyocytes
Authors: Sunagawa Yoichi , Morimoto Tatsuya , Kawamura Teruhisa , Takaya Tomohide , Wada Hiromichi , Shimatsu Akira , Hasegawa Koji , Fujita Masatoshi , Kita Toru
Published: July 2021

Introduction:
A zinc finger protein GATA-4 is one of the factors involved in transcriptional regulation during myocardial cell hypertrophy. In response to hypertrophic stimuli, GATA-4 forms a large complex with ERK, NFATc and an intrinsic histone acetyltransferase, p300. Disruption of this complex results in the inhibition of hypertrophic responses in cardiomyocytes.

Hypothesis:
We assessed the hypothesis that proteomics analysis may identify novel GATA-4-binding partners required for myocardial cell hypertrophy.

Methods:
GATA-4 was stably expressed as FLAG-HA-epitope fusion in HeLa cells by retroviral transduction. GATA-4 complex was purified from nuclear extracts of these cells by sequential immunoprecipitation with an anti-FLAG antibody followed by an anti-HA antibody (Tandem Affinity Purification).

Results:
By mass spectrometric analyses, we identified 73 GATA-4 binding proteins, including histone modifying factors, methyltransferase, HDAC and unknown proteins. One was cyclin-dependent kinases-9 (cdk9), a component of Positive Transcription Elongation Factor b (P-TEFb). Immunoblotting analyses demonstrated that GATA-4 formed a complex with p300, cdk9 and cyclin T1, another component of P-TEFb. A dominant-negative form of p300 disrupted the interaction of GATA-4 with cdk9 or cyclin T1. Conversely, a dominant-negative form of cdk9 and a cdk9 kinase inhibitor, 5,6-dichloro-1-h-ribofuranosyl-benzimidazole (DRB) inhibited p300-induced activation of GATA-4-dependent transcription as well as the acetylation of GATA-4. Stimulation of cardiomyocytes with phenylephrine (PE) increased the binding of GATA-4/p300 with cdk9 or cyclin T1. DN-cdk9 and DRB not only disrupted the complex of GATA-4/p300 with cdk9 or cyclin T1, but also repressed PE-induced hypertrophic responses such as myofibrillar organization, increase in cell size and promoter activation of the endothelin-1 and atrial natriuretic factors in cardiomyocytes.

Conclusion:
These findings demonstrate that cdk9 and cyclin T1 form a functional protein complex with GATA-4/p300 and that this large complex is a prerequisite for hypertrophic responses in cardiac myocytes.
Abstract 553: In Vivo Cardioprotection by Postconditioning is Mediated by Endogenous PAR2 Activation
Authors: Jiang Rong , Deneve Jeremiah , Eldaif Shady , Wang Ning-Ping , Zhao Zhi-Qing , Vinten-Johansen Jacob
Published: July 2021

Background
: Protease activated receptor 2 (PAR2) is a member of the seven transmembrane G-protein coupled receptor (GPCR) family. Activation of PAR2 is cardioprotective in ex vivo and in vivo myocardial ischemia reperfusion model, potentially by cognate ligands released at reperfusion (R). Postconditioning (postcon), defined as alternating brief (seconds) episodes of R and ischemia applied at the onset of R , is also cardioprotective. This cardioprotection involves activation of GPCR by adenosine, bradykinin and opioids. However, the role of the GPCR PAR2 in cardioprotection by postcon has not been investigated.

Hypothesis
: This study tested the hypothesis that cardioprotection by postcon is mediated in part by endogenous PAR2 activation.

Methods
: Rats were randomly assigned to one of 5 groups with 30 min left coronary artery (LCA) occlusion followed by 3 h reperfusion:

Control: no intervention was applied either before or after LCA occlusion (n =8);

Postcon alone: 3 cycles of 10-s full reperfusion and 10-s re-occlusion were initiated at the onset of R (n=8);

PAR2 antagonist alone: the selective PAR2 antagonist (FSLLRY-NH2, 1 mg/Kg) was injected 5 min before R (n=8);

PAR2 antagonist + Postcon: PAR2 antagonist (1 mg/Kg) was administered 5 min before Postcon (n=8);

Delayed PAR2 antagonist: PAR2 antagonist (1 mg/Kg) was given 5 min
after
the postcon protocol (n=8).

Results:
Area at risk (AAR) was comparable in all groups (35–38%). Compared to control, infarct size (TTC, area of necrosis/AAR, %) was significantly reduced by postcon alone (39.0% ± 1.3% vs 53.7% ± 1.5%, P<0.05). The PAR2 antagonist alone administered just before R had no effect on infarct size (57.4% ± 2.4% vs 53.7% ± 1.5%). Interestingly, the infarct sparing effect of postcon was completely reversed by PAR2 antagonist administered
before
postcon to control values ( 56.7% ± 2.7% *). Furthermore, the infarct sparing effect of postcon was also blocked by PAR2 antagonist given after postcon (50.3% ± 3.3% *). These results suggest that endogenous PAR2 activation induced by postcon during the early moments of R is cardioprotective.

Conclusions
: Cardioprotection by postcon is mediated, in part, by activation of endogenous PAR2, and suggests a general activation of GPCR. *P<0.05 vs Postcon.
An Uncommon Cause of Stroke in a 41-Year-old Female
Authors: Merchant Faisal M
Published: July 2021

Abstract 1761

Faisal M Merchant, Ricardo C Cury, Stuart Houser, Wilfred Mamuya, Massachusetts General Hospital, Boston, MA

Faisal M Merchant, 2007 Finalist and Presenting Author
2007 Laennec Clinician/Educator Lecture—Unraveling the Mysteries of Diastology
Authors: Nishimura Rick
Published: July 2021

Diastolic dysfunction plays a critical role in the pathophysiology of producing signs and symptoms of heart failure. Heart failure with a normal ejection fraction (HFnlEF) is one of the leading causes of hospital admissions today and is associated with significant morbidity and mortality. It is thus important to understand the pathophysiology of diastolic dysfunction, which itself is a complex series of multiple interrelated events, including relaxation, suction, ventricular interaction, ventricular arterial coupling, pericardial restraint, and myocardial viscoelastic forces.

It was difficult for the clinician to understand “diastology” in the past. Initial studies were limited to complex equations derived from animal models and were difficult to apply to patient care. The development of radionuclide angiography and Doppler echocardiography allowed noninvasive rapid assessment of volumetric filling and flow velocity curves, which began to provide insight into the complex process of diastolic filling for the clinician. As our understanding of diastology evolved over the past 2 decades, it has become clear that we now need to pursue new areas to understand this fascinating subject and apply it to patient care. These areas include the underlying mechanism HFnlEF (ventricular-vascular coupling versus true myocardial stiffness), relationship of rest versus exercise hemodynamics, and the complex ventricular fiber “twisting and shortening” of both contraction and relaxation.
Formation of Temporary Niches Is Required for Bone Marrow Cells To Adopt the Cardiomyogenic Fate In Vivo
Authors: Rota Marcello
Published: July 2021

Abstract 287

Marcello Rota, Jan Kajstura, Toru Hosoda, Claudia Bearzi, Serena Vitale, Grazia Esposito, Grazia Iaffaldano, Elena Padin-Iruegas, Arantxa Gonzalez, Roberto Rizzi, Narissa Small, New York Medical College, Valhalla, NY; John Muraski, San Diego State University, San Diego, CA; Xiongwen Chen, Temple University, Philadelphia, PA; Konrad Urbanek, New York Medical College, Valhalla, NY; Roberto Bolli, University of Louisville, Louisville, KY; Steven R Houser, Temple University, Philadelphia, PA; Annarosa Leri, New York Medical College, Valhalla, NY; Mark A Sussman, San Diego State University, San Diego, CA; Piero Anversa, New York Medical College, Valhalla, NY

Marcello Rota, 2007 Finalist and Presenting Author
Receptor-independent Effects of Estrogen on the HERG Channel Predispose Women to Drug-induced Arrhythmias
Authors: Kurokawa Junko
Published: July 2021

Abstract 289

Junko Kurokawa, Tokyo Medical & Dental University, MRI, Tokyo, Japan; Masaji Tamagawa, Chiba University Graduate School of Medicine, Chiba, Japan; Nobuhiro Harada, Shinichiro Honda, School of Med, Fujita Health University, Toyoake, Japan; Haruaki Nakaya, Chiba University Graduate School of Medicine, Chiba, Japan; Tetsushi Furukawa, Tokyo Medical & Dental University, MRI, Tokyo, Japan

Junko Kurokawa, 2007 Finalist and Presenting Author