bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17124: Aortic Valve Calcification as a Predictor of Post-TAVR Pacemaker Dependence
Authors: Sharma Esseim , Chu Antony F , McCauley Brian D
Published: July 2021

Introduction:
Atrioventricular block requiring permanent pacemaker (PPM) implantation is a common complication of TAVR. Our group has previously reported that a significant number of patients receiving PPM immediately post-TAVR do not require right ventricular (RV) pacing at 30 days. The mechanism of AV block during TAVR is not fully understood, but is thought to partly be due to the mechanical stress of TAVR deployment and resultant tissue edema, resulting in possible injury to the nearby compact AV node. Aortic valve calcification (AVC) may worsen this condition and has been associated with an increased risk for post-TAVR PPM implantation. We performed a retrospective analysis to determine if AVC is predictive for long-term RV pacing in post-TAVR pacemaker patients at 30 days.

Methods:
Prospectively collected data of 262 consecutive patients who underwent TAVR with placement of a balloon-expandable valve at Rhode Island Hospital from March 2012 to October 2016 were analyzed. AVC data were derived from contrast-enhanced computed tomography and characterized by leaflet sector and region.

Results:
A total of 25 patients (11.1%) required post-TAVR PPM implantation. Seventeen patients did not require RV pacing at 30 days. Nine of these 17 patients had no RV pacing requirement within 10 days. Non-coronary leaflet (NCL) calcium volume was significantly higher in patients who were pacemaker dependent at 30 days (
p
=0.01) and a calcium volume of >200mm
3
in the NCL was significantly associated with pacemaker dependence at 30 days (OR 51.9, 2.3-1170.2,
p
= 0.01). Pre-existing RBBB (OR 105.4, 4.52-2458.5, p=0.0002), bifascicular block (OR 12.50, 1.60-97.65, p=0.02), intra-procedural complete heart block (OR 12.83, 1.26-130.52, p =0.03), and QRS duration >120ms (OR 70.43, 3.23-1535.22, p=0.0002) were also significantly associated with pacemaker dependence at 30 days.

Conclusions:
Quantification of AVC by non-coronary leaflet calcium volume was found to be a novel predictor for RV pacing dependence at 30 days. The association of NCL calcification and pacemaker dependence may be related to the proximity of the conduction bundle to the non-coronary leaflet. Further studies are necessary to improve risk prediction for long-term RV pacing requirements following TAVR.
Abstract 17137: Unmasking Pathological Mechanisms of Long QT Syndrome
KCNH2
H70R Variant Using Human iPSC-Cardiomyocytes
Authors: Feng Li , Kim Gina , Eichel Catherine A , Liu Fang , Lim Evi , Anderson Corey L , Orland Kate M , Zhang Jianhua , Eckhardt Lee L , Robertson Gail A , January Craig T , Kamp Timothy J
Published: July 2021

Introduction:
Inherited long QT syndrome type 2 (LQT2) results from loss-of-function mutations in the
KCNH2
gene encoding the hERG channel, which conducts
I
Kr
, the rapid component of the delayed rectifier K
+
current. The N-terminal Per-Arnt-Sim (PAS) domain present on the hERG1a subunit, but not the hERG1b subunit, is the site of multiple LQT2-linked missense variants. The mechanism of loss of function by many of these missense PAS variants is unclear given conflicting results from different heterologous expression systems expressing hERG1a.

Hypothesis:
Patient-specific LQT2 human iPSC-cardiomyocytes (hiPSC-CMs) which naturally express hERG1a/1b carrying the
KCNH2
H70R variant in the PAS domain will exhibit loss of
I
Kr
associated with APD prolongation due to impaired channel protein trafficking.

Methods and Results:
Human iPSCs were derived from a patient carrying the LQT2-associated PAS domain mutation
KCNH2
H70R, which has been reported to cause impaired hERG channel trafficking without effects on channel gating when expressed in HEK 293 cells but accelerated deactivation kinetics of I
hERG
when expressed in
Xenopus laevis
oocytes. Two clones of
KCNH2
H70R and unrelated control hiPSCs (DF19-9-11T) were differentiated using monolayer-base, small molecule protocol to CMs, evaluated with whole-cell patch clamp. Action potentials from single hiPSC-CMs paced at 1Hz were prolonged in the hERG-H70R group compared to control (APD
90
439.9 ± 15.3 ms vs. 363.7 ± 29.0ms,
p
=0.003, H70R: n=11, control: n=9, Temp 36 ± 1°C). Voltage clamp studies showed hERG-H70R hiPSC-CMs had a significantly smaller peak tail I
Kr
current density (1.1 ± 0.3 vs. 2.9 ± 0.5 pA/pF,
p
<0.001, H70R: n=11, control: n=7, Temp 36 ± 1°C). The voltage dependence of I
Kr
activation (V½ and k) were not affected by the mutation; however, the fast (τf) and slow (τs) deactivation time constants were significantly decreased in hERG-H70R hiPSC-CMs. Further, Western blot characterization revealed impaired trafficking of hERG-H70R channels relative to control.

Conclusions:
The LQT2 PAS domain variant hERG-H70R results in loss of function of I
Kr
by both reduced membrane trafficking and accelerated deactivation of hERG in a hiPSC-CMs model which informs therapeutic approaches.
Abstract 17141: Mavacamten Improves Left Ventricular Relaxation and Compliance in Obstructive Hypertrophic Cardiomyopathy Through Direct Myosin Modulation
Authors: Heitner Stephen , Jacoby Daniel , Lester Steven , Owens Anjali T , Wang Andrew , Shah Amil , Hegde Sheila , Fang Liang , Sehnert Amy , Semigran Marc
Published: July 2021

Introduction:
Obstructive hypertrophic cardiomyopathy (oHCM) consists of a constellation of LV hypercontractility, LV outflow tract obstruction (LVOTO), and impaired relaxation, often resulting in dyspnea and reduced exercise capacity. In healthy dogs, the novel myosin modulator mavacamten (MAVA), decreased LV hypercontractility and improved compliance. In the PIONEER-HCM clinical study, improvements in post-exercise LVOT gradient, exercise capacity, and symptoms were reported. To examine whether MAVA could also limit residual myosin-actin cross-bridges during diastole, and improve LV compliance, its effects on diastolic indices were evaluated.

Methods:
In PIONEER-HCM, an open-label, multi-site, prospective study, oHCM subjects received MAVA for 12 weeks at either 10-20 mg/d (n = 11, Cohort A; 10 completed) or at 2-5 mg/d (n = 10, Cohort B). Echo-Doppler indices of LV filling and relaxation were compared at baseline to week 12. The p-values are from Wilcoxon signed rank tests, evaluating the distribution of within-subject 12-wk changes from baseline around a null of zero.

Results:
MAVA reduced hypercontractility in a dose-dependent fashion, with relief of LVOTO in all subjects achieving plasma MAVA concentration >350 ng/ml (data previously reported). There was also an increase in mitral annular velocity during early diastole (e’
lat
). There was a concomitant reduction in E/e’
lat
and increase in LV end-diastolic volume (LVEDV) consistent with improved LV compliance (Table). MAVA improved dyspnea score with a trend towards reduction in NT-proBNP.

Conclusions:
Administration of MAVA is associated with improvement in measures of myocardial relaxation (e’
lat
) and compliance in parallel with reduction in LVOT gradient. These findings are consistent with preclinical findings reported in healthy dogs and support additional evaluation of MAVA in patients with obstructive or non-obstructive HCM.
Abstract 17175: Trendsin Alcoholic Cardiomyopathy Hospitalizations and In-Hospital Mortality and Comorbidity. United States, 2005-2014
Authors: Sulaiman Samian , Jahangir Arshad , Muppidi Vijayadershan , Asfaw Addis , Shahreyar Muhammad , Yousef Nazdar , Wingert Romina
Published: July 2021

Background:
Yearly trends and prevalence of alcoholic cardiomyopathy (ACMP) hospitalizations and its associated in-hospital mortality, arrhythmia, complications and outcomes are not well studied on a national level.

Methods:
We used Nationwide Inpatient Sample database (2005-14) and identified 25402 hospitalizations for adults (≥18 yrs) with a primary or secondary diagnosis of ACMP . Since ACMP is a diagnosis of exclusion, all patients with a co-diagnosis of CAD or other causes of cardiomyopathy were excluded.

Results:
Taking the growth of the US general population into account, there was a decreasing number of ACMP hospital stays per 100,000 persons (4.38 in 2005 vs 3.62 in 2014; p < 0.001). Arrhythmias were present in in 48.7% of hospital stays. In-hospital mortality was 4.2% down-trending over years (4.3% 2005 vs 3.7% 2014) but this was not statistically significant (p = 0.78). Approximately 2.1% experienced cardiac arrest(uptrend from 1.4% to 3.2% in 2005-14; p <0.001). Prevalence of arrhythmia in this population has increased from 2005 to 2014 (46.5% vs 51.6%; p <0.001). Mean age was 55.01 ±12.2 yrs and 85.2% were male. Patients with arrhythmia were older (57.08 vs 53.03; p<0.01), had more comorbidities (Elixhauser index 2.55 vs 1.85; p < .01). Gender and racial differences were noted between arrhythmia and non-arrhythmia group respectively: Male (88.6% vs 82%; p< 0.01),White (68.2% vs 57.4%), Black (18.8% vs 28.5%) (p < 0.01) . AFib was the most common type of arrhythmia (30.7%), followed by V Tach (8.7%), unspecified arrhythmia (8.6%), and AFlutter (5.6%). Median charge per hospital stay was $25909. Median length of stay was 4 d. Despite that the Median length of stay (4 days) has not changed (4 days in 2005 vs 5 days in 2014; p = 16%), Median charge per hospital stay has increased from $18223.5 to $34056 : p <0.01. Cardioversion was performed in 1.2 %, Catheter ablation in 0.4 %, PPM implantation in 0.7 %, ICD in 1.5 %, cardiac catheterization in 16 % and VAD in 0.1% of hospitalizations for alcoholic cardiomyopathy. Utilization of these procedures has increased from 12% in 2005 to 14.6% in 2014 (p = 2.6%)

Conclusion:
There was a decreasing number of ACMP hospitalizations per 100,000 of US population. Despite the increased prevalence of arrhythmias in this population over years, the in-hospital mortality has not change, but rate of cardiac arrest has increased. The Median length of hospital stay has not changed, but the healthcare cost has significantly increased. This could be explained by the increased utilization of inpatient cardiac procedures.
Abstract 17190: Dual Hit of HIV-1 and Opioids Promote Oxidative Stress Mediated Pulmonary Endothelial Dysfunction
Authors: Sharma Himanshu , Agarwal Stuti , Chen Ling , Dhillon Navneet K
Published: July 2021

Introduction:
HIV related pulmonary hypertension is one of the serious non-infectious cardiovascular complications in HIV infected individuals, especially among intravenous drug users. We previously demonstrated that opioids in combination with viral protein(s) result in reactive oxygen species (ROS) mediated induction of autophagy in pulmonary endothelial cells leading to shift in the cells from apoptosis to apoptosis resistant proliferative status associated with angio-proliferative remodeling observed in PAH. Here, we delineate the major sources of HIV-1 and morphine induced oxidative burst and its role in development of PAH using in-vivo model.

Methods:
Human pulmonary microvascular endothelial cells (HPMECs) were treated with morphine and HIV-Tat in the presence or absence of ROS scavengers followed by measurement of ROS. Mitochondrial specific superoxide radicals were measured with MitoSOX dye and ratio of mitochondrial DNA to nuclear DNA was determined by real-time PCR. To assess the
in-vivo
effect of HIV-1 and morphine on pulmonary vascular dysfunction, male HIV-Tg/WT Fischer rats (n=7-13per group) were subcutaneously administered 10 mg/kg body wt. morphine or saline daily IP for 21 days. Right ventricle systolic pressure (RVSP) and fulton Index were measured along with immunohistochemistry analysis of lungs.

Result:
Increased oxidative stress in HPMECs in response to combined treatment of morphine and tat (M+T) was noted to be contributed by mitochondria, NADPH oxidase and xanthine oxidase as observed by the decrease in ROS production of M+T treated cells on pre-treatment with ROS scavenger viz., Mitotempo (mitochondria), VAS3947 (NADPH oxidase) and allopurinol (Xanthine oxidase). However, M+T mediated early apoptosis and late hyperproliferation of HPMECs was prevented in presence of NADPH oxidase inhibitor. In parallel we observed elevated mitochondrial specific ROS at 2 hr and increased mitophagy at 3h followed by increase in total mitochondrial mass at 4-6h of MT treatment. Further, we observed significant increase in RVSP and RV hypertrophy in HIV-Tg rats exposed to morphine compared to WT rats. Immunohistochemical analysis also showed significant pulmonary vascular remodelling including endothelial proliferation in lung sections from HIV+morphine rats.

Conclusion:
Our findings suggest NADPH oxidase specific ROS role in autophagy-dependent increased proliferation of M+T treated HPMECs. Further our in-vivo findings provide evidence of potentiation of PAH development with the dual hit HIV-1 and opioids.
Abstract 17193: Effect of Long Term Canagliflozin Use on Body Weight and Blood Pressure: A Systematic Review and Meta-Analysis
Authors: Khan Muhammad S , Siddiqi Tariq J , Usman Muhammad S , Memon Muhammad M , Khan Sadiya S , Shah Sanjiv J
Published: July 2021

Introduction:
Although Canagliflozin, an FDA-approved sodium-glucose cotransporter 2 inhibitor (SGLT2i), is known to reduce body weight and blood pressure (BP) in the short-term, it is unclear whether this effect persists in the long-term. Furthermore, it remains uncertain whether the reduction in BP and body weight is dose-dependent.

Objective:
To conduct a meta-analysis to study the effects of long term Canagliflozin use on BP and body weight in type 2 diabetes mellitus (T2DM) patients and stratify the results by dosage.

Methods:
MEDLINE and Scopus were queried in May 2018 for randomized controlled trials (RCTs) of Canagliflozin that had a follow-up period of at least one year and reported change in BP and percentage change in body weight. Data from included studies were pooled using a random effects model and results were presented as weighted mean differences (WMDs) with 95% confidence intervals (CIs). Subgroup analysis according to dosage (100mg/300mg) was performed. Chi-squared test was conducted to test for subgroup differences.

Results:
Five RCTs (N=15,230 participants) were included in the final analysis. Canagliflozin also led to significant reduction in body weight when compared to controls (WMD: -3.32% [-4.04, -2.60]; p<0.001); however, this effect was not found to be dose-dependent (p=0.76). Both systolic (WMD: -4.40 mmHg [-5.18, -3.62]; p<0.001) and diastolic (WMD: -1.68 mmHg [-2.14, -1.23]; p<0.001) BP were significantly lower with long-term canagliflozin use, when compared to placebo (Figure 1). This effect was significantly stronger in the 300mg subgroup, when compared to the 100mg subgroup for both systolic (p=0.02) and diastolic (p=0.01) BP. There was no significant change in the risk of hypotension with the use of canagliflozin (Odds ratio: 1.59 [0.80, 3.19]; p=0.19).

Conclusion:
Long-term Canagliflozin is associated with reduced body weight and may be one mechanism for the beneficial BP response observed
.
Favorable changes in body weight and BP may be responsible for improved cardiovascular outcomes in T2DM patients with Canagliflozin.
Abstract 17263: Pre-Clinical Left Ventricular Myocardial Remodeling in Patients With Friedreich’s Ataxia: A Cardiac MRI Study
Authors: Takazaki1 Karen A , Quinaglia A. C. Silva Thiago , Martinez Alberto , Neilan Tomas , SHAH Ravi , Jerosch-Herold Michael , Coelho-Filho Otavio R , França Marcondes C
Published: July 2021

Background:
Heart Failure (HF) is the most common cause of death in Friedreich’s ataxia (FRDA), an inherited mitochondrial disease. Myocardial fibrosis is a well-documented histopathological feature among FRDA patients with HF.

Objectives:
In this study we will investigate the myocardial extracellular volume fraction (ECV) and intracellular water lifetime (τ
ic
), using T1-weighted CMR imaging, in a cohort of patients with FRDA without signs of heart failure. We will also investigate whether myocardial tissue phenotyping by CMR can highlight particular characteristics of LV remodeling in FRDA’s cardiomyopathy, beyond those currently assessed with imaging-based classification of disease severity.

Methods:
Twenty-six FRDA’s patients (age 26.6±9.3 years, 15 women) without signs of HF, and 10 healthy controls (32.6±7.3 years, 5 women) underwent cardiac magnetic resonance (CMR) studies for assessment of left ventricular (LV) function, myocardial T1, late gadolinium enhancement (LGE), extracellular volume fraction (ECV), and intracellular water-lifetime (τ
ic
) as marker of cardiomyocyte size. Neurological decline was determined using the FRDA rating scale (FARS 3).

Results:
FRDA patients had normal LV ejection fraction (LVEF: 67.66±11.4 vs. 63.9±9.0, P=0.311), larger LV mass index (LVMASSi: 61.03±22.1 vs. 45±4.2g/m
2
, P<0.001), and decreased LV end-diastolic volume index (LVEDVi 53.42±12 vs. 75.7±16.1, P=0.002), compared with controls. ECV and τ
ic
, were increased in FRDA patients (ECV: 0.36±0.05 vs. 0.25±0.02, P<0.0001; τ
ic
: 0.13±0.07 vs. 0.06±0.03, P=0.001). ECV was positively associated with LV mass-to-volume ratio (r=0.628, P<0.001). FARS 3 correlated positively with disease duration (r=0.669, P<0.001), and negatively with τ
ic
, (r=0.478, P=0.039). LVMASSi and cardiomyocyte mass-index [(1–ECV)LVMASSi] declined with age, indicating that LV hypertrophy may transition to a “burn-out” phase with LV atrophy.

Conclusions:
LV hypertrophy in FRDA reflects an expansion of the myocardial interstitium and an increase in cardiomyocyte size. In contrast, the neurological decline was more likely with decreasing cardiomyocyte size, possibly an early sign of myocardial “burn-out” in FRDA.
Abstract 17289: Incidence of Cardiomyopathy and Mortality in Patients With Cobalt and Chromium Metal Hip Arthroplasty
Authors: Ponamgi Shiva P , Sharma Sunita , DeSimone Christopher V , Wyles Cody , Philip Sun Philip , Yogeswaran Vidushei , Padmanabhan Deepak , El-Harasis Majd , Hodge David , Slusser Joshua , Matthew Abdel Matthew , Asirvatham Samuel J
Published: July 2021

Introduction:
One million patients around the world have had total hip arthorplasty with 35% of them having metal-on-metal implants. Although there have been some case reports of cobalt cardiotoxicity from arthroprosthetic cobaltism resulting in dilated cardiomyopathy, incidence of cardiomyopathy and mortality in these patients is unknown.

Objective:
We therefore sought to determine the incidence of new onset cardiomyopathy (EF <40%) and associated mortality, in patients with metal hip arthroplasty.

Methods:
We retrospectively examined the records of the patients form our institutional total hip arthroplasty registry (Metal on Metal: MoM, Metal on Polyethylene: MoP, Ceramic on Ceramic: CoC and Ceramic on Polyethylne: CoP). Among 122 patients with baseline and follow up echocardiograms, cobalt and chromium levels were available in 12 patients, none of which developed incident cardiomyopathy.

Results:
The mean age of the population with metal group (MoM and MoP) was 53 years, predominantly males. During the follow up period of 10 years, the cumulative incidence (KM curve probabilities) of low EF <=40% in our study population was 14% in metal group as compared to 5% in non-metal group (CoC and CoP), (p value 0.51). At 15 years of follow up, among 122 patients, there were16 deaths in the metal group (81) and only 2 deaths in the non-metal group (41) (p value 0.15).

Conclusions:
In conclusion, although the incidence of cardiomyopathy as well as mortality is low in patients with metal hip arthroplasty and not significantly, further studies maybe needed to assess its effect on diastolic dysfunction.
Abstract 17305: The ER Unfolded Protein Response Effector, ATF6, Promotes Proliferation and Maintains Pluripotency in Cardiac Stem Cells
Authors: Stauffer Winston T , Doroudgar Shirin , Stephens Haley N , Blackwood Erik A , Glembotski Christopher C
Published: July 2021

Recent studies have suggested that multipotent stem cells residing in the adult heart, called cardiac stem cells (CSCs), mitigate damage in the infarcted or failing heart. Investigating the factors governing CSC proliferation and differentiation is key to understanding what role these cells play in the heart and in future therapeutic strategies. Additionally, activating transcription factor 6 (ATF6), an effector of the endoplasmic reticulum (ER) unfolded protein response (UPR), plays critical roles in development, as well as in the differentiation of certain stem cell types, though it has not been studied in this regard in the heart. Our lab has demonstrated that ATF6 in cardiac myocytes is cardioprotective
in vivo
during ischemia/reperfusion partly by virtue of its ability to induce an antioxidant gene program that reduces damaging reactive oxygen species (ROS). However, ATF6, and its involvement in antioxidant gene induction, have not been studied in CSCs. Therefore, here we hypothesized that activation of the ATF6 branch of the UPR in CSCs is important for their proliferation and differentiation, given that ROS is known to be essential for these processes. To address this hypothesis, we subjected cultured mouse CSCs to simulated ischemia and observed increased ATF6 target gene mRNA levels. This demonstrates that, despite their undifferentiated status, CSCs have a functional UPR, which can be activated in response to ischemic stress. ATF6 loss of function (LOF) in CSCs, via RNAi or chemical inhibitor, yielded a basal decrease in cell viability and an increase in several differentiation markers, similar to the effect of dexamethasone differentiation stimulus. Increased ROS was also observed in an ATF6 LOF model. Strikingly, cotreatment with a chemical ROS inhibitor significantly rescued cell viability and reduced markers of differentiation in CSCs with reduced ATF6 function. These results suggest that CSCs require a basal level of ATF6 activity to maintain their proliferation and pluripotentcy
in vitro
and that this is mediated by the role of ATF6 in the mitigation of ROS. This is an important finding given that stem cell expansion
in vitro
is a critical step in the characterization of stem cells and their use in many therapeutic treatment strategies.
Abstract 17317: Differential Coupling and Regulation of GIRK-Dependent Muscarinic and Adenosine Receptor Signaling in Mouse Sino-Atrial Nodal Cells
Authors: Anderson Allison , Wickman Kevin
Published: July 2021

Introduction and Hypothesis:
Parasympathetic slowing of heart rate is largely mediated by muscarinic receptor (M2R) activation of the G protein gated inwardly-rectifying potassium (GIRK) channel on sinoatrial-nodal (SAN) cells and atrial myocytes. The strength of M2R-GIRK signaling is negatively regulated by regulator of G protein signaling 6, RGS6. Genetic ablation of RGS6 in mice gives rise to enhanced M2R-GIRK signaling in SAN cells, resulting in both exaggerated M2R-induced bradycardia and increased susceptibility to pacing-induced atrial fibrillation. Adenosine receptor (A1R) activation, which can provoke atrial arrhythmias in human patients, can also activate GIRK channels, however, the details of A1R-GIRK signaling are poorly understood. Here, we investigated A1R-GIRK signaling in mouse SAN cells and tested the hypothesis that RGS6 negatively regulates A1R-GIRK signaling.

Methods and Results:
Using whole-cell patch-clamp electrophysiology, we measured the efficacy and potency of M2R- and A1R- GIRK signaling in adult SAN cells from wildtype and Rgs6
-/-
mice. We found SAN cells from Rgs6
-/-
mice displayed both prolonged channel deactivation kinetics and increased channel sensitivity to CCh-induced currents as compared to wild-type SAN cells. Surprisingly, we found no difference in kinetics or channel sensitivity of A1R-GIRK responses in Rgs6
-/-
SAN cells. We did observe, however, a striking, significant increase in the amplitude of the A1R-GIRK response in Rgs6
-/-
SAN cells compared to wild-type controls. Furthermore, occlusion studies in wild-type SAN cells suggest that M2R activates nearly all of the GIRK channels present in SAN cells, while A1R activation results in only partial GIRK channel activation. Intriguingly, RGS6 ablation seems to allow a larger proportion of GIRK channels to be activated by A1R. Recordings from mice lacking cardiac GIRK channels confirm that M2R- and A1R- induced currents are GIRK-dependent.

Conclusions:
Our results suggest that M2R-GIRK and A1R-GIRK are coupled differently within mouse sino-atrial nodal cells, resulting in differential regulation by RGS6.
Abstract 104: N-Acetyl Cysteine Improves Post Reperfusion Myocardial Dysfunction in a Rat Model of Cardiac Arrest and Return of Spontaneous Circulation
Authors: He Fenglian
Published: July 2021

N-acetylcysteine improves post reperfusion myocardial dysfunction in a Rat Model of Cardiac Arrest and return of spontaneous circulation

Introduction:
Studies have demonstrated that N-acetylcysteine (NAC) can attenuate regional myocardial ischemia/reperfusion injury and improved myocardial dysfunction. However, it is not clear whether NAC could protect post reperfusion myocardial dysfunction (PRMD) after cardiac arrest (CA) and return of spontaneous circulation (ROSC). In this study, we investigated the effect of NAC on post reperfusion myocardial dysfunction in a rat model of CA and ROSC.

Hypothesis:
NAC reduces the severity of PRMD in a rat model of CA and ROSC.

Method:
Ten healthy male Sprague-Dawley rats weighting 450g–550g were utilized, and randomly divided into two groups: 1) control group; 2) NAC group (150mg/kg). Ventricular fibrillation (VF) was induced. After 8 mins of VF, CPR was initiated for 8 mins, and defibrillation was then attempted. Myocardial function was measured by echocardiography at baseline, 2, 4 and 6 hours after successful resuscitation.

Result:
Except one in the control group, all animals were resuscitated. Myocardial function of post-resuscitation was significantly decreased in all animals. However, myocardial function gradually improved in animals treated with NAC when compared with those in control groups (Figure).

Conclusion:
In a rat model of cardiac arrest, NAC improves post-resuscitation myocardial dysfunction
Figure
The post-resuscitation myocardial dysfunction. BL, baseline; VF, ventricular fibrillation; CO, cardiac output; EF, ejection fraction; MPI, myocardial performance index; CPR, cardiopulmonary resuscitation; C group,control group; N group, NAC intervention group;

*
p

< 0.05.vs. the C group.
Abstract 118: The Epidemiology of Airway Management Following Pediatric Out-of-Hospital Cardiac Arrest in the United States
Authors: Naim Maryam Y , Griffis Heather , Berg Robert A , Bradley Richard N , Hansen Matthew L , Markenson David , McNally Bryan F , Nadkarni Vinay M , Vellano Kimberly , Rossano Joseph W
Published: July 2021

Introduction:
Bag mask ventilation (BMV) has been associated with improved survival following out of hospital cardiac arrest (OHCA), however advanced airway placement remains part of pre-hospital protocols for many emergency medical services (EMS) agencies.

Hypothesis:
To characterize airway management for pediatric OHCA and assess whether BMV alone vs. BMV plus advanced airway (supraglottic airway or tracheal intubation) is associated with neurologically favorable survival.

Methods:
Analysis of the Cardiac Arrest Registry to Enhance Survival database. Inclusion criteria were age ≤ 18 years, non-traumatic OHCA from 2013 through 2017, resuscitated by EMS. To adjust for covariate imbalance, propensity score matching and entropy balancing were utilized; variables included age category, sex, bystander CPR, and shockable rhythm. The primary outcome was favorable neurologically favorable survival defined as a cerebral performance category scale of 1 or 2.

Results:
Of 5241 cardiac arrests, 2588 (49.3%) had BVM and 2653 (50.6%) had advanced airway placement. The majority 5118 (97.7%) were resuscitated by agencies using both BMV and advanced airways. Advanced airway placement was more common in older children compared to infants, arrests with bystander CPR, in white and Hispanic children, witnessed arrests, arrests with a shockable rhythm, and AED use (Table). Neurologically favorable survival was significantly higher with BMV compared to advanced airways in bivariate analysis (11.4% vs. 5.7%, p<0.001). In multivariable analysis, advanced airway placement was associated with lower neurologically favorable survival (adjusted proportion 4.9% vs. 13.5% BVM, OR 0.21, 95% CI 0.17, 0.28). These results were robust on propensity analysis 3.0% advanced airway vs.11.9% BMV (OR 0.18, 95% CI 0.14, 0.25), and entropy balance 5.9% advanced airway, 15.0% for BMV (OR 0.28, 95% CI 0.22).

Conclusion:
In pediatric OHCA, advanced airways are placed in half of cardiac arrests where resuscitation is attempted. Advanced airway, compared to BMV alone management, is associated with lower neurologically favorable survival.
Abstract 127: The Effect of Cutoff Frequency Range on Amplitude Spectrum Area Performance in Predicting Defibrillation Outcome
Authors: Wu Xiaobo , Quan Weilun , Bradley Jennifer , Peberdy Mary Ann , Ornato Joseph , Tang Wanchun
Published: July 2021

Introduction:
Both clinical and experimental studies have demonstrated that ventricular fibrillation (VF) waveform-based amplitude spectrum area (AMSA) predicts defibrillation outcome with high sensitivity and specificity. A commonly used cutoff frequency range for calculation of AMSA is 4-48 Hz, but the median VF frequency in patients is less than 7 Hz. In the present study, we investigated whether the AMSA performance in predicting defibrillation outcome may be affected by different cutoff frequency ranges.

Hypothesis:
A selected cutoff frequency range would affect AMSA performance in predicting defibrillation outcome in patients.

Methods:
A total of 450 segments (179-defibrillation success and 271-defibrillation failure) of VF waveforms from patients with out-of-hospital cardiac arrest were analyzed. Each 4.096-s segment prior to defibrillation was acquired with a sampling rate of 250 Hz. Using MATLAB (MathWorks, Natck, MA), the AMSA of each segment of VF waveform was calculated with five cutoff frequency ranges (Shown in Figure 1). Sensitivity and specificity were calculated when defibrillation success rate was 50% which was estimated by a logistic regression curve. Area under the receiver operating characteristic curve (AUC) was used to evaluate AMSA performance within different cutoff frequency ranges.

Results:
AMSA threshold was decreased from 20.5 to 6.5 mV·Hz when the cutoff frequency range was changed from 3-48 Hz to 3-10 Hz (Figure 1). Sensitivity of AMSA in 3-10 Hz was increased by 81.3% compared with that of AMSA in 3-48 Hz. Specificity of AMSA in 3-10 Hz was decreased by 8.1% compared with that of AMSA in 3-48 Hz. The corresponding AUC was increased from 0.724 (3-48 Hz) to 0.768 (3-10 Hz).

Conclusions:
A cutoff frequency range of 3-10 Hz significantly increases the sensitivity of AMSA for predicting defibrillation success in patients with cardiac arrest with a slight decrease in specificity.
Abstract 128: Detection of Chest Compression Pauses by Automated External Defibrillators
Authors: Ruiz de Gauna Sofía , Ruiz Jesus M , Leturiondo Mikel , Saiz Purificación , Leturiondo Luis A , Arana Iker , Alonso Daniel , Ibarguren Karlos
Published: July 2021

Introduction:
Quality of cardiopulmonary resuscitation (CPR) improves if interruptions in chest compressions are minimized. Pauses in chest compressions can be deliberate (for rhythm ventilation or rhythm assessment) or inadvertent (rescuer distraction). Enhancing automated external defibrillators (AEDs) with the functionality of detecting chest compression pauses would be beneficial during resuscitation efforts and for debriefing purposes.

Objective:
To design and assess a method for the automated detection of chest compression pauses based on the transthoracic impedance (TI) signal acquired through AED defibrillation pads.

Methods:
Thirty-five AED recordings were randomly selected from a database collected by the Basque Country emergency medical service system (Spain). Recordings contained the ECG and the TI signals, and were randomly split into a training (10 episodes) and a test subset. Two experts on AED signal processing annotated the chest compression fraction (CCF) per episode, defined as the percent of total resuscitation time that compressions were performed. Our method computes the autocorrelation function (ACF) of the TI signal using consecutive 2-s segments. If the highest peak of the ACF in a predefined time interval is below a threshold, the 2-s segment is classified as a compression pause. The method was optimized using the training set.

Results:
Median (interquartile range, IQR) duration of the episodes in the test set was 1270 s (1113, 1605). CCF was 70.32% (66.12, 75.53). Sensitivity/positive predictive value in the detection of chest compression pauses were 97.64%/92.4%. The unsigned difference between annotated and computed CCF was 1.12% (0.43, 1.55).

Conclusions:
Computing the autocorrelation of the TI signal acquired through defibrillation pads could allow reliable detection of chest compression pauses. This method is simple and easy to implement in AEDs, and could be used to compute CCF for debriefing after resuscitation. Moreover, during real-time performance, AEDs could advise rescuers of inadvertent pauses or even proceed to rhythm analysis during ventilation pauses.
Abstract 136: Family Member Perceptions of Decision-Making for Comatose Survivors of Cardiac Arrest
Authors: Perman Sarah M , Siry Bonnie , Reich Jennifer A , Abella Benjamin S , Daugherty Stacie L , Havranek Edward P
Published: July 2021

Introduction:
Out-of-hospital cardiac arrest (OHCA) is an unexpected event that can render patients incapable of decision-making, requiring a surrogate decision maker (SDM), most often a family member, to be engaged. Yet how SDMs understand the information provided, and how they view their experience of making decisions for cardiac arrest patients is not well understood.

Methods:
This inductive qualitative study utilized data from semi-structured open-ended interviews with SDMs for OHCA patients. SDMs were approached: 1) at the bedside for consent to contact; and 2) 30 days after discharge/death to consent to interview. Interviews were conducted using a semi-structured interview guide, recorded, and transcribed for analysis. Transcripts were read in entirety and thematically coded by two investigators.

Results:
Over a 5-month period (1/18-5/18), 7 SDMs consented; however, 11 individuals were interviewed, as 3 SDMs invited family members to join the interviews. SDMs were living spouses (2), adult children (2), a parent (1) and siblings (2). Within this sample, 71.4% (5/7) of SDMs decided to withdraw life sustaining therapy or discontinue resuscitative efforts for their family member. Overall, experiences varied dramatically, with some families reporting a positive experience and others clearly reporting concerns about how the decision making process occurred. Major themes identified that affected the experience of decision-making include how SDMs perceived provider communication style, how they processed medical uncertainty from the providers, confidence in their decisions, and finally, conflict/discordance between the medical team and family. Families identified the following factors that might improve the decision making process for future SDMs; 1) updated “goals for the day”; 2) access to medical records; 3) Access to protocols for post-arrest patients; 4) a consistent liaison to the medical team; 5) consistent messaging amongst the care team.

Conclusions:
In this sample of SDMs, experiences with decision-making were variable. Notably, communication factors predominated in SDMs experience with decision-making. Finally, multiple important factors were identified to assist future SDMs in decision making for post-OHCA patients.
Abstract 198: Public Perceptions on Why Women Receive Less Bystander CPR Than Men in Out of Hospital Cardiac Arrest
Authors: Perman Sarah M , Shelton Shelby K , Knoepke Christopher , Rappaprt Kathryn , Matlock Daniel D , Adelgais Kathleen , Havranek Edward P , Daugherty Stacie L
Published: July 2021

Introduction:
Women who suffer an out of hospital cardiac arrest have been observed to receive less bystander cardiopulmonary resuscitation (CPR) than men. Potential reasons for why women receive less bystander CPR than men are largely unknown.

Methods:
Mechanical Turk (MTurk), Amazon’s crowdsourcing platform, was used to pilot a national survey asking participants why they believe women receive less bystander CPR than men. Eligible participants were adults (18 years or over) located in the US. Participants were reimbursed $1 for their participation. To ensure adequate knowledge on the subject, survey responses were excluded if they incorrectly defined CPR. Participant demographics as well as familiarity with CPR were queried. Participants were asked to answer the following free-text question “Do you have any ideas on why women may be less likely to receive CPR than men when they collapse in public?” Descriptive statistics were used to define the cohort. The free text response was coded using thematic analysis and major themes were identified via classical content analysis.

Results:
Within 55 minutes of deploying the pilot survey, 54 individuals responded. All respondents answered the knowledge question correctly, and none were excluded. Mean age was 36.9 ±9.6 years and 38.9% were female. Participants were geographically distributed as follows: 13% West, 13% Southwest, 16.7% Midwest, 27.8% Southeast, 29.6% Northeast. Predominant themes identified for why women might receive less bystander CPR than men are identified in Table 1. Within this cohort, 27.8% were trained in CPR, and only 5.6% of respondents had actually performed CPR on a person.

Conclusions:
In this pilot survey, public perceptions identified social norms regarding fear of inappropriate touching and hurting women as significant contributors to reasons for why women receive less bystander CPR than men. Additional work using a larger national sample to confirm and expand on these findings is ongoing.
Abstract 220: More Patience to the Patient? -The Timing of Initiating Targeted Temperature Management
Authors: Su Pei-I , Chang Chih-Heng , Huang Chien-Hua , Tsai Min-Shan , Chang Wei-Tien , Ma Huei-Ming , Chen Wen-Jone
Published: July 2021

Introduction:
The timing of Targeted Temperature Management (TTM) after Return of spontaneous circulation (ROSC) is controversial. Spontaneous neurological recovery can avoid the resource-wasting and adverse events of TTM. The purpose of this study is to determine the percentage of spontaneous recovery in a three-hour interval post ROSC, and to predict factors of recovery to Glasgow-Coma-Scale (GCS) Motor response 6 (M6).

Hypothesis:
Some patients may recover to GCS M6 in the early post ROSC period. These patients may also have favorable neurological outcome at discharge.

Methods:
This was a single center observational study which enrolled 541 patients with ROSC after OHCA. We recorded the motor response post ROSC, the motor response at 3hr, the patients’ characteristics, and resuscitation variables. Predictors of GCS M6 were assessed by multiple logistic regression analysis.

Results:
Graph 1 showed the number of patients with motor response change in a three-hour interval. All 96 patients with GCS M6 at 3hr had favorable neurological outcome, except 6 died from cardiogenic shock and 7 died from terminal cancer status. GCS M6 at 3hr, instead of GCS M6 post ROSC, was a predictor for favorable neurological outcome (OR, 2.09; 95%CI, 1.80-2.42; P= 0.0001) when adjusted with demographic and resuscitation variables. There were three factors predicting the GCS M6 at 3hr, including the cumulative epinephrine dose (OR, 0.81; 95% CI, 0.70 - 0.93; P=0.003), the CPR duration (OR, 0.957; 95% CI, 0.93 -0.98; P=0.001), and the initial shockable rhythm (OR, 4.41; 95% CI, 2.44 - 7.85; P=0.0001).

Conclusions:
A significant portion of patients had spontaneous recovery to GCS M6 within 3 hours, and had favorable neurological outcome. Certain factors could be used to predict the recovery in early post ROSC period. The optimal timing of TTM could be re-evaluated. Close monitoring GCS together with appropriate usage of sedation are critical for patients with higher chance of neurological recovery.
Abstract 222: Role of Pathologic Calpain Activity in Post-Cardiac Arrest Hypothermic Targeted Temperature Management
Authors: Jinka Tulasi R , Chalek Adam , Katzman Jacob , Ren Xiaodan , Neumar Robert W
Published: July 2021

Objective:
Optimization of post-cardiac arrest hypothermic-targeted temperature management (HTTM) is limited by an inadequate understanding of the fundamental mechanisms of action. This study tested the hypothesis that post-cardiac arrest HTTM reduces delayed secondary neuronal cytosolic Ca
2+
overload that causes pathologic calpain activity and neuronal death after cardiac arrest (CA)

Methods:
Male Long Evens rats were subjected to 8-minute asphyxial CA (ACA) followed by CPR. Rats that achieved return of spontaneous circulation (ROSC) were block randomized to normothermic- targeted temperature management (NTTM; n=13), hypothermic-TTM at 36
o
C (HTTM-36;n=13) or 33
o
C (HTTM-33;n=10). HTTM was initiated 1h after ROSC and maintained for 24h. Neurologic function score was assessed daily. Rats were euthanized at 48h post-ROSC. Regional brain homogenates were generated in a subset of animals for Western blot analysis of calpain-cleaved alpha-spectrin as a measure of pathologic calpain activity (n=6/group). Sham rats were used as uninjured controls (n=9)

Results:
Survival at 48h post-ROSC was 69%, 69%, and 90% in the NTTM, HTTM-36 and HTTM-33 groups respectively (p>0.05: chi-squared). Survival with good neurologic function (GNF: defined as NFS
>
450 out of 500) was 0%, 15%, and 60% in the NTTM, HTTM-36 and HTTM-33 groups respectively (p<0.05 for HTTM-33 vs. HTTM-36 and NTTM: chi-squared). Compared to NTTM, pathologic calpain activity in the hippocampus, cortex, caudoputamen, and cerebellum was decreased by 23±20%, 38±56%, 40±55%, 62±20% in the HTTM-36 groups and 33±13%, 55±72%, 66±89%, 69±17% in the HTTM-33 group respectively (p <0.05 for HTTM-33 and HTTM-36 cerebellum, p> 0.05 for all other regions: ANOVA, Tukey’s post-hoc)

Conclusion:
In this rat model of asphyxial cardiac arrest, HTTM with a target temperature of 33°C improved 48-hour survival with GNF compared to HTTM with a target temperature of 36°C and NTTM. Post-cardiac arrest regional brain calpain activity was significantly reduced with HTTM at 33°C and 36°C compared to NTTM in the cerebellum, but not other brain regions. Further work is needed to explore the potential causal link between the reduction of pathologic calpain activity and the neuroprotective effect of post-cardiac arrest HTTM
Abstract 229: Engagement With Text Messaged CPR Reminder Videos After Hands-Only CPR Training in Undergraduate Students
Authors: Vanscoy Rachel , Boyd Lyndsay , Benisek Alexis , Gibbons Emily , Panchal Ashish R
Published: July 2021

Background:
Ultra-brief CPR videos have been used to help facilitate community CPR through increased public lay-person viewing of CPR skills. Similar videos have also been used as video reminders following CPR training to increase skill retention. However, real-life engagement in watching reminder skills videos after CPR training is unknown. The objective of this study is to evaluate the engagement of undergraduate students in watching CPR training reminder videos sent via text message following community-based Hands-Only CPR training.

Methods:
Undergraduate students at the Ohio State University (age > 18 years old) were recruited for Hands-Only CPR training. After training, students received text message refresher videos via personalized links for 6 months. Initial Hands-Only CPR training was conducted through a 1-hr standardized course followed by confirmation of skills acquisition by Laerdal Resusci Anne
®
QCPR manikins during 2 minutes of Hands-Only CPR. CPR metrics evaluated included mean compression depth and rate (mean ± standard deviation). Following training, participants were sent one ultra-brief video per month for five months via text messaging. Our outcome of interest was engagement with viewing the reminder videos measured as the number of views per month per individual.

Results:
A total of 101 students (52 men and 49 females) were recruited during the 2017-18 academic school year. Initial Hands-Only CPR training was conducted with participants meeting guidelines for quality CPR with mean depth of 53 ± 9 mm and mean compression rate of 108 ± 10. During the 6 month post training period, 85% of participants watched the video at least once, 75% watched the video at least twice, and 50% watched three or more times. Only 14% did not watch any reminder videos. There was no difference in watching reminder video based on gender.

Conclusion:
Engagement of Hands-Only CPR trained undergraduate students in viewing a CPR reminder video at least twice in 6 months was high at 75%. Future research will be directed at determining whether reminder video viewings lead to retention of CPR skills.
Abstract 235: End-Tidal CO2 Monitoring in Non-Intubated Traumatic Brain Injury Patients Receiving O2 via Nasal Cannula vs. Non-Rebreather Mask
Authors: Barnhart Bruce J , Spaite Daniel W , Helfenbein Eric , Babaeizadeh Saeed , Jorgenson Dawn B , Hu Chengcheng , Rice Amber D , Keim Samuel M , Perez Octavio
Published: July 2021

Background:
The advent of highly sensitive End-Tidal CO2 (ETCO2) sensors allows effective monitoring of intubated patients in many emergency care settings, including EMS. Previous work has explored the use of ETCO2 monitoring in non-intubated patients with sensors placed in the nares. However, nothing is known about the effect of passive oxygen delivery [nasal cannula (NC) or non-rebreather mask (NRB)] on ETCO2 measurement.

Objective:
To compare ETCO2 measurements in non-intubated Traumatic Brain Injury (TBI) patients receiving O2 via NC vs NRB in the prehospital setting.

Methods:
A subset of major TBI cases (CDC Barell Matrix Type-1) in the Excellence in Prehospital Injury Care (EPIC) TBI Study (NIH/NINDS-1R01NS071049; ClinicalTrials.gov-NCT01339702) were evaluated 4/13-3/17). Non-intubated cases from 6 EMS agencies providing monitor data (Philips MRx) were included when continuous ETCO2 data were available. Statistics: Two-tailed t test, α = 0.05.

Results:
The 104 included cases had median age of 50.5 (range: 9-91; male: 67%). 39 (37.5%) received O2 via NC and 65 (62.5%) via NRB. Mean ETCO2: NC cases: 27.7 mmHg (95% CI: 25.7, 29.8); NRB: 30.0 (28.1, 31.8; p=0.132). There were also no significant differences among the mean lowest recorded values (p=0.449) or the mean highest values (p=0.275).

Conclusion:
We believe this is the first report comparing ETCO2 values based upon the method of passive O2 delivery in non-intubated patients. The minor differences between NC vs NRB-oxygenated patients was neither statistically nor clinically significant. This is surprising since: 1) the O2 flow rates and 2) the open-air (NC) vs mask (NRB) delivery methods are so dramatically different. Future study is needed to identify the clinical implications of using noninvasive ETCO2 measurement as a tool for monitoring ventilatory status and changes in non-intubated TBI (and other) patients.