bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 329: Six at Six: Interleukin-6 Measured at 6 Hours After Cardiac Arrest Is a Good Predictive Biomarker of Outcome of Post--Cardiac Arrest Syndrome in Humans
Authors: Shinozaki Koichiro , Becker Lance B , Oda Shigeto , Hirasawa Hiroyuki
Published: July 2021

Introduction:
As early as 3h after cardiac arrest (CA), the blood level of various cytokines increases and may be associated with outcome of post cardiac arrest syndrome (PCAS). However, it remains uncertain whether blood levels of these cytokines including IL-6 have significance as predictors of outcome following cardiac arrest.

Objective:
To demonstrate any association between circulating IL-6 level, one of major pro-inflammatory cytokines, and mortality in PCAS of humans.

Methods:
This was a multicenter observational study conducted between 2006-09 in Chiba, Japan, involving non-trauma CA adult patients. All patients admitted to acute care units were included. Patient characteristics were extracted following an Utstein template. The primary outcome was mortality through the end of the study. IL-6 blood levels were measured on admission, at 6hr, and 24hr after CA. Patients were classified into three groups (high, middle, and low) according to IL-6 levels at each time point. We evaluated the association of IL-6 levels with survival using the Kaplan-Meier method. A Cox proportional hazard model with a step-wise selection procedure was used to identify independent variables associated with overall survival.

Results:
A total of 227 patients were included in this study. Survival time in “High IL-6” group was shorter than “Low” group. There were significant differences in blood level of IL-6 in the three groups, high (>811pg/mL), mid (811-93pg/mL), and low (<93pg/mL), only at 6hr (long rank; high vs. low p<0.001, high vs. mid p=0.07, and mid vs. low p=0.001 on admission; p<0.001, p<0.001, and p<0.001 at 6hr, respectively; p<0.001, p<0.001, and p=0.936 at 24hr, respectively). Three factors were identified as independent predictors of early death; no bystander CPR (hazard ratio [95% confidential interval], 2.59 [1.10-6.10], p=0.03), a lack of therapeutic hypothermia (2.68 [1.70-4.22], p<0.001), and IL-6 levels at 6hr (high, reference; mid, 0.41 [0.25-0.66], p<0.001; low, 0.11 [0.06-0.20], p<0.001).

Conclusions:
IL-6 measured at 6hr can predict mortality. It should be studied further to see if it can help direct therapeutic decision-making and whether it can define optimal populations for study in clinical trials.
Abstract 332: Differences in Vital Signs Between Elderly and Non-Elderly Patients Prior to Ward Cardiac Arrest
Authors: Churpek Matthew M , Yuen Trevor C , Winslow Christopher , Hall Jesse B , Edelson Dana P
Published: July 2021

BACKGROUND:
Vital signs and composite risk scores, such as the Modified Early Warning Score (MEWS), are used to identify high-risk patients, trigger rapid response teams, and assist with triage decisions. Although age-related vital sign changes are known to occur, little is known about the differences in vital signs between elderly and non-elderly patients prior to ward cardiac arrest (CA). We compared the accuracy of vital signs and the MEWS for detecting CA between elderly and non-elderly patients.

METHODS:
All patients hospitalized on the wards from five hospitals were included in the study. Patient characteristics and vital signs prior to CA were compared between elderly (age ≥65 years) and non-elderly (age <65 years) patients. The area under the receiver operating characteristic curve (AUC) was also calculated for vital signs and the MEWS for elderly and non-elderly ward patients for CA.

RESULTS:
A total of 269,956 admissions with documented age occurred during the study period, which included 422 index ward CAs. Within four hours of CA, elderly patients had significantly lower mean heart rate (88 vs. 99 beats per minute; P<0.001), diastolic blood pressure (60 vs. 66 mm Hg; P=0.007), and shock index (0.82 vs. 0.93; P<0.001), and higher pulse pressure index (0.45 vs. 0.41; P<0.001) and temperature (97.6 vs. 97.3 °F; P=0.047). The AUCs for all vital signs and the MEWS were higher for non-elderly patients than elderly patients (MEWS AUC 0.85 (95% CI 0.82-0.88) vs. 0.71 (95% CI 0.68-0.75); P<0.001). While the incidence of CA increased with age, accuracy of the MEWS decreased (Figure).

CONCLUSIONS:
Vital signs are much more accurate for detecting CA on the wards in non-elderly patients compared to elderly patients, which has important implications for how they are used for identifying critically ill patients. Further investigation into improving the accuracy of risk stratification for elderly patients is necessary in order to decrease their risk for this devastating event.
Abstract 339: Capillary Transmitted Light Intensity for the Monitoring of Tissue Perfusion: CLIP Study
Authors: Morimura Naoto , Sakamoto Tetsuya , Matsumori Kyoko , Takahashi Kohei , Doi Tomoki , Otsuka Tsuyoshi , Nakamura Kyota
Published: July 2021

Background:
We developed a new device for quantifying capillary refill time (CRT) by applying the pulse oximeter principle, and reported the excellent correlation between quantitative CRT (Q-CRT) and tissue hypoperfusion status as represented by arterial blood lactate levels in critically ill patients in the pilot study.

Methods:
Diagnostic accuracy study was undergone in ICU of a tertiary emergency medical center. While the pulse oxygen saturation sensor was placed on the finger of the patients, transmitted light intensity was measured with a pulse oximeter (OLV-3100, Nihon Kohden Corp., Japan) before start and during compression of the finger. Correlation between delta Ab, defined as the absorbance of light intensity of infra-red (A-ir) minus that of red (A-r), and arterial blood lactate level was analyzed.

Results:
The delta Ab was analyzed a total of 69 waveforms in 23 patients. The sensitivity, specificity, positive predictive value, and negative predictive value of the delta Ab less than 0.06 for predicting a lactate level more than 2.0 mmol/l were 100%, 93%, 89%, 100%, respectively.

Conclusions:
The delta Ab was well correlated to high level of blood lactate level in critically ill patients. Further study will confirm to place the delta Ab as one of non-invasive predictors of tissue perfusion status.
Abstract 344: Massive Transfusion Prediction Scores Can Also Predict Early Traumatic Coagulopathy
Authors: Ogura Takayuki , Nakano Minoru , Nakamura Mitsunobu , Fujizuka Kenji
Published: July 2021

BACK GROUND:
The aggressive administration of plasma has been recommended for the improvement of traumatic coagulopathy. The survival benefit has been found in trauma resuscitation with rich plasma, and this benefit seems to be related to early use of this blood product. However, to our knowledge, no method for the recognition or prediction of traumatic cougulopathy at the point of a patient’s arrival has been established. The aim of this study was to test the predictive value of massive transfusion prediction scores for early traumatic coagulopathy.

METHOD:
We reviewed records of severe trauma patients admitted to our center from Jan. 2008 to Mar. 2014, whose Injury Severity Score was 16 or more. Traumatic Bleeding Severity Score (TBSS), Trauma Associated Severe Hemorrhage Score (TASH Score), and Assessment of Blood Consumption Score (ABC Score) were calculated. Early traumatic coagulopathy was defined as 150mg/dl or less of fibrinogen and 1.5 or more of PT-INR within 6 hours from injury, although transfusion and crystalloid infusion was provider dependent. Cardiopulmonary arrest patients on arrival and simple head or spine trauma patients were excluded. Each predictive value for early traumatic coagilopathy was tested by area under the receiver operating characteristic curve (AUC). Receiver operating characteristic curve comparison was performed to compare the accuracy between TBSS, TASH Score, and ABC Score. Each spearman’s rank correlation coefficient for the amount of fresh frozen plasma transfused within 24 hours form injury was checked.

RESULT:
388 patients were enrolled in this study. The AUC of TBSS (0.927) was significantly higher than that of TASH Score (0.856) or ABC Score (0.726) (both Bonferoni adjusted p<0.01). Each Spearman’s rank correlation coefficient for the amount of fresh frozen plasma was 0.732 (TBSS, p<0.01), 0.658 (TASH Score, p<0.01), and 0.471 (ABC Score, p<0.01).

Conclusion:
Massive transfusion prediction scores can also predict the early traumatic coagulopathy. TBSS had the highest predictive value and strong correlation between the score and the needed plasma. The calculation of TBSS is simple. Therefore, TBSS will rapidly predict the need for rich plasma transfusion.
Abstract 44: Time to Epinephrine Impacts Mortality Following Pediatric In-Hospital Nonshockable Cardiac Arrest
Authors: Andersen Lars W , Berg Katherine , Saindon Brian Z , Massaro Joseph M , Raymond Tia T , Berg Robert , Nadkarni Vinay , Donnino Michael W
Published: July 2021

Background:
Delay in administration of the first epinephrine dose has been shown to be associated with a lower chance of good outcome in adult, in-hospital, non-shockable cardiac arrest. Whether this association is true in pediatric in-hospital non-shockable cardiac arrest remains unknown.

Methods:
We utilized the Get With the Guidelines - Resuscitation national registry to identify pediatric patients (age < 18 years) with an in-hospital cardiac arrest between 2000 and 2010. We included patients with an initial non-shockable rhythm who received at least one dose of epinephrine. To assess the association between time to epinephrine administration and survival to discharge we used multivariate logistic regression models with adjustment for multiple predetermined variables including age, gender, illness category, pre-existing mechanical ventilation, monitored, witnessed, location, time of the day/week, year of arrest, insertion of an airway, initial rhythm, time to initiation of cardiopulmonary resuscitation, hospital type and hospital teaching status. Secondary outcomes included return of spontaneous circulation (ROSC) and neurological outcome.

Results:
1,131 patients were included. Median age was 9 months (quartiles: 21 days - 6 years) and 46% were female. Overall survival to hospital discharge was 29%. Longer time to epinephrine was negatively associated with survival to discharge in multivariate analysis (OR: 0.94 [95%CI: 0.90 - 0.98], per minute delay). Longer time to epinephrine was negatively associated with ROSC (OR: 0.93 [95%CI: 0.90 - 0.97], per minute delay) but was not statistically significantly associated with survival with good neurological outcome (OR: 0.95 [95%CI: 0.89 - 1.03], per minute delay).

Conclusions:
Delay in administration of epinephrine during pediatric in-hospital cardiac arrest with a non-shockable rhythm is associated with a lower chance of ROSC and lower survival to hospital discharge.
Abstract 55: The CAHP (Cardiac Arrest Hospital Prognosis) Score: Predicting Neurological Outcome After Out-of-Hospital Cardiac Arrest
Authors: Maupain Carole , Bougouin Wulfran , Lionel Lamhaut , Deye Nicolas , Jost Daniel , Geri Guillaume , Perier Marie-Cecile , Beganton Frankie , Marijon Eloi , Jouven Xavier , Cariou Alain , Dumas Florence
Published: July 2021

Background:
Out-of-hospital cardiac arrest (OHCA) carries a very poor prognosis. Early prognostication of patients admitted in ICU after resuscitated OHCA is a key issue but remains challenging. The aim of that study was to establish a new scoring system to predict poor neurological outcome in these patients.

Materials and Methods:
The CAHP (Cardiac Arrest Hospital Prognosis) score was developed from the Sudden Death Expertise Center registry (SDEC, Paris, France). Objective risk factors were weighted on the basis of a logistic regression analysis. The primary outcome was poor neurological outcome defined as Cerebral Performance Category 3, 4 or 5. Thresholds were defined to distinguish low, moderate and high-risk groups. The CAHP score was then validated in an external dataset (Parisian OHCA Registry). Score calibration and discrimination characteristics were assessed in the validation dataset.

Results:
The developmental dataset included 819 patients admitted in ICU from May 2011 to December 2012. After logistic regression, 7 variables were independently associated with poor neurological outcome: age, initial shockable rhythm, time form collapse to basic life support (BLS), time from BLS to return of spontaneous circulation (ROSC), location of cardiac arrest, epinephrine dose during resuscitation and arterial pH at admission. These variables were included in the CAHP score. 3 risks groups were identified: a low risk group (score ≤ 150, 39 % of unfavorable outcome), medium risk group (score 150-200, 81% of unfavorable outcome) and high-risk group (CAHP score ≥ 200, 100 % of unfavorable outcome). AUC of the CAHP score was 0.93. In the external validation dataset, discrimination value of the CAHP score was consistent with an AUC of 0.85.

Conclusion:
The CAHP score is a simple and objective tool for early assessment of prognosis in patients admitted to ICU after OHCA. Moreover it allows to stratify the probability of poor neurological outcome by identifying a very high-risk category of patients (score ≥ 200).
Abstract 60: Survival After Ventricular Fibrillation in Sao Paulo Metro
Authors: Gianotto-Oliveira Renan , Gonzalez Maria M , Vianna Caio B , Alves Maurício M , Timerman Sergio , Kalil-Filho Roberto , Kern Karl B
Published: July 2021

Background:
Automated external defibrillators (AEDs) in public places can improve the rate of survival among patients who have had an out-of-hospital cardiac arrest (OHCA). Sao Paulo Metro carries about 4.5 million people per day and since 2006, the security officials of metro (lays rescuers) are trained in cardiopulmonary resuscitation (CPR) and handling of AED. This program also included the installation of AEDs in every metro station.

Methods:
From September 1, 2006, through November 31, 2012, we conducted a prospective, longitudinal, observational study involving patients who had cardiac arrest in Sao Paulo Metro and were attempted by security officials of metro. The outcome of each patient was followed through medical records of the hospitals to which patients were referred. Reading the AED registration of each patient was performed. The primary end-point was minimal neurologic impairment after hospital discharge.

Results:
A total of 102 sudden collapses were included in the study; 86 were cardiac arrest and 62 of these patients had ventricular fibrillation with initial cardiac rhythm. The percentage of patients who achieved sustained return of spontaneous circulation was 45 (73%), 34 (55%) of patients arrived alive at the hospital and 23 (37%) were discharged and were alive at 1 year with minimal neurologic impairment. Comparing the periods of the Sep/2006-Nov/2009 with Oct/2009-Nov/2012, respectively, the rate of patients without neurological impairment before discharge and at 1 year was 22% versus 45% (p=0.072). Multivariate logistic regression analysis revealed that the time interval in minutes between collapse and first shock was the only variable independently associated with the primary end point (odds ratio = 0.13, 95 % CI 0.05 to 0.38, p <0.0001).

Conclusion:
The study supports a significant beneficial impact of implementation of PAD program in Sao Paulo Metro. Shorter intervals between arrest and defibrillation are necessary to achieve the highest survival rates. These results support strategic expansion of PAD programs in similar places in Brazil.
Abstract 65: Evaluating the Role of Continuously Monitoring Regional Cerebral Oxygen Saturation in Predicting the Return of Spontaneous Circulation in Cardiac Arrest Patients: Does the Use of an Electrocardiogram Alone Provide Adequate Information During Cardiopulmonary Resuscitation?
Authors: Kano Hitoshi , Saito Tomoyo , Matsui Toshihisa , Endo Akio , Nagama Masaki , Iwanaga Wataru , Takahashi Kanako , Makise Hiroshi
Published: July 2021

During CPR as it is currently administered, treatments are selected from an algorithm derived by monitoring with ECG alone. One of the reasons for this is that no other devices are presently thought to be effective in helping to make treatment determinations. Monitoring of regional cerebral oxygen saturation with near infrared light is non-invasive and provides information on brain tissue oxygenation and hemodynamics. The results of our study suggest that measurements derived from continuously monitoring regional cerebral oxygen saturation during CPR can be considered an effective method of predicting the ROSC in cardiac arrest patients.

Methods:
In 95 patients with out-of-hospital cardiac arrest, the tissue oxygenation index (TOI) was continuously monitored (NIRO-200NX, Hamamatsu Photonics). We investigated the following parameters with respect to whether or not ROSC was achieved: TOI value at the contact of patients (initial TOI); TOI value just before ROSC (pre-ROSC TOI); and the maximum TOI during CPR (maximum TOI).

Results:
All the patients monitored received treatment with shocks or drugs and the initial TOI was 35.3±7.3%. For 74 patients who did not achieve ROSC, the maximum TOI was 41.0±7.4%, whereas for 21 patients who did achieve ROSC, the pre-ROSC TOI was 51.3±3.6% and the maximum TOI was 64.3±11.4%. ROSC was not achieved in the patients with maximum TOI below 45%.

Conclusion:
The pre-ROSC TOI was significantly higher than the maximum TOI in the patients who did not achieve ROSC which suggests the possibility of predicting ROSC by monitoring the increase in TOI. In cases where the TOI remains low, there is a possibility that ROSC should not be expected. In such cases, it may be desirable to attempt to improve the quality of CPR to increase the TOI before delivering shocks or administering drugs.
Abstract 74: The Survival Benefit of Coronary Angiography After Cardiac Arrest Is Observed Only in Patients with Shockable Rhythms
Authors: Preston Robert J , Stratford Chris , Taillac Peter , Youngquist Scott
Published: July 2021

BACKGROUND:
The identification and treatment of a reversible cause of arrest is considered an important step in post arrest care. Observational data suggests a survival benefit is derived from the performance of coronary angiography in post cardiac arrest patients who survive to hospital admission. We hypothesized that the benefit of this therapy would be diminished in victims who presented with non-shockable rhythms.

METHODS:
We analyzed a prospectively-collected registry of all cardiac arrests in the state of Utah between July 1, 2012 through December 31, 2013. We compared outcomes of patients surviving to hospital admission, stratified by presenting rhythm and performance of angiography. Logistic regression was used to control for confounders.

RESULTS:
During the study period, 464/1,534 (30.2%) out-of-hospital cardiac arrest victims survived to hospital admission. Coronary angiography was performed in 133 (28.7%). Neurologically-intact survival was higher in patients with shockable rhythms who underwent angiography compared with those who didn’t (73% vs 32%, p<0.0001, TABLE). However, this survival benefit was not apparent in patients with a presenting rhythm of asystole or pulseless electrical activity (17% vs 20%, p=0.7). When stratified by presenting rhythm and controlling for age, witnessed arrest, bystander CPR, and gender, only victims with an initial shockable rhythm demonstrated increased odds of neurologically-intact survival (OR 5.9, 95% CI 2.9-11.7, p<0.0001)

CONCLUSIONS:
Our analysis suggests that post arrest angiography, on average, provides a survival advantage only among victims with an initial shockable rhythm. However, this data is observational and prone to selection bias and residual confounding.
Abstract 75: Ventricular Fibrillation in Cardiac Arrest with Nonshockable Initial Rhythm
Authors: Rosell-Ortiz Fernando , Mellado-Vergel Francisco J , Fernández-Valle Patricia , Caballero-García Auxiliadora , González-Lobato Ismael , Vergara-Pérez Santiago , Ruiz-Montero María M , Martínez-Lara Manuela , Vivar-Díaz Itziar , García del águila Javier
Published: July 2021

The initial shockable rhythm in cardiac arrest is a well known factor of good prognosis. Little is known about the influence of the onset of ventricular fibrillation during resuscitation at cardiac arrest whose initial rhythm was non-shockable.

Methods:
Retrospective analysis of a continuous registry of out-of-hospital cardiac arrest (OHCA) Inclusion criteria, all consecutive patients suffering OHCA attended by emergency teams in Andalusia, Spain. Period January 2008 - December 2012.

Results:
5067 patients were included. According to the initial cardiac arrest rhythm 1038 (20.5%) cases presented initial shockable rhythm (SR) and 4029 (79.5%) with non-shockable initial rhythm (NSR). Of these patients 150 (3%) reported one or more episodes of ventricular fibrillation during resuscitation (NSRVF). The main clinical characteristics of these three groups are shown in Table 1. Variables associated with good neurological status at hospital discharge are shown in Table 2.

Conclusions:
NSRVF patients present higher survival with good neurological status than NSR patients. These patients may represent a third prognostic group in cardiac arrest with a survival rate between shockable and non-shockable initial rhythms.

Table 1. Clinical data of patients regarding rhythm of cardiac arrest

Table 2. Variables associated with good neurological status at discharge (CPC
1-2
) SD: Standard deviation. IQR: Interquartile range. OR: Odds Ratio. CI: Confidence Interval. ET: Emergency Team. VF: Ventricular Fibrillation. CPR: Cardiopulmonary resuscitation. CPC: Cerebral Perfomance Category. ROSC: Return of spontaneous circulation
Abstract 9: The Effect of CPR Quality: A Potential Confounder of CPR Clinical Trials
Authors: Yannopoulos Demetris , Abella Benjamin , Duval Sue , Aufderheide Tom
Published: July 2021

Background:
The Resuscitation Outcomes Consortium (ROC)-PRIMED clinical trial evaluated an active inspiratory impedance threshold device (ITD) during standard CPR (intended to improve CPR hemodynamics) on survival to hospital discharge with favorable neurological outcome (modified Rankin Score [mRS] ≤3) in adults with out-of-hospital cardiac arrest and found no benefit. CPR quality varied widely in the trial. We hypothesized the quality of CPR provided would have a significant interaction with the intervention.

Methods:
We used the NIH public access ROC-PRIMED database. A large proportion of patients had CPR quality parameters (compression rate, depth and fraction) collected. “Quality CPR” was considered delivered if simultaneous provision of the following occurred: a compression rate of 80-120, depth of 4-6 cm and fraction of >50%, consistent with American Heart Association guidelines at the time of the study. We assessed for interaction between each individual parameter of “quality CPR” and their combinations with the active and sham ITD for survival with mRS≤3. Interaction was considered to be significant when p<0.1.

Results:
Overall, a total of 848 and 827 patients in the active and sham ITD groups had documented “quality CPR” performed. Including all presenting rhythms, use of an active ITD increased survival to hospital discharge with MRS ≤3 compared to sham (61/848 [7.2%] versus 34/827 [4.1%], respectively; p=0.006, OR: 1.8, 95% CI: 1.17, 2.78). There was significant interaction between the active and sham ITD and compression rate, depth and fraction as well as their combinations. (Table 1)

Conclusion:
When “quality CPR” was delivered, the active ITD improved survival with mRS≤3 by an absolute 3.1%. CPR quality parameters showed significant interaction with the active and sham ITD. The quality of CPR delivered is a potential confounder of CPR clinical trials and should be appropriately controlled.
Abstract 9389: Thrombus Formation Processes are Dependent on Endothelial Injuries: Examined by in vivo Two-photon Molecular Imaging
Authors: Nishimura Satoshi
Published: July 2021

Aim:
The cellular mechanisms of thrombotic diseases associated with cardiovascular events remains unclear, largely because of an inability to visualize thrombus formation. Thus, we developed in vivo imaging technique based on single- and multi-photon microscopy and laser injuries technique to revealed the multicellular processes during thrombus development.

Methods:
We visualized the cell dynamics including single platelet behavior, and assessed dynamic cellular interplay in two thrombosis models using two photon microscopy to CAG-eGFP mice (Figure a, b).

Results:
First, we visualized that rapidly developing thrombi composed of discoid platelets without EC disruption was triggered by ROS induced by laser irradiation (Figure c). In this model, thrombus consisted by discoid platelet aggregations without leukocyte recruitment and not affected by Gr-1 antibody. The second model is, thrombus with EC disruption. High power laser induced EC erosion and extravasations of circulating leukocytes with thrombus development. Inflammatory cytokine, adhesion molecules dynamically control these two processes, and Gr-1 antibody significantly suppressed these steps. (Figure d) Leukocyte was immediately recruited into the subendothelial layers with bleeding and hemostatic reactions, and TLR4 signaling contributed to these steps. Pretreatmet of LPS or ischemic procedures markedly enhanced these steps. Thrombus included calcium activated cores and deformed platelets. Immigrated leukocyte also showed the increase of intracellular calcium.

Summary:
These results indicated that endothelial function, especially inflammatory status, determined the thrombotic reaction. Leukocyte also contributed with TLR4 signaling. In sum, using our imaging system can be a powerful tool to analyze thrombus formation and evaluate the therapeutic strategies.
Abstract 9412: The Significance of Aldehyde Dehydrogenase 2 Polymorphisms in Coronary Spastic Angina
Authors: Mizuno Yuji , Harada Eisaku , Morita Sumio , Morikawa Yoshinobu , Nakagawa Hitoshi , Katoh Daisuke , Kashiwagi Yusuke , Murohara Toyoaki , Yoshimura Michihiro , Saito Yoshihiko , Yasue Hirofumi
Published: July 2021

Introduction:
Coronary spasm plays an important role in the pathogenesis of coronary heart disease and coronary spastic angina (CSA) is prevalent in East Asia including Japan. Oxidative stress is thought to be one of important factors in pathogenesis of coronary spasm. Interestingly, East Asians have been shown to have a frequent mutation of the aldehyde dehydrogenase 2 (ALDH2) gene (ALDH2*2) that leads to reducing of anti-oxidative effect and intolerance to alcohol ingestion (alcohol flushing). Furthermore, we previously reported that coronary spasm could be induced by alcohol intake in CSA patients.

Hypothesis:
We herein examined whether CSA is associated with ALDH2 polymorphisms by using single nucleotide polymorphism (SNP) genotyping method.

Methods:
The study subjects consisted of 155 patients in whom intracoronary injection of acetylcholine were performed on suspicion of coronary spastic angina. They were divided into 95 CSA patients (67 men/ 28 women, mean age 67 ± 10) and 60 non-CSA patients (26 men/ 34 women, mean age 65 ± 13). SNP genotyping test for ALDH2 along with clinical data for CSA risk factors were investigated.[[Unable to Display Character:  ]]

Results:
Gender (male), uric acid and smoking were higher (P = 0.001, P = 0.0014 and P = 0.001, respectively) and HDL cholesterol level was lower (P = 0.0021) in the CSA patients than in the non-CSA patients. There was a significant difference on the rate of CSA between ALDH2*1/*1 (wild type) and ALDH2*1/*2 or ALDH2*2/*2 (non-activated genotype) (51.2% vs. 73.2%, P = 0.005). Multivariable logistic regression analysis including age, ALDH2 non-activated genotype, smoking, and HDL cholesterol as independent variables revealed that ALDH2 non-activated genotype, HDL cholesterol and smoking were significant predictors of CSA (P = 0.007, P = 0.030 and P = 0.016, respectively). Furthermore, this study showed that ALDH2*2/*2 is a significant risk factor for CSA (90.9%) and multi-vessel spasm (80%).[[Unable to Display Character:  ]]

Conclusions:
ALDH2 non-activated genotype as well as smoking and HDL cholesterol, was significantly associated with CSA in Japanese patients.
Abstract 9439: Incidence of New Coronary Calcification: What is the Warranty Period of CAC = 0 in the Multi-Ethnic Study of Atherosclerosis?
Authors: Desai Dhaval , Nasir Khurram , Dardari Zeina , Kaufman Joel , Blankstein Ron , Carr J. Jeffrey , Agatston Arthur , Lima Joao , Szklo Moyses , Blumenthal Roger , Budoff Matthew , Blaha Michael
Published: July 2021

Background:
While CAC=0 is associated with excellent prognosis, progression to CAC>0 has been shown to confer increased risk. The time interval at which a repeat CAC scan would be reasonable - the “warranty period” of CAC=0 - is currently poorly defined.

Methods:
We studied 3116 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with baseline CAC=0 and at least 1 follow-up CAC scan per MESA protocol (up to 10 years after baseline). Cumulative incidence of incident CAC was calculated yearly. Cumulative survival fee of CAC was calculated using Kaplan-Meier statistics and additionally modeled using a parametric survival model with Weibull distribution. The warranty period of CAC=0 was defined distribution as the time needed for 15%, 20%, or 25% (number needed to scan [NNS] 6, 5, or 4) to progress to detectable CAC.

Results:
The mean age of the subjects was 58 ± 9 years with 63% women and mean FRS of 8 ± 6%. Cumulative prevalence of CAC>0 increased with time, from 11% at 2 years to nearly 50% at 10 years. The cumulative incidence rate of CAC>0 was non-linear, increasing from approximately 2.5 per 100 person-years at 2 years to 5-6 per 100 person-years from years 4 to 10. The table shows the estimated warranty period of CAC=0 by gender and baseline FRS CHD risk. Among men, using an acceptable detection rate of 25% (NNS=4 to detect CAC>0), the estimated warranty period of a low, intermediate, and high risk man was 6, 5, and 3 years. For women, the equivalent warranty period was 7, 5, and 4 years. In general, rescanning at 5 years will enable selection of 50% of the individuals with baseline CAC=0 who will go on to have CHD events following their repeat scan over 10-year follow-up.

Conclusions:
Although limited by lack of yearly CAC scanning, modeling in MESA allows estimation of the warranty period of CAC=0. A general rule would be to rescan low risk CAC=0 patients at 6-7 years and intermediate risk at 4-5 years, although exact warranty periods vary by gender and desired yield of repeat testing.
Abstract 9761: Novel Modulators of Low Density Lipoprotein Receptor Metabolism
Authors: Elshourbagy Nabil , Meyers Harold , Medve Caitlin , Mousa Shaker , Abdel-Meguid Sherin
Published: July 2021

Intervention with drugs to reduce Low Density Lipoprotein-cholesterol (LDL-C) has proven to decrease the risk of subsequent cardiovascular events, including mortality. Our goal is to develop novel, small molecule, LDL-C lowering drugs by targeting the Low Density Lipoprotein Receptor (LDLR) degradation pathway, which is modulated by the protease proprotein convertase subtilisin-like kexin type 9 (PCSK9). PCSK9 has been shown to bind to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR; it enhances the degradation of the LDLR by an unknown. We successfully integrated virtual screening methods and cell based assays into a simple, efficient procedure and identified compounds that interfere with the PCSK9-LDLR interaction. Using the atomic coordinates of the crystal structure of the PCSK9/LDLR-EGF-A complex, about a million drug-like compounds were docked
in silico
into the region of PCSK9 where LDLR-EGF-A binds. We selected 179 top scoring compounds that showed the best fit in the binding site as well as the greatest number of interactions with PCSK9. These compounds were tested in (a) our PCSK9/LDLR dependent HEK293 cell-based recombinant assay and (b) the endogenously expressed LDLR in HepG2/PCSK9 dependent cell based assay for their ability to upregulate the LDLR. From these screening campaigns, eleven compounds consistently exhibited concentration dependent increase in the LDLR as comparable to control, with IC
50
s in the low micromolar range. Three of the top picks were shown to exhibit a 5 to 10 fold up-regulation at 1.6 μM in two cell lines. In addition, these compounds also exhibited an increase in the fluorescently labeled DiI-LDL uptake in the nanomolar range
in situ
. Furthermore, in a two week animal study, subcutaneous injection of 4 mg/kg of one of these compounds resulted in a 32% reduction of the total cholesterol level in mice fed a high fat/high cholesterol diet as compared to 27% cholesterol reduction obtained with 40 mg/kg Atorvastatin. To our knowledge, no small molecule antagonist against PCSK9 has been reported, only mAbs. Thus, identifying such an oral small molecule PCSK9 inhibitor represents a tremendous advance and opportunity for drug development.
Abstract 9764: Clinical Characteristics and Temporal Trends Among Patients Presenting Late (>12 Hours After Symptom Onset) With ST-Elevation Myocardial Infarction - A Report From the NCDR®
Authors: Sharma Praneet K , Roe Matthew T , Kureshi Faraz , Holmes DaJuanicia N , Nallamothu Brahmajee K , Cohen David J
Published: July 2021

Background:
Late presentation after ST-elevation myocardial infarction (STEMI) is associated with poor outcomes. However, contemporary data regarding management and outcomes of such patients are lacking.

Methods:
Using data from the ACTION Registry-GWTG, we identified 170,247 patients who presented with STEMI to 688 US sites, between 7/08 and 12/13. Patients were stratified according to time from symptom onset to presentation as timely presenters (<12 hours) and late presenters (≥12 hours). Baseline characteristics, management and in-hospital outcomes were compared between the groups. Among late presenters, temporal trends in reperfusion strategy were also examined.

Results:
A total of 9389 patients (5.5%) had late presentation and 160,858 (94.5%) had timely presentation. Late presenters were more frequently elderly, female and of non-White ethnicity (Table). Late presenters were less likely to have prior MI or prior revascularization, but more likely to have diabetes. Compared with timely presenters, late presenters had worse in-hospital outcomes including mortality (6.3% vs. 5.2%; p<0.0001). Over the 6-year study period, the proportion of late presenters decreased slightly (5.8 vs. 5.4% respectively; p=0.03), while the proportion of late presenters undergoing primary PCI increased from 65% to 71% (p<0.001). Over the same time-period, among late presenters, median time from symptom onset to presentation increased slightly, door to balloon time decreased, and in-hospital mortality remained unchanged (6.0% vs. 6.0%).

Conclusions:
In contemporary practice, a modest proportion of STEMI patients continue to present >12 hours after symptom onset. Despite increased use of primary PCI and reduction in door-to-balloon times, the unadjusted mortality remains high among late presenters. Continued efforts to educate the public in order to reduce the proportion of late presenters remains warranted.
Abstract 9783: Predictors of Survival in Patients Undergoing Trans-Catheter Aortic Valve Closure for Significant Left Ventricular Assist Device Associated Aortic Insufficiency
Authors: Retzer Elizabeth M , Tabit Corey E , Estrada J R , Uriel Nir , Paul Jonathan D , Nathan Sandeep , Friant Janet , Lang Roberto , Jeevanandam Valluvan , Shah Atman P
Published: July 2021

Introduction:
Left ventricular assist devices (LVADs) have been shown to increase survival and quality of life in patients with end-stage congestive heart failure. However, severe aortic insufficiency (AI) can develop in up to 50% of patients with LVADs at 12 months resulting in significant morbidity and mortality. Trans-catheter treatment of LVAD associated AI has emerged as a potential alternative to surgical treatment, but long term clinical benefits are yet to be determined.

Methods:
We conducted a retrospective analysis of all patients undergoing trans-catheter aortic valve closure using an Amplatzer Multi-Fenestrated Septal Occluder “Cribiform” device (AGA Medical, Plymouth, Minnesota) at our institution between September 2011 and September 2013 to assess potential clinical and procedural factors associated with survival. Unpaired student’s t-tests were used to compare baseline patient demographics and procedural characteristics, as well as patient outcomes immediately post procedure and at 6 months. A p-value of <0.05 was considered statistically significant.

Results:
A total of 8 patients (75% male, median age 59 years) were included in this analysis. Technical success of the procedure including total cessation of AI without evidence of coronary compromise was accomplished in 100% of patients with a 6 month survival rate of 38% (3/8). Predictors of survival include the absence of significant co-morbidities such as chronic renal insufficiency, smaller occlusion device placement, and the absence of right heart failure (Table 1).

Conclusions:
Trans-catheter aortic valve closure successfully treats late severe AI in LVAD patients, however, the presence or development of right heart failure portends a worse prognosis. Further studies are needed to investigate the potential right ventricular failure in patients undergoing trans-catheter aortic valve closure.
Abstract 98: The Association Between Manual Mode Defibrillation, Preshock Pause Duration and Appropriate Shock Delivery When Employed by Basic Life Support Paramedics During Out-of-Hospital Cardiac Arrest
Authors: Cheskes Sheldon , Hillier Morgan , Zhan Cathy , Byers Adam , Verbeek P R , Drennan Ian , Morrison Laurie J
Published: July 2021

BACKGROUND:
Pre-shock pause duration of < 20 seconds is associated with improved survival after cardiac arrest. Manual mode defibrillation has been associated with the shortest duration of pre-shock pause but is largely practiced by paramedics (EMT-P) whereas defibrillator only providers (EMT-D) routinely use the defibrillator in automatic mode.

OBJECTIVE:
We sought to explore the relationship between manual mode defibrillation, pre-shock pause duration and shock appropriateness when defibrillation is provided by EMT-P vs. EMT-D level of providers.

METHODS:
We performed a retrospective review of all treated non-traumatic adult OHCA presenting in a shockable rhythm over a one year period beginning January 1, 2012. Our primary outcome measure was the proportion of manual mode shocks delivered by EMT-D’s with pre- shock pause duration of < 20 secs when compared to EMT-P’s. Our secondary outcome measures were the duration of pre-, post- and peri-shock pause and the proportion of appropriate shocks (defined as correct identification and shock delivery to patients in a shockable rhythm) delivered by either level of provider. This study had a power of 90% to detect an absolute difference of 15% between provider levels in proportion of shocks delivered with pre-shock pause duration <20 secs.

RESULTS:
Among 2019 treated OHCA, 335(20%) presented in a shockable rhythm. Manual defibrillation was performed in 155 (46%) of these cases (196 shocks by EMT-P, 143 shocks by EMT-D). There were no differences in the proportion of shocks delivered with pre-shock pause duration <20 secs (EMT-P 82.8% vs EMT-D 84.8%, p =.65) nor pre-shock pause duration (sec) (median, Q1, Q3); EMT-P: 12.0 (7.0,17.0) vs. EMT-D: 11.0 (5.0,17.0), p= .13 while EMT-D had shorter peri- shock pause duration (sec) (median, Q1, Q3); EMT-P: 17.0 (12.0, 23.0) vs. EMT-D: 15.0 (9.0, 22.0), p =.03. There were no differences in the rate of inappropriate shocks (EMT-P 1.0% vs EMT-D 0.7%), p=1.0.

CONCLUSIONS:
Manual mode defibrillation by EMT-D’s produced similar measures of pre-shock pause when compared to EMT-P’s without increasing the rate of inappropriate shocks. More widespread use of EMT-D manual mode defibrillation may have the potential to decrease shock pause duration and improve survival.
Abstract 9946: Impact of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease
Authors: Kobayashi Yuhei , Honda Yasuhiro , Fearon William F , Tanaka Shigemitsu , Fitzgerald Peter J , Lee David P , Yeung Alan C , Tremmel Jennifer A
Published: July 2021

Background:
Coronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) is typically used to interrogate microvascular function; however its variability limits reliability. Alternatively, the index of microcirculatory resistance (IMR) is a direct measure of the microvasculature, but has been less thoroughly studied. We investigated sex differences in CFR and IMR in patients with angina in the absence of obstructive coronary artery disease (CAD).

Methods:
We prospectively enrolled 117 women and 40 men with angina in the absence of obstructive CAD. We performed CFR, IMR, fractional flow reserve (FFR), and quantitative coronary angiography (QCA) in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (Tmn: an inverse correlate to absolute flow) at rest and hyperemia. IMR was measured as distal coronary pressure at hyperemia x hyperemic Tmn.

Results:
All patients had minimal or no atherosclerosis by QCA (%diameter stenosis: 23.2±12.3%), and epicardial disease was milder in women (FFR: 0.88±0.04 vs. 0.87±0.04, p=0.04). IMR was similar between the sexes (20.7±9.8 vs. 19.1±8.0, p=0.45), but CFR was lower in women (3.8±1.6 vs. 4.8±1.9, p=0.004). This was primarily due to a shorter resting Tmn in women (p=0.005), while hyperemic Tmn was identical (p=0.79) (Figure). The shorter resting Tmn in women, reflecting increased resting coronary flow, accounted for the lower CFR. In multivariate analysis, female sex was an independent predictor of lower CFR and shorter resting Tmn, but not a predictor of IMR or hyperemic Tmn.

Conclusions:
Despite women and men having similar microvascular function by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The impact of sex differences should be considered in interpretation of physiologic indices using resting coronary flow.
Abstract 11: mActive: A Blinded, Randomized mHealth Trial Supporting Digital Tracking and Smart Texting for Promotion of Physical Activity
Authors: Martin Seth S , Feldman David I , Blumenthal Roger S , Jones Steven R , Post Wendy S , Ndumele Chiadi E , Ratchford Elizabeth V , Coresh Josef , Blaha Michael J
Published: July 2021

Introduction:
The recent advent of smartphone-linked wearable pedometers offers a novel opportunity to promote physical activity using mobile health (mHealth) technology.

Hypothesis:
We hypothesized that digital activity tracking and smart (automated, real-time, personalized) texting would increase physical activity.

Methods:
mActive (NCT01917812) was a 5-week, blinded, sequentially-randomized, parallel group trial that enrolled patients at an academic preventive cardiovascular center in Baltimore, MD, USA from January 17
th
to May 20
th
, 2014. Eligible patients were 18-69 year old smartphone users who reported low leisure-time physical activity by a standardized survey. After establishing baseline activity during a 1-week blinded run-in, we randomized 2:1 to unblinded or blinded tracking in phase I (2 weeks), then randomized unblinded participants 1:1 to receive or not receive smart texts in phase II (2 weeks). Smart texts provided automated, personalized, real-time coaching 3 times/day towards a daily goal of 10,000 steps. The primary outcome was change in daily step count.

Results:
Forty-eight patients (22 women, 26 men) enrolled with a mean (SD) age of 58 (8) years, body mass index of 31 (6), and baseline daily step count of 9670 (4350). The phase I change in activity was non-significantly higher in unblinded participants versus blinded controls by 1024 steps/day (95% CI -580-2628, p=0.21). In phase II, smart text receiving participants increased their daily steps over those not receiving texts by 2534 (1318-3750, p<0.001) and over blinded controls by 3376 (1951-4801, p<0.001). The unblinded-texts group had the highest proportion attaining the 10,000 steps/day goal (p=0.02) (Figure).

Conclusions:
In present-day adult smartphone users receiving preventive cardiovascular care in the United States, a technologically-integrated mHealth strategy combining digital tracking with automated, personalized, real-time text message coaching resulted in a large short-term increase in physical activity.
Abstract 15: Trends in Consumption of Key Foods and Nutrients Linked to Cardiometabolic Risk Among Us Adults, 1999 to 2012
Authors: Rehm Colin D , Mozaffarian Dariush
Published: July 2021

Introduction:
Most prior studies of US diet trends have evaluated macronutrients (e.g., total fat), rather than the foods and other nutrients most strongly linked to cardiometabolic risk. Assessment of these trends, including heterogeneity by age, sex, race, and education, is crucial to identify challenges and opportunities to improve the diet of Americans.

Objective:
To characterize trends in US dietary intakes of foods and nutrients related to cardiometabolic health.

Methods:
We evaluated repeated cross-sectional diet assessments among 33,929 US adults age 20+y from 6 consecutive cycles of NHANES (1999-2012). Based on an in-person 24-hour dietary recall, we evaluated energy-adjusted intakes for vegetables, fruits, whole grains, processed meat, poultry, nuts/seeds, 100% fruit juice, and sugar-sweetened beverages (SSBs); and sodium, potassium, fiber, seafood omega-3’s, and total polyunsaturated fat, among others. Analyses were further stratified by age, sex, race, and education.

Results:
Among all adults, significant increases were seen in yogurt, nuts/seeds, whole grains, dark-green vegetables, fruit, and poultry; processed meat also increased (Figure). Decreases were observed in potatoes, unprocessed red meats, milk, fruit juice, and SSBs. Energy-adjusted intakes of sodium, fiber, and polyunsaturated fat increased; potassium and seafood omega-3’s did not change (not shown). Trends were generally consistent within population subgroups, with some exceptions. The increase in nuts/seeds was strongest among the well-educated, the decrease in SSBs was strongest in adults 20-34y and the increase in yogurt consumption was limited to women.

Conclusion:
Overall US dietary habits are improving, consistent with continuing declines in population blood pressure and cholesterol; although processed meat and sodium intake are increasing. Disparities in dietary intakes by race and education did not markedly change, suggesting that additional efforts be explored to reduce disparities.