bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19601: Absence of Adverse Cardiovascular Risk Factors for Over 35 Years is Associated with Better Health-Related Quality of Life at Older Ages: The Chicago Healthy Aging Study (CHAS)
Authors: Allen Norrina B , Vu Thanh Huyen T , Pirzada Amber , Garside Daniel , Daviglus Martha
Published: April 2024

Background:
Absence of adverse cardiovascular (CV) risk factors (RF) or having a favorable CV RF profile during middle-age is associated with better health-related quality of life at older ages. However, the impact of having no adverse CV RFs throughout middle- and older-age remains unknown. Objective: To examine the impact of remaining free of all adverse CV RFs for over 35 years on health-related quality of life among participants of the Chicago Health Aging Study (CHAS).

Methods:
The CHAS study conducted physical examinations at baseline (1967-1973) and follow-up (2007-2010). Absence of adverse CV RF profile was defined as having all the following: blood pressure <140/<90 mm Hg and not taking antihypertensive medication, serum cholesterol level <240 mg/dL and not taking cholesterol-lowering medication, BMI <30, no diabetes and not currently smoking. Health-related quality of life was measured at follow-up using the SF-36. We compared the SF-36 component scores (range 0-100, higher scores associated with better health-related quality of life) for individuals who continued to remain free of adverse CV RF profile in older age (i.e. from baseline to follow-up) vs. those with elevated levels of CV risk factors at baseline and/or at follow-up using linear regression models adjusted for age, sex, race, and highest educational attainment.

Results:
Among 1395 CHAS participants 8.8% (123) remained free of adverse CV risk factors for over 35 years from middle to older-age. Individuals who continued to have no adverse CV risk factors were more likely to be white (95.3% vs 87.4%; p<0.01) and have a graduate school education (35% vs 19%; P<0.001). Also, they had higher (better) adjusted physical component scores (54.0 vs 51.7; P=0.005), general health scores (77.0 vs 72.9; P=0.008), and physical functioning scores (99.5 vs 94.1; P=0.003) compared to those with adverse RFs. No differences were observed for the mental component score or the pain index, mental health index, role-emotional, role-physical, social functioning or vitality subscales.

Conclusions:
Remaining free of adverse cardiovascular risk factors for over 35 years from middle to older-age is associated with better physical quality of life at older ages.
Abstract 19619: A Novel Role of the Valosin-Containing Protein (VCP) In Cardiac Protection via Regulation of Mitochondrial Protein Nitrosylation
Authors: Rashed Eman R , Dai Huacheng , Qiu Hongyu
Published: April 2024

Introduction:
We have previously shown that over expression of the valosin-containing protein (VCP) in a cardiac specific transgenic (TG) mouse conferred a cardiac protection against ischemia as well as a dose dependent induction of inducible isoform of nitric oxide synthase (iNOS). However, the link between iNOS and the VCP-conferred cardiac protection remains unclear.

Hypothesis:
Our hypothesis is that VCP elicits cardiac protection by the induction of inducible isoform of nitric oxide synthase (iNOS), leading to the nitrosylation of mitochondrial proteins, resulting in the stimulation of mitochondrial respiration.

Methods
and

Results
. Biotin switch was used to identify S-nitrosylated proteins in the VCP TG mouse heart, which a majority of them were found to be mitochondrial proteins involved in the regulation of mitochondrial metabolism and respiration, including succinate semialdehyde dehydrogenase, mitochondrial heat shock protein 60, cytochrome c1. One of the most upregulated nitrosylated proteins was Malic enzyme 3 (Me3), an enzyme which catalyzes the oxidative decarboxylation of malate to pyruvate, was significantly increased by 2.5 fold (p<0.01) in TG mouse compared to WT, although the total protein level was unchanged. Reciprocally, we found a significant decrease by 50% of S-nitrosylated complex I subunit, (NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 9 (NDUFA9)), in VCP TG heart compared to WT (p<0.05). Since S-nitrosylation serves to inhibit Complex I activity, this reduction indicates a reversal of this inhibition by VCP. Basal cardiac mitochondrial respiration was measured using a Clark type oxygen electrode on VCP TG mice (n = 5) and wild-type (WT) mice (n = 6). Mitochondrial State 3 respiration was significantly (p < 0.01) elevated in the VCP TG (72 ±2 nmol O2/min/mg prot) mice compared to WT (45.9 ±6 nmol O2/min/mg prot) with no difference in State 4 or State 2, indicating that VCP over expression enhances the capacity for ATP production without a change in basal levels of respiration.

Conclusion:
In conclusion, our data reveals a critical and novel role of VCP in mediating cardioprotection through the stimulation of mitochondrial function by inducing nitrosylation of mitochondrial proteins via increased expression of iNOS.
Abstract 19634: Myocardial Deformation Findings Suggest Early Diastolic Dysfunction in Preterm Infants and Adaptation to Ongoing Myocardial Diastolic Dysfunction During Maturation
Authors: Hirose Akiko , Khoo Nee , Aziz Khalid , Al-Rajaa Najlaa , Van den boom Jutta , Savard Winnie , Brooks Paul , Hornberger Lisa K.
Published: April 2024

Background
We have recently demonstrated that the ventricular filling in the preterm infant occurs less so in early diastole than observed in term infants of comparable postnatal age using traditional parameters which are preload sensitive. In the present study we sought to re-explore ventricular function using more preload independent parameters including myocardial deformation and twist to better characterize the evolution of myocardial function following preterm delivery. We hypothesized differences exist in early filling myocardial deformation rates and twist in the preterm heart.

Methods
We prospectively enrolled preterm infants (PI, n=30; GA 27.43±1.23 weeks) at 28 days of age who were clinically stable. After excluding structural pathology, spectral and tissue Doppler velocity and 2-dimensional deformation assessments were made with comparison to 30 healthy term infants of similar postnatal age (27±6.8 days). In 16 preterm infants, follow up echocardiography was performed near term (corrected GA 38.5±2.3 weeks).

Results
Compared to healthy controls, PI at 28 days had decreased peak mitral valve (MV) E wave velocity (p<0.05), E/A ratio (p<0.01), annular e’ velocity (p<0.0001), e[[Unable to Display Character: ]]/a[[Unable to Display Character: ]] ratio (p<0.0001), and increased MV E/e’ (p<0.01), and at followup MV e[[Unable to Display Character: ]]/a[[Unable to Display Character: ]] (p<0.05) and E/e’ (p<0.01) remained abnormal compared to controls.There was no significant difference in left ventricular (LV) twist and twist rate, or longitudinal strain and strain rate (SR). Basal circumferential early diastolic SR (eSR), however, was lower in PI at 28days compared to term controls (p<0.01), and there was greater late diastolic SR at followup of PI close to term (p<0.05) Despite higher heart rates in PI at 28 days (162±15 vs. 141±15 bpm), there was no significant linear relationship between HR and any of the functional parameters assessed.

Conclusion
Myocardial deformation and twist suggest preterm infants have normal left ventricular systolic function. The subtle reduction in early diastolic SR in PI at 28 days supports early diastolic differences from controls. The presence of increased late diastolic SR at followup near term may indicate adaptation to persistent diastolic dysfunction consistent with ongoing myocardial maturational delay in postnatal life.
Abstract 19654: Absence of Cardiovascular Implantable Electronic Device Infection in Remote Implantations Demonstrated by Fluorine-18 Positron Emission Tomography
Authors: Beck Hiroko , Mesubi Olurotimi , Smith Mark , Saliaris Anastasios , See Vincent , Ogu-Esuala Kelechi , Dilsizian Vasken , Shams Omar , Shorofsky Steven , Dickfeld Timm
Published: April 2024

Background:
Cardiovascular implantable electronic device (CIED) infection can be very challenging and unnecessary device extraction can expose the patient to significant morbidity and mortality. Recent publications suggests that fluorine-18 (
18
F-FDG) positron emission tomography (PET) has a high sensitivity and specificity to differentiate pocket and/or lead infections from non-infected devices older than 6 months. However, control groups were small (n≤10 patients) and the prevalence of increased
18
F-FDG uptake in not-infected CIED patients is unknown.

Method:
All patients with remote (>6month) ICD implantation and no clinical/laboratory evidence of infection undergoing 18FDG-PET in preparation for VT ablation from 2006 to 2011 were identified in a single tertiary center. Semi-quantiative ssessment of
18
F-FDG uptake was assessed in 4 sites (generator pocked, innominate vein, superior vena cava (SVC), and intracardiac space (right atrium/ventricle). using a semi-quantitative score assessing .Uptake was categorized in none (score = 0), mild (≤thoracic background activity[t1] ; score = 1), moderate (>thoracic background activity; score = 2), and severe hypermetabolism (very intense uptake; score = 3).

Results:
65 contiguous patients were enrolled in this study. 18FDG PET signal uptake scores were 0 in 0%, 0%, 0%, 0% for generator pocket, innominate vein, SVC and intracardiac position, respectively. Resulting semiquantitative scores were 0.0±0.0 in (locations) and 0.1±0.

Conclusion
This as far as we know largest series on 18FDG PET scans in patients with remote device implantation demonstrates no incidence of increased tracer uptake in non-infected patients localized in ¼ This supports a potential use of
18
F-FDG PET/CT in differentiating patients with CIED infection from chronic implant changes, providing a new potentially new path in management of CIED infection.
Abstract 19655: AVR Elevation Predicts Early Revascularization but not Cardiac Events in Patients Undergoing Exercise Stress Myocardial Perfusion Imaging
Authors: Baheti Aparna , McArdle Michael , Beller George , Bourque Jamieson
Published: April 2024

Introduction:
Lead AVR elevation has been associated with a high prevalence of multivessel disease in patients undergoing exercise stress. Myocardial perfusion imaging (MPI) may be falsely negative in multivessel disease due to balanced ischemia, leading to false reassurance. We sought to identify the prevalence of early revascularization and subsequent cardiac events in a cohort undergoing exercise stress SPECT MPI.

Methods:
We analyzed clinical data and prospectively-collected events on a cohort of 587 consecutive patients referred for exercise SPECT MPI. Standard exercise protocols were used. AVR elevation was defined as ≥1mm in 3 consecutive beats. Follow-up was 98% complete with a median time of 3.75 years. Cardiac events included cardiac death and nonfatal myocardial infarction. Early revascularization rates were compared by chi-square analysis. The effect of AVR elevation on cardiac events was assessed using Cox proportional hazards analysis.

Results:
The cohort had a median age of 60.0 years and 61.4% were male. Patients with AVR elevation had a higher prevalence of hypertension, dyslipidemia, and known CAD. Early revascularization was 10-fold higher in patients with AVR-elevation (8.3% versus 0.81%, p<0.001). In the 568 patients without early revascularization, there were 24 cardiac events (1.1%/year), of whom only 10 (41.7%) had AVR elevation on their initial stress test. AVR elevation was not a significant predictor of cardiac events by Cox analysis (Hazard Ratio 2.0 (95% CI 0.8-5.1), p=0.137).

Conclusion:
AVR elevation on exercise electrocardiography strongly predicts early revascularization. However, there was a low cardiac event rate in the remaining patients, and events were not predicted by AVR elevation. This idicates a low risk of clinically significant false-negative SPECT in this subgroup.
Abstract 19668: Primary Care Physician Density and Heart Failure Hospitalization Rates: The Atherosclerosis Risk in Communities (ARIC) Study -Community Surveillance
Authors: Allen Norrina B , Wruck Lisa , Kucharska-Newton Anna , Carnethon Mercedes , Baggett Chris , Rosamond Wayne
Published: April 2024

Background:
Prior research has demonstrated an association between the density of primary care physicians and avoidable hospitalizations. We aimed to determine the association of primary care physician density on rates of acute decompensated heart failure (ADHF) admissions among residents of the four communities in the Atherosclerosis Risk in Communities (ARIC) Study.

Methods:
We examined hospitalization rates for ADHF from 2005-2008 among Primary Care Service Areas (PCSA) included in the ARIC community surveillance areas. Validated ADHF hospitalizations were assigned to a PCSA based on the patients’ address. We calculated age, sex and race-adjusted rates for each PCSA using indirect standardization, weighted to account for the stratified random sample. Physician density was defined as the age and sex-adjusted rate of primary care physicians per 100,000 population in 2005, from the AMA Masterfile and centered on the US average. We used GEE Poisson models to examine the association of ADHF hospitalization rates with physician density taking into account the nested structure of the data and adjusted for median family income.

Results:
This study included 7,233 ADHF hospitalizations from the 3 ARIC surveillance areas (Jackson, MS; Minneapolis, MN; Washington Co., MD) which included more than 1 PCSA. Adjusted physician densities ranged from 55.6 - 92.8 primary physicians per 100,000 pop. Adjusted ADHF hospitalization rates decreased with increasing primary care physician density (see figure). For every increase in the density of primary care physicians of 10 physicians per 100,000 the adjusted rate of ADHF decreased by 24% (p<0.0001). Findings were consistent when family practitioners and internal medicine physician densities were examined separately.

Conclusion:
Primary care physician densities are associated with heart failure hospitalization with PCSAs. Increasing the availability of primary care physicians may improve heart failure outcomes in the US.
Abstract 19680: Fatalism does not Decrease Effectiveness of interventions to Improve Cardiovasuar Health
Authors: Lennie Terry A , Frazier Susan K , Biddle Martha , Novak M J , Casey Baretta , Mudd Gia , Moser Debra K
Published: April 2024

Background:
There is a long standing belief that lifestyle interventions to decrease cardiovascular disease (CVD) risk are less effective in individuals who have a fatalistic (preordained) view of health. Rural Appalachian Kentucky is a region perceived to have a culture that includes fatalistic views toward health, which may make lifestyle interventions less effective. One of the most challenging lifestyle modifications is change in diet.

Objective:
To compare responses of adults with high vs. low levels of fatalism to a life-style intervention to decrease modifiable CVD risk factors including diet.

Methods:
A total of 280 adults with at least one CVD risk factor participated in a 6-month individualized education and goal setting intervention to promote heart healthy lifestyles. As part of the assessment, participants completed food frequency questionnaires (FFQ) at baseline and post-intervention. Fatalism was measured by the Fatalism Scale. Median split of Fatalism Scale scores was used to divide the sample into 2 groups: higher vs. low levels of fatalism. Repeated measures analysis of variance was used to compare post intervention intake of total fat, saturated fat, calories, total sugar, added sugar, number of daily fruit, vegetable, sweets, and fried food servings between groups.

Results:
There was a significant decrease post-intervention in total fat, saturated fat, calories, added sugar, and number of sweets and fried foods consumed; while the number of fruit servings consumed daily increased. There were no significant differences post-intervention in nutrient intake between adults with lower vs. higher levels of fatalism; both groups made similar modifications in eating habits.

Conclusion:
Adults with high levels of fatalism are willing to make appropriate lifestyle changes to decrease their CVD risk. These results provide evidence to dispel the myth that people living in this region are resistant to changes that will improve their health.
Abstract 19685: Statins and Tinnitus: An Innovative Analysis
Authors: Golomb Beatrice A , Hathaway Meskimen Athena
Published: April 2024

Background: Some patients cite tinnitus as a statin adverse effect (AE), often attending acknowledged statin AEs, but trends to tinnitus benefit have also been reported. Oxidative stress promotes tinnitus. Since statins have both antioxidant and prooxidant effects, tinnitus effects might depend on which predominate. Prooxidant predominance has been linked to statin muscle/fatigue AEs. We therefore conjectured that change in tinnitus (αTinnitus) on statins but not placebo would significantly relate to change in a fatigue outcome (αFatigue) that statins affect. Method: In a 6 month double-blind placebo-controlled RCT, 1016 adults (median age 57) without diabetes or CVD (LDL 115-190mg/dL) were randomized equally to simvastatin (simva) 20mg, pravastatin (prava) 40mg, or placebo. We elicited change-in (α)Tinnitus from baseline, and summed self-rated α exertional fatigue with the inverse of α energy to produce “αFatigue.” Ordinal logit with robust SEs examined a) statin effect on αTinnitus, stratified at median age; and b) prediction of αTinnitus by αFatigue.Analyses stratified by randomization arm and adjusted for age and baseline tinnitus. Results: In the younger stratum (age < median), prava (vs placebo) increased tinnitus (β(SE)=.94(.43)p=.028) with borderline increase on combined statins (β(SE)=.58(.31)p=.064). No effect was observed with simva or in the older stratum. However, for each statin group but not placebo, αTinnitus was significantly predicted by αFatigue (see Table 1). Discussion: αTinnitus on statins was significantly predicted by αFatigue on statins, which (other evidence suggests) may serve as a marker of prooxidant predominance. Findings were consistent across statin groups (p<.05 for all), with no suggestion of a similar finding on placebo (p=0.9). These findings comport with a view by which bidirectional effects of statins on oxidative stress/energetics may contribute to variable and perhaps bidirectional effects on tinnitus.
Abstract 19696: Hypertension and Elevated hs-CRP Predict Occult Cardiovascular Disease in Asymptomatic Survivors of Hodgkin's Lymphoma Treated with Chest Radiation
Authors: Chen Ming Hui , Ng Andrea K , Zhou Jing , Gauvreau Kimberlee , Mauch Peter
Published: April 2024

Background:
Cardiovascular disease (CVD) is the leading cause of mortality in

Hodgkin’s lymphoma (HL) survivors treated with chest radiation therapy (RT). The contribution of traditional cardiovascular risk factors (CRFs) to CVD development in this irradiated population is unclear since most studies are retrospective.

Methods:
Two hundred and ten asymptomatic HL survivors treated with RT at 3 Harvard hospitals were recruited and assessed for treatment- and patient-related CRFs. Each patient underwent an outpatient cardiology visit and laboratory testing. Blood pressure (BP) measurement, electrocardiogram, and resting and stress echocardiography were performed. CVD detected on screening was correlated with patient-related

CRFs.

Results:
One hundred eighty-two HL survivors (59% female, mean age 44.1 ± 8.7 years, follow-up time 15.1 ± 7.2years) completed cardiac screening and formed the cohort. 81% of patients had ≥ 1 modifiable CRF. 26% (47) of patients (53% female, mean age 45.3 ± 9.0 years, follow-up time 16.9 ± 8.3 years) had occult coronary artery disease (CAD), at least moderate valve disease, or left ventricular systolic dysfunction (LVSD). Hypertension (OR=4.9, p=0.0003), elevated high-sensitivity C-reactive protein (hs-CRP) (OR=2.9, p=0.01), and older age (OR= 1.1, p=0.006) were correlated with CAD/valve disease. LVSD was not correlated with patient CRFs. For every 5mmHg decrease in systolic BP or in diastolic BP, the odds of CAD/valve disease decrease 22% or 26% respectively.

Conclusions:
This is one of the most comprehensive prospective assessments of CRFs in HL survivors. Hypertension and hs-CRP are common and sensitive markers of CAD/valve disease in asymptomatic survivors treated with chest RT, and may allow better identification of those with occult CVD treated with chest radiation.
Abstract 19703: Real-Time Microscopic Assessment of Ischemia-Reperfusion with Intravital Autofluorescence Imaging
Authors: Lu Hsueh-Han , Chang Wei-Tien , Wu Yao-Ming , Liau Ian
Published: April 2024

Background:
Real-time microscopic characterization of ischemia and reperfusion (IR)
in vivo
is essential to improve our understanding of the underlying pathogenesis of IR injury, but histopathological examination post reperfusion remains a common means to assess IR. The mitochondrial flavoprotein switches between non-fluorescent and fluorescent state as it undergoes redox change. We herein sought to visualize IR microscopically in a real-time and label-free manner in vivo based on the autofluorescence of this intrinsic indicator.

Methods:
Intravital autofluorescence microscopy was employed to image hepatic IR in vivo on a rat model. Time-lapse autofluorescence images of the liver tissue and time-varying intensity of the autofluorescence were recorded continuously on liver subject to short and long durations of ischemia. FITC-dextran was injected intravenously to highlight sinusoids with circulating blood.

Results:
The autofluorescence decreased by ~30% immediately after ischemia, but restored gradually after reperfusion. The recovery rate depended strongly on the duration of ischemia: the intensity restored to the baseline within 10 min for 20-min ischemia whereas the recovery was significantly slower (> 30 min) for 60-min ischemic time. Results of complementary experiments on cultured hepatocytes
in vitro
including (1) emission spectral measurements, (2) autofluorescence imaging on cells undergoing simulated IR, and (3) inhibitory assay all support strongly that the autofluorescence change observed during IR is associated with hypoxia-reoxygneartion of tissue. The intravital imaging further revealed that the retarded autofluorescence recovery is associated with delayed reoxygenation that was caused by impaired microcirculation.

Conclusions:
Our work demonstrates that the autofluorescence of mitochondrial flavoprotein is a sensitive endogenous indicator that enables visualization of the hypoxia-reoxygenation of tissues associated with IR at the microscopic level in real time. This approach should be extendible to investigate IR of other vital organs.
Abstract 19717: Cardiac Structural and Sarcomere Genes Associated with Cardiomyopathy Exhibit Marked Intolerance of Genetic Variation
Authors: Pan Stephen , Caleshu Colleen A , Dunn Kyla E , Foti Marcia J , Moran Maura , Soyinka Oretunlewa , Ashley Euan A
Published: April 2024

Background -
The clinical significance of variants in genes associated with inherited cardiomyopathies can be hard to determine as a result of uncertainty regarding population genetic variation and the recent finding of a surprising amount of tolerance in the genome even to loss of function variants. We hypothesized that genes associated with cardiomyopathy might be particularly resistant to the accumulation of genetic variation.

Methods and Results -
We analyzed the rate of single nucleotide genetic variation in the coding regions of all known genes sequenced from the exomes of over 5,000 individuals from the National Heart, Lung, and Blood Institute’s Exome Sequencing Project (ESP), as well as the rates of structural variation from the Database of Genomic Variants (DGV). Most variants were rare, with over half being found in only one individual. Cardiomyopathy associated genes exhibited very low rates of variation. Nonsense variants in particular were extremely rare in these genes, appearing at a rate 96.1% lower than in other Mendelian disease genes, and 98.7% lower than genes without Mendelian disease association. We tested the utility of in-silico algorithms to predict variant pathogenicity using a set of variants in MYBPC3, MYH7, and TNNT2 with strong evidence for disease causality compared with variants from the ESP data. Algorithms based on conservation at the nucleotide level (GERP, PhastCons) did not perform as well as amino acid level prediction algorithms (Polyphen-2, SIFT). Variants previously judged causal for disease were found in the ESP data at a prevalence higher than expected.

Conclusion -
Genes previously associated with cardiomyopathy carry very low rates of population variation. The existence in population data of variants previously held to be causal suggests that even for Mendelian disease genetics, a probabilistic weighting of multiple variants may be preferred over the ‘single gene’ causality model.
Abstract 19745: Brugada, Long QT and Cardiac Conduction Disease Overlap Syndrome Associated with the SCN5A-E1784K Mutation: Clinical Phenotype, Genetic Background and Potential Therapy
Authors: Hu Dan , Veltmann Christian , Barajas-Martinez Hector , Pfeiffer Ryan , Belardinelli Luiz , Strupp Gerhard , Papavassiliu Theano , Borggrefe Martin , Wolpert Christian , Schimpf Rainer , Antzelevitch Charles
Published: April 2024

INTRODUCTION:
Phenotypic overlap of type 3 long QT syndrome (LQT3), Brugada syndrome (BrS) and cardiac conduction disease (CCD) is observed with some SCN5A mutations.
SCN5A
-E1784K is the most common mutation associated with LQT3 and BrS. The present study examines the genotype-phenotype relationship in a 76 member European family carrying the
SCN5A
-E1784K mutation and the common polymorphism
SCN5A
-H558R.

METHODS:
Clinical work-up and genetic analysis were performed following informed consent. Functional characterization was achieved by expression of the
SCN5A
variants in TSA201 cells. Peak (I
Na,P
) or late (I
Na,L
) sodium channel current was recorded using whole cell patch-clamp techniques.

RESULTS:
A total of 35 family members (19 male and 16 female, mean age 29.8 ± 15.9 years) were evaluated. Thirteen patients died prior to initiation of the study. Twenty-eight family members refused genetic screening. Of the 35 genotyped family members, 17 were positive for the E1784K mutation in
SCN5A
(Table 1). All 17 displayed LQT intervals and either BrS or prolonged PR (as a surrogate of CCD). The presence of H558R did not significantly alter the phenotype of carriers positive for E1784K. Fourteen patients positive for E1784K underwent ICD implantation; 4 developed VF and received appropriate defibrillation shocks during a follow-up period of 8±3 months. Co-expression of
SCN5A
-E1784K and
SCN5A
-WT reduced I
Na,P
to 70.03% of WT, shifted steady-state inactivation by -11.03mV and increased INa,L from 0.14% to 1.86% of I
Na,P
. Similar changes were observed when E1784K was co-expressed with H558R. Ranolazine (10 µM) reduced INa,L of E1784K+WT by 65% without significantly affecting INa,P.

CONCLUSION:
We demonstrate strong genotype-phenotype correlation and complete penetrance for LQTS and BrS/CCD in a large family harboring the E1784K missense mutation in SCN5A. Ranolazine, by virtue of its ability to suppress I
Na,L
, may be an effective therapy for these cases of LQT3.
Abstract 198: Neither Hypoxia Nor Hyperoxia Is Associated with Mortality in a Cohort of Postarrest Patients
Authors: Gaieski David F , Grossestreuer Anne V , Perman Sarah M , Leary Marion , Donnino Michael W , Cocchi Michael N , Peberdy Mary Ann , Ornato Joseph P , Clore John N , Callaway Clifton W , Rittenberger Jon C , Abella Benjamin S
Published: April 2024

Introduction: During and after resuscitation from cardiac arrest, patients often receive supplemental oxygen with high FiO
2
. Recent human data suggest that arterial hyperoxia is associated with worse outcomes.

Hypothesis: Neurologically intact survivors are more likely to be normoxic rather than hypoxic or hyperoxic.

Methods: This was a retrospective chart review of 111 post-arrest patients treated with therapeutic hypothermia, hemodynamic optimization, and other aspects of modern critical care, who were prospectively enrolled in a multicenter clinical study examining mitochondrial dysfunction from ischemia-reperfusion injury (COMICA Study Group). Demographic variables were analyzed using chi-square tests. Comparisons of means were completed using a students t-test. Logistic regression analyses were performed to assess the relationship between hypoxia (PaO
2
300 mm Hg), mortality, and neurologic outcomes.

Results: Patients were 61± 16.8 years, 59.5% male, and had an initial rhythm of VF/VT in 50.5% of cases. We found the vast majority of patients in this study had PaO
2
values in the optimal range at all time points (79% 0 hr; 95% 12 hrs; 92% 24 hrs; 95% 36 hrs; 93% 48 hrs) and no differences between mean values for survivors and non-survivors (see Table 1) or those with good vs. poor neurologic outcomes. Logistic regression did not yield any statistically significant results when controlling for gender and initial rhythm.

Conclusions: In a cohort of patients enrolled in a multi-center study of post-arrest mitochondrial dysfunction, we found that the vast majority of patients had arterial oxygen levels optimized rapidly after ROSC and no differences in mean PaO
2
levels between survivors and non-survivors or those with good vs. poor neurologic outcomes. At high-volume centers using protocol-driven post-arrest care, optimal PaO
2
levels can be achieved in the majority of patients rapidly after ROSC.
Abstract 200: Regional Difference in Emergency Medical Services Dispatcher Cardiopulmonary Resuscitation Prearrival Instructions for Patients with Out-of-Hospital Cardiac Arrest in Japan
Authors: Hanada Hiroyuki , Hase Mamoru , Yonemoto Naohiro , Nonogi Hiroshi , Nagao Ken , Kimura Takeshi ,   J-ReSS Group
Published: April 2024

[Background] The 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommend that dispatchers should recommend cardio-pulmonary resuscitation (CPR) for unresponsive patients who are not breathing normally. This guideline also recommended special education for dispatchers. Every regional medical control system (the organization which was specially designed for presenting protocols to regional emergency medical system (EMS) and evaluating EMS operation) created dispatcher protocols to recognize cardio-pulmonary arrest and to helping CPR by bystander from July 2009 in Japan. Unfortunately, dispatchers in every regional emergency EMS could not be always specially educated.

[Goal] To evaluated regional difference in EMS dispatch prearrival CPR instruction for patients with out-of-hospital cardiac arrest (OHCA).

[Methods and Results] From January 1, 2005, through December 31, 2010, we conducted a prospective, population-based, observational study involving the consecutive patients across Japan who had OHCA (n=670,314). Dispatcher recommended CPR increased year by year, 33.8% of OHCA during 2005, 37.7% during 2006, 41.7% during 2007, 44.3% during 2008, 45.3% during 2009 and 46.3% during 2010 across Japan. Regional differences were shown in the figure.

[Conclusion] Although EMS dispatch CPR has been increased year by year, bystander CPR recommended by EMS dispatcher has been still less than 50% of all OHCA in Japan. There were regional differences in recommendation of CPR by dispatcher across Japan. Both EMS recommendation of CPR and CPR by bystander responding to EMS recommendation were lowest in Tokyo metropolitan area. Certain detailed protocols which can be done easily even after small amount of educational time for EMS dispatcher are needed.
Abstract 209: Time Intervals and Rearrest After Out-of-Hospital Cardiac Arrest
Authors: Koller Allison C , Salcido David D , Callaway Clifton W , Menegazzi James J
Published: April 2024

Background: Re-arrest (RA) occurs when a patient loses pulses following return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA), but the exact causes of RA are not fully understood. Time-to-treatment intervals may affect patient outcome and could be a plausible contributor to RA.

Objectives: To compare emergency medical services (EMS) time intervals between cases with and without RA. We hypothesized that RA cases will have significantly longer time intervals than no-RA cases.

Methods: The Institutional Review Board of the University of Pittsburgh approved this study. Cases of EMS-treated, non-traumatic OHCA from 2006 to 2011 with at least one instance of prehospital ROSC were retrospectively gathered from the Pittsburgh site of the Resuscitation Outcomes Consortium. Prehospital event times were derived from computer assisted dispatch records. We calculated time intervals to the nearest minute, including 911 call to EMS arrival, arrival to first EMS CPR, EMS CPR to ROSC, and 911 call to arrival at the emergency department (ED). RA status was determined from electronic defibrillator downloads and patient care reports. We used logistic regression to examine the association between RA and each time interval while controlling for patient demographic and clinical variables with alpha = 0.05.

Results: Two-hundred and thirty-five cases were analyzed, and 79 (34%) cases had an instance of RA. Mean time intervals and patient demographics are in Table 1. The RA group had a significantly higher proportion of males and shocked cases than the non-RA group. Odds ratios for the outcome of RA by time interval are as follows: 911 to arrival: 1.09 (CI: .98 - 1.21, p = 0.10); arrival to CPR: 1.02 (CI: 0.89 - 1.19, p = 0.74); CPR to ROSC: 0.99 (CI: 0.96 - 1.02, p = 0.86); 911 to ED: 0.99 (CI: 0.96 - 1.01, p = 0.35).

Conclusion: EMS time intervals for OHCA were not predictive of RA.
Abstract 210: The Association of Body Mass Index with Time to Target Temperature and Outcomes in Postarrest Patients Treated with Therapeutic Hypothermia via an External Cooling System
Authors: Leary Marion , Cinousis Marisa J , Sheak Kelsey , Iannacone Stephen , Kolansky Daniel , Mikkelsen Mark , Abella Benjamin S , Fuchs Barry
Published: April 2024

Background:
Regarding the use of TH for post-cardiac arrest patients, preliminary evidence suggests that more rapid attainment of target temperature (32-34
o
C) may improve outcomes. We hypothesized that the time to achieve target temperature is increased as Body Mass Index (BMI) increases and that this may impact clinical outcomes.

Objective:
To assess for an association of BMI with time to target temperature, skin complications, survival to hospital discharge, and good neurologic outcome (GCS 14-15) in survivors.

Methods:
Single-center retrospective cohort of cardiac arrest patients who underwent TH using an external cooling system between 7/2007 - 6/2012. We examined the association between BMI (weight in kilograms divided by height in meters squared) and time from initiation of cooling to attainment of target temperature. The cohort was categorized into two groups based on their BMI, (see table 1). The Wilcoxon rank-sum was used to compare time to target temperature by BMI status, categorized as obese and non-obese and the chi-squared was used to compare categorical variables.

Results:
Of the 179 patients treated with TH, 135 were evaluable. The median age of the cohort was 60 yrs, (IQR 46, 69); 64/135 (47%) were female and 37/135 (27%) had VF/VT as the initial rhythm. Mean time to target temperature was 216 min (IQR 135, 359). Obese compared to non-obese patients required a longer time to achieve target temperature (p=0.07) and obese patients were significantly more likely to have skin breakdown (p=0.01). There was no survival difference between obese and non-obese patients in terms of discharge (53% vs. 45%, p=0.39), nor good neurologic outcome (76% vs. 62%, p=0.26).

Conclusions:
Obese patients were significantly more likely to experience skin breakdown as a result of TH. There was a suggestion that time to target temperature was prolonged in obese patients. Whether outcomes could have been improved in obese patients if time to target temperature was reduced, is unknown.
Abstract 223: Kynurenine Pathway Activation Following Resuscitation from Cardiac Arrest: An Experimental and Clinical Investigation---from a Rat and a Pig Model to a Preliminary Clinical Validation
Authors: Ristagno Giuseppe , Brunelli Laura , Fries Micheal , Fumagalli Francesca , Bagnati Renzo , Pastorelli Roberta , Latini Roberto
Published: April 2024

Background. Kynurenine pathway (KP) is a major route of the tryptophan catabolism, mainly activated upon several inflammatory stimulation and involved in the pathogenesis of numerous cerebral disorders shock states. In the present study, tryptophan and KP metabolites concentrations were measured in plasma from rats, pigs, and humans resuscitated from cardiac arrest (CA). We hypothesized that the KP would be markedly activated following CA.

Methods. Plasma was obtained from: A: 18 rats, subjected to 6 min CA and 6 min CPR; B: 10 pigs, subjected to 10 min CA and 5 min CPR with post-arrest normo- (n=5) or hypothermia treatment (n=5); and C: 3 healthy human volunteers and 5 patients resuscitated from CA, with or without hypothermia. Metabolites were extracted and levels analyzed by mass spectrometry with high performance liquid chromatography. Assessements were available at baseline and hrs and days post-arrest (Figure). The specific KP metabolites were subsequently correlated with specific functional measurements and survival.

Results. KP activaction after CA was observed in rats, pigs, and humans. More specifically decreases in tryptophan occurred after resuscitation period and were accompanied by significant increases in its major metabolites, 3-hydroxyanthranilic acid (3-HAA) and kynurenic acid in each species, that persisted up to 3-5 days post-arrest (p<0.01, Figure). In rats, changes in KP metabolites reflected changes in post-resuscitation myocardial dysfunction. In pigs, decreases in tryptophan (r=-0.728, p=0.017) and increases in 3-HAA (r=0.792, p<0.01) were significanlty related to the severity of hippocampal injuries. In humans, post-arrest increases in 3-HAA were inversly related with 72 hr survival (r=-0.94, p=0.18).

Conclusions. In this fully translational investigation, the KP was activated early following resuscitation from CA. KP activation might account for the severity of post resuscitation syndrome and ultimately to survival.
Abstract 228: Neurological Outcomes of Cardiac Arrest Survivors with Myoclonus Following Resuscitation
Authors: Seder David B , Riker Richard R , Unger Barbara , Sunde Kjetil , Rupertsson Sten , Mooney Michael , Stammet Pascal , Friberg Hans , Nielsen Niklas ,   International Cardiac Arrest Registry
Published: April 2024

Objectives:
Historically, myoclonus was thought to portend a hopeless prognosis after cardiac arrest (CA). We evaluated the outcomes and characteristics of CA survivors with myoclonus in a large prospective registry.

Methods:
Retrospective review of the International Cardiac Arrest Registry (INTCAR)

Findings:
Of 2564 patients entered into INTCAR between 12/2008-12/2011, 466 (18%) had myoclonus, with an average age of 61.8 (SD 15.9) years, 84% OHCA, initial rhythm VT/VF in 47%, asystole in 28%, and PEA in 21%. Mean “no flow” interval was 8.6 (7.2) minutes, “low flow” interval 17 (15.2) minutes, and total time to return of circulation (TTROSC) 25.6 (15.5) minutes. Therapeutic hypothermia (TH) was applied in 444 (95%) patients, and 334 (72%) had EEG monitoring. Good Outcome (GO) with CPC1-2 occurred in 27 patients at ICU discharge, increasing to 43 (9.2%) at hospital discharge. For patients with GO, mean age was 53.6 (15.6), 79% VT/VF, and TTROSC was 18.6 (12.8) minutes. The EEG showed continuous activity with diffuse slowing in 61% of GO patients, and median hospital LOS was 14.5 days [IQR 9-22]. Of 423 myoclonus patients with poor outcome (PO = CPC3-5), life support was withdrawn in 330 (78%); due to neurological futility in 293 (89%), and the EEG (n=306) showed burst suppression in 152 (49.7%), status epilepticus in 102 (33.3%), severe background attenuation in 75 (24.5%) and continuous activity with diffuse slowing in 75 (24.5%). Among PO patients, 49 (11.6%) did not receive or complete TH. Median hospital LOS in this cohort was 5 [IQR3-7] days. Of 293 patients that died of “neurological futility”, 131 (45%) died less than 5 days after CA.

Conclusions:
Myoclonus after cardiac arrest should not be considered uniformly fatal. Despite early withdrawal or less than fully aggressive life supportive measures in many patients, 9.2% of myoclonus patients in a large registry population had good outcomes.
Abstract 230: Epidemiology and Outcomes of Emergency Medical Services-Assessed Out-of-Hospital Cardiac Arrest in Korea: A Nationwide Observational Study from 2006 to 2010
Authors: Shin Sang Do , Ro Young Sun , Song Kyoung Jun , Lee Eui Jung , Ahn Ki Ok
Published: April 2024

Background

The goal of this study is to better understand the epidemiologic features and the patient-community-emergency medical service (EMS)-hospital factors affecting outcomes of out-of-hospital cardiac arrest (OHCA).

Methods and Results

This study was performed in an EMS system with a single-tiered basic-to-intermediate service level and approximately 900 destination hospitals for eligible OHCA cases. A nationwide OHCA database including demographic, Utstein, EMS, and hospital factors and outcomes was constructed using EMS run sheets of eligible cases transported by 119 EMS ambulances and followed by medical record review for 2006 to 2010. Cases with unknown outcome were excluded. The primary end points were survival to discharge. The epidemiologic characteristics of OHCA were described and adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for main outcome, adjusting for potential predictors.

There were 97,291 EMS-assessed OHCAs excluding 14,798 cases because the medical records were not available (N=10,626) and the survival outcomes were unknown (N=4,172). Of these, 73,826 (75.9%) OHCAs were resuscitation attempted by EMS. The survival to discharge was 3.0% for EMS-assessed (3.3% for cardiac origin vs. 2.3% for non-cardiac origin), 3.6% for EMS-treated (4.0% for cardiac vs. 2.7% for non-cardiac), and 20.9% for cardiac origin with shockable rhythm. The drowning, intoxication, and asphyxia induced OHCAs had statistically better survival rates than cardiac origin. The odds for survival to discharge are significantly lower for elderly, asystole as primary ECG, OHCA with cardiac origin occurred in winter or 6PM to midnight, un-witnessed, no bystander cardiopulmonary resuscitation, OHCA with longer EMS response, and being transported to lower level of ED.

Conclusions

In this nationwide cohort study from 2006 to 2010, the standardized incidence rate increased 46.3 in 2006 to 52.0 per 100,000 person-years for EMS-assessed OHCA and overall survival rate was 3.0%. Potential factors for poor outcome were systemically identified in individual, community, EMS, and hospital chain.
Abstract 231: Predicting Outcome After Out-of-Hospital Cardiac Arrest: Results of a National Registry
Authors: Stelzig Katharina , Busch Hans-Jörg , Pittl Undine , Pfeifer Rüdiger , Killermann Dirk , Wolfrum Sebastian
Published: April 2024

Background: Advanced post-resuscitation

care including mild therapeutic hypothermia reduces mortality and improves neurological outcome after OHCA. The aim of the current registry is to identify clinical parameters in OHCA patients treated with a modern post-resuscitation care in order to identify predictors of survival and neurological recovery.

Methods and Results: Data sets of 881 OHCA patients treated between 2002-2011 in 4 German university hospitals were analyzed retrospectively. ICU mortality was 36.5% increasing to 45.6% and 53.9% after 1 and 6 months, respectively. Several factors, such as age, initial rhythm, duration of no-flow phase and others were identified as predictive factors for 6 months mortality but not for a survival with good neurological outcome. Interestingly,temperature between hours 8 and 36 after start of cooling were lower in long-term survivors as compared to those who died (Fig A). There was no effect of cooling velocity, duration of cooling and re-warming velocity neither on survival nor neurological recovery after 6 months . In 497 patients neuron specific enolase (NSE) was measured. NSE levels between day 1 and 3 significantly predicted survival (Fig B) and a cut-off of 80µg/L was identified for a markedly increased mortality.

Conclusions: Even after implementation of an improved post resuscitation care, mortality after cardiac arrest is still high. Interestingly, target temperature slightly above the corridor of 32-34°C is associated with increased mortality. Furthermore, in this large cohort NSE has been shown to be a good predictor of long-term mortality with a cut-off markedly higher than previously proposed in the pre-hypothermia era.
Abstract 233: Initial Arrest Rhythm and Outcome in Patients Undergoing Primary PCI for ST-Segment Elevation Myocardial Infarction Complicated by Out-of-Hospital Cardiac Arrest
Authors: Thomas Joseph L , Tadeo Richard , Koenig William , Sung Gene , Eckstein Marc , French William J , Niemann James T , Shavelle David M
Published: April 2024

Background
: The prognosis of patients with out of hospital cardiac arrest (OHCA) varies by the initial arrest rhythm. Patients with shockable rhythms such as ventricular tachycardia (VT) or ventricular fibrillation (VF) have better survival than those with nonshockable rhythms including asystole and pulseless electrical activity (PEA). The impact of initial arrest rhythm on outcome in ST-segment elevation myocardial infarction (STEMI) complicated by OHCA is unknown.

Methods
: The Los Angeles County Emergency Medical Services STEMI Receiving Center System coordinates and provides care for patients with STEMI and OHCA within a network of 33 primary PCI centers serving the 9.8 million residents of Los Angeles County. Between April and December 2011, a total of 61 patients with STEMI with OHCA and restoration of spontaneous circulation (ROSC) were treated with primary PCI. Patient characteristics and outcomes were analyzed based on initial arrest rhythm.

Results:
61 patients with STEMI, OHCA and ROSC were treated with primary PCI during the study period. Over 80% of these patients had a door to balloon time of ≤ 90 minutes. 50 patients had a shockable initial arrest rhythm (VT, VF or AED analyzed/defibrillated) and 11 had a nonshockable rhythm (asystole, PEA). Initial neurologic status following ROSC was similar between groups but patients with initial asystole or PEA had worse neurologic status at discharge. The presence of a shockable initial rhythm was associated with a numerically superior rate of hospital survival but this did not reach statistical significance.

Conclusions:
Similar to the general cardiac arrest population, a shockable initial arrest rhythm is associated with better outcomes in patients with STEMI and OHCA. Analyses of patients with STEMI complicated by OHCA should be stratified by initial arrest rhythm as significant pathophysiologic differences may exist between these groups.