bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 87: Duration of Longest Chest Compression Interruption Predicts Poor Cardiac Arrest Survival Independent of Chest Compression Fraction
Authors: Brouwer Tom F , Walker Robert G , Chapman Fred W , Koster Rudolph W 
Published: April 2024

Background
Long pauses in chest compressions (cc) are thought to be harmful. However, prior clinical analyses have only evaluated peri-shock pauses (PSP) of the first 1 - 3 shocks, or cc fraction over the first few minutes of the resuscitation. We analyzed full recordings from a large cohort of resuscitations to explore relationships between long PSPs, long pauses for other reasons (non-PSP), and survival.
Methods
In an observational study of prospectively collected data, we enrolled all patients with cardiac cause out-of-hospital cardiac arrest presenting with VT/VF during calendar year 2009 in five EMS systems. Continuous ECG and impedance recordings from all defibrillators (AED and manual) used during resuscitation were analyzed to measure longest PSP (longest interval without cc containing a shock), and longest non-PSP (longest interval without cc prior to the last shock, and not containing a shock). Because pause durations are inversely related to cc fraction, we also measured cc fraction over the entire resuscitation.
Results
In 319 enrolled patients, survival rate was 38% and CC fraction was median (IQR) 79% (71%, 84%). Longest PSP was 26 (16, 42) sec and longest non-PSP was 24 ( 11, 38) sec. Both the longest PSP [Odds Ratio (OR) = 0.91 per 5 sec increment (0.86, 0.97)] and the longest non-PSP [OR = 0.84 (0.76, 0.92)] were significantly associated with survival to discharge in a multivariate regression model adjusting for recognized Utstein predictors. These significant associations did not change when additionally adjusted for cc fraction. In 36% of patients, the longest non-PSP was ≥ the longest PSP. Survival was significantly lower in this group than in the 64% of patients where the longest PSP was longer than any non-PSP (27% vs 44%, p=0.004), despite a higher median CC fraction (80% vs 77%, p=0.04).
Conclusions
Prolonged cc pauses have a significant negative association with survival that is not explained by chest compression fraction. The longest non-PSP had a lower odds ratio for survival than the longest PSP, and it was the longest pause prior to the last shock in more than a third of the cases. Avoiding long pauses for interventions other than defibrillation may be even more important than minimizing PSPs or further increasing chest compression fraction.
Abstract 9637: Outcomes in Pediatric Cardiac Arrest with Pulseless Ventricular Tachycardia or Ventricular Fibrillation with use of Amiodarone versus Lidocaine
Authors: Valdes Santiago O , Donoghue Aaron J , Hoyme Derek B , Berg Marc D , Berg Robert A , Samson Ricardo A 
Published: April 2024

BACKGROUND: Current PALS guidelines recommend amiodarone for cardiac arrest associated with refractory pulseless ventricular tachycardia (pVT) and ventricular fibrillation (VF), based on a single pediatric study and extrapolation from adult data. We sought to compare outcomes of refractory pVT/VF arrest treated with amiodarone or lidocaine.
METHODS: Retrospective cohort study from the Get With the Guidelines-Resuscitation database for in-patient cardiac arrest. Patients < 18 years old with pVT/VF cardiac arrest treated with amiodarone, lidocaine or both were included. Patients receiving amiodarone or lidocaine prior to arrest were excluded. Univariate analysis compared Utstein outcomes (ROSC, 24 hour survival, survival to discharge) between those receiving amiodarone, lidocaine or both (chi square analysis). Multivariate analysis was done to estimate the association between amiodarone and lidocaine and survival outcomes while controlling for potential confounders among patient, event and treatment characteristics.
RESULTS: A total of 358 patients met all inclusion criteria. Utstein outcomes are summarized below. Univariate analysis demonstrated significant differences between groups in ROSC and 24 hour survival; survival to discharge did not differ significantly. Multivariate analysis showed improved 24 hour survival with lidocaine compared to amiodarone (adjusted odds ratio 1.78, 95% CI 1.12 - 2.84) while controlling for the above confounders. Neither amiodarone or lidocaine was significantly associated with ROSC or survival to discharge.
CONCLUSIONS: For children with in-hospital refractory pVT/VF, lidocaine use without amiodarone was independently associated with improved 24 hour survival. Amiodarone alone or in combination with lidocaine was not associated with superior rates of ROSC, survival at 24 hours, or survival to discharge. Lidocaine should be considered in the treatment of pediatric cardiac arrest with pVT/VF.
Abstract 18012: Insights into the Cardiorenal Syndrome Type II in the Rat
Authors: Angelini Annalisa , Castellani Chiara , Virzì Maria G , Fedrigo Marny , Thiene Gaetano , Valente Marialuisa , Ronco Claudio , Vescovo Giorgio 
Published: April 2024

Cardiorenal Syndrome Type II (CRSII) is kidney function deterioration in the presence of Chronic Heart Failure (CHF). The mechanisms leading to kidney damage in CHF are however still obscure.
We studied the development of kidney injury in a model of right CHF monocrotaline (MCT) treated rats.

Methods:
10 Sprague-Dawley rats were treated with MCT for 4 weeks until they developed HF. 11 were taken as control (C). Heart failure was confirmed on transverse heart histologic sections looking at RV hypetrophy /dilatation and BNP plasma levels. Cytokine profile was assessed by Multiplex array on sera. pNGAL, pCreatinine (ELISA), kidney tissue NGAL (RT-PCR) were performed. Kidney cell apoptosis was assessed by TUNEL.

Results:
MCT rats showed higher BNP values (MCT 4.7±1.2 vs C 1.5±0.5pg/mL p<0.004 ), marked RV Hypetrophy and dilatation (RVMass/RVVolume MCT 1.46±0.31vs C 2.4±0.8 p<0.01). TNFα (MCT 1325.37±559.95vsC84.46±64.50 pg/ml ), IL1(MCT183.71±51.61vsC78.31±26.07), IL4 (MCT 731.67±154.83 vs C 316.62±12.55pg/ml), IL6 (MCT 5314.983±1632.98 vs C1754.01±188.85), IL10 (MCT2613.10±934.04vs C847.70±152.19 pg/ml) were all increased (p<0.05) as well as Creatinine (MCT 0.95±0.4 vs C 0.57±0.4 ug/mL, p<0.05). Both plasma (MCT 0.56±0.28 vs C 0.25±0.16 ug/mL,p<0.02) and kidney tissue NGAL (MCT 70.7±8.7vs C 32.1±9.9 AU, p<0.001) were significantly increased and a higher number of kidney apoptotic cells was found (MCT 184.01±47.6 vs C 16.3±11.6 cells/mm2, p< 0.0001). In C rats apoptosis was found only on tubular or vascular cells, while in MCT also a lot of interstitial cells was found. In MCT rats apoptosis was found in medullar part of kidney with focal aspect.

Conclusion:
CHF in the rat is accompanied by deterioration of kidney function (CRSII). A rise of creatinine and NGAL, an early biomarker of kidney damage, was detected. Kidney cells apoptosis triggered by circulating pro-inflammatory cytokines represent the final insult to the kidney due to the CHF-induced perturbation of neuro-endocrine and inflammatory milieu.
Abstract 18112: Low-Energy Shock Wave Treatment Induces Angiogenesis in Ischemic Muscle by Stimulation of Toll-Like Receptor 3 Signaling
Authors: Holfeld Johannes , Tepeköylü Can , Kozaryn Radoslaw , Albrecht-Schgoer Karin , Krapf Christoph , Kirchmair Rudolf , Bernhard David , Zacharowski Kai , Urbschat Anja , Grimm Michael , Paulus Patrick 
Published: April 2024

Introduction:
Low energy shock waves (SW) have been shown to induce angiogenesis in ischemic myocardium. The mechanism translating the physical stimulus to a biological signal is unknown. Toll-like receptor (TLR)-3 is activated by RNA binding. It plays a key role in inflammation and angiogenesis.

Hypothesis:
SW cause cellular cavitation, thus liberating cytoplasmic mRNA that activates TLR-3 as does the specific agonist Poly I:C. Effects are suppressed in TLR-3 silenced cells and in TLR-3 knock out mice.

Methods:
The effect of SW was tested in human umbilical vein endothelial cells (HUVECs): untreated (control) vs. SW treated (SW group) vs. treated with 200 μg/ml Poly I:C (agonist). TLR-3 gene silencing was done with siRNA. Hind limb ischemia was performed in wild type and TLR-3 kock-out mice. Expression of mRNA and proteins of the TLR-3 signaling pathway as well as typical angiogenic genes and proteins were measured. Laser doppler perfusion imaging and necrosis score were assessed for clinical outcome evaluation (n=6).

Results:
Shock wave treatment of HUVECs shows increase of mRNA expression (% of control) as does Poly I:C after 2 hours: TLR-3 (SW group 123.8 ± 8.0 and agonist group 237.7 ± 14.1, p<0.0001), Tie-2 (SW group 154.3 ± 20.0 and agonist 125.7 ± 12.3, p<0.008).

TLR-3 gene silencing in SW treated HUVECs causes loss of response for TLR-3 mRNA (107.0 ± 13.3) as compared to SW group (378.3 ± 14.2) or agonist (1261 ± 72.1), both p<0.0001.
SW treated TLR-3 knock-out mice showed no improvement of perfusion ratio 4 weeks after hind limb ischemia (0.52 ± 0.07 vs. 0.53 ± 0.02 controls, p>0.05), whereas SW treated wild type animals improved significantly (0.78 ± 0.03 vs. 0.48 ± 0.08 controls, p=0.015). Pro-angiogenic genes and proteins were up-regulated significantly. All known TLR-3 signaling pathways were involved as shown by significant increase of key proteins Trif, TRAF6 and IRF3.

Conclusion:
Low energy shock waves induce angiogenesis in ischemic muscle by stimulation of Toll-like receptor 3 signaling in endothelial cells. Effects are suppressed in TLR-3 silenced cells and in TLR-3 knock-out mice.
Abstract 18363: Activation of the Hippo Pathway, Associated With Suppression the Canonical Wnt Signaling, Contributes to the Pathogenesis of Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Chen Suet Nee , Gurha Priyatansh , Lombardi Raffaella , Ruggiero Alessandra , Willerson James , Marian Ali J 
Published: April 2024

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an enigmatic disease characterized by excess fibro-adipocytes in the heart, cardiac arrhythmias and heart failure. Molecular genetic studies have identified mutations in several desmosome proteins as causes of ARVC. Our objective is to delineate the molecular links between the desmosomes and fibro-adiposis in ARVC.
Expression levels and localization of plakophilin 2 (PKP2), plakoglobin (JUP), desmocollin 2 (DSC2), desmosome proteins and connexin 43 (GJA1), a member of Gap junction, in the human hearts with ARVC, were reduced. To test whether molecular remodeling of the junctions affected signaling pathways, we analyzed the Hippo kinase pathway, which is regulated by cell-cell contact and known to suppress the canonical Wnt signaling, the latter implicated in the pathogenesis of ARVC. Accordingly, Merlin, an upstream regulator of the Hippo kinase cascade, was activated and YAP, the downstream effector was inactivated by phosphorylation. To gain mechanistic insights, expression of Pkp2, the most common causal gene for ARVC, was stably knocked down using shRNA in the HL-1 cells. Transcriptome analysis showed reduced mRNA levels of the canonical Wnt and Hippo targets including Ctgf, an inhibitor of adipogenesis. KD of PKP2 was associated with a dramatic reduction in pPKC-α level, in accord with the known function of PKP2 as a platform for phosphorylation of PKC-α. Reduced pPKCα, an inhibitor of Merlin through phosphorylation, was associated with activation of Merlin and cascade phosphorylation of MST1, LATS1/2 and YAP, constituents of the Hippo pathway. Consequently, signaling through TEAD, the transcription factor of the Hippo pathway, was reduced and sequestration of pβ-catenin in the cytoplasm was increased, leading to suppression of the canonical Wnt signaling and enhanced adipogenesis. KD of pLAT1/2 using shRNAs partially rescued the molecular phenotype.
Thus, human ARVC is characterized by molecular remodeling of the intercalated discs, which results in inactivation of PKCα, phosphorylation of the Hippo kinases, suppression of the canonical Wnt signaling and enhanced adipogenesis. The findings implicate the Hippo pathway in the pathogenesis of ARVC.
Abstract 352: Risk Index of Sudden Death by Long QT Syndrome and Wolff-Parkinson-White Syndrome in School
Authors: Ayusawa Mamoru , Sumitomo Naokata 
Published: April 2024

Objectives:
To clarify the epidemiological risk of sudden death by QT prolongation and WPW syndrome in school life.

Materials and Methods:
Based on the data reported to the mutual aid insurance system for school from 1993 to 2009, sudden deaths of long QT syndrome and WPW syndrome those who had been found by screening system in school. Epidemiological data was compared. Prevalence of both diseases found in the screening system in this period to calculate the risk index of sudden death was compared in both diseases.

Results:
The prevalence of QT prolongation was 0.14 in 1,000. Fourteen sudden death cases were reported in 17 years, girls occupied 58.8%. Seven cases were in elementary school, and five cases in middle school students. Time zone is known in eight cases, six cases are in the morning, two cases in the afternoon.

The prevalence of WPW syndrome found by screening system was 1.07 in 1,000. Eighteen sudden death cases were reported in 17 years, girls occupied 16.7%, one case in elementary school; two cases in the junior high school, and 15 cases were high school students. Time zone is known in six cases, all cases occurred in the afternoon.
The number of sudden death in each disease divided by prevalence found by screening system was 8.6 in QT prolongation cases, and 1.2 in WPW syndrome cases.
Risk of sudden death by QT prolongation was about seven times of WPW syndrome.

Conclusion:
This index is informative for a better understanding to the description of the risk need for attention of family, students and caregivers in schools.
Abstract 14866: Athletic Heart Screening: Usefulness of Echocardiography and Economic Impact
Authors: Bendaly Edgard 
Published: April 2024

Background:
The athletic heart screen (AS) for sudden cardiac death (SD) detection is controversial in the USA. EKG use is common in AS programs but ECHO is uncommon. Our study aims to determine the effectiveness of ECHO in identifying athletes at risk for SD that would have been missed without ECHO and to evaluate the cost of AS.

Methods:
AS and medical records were reviewed. AS consisted of a self-completed questionnaire, EKG and limited ECHO. AS were abnormal at the discretion of the reader at the time they were reviewed. Data is expressed as percentage. Cost is calculated using average reimbursement for the ensuing initial cardiac evaluation.

Results:
In 10 years, 2016 AS were randomly assigned to 5 pediatric cardiologists. There were 336 (16.7%) abnormal AS. The rate of abnormal AS was 79/244 (12.1%), 19/190 (10%), 82/630 (31.2%), 7/63 (11%), and 164/889 (18.4%) for the reviewers, representing a wide variability in the percentage of abnormal AS among reviewers.

This resulted in 166 (49.4%) initial cardiac evaluations leading to 207 noninvasive testing in addition to repeat EKG in some cases. Testing included ECHO, Holter, stress test and cardiac CT and MRI. Initial evaluation was normal in 103 (62.0%) cases. Invasive interventions included: 3 small ASD closures, 1 moderate PDA closure, an EP ablation for WPW, and 1 surgery for abnormal right coronary artery origin (ARCA). In the remaining 57 (34.3%) cases, the cardiac abnormalities identified were mild including: prominent aortic root, premature complexes, and mild left-sided valve abnormalities in asymptomatic individuals. Conservatively, 2 diagnoses would be low risk for SD: WPW and ARCA representing <0.1% of all AS performed.
An abnormal AS was made by ECHO in 184/336 (54.8%) cases leading to 105 evaluations: 55 (52.4%) were normal, 45 (42.8%) had mild abnormalities, and 5 (4.8%) had the ASD and PDA closures, and the coronary surgery.
The cost of 2016 AS was $100,000. The cost of the 166 first evaluations performed including noninvasive testing was $160,462.

Conclusions:
AS results are reviewer-dependent and low yield for detecting conditions at high risk for SD. The addition of ECHO can identify mild congenital heart disease and coronary abnormalities at the expense of increasing costs, acutely and long term.
Abstract 15182: Factors Associated With Aortic Dissection in Patients With
TGFBR1
Or
TGFBR2
Mutations: Results From the Montalcino Aortic Consortium
Authors: Jondeau Guillaume , Ropers Jacques , Regalado Ellen , Braverman Alan , Evangelista Arturo , Teixedo G , De Backer Julie , Naudion Sophie , Zordan Cecile , Morisaki Takayuki , Morisaki Hiroko , Muino Mosquera L , von Kodolitsch Yskert , Dupuis-Girod Sophie , Morris Shaine A , Jeremy Richmond , Odent Sylvie , Langeois Maud , Spentchian Myrtille , Milleron Olivier , Boileau Catherine , Pyeritz Reed , Milewicz Dianna ,   Montalcino Aortic Consortium
Published: April 2024

Introduction:
Natural history of patients with
TGFBR1
or
TGFBR2
mutations is not well known

Hypothesis:
Physical features may indicate high risk patients

Methods:
Data were collected on 403 patients with either
TGFBR1
or
TGFBR2
mutations. We compared the phenotypic features of patients with and without aortic dissection.

Results:
Patients with aortic dissection were diagnosed when older, suggesting delay in diagnosis being one of the main parameter related to the occurrence of this deadly complication.

Features of Loeys Dietz Syndrome (arterial tortuosity, hypertelorism, broad or bifid uvula and wide scars) were more frequently associated with dissection,suggesting that these features may help identifying high risk patients, in whom aortic surgery may have to be proposed earlier.
In contrast, the systemic score proposed for the diagnosis of Marfan syndrome was not helpful in recognizing high-risk patients.
Of note, a systemic score ≥ 7 was present in 1/5 of the population.

The risk of aortic dissection was similar in patients carrying a
TGFBR1
mutation or a
TGFBR2
mutation (35/159 (22%) vs. 57/244 (23%). However,

- The last maximal aortic root diameter before or at the time of type A aortic dissection was greater in
TGFBR1
than in
TGFBR2
(65 (22) vs. 50 (12)mm ; p= 0.039).

- Type B aortic dissection was less frequently reported in
TGFBR1
(6% vs 12% of the patients)

- Lastly aortic event (surgery or dissection) occurred more frequently in males than in females carrying a
TGFBR1
mutation {53.7% of males (median age 27 years [21-39]) and 29.3% of females (34 years [28-44]), p=0.003} but not a
TGFBR2
mutation (46.2% of males (median age 32 [20-41]) and 40.5% of females (30 years [19-42], NS}

Conclusions:
Aortic dissection was associated with delayed/unknown diagnosis, and the presence of clinical features of LDS. The prevalence for aortic events differs between men and women with
TGFBR1
mutation but not
TGFBR2
mutations
Abstract 13441: The QTc Interval Does Not Predict Mortality at the Emergency Department
Authors: Vandenberk Bert , Siau Caroline , Vandael Eline , Foulon Veerle , Verelst Sandra , Willems Rik 
Published: April 2024

Introduction:
The Bazett corrected QT interval (QTcB) has been shown a predictor of outcome at the Emergency Department (ED). Since the known limitations of QTcB at higher heart rates, we investigated the use of a recently proposed QRS width dependent QTc algorithm (QTcA) at the ED.

Methods:
We performed a retrospective age- and sex-matched cohort study, powered to detect mortality differences between normal and prolonged (> 450/470 ms in men and women respectively) QTcB at the ED. QTcA, Fridericia formula is used when QRS<120ms and Rautaharju when ≥120ms, was compared with QTcB. Cox regression modeling for in-hospital mortality was performed.

Results:
In total 1930 patients, age 72 ± 16 y, 63% male and mean triage code 2.5 ± 0.6, were included. The mean heart rate was 81 ± 22 bpm. 18% patients had a QRS duration ≥120ms and 81% had sinus rhythm. In-hospital mortality was 4.4% and 1 y mortality was 19.5%.

Using QTcB, 50% of patients had prolonged QTc, whereas only 17.4% using QTcA. In-hospital mortality in the prolonged QTcB group was significantly higher (6.0%) compared to the control group (2.8%, p<0.001), whereas with QTcA mortality rates were similar (5.4% vs 4.2% respectively, p=0.349). Also, 1 y mortality was significantly higher in patients with prolonged QTcB (22.6% vs 16.4%, p=0.001), while prolonged QTcA showed only a trend to worse survival (22.9% vs 18.8%, p=0.080).
In univariate Cox regression for in-hospital mortality, QTcB was a predictor of mortality (HR 1.004, 95%CI 1.000 - 1.009), while QTcA was not (HR 1.001, 95%CI 0.995 - 1.008).
After multivariate analysis QTcB did not remain as independent predictor of mortality. Independent predictors were heart rate (HR 1.02, 95%CI 1.01-1.03), history of cardiovascular disease (HR 1.66, 95%CI 1.00-2.76), witnessed arrhythmia requiring CPR (HR 3.79, 95%CI 1.66-8.67), neurological events (CVA, epileptic insult, IC bleeding or hematoma) (HR 3.51, 95%CI 1.91-6.43), age-adjusted Charlson Comorbodity Index (HR 1.18, 95%CI 1.10-1.27), lower eGFR (HR 0.99, 95%CI 0.98-1.00) and higher leukocyte count (HR 1.02, 95%CI 1.01-1.03).

Conclusion:
Several easily obtainable parameters and risk factors can be useful for risk stratification at the ED, however adequate corrected QT was not an independent predictor of mortality.
Abstract 11926: Angiotensin-(1-7)/mas Receptor Agonist Protects Hippocampus Neurons In Mouse Model Of Vascular Dementia
Authors: Hoyer-kimura Christina H , Konhilas John P , Mansour Heidi , Polt Robin L , Hay Meredith 
Published: April 2024

Decreased brain blood flow, increased inflammation, and increased reactive oxidative species (ROS) are correlated to accelerated progression of both vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer's disease related dementia (ADRD). It has been previously demonstrated that VCID models with blood brain barrier dysfunction exhibit hippocampal neuronal loss and impaired cognitive function.
Our novel synthetic glycosylated Angiotensin-(1-7) derivative (PNA5), has an enhanced half-life and is optimized for better blood-brain-barrier penetration. In our preclinical VCID model, PNA5 treatment inhibits brain ROS production, and reverses cognitive deficits.

We hypothesized that 1) neuronal cell count in the CA1 region of the hippocampus will be decreased in our heart failure (HF) induced VCID mouse model and 2) PNA5 treatment will mitigate neuronal cell loss within the hippocampus and protect cognitive function. VCID was induced in adult male C57BL/6J mice (10-15/group), via HF. Control mice underwent sham surgery. Following 5 weeks post coronary ligation, mice were treated with either 1) saline or 2) 50 micrograms/kg/day PNA5, via daily subcutaneous injection for 21 days. Novel-object recognition was used to measure cognitive function and is represented as a DRatio. VCID-Saline mice displayed cognitive impairment (DRatio mean -0.02, SE
+
0.07) compared to Control-Saline (DRatio 0.57
+
0.1). Cognitive function was rescued by PNA5 treatment (DRatio 50micrograms/kg/day 0.61
+
0.09). Hippocampal neuronal cell loss was determined through analysis of free-floating formalin fixed 16micron cryosection brains, stained with NeuN (ab177487, 1:500) and counted using ImageJ. CA1 Hippocampal regions (-1.6 to -2.0 millimeters from bregma) were imaged at 40x magnification. Data were analyzed by one-way ANOVA. VCID-Saline mice displayed a significant decrease in neurons in the CA1 region (3.35
+
0.11 cell/ pixel linear area) compared to Control-Saline mice (3.94
+
0.12). Mice treated with PNA5 had significantly higher CA1 neuronal cell count (3.87
+
0.17) in comparison to VCID-Saline treated mice. These data suggest that PNA5 protects against VCID cognitive impairment and prevents neuronal cell loss in VCID mouse models.