bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10343: Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Peripheral Artery Disease and Non-valvular Atrial Fibrillation: Insights From the Aristotle Trial
Authors: Hu Peter , Lopes Renato D , Stevens Susanna , Wallentin Lars , Thomas Laine , Alexander John H , Hanna Michael , Lewis Basil S , Verheugt Freek W , Granger Christopher B , Jones William S
Published: April 2024

Introduction:
Vascular disease has been incorporated in the CHA2DS2-VASc risk tool to predict the risk of stroke/systemic embolism in patients with atrial fibrillation (AF).

Hypothesis:
This post hoc analysis of the ARISTOTLE trial aimed to determine the absolute rates of stroke/systemic embolism and bleeding associated with peripheral artery disease (PAD) as well as the efficacy and safety of apixaban vs warfarin in AF patients with and without PAD.

Methods:
ARISTOTLE randomized patients with AF and risk of stroke to apixaban and warfarin for the prevention of stroke/systemic embolism.

Results:
A total of 884 (4.9%) patients had PAD at baseline as defined by site investigators on the case report form. Patients with versus without PAD had non-significantly higher rates of stroke/systemic embolism [HR 1.32, 95% CI 0.93-1.88, p=0.12] and major or clinically relevant non-major (CRNM) bleeding [HR 1.12, 95% CI 0.90-1.39, p=0.31]. Those with PAD had an increased risk of all-cause death [HR 1.36, 95% CI 1.11-1.67, p=0.003] and CV death [HR 1.44, 95% CI 1.08-1.90, p=0.01] when compared with those without PAD. The effect of apixaban vs warfarin for the prevention of stroke/systemic embolism was similar in patients with PAD [HR 0.66, 95% CI 0.33- 1.31] and without PAD [HR 0.80, 95% CI 0.66-0.96, interaction p=0.61] [Table]. Patients with PAD appeared to have less reduction in major or CRNM bleeding with apixaban compared with warfarin [HR 1.04, 95% CI 0.69-1.57] versus those without PAD [HR 0.66, 95% CI 0.59-0.73, interaction p=0.03].

Conclusions:
Patients with PAD in ARISTOTLE had non-significantly higher risk of stroke/systemic embolism when compared with patients without PAD. The benefits of apixaban versus warfarin on stroke and all-cause death are similar in patients with and without PAD. However, the reduction in bleeding with apixaban seemed to be greater in patients without PAD than in patients with PAD (interaction p=0.03).
Abstract 10411: Significance of Inflammation and Neoangiogenesis of Epicardial Adipose Tissue on Coronary Atherosclerosis Based on Computed Tomography Analysis
Authors: Kitagawa Toshiro , Yamamoto Hideya , Tsushima Hiroshi , Senoo Atsuhiro , Sentani Kazuhiro , Yasui Wataru , Kihara Yasuki
Published: April 2024

Background:
Previous studies indicate that epicardial adipose tissue (EAT) biologically contributes to coronary atherosclerosis progression. The inflammation and neoangiogenesis have been reported to be biological markers of ‘diseased’ adipose tissues. We evaluated the relation of EAT pathologies, represented by inflammation and neoangiogenesis, to computed tomography (CT)-based coronary atherosclerosis.

Methods:
We enrolled 45 patients undergoing cardiac CT examination before elective cardiac surgery (coronary artery bypass graft [CABG], n = 21; non-CABG, n = 24). Each patient was evaluated with visceral adipose tissue (VAT) area, EAT volume, coronary calcium score (CCS), and presence of non-calcified coronary plaque (NCP) on CT angiography. During each cardiac surgery, histological samples for immunohistochemistry were obtained from EATs adjacent to the left anterior descending and right coronary arteries. Each patient was assessed with the numbers of CD-68+ individual macrophages and CD-31+ neovessels in a total of 6 random high-power fields (x400) of EAT samples.

Results:
The EAT volume had no correlation with macrophage infiltration (r = 0.09, p = 0.53) or neoangiogenesis (r = 0.08, p = 0.59) in EAT. In the comparisons of EAT pathologies based on CCS levels or NCP presence, the moderate CCS (101-400) or NCP present group had more macrophage infiltration and neoangiogenesis in EAT (Fig 1). On multivariate analyses adjusting for age, sex, CABG vs. non-CABG, VAT area, and EAT volume, both the moderate CCS and NCP presence showed significant correlation with increased macrophage infiltration (β = 0.65; p < 0.0001, and β = 0.49; p = 0.0089, respectively) and neoangiogenesis (β = 0.55; p = 0.0011, and β = 0.53; p = 0.012, respectively) in EAT (Fig 2).

Conclusions:
The EAT biological activities independently correlate with moderate, rather than severe, coronary calcium and NCP formation, suggesting the stage in the process of coronary atherosclerosis growing.
Abstract 10437: Epinephrine in Cardiac Arrest: A Randomized, Multicenter, Double-blinded, Placebo-Controlled Experimental Trial
Authors: Lin Steve , Sundermann Matthew L , Dorian Paul , Fink Sarah , Halperin Henry , Kiss Alex , Koller Allison C , McCracken Brendan M , Morrison Laurie J , Neumar Robert W , Niemann James T , Ramadeen Andrew , Salcido David D , Tiba Mohamad H , Youngquist Scott T , Zviman Menekam , Menegazzi James J
Published: April 2024

Introduction:
Epinephrine is universally used in cardiac arrest primarily to increase coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR). The effect of different modes of epinephrine administration and the persistence of effect with repeated doses are not known.

Methods:
We conducted a preclinical, randomized, multicenter, double-blinded, placebo-controlled experimental trial of 45 swine from five different laboratories (Ann Arbor, MI; Baltimore, MD; Los Angeles, CA; Pittsburgh, PA; Toronto, ON) using a standard treatment protocol. Ventricular fibrillation was induced and left untreated for 6 min before starting continuous CPR, which included mechanical chest compressions (100/min) and manual ventilations using a bag-valve-mask with 100% O2 (10 breaths/min). After 2 min of CPR onset, nine animals from each lab were centrally randomized to one of three treatment arms: 1) Continuous IV epinephrine infusion (0.00375mg/kg/min) for 12 min and placebo IV normal saline (NS) boluses every 4 min, 2) Three IV epinephrine boluses (0.015mg/kg) every 4 min and placebo IV NS infusion, or 3) Placebo NS infusion and boluses. The primary outcome was mean CPP during the drug therapy period (2-14 minutes after CPR onset). Differences in CPP were analyzed using repeated measures regression modeling.

Results:
There was no statistical difference in mean minute CPP (mmHg) between the three groups: 14.4±6.8 (infusion), 16.9±5.9 (bolus), and 14.4±5.5 (placebo) (p=NS). Repeated bolus doses of epinephrine caused transient increases in CPP that tended to peak at ~2 min after drug administration (Figure).

Conclusion:
Standard dose epinephrine, whether given by infusion or repeated boluses during CPR, did not significantly improve average CPP over time compared to placebo. Tachyphylaxis to epinephrine may occur regardless of mode of administration. This study raises important questions about optimal epinephrine dosing and administration strategy.
Abstract 10441: Development of
in vivo
Tissue-Engineered Vascular Grafts With an Ultra Small Diameter of 0.6 mm (MicroBiotubes)
Authors: Ishii Daizo , Enmi Jun-Ichiro , Iida Hidehiro , Satow Tetsu , Takahashi Jun C , Kurisu Kaoru , Nakayama Yasuhide
Published: April 2024

Introduction and Hypothesis:
Small-caliber arterial substitutes are needed for various revascularization procedures. Biotubes, in vivo tissue-engineered autologous tubular tissues, have high performance potential as a reliable aortic vascular graft with diameter of over several mm. This study challenged the development of micron-ordered caliber Biotubes (MicroBiotubes: MBs) with diameter of 0.6 mm and their quality and patency were non-invasively observed by optical coherence tomography (OCT) and magnetic resonance angiography (MRA), respectively.

Methods:
The mold for multiple preparing of MBs was assembled by several stainless wires covered with silicone tubes with outer diameter of 0.6 mm (Fig. 1A). The molds were surgically embedded into the dorsal subcutaneous pouches of rats. After 2 months, the molds were harvested with surrounding tissues and MBs were obtained, as encapsulated connective tissues, by removing the molds. MBs (length, 10 mm) after storing in 70% ethanol were allogenicaly implanted in rat femoral arteries (diameter, ca. 0.5 mm) by end-to-end anastomosis without use of any anticoagulant agents (Fig. 1B).

Results:
The OCT imaging showed homogeneous wall thickness without damage of MBs with a diameter of 0.6 mm. Patency at immediately after implantation was confirmed also by the imaging and at 1 month was by MRA (83.3%, n=6). Vascular structure with multi-layered elastic fiber and collagen fiber was constructed with endothelial cells and α-SMA-positive cells. The high patency was maintained for 6 months (Fig. 1C).

Conclusions:
The world’s smallest caliber vascular grafts with high patency and in situ regenerative activity were developed. The Biotubes could acquire high reliability for vascular grafts with diameter ranging from micrometer to centimeter.
Abstract 10832: Variability of LDL-C Lowering Responses to Statin Therapy in Achievement of ACC/AHA Target Levels
Authors: Toth Peter P , Bays Harold , Farnier Michel , Jensen Erin , Tomassini Joanne , Polis Adam , Foody JoAnne , Tershakovec Andrew
Published: April 2024

Objective:
The recently published ACC/AHA 2013 cholesterol guidelines do not specify lipid target levels, but rather treatment of patients classified by cardiovascular risk to achieve LDL-C reductions of ≥50% and ≥30 - <50% with high and moderate intensity statin therapy respectively. This analysis evaluated the variability of treatment responses to statin therapy for these parameters in statin-naïve patients with hypercholesterolemia (HC).

Methods:
Data pooled from 14 randomized, controlled, double-blind clinical trials in HC patients were categorized per the 4 risk groups specified by ACC/AHA 2013 guidelines: 1) atherosclerotic cardiovascular disease (ASCVD), 2) baseline LDL-C >190 mg/dL, 3) diabetes (DM) and 4) 10 year ASCVD risk ≥7.5% (no ASCVD or DM). Mean % change from baseline in LDL-C, the percentage of patients who attained LDL-C reductions of ≥50% and ≥30 - <50% and variability of LDL-C lowering responses on recommended therapy among risk groups were assessed.

Results:
Mean % LDL-C changes from baseline ranged from -49.5 to -52.2% and -37.7 to -40.5% on high and moderate intensity statins, respectively across risk groups (Figure). The percentages of patients who achieved LDL-C reductions of ≥50% on high intensity statins were 62 - 70%, and who attained reductions ≥30 - <50% were 52 - 60% (77 - 89% for ≥30%) on moderate intensity therapy. The variability of % changes from baseline in LDL-C (SE = 0.7 to 2.1) and proportions of patients who achieved target LDL-C reductions were generally similar across risk groups for high and medium intensity statins.

Conclusion:
In this analysis, only 2/3 of patients achieved LDL-C reductions ≥50% on high intensity statins and ~80% of patients attained reductions ≥30% on moderate statin therapy. These results highlight the importance of assessing the response of patients to cholesterol lowering therapy when following the AHA/ACC guidelines and consideration of alternatives for those patients in need of greater LDL-C lowering.
Abstract 10882: Scaling to Lean Body Mass Accurately Classifies Abnormal LV Mass in Obese Children
Authors: Chowdhury Shahryar M , Henshaw Melissa H , Carter Janet , Thomas Tyler N , Atz Andrew M
Published: April 2024

Introduction:
Scaling LV mass to BSA or height leads to inaccuracies in the diagnosis of LV hypertrophy in the obese pediatric population. Lean body mass (LBM) is free of the scaling biases seen with BSA and height. Our objectives were to 1) validate predictive equations for LBM, 2) determine the ideal scaling variable for LV mass, and 3) compare the diagnostic accuracy of predicted LBM (LBMp), BSA, and height in detecting abnormal LV mass in obese children.

Methods:
Obese subjects ages 4 to 21 were recruited prospectively. Height, weight, sex, race and body mass index z-score were used to calculate LBMp. LV mass was measured by echocardiography. Dual-energy X-ray absorptiometry was used to measure LBM (LBMm). Bland-Altman plots were used to assess agreement between LBMp and LBMm. Linear regression was performed to assess the ideal scaling variable for LV mass. Centile curves of LV mass vs. LBMm as the reference-standard were compared with curves derived from LBMp, BSA, and height
2.7
to assess their accuracy in detecting elevated LV mass.

Results:
309 subjects were enrolled for predictive equation validation, 195 had echocardiography performed. Mean age was 11.8 ± 3.4 years. The mean difference between LBMp and LBMm was 1.5% (95% limits of agreement: -16.5%, 19.4%). LBMm had the strongest relationship with LV mass (R
2
= 0.83, p < 0.01) compared to LBMp (R
2
= 0.81, p < 0.01), BSA (R
2
= 0.77, p < 0.01), and height
2.7
(R
2
= 0.67, p < 0.01). Of the clinically derived variables, LBMp was the only measure to retain a relationship with LV mass upon multivariable regression (partial r = 0.89). LBMp was the most accurate scaling variable in detecting LV hypertrophy (PPV = 85.7%, NPV = 99.3%) compared to BSA and height
2.7
.

Conclusions:
LBM predictive equations are accurate in obese children. LBM is the strongest predictor of LV mass in obese children. LBMp is the most accurate anthropometric scaling variable for LV mass in LV hypertrophy detection. LBMp should be considered for widespread clinical use as the body size correcting variable for LV mass in obese children.
Abstract 10894: Cerebral Energy Metabolism and Pools of Neurotransmitters Related to the Use of Deep Hypothermic Circulatory Arrest in Infant Piglets
Authors: Kajimoto Masaki , Ledee Dolena R , Olson Aaron K , Isern Nancy G , Des Rosiers Christine , Portman Michael A
Published: April 2024

Introduction:
Complex congenital cardiac defect repair in infants often requires deep hypothermic circulatory arrest (DHCA). As immediate or late neurological complications still occur, adjunctive selective cerebral perfusion (SCP) theoretically provides superior neural protection by supplying oxygen and substrate and maintaining energy metabolism.

Hypothesis:
SCP preserves glucose utilization, energy metabolism, and glutamate cycling in comparison to DHCA alone.

Methods:
Fourteen male Yorkshire piglets (age 34-44 days) were assigned randomly to 2 groups (DHCA or SCP for 60 minutes at 18°C). Cerebral perfusion through 1st branch of aorta was maintained at 40 ml/kg/min during SCP. After the completion of rewarming, 13-Carbon-labeled glucose (
13
C-glucose) was infused through common carotid artery for 1 hour under continuous cardiopulmonary bypass support and then cerebral tissue was extracted. Gas chromatography-mass spectrometry and nuclear magnetic resonance were used for cerebral metabolic analysis in the frontal cortex of brain.

Results:
There were no operative or technical complications in any groups. Cerebral rSO
2
in simple DHCA dropped substantially to ~ 25% during DHCA, but maintained over 80% in SCP. Apoptosis by TUNEL assay was significantly less in SCP at 2.5 hours after DHCA. ATP levels in the extracted cerebral tissue were similar between 2 groups but glycogen store were higher in SCP. Absolute levels of lactate and citric acid cycle intermediates and their
13
C-enrichment were similar in the cerebral tissue between the 2 groups. However, SCP increased absolute and
13
C-enrichment for glutamate and compared to DHCA, while gamma aminobutyric acid (GABA) increased in DHCA.

Conclusions:
SCP added to DHCA does not provide additional ATP preservation or modify glucose oxidation. However, SCP does alter glucose cycling into alternate pathways, leading to preservation of glycogen, and shifts flux away from GABA, a major inhibitory neurotransmitter, and towards glutamate. These flux changes suggest that SCP decreases synaptic inhibition, which may relate to the reduced neural apoptosis.
Abstract 10900: Persistent Alterations in Energy Metabolism and Oxygen Consumption Following Cardiac Arrest
Authors: Shinozaki Koichiro , Lampe Josha W. , Kim Junhwan , Da Tong , Yin Tai , Becker Lance B.
Published: April 2024

Introduction:
Although metabolic problems after cardiac arrest (CA) have been postulated, the actual measurement of metabolic alterations after CA remain undescribed. The measurement of oxygen extraction (VCO2), carbon dioxide excretion (VCO2), and respiratory quotient (RQ), reflect the energy metabolism and may provide insight into the post-arrest metabolism.

Objective:
To investigate metabolism alterations after CA, which may be detected via changes in VCO2, VO2, and RQ. Secondarily to test whether it is affected by therapeutic temperature management (TTM)

Methods:
Sixteen male rats underwent a protocol for 10 minutes of asphyxial CA and return of spontaneous circulation (ROSC). Three groups were compared: Group1: controls (no-CA, n=5), group2: CA (n=6), and group3: CA with TTM (n=5). Within the TTM group, the body was cooled to 33 °C. Capnography was recorded and O2 extraction was measured for 120min to measure VCO2 and VO2. RQ was the ratio of VCO2/VO2.

Results:
The post arrest VCO2 was 1.5 fold higher in the CA group than in the controls (17.3±2.2mL/kg/min versus 11.2±1.0mL/kg/min, p<.01) in minutes 20 through 60. The VCO2 value in CA was normalized after 60min. VCO2 (12.5±1.3 mL/kg/min, p<.01) in TTM-treated CA was significantly lower than untreated CA. The post arrest VO2 was greater in the CA group than in the controls, starting 15min after ROSC, and gradually increased to an extraction rate 2.1 fold higher (29.8±6.0mL/kg/min) than controls (14.1±1.6mL/kg/min, p<.01). There were no differences in VO2 between TTM-treated and untreated CA. RQs in TTM-treated and untreated CA were significantly and persistently lower than controls (0.5±0.1, 0.5±0.1 vs. 0.9±0.1, p<.01).

Conclusions:
VO2 in rats after CA was markedly elevated after ROSC and RQ decreased to extremely low levels. VCO2 showed some attenuation by TTM, however surprisingly TTM did not affect VO2 or RQ. These results suggest that profound alterations in oxygen extraction occur after CA and may be measured non-invasively in patients. The finding of a lowered RQ has not be described previously, appears to be driven by increased VO2, and may be due to non-CO2 generating oxygen utilization. If true, this may have great importance for mechanism, monitoring, and customized treatment of CA.
Abstract 10945: Impact of Natural or Postoperative Survival Patterns in Long-term Outcome of Adult Survivors With Congenital Heart Disease
Authors: Gallego Pastora , Oliver Jose M , Gonzalez Garcia Ana E , Garcia Hamilton Diego , Yotti Alvarez Raquel , Ferreira Gonzalez Ignacio , Fernandez Aviles Francisco
Published: April 2024

Background:
Life expectancy of adult survivors with congenital heart disease (CHD) is related to CHD complexity but impact of natural or postoperative survival patterns on long-term outcome have not been reported.

Methods:
In a prospective cohort of 3,334 adults (50.6% males) with CHD, followed up to 24 years in a single tertiary centre, we analyzed all-cause mortality, annual death rate, median age of survival (MAS) and standardized mortality ratio (SMR). Data provided by the Spanish national death index were used for mortality analysis. Lesions were classified into 3 groups according to CHD complexity: simple (1,647); moderate (1,283); and severe (404). Patients were then classified into 4 subgroups according to survival pattern: repaired in childhood (1,377); repaired in adulthood (759); CHD that did not require operation (1,035); and inoperable CHD (163).

Results:
Median age at first examination was 22 years (IQ range 18-39) and median follow-up time 10.6 years (1-18). At the end of the study 336 patients had died (prevalence 10%; annual death rate 0.89%). In inoperable patients the estimated MAS was significantly lower (48.9 yrs; 95% CI 44-53), but there were not significant differences in MAS between patients repaired in childhood (75.9 yrs), repaired in adulthood (76.0 yrs) or that did not require repair (77.5 yrs). SMR in this latter group was 1.70 (95% CI 1.3-2.1)] but patients repaired in adulthood, repaired in childhood or inoperable had an increased SMR of 2.06 (95% CI 1.7-2.5), 5.87 (95% CI 4.5-7.7) and 24.1 (95% CI 18-33) respectively. The table shows a classification of long-term outcome depending on CHD complexity and survival pattern.

Conclusion:
Adult survivors that do not require intervention and patients with repaired simple CHD have excellent life-long prognostic indexes. Excess mortality was demonstrated in repaired moderately complex CHD . Patients with CHD of great complexity have the worst prognosis, especially those that are inoperable.
Abstract 10964: Hyperfibrinolysis in Patients With out of Hospital Cardiac Arrest May Contribute to Poor Outcome
Authors: Koami Hiroyuki , Sakamoto Yuichiro , Inoue Satoshi
Published: April 2024

Introduction:
Hyperfibrinolysis (HF) in out-of-hospital cardiac arrest (OHCA) is often encountered in the emergency department (ED). However, only a few studies on the coagulopathy in post cardiac arrest syndrome (PCAS) were reported and it still remains a matter of debate. In recent years, thromboelastometry (ROTEM
®
), known as point-of-care testing, quickly provides a more complete picture of coagulation and fibrinolytic status.

Hypothesis:
We hypothesized that HF diagnosed by ROTEM in OHCA might be associated with poor outcome.

Methods:
48 OHCA patients transported to the Saga University Hospital with ROTEM performed in the ED from January 2013 to December 2014 were enrolled in this study. A 15% or more of maximum lysis (ML) in EXTEM test and a 20 % or more improvement of ML in APTEM test compared with that in EXTEM were defined as HF. All patients were divided into two groups based on the presence of HF. Clinical characteristics, initial cardiac rhythms at the scene and ED, time from onset to blood sampling, complete blood test, standard coagulation test, blood gas analysis, ROTEM findings (EXTEM/ INTEM/ FIBTEM/ APTEM) and clinical outcome were evaluated.

Results:
HF was observed 72% of all OHCA patients, which wasn’t significantly related to epinephrine injection before blood sampling (p=0.510). Univariate analysis revealed that HF contributed to lower CRP values (p=0.050) and accelerated fibrinolytic parameters of ROTEM (EXTEM/INTEM/FIBTEM; p<0.01). Any other parameters including initial cardiac rhythms and time from onset to blood sampling were not significantly different in the two groups. As for clinical outcome, the ratio of return of spontaneous circulation (ROSC) reached 10% (before the ED), 40% (after the ED), 18.8% (6hours after admission), 12.5% (24hours after admission), respectively. There was no statistical difference between HF and clinical outcome in this period. However, it should be noted that only 2 patients (4.2%) without HF survived for more than 28 days. HF had a tendency to poor 28-day mortality (p=0.069). In addition, Kaplan-Meier and log-rank analysis showed HF was a predictive factor for poor outcome of PCAS (p=0.099).

Conclusions:
HF in OHCA is associated with poor clinical outcome.
Abstract 11007: Biochemical Urinalysis Predicts the Type of Decongestion and Worsening Renal Function due to Tolvaptan Administration in Patients With Acute Decompensated Heart Failure
Authors: Sakaguchi Taiki , Hirata Akio , Kashiwase Kazunori , Higuchi Yoshiharu , Koretsune Yukihiro , Kusuoka Hideo , Yasumura Yoshio
Published: April 2024

Introduction:
The diuretic response to tolvaptan (TLV) varies among patients with acute decompensated heart failure (ADHF). Although TLV is known to induce the excretion of free water, the accelerated excretion of sodium and urea has also been observed to varying degrees.

Purpose:
To classify the types of decongestion induced by TLV based on the initial induction of urinary sodium and urea excretion.

Methods:
We analyzed 90 ADHF patients who had been administered TLV. As markers of the initial TLV-induced excretion of sodium and urea, we measured changes in the fractional excretion of sodium (ΔFENa) and urea (ΔFEUN) prior to the first TLV administration and after eight hours. To evaluate the clinical course until normalization, 3-day and 7-day changes in body weight (ΔBW3, ΔBW7) and the inverse of hematocrit (Δ1/Ht3, Δ1/Ht7) after TLV administration were analyzed as markers of whole body and intravascular dehydration, respectively. Worsening renal function was assessed using 7-day changes in serum urea nitrogen (ΔUN7) and creatinine (ΔCr7) concentration.

Results:
Our analysis revealed negative correlations between ΔFEUN and ΔBW3 (r=-0.65, p<0.001) and between ΔFENa and Δ1/Ht3 (r=-0.53, p<0.001). Based on these findings, subjects were categorized into three groups. Firstly, subjects with positive and negative ΔFEUN were designated responders (n=60) and non-responders (n=30), respectively. Responders were further categorized based on the median value of ΔFENa (0.7%), where ΔFENa≥0.7 was the Natriuresis Group (n=30) and ΔFENa<0.7 was the Aquaresis Group (n=30). During the 7 days after TLV administration, whole body dehydration was lowest in non-responders, intravascular dehydration was highest in the Natriuresis Group, and worsening renal function was lowest in the Aquaresis Group (Table).

Conclusions:
The initial induction of urinary sodium and urea excretion by TLV was able to predict the type of decongestion and worsening renal function in ADHF patients.
Abstract 11472: Higher Level of Chronic Illness Management in Heart Transplant Centers is associated With Better Patient Survival: The Intercontinental BRIGHT Study
Authors: De Geest Sabina M , Denhaerynck Kris , Berben Lut , Vanhaecke Johan , Russell Cynthia , Dobbels Fabienne ,   on behalf of the BRIGHT study team
Published: April 2024

Innovation in care processes based on chronic illness management (CIM) has shown to improve outcomes in chronically ill. We hypothesized that higher level of CIM in post-heart transplant (HTx) follow-up care is associated with better patient survival.

The BRIGHT study, a multi-center, cross sectional study included a convenience sample of 36 HTx centers in 11 countries and 4 continents. Patients were selected by stratified random sampling. CIM was assessed both by clinicians’ report (N=82, mean age: 47.6±10.2 y., 85% f.) (55 item CIMI BRIGHT instrument) and patients’ report (N=1026, mean age: 54.0±13.2 y., 27% f., mean years post-HTx; 3.4±1.4)(11 item PACIC scale). CIM data were aggregated at center level. Three groups were built: (1) positive deviants: both patients’ and clinicians’ median CIM scores above median CIM score of 36 centers;(2) negative deviants: both median CIM scores below median of all centers; (3) mixed group: incongruence in median CIM scores between patients and clinicians. Center's mean patient survival at 1, 3, 5, 10 and 15 years was reported by the HTx center director using a structured questionnaire. We used mixed regression analysis, contrasting positive to negative deviants in a confounder-adjusted analysis.

We found major variability in CIM scores (PACIC mean 39±10.5; CIMI BRIGHT mean 165±17.1, range: 136-197) and mean survival rates (1 year: 84%±5.3 ; 5 year 73%±15.8) among HTx centers. Thirty-two percent of centers were positive deviants, 32% negative deviants and 36% belonged to the mixed group. Figure 1 shows center's mean patient survival at 1, 3, 5, 10 and 15 years for the 3 groups. As hypothesized, mortality was lower in positive vs. negative deviants especially at 1 year post-HTx (p<0.008).

The association between higher levels of CIM and lower mortality in HTx patients highlights a potential pathway for improving outcomes after HTx by investing in innovative systems of care based on principles of CIM.
Abstract 11510: Missed Opportunities in Use of Medical Emergency Teams Prior to In-Hospital Cardiac Arrest
Authors: Chan Maya L , Tang Fengming , Chan Paul S
Published: April 2024

Background:
Hospitals often employ Medical Emergency Teams (MET) to respond to patients with acute physiological decline to prevent in-hospital cardiac arrest (IHCA). However, it is unknown how often patients fail to have a MET evaluation preceding IHCA, and whether these patients have severe vital sign abnormalities suggesting missed opportunities for MET activation.

Methods:
Within Get With The Guidelines-Resuscitation, we identified 29,956 patients with IHCA on general inpatient or telemetry floors from 240 hospitals that submitted data on both IHCA and MET evaluations. We determined the proportion without MET evaluation before IHCA. Among those without MET evaluation, we examined the frequency of vital sign abnormalities 1, 2, and 4 hours before IHCA. We used stringent definitions for the following six vital sign abnormalities: heart rate >150 or <30 beats per minute, respiratory rate >35 or <8 breaths per minute, systolic blood pressure <80 mm Hg, and oxygen saturation level of <80%.

Results:
Overall, the vast majority (24,733 [82.6%]) of patients with IHCA did not have a preceding MET evaluation. Vital sign data were available for 18,064 patients without MET evaluation. Of these patients, 7109 (39.4%), 5536 (30.6%), and 2368 (13.1%) had at least one severe vital sign abnormality ≥ 1, 2, and 4 hours before IHCA, respectively (TABLE). Furthermore, 13.7% had a Modified Early Warning Score (MEWS) ≥ 4 at least 1 hour before IHCA.

Conclusion:
Although MET teams are designed to prevent IHCA, many patients with severe vital sign abnormalities prior to IHCA did not have a MET evaluation. These findings suggest missed opportunities to use MET teams efficiently in hospitals.
Abstract 11558: Increase in Norepinephrine After Energy Drink Intake in Healthy Adults
Authors: Svatikova Anna , Covassin Naima , Somers Kiran , Somers Krishen , Soucek Filip , Kara Tomas , Bukartyk Jan
Published: April 2024

Introduction:
The popularity of energy drinks among young adults is rising. Warnings have been issued regarding potential health risks including adverse cardiovascular complications. We and others have previously shown that energy drink consumption increases blood pressure. The mechanisms are not fully understood.

Hypothesis:
We hypothesized that increase in blood pressure after drinking a commercially available energy drink, compared to a placebo, is secondary to increased sympathetic activation.

Methods:
In a randomized, double-blind, placebo-controlled, cross-over study, we studied 25 healthy subjects, age 29±1 years, who were free of known disease, had no known cardiovascular risk factors, and were not on any medications. Each subject consumed a can, 16-fluid ounces, of Rockstar energy drink or a placebo drink in random order on two separate days. Blood pressure (n=25) and plasma norepinephrine levels (n=23) were measured before and 30-minutes after drink consumption.

Results:
Despite the increase in blood pressure after drinking Rockstar energy drink, which would be expected to elicit reflex reductions in central sympathetic outflow, plasma norepinephrine levels increased markedly after energy drink consumption vs placebo (73.6±9.7% vs 30.9±9.7%, respectively, P=0.003; Figure). Specifically, plasma norepinephrine levels increased from 149.8±11.7pg/ml to 249.8±17.3pg/ml after the energy drink consumption and from 139.9±11.7pg/ml to 178.6±17.3pg/ml after placebo (P=0.0007 for timeхtreatment comparison).

Conclusions:
Increased blood pressure after consumption of commercially available energy drink is associated with significantly increased catecholamine levels in young healthy adults. These acute hemodynamic and adrenergic changes may predispose to increased cardiovascular risk by triggering arrhythmias or ischemia, particularly in individuals with a vulnerable cardiovascular substrate.
Abstract 11562: Computational Fluid Dynamics in Type B Aortic Dissection: A Systematic Review
Authors: Sun Zhonghua
Published: April 2024

Introduction:
Computational fluid dynamics (CFD) has been increasingly used to analyse cardiovascular hemodynamics through simulations to predict the behaviour of blood flow in the cardiovascular system.

Hypothesis:
It is hypothesized that CFD modelling assists in clinical decision-making by providing detailed analysis of flow patterns in patients with aortic dissection.

Methods:
A search of biomedical database for English literature was performed to identify studies investigating the CFD applications in type B aortic dissection. Only studies dealing with patient’s data were included, while reports based on phantom studies were excluded from the analysis.

Results:
Twelve studies were found to meet selection criteria and were included in the analysis. CFD simulations were based on a selected CT or MRI imaging data in 8 studies, while in the remaining four studies, CFD simulations were derived from 3 cases in two studies, and 4 and 8 cases in one study, respectively. CFD models and simulations were found to successfully capture the complex regions of hemodynamic flow by demonstrating low velocities in the false lumen and high velocities in the true lumen. In the true lumen, high time-averaged wall shear stress (TAWSS) was seen in the regions around the tear, while in the false lumen, TAWSS was less uniform due to recirculating flow in the dilated region (Figure). Presence of an additional re-entry tear was shown to provide an extra return path for blood back to the true lumen during systole, and an extra flow path into the false lumen during diastole. Following endovascular stent grafting, large WSS magnitudes were eliminated in the true lumen, while in the false lumen, the maximum WSS was reported to be reduced by more than a factor of 2.

Conclusions:
CFD offers insight into the hemodynamic factors such as velocity field and wall shear stress, and CFD models and simulations improve understanding of hemodynamics in type B aortic dissection.
Abstract 11574: Ventricular Arrhythmia Ablation Lesions in Children and Adolescents: Acute Magnetic Resonance Imaging With Outcome Correlation
Authors: Grant Elena K , Berul Charles I , Cross Russell R , Moak Jeffrey P , Hamann Karin S , O'Brien Kendall J , Hansen Michael , Kellman Peter , Ratnayaka Kanishka , Olivieri Laura J
Published: April 2024

Introduction:
Catheter ablation for arrhythmias is not always 100% effective when using current techniques. Failure of ablation may be secondary to inadequate lesion development. Peri-procedural visualization of ablation lesions may identify inadequate lesions or gaps to guide further ablation and reduce risk of arrhythmia recurrence.

Methods:
This pilot feasibility study assessed acute post-procedure ablation lesions by MRI, and correlated these findings with clinical outcomes. Six patients who underwent ventricular tachycardia ablation were transferred immediately post-ablation to a 1.5T MRI scanner for imaging. Late gadolinium enhancement (LGE) imaging was performed using a novel motion-corrected, phase sensitive inversion recovery sequence while free breathing. Immediate and short term arrhythmia recurrences were assessed.

Results:
Patient characteristics include median age 14.5 yrs (11 - 17 yrs), median weight 59 kg (43 - 81kg), normal cardiac anatomy (n = 4), anomalous coronary artery post repair (n = 1), and cardiac rhabdomyomas (n = 1). All patients underwent radiofrequency catheter ablation of ventricular arrhythmia with acute procedural success. LGE was identified at the reported ablation site in 5/6 patients, and not seen in 1 patient. The 5 patients with identifiable lesions were arrhythmia- and symptom-free at follow-up, ranging 1-6 months. The 1 patient in whom a lesion could not be identified had recurrence of frequent premature ventricular contractions within 2 hours post-procedure, confirmed on Holter monitoring 1 month later.

Conclusions:
Ventricular ablation lesion visibility by MRI in the acute post-procedure setting is feasible, and lesions identifiable with MRI may correlate with clinical outcomes. MRI identification of gaps or inadequate lesions may provide the unique temporal opportunity for additional ablation therapy to decrease arrhythmia recurrence.
Abstract 11581: Longer Receptor Residence Times Improve the Effectiveness of CCR2 Antagonists in the Prevention of Atherosclerosis
Authors: Bot Ilze , Ortiz Zacarias Natalia V , de Vries Henk , van Santbrink Peter J , van der Velden Daniel , Kuiper Johan , Stamos Dean , IJzerman Adriaan P , Heitman Laura H
Published: April 2024

The chemokine receptor CCR2 is known to be critically involved in atherosclerosis development, rendering blockade of the CCL2-CCR2 axis of therapeutic interest. CCR2 antagonists have, however, limited clinical success. Interestingly, it was shown for other drug targets that a measure for the dissociation of the drug-receptor complex, the so-called residence time (RT), can have a crucial impact on a drug’s efficacy. In this study, we thus aimed to determine whether an increased RT improves the therapeutic effectiveness of CCR2 antagonists.

Carotid artery atherosclerosis was induced by collar placement in apoE
-/-
mice, followed by treatment with the short RT CCR2 antagonist 15b (RT=15 min, 150 μg/day), the long RT CCR2 antagonist 15a (RT=714 min, 150 μg/day) or vehicle control. After four weeks, atherosclerotic plaques were analyzed.

Treatment with the CCR2 antagonists did not affect body weight or plasma cholesterol levels. At sacrifice, circulating CCR2
+
monocyte numbers were only significantly reduced in the long RT 15a-treated mice (controls: 14.9±3.2*10
3
, 15b: 9.1±3.1*10
3
and 15a: 4.5±1.0*10
3
cells/mL, *P<0.05). Atherosclerotic plaque size was reduced from 64.4±11.8*10
3
μm
2
in control mice to 33.2±6.8*10
3
μm
2
in 15b-treated mice (-49%, *P<0.05), and even up to 17.6±4.1*10
3
μm
2
in 15a-treated mice (-73%, **P<0.01). Interestingly, relative plaque macrophage content was only decreased in 15a-treated mice compared to both control and 15b-treated mice (controls: 46±4%, 15b: 45±6%, 15a: 25±8%, *P<0.05), while neutrophil and mast cell numbers were not affected. In the aortic root, 15b did not significantly affect plaque size (controls: 252±25*10
3
μm
2
vs 15b: 196±17*10
3
μm
2
), while the long RT CCR2 antagonist 15a inhibited plaque development to 157±15*10
3
μm
2
(-38%, **P<0.01). Also at that site of lesion development, macrophage area was only significantly reduced in the 15a-treated mice (controls: 35±4%, 15b: 32±3%, 15a: 23±4%, *P<0.05 compared to controls).

In conclusion, our data demonstrate that the CCR2 antagonist with a long residence time was more effective in inhibiting atherosclerotic plaque development compared to the short RT antagonist, which implies that receptor residence time is an important parameter in drug development.
Abstract 11684: Involvement of Enhanced Inflammatory Changes in the Perivascular Adipose Tissue in the Pathogenesis of Coronary Hyperconstricting Responses After Drug-Eluting Stent Implantation in Pigs
in vivo (Best of Basic Science Abstract)
Authors: Ohyama Kazuma , Matsumoto Yasuharu , Amamizu Hirokazu , Uzuka Hironori , Nishimiya Kensuke , Hirano Michinori , Takahashi Jun , Ito Kenta , Shimokawa Hiroaki
Published: April 2024

Background:
Recent studies implicated that perivascular adipose tissue (PVAT) plays an important role in cardiovascular disease as a source of various inflammatory mediators with resultant coronary vasomotion abnormalities. In this study, we examined whether inflammatory changes in the PVAT are associated with coronary hyperconstricting responses after drug-eluting stent (DES) implantation in pigs in vivo.

Methods and Results:
Everolimus-eluting stents (EES) were randomly implanted in pigs into either the left anterior descending or circumflex coronary artery while non-stented artery was used as a control. At 1 month after the implantation, coronary vasoconstricting responses to intracoronary serotonin (100 μg/kg) were examined by coronary angiography in vivo. Then, stented vessels were harvested for immunohistological study for inflammatory changes in the PVAT at the stent edges. Coronary vasoconstricting responses to serotonin were significantly enhanced at the edges of the EES site as compared with the control site (P<0.05, n=12). Histological analysis showed that the extent of inflammatory changes in the PVAT as evaluated by CD68 (macrophage maker) and interleukin-1β (IL-1β) were significantly enhanced at the EES site compared with the control site (both P<0.05) (Figure). Furthermore, there were significant positive correlations between the extent of inflammatory changes in the PVAT and that of coronary vasoconstricting responses (both P<0.001) (Figure).

Conclusions:
These results suggest that inflammatory mediators in the PVAT (e.g. macrophages, IL-1β) are involved in the pathogenesis of DES-induced coronary hyperconstricting responses in pigs in vivo.
Abstract 11695: The Kinetics of Circulating Monocyte Subsets and Microbial Translocation in the Acute Phase of ST-Elevation Myocardial Infarction Reveals Prognostic Values for Cardiovascular Outcomes
Authors: Zhou Xin , Liu Xin-Lin , Ji Wen-Jie , Ren Dong , Guo Zhao-Zeng , Ma Yong-Qiang , Zhang Zhuoli , Thorp Edward B , Benefield Brandon C , Lee Daniel C , Zhao Ji-Hong , Zawada Adam M , Li Yu-Ming , Heine Gunnar H
Published: April 2024

Introduction:
In experimental myocardial infarction (MI), a rise in cell counts of circulating monocyte subsets contributes to impaired myocardial healing, and to atherosclerotic plaque destabilization.The underlying pathophysiological mechanisms for the post-MI monocytosis and the prognostic role of monocyte subsets in patients suffering ST-elevation MI (STEMI) are still unclear.

Hypothesis:
The kinetics of the three monocyte subsets (classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes) and gut microbial translocation are associated with cardiovascular outcomes after STEMI.

Methods:
In 100 STEMI patients treated with primary percutaneous coronary intervention (PCI), monocyte subsets and microbial translocation markers (lipopolysaccharide [LPS] and D-lactate) were measured on Days 1, 2, 3, 5 and 7 of STEMI onset, compared with 35 stable coronary heart disease patients and 35 healthy volunteers. All STEMI patients were prospectively followed for the first occurrence of an adverse cardiovascular event.

Results:
From Day 1 to Day 7, a parallel increase in CD14++CD16- cell counts, CD14++CD16+ cell counts, and gut permeability markers was observed, with peak levels on Day 2. During a median follow-up of 1.5 years, 25 events were recorded. Univariate Kaplan-Meier analysis revealed that Day 2 CD14++CD16- cell counts (
P
=0.022), CD14++CD16+ cell counts (
P
=0.024) and Δ LPS (Day 2 – Day 1;
P
=0.027) each predicted the primary endpoint when stratified by median values. After adjustment for confounders, Day 2 CD14++CD16+ monocyte counts showed the strongest predictive value (per SD increase: hazard ratio [HR]: 2.127; 95% CI 1.313 to 3.446;
P
=0.002) for cardiovascular events.

Conclusions:
The expansion of the CD14++CD16+ monocyte subset on Day 2, which is associated a transient increase in microbial translocation, independently predicts adverse cardiovascular outcome in STEMI patients treated with primary PCI.
Abstract 11730: Endogenous MAFbx Mediates Cardiac Rupture After Myocardial Infarction in Mice
Authors: Chikata Akio , Usui Soichiro , Takashima Shinichiro , Kato Takeshi , Murai Hisayoshi , Furusho Hiroshi , Kaneko Shuichi , Sadoshima Junichi , Takamura Masayuki
Published: April 2024

Rationale:
Muscle atrophy F-box (MAFbx/atrogin-1), an E3 ubiquitin ligase, plays a critical role in mediating skeletal muscle atrophy and induces proteasomal degradation in cardiomyocytes. Loss of function of MAFbx inhibits pressure overload-induced pathological cardiac hypertrophy, in part through stabilization of IκB. The role of MAFbx in regulating cardiac remodeling following myocardial infarction (MI) remains unclear.

Objective:
We investigated the role of MAFbx in regulating cardiac remodeling following MI.

Methods and Results:
Permanent coronary ligation of the left coronary artery was applied to MAFbx knockout (KO) and wild-type (WT) mice. Expression of MAFbx in WT mice was significantly increased in the risk area of the LV after MI. The mortality rate due to cardiac rupture following MI was significantly decreased in MAFbx KO mice compared to WT mice (25.3% in KO mice (n=61) vs. 47.7% in WT mice (n=59) P=0.03). There was no difference in the infarct sizes 3 days after MI or the number of TUNEL-positive cardiomyocytes between MAFbx KO mice and WT mice. DNA microarray analyses revealed that the gene expression pattern in hearts after MI demonstrated clear clusters for MAFbx KO and WT. Interestingly, upregulation of matrix metalloproteinase (MMP)-9, interleukin 1β, proinflammatory cytokines, and NLRP3, an inflammasone component, were attenuated in MAFbx KO mice. MMP-9 activity was also decreased in MAFbx KO in the risk area 3 days after MI compared to in WT mice. Flow cytometry revealed that myocardial leukocyte infiltration one day after MI was suppressed in MAFbx KO mice. Immunofluorescence double-labeling showed that expression of NLRP3 in both cardiomyocytes and non-cardiomyocyte cells was decreased in MAFbx KO mice.

Conclusions:
These results suggest that MAFbx plays an important role in the excessive inflammation, including leukocyte infiltration, inflammasome formation, and production of proinflammatory cytokines, following MI. Inhibition of MAFbx reduces mortality due to cardiac rupture after MI, in part through decreased MMP9 activity and leukocyte infiltration.
Abstract 11756: St-segment Elevation Myocardial Infarction in Young Patients - Analysis of Age Specific Risk Factors and Outcome-parameters
Authors: Fach A. , Schmucker J. , Mata Marin L. A , Wienbergen H. , Bünger S. , Conradi P. , Fiehn E. , Hambrecht R.
Published: April 2024

Introduction:
ST-segment elevation myocardial infarction (STEMI) is relative rare in a population younger than 45years(y45). Despite the socio-economic impact, the specific risk factor (RF) profile in Y45 has been less studied as compared to older patients(pts).

Hypothesis:
This study compared STEMI pts in terms of age specific RF, severity of myocardial infarction (MI) and outcomes between 2006 and 2014.

Methods:
The Bremen heart center is exclusively responsible for emergency PCI in a metropolitan region of about 1 million inhabitants. Since 2006 all consecutive pts with STEMI were included in the Bremen Heart Registry.

Results:
Of the 6329 included pts 450 (7%) were y45. Young pts were significantly often active smokers (85 vs 40%, p<0.01), characterized by a positive family history (FH) for cardiovascular disease (CVD) (44 vs 21%, p<0.01) and obesity (body mass index >30kg/m
2
: 29 vs 24%, p=0.04). These results were confirmed in a multivariate logistic regression model (table). While the number of young active smokers per year was constant (2006-09: 85% vs 81% in 2010-14, p=0.1), the proportion of obese pts increased significantly over time (2006-09:23% vs 36% in 2010-14, p<0.01). Y45 more often suffer larger MI (creatin kinase >3.000U/l: OR 1.7, 95% CI 1.3-2.1) and require prehospital resuscitation (OR 1.6, 95% CI 1.2-2.2). Despite these facts 30 day mortality (30dm) (2.4 vs 11.1%, p<0.01) and 1year mortality (1ym) (3.6 vs 14.5%, p<0.01) was significantly lower in y45.

Conclusions:
The results of this large registry-study demonstrate that STEMI in y45 is characterized by more extensive MI and higher rates of pre-hospital resuscitation events. Nether the less the 30dm and 1ym is significantly lower than in older pts. The dominating RF in young STEMI pts was active smoking (85%), followed by a positive FH and obesity. To optimize prevention strategies further investigations have to be enforced elucidating specific genetic determinants of CVD in young pts.