bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9577: Non-Invasive Estimation of Pulmonary Blood Flow Using Photoacoustic Spectroscopy in Patients with Congenital Heart Disease
Authors: Rhodes Jonathan , Fromm Brian S , Porras Diego , Opotowsky Alexander , Alexander Mark E , Curran Tracy J , O'Neill Julieann , Smith Jennifer L , Solly Kathleen M
Published: April 2024

Background:
Measurements of pulmonary blood flow (PBF) using inert gas rebreathing technology have recently been enhanced by the introduction of photoacoustic spectroscopy (PAS). PAS is non-invasive, non-toxic, and can estimate PBF in <5 min. It has been employed successfully in adults with structurally normal hearts. Experience in patients with congenital heart disease (CHD) is, however, limited and its validity in patients with intracardiac shunts has not been evaluated. We compared estimates of PBF obtained with PAS technology to those obtained at cardiac catheterization.

Methods:
Fick-based estimates of PBF (using assumed oxygen consumption) were compared to PAS estimates in 50 CHD patients; 28 without intracardiac shunts, 10 with right to left (R-->L) shunts and 12 with left to right (L-->R) shunts. PAS estimates were acquired 1 day prior to catheterization while the patients were conscious, in a recumbent position. Fick-based estimates were acquired by individuals blinded to the PAS results.

Results:
Median age was 18.5 yrs (range 8-78). Among subjects without shunts or with R-->L shunts, Fick and PAS-based estimates of PBF correlated reasonably well (r=0.59 and 0.75, respectively; p<0.01 for both groups; r=0.72, p<0.0001 combined). Bland-Altman analysis revealed good agreement (mean bias 0.3±0.5 l/min/m
2
; 95% limits of agreement -0.8 - +1.3 l/min/m
2
), similar to historical comparisons of Fick and thermodilution techniques. In contrast, the correlation between PBF estimates among subjects with L-->R shunts was poor (r=0.24; p>0.05).

Conclusion:
PAS provides accurate, rapid estimates of PBF in children and adults with CHD who have no residual shunt, as well as those with R-->L shunts. Measurements in subjects with L-->R shunts are less reliable, likely due to early re-circulation. Algorithms that take this phenomenon into account may improve the reliability of PAS measurements in patients with L-->R shunts.
Abstract 9593: Effects of Atorvastatin and Rosuvastatin on Renal Function: A Meta-analysis
Authors: Savarese Gianluigi , Musella Francesca , Volpe Massimo , Paneni Francesco , Perrone-Filardi Pasquale
Published: April 2024

Objective:
To compare the effects of Atorvastatin (A) and Rosuvastatin (R) on glomerular filtration rate (GFR) and new onset proteinuria in patients at high cardiovascular risk.

Methods:
Randomized trials on A or R treatments reporting clinical end-points were included in the meta-analysis. Influence of treatments on GFR and new onset proteinuria was assessed.

Results:
23 trials enrolling 29,147 participants were included. A significant reduction in GFR was detected in placebo-treated compared to statin-treated patients (standard mean difference [SMD]:0.056, 95% confidence interval [CI]:0.028 to 0.083, p<0.01). In particular, a significant reduction in GFR was detected in placebo compared to either R-treated (SMD:0.052, CI:0.022 to 0.081, p=0.001) or A-treated patients (SMD:0.084, CI:0.008 to 0.161, p=0.031). No significant difference in GFR was detected in 5 head-to-head studies comparing A to R (SMD: 0.043, CI:-0.041 to 0.126, p=0.319). In 9 studies comparing A to R, R treatment significantly increased the risk of proteinuria when compared to A (odds ratio [OR]:0.656, CI:0.440 to 0.977, p=0.038, heterogeneity p=0.026), but this effect was no longer significant when studies using highest therapeutic doses of R (40 mg/daily) were excluded from analysis, abolishing significant heterogeneity (OR:1.505, CI:0.827 to 2.739, p=0.181). Additionally, when trials comparing highest doses of A (80 mg/daily) and R (40 mg/daily) were analyzed, both A 80 mg and R 40 mg reduced GFR; but GFR tended to be significantly less reduced by A compared to R (SMD: 0.109, CI: -0.001 to 0.220, p=0.051). Finally in 7 trials enrolling only patients with chronic kidney disease (but not on dialysis), statin treatment (by either A or R) led to significant improvement in GFR compared to placebo (SMD:0.213, CI:0.043 to 0.382, p<0.01). However, GFR was improved by A (SMD:0.246, CI:0.024 to 0.468, p=0.030), but it was not significantly changed by R treatment (SMD: 0.166, CI: -0.097 to 0.429, p=0.216).

Conclusions:
A and R show similar reno-protective effects in patients at high cardiovascular risk, with comparable rates of new onset proteinuria when commonly used doses are considered. In patients with chronic kidney disease, no further deterioration of GFR is observed.
Abstract 9643: Effect of Partial Fatty Acids Oxidation Inhibition With Trimetazidine on Survival in Heart Failure: Results From an International Multicentre Retrospective Cohort Study
Authors: Sisakian Hamayak , Rosano Giuseppe , Baek Sang H , Di Napoli Pericle , Alberti Luca , Kang Seok-Min , , Calori Giliola , Sahakyan Laura , Sanosyan Armen , Vitale Cristina , Marazzi Giuseppe , Margonato Alberto , Belardinelli Romualdo , Fragasso Gabriele
Published: April 2024

Background:
Trimetazidine (TMZ) shifts myocardial energy production from free fatty acids to glucose oxidation, a more efficient metabolic pathway. Previous small studies in patients with chronic heart failure (CHF) have shown that TMZ can improve contractile left ventricular function, exercise capacity and NYHA class compared to placebo. However, no data on the effects of TMZ on survival in patients with CHF have ever been produced.

Methods:
In this international multicentre retrospective cohort study 669 patients (521 post-ischaemic) from the CHF clinics of our institutions were recruited. 362 patients (288 post-ischaemic) were on TMZ (20 mg tid or 35 mg bid) due to symptoms persistence (dyspnoea on exertion, fatigue, orthopnoea, oedema, alone or in combination) despite up titration of optimal CHF medical therapy, while the remaining patients continued conventional CHF therapy alone. Effects of TMZ administration were evaluated by Kaplan-Meier survival analysis and Cox-Regression survival analysis. Obtained results were corrected with propensity score (PS) in order to minimize selection bias. The protocol has been registered in the Italian Pharmaceutical Agency (AIFA) - Italian Ministry of Health, on the observational studies registry, ID number 458.

Results:
Kaplan-Meier analysis for global mortality showed 11•3% improved global survival (p=0•015) and 8•5% improved survival for death from cardiovascular disease (CVD) causes (p=0•050) in the TMZ group. Cox regression analysis for global mortality showed a significant risk reduction for TMZ treated patients with a PS-corrected hazard ratio (HR)= 0•189 (confidence interval - CI 95%: 0•079-0•454; p=0•0002). TMZ also showed a good risk reduction profile for CVD death causes (PS-adjusted HR=0•072, CI 95%: 0•019-0•268, p=0•0001). The rate of hospitalization for cardiovascular causes was reduced by 10.4% at 5 years (p < 0•0005) with increased hospitalization-free survival of •8 months.

Conclusions:
TMZ is effective in reducing both global and cardiovascular mortality and event-free survival in patients with CHF. The addition of TMZ on top of optimal medical therapy improves long-term survival in CHF patients.
Abstract 9654: Dipeptidyl Peptidase-4 Inhibitors May Reduce the Risk of Major Adverse Cardiovascular Events and All-cause Mortality In Patients With Type 2 Diabetes: Meta-analyses Oof Randomized Controlled Trials
Authors: Sun Xin , Hazzan Afeez A , Bala Malgorzata , Busse Jason W , Johnston Bradley C , Carrasco-Labra Alonso , Jankowski Milosz , Neumann Ignacio , Ferreira-González Ignacio , Fernandez-Balsells Merce , Rios Lorena , Bassler Dirk , Briel Matthias , Lopes Luciane , Nordmann Alain , Tikkinen Kari A , Ismaila Nofisat , Zhou Qi , Mukherjee Jayanti , Frederich Robert , Iqbal Nayyar , Walter Stephen , Guyatt Gordon
Published: April 2024

Background:
Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists, both of which have an incretin effect, represent novel, effective therapeutic approaches to treating hyperglycemia in type 2 diabetes mellitus (T2DM). Their impact on cardiovascular (CV) outcomes, however, is still under investigation.

Hypotheses:
We assessed the impact of DPP-4 inhibitors and GLP-1 agonists on the risk of a composite of cardiovascular death, myocardial infarction, and stroke (MACE), and on all-cause mortality (ACM) in T2DM.

Methods:
We searched Medline, EMBASE, and Cochrane Library for randomized controlled trials (RCTs) published up to February 2010 that compared an incretin agent versus usual care, placebo, or other active agents for patients with T2DM, and reported a pre-specified CV outcome. We also searched a major trial registry, FDA and EMEA databases, and contacted authors about unclear CV outcome information. We undertook Der-Simonian and Laird random effect meta-analyses of MACE and all-cause mortality, using inverse-variance weights and continuity correction of 0.005. We excluded total-zero-event trials. We conducted subgroup analyses using a small number of pre-specified hypotheses, including study duration, type of control, treatment mode, and risk of bias.

Results:
Of 61 eligible trials, data on MACE was available in 33 trials of DPP-4 inhibitors (107 events /24341 patients), and 9 of GLP-1 agonists (12/3745), and ACM in 20 trials of DPP-4 inhibitors (45/17317), and 3 of GLP-1 (3/1404). There was a significant reduction in MACE (RR 0.53, 95% CI 0.33 to 0.85) between DPP-4 inhibitors and control, and a non-significant reduction in ACM (RR 0.46, 95% CI 0.19 to 1.07). No significant differences were found between GLP-1 agonists and control in MACE (RR 0.77, 95% CI 0.13 to 4.61) or ACM (RR 3.53,0 to >999). There was no significant heterogeneity detected in all analyses (p>0.1). Subgroup analyses did not show any significant differences in treatment effect, except that the effect on all-cause mortality differs by treatment mode (monotherapy vs. combination/add-on therapy, interaction p=0.04).

Conclusion:
DPP-4 inhibitors may reduce the risk of MACE and ACM. The effect of GLP-1 agonists on CV outcomes remains uncertain.
Abstract 9693: The Least of Three Evils: Anemia, Transfusion, or Both?
Authors: Loor Gabriel , Rajeswaran Jeevanantham , Li Liang , Blackstone Eugene H , Sabik Joseph F , Koch Colleen G
Published: April 2024

Objectives:
Anemia and red blood cell (RBC) transfusion have been associated with increased perioperative morbidity. Patients with anemia undergoing cardiac surgery are the most likely to receive RBCs, which results in a double negative exposure. We sought to clarify the independent effects of anemia, RBC transfusion, and their combination on risk of organ dysfunction and mortality.

Methods:
From 11/1/2004 to 10/30/2009, 7,942 patients underwent cardiac surgery and did not receive RBCs, and 1,202 received only intraoperative transfusions. Patients were divided into 4 groups: intraoperative hematocrit (HCT) >25% and <25% without RBC transfusion and >25% and <25% with transfusion. The relationship between HCT, transfusion, and outcome was studied using propensity-score analysis. Outcomes included eGFR, troponin, ventilation time, hospital stay and mortality.

Results:
Following risk adjustment, comparison of all 4 groups showed that lower HCT and RBC transfusion were independently associated with increased risk of morbidity and mortality. However, patients with severe anemia (HCT <25%) and transfusion had the worst renal function (lowest eGFR,
P
=.0008), most myocardial injury (highest troponin values,
P
=.01), longest postoperative ventilator requirement (
P
<.0001), longest stay (
P
<.0001) and highest mortality (
P
=.007; Figure).

Conclusions:
The least of 3 evils is to tolerate mild to moderate anemia, followed by transfusion, if severe anemia can be avoided. Exposure to both anemia and transfusion is associated with the highest risk of adverse outcome.
Abstract 9716: Who Needs a Statin? Impact of the New Expert Panel Guidelines for Screening and Management of Dyslipidemia in Children and Adolescents
Authors: McCrindle Brian W , Tyrrell Pascal , Kavey Rae-Ellen W
Published: April 2024

Introduction:
Recent Expert Panel guidelines commissioned by the National Heart, Lung and Blood Institute recommended universal and targeted lipid screening for children and adolescents, together with specification of lipid cutpoints and additional risk factors used in decision-making regarding initiation of lipid-lowering drug therapy. Given the current epidemic of childhood obesity and associated dyslipidemia, we sought to determine the potential impact of these guidelines on the estimated proportion of adolescents would potentially screen positive and be recommended for medication.

Methods:
We examined serial cross-sectional assessments using National Health and Nutrition Examination Survey data (1999-2010) of US children ages 12 to 17 years. The weighted proportion of participants meeting guideline screening and management lipid and risk factor cutpoints was determined, and compared to that obtained by applying previous guidelines.

Results:
Based only on non-fasting lipid measurement, 24.7% of screened individuals would have dyslipidemia (non-HDL >145 mg/dL + HDL <40 mg/dL) and require further evaluation. Using fasting assessment, 20.3% would screen positive, with 6.6% having high LDL (>130 mg/dL). Of those with fasting assessment, 17.2% were obese, 9.2% smoked, and 2.7% had hypertension. Assuming no improvement with lifestyle therapy and incorporating additional risk factors in decision-making, 0.85% (215,900 US children) might be recommended for statin therapy based on the new guidelines. For severely obese children with BMI > 97
th
%ile, 3.1% might be recommended for statin therapy. Applying previous guidelines, 0.50% would meet National Cholesterol Education Program 1992 criteria and 1.00% would meet American Academy of Pediatrics 2008 criteria for medication.

Conclusions:
Despite the recommendation for universal screening and greater specification regarding risk factors, only a small proportion of adolescents will be recommended for drug therapy with the new guidelines, appropriately targeting those with clustering of risk factors commonly associated with severe obesity, as well as those with familial dyslipidemias.
Abstract 9727: High Serum Level of Tenascin-c is Related to Coronary Plaque Rupture in Patients With Acute Coronary Syndrome
Authors: Sakamoto Nobuo , Misaka Tomofumi , Mizukami Hiroyuki , Suzuki Satoshi , Sugimoto Koichi , Yamaki Takayoshi , Kunii Hiroyuki , Nakazato Kazuhiko , Suzuki Hitoshi , Saitoh Shu-ichi , Takeishi Yasuchika
Published: April 2024

Purpose:
Tenascin-C is a multifunctional protein and increases the expression of matrix metalloproteinases which lead to atherosclerotic plaque instability. Destabilization of coronary plaque is relevant to plaque rupture resulting in acute coronary syndrome (ACS). We hypothesized that serum tenascin-C level is higher in patients with ACS than in those with stable effort angina (SAP), and high serum level of tenascin-C is associated with plaque rupture in patients with ACS.

Methods:
Consecutive 52 ACS patients who underwent emergent percutaneous coronary intervention (PCI) and consecutive 66 patients with SAP who underwent elective PCI were enrolled in this study. Blood samples were obtained from ascending aorta just prior to the PCI procedures, and circulating serum level of tenascin-C was measured using there samples. After coronary guidewire crossing, intravascular ultrasound (IVUS) was performed for assessment of plaque characterization including coronary plaque rupture.

ACS patients were assigned to two groups according to whether there was ruptured plaque (ACS-ruptured group) or not (ACS-non-ruptured group).

Results:
There were 23 patients in ACS-ruptured group and 29 patients in ACS-non-ruptured group. Clinical characteristics and IVUS findings of the lesion did not differ among SAP, ACS-ruptured and ACS-non-ruptured groups. Serum tenascin-C level in ACS-ruptured group was significantly higher than SAP patients, whereas there was no significant difference between ACS-non-ruptured group and SAP group. Importantly, in ACS-ruptured group, serum tenascin-C level was significantly higher than ACS non-ruptured group.

Conclusions:
Our data demonstrate that serum tenascin-C level is related to the pathological condition of ACS, especially the ruptured plaque estimated by IVUS observation. These results suggest that serum tenascin-C level is a novel biomarker for coronary plaque rupture in patients with ACS.
Abstract 9738: Use of the Syntax Score In Predicting Outcome After Unrestricted Use of 'limus' Stents
Authors: Kang Jeehoon , Park Kyung Woo , Kang Si-Hyuck , Ahn Hyo-Suk , Lee Hae-Young , Kang Hyun-Jae , Koo Bon-Kwon , Chae In-Ho , Youn Tae-Jin , Oh Byung-Hee , Park Young-Bae , Kandzari David , Kim Hyo-Soo
Published: April 2024

Background
The SYNTAX score (SS) and clinical SS (cSS) are widely used to assess coronary lesion complexity, and are useful indices in predicting outcomes after percutaneous coronary intervention. However, SS was derived from a study that exclusively used paclitaxel eluting stents, and its applicability to patients receiving ‘limus’ eluting stents is unclear. Thus, we investigated the validity of the SS and cSS in predicting clinical outcomes from a cohort where ‘limus’ stents were used unrestrictedly. We also compared the predictability of the scores in everolimus eluting stents (EES) versus sirolimus eluting stents (SES).

Methods
Patients were from the Efficacy of Xience/Promus versus Cypher in rEducing Late Loss after stenting (EXCELLENT) registry and the SS was evaluated at an independent angiographic core lab. The 1-year patient oriented composite endpoint (POCE) (all cause death, any myocardial infarction (MI), and any revascularization) and target lesion failure (TLF) (cardiac death, target vessel MI, and target lesion revascularization) were the major analysis endpoints. The area under the curve (AUC) of a receiver operating characteristic was used as the predictability of SS and cSS.

Results
Among 5102 patients (7003 lesions) enrolled, 3047 patients (4235 lesions) received EES and 2055 patients (2768 lesions) received SES. Tertiles for SS were defined as low SS<8, 8≤mid SS≤16, high SS>16. From the whole population, both POCE (4.2% vs. 7.7% vs. 12.2%, p<0.001) and TLF (1.6% vs. 2.4% vs. 4.5%, p<0.001) increased significantly along with increasing SS tertiles, and SS was an independent predictor of POCE and TLF in multivariate analysis (p<0.001 for all) The predictability of SS and cSS was similar for POCE (AUC: 0.635 vs. 0.629, for SS vs. cSS, p=0.599) but cSS was superior to SS in predicting TLF (AUC: 0.625 vs. 0.680, for SS vs. cSS, p=0.008). When stratified according to each stent, higher SS tertiles were significantly associated with increased risk of POCE and TLF in both EES and SES.

Conclusion
Both SS and cSS were applicable to unrestricted use of ‘limus’ stents to predict the risk of 1-year adverse clinical outcomes. The predictability of SS and cSS was similar for POCE but the inclusion of clinical variables improved predictability of the SS for TLF.
Abstract 9760: Plasma Levels of Nitric Oxide Metabolites Are Markedly Reduced In Normotensive Individuals With Electrocardiographically Determined Left Ventricular Hypertrophy
Authors: Kamezaki Fumihiko , Tsutsui Masato , Adachi Tetsuo , Takahashi Masao , Sonoda Shinjo , Takeuchi Masaaki , Otsuji Yutaka
Published: April 2024

Objective:
It has recently been revealed that normotensive subjects with electrocardiographically determined left ventricular hypertrophy (ECG-LVH) are at risk of multiple cardiovascular diseases, but the underlying mechanism remains to be elucidated. To address this point, we examined the hypothesis that normotensive individuals with ECG-LVH show reduced plasma levels of metabolites of nitric oxide (NO), a critical regulator of cardiovascular function.

Methods:
A total of 579 Japanese male workers (40-65 years of age) were studied. Since hypertension (blood pressure ≥140/90 mmHg) or medications could influence plasma NOx (NO metabolites, nitrite and nitrate), workers with such factors were excluded from the study. ECG-LVH was assessed by the Sokolow-Lyon voltage criteria and the Cornell voltage-duration product. The subjects were categorized by quartiles of plasma NOx level, and a multivariate logistic regression analysis was conducted relating ECG-LVH to NOx quartiles after adjustment for potential confounders.

Results:
The mean levels of plasma NOx were markedly lower in individuals with ECG-LVH (n=73, 28.9±19.2 μ mol/l) than in those without (n=506, 42.5±31.2 μ mol/l) (
P
<0.0001). The multivariate-adjusted odd ratio for the presence of ECG-LVH compared with the forth quartile of NOx (≥51.9 μ mol/l) was 1.38 (95% CI 0.55-3.59) for the third (NOx 33.1-51.8 μ mol/l), 1.83 (0.76-4.64) for the second (NOx 21.3-33.0 μ mol/l) and 4.93 (2.31-11.47) for the first quartile (NOx ≤21.2 μ mol/l). Similar result was obtained when subjects were stratified by waist circumference. The mean levels of plasma extracellular superoxide dismutase (EC-SOD), a major antioxidant in the cardiovascular system, were comparable in individuals with and without ECG-LVH. On the other hand, plasma EC-SOD levels were significantly decreased with lower quartiles of NOx (
P
<0.01).

Conclusion:
This study demonstrated for the first time that plasma NOx levels are markedly reduced in normotensive individuals with ECG-LVH. These results indicate that disrupted NO production through the involvement of down-regulation of the antioxidant enzyme may explain, at least in part, the potential mechanism for increased cardiovascular risk in normotensive individuals with ECG-LVH.
Abstract 9785: The Contribution of CaMKII and PKA to the Development of an Increased RyR-dependent SR Ca Leak in Human Cardiac Pathology
Authors: Fischer Thomas H , Herting Jonas , Renner André , Tirilomis Theodor , Neef Stefan , Gummert Jan , Friedrich Schöndube A , Hasenfuss Gerd , Maier Lars S , Sossalla Samuel
Published: April 2024

The mechanisms of a progressive ryanodine receptor type 2 (RyR2) dysregulation in the transition from human cardiac hypertrophy (Hy) to heart failure (HF) are still unclear. Inhibition of Ca
2+
/calmodulin-dependent kinase II (CaMKII) reduces the sarcoplasmic reticulum (SR) Ca
2+-
leak and improve contractility in human HF. However, the relative contribution of CaMKII and protein kinase A are still not clear. Western blot experiments from tissue samples (n=12) of patients with afterload-induced Hy and preserved ejection fraction (EF>50%) revealed an increase in RyR2 expression by 82±22% (
P
=0.05) compared to healthy controls (n=5). The phosphorylation status of RyR2 at S2809 and S2815 was not altered. In human end-stage HF (n=8), a pronounced hyperphosphorylation of RyR2 could be detected at the CaMKII-dependent site S2815 (by 311±72%,
P
<0.05) whereas the PKA-dependent site S2809 lacked differential regulation. The comparison of HF patients with and without β-blocker medication (n=7 vs. 4) did not reveal any differences as to RyR2 phosphorylation status. When isolated myocytes were paced at 1 Hz and scanned for diastolic Ca
2+
sparks (confocal microscopy, Fluo 3) a higher Ca
2+
-spark frequency (by 82±26%
P
<0.05) was detected in HF (n=93) compared to Hy (n=94). Interestingly, PKA inhibition with H89 (5 μM) only accomplished a decrease of SR Ca
2+
-leak in Hy (by 59±13%,
P
=0.05, n=85 vs. 115) but not in HF (n=85 vs. 74). Stimulated Ca
2+
transients (0.5 Hz, n=31 vs. 23), SR Ca
2+
content (caffeine, n=23 vs. 22) and fractional SR Ca
2+
release (n=21 vs. 15) were not changed by H89 treatment in HF (epifluorescence microscopy, Fura 2). CaMKII inhibition by AIP (1 μM), in contrast, could significantly reduce SR Ca
2+
leak in Hy (by 63±14%,
P
<0.05, n=93 vs. 103) as well as in HF. Thus, in human Hy with preserved EF both kinases seem to functionally regulate RyR2 gating. In end-stage human HF, however, the diastolic SR Ca
2+
leak seems to be induced by CaMKII rendering an inhibition of CaMKII a promising pharmacologic toehold.
Abstract 98: New Technique of Gas Adiabatic Expansion for Brain and General Hypothermia in Rabbit
Authors: Fontaine Guy H , Lapostolle Frederic , Pages Alban , Piquet Julie , Lalot Adrien , Didon Jean Philippe , Schmid Johan Jacob , Jouven Xavier , Chachques Jean Charles
Published: April 2024

Background:
Irreversible brain damage is a major issue in the acute treatment of OHCA. Brain protection by fossa nasalis cooling on the field has been reported. We propose a new technique to produce cooling by adiabatic gas expansion. Preliminary in vitro and animal studies have demonstrated that Carbon Dioxyde was able to produce significant cooling. The purpose of this work was to quantify the amount of cooling produced by this method on a rabbit model.

Method:
Study population consisted of 8 New-Zealand rabbits 3.5 kg studied under ketamine anesthesia without ventilation. Three lead ECG were displayed and sampled. Temperatures in °C, were measured by thermocouples every minute: close to the injector exit located inside a 12mm Ø, 2mm thick PVC canula inserted in the mouth up to the oropharynx, in the mouth close to the canula, in the nasopharynx (equivalent to tympanic) and in the rectum. Temperature curves were displayed on line on a computer screen. Data were processed by Statistica v6.0. A p value ≤ 0.05 was considered as significant. After stabilization of temperatures, gas regulated at around 500 psi was delivered during a period of 13 ± 2.7 min and expanded at the exit of the injector.

Results:
The initial 90% drop of temperature was obtained near the injector in 3 ± 1.47 minutes. The table below compares the temperatures recorded at the Start of cooling and at the End of this experiment.

A significant low temperature was observed near the injector (-16.9°C), the nasopharynx (37.7°C) and the oropharynx (31.2°C). A tendency not reaching statistical significance was obtained on the core temperature (39.4°C).

No adverse side effect was observed during and after the experiment especially no injury to the throat by direct visual inspection.

Discussion:
Core temperature drop was similar to that reported in pigs after nasopharynx PFC evaporation (Yu et al Crit Care Med. 2010). The lowest temperature (-16.9°C) was recorded as expected at the exit of gas, however, oral and nasal temperatures remained within tolerable values. Stronger effect on nasal temperature can be due to better mechanical contact of the canula against the upper oropharynx wall. Non-significant core cooling was probably due to the limit imposed by distance despite normal blood circulation. Nevertheless, a clear tendency was obtained as previously observed with other techniques of fossa nasalis cooling.

Conclusion:
This study demonstrates for the first time that carbon dioxyde adiabatic expansion in the mouth is effective for brain and body hypothermia in a rabbit model. This new technique which is simple, not expensive and easy to use by a lay person opens new vistas for the treatment of OHCA which can be started intra-arrest before CPR.
Abstract 9893: Preoperative Lower Cholesterol Level is the Independent Risk Factor of Severe Postoperative Mortality in Patients With Ruptured Abdominal Aortic Aneurysm
Authors: Nakayama Atsuko , Morita Hiroyuki , Miyata Tetsuro , Nagayama Masatoshi , Sumiyoshi Tetsuya , Nagai Ryozo
Published: April 2024

Background:
Hypocholesterolemia is reported to be the critical risks of hemorrhagic stroke, but the influence of hypocholesterolemia on large vessels such as abdominal aortic aneurysm (AAA) is unknown.

Methods:
We conducted a retrospective cohort study on 1053 consecutive patients receiving the surgical repair for infrarenal AAA in multicenter in Tokyo from 2003 through 2011. Laboratory data including total cholesterol levels were measured immediately before surgery. Cox hazards model were used to evaluate the risk factors for the postoperative mortality as well as major adverse cardiac events (MACE; composite of cardiovascular death without postoperative in-hospital death, acute coronary syndrome, cerebrovascular disorder).

Results:
The average follow-up period was 2.5 ± 2.1 years. In the multiple Cox analysis adjusted for age, gender, aneurysm size, smoking, hypertension, diabetes, past history of coronary disease, past history of chronic obstructive pulmonary disease, anemia, shock, statin use, β-blocker use and angiotensin II receptor blocker use, anemia (hemoglobin level < 10 g/dl), shock and hypocholesterolemia (total cholesterol level < 120 mg/dl) before surgery were found to be the risk factors of all postoperative death in patients with ruptured AAA (HR3.3; 95%CI 2.0-5.3, HR2.5; 95%CI 2.0-4.7, HR;5.4 CI 3.0-9.7, respectively, n=183). Meanwhile, there found to be no risk factor of all death in non-ruptured AAA (n=870). Furthermore, the mortality of patients with each total cholesterol level 120 - 140, 140 - 160, and 160 - 180 mg/dl was higher than that of total cholesterol level > 180 mg/dl (HR3.2; 95%CI 1.9-5.2, HR2.7; 95%CI 1.6-4.4, HR1.8; 95%CI 1.0-3.2, respectively). Receiver operator characteristic (ROC) curve analysis showed hypocholesterolemia is the most significant predictor of postoperative in-hospital death in patients with ruptured AAA (the area under the ROC curve = 0.77). The risk factor of MACE was identified to be the existence of preoperative coronary artery disease.

Conclusions:
The risk factors of poor mortality in patients with ruptured AAA were anemia, shock and hypocholesterolemia. The lower total cholesterol level indicated the more severe mortality of ruptured AAA.
Abstract 9901: Essential Function of Tmem100 for Endothelial Differentiation and Vascular Development Downstream of ALK1 Signaling
Authors: Somekawa Satoshi , Sakabe Masahide , Hayashi Hisaki , Sato Genki E , Inada Ken , Ito Munehiro , Uemura Shiro , Nakagawa Osamu , Saito Yoshihiko
Published: April 2024

Introduction:
Among members of the TGFβ superfamily, bone morphogenetic protein (BMP) 9 and BMP10 regulate vascular development through activation of activin receptor-like kinase 1 (ALK1/ACVRL1) receptor. ALK1-mediated intracellular signaling is implicated in the etiopathogenesis of human diseases, but functional proteins downstream of ALK1 signaling are largely unknown. We previously reported that
TMEM100
, a gene encoding an intracellular transmembrane protein, is activated by BMP9 and BMP10 through ALK1 receptor. We further demonstrated that
Tmem100
null mice showed embryonic lethality due to impaired differentiation of arterial endothelium and defects of vascular morphogenesis, which phenocopied most of vascular abnormalities observed in
Alk1
null embryos. However, the mechanisms of vascular defects caused by the
Tmem100
deficiency and responsible cell type remain to be investigated.

Methods and Results:
To clarify which vascular cell type is contributed to developmental defects by the
Tmem100
deletion, we generated
Tmem100
conditional knockout mice using the Cre-loxP system. The deletion of endothelial
Tmem100
caused impairment of vascular morphogenesis and embryonic lethality, which was virtually identical to the phenotypes of global null mice. To understand the mechanisms of vascular defects, we performed a microarray analysis using the yolk sac. We observed a significant decrease in the expression of Notch- and Akt-downstream genes, such as
Hrt1/Hey1
,
Hrt2/Hey2
,
Klf2
and
eNos
, in
Tmem100
null yolk sac as well as embryos. Expression of activated Notch1 receptor, Notch ICD, and Akt phosphorylation were down regulated in
Tmem100
null yolk sac and embryos. Notch and Akt signaling regulates arterial development, and dysregulation of these signaling pathways was also observed in
Alk1
null embryos, suggesting that TMEM100 works for proper vascular development downstream of ALK1 signaling, at least in part, by the regulation of these signaling pathways.

Conclusion:
TMEM100 functions in endothelial cells play indispensable roles during vascular development and morphogenesis downstream of ALK1-mediated signaling.
Abstract 9918: Novel and Profound Lipid Effects of GSK1292263, a Potent and Selective GPR119 Agonist, in Dyslipidemic Subjects
Authors: Nunez Derek J , Bush Mark , Collins David , McMullen Susan , Gillmor Dawn , Poss Gerri , Schott Robert , Feldman Paul
Published: April 2024

GSK1292263 (GSK263), a GPR119 agonist, improves glucose regulation in animal models of diabetes, but has no effect on plasma glucose in type 2 diabetics. Unexpectedly, GSK263 lowered fasting LDLc and triglycerides (TG), while increasing HDLc in these diabetic subjects. The study aim was to determine whether GSK263 improves lipid profiles in dyslipidemic, non-diabetic subjects when dosed alone or with atorvastatin (NCT# 01218204). Eligible subjects on statin/Vytorin therapy were washed off these drugs for 4 weeks. After washout, they were randomized to receive (i) 100mg (n=11), 300mg (n=12) or 800mg (n=13) QD of GSK263 or placebo (n=11) for 2 weeks; or (ii) 10mg atorvastatin (A10) or 80mg atorvastatin (A80) for a 4-week Run-in period. After the atorvastatin Run-in, (i) A10 was co-dosed with: 100mg (n=11), 300mg (n=11), 800mg (n=11) QD GSK263, placebo (n=12) or 10mg ezetimibe (n=13), and (ii) A80 was co-dosed with: 800mg (n=12) QD GSK263 or placebo (n=13). Fasting plasma lipids and NMR lipoprotein particles (LipoProfile) were measured at baseline and after 2 weeks of dosing. By ANCOVA (change from baseline), 800mg GSK263 significantly increased fasting HDLc by 20.7% (95% CI 9.8 to 31.6%), reduced fasting LDLc by 21.8% (95% CI -32.1 to -11.2%), and reduced fasting TGs by 54.8% (95% CI -70.8 to -38.9%) when compared to placebo. TG AUCs (wm 0-24h) fell by 41.3% (95% CI -61.9 to -20.8%). Similar effects were seen when co-dosed with A10 and A80. The lipid effects were dose-dependent, with GSK263 100mg having minimal effect. GSK263 may reduce apoB100, apoE and CRP, but had no clear effect on apoA1. NMR analysis suggests that GSK263 (i) reduced VLDL and chylomicron particle number and VLDL particle size, (ii) reduced LDL and IDL particle number and increased LDL particle size, and (iii) increased HDL particle number and size, especially when co-administered with atorvastatin. GSK263 was generally well tolerated over the dose range of 100mg to 800mg QD administered for 14 days. The majority of AEs associated with GSK1292263 were mild in intensity. GSK263 has significant effects on plasma lipids and lipoprotein particles in dyslipidemic patients when dosed alone and with atorvastatin. Studies are on-going to investigate the novel mechanisms underlying these lipid effects.
Abstract 9919: PH-low Insertion Peptide (pHLIP) Targets Ischemic Myocardium
Authors: Andreev Oleg A , Anyukhovsky Evgeny P , Sosunov Alexandre A , Moshnikova Anna , Reshetnyak Yana , Sosunov Eugene A
Published: April 2024

pHLIP molecule (∼3 kD) inserts into a lipid bilayer when ambient pH is low. Originally, this property was used for targeted delivery of small molecules, liposomes and nanoparticles conjugated with pHLIP to visualize and treat tumors. Since cardiac ischemia causes a decrease in tissue pH we hypothesized that pHLIP can selectively bind to ischemic myocardium. METHODS. We studied pH-sensitive (Var7) and a pH-insensitive (kVar7) variants of pHLIP conjugated with fluorescent dye Alexa488 in three models. (1) Local myocardial ischemia was induced by repetitively occluding (10 min) and reperfusing (5 s) left coronary artery of anesthetized mice for 2 hr; 100 μL of 80 μM pHLIP were administered IV 3 min prior to the first occlusion. In the end, hearts were excised and retrogradely perfused with Evans Blue to delineate the area at risk. Hearts were frozen and sectioned to measure mean intensity of fluorescence (F). (2) Low flow (5% of normal flow rate) global ischemia was induced in Langendorff-perfused mouse hearts paced at 5 Hz and perfused with 1 μM pHLIP for 15 min. (3) Effects of 10 μM pHLIP on transmembrane potential and developed force were studied in isolated preparations of paced (4 Hz) murine left atrial appendages (AA) at normal and low (6.5) pH. RESULTS. In the model of local ischemia, when pH-sensitive Var7 was used, area of bright fluorescence coincided with the area at risk. F in the area at risk normalized to F in intact myocardium was higher with Var7 (3.89±.43, n=4) than with pH-insensitive kVar7 (1.11±.09, n=5, p.05). In global ischemia, F was higher in the hearts perfused with Var7 vs either kVar7 or Var7 in the absence of ischemia (Var7: 76±8, n=5; kVar7: 25±5, n=4; Var7 + no ischemia: 12±4, n=3, p<.05). In AA exposed to pH 6.5 (but not at pH 7.4), F was higher with Var7 than with kVar7 (76±9 vs 28±3, n=5; p<.05). Neither at the normal or low pH, pHLIP variants affected parameters of transmembrane potential or developed force. CONCLUSIONS. pH-sensitive pHLIP selectively binds to ischemic myocardium without affecting either ectrical or mechanical activity. Based on analogy with applications in oncology, pHLIP can be used for targeted delivery of contrasting agents and drugs to ischemic regions of the heart.
Abstract 9941: Prior Myocardial Infarction is Associated with Endothelial Dysfunction in Women with Microvascular Coronary Dysfunction
Authors: Agarwal Megha , Kothawade Kamlesh , Shufelt Chrisandra , Lentz Greg , Mehta Puja , Sedlak Tara L , Minissian Margo , Hobel Zachary , Kar Saibal , Azarbal Babak , Samuels Bruce , Bairey-Merz C. Noel
Published: April 2024

Background:
Patients with signs and symptoms of ischemia but no obstructive coronary artery disease (CAD) often have microvascular coronary dysfunction (MCD). MCD is associated with an elevated risk of myocardial infarction (MI), yet the pathophysiological mechanism(s) are not well understood. We compared endothelial-dependent and endothelial-independent pathways in women with MCD with and without a prior history of MI.

Methods:
67 women with persistent chest pain, clinical evidence of myocardial ischemia, and no obstructive CAD by angiography, underwent clinically-ordered coronary reactivity testing, which included infusion of intracoronary acetylcholine (ACH), adenosine and nitroglycerin to determine percent change in coronary artery diameter and flow. History of prior MI was obtained through supervised, self-reported questionnaire and confirmed with medical record evidence of elevated troponin when available. Data were analyzed using a Wilcoxon signed-rank test.

Results:
Overall 10 (15%) women (51±12 years) had a history of MI (4 confirmed by available medical records) and 57 (55±9 years) had no prior MI (No-MI). There were no group differences in rates of age, hypertension, dyslipidemia, body mass index, smoking history, family history of heart disease, or diabetes (data not shown). Intracoronary ACH response (endothelial-dependent pathway) was significantly lower in the group with prior MI compared to no-prior MI group (figure). Measurements of coronary flow reserve with adenosine infusion and coronary vasodilation with nitroglycerin infusion (both endothelial-independent pathways) were not different between groups.

Conclusions:
Prior MI in women with MCD is associated with endothelial dysfunction. Future study should consider coronary endothelial dysfunction as a MCD treatment target in women with a history of MI and no obstructive CAD.
Abstract 9964: Vorapaxar, a Platelet Thrombin-Receptor Antagonist, in Medically Managed Patients with Non-ST-Segment Elevation Acute Coronary Syndrome: Results from the TRACER Trial
Authors: Held Claes , Tricoci Pierluigi , Huang Zhen , Van de Werf Frans , White Harvey , Armstrong Paul , Ambrosio Giuseppe , Aylward Philip , Moliterno David , Wallentin Lars , Chen Edmond , Erkan Aycan , Jiang Lixin , Strony John , Harrington Robert , Mahaffey Kenneth
Published: April 2024

Purpose: This is a prespecified post-randomization subgroup analysis to evaluate efficacy and safety outcomes of vorapaxar in the TRACER trial in patients that were medically managed without revascularization procedures during index hospitalization.

Methods:
Vorapaxar, a novel platelet-protease-activated receptor-1 antagonist, was randomized with placebo in 12,944 patients with NSTE ACS. We explored the effect of vorapaxar vs placebo among medically managed patients at discharge (n=4194; 32.4 %) vs those undergoing revascularization (n=8750; 67.6%) from discharge to end of follow-up, with adjustments for baseline differences. Events rates are provided as 2-yr Kaplan-Meier estimates.

Results:
The medically managed patients were more likely to be older and female and have prior MI, prior CABG, and decreased renal function. The 2-yr event rate of the primary outcome (CV death, MI, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization) was 16.9% with vorapaxar and 17.3% with placebo (HR 0.95; 95% CI 0.81-1.14), with no interaction between study drug and management strategy (p=0.63). The rate of the key secondary endpoint (CV death, MI, and stroke) was 13.9% with vorapaxar and 15.1% with placebo (HR 0.88; 95% CI 0.73-1.07), with no interaction (p=0.86). Lower MI rates were observed in medically managed patients treated with vorapaxar (9.3% vs 11.1% [HR 0.79; 95% CI 0.63-0.99). Vorapaxar significantly increased GUSTO moderate or severe bleeding in medically managed patients (HR 1.52; 95% CI 1.04-2.22) and in patients undergoing revascularization (HR 1.32; 95% CI 0.99-1.76). In the medical group, intracranial hemorrhage (ICH) occurred in 18 patients with vorapaxar and in 1 patient with placebo, whereas ICH occurred in 17 vorapaxar patients and 9 placebo patients treated with revascularization, with no significant interaction (p=0.056).

Conclusion:
In patients with NSTE ACS treated medically, the efficacy of vorapaxar was consistent with the main findings of the TRACER trial. Bleeding hazard with vorapaxar tended to be higher in medically treated patients, possibly due to patient selection factors.
Abstract 9965: Prediction and Diagnosis of Perioperative Myocardial Infarction with High-sensitivity troponin T
Authors: Nagele Peter , Brown Frank , Scott Mitchell , Gage Brian F , Miller J. Philipp
Published: April 2024

Introduction
The role of high-sensitivity troponin assays in the prediction and diagnosis of perioperative myocardial infarction is unknown.

Methods
This is an ancillary study of the Vitamins in Nitrous Oxide (VINO) Trial where 625 patients with or at risk for coronary artery disease undergoing major noncardiac surgery were studied..Plasma hsTnT (Roche) and standard troponin I (Siemens) were measured serially and 12-lead ECGs were obtained.

Results
At baseline 75% of patients (455/606) had a measurable preoperative hsTNT and 25% had a hsTnT <3 pg/mL. The median hsTnT was 7.4 pg/mL (IQR 2.3 - 15.2). Postoperatively, 409/568 patients (72%) had an increase in hsTnT (median 2.9 pg/mL; IQR 0 - 7.4) and 159/569 (28%) had no change. The median peak hsTnT was 12.2 pg/mL (IQR 6.1 - 23.0). Peak and delta hsTnT and troponin I measurements were tightly correlated (r= 0.99 and 0.99, respectively). Eighty-two patients (13%) had a clinically relevant postoperative TnI elevation >0.07 ng/mL and 30/605 (5%) had a myocardial infarction. Using the median preoperative hsTnT concentration of 7.4 pg/mL, patients above this level had a nearly 3-fold risk to develop a clinically significant postoperative troponin elevation (odds ratio 2.80, 95% CI: 1.69 - 4.63, p< 0.001) and to develop postoperative myocardial infarction (odds ratio 2.94, 95% CI 1.29 - 6.71, p= 0.007). At 7.4 pg/mL, the sensitivity and specificity for postoperative troponin elevation were 71% and 54% and for postoperative myocardial infarction 73% and 52% (Figure 1).

Conclusions:
Preoperative hsTNT concentrations can be detected in most adult patients with or at risk for coronary artery disease before surgery and may be useful in preoperative risk-stratification for postoperative myocardial infarction. Postoperative increase in hsTnT (delta hsTnT) is common among patients with cardiovascular risk factors and may be useful as objective quantification of perioperative myocardial injury.
Abstract 9967: Microvolt T-wave Alternans in Adults with the Chosen Forms of Congenital Heart Disease
Authors: Trojnarska Olga , Cieplucha Aleksandra , Bartczak Agnieszka , Grajek Stefan
Published: April 2024

Introduction.
Sudden cardiac death (SCD) in adults with congenital heart diseases (CHD) is usually caused by ventricular arrhythmia (VA). Among the noninvasive methods of risk stratification for SCD is microvolt T-wave alternans (MTWA), reflecting repolarization inhomogeneity. We sought to determine the incidence of MTWA among adults with chosen forms of CHD as well as its coincidence with VA and other findings presumably associated SCD.

Methods and Results.
The study group: 102P with CHD characterized by pathology within right ventricle or single ventricle physiology (transposition of the great arteries after atrial switch, univentricular heart, Ebstein’s anomaly, congenitally corrected transposition of the great arteries, Eisenmenger syndrome, double-outlet right ventricle, common arterial trunk, unoperated tetralogy of Fallot). Controls: 45 volunteers age and sex-matched. All subjects underwent spectral MTWA test, ambulatory ecg monitoring, cardiopulmonary test, BNP assessement. MTWA positive and indeterminate were labeled ‘abnormal’ and were present more often in the study group, compared to controls (39,2% vs 2,3%, p=0,00001). Among subjects with abnormal MTWA sustained ventricular tachycardia (sVT) was observed more often compared to MTWA(-): 19,4% vs 3,6%, p=0,026. The patients with abnormal MTWA had a lower blood saturation (p=0,047), more often were males (p=0,031), had higher NYHA class (p=0,04), worse cardiopulmonary parameters: %PeakVO2 (p=0,034), %HRmax (p=0,003). Factors associated with abnormal MTWA: sVT (OR=20,7 p=0,037), male gender (OR=15,9 p=0,001) in multivariate regression; in univariate analysis: male gender (OR=2,7, p=0,021), presence of VA (OR=2,6, p=0,049), NYHA > I (OR=2,06, p=0,033), %HRmax, %PeakVO2, VE/VCO2 slope (OR=0,94, p=0,005; OR=0,97, p=0,042; OR=1,05, p=0,037).

Conclusions.
The abnormal MTWA occurs significantly more often in adults with the chosen forms of CHD than among healthy subjects. The probability of abnormal MTWA increases in patients with malignant VA, in males and among subjects with heart failure and cyanosis. MTWA might be of potential role in risk stratification for SCD.