bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 8230: Arachidonic 12-lipoxygenase-induced Inflammation Promotes The Development Of Diabetic Cardiomyopathy
Authors: Kayama Yosuke , Sakamoto Masaya , Suzuki Hirofumi , Date Taro , Minamino Tohru , Komuro Issei , Yoshimura Michihiro
Published: April 2024

Diabetic mellitus increases the risk of heart failure independently of underlying coronary artery disease, and many believe that diabetes leads to cardiomyopathy. The underlying pathogenesis is partially understood, but precise mechanism underlying diabetic cardiomyopathy is still unknown. To investigate the molecular mechanisms of diabetic cardiomyopathy, we created a diabetic cardiomyopathy model (streptozotocin (STZ) injection rat) and performed microarray analysis. Echocardiography showed that STZ injection rat developed diastolic and systolic dysfunction and cardiac fibrosis was increased in STZ injection rat. Among the genes analyzed, arachidonic 12-lipoxygenase (12-LOX) was upregulated in the heart of STZ rat. Northern blotting and ELISA analysis demonstrated that mRNA level of 12-LOX and production of 12(s)-HETE, a major metabolite of 12-LOX, were upregulated in the heart of STZ rat compared to those of control rat heart. Until recently, 12-LOX has been reported to play an important role in the development of atherogenesis, diabetes, and neurogenerative disease. However, the role of 12-LOX in diabetic cardiomyopathy has not been examined. To determine the role of 12-LOX in STZ injection heart, we created STZ injection mice (WT-STZ) and compared to those of 12-LOX KO (KO-STZ) mice. Disruption of 12-LOX significantly reduced cardiac fibrosis and improving diastolic and systolic dysfunction. Moreover the expression of inflammatory cytokine genes such as MCP-1 and TNF-α and STZ-induced reactive oxygen species were significantly inhibited by disruption of 12-LOX. In vitro experiment reveal that hyperglycemia induced expression of 12-LOX as well as MCP-1 and TNF-α by neonatal cardiomyocyte. Treatment with Cinnamy1-3,4-dihydroxy-α-cyanocinnamate (CDC) , a inhibitor of 12-LOX, decreased the expression of MCP-1 and TNF-α by cardiomyocyte under high glucose stimulation. Our results suggest that cardiac 12-LOX-induced inflammation is involved in the development of diabetic cardiomyopathy and that inhibition of 12-LOX could be a novel treatment for this condition.
Abstract 8299: Loss of Apelin Exacerbates Post-Myocardial Infarction Remodeling and Myocardial Ischemia-Reperfusion Injury
Authors: Wang Wang , Bodiga Sreedhar , Kassiri Zamaneh , Penninger Josef M , Oudit Gavin
Published: April 2024

Objectives:
Apelin (APLN), the endogenous peptide ligand of the APJ receptor, improves heart function in patients with heart failure and apelin peptides mediate positive inotropic effects and vasodilation. We hypothesize that there is an exacerbated myocardial ischemic injury in APLN knockout (KO) mice compared to littermate WT.

Methods:
Male WT (C57Bl/6) and APLN knockout mice were subjected to myocardial infarction (MI) using the LAD ligation technique and mortality and heart function were monitored. Langendorff perfused ex vivo hearts from WT and APLN KO mice were subjected to 30 min global ischemia followed by 40 min reperfusion.

Results:
LAD ligation in APLN KO mice resulted in greater mortality based on Kaplan-Meir survival analysis (76% vs 48%; p<0.01) at 1 week post-MI. Echocardiography showed greater reduction in ejection fraction in APLN KO mice (18.1±3.5 vs 29.3±3.1%; p<0.05) with greater LV dilation (LV end-diastolic volume=196±14.2 vs 161±13.1 μ L; p<0.05; n=8) at 1 week post-MI. In response to global ischemia-reperfusion (I/R) injury, functional recovery was significantly decreased in APLN KO hearts with LV developed pressure=19.5±2.8 vs 33.8±4.1 mmHg (WT; p<0.05; n=5) at the end of 40 min of reperfusion with significant lowering of the dP/dtmax=1289±65 mmHg/s (WT) versus 610±65 mmHg/s (APLN KO; p<0.05) and dP/dtmin=-657±34 mmHg/s (WT) versus -329±25 mmHg/s (APLN KO; p<0.05) and the rate-pressure product averaging 9975±253 bpm*mmHg (WT) versus 4208±212 bpm*mmHg (APLN KO; p<0.05). Creatine kinase in the coronary perfusate showed a greater increase in APLN KO compared to WT (102.7±17.7 vs 57.5±8.9 U/L; p<0.05) mice in response to I/R injury. Western blot analysis showed reduced phosphorylation of Akt, GSK3β and ERK1/2 in the ischemic-reperfused APLN KO hearts compared with WT hearts.

Conclusions:
Loss of apelin increases MI-induced mortality, exacerbates post-MI adverse modeling and enhances the susceptibility to I/R injury. Enhancing apelin function may represent a novel therapy for minimizing the myocardial damage in patients with heart disease.
Abstract 8302: Lidocaine Abolishes the Sympathetic and Blood Pressure Responses in Limb Venous Distension Reflex
Authors: Cui Jian , McQuillan Patrick , Sinoway Lawrence I
Published: April 2024

Introduction-
We have recently shown that saline infusion into the veins of an arterially occluded human forearm evokes a systemic response with an increase in muscle sympathetic nerve activity (MSNA) and blood pressure (BP).

Hypothesis-
Limb veins distension per se activates afferent nerves within (or close to) the vessel wall, and evokes a systemic sympathoexcitatory reflex.

Methods-
Thus, we examined MSNA and BP responses as albumin was infused into the venous circulation of an arterially occluded forearm. These MSNA and BP responses were compared with those seen with a saline infusion. Albumin preferentially remains within the vascular space whereas saline distributes within the entire limb extracellular space. BP (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects on 3 separate visits. In the saline trial, 5% forearm volume saline was infused into an arterially occluded arm. In the albumin trial (n=11), the same volume of albumin solution (5% concentration) was infused. In separate studies, 90 mg of lidocaine was added to the saline infusion (n=6).

Results-
MSNA and mean BP rose towards to the end of infusion in both saline and albumin trials. A larger (i.e. the peak response at the end of infusion: delta 14.3±2.7 vs. delta 8.5±1.3 bursts/min,
P
<0.01) and a sustained (i.e. the 30-60 sec of post infusion: delta 15.0±3.0 vs. delta 5.9±2.4 bursts/min,
P
<0.05) MSNA response was noted with albumin infusion as compared to saline infusion. The BP response with albumin infusion was also greater and sustained than saline infusion (all
P
<0.05). The 90 mg of lidocaine added to the saline infusion abolished >90% of the MSNA and BP responses.

Discussion and Conclusion-
These data suggest that vein distension is crucial to evoking the response seen. The lidocaine trial confirms that this venous distension evokes an autonomic reflex. We suggest that venous distension importantly contributes to autonomic and cardiovascular control in humans.
Abstract 8416: Clinical Predictors of Short- and Long-Term Mortality Among Patients with Cardiovascular Implantable Electronic Device Infection
Authors: Habib Ammar , Le Katherine Y , Lohse Christine M , Friedman Paul A , Hayes David L , Wilson Walter R , Steckelberg James M , Baddour Larry M , R Muhammad
Published: April 2024

Device infection is associated with increased mortality in cardiovascular implantable electronic device (CIED) recipients. However, published data regarding clinical predictors of mortality in patients with CIED infection are limited. In current investigation, we sought to identify patient and device-related factors associated with mortality in CIED infection cases. We performed a retrospective review of all cases of CIED infection admitted to Mayo Clinic Rochester from 1991 to 2008. Survival data were obtained from hospital medical records and United Sates Social Security Index. Key data regarding patient demographics, device features, comorbid conditions, clinical presentation, echocardiographic findings and management strategies were abstracted. Potential risk factors for short (30-day) and long-term mortality were analyzed using univariate and multivariable logistic and Cox proportional hazards regression models, respectively. 415 cases of CIED infection were identified from the institutional database. The mean duration of follow-up for the 243 patients who were alive at last follow-up was 6.9 years. In multivariable model, congestive heart failure (CHF, Odds ratio 9.31, 95% CI 2.08-41.67), chronic corticosteroid use (OR 4.04, 1.40-11.60) and presentation with CIED-related infective endocarditis (CIED-IE), (OR 5.6, 2.25-13.92) were associated with increased odds of short-term mortality. Independent predictors of long-term mortality on multivariable model included patients' age (hazard ratio for 10-year increase 1.2, 95% CI 1.06-1.36), CHF (HR 2.01, 1.42-2.86), metastatic malignancy (HR 5.99, 1.67-21.53), corticosteroid use (HR 1.97, 1.22-3.18), renal failure (HR 1.94, 1.37-2.74) and CIED-IE (HR 1.68, 1.17-2.41). Our investigation provides some novel insights into predictors of short- and long-term mortality in CIED infection cases. While comorbid conditions and immunocompromised host status were primary determinants of both short- and long-term mortality, complicated device infection (CIED-IE) is the only predictor that presents an opportunity for intervention where mortality may be reduced by early diagnosis and expedited device removal.
Abstract 8422: Cardiac Protein Abnormalities of Human Left Ventricular Tissue in Ischemic and Dilated Cardiomyopathy
Authors: Rivera Miguel , Rosello-Lleti Esther , Salvador Antonio , Cortes Raquel , Martinez-Dolz Luis , Almenar Luis , Lago Francisca , Azorin Inmaculada , Gonzalez-Juanatey Jose , Sanchez-Lazaro Ignacio , Bertomeu Vicente , Montero Anastasio , Hove Leif , Cinca Juan , Portoles Manuel , Alonso Jana
Published: April 2024

Introduction:
The development of heart failure (HF) is characterized by progressive alteration of left ventricle structure and function. A proteomic approach could lead to the detection of variations in protein expression of left ventricular tissue from patients with ischemic (ICM) and dilated cardiomyopathy (DCM).

Methods:
24 explanted human hearts, 12 from patients with ICM and 12 with DCM undergoing cardiac transplantation and 6 non-diseased donor hearts (CNT) were analyzed by 2DE. Proteins of interest were identified by mass spectrometry and validated by Western blotting and immunofluorescence.

Results:
We encountered 35 differentially regulated spots in the comparison CNT vs. ICM, and 33 in CNT vs. DCM. We identified G3P up-regulation in both ICM (2.53-fold, p<0.0001) and DCM (2.89-fold, p<0.0001). HSP71 was up-regulated only in ICM (3.31-fold, p<0.0001). G3P was related with ventricular function parameters (left ventricular end-systolic diameter (p=0.001), end-diastolic diameter (p=0.001)) in our HF patients. HSP71 was also related with these functional parameters (p<0.05).

Conclusions:
We have shown by proteomics analysis that HF is associated with changes in proteins involved in the cellular stress response, respiratory chain and cardiac metabolism. Although we found altered expression of proteins common to both ischemic and dilated etiology, we also found different proteins altered in both groups. In addition, for the first time left ventricular function was related with changes in G3P and HSP71.
Abstract 8426: Racial Differences in Heart Transplant Wait-List and Early Post-Transplant Mortality in the United States
Authors: Singh Tajinder P , Almond Christopher S , Taylor David O , Graham Dionne
Published: April 2024

Background:
Racial differences in long-term outcomes after heart transplant (HT) are well known. However, racial differences in outcomes among those listed for a HT in the United States (US) have not been characterized. We sought to assess racial and ethnic differences in risk factors and in risk of wait-list and early post-transplant mortality among patients (pts) listed for a HT in the US in the current era

Methods and Results:
We identified all pts ≥18 yrs of age listed for a primary HT in the US during July, 2006- June, 2009 in the Organ Procurement and Transplant Network database. Of 7361 pts analyzed, 69% were white, 20% black, 7% Hispanic and 3% were “other’. Black and Hispanic pts were younger than white pts and were more likely to have blood type O (black 48%, Hispanic 53%, white 42%), dilated cardiomyopathy (71%, 56%, 39%, respectively), pulmonary artery wedge pressure >20 mm Hg (55%, 54%, 47%, respectively), listing status 1A or 1B (68%, 63%, 53%, respectively) and public medical insurance (25%, 26%, 10%, respectively) (P<0.001 for all). Overall, 11.5% of white, 12.5% of black and 14.8% of Hispanic pts listed for a HT died on the wait-list or became too sick to transplant. In an analysis adjusted for age, diagnosis, listing status, pulmonary artery wedge pressure, support variables (inotropes, ventilator, mechanical support, implantable cardioverter defibrillator) and renal function, both black (hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.99, 1.43) and Hispanic (HR 1.65, 95% CI 1.25, 2.05) pts were at higher risk of dying on the wait-list or becoming too sick to transplant compared to white pts (P=0.002). These risks remained unchanged after further adjustment for blood type and medical insurance. Compared to white HT recipients, post-transplant in-hospital mortality was higher in black recipients (Odds ratio [OR] 1.47, 95% CI 1.13, 1.91) but was not different in Hispanic recipients (OR 0.87, CI 0.57, 1.32).

Conclusions:
Black and Hispanic pts listed for a HT in the US appear to be at higher risk of dying on the wait-list or becoming too sick to transplant compared to white pts. Black pts also appear to be at higher risk of early post-transplant mortality. Understanding the mechanisms for these racial differences in outcomes requires further investigation.
Abstract 8453: 2D Speckle Tracking Strain for Functional Characterization of Right Ventricular Wall Motion
Authors: Ashraf Muhammad , Hickey Edward , Hui Ling , Sahn David J
Published: April 2024

Background:
Left ventricular (LV) twist appears to play an important role in effective ejection fraction (EF). MRI based tagging methods are limited for tracking right ventricular (RV) free wall motion, especially for the normal thin free wall. We used a new motion analysis program based on tracking speckles in B-mode echo images to study RV motion.

Methods:
For our study, 6 small (2-3kg) piglets were intubated and anesthetized; median sternotomy was done to expose the heart. We used a 10MHz sector probe and a 13MHz linear probe to acquire 2D and tissue Doppler images of the RV from the surface of the heart, using liver as a standoff to improve extent and clarity of the RV free wall images. Short axis views were acquired on a GE Vivid 7 Dimension ultrasound system at frame rates >100/sec. The study was conducted at 3 hemodynamic states of baseline and after 10% and 20% volume loading. Data was later analyzed offline in EchoPac using 2D speckle tracking.

Results:
There was a minimal component of rotation in the free wall of the RV (1°-2°) but more in the septum (5°-8°), which was similar to the rotation of the LV free wall for that level. Strain values were similar in both free wall and the RV side of the septum. With volume loading, there was an increase in the septum (mean 2° ± 1°) amplitude of twist and a decrease in time to peak twist, but the RV free wall showed no significant change.

Conclusions:
These findings are consistent with observations that the septum plays an important role in RV dynamic function.
Abstract 8526: Comparison of Transradial Coronary Angiography via Right or Left Radial Artery Approaches in Contemporary Real World Cardiology Practice. A PREVAIL Study data subanalysis
Authors: Pelliccia Francesco , Trani Carlo , Nazzaro Marco , Berni Andrea , Patti Giuseppe , Patrizi Roberto , Pironi Bruno , Mazzarotto Pietro , Gioffrè Gaetano , Pristipino Christian
Published: April 2024

Introduction.
Previous studies in small subgroups of patients undergoing transradial catheterization have suggested that the right radial artery approach may encounter more technical difficulties than the left radial approach.

Hypothesis.
We performed a subanalysis of the PREVAIL study in order to test the hypothesis that the two approaches are actually different in the contemporary real world practice.

Methods.
PREVAIL study was a prospective, observational survey of unselected consecutive patients undergoing invasive cardiovascular procedures at 9 Italian hospitals over a one month observation period specifically aimed at assessing the outcomes of radial approach in contemporary real world. The choice of arterial approach (radial vs femoral, right radial vs left radial) were left to the discretion of the operator. Pre-specified end-points of this subanalysis were the procedural characteristics, expressly defined in the case report form to control for confounders

Results.
Of 1,052 patients consecutively enrolled, 509 patients underwent transradial catheterization (304 right radial and 205 left radial approach). The clinical characteristics were similar between the 2 groups. A similar proportion of patients in the 2 groups had coronary angiography only (59% vs 61%) or percutaneous coronary intervention (41% vs 39%), with no difference in urgent cases (37% vs 34%). Also, procedural success rates were similar in the 2 groups (97% vs 96%, respectively). As compared with left radial, the right radial group had longer total duration of the procedure (46+29 vs 33+24 min, P<0.0001) and fluoroscopy time (765+787 vs 533+502 s, P<0.0001). No differences were found in quantity of contrast injected (182+115 vs 176+112 ml) and numbers of catheters used per procedure (2.8+1.1 vs 2.8+1.1). Similar results were obtained when only operators with high (>65%) right radial vs left radial volume were compared.

Conclusions.
The right and left radial artery approaches are feasible and effective to perform coronary angiography and intervention. In contemporary real world, however, patients undergoing the left radial route had shorter procedures and lower radiological exposure as compared to those undergoing a right radial approach.
Abstract 8551: Left Atrial Strain by Speckle Tracking Echocardiography In Patients with Heart Failure - An Independent and Incremental Predictor of Cardiac Death or Need of Heart Transplantation
Authors: Helle-Valle Thomas , Opdahl Anders , Broch Kaspar , Gude Einar , Andreassen Arne , Smiseth Otto A , Gullestad Lars
Published: April 2024

Background:
We have recently shown that left atrial (LA) stretching during atrial filling, measured as peak LA strain by speckle tracking echocardiography (STE), is a strong and independent predictor of cardiac death or heart transplantation (HTx) in patients with heart failure (HF). Furthermore, our study demonstrated that while logNT-proBNP and left ventricular ejection fraction (LVEF) were independent predictors of these end points, age, LA area and E/e’ were not. In the present study we investigate if LA strain adds predictive power to that provided by NT-proBNP and LVEF.

Methods:
We included 143 patients (age 54±11 years), with ischemic or dilated cardiomyopathy (NYHA II-IV, LVEF= 31±13%). Peak LA strain by STE and LVEF were measured. Time to death or HTx (Cox model) was adjusted for age, logNT-proBNP and LVEF in addition to LA strain. We computed receiver-operating characteristic (ROC) curves and tested for equality of the areas under the curve (AUC) for models with and without LA strain.

Results:
Median follow-up time was 3.0 years. There were 39 events and median time to event was 0.7 years (range 0.1 to 4.3). LVEF (P=0.008), logNT-proBNP (P=0.007) and LA strain (P=0.007) were independent predictors of cardiac events. When LA strain was added to age, LVEF and logNT-proBNP, AUC demonstrated significantly better predictive power (0.68±0.05 vs. 0.73±0.05, P=0.048; Figure 1).

Conclusion:
LA strain by STE is an independent and incremental predictor of death or need of HTx in patients with moderate to severe HF. This finding suggests that LA strain by STE may serve as a marker in the risk stratification of patients with HF.
Abstract 8556: Inhibition of Grk2 Augments Cardiac Beta2-Adrenergic Receptor-Dependent Contractility via Prevention of Receptor Interaction with Phosphodiesterase Type 4d
Authors: Lymperopoulos Anastasios , Rengo Giuseppe , Gao Erhe , Koch Walter J
Published: April 2024

β
1
- and β
2
-adrenergic receptors (βARs) are G-protein coupled receptors (GPCRs) that play clearly distinct roles in cardiac physiology/pathology. For instance, cardiomyocyte contraction is readily stimulated by β
1
AR but not β
2
AR signaling. This might be explained by differences in assembly of macromolecular signaling complexes: β
1
AR forms a signaling complex with phosphodiesterase (PDE) type 4D8 directly, and agonist binding dissociates this complex. Conversely, GPCR kinase (GRK)2-induced β
2
AR phosphorylation leads to recruitment of a complex consisting of β-arrestin (βarr), a universal GPCR adapter/scaffolding molecule, and another PDE4D variant, PDE4D5. This PDE4D recruitment is postulated to constrain β
2
AR pro-contractile signaling by limiting compartmentalization of 3′-5′-adenosine monophosphate signaling. Thus, herein, we sought to investigate the effect of inhibition of this complex recruitment on β
2
AR pro-contractile signaling in vivo. In order to block β
2
AR-PDE4D interaction in cardiac myocytes in vivo, we crossed β
1
AR knockout (B1KO) mice, which do not express β
1
AR, with M27 mice, which overexpress, specifically in cardiac myocytes, the GRK2 inhibitor GRK2ct (or βARKct). By blocking GRK2-mediated phosphorylation, βarr-dependent PDE4D recruitment to β
2
AR is prevented. We studied the offspring both under normal conditions and after surgically induced myocardial infarction (MI). Contractility was significantly augmented in M27/B1KO mice compared to B1KO's, both in healthy mice (ejection fraction (EF): 69+1.8% vs. 57+1.7% respectively, p<0.05, n=8) and at 4 weeks after MI (EF: 42.6+0.1% vs. 25+3.9% respectively, p<0.05, n=8). In addition, GRK2ct expression attenuated cardiac dilatation of B1KO's at 4 weeks post-MI. At the molecular level, M27/B1KO hearts displayed significantly less membrane recruitment of both PDE4D5 and PDE4D3 compared to B1KO hearts, as evidenced by western blotting in cardiac membrane preparations, indicating less β
2
AR-PDE4D interaction. Thus, cardiac GRK2 inhibition by GRK2ct increases β
2
AR-dependent contractility both normally and in post-MI heart failure. The underlying mechanism appears to involve inhibition of the GRK2/βarr-mediated PDE4D recruitment to the receptor.
Abstract 8557: Arterial Hypotension Under-Estimates Functional Significance of Stenosis by FFR
Authors: Verdier-Watts Florence , Rioufol Gilles , Sanchez Ingrid , Bonnefoy Eric , Caignault Jean-Raymond , Finet Gerard
Published: April 2024

Background
It is widely aknowledged that hemodynamics in the cathlab don't influence FFR. Mathematic modelisations suggest however an inverse relationship between arterial pressure and FFR

Methods
We prospectively studied coronary stenosis with FFR (IC 150 µg adenosin) in patients with mean arterial pressure (Pa) below 85 mmHg. We performed a second measurement after increasing Pa with 0.5 mg neosynephrin IV. The LVEF was normal and the explored-artery free of any history of ACS

Results
From 2007 to 2010, 14 stenosis (mean stenosis 60±21%) in 12 patients (100% male, 59±11 y) with mean Pa=69 mmHg were studied. After neosynephrin injection Pa increases to 100 mmHg without cardiac frequency variation (65 bpm to 62 bpm). Mean FFR decreases from 0.81±0.11 to 0.75±0.12 (p<0.0001). Five lesions with initial 0.8≤FFR<0.9 dropped below the threshold of 0.80.

Conclusions
In the clinical setting we confirm that in borderline physiological conditions, FFR is sensitive to perfusion pressure. In case of arterial hypotension during measurement, a non significant FFR <0.90 should be re-tested after normalisation of the arterial pressure.
Abstract 8620: Real-Time Prediction of Cardiac Arrest in Critically Ill Patients Presenting to the Emergency Department Using a Neural Network Score Incorporating Heart Rate Variability Compared with the Modified Early Warning Score
Authors: Ong Marcus , Ng Christina HL , Goh Jun Yang , Liu Nan , Koh Zhi Xiong , Shahidah Nur , Zhang Tongtong , Fook-Chong Stephanie , Lin Zhiping
Published: April 2024

Aims
A key aim of triage is to identify those with high risk of cardiac arrest as they require intensive monitoring, resuscitation facilities and early intervention. We aim to validate a novel neural network (NN) score incorporating Heart Rate Variability (HRV) for triage of critically ill patients presenting to the emergency department by comparing the area under the curve, sensitivity and specificity with the modified early warning score (MEWS).

Methods
We conducted a prospective observational study of critically ill patients in an emergency department of a tertiary hospital. At presentation, HRV parameters generated from a 5-minute electrocardiogram recording are incorporated with age and vital signs to generate the NN score for each patient. The patients are then followed up for outcomes of cardiac arrest or death.

Results
From June 2006 to June 2008, we enrolled 925 patients. The area under the receiver operating characteristic (ROC) curve for NN scores in predicting cardiac arrest within 72 hours is 0.781 (95% CI: 0.724-0.839) as compared to 0.680 (95% CI: 0.597-0.762) for MEWS. As for in-hospital death, the area under the curve for NN score is 0.741 (95% CI: 0.688-0.795) as compared to 0.693 (95% CI: 0.638-0.748) for MEWS. A cutoff NN score of ≥ 60 predicted cardiac arrest with a sensitivity of 84.1% (95% CI: 66.1-91.1), specificity of 72.3% (95% CI: 69.2-75.2) and NPV of 98.8% (95% CI: 97.5-99.4). A cutoff MEWS of ≥ 3 predicted cardiac arrest with a sensitivity of 74.4% (95% CI: 58.5-86.0), specificity of 54.2% (95% CI: 50.8-57.5) and NPV of 97.8% (95% CI: 95.9-98.8).

Conclusion
We found NN scores to be more accurate than MEWS in predicting cardiac arrest within 72 hours and death. This has potential to develop real-time bedside device for triage based on cardiac arrest prediction.
Abstract 8625: Impact of Red Blood Cell Distribution Width on Mortality in Diabetic Patients After Percutaneous Coronary Intervention
Authors: Tsuboi Shuta , Miyauchi Katsumi , Dohi Tomotaka , Ogita Manabu , Miyazaki Tadashi , Nishino Akihisa , Yokoyama Ken , Kurata Takeshi , Yokoyama Takayuki , Daida Hiroyuki
Published: April 2024

Background:
A high red blood cell distribution width (RDW) has been identified as a novel prognostic marker in patients with heart failure. RDW, a measurement of the variability in size of circulating erythrocytes, is obtained routinely by standard blood cell count and used in the differential diagnosis of anemia. But little is known about correlates of RDW with long-term outcomes in diabetic patients with coronary artery disease (CAD). Therefore, we investigated that RDW would be predictive value of prognosis in diabetic patients with CAD treated with percutaneous coronary intervention (PCI).

Method and Results:
Five hundred ninety-two patients (mean age 66.5±9.0 years, male 80%) with stable CAD who underwent elective PCI were enrolled and followed up for a mean of 4.2 years. Primary endpoint was all cause mortality. Patients were divided into two groups as high or low RDW according to the mean baseline RDW (13.3%). Patients with higher RDW values were significantly older and lower ejection fraction and hemoglobin level. Patients with high RDW (mean 14.0 ± 1.2%) had higher mortality than those with low RDW (mean 12.6 ± 0.3%); (Kaplan Meier, log-rank p=0.01). After adjustment for baseline characteristics using multivariate Cox regression analysis high RDW was an independent predictor of death with a HR of 2.40 (95%CI 1.13-5.31, p=0.02) after adjustment of age, gender, ejection fraction, hemoglobin and serum creatinine.

Conclusion:
High RDW levels strongly associated with increased risk for long term mortality in diabetic patients undergoing coronary intervension.
Abstract 8635: Novel Role of the Osteoclast-Associated Receptor (oscar) In Oxidative Stress-Mediated Atherogenesis
Authors: Goettsch Claudia , Lauckner Stefanie , Sinningen Kathrin , Schoppet Michael , von Bergen Martin , Kalkhof Stefan , Aikawa Elena , Hofbauer Lorenz C
Published: April 2024

Cross talk between the vascular and the immune system plays a crucial role in cardiovascular diseases including atherosclerosis and ectopic calcification. The osteoclast-associated receptor (OSCAR) is a regulator of osteoclast differentiation and dendritic cell maturation, and recently was implicated as a modulator of osteoimmunology. But the role of OSCAR in vascular biology and its impact on atherogenic processes provoked by pro-inflammatory stimuli is unknown. We recently identified OSCAR on the surface of human primary endothelial cells. Endothelial cell survival was significantly enhanced by activation of OSCAR (+22 %, p<0.001). In contrast, apoptosis was inhibited, as measured by DNA fragmentation (−19 %, p<0.01) and by determination of caspase 3/7 activity (−22 %, p<0.05). Furthermore, OSCAR overexpression increased adhesion of monocytic cells to the endothelium up to 2-fold (p<0.05). In an in-depth proteomic study using stable isotope labelling with amino acids in cell culture (SILAC) more than 2,500 proteins (FDR < 1%) were reproducibly quantified by nano-HPLC/nano-ESI-MS in OSCAR expressing endothelial cells. 116 proteins were determined to be significantly regulated due to OSCAR overexpression, which are mainly involved in cell proliferation, anti-apoptosis, and stress response. Stimulation of endothelial cells with oxidized low-density lipoprotein (oxLDL) caused a time-dependent and dose-dependent induction of OSCAR that was LOX-1-dependent and Ca
2+
-dependent. Specific inhibition of the nuclear factor of activated T cells (NFAT) pathway prevented the oxLDL-mediated increase of endothelial OSCAR expression, and oxLDL induced binding of NFATc1 to the OSCAR promoter as assessed by EMSA and OSCAR promoter analysis. Interestingly,
in vivo
modified LDL from patients with diabetes mellitus stimulated OSCAR mRNA expression in human endothelial cells 2.5-fold (p<0.01). Furthermore, ApoE knockout mice fed a high-fat diet showed enhanced aortic OSCAR expression (+220%, p<0.01), accompanied by increased NFATc1 expression. Our data suggest that OSCAR, originally described as immunological mediator and regulator of osteoclast differentiation, may also participate in cell activation and inflammation in atherosclerosis.
Abstract 8656: Age-Related Macular Degeneration and Incident Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis
Authors: Fernandez Antonio B , Wong Tien Y , Klein Ronald , Collins Dorothea , Burke Gregory , Cotch Mary Frances , Klein Barbara , Sadeghi Mehran M , Chen Jersey
Published: April 2024

Background:
Age-related macular degeneration (AMD) has been linked to cardiovascular risk factors, but it is unclear whether or not AMD represents a marker for subsequent coronary heart disease (CHD) and cardiovascular disease (CVD) events, including stroke.

Aim:
To determine whether AMD is a risk indicator for CHD/CVD events independent of other known risk factors in a multi-ethnic cohort.

Methods:
Retinal photographs from participants in the Multi-Ethnic Study of Atherosclerosis (MESA) without known CVD were evaluated for AMD. A Cox proportional hazard regression model was used to examine the association between AMD with subsequent CHD/CVD events, adjusting for clinical CVD risk factors. Additional analyses were conducted evaluating the strength of association between AMD and CHD/CVD stratifying by patient age and race.

Results:
Among 5951 participants with gradable retinal photographs, there were 895 participants with AMD. Over a mean follow-up period of 5.4 years, there was no statistically significant difference in incident CHD or CVD between the AMD and non-AMD groups (5.0% vs. 3.9%, p=0.13 for CHD and 6.6 vs. 5.5%, p=0.19 for CVD, respectively). In Cox regression models adjusting for CVD risk factors, there were no significant relationship between presence of any AMD and CHD/CVD events (HR=0.99, 95% CI 0.74-1.33, p=0.97). No significant association was found between subgroups of early AMD or late AMD and incident CHD/CVD events.

Conclusions:
In persons without a history of cardiovascular disease, AMD was not found to be significantly associated with an increased risk of CHD or CVD events.
Abstract 8661: Dietary Omega-3 Fatty Acids Prevent the Association Between Impaired Fetal Growth and Arterial Wall Thickening in Children: A Randomized Controlled Trial
Authors: Skilton Michael , Ayer Julian G , Harmer Jason A , Webb Karen , Leeder Stephen R , Marks Guy B , Celermajer David S
Published: April 2024

Introduction:
Impaired fetal growth is an independent cardiovascular risk factor, and is associated with early arterial wall thickening in young children. No preventive strategy has been identified.

Hypothesis:
That dietary omega-3 fatty acid supplementation during early childhood will prevent the association between impaired fetal growth and carotid arterial wall thickening in childhood.

Methods:
The CAPS study was a trial in 616 newborns randomized to one of two daily 500mg oil supplements, from the start of bottle feeding or 6-months of age until 5-years of age. The omega-3 group received a fish oil supplement and canola-based margarines / cooking oils; the control group received sunflower oil supplement and omega-6 fatty acid rich margarines / cooking oils. Children born at term were recruited antenatally from hospitals in Sydney, Australia, between September 1997 and December 1999. 363 non-diabetic children with birth weight <90th centile participated in the CardioCAPS substudy at age 8 years (control group: n=176; omega-3 group: n=187). Primary comparison was an analysis of heterogeneity between groups for the association of fetal growth (birth weight adjusted for gender and gestational age) with ultrasound measured carotid artery intima-media thickness (IMT), at age 8 years.

Results:
In the control group, fetal growth was inversely associated with carotid IMT (β-coefficient = -0.027 mm [SE 0.013] per kg birth weight, P=0.04), but this association was prevented in the omega-3 group (β-coefficient = 0.014 mm [SE 0.012] per kg birth weight, P=0.24). This association differed significantly between the two groups (figure).

Conclusion:
The inverse association of fetal growth with early arterial wall thickness may be prevented by dietary omega-3 fatty acid supplementation over the first 5 years of life. Figure. Dietary omega-3 fatty acids mitigate the inverse association of fetal growth with carotid IMT in childhood.
Abstract 8680: Long Term Outcomes in Patients with Borderline Prolonged QRS Durations Following Cardiac Resynchronization Therapy
Authors: Rickard John , Sengupta Jay , Martin David O , Tang WH W , Tchou Patrick J , Chung Mina K , Lindsay Bruce D , Wilkoff Bruce L
Published: April 2024

Background:
The majority of patients enrolled in clinical trials of cardiac resynchronization therapy (CRT) have had significant QRS prolongation with some studies excluding patients with a QRS duration ≤130ms. Current ACC/AHA/HRS guidelines suggest CRT is appropriate for patients with significant LV dysfunction and a QRS duration ≥120ms. Long-term outcomes in patients with only mildly prolonged QRS durations following CRT have not been evaluated.

Methods:
We collected clinical and electrocardiographic data on a cohort of 895 patients who presented for the initiation of CRT at our institution between 10/29/2003 and 8/6/2007. For inclusion in the final cohort, patients had a valid US social security number, NYHA class II-IV heart failure, a QRS duration ≥ 120 ms, and an LVEF≤40%. Patients with mild baseline QRS prolongation (QRS duration 120-130ms) were compared to patients with more significant QRS prolongation (QRS>130ms) in terms of all-cause mortality.

Results:
694 patients met inclusion criteria of which 65 met criteria for a mildly prolonged QRS duration. Over a mean follow up of 4.3±2.0 years, there were 273 deaths, 35 in the mildly prolonged group (53.8%) vs. 238 in patients with significant QRS prolongation (27.8%)(p=0.016). In Cox multivariate regression analysis, patients with mild QRS prolongation had significantly worse long term outcomes compared to those with more significant prolongation(hazard ratio 1.5 (1.02-2.21, p=0.038).

Conclusions:
Patients with left ventricular dysfunction and only mild QRS prolongation undergoing CRT have increased all-cause mortality compared to more traditionally studied patients with significant QRS widening.
Abstract 8682: Microarray and Proteomic Analysis of Cardioprotection in the Mature and Aged Male and Female: Role of the Mitochondrion and Mitochondrial Pathways
Authors: Black Kendra M , Barnett Reanne , Bhasin Manoj K , Daly Christian , Dillon Simon J , Libermann Towia A , Masuzawa Akihiro , Levitsky Sidney , McCully James D
Published: April 2024

Background:
Recently we have shown that cardioprotection afforded by cardioplegia is modulated by RNA and protein dependent mechanisms and is significantly decreased with age and in particular is significantly decreased in the aged female, however, the pathways associated with these differences were unknown.

Methods:
Mature male and female (15 to 20 weeks; n=6 each) and aged male and female (>32 months; n=6 each) New Zealand White rabbits were used for in situ blood perfused cardiopulmonary bypass (CPB). Control hearts received 30 min sham global ischemia (GI) and 120 min sham reperfusion. GI hearts received 30 min GI, achieved by crossclamping of the aorta. Cardioplegia hearts received cold blood cardioplegia prior to GI. Following 30 min GI the crossclamp was released and the hearts were reperfused for 120 min. RNA and proteins were isolated and microarray and proteomic analysis was performed on matched samples.

Results:
Microarray analysis showed that cardioplegia up-regulated genes for transcription and the mitochondrion in mature male and female hearts and cytoskeleton dependent intracellular transport and cell-substrate function in aged male and female hearts. Proteomic analysis identified 362 proteins of which 132 were common to all groups. Principal component analysis indicated differential protein expression in each treatment in the mature male and female and aged male, but in the aged female there was no difference in the proteins expressed during GI and cardioplegia. Cardioplegia up-regulated glycolytic and gluconeogenic pathways in the mature and aged male and oxidative phosphorylation, the electron transport chain, propanoate and pyruvate metabolism and the induction of apoptosis in the mature and aged female. The tricarboxylic acid cycle was uniquely up-regulated by cardioplegia in the aged female but not glycolysis or gluconeogenesis.

Conclusions:
These data demonstrate that the mitochondrion and mitochondrial pathways play a key role in age and gender specific cardioprotection. The identification of these specific pathways will allow for the development of age and gender specific cardioprotection which should significantly decrease morbidity and mortality in the aged female undergoing open heart surgery.
Abstract 8687: C-peptide Levels Predict Cardiovascular And Diabetes Related Mortality In Non-diabetic Adults
Authors: Patel Nileshkumar , Taveira Tracey H , Choudhary Gaurav , Wu Wen Chih
Published: April 2024

Objective:
Insulin resistance (IR), characterized by high endogenous insulin levels with or without clinical diabetes mellitus (DM), is an established pathophysiological precursor to the development of cardiovascular disease (CVD). Since IR can be intervened upon and endogenous insulin production is best measured by c-peptide levels, we sought to evaluate whether c-peptide levels can predict future CVD and DM related mortality before the onset of DM.

Methods:
US adults 40-74 years of age without clinical DM were identified based on a negative history, glucose tolerance test, fasting glucose or glycated hemoglobin levels from the III National Health and Nutrition Examination Survey (1988-1994) and followed through 12/31/2006. Vital status was obtained via linkage with the National Death Index and ICD-10 for causes of death. Participants were stratified by their degree of IR as measured by quartiles of fasting c-peptide levels and weighted analysis conducted to compare their cumulative risk of CVD and/or DM related mortality using lowest c-peptide quartile as the referent. Cox proportional hazard ratios (HR) adjusted for potential confounding. Analyses were repeated in subgroups of low CVD risk.

Results:
We identified 5,124 subjects, representative of 61,594,485 US adults without DM, mean age 54.9 ± 10.5, 48.4% male, 81.8% of Caucasian race. Quartiles of c-peptide levels were significantly associated with both CVD and DM death separately, and combined (table). Subgroup analyses suggested that c-peptide levels further stratified combined CVD/DM death risk in patients with traditionally low CVD/DM risk (ldl <130mg/dl, normal glucose, BMI <25kg/m2, BP<140/90 mmHg).

Conclusion:
C-peptide levels predict CVD and DM related death in non-diabetic adults beyond traditional CVD/DM risk factors and may be a useful biomarker to identify otherwise unrecognized high risk subjects with significant IR for early intervention.
Abstract 87: Brainstem Reflex Score Within 24 Hours of Hospital Admission Predicts Survival Post Cardiac Arrest
Authors: Eid Shaker M , Lakshmanadoss Umashankar , Nazarian Skon M , Llinas Rafael , Vaidya Dhananjay , Stewart Kerry J , Chandra-Strobos Nisha
Published: April 2024

Background:
Post Arrest Prognosis continues to be based on the neurologic exam at >72 hours. We investigated whether a novel, simple clinical tool at 24 hours could predict survival-to-discharge post cardiac arrest.

Methods:
Data was collected on 123 survivors of non-traumatic out-of-hospital cardiac arrest (age 63 ± 15, 62% males) according to Utstein guidelines. Daily neurologic examination was performed and a brainstem reflex score (BRS) was derived from five brainstem reflexes: 1) pupillary reflex, 2) corneal reflex, 3) cough/gag reflex, 4) oculocephalic reflex (doll's eye), and 5) spontaneous breathing. We assumed that each brainstem reflex has an equal impact and assigned one point for each reflex present, giving a range of the BRS from 0 (worst) to 5 (best). BRS ≥3 was tested for association with survival and good neurologic outcome (CPC 1+2). Univariate and multivariate logistic regression analysis were used for assessment of outcome predictors. Data are reported as percentage, mean and standard deviation or odds ratio.

Results:
Of 123 patients, 84 (68.3%) had a witnessed arrest, 43 (34.9%) received bystander CPR, 25 (20.3%) had VF/VT as their initial arrest rhythm and time to return of spontaneous circulation {ROSC} was 35.5 ± 32.3 min (95% CI 29.4 - 41.6). Also, 86 (69.9%) were sedated during the initial 24 hours, 53 (43.1%) received hypothermia and only 31 (25.2%) survived to discharge. Univariate analysis identified and multivariate analysis confirmed, as noted below, that BRS ≥3 at 24 hours is an accurate, early predictor of survival to discharge. Although BRS also emerged as a predictor of good neurologic outcome on univariate analysis (OR=5.17, 95% C.I. 1.88-14.24, p=0.001) this association was not confirmed on multivariate testing (OR=1.90, 95% C.I. 0.16-22.40, p=0.610).

Conclusion:
BRS is a simple clinical tool that can be universally used and appears to be highly predictive of survival to discharge. This observation needs to be tested in larger cohorts.
Abstract 8706: Impact of Small Dense Low-Density Lipoproteins Cholesterol on Cardiovascular Disease in an Urban Japanese Cohort: The Suita Study
Authors: Arai Hidenori , Kokubo Yoshihiro , Watanabe Makoto , Sawamura Tatsuya , Okamura Tomonori , Miyamato Yoshihiro
Published: April 2024

Aim:
Increased plasma low-density lipoprotein cholesterol (LDL-C) concentrations have been shown to be one of the major risk factors for cardiovascular disease (CVD). Clinical evidence also indicates that small dense LDL (sd-LDL) particles are more atherogenic than large buoyant LDL particles. Because there was no easy assay to measure the amount of sd-LDL-C, few studies have addressed the association between sd-LDL-C and CVD. In this study, we hypothesized that higher sd-LDL-C is associated with increased risk for CVD. To this end, we examined the association between sd-LDL-C and CVD in Japanese by using a new kit to measure sd-LDL-C.

Methods:
We studied 2034 Japanese individuals (30 to 79 years old without stroke or coronary heart disease (CHD)) in the Suita Study, who completed measurement of direct LDL-C and sd-LDL-C by a kit based on the precipitation method with filtration, and then followed for 11.7 years on average. We calculated the Cox proportional adjusted hazard ratios (HRs) of LDL-C, sd-LDL-C, and sd-LDL-C/LDL-C ratio quartiles for incident CAD, stroke, and CVD (CHD + stroke) adjusting for age, sex, body mass index, diabetes, blood pressure category (defined on the basis of the ESH-ESC 2007 criteria), smoking and drinking at baseline.

Results:
The mean age of this cohort was 59.3 years old and 52.4% was women. The HR of the 4th quartile of sd-LDL-C for the development of CAD was 3.35 (95% confidence intervals: 1.38 to 8.13), which was higher than that in the analysis using LDL-C quartiles. In multivariable adjustment, the HR of the 4th quartile was almost similar. When we used the quartiles of sd-LDL/LDL ratio, increased sd-LDL/LDL ratio was associated with the incidence of CVD, CAD, and stroke. Sex-specific analysis showed that the association of sd-LDL-C with CAD and CVD was statistically significant in men, but not in women.

Conclusions:
We demonstrated that increased levels of sd-LDL-C are significantly associated with the development of CVD. Our data indicate that sd-LDL-C is a better risk factor for CVD than LDL-C for risk assessment.
Abstract 8718: Increase in the Incidence of Bacterial Endocarditis Concurrent with Changes in Guidelines
Authors: Cosgrove Nora M , Gandhi Sampada K , Cheng Jerry Q , Cabrera Javier , Pantazopoulos John S , Deng Yingzi , Moreyra Abel E , Kostis John B ,   For the Myocardial Infarction Data Acquisition System (MIDAS) Study Group
Published: April 2024

Introduction:
Changes in guidelines for the prevention of bacterial endocarditis (SBE) have recommended progressively less intensive antibiotic prophylaxis. However, the effect of the changes on the incidence of SBE has not been studied.

Methods:
Using the Myocardial Data Acquisition System (MIDAS), a statewide database including all admissions with cardiovascular disease in all non-federal hospitals in NJ, we identified 24,161 SBE admissions (ICD codes 421.0, 421.1, 421.9, 424.9) from 1994 to 2007. Age and gender adjusted incidence was computed using the 2000 Census.

Results:
SBE incidence showed an increase beginning in 2001. However, when SBE incidence as a reason for admission was examined (SBE as primary diagnosis, n=7,618), there was no appreciable change during the 14 year study period. On the contrary, by fitting a piecewise linear model, admissions with SBE as a secondary diagnosis in patients admitted for another condition (n=18,476) exhibited a significant increase between 2005 and 2007 (slope 115±10, p=0.0016) but no significant change between 2001 and 2005 (slope 11±5, p=0.0701) or after 2007 (slope 9±22, p=0.7660). The reason for admission of patients admitted for SBE as a secondary diagnosis included diseases of the circulatory system (31.5%), complications of surgery or fracture (11.6%), infections and parasitic diseases (15%) and diseases of the respiratory and digestive system (16.2%), other (25.7%). Sensitivity analysis indicated similar increases in the incidence of SBE as a secondary diagnosis regardless of the primary reason for admission.

Conclusions:
There has been an increase in age and gender adjusted SBE incidence in NJ under the study period beginning in 2002. This is due only to an increase of SBE as a secondary diagnosis, while SBE as a reason for admission remained stable. Whether this is causally related to the changes in the guidelines needs further investigation.