bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 8995: The Munich Triathlon Heart Study: Ventricular Function, Myocardial Velocities and 2-d Strain In Healthy Children Before and After Endurance Stress
Authors: Hauser Michael , Kuehn Andreas , Petzuch Curt , Schoen Patrick , Elmenhorst Julia , Schoenfelder Martin , Oberhoffer Renate , Vogt Manfred O
Published: April 2024

Objectives:
Intense exercise has been shown to have negative effects on systolic- and diastolic ventricular function in adults. Very little is known about the normal reaction of the growing heart to endurance stress.
Design:
Longitudinal follow-up study pre- and post age adopted triathlon
Setting:
Tertiary paediatric cardiac centre
Patients:
26 healthy children (18 males, 7.9-16.4 years, mean 12.6 years) took part in an age adapted triathlon circuit.

Methods:
The athletes were investigated by 2-D-echo/speckle tracking, M-mode, PW-Doppler, colour-Doppler and colour codes tissue Doppler two to four weeks before and immediately after the race.

Results:
After the competition there was an increase in cardiac output, mediated by an increase in heart rate and not by an elevated preload, according the mechanism of Frank-Starling. 2-D speckle tracking shows a reduced longitudinal strain in the right ventricle and additionally reduced circumferential strain in the left ventricle with attenuation of the systolic function. The late diastolic inflow velocities are increased in both ventricles, indicating reduced diastolic function due to an impairment of myocardial relaxation.

Conclusion:
Systolic- and diastolic function were attenuated in children and adolescents after participating in an age adopted triathlon which took place in Munich 2009. The sequelae of these alterations are unclear and especially the growing heart might be more susceptible to myocardial damage caused by intense endurance stress.
Abstract 9046: Childhood Underweight Affects Left Ventricular Geometry and Function
Authors: Harada Kenji , Harada Yukiko
Published: April 2024

Background:
Obesity is associated with structural and functional changes in the heart. Childhood underweight is also associated with an increased risk of later cardiovascular disease. In contrast to overweight/obesity, much less is known about underweight-related changes in left ventricular (LV) geometry and function. Myocardial performance index (MPI) combines both systolic and diastolic phases of cardiac cycle and has been shown to be useful for assessing global LV function. The purpose of the study is to assess the relationships between BMI z-score and LV geometry and MPI in children.

Methods:
Echocardiography with tissue Doppler imaging was performed in 643 children aged 7 to 15 years (BMI z-score -2.4 to +6.8). Subjects were divided into 9 groups according to BMI z-score. Cardiac dimensions, LV end-diastolic volume, LV mass, ejection fraction, isovolumic relaxation time (IRT), and tissue Doppler-derived MPI were measured.

Results:
There were significant relationships between BMI z-score and LV mass, LVEDV, and mass to volume ratio (r = 0.37, 0.23, and 0.39, p < 0.01, respectively). LVEF did not correlate with BMI z-score. A U-shaped association was observed between BMI z-score and MPI, and MPI at both BMI z-score <-2.0 and BMI z-score ≥ +3.0 were significantly greater compared with normal weight children as shown in Figure. There was a J-shaped association between BMI z-score and IRT with a significant increase at higher BMI (z-score ≥ +2.0).

Conclusions:
The present study suggests that lower BMI is associated with LV hypotrophy and increased MPI. Childhood underweight as well as overweight has a negative effect on cardiovascular function. Our findings suggest that primary prevention programs should be initiated in not only overweight but also underweight children.
Abstract 9103: Rivaroxaban Use is Associated with Reduced Risk of Myocardial Infarction-Insights from a Meta-analysis and Trial Sequential Analysis of Randomized Clinical Trials
Authors: Chatterjee Saurav , Sharma Abhishek , Uchino Ken , Biondi-Zoccai Giuseppe , Lichstein Edgar , Mukherjee Debabrata
Published: April 2024

Introduction:
There has been recent evidence to suggest an increased risk of myocardial infarction (MI) with the use of the direct thrombin inhibitor, dabigatran etexilate-approved in the US for prevention of stroke in non-valvular atrial fibrillation. Hypothesis: We systematically evaluated the risk of MI associated with use of the other drug, recently approved for the same indication-rivaroxaban, an oral factor Xa inhibitor.

Methods:
We searched PubMed, CINAHL, Cochrane CENTRAL, Scopus, and the Web of Science. Randomized controlled trials of rivaroxaban that reported on myocardial infarction as clinical outcomes. The fixed-effects Mantel-Haenszel (M-H) test was used to evaluate the effect of rivaroxaban on MI, in the absence of heterogeneity. Trial sequential analysis (TSA) was performed to ensure validity of our findings.

Results:
Seven trials were selected (N=45,566), including 1 study of stroke prophylaxis in atrial fibrillation, 2 in acute coronary syndrome, and 4 of short-term prophylaxis of deep venous thrombosis. Control arms included warfarin, enoxaparin, or placebo administration. Rivaroxaban was associated with a significantly lower risk of MI than that seen with agents used in the control group; OR, 0.82; 95% CI, 0.72-0.93; P=0.002). No heterogeneity was noted in the risk (I2=0%; P=0.82), TSA reinforced validity of our findings.

Conclusions:
Rivaroxaban is associated with a significantly lower risk of MI in a broad spectrum of patients when tested against different controls. We recommend the use of rivaroxaban over dabigatran for nonvalvular AF particularly in patients at high risk of acute coronary events.
Abstract 9131: Clinical, Biochemical and Genetic Predictors of Late Coronary Artery Bypass Graft Failure
Authors: Yanagawa Bobby , Algarni Khaled D , Singh Steve , Deb Saswata , Vincent Jessica , Feder-Elituv Randi , Desai Nimesh D , Rajamani Karthik , McManus Bruce M , Liu Peter P , Cohen Eric , Radhakrishnan Sam , Dubbin James , Schwartz Leonard , Fremes Stephen E
Published: April 2024

BACKGROUND:
We tested the

hypothesis

that
known clinical and biochemical risk factors for atherosclerosis have prognostic promise as novel biochemical markers to predict coronary artery bypass graft (CABG) failure
. We also utilized a high-throughput microarray analysis to identify novel single nucleotide polymorphisms (SNPs) genetic predictors of graft failure and to better understand the pathogenesis of graft occlusion.

METHODS AND RESULTS:
This is a nested case-control sub-study of the Radial Artery Patency Study (RAPS) 5 year follow-up (
NCT00187356
). Between June 1996 and January 2001, 87 patients underwent CABG. Of these, 26 patients (29.9%) had an occluded study graft (saphenous vein graft or radial artery) at angiographic follow-up (8.0±1.1 years). Clinical parameters as well as late angiography and concurrent blood biomarker analysis and surgical outcomes data were included in a multivariable analysis to determine independent predictors of graft failure. Risk factors of long term graft failure were fibrinogen (OR 3.94; 95%CI [1.33-11.63], p=0.01), creatinine (OR 1.06; 95%CI [1.02-1.10], p=0.006) and diabetes mellitus (OR 5.15; 95%CI [1.08-24.59], p=0.04). Interestingly, HDL (OR 0.74, 95%CI [0.53-1.02], p=0.06) was weakly protective against long term graft failure but other lipid markers, LDL and total cholesterol were not predictors. We identified the association of several human single nucleotide polymorphisms with graft failure including a novel link with mutations in
glutathione-s-tranferase α3
. Human coronary arteries and bypass grafts demonstrated increased GSTα3 expression in atherosclerotic plaques and in tissues surrounding occluded saphenous vein grafts.

CONCLUSION:
We identify diabetes to be a clinical predictor and plasma fibrinogen, creatinine and HDL as potential novel biomarkers which, together may help to risk stratify patients for development of graft failure. We further demonstrate a novel association between GSTα3 and graft failure, a potential pathogenetic mechanism of saphenous vein graft occlusion.
Abstract 9157: Rightward Shift Of V-slope In Cardiopulmonary Exercise Testing (CPX) As A Marker Of Increased Exercise Tolerance
Authors: Nishijima Hirotaka , Kondou Kazuo , Yonezawa Kazuya
Published: April 2024

INTRODUCTION:
A new method to detect change in exercise tolerance is presented. It is based on our observation that rightward shift of the v-slope relative to the R=1 line, due to exercise-induced increased tissue CO2 store, correlated with increased anaerobic threshold (AT) and VO2 max.

METHODS:
The records of 166 patients who underwent CPX during cardiac rehabilitation (CR, 3-6 months) were retrospectively reviewed. The mean age was 64(SD:11) with 143 males and 23 females. The underlying heart disease was ischemic. CPX using upright bicycle was submaximal, mostly terminated with the appearance of AT. CR was hospital (mean 3.1 visits/month) and home based. The mean time between the 1st and 2nd tests was 135(29) days. AT was determined blind by an experienced evaluator. Pre and post CR v-slope data sets were plotted together. Exercise data points in the pre-post shared range were selected. Each v-slope was regressed for the quadratic equation. At the y-axis mid-point (line A-B) the distance between R=1 and each regression line was read off (Rightward Shift: RS, ml/min VO2).

RESULTS:
The changes in basic exercise variables were as follows: highest HR (b/min), from 111(22) to 117(18) (ns); highest VO2 (ml/min/kg), 14.6(3.5) to 17.0(4.1) (p<0.001), and body weight (kg), 66.1(10.9) to 66.7 (10.9)(p<0.006). AT (ml/min VO2) increased from 670(217) to 721(251) (p<0.0004). RS increased from 35(61) to 49(60) (p<0.0003). Also, the baseline RS significantly correlated with AT (r=0.68, p<0.001).

CONCLUSION:
A completely new method to detect changes in exercise tolerance is described. It calculates a shift in 2 v-slopes. At baseline the degree of rightward shift was associated with an increase in AT. After cardiac rehabilitation v-slope shifted further rightwards as AT increased. The shift method was as sensitive as AT to detect changes in exercise tolerance. There is no need for maximal exercise or an evaluator to read a v-slope. The procedure can be automated.
Abstract 9164: Low Doses of Ranolazine and Dronedarone in Combination Exert Potent Protection against Atrial Fibrillation and Vulnerability to Ventricular Arrhythmias during Acute Myocardial Ischemia
Authors: Verrier Richard L , Pagotto Vitor P , Kanas Alexandre F , Sobrado Marcel F , Nearing Bruce D , Zeng Dewan , Belardinelli Luiz
Published: April 2024

Background:
Coronary artery disease carries dual risk for atrial fibrillation (AF) and sudden cardiac death. We examined whether low-dose ranolazine and/or dronedarone can protect against AF and vulnerability to ventricular tachyarrhythmias.

Methods, Results:
In chloralose-anesthetized, open-chest Yorkshire pigs (N=19), proximal segment of left circumflex (LCx) coronary artery was occluded to reduce flow by 75%. Electrode catheter was positioned on left atrial appendage to measure AF threshold (AFT) before and during LCx coronary artery stenosis prior to and at one hour after dronedarone (0.5 mg/kg i.v. bolus over 5 min) and/or ranolazine (0.6 mg/kg, i.v. bolus, followed by 0.035 mg/kg/min). Without drugs, LCx coronary artery stenosis lowered AFT from 25.2±1.7 control (mean±SEM) to 4.9±1.0 mA baseline (p<0.01). At these low doses, neither ranolazine (plasma concentration: 2.4±0.6 μ M) nor dronedarone (plasma concentration: 20.9±3.5 nM) alone blunted ischemia-induced reduction in AFT, but combination was effective (from 25.2±1.7 control to 22.0±3.0 mA, NS). Combined but not separate administration blunted ischemia-induced surge in T-wave heterogeneity (TWH), a marker of risk for ventricular tachyarrhythmias. Without drug, TWH increased from 43.1±11.1 control to 149.7±15.1 μ V baseline during stenosis (p<0.001); with both agents, TWH increased only from 61.7±13.7 control to 83.7±15.8 μ V during stenosis (NS) (Fig.).

Conclusions:
Combined administration of low doses of ranolazine and dronedarone exerts a potent, antiarrhythmic action consistent with synergy due to direct effects on myocardial electrical properties not on coronary flow, which was controlled.
Abstract 9206: Myocardial Mechanics in Asymptomatic Versus Symptomatic Patients with Severe Aortic Stenosis
Authors: Carasso Shemy , Mutlak Diab , Lessick Jonathan , Aronson Doron , agmon Yoram
Published: April 2024

Background:
Symptomatic patients (pts) with severe aortic stenosis (AS) demonstrate abnormal left ventricular (LV) mechanics. We compared LV mechanics in asymptomatic and symptomatic pts with severe AS using 2-D myocardial strain imaging.

Methods:
The study group included 62 pts with severe AS (aortic valve area [AVA] ≤1.0cm2), normal LV ejection fraction (LVEF>50%), and without segmental wall motion abnormalities. LV longitudinal and circumferential strain and rotation were measured in 30 asymptomatic pts and compared to 32 age and gender-matched pts with AS-related symptoms and to 25 normal subjects without AS.

Results:
Patients with asymptomatic severe AS demonstrated less decreased longitudinal strain, higher (supernormal) apical circumferential strain, and extreme (supernormal) apical rotation, compared to symptomatic patients.

Conclusions:
Compensatory mechanisms of myocardial mechanics in asymptomatic pts with severe AS (increased apical circumferential strain and rotation) are lost with the appearance of symptoms. Thus, myocardial mechanics may help in the follow up of pts with severe AS and timing of valve surgery.
Abstract 9207: Zofenopril and Ramipril Plus ASA in Post-myocardial Infarction Patients With Left Ventricular Systolic Dysfunction: A Post-hoc Analysis in Preserved or Impaired Left Ventricular Fraction at Entry
Authors: Borghi Claudio , Ambrosioni Ettore
Published: April 2024

Introduction:
in the randomized, double-blind, parallel-group, multicenter, international SMILE-4 Study zofenopril 60 mg plus acetyl salicylic acid (ASA) was more effective than ramipril 10 mg plus ASA 100 mg in reducing 1-year occurrence of major cardiovascular (CV) events in patients with acute myocardial infarction (AMI) complicated by left ventricular dysfunction (LVD).

Objective:
to compare zofenopril and ramipril efficacy in combination with ASA in a subgroup of patients of the SMILE-4 with preserved (>40%) or impaired (≤40%) left ventricular ejection fraction at the time of enrolment in the study.

Methods:
the SMILE-4 was a phase IIIb, randomized, double-blind, parallel-group, multicenter, European study comparing the safety and efficacy of zofenopril 60 mg/day and ramipril 10 mg/day plus ASA 100 mg/day, in patients with LVD (clinical signs of heart failure or a left ventricular ejection fraction or LVEF <45%) following AMI. We analyzed the 1-year combined occurrence of death or hospitalization for CV causes. Information on LVEF at baseline was available in 710 out of the 716 patients of the intention-to-treat population.

Results:
in the main study population the primary outcome was significantly reduced by zofenopril vs. ramipril (odds ratio, OR and 95% confidence interval, CI: 0.70, 0.51-0.96; p=0.028). Overall, 448 (63.1%) patients had preserved and 262 (36.9%) impaired LVEF at baseline. In the first group, the rate of major CV events was significantly lower under zofenopril than under ramipril (22.5% vs. 32.8%; OR: 0.60, 0.39-0.91; p=0.016). This was the case also for the group of patients with impaired LVEF, though between-group difference was not statistically significant (37.7% zofenopril vs. 44.4% ramipril; OR: 0.77, 0.47-1.26; p=0.297). The reduction in the risk of major CV events was significantly larger (p=0.019) in patients with preserved LVEF at baseline.

Conclusions:
this retrospective analysis of the SMILE-4 Study confirmed the superiority of zofenopril plus ASA as compared to ramipril plus ASA in the prevention of long-term CV outcomes. The benefit was particularly evident in subjects with preserved left ventricular function at study entry.
Abstract 9286: Patterns of Red Blood Cell Transfusion Use in Patients Undergoing Percutaneous Coronary Intervention in Contemporary Clinical Practice
Authors: Sherwood Matthew W , Wang Yongfei , Curtis Jeptha P , Peterson Eric D , Rao Sunil V
Published: April 2024

Background Previous studies have shown marked variation in the use of red blood cell transfusion (RBCT) among patients with acute coronary syndromes. Contemporary post-procedure RBCT patterns in patients undergoing PCI are unclear.

Methods Using the NCDR Cath-PCI database we evaluated frequency of RBCT in 1323965 patients undergoing PCI at 1282 hospitals between 7/2009-9/2011 excluding those who underwent in-hospital CABG. Site-level variation in RBCT use was examined; differences in patient baseline characteristics and in-hospital outcomes were compared between patients who did and did not receive RBCT. Logistic regression was used to determine the adjusted association between RBCT and in-hospital death, MI, or stroke.

Results Of the total sample, 29255(2.2%) patients received RBCT. These patients were older, more often female, and more often had HTN, prior CHF, prior MI, cerebrovascular disease, peripheral arterial disease, diabetes, or be on dialysis. Patients receiving RBCT had lower median pre-procedure Hgb (10.7 g/dl vs 13.7 g/dl, P<0.01) and post-procedure Hgb (8.6 g/dl vs 12.7 g/dl, P<0.01) and more often experienced a post-PCI bleeding event (36% vs 1%, P<0.01). RBCT was more frequent in patients with post-procedure Hgb <10 g/dl, irrespective of PCI indication. With respect to site-level variation, 17% of hospitals gave no RBCT, 76% of hospitals used RBCT in 1-4% of patients, while just 7% of hospitals used RBCT in ≥5% of patients (Figure). After adjustment, the use of RBCT was significantly associated with in-hospital death, MI, or stroke (OR 2.18; 95% CI 2.09-2.26). Similar results were seen after excluding patients who bled.

Conclusions In contemporary PCI practice, there is marked site-level variability in the use of RBCT. After adjustment for potential confounders, RBCT is associated with a higher risk for in-hospital adverse events. These data underscore the importance of understanding the appropriate role of RBCT in patients undergoing PCI.
Abstract 9312: Predictors of Survival in Primary Cardiac Amyloidosis
Authors: Bitar Abbas , Suradi Hussam , Das Mithilesh , Benson Merrill
Published: April 2024

Background:
Cardiac involvement in primary amyloidosis (AL) is associated with poor prognosis. We studied the prognostic significance of clinical, ECG and echocardiographic parameters of patients with primary cardiac amyloidosis.

Methods:
60 patients with primary amyloidosis and cardiac involvement documented by endomyocardial tissue biopsy were studied.

Results:
60 patients (mean age 57.94±10.22 years; 71.67% male and 86.67% Caucasian) were studied. The median survival was 12.23 (median) ±4.43 months, 50% of patients survived for more than 1 year. Congestive heart failure (NYHA II-IV) was present in 60% of patients. Low voltage, Q wave, conduction abnormalities, first degree AV block and abnormal QRS axis were present in 54.24%, 51.72%, 71.67%, 21.67% and 57.72% respectively. Echocardiogram revealed LVH, mitral regurgitation, left atrial enlargement, speckled appearance and pericardial effusion in 82.76%, 62%, 63.16%, 8.77% and 42.11% respectively. LVEF, RVSP, IVS and LVPW were 0.479±.129, 40.88±10.31 mmHg, 1.46±0.34 cm and 1.43±0.33cm respectively. CHF (NYHA II-IV), IVS, LVPW and LVEF were significant on univariate survival analysis (p<0.05). Multivariate predictors of survival were CHF (NYHA II-IV) ( p=0.027, HR 3.04 [95% CI: 1.1-8.1]) and IVS< 1.5cm (p=0.012, HR:3.51 [95% CI: 1.3-9.3]). Median survival of patients with CHF (NYHA II-IV) was 7.58±1.74 months contrary to those without CHF who had a median survival of 31.2±11.41 months.

Conclusion:
In patients with primary amyloidosis and cardiac involvement, lenght of survival is strongly associated with CHF (NYHA II-IV) and IVS thickness compared to other electrographic and echocardiographic parameters.
Abstract 9345: CaMKII Integrates Oxidative Stress and Calcium Signaling in Atrial Fibrillation
Authors: Purohit Anil , Dominic Swaminathan Paari , Rokita Adam , Chen Biyi , Voigt Niels , Koval Olha M , Luczak Elizabeth D , Gao Zhan , Guan Xiaoqun , Li Na , El-Accaoui Ramzi N , Yang Baoli , Weiss Robert M , Wehrens Xander H , Song Long-Sheng , Dobrev Dobromir , Anderson Mark E
Published: April 2024

Introduction:
Emerging evidence suggests that abnormal calcium (Ca
2+
) signaling and oxidative stress play an important role in Atrial Fibrillation (AF). We hypothesized that oxidative activation of CaMKII leads to increased sarcoplasmic reticulum (SR) Ca
2+
release and delayed afterdepolarizations (DAD) to cause AF.

Methods:
We established a mouse model of AF by implanting subcutaneous angiotensin II (Ang II) eluting osmotic pumps for three weeks followed by in vivo right atrial burst pacing. We measured oxidized CaMKII (ox-CaMKII) in atria from Ang II infused mice and from patients in AF or sinus rhythm. We developed ox-CaMKII resistant knock-in mice by replacing key methionines (281/282) with valines (MM-VV) in the predominant myocardial isoform (CaMKIIδ) and mice with transgenic myocardial expression of methionine sulfoxide reductase A (MsrA), an enzyme that reduces ox-CaMKII, to test if ox-CaMKII was required for AF promoted by Ang II.

Results:
ox-CaMKII is elevated in atrial tissue from patients with AF and from mice infused with Ang II compared to patients in sinus rhythm or mice infused with saline. Mice treated with Ang II are highly susceptible to AF, while AF was rarely induced in saline infused mice. MM-VV mice and MsrA transgenic mice were resistant to AF and did not show increased ox-CaMKII after Ang II infusion. Atrial myocytes from Ang II treated wild type mice showed significantly increased DADs and SR Ca
2+
sparks compared to saline treated controls. Ang II treatment did not increase calcium sparks in MM-VV mice.

Conclusions:
Oxidative activation of CaMKII is an important molecular pathway for AF and strategies that decrease the level of ox-CaMKII can prevent AF.
Abstract 94: Is the Impedance Cardiogram a Potential Indicator of Effective External Cardiac Massage in a Human Model? A Study to Establish If There Is a Linear Correlation Between the Impedance Cardiogram and Depth in a Cardiac Arrest Setting
Authors: Di Maio Rebecca , Howe Andrew , McCanny Paul , Navarro Cesar , Crispino-O’Connell Gloria , McIntyre Allister , Patton Mike , McEneaney David , Adgey Jennifer
Published: April 2024

Purpose of the Study: The 2010 AHA guidelines currently recommend a depth of at least 2 inches (5cm) during external cardiac massage. The purpose of this study was to assess the hypothesis that if using an alternative measure to depth could assist in quantifying the effectiveness of CPR in an out-of-hospital setting and to determine how achievable depths of at least 2 inches are in cardiac arrest patients.

Materials and Methods: A total of 32 cardiac arrest patients were recruited by EMS operators in Belfast and cardiologists in Craigavon Area Hospital (CAH). Patient baseline characteristics are summarised below in the results section. A subset of the patients enrolled had simultaneous recordings of Impedance Cardiogram (ICG) and depth (mm) during CPR. The Impedance Cardiogram (ICG)/Thoracic Impedance (non-invasive measure of cardiac output) was recorded via 2 standard defibrillation electrodes, as a method of detecting the presence of effective CPR. Ethical approval was granted by Ethical Committee Northern Ireland and the study was conducted in accordance with ISO 14155:2011; GCP standards. Depth and rate of CPR were continuously measured using Q-CPR
®
, Philips. CPR was administered manually by trained ALS operators. Recordings from each experiment were acquired using Philips Q-CPR review software and HeartSine download software for statistical analysis using R
®
.

Results: Patients were aged between 32 and 93 years (mean 77 years), 64% of this cohort was male. Excluding cases CPR traces with excessive motion artefact, a total of 1883 compressions were administered in patients with a mean weight of 73.85kg. The mean compression depth achieved was 1.79 inches. A strong linear correlation was achieved between depth (mm) using Q-CPR
®
and the Impedance cardiogram (ICG)/ thoracic impedance (ohms); r=0749.

Conclusions: It can be concluded that a depth of 2 inches is difficult to achieve both in-hospital and by EMS operators even with the support of real-time CPR feedback. An algorithm will incorporate the results from this study, providing feedback to the operator on the quality of CPR by measuring the ICG amplitude which has been strongly correlated with standard measures of depth as well as a number of physiological parameters.
Abstract 9410: Quantification and Characterization of Noncalcified Coronary Plaque by High Definition Computed Tomography : Comparison with Integrated Backscatter Intravascular Ultrasound
Authors: Takuma Tsuda
Published: April 2024

Background:
Noninvasive assessment of coronary plaque is important for coronary risk stratification. The utility of 64-slice CT remains unclear for evaluation of coronary plaque component. Recently high definition computed tomography (HDCT) with new gemstone detector has been developed, which has high spatial resolution. We evaluated the accuracy of HDCT for quantification and characterization of noncalcified coronary plaque compared with integrated backscatter intravascular ultrasound (IB-IVUS).

Methods:
We enrolled consecutive 33 patients with unstable or stable angina. Noncalcified plaque of target lesion was evaluated by HDCT and the findings were compared with those of IB-IVUS at the same sites. Plaque was classified as lipid (-42 to 60 HU: Hounsfield unit), fibrous (61 to 112 HU) or calcified (>500 HU) by HDCT and we evaluated minimum lumen area (MLA), percentage of stenosis (%stenosis), total plaque volume, lipid volume, percentage of lipid volume (%lipid), fibrous volume and percentage of fibrous volume (%fibrous).

Results:
A total 38 noncalcified coronary plaques were evaluated. HDCT was well correlated with IB-IVUS for assessing MLA (2.53 ± 0.89mm vs. 2.62 ± 0.71mm, r=0.658, P<0.001), %stenosis (65.6 ± 12.4% vs. 63.5 ± 12.9%, r=0.870, P<0.001), plaque volume (156.2 ± 87.8mm
3
vs. 144.0 ± 100.6mm
3
, r=0.886, P<0.001), lipid volume (86.1 ± 52.7mm
3
vs. 76.5 ± 65.0mm
3
, r=0.901, P<0.001), %lipid (53.7 ± 10.6% vs. 49.8 ± 12.2%, r=0.570, P<0.001), fibrous volume (56.2 ± 25.6mm
3
vs. 57.5 ± 35.8mm
3
, r=0.761, P<0.001) and %fibrous (38.7 ± 11.0% vs. 42.4 ± 10.0%, r=0.747, P<0.001).

Conclusion:
HDCT with new gemstone detector can accurately quantify and characterize noncalcified coronary plaque compared with IB-IVUS. HDCT can be a useful tool for noninvasive assessment of vulnerable plaque.
Abstract 9455: Change of Heart Rate Variability and Correlation With Cardiac Function During Development Process of Chronic Heart Failure in Large Animal Model
Authors: Kishimoto Yuichiro , Ohnuma Kentaro , Arakawa Mamoru , Umeki Akihide , Takewa Yoshiaki , Nishimura Motonobu , Tatsumi Eisuke
Published: April 2024

Introduction; Heart rate variability (HRV) is conceived to have a close relationship with prognosis of heart failure (HF). However, there is few study on HRV during diagnostic and treating process of HF in clinical settings. By investigating this process, HRV may become a more useful approach for non-invasive estimation of cardiac function. In this study, we examined the change of HRV and its correlation with cardiac function throughout the entire course of progressing HF in newly developed large animal chronic heart failure (CHF) models created by combination of micro-embolization and rapid pacing. Methods; CHF was introduced in 12 adult goats (60.9±4.1 kg) by coronary microsphere embolization (50μm, 0.201±0.014 million) to the left anterior descending artery and subsequent rapid ventricular pacing (HR[[Unable to Display Character: ≒]]200) for 5 weeks. Electrocardiogram was recorded continuously for 24 hours under pacing off per week. HRV was analyzed by Memcalc/CHIRAM (Suwa Trust, GMS Inc.), which calculated time-domain index (SDNN etc.) and frequency domain index (LF, HF etc.), evaluated correlation with left ventricle ejection fraction (EF) and cardiac output (CO). Results; Ten goats survived and developed CHF successfully, showing decreased EF (from 90.4±4.1% to 48.3±5.6%) and CO (from 5.6±0.5L/min to 4.0±0.6 L/min). All indexes of HRV were decreased along with progress of HF (SDNN decreased from 166.1±39.1msec to 51.9±33.3msec). LF/HF which is the index of sympathetic nerve activity increased from 1.4±0.9 to 10.7±8.3. A strong correlation was observed between SDNN and cardiac function (Fig). Two cases of sudden death in course showed significant decrease of HRV as compared with the surviving cases. Conclusions; HRV was decreased along with progress of HF, strongly indicating aggravation of sympathetic nerve activity. These findings suggest that HRV analysis has a potential to become a useful and reliable approach for non-invasive estimation of cardiac function and severity of HF.
Abstract 9472: Pretreatment with Novel Angiotensin type I Receptor Antagonist, Fimasartan, Prevents Doxorubicin-Induced Cardiac Toxicity and Improves Survival
Authors: Chang Sung-A , Lim Byung Kwan , Lee Yoo-Jung , Hong Mi-Kyung , Ju Eun Sun , Choi Jin-Oh , Jeon Eun-Seok
Published: April 2024

Background:
Cardiac toxicity are important complications of Doxorubicin-based chemotherapy. Protective effect of angiotensin receptor blockers (ARBs) in heart failure been established; however efficacy of ARB on prevention of doxorubicin induced cardiomyopathy and the survivals were not been investigated. We performed a preclinical study to evaluate the preventive effect of a novel ARB, fimasartan, in doxorubicin-induced cardiomyopathy.

Method:
All animals (n=63) were randomly assigned into 3 groups; daily treated with vehicle (Dox-only), 5mg/Kg (Low-fima), and 10mg/Kg of fimasartan (High-fima). Doxorubicin (3mg/kg) was injected intravenously once a week for 6 weeks. Fimasartan were administered daily for 8 weeks via gastric gavage. Echocardiography was performed in baseline, 6th and 8th week. Hemodynamic assessment was performed at 9th week using the miniaturized conductance catheter system.

Result:
8-wk survival rate in High-Fima was higher (100%), than those in Low-fima (75%), and in Dox-only group (50%, p<0.05). Echocardiography showed preserved LV systolic function in in High-Fima after 8weeks of treatment (LV EF=72±7%), but not in Dox-only group (54.6±8.4%, p=0.002). LV end-systolic and end-diastolic dimension increased progressively in Dox-only group; however remodeling was attenuated in Low-fima and High-fima group. Hemodynamic study showed higher positive (5931±1354 mmHg/sec) and negative dP/dt (-5410.3±1338.2) in High-fima group, than Dox-only group. (3425±947, -3123±1127 mmHg/sec, p<0.001). Animals in Dox-only group looked very sick and showed severe anorexia, rat shedding, eye discharge and ascites compared to Low- and High-fima group.

Conclusion:
A novel ARB, fimasartan, prevents doxorubicin-induced cardiomyopathy and improves survivals in dose-dependent manner in doxorubin-induced cardiomyopathy. It shows possibility of fimasartan as a treatment option to prevent doxorubicin-induced cardiomyopathy.
Abstract 9477: Retinoblastoma Protein-associated Protein 48 and 46 Form Repressor Complex With p300/GATA4 And Inhibit Hypertrophic Responses in Cardiomyocytes
Authors: Sunagawa Yoichi , Katanasaka Yasufumi , Watanabe Yuichi , Suzuki Hidetoshi , Hajika Naruto , Wada Hiromichi , Shimatsu Akira , Fujita Masatoshi , Hasegawa Koji , Morimoto Tatsuya
Published: April 2024

Introduction:
A zinc finger protein GATA4 associates with an intrinsic histone acetyltransferase p300 and regulates myocardial transcriptional activities in response to hypertrophic stimuli. Retinoblastoma protein (Rb)-associated protein 48 and 46 (RbAp48, RbAp46) form a repressor complex with HDACs and are implicated in chromatin remodeling and transcriptional repression. We showed that RbAp48 and 46 are novel component of the p300/GATA4 complex. However, precise functional relationships among p300, GATA4 and RbAp48/46 and their roles in hypertrophic responses remain unknown. Hypothesis: We have assessed the hypothesis that RbAp48/46 regulate hypertrophic responses in cardiomyocytes by modulating functions of the p300/GATA4 complex.

Methods and Results:
Immunoprecipitation followed by Western blotting in HEK293T cells demonstrated that overexpression of RbAp48/46 inhibited p300-induced GATA4 acetylation and the association between p300 and GATA4. Conversely, knockdown of RbAp48/46 by siRNA reversed these changes. RbAp48/46 inhibited not only p300-induced DNA binding activity of GATA4 onto the atrial natriuretic factor (ANF) and endotheline-1 (ET-1) promoters, but also p300/GATA4-induced ANF and ET-1 promoters activities. In cardiomyocytes, overexpression of RbAp48/46 significantly inhibited phenylephrine (PE)-induced GATA4 acetylation, activation of ANF and ET-1 promoters, and myocardial cell hypertrophy. On the other hand, knockdown of both RbAp48 and 46 by shRNA reversed these changes. PE decreased the binding between GATA4 and RbAp48/46, and the recruitment of RbAp48/46 onto the GATA element of the ANF promoter. Although RbAp48/46 were co-localized with GATA4 in the nucleus of cardiomyocytes at the basal state, PE stimulus induced the export of RbAp48/46 to cytoplasm. LMB, a inhibitor of chromosomal region maintenance 1 (CRM1), inhibited nuclear export of RbAp48/46.

Conclusion:
These findings demonstrate that RbAp48/46 interact with GATA4, disasociate GATA4 from p300, and inhibit its acetylation as well as hypertrophic responses in cardiomyocytes. The nuclear export of RbAp48/46 by hypertrophic stimuli may trigger hypertrophy-responsive transcription by releasing these inhibitions.
Abstract 9480: Contrasting Effects of Imidapril and Losartan on Matrix Metalloproteinase in Human Abdominal Aortic Aneurysm
Authors: Miyoshi Toru , Yonezawa Tomoko , Nakamura Kazufumi , Yoshida Masashi , Morita Hiroshi , Yoshida Masashi , Doi Masayuki , Aoki Atsushi , Kusano Kengo , Ninomiya Yoshifumi , Ito Hiroshi
Published: April 2024

Background:
Abdominal aortic aneurysm (AAA) is characterized is characterized by the destruction of tissue architecture due to chronic inflammation. Emerging clinical evidence showed the effectiveness of angiotensin-converting enzyme inhibitor (ACEI) on the prognosis of AAA more than angiotensin II receptor blockers (ARB). We investigated the effects of an ACEI, imidapril and an ARB, losartan, on the activity of matrix metalloproteinase (MMP)-2 and -9 in human and murine AAA tissues.

Methods:
Five specimens were obtained as a whole abdominal aortic tissue (from proximal margin to distal margin). A whole sample was categorized into three zone; zones of margin, middle, and maximum diameter. Whole tissues were cut into around one inch of pieces, and then characterized for the histological parameters. The activities of MMPs were detected on AAA tissues by in situ gelatin zymography.

Results:
The MMP activities were increased in middle zone compared with other zones. The
in sizu
gelatin zymograhy showed that MMP activities on human AAA tissue in middle zone were significantly reduced by adding imidapril compared with losartan into reaction reagents. In addition,
in vitro
experiments showed that activities of human MMP-9 in a tube were significantly inhibited by imidapril, but not losartan in dose dependent manner. Next, we investigated the effects of imidapril (10mg/kg/day), losartan (10mg/kg/day), and hydralazine (10mg/kg/day) on CaCl
2
-induced AAA in mice. Six week after CaCl
2
-treatment, imidapril significantly prevented the enlargement of aorta compared to treatments with losartan and hydralazine (28%, 60% and 84%, respectively, p<0.01), while blood pressures were similarly lowered among three groups. The elevated expressions of MCP-1 and TNF-alpha and the recruitment of macrophages to AAA lesion were significantly reduced in imidapril-treated mice compared to losartan and hydralazine-treated mice. The
in situ
gelatin zymographies in mice also showed that lower MMP activities in AAA in imidapril treated mice compared with losartan and hydralazine treated mice.

Conclusion:
The direct inhibitory effect of imidapril on gelatinolytic activities may contribute to the protection of AAA.
Abstract 9485: Translocation of miRNA from Mesenchymal Stem Cells Protects Cardiomyocytes against Ischemic Injury in vitro
Authors: Yu Bin , Pasha Zeeshan , Yang Yueting , Wang Yigang , Millard Ronald W , Ashraf Muhammad , Xu Meifeng
Published: April 2024

microRNAs (miR) play an important role in cell survival. In this study, we investigated whether mesenchymal stem cells (MSC) mediated cardioprotection was associated with the regulation of miR as well as their targeted proteins.

Methods:
MSC were harvested from rat bone marrow. Cardiomyocytes (CM) were obtained from neonatal rat ventricles. In vitro cardioprotection by MSC was assayed by lactate dehydrogenase (LDH) release, Annexin-V staining, and DNA fragmentation following cells exposure to hypoxia for 48 hours. The expression of miR in MSC and CM was assessed by quantitative real-time PCR. miR targeted proteins were evaluated using a luciferase reporter assay and western blotting. To further investigate the role of miR, pre-miR precursor molecules were introduced into MSC using Lipofectamine 2000.

Results:
miR-221 was expressed 12-fold more in MSC than in CM (p<0.05). The p53-upregulated modulator of apoptosis (PUMA), one of miR-221 targeted proteins, was lower in MSC than in CM (Fig. A). When co-cultured with CM in a dual-chamber system, MSC markedly reduced LDH release and the number of annoxin-V positive CM, and increased CM survival in hypoxic culture. Transfection of miR-221 into MSC significantly increased MSC mediated cardioprotection compared to MSC transfected with negative control miR. In CM co-cultures with MSC, miR-221 transferred from MSC to CM was confirmed by using fluorescence
in situ
hybridization (FISH) and immunostaining. Moreover, less PUMA protein was found in CM co-cultured with MSC than in CM cultured alone (Fig. B).

Conclusions:
Cardioprotective effects of MSC are putatively associated with intercellular translocation of specific miR and regulation of their targeted proteins such as PUMA in CM.
Abstract 9512: Postconditioning With Lactate-Enriched Blood Potentiates the Protective Effect of Postconditioning Alone in Patients With Acute Myocardial Infarction
Authors: Koyama Takashi , Baba Akiyasu , Shibata Masaru , Moritani Kazunori , Shimada Megumi , Akaishi Makoto
Published: April 2024

Objective:
The infarct-limiting effect of postconditioning (PC) could not be shown in recent clinical trials. We tested the hypothesis that modification of the original protocol to increase the delay in recovery from intracellular acidosis would potentiate the protective effect of PC.

Methods:
Consecutive 7 patients with acute MI in various stages of the condition underwent primary PCI by using the modified PC protocol in which the duration of each brief reperfusion was prolonged from 10 s to 60 s in a stepwise manner. Lactated Ringer’s solution (20-30 mL) containing 28 mM lactate was injected directly into the culprit coronary artery at the end of each brief reperfusion and the balloon was quickly inflated at the site of the lesion, whereby lactate could be trapped inside the ischemic myocardium. Each brief ischemic period lasted 60 s. After 7 cycles of balloon inflation and deflation, full reperfusion was performed. The aim of this protocol was to achieve controlled reperfusion with tissue oxygenation and minimal lactate washout. After these procedures, stenting was performed.

Results:
All patients were successfully reperfused and experienced neither worsening of chest pain nor worsening of ST deviation during reperfusion. Reperfusion arrhythmia, including bradycardia, was not evoked by reperfusion in any of the 7 patients. TIMI grade flow III was achieved in all patients. Moreover, marked myocardial staining with contrast medium (area surrounded by white arrows) and/or early visualization of venous drainage (black arrows) were observed in all patients, indicating unimpaired microcirculation. The peak CK value (1074±1082 IU/L) was lower than expected in each situation. Radioisotope imaging revealed well-preserved myocardial viability in all patients.

Conclusion:
PC with lactate-enriched blood consistently suppresses the various detrimental effects of reperfusion and potentiates the protective effect of postconditioning alone in patients with acute MI.
Abstract 9566: LRP1 Deficiency Promotes Smooth Muscle Cell Apoptosis in Atherosclerotic Plaques via PDGF Receptor Mediated Downregulation of Bcl-2
Authors: Vantler Marius , Zhou Li , Moritz Schwab , Zierden Mario , Caglayan Evren , Zimmermann Wolfram H , Tallquist Michelle , Herz Joachim , Rosenkranz Stephan
Published: April 2024

Apoptosis of smooth muscle cells (SMCs) promotes instability of atherosclerotic plaques. Apoptosis is believed to be suppressed by growth factor dependent activation of PI 3-kinase (PI3K). We investigated the effect of LRP1 knockout driven elevated platelet-derived growth factor beta receptor (PDGFR) signaling on SMC apoptosis in atherosclerotic plaques. We quantified apoptotic TUNEL-positive SMCs in lesions from 12 months old LDLR-/-/smLRP1-/- double knockout mice. LDLR (low-density lipoprotein receptor) deficiency accelerates atherosclerosis in mice. LDLR-/-/smLRP1-/- increased the percentage of TUNEL-positive cells compared to LDLR-/-/smLRP1+/+ controls (3.6±0.7% vs. 0.7±0.3%,respectively, P < 0.05, n = 6). Mutation of the PI3K binding site in the PDGFR in LDLR-/-/smLRP1-/--F2/F2 mice suppressed SMC apoptosis (2.4%±0.3%, P < 0.05, n = 6) suggesting that the PDGFR exerts proapoptotic effects via PI3K. In vitro studies (Cell Death Detection ELISA) revealed that chronic stimulation of SMCs with PDGF-BB (96 h) led to 3.1±0.4-fold increased apoptosis (n=3, P<0.05). To characterize proapoptotic PDGFR driven signaling pathways we analysed PDGFR mutants in which the binding sites for different signaling molecules were deleted. Lack of PI3K binding completely abolished the proapoptotic effect, whereas a mutant which only binds PI3K was able to induce apoptosis like the WT receptor. Further analysis of PDGFR mutants revealed that activation of PI3K led to induction of c-Myc and decreased expression of antiapoptotic Bcl-2 as assessed by RT-PCR and Westernblotting. siRNA mediated knockdown of c-Myc prevented both, Bcl-2 downregulation and PDGF induced apoptosis. Consistently, immunohistochemical analysis of atherosclerotic plaques from LDLR-/-/smLRP1-/- and LDLR-/-/smLRP1-/--F2/F2 mice revealed that PDGFR dependent activation of PI3K impairs the expression of antiapoptotic Bcl-2. In conclusion, our study identified a new PDGFR driven proapoptotic signaling pathway in SMCs. Chronically elevated PDGFR/PI3K signaling downregulates Bcl-2 via induction of c-Myc. This has direct implications in atherogenesis, as PDGF promotes cell death in atherosclerotic plaques, which can ultimately lead to plaque instability and rupture.
Abstract 9569: Incidence of Acute Coronary Syndrome in the General Medicare Population, 1992-2009: A Real-World Perspective
Authors: Shroff Gautam R , Heubner Brooke M , Schein Jeff , Crivera Concetta , Herzog Charles A
Published: April 2024

Introduction:
Acute coronary syndrome (ACS) is a major cause of mortality and morbidity among elderly patients in the US. We examined temporal trends in the incidence of ACS in Medicare patients over nearly two decades employing administrative data.

Methods:
The 5% Medicare database (~ 1.8 million pts/cohort yr) was used to identify ACS pts (age 65+, no ESRD) between 1992-2009. Medicare claims were used to identify patients hospitalized with ACS using the following ICD-9-CM diagnostic codes: acute myocardial infarction (AMI, 410) and unstable angina (UA, 411).

Results:
The incidence of ACS in the elderly Medicare population remained 2.4-2.5% between 1999-2002 and subsequently decreased to 1.7% by 2009 ("A" in the Figure). The trend was similar for all age, gender and race groups ("B" in the Figure) with the exception of patients > 84 years, for whom the incidence of ACS increased from 2.8% in 1992 to 3.4% in 2002, before declining to 2.6% in 2009. The decrease in incidence of ACS since 2001 was driven by a decrease in diagnosis of UA (1.6-1.7% in 1992-1997 to 0.6% in 2009) but not in the diagnosis of AMI (holding steady between 1.2-1.4%), perhaps reflecting the introduction of more sensitive cardiac biomarkers.

Conclusion:
Improved cardiovascular outcomes in the US have also impacted elderly patients with ACS. In the last decade, there has been a steady progressive decline in the incidence of ACS in Medicare patients.
Abstract 9571: Activation of LXRα but Not LXRβ Protects the Heart from Ischemia/Reperfusion Injury
Authors: Pu Jun , He Qing , Gao Erhe , Lau Wayne Bond , Koch Walter J. , Ma Xin-Liang , He Ben
Published: April 2024

Objective:
Liver X receptors (LXRs) play a critical regulatory role in metabolism and inflammation, and have been demonstrated to be involved in vascular physiology/pathology. However, LXR function in cardiac biology remains largely unknown. Importantly, no data exists concerning the role of LXRs in myocardial ischemia/reperfusion (MI/R) injury.

Methods and Results:
Two LXR isoforms, LXRα (NR1H3) and LXRβ (NR1H2), were detected in the mouse heart. Exposure to MI/R resulted in upregulated LXRα expression in ischemic/reperfused myocardium, whereas LXRβ expression remained largely unaffected. LXR activation by natural and synthetic agonists reduced myocardial infarction and improved contractile function following MI/R injury. The cardioprotective effects of LXR agonists were completely abrogated by knock-down of endogenous cardiac LXRα, but not LXRβ, via in vivo intramyocardial siRNA transfection. LXRα knock-out mice manifested exacerbated apoptosis and infarct size with poorer contractile function post-MI/R compared to WT mice, whereas MI/R injury was similar between LXRβ knock-out and WT mice. Mechanistically, LXR agonists inhibited both endoplasmic reticulum stress (as evidenced by decreased activation of CCAAT/enhancer-binding protein homologous protein and caspase-12) and mitochondrial dysregulation (as evidenced by decreased release of mitochondrial cytochrome c and attenuated caspases-9 activation), and subsequently reduced cardiomyocyte apoptosis. Furthermore, LXR activation inhibited MI/R-induced oxidative stress (i.e., superoxide production and NADPH oxidase expression) and nitrative stress (i.e., peroxynitrite formation and inducible nitric oxide synthase expression) in ischemic/reperfused myocardium.

Conclusion:
Our study provides the first evidence supporting LXRα as a novel cardiac protective receptor against MI/R injury via inhibition of both endoplasmic reticular stress and the mitochondrial apoptotic pathway. LXRα may potentially be an attractive molecular target for the treatment of ischemic heart disease.