bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9208: Association of Polymorphism in Glutamate-Cysteine Ligase Modifier Subunit Gene with Idiopathic Dilated Cardiomyopathy
Authors: Kawabata Ken-ichi , Kobayashi Tsuyoshi , Fujioka Daisuke , Tamaru Shyun , Watanabe Yousuke , Watanabe Kazuhiro , Mishina Hideto , Sano Keita , Nakamura Takamitsu , Saito Yukio , Kitta Yoshinobu , Obata Jyun-ei , Kugiyama Kiyotaka
Published: April 2024

Myocardial mitochondrial dysfunction due to oxidative stress contributes to the pathogenesis of cardiomyopathy. Reduced glutathione (GSH) plays a crucial role in antioxidant defense mechanisms, and it is synthesized by glutamate-cysteine ligase (GCL) which is composed of catalytic (GCLC) and modifier (GCLM) subunits. We have found a polymorphism (-588C/T) in the 5’-flanking region of the GCLM gene in which the T allele showed lower promoter activity (40% of C allele) in response to oxidants and is associated with lower plasma GSH levels. This study examined the hypothesis that this polymorphism of GCLM gene may be associated with dilated cardiomyopathy (DCM). And, we studied potential role of GCLM in myocardial mitochondrial function using GCLM deficient (GCLM
-/-
) mice.

Methods and Results:
The frequency of the polymorphism (-588C/T) of the GCLM gene was determined in 205 consecutive patients with non-familial idiopathic DCM and age- and sex-matched 253 normal healthy subjects. The T allele was highly frequent in patients with DCM, compared with control subjects (CT and TT genotypes: 36.2% in DCM vs. 18.6% in controls; P < 0.0001), and it was a significant risk factor for DCM, that was independent of hypertension, diabetes, smoking and BMI (OR 3.13, 95% CI 2.28 to 4.44; P < 0.0001). The mitochondrial GSH levels in myocardium were lower in GCLM
-/-
mice (39% of baseline GCLM
+/+
). Mitochondrial respiratory function in the myocardium of GCLM
-/-
mice had a reduction in the ADP-stimulated state 3 activity (60% of GCLM
+/+
). Hypoxia re-oxygenation induced greater mitochondrial damages in cultured GCLM
-/-
cardiomyocytes than GCLM
+/+
cardiomyocytes, as evidenced by reduced membrane potential, increased protein carbonyl content, and increased GSSG/GSH rate in the isolated mitochondria. After myocardial ischemia-reperfusion, GCLM
-/-
mice had a greater dilation and systolic dysfunction of left ventricle (LV) than GCLM
+/+
mice.

Conclusions:
The -588T polymorphism of the GCLM gene is associated with non-familial idiopathic DCM. This association is supported by the animal study that GCLM deletion increased susceptibility of myocardial mitochondria to oxidative damage through mitochondrial GSH reduction, which may potentially contribute to LV dysfunction.
Abstract 9262: Prognostic Value of Myocardial Viability by Delayed Enhanced MR in Patients with Coronary Artery Disease and Low Ejection Fraction. Impact of Revascularization Therapy
Authors: Gerber Bernhard L , Rousseau Michel , Ahn Sylvie A , le Polain de Waroux Jean-Benoît , Pouleur Anne-Catherine , Vancraeynest David , Pasquet Agnès , Vanoverschelde Jean-Louis
Published: April 2024

Background.
Prior works showed that delayed-enhanced cardiac magnetic resonance (DE-cMR) predicts recovery of left ventricular dysfunction (LVD) after revascularization in coronary artery disease (CAD). We sought to evaluate impact of myocardial viability assessment by DE-cMR and of revascularization therapy on survival of patients (pts) with low ejection fraction (EF).

Methods and Results.
We prospectively evaluated survival of 144 consecutive pts (130 males, 65±11 years) with CAD and LVD (EF 24±7%) undergoing DE-cMR. 86 pts underwent complete revascularization of dysfunctional myocardium (79 CABG, 7 PCI), while 58 pts remained under medical treatment. Pts were considered to have viable myocardium if >4 dysfunctional segments had <50% transmurality of DE. Over 3-years median follow-up 49 pts died. 3-year survival was significantly worse in pts with dysfunctional viable myocardium remaining under medical treatment (48%) than in medically treated pts with non-viable myocardium (77%, p=0.02 by log-rank test). By contrast, in revascularized pts, survival was similar whether myocardium was viable or not (88 and 71% survival respectively, p=NS). Hazard of death of medically treated viable myocardium was 4.56 [95% CI 1.93-10.8]. Cox multivariate analysis indicated that interaction of revascularization and viability provided significant additional value (X2=13.1, p=.004) to baseline predictors of survival (NYHA class, wall motion score and peripheral arterial disease). More importantly, in 43 pairs of propensity score matched pts for treatment selection, hazard of death (2.5 [95% CI 1.1-6.1, p=0.02]) remained significantly higher for medically treated rather than revascularized viable myocardium (Figure).

Conclusions.
Without revascularization, presence of viable myocardium by DE-cMR is an independent predictor of mortality in pts with ischemic LVD. This observation may be useful for preoperative selection of pts for revascularization.
Abstract 9264: Predicting Acute Coronary Heart Disease Events in Women
Authors: McSweeney Jean C , Cleves Mario , Fischer Ellen , Wei Jeanne , Moser Debra
Published: April 2024

Background:
Coronary heart disease (CHD) is treatable if detected early yet few instruments measure women's prodromal symptoms (PS) of CHD. The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey (MAPMISS) identifies women's PS but prospective cohort data regarding the MAPMISS' predictability is limited.

Purpose:
To conduct a longitudinal observational cohort study designed to assess the ability of the MAPMISS' PS score to predict CHD events requiring clinical intervention in women, and to identify the most predictive components of the MAPMISS' PS score.

Methods:
Women referred for initial cardiac evaluation to clinics in Arkansas and Kentucky were eligible to participate; those with previous cardiac events and cognitive impairment were excluded. A total of 1114 women participated. The MAPMISS questionnaire was administered at time of enrollment and subsequently every 3 months for two years. The MAPMISS contains 33 PS. Each PS is weighted by its reported severity (0-3, 3=most severe) and frequency (less than monthly to daily, 0.125-7, 7=daily), and summed across symptoms (range 0-693). Cox proportional-hazards models adjusted by age and race were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (CI) for CHD events. Prodromal symptoms were entered in the Cox model as time dependent covariates.

Results:
Of the 1114 women, 1097 (98.5%) completed the study. Of these, 77 (7%) reported having an adverse cardiac event during the two-year follow-up. The total PS score was a significant predictor of adverse cardiac events (p<0.001). Back pain, between/under shoulder blades, was the strongest predictor of adverse cardiac events (HR=3.17, 95%CI = 1.28- 7.85), followed by change in thinking or remembering (HR=2.90, 95%CI = 1.20- 7.04), and non-specific, generalized chest pain (HR=2.97, 95%CI = 1.04- 8.50). Women reporting one or more of these three symptoms were over 5 times as likely to have an adverse cardiac event as women with none of these symptoms (HR=5.25, 95%CI = 2.37- 11.64).

Conclusion:
The total PS score from the MAPMISS could be useful in screening women at risk of an adverse cardiac event.
Abstract 9342: Ivabradine Reduces Interstitial Fibrosis and Enhances the Recovery of Cardiomyocyte Excitation-Contraction Coupling Produced by Mechanical Unloading
Authors: Navaratnarajah Manoraj , Ibrahim Michael , Siedlecka Urszula , Gandhi Ajay , Shah Adarsh , Van Doorn Carin , Dias Priyanthi , Yacoub Magdi H , Terracciano Cesare M
Published: April 2024

Improved Ca2+ handling in patients with end stage heart failure (HF) is associated with myocardial recovery during left ventricular assist device (LVAD) therapy. LVAD-induced myocardial atrophy and fibrosis are postulated to oppose recovery. Ivabradine (IVA) displays positive structural and excitation-contraction (EC) coupling effects in animal models of HF, and has been used effectively in human HF therapy. However, the effects of IVA during mechanical unloading (MU) are unknown. We studied the chronic effects (4 weeks) of oral IVA (10mg/kg/day), alone and in combination with MU (heterotopic abdominal transplantation), on whole heart/cardiomyocyte structure and function in rat cardiomyopathy (12 weeks) induced by left coronary artery ligation. IVA improved ejection fraction (p<0.01) compared with untreated HF group. IVA caused regression of HF-induced myocyte hypertrophy but did not affect MU-induced myocyte atrophy (cell volume measured by di-8-ANNEPS staining and confocal microscopy (µm3)): IVA 52070 ± 15850 (n =50) p<0.001 vs HF 59710 ± 13610 (n=52), MU+IVA 25569 ± 6171 (n= 40) p >0.05 vs MU 27052 ± 8422 (n=45). IVA reduced HF-induced myocardial fibrosis, an effect that was maintained during MU (interstitial fibrosis measured histologically using picrosirius red staining (% area)): IVA 3.1 ± 0.3 p<0.001 vs HF 7.6 ± 0.3, MU+IVA 2.4 ± 0.2 p< 0.001 vs MU 7.9 ± 0.4 (n=70 for all groups). IVA when used alone or in combination with MU had positive effects on EC coupling of isolated ventricular myocytes. Time to peak (TTP (s)) for sarcomere shortening and for Ca2+ transient (CaT) were reduced by IVA therapy alone: IVA: 0.12 ± 0.05 p< 0.001 vs HF 0.16 ± 0.01 and IVA: 0.07 ± 0.05 p< 0.001 vs HF 0.12 ± 0.02, respectively (n=40 for all groups). IVA enhanced the recovery of both sarcoplasmic reticulum (SR) Ca2+ content and CaT amplitude achieved by MU (SR Ca2+ content (ratio units): MU+IVA 0.27 ± 0.07 (n=45) p< 0.05 vs MU 0.24 ± 0.50 (n=40), and CaT amplitude (ratio units): MU+IVA 0.25 ± 0.06 (n=45) p<0.001 vs MU 0.18 ± 0.05 (n=40). We conclude that IVA reduces interstitial fibrosis and enhances MU-induced recovery of CaT amplitude and SR Ca2+ content in rodent HF. Such effects may be exploited to enhance myocardial recovery in HF patients treated with LVADs and requires further studies.
Abstract 9356: Diastolic Function Determines the Adrenergic Augmentation of Early Diastolic Intra-Ventriclular Pressure Gradient and Its Spatial Distribution
Authors: Ohara Takahiro , Niebel Cassie L , Stewart Kelley C , Charonko John J , Burgess Pamela R , Pu Min , Vlachos Pavlos P , Little William C
Published: April 2024

Introduction:
Early diastolic left ventricular (LV) filling results from a progressive intra-ventricular pressure gradient (IVPG) extending from the left atrium to the LV apex.

Hypothesis:
Adrenergic stimulation enhances the progressive IVPG in normal subjects but not in patients with diastolic dysfunction.

Methods:
We studied 218 consecutive patients undergoing stress echocardiography who had no inducible ischemia, of which 29 were graded as normal diastolic function, 20 impaired relaxation (IR), 103 pseudo-normal filling (PN) and 66 restrictive filling (RF) according to the EAE/ASE recommendations. Color M mode Doppler (CMMD) images in the apical four chamber view were obtained at rest and during peak dobutamine infusion (20-40 mcg/kg/min). Total IVPG from the mitral annulus to LV apex, IVPG from the mitral annulus to mid LV (2 cm into the LV from the mitral annulus) and IVPG from mid LV to LV apex were calculated using the CMMD data to integrate the Euler equation.

Results:
Mean age±SD was 60±12 years old. Male 51%. EF 59±8%. Total IVPG from the mitral annulus to LV apex was not different between groups at rest. The total IVPG increased more with dobutamine in normal subjects than in patients with diastolic dysfunction (Figure 1). The responses of IVPG from the mitral annulus to mid LV were not different among groups. The difference in the response of the total IVPG was due to the more marked augmentation of IVPG from mid LV to LV apex in normal subjects (Figure 2).

Conclusions:
Diastolic dysfunction is associated with an inadequate adrenergic augmentation of the IVPG from mid LV to LV apex reflecting less apical suction.
Abstract 9362: Argon Reduces Neurohistopathological Damage and Preserves Functional Recovery After Cardiac Arrest in Rats
Authors: Bruecken Anne , Fera Carmen , Meinhardt Axel , Weis Joachim , Rossaint Rolf , Fries Michael
Published: April 2024

Introduction:
Xenon has profound neuroprotective effects in various models of neurological injury and is currently undergoing phase two clinical trials in cardiac arrest patients. However, xenon is very costly which might preclude a widespread use. We hypothesized that the more available Argon might also protect central nervous tissues and functional recovery in a rodent model of global cerebral ischemia.

Material and Methods:
14 male Sprague-Dawley rats were subjected to 7 mins of cardiac arrest and 3 mins of cardiopulmonary resuscitation (CPR). One hour after successful CPR, animals were randomized to ventilation with 70% Argon for 1h in comparison to untreated controls receiving 70% Nitrogen. A neurologic deficit score was calculated on seven days following the experiment before the animals were killed and the brains harvested for histopathological analyses.

Results:
All animals survived. Untreated controls exhibited severe neurological dysfunction while animals from the Argon group showed significant improvements at all points in time (Fig. 1). This was paralleled by a significant reduction in the degree of necrotic cell damage in the neocortex and the hippocampal CA 3/4 region (Fig. 2).

Conlusions:
Our study demonstrates that a single one hour application of 70% Argon provided a significant reduction in histopathological damage of the neocortex and hippocampus which was associated with a marked improvement in functional neurological recovery.
Abstract 9367: Speckle-Tracking and Tissue-Doppler Stress Echocardiography in Arterial Hypertension
Authors: Hensel Kai , Littwitz Henning , Leischik Roman
Published: April 2024

OBJECTIVE:
2D-strain (2DS) and tissue-Doppler imaging (TDI) was combined with physical stress echocardiography to assess differences in LV function between hypertensive patients and healthy controls under physical exercise. We hypothesized whether LV peak strain is an early marker to identify hypertensive patients at high risk for congestive heart failure.

METHODS:
Individuals with isolated arterial hypertension (n=30) who had no other cardiac or non-cardiac diseases were compared with a random collection of completely healthy controls (n=30). LV function was assessed with 2DS and TDI: At rest, low (50 Watts) and high resistance (150 Watts) of physical challenge on a bicycle. Global longitudinal (LS), circumferential (CS) and radial strain (RS) were assessed. Subsequently, intra- and inter-observer reliability analyses were performed (Bland-Altmann test)

RESULTS:
Compared to the hypertensive group (mean blood pressure (MBP) = 79.1 ± 13.6 mmHg), healthy volunteers (MBP = 84.5 ± 15 mmHg) were shown to have significantly higher values of CS (p=0.027) and LS (p=0.036) using 2DS at rest. At 50 Watts of resistance the same differences could be shown with a higher degree of statistical significance. At 150 Watts of resistance the control group (MBP = 119.9 ± 16.8 mmHg) had significantly higher levels of contractility in CS (p=0.023), LS (p=0.000) and RS (p=0.005) than hypertensive patients (MBP = 125.7 ± 15.1 mmHg). TDI showed similar results, while significant differences could only be proven at the highest level of physical challenge. The influence of physical challenge on cardiac strain was shown most distinctively by TDI in LS (p=0.000) and CS (p=0.007) in the control group.

CONCLUSIONS:
Compared to the healthy control group, patients with arterial hypertension were found to have reduced levels of left ventricular contractility. This promotes peak strain as an early parameter for LV deterioration due to arterial hypertension. In the assessment of the impact of hypertensive heart disease on LV contractility, 2DS was shown to be more sensitive for strain analysis at rest whereas TDI detected more differences in contractility under physical exercise. Given these results, quantitative deformation imaging is a promising addition to stress echocardiography.
Abstract 9383: Selective Tissue Factor/Factor VIIa Inhibitor ER-410660 and its Prodrug E5539 Have an Anti-Venous Thrombotic Effect with Low Risk of Bleeding
Authors: Nagakura Tadashi
Published: April 2024

The “extrinsic coagulation pathway” is activated by complex formation between tissue factor (TF) and factor VIIa (FVIIa). The onset of thrombosis is associated with the specific expression of TF. Compounds that inhibit the TF/FVIIa complex might therefore have therapeutic and/or prophylactic uses for diseases associated with thrombus formation. TF/FVIIa inhibitors might also reduce the risk of bleeding as they leave the intrinsic pathway intact and so maintain normal hemostasis. We assessed this hypothesis using a series of triazolone derivatives that acted as potent and selective TF/FVIIa inhibitors. Based on human intravenous pharmacokinetic data from a microdosing study, we identified ER-410660 as a candidate for prodrug formation to improve oral availability. ER-410660 showed potent and selective inhibition of the TF/FVIIa complex with an IC
50
of 5.7 nM. The compound selectively prolonged the prothrombin time (PT) in human, rhesus monkey, and rat plasma (a 50% increase of PT was obtained at 2.0, 1.7, and 19 μM, respectively). Intravenous (iv) administration of ER-410660 dose-dependently inhibited thrombin generation caused by TF-injection in the rhesus monkey with an ED
50
of 40 (95% CI, 25-55) μg/kg. ER-410660 (iv) reduced venous thrombus weights in a TF-administered stasis-induced venous thrombosis model in rats with an ED
50
of 0.18 (95% CI, 0.11-0.25) mg/kg. The anti-hemostatic effect of ER-410660 (iv) was evaluated in a rat tail-cut model. The total bleeding time was doubled at 7.1 (95% CI, 6.1-11) mg/kg, which was 39-fold higher than the ED
50
value in the rat venous thrombosis model. E5539, an orally available form of ER-410660, was discovered by prodrug formation. Oral E5539 at doses of 3, 10, and 30 mg/kg reduced plasma thrombin-antithrombin (TAT) complex levels elevated by TF-injection in a dose-dependent manner. The TAT level was reduced to 50% of the control at an ED
50
value of 12 (95% CI, 8.0-17) mg/kg. These proof-of-concept studies in animal models suggest that selective TF/FVIIa inhibitors such as ER-410660 and its prodrug E5539 could act as novel anticoagulants with a low risk of bleeding.
Abstract 9384: Differential Association of Epicardial Fat with Coronary Plaque in Patients with Acute Coronary Syndrome or Stable Angina Pectoris: Analysis by Integrated Backscatter Intravascular Ultrasound
Authors: Harada Ken , Amano Tetsuya , Uetani Tadayuki , Kato Masataka , Kato Bunichi , Yoshida Tomohiro , Ando Hirohiko , Kunimura Ayako , Shimbo Yusaku , Kitagawa Katsuhide , Harada Kazuhiro , Ishii Hideki , Matsubara Tatsuaki , Murohara Toyoaki
Published: April 2024

Introduction:
Epicardial fat is implicated in the pathogenesis of coronary atherosclerosis, but its precise contribution to this condition remains unclear.

Objective:
To evaluate the relations between epicardial adipose tissue and coronary plaque in patients with acute coronary syndrome (ACS) and those with stable angina pectoris (SAP).

Methods:
Atotal of 62 individuals (mean age, 67 ± 11 years; 64% men) who underwent percutaneous coronary intervention, including 20 patients with ACS and 42 patients with SAP, were enrolled in the study. Conventional and integrated backscatter intravascular ultrasound (IB-IVUS) was performed to assess coronary plaque in the patients. Plaque components were classified as calcified, dense-fibrous, fibrous, or lipid with the IB-IVUS system. The average plaque volume (total plaque volume/lesion length) and the percentage volumes of individual plaque components were calculated. Epicardial fat volume (EFV) was also measured by 64-slice computed tomography within 1 week of percutaneous coronary intervention.

Results:
There was no significant difference between ACS and SAP patient characteristics. EFV was significantly higher in patients with ACS than in those with SAP (117 ± 36 vs. 103 ± 40 ml,
p
< 0.05). Multivariate regression analysis revealed that EFV was positively correlated with the percentage volume of dense-fibrous plaque (
r
= 1.49,
p
< 0.05) and negatively correlated with average plaque volume (
r
= -0.58,
p
< 0.05) in patients with ACS. However, no correlation between EFV and coronary plaque profile was apparent in patients with SAP.

Conclusions:
EFV was associated with the development of dense-fibrous plaque in ACS patients, whereas the average plaque volume decreased with increasing EFV in these patients. Our findings support the hypothesis that increased epicardial fat may contribute to the pathogenesis of ACS.
Abstract 94: Are Longer Resuscitation Efforts Associated with Improved Survival During In-Hospital Arrest? An Analysis from the GWTG--Resuscitation
Authors: Goldberger Zachary D , Chan Paul S , Berg Robert A , Kronick Steven L , Lu Mingrui , Banerjee Mousumi , Hayward Rodney A , Krumholz Harlan M , Nallamothu Brahmajee K
Published: April 2024

Background
How long resuscitation attempts should continue prior to the termination of efforts is unknown for in-hospital cardiac arrests. We hypothesized that resuscitation duration in non-survivors varies across hospitals and that patients at hospitals with longer attempts have improved survival.

Methods
We identified 70,156 patients with in-hospital cardiac arrests between 2000 and 2009 at 440 hospitals within a large national registry. We stratified hospitals into quartiles of equal size based on their median duration of resuscitation attempts prior to the termination of efforts in patients who did not achieve return of spontaneous circulation (ROSC). Through hierarchical modeling, we then assessed whether patients at hospitals with longer median resuscitation durations among their non-survivors had higher risk-adjusted survival.

Results
The overall proportion of patients achieving ROSC was 48.5%. Among non-survivors, the median resuscitation duration was 20 minutes, with efforts terminated within 10 minutes in 15.5% and within 30 minutes in 76.3%. Compared with patients at hospitals in the quartile with the shortest resuscitation duration among their non-survivors, patients at hospitals with longer resuscitation durations had an increasing likelihood of achieving ROSC (p<0.001 for trend, Table). These findings were driven largely by a higher likelihood of achieving ROSC at later points during the cardiac arrest for patients at hospitals with longer resuscitation durations, and were most pronounced for cardiac arrests due to pulseless electrical activity and asystole. Rates of survival to discharge showed a similar pattern of results.

Conclusions
Duration of resuscitation attempts varies substantially across hospitals during in-hospital cardiac arrest. Patients at hospitals with longer resuscitation durations have a higher likelihood of ROSC and survival to discharge.
Abstract 9400: Inhibition of IκB Phosphorylation by a Novel IKK Inhibitor IMD-1041 Attenuates Myocardial Dysfunction After Infarction
Authors: Matsumoto Ryo , Suzuki Jun-Ichi , Ogawa Masahito , Watanabe Ryo , Muto Susumu , Itai Akiko , Hirata Yasunobu , Nagai Ryozo , Isobe Mitsuaki
Published: April 2024

Background:
Ischemia after myocardial infarction (MI) frequently causes left ventricular (LV) dysfunction. This condition is due to inflammatory reactions and fibrosis of myocardium. LV remodeling after MI is the pathological process which includes expansion of the infarcted area, ventricular dilatation and distortion of the ventricular shape. Recently, several studies have demonstrated that nuclear factor-kappa B (NF-κB) is related to inflammation and LV remodeling and that NF-κB is activated in infarcted hearts. However, the effects of the continuous inhibition of NF-κB for the prevention of LV dysfunction after MI are still controversial. A novel IKK inhibitor IMD-1041, which inhibits phosphorylation of I-κB via inhibition of IKK-β, is under clinical trial for chronic obstructive pulmonary disease. In spite of these progressive studies on pulmonary disease, the effects of IMD-1041 on cardiovascular disease are not yet well examined. The aim of this study was to investigate the effects of IMD-1041 on myocardial remodeling after infarction.

Methods and Results:
To analyze the effects of IMD-1041 on myocardial dysfunction after MI, we continuously administered IMD-1041 (low dose; 30mg/kg/day, high dose; 100mg/kg/day) or vehicle (0.5% CMC) orally to mice with ligation of the left anterior descending coronary artery (LAD). After 28 days of ligation, MI mice exhibited LV dilatation and contractile dysfunction. However, IMD-1041 treatment significantly improved cardiac function, as indicated by the preservation of fractional shortening (30mg/kg/day of IMD-1041, 25.8±0.8%, n=12; 100mg/kg/day of IMD-1041, 29.3±0.6%, n=12; vehicle-treated, 21.6±1.6%, n=11; P<0.05). Histological analysis also showed that IMD-1041 treatment effectively inhibited LV remodeling through reduction of the ratios of fibrosis per whole area compared with vehicle control group (30mg/kg/day of IMD-1041, 21.5±2.0%, n=12; 100mg/kg/day of IMD-1041, 24.0±1.7%, n=12; vehicle-treated, 33.2±3.6%, n=11; P<0.05).

Conclusion:
These results suggest that IMD-1041 treatment effectively improves LV remodeling after MI through attenuation of myocardial fibrosis. It may provide an effective approach to prevent myocardial dysfunction.
Abstract 9424: Caloric Restriction Augments Cardiomyocyte Autophagy to Mitigate Postinfarction Cardiac Remodeling and Heart Failure
Authors: Watanabe Takatomo , Takemura Genzou , Kanamori Hiromitsu , Tsujimoto Akiko , Kazuko Goto , Ogino Atsushi , Takeyama Toshiaki , Kawaguchi Tomonori , Morishita Kentaro , Fujiwara Hisayoshi , Fujiwara Takako , Minatoguchi Shinya
Published: April 2024

We previously reported that cardiomyocyte autophagy is an innate mechanism that protects against progression of postinfarction cardiac remodeling. In the present study, we examined effect of caloric restriction (CR), a potent inducer of autophagy, on post infarction cardiac remodeling. Myocardial infarction (MI) was induced in mice by ligating the left coronary artery. After one week of MI, mice were randomly divided into the following four groups. The control group was fed ad libitum (100%). Others were fed restricted diet: 80%, 60%, and 40% of the total calorie which was taken by control mice. The water was provided ad libitum. Three weeks later, we performed echocardiography and catheter to evaluate the left ventricular (LV) function. There was no mouse that died through the period. The body weight was decreased in CR groups (post/pre ratio: 1.08±0.01 in control, 0.83±0.01 in 80% CR, 0.76±0.01 in 60% CR, 0.70±0.01 in 40% CR, p<0.001). However, there was no difference in heart/body weight ratio. The dilatation and hypofunction of the LV were apparent in the control group: left ventricular diastolic dimension (LVDd) = 4.9±0.1 mm; left ventricular ejection fraction (LVEF) = 27±3.3%; and dP/dT = 4677±277 mmHg/s. However, both dilatation and hypofunction were significantly mitigated in groups undergoing CR: in 80%, 60%, and 40% CR, respectively, LVDd = 4.0±0.1 mm, 3.4±0.2 mm and 4.0±0.1 mm; LVEF = 36±2.8%, 51±4.3% and 43±1.5%; and dP/dT = 6849±221 mmHg/s, 7758±638 mmHg/s and 6923±553 mmHg/s, among which the 60% CR group showed the strongest therapeutic effect on postinfarction cardiac remodeling (control vs. 60% CR: p<0.001). Cardiomyocyte autophagy was markedly activated in CR groups as evidenced by the overexpressed microtubule-associated protein 1 light chain 3-II (LC3-II) and specific ultrastructural findings including autophagosome formation. In conclusion, caloric restriction enhances cardiomyocyte autophagy and mitigates postinfarction cardiac remodeling and dysfunction; the optimal caloric restriction is suggested to be 60%. These findings suggest an important clinical implication that a dietary protocol can be a preventive strategy against progression of postinfarction left ventricular remodeling and heart failure.
Abstract 9483: Oxidative Stress Induced by Acute Sodium Loading is Associated with Diastolic Dysfunction in Prehypertensives
Authors: Hummel Scott L , Kolias Theodore J , Weder Alan B
Published: April 2024

Introduction:
In 'salt-sensitive’ animals, chronic sodium (Na) loading causes oxidative stress and ventricular diastolic dysfunction. In humans, less is known about how early in the course of hypertension these responses begin, or if they differ following acute Na loading.

Hypothesis:
Acute Na loading in prehypertensives induces systemic oxidative stress that in turn is associated with post-Na loading ventricular diastolic dysfunction.

Methods:
We studied 14 prehypertensive humans (10 male, 4 female; age 28 ± 7 years, blood pressure 132 ± 12/ 77 ± 9 mmHg) over 6 days. Subjects ate a low-Na (20 mMol) diet on days 1-4. On day 5, they received 2 liters of 0.9% saline (308 mMol Na) intravenously over 2 hours, then 130 mMol Na over two high-Na meals. Urinary F-2 isoprostanes from overnight collections were used to measure systemic oxidative stress. Transthoracic echocardiograms were done on day 4 and day 6. Since standard diastolic function measures are less sensitive in structurally normal hearts, we used novel speckle tracking software (EchoInsight, Epsilon Imaging) to obtain a newer measure, global early diastolic strain rate (DSR). We used t-testing and linear regression to evaluate the association between ΔF2-isoprostanes and ΔDSR with Na loading.

Results:
F2-isoprostanes increased post-Na loading (4.1 ± 2.1 to 7.3 ± 7.4 pg/mMol Cr, p = .08), as did DSR (0.89 ± 0.20 to 1.08 ± 0.27 s
-1
, p = .06). However, subjects below the median ΔF2-isoprostanes (group A) had significant increase in DSR post-Na loading; while those above the median ΔF2-isoprostanes (group B) did not (
Figure
). On linear regression, adjusted for urinary volume excretion, ΔDSR was inversely related to ΔF2-isoprostanes (β -.03, p < .02; r
2
= 0.53). In contrast to DSR, other diastolic function measures were unrelated to ΔF2-isoprostanes.

Conclusions:
Oxidative stress generated by acute Na loading is associated with impaired diastolic function in prehypertensive humans with structurally normal hearts.
Abstract 9489: Clinical Impact of Integrated Backscatter Intravascular Ultrasound (IB-IVUS) Analysis for Predicting Coronary No-Reflow Phenomenon After Percutaneous Coronary Intervention
Authors: Daidoji Hyuma , Takahashi Hiroki , Otaki Yoichiro , Tamura Harutoshi , Arimoto Takanori , Shishido Tetsuro , Miyashita Takehiko , Miyamoto Takuya , Watanabe Tetsu , Kubota Isao
Published: April 2024

Background and Aims
Coronary no-reflow phenomenon after percutaneous coronary intervention (PCI) is associated with a poor prognosis. It is important to predict and prevent coronary no-reflow after PCI and to use distal protection device appropriately. Previous studies showed that integrated backscatter intravascular ultrasound (IB-IVUS) provided high diagnostic accuracy for tissue characterization of coronary plaques based on histology. The purpose of this study was to investigate the relationship between plaque components assessed by IB-IVUS and coronary no-reflow after PCI.

Result
The 177 lesions (acute coronary syndrome (ACS), n=69; non-ACS, n=108) in 168 consecutive patients (mean age 69 ± 11 years old) who received PCI using IB-IVUS were enrolled. No-reflow, including transient filter no-reflow by using distal protection device, was observed in 18 ACS lesion (26%) and 12 non-ACS lesion (11%). In both ACS and non-ACS patients, lipid volume at stent deployment lesion, lipid area at minimum lumen site (MLS) and percentage of lipid area (%Lipid) at MLS were significantly larger in no-reflow group compared with the normal-reflow group. A receiver operating characteristic (ROC) analysis was performed to assess lipid volume, lipid area at MLS and %Lipid at MLS to predict coronary no-reflow. In ACS patients, the cut-off values for lipid volume, lipid area at MLS and %Lipid at MLS were determined by ROC analysis as 97mm
3
, 7.2mm
2
and 62%, respectively. Otherwise, in non-ACS patients, the cut-off values for lipid volume, lipid area at MLS and %Lipid at MLS were determined as 93mm
3
, 6.1mm
2
and 64%, respectively.

Conclusion
Our present study suggests that lipid rich plaque assessed by IB-IVUS should be considered as one of important predictors of coronary no reflow after PCI. These cut-off values determined by present IB-IVUS study could improve our approach to coronary no reflow risk stratification in patients with coronary artery disease.
Abstract 9493: Plasma Levels Of Soluble CD36 In Type 2 Diabetes - A Link Between Platelet Activation, Inflammation And Oxidative
Stress
Authors: Davì Giovanni , Liani Rossella , Halvorsen Bente , Sestili Simona , Handberg Aase , Santilli Francesca , Formoso Gloria , Aukrust Pål
Published: April 2024

INTRODUCTION
Inflammation, oxidative stress and platelet activation are involved in the pathogenesis of type 2 diabetes (T2DM) and its complications. Soluble CD36 (sCD36) has been proposed to early identify diabetic subjects at risk of developing accelerated atherothrombosis.

HYPOTHESIS
We aimed at characterizing the platelet contribution to sCD36 in T2DM, to correlate its formation with the extent of
in vivo
lipid peroxidation and to investigate the effects of low-dose aspirin on these processes.

METHODS
A cross-sectional comparison of sCD36, soluble CD40L (sCD40L) as a marker of platelet-mediated inflammation, urinary 11-dehydro-TxB
2
and 8-iso-PGF
2α
,
in vivo
markers of platelet activation and lipid peroxidation, respectively,was performed between 200 T2DM patients (94 of them on low-dose aspirin) and 47 healthy controls.

RESULTS
sCD36 (median [IQR]: 0.72 [0.31-1.47] vs 0.26 [0.2-0.37], p=0.003) and urinary 11-dehydro-TxB
2
levels (666 [293-1336] vs 279 [160-396], p≤0.0001) were significantly higher in T2DM patients not on aspirin (n=106) than in healthy subjects. These variables were significantly lower in aspirin-treated diabetics than in untreated patients (p<0.0001). Among patients not on aspirin, those with long-standing diabetes had significantly higher sCD36 levels in comparison to patients with diabetes duration <1 year (1.01 [0.62-1.86] vs 0.44 [0.22-1.21], p=0.001). Consistently, in the same group of patients, a significant linear correlation was found between sCD36 and diabetes duration (rho=0.347; p=0.0001), fasting blood glucose (rho=0.378; p=0.002) and HbA
1c
(rho=0.255; p=0.026). sCD36 linearly correlated with urinary 11-dehydro-TxB
2
, 8-iso-PGF
2
α
and sCD40L in diabetics not on aspirin. On multiple regression analysis, 11-dehydro-TxB
2
(
β
=0.360; SEM=0.0001, p=0.001), 8-iso-PGF
2α
(
β
=0.469; SEM=0.0001, p<0.0001) and diabetes duration (
β
=0.244; SEM=0.207, p=0.017) independently predicted sCD36 levels.

CONCLUSIONS
sCD36 may be a link among hyperglycemia, inflammation, lipid peroxidation and platelet activation. Because it can only incompletely be down-regulated by low-dose aspirin, additional antiplatelet strategies in T2DM should be investigated to interrupt CD36-dependent platelet activation.
Abstract 9501: Key Role of Low High Density Lipoprotein Cholesterol for the Association of the Metabolic Syndrome with Inflammation in Patients with Peripheral Arterial Disease
Authors: Rein Philipp , Saely Christoph H , Boehnel Christian , Beer Stefan , Vonbank Alexander , Kiene Veronika , Drexel Veronika , Drexel Heinz
Published: April 2024

The association of the metabolic syndrome (MetS) and of the individual MetS stigmata with inflammation in patients with peripheral arterial disease (PAD) has not been investigated yet and is adressed in the present study.

We enrolled 410 consecutive patients who underwent routine duplex sonography for the evaluation of suspected or established PAD Fontain stages I-III and in whom PAD was verified sonographically. According to National Cholesterol Education Programme Adult Treatment Panel III criteria, the MetS was defined in the presence of at least 3 out of the 5 quantitatively defined criteria large waist circumference, low HDL cholesterol, high triglycerides, high blood pressure, and elevated fasting glucose. In univariate analyses, CRP was higher in patients with the MetS (n=200) than in those who did not have the MetS (0.94±1.88 vs. 0.56±1.18 mg/dl; p=0.001), and also was higher in patients who fulfilled the large waist (0.93±1.93 vs. 0.59±1.16 mg/dl; p = 0.009) and the low HDL criteria (1.10±1.66 vs. 0.61±1.52 mg/dl; p<0.001) than in those who did not. Importantly however, after adjustment for gender, smoking, BMI and LDL cholesterol by means of ANCOVA only the low HDL cholesterol criterion (F=6.06; p=0.014) remained significantly associated with CRP. The significant and independent association of low HDL with CRP was confirmed after additional adjustment for all other MetS traits (F=7.76; p=0.006).

We conclude that among patients with sonographically proven PAD, low HDL cholesterol drives the association between the MetS and subclinical inflammation. This observation is well in line with the paramount role of low HDL cholesterol as a marker of cardiovascular risk.
Abstract 9540: Time-Course of Cardiac Improvement During Mechanical Unloading Predicts Outcome After Weaning From Ventricular Assist Devices
Authors: Dandel Michael , Weng Yuguo , Siniawski Henryk , Lehmkuhl Hans B , Drews Thorsten , Krabatsch Thomas , Potapov Evgenij , Knosalla Christoph , Hetzer Roland
Published: April 2024

Background:
Detection of cardiac improvement which allows long-term transplant-free outcome after weaning from ventricular assist devices (VADs) is a major goal. In patients with normalization of left ventricular (LV) diameters during unloading, the pre-explantation “off-pump” LVEF allows the distinction between patients with and without the potential to remain stable after weaning. However, some patients with LVEF > 45% before VAD removal show early recurrence of heart failure (HF). We assessed this aspect and aimed to find out if unstable improvement can already be recognized before VAD removal.

Methods:
Among 94 patients weaned from VADs since 1995, a homogenous group of 46 patients with non-ischemic chronic cardiomyopathy (CCM) was selected for the evaluation of ECHO data obtained during serial “off-pump” trials before VAD explantation.

Results:
In the evaluated patients, post-weaning 10-year survival without HF recurrence reached 66.0 ± 7.6%. In patients with LV end-diastolic diameter (LVEDD) ≤ 55mm and LVEF ≥ 45% at the time of VAD removal, pre-explantation stability of LVEF and/or LVEDD (no or less than 10% alteration in comparison to the best of all off-pump values until VAD removal) showed a 94.1% predictive value for cardiac stability during the first 5 post-weaning years. Pre-explantation alterations of LVEF with > 10% of best “off-pump” values or a decrease of > 10% of the LV end-diastolic relative wall thickness (RWT) during the final off-pump trials in patients with pre-explantation LVEF of between 45% and 50% showed predictive values of 87.5% and 83.3%, respectively, for HF recurrence during the first 3 post-weaning years. The stability of LV systolic wall motion peak velocity (Sm) during off-pump trials and between the detection of maximum cardiac improvement and time of VAD removal also appeared predictive for 5 year post-weaning stability. Patients needing > 6 months for LVEF improvement to ≥ 45% showed 79.1% probability for HF recurrence during the first 3 years.

Conclusions:
The pre-explantation time-course of LVEF, LVEDD, RWT and Sm is predictive for the long-term post-weaning stability of unloading-induced cardiac recovery. Assessment of these parameters during serial off-pump trials can improve weaning decisions in CCM patients.
Abstract 9542: Effects of Aerobic Exercise on Biomarkers After an Implantable Defibrillator (ICD)
Authors: Flo Gayle L , Dougherty Cynthia M , Burr Robert L , Kudenchuk Peter J , Glenny Robb
Published: April 2024

Aerobic exercise reduces risk factors for CVD and improves cardiac mortality. However, the effects of aerobic exercise on cardiac function in those with an implantable cardioverter defibrillator (ICD) has not been well described. Aerobic exercise that is carried out without a signifiant increase in arrhythmias or a reduction in cardiac function would be considered safe and hold promise for prescribing exercise in this population. The
purpose
of this study is to describe the effects of moderate intensity aerobic exercise on B-type naturetic peptide (BNP) in those who have an ICD.

Methods:
Patients with ICDs (primary or secondary prevention) were randomized to either 8 weeks of aerobic conditioning exercise [home walking 1 hour/day on 5 days/week at 60-80% of maximum HR] or usual care. Usual care patients did not significantly change their level of activity during the 8 week period. Serum BNP was measured in a non-fasting state before the exercise program and again at 8 weeks.

Results:
117 subjects completed baseline and 8 week follow-ups (59 usual care and 58 exercise, age 55.6±12.3; male 78%; primary prevention ICD 40%; Caucasian 83%; EF% 39.7±16; BMI 29.3±5.9). 100% of patients were taking beta blockers, 61% ACE inhibitors, 29% diuretics, 8% had DM, 40% had MI, 55% with HF, and 29% had hypertension. Overall, 83% in the exercise group met the expected total days of walking/week and 99% have met the exercise time requirement. Comparisons (mean+SD) between exercise and usual care groups on BNP at 8 weeks indicated that there was no significant difference in BNP with exercise (usual care 202.66+365.93 vs exercise 222.34+249.7, t=0.95, p=0.21). Additionally, 51% had baseline BNP values that were elevated (> 101 mg/dl). For those in the exercise group that had elevated baseline BNP levels, BNP was reduced with exercise (273+181 to 242+203). This was not true for usual care (236+165 to 250+214). A repeated measures factorial interaction test of [group x BNP level] was significant (F[1,113]=6.581, p= 0.012).

Conclusions:
Home walking exercise for 5 hours/week x 8 weeks in those with an ICD can be completed without significant increases in serum BNP. The level of exercise prescribed can be safely performed in patients with an ICD without significant increases in HF symptoms or BNP.
Abstract 9583: Remote Preconditioning Has a Powerful Antiarrhythmic Effect Independent of the Reperfusion Injury Salvage Kinase Pathways
Authors: Dow Joan , Simkhovich Boris Z , Bhandari Anil , Kloner Robert A
Published: April 2024

Background:
There is continuing need for non pro-arrhythmic antiarrhythmic therapies for life threatening ventricular arrhythmias associated with myocardial ischemia/reperfusion. A new form of endogenous cardio-protection, remote ischemic preconditioning (RPC) showed promise for reducing myocardial infarct size, but its effect on ventricular arrhythmias is largely unknown. The purpose of this study was to determine the effects of RPC on arrhythmias in a non-infarct producing model.

Methods:
Anesthetized open chest rats were exposed to 5 minutes of proximal left coronary artery occlusion and 10 minutes of reperfusion. Rats were either untreated controls (Ctrl, n=17) or received RPC (n=14) with 5 minutes bilateral femoral occlusions followed by 5 minutes of reperfusion times 3, started 30 minutes before coronary occlusion. Reperfusion arrhythmias were quantitated and in some rats Western Blot Analysis for pAKT and p-p70S6 kinase were studied.

Results:
Ischemic risk zone (blue dye technique) was similar in Ctrl (35% of LV) and RPC (32%) as were heart rate and blood pressure throughout the study. At reperfusion, onset of ventricular tachycardia (VT) was delayed in RPC group (45.8 ± 17.1 sec; mean + SEM) versus Ctrl (11.5 ± 3.3 sec; p=0.04). The number of episodes of VT was 18.1 ± 5.1 in Ctrl versus 5.2 ± 1.7 in the RPC group (p=0.01) and duration of VT was 67.2 ± 13.2 sec in Ctrl versus 24.9 ± 11.1 sec in RPC (p=0.019). Sustained VT (≥ 10 sec) occurred in 12 controls and 4 RPC rats (p=0.03); and duration of sustained VT was 40.2 ± 9.9 sec in Ctrl versus 14.6 ± 7.2 sec in RPC (p=0.03). Ventricular fibrillation occurred in 3 controls and 1 RPC rat. Mean number of ventricular premature beats was 38.2 ± 11.4 in Ctrl and 14.1 ± 3.1 in RPC rats (p=0.04). At the end of reperfusion p-Akt level in the risk area in control hearts was 2 times higher compared to the non-ischemic area, and was not different from its level in the risk area in the RPC hearts. In addition, the risk area in both Ctrl and RPC hearts demonstrated no difference in the p-p70S6 kinase level.

Conclusion:
Remote ischemic preconditioning of the lower limbs induced a powerful delay in/and reduction in ischemia/reperfusion induced ventricular arrhythmias, but without evoking the reperfusion injury salvage kinase pathway.
Abstract 96: Favorable Survival of In-Hospital Compared with Out-of-Hospital Refractory Cardiac Arrest Patients Treated with Extracorporeal Membrane Oxygenation: An Italian Tertiary Care Center Experience
Authors: Avalli Leonello , Greco Gianluca , Sangalli Fabio , Galbiati Lucia , Trabucchi Margherita , Formica Francesco , Costa Cristina , Ristagno Giuseppe , Fumagalli Roberto
Published: April 2024

Objective:
Extracorporeal membrane oxygenation (ECMO) support has been suggested to improve survival in patients with refractory in- and out-of-hospital cardiac arrest (IHCA, OHCA). Aim of the present study was to report our experience on the use of ECMO in adult patients with refractory IHCA and OHCA. We have further examined outcome differences between IHCA and OHCA and factors accounting for such differences.

Methods:
Forty-two patients (31 males) with refractory cardiac arrest, 24 IHCA and 18 OHCA, were enrolled in this single centre, retrospective, observational study, from January 2006 to December 2010.

Results:
There was significant difference in the time of no-flow (duration of untreated cardiac arrest) between the OHCA and IHCA patients (p<0.001). The time of low flow (duration of CPR prior to ECMO) was also significantly longer in the OHCA group compared with the IHCA one (77 mins vs 55 mins, p<0.001). ECMO implantation was successful in 38 (90%) of the 42 patients. ECMO support was positioned: 3 times (8%) in the operating room, 6 (16%) in the cardiac surgery intensive care unit, 21 (55%) in the emergency department, 5 (13%) in the catheterization laboratory and 3 (8%) in general ward. A total of 14 IHCA (58%) and 3 OHCA (16%) patients were weaned from ECMO (p<0.05). 11 IHCA (46%) and 1 OHCA (5% p<0.05) were discharged from intensive care unit (ICU). Among IHCA patients, 10 were alive at 6 months, 9 of whom (38%) with good neurological outcome. Among OHCA patients weaned from ECMO, one was alive at six months with good neurological outcome (5%, p<0.05 vs IHCA).

Conclusions:
ECMO support should be considered as a resuscitation alternative in selected patients. More specifically, patients with witnessed IHCA have more benefits from ECMO treatment compared to those who experience an out-of-hospital cardiac arrest.