bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 8437: Volumetric Studies of the Right Ventricle Using Anatomically Accurate Expandable Latex Models
Authors: McAlister Kya , Panosian Jill , Ashraf Muhammad , Sahn David J
Published: April 2024

Background:
Right ventricular (RV) anatomy is far more complex than left ventricular anatomy due to its challenging three-dimensional shape. Recently, TomTec imaging has developed new software known as 4D RV-Function. It is the first software for 3D echo data. This program allows one to study and envisage RV function and RV anatomy.

Methods:
Clay molds were made from the RVs of 5 sheep hearts. Each mold was layered with liquid latex to form a sac of the right ventricle. A hole was cut at the top of each latex RV model and a tube placed within it for attaching to the pulsatile pump. 4D images were acquired using a GE Vivid I9 ultrasound system. The obtained 4D images were then entered into TomTec's 4D RV Function imaging program to execute the volumes.

Results:
At all steady states, there was a good correlation between the volumes from TomTec's 4D RV Function analysis program and the actual volumes that were emptied out of the heart at systole and diastole (R=0.93, p<0.001).

Conclusions:
Volumes of different right ventricle models could be defined quite accurately using TomTec's 4D RV Function program. This will prove useful in the future because it will not only increase diagnostic confidence, but it will ultimately improve the management and treatment of patients with congenital heart disease, heart failure, and pulmonary hypertension.
Abstract 8462: A Crucial Role of Semaphorin3E, an Anti-angiogenic Factor, in the Regulation of Insulin Resistance
Authors: Moriya Junji , Shimizu Ippei , Tateno Kaoru , Okada Sho , Yokoyama Masataka , Nojima Aika , Ito Takashi , Ogasawara Yohko , Komuro Issei , Kobayashi Yoshio , Minamino Tohru
Published: April 2024

The neurovascular-guiding molecules known as semaphorins and their specific receptors (plexins) regulate vascular pattern formation and play an important role in the development of vascular network during embryogenesis. We have recently reported that semaphorin3E (Sema3E), one of the class 3 semaphorins, and its specific receptor plexinD1 negatively regulate postnatal angiogenesis by suppressing the vascular endothelial growth factor signaling pathway. We also found that Sema3E expression was significantly up-regulated via a p53-dependent pathway under ischemia or diabetic conditions and that this up-regulation accounted for impaired angiogenesis of diabetic mice. Although Sema3E was found to play a critical role in the pathogenesis of impaired angiogenesis of diabetes, it remains unclear whether Sema3E is involved in glucose homeostasis. Here we report that the Sema3E/plexinD1 axis is also involved in the regulation of insulin sensitivity and glucose tolerance. First, we found that expression of Sema3E was markedly up-regulated in skeletal muscle and adipose tissue of diabetic mice compared with non-diabetic mice. To examine the effect of Sema3E inhibition on glucose homeostasis in vivo, we treated diabetic mice with plexinD1-Fc that acts as an inhibitor of Sema3E. The results showed that inhibition of Sema3E significantly improved insulin resistance and glucose intolerance compared with vehicle-treated diabetic mice and that this improvement was associated with decreased body weight and visceral fat mass assessed by computed tomography. Moreover, when fed on a high fat/high sucrose diet, Sema3E-deficient mice showed better insulin sensitivity and glucose tolerance than wild-type mice. Conversely, forced expression of Sema3E by gene transfer resulted in impaired glucose tolerance and insulin sensitivity. These results indicate a crucial role for Sema3E not only in the pathogenesis of impaired angiogenesis, but also in glucose homeostasis of diabetes. Inhibition of Sema3E would be a novel strategy for the treatment of insulin resistance as well as impaired angiogenesis of diabetes.
Abstract 8488: PR Interval Prolongation is Associated with Endothelial Dysfunction and Activation of Vascular Repair in High Risk Cardiovascular Patients
Authors: CHAN Yap-Hang , SIU Chung-Wah , YIU Yuen-Fung , YIU Kai-Hang , LI Sheung-Wai , LAM Tai-Hing , LAU Chu-Pak , TSE Hung-Fat
Published: April 2024

Background:
Recent studies showed that PR prolongation is associated with substantially increased risk of adverse clinical outcomes due to unclear mechanisms.

Objective:
To investigate the relations between PR interval and indices of vascular function and endothelial repair in patients at high risk of cardiovascular events.

Methods:
A total of 149 patients (mean age 63.6 ± 10.2 years; male 57%) with prior coronary artery disease, ischemic stroke and / or diabetes mellitus (diagnosed >6 months) were recruited from our medical outpatient clinics. Vascular function was non-invasively measured by flow-mediated dilatation (FMD) using high-resolution vascular ultrasound (Agilent Sonos, USA). CD133+/KDR+ circulating endothelial progenitor cells (EPC) were measured by flow cytometry. PR interval was determined from 12-lead electrocardiogram.

Results:
Mean PR interval was 170±26 ms, with PR prolongation >200 ms present in 14 subjects (9%). Mean FMD was 3.4±2.5%. PR interval was associated negatively with FMD (Pearson R=−0.27,
P=0.001
) but positively with CD133+/KDR+ EPC (Pearson R=0.23,
P=0.006
). Compared with PR interval ≤200ms, patients with PR prolongation >200ms had significantly lower FMD (1.5±1.4% versus 3.6±2.6%,
P=0.003,
Figure 1
) but increased CD133+/KDR+ EPC (log-transformed, unit [x10
−3
/ ml]) (1.05 ± 0.33 versus 0.70 ± 0.41,
P=0.00
3,
Figure 2
). Adjusted for potential confounders by the multivariable model (age, gender, smoking history, systolic and diastolic blood pressure, resting heart rate, serum LDL and HDL- cholesterol, triglycerides, fasting glucose, use of aspirin/ statins), PR prolongation was independently associated with reduced FMD by −1.5% (95%CI [−3.0% to −0.1%],
P=0.039
) and increased CD133+/KDR+ EPC (log, unit [x10
−3
/ ml]) by 0.26 (95%CI [0.05 to 0.48],
P=0.017
).

Conclusions:
PR prolongation is associated with endothelial dysfunction with evidence of endothelial repair activation in high risk cardiovascular patients.
Abstract 8530: Effect of Erythropoietin on Level of Circulating Endothelial Progenitor Cells and Outcome in Patients After Acute Ischemic Stroke
Authors: Yip Hon-Kan
Published: April 2024

Introduction:
Erythropoietin (EPO) enhances circulating level of endothelial progenitor cells (EPCs) which has been reported to be associated with prognostic outcome in ischemic stroke (IS) patients. This study aimed at evaluating the time course of circulating EPC level and the impact of EPO therapy on EPC level and clinical outcome in patients after acute IS.

Methods:
Totally 196 patients were prospectively randomized to receive either EPO therapy (group 1) (5,000 IU each time, subcutaneously) at 48h and 72h after acute IS, or serve as placebo (group 2). Circulating level of EPCs [double-stained markers: CD31/CD34 (E
1
), CD62E/CD34 (E
2
) and KDR/CD34 (E
3
)] was determined using flow cytometry at 48h and on days 7 and 21 after IS. EPC level was also evaluated once in 60 healthy volunteers.

Results:
Circulating EPC (E
1
−E
3
) level at 48h after IS

was remarkably higher in patients than in control subjects (p<0.02). At 48h and on day 7 after IS, EPC (E
1
−E
3
) level did not differ between groups 1 and 2 (all p>0.1). However, by day 21, EPC (E
1
−E
3
) level was significantly higher in group 1 than in group 2 (all p<0.03). Additionally, 90-day recurrent stroke rate was notably lower in group 1 compared with group 2 (p=0.022). Multivariate analysis demonstrated that EPO therapy [95% confidence interval (CI), 0.153 to 0.730; p=0.006] and EPC (E3) (95% CI, 0.341 to 0.997; p=0.049) level were significantly and independently predictive of reduced 90-day major adverse neurological event (MANE) (defined as recurrent stroke, National Institutes of Health Stroke scale≥8, or death).

Conclusions:
EPO therapy significantly improved circulating EPC level and 90-day MANE (The following Figure shows the schematic overview of the trial protocol).
Abstract 8537: Twice Daily Dosing of Aspirin Ii Biologically More Effective in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease
Authors: Dillinger Jean-Guillaume , Drissa Akram , Sideris Georgios , Bal-Dit-Solier Claire , Voicu Sebastian , Drouet Ludovi , Henry Patrick
Published: April 2024

Background
The efficacy of aspirin in preventing cardiovascular events appears to be lower in DM patients than in general population. We have previously demonstrated a time-dependent aspirin efficacy suggesting that once daily aspirin does not provide 24h stable biological efficacy, mainly in patients with DM, inflammatory markers and active smokers.

Objective:
To compare biological efficacy of 150 mg/day aspirin given once daily (OPD) as compared to 150mg/day divided in 75 mg in the morning and 75 mg in the evening (BID) in a cross over study in patients with DM.

Methods:
A randomized monocentric prospective study with cross over is realized in 92 patients with DM and previous acute coronary syndrome with high risk of biological aspirin resistance (elevated hsCRP, elevated fibrinogen or current smoking). Blood samples are analyzed the morning just before aspirin intake in a blinded fashion. Primary endpoint is the percentage of aspirin resistant patients measured by light transmission aggregometry using arachidonic acid 0.5mg/mL (LTA-AA). PFA-100 testing, using epinephrine cartridges is also performed. Patients are considered resistant if aggregation is ≥20% with LTA-AA or if PFA-100 epinephrine closure time was ≤193 seconds.

Results:
Mean HbA1c is 7.4%±1.2% and 43% of patients are treated with insulin. Mean age is 64±10 y.o., 85% are male, 34% are active smokers and 52% are treated with clopidogrel. There is no difference in mean platelet count (270±78G/L), fibrinogen (3.6±1.0g/L) and hsCRP (5.5±6.9mg/L). Using LTA-AA, mean residual aggregation was 19.7±15.4% on OPD versus 11.9±10.4% on BID (p<0.001). Biological aspirin resistance (residual aggregation ≥ 20%) significantly decrease from 42% on OPD to 17% on BID corresponding to a decrease of 62% (p=0.0005). Interestingly, 24 patients resistant on OPD became sensitive on BID. Inversely, only one patient resistant on BID become sensitive on BID. Based on PFA-100, 41% of patients were resistant on OPD versus 29% on BID (p=0.12). Similar results are found in patients with or without clopidogrel.

Conclusions
In diabetic patients with elevated inflammatory markers or active smoking, the same dose of aspirin BID is biologically more effective than OPD.
Abstract 8573: L-carnitine Prevents Heart Failure with Preserved Ejection Fraction in Associated with Attenuation of Cardiac Fibrosis
Authors: Omori Yosuke , Ohtani Tomohito , Sakata Yasushi , Mano Toshiaki , Takeda Yasuharu , Tamaki Shunsuke , Tsukamoto Yasumasa , Kamimura Daisuke , Aizawa Yoshihiro , Ikeya Yukitoshi , Miwa Takeshi , Soga Tomoyoshi , Yamamoto Kazuhiro , Komuro Issei
Published: April 2024

Backgrounds:
Prognosis of heart failure with preserved ejection fraction (HFpEF) has not been improved because of unknown pathophysiology and unestablished therapeutic strategy. Cardiac fibrosis is known to play a crucial role in the development of HFpEF.

Methods and Results:
The comprehensive and quantitative analysis of metabolites with capillary electrophoresis time-of-flight mass spectrometry was conducted to find a substance which may be related to the development of HFpEF, and revealed decreased plasma free-carnitine levels in Dahl salt-sensitive rats (DSR) fed high-salt diet, a model of hypertensive HFpEF. We confirmed this result with enzymatic cycling method by showing decreased plasma and left ventricular (LV) free-carnitine levels with increased urinary free-carnitine excretion in HFpEF rats compared to control DSR fed normal chow. We also found that blood free-carnitine levels were decreased in HFpEF patients compared to age-matched normal volunteers. Expression of organic cation/carnitine transporter 2, which transports free-carnitine into cells, was decreased in the LV and kidney of HFpEF rats. L-carnitine administration to HFpEF rats increased plasma and LV levels of free-carnitine, and prevented HFpEF with decreased myocardial stiffness constant and decreased area of LV fibrosis. In cultured cardiac fibroblasts, L-carnitine attenuated the angiotensin II-induced increase in
3
H-proline incorporation. L-carnitine increased prostacyclin production and expression of fatty acid desaturase 1/2, rate-limiting enzymes in forming arachidonic acid, in the LV of DSR and cultured cardiac fibroblasts. LV arachidonic acid levels were increased in HFpEF rats by L-carnitine administration.

Conclusions:
L-carnitine may be effective in the prevention of HFpEF through enhanced production of prostacyclin and prevention of LV fibrosis and stiffening. L-carnitine supplementation may become a therapeutic option for HFpEF.
Abstract 8592: Cross-Talk Between the Toll-Like Receptor 4 and Notch1 Pathways Augments the Inflammatory Response to Endotoxin in the Interstitial Cells of Stenotic Human Aortic Valves
Authors: Zeng Qingchun , Jin Chunhua , Ao Lihua , Lee Joon , Cleveland Joseph C , Fullerton David A , Meng Xianzhong
Published: April 2024

Due to limited knowledge of the mechanisms of aortic valve stenosis, pharmacological intervention of this cardiovascular disease remains unavailable. Aortic valve stenosis is a chronic inflammatory disease, and aortic valve interstitial cells (AVICs) play an important role in the valvular inflammatory response. Oral bacteria have been found in stenotic aortic valve leaflets, and we recently found that stimulation of TLR4 in human AVICs induces the expression of ICAM-1 and BMP-2. While AVICs from stenotic aortic valves has an enhanced response to the TLR4 agonist endotoxin, the mechanism underlying the enhanced response is unknown. Activated Notch1 is found to modulate NF-κB activity in human leukemic T-cells, and endotoxin induces Notch1 activation in cultured macrophages. We tested the
hypothesis
that xcessive cross-talk between the TLR4 and Notch1 pathways augments the inflammatory response to endotoxin in diseased AVICs. The
purposes
of this study were to investigate: 1) whether TLR4 stimulation results in enhanced Notch1 activation in diseased AVICs, 2) whether inhibition of Notch1 attenuates the inflammatory response to TLR4 stimulation in diseased cells and 3) whether activation of Notch1 augments the inflammatory response to TLR4 stimulation in healthy AVICs.

Methods and results:
Human AVICs were isolated from normal and stenotic aortic valve leaflets. IL-6, MCP-1 and ICAM-1 were analyzed following treatment with endotoxin. Cells from diseased valves produced greater levels of cytokines and ICAM-1, and exhibited enhanced Jagged1 release and Notch1 activation after TLR4 stimulation. Inhibition of Notch1 greatly reduced the inflammatory response in diseased cells. Stimulation of Notch1 with Jagged1 or over-expression of Notch1 intracellular domain in healthy AVICs enhanced the production of cytokines and ICAM-1 induced by TLR4 stimulation.

Conclusion:
Notch1 enhances the inflammatory response to TLR4 stimulation in human AVICs. Excessive crosstalk between the TLR4 and Notch1 pathways is responsible, at least in part, for the augmentation of the inflammatory response to TLR4 agonist in AVICs of stenotic aortic valves. The Notch1 and TLR4 pathways could be therapeutic targets for regulation of aortic valve inflammatory response.
Abstract 8594: Rapid ST-upslope on Exercise Electrocardiogram Predicts Reduced Long Term Mortality from Coronary Heart Disease.
Authors: Hodnesdal Christian , Prestgaard Erik , Erikssen Gunnar , Gjesdal Knut , Kjeldsen Sverre , Liestol Knut , Skretteberg Per Torger , Erikssen Jan , Bodegard Johan
Published: April 2024

Aims
The prognostic value of a rapid ST-upslope on exercise electrocardiogram (ECG) is unknown among healthy individuals, but it may be associated with a well-balanced control of the autonomic nervous system. We aim to test the hypothesis that rapid ST-upslope is associated with reduced risk of dying from coronary heart disease (CHD).

Methods and results
A group of healthy middle-aged men (n=2014) participated in a cardiovascular survey examination. They underwent an examination program including a symptom limited ECG bicycle exercise test. Exercise induced ST- segments were categorized in three groups: normal ST-segment (n=1383), rapid ST- upslope (n=401) and ST-depression (n=230). Survival analyses were adjusted for smoking status, total cholesterol, systolic blood pressure, maximal heart rate, and physical fitness. The rapid ST-upslope group was associated with a 30% decreased risk of CHD-death (Hazard Ratio (HR) = 0.70 [95%CI 0.51-0.95]) compared to the normal ST-segment group (see image below). The risk of CVD-death was numerically lower in the rapid ST-upslope group (0.82 [95%CI 0.65-1.04]) compared to the normal ST-segment group. The ST-depression group was associated with a 1.45-fold (HR = 1.45 [95%CI 1.09-1.90]) increased risk of CHD-death compared to the normal ST-segment group.

Conclusions
The rapid ST-upslope on exercise ECG was a common finding (20%) among healthy middle aged men and was associated with a 30% reduced risk of dying from CHD compared to individuals with normal ST-segment. We suggest that rapid ST-upslope on exercise ECG is the true healthy state.
Abstract 8596: Reproducibilty of the Syntax Score (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) in a Real World Setting: Implications for the Choice of Contemporary Revascularisation Strategy
Authors: Savage Henry O , Gerber Robert T , Tang Kare , Sachdev Bhavesh , Cole Graham , Watson Geoffrey , Patterson Tiffany , Assomoll Ravi , Noor Badhusha , Sharp Andrew S , Ali Aamir , Khamis Ramzi , Francis Darryl
Published: April 2024

INTRODUCTION:
The two year results from the Syntax study indicate that percutaneous coronary intervention (PCI) may be an acceptable alternative to CABG in subjects with a low (<22) and intermediate (23-32) Syntax Score (SS). Patients with high SS (≥33) appear to have worse outcome from PCI. It has been suggested that CABG should remain the treatment in this cohort. The Syntax investigators report good reproducibility for the SS; however, the inter and intra operator variability has not been tested outside the core lab environment. This is pertinent as more cardiac multidisciplinary meetings (MDT) are using the SS to help guide revascularization strategy.

METHODS:
20 patients presented at our MDT were randomly selected and 11 cardiologists of differing experience independently scored these angiograms on two separate occasions, after completing the teaching module at www.syntaxscore.com.

RESULTS:
There was wide variation in SS for each angiogram with 8.4±1.3 min required per SS (Figure). Moreover, variation did not conform over the two sittings to operator experience or to lesion complexity (Mean Difference between scores per operator 9±4). The total mean scores from all operators were taken as a gold standard result with respect to tertile allocation. Operators allocated 50% of patients to a different tertile, with only 2 patients placed by all operators in the same tertile of risk. Additionally, at the second sitting the same operators cast the same angiogram into a different tertile of risk from their original assessment on 46% of occasions.

CONCLUSION:
Syntax scoring in a real world MDT setting was not reproducible and demonstrated significant intra and inter operator variability between subjects. MDT discussions incorporating this score should be aware of this and weigh the significance of the score accordingly when forming decisions about revascularization strategy.
Abstract 8638: Acute Massive Mitral Regurgitation Due to Rapture of Chordae Tendineae Affects Infants with High Rates of Mortality and Morbidity: Results From a Japanese Nationwide Survey
Authors: Shiraishi Isao , Sakaguchi Heima , Kitano Masataka , Kurosaki Kenichi , Yamada Osamu , Ikeda Yoshihiko , Morisaki Takayuki , Sagawa Koichi , Yamagishi Hiroyuki , Kato Hitoshi , Nakanishi Toshio , Hoashi Takaya , Kagisaki Koji , Ichikawa Hajime
Published: April 2024

Introduction:
Acute massive mitral insufficiency due to rupture of chordae tendineae is a rare but sometimes fatal condition in children. Serious symptoms such as dyspnea or cyanosis suddenly appear in healthy children. Although early diagnosis and appropriate medical and surgical treatments are necessary, this disease has not been well summarized in literatures and has not been well recognized by general pediatricians, either. Since the number of reported cases has been recently increasing in Japan, we have developed a nationwide survey of the disease.

Hypothesis:
We assessed the hypothesis that a Japanese nationwide survey clarifies etiology, clinical characteristics, treatments, and prognosis of the disease.

Method:
A questionnaire was sent to 511 pediatric institutes in Japan to unveil clinical and laboratory findings, surgical procedures, and prognosis of the patients during the recent 10 years.

Results:
A total of 88 children's data were analyzed. Males and females were 49 and 39, respectively. The number of patients was increasing during the recent 5 years (peaked in 2009, 17 cases). The age at onset mainly ranged from 4 to 6 months (68 cases, 77%) with a median at 5 months. The average body weight at birth and at onset was 2.97+/-0.48kg and 6.83+/-1.19kg, respectively. Seven patients had a history of Kawasaki disease. Maternal-derived serum anti-SSA antibody was detected in 2 patients. Average values of WBC, CRP, and cardio-thoracic ratio at diagnosis were 17,040+/-8,210/uL and 2.53+/-2.83mg/dl, and 55.4+/-5.8%, respectively. Forty-five patients (51%) underwent mitral valve repair and 25 patients (28%) underwent mitral valve replacement. Histopathological examinations of the mitral tissue were performed in 21 cases, showing mononuclear cell infiltration in 10 cases (48%) and myxoid change in 7 cases (33%). Six patients (6.8%) died before (4 cases) and after (2 cases) surgical operation. Moderate to severe brain damage remained in 10 patients (11%).

Conclusions:
Acute rupture of mitral chordae tendineae affects infants with high rates of mortality and morbidity. Since the incidence is recently increasing, precise recognition, early diagnosis, and appropriate medical and surgical treatments are strongly recommended.
Abstract 8710: A Crucial Role of Nox2 In Middle-Age Obese-Related Hyperglycaemia and Endothelial Dysfunction in Mice
Authors: Du Junjie , Li Jian-mei
Published: April 2024

Middle-age obese is often associated with multiple organ oxidative stress and is a major risk factor for the development of cardiovascular diseases. In this study, we investigated the role of Nox2, a superoxide-generating enzyme, in a mouse model of high fat diet-induced middle-age metabolic disorders and vascular dysfunction. Littermates of C57BL/J6 wild-type and Nox2 knockout mice (7 m old, n=10) were fed with high fat diet (HFD, 45% kcal fat, 20% kcal protein and 35% kcal carbohydrate) or normal chow diet (NCD, 12% kcal fat, 28% kcal protein and 60% kcal carbohydrate) for 16 weeks, and were used at 11 m of age Compared to age-matched NCD-fed mice, wild-type mice fed with HFD showed significant increases in body weight (NCD 42±2.3 vs HFD 56±3.2g) and the levels of fasting glucose (NCD 7.4±3.3 vs HFD 8.8±2.2 mM). These metabolic changes were accompanied by significant increases (42±5%) in NADPH-dependent ROS production by aortas as measured by lucigenin-chemiluminescence, and a decrease in endothelium-dependent vessel relaxation to acetylcholine (Emax NCD 80.45±7.39% vs HFD 74.41±1.74%) as assessed by an organ bath. The systolic BP was also significantly elevated (NFD 127±8 vs HFD 142±12mmHg) (all P<0.05). Compared to WT mice, Nox2 knockout mice fed with HFD had similar scale of increase in body weight (NCD 38±3.6 vs HFD 49±2.6g, P<0.05). However, there was no significant increase in the levels of fasting glucose (NCD 7.5±0.8 vs HFD 6.7±1.5 mM). The aortic NADPH-dependent ROS production remained unchanged and the endothelium- dependent vessel relaxation to acetylcholine was well preserved (Emax NCD 80.53±11.3 vs HFD 78.18±5.6%). There was no significant increase in systolic BP (NCD 123±14 vs HFD130±9mmHg) in HFD-fed Nox2 knockout mice. In conclusion, Nox2 and Nox2-derived ROS play a key role in mediating dietary obesity-related hyperglycaemia and endothelial dysfunction after middle-age, and Nox2 may present a therapeutic target for the prevention and treatment of these diseases.
Abstract 8715: Multidirectional Left Ventricular Performance Using Three-Dimensional Speckle-Tracking Strain in Patients with Chronic Right Ventricular Pacing and Preserved Ejection Function
Authors: Tanaka Hidekazu , Matsumoto Kensuke , Tatsumi Kazuhiro , Hiraishi Mana , Miyoshi Tatsuya , Kaneko Akihiro , Tsuji Takayuki , Ryo Keiko , Fukuda Yuko , Kawai HIroya , Hirata Ken-ichi
Published: April 2024

Background:
Right ventricular (RV) pacing has a detrimental effect on global left ventricular (LV) function even in some patients with preserved ejection fraction (EF), but its mechanism remains unclear. Our objective was to evaluate early subtle changes by chronic RV pacing in patients with preserved EF using novel three-dimensional (3-D) speckle-tracking strain.

Methods:
We studied 112 subjects; 52 patients with chronic RV pacing and preserved EF (all ≥ 50%), an EF-matched 20 normal controls, and 30 heart failure (HF) patients with chronic RV pacing and reduced EF (all≤35%). Radial, circumferential and longitudinal dyssynchrony and function were quantified as standard deviation of time-to-peak strain and global peak strain using 3-D speckle-tracking strain from all 16 LV segments (Aplio Artida, Toshiba Corp.).

Results:
The degree of radial and circumferential dyssynchrony and function in patients with chronic RV pacing and preserved EF and controls were similar (radial dyssynchrony: 28±20ms vs. 26±19ms, circumferential dyssynchrony: 31±14ms vs. 29±14ms, and global radial strain: 37±20% vs. 39±12%, global circumferential strain: 27±14% vs. 30±11%, respectively). Patients with chronic RV pacing and preserved EF, however, had greater longitudinal dyssynchrony with 42±22ms vs. 27±13ms, and lower global longitudinal strain with 21±13% vs. 30±19% compared to controls (both p<0.05). Furthermore, longitudinal strain in septum was significantly lower than that in posterior-lateral wall (19±9% vs. 27±10%, p<0.05), and longitudinal dyssynchrony at apex was significantly larger compared to mid and basal level (51±14ms vs. 40±9ms and 38±8ms, p<0.05) in patients with chronic RV pacing and preserved EF. In contrast, HF patients with chronic RV pacing and reduced EF had greater radial, circumferential and longitudinal dyssynchrony, and lower global radial, circumferential and longitudinal strain compared to controls (all p<0.001).

Conclusion:
Longitudinal dyssynchrony was observed in patients with chronic RV pacing and preserved EF with impaired longitudinal function. 3-D speckle-tracking strain was useful at evaluating early subtle changes by chronic RV pacing, and may play a clinical role at predicting future global LV dysfunction.
Abstract 8773: Aborted Sudden Cardiac Death in Patients with Early Repolarization on Electrocardiography in Japanese Population
Authors: Maeda Shingo , Yamauchi Yasuteru , Okada Hiroyuki , Tao Susumu , Kagiyama Nobuyuki , Naito Takaki , Yamaguchi Tetsuo , Hara Nobuhiro , Konishi Yuji , Umemoto Tomoyuki , Miyamoto Takamichi , Obayashi Tohru , Suzaki Shinichiro , Hirao Kenzo , Isobe Mitsuaki
Published: April 2024

Background:
It is well known that an early-repolarization (ER) pattern in the inferior or lateral precordial leads is associated with ventricular fibrillation (VF). This study aimed to investigate the characteristics of the ER pattern during electrocardiography in resuscitated cardiopulmonary arrest (CPA) patients.

Methods:
This study included 1,951 consecutive CPA patients who were carried in our emergency room between January 2009 and June 2010. The patients were eligible for enrollment, if they had experienced an unexplained cardiac arrest (with documented cardiovascular collapse with ventricular tachycardia or VF) that required cardiopulmonary resuscitation to restore sinus rhythm. The ER patterns were evaluated for the presence of early repolarization in the inferior and lateral leads. Early-repolarization patterns were stratified according to the degree of the J-point elevation (≥ 0.1 mV or > 0.2 mV) that was either notched (a positive J deflection inscribed on the S wave) or slurred (a smooth transition from QRS to ST-segment) in at least two consecutive inferior or lateral leads.

Results:
Forty-one patients were successfully resuscitated. ST elevation of more than 0.1mV was observed in 17 patients (41%), (mean age = 61 ± 20 years, 3 female): 14 (34%) in the inferior leads and 3 (7%) in the lateral leads. In these subjects, 10 had structural heart disease (group-S) and 7 were diagnosed with ER syndrome (group-ER). A slurred J-point elevation was more often recorded in group-ER and notched J-point elevation more often in group-S (p < 0.05). Further, the magnitude of the J-point elevation was significantly higher in group-ER than in group-S (1.7 ± 0.6 vs. 1.2 ± 0.3 mV, p < 0.05). The degree of the slurred J-point elevation decreased two days after hospitalization in group-ER. There were no significant differences in the other parameters between the two groups.

Conclusion:
A slurred and higher J-point elevation might be associated with increased risk of sudden cardiac death in ER syndrome.
Abstract 8809: Time Course of Appropriate ICD Therapy in Patients from the OMNI Registry: Implications for Duration of Driving Restriction.
Authors: Kim Michael H , Yang Fang , Sakaguchi Scott , Goldberger Jeffrey J
Published: April 2024

Intro:
AHA/HRS recommendations restrict driving in ICD patients (pts) for 6 months after implant for secondary prevention (SP) or primary prevention (PP) with an appropriate therapy (AT: antitachycardia pacing or shock) for ventricular arrhythmias (VA). Data supporting this are limited.

Methods:
The OMNI Registry was queried for appropriate ICD therapies for VA and assessed for the time course to first AT and appropriate shock (AS). Time to 2
nd
and 3
rd
AT/AS was recorded in the overall group and selected subgroups: 1) syncope (S) vs no S (NS); 2) PP vs SP. Episodes were adjudicated by a blinded events committee.

Results:
2255 Pts, mean age 67 years (73 % M), mean LVEF 28 % were enrolled. Pts included both PP (74 %) and SP (26 %). S occurred in 22 % of pts prior to implant. Overall, 624/2255 pts (27.7 %) received a first AT in a mean of 13 ± 13 months post-implant. Of these, a 2
nd
or 3
rd
AT (AT2 or AT3, respectively) occurred in a mean of 5.4 ± 8.1 months (AT2 after AT1; 387/624; 62 %) and 3.1 ± 6.2 months (AT3 after AT2; 285/387; 74 %). 326/2255 pts (14.5 %) received a first AS (AS1) in a mean of 14.8 ± 13.7 months. 182/326 pts (56 %) had a second AS (AS2) in a mean of 4.1 ± 7.2 months; 117/182 pts (64 %) had a third AS (AS3) in a mean of 3.2 ± 7.1 months. In pts with S vs NS, both incidence and time to AT1/AS1 were similar. Rates of further AT/AS events were also similar with AS2 occurring at 4 months for both S and NS. Pts implanted for SP received both AT1 (mean 11 vs 14.3 months) and AS1 (mean 11.8 vs 16.6 months) earlier than PP pts. SP pts had higher rates of AT/AS after the first AT/AS (SP vs PP: AT2 70 % vs 58 %; AS2 72 % vs 47 %). In both PP and SP, AS2 occurred in about 4 months.

Conclusions:
In this real world sample of ICD pts, guideline recommended 6 month driving restrictions appear more reasonable when applied after AS1 than AT1. Measured over the first 3 VA events, each VA increases the risk of a subsequent VA, and decreases the mean time to the subsequent VA. Such pts may require stricter driving restrictions than pts after a first VA event.
Abstract 8829: The Disruption of Natural Killer T Cell Exacerbates Cardiac Hypertrophy and Heart Failure Due to Pressure Overload in Mice
Authors: Takahashi Masashige , Fukushima Arata , Homma Tsuneaki , Sobirin Mochamad A , Suga Tadashi , Takada Shingo , Ono Taisuke , Masaki Yoshihiro , Kadoguchi Tomoyasu , Yokota Takashi , Kinugawa Shintaro , Tsutsui Hiroyuki
Published: April 2024

Background
Chronic inflammation has been reported to be involved in the development of cardiac remodeling and failure. Natural killer T (NKT) cells, a subset of T lymphocytes, have capacity to produce various inflammatory cytokines and orchestrate tissue inflammation. Our previous study demonstrated that the pharmacological activation of NKT cells attenuated the development of heart failure (HF), which was mediated by the enhanced expression of interleukin-10. However, no previous studies have examined the pathophysiological role of NKT cells in pressure overload-induced HF. We thus hypothesized that the disruption of NKT cell could exacerbate cardiac hypertrophy and HF after pressure overload in mice.

Methods
Transverse aortic constriction (TAC) operation was performed in male C57BL/6J wild-type(WT) and NKT cell knockout (KO) mice, and sham operation was also performed; WT+Sham (n=5), KO+sham (n=5), WT+TAC (n=29), and KO+TAC (n=34). After 14 days, echocardiography was performed, and gene expressions in left ventricle (LV) tissues were quantified by RT-PCR.

Results
Survival rate during 28 days was significantly lower in KO+TAC than WT+TAC (16% vs. 61%, P<0.05), and no mice died in sham groups. NKT cell receptor was increased by 60% in LV from TAC compared to Sham at 14days. LV end-diastolic dimension (4.60±0.14vs3.57±0.08 mm, p<0.05) were greater, and LV fractional shortening (17.1±0.8 vs 30.4±4.3 %, p<0.05) was lower in KO+TAC than in WT+TAC. LV weight and lung weight/body weight were significantly lower in KO+TAC than in WT+TAC. No such changes were observed in either WT+Sham or KO+Sham. In parallel, myocyte cross-sectional area and collagen volume fraction were greater in KO+TAC than in WT+TAC. Interleukin-10 (IL-10) mRNA expression was completely abolished in KO+TAC compared to TAC.

Conclusions
The disruption of NKT cell exacerbated the development of HF after TAC through the diminished expression of cardioprotective cytokine, IL-10. NKT cells play a critical role in the development of pressure-overload hypertrophy and failure.
Abstract 8831: Micro RNA Could Play Key Roles in Progression of Myocardial Fibrosis in Patients with Heart Failure
Authors: Kinoshita Kohsuke , Izawa Hideo , Kato Yasuchika , Yokoi Hiroatsu , Fujiwara Wakaya , Cheng Xian Wu , Hirashiki Akihiro , Mizoguchi Yoshikazu , Ohtsuki Masatsugu , Ishii Jun-ichi , Morimoto Shin-ichiro , Murohara Toyoaki , Ozaki Yukio , Nomura Masanori
Published: April 2024

Purpose:
MicroRNAs (miRNAs) are recently discovered, posttranscriptional regulators of gene expression. Roles of miRNAs in the development of heart failure are largely unknown. Myocardial fibrosis had been fully demonstrated to be involved in pathogenesis of heart failure. However, the molecular mechanisms that underlie myocardial fibrosis remain incompletely understood. We hypothesized that miRNAs might play key roles in the pathogenesis of myocardial fibrosis in patients with heart failure, resulting in progression of heart failure.

Methods:
This study comprised of 22 patients with idiopathic dilated cardiomyopathy (DCM). We first performed a genome-wide miRNA expression profiling for a total of 650 miRNAs using endomyocardial biopsy specimens obtained from 8 patients. We used the median value of collagen volume fraction (CVF) in endomyocardial biopsy specimens as cutoff to divide these 8 patients into 2 groups. From this screening study, we selected 7 miRNAs related to myocardial fibrosis. We then performed real-time PCR in endomyocardial biopsy specimens from remaining 14 patients with DCM to quantify these 7 miRNAs expressions.

Results:
In the first screening study, 7 miRNAs were differentially expressed significantly (p < 0.01) in 4 patients with severe myocardial fibrosis compared with 4 patients with less severe myocardial fibrosis (CVF: 4.4 ± 0.9 vs. 2.3 ± 0.3 %, respectively). The real-time PCR in endomyocardial biopsy specimens from remaining 14 patients with DCM revealed that expressions of miRNA-1, miRNA-23, miRNA-210, and miRNA-624 were significantly reduced in 7 patients with severe fibrosis compared with 7 with less severe fibrosis (CVF: 5.8 ± 1.3 vs. 2.0 ± 1.0 %, respectively).

Conclusion:
We demonstrated that 4 specific miRNAs could play key roles in myocardial fibrosis in patients with DCM. These findings could provide insight into a key conundrum that pervades pathogenesis of heart failure.
Abstract 8844: 10-Year Mortality is Very High, and Warfarin Use Very Low, in Patients with Myocardial Infarction and Atrial Fibrillation
Authors: Vavalle John P , Lopes Renato , May Christopher H , Starr Aijing Z , Shaw Linda K , Mehta Rajendra H , Al-Khatib Sana M , Alexander John H , Granger Christopher B
Published: April 2024

Background:
Patients hospitalized for myocardial infarction (MI) who have atrial fibrillation (AF) are recommended to use warfarin for stroke prophylaxis if CHADS
2
score ≥ 2. The long-term use of warfarin in these patients and associated outcomes are not well known. Herein, we describe the use of warfarin out to one year after hospitalization and identify predictors of 10-year mortality in this population.

Methods:
Patients with acute MI (STEMI and NSTEMI) and AF during hospitalization undergoing cardiac catheterization between January 1, 2005 and December 31, 2007 were identified from the Duke Databank for Cardiovascular Disease. Anti-thrombotic medication use at 6 months and 1 year was assessed by mailed and telephone surveys. Multivariable Cox proportional hazards modeling was used to identify predictors of 10-year mortality.

Results:
A total of 882 patients were identified with a median age of 72 years (64, 79). The use of warfarin was low at discharge (24%), and increased only slightly at 6 months (26%), and one year (27%), despite decreasing clopidogrel use and stable aspirin use over that time (
Figure 1
). With a higher CHADS
2
score, warfarin use increased (CHADS
2
0, 18%; CHADS
2
1, 21%; CHADS
2
≥2, 27%; p=0.06). In general, patients who received warfarin at discharge had similar baseline characteristics compared with those who did not. The 10-year mortality rate in this study was high and similar regardless of whether warfarin was (71.0%) or was not (70.7%) used at discharge (p=0.12). The strongest predictors of 10-year mortality in this population were: older age (HR 1.44 per 10 year, 95% CI 1.31-1.59), history of heart failure (HR 1.63, 95% CI 1.35-1.97), and higher Charlson comorbidity index (HR 1.19, 95% CI 1.11-1.27).

Conclusions:
Patients with MI and AF have high 10-year mortality. The use of warfarin was low, even among patients with high CHADS
2
score, remained low out to one year after discharge, and is not explained by the use of alternative antithrombotic regimens.
Abstract 8884: Predictors of Adverse Effects on Coronary Artery Bypass Surgery for Patients with Previous History of Cerebrovascular Accident
Authors: Oi Keiji , Miyata Hiroaki , Motomura Noboru , Sakata Ryuzo , Yoshida Tetsuya , Yokoyama Kenji , Takeshita Masashi , Takamoto Shinichi
Published: April 2024

Background:
Past history of cerebrovascular accident (CVA) is a serious risk factor for increased mortality and morbidity, such as CVA recurrence, after coronary artery bypass grafting (CABG). Purpose of this study is to elucidate the independent predictors of adverse outcomes after CABG among the population with CVA history using a national database.

Methods and Results:
Patient data were acquired and analyzed from Japan Cardiovascular Surgery Database (JCVSD) registry. 13109 patients undergoing isolated CABG between January 2008 and December 2009 were enrolled in the JCVSD registry. Of these, all the patients with CVA history were included in the analysis as study group (SG; n = 1695). Postoperative CVA occurred in 6.0% (102/1695) of SG and 2.8% (318/11414) of patients without CVA history (Control) (P<.001). Operative mortality of SG and Control were 2.9% and 1.9%, respectively (P=.008). Major morbidity and mortality of SG and control were 17.4% and 12.2%, respectively (P<.001). Multivariate analysis of SG identified five independent preoperative predictors for the CVA recurrence, eight for the operative mortality and 12 for the major morbidity and mortality. The analysis also identified two independent operative predictors for the CVA recurrence, four for the operative mortality and six for the major morbidity and mortality. The table shows the predictors of these adverse effects.

Conclusions:
Independent predictors of CVA recurrence, major morbidity and mortality were identified through subgroup analysis of the JCVSD registry. Patients who suffered CVA recurrence or other adverse effects had a greater prevalence of concomitant medical illnesses. In conclusion, use of internal mammary artery, off-pump CABG, otherwise shorter cardiopulmonary bypass time, shorter operation time and optimal numbers of distal anastomoses are effective in reducing the risk of CVA recurrence or other adverse effects on CABG for patients with CVA history.
Abstract 8885: Prognostic Significance of Dyspnea versus Chest Pain in Patients Referred for Stress Echocardiography
Authors: Yao Siu-Sun , Agarwal Vikram , Chaudhry Farooq A
Published: April 2024

Background:
Stress echo (SEcho) is an established modality for diagnosis and risk stratification of patients with known or suspected coronary artery disease. The purpose of this study was to examine the prognostic significance of dyspnea versus chest pain in patients referred for SEcho.

Methods:
We evaluated 1335 patients (63 ± 13 years; 40% male) undergoing SEcho (49% treadmill, 51% dobutamine). Resting left ventricular ejection fraction and regional wall motion were assessed. The left ventricle was divided into 16 segments and scored on 5-point scale of wall motion. Abnormal SEcho was defined as stress-induced ischemia (wall-motion score of ≥1 grade). Followup (3.5 ± 1.5 years) for non-fatal myocardial infarction (n = 42) and cardiac death (n = 39) were obtained.

Results:
By univariate analysis, both number of new ischemic wall motion abnormalities (p<0.0001) and ejection fraction (p<0.0001) were significant predictors of cardiac events. Cumulative survival was signficantly worse in patients with dyspnea vs. chest pain (2.3%/year vs. 1.4%/year, p=0.02). SEcho was further able to risk stratify normal (n = 289) vs. abnormal (n = 155) groups for dyspnea (1.0%/year vs. 4.4%/year; p < 0.001), and normal (n = 608) vs. abnormal (n = 283) groups for chest pain (0.8%/year vs. 2.9%/year; p < 0.001)(Figure). Multivariate logistic regression analysis identified number of new ischemic wall motion abnormalities as the strongest predictor of cardiac events (RR 1.7, 95% CI 1.0-2.9, p<0.05).

Conclusions:
In patients referred for stress echocardiography, self-reported dyspnea identified a group of patients at increased risk for cardiac events. Stress echocardiography results (normal or abnormal) was further able to risk stratify both dyspnea and chest pain subgroups. Assessment of dyspnea should be incorporated into routine clinical evaluation of patients referred for stress echocardiography.
Abstract 8888: Statin Therapy In Patients with Chronic Kidney Disease Undergoing Percutaneous Coronary Interventions Is Associated with Better One Year Outcomes. An Analysis from the Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) Registry
Authors: Dasari Tarun W , Cohen David J , Kleiman Neal S , Keyes Michelle J , Hanna Elias B , Saucedo Jorge F
Published: April 2024

Background:
Primary and secondary prevention trials have shown that statin therapy reduces cardiovascular morbidity and mortality in patients with coronary artery disease. However, there has been a paucity of data concerning the benefits of statin use in patients with advanced chronic kidney disease (CKD) since they have been excluded from most trials.

Methods and results:
Of 10,148 patients entered into EVENT, a multicenter registry of unselected patients undergoing attempted PCI from July 2004- December 2007, we studied 2313 patients with advanced CKD (estimated glomerular filtration rate < 60 mL/min based on the Modified Diet in Renal Disease calculation). Patients were stratified into those discharged on statins (n=1837, 79%) or not receiving statins at discharge (n=476, 21%). Patients discharged on statins were more often male and had higher prevalence of hypertension, recent myocardial infarction (MI) and greater use of beta blockers. One year mortality was 5.7% among statin users vs. 8.7% among non-users (HR 0.65; 95% CI: 0.45-0.93). When adjusted for covariates (age, gender, hypertension, recent MI (< 7 days), ejection fraction, NYHA Class and medical therapy differences at discharge (warfarin, beta blockers, ACEi), one year all-cause mortality and composite end point of death/MI/repeat revascularization favored statin (HR 0.55 [0.34, 0.88] and 0.71 [0.51, 0.99] respectively).

Conclusion:
The proportion of patients with advanced CKD not discharged on statins post PCI is still high (21%). The current registry analysis showed favorable one year survival in patients discharged on statins following percutaneous coronary intervention in patients with advanced CKD, suggesting the need to investigate broader statin use in this clinical setting.
Abstract 8893: High Purity Eicosapentaenoic Acid in Addition to a Strong Statin Makes Regression of Coronary Plaque in Patients with Angina Pectoris
Authors: Wakita Yoshinori , Wakida Yasushi , Itou Takahumi , Mizuno Rika
Published: April 2024

Background:
Japan EPA Lipid Intervention Study ( JELIS ) indicated the efficacy of EPA in addition to the first generation statin for coronary events. However, there are few studies on the efficacy of additional EPA to a strong statin in a manner of randomized controlled study. Objective: To evaluate the efficacy of additional EPA for coronary plaque volume ( CPV ) using intracoronary ultrasound ( IVUS ).

Methods:
Forty patients ( mean age 70 yo ) with angina pectoris who underwent percutaneous coronary intervention ( PCI ) and were administrated 2mg/day of pitavastatin were randomly assigned to EPA-group ( n=20 ) and non-EPA-group ( n=20 ). The patients in EPA-group were additionally administered 1800mg/day of EPA for more than 6 months. In all patients IVUS was performed at the day of PCI and average 8 months later. CPV were obtained at the site with apparent plaque but without clinically significant stenosis. At the same timing, pulse wave velocity ( PWV ) and carotid echography were recorded.

Results:
There were no significant changes in lipids profile, PWV and carotid echography index after randomization between 2 groups. There was significant reduction of CPV in EPA-group compared with non-EPA-group ( -21.9% vs -1.5% for total atheroma volume and -10.9% vs 4.4% for percent change in percent atheroma volume, respectively; P<0.01 ). EPA/AA ratio was increased in EPA-group ( 0.4±0.3 to 1.2±0.5; p<0.01 ).

Conclusion:
EPA reduced CPV even under the strong statin administration.