bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9303: Dodecafluoropentane Emulsion Decreases Cerebral Infarcts in a Rabbit Embolic Stroke Model
Authors: Woods Sean D , Skinner Robert D , Brown Aliza T , Lowery John D , Roberson Paula K , Culp William C
Published: April 2024

Introduction
Dodecafluoropentane emulsion (DDFPe) absorbs, transports, and delivers very high levels of oxygen in vitro and in vivo, with the potential to protect tissues during varied ischemic episodes including stroke. DDFPe may be beneficial by protecting cells during hypoxic perturbations such as myocardial infarction, cardiac surgery, carotid interventions, or stroke. For clinical success in current stroke therapy, tPA must be given within 4.5-hours of onset. Agents that can extend this time frame by delaying ischemic damage have the potential to increase access to thrombolysis treatment and improve outcomes. Using a rabbit model of acute insoluble embolic stroke, we describe the efficacy of DDFPe at decreasing infarct volumes.

Hypothesis
We assessed the hypothesis that treatment with DDFPe effectively decreases infarct volumes without lysis of the arterial occlusion.

Methods
New Zealand White rabbits (N=45, 5.1±0.50 kg) received angiography and three embolic spheres (700-900 µm diameter) were injected into the internal carotid artery, permanently occluding the middle cerebral artery. Rabbits were randomly assigned to control (N=7, embolized without treatment) or one of three DDFPe treatment start times: pre-treatment 30-min before stroke (N=7), hyperacute treatment 0-30 min after stroke (N=13) or acute treatment 1-3 hours after stroke (N=18). DDFPe dose was 2% w/v intravenous injection, 0.6 ml/kg, at the group start time and repeated every 90 minutes as time allowed. Following euthanasia at 4 hours infarct volume was measured using vital stains on brain sections.

Results
Percent infarct volumes were decreased (P=0.001) for all DDFPe treated rabbits (0.73±0.51%, N=38) compared with controls (3.57±0.67%). DDFPe pre-treatment (0.64±0.65%), hyperacute treatment (0.73±0.48%) and acute treatment (0.76±0.40%) all significantly decreased infarct volumes compared to controls (P=0.021, 0.021, and 0.005, respectively).

Conclusions
DDFPe protects ischemic brain from hypoxia and decreases infarct volumes. Further testing is warranted of DDFPe as a therapeutic agent where delivery of oxygen may be of great benefit. Potential clinical applications may be much broader and development is urgently needed.
Abstract 9315: Regional Heterogeneity of Systolic Dysfunction Leads to Ventricular Dyssynchrony in Patients with Idiopathic Dilated Cardiomyopathy and Narrow QRS Complex; 3-Dimensional Speckle-Tracking Strain Analysis
Authors: matsumoto kensuke , Tanaka Hidekazu , Miyoshi Tatsuya , Hiraishi Mana , Kaneko Akihiro , Tsuji Takayuki , Yamawaki Kohei , Ryo Keiko , Fukuda Yuko , Norisada Kazuko , Tatsumi Kazuhiro , Ohnishi Tetsuari , Kawai Hiroya , Hirata Ken-ichi
Published: April 2024

Background:
Although left ventricular (LV) mechanical dyssynchrony is commonly observed in patients with wide QRS complex, some patients with a relatively narrow QRS complex also present with significant mechanical dyssynchrony. Moreover, regional heterogeneity of LV contraction, known as dyssynergy, in idiopathic dilated cardiomyopathy (IDC) patients has been previously reported, but no comprehensive analysis of this abnormality has been made nor is its association with LV dyssynchrony fully understood. The objective was to test, by means of novel 3-dimensional (3-D) speckle-tracking strain, the hypothesis that regional heterogeneity of myocardial systolic dysfunction is associated with LV dyssynchrony.

Methods:
We studied 54 consecutive IDC patients with ejection fraction (EF) of 34±12% and QRS duration of 102±13ms (all<120ms), and 30 age-matched normal controls. The 3-D speckle-tracking LV dyssynchrony (LV dyssynchrony index) was quantified from all 16 LV sites to determine the standard deviation of time-to-peak strain. Similarly, regional heterogeneity of LV systolic function (LV dyssynergy index) was quantified from all 16 LV sites to establish the standard deviation of peak 3-D speckle-tracking strain.

Results:
The LV dyssynergy and dyssynchrony indices of IDC patients were significantly larger than those of normal controls (10.8±2.2 vs. 8.3±1.5%, and 81±39 vs. 24±8 ms, respectively, p<0.001). Furthermore, IDC patients showed significantly higher Z-scores for septum and inferior regions than for the free wall (3.34±1.21 vs. 1.69±1.06, and 2.79±1.30 vs. 1.69±1.06, respectively, p<0.001). An important findings of multivariable analysis was that the LV dyssynergy index (β=0.70, p<0.001) and LVEF (β=-0.34, p=0.001) were independent determinants of the LV dyssynchrony index.

Conclusions:
3-D speckle-tracking strain revealed that the myocardial systolic dysfunction of IDC patients with a narrow QRS complex has a consistent and marked heterogeneous regional distribution. This regional heterogeneity as well as systolic dysfunction is thought to lead to LV dyssynchrony. The study presented here offers new insights into LV dyssynergy and dyssynchrony.
Abstract 9328: Living Alone and Cardiovascular Events in Stable Outpatients at Risk of or with Atherothrombosis: Insight From the REACH Registry
Authors: Udell Jacob A , Steg Ph. G , Scirica Benjamin M , Smith Sidney C , Ohman E. M , Eagle Kim A , Goto Shinya , Cho Jang Ik , Bhatt Deepak L , REACH Registry Investigators
Published: April 2024

Background:
Living alone (LA), a proxy for social support, has been inconsistently linked with CVD.

Methods:
Outpatients from 29 countries at risk of, or with, atherothrombosis were enrolled in the REACH registry and followed for 4 years. Event rates for mortality, vascular events (CV death, MI, or stroke), CHF, bleeding, and vascular procedures were examined by living arrangement with sequential risk adjustment for age, gender, CV risk factors, therapy, degree of preexisting atherothrombosis, and sociodemographic factors. Effect modification was tested by age, gender, geography, ethnicity, education, and employment.

Results:
Among the 44,617 REACH patients with reported living arrangements, 8,605 (19%) were living alone. LA strongly correlated with 4-year mortality (11.4% vs. 9.3%, crude HR, 1.16 [95% CI 1.08-1.24]; p<0.001), risk of vascular events (12.9% vs. 11.9%, crude HR, 1.27 [1.18-1.37]; p<0.001) along with CV death, hospitalization for CHF, bleeding, and vascular procedures. However, after multivariable adjustment the effect of LA on mortality (adjusted HR 1.17 [0.99-1.25] and risk of vascular events (adjusted HR 1.08 [0.98-1.18]) was attenuated. LA remained associated with increased risks of CHF (HR 1.09 [1.00-1.18]), vascular procedures (HR 1.44 [1.21-1.72]), PCI (HR 1.33 [1.04-1.69]), and limb amputation (HR 3.32 [95% CI 1.89-5.82]). There was effect modification by age and employment status, with an inverse correlation between LA and mortality in those older than 80 years or retired.

Conclusion:
In the REACH population, age, current risk factors, and past CV events accounted for most of the association between LA and increased mortality or risk of major vascular events. However, LA was associated with several serious CV events such as risk of CHF, PCI and limb amputation. Elderly retired individuals who live alone may have more favorable prognosis from CVD than others living alone.
Abstract 9350: Cerebral Perfusion and Cognitive Function in Post-Stroke Patients with Hypertension
Authors: Matsumoto Shuji , Shimodozono, Megumi , Noma, Tomokazu , Kawahira Kazumi
Published: April 2024

Objective:
To estimate cerebral perfusion and cognitive function in post-stroke patients with hypertension before and after hypotensive therapy.

Research design and methods:
The treatment group comprised 28 post-stroke patients (mean age ± standard deviation [SD], 57.8 ± 8.3 years) with previously untreated or ineffectively treated essential hypertension. All patients underwent brain xenon-enhanced computed tomography (Xe-CT) scanning and comprehensive neuropsychological testing, both before and after 24 weeks of hypotensive therapy using the angiotensin II receptor blocker (ARB) olmesartan medoxomil. The control group comprised 20 age-matched post-stroke patients (mean age ± SD, 56.6 ± 8.5 years) without hypertension, carotid atherosclerosis, coronary artery disease, or psychiatric disorders.

Results:
The hypertensive patients had significantly lower levels of cerebral perfusion (4-8%) in all brain regions, a 25% decrease in attention and psychomotor speed, and an 18% decrease in mentation compared with the control subjects. Following 6 months of hypotensive therapy, the hypertensive patients experienced an increase in cerebral perfusion by 8-15% in all brain regions, an 18-36% improvement in attention and psychomotor speed, and an average 19% improvement in abstract mentation.

Conclusions:
Hypertensive patients showed marked signs of cerebral hypoperfusion and impaired cognitive function, as indicated by decreased attention, reduced psychomotor speed, and slow mentation; however, these symptoms were improved by 24 weeks of hypotensive treatment with an ARB.
Abstract 9354: Mechanisms of Random Wave Propagation Perpetuated After Pulmonary Vein Isolation: Comparison Between Paroxysmal and Persistent Atrial Fibrillation
Authors: Yamabe Hiroshige , Koyama Junjiroh , Hoshiyama Tadashi , Kanazawa Hisanori , Ogawa Hisao
Published: April 2024

Background:
The precise mechanisms of random wave propagation perpetuated after pulmonary vein isolation (PVI) in atrial fibrillation (AF) has not been well clarified.

Objectives:
The purpose of this study was to define the mechanism of random wave propagation perpetuated after PVI in AF. We further clarified the difference in this perpetuating mechanism between paroxysmal and persistent AF.

Methods:
Endocardial mapping of the left atrium was performed before and after PVI in 7 paroxysmal and 7 persistent AF patients using a three-dimensional non-contact mapping system (EnSite 3000). We analyzed the difference in the left atrial activation sequence between paroxysmal and persistent AF, especially in relation to the complex fractionated electrograms (CFAE) region.

Results:
Random wave propagation after PVI was maintained by the combination of focal discharge, the activation around the isolated PV and mitral annulus, wave break and pivoting activation anchored around the functional conduction block region. The frequency of pivoting activation, wave break and wave fusion were significantly higher in the persistent AF than in the paroxysmal AF (8.4±10.4 vs. 2.0±3.5 times/sec; p<0.001, 1.9±3.2 vs. 0±0 times/sec; p<0.05, and 12.1±3.3 vs. 6.3±13.4 times/sec; p<0.005). However, the frequency of focal discharge derived from non-PV region in persistent AF was lower than in paroxysmal AF (0.3±0.6 vs. 3.2±8.8 times/sec; p<0.03). The area of CFAE was significantly reduced following PVI both in paroxysmal and persistent AF (18.0±16.9 to 2.2±4.9 cm
2
; p<0.0001, 26.8±22.3 to 6.6±2.9 cm
2
; p<0.0001). However, the area of CFAE in persistent AF was significantly larger than that in paroxysmal AF both before (p=0.003) and after PVI (p<0.002). Pivoting activation and wave break were observed on the residual CFAE region which was still observed after PVI.

Conclusions:
Activation sequence of the wave during ongoing AF perpetuated after PVI was more disorganized in persistent AF than in paroxysmal AF. Disorganized activation after PVI in persistent AF was caused by the pivoting activation and wave break associated with the residual CFAE region.
Abstract 9389: Histone Deacetylase 4 Causes Vascular Inflammation and Mediates Development of Hypertension in Spontaneous Hypertensive Rats
Authors: Usui Tatsuya , Okada Muneyoshi , Mizuno Wataru , Oda Mayuko , Ide Natsuki , Hara Yukio , Yamawaki Hideyuki
Published: April 2024

Histone deacetylases (HDAC)s are transcription factors which play important roles on structural remodeling of chromatin. It is recently clarified that HDAC4 mediates heart failure and vascular smooth muscle cells (SMCs) hypertrophy. Moreover our recent study demonstrated that HDAC4 protein increases in mesenteric artery from spontaneous hypertensive rats (SHR) compared with Wistar Kyoto rats (WKY). Vascular inflammation is essential for pathogenesis of hypertension. We therefore examined whether HDAC4 affects on vascular inflammatory responses and mediates hypertensive vascular diseases. Protein expression (n=6-7, P<0.01) and activity (n=3-5, P<0.01) of HDAC4 in rat mesenteric arterial SMCs were increased by TNF-α (10 ng/ml, 1-3 h). An HDACs inhibitor, trichostatin A (TSA) (10 μM, pretreatment for 30 min), inhibited TNF (10 ng/ml, 24 h)-induced vascular cell adhesion molecule (VCAM)-1 expression (n=4, P<0.01). TSA also inhibited TNF (20 min)-induced phosphorylation of NF-κB (n=4, P<0.01). HDAC4 siRNA inhibited TNF-induced VCAM-1 (n=3-6, P<0.01), monocyte adhesion (n=6, P<0.05), phosphorylation (n=3-6, P<0.05) and transcriptional activity (n=4-5, P<0.05) of NF-κB. Furthermore, HDAC4 siRNA inhibited TNF-induced reactive oxygen species (ROS) production (n=4, P<0.01). In vivo study, blood pressure (n=4, P<0.05), ROS production (n=2) and VCAM-1 expression (n=4) in isolated mesenteric artery were increased in SHR compared with WKY, which were prevented by a long-term TSA treatment to SHR (100, 500 μg/kg/day, 3 weeks). In isolated mesenteric artery, the increased angiotensin II-induced contraction in SHR was reversed by a TSA treatment (n=4-6, P<0.01). The endothelium-dependent relaxation induced by acetylcholine in SHR was augmented by TSA (n=6-8, P<0.01). The present results indicate that in vascular SMCs TNF-induced HDAC4 mediates vascular inflammation via VCAM-1 induction through ROS-dependent NF-κB activation. It is also suggested that pro-inflammatory effects as well as hypercontractile effects of HDAC4 may mediate the development of hypertension in SHR. Our results may imply that HDAC4 is a promising important target for drug therapy against essential hypertension.
Abstract 9407: Overexpression of R120g αβ -Crystallin Causes Cardiac Arrhythmias, Reduced Heart Rate Variability, Alteration in the Expression Of Ca2+ Handling Proteins and Er Stress in Mice
Authors: Jiao Qibin , Sanbe Atsushi , Minamisawa Susumu
Published: April 2024

Upregulation of αβ-crystallin (Cryαβ), a small heat shock protein, is associated with a variety of diseases, including desmin-related myopathies. Cryαβ, which binds to both desmin and cytoplasmic actin, may participate as a chaperone in intermediate filament formation and maintenance, and Cryαβ is abundant in cardiac and skeletal muscle. A mutation from arginine at the 120 amino acid residue to glycine (R120G) of Cryαβ has been linked to a familial desminopathy. Mice with cardiac specific overexpression of the R120G mutation in Cryαβ (CryαβR120G) have been known to suddenly die at 6-7 months without any obvious symptoms of heart failure. Therefoe, we investigated the cause of death in CryαβR120G transgenic mice. We prepared protein samples from the left ventricular tissues of the young and old mice (Young: 10 weeks, Old: 28 weeks), and examined a change in Ca2+ handling proteins. We found that the expression levels of SERCA2 and other Ca2+ handling proteins including phospholamban, ryanodine receptor 2, and calsequestrin 2 were significantly decreased in old CryαβR120G transgenic mice. Old CryαβR120G transgenic mice exhibited lower heart rate variability (HRV) such as heart rate, total power, and low frequency. In addition, continuous ECG monitoring uncovered that overexpression of CryαβR120G causesd cardiac arrhythmias such as ventricular tachycardia, atrioventricular block, and atrial flutter. We also found that the expression levels of endoplasmic reticulum (ER) degradation enhancing, α-mannosidase-like protein, inositol requirement 1, and x-box binding protein 1 mRNAs were significantly increased in old CryαβR120G transgenic mice, indicating that CryαβR120G transgenic mice exhibited ER stress. Thus the present study demonstrated that CryαβR120G lead to various arrhythmias, decreased autonomous tone, impaired Ca2+ regulation via the sarcoplasmic reticulum and enhanced ER stress with a concomitant decrease in lifespan.
Abstract 9460: Inhibition of Soluble Epoxide Hydrolase (sEH) Reduces Atherogenesis in Mice
Authors: Stachon Peter , Wolf Dennis , Hildgendorf Ingo , Willecke Florian , Schoenbeck Uwe , Bode Christoph , Zirlik Andreas
Published: April 2024

Background:
Epoxyeicosatrienoic acids (EETs) are short-living, endothelium-derived factors efficiently promoting vasodilatation and angiogenesis. Recently, EETs have been identified as potent anti-inflammatory agents and stimulators of lipid metabolism. Physiologically, EETs are rapidly converted into dihydroxyeicosatrienoic acids by the soluble epoxide hydrolase (sEH). Thus, inhibition of sEH revealed potent anti-inflammatory properties. Here, we test the hypothesis that inhibition of soluble epoxide hydrolase by the orally available compound
BIX01753
modulates atherogenesis in vivo.

Methods and Results:
A prevention arm was designed to test for the potency to inhibit de novo atherosclerosis. LDLR-deficient mice either received a high cholesterol diet, a high cholesterol diet supplemented with two doses of
BIX01753
, or a low cholesterol diet for 16 weeks. When fed the high cholesterol diet and the higher dose of the sEH-inhibitor, mice showed significantly lower lipid depositions in the abdominal aorta as compared to the control (39±2% vs. 29±2% Oil-Red-O positive area, n=17, p=0.03), but not with the lower dose. Intimal lesion size in sections of the aortic arches, generally considered as an indicator of late atherosclerotic lesions, decreased up to 29±4% (n=15, p<0.01), whereas the size of older lesions in aortic roots was not altered significantly. Interestingly, mice fed the sEH-inhibitor showed no changes for the content of smooth muscle cells or collagen in aortic roots. However, there was a slight tendency towards more inflamed lesions, as demonstrated by the increase in macrophage content (4±1% vs. 6±1%, p=0.08). To test the effect of sEH-inhibition on established plaques, mice were first fed a cholesterol diet for 16 weeks and then additionally fed the diet supplemented with
BIX01753
for another 8 weeks. Consistently, mice fed the sEH-inhibitor showed a reduction in lipid depositions of 20±4% as compared to the control (n=15, p=0.02).

Conclusions:
We present the finding that inhibition of soluble epoxide hydrolase (sEH) concentration-dependently attenuated atherosclerotic lesions in a model of murine atherogenesis. These findings identify the soluble epoxide hydrolase as potential target in the treatment of atherosclerosis.
Abstract 9462: Plaque Characteristics on Computed Tomography Coronary Angiography Which Developed Acute Coronary Syndrome More Than One Month Later
Authors: Fujimoto Shinichiro , Kondo Takeshi , Kodama Takahide , Orihara Tadaaki , Sugiyama Junichi , Kondo Makoto , Endo Akira , Fukazawa Hiroshi , Nagaoka Hideki , Oida Akitsugu , Takase Shinichi
Published: April 2024

Backgrounds:
64 or 320-slice CTCA were undergone in 8777 consecutive patients at our center for evaluation of coronary artery disease (CAD) (known CAD: 2319). Of 8777, 27 (M/F=25/2, 67±10 yrs, period to ACS onset: 541±500 days, known CAD: 15) patients developed ACS after having passed more than 30 days from CTCA examination (Patients of culprit lesions which were stent site were excluded.). We examined the culprit plaque characteristics of on CTCA for ACS in the 27 patients.

Methods:
64 or 320-slice CTCA were undergone in 8777 consecutive patients at our center for evaluation of coronary artery disease (CAD) (known CAD: 2319). Of 8777, 27 (M/F=25/2, 67±10 yrs, period to ACS onset: 541±500 days, known CAD: 15) patients developed ACS after having passed more than 30 days from CTCA examination (Patients of culprit lesions which were stent site were excluded.). We examined the culprit plaque characteristics of on CTCA for ACS in the 27 patients.

Results:
Culprit lesions were observed at LMT in 2, RCA in 9, LAD in10, LCX in 6 cases. Nineteen cases (70.4%) were observed in the proximal or mid portion of the three major coronary arteries. No significant stenosis (≤50%) were observed in 21 cases (80.8%). Positive remodeling (PR: remodeling index>1.1) were found in 20 (74.1%) and low attenuation plaque (LAP: CT values≤50HU) were found in 14 (51.9%) cases. No calicification was observed in 5, spotty calcification in 8, moderate calcification in 10 and severe calcification in 4 cases. The period to ACS onset tended to be shorter in ≥50% stenosis, and age was significantly younger with PR(+) group. The VPs were classified by CTCA findings into 4 types; Type I(PR(+) and LAP(+)) was observed in 14(52%), Type II(PR(+) and LAP(-)) in 6(22%), Type III(PR(-) and LAP(-)) in 4(15%), and Type IV(PR(-) and severe calcification) in 3(11%) pts.

Conclusions:
Although ACS occurred from various plaque characters in CTCA, about half of ACS were derived from Type I (PR(+) and LAP(+)) plaques in the younger patients.
Abstract 9476: Atrial Septostomy in Patients with Pulmonary Arterial Hypertension
Authors: Fenstad Eric R , Le Rachel J , McGoon Michael D , Reeder Guy , Hagler Donald J , Cabalka Allison K , Kane Garvan C , Frantz Robert P
Published: April 2024

Introduction:
Creation of an atrial septal defect via atrial septostomy (AS) is a therapeutic option traditionally utilized for PAH in settings where medical therapy was unavailable. Its utility in the context of progressive disease despite medical therapy remains incompletely understood.

Hypothesis:
AS may be a useful option in patients with symptomatic PAH despite medical therapy and may improve functional class.

Methods:
Single center retrospective study of all adult PAH patients receiving AS at a tertiary PAH referral center.

Results:
Eleven atrial septostomy procedures were performed in 8 patients who were refractory to maximal medical management. All patients were WHO functional class III or IV and average patient age was 40 ± 13 years with a female predominance (89%). Mean RA pressure was 18 ± 4 mm Hg with cardiac index of 2.28 ± 0.82 L/min/m
2
prior to AS. Mean pulmonary artery pressure was 63 mm Hg with a pulmonary artery saturation of 48% and average systolic blood pressure of 97 mm Hg. Baseline NT-proBNP was 5573 ± 4589 pg/ml with a mean 6 minute walk distance (6MWD) of 311 ± 131 meters. Five of the 11 procedures resulted in functional class improvement. Functional class change did not relate to change in 6MWD or NT-pro BNP level. Three patients had repeat AS due to spontaneous narrowing of the original septostomy, with a mean duration of 220 ± 135 days between procedures. One patient died within 30 days of the procedure and another at day 88 while one patient received a heart/lung transplant at day 42 post AS. Mean follow up was 243 ± 183 days. The REVEAL risk scores ranged from 10 to 15, with predicted 1 year survival from pre-septostomy clinical data ranging from 22% to 80% (mean predicted survival of 57%). Actual transplant free survival at 1 year was 63%.

Conclusions:
Selected patients at high risk for 1 year mortality may receive symptomatic benefit from atrial septostomy. One year mortality remains high, and not significantly different from that predicted by the REVEAL score. Atrial septostomy may be a palliative treatment option for patients who are refractory to maximal medical therapy but further long term investigation is necessary.
Abstract 9477: Gender Differences in Clinical Characteristics and Risk Factors of Patients with Vasospastic Angina -A Report from the Nationwide Multi-Center Registry by the Japanese Coronary Spasm Association
Authors: Kawana Akiko , Yasuda Satoshi , Takagi Yusuke , Tsunoda Ryusuke , Ogata Yasuhiro , Seki Atsushi , Sumiyoshi Tetsuya , Matsui Motoyuki , Goto Toshikazu , Tanabe Yasuhiko , Sueda Shozo , Sato Toshiaki , Ogawa Satoshi , Kubo Norifumi , Momomura Shin-ichi , Ogawa Hisao , Shimokawa Hiroaki
Published: April 2024

Background:
Recently, much attention has been paid to gender differences in cardiovascular medicine. Previous studies showed that vasospastic angina (VSA) is more common in male. However, the gender differences in clinical characteristics and outcomes of VSA patients remain to be fully elucidated. Thus, we addressed this important issue in the nationwide multi-center registry by the Japanese Coronary Spasm Association.

Methods:
We enrolled a total of 1,429 VSA patients (male/female, 1090/339; median 66 years) from 47 institutes in Japan between September 2007 and December 2008 with a median follow-up period of 32 months. The primary endpoint was defined as major adverse cardiac events (MACE), including cardiac death, non-fatal myocardial infarction (MI), unstable angina and heart failure.

Results:
In comparison with the female patients, the male patients were characterized by younger age (median 66 vs. 69 years, P<0.001), higher incidence of smoking (72 vs. 20%, P<0.001), previous MI (7 vs. 3%, P=0.003), organic coronary stenosis >50% (16 vs. 9%, P=0.001) and ST elevation during spontaneous angina attacks (21 vs. 11%, P<0.001). For the treatment of VSA, Ca channel blocker was used in more than 90% of patients in both genders, whereas antiplatelet was more frequently used in male than in female (50 vs. 38%, P<0.001). Although 5-year MACE-free survival rate was comparable (male 91 vs. female 94%), Cox proportional hazard model demonstrated that the risk factors of MACE were considerably different between genders; male patients were more associated with structural abnormality (e.g., organic stenosis, previous MI), whereas female patients with electrical abnormality (e.g., VT/VF during spontaneous attack) (
Table
).

Conclusions:
These results indicate that there are substantial gender differences in the clinical characteristics and the risk factors of MACE in VSA patients, suggesting the importance of gender-specific management of the disorder.
Abstract 9491: Prognostic Implications of Right Ventricular Longitudinal Peak Systolic Strain on Long-Term Outcome in Patients with Pulmonary Hypertension
Authors: Haeck Marlieke L , Scherptong Roderick W , Ajmone Marsan Nina , Holman Eduard , Vliegen Hubert W , Schalij Martin J , Bax Jeroen J , Delgado Victoria
Published: April 2024

Purpose:
The performance of the right ventricle (RV) is an important prognostic marker in patients with pulmonary hypertension (PH). Two-dimensional speckle tracking strain analysis allows angle independent evaluation of RV systolic function. The aim of this study was to assess the prognostic value of RV longitudinal peak systolic strain (LPSS) on the long-term survival in patients with pulmonary hypertension of all aetiologies.

Methods:
One-hundred fifty patients with PH of all aetiologies (age 59±15 yrs; NYHA 2.56±0.68; mean systolic artery pressure 62±20 mmHg) were analyzed. RV LPSS was assessed by 2-dimensional speckle tracking echocardiography at baseline. All cause mortality was noted during follow-up.

Results:
During a mean follow-up of 2.7±1.8 years, 37 (26%) patients had died. The study population was divided according to the value of -19% RV LPSS. Both groups of patients were comparable in terms of age, gender, LV ejection fraction, WHO PH group and systolic artery pressure. Patients with RV LPSS ≥ -19% had significant lower TAPSE (16±4 mm vs. 18±4 mm, p<0.001), RV FAC (32±13% vs 37±9%, p=0.027), larger RV diastolic area (23±7 vs. 20±5, p=0.008) and worse NYHA functional class (2.7±0.6 vs. 2.3±0.8, p=0.003). Kaplan-Meier curve demonstrated a significant worse survival in patients with RV LPSS ≥ -19% (figure 1, log-rank p=0.002). After multivariate correction, RV LPSS ≥ -19% was significantly associated to all-cause mortality (HR 3.36, 95% CI 1.13-9.96, p=0.029).

Conclusions:
RV LPSS is associated with long-term survival of patients with pulmonary hypertension of all aetiologies. RV LPSS may be a valuable parameter to risk stratify these patients.
Abstract 9560: Clinical Trial Simulations of Dyslipidemic Patients in a Mechanistic Model of Cardiovascular Disease Predict Little Impact on CHD Events by CETP Inhibitors
Authors: Wahba Karim , Lo Arthur , Kadambi Ananth , Powell Lyn M
Published: April 2024

The Entelos® CV PhysioLab® platform, a mechanistic model of CHD, quantitatively predicts cholesterol metabolism and plaque growth in the coronary artery over time through the dynamic simulation of relevant biological pathways. Statistical methodologies are used to translate predicted changes in circulating lipids and plaque characteristics to predictions of CHD risk. Such predictions can be made for approved or novel therapeutics over time in virtual populations representing a diverse set of patient populations that can be created. PK and PD effects of cholesteryl ester transfer protein (CETP) inhibitors, torcetrapib (60 mg qd), dalcetrapib (600 mg qd) and anacetrapib (100mg qd) were implemented in the platform, calibrated to published data and administered to simulated patients to predict effects on lipoprotein profile and the mean hazard ratio (HR) relative to the same simulated patients on a statin treated background (statin treated mean LDL-C 84 ± 15 mg/dL, HDL-C 44 ± 9 mg/dL). An additional effect of the reported increase on blood pressure was implemented for torcetrapib simulations only. Predicted changes in lipoproteins and 4 year HRare shown in the table. When the mechanistic effects of the reported increase in systolic blood pressure with torcetrapib are added to the lipoprotein changes that result from appropriate CETP inhibition, simulations predict an increased HR similar to that seen in the ILLUMINATE study. Dalcetrapib simulations do not predict any clinically meaningful changes in HR. Finally, despite an additional decrease in LDL-C and the largest increase in HDL-C, anacetrapib simulations predict a very small reduction in HR. Simulations also define a subpopulation within whom the inhibition of CETP activity is more beneficial with the general characteristics of high TG and low HDL-C. 1Additional effect on blood pressure was included in simulations
Abstract 9572: Post-Stenotic Dilatation in Asymptomatic Aortic Stenosis
Authors: Bahlmann Edda , Devereux Richard B. , Nienaber Christoph A. , Cramariuc Dana , Gohlke-Baerwolf Christa , Ray Simon , Wachtell Kristian , Kuck Karl Heinz , Gerdts Eva
Published: April 2024

Background:
Post-stenotic aortic root dilation is often observed in aortic stenosis (AS) patients, but the relation to AS severity has not been reported from a large population of asymptomatic AS patients.

Methods:
Baseline data in 1223 patients with asymptomatic AS (mean age 67 years, 39% women) in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study was used. Annular diameter was measured from inner to inner edge in mid-systole. Inner and leading edge aortic root diameter was measured at the levels of sinus of Valsalva, sinotubular junction and supracoronary. Predicted aortic diameters were calculated from age and body size adjusted equations derived in normal adults.

Results:
On average, mean aortic annulus diameter was 2% larger, sinus of Valsalva diameter 11% larger, sinotubular junction diameter 22% larger and supracoronary diameter 32% larger in SEAS participants than that predicted from body size. Enlarged aortic diameter was found in 42%, 78%, 96% and 98% of patients at these levels and associated with larger inner diameter and thicker aortic wall (both p<0.01). In multivariate regression analysis, larger sinus of Valsalva or sinotubular junction diameter was independently associated with more severe AS (Table).

Conclusions:
Post-stenotic aortic root dilatation is common in asymptomatic AS with increasing prevalence from proximal to distal part. Aortic root dilation at the sinus of Valsalva and sinotubular junction level was associated with higher AS severity.
Abstract 9577: 25-year Trends In First-time Hospitalization For Acute Myocardial Infarction, Subsequent Short- And Long-term Mortality, And The Prognostic Impact Of Gender And Comorbidity: A Danish Nationwide Cohort Study
Authors: Schmidt Morten , Jacobsen Jacob , Lash Timothy L , Bøtker Hans E , Sørensen Henrik T
Published: April 2024

Background:
A marked decrease in incidence of acute myocardial infarction and associated mortality has occurred since 1980. No studies have reported on 25-year trends in a nationwide unselected population. We examined 25-year trends in first-time hospitalization for acute myocardial infarction in Denmark, subsequent short- and long-term mortality, and the prognostic impact of gender and comorbidity.

Methods:
We conducted this nationwide population-based cohort study using medical registries. We identified all 234,331 patients with a first-time hospitalization for myocardial infarction from 1984 through 2008. We calculated the standardized incidence rate of myocardial infarction and 30-day and 31-365-day mortality by gender. We defined no, low, moderate, and high comorbidity levels according to the Charlson Comorbidity Index. We used Cox regression to compute mortality rate ratios comparing comorbidity categories.

Results:
The standardized incidence rate per 100,000 persons decreased in the 25-year period by 37% for women (from 209 to 131) and by 48% for men (from 410 to 213). The 30-day mortality declined from 31.4% in 1984-1988 to 14.8% in 2004-2008. The 31-365-day mortality declined from 15.6% in 1984-1988 to 11.1% in 2004-2008. After adjustment for age at time of myocardial infarction, men and women had the same one-year risk of dying. The mortality reduction was independent of comorbidity level. Comparing patients with high and with no comorbidity during 2004-2008, the mortality rate ratio, adjusted for age and gender, was 1.96 (95% confidence interval: 1.83 to 2.11) within 30 days and 3.89 (95% confidence interval: 3.58 to 4.24) between 31 and 365 days.

Conclusion:
The rate of first-time hospitalization for myocardial infarction and subsequent short-term mortality both declined by nearly half between 1984 and 2008. The reduction in mortality occurred for all patients, independent of gender and comorbidity. However, comorbidity burden was a strong prognostic factor for short and long-term mortality, while gender was not.
Abstract 9578: Single-Item Self-Report Medication Adherence Question Predicts Hospitalization and Death in Patients with Heart Failure
Authors: Wu Jia-rong , DeWalt Darren A , Baker David W , Schillinger Dean , Ruo Bernice , Bibbins-Domingo Kirsten , Macabasco-O'Connell Aurelia , Holmes George M , Broucksou Kimberly A , Erman Brian , Hawk Victoria , Cene Crystal W , DeLong Jones Christine , Pignone Michael
Published: April 2024

Background:
Sub-optimal adherence to heart failure (HF) medications contributes to worse outcomes. Having a simple means of identifying sub-optimal adherence could help identify at-risk patients for interventions.

Objective:
To determine whether a single-item self-report medication adherence question predicts hospitalization and death in patients with HF.

Methods:
We performed an observational study in 597 patients with HF (male 52%, age 61±13 years, NYHA III/IV 31%) within a 4-site randomized trial. Patient demographic and clinical variables were collected at baseline by interview and medical record review. Self-report medication adherence was assessed at baseline using a single item question: “Over the past 7 days, how many times did you miss a dose of any of your heart medication?” Patients who reported no missing dose were defined as adherent; those missing ≥ 1 dose were non-adherent. The primary outcome was combined all-cause hospitalization or death over 1 year; secondary endpoint was HF hospitalization. Outcomes were assessed based on blinded chart reviews and HF outcomes were determined by a blinded adjudication committee. We used negative binomial regression to examine the relationship between medication adherence and incidence of hospitalization and death, adjusting for site, demographic (age, gender, ethnicity, socioeconomic status) and clinical (HF symptoms, systolic dysfunction, β-blocker use, hypertension, and history of CVD) factors.

Results:
Seventy-three percent of patients reported perfect adherence to their heart medicine at baseline. Patients with perfect medication adherence had a lower rate of events (0.71 events / year) compared with those with any non-adherence (0.90 event / year). After adjusting for site, adherent patients had an incidence rate ratio (IRR) of 0.79 (95% CI: 0.67-0.92) for all-cause hospitalization or death, and 0.79 (95% CI: 0.75-0.83) for HF hospitalization. When adding demographic and clinical factors to the model, the adjusted IRR for all-cause hospitalization and death = 0.77 (95% CI: 0.68-0.86) and for HF hospitalization = 0.83 (95% CI: 0.65-1.06).

Conclusion:
A single question on medication adherence at baseline predicts hospitalization and death over 1 year in patients with HF.
Abstract 9579: Inhibition of Adverse Myocardial Remodeling and Improvement of Cardiac Function with Postconditioning: Comparison with Preconditioning
Authors: Wang Ning-Ping , Wang Zhang-Feng , Philip Tiji , Zhao Zhi-Qing
Published: April 2024

We have reported that postconditioning (Postcon) reduces infarct size and preserves cardiac function during extended reperfusion. This study tested the hypothesis that modulation of adverse cardiac remodeling with Postcon is associated with enhancement of angiogenesis and prevention of fibrosis by recruiting host myofibroblasts. Fifty-eight rats were subjected to 45 min ischemia followed by 7 and 42 d reperfusion, respectively. Four cycles of 10/10 s Postcon or two cycles of 5/5 min preconditioning (Precon) were applied at the onset of reperfusion or before ischemia, respectively. At 7 d reperfusion, expression of collagen I and III (Western blot) was significantly down-regulated (85±8* and 89±6* vs. 128±10 Abr. u), and MMP2/TIMP4 ratio (Zymography) was reduced (0.9±0.2* and 1.0±0.6* vs. 4.1±0.8) in the Postcon and Precon groups relative to the Control. The population of myofibroblasts (immunohistological staining) within the infarct area increased significantly relative to the Control (78±9* and 69±10* vs. 45±3//HPF) in these two groups, consistent with significantly enhanced immunoreactivity of VEGF. Along with these changes, angiogenesis was significantly enhanced relative to the Control, evidenced by increased number of α-smooth muscle actin-positive vessels (38±4*, 31±8* vs. 12±3/HPF) and vWF-positive vessels (45±4*, 41±7* vs. 22±5/HPF), respectively. At 42 d reperfusion, histological examination with Masson Trichome staining revealed that the extension of fibrotic zone was markedly reduced with increased mass of viable myocardium in the Postcon and Precon groups. Furthermore, echocardiography showed improvements in end-systolic volume (0.5±0.1*, 0.4±0.2* vs. 0.8±0.3 ml), fractional shortening (29±5*, 27±7* vs. 22±4%) and ejection fraction (56±9*, 50±6* vs. 39±7%) in the Postcon and Precon groups compared with the Control. The wall thickness of the infarct middle anterior septum in the Postcon and Precon was significantly greater than that in the Control (1.7±0.01*, 1.6±0.02* vs. 1.1±0.01 mm). We conclude that Postcon and Precon inhibit adverse myocardial remodeling and preserve cardiac function, potentially mediated by proliferated myofibroblasts and enhanced angiogenesis. * P<0.05 Postcon and Precon vs. Control.
Abstract 9581: Bendavia, a Novel Mitochondrial-Targeted Cytoprotective Compound Reduces Ischemia/Reperfusion Injury: Experience in 3 Independent Laboratories
Authors: Kloner Robert A , Hale Sharon L , Gorman Robert C , Shuto Takashi , Koomalsingh Kevin J , Gorman Joseph H , Sloan Ruben C , Frasier Chad R , Kypson Alan P , Brown David A
Published: April 2024

Bendavia is a mitochondrial-targeting compound proposed to maintain cardiac mitochondrial function and decrease permeability transition pore (PTP) opening during ischemia/reperfusion (IR). Our labs assessed the cardioprotective effects of Bendavia using cellular and large animal models of IR when reactive oxygen species (ROS) generation is elevated. Left ventricular guinea pig cardiomyocytes were either untreated or incubated with 1nM Bendavia and exposed to 20 min of cellular anoxia plus 30 min of reoxygenation in a hypoxia chamber. Following reoxygenation 54% of control cells survived to the end of reoxygenation versus 93% of Bendavia-treated cells (p<0.05). Myocytes displayed bursts in ROS production immediately prior to cell death that were prevented by Bendavia. Similarly, Bendavia maintained mitochondrial membrane potential in cells exposed to oxidative challenge, suggesting that scavenging mitochondrial ROS with Bendavia sustained mitochondrial energetics by keeping PTP closed. A second study determined the effect of Bendavia on infarct size in anesthetized sheep (60 min coronary occlusion, 3 hr reperfusion). Bendavia infusions of 0.005, 0.05 and 0.5 mg/kg/hr were administered 30 min after occlusion and reduced mean infarct size by 25%, 16% and 17%, respectively (p≤0.05 versus vehicle). Cyclosporin A reduced infarct size by <10% in this same study (p=NS). In a third study anesthetized rabbits received 30 min of coronary artery occlusion plus 3 hr of reperfusion. Rabbits received placebo or Bendavia at 10 or 20 min after occlusion or immediately before reperfusion. At 3 hr of reperfusion, no reflow was assessed by Thioflavin S injection. For any size of ischemic risk zone, the no reflow zone was significantly smaller in the Bendavia group than control group (p=0.0085). There was an overall 21% reduction in no reflow and 11% reduction in infarct size in the Bendavia group. Cardiac hemodynamics were not influenced by Bendavia or Cyclosporin A in either the sheep or rabbit studies. In 3 separate labs studying IR injury, Bendavia protected cardiomyocytes along with reducing infarct size and limiting no reflow when given after ischemia, but prior to reperfusion, making the compound an attractive candidate for clinical studies in cardiac IR injury.
Abstract 9613: Left Ventricular Dyssynchrony (LVD) in Children With End-Stage Renal Disease
Authors: Kobayashi Daisuke , Patel Sheetal , Mattoo Tej , Valentini Rudolph , Aggarwal Sanjeev
Published: April 2024

Introduction:
Left ventricular dyssynchrony (LVD) adversely affects systolic performance and regional myocardial perfusion and metabolism. The association between LVD and end-stage renal disease (ESRD) in children has not been previously investigated.

Hypothesis:
1. LVD in children with ESRD would be significantly increased compared to controls 2. Children undergoing peritoneal (PD) and hemodialysis (HD) would have comparable LVD.

Methods:
Prospective observational study in which real-time 3-D echocardiographic data were acquired in 27 stable children with ESRD (13 PD and 14 HD) and 29 normal controls. For children with HD, data were acquired before and after a HD session. Dyssynchrony index (SDI) was defined as standard deviation of the time to reach minimum regional volume for 16, 12 and 6 segments. SDI was normalized to duration of cardiac cycle (SDIp). Left ventricular mass (LVM) was obtained from the short-axis view on M-mode echocardiography and was normalized to height
2.7
(LVM index). Means were compared by paired t test.

Results:
The mean age of children with ESRD was higher than that of controls (13.8 vs 11.3 years; p= 0.012) while gender distribution, height, weight and body surface areas were comparable. SV, ESV, SDI, SDIp, LVM and LVM index were significantly higher in those with ESRD (Table). Demographics and HR were comparable between HD and PD subgroups while EDV, ESV, SV, SDI 16 and 12 segments, SDIp 16 segments and LVM were significantly higher in the HD group (P <0.05). SDI and SDIp 16 segments significantly improved after a HD session (p <0.05); LVM and LVM index remained unchanged. There was no correlation between SDIp and LVM.

Conclusions:
Children with ESRD have significant LVD and increased LVM compared to controls. LVD and increased LVM in those undergoing HD and the improvement in synchrony following a HD session suggest that volume may modulate LVD. We speculate that LVD in children with ESRD may have pathogenic implications.
Abstract 9661: Differences in Pathophysiology of Plaques Between Target Lesion and Non-Target Lesion Events After Successful Percutanous Cornary Intervention: Insights from Integrated Backscatter Intravascular Ultrasound
Authors: Kumagai Soichiro , Ishii Hideki , Amano Tetsuya , Uetani Tadayuki , Hayashi Mutsuharu , Yoshikawa Daiji , Kurebayashi Nobutake , Sato Bunmei , Hayakawa Seiichi , Tanaka Miho , Matsubara Tatsuaki , Murohara Toyoaki
Published: April 2024

Objectives:
We sought to determine the morphologic predictors of major adverse cardiac events (MACEs) after perctaneous coronary intervention (PCI), using integrated backscatter intravascular ultrasound (IB-IVUS).

Methods:
Conventional and IB-IVUS using 40-MHz (motorized pullback 0.5mm/s) intravascular catheter were performed in 295 consecutive patients indicated for PCI. Three-dimensional analyses were performed to determine the total plaque volume and the volume of each plaque component (lipid, fibrous, and calcified). MACEs were defined as death, nonfatal myocardial infarction, heart failure required hospitalization, any repeat revascularization for the index target lesion (TLR), and non-target ischemic events. Non-target ischemic events were defined as nonfatal myocardial infarction, any repeat revascularization for angina involving the non-target vessel or the target vessel outside the index lesion.

Results:
The median follow-up interval was 982 days. During the follow-up period, MACEs were observed in 78 (26.4%) patients including TLR in 40 (13.6%) and non-target ischemic events in 31 (10.5%). With the Cox proportional hazard model after adjustment for confounders, MACEs were associated with chronic kidney disease (OR 2.26, 95% CI 1.25-4.08, p=0.007) and diabetes (OR 1.75, 95% CI 1.06-2.89, p=0.03). But as for each components, TLR were significantly associated with percentage of plaque volume (OR 1.06, 95% CI 1.01-1.10, p=0.04), and non-target lesion ischemic events were significantly associated with percentage of lipid volume (OR 1.03, 95% CI 1.00-1.06, p=0.03).

Conclusions:
Greater plaque burdens were significantly associated with TLR, while lipid-rich contents were relevant to non-target lesion events. These findings may have implications regarding the differences in pathophysiology of plaques between the TLR and non-target lesion events.