bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 8559: Efficacy of Implantable Cardiac Defibrillators for the Prevention of Sudden Cardiac Death in Patients with Cardiac Sarcoidosis
Authors: Kron Jordana , Bogun Frank M , Crawford Thomas C , Sarsam Sinan H , Mehta Davendra , Greenspon Arnold J , Ortman Matthew , DeLurgio David B , Valadri Ravinder R , Narasimhan Calambur , Nalla Swapna , Singh Jagmeet P , Danik Stephan B , Benditt David G , Almquist Adrian K , Krahn Andrew D , Cooper Joshua M , Markowitz Steven M , Morales Jacquelene , Wolfe Luke G , Feinstein Shawn D , Ellenbogen Kenneth A
Published: April 2024

Introduction
Patients with cardiac sarcoidosis (CS) are at increased risk for sudden death from ventricular arrhythmias. There is little evidence regarding the efficacy and safety of implantable cardiac defibrillators (ICDs) in this population.

Hypothesis
Data on demographic, clinical, and ICD intervention history was retrospectively collected on 138 CS patients with ICDs from 11 academic centers throughout the U.S., Canada, and India. We hypothesized that patients with CS would have a high incidence of appropriate ICD therapies.

Results
Sixty-two of 138 CS patients (44.92%) had an appropriate ICD therapy (ATP or shock) with 39 patients (28.3%) receiving 5 or more therapies (Figure). Forty-eight of 131 patients (36.64%) received an appropriate shock. Thirty-seven of 136 patients (27.21%) had an inappropriate shock. The incidence of appropriate therapy (ATP or shock) was 10.4%/year and the incidence of appropriate shock was 8.5%/year. Twenty-two patients (15.9%) experienced an adverse event, the most common being lead dislodgement in 11 patients (8%). Appropriate therapies (ATP or shock) were more common in patients with syncope 24/37 (65%) versus patients who did not have syncope 38/101 (38%) (p = 0.0065). Appropriate therapies were more common in patients who had ventricular pacing on baseline EKG, 9/10 (90%), compared with those who did not, 53/128 (41%) (p=0.0053). The mean age of patients who received an appropriate therapy (n=59) was 51.7 ± 11.6 compared with 56.9 ± 10.2 for those who did not receive appropriate therapy (n=74) (p = 0.0066). Immunosuppressive medications including steroids, methotrexate, azathioprine, and hydroxychloroquine were not associated with reduced number of appropriate therapies.

Conclusions
Patients with CS have high rates of appropriate ICD therapies. This population also has high rates of inappropriate shocks and adverse events. Syncope, ventricular pacing, and younger age may identify the highest risk CS patients.
Abstract 8570: A Randomized, Double-blind, Controlled, Comparative Trial of Formula Food Containing Soy Protein versus Milk Protein in Visceral Fat Obesity: FLAVO study
Authors: Uehara Yoshinari , Masaya Takahira , Noda Keita , Zhang Bo , Mitsutake Ryoko , Ogawa Masahiro , Kakuma Tatsuyuki , Saku Keijiro
Published: April 2024

To clarify the efficacy of soy at reducing visceral fat, we planned a randomized, double-blind, controlled, comparative trial that compared formula food containing soy bean protein (SP) to the same food in which soy was replaced by milk protein (MP). Forty-eight participants were enrolled for the treatment of visceral fat obesity: visceral fat area greater than 100cm
2
as calculated by CT. The SP formula contained 12g of soy bean protein, 9g of milk protein, and other nutrients, and was administered for 20 weeks in the morning, while in the MP formula soy bean protein was replaced by milk protein. During the 20 weeks of the trial period, visceral fat area and subcutaneous fat area in MP group were significantly reduced, while those in SP group did not change as assessed by an analysis of covariance. While waist circumference was reduced in both SP and MP groups, BW and BMI were significantly reduced only in MP group. Based on a mixed-effects model, the difference in log-transformed visceral fat profiles between the two groups was statistically significant (p<0.05), while a negative relationship was observed between the changes in visceral fat and adiponectin in the MP group (p<0.001), but not in SP group. In conclusion, formula containing milk protein is superior to that containing soy bean protein for reducing visceral and subcutaneous fat.
Abstract 8579: Age Related Change in Aortic Stiffness in the Thoracic and Abdominal Aorta Among African Americans: The Jackson Heart Study
Authors: Chotenimitkhun Runyawan , Hamilton Craig A , Jeffries Neal , Harman Jane L , Taylor Herman , Carr J. J , Hundley W. G
Published: April 2024

Introduction :
Age-related stiffening of the aorta is associated with increased aortic wall thickness (WT) in whites, but this relationship has not been clearly demonstrated in African Americans. We sought to determine this relationship in the Jackson Heart Study (JHS), a community-based prospective study of cardiovascular disease among 5,301 African Americans in the Jackson, Mississippi area.
Hypothesis :
Thoracic and abdominal measures of aortic pulse wave velocity (PWV), a measure of aortic stiffness, correlate with age related increases in WT in African Americans.

Methods and Results :
Beginning in 2009 (JHS Visit 3), 229 (67% women) consecutively recruited participants, aged 62+10 (39-87) years (89% hypertension, 39% diabetes, and 8% current smokers) underwent magnetic resonance imaging (MRI) measures of PWV and WT in the ascending and the descending thoracic aorta (aTA, dTA), and the abdominal aorta (AA). We determined the association between regional PWV and WT, age, gender, systolic blood pressure, body mass index, hemoglobin A1c, triglyceride, and high-density lipoprotein in a multivariable model. With age, regional PWV increased in the aTA and dTA (p<0.0001 for both), but not the AA (p=0.09; Figure 1); a 10 year increase in age corresponded to a 26%, 21% and 5.7% increase in PWV in the aTA, dTA and AA, respectively. The mean WT was 3.05+0.71 mm, 3.02+0.81 mm, and 2.04+ 0.78 mm in the aTA, dTA, and AA, respectively. After controlling for all variables in the model above, PWV showed a strong inverse relationship to WT: a 1% increase in WT was associated with a 0.26% decrease in PWV (p< 0.0001); this was true independent of the aortic region (p=0.08).

Conclusion :
Regional PWV increases with age in African Americans, but unlike whites, is inversely related to aortic WT. These data suggest that age-related stiffening of the aorta in African Americans may be related to factors that operate independent of wall thickness.
Abstract 8622: Transmural Dispersion of Repolarization in Febrile Children with Kawasaki Disease
Authors: Hata Tadayoshi , Fujino Masayuki , Kuriki Marina , Horio Kayo , Omeki Yumi , Uchida Hidetoshi , Eryu Yoshihiko , Boda Hiroko , Miyata Masafumi , Yamazaki Toshio
Published: April 2024

Introduction:
The instability of myocardial repolarization is generally mediated by myocardial failure. We assessed the hypothesis that transmural dispersion of repolarization is increased in the inflamed myocardium in patients with acute-phase Kawasaki disease.

Method:
Consecutive 25 infants (M:F = 15:10 ) with Kawasaki disease aged 2.6 ± 2.2 years and 25 age-matched control infants were included. RR interval, QT interval and Tp-e time (CM5 lead) were calculated using analysis software (Acqknowledge Ver. 3.9, Biopac Systems Inc. CA, USA). Tp-e time was corrected by Fridericia equation (Tp-eC). These parameters were compared in the acute phase (6.9 ± 3.0 days after onset) and recovery phase (23.0 ± 13.3 days after onset) or control. The relationship between Tp-e/QT, Tp-eC and C reactive protein, body temperature on admission were evaluated by regression analysis.

Results:
1) The Tp-e/QT in the acute phase were significantly higher than that in the recovery phase (Mean ± SD: 0.248 ± 0.055 vs 0.215 ± 0.022, p<0.05 ) and control group (0.220 ± 0.025, p<0.005). 2) The Tp-eC in the acute phase was significantly higher than that in the recovery phase (89.99 ± 16.86 vs 82.11 ± 7.45, p<0.05) and control group (80.02 ± 10.46, p<0.01). 3) In acute phase, significant positive correlation was observed between Tp-e/QT and C reactive protein or body temperature (r = 0.677 and 0.672, respectively). Further, between Tp-eC and C reactive protein or body temperature (r = 0.482 and 0.583, respectively).

Conclusions:
Transmural dispersion of repolarization assessed by Tp-e/QT and Tp-eC was increased in the acute phase of Kawasaki disease, which exhibits the sub-clinical lability of ventricular repolarization. These repolarization properties of the myocardium were considered a useful indicator to assess arrhythmogenesis in patients with Kawasaki disease.
Abstract 8634: Serial Changes of Neointimal Coverage Conditions and Characteristics are different between Sirolimus-Eluting Stents and Paclitaxel-Eluting Stents Implantation: Follow-Up Optical Coherence Tomography Study
Authors: Nakamura Daisuke , Nishino Masami , Lee Yasuharu , Yoshimura Takahiro , Taniike Masayuki , Makino Nobuhiko , Kato Hiroyasu , Egami Yasuyuki , Shutta Ryu , Tanouchi Jun , Yamada Yoshio
Published: April 2024

Background:
The long-term detailed changes of neointima coverage and characteristics in Sirolimus-eluting stent(SES) and Paclitaxel-eluting stent(PES) remains to be clarified.

Methods:
Of 18 SES (14 patients) and 13 PES (12 patients), OCT was used to visualize 2486 and 1361 stent-struts at 8 months after implantation 2199 and 1309 stent-struts at 20 months after respectively. The OCT parameters, including incidence of uncovered struts and malapposed struts and neiointimal hyperplasia thickness (NIH thickness) and NIH% were compared between SES and PES and between 8 months after and 20 months after for SES and PES.,The neointimal charecteristics were classified into 3 groups:high without PLIA(high density neointima without peri-strut low-intensity area(PLIA),high with PLIA and non-high .PLIA was defined as a region around stent struts with a homogeneous,lower intensity appearance

Results:
Uncovered ratio and malapposed ratio was significantly higher in SES than in PES both at both follow-up. NIH thickness and %NIH was higher in PES than in SES at both follow-up. Uncovered ratio significantly decreased in SES from 8months to 20months after, and in PES nonsiginificantly decreased . Malapposed ratio nonsignificantly decreased in both groups. NIH% and NIH thickness significantly increased in SES ,but NIH% and NIH thickness significantly decreased in PES from 8months after to 20months after. High signal neointima accounts for more than 90% in both groups.However it decreased in SES ,while increased in PES. High with PLIA nonsignificantly increased in SES ,but decreased in PES. Non-high signal neointima decreased both in SES and in PES.(Table)

Conclusions:
Uncovered struts and malapposed struts gradually alleviated in both SES and PES while neointimal hyperplasia condition and characteristics showed different patters; increasing in SES but decreasing in PES.
Abstract 8649: Aerobic Exercise Training Improves Heart Rate Variability, as Reflected by PD2i, in Individuals with Low PD2i
Authors: Weiss Daniel N , Goulopoulou Stella , Skinner James E , Jerry Anchin M , Kanaley Jill A
Published: April 2024

Point Correlation Dimension (PD2i) is a non-linear measure of heart rate variability complexity that has been shown to be able to predict the risk of sudden arrhythmic death, such that a value ≤ 1.4 increases risk substantially, with a value ≤2 denoting the presence of autonomic dysfunction. It is unclear, however, if exercise, a lifestyle behavior recommended to sedentary individuals, can favorably alter PD2i. The purpose of this study was to determine if 16 weeks of moderate intensity aerobic exercise training would raise PD2i in sedentary lean and obese, middle aged men and women (age 40-57 yr). PD2i was measured at rest and in response to 5 min of upright tilt pre and post the 16 week exercise training regimen. Subjects were stratified into 2 groups according to their pre-regimen resting PD2i: low PD2i≤ 2 (lPD2i, n=14) and normal PD2i >2 (nPD2i, n=45 ). At rest, there was a training by group interaction such that PD2i increased substantially with exercise training in the lPD2i group but not in the nPD2i group (lPD2i pre 1.94±0.2, post 2.46±0.2; nPD2i pre 2.95±0.1, post 3.0±0.09, P=0.02). In response to the sympathetic stress of upright tilt (known to acutely lower PD2i), both groups had an appropriate decrease in PD2i (P<0.001) and an overall effect of training (P=0.04), but there was no training by group interaction on this response. During recovery from tilt, the lPD2i group had a significant improvement in PD2i with training (lPD2i pre 2.21±0.2, post 2.92±0.2; nPD2i pre 3.26±0.1, post 3.22±0.1, P=0.009), while there was no change in the nPD2i group. In conclusion, a 16 wk moderate intensity training program improves resting and recovery PD2i in those with low initial resting values, and this improvement may reduce their risk of sudden arrhythmic death.
Abstract 8670: Homocysteine Induces Reactive Oxygen Species-dependent Apoptosis of Arterial Smooth Muscle Cells Coinciding with (peri)nuclear Nox4 Translocation
Authors: Hahn Nynke E , Sipkens Jessica A , wassink Melissa , Vonk Alexander B , Stehouwer Coen D , Rauwerda Jan A , van Hinsbergh Victor W , Meischl Christof , Niessen Hans W , Krijnen Paul A
Published: April 2024

Background:
Elevated levels of homocysteine form a vascular risk factor. Although a jeopardizing role of homocysteine on endothelial cells has been shown, its effect on smooth muscle cells is contradicting, varying from induction of proliferation to induction of cell death. Recent studies have shown that NADPH oxidase-mediated reactive oxygen species play a role in homocysteine-induced apoptosis in cardiomyocytes and endothelial cells. However to the best of our knowledge, this has not been studied in smooth muscle cells.

Methods:
Human arterial smooth muscle cells were incubated with 100 µM homocysteine during 24 hours and were analyzed for cell viability using FACS analysis and caspase 3 activity. The effects of homocysteine on the expression of different NADPH oxidase proteins and -mediated reactive oxygen species production were studied using digital-imaging microscopy.

Results:
Incubation of arterial smooth muscle cells with 100 µM homocysteine during 24 hours induced a significant increase in single annexin V positive cells. This increase coincided with a significant increased caspase 3 activity. Furthermore, homocysteine resulted in a significant shift of NADPH oxidase 4 from the cytoplasm to (peri)nuclear regions and a significant increased reactive oxygen species production in the (peri)nucleus and the cytoplasm. No effects of homocysteine on expression levels, nor location of NADPH oxidase 1 and 2 were found. Inhibition of NADPH oxidase-mediated reactive oxygen species production with the flavoenzyme inhibitor diphenylene iodonium led to significant decreased apoptosis levels as assessed by quantification of caspase 3 activity.

Conclusion:
100 µM homocysteine during 24 hours induced reactive oxygen species-dependent apoptosis of human arterial smooth muscle cells coinciding with (peri)nuclear NADPH oxidase 4 translocation.
Abstract 8683: Systemic to Pulmonary Collateral Flow as Measured by Cardiac Magnetic Resonance Imaging is Associated with Acute Post-Fontan Clinical Outcomes
Authors: Glatz Andrew C , Rome Jonathan J , Small Adam J , Gillespie Matthew J , Dori Yoav , Harris Matthew A , Keller Marc S , Fogel Mark A , Whitehead Kevin K
Published: April 2024

Introduction:
Systemic-pulmonary collateral (SPC) flow occurs commonly in single ventricle patients after superior cavo-pulmonary connection, with unclear clinical significance. We sought to evaluate the association between SPC flow and acute post-Fontan clinical outcomes using a novel method of quantifying SPC flow by cardiac magnetic resonance (CMR).

Hypothesis:
In single ventricle patients with Stage 2 physiology, a greater amount of SPC flow, as quantified by CMR, will be associated with prolonged hospital and chest tube duration following Fontan completion.

Methods:
We performed a retrospective medical record review of the Fontan hospitalization of all patients who had SPC flow quantified by CMR prior to Fontan completion in order to evaluate associations between measures of SPC flow and post-Fontan clinical outcomes.

Results:
Forty-four subjects were included who had Fontan completion between May, 2008 and September, 2010. SPC flow prior to Fontan measured 1.5 ± 0.9 L/min/m
2
, accounting for 31 ± 11% of total aortic flow and 44 ± 15% of total pulmonary venous flow. There was a significant linear association between natural log-transformed duration of hospitalization and SPC flow as a proportion of total aortic (rho=0.31, p=0.04) and total pulmonary venous flow (rho=0.29, p=0.05). After adjustment for Fontan type and presence of a fenestration, absolute SPC flow was significantly associated with hospital duration ≥ 7 days (OR=9.2, p=0.02) and chest tube duration ≥ 10 days (OR=22.7, p=0.009). Similar associations exist for SPC flow as a percentage of total aortic (OR=1.09, p=0.048 for hospitalization ≥ 7 days; OR=1.24, p=0.007 for chest tube duration ≥ 10 days) and total pulmonary venous flow (OR=1.07, p=0.048 for hospitalization ≥ 7 days; OR=1.18, p=0.006 for chest tube duration ≥ 10 days).

Conclusion:
A greater amount of SPC flow before Fontan, as measured by CMR, is associated with increased duration of hospitalization and chest tube following Fontan completion.
Abstract 8684: Atrial Fibrillation is Associated with Higher Risk of Dementia and Post-Dementia Hospitalization Mortality in Individuals Without Stroke: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Chen Lin Y , Lopez Faye , Gottesman Rebecca , Huxley Rachel , Agarwal Sunil K , Loehr Laura , Mosley Thomas , Alonso Alvaro
Published: April 2024

Background
Atrial fibrillation (AF) is associated with higher risk of dementia in stroke patients. This association in patients without stroke is unclear. We sought to determine whether AF is associated with higher risk of dementia hospitalization and post-dementia hospitalization mortality in subjects without stroke in the ARIC cohort.

Methods
We included 15,264 subjects (age 45-64 yrs) enrolled in 1987-89, free of stroke before AF, free of stroke between AF and dementia hospitalization, and followed through 2007. AF events and dementia hospitalizations were identified from hospitalization discharge codes; AF was also identified from 4 exam ECGs. Stroke events were identified via annual phone calls, hospital record searching, and were physician-adjudicated. All-cause mortality was determined by cohort surveillance of the National Death Index and annual phone calls. We ran multivariable proportional-hazards models to assess associations between AF (time-varying exposure) and the outcomes: dementia hospitalization and post-dementia hospitalization mortality. Models were adjusted for age, sex, race, center, education, occupation, smoking, BMI, hypertension, diabetes, heart failure, and coronary heart disease.

Results
During follow-up (median 18.7 yrs), there were 1,496 AF cases, 572 dementia hospitalizations, and 320 post-dementia hospitalization deaths. The multivariable HR (95% CI) of dementia hospitalization associated with AF was 1.44 (1.09-1.92), p=0.01. At 15 years, 12.9% of participants with AF and 2.1% without AF were hospitalized with dementia (log-rank test, p<0.0001) (Figure). The multivariable HR (95% CI) of post-dementia hospitalization mortality associated with AF was 1.68 (1.16-2.24), p=0.006.

Conclusions
In persons without stroke, AF is associated with higher risk of dementia hospitalization and post-dementia hospitalization mortality. AF may increase risk of dementia via mechanisms other than cardio-embolic stroke.
Abstract 8694: Phosphodiesterase 3 Inhibitor Prevents Thrombotic Diseases Without Affecting Hemostatic Function
Authors: Yoshida Hideo , Sasaki Yusuke , Itoh Shinsuke , Kondo Shoichi , Tanabe Sohei , Inoue Yoshihiro
Published: April 2024

Introduction:
Conventional anti-platelet therapy is associated with increased risk of bleeding. Recently, the results of the second Cilostazol Stroke Prevention Study (CSPS 2) showed similar efficacy but fewer hemorrhagic events with the phosphodiesterase (PDE)3 inhibitor cilostazol vs. aspirin.

Hypothesis:
We hypothesized that PDE3 inhibition reduces thrombus formation without affecting hemostasis, and leads to beneficial effects in experimental cerebral infarction and peripheral artery disease (PAD) models

Methods:
We used a cilostazol analog, K-134, as a more potent and selective PDE3 inhibitor. To evaluate the anti-thrombus activity of K-134, we measured mortality rate in a pulmonary embolism model established by collagen infusion into mice via the tail vein 10 min after oral administration of K-134. We also studied its influence on tail vein bleeding times. To investigate whether K-134 can ameliorate other thrombotic diseases, we established a rat cerebral infarction model by photochemically induced thrombosis-mediated occlusion of middle cerebral arteries and a PAD model by laurate injection-mediated peripheral arterial injury. Pathological signs in the areas of necrosis in the hind legs in the PAD model were classified as Grade 0 to 5.

Results:
K-134 decreased mortality in the mouse pulmonary embolism model when orally administered at 3, 10, and 30 mg/kg (
n
= 29-30,
P
< 0.01 vs. control, ED50 = 2.1 mg/kg) but did not prolong bleeding time even at 100 mg/kg compared to control (
n
= 30, 98 ± 6 vs. 84 ± 7 s., not significant). In contrast, warfarin prolonged bleeding time (
n
= 29-30, 139 ± 7 vs. 84 ± 7 s.,
P
< 0.01). Preoperative administration of K-134 at 30 mg/kg reduced brain infarct size compared to control in the rat cerebral infarction model (
n
= 12, 87.5 ± 5.6 vs. 126.8 ± 7.5 mm
3
,
P
< 0.01). Furthermore, 30 mg/kg K-134 inhibited the progression of lesions compared with controls in the PAD model (
n
= 12-15, mean grade of pathological sign: 2.3 ± 0.2 vs. 3.5 ± 0.3,
P
< 0.05).

Conclusion:
PDE3 inhibition is an attractive approach for the secondary prevention of cerebral infarction and treatment of peripheral arterial disease.
Abstract 8795: Cardiac Cachexia is Associated with Abnormal Liver Metabolism and Pro-Inflammatory Responses in a Rat Model of Heart Failure
Authors: Kato Takao , Shioi Tetsuo , Niizuma Shinichiro , Kawashima Tsuneaki , Okuda Junji , Kawamoto Akira , Tamaki Yodo , Iwanaga Yoshitaka , Soga Tomoyoshi , Kita Toru , Kimura Takeshi
Published: April 2024

Introduction:
Cachexia, namely body wasting, is a common complication in heart failure (HF). Although neurohumoral and immune abnormalities are associated with the condition, the mechanism by which the imbalance of catabolism and anabolism occurs is not known.

Hypothesis:
We assessed the hypothesis that the liver is important in the pathogenesis of cardiac cachexia, since the liver plays a critical role in systemic metabolic regulation.

Methods:
We analyzed markers of cachexia in Dahl salt-sensitive rats fed a high salt diet which develop hypertension and, subsequently, HF. Dahl rats fed a low salt diet were used as a control. Glucose uptake of the liver was estimated using
18
F-deoxyglucose (
18
FDG). The amount of metabolites in glycolysis and the Krebs cycle was measured employing metabolome analysis.

Results and Conclusion:
The body weight of HF rats was decreased compared with control rats (354±9 vs. 425±13 g, n=6, p<0.05). Food intake was reduced compared with controls by 29% (p<0.05). Blood sugar and insulin levels were decreased by 34 and 54%, respectively (p<0.05). Blood retinol binding protein (RBP), a hepatic protein, was decreased by 53% (p<0.05). The blood levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were increased. These results indicate that Dahl rats serve as a model of cardiac cachexia. Despite the apparent fasting condition, blood free fatty acid levels were decreased by 53% (p<0.05) and triglyceride (TG) levels were increased 2.0-fold (p<0.05). Next, we analyzed the livers of HF rats.
18
FDG uptake was increased 1.7-fold (p<0.05). The concentrations of some metabolites in the glycolytic pathway increased, and those in the Krebs cycle decreased. Gene expression related to lipogenesis increased and the TG content of the liver increased 1.8-fold (p<0.05). Gene expressions of sterol regulatory element-binding protein (SREBP)-1c and SREBP-2, key enzymes in lipogenesis, increased 3.1- and 1.9-fold, respectively (p<0.05). The protein levels of SREBP-1c and SREBP-2 also increased. The gene and protein expressions of TNF-α and IL-1β increased in the liver. In conclusion, cardiac cachexia was associated with abnormal lipogenesis and proinflammatory responses in the liver, which might act as a maladaptive response in HF.
Abstract 8832: Impact of Time Delay to Treatment on Ischemic Microvascular Damage and In-Hospital Complications in Patients with ST-Segment Elevation Myocardial Infarction
Authors: Yamamuro Atsushi , Kaji Shuichiro , Kinoshita Makoto , Ehara Natsuhiko , Kitai Takeshi , Kim Kitae , Kobori Atsushi , Tani Tomoko , Morioka Shigefumi , Kita Toru , Furukawa Yutaka
Published: April 2024

Background:
Primary percutaneous coronary intervention (PCI) is more effective than thrombolytic therapy for the treatment of ST-segment elevation myocardial infarction (STEMI) when delivered by an experienced team soon after the onset of symptoms. However, data from experimental studies suggest that the extent of microvascular damage is worsened by longer durations of ischemia. The impact of ischemic time on microvascular damage and in-hospital complications has been insufficiently studied. The purpose of this study was to examine the effects of recanalization within 120 minutes on the coronary microvascular integrity and in-hospital event rate.

Methods:
Two hundred and eleven consecutive patients with first anterior STEMI who underwent successful PCI were subjected to coronary flow measurement with a Doppler guidewire. The coronary flow velocity spectrum provided the following parameters: systolic peak velocity (SPV) and diastolic deceleration time (DDT). We defined the presence of microvascular obstruction as DDT of ≤ 600 ms and the presence of systolic flow reversal. We classified the patients into two categories according to time from symptom onset to first balloon inflation: ≤ 120 minutes (group 1), 120 < minutes (group 2). The in-hospital event rate was compared among the 2 groups.

Results:
As for the relationship between the ischemic time and the severity of microvascular damage, earlier reperfusion was associated with a significantly lower risk of microvascular obstruction: 0/12 (0%) for group 1 and 89/199 (45%) for group 2 (p<0.05). The ischemic time was significantly correlated with the DDT (group 1 vs. group 2; 806±122 vs. 563±247 ms, p<0.05) and the SPV (22±11 vs. -8±25 cm/s, p<0.05). The in-hospital event rates for malignant arrhythmia and congestive heart failure were significantly higher in patients with late reperfusion group (0/12 patients, 0% vs. 87/199 patients, 44%; p<0.05; 0/12 patients, 0% vs. 49/199 patients, 25%; p<0.05, respectively).

Conclusions:
Early recanalization within 120 minutes critically determines coronary microvascular integrity, and recanalization delays in time to reperfusion with primary PCI adversely affect in-hospital complications in higher risk patients, such as those with anterior STEMI.
Abstract 8846: Relationship Between Left Appendage Volume and Function, and Left Atrial Function: A Real-Time Three-Dimensional Transesophageal Echocardiography Study
Authors: Fukuoka Yoko , Izumo Masaki , Saitoh Takeji , Kuwahara Eiji , Tanaka Jun , Gurudevan Swaminatha V , Tolstrup Kirsten , Siegel Robert J , Shiota Takahiro
Published: April 2024

Background:
Left atrial appendage (LAA) has multilobed complicated structure. Therefore, attempts to quantitate LAA size and function by 2-dimensional (2D) methods may not offer acurate evaluations. Recent development of real-time 3-dimensional transesophageal echocardiography (RT3D-TEE) has enabled us to examine morphology and to determine absolute volumes of LAA without geometrical assumptions. The association between LAA volume and function, and left ventricular (LV) and left atrial (LA) function has not been well investigated.

Methods:
Eighty-nine pts who underwent RT3D-TEE for evaluation of thrombus in LAA were studied. All measurements were performed off-line software. LAA maximal (max) orifice area, max and minimal (min) volumes, and ejection fraction (LAAEF) were assessed (Figure). LAA emptying flow velocity was also measured. We determined max and min LV and LA volume (LAV) by the Simpson method with 2D transthoracic echocardiography. LAV total emptying fraction (LAEF) was determined as (max LAV - min LAV)/ max LAV. Similarly in pts with sinus rhythm, active and passive LAEF were calculated. Pulsed Doppler E, tissue Doppler E' and E/E' were also measured. Additionally, as a parameter of LA compliance, we measured time velocity integral of systolic pulmonary venous flow (SVTI).

Results:
LAA volume was significantly correlated with max LAV, min LAV, E/E' and SVTI. LAAEF was significantly correlated with age, all LAEFs, E/E' and SVTI. There was no correlation between LAA volume and LAAEF (Table). Multiple regression analysis revealed that max LAV and E/E' (both, p<0.01) were independently correlated with 3D derived LAA volume, and active and passive LAEF were independently correlated with 3D derived LAAEF (p=0.02 and p=0.05, respectively).

Conclusion:
LAA volume determined by RT3D-TEE was independently associated with E/E' and max LA volume. Moreover, LAA function was independently associated LA function.
Abstract 8877: Redefining the Role of Angiotensin II Type 1 and Type 2 Receptors in Cardiomyocyte Apoptosis
Authors: Wang Xianwei , Khaidakov Magomed , Mitra Sona , Mehta Jawahar L
Published: April 2024

Purpose of the study:
Angiotensin II exerts its effects by activating its receptors, primarily type 1 (AT1R) and type 2 (AT2R). The role of AT1R and AT2R in cardiomyocyte apoptosis remains controversial. To define the precise role of AT1R and AT2R on cardiomyocyte biology, we studied the apoptotic response of AT1R or AT2R overexpression in HL-1 cardiomyocytes. Materials and

Methods:
HL-1 cells were transfected with AT1R and AT2R cDNA, and cell apoptosis and the expressions of apoptotic genes, NADPH oxidase, ROS, iNOS and eNOS were detected in this study.

Results:
We observed that AT1R overexpression increased endogenous AT2R expression, but AT2R overexpression did not affect endogenous AT1R expression. Caspase-3 staining, cell cycle analysis and Bax/Bcl2 Western analysis indicated that overexpression of AT1R or AT2R resulted in cardiomyocyte apoptosis (Fig A). Further, we observed that AT1R overexpression significantly increased Nox2, p47
phox
and p67
phox
(subunits of NADPH oxidase) and ROS generation; in contrast, AT2R overexpression decreased p67
phox
expression without significant effect on other NADPH oxidase subunits or ROS generation (Fig B). Both AT1R and AT2R overexpression markedly increased iNOS expression (AT2R>AT1R) (Fig B). To delineate the contribution of upregulation of AT2R by AT1R overexpression and subsequent increase in iNOS resulting in apoptosis in cardiomyocytes; AT1R over-expressing cells were treated with AT2R blocker PD133319; this treatment significantly inhibited AT1R overexpression-induced iNOS and apoptosis.

Conclusion:
These findings suggest that AT2R overexpression induces cardiomyocyte apoptosis via iNOS upregulation; AT1R overexpression induces cardiomyocyte apoptosis at least in part via endogenous AT2R increase and resultant upregulation of iNOS.
Abstract 8886: Five-Year Clinical Outcomes of Patients with Sirolimus-Eluting Stent Implantation for Chronic Total Occlusion: Insihgt from the j-Cypher Registry
Authors: Kato Masafumi , Nishikawa Hideo , Morimoto Takeshi , Uchida Fumiya , Miyata Kazuaki , Iwata Akio , Suzuki Hiroyuki , Mitsudo Kazuaki , Kimura Takeshi
Published: April 2024

Introduction
Little is known about long-term efficacy and safety of sirolimus-eluting stent (SES) implantation for chronic total occlusion (CTO), compared with for non-CTO.

Hypothesis
Successful recanalization of CTO with SES confers equally favorable clinical outcome as that of non-CTO.

Methods
The design of the j-Cypher registry was multicenter prospective enrollment of consecutive patients who underwent SES implantation from 41 centers in Japan. From 5 year follow-up information of the j-Cypher registry, we divided 10759 patients treated exclusively and successfully with SES into 2 groups (CTO group: 1210 patients underwent revascularization for CTO, non-CTO group: 9549 patients for non-CTO only). A CTO was defined as complete obstruction with estimated duration ≥1 month. Baseline characteristics and cumulative incidences of major adverse cardiovascular events were compared between the 2 groups. Furthermore the 2 groups were stratified according to their ejection fraction (EF<40% or ≥40%) and studied on their 5 year overall mortality.

Results
The median follow-up duration was 1,640 days. The CTO group was younger (67±11 years vs. 69±10 years, p<0.001), had less diabetes mellitus (44% vs. 48%, p=0.023), and had more multivessel disease (61% vs. 49%, p<0.001). The crude event rates through 5 years such as total death (13% vs. 14%, p=0.562), myocardial infarction (4.2% vs. 3.6%, p=0.349), and definite stent thrombosis (1.9% vs.1.6%, p=0.758) did not differ significantly among the 2 groups, though target lesion revascularization was significantly higher in CTO group (21% vs. 15%, p<0.001). In stratified analysis by EF<40%, CTO group showed better overall survival rate (Figure A), despite no significant difference between the 2 groups with EF≥40% (Figure B).

Conclusions
SES implantation for CTO seems equivalently effective and safe to that for non-CTO. Stratified by EF<40%, SES implantation for CTO could bring better long-term survival.
Abstract 8939: Mild And Moderate Pre-dialysis Chronic Kidney Disease Is Associated With Increased Coronary Artery Calcium
Authors: Roy Sion K , Cespedes Albert , Li Dong , Choi Tae-young , Budoff Matthew J
Published: April 2024

BACKGROUND
It is increasingly evident that patients with chronic kidney disease (CKD) are more likely to die from heart disease than kidney failure. We evaluated whether pre-dialysis CKD is an independent risk factor for coronary artery calcium (CAC) in patients undergoing multi-detector computed tomography (MDCT) for CAC scoring.

METHODS
We analyzed 544 consecutive patients who underwent MDCT at our center. Eleven patients requiring regular hemodialysis were excluded. Patients were divided into three groups: normal GFR (GFR>90 ml/min/1.73 m
2
), mild CKD (90≥GFR>60 ml/min/1.73m
2
) and moderate CKD (60≥GFR>30 ml/min/1.73m
2
). Continuous and categorical variables were compared using ANOVA and the χ
2
statistic. A multiple logistic regression model was used for detecting the association between total CAC score and GFR. An unadjusted model was used, followed by a second model adjusted for covariates known to be related to CAC. Another multivariable binary logistic model predicting presence of CAC (>10) was performed and odds of incidence of CAC (>10) were calculated among the three GFR sub-groups respectively.

RESULTS
In the unadjusted analysis, patients with mild CKD had mean CAC scores 174 points higher than those with the referent normal GFR (p=0.03), while patients with moderate CKD had mean CAC scores 575 points higher than the referent (p<0.001). After adjustment for the proper covariates, patients with mild CKD had mean CAC scores 175 points higher than those with normal GFR (p=0.048), while those with moderate CKD had mean CAC scores 693 points higher than the referent (p<0.001). Without adjustment, in the full population, patients with mild CKD were 1.9 times more likely to have incident CAC (defined as CAC score>10) (95p%CI 1.3-2.9, p=0.002), while patients with moderate CKD were 4.1 times more likely to have incident CAC when compared to the group with normal GFR (95p% CI 2.3-7.8, p<0.001). After adjustment for covariates, patients with mild CKD were found to be 2.2 times more likely (95p%CI 1.3-3.7, p=0.004) and patients with moderate CKD were 6.4 times more likely (95p% CI 2.9-14.3, p<0.001) to have incident CAC compared to the referent group.

CONCLUSION
Mild and moderate pre-dialysis CKD are independent risk factors for increased mean and incident CAC.
Abstract 9004: Creatine Kinase Over-Expression Improves ATP Kinetics and Contractile Function in the Post-Ischemic Myocardium
Authors: Akki Ashwin , Su Jason , Gupta Ashish , Chacko Vadappuram , Wang Yibin , Steenbergen Charles , Weiss Robert G
Published: April 2024

ATP is the biochemical fuel for myocardial contraction but it is depleted during prolonged ischemia and its depletion may limit post-ischemic mechanical function. Because it has been difficult to augment ATP synthesis during and after ischemia, we generated mice that overexpress the myofibrillar isoform of Creatine Kinase (CKM), the primary energy reserve reaction of the heart, in cardiac-specific, conditional fashion to test the hypothesis that enhanced CKM expression increases ATP delivery via Creatine Kinase (CK) in ischemic-reperfused hearts and improves functional recovery. CKM mice were generated using a tet-off system. Gene induction was achieved by switching from a doxycycline diet (650mg/kg diet) to regular diet 4 weeks prior to the study. Isolated, retrograde-perfused hearts from control and CKM mice were subjected to 25 minutes of global ischemia and 40 minutes of reperfusion while cardiac function (rate pressure product, RPP) was monitored using a left ventricular balloon connected to a pressure transducer. A combination of 31P nuclear magnetic resonance magnetization transfer experiments at 11.7T and biochemical assays were used to measure the CK pseudo first-order rate constant (kf), the rate of ATP synthesis via CK (CK flux), intracellular pH and in vitro CK activity. Pre-ischemic kf and CK flux were three-fold higher in CKM than control hearts with no difference in RPP (Table). During ischemia, intracellular pH fell more in control than CKM hearts (6.10±0.29 vs. 6.46±0.08, p<0.05) with no difference in PCr and ATP levels between the two groups. Post-ischemic kf, PCr, CK flux and functional recovery were significantly higher in CKM vs. control hearts as was CK activity (21.6±7.23 vs 7.59±1.42 IU/mg protein, p<0.01). These observations demonstrate that augmenting CKM expression attenuates ischemic acidosis and improves not only [PCr] and rate of ATP synthesis in the post-ischemic myocardium but also recovery of contractile function.
Abstract 9029: Fate Mapping of Monocytes Shows Rapid Turnover Kinetics in Acute Myocardial Infarction
Authors: Leuschner Florian , Ueno Takuya , Gorbatov Rostic , Higgins John M , Pittet Mikael J , Swirski Filip K , Weissleder Ralph , Nahrendorf Matthias
Published: April 2024

While previous studies have addressed monocyte behavior in circulation, less is known about the kinetics of these cells once they enter inflamed tissue. It is commonly believed that monocytes are recruited shortly after ischemic injury, and remain in the infarct until inflammation resolves, although this assumption has not been tested experimentally. We therefore studied the turnover of monocytes in infarcted myocardium of mice after coronary ligation (MI).

Methods and Results:
Bromodeoxyuridine (BrdU) was injected 24 and 12 hrs prior to analysis into mice with MI for pulse-chase experiments. Cell cycle analysis showed no proliferation of monocytes in the infarct tissue. Flow cytometry of cells retrieved 3 days after MI revealed that 43 ± 4 % of monocytes in the infarct had incorprated BrdU into their DNA, and hence were produced and recruited after the first BrdU pulse (i.e. within the last 24 hrs). Monocyte subset analysis revealed faster kinetics for inflammatory Ly-6C-high monocytes when compared to the non-inflammatory Ly-6C-low monocyte subset. To evaluate these rapid cell fluxes with a second, independent method, we transplanted infarcted hearts between isogenic mice with diverging CD45 leukocyte surface markers on day 3 after MI. Transplantations of non-infarcted hearts served as controls. Flow cytometric analysis showed that 6 hrs after transplantation 20 ± 1 % of the monocytes in the infarct were newly recruited from the transplant recipient mouse. This number increased to 40 ± 3 % at 12 hrs, and after 24 hrs the majority (60 ± 0.5%) of monocytes in the infarct derived from the recipient. These data were fitted using a mathematical model of monocyte dynamics (least-squares fit R2 > 99%; N (t) = e-(t/20) ), which reported an average monocyte residence time of 20 hours.

Conclusion:
We observed surprisingly fast monocyte turn-over in acute infarcts with an average tissue residence time of 20 hours.
Abstract 9070: Secretoneurin is Produced in the Ischemic Border Zone of Animals with Myocardial Infarction and Heart Failure, Attenuates Ischemic Injury, and is Associated with the Progression of Heart Failure in Patients
Authors: Røsjø Helge , Stridsberg Mats , Florholmen Geir , Stensløkken Kåre-Olav , Ottesen Anett H , Sjaastad Ivar , Husberg Cathrine , Dahl Mai Britt , Høiseth Arne D , Øie Erik , Louch William E , Omland Torbjørn , Christensen Geir
Published: April 2024

Background:
Secretoneurin (SN) is a peptide belonging to the granin protein family. As two other granin proteins, chromogranin A and B, are increased in cardiac tissue in heart failure (HF), we hypothesized that SN could play a role in cardiovascular pathophysiology.

Methods:
Production and functional aspects of SN were assessed in experimental models and circulating levels measured in two cohorts of HF patients.

Results:
Pro-SN mRNA levels were 11.5 fold increased in viable left ventricular (LV) tissue of mice subjected to coronary artery ligation and with echocardiographical confirmed HF. Protein levels were also increased in the LV of HF animals vs. sham-operated animals, including in the ischemic border zone where we observed increased processing from pro-SN to shorter SN fragments (>100% increase, p=0.001). Immunohistochemistry localized myocardial SN production to cardiomyocytes. We did not observe increased SN production in other organs than the LV. Perfusing isolated cardiomyocytes with SN rapidly induced Stat3 and Erk1/2 phosphorylation, protected from hydrogen peroxide-induced cardiomyocyte apoptosis
in vitro
, and reduced ischemia-reperfusion injury by 30% (p<0.05) in the isolated perfused rat heart. Circulating levels of SN were increased in patients with stable and acute HF compared to control subjects and increased in proportion to HF severity as evaluated by NYHA functional class (p=0.04 for trend). In 68 patients hospitalized for acute HF, admission SN levels provided excellent discrimination for all-cause mortality (n=17) during a median follow-up of 373 days: Hazard ratio [per 0.05 nmol/L increase of SN] 2.34 (95% CI 1.63-3.38), p<0.001. Adjustment for established clinical risk factors including comorbidities, renal function, and LV ejection fraction in multivariate analysis did not attenuate the association between SN levels and mortality: HR 2.43 (95% CI 1.63-3.61), p<0.001.

Conclusion:
SN production is increased in viable cardiomyocytes adjacent to the infarcted area in animals with myocardial infarction and HF, which could be beneficial as SN protects from myocardial ischemia. Based on our results, SN could represent a protective feedback response that is activated in proportion to the severity of HF.
Abstract 9113: Therapeutic Neovascularization Targeting Notch Signaling
Authors: Tateno Kaoru , Minamino Tohru , Yoshida Yohko , Moriya Junji , Okada Sho , Shimizu Ippei , Yokoyama Masataka , Ito Takashi , Nojima Aika , Komuro Issei , Kobayashi Yoshio
Published: April 2024

Implantation of mononuclear cells (MNC) has become a widely used method to induce therapeutic angiogenesis. However, according to multiple clinical trials published recently, MNC transplantation shows no beneficial effect upon approximately forty percent of the critical limb ischemia cases. To improve such outcomes, it may be a reasonable strategy to clarify the precise molecular mechanism underlying the therapeutic responsiveness, and to establish a novel molecular targeting therapy. Here, we show that Notch signaling can be a promising candidate. We previously reported that, in mice hind limb ischemia model, MNC therapy induced therapeutic muscle regeneration and neovascularization through activation of Notch signaling. We newly found that expression of Jagged-1, a Notch ligand, was significantly decreased in MNC harvested from patients who later suffered major limb amputation following cell therapy, indicating that Notch signaling has a pivotal role in the determination of therapeutic responsiveness by MNC implantation, also in a clinical setting. These results warranted us to further investigate and establish therapeutic neovascularization targeting Notch signaling. We first introduced Jagged-1 into hematopoietic cell line Ba/F3 with retrovirus, and transplanted them into ischemic limb of mice. The cells over-expressing Notch ligands were capable not only to enhance Notch signaling in ischemic muscle tissue, but also to significantly improve limb perfusion. To overcome safety concerns using viral constructs, we established another method utilizing agonistic antibody designed specifically against mice Notch-1 receptor. Like the retroviral cells, the antibody enhanced Notch signaling in ischemic muscle. When used in combination with MNC transplantation, the agonistic antibody significantly improved blood flow recovery from limb ischemia. These results warrant us to design a translational research that utilizes antibody medicine targeting Notch signaling for patients with critical limb ischemia.
Abstract 9203: Detecting Myocardial Ischemic Territories in the Setting of Acute Coronary Obstructions at Rest with Cardiac Phase-Resolved Blood Oxygen Level Dependent (CP-BOLD) MRI
Authors: Tsaftaris Sotirios , Zhou Xiangzhi , Tang Richard , Li Debiao , Dharmakumar Rohan
Published: April 2024

Introduction:
In the setting of ACS, particularly in non ST elevation myocardial infarction (NSTEMI), triaging patients for coronary catheterization from the emergency department can benefit from an imaging approach that does not resort to provocative stress or exogenous contrast media. We propose a MRI method that has the capacity to non-invasively and rapidly identify ischemic territories and assess functional status under resting conditions.

Hypothesis:
Tested in a canine model, we hypothesize that on the basis of phasic changes in blood volume and oxygenation it is possible to arrive at an imaging metric that can identify myocardial territories affected by acute coronary obstruction without exogenous contrast media at rest.

Methods:
Flow and motion compensated CP-BOLD and standard cine (cine) images were acquired at 1.5T in 11 canines at baseline and under severe LAD stenosis at rest. First-pass perfusion was performed in order to identify the affected and remote (healthy) territories in end-systolic (ES) and end-diastolic (ED) images. S/D, defined as a ratio of the mean intensity between ES and ED were computed from CP-BOLD and cine images. Two-way repeated measurement ANOVAs were used to test the effects of region (remote, affected) and condition (baseline, stenosis) and their interaction on S/Ds.

Results:
On CP-BOLD, affected regions had S/D<1 consistent with the expectations of physiologic changes in blood volume and oxygenation. No effects were found on S/D computed from cine, indicating that the BOLD sensitivity from CP-BOLD MRI is the principal mechanism enabling the detection of myocardial ischemic territories at rest.

Conclusions:
S/D < 1 (from CP-BOLD MRI) can serve as a potential biomarker for identifying ischemic territories under rest. Since cardiac-phased resolved images are acquired with CP-BOLD, functional changes can also be determined without additional scans, permitting rapid assessment of ACS. The method remains to be tested in patients.