bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 8722: Temporal Trends in Incidence of Stroke Among Children: a 14-Year Statewide Study
Authors: Gandhi Sampada K , McKinney James S , Sedjro Jeanine E , Cheng Jerry Q , Deng Yingzi , Cosgrove Nora M , Cabrera Javier , Kostis John B ,   For the Myocardial Infarction Data Acquisition System (MIDAS) Study Group
Published: April 2024

Objectives:
Although a rare condition, stroke is one of the top 10 causes of death among children. However, little is known about current trends in the incidence of pediatric stroke. We examined all hospitalizations with a diagnosis of stroke in children admitted to all non-federal New Jersey hospitals from 1994-2007.

Methods:
Children (age >30 days to ≤19 years) admitted with a primary or secondary diagnosis of stroke for the first time were included in the analysis. Demographic and clinical information were assessed using the Myocardial Infarction Data Acquisition System (MIDAS) statewide database.

Results:
During the 14 year study period, 1,034 children were admitted with a first time hospitalized stroke. The time trend of incidence followed a quadratic function where the rate decreased from 1994 to a nadir at 1999-2001 and increased after this year (p=0.0003). Interestingly, this parabolic relationship could be explained by two factors: better treatment of sickle cell disease with blood transfusions after year 1998 (p=0.0001), and an improved diagnostic accuracy with increasing use of diffusion-weighted MRI since 2001 (p=0.0002). In addition, increased prevalence of hypertension and obesity among children, better awareness of stroke and more referrals of young patients to neurologists may have contributed to the rise in the incidence of pediatric stroke in recent years. When strokes were categorized into ischemic and hemorrhagic, the incidence of the former showed a quadratic trend mimicking the overall shape described above (p=0.0001), while the incidence of hemorrhagic stroke remained stable during the study period (p=0.12).

Conclusion:
After an initial decrease concurrent with changes in treatment of sickle cell disease, the incidence of pediatric stroke is on the rise due to more widespread use of diffusion-weighted MRI and increased prevalence of hypertension and obesity.
Abstract 8741: Depressive Symptoms and Medication Adherence have a Synergistic Effect on Cardiac Event-Free Survival in Patients with Heart Failure
Authors: Wu Jia-Rong , Lennie Terry , Dekker Rebecca , Chung Misook , Moseer Debra K
Published: April 2024

Background:
Depressive symptoms and medication nonadherence predict hospitalization and death in patients with heart failure (HF). Patients with depressive symptoms have lower medication adherence. However, the combined effects of depressive symptoms and medication nonadherence on hospitalization and death have not been investigated in patients with HF.

Objective:
To explore the combined effect of depressive symptoms and medication adherence on cardiac event-free survival in patients with HF.

Method:
This was a longitudinal study of 218 patients with HF (male 65%, age 60±12 years, NYHA class III/IV 56%). Medication adherence was assessed using a valid and objective measure, the Medication Event Monitoring System (MEMS). Depressive symptoms were measured using the Patient Health Questionnaire (PHQ). Patients were followed for up to 4 years to collect data on cardiac event-free survival (i.e., cardiac emergency department visit, hospitalization, and death). Patients were grouped using an evidence-based cutpoint of 88% on medication adherence from the MEMS data and a score 10 on the PHQ. Kaplan-Meier, log-rank tests and Cox regressions were used to compare cardiac event-free survival among groups.

Results:
Depressive symptoms and medication adherence were independent predictors of cardiac event-free survival (
p
< .001 and = .006, respectively, Figure 1). Patients who had depressive symptoms and were nonadherent had a 4.95 times higher risk of cardiac events than those who had no depressive symptoms and were adherent (Figure 2).

Conclusion:
Depressive symptoms and medication nonadherence work synergistically to reduce cardiac event-free survival in patients with HF.
Abstract 8767: Reduction of AF Recurrences after Pulmonary Vein Isolation Using Adenosine Triphosphate with a Sufficient Observation Period
Authors: Maeda Shingo , Yamauchi Yasuteru , Okada Hiroyuki , Tao Susumu , Kagiyama Nobuyuki , Naito Takaki , Yamaguchi Tetsuo , Hara Nobuhiro , Konishi Yuji , Umemoto Tomoyuki , Miyamoto Takamichi , Obayashi Tohru , Hirao Kenzo , Isobe Mitsuaki
Published: April 2024

Background:
It is well known that additional radiofrequency (RF) applications to eliminate transient pulmonary vein (PV) reconnections induced by adenosine triphosphate (ATP) lead to a reduced recurrence of atrial fibrillation (AF) after PV isolation (PVI). However, no studies have explored the utility of ATP with a sufficient observation period.

Methods:
Of 322 consecutive patients (81 female; mean age 62 ± 11 years) with paroxysmal (PAF) or chronic AF (CAF) that underwent a PVI procedure, 222 had PAF, and 100 CAF. All patients received an extensive PVI procedure, and the CAF patient received an additional left atrial ablation. After the procedures, all patients underwent a right cavotricuspid isthmus ablation during the observation period and all received 20mg of ATP to assess for any dormant PV conduction. If the patients had reconnections of the PVs, additional RF energy was delivered till no reconnections were observed during the ATP injections.

Results:
Forty six gaps (14%) were observed after the observation period, but 69 transient gaps (21%) were recorded during the ATP injections. All transient PV reconnection gaps were abolished by additional RF applications. During a mean follow-up period of 12 ± 5 months, recurrences of AF were observed in 43 patients (26 in PAF patients, 17 in CAF patients). In patients with recurrent AF (group-R), the observation period was significantly shorter than on those without recurrent AF (group-S) (group-R vs. group-S = 17 ± 12 vs. 26 ± 17 min, P < 0.01, PAF patients: 18 ± 14 vs. 26 ± 17 min, P < 0.05, CAF patients: 17 ± 9 vs. 25 ± 15 min, P < 0.05, respectively). There were no significant differences in the left atrial diameter (group-R vs. group-S = 37 ± 6 vs. 39 ± 8 mm, P = NS) between group-R and group-S. Further, there were no significant differences in the other parameters between the two groups.

Conclusion:
The results of this study demonstrate that remapping more than 25 minutes after the PVI was efficient for finding recurrence gaps, similar to with ATP injections. A sufficient observation period and the use of ATP may be useful methods to reduce AF recurrences after PVI in both PAF and CAF patients.
Abstract 8789: Serial Measurements of C-Reactive Protein in Predicting Clinical Outcomes in Patients with Acute Aortic Intramural Hematoma
Authors: Kitai Takeshi , Kaji Shuichiro , Yamamuro Atsushi , Kim Kitae , Ehara Natsuhiko , Kobori Atsushi , Kinoshita Makoto , Tani Tomoko , Kita Toru , Furukawa Yutaka
Published: April 2024

Background:
Inflammation is involved in the pathogenesis and progression of acute aortic dissection, and a high circulating C-reactive protein (CRP) level may be a risk factor for adverse events in patients with aortic dissection. However, there is no data regarding time course in CRP levels during acute phase in patients with aortic intramural hematoma (IMH). The aim of this study was to evaluate the prognostic relevance of serial CRP measurements in patients with IMH.

Methods:
A total of 180 IMH patients (age; 70±11 years, male/female; 105/75) who were admitted to our institution within 48 hours from the onset, were evaluated. CRP data were obtained at admission, 2 days, 1 week, 2 weeks from the onset and maximal values during hospitalization. Patients who underwent surgery within 2 weeks from the onset were excluded. Clinical outcomes were evaluated with a mean follow-up of 5.1±3.9 years.

Results:
CRP levels were 3.0±4.6, 8.7±5.9, 9.0±5.5, and 5.7±4.5 mg/dL at admission, 2 days, 1 week and 2 weeks, respectively. Maximal value of CRP was 12.4±6.3 mg/dL. There were 23 deaths including 9 cases of aortic rupture, and 23 patients underwent surgical or percutaneous repair during follow-up and 19 patients showed progression to classic aortic dissection or aortic aneurysm without surgery. CRP levels at 2 weeks of patients with aorta-related events were significantly higher than that of patients without the events (8.8±5.2 vs 4.5±3.6; P<0.001). Receiver-operating characteristic curve analysis identified CRP level of 5.0 mg/dL at 2 weeks as a cut off for predicting aorta-related events, with sensitivity, specificity, and positive and negative predictive values of 71%, 66%, 35%, and 86%, respectively. The aorta-related event free survival was significantly higher in patients with lower CRP (≤5.0) at 2 weeks (P<0.001,Figure).

Conclusions:
Sustained high levels of CRP at 2 weeks from the onset were associated with a progressive disease course in patients with IMH.
Abstract 8854: Increased Carotid Intima-Media Thickness and Arterial Stiffness are Associated with Lone Atrial Fibrillation
Authors: Chen Lin Y , Schussler Stefanie , Gong Lingli , Foo David C , Wong Raymond C , Seow Swee-Chong , Ling Lieng H
Published: April 2024

Background
Increased carotid intima-media thickness (cIMT) and pulse pressure are associated with common acquired atrial fibrillation (AF). It is unknown whether cIMT and indexes of arterial stiffness are associated with lone AF-onset of AF in patients <60 years in the absence of risk factors for AF. We sought to determine whether cIMT, arterial compliance (AC), carotid-femoral pulse wave velocity (CFPWV), and β stiffness index are associated with lone AF.

Methods
Consecutive patients referred to the arrhythmia clinic for lone AF (onset <60 years) in the absence of hypertension, diabetes, and structural heart disease were included in the study. Patients <60 years seen in the general cardiology clinic without AF, hypertension, diabetes, and structural heart disease were included as controls. cIMT was measured by high resolution B-mode ultrasound. CFPWV was measured by applanation tonometry. AC and β stiffness index were measured using direct radiofrequency tracking of carotid artery pulsatility using Aloka eTracking software. All measurements were obtained during sinus rhythm. Multivariable logistic regression was used to assess association between lone AF and these exposures (modeled as quartiles): cIMT, AC, CFPWV, and β stiffness index.

Results
We enrolled 133 lone AF cases (all variables presented as mean ± standard deviation - age at onset: 44.9 ± 10.6 years, cIMT: 0.68 ± 0.16 mm, AC: 0.73 ± 0.31 mm
2
/Kpa, CFPWV: 7.8 ± 1.8 m/s, β stiffness index: 10.9 ± 4.4) and 171 controls (age at enrollment: 46.7 ± 9.4years, cIMT: 0.61 ± 0.13 mm, AC: 0.84 ± 0.30 mm
2
/Kpa, CFPWV: 7.1 ± 1.3 m/s, β stiffness index: 8.6 ± 3.1). In multivariable logistic regression analyses, cIMT (OR, 1.6 per quartile increment; 95% CI, 1.2 to 2.1; p=0.002), AC (OR, 0.7 per quartile increment; 95% CI, 0.5 to 0.9; p=0.004), CFPWV (OR, 1.4 per quartile increment; 95% CI, 1.1 to 1.8; p=0.02), and β stiffness index (OR, 1.7 per quartile increment; 95% CI, 1.3 to 2.4; p=0.0005) were found to be associated with lone AF after adjusting for age, gender, and left atrial volume index.

Conclusions
Increased cIMT and arterial stiffness are associated with lone AF. Lone AF is not only an ‘electrical disease’. Morphological and functional changes in the arteries may increase risk of lone AF, as in common acquired AF.
Abstract 8890: Artificial Baroreceptor Fully Antagonizes Baroreflex Failure Induced Volume Intolerance
Authors: Hosokawa Kazuya , Funakoshi Kouta , Sakamoto Takafumi , Onitsuka Ken , Sakamoto Kazuo , Tobushi Tomoyuki , Takeo Fujino , Saku Keita , Murayama Yoshinori , Ide Tomomi , Sunagawa Kenji
Published: April 2024

Backgrounds:
Patients with heart failure with preserved ejection fraction have severe atherosclerosis and thereby baroreflex failure resulting from stiffened baroreceptors. We demonstrated that baroreflex failure induces striking volume intolerance and predisposes to pulmonary edema irrespective of left ventricular (LV) function. At present, however, there is no treatment for baroreceptor failure. The aim of this study is to develop artificial baroreceptor (ABaro) to restore physiological volume buffering function.

Methods:
We vascularily isolated the baroreceptor regions in 14 Sprague-Dawley rats. The intra-carotid sinus pressure (CSP) was controlled by a servo-controlled pump. We randomly perturbed CSP and identified the transfer function from CSP to arterial pressure (AP). We randomly, electrically stimulated aortic depressor nerves (ADN) and identified the transfer function from ADN stimulation to AP. Taking the ratio of those two transfer functions yielded the transfer function (H
ABS
) required for the ABaro. ABaro translates AP real-time to ADN stimulation according to H
ABS
. We implemented ABaro and observed the left atrial pressure (LAP) response against stepwise infusions of dextran (Fig. 1). ABaro fully restored the physiological LAP-infused volume relationship (Fig. 2) and markedly increased the infused volume required to raise LAP to 20 mmHg (native: 20.1±3.2, baroreflex failure: 16.6±4.4, ml/kg ABaro: 21.0±3.0 ml/kg).

Conclusion:
ABaro reinstitutes the native baroreflex and would be an attractive tool in preventing pulmonary edema in patients with poor baroreceptor function irrespective of LV systolic function.
Abstract 8921: Long-Term Effects of Smoking and Smoking Cessation on Exercise Stress Testing: Three-Year Outcomes From a Randomized Clinical Trial
Authors: Asthana Asha , Piper Megan E , McBride Patrick E , Ward Ann , Fiore Michael C , Baker Timothy B , Stein James H
Published: April 2024

Background
The long-term effects of continued smoking and smoking cessation on prognostic markers obtained during treadmill stress testing (TST) are unknown. This study evaluated the long-term effects of smoking cessation and continued smoking on TST parameters that predict cardiovascular disease (CVD) risk.

Methods
In a prospective, double-blind, randomized, placebo-controlled trial of 5 smoking cessation pharmacotherapies, symptom-limited TST was performed to determine peak METs, rate-pressure product (RPP), heart rate (HR) increase, HR reserve, and 60-second HR recovery, before and 3 years after the target smoking cessation date. Relationships between TST parameters and treatments among successful abstainers and continuing smokers were evaluated using multivariable analyses.

Results
At baseline, the 600 current smokers (61% female) were mean (standard deviation) 43.4 (11.5) years old and smoked 20.7 (8.4) cigarettes/day. Their exercise capacity was 8.7 (2.3) METs, HR reserve was 86.6 (9.6)%, HR increase was 81.1 (20.9) beats/minute, and HR recovery was 22.3 (11.3) beats. Cigarettes/day and pack-years were independently and inversely associated with baseline peak METs (p<0.001), RPP (p<0.01, pack-years only), HR increase (p<0.05), and HR reserve (p<0.01). After 3 years, 168 (28%) had quit smoking. Abstainers had greater improvements than continuing smokers (all p<0.001) in RPP (+2,055 mmHg*beats/minute), HR increase (+5.9 beats/minute), and HR reserve (+3.7%), even after statistical adjustment (all p<0.001).

Conclusions
Smokers with a higher smoking burden have lower exercise capacity, lower HR reserve, and a blunted exercise HR response. After 3 years, TST improvements suggestive of improved CVD prognosis were observed among successful abstainers, despite weight gain.
Abstract 8968: Reduction of Non-hdl-cholesterol by More Than 5% with NCEP Diet Reduces CHD Risk
Authors: Nakamura Haruo , Mizuno Kyoichi ,   MEGA Study Group
Published: April 2024

Background and aims:
Dietary management is considered to be very important to lower plasma lipids. Non-HDL-cholesterol may be a better indicator of coronary heart disease (CHD) than traditional lipid risk markers (LDL-cholesterol, HDL-cholesterol), which was confirmed in previous studies. However the extent to which non-HDL-cholesterol must be lowered to decrease CHD risk with diet remains to be clarified. To answer this question, we conducted a post-hoc analysis of the dietary treatment group in a large-scale randomized primary prevention trial in Japanese.

Materials and methods
7832 patients with mild hypercholesterolemia were randomly allocated to either diet alone (n=3966) or diet+pravastatin (n=3866) and followed for an average of 5 years. The patients were instructed to follow the National Cholesterol Education Program (NCEP) guideline step 1 diet, which is low in cholesterol and saturated fats, with the addition of fish, like in the usual Japanese diet. Incidence rates of CHD, CHD+cerebral infarction (CI), and all cardiovascular events were calculated by the Cox proportional hazard model according to the reduction rates of non-HDL-cholesterol.

Results
Baseline non-HDL-cholesterol level in the diet group was 184.4±18.6 mg/dL. CHD incidence was significantly reduced by 42% (p=0.02) and by 50% (p=0.007) in relation to a 3% and 5% lowering of non-HDL-cholesterol respectively. The total cardiovascular event rate was significantly reduced by 34% (p=0.02) with a 5% lowering of non-HDL-cholesterol. Neither stroke nor all-cause mortality was affected significantly. On treatment non-HDL-cholesterol levels were less than 174 mg/dL, indicating the reduction of CHD and cardiovascular events.

Conclusion
A reduction of 5% or more of non-HDL-cholesterol with the modified NCEP step 1 diet was associated with a significant reduction in CHD and cardiovascular events.
Abstract 8973: p21-Activated Kinase-Mineralocorticoid Receptor Pathway Aggravates Cardiac Inflammation and Remodeling in Hypertensive Rats with Large Blood Pressure Variability
Authors: Yasuoka Suguru , Kai Hisashi , Kajimoto Hidemi , Kudo Hiroshi , Takayama Narimasa , Anegawa Takahiro , Aoki Yuji , Iwamoto Yoshiko , Fukuda Kenji , Imaizumi Tsutomu
Published: April 2024

Background:
Hypertensive patients with large blood pressure variability (BPV) show aggravated end-organ damage. There is increasing evidence that aldosterone contributes to hypertensive organ damage via mineralocorticoid receptor (MR) activation. Recently, Rac-p21-activated kinase (PAK) pathway is highlighted as an activator of MRs in the renal tubular cells. The aims of this study were to investigate whether large BPV would activate MRs in the hearts in SHR and to determine whether a specific MR blocker, eplerenone, at a non-depressor dose would prevent the large BPV-induced aggravation of hypertensive cardiac remodeling.

Methods and Results:
SHRs (n=76) were fed with normal salt diet. A rat model of a combination of hypertension and large BPV was created by performing bilateral sinoaortic denervation (SAD) in SHR. SAD increased BPV (P<0.05) without changing mean BP in SHR. Large BPV induced perivascular macrophage infiltration and aggravated myocardial fibrosis and cardiac myocyte hypertrophy, resulting in LV systolic dysfunction (P<0.05 for each). Immunohistostaining revealed the expressions of MR and PAK in the coronary medial cells and to a lesser extent the cardiac myocytes in SHR. Large BPV induced the translocation of the MRs into the nuclei (i.e. MR activation) and increased PAK phosphorylation (i.e. PAK activation) in the coronary medial cells. Chronic administration of a subdepressor dose of eplerenone prevented the MR translocation, macrophage infiltration, myocardial fibrosis, myocyte hypertrophy, and LV dysfunction (P<0.05 for each), while not affecting BPV. Circulating levels of aldosterone, corticosterone, active renin, and angiotensin II were not changed by large BPV in SHR.

Conclusion:
Large BPV activated PAK and MR in the coronary medial cells and aggravated perivascular inflammation, cardiac remodeling, and LV dysfunction in SHR, which were prevented by eplerenone. Thus, the PAK-MR pathway activation may play a role in cardiac inflammation and remodeling induced by large BPV superimposed upon hypertension. Eplerenone may be useful for treatment of hypertensives with large BPV.
Abstract 9020: Utilizing Speckle Tracking Echocardiography to Analyze Strain Patterns in Pediatric Patients with Suspected Myocarditis
Authors: Prasad Aparna , Klugman Darren , Gierdalski Marcin , Cross Russell
Published: April 2024

Background:
Myocarditis is a rare disease involving inflammation of the myocardium which causes significant morbidity and mortality in children. Currently, endomyocardial biopsy is the only definitive way to diagnose myocarditis but techniques such as echocardiography and cardiac MRI can be utilized to aid in diagnosis. New advances such as speckle tracking echocardiography (STE) can analyze myocardial strain patterns which are a more sensitive measure of ventricular function. The primary aim of this study is to determine if 2D strain imaging via STE in children with suspected myocarditis correlates with other methodologies currently used in making the diagnosis.

Methods:
A retrospective review was conducted to identify all patients with suspected myocarditis from 2004-2010.Standard 2D echocardiograms were analyzed off-line using the Syngo Velocity Vector imaging software to determine global strain and strain rate in the longitudinal and circumferential views.

Results:
A total of 66 patients with suspected myocarditis were compared to 29 age matched controls. Of the 66 study patients, 48% (32/66) underwent endomyocardial biopsy and/or MRI. Global longitudinal and circumferential strain and strain rates were lower in the suspected myocarditis group compared to controls (
P
<0.005). Patients who underwent further workup with either biopsy and/or MRI had significantly decreased circumferential strain rate (
P
<0.03) and especially decreased longitudinal strain rate (
P
<0.003) when compared to those who did not have further diagnostic testing with biopsy or MRI. Furthermore, all patients with biopsy or MRI proven myocarditis had decreased longitudinal and circumferential global strain and strain rates as compared to controls (
P
<0.0008).

Conclusions:
: STE can be a useful diagnostic tool in identifying patients with suspected myocarditis. In our study, all global strain and strain rate values were significantly decreased in patients with proven myocarditis as compared to controls. Specifically, longitudinal strain rate may be a more sensitive diagnostic tool to select patients who merit further testing. Further work is needed to determine if STE correlates with segmental abnormalities on MRI in children with suspected myocarditis.
Abstract 9108: Identification and Validation of Protein Modules Driving Chromatin Remodeling in Cardiac Hypertrophy and Failure
Authors: Franklin Sarah , Mouillesseaux Kevin , Ren Shuxun , Wang Yibin , Chen Jau-Nian , Vondriska Thomas M
Published: April 2024

Chromatin remodeling is a necessary precursor to global changes in gene expression-however, the mechanisms for genome-wide changes in chromatin state are poorly understood. In the heart, diseases like hypertrophy and failure are well known to be driven by large gene expression changes that enact a fetal-like phenotype, particularly in the areas of metabolism, calcium handling and contraction. Previous work has investigated classes of histone modifying enzymes that alter chromatin accessibility during cardiac hypertrophy. What remains unknown is how changes in histone modifications and transcription factor activation are interfaced at the level of nucleosome remodeling. To discover modules of proteins involved in nucleosome remodeling in heart failure, quantitative proteomics was used to measure chromatin-associated proteins during different stages of heart disease in a mouse model of pressure overload (transverse aortic constriction). Out of 733 proteins detected, 366 of which showed quantitative changes during disease, unsupervised clustering was used to reveal modules of proteins with statistically similar (p<0.01) changes in expression. These modules were prioritized using gene ontology-based bioinformatics: a candidate module, containing 63 proteins, showed significant increase in all members during hypertrophy and further increased during failure. To investigate the role of this module in cardiac phenotype, a high-throughput loss of function screen was carried out using morpholino-based knockdown in zebrafish. Candidates were further prioritized based on their predicted involvement in nucleosome insertion/eviction. Among the initial proteins investigated were Ncl, Nap1l4 and Rcc1. Loss of Ncl led to defects in cardiac function and morphology exhibited by severe edema, regurgitation and dysregulation of chamber size and patterning. In addition, siRNA-mediated knockdown was used to investigate the function of individual members in neonatal rat ventricular myocytes. This investigation reports on a novel discovery method in a clinically-relevant model of heart failure, interfaced with a rapid phenotypic screening tool in zebrafish to identify and physiologically characterize novel chromatin remodelers in the heart.
Abstract 9164: Who Receives ASA for Primary Prevention in Canada?: Insight From the PRIMARY CARE AUDIT OF GLOBAL RISK MANAGEMENT (PARADIGM) Study
Authors: Gupta Milan , Ostrovski Ilia , Kajil Mahesh , Tsigoulis Michelle , Verma Subodh
Published: April 2024

BACKGROUND:
The role of ASA for primary CVD prevention is controversial. We assessed the use of ASA in healthy, middle-aged subjects in the PARADIGM study.

METHODS:
PARADIGM enrolled 3015 men >40 or women >50 to assess trends in CV risk assessment. Subjects with diabetes, vascular disease, or those receiving lipid lowering drugs were excluded. We report on the 406 subjects (13.5%) who were receiving ASA for primary CVD prevention.

RESULTS:
Subjects prescribed ASA, compared to those not, were more likely to be older (61.6 vs. 55.5y, p<0.0001), male (p<0.001), white Caucasian (88.9 vs. 66.6%, p<0.0001), past/current smokers (43.8 vs. 33.3%, p=0.0004), hypertensive (60.8 vs. 25.7%, p<0.00001), and to have a CV family history (30.9 vs. 23.3%, p=0.002). SBP, DBP, creatinine, hsCRP, waist circumference (WC) and BMI were discriminators of ASA use (all p<0.0005). LDL-c fasting glucose, IFG, and HbA1c did not differ between those prescribed ASA or not. Mean modified FRS for those prescribed ASA vs. not were 22.3 vs. 13.5% respectively (p<0.00001). Of those prescribed ASA, FRS categories were 18% low, 47.8% intermediate, and 34.2% high. In ASA-treated subjects, rates of smoking, HT, family history and mean BP, BMI and hsCRP were similar between genders. Mean HDL and LDL (both p<0.0001), glucose (p=0.05), and HbA1c (p=0.0001), were higher in women than men. Mean FRS was lower in ASA-treated women (14.4 vs. 27.0%, p<0.00001). FRS categories for ASA-treated women vs men were: low (34.4 vs 8.2%), intermediate (43 vs. 34.5%), and high (22.5 vs. 57.3%, all p<0.00001).

CONCLUSIONS:
In PARADIGM, 13.5% of men >40 and women >50 received ASA for primary CVD prevention. Smoking, HT, family history, hsCRP and abdominal obesity were discriminators of ASA use, yet lipid and glycemic levels were not. Two thirds of ASA-treated subjects had low/intermediate FRS. The majority of ASA use in women was in those with low or intermediate risk scores.
Abstract 9215: Flavonoids Baicalein Mitigates Post-Resuscitation Myocardial Dysfunction and Improves Survival via PI3K-Akt-eNOS Pathway
Authors: Chang Wei-Tien , Lee Chun-Pei , Chien Chiang-Ting , Shao Zuo-Hui , Huang Chien-Hua , Hsu Chiung-Yuan , Tsai Min-Shan , Cheng Hsiao-Ju , Chen Shyr-Chyr , Lee Yuan-Teh , Vanden Hoek Terry L , Chen Wen-Jone
Published: April 2024

Background:
Post-resuscitation myocardial dysfunction is a model of global ischemia-reperfusion (IR) injury that is associated with poor prognosis. Flavonoids baicalein has been shown to reduce myocardial IR injury. We therefore investigated the role of baicalein in mitigating post-resuscitation myocardial dysfunction and the potential protective mechanisms.

Methods:
Using an established rat model of asphyxia cardiac arrest and CPR, we administered baicalein (20 mg/kg) 2 h before cardiac arrest and compared the left ventricular (LV) function with those of standard CPR control. The arterial blood was sampled for measurement of reactive oxygen species (ROS) using chemiluminescence method. The LV systolic and diastolic functions were assessed by dP/dt max and -dP/dt max. Two hours after return of spontaneous circulation (ROSC), the heart was harvested for measurement of malondialdehyde (MDA), phosphorylation of Akt and endothelial nitric oxide synthase (eNOS). In a subgroup with minimal invasive procedures, the survival and neurological outcomes were monitored up to 3 days.

Results:
In standard CPR group, the systemic ROS generation and myocardial MDA were increased in the post-resuscitation phase. The dP/dt max and -dP/dt max were significantly compromised. Treatment of baicalein reduced systemic ROS and myocardial MDA (both
P
<0.001), and improved post-CPR dP/dt max and -dP/dt max (
P
<0.05 and 0.01, respectively). The survival and neurological outcomes were also ameliorated (Logrank
P
< 0.001 and
P
< 0.01, respectively). In terms of the protective mechanism, the phosphorylated Akt (p-Akt) and eNOS (p-eNOS) of the heart 2 h post-CPR were both increased in baicalein group. If NOS inhibitor

N
ω

-nitro-L-arginine methyl ester (10 mg/kg) was cotreated with baicalein, the improved dP/dt max and -dP/dt max were diminished. The survival and neurological outcomes also became worse. If phosphoinositide 3 kinase (PI3K) inhibitor wortmannin (15 μ g/kg) was cotreated, the increased p-Akt and p-eNOS were reversed. The improvements in LV function and survival/neurological outcomes were also abrogated.

Conclusion:
Baicalein improves post-resuscitation myocardial dysfunction and prognosis through antioxidant protection and PI3K-Akt-eNOS signaling.
Abstract 9223: In vivo Assessment of Pulmonary Arterial Wall Fibrosis by Intravascular optical Coherence Tomography in Pulmonary Arterial Hypertension: A New Prognostic Marker of Adverse Clinical Follow-Up
Authors: Enric Domingo , Grignola Juan Carlos , Aguilar Rio , Arredondo Christian , Montero Maria Angeles , Lopez Manuel , Bravo Carlos , Vazquez Manuel , Bouteldja Nadia , Roman Antonio
Published: April 2024

The aim of the study is to quantify pulmonary artery (PA) wall fibrosis by intravascular optical coherence tomography (OCT) in severe pulmonary arterial hypertension (PAH) and to correlate it with clinical follow-up. Histological and OCT study of PA specimens is also performed. OCT is an imaging modality for studying vessel wall structure with higher resolution than intravascular ultrasound. Nineteen consecutive PAH patients , aged 54±16 (4 men) , functional class II-III were studied with simultaneous right heart catheterization and OCT in inferior lobe PA segments (2-4 mm diameter). Relative PA wall fibrosis (%fibrosis) was obtained by OCT (area of fibrosis/PA cross sectional area×100). All patients were prospectively followed up. Physicians who carried out the clinical follow-up were blind to the OCT results. Patients were initially divided into 2 groups, low and high degree of fibrosis, according to the median value of PA wall OCT % fibrosis. Clinical deterioration had been initially defined in terms of either mortality, lung transplantation, need of intravenous prostaglandins or onset of clinical right ventricular failure. OCT measurements showed a high intra and interobserver agreement. There was a good correlation between OCT and histological fibrosis in PA wall from explanted lungs. In the whole group area of fibrosis was 1.4±0.8 mm
2
and % fibrosis was 22.3±8. All patients were prospectively followed-up with an average follow-up of 3.5 years (2.5-4.5 years). Patients were divided into 2 groups, low and high degree of fibrosis, according to the median value of PA wall OCT fibrosis percentage ( 22% ). There were 10 patients with a high degree of fibrosis ( ≥ 22% ) and 9 with a lower degree of fibrosis (<22% ). Clinical events, as previously defined, were present in 6 patients ( 1 death, 1 lung transplantation, 2 intravenous prostaglandins, 2 right heart failure ) out of 10 patients with high fibrosis and in 0 out of 9 patients with low fibrosis ( p<0.01).

In PAH, the severity of PA remodeling assessed by quantification of PA wall fibrosis by OCT was significantly predictive of severely unfavorable clinical outcome. There was a good correlation between OCT and histological fibrosis in explanted PA.
Abstract 9251: Increasing Prevalence and Decreasing Mortality in Pulmonary Hypertension Related Hospitalizations in the United States: An Analysis of Over 20,000 Hospital Admissions
Authors: Rossano Joseph W , Crystal Matthew A , Morales David L , Graves Daniel E , Hanna Brian D , Mallory George B
Published: April 2024

Introduction:
Pulmonary hypertension (PH) is a serious but uncommon disorder. However, few large scale data exist on the prevalence or mortality associated with PH hospitalizations in children. Risk factors for hospital mortality are also unknown.

Hypothesis:
The prevalence of pediatric PH admissions has increased, but the mortality has decreased, over the 7-year period from 2000 - 2006.

Methods:
A retrospective analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Database was performed for pediatric (age ≤ 20 years) PH related admissions for the years 2000, 2003, and 2006. The database is a nationwide sampling of pediatric hospital discharges and is weighted to provide national estimates.

Results:
In 2000 there were 7,348 (95%CI 6,176 to 8,521) pediatric PH related admissions and in 2006 there were 9,378 (95%CI 8,068 to 10,687) admissions (p<0.001). Congenital heart disease was the most common associated diagnosis in all years (range 46.5% to 50.4%). Bronchopulmonary dysplasia (BPD) with PH increased over time from 4.2% in 2000 to 10.2% in 2006 (p<0.001). Several comorbidities increased over time including sepsis, acute renal failure, and respiratory failure (p<0.05 for all). Overall hospital mortality was greater for patients with PH (6.2%) compared to patients without PH (0.4%) (OR 17.7, 95%CI 16.1 to 19.4). Mortality for PH patients decreased over time from 7.7% in 2000 to 4.8% in 2006 (p<0.001). Mortality was greatest among infants (8.2%), those with BPD (9.5%), respiratory failure (19.9%), renal failure (38.2%), and with extracorporeal membrane oxygenation (ECMO) (34.1%). On multivariable analysis, factors associated with increased mortality included earlier year (OR 2.0, 95% CI 1.6 to 2.5), respiratory failure (OR 4.5, 95% CI 3.6 to 5.7), ECMO (OR 4.8, 95% CI 3.1 to 7.4), and acute renal failure (OR 6.3, 95% CI 4.2 to 9.4).

Conclusions:
There were 2,000 more PH related hospitalizations in children in 2006 than in 2000. Comorbidities increased over this time period; however, hospital mortality decreased over 60%. These findings have critical implications for pediatric hospital utilization and planning. Increased off-label application of PH pharmacotherapeutic agents may have contributed to the improved survival.
Abstract 9265: Effects of One Year of Endurance Exercise Training on ‘Dynamic’ Starling Mechanisms in Heart Failure with Preserved Ejection Fraction
Authors: Fujimoto Naoki , Shibata Shigeki , Hastings Jeffrey L , Prasad Anand , Bhella Paul S , Carrick-Ranson Graeme , Palmer Dean , Levine Benjamin D
Published: April 2024

Background:
Left ventricular (LV) and arterial stiffening occurs with aging, which can be prevented by lifelong exercise training. Heart failure with preserved ejection fraction (HFpEF) is a disease of the elderly with stiff LV and arteries. However, it is unknown whether exercise training in HFpEF could improve beat-to-beat ‘dynamic’ Staring mechanism, which reflects the interaction between LV and arterial stiffness or LV-arterial coupling.

Methods:
Seven patients with HFpEF (age 75 ± 6 yrs) and 9 healthy sedentary controls (age 71 ± 3 yrs) were enrolled and participated in 1 year of endurance exercise training. Maximal oxygen uptake (VO
2
max) was measured during incremental treadmill exercise. All subjects underwent right heart catheterization; beat-to-beat LV end-diastolic pressure (LVEDP; estimated from pulmonary arterial diastolic pressure) and stroke volume (SV) index (from pulse contour analysis) were obtained during controlled breathing (0.2 Hz, 12 breaths/min) before and after 1 year of training. Spectral transfer function analysis was used as an index of the dynamic Starling mechanism (Shibata JAP2011), and effects of exercise training on the ‘dynamic’ Starling mechanism in HFpEF and healthy controls were compared. By the end of the 1 year of training, the exercise duration was about 200 minutes/wk.

Results:
VO
2
max was significantly larger in healthy controls at baseline. After exercise training, VO
2
max was unaffected in HFpEF, but increased in healthy controls (HFpEF: 12.6 ± 3.6 vs. 12.8 ± 3.3 ml·kg
-1
·min
-1
, p = 0.71, healthy control: 22.8 ± 3.4 vs. 27.2 vs. 4.3 ml·kg
-1
·min
-1
, p < 0.01, ANOVA p < 0.01). The ‘dynamic’ Starling mechanism (transfer function gain between LVEDP and the SV index) at baseline was impaired in HFpEF patients compared to the healthy control (HFpEF 0.26 ± 0.14 vs. 0.40 ± 0.09 ml·ml
-2
·mmHg
-1
, p = 0.026). Transfer function gain was improved by 65% after exercise training in healthy controls (p = 0.035), while gain in HFpEF was not improved by exercise training (0.26 ± 0.14 vs. 0.29 ± 0.17 ml·ml
-2
·mmHg
-1
, p = 0.78).

Conclusion:
A year of exercise failed to improve beat-to-beat LV-arterial coupling in HEpEF, while it was improved in healthy controls. These results may partly explain why no improvement was observed in VO
2
max in HFpEF.
Abstract 9272: Tachy-Brady Syndrome: The Critical Role of Adenosine-induced Sino-Atrial Conduction Block in Post-Tachycardia Pauses
Authors: Glukhov Alexey V , Vargas-Pinto Pedro , Billman George E , Carnes Cynthia A , Fedorov Vadim V
Published: April 2024

Introduction:
In patients with sino-atrial nodal (SAN) dysfunction, long pauses lasting several seconds are often observed after rapid atrial pacing or paroxysmal tachycardia. Clinical studies suggest that adenosine may play an important role in the SAN dysfunction observed during metabolically compromised myocardial states, but the mechanism is unclear.

Methods:
We studied SAN dysfunction produced by a combination of adenosine and fast atrial pacing in an isolated coronary-perfused canine SAN preparation using high resolution optical mapping (n=7). Sinus cycle length (SCL) and direct SA conduction time (SACT) were measured during perfusion of Adenosine (1-100 µM, n=6), selective A1 receptor agonist CCPA (1-3 µM, n=3), and A1 antagonist DPCPX (1-3 µM, n=4). Corrected SAN recovery time (cSNRT) was measured after 1 minute of slow atrial pacing (3.3 Hz) and tachypacing (7-8 Hz).

Results:
Adenosine and CCPA significantly increased the SCL (469±66 vs. 674±175 ms, p=0.03), and SACT (44±11 vs. 94±15 ms, p<0.001) dose-dependently, as well as increasing cSNRT after slow atrial pacing (from 70±28 ms to 232±63 ms, p<0.001). Moreover, at high drug concentrations, termination of atrial tachypacing produced pauses up to 3.3±4.4 sec in 5 out 7 preparations due to complete conduction block between the SAN and atria, despite a stable SAN intrinsic rate (figure). Conduction block was preferentially related to depressed excitability in SAN conduction pathways. DPCPX restored the adenosine-induced changes of SCL, SACT and cSNRT back to control.

Conclusion:
These data directly demonstrate that post-tachycardia atrial pauses during adenosine perfusion resulted from depressed conduction between the SAN and atria (exit block) rather than from slowed pacemaker automaticity. Thus, these data suggest an important modulatory role for adenosine in tachy-brady syndrome: particularly in patients with ischemia or heart failure, conditions known to increase adenosine production.
Abstract 9277: Assessment of Coronary Flow Reserve for the Prediction of Long-Term Outcome in Patients with Non-Obstructive Coronary Artery Disease; Transthoracic Doppler Echocardiographic Study
Authors: Nakanishi Koki , Fukuda Shota , Shimada Kenei , Miyazaki Chinami , Otsuka Kenichiro , Taguchi Haruyuki , Muro Takeshi , Kawarabayashi Takahiko , Yoshikawa Junichi , Yoshiyama Minoru
Published: April 2024

Introduction
. Coronary flow reserve (CFR) is dependent on microvascular blood flow which reflects the combined effects of the epicardial coronary stenosis and microvascular dysfunction. Various coronary risk factors cause impaired CFR, even in the absence of obstructive coronary artery narrowing. However, its prognostic importance for long-term outcome has not been fully discussed.

Methods
. 272 patients (181 men, mean age 68 ± 12 years) with known or suspected coronary artery disease underwent transthoracic Doppler echocardiographic examination for the assessment of CFR in left anterior descending (LAD) artery. Angiolography revealed non-obstructive narrowing of LAD (<70%) in these patients. The cardiovascular events included cardiac death, myocardial infarction, unstable angina pectoris, and congestive heart failure.

Results
. During a mean follow-up of 4.0 ± 1.9 years, cardiovascular events occurred in 32 patients, including cardiac death (n = 5), myocardial infarction (n = 6) and unstable angina (n = 9), congestive heart failure (n = 12). Multivariate analysis identified hemoglobin (p = 0.02), left ventricular mass index (p = 0.02), C-reactive protein (p = 0.01), and CFR (p <0.001) as significant and independent predictors of cardiovascular events. The ROC curve provided CFR <2.3 as the best cut-off value predicting late cardiovascular events (sensitivity was 0.82 and specificity was 0.69). No cardiovascular events occurred in patients with CFR ≥4.0.

Conclusions.
We demonstrated that the measurement of CFR provided independent prognostic information in patients without obstructive narrowing of LAD. Close follow-up and strict control of coronary risk factors may be required in patients with CFR <2.3, even without obstructive narrowing of coronary arteries.
Abstract 9281: Usefulness of Lipoprotein(a) to Predict Progression of Non-Culprit Coronary Lesions after Acute Myocardial Infarction for Paients with Normal Low-Density Lipoprotein Cholesterol
Authors: ikenaga Hiroki , Ishihara Masaharu , Inoue Ichiro , Kawagoe Takuji , Shimatani Yuji , Miura Fumiharu , Nakama Yasuharu , Dai Kazuoki , Ohtani Takayuki , Miki Takashi , Nakamura Masayuki
Published: April 2024

Purpose:
Lipoprotein(a) [Lp(a)] is associated with development of new coronary lesions after acute myocardial infarction (AMI) and Lp(a) value remains consistent within individuals across their lives. However, the efficacy of Lp(a) in patients with normal low-density lipoprotein cholesterol (LDL-C) was unclear. This study was undertaken to assess the efficacy of Lp(a) in patients with LDL-C.

Methods:
Lp(a) was measured 1 week after AMI in 410 patients who underwent primary percutanious coronary intervention (PCI) within 24 hours after symptom onset. Patients were stratified into two groups based on Lp(a); high Lp(a) group (>40mg/dl:n=95) was compared with low Lp(a) group. Furthermore, patients were stratified into two groups based on LDL-C; high LDL-C group (>120mg/dl) was compared with normal LDL-C group (≤120mg/dl). Clinical follow-up was obtained up to 1 years. Major Cardiac Coronary Event (MACE) was defined as cardiac death, myocardial infarction (MI) and/or revascularization for new lesions.

Results:
There was no significant difference with age, sex, hypertension, diabetes, infarct location, multivessel disease, final TIMI 3 and use of cardiovascular drugs between high Lp(a) group and low Lp(a) group. High Lp(a) was associated with higher 1-year cumulative incidence of MACE (25.2% vs 11.1%, p<0.001) and new lesion revascularization (22.1% vs 6.6%, p<0.001). Multivariate analysis showed that Lp(a) was an independent predictor for MACE (OR 1.64, 95% CI: 1.31-2.06, p<0.001) and new lesions requiring revascularization (OR 1.67, 95% CI: 1.32-2.13, p<0.001). In patients with normal LDL-C, Lp(a) was associated with the incidence of new lesion revascularization during 1-year (p=0.01, figure B) as same as in patients with high LDL-C (p=0.007, figure A).

Conclusions:
These results suggest that Lp(a) could predict MACE after AMI regardless of LDL-C.
Abstract 9293: 320 Slice Computed Tomography Imaging-Based Semiquantitative Assessment of Left Ventricular Wall Motion: Comparison with Transthoracic Echocardiography
Authors: Kataoka Akihisa , Funabashi Nobusada , Takaoka Hiroyuki , Uehara Masae , Takahashi Akiyo , Kobayashi Yoshio
Published: April 2024

Methods:
Retrospective review of ECG-gated 320 slice CT (Aquilion one, Toshiba Medical) of 22 subjects with asynergy of LV wall motion TTE (13 men, 9 female, mean age 68.5±10.5 years, 5 old myocardial infarction, 5 hypertrophic cardiomyopathy, 4 cardiac sarcoidosis, 2 takotsubo cardiomyopathy, 2 idiopathic arrhythmia, 1 dilated cardiomyopathy, 1 left ventricular non compaction, and 1 drug-induced cardiomyopathy). Retrospective, ECG-gated, conventional enhanced 320-slice CT with tube current dose modulation was performed with a slice thickness of 0.5mm and a tube voltage of 120 kilovolts. CT images were reconstructed every 5% from 0-95% of the R-R interval of the ECG and 4D CT images were generated (Virtual Place, Aze) and LV wall motion was evaluated at 17 segments by American Society of Echocardiography criteria, by two experienced cardiologists, as was TTE. They analyzed TTE (IE-33, Philips) retrospectively, blinded to the CT results.

Results:
For 374 segments, kappa coefficients for the 5 classifications (aneurysmal, dyskinesis, akinesis, hypokinesis, normal kinesis) by the two assessors were 0.458 and 0.606 for CT and TTE data, respectively. Agreement between CT and TTE was 0.255 and 0.555 for the two observers. Kappa coefficients of the 7 classifications (aneurysmal, dyskinesis, akinesis, severe, moderate and mild hypokinesis, normal kinesis) by the two assessors were 0.367 and 0.439 for CT and TTE data, respectively. Agreement between CT and TTE was 0.158 and 0.423 for the two.

Conclusions:
Semiquantitative LV wall motion assessment by 320 slice CT and TTE showed good inter-observer agreement but there were some discrepancies between 320 slice CT and TTE by the two assessors.