bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16710: Evidence of Ischemic Memory From Strain Rate Analysis of Diastolic Function During/After Percutaneous Coronary Intervention
Authors: Sampat Unnati , Prasad Anand , Mahmud Ehtisham , Ilapakurti Manjusha , Palakodeti Vachaspathi , DeMaria Anthony N
Published: April 2024

Introduction
The ability to detect ischemia occurring prior to the time of examination (ischemic memory) would be of great clinical value. Studies have shown that abnormal left ventricular (LV) diastolic function may be a sensitive marker of myocardial ischemia.HypothesisWe hypothesized that analysis of diastolic function by strain imaging (SI) could detect abnormalities due to myocardial ischemia for some time after percutaneous coronary intervention (PCI).

Methods
We performed echograms on 31 pts having angiography, 18 controls (CON) without obstructive CAD and 13 undergoing single vessel PCI (ISCH), at baseline, during balloon occlusion, and for 15, 30, and 60 minutes afterwards. SI analysis of the ischemic segment using speckle tracking was done in parasternal short axis views. The end systolic strain at the closure of the aortic valve (A) and at the time of one-third of diastole (B) were measured. A strain imaging diastolic index (SIDI) was calculated as A-B/Ax100% to examine diastolic performance.

Results
(see Table)Baseline characteristics for CON were similar to ISCH: mean age 61 ±14 years, HR 70 ±12, BP 135/70 ±27/13mmHg, male 69%, DM 38%, HTN 100%. SIDI values for ISCH decreased during balloon occlusion and remained low at 60 minutes after reperfusion. SIDI values in CON did not change significantly from baseline for 60 minutes after the procedure. (A) for ISCH decreased from 30.5 ±4% at baseline to 11.4 ±2% at 15 minutes after balloon occlusion and improved slightly to 15.8 ±2% at 60 minutes after reperfusion. (A) values in CON were unchanged from 22.6 ±8% at baseline to 20.8 ±9% at 60 minutes after procedure.

Conclusions
Abnormalities of systolic and diastolic strain (manifested by a decrease in SIDI values) occur in response to the induction of myocardial ischemia by PCI. As compared to the change in systolic strain, the change in SIDI values is of greater magnitude, is persistent at 60 minutes after reperfusion, and may be a useful marker of ischemic myocardial memory.
Abstract 16722: Myocardial Infarction and Sudden Cardiac Death in Olmsted County, Minnesota, Before and After Smoke-Free Workplace Laws
Authors: Hurt Richard D , Weston Susan A , Ebbert Jon O , McNallan Sheila M , Croghan Ivana T , Schroeder Darrell R , Roger Veronique L
Published: April 2024

Objective:
To determine if the implementation of smoke-free workplace laws reduced the incidence of the acute coronary events including myocardial infarction (MI) and sudden cardiac death (SCD).

Background:
Nonsmokers chronically exposed to second-hand smoke (SHS) are at increased risk of death from heart disease. However, a nonlinear dose relationship exists between SHS exposure and coronary heart disease (CHD) such that the relative risk of CHD is 1.31 for nonsmokers and 1.78 for smokers. Reductions in admissions for MI in locales where smoke-free workplace laws have been implemented have been observed, but none have assessed SCD. On January 1, 2002, a smoke-free restaurant law (Ordinance #1) was implemented in Olmsted County, Minnesota, and on October 1, 2007, all workplaces became smoke-free (Ordinance #2).

Methods:
Under the auspices of the Rochester Epidemiology Project, we measured the incidence of MI and SCD during the 18-month calendar period before and after implementation of each smoke-free ordinance. All MI were validated using biomarkers, cardiac pain, and Minnesota coding of the ECG. SCD was defined as out-of-hospital deaths assigned to CHD (ICD-9 codes 410 through 414).

Results:
For the overall study period of the 18 months before the implementation of the smoke-free restaurant ordinance and 18 months after the implementation of the smoke-free workplace ordinance, we observed a 45% decline in the incidence for MI (p <0.01) and a 50% decline in the incidence for SCD (p <0.01). See Table. During this same period, the prevalence of hypertension, diabetes, hypercholesterolemia, and obesity either remained constant or increased while the prevalence of smoking among adults declined by 23% (22% to 17%).

Conclusion:
In the Olmsted County population, substantial declines in the incidence of MI and SCD were observed after smoke-free laws were implemented. Smoke-free workplace laws may not only be associated with a decrease in MI but SCD as well.
Abstract 16747: Interaction Between Polymorphisms in Inflammation-Related Genes and Atrial fibrillation in Patients with Dilated Cardiomyopathy
Authors: Ogimoto Akiyoshi , Suzuki Jun , Inoue Katsuji , Nishimura Kazuhisa , Nagai Takayuki , Shigematsu Yuji , Okayama Hideki , Higaki Jitsuo
Published: April 2024

Background:
Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and a leading cause of cardiovascular morbidity. Recently, we reported the G allele at -2518 in the monocyte chemoattractant protein 1 (
MCP-1
) gene may be a novel genetic marker of susceptibility to nonfamilial idiopathic dilated cardiomyopathy (DCM). In addition, it has been suggested that inflammation have a possible role in the development of AF. We hypothesized that polymorphisms in inflammation-related genes might be associated with AF in patients with DCM.

Methods and Results:
We genotyped polymorphisms (rs3759324 and rs1143629) in inflammation-related genes (lymphotoxin beta receptor,
LTBR
and interleukin-1beta,
IL1B
) in 83 patients with DCM by using the TaqMan method. Patients were classified into AF group (n=21) if they had AF, and sinus rhythm (SR) group (n=62) if they had SR. Logistic-regression methods were used to determine the potential effect of each genotype and the interaction between them on the risk of AF. There was no significant increase in risk of AF with each polymorphism alone. However, there was a marked increase in the risk of AF among persons who were homozygous for both variants (The
LTBR
C/C and
IL1B
G/G genotypes, odds ratio 4.56, P=0.02).

Conclusion:
The
LTBR
C/C and
IL1B
G/G genotypes act synergistically to increase the risk of AF in patients with DCM. These data suggest that inflammation-related genes predispose to AF in patients with DCM.
Abstract 16750: Discordant Stress Echocardiography Test Results with Normal Stress Echocardiogram Imaging Does Not Predict a Low Probability for Significant Coronary Artery Disease
Authors: Reddy Bhavananda T , Nitzel Cory M , Gillespie Hamilton S , Rosen Boaz , McGann Chris
Published: April 2024

Introduction:
Prior studies have indicated that when compared to stress electrocardiography (ECG) alone, the addition of echocardiography conveys a higher sensitivity and specificity for the diagnosis of coronary artery disease (CAD). Limited data is available focusing on discordant stress testing results, defined as abnormal electrocardiography and normal echocardiography. Our hypothesis is that discordant results should not be equated with a low probability for significant obstructive CAD.

Methods:
A retrospective analysis of 147 discordant stress echocardiography test results in patients who underwent subsequent coronary imaging either with invasive or CT angiography was performed. Discordant stress tests were defined as ECG results with ST segment depressions >1.0 mm at peak exercise or at target heart rate on Dobutamine stress and normal rest and stress echocardiogram wall motion. Coronary stenoses were determined quantitatively with ≥70% stenosis or ≥50% for left main coronary artery stenosis defined as significant obstructive CAD.

Results:
Out of 147 cases (mean age 61±10 years, 56% male) with discordant stress echocardiography tests, 51 (35%) were found to have significant obstructive CAD on angiography. Though a larger number of patients underwent exercise (111) vs. Dobutamine (36) stress, correlation with significant obstructive CAD was similar (34% vs. 36%, respectively, p value=0.98).

Conclusion:
Greater than one third of patients with discordant stress echocardiography test results have significant obstructive CAD.
Abstract 16955: The Direct Renin Inhibitor Aliskiren Improves Vascular Remodeling in Transgenic Rats Harboring Human Renin and Angiotensinogen Genes
Authors: Savoia Carmine , Arrabito Emanuele , Parente Rosa , Zezza Luigi , Sada Lidia , Madaro Luca , Nicoletti Carmine , Muller Dominik D , Volpe Massimo
Published: April 2024

The renin inhibitor aliskiren (ALK) reduces blood pressure and improves cardio-renal organ damage in hypertensive double transgenic rats (dTGRs) which express both human renin and angiotensinogen. Little is known about the effect of ALK on hypertension-related vascular structural alterations of resistance arteries. We tested the hypothesis that chronic treatment with ALK improves vascular remodeling of resistance arteriesin in dTGR. dTGRs (5 weeks old) were treated with ALK (3 mg/kg/day, n=5) or ramipril (RAM, 1 mg/kg/day, n=5) for 14 days and compared with age-matched untreated dTGRs. Blood pressure (BP) was measured by tail-cuff method. Resistance arteries media-to-lumen ratio (M/L) was evaluated on mesenteric arteries as pressurized preparations. The expression of AT1 receptor, AT2 receptor, eNOS and the NADPH subunit gp91phox was evaluated in aorta by immunoblotting. The reactive oxygen species (ROS) production was evaluated in aorta by Dihydroethidium (DHE) staining. BP was similarly reduced in both ALK-treated and RAM-treated rats compared to untreated dTGRs (167±1.18 mmHg and 169.4±1.5 mmHg vs 196.8 ±3.9 mmHg, respectively P<0.05; reduction of -15% and -14%; P<0.05). M/L was equally reduced in ALK-treated and RAM-treated rats compared to untreated rats (6.3±0.5 % and 6.4±0.2 % vs 9.8±.04%, respectively; P<0.05). AT1 and AT2 receptor expression was similar in all the groups. eNOS expression was increased only in ALK-treated rats (+41.3±6.3 % vs untreated dTGRs, p<0.05). gp91phox was slightly reduced in both ALK-and RAM-treated dTGRs. Both ALK and RAM similarly reduced ROS production in dTGRs compared to untreated rats (14.7±0.2 AU and 13.9±0.3 AU vs 18.1±0.9 AU, respectively; p<0.05). In conclusion equieffective antihypertensive dose of ALK or RAM improved oxidative stress and reduced M/L of mesenteric arteries. Only ALK increased the eNOS bioavailability. Hence, in dTGRs renin inhibition compares favorably to ACE inhibition in improving vascular remodeling.
Abstract 17014: Pericardial Fluid Levels of Granulocyte Colony-Stimulating Factor are Closely Correlated with Left Ventricular Remodeling in Post-Myocardial Infarction Patients Undergoing Coronary Artery Bypass Grafting Surgery
Authors: Miyamoto Shoichi , Fujita Masatoshi , Inoko Moriaki , Haruna Tetsuya , Izumi Toshiaki , Nakane Eisaku , Katoh Takao , SAJI Yosiaki , Ueyama Koji , Nohara Ryuji
Published: April 2024

Purpose:
Granulocyte colony-stimulating factor (G-CSF) has been demonstrated to play an important role in the progression of left ventricular (LV) remodeling following myocardial damage by regulating the enzymatic systems of proteolysis and antiproteolysis. The purpose of this study was to investigate whether G-CSF acts as autocrine/paracrine factors and is accumulated in pericardial fluids, and to evaluate whether LV dysfunction or myocardial ischemia is related to the production and release of G-CSF.

Methods and Results:
We measured the concentrations of G-CSF and N-terminal pro-brain natriuretic peptide (NT-proBNP) in both plasma and pericardial fluid in 22 post-myocardial infarction (MI) patients undergoing coronary artery bypass grafting surgery for unstable angina (n=8) or stable angina (n=14). The G-CSF level was significantly higher in pericardial fluid than in plasma (89±93 vs. 15±8 pg/ml, p<0.001). Interestingly, pericardial fluid levels of G-CSF were significantly higher in patients with impaired LV function (less than 55% in LV ejection fraction) than in those with normal LV function (145±95 vs. 21±7 pg/ml, p<0.001). Pericardial fluid G-CSF levels were correlated with LVEDVI (r=0.746, p<0.0001) and LVESVI (r=0.843, p<0.0001) than did plasma G-CSF level (LVEDVI: r=0.233, p=NS; LVESVI: r=0.259, p=NS). G-CSF levels in pericardial fluid but not in plasma were inversely correlated with LV ejection fraction (r=-0.824, p<0.0001). In addition, pericardial fluid G-CSF levels were correlated with pericardial fluid NT-proBNP levels indicating LV remodeling following MI (r=0.427, p<0.05). However, pericardial fluid G-CSF levels in patients with unstable angina were not significantly elevated compared to those with stable angina (117±102 pg/ml vs. 73±88 pg/ml, p=NS).

Conclusions:
G-CSF accumulated in pericardial fluid may play an important role in the LV remodeling process by promoting proteolysis, and G-CSF may be secreted from the heart into the pericardial space in response to not myocardial ischemia but LV dysfunction.
Abstract 17032: Case Mix Predicts Hospital Performance on Measures of Patient Experience
Authors: Joynt Karen E , Orav E. John , Jha Ashish K
Published: April 2024

The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) is the national assessment of hospital performance on patient experience with care, with over 95% of acute-care U.S. hospitals participating. The Value-Based Purchasing (VBP) program ties Medicare payments to hospitals’ performance on this metric. Some have expressed concern that sicker patients may rate their hospital experience more poorly, potentially putting hospitals that care for the sickest patients at a disadvantage. However, we lack empirical data to support or refute this notion. We used the latest available national HCAHPS and Medicare data to assess whether hospitals’ performance on HCAHPS measures varied by case mix, defined by patients’ predicted mortality. We examined how variations based on case mix compared with variations based on structural characteristics such as size and teaching status. We found that hospitals that cared for sicker patients were more often urban, non-profit hospitals that were larger, located in the northeast or west and more likely to have a teaching affiliation. In bivariate analyses, we found that hospitals with the sickest patients (those in the highest quartile of predicted mortality) had substantially lower HCAHPS performance compared with hospitals with the least sick patients (lowest quartile of predicted mortality) (as measured by proportion of patients giving the hospital a 9 or 10, 62.6% versus 69.4%, p<0.001). In multivariable analyses adjusting for size, teaching status, and other hospital characteristics, the differences in HCAHPS performance across quartiles of predicted mortality narrowed somewhat (63.3% versus 68.5%, p<0.001). The differences based on case mix were larger than those based on size, teaching status, location, or any of the other covariates we examined. As Medicare implements VBP, our findings suggest that hospitals with the sickest patient population are at greater risk of being financially penalized.
Abstract 17066: A Metabolic Basis for Histone Acetylation and a Potential Mechanism of Epigenetic Regulation in Right Ventricular Failure
Authors: Sutendra Gopinath , Dromparis Peter , Haromy Alois , Stenson Trevor H , Michelakis Evangelos
Published: April 2024

Right ventricular (RV) failure is the most critical determinant of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). There is an increasing awareness of important differences between the left ventricle (LV) and RV. Recently, histone deacetylase (HDAC) inhibitors, which increase histone acetylation, have had promising results on maladaptive LV hypertrophy. However, in RV hypertrophy (RVH), HDAC inhibition resulted in RV failure. Recently, nuclear acetylation processes have been shown to be dependent, in part, on the mitochondria. Since there is evidence of mitochondrial diversity between the RV and LV, we hypothesized that histone acetylation may have a metabolic basis and explain the transition to RV failure. In order to study histone acetylation and its relation to metabolism and disease progression in the failing RV, we used a rat model of monocrotaline (MCT)-induced PAH, in which we studied animals with normal RV function (n=6, RVSP=38±2 mmHg, CO=102±2 ml/min and RV/LV+Septum=22±1), compensated RVH (CRV; n=10, RVSP=66±8 mmHg, CO=80±13 ml/min and RV/LV+Septum=48±3, 2-3 weeks post-MCT) and decompensated RVH (DRV; n=9, RVSP=52±2 mmHg, CO=67±10 ml/min and RV/LV+Septum =58±2, 4-6 weeks post MCT). Compared to control, the myocardium (RV free wall) from CRV animals exhibited decreased mitochondrial activity shown by increased mitochondrial membrane potential and decreased mitochondrial-derived reactive oxygen species (mROS). This was associated with increased RV glucose uptake measured by PET in vivo, suggesting a shift of metabolism away from mitochondria towards glycolysis. CRV animals also showed decreased histone-3 (H3) acetylation (IHC/immunoblot). In contrast, DRV animals showed decreased RV glucose uptake, increased mROS as well as induction of the mitochondrial uncoupling-protein 2 in DRV myocardium. These metabolic/mitochondrial changes were associated with an increase in H3 acetylation in the DRV compared to the CRV animals. We show that metabolism and H3 acetylation closely follow mitochondrial remodeling and that these changes separate CRV from DRV potentially opening a new window in our understanding of RV failure.
Abstract 17074: T1-Weighted MR Imaging of Aortic Angiogenesis in Rabbits with an Ultralow New Low Gadolinium
Authors: Pan Dipanjan , Wang Kezheng , Schmieder Anne H , Caruthers Shelton D , Senpan Angana , Wickline Samuel A , Shen Baozhong , Lanza Gregory M
Published: April 2024

Background:
The recent discontinuation of the AIM-HIGH study suggests that even HDL and TG levels do not adequately predict cardiovascular disease outcome. Angiogenesis, an integrated intramural biomarker of plaque progression, has been quantitatively and rapidly used for T1-weighted MR imaging with targeted gadolinium nanoparticles (PFC NPs), but new agents with even lower lanthanide levels are desired.

Objective:
We hypothesized that targeted manganese-oleate core NCs that present 30-fold less Gd than PFC NPs could provide strong, T1-weighted MR imaging of neovascular α
v
β
3
-integrin expression in vivo.

Methods and Results:
Vascularly-constrained (D
av
=140 nm, ζ=-13mV) nanocolloids (NC) of Mn oleate (20% v/v) were synthesized using only 1.25mole% of Gd as (versus 30 mole% for PFC NPs), 0.25 mole% of a quinolone-derived α
v
β
3
-integrin antagonist, and 98.5 mole% lecithin. Cholesterol fed New Zealand White rabbits (n=8/group) received α
v
β
3
-Mn(Gd)-NC or nontargeted Mn(Gd)-NC i.v. (1ml/kg); 8 rabbits on normal chow received α
v
β
3
-Mn(Gd)-NC. Dynamic MR imaging (3.0T) of the descending thoracic aorta wall revealed a marked signal enhancement (47±5%) at 2h. In comparison, the nontargeted-MnGd-NC had lower (20±5%) signal enhancement than targeted NPs (p<0.05). Rabbits fed a normal diet and treated with α
v
β
3
-MnGd NP had the lowest signal increase, 12±3%, which did not differ from the nontargeted treatment. Histology corroborated the prominent, neointimal proliferation among cholesterol-fed, and homing specificity.

Conclusions:
Angiogenesis imaging offers a direct intramural measure of atherosclerotic disease progression and α
v
β
3
-Mn(Gd)-NC provides a sensitive MR molecular imaging approach with gadolinium decreased to 300-fold less than clinical single dose Gd-DTPA.
Abstract 17129: Altered Subendocardial Perfusion Reserve in Patients with Normal-High Blood Pressure Assessed by Quantitative Analysis of Myocardial Perfusion MRI
Authors: Nakajima Hiroshi , Sakuma Hajime , Onishi Katsuya , Nakamori Shiro , Nagata Motonori , Ishida Masaki , Kitagawa Kakuya , Dohi Kaoru , Nakamura Mashio , Ito Masaaki
Published: April 2024

Background
Myocardial perfusion reserve (MPR) reflects endothelial function of the coronary artery and can be altered by various atherosclerotic risk factors. We previously reported that hypertension is associated with impairment of MPR, especially subendocardial MPR. However, information is limited regarding the impact of normal-high blood pressure (systolic blood pressure (SBP) of 130-139mmHg, diastolic blood pressure (DBP) of 85-89mmHg, or both) on MPR.

Purpose
To determine if MPR was already altered in patients with normal-high blood pressure by using a quantitative analysis of stress-rest myocardial perfusion MRI.

Method
We studied 73 subjects without hypertension (SBP<140mmHg and DBP<90mmHg) who did not exhibit regional myocardial ischemia and myocardial scar on stress CMR study. Subjects were divided into two groups (Normal-high group: n=19, 68±9 year-old, 17 men; Normal-optimal group (SBP<130mmHg and DBP<85mmHg): n=54, 68±10 year-old, 33 men) according to blood pressure. Stress-rest myocardial perfusion MRI was acquired with blood signal saturation correction, and absolute subendocardial and epicardial myocardial blood flow (MBF) and MPR were quantified. MPR were calculated as stress MBF divided by rest MBF.

Result
The averaged transmural MPR in subjects with normal-high blood pressure was significantly lower than that in normal-optimal group.(2.74±1.61 vs. 3.80±2.03, p=0.043). When subepicardial MBF and subendocardial MBF were analyzed separately, MPR in subepicardial myocardium did not demonstrate significant difference between two groups (3.09±1.66 vs. 4.29±2.49, p=ns). In contrast, MPR in subendocardial myocardium was significantly reduced in the high-normal group than in the normal-optimal group. (2.57±1.51 vs. 3.65±1.66, p=0.015)

Conclusion
In the current study evaluating subjects without regional myocardial ischemia or significant coronary artery disease, subendocardial MPR was significantly decreased in the group with normal-high blood pressure. The result of this study suggests that endothelial function of the coronary artery is already altered in patients with normal-high blood pressure.
Abstract 17405: MicroRNA-205 Knockdown Induces Preadipocyte Cell Proliferation and Adipogenesis in Visceral Adipose of Obese Mice
Authors: Adi Nikhil C , Adi Jennipher N , Kurlansky Paul , Agatston Arthur , Webster Keith A
Published: April 2024

Introduction:
Central obesity involves deposition of fat around the trunk and in visceral adipose (VA) tissue. It is more common in men and carries a higher risk of CVD, dyslipidemia and T2D. In obese individuals, the increase in adiposity results from increases in the number and size of adipocytes, while the degree of hypertrophy relative to hyperplasia influences the level of body fat and the metabolic consequences of obesity.

Hypothesis:
miR-205 expression is increased in differentiated adipocytes and its inhibition leads to visceral adiposity.

Methods:
NONcNZO10 (NZ10) mice with polygenic susceptibility to T2D or SWR controls were fed Control (CD) or South Beach (SD; high protein/unsaturated fat) diets for 25 weeks. After 12 hr. fasting the mice were sacrificed and VA was collected. Total RNA was isolated and subjected to Sanger 14 multi-species miRNA microarray. Mouse 3T3-L1 preadipocytes were cultured in either preadipocyte maintenance medium or DM2 adipogenic differentiation medium. Preadipocytes were transfected with both pre and anti-miR-205 precursor and inhibitor molecules using OPTI-MEM and NeoFx transfection agent.

Results:
Visceral adiposity was not induced in the control SWR fed either diet or NZ10 mice fed south beach diet as can be assessed by their body weights and percent fat levels (p<0.01). NZ10mice fed CD were hyperglycemic with impaired glucose tolerance test and hyperinsulinemic; gene expression analysis showed significant induction of key adipogenic genes; PPAR gamma and FABP4 in the VA of these mice. Microarray and real time PCR data revealed 10-fold down regulation of miR-205 in the VA of NZ10 mice fed CD vs SD or SWR mice fed either diet. miR-205 inhibition using anti-miR-205 inhibitor molecules in 3T3-L1 cells significantly increased cell proliferation as assessed by BrdU assay (p<0.001). Oil Red O staining of differentiating adipocytes with miR-205 knocked down showed increased staining for lipids (p<0.001). Also real time PCR analysis revealed increased mR-205 expression in differentiated adipocytes over preadipocytes (p<0.001).

Conclusions:
miR 205 inhibition increases preadipocyte cell proliferation and adipogenesis in the visceral adipose of obese mice.
Abstract 17454: ADP Ribosyl Cyclase (CD38) Degrades the NADP(H) Pool Causing Endothelial Nitric Oxide Synthase Dysfunction in the Postischemic Heart
Authors: Reyes Levy A , Zweier Jay L
Published: April 2024

In postischemic myocardium impaired endothelial function occurs with endothelial nitric oxide synthase (eNOS) dysfunction and this limits vasodilation and tissue perfusion. Recently, we have shown in the isolated rat heart, that during ischemia/reperfusion (I/R) injury both tetrahydrobiopterin (BH
4
) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) are depleted, and when these lost eNOS cofactors/substrates are repleted the activity of the dysfunctional enzyme is largely restored and vasodilation markedly improved. In addition to its role as an obligatory NOS substrate, NADPH is also required for maintenance of BH
4
levels through dihydrofolate reductase. We observe that endothelial NADP(H) levels are >80% depleted in reperfused hearts following 30 min of global ischemia and NADPH repletion yields a marked 30% increase in coronary flow. However, while NADPH repletion is highly beneficial, the pathway of its degradation was unknown. We show that following 30 min I and R, the oxidized form of NADPH, NADP
+
, falls in the whole heart tissue to 29% ± 1% of pre-ischemic levels and to less than 10% in the endothelium, which limits its availability to replenish NADPH in turn hindering vasodilation. We further show that the fall of NADP
+
coincides with the production of nicotinamide and 2-phospho-cyclic adenosine diphosphoribose (2-P-cADPR), a signaling molecule with the potential to liberate Ca
2+
via IP
3
pathway. These data suggest that the enzyme ADP Ribosyl Cyclase (CD38) is activated and depletes NADP
+
. Treatment with the CD38 inhibitor -NAD
+
enhanced the recovery of postischemic coronary flow. CD38 is known to be activated by oxidative stress. Thus, we observe that CD38 is activated in the postischemic heart and degrades the NADP(H) pool with production of cADPR which can induce release of Ca
2+
from intracellular stores. Thus, inhibition of CD38 provides a promising new approach to improve the recovery of endothelial function in the postischemic heart.
Abstract 17486: Circulating Oxidized Low-Density Lipoprotein Levels are Associated with Coronary Lesion Complexity in Patients with Acute Coronary Syndrome: An Optical Coherence Tomography Study
Authors: Matsuo Yoshiki , Kubo Takashi , Iwaguro Tetsuya , Wada Teruaki , Ueno Satoshi , Okumoto Yasushi , Akagi Hideharu , Tanaka Atsushi , Akasaka Takashi
Published: April 2024

Background:
It has been shown that elevated oxidized low-density lipoprotein (ox-LDL) levels are associated with plaque vulnerability. The aim of this study was to investigate whether circulating ox-LDL levels are correlated with coronary lesion complexity assessed by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS).

Methods and Results:
OCT was used to determine plaque morphology in 80 patients with ACS. Blood samples were collected before coronary angiography and circulating levels of malondialdehyde (MDA)-modified LDL, one of ox-LDL, were measured by using enzyme-linked immunosorbent assay. Patients were divided into a high MDA-modified LDL group (high MDA, ≥155 U/L) and low MDA-modified LDL group (low MDA, < 155 U/L) according to median MDA-modified LDL levels. Plaque ruptures and thin cap fibroatheromas (TCFAs) were more frequently observed in high MDA patients compared to low MDA patients (87% vs. 56%, P<0.01; 65% vs. 43%, P<0.05, respectively). The frequency of thrombi was not different between two groups. The MDA-modified LDL levels in patients with complicated lesions (defined as lesions with plaque rupture or rupture with thrombi) were significantly higher compared to non-complicated lesion (P<0.05). A multivariate logistic regression model revealed that the presence of complicated lesion correlated with MDA-modified LDL levels (
P
=0.03; odds ratio, 3.13; 95% CI, 1.09 to 8.93).

Conclusion:
Circulating MDA-modified LDL levels were associated with coronary plaque complexity assessed by OCT. MDA-modified LDL might be a useful biomarker for plaque vulnerability in ACS patients.
Abstract 17516: Screening for Heart Disease in Rural China with Fingerstick BNP and Echo: Results of the ALERT (Asia Pacific Link to Evaluation and Referral for Treatment) Trial
Authors: Maisel Alan S , DeFilipi Chris , Richards Mark , Yin Mary , Dayi Hu
Published: April 2024

China is faced with a large percentage of the population with limited health care access, especially in rural areas. We proposed that a finger stick BNP test might identify children with compromised congenital heart disease as well as adults with cardiac dysfunction. Along with Peking's Peoples Hospital and the Chinese Red Cross, we traveled to three rural hospitals in Ruijin Jiangxi province, where significant congenital heart disease (CHD) exists. A notice was sent to all three communities that anyone with heart problems, symptoms of heart disease, or who would like to be screened for heart disease could attend. After consent was signed, a questionnaire (history and symptoms) was filled out, followed by blood pressure, ECG, echocardiography, and finger stick BNP (Alere, inc) test. Those with significant heart disease were referred on the spot to a cardiologist and/ or a cardiac surgeon. In this first session, we screened 38 children (at least 5 years old) and 142 adults (37% male, mean age 60). In children, while no absolute level of BNP was related to the presence or absence of CHD, finger stick BNP levels great than 35 pg/ml were associated with significant cardiac compromise. The area under the ROC curve was 0.75. In adults, BNP levels > 150 pg/ml identified those with significant systolic or diastolic dysfunction or valvular disease with only 4% false positives (area under ROC= 0.90). Thus, it appears that a simple finger stick BNP test can identify those children with significant congenital heart disease and adults with advanced heart disease who should move to the “front-lines” of health care management.
Abstract 17532: How to Assess the Best Left Atrial Function by Speckle Tracking: Recommendations for a Standard Method
Authors: Rimbas Roxana Cristina , Mihaila Sorina , Dulgheru Raluca Elena , Vinereanu Dragos
Published: April 2024

2D speckle-tracking echocardiography (STE) is a novel, feasible technique for the assessment of longitudinal myocardial left atrial (LA) function. Normal ranges, and also cutoff values to diagnose LA dysfunction with different diseases have been reported. However, 2 different methods, based on P-wave and R-wave as the reference point for generation of strain curves, have been used. Therefore, we compared these 2 methods, in order to define which one provides the most correct assessment of all LA functions.

Methods:
20 normal subjects (46±14 yrs, 11 men) with adequate 2D images in 4C view were evaluated for LA function by STE. We used 2 different methodologies, P-wave and R-wave as a reference point, for the evaluation of LA strain, strain rate, and derived times. Active LA function was assessed from negative global strain at atrial contraction (GSA-), time from P to peak negative strain (TGSA-), and late diastolic strain rate (GSRL); passive function from positive global strain at AVC (GSA1+) and at MVO (GSA2+), and time from R-wave to both peaks (TGSA1 and TGSA2), late positive global strain (GSAL), and also from early negative diastolic global strain rate (GSRE); reservoir function from the sum of GSA- and GSA1+ (SUMGSA), positive global strain rate at the beginning of LV systole (GSR+), and time from P to peak (TGSR+).

Results:
Active LA function (GSA-) was significantly lower, whereas passive and reservoir functions were significantly higher (GSA1+, GSA2+, GSAL, SUMGSA) with R-wave method (both p<0.001; see table). There were no differences between methods regarding all derived times and strain rate indices.

Conclusions:
The 2 methods used to assess LA functions by STE do not provide similar results. The R-wave method essentially ignores active function, and overestimates late conduit function by comparison with the P-wave method, and therefore, we suggest that using P-wave as a reference point for generation of strain curves might estimate correctly all LA functions.
Abstract 17730: Aberrant Endothelial FGF Signaling Due to Disruption of MicroRNAs 424/503 in Pulmonary Arterial Hypertension
Authors: Kim Jongmin , Kojima Yoko , Kang Yujung , Aldred Micheala , McLean Danielle , Comhair Suzy , Erzurum Serpil , Chun Hyung J
Published: April 2024

Pulmonary arterial hypertension (PAH) is a disease characterized by the vascular remodeling of the pulmonary arterioles, including formation of plexiform and concentric lesions comprised of proliferative endothelial cells. We recently found that disruption of the G protein-coupled receptor signaling axis comprised of the ligand apelin and the receptor APJ leads to significant worsening of hypoxia induced pulmonary hypertension (PH) in mice, and found that the pathway is also perturbed in clinical PAH. To characterize novel downstream endothelial targets which may be utilized by apelin-APJ signaling to protect against the vascular remodeling processes in PAH, we carried out a microRNA (miRNA) array analysis of pulmonary artery endothelial cells (PAECs) subjected to knockdown of apelin, APJ, or both. We identified two miRNAs (miR-424 and miR-503) that are highly expressed in PAECs, but are significantly downregulated in the context of apelin/APJ knockdown. Remarkably, we found marked decrease in levels of miR-424 and miR-503 in the experimental monocrotaline (MCT) rat model of PH, as well as in PAECs isolated from a subset of patients with clinically diagnosed PAH. Our in vitro functional studies demonstrated that both miR-424 and miR-503 exert anti-proliferative, anti-angiogenic effects, via a mechanism that targets two key components of the fibroblast growth factor (FGF) signaling pathway, namely FGF2 and FGFR1. Consequently, we found marked increase in protein levels of FGF2 and FGFR1 in PAECs from PAH patients, as well as lungs of rats with MCT induced PH. Lastly, we found that restoration of miR-424/503 expression in the MCT induced model of PH by intranasal lentiviral delivery can significantly decrease FGF2 and FGFR1 expression and ameliorate the severity of the disease as demonstrated by decreased right ventricular systolic pressure (38 vs. 24.3 mmHg, p<0.001, n=5-8/group) and RV/LV+septum weight ratio (0.52 vs. 0.43, p<0.05). We conclude that miR-424/503 play a critical role in maintaining pulmonary vascular homeostasis, and that disruption of their expression serves a critical contribution to the aberrant endothelial proliferation that is a hallmark of PAH.
Abstract 17741: Angiotensin II Enables Leukocyte/Endothelium Integrated Signaling Mechanisms That are Causative of Endothelial Dysfunction in Insulin Resistance
Authors: Scalia Rosario , Eguchi Satoru , Landesberg Gavin
Published: April 2024

Recent studies have linked vascular AngII/AT1r signaling to the calcium-dependent protease µ-calpain. We have recently reported that activation of endothelial-expressed µ-calpain by AngII/AT1r signaling induces leukocyte-endothelium interactions in the post-capillary venules of the microcirculation. Accordingly, we hypothesized that: 1) AngII/calpain signaling impairs endothelium-dependent relaxation in the arterial system of the obese, insulin resistant Zucker Fatty (ZF) rat, and 2) neutrophil derived myeloperoxidase (MPO) synergizes with AngII/AT1r signaling to sustain calpain activation in the vascular wall of ZF rats. We used wire myography to study endothelium-dependent relaxation and vascular reactivity of the rat and mouse aorta. Aortic rings isolated from ZF rats exhibited reduced endothelium-dependent relaxation to ACh and increased contractility to Norepinephrine (p<0.01 versus control Lean Zucker (ZL) rats). Incubation of aortic rings with either 1-µm AT1r blocker losartan or 10-µM calpain inhibitor ZLLal restored endothelium-dependent relaxation in aortic rings from ZF rats (p<0.05 versus untreated ZF aortic rings). Furthermore, endothelium-dependent relaxation to ACh was preserved in µ-calpain deficient mice fed a high-fat diet for 12 consecutive weeks. Plasma and aortic levels of MPO were also elevated in ZF rats (p<0.01 versus ZL rats) and reduced by losartan treatment (p<0.05 versus untreated ZF rat).
Ex vivo
studies demonstrated that AngII acutely induces MPO release from control neutrophils, a phenomenon that was prevented by pre-incubation of neutrophils with 1-µM Losartan. Biochemical studies in rat aortic endothelial cells confirmed that MPO significantly synergizes AngII/AT1r-induced calpain activation. Taken together our data demonstrate that AngII/AT1r signaling impairs endothelium-dependent relaxation in the obese, insulin resistant organism by a mechanism that implicates neutrophil-derived MPO and endothelial expressed calpain. These data uncover:
1)
a novel integrative mechanisms responsible for hypertension in obesity with insulin resistance and
2)
new molecular targets of the pleiotropic actions of AT1r blocker on the blood-vascular system.
Abstract 17811: Rate of Cardiac Recovery with Combined Pharmacological Therapy and Continuous Flow LVAD Support
Authors: Patel Snehal R , Bhatia Vivek , Edwards Pauline , Nucci Cecilia , Goldstein Daniel , Maybaum Simon
Published: April 2024

Introduction:
Bridge to recovery has remained a tantalizing option for LVAD therapy despite disappointing rates of cardiac improvement in the literature. Most of these prior studies were limited by lack of adjuvant heart failure medical therapy (HFMED) or were reported in the first generation pulsatile pumps. We assessed the hypothesis that frequent visits for uptitration of HFMED in continuous flow (CF) LVAD recipients would lead to cardiac recovery in a meaningful proportion of patients.

Methods:
Since 2006 we have defined all non-ischemics (DCM) and acute ischemics (CAD) as our recovery population. These recipients are seen biweekly for protocol driven up-titration of HFMED to a target MAP of 70mmHg. One month after achieving maximal tolerated HFMED, cardiac function is assessed by echocardiogram with an LVAD-weaned study where LVAD flow is reduced to an assumed net-zero flow of 6200rpm for 15 minutes.

Results:
Between June 2006 and January 2011, 70 patients received a CF LVAD at our institution and 30 formed our recovery population. Of these, 4 died and 5 went to transplant prior to reaching HFMED while 3 were excluded because of complications that occurs during LVAD support. Data from the remaining 18 (60%) formed the study cohort. Five (17%) subjects demonstrated normalization of biventricuclar size and function (Table 1) and 3 (10%) went on to device explantation after further study. Duration of HF tended to be shorter in the recovered patients.

Conclusions:
In our experience, utilizing frequent follow-up for aggressive uptitration of HFMED, 17% of CF LVAD patients with DCM or acute CAD could be managed to complete recovery. Further investigation of this approach is warranted.
Abstract 17849: Additional Use of Methotrexate Improved Clinical Findings and Metabolic Profile in Patients with Cardiac Sarcoidosis Refractory to Corticosteroids
Authors: Yazaki Yoshikazu , Seki Toshimasa , Horigome Mitsuaki , Hongo Minoru , Ikeda Uichi
Published: April 2024

Background.
Corticosteroids are indicated in cardiac sarcoidosis (CS). However, some patients worsen clinically despite corticosteroid treatment, and are suffering from steroid-related side effects. Methotrexate (MTX) is one of the most commonly used cytotoxic agents and has steroid-sparing effects for autoimmune diseases. Furthermore, aniti-inflammatory property of this agent may affect the pathogenesis of chronic heart failure. We hypothesized that MTX has a potential to improve clinical findings and reduce side effects of corticosteroids in patients with refractory CS.

Methods.
Out of 30 ambulatory CS patients treated with corticosteroids, we added MTX in combination with maintenance dose of corticosteroids for 7 patients who were suffering from relapse or deterioration and steroid-related side effects such as poorly controlled diabetes, osteoporosis or psychosis. All of the 7 were treated with 7.5mg of MTX once a week. A mean duration of corticosteroid treatment in the 7 patients was 61 months (32 to 95 months).

Results.
During a mean follow-up of 30 (12 to 46) months, no cardiac event and no major side effect occurred. The addition of MTX reduced maintenance steroid doses without further deterioration (8.3±3.4 to 6.4±2.2mg, p<0.05) during the follow-up periods. Although LVEF was not significantly increased, plasma BNP level was significantly decrease from 120±106 to 75±68pg/ml (p<0.05). There were significant improvements in diabetes (HbA1c:7.6±1.9 to 7.2±2.0%, p<0.05) and lipid profile (Triglyceride levels: 226±124 to 167±118mg/dl, p<0.05). Increased uptake of
99m
Tc-sestamibi and decreased uptake of
67
Ga in the myocardium were clearly observed in 2 patients after the addition of MTX.

Conclusion.
MTX is safe and helpful in combination with corticosteroids improving clinical findings, allowing for lower steroid doses, and reducing side effects of corticosteroids in patients with CS.
Abstract 17968: Concomitant Atrial Fibrillation Surgery Does Not Increase the Risk for Mortality and Morbidity After Coronary Artery Bypass Grafting
Authors: Fukahara Kazuaki , Miyata Hiroaki , Motomura Noboru , Doi Toshio , Nagura Saori , Yoshimura Naoki , Takamoto Shinichi
Published: April 2024

Introduction:
As a result of the increasing age of patients requiring myocardial revascularization for ischemic heart disease, preexisting atrial fibrillation (AF) is increasing among the patients who undergo coronary artery bypass grafting (CABG). However the impact of concomitant AF surgery on the early outcomes in patients after CABG remains unknown. The aim of this study was to assess the influences of concomitant AF surgery on the risk for mortality and morbidity after CABG.

Methods:
By using the Japan Adult Cardiovascular Surgery Database (JACVSD), the outcomes of patients with preoperative AF who underwent CABG were analyzed and compared between patients who underwent concomitant AF surgery with CABG and isolated CABG without AF surgery. A logistic regression model was used to assess whether concomitant AF surgery increased risk in CABG cohort and propensity-matched analysis was also performed based on preoperative variables.

Results:
From January 2004 to December 2008, a total of 19,495 patients underwent first-time CABG and 905 (4.6%) patients of them had preoperative AF. Of these, 253 (28.0%) patients had a concomitant AF surgery (AF surgery group) and 652 patients underwent isolated CABG (isolated CABG group). Overall, operative mortality (2.0% in AF surgery group, 3.1% in isolated CABG group) and major morbidity (18.6% in AF surgery group, 20.9% in isolated CABG group) were similar, and concomitant AF surgery did not have a significantly higher risk of mortality (odds ratio =0.78, 95% confidence interval 0.22-2.73; p=0.70) or major morbidity (odds ratio =1.11, 95% confidence interval 0.67-1.82; p=0.69).The propensity score matching analysis identified each 144 patients in both groups and neither operative mortality (2.8% in AF surgery group, 2.1% in isolated CABG group, p=0.70) nor major morbidity (18.8% in AF surgery group, 19.4% in isolated CABG group, p=0.88) had significant deference.

Conclusions:
From the analysis of overall data of JACVSD, mortality and major morbidity were slightly higher in isolated CABG group and it supposed that AF correction surgery might be performed in lower risk patients. Even after propensity matching, concomitant AF surgery was performed safely without increasing the risk for mortality and morbidity.
Abstract 181: A Feasability Study of Cerebral Oximetry in Cardiac Arrest
Authors: Parnia Sam
Published: April 2024

Background:
To date there has been no reliable “real time” monitoring available to determine cerebral perfusion during cardiac arrest. Whilst cerebral oximetry using near infra read spectroscopy has been utilized as a non invasive marker of cerebral perfusion during surgery, it has not been integrated into routine cardiac arrest care. Furthermore, the optimal measurement parameters that are associated with return of spontaneous circulation (ROSC) have not been determined.

Objectives:
To investigate the feasibility of using a commercially available cerebral oximeter (Invos 5100c, Somanetics, Troy, USA) to measure regional brain oxygen saturation(rSO2) during in-hospital cardiac arrest and determine the optimal rS02 parameters that correspond with ROSC.

Methods:
Cerebral oximetry was applied to 14 in-hospital cardiac arrest patients and continuous data was collected until either ROSC was achieved or CPR was terminated. The mean rSO2, median rSO2, as well as mean and median rSO2 in the last five minutes prior to ROSC or termination of CPR were measured.

Results:
The use of cerebral oximetry during cardiac arrest and the application of the sensor (completed in 60 ±30s) did not interfere with patient care. ROSC was achieved in 21% (n=3) of cases. Patients with ROSC had a significantly higher total mean (32±5 vs 21±7 p<0.05), median (31±5 vs 20±8 p<0.05), mean rSO2 in final 5 minutes (53±11 vs 17±5 p< 0.0001), median rS02 in final 5 minutes (47±6 vs 17±5 p< 0.0001) than non ROSC patients. In 14% (n=2) of cases, there was a failure to obtain rS02 measurements despite manufacturers recommendations being followed. This observation was only seen in the non ROSC group.

Conclusion:
The use of cerebral oximetry during cardiac arrest does not interfere with CPR and may be a predictor of ROSC. Although higher mean and median rS02 measurements correlate with ROSC, a rise in rS02 over a five minute period during cardiac arrest may be a better indicator of ROSC. Cerebral oximetry may potentially be used as a marker of organ perfusion as well as ROSC in cardiac arrest.