bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9575: Myocyte-Specific Catalase Overexpression Prevents Age-Related Left Ventricular Diastolic Dysfunction: Association with Reduction of Oxidation of SERCA at Cysteine 674
Authors: Qin Fuzhong , Ivan Luptak , Siwik Deborah , Wang Lei , Kang James , Cohen Richard , Colucci Wilson
Published: April 2024

Background:
Age-related myocardial diastolic dysfunction is associated with impaired calcium handling and reduced sarcoplasmic reticulum calcium ATPase (SERCA) activity. Oxidative sulfonylation of SERCA at cysteine 674 inhibits SERCA activity. We tested the hypothesis that a) aging is associated with sulfonylation of SRECA at cysteine 674, and b) cardiac myocyte-specific over-expression of catalase would decrease SERCA sulfonylation, restore SERCA activity, improve myocyte function and correct diastolic dysfunction.

Methods and Results:
Young (Y, 5-month) and senescent (S, 21-month) wild-type (WT) or CAT mice were compared (n=8-13). In S-WT there was markedly impaired diastolic function as reflected by a) decreased peak early-to-late diastolic transmitral velocity ratio (E/A, 1.36±0.06 vs. 1.96±0.10 in Y-WT or 1.89±0.06 in Y-CAT, P<0.01), b) decreased early myocardial tissue velocity (E
m
, mm/s, 20.1±0.6 vs. 26.6±0.1 in Y-WT or 24.9±0.7 in Y-CAT, P<0.01), and c) leftward/upward shift in the end-diastolic pressure volume relationship by Langendorff perfusion. Diastolic dysfunction in S-WT was associated with decreased SERCA activity (nmol/mg protein/min, 3.37±0.45 vs. 5.50±0.55 in Y-WT, P<0.01) and increased oxidation of SERCA at cysteine 674 (Scores, 2.4±0.3 vs. 1.1±0.2 in Y-WT or 1.1±0.1 in Y-CAT, P<0.02). Likewise, in isolated myocytes from S-WT there was slowed relaxation (+dL/dt, μ m/s, 1.35±0.07 vs. 2.68±0.17 in Y-WT, P<0.01) and prolongation of Ca
2+
reuptake (Tau, ms, 46.7±0.15 vs. 35.7±0.16 in Y-WT, P<0.01). In senescent mice with CAT overexpression (S-CAT) there was complete normalization of LV diastolic function (E/A, 1.97±0.12; E
m
, 24.9±1.4), SERCA activity (6.10±0.36 nmol/mg/min), SERCA oxidation (Score, 1.23±0.08), myocyte relaxation (+dL/dt, 2.34±0.14 μ m/s) and myocyte calcium handling (Tau, 38.3±0.08 ms).

Conclusion:
Age-related impairment of SERCA activity is associated with sulfonylation of cysteine 674. Myocyte-specific overexpression of CAT, which prevents aging-induced LV diastolic dysfunction and myocyte calcium dysregulation, prevents SERCA sulfonylation at cysteine 674 and restores SERCA activity, suggesting that SERCA sulfonylation plays a central role in the age-related myocyte dysfunction.
Abstract 9588: Low Flow, Low Gradient and Severe Aortic Stenosis in Patients with Preserved Ejection Fraction: Is There a Role for Hemodynamic Catheterization?
Authors: Adams Jonathon , Challa Suresh , Najib Mohammad , Mathew Verghese , Rihal Charanjit , Chaliki Hari
Published: April 2024

Introduction-
Recent studies based on echocardiographic data have described an entity termed paradoxical low-flow, low-gradient severe aortic stenosis (AS) with preserved ejection fraction (EF). It is not clear whether this condition is also seen in patients who undergo hemodynamic catheterization.

Objective-
To determine the prevalence of low-flow in patients with low mean gradient (MG) severe AS despite preserved EF as determined by echocardiography who subsequently undergo hemodynamic catheterization.

Methods-
We retrospectively reviewed medical records of 259 patients who underwent hemodynamic catheterization at Mayo Clinic from 2000-2009 to assess the severity of AS within 6 months of their echocardiographic study.

Results-
A total of 35 patients (mean age 75±9yrs; 49% males) had MG (≤ 40 mm Hg) and aortic valve area (AVA ≤ 1 cm2) despite preserved EF (≥50%) as determined by echocardiography. A total of 7/35 patients (20%) had low flow by echocardiography, defined as stroke volume index (SVI) ≤ 35 ml/m2 (median SVI of 32 ml/m2, inter-quartile range 30-33 ml/m2). Among the same 35 patients, there were 23 patients who had both low MG (≤ 40 mm Hg) and severe AS (AVA ≤ 1 cm2), while a total of 14/35 patients (40%) had low MG, severe AS as well as low flow (median SVI of 32 ml/m2, inter-quartile range 29-33 ml/m2) as determined by hemodynamic catheterization. A statistically significant correlation with modest association was observed between invasive and noninvasive measurements of MG, SVI, and AVA (r=0.48 ; p = 0.003; r=0.48; p = 0.004 ; r=0.36; p=0.03 respectively) in our study group of 35 patients. In most patients (94%) MG by catheterization was also ≤ 40 mm Hg. However, agreement between echocardiography and catheterization to identify patients with paradoxical low-flow, low MG, severe AS was poor (kappa = 0.03).

Conclusions-
1) Paradoxical low flow, low-gradient severe aortic stenosis is also observed in patients who undergo hemodynamic catheterization. 2) Further studies are needed to better understand the pathophysiology, best method for diagnosis and true prevalence of this entity.
Abstract 9598: Off-Pump Coronary Artery Bypass Surgery is Associated with Worse Arterial and Saphenous Vein Graft Patency and Less Effective Revascularization in All Coronary Territories: Results From the Veterans Affairs Randomized On/Off Bypass Trial
Authors: Hattler Brack , Messenger John C , Shroyer A. L , Collins Joseph F , Haugen Scott J , Garcia Joel A , Baltz Janet H , Cleveland Joseph C , Grover Frederick L
Published: April 2024

Background:
From February 2002 to May 2007, the Randomized On/Off Bypass (ROOBY) Trial randomized 2,203 patients to off-pump vs. on-pump CABG. ROOBY hypothesized that there would be no difference between treatments in 1-year arterial conduit patency, SVG patency, and/or effective revascularization (ER).

Methods:
Angiography was obtained in 685 (62%) off-pump and 685 (62%) on-pump patients. A blinded angiographic core lab assessed angiograms for FitzGibbon's patency class (A = widely patent, B = flow limiting, O = occluded) and ER (defined as the major diseased coronary artery within each major coronary territory was revascularized by a FitzGibbon class A graft with no new stenosis distal to the graft anastamosis). Angiographic findings were compared for off-pump versus on-pump using appropriate statistical tests.

Results:
There were no differences in baseline patient characteristics between arms. FitzGibbon class A patency rates were significantly worse off-pump than on-pump for arterial conduits (85.8% vs. 91.4%, p = 0.003) and SVGs (72.7 vs. 80.4%, p < 0.001). Fewer off-pump patients had ER to all diseased territories (50.1% vs. 63.9% on-pump, p < 0.001). Each major coronary territory had worse ER off-pump than on-pump (see table). The 1-year composite adverse event rate (death, non-fatal MI or repeat revascularization) was 16.4% in patients with ineffective revascularization vs. 5.9% in patients with ER to all 3 coronary territories (p <0.01).

Conclusion:
Off-pump CABG resulted in significantly worse FitzGibbon patency for arterial and SVG conduits and less effective revascularization than on-pump CABG. Overall, patients with less effective revascularization had more 1-year adverse events.
Abstract 9634: Luteolin Inhibits the Wall Expansion of Aortic Anuerysm in Mice Model
Authors: Nakayama Atsuko , Morita Hiroyuki , Nagai Ryozo
Published: April 2024

Background:
Luteolin is a food-derived flavonoid and its antioxidant, anti-inflammatory, and antiallergic functions are reported. Abdominal aortic aneurysm (AAA) is well-known disease that needs surgical repair before rupture of aortic wall. But little is known about the nonsurgical treatment for AAA.

Method:
Female ApoE-/- mice at age 9 weeks were fed with chow containing 0.5% luteolin for 3 weeks and then were infused with angiotensin II (Ang II; 1.0 μ g/kg/min) for 4 weeks by an osmotic mini-pump. Control ApoE-/- mice and Ang II infused ApoE-/- mice with normal chow were also prepared for comparison. Their body weight, blood pressure and ultrasonographic diameter of abdominal aorta were measured every week until sacrifice at age 16 weeks.

Result:
The body weight was similar in three groups (control 22.8±1.0 g, Ang ll with normal food group [Ang II +Luteolin-] 23.0±1.5 g, Ang II with luteolin food group [Ang II +Luteolin+] 23.4±1.7 g). Systolic blood pressure at sacrifice was extremely high in Ang II infused mice, but no difference between Ang II +Luteolin- and Ang II +Luteolin+ (control 94±4 mmHg, Ang II +Luteolin- 159±39 mmHg, Ang II +Luteolin+ 168±48 mmHg). The diameter of abdominal aorta at first was similar in three groups, and gradually increased with Ang II infusion. The max diameter at sacrifice was significantly smaller in Ang II +Luteolin+ than in Ang II +Luteolin- (1.1±0.2 mm vs. 1.9±0.5 mm, P<0.01). Histopathologic studies showed less frequent disruption of elastic media in Ang II +Luteolin+ than in Ang II +Luteolin-.

Conclusion:
Luteolin inhibits the wall expansion of aorta in Ang ll-infused ApoE-/- mice model.
Abstract 9648: Neointimal Tissue Component Assessed by Tissue Characterization With 40MHz Intravascular Ultrasound Imaging - Comparison of Drug-Eluting Stents and Bare-Metal Stents
Authors: Tsujita Kenichi , Takaoka Naoko , Kaikita Koichi , Hokimoto Seiji , Ono Takamichi , Chitose Tadasuke , Horio Eiji , Sato Koji , Mizobe Michio , Nakayama Naoki , Saito Michiyo , Tayama Shinji , Sugiyama Seigo , Yamabe Hiroshige , Nakamura Sunao , Ogawa Hisao
Published: April 2024

Background:
Drug-eluting stents (DES) can cause impaired arterial healing, which constitutes the most important pathological substrate underlying late DES thrombosis. Intravascular ultrasound (IVUS)-based tissue characterization allows for the in vivo identification of neointimal tissue components. The present study used iMap IVUS system to compare neointimal tissue components between DES and bared-metal stents (BMS).

Methods:
Follow-up IVUS data after coronary stenting (9.8±9.4 months from index procedures) was obtained from consecutive 61 lesions (34 in DES, 27 in BMS). Region of interest was placed in neointima hyperplasia and plaque behind stent. The iMap tissue components (fibrotic, lipidic, necrotic, and calcified) were measured in every recorded frame and expressed as percentages of mean neointimal and plaque behind stent cross-sectional area for the stented segment.

Results:
Patients' characteristics were comparable between DES and BMS. Compared with BMS, smaller (2.9±0.4mm vs. 3.2±0.4mm, P=0.004) and longer (34±18mm vs. 26±14mm, P=0.03) DES were implanted. Although there was no significant difference in minimum lumen area at follow-up between DES and BMS, average neointimal area was significantly smaller in DES compared with BMS (1.6±0.8mm2 vs. 3.4±2.4mm2, P=0.02). The iMap analyses showed that neointima after DES placement was composed of smaller fibrotic component (70±8% vs. 77±10%, P=0.045), larger necrotic (13±5% vs. 9±3%, P=0.02) and calcified (12±4% vs. 5±4%, P=0.004) components compared with BMS, whereas the plaque component behind stent was identical. Logistic regression analysis showed that only intra-DES neointima was a significant predictor of necrotic neointima at follow-up.

Conclusion:
DES implantation would be associated with iMap-derived necrotic and less-fibrotic neointimal formation. In vivo iMap evaluation of neointimal tissue may provide useful information in detecting impaired healing after stenting.
Abstract 9672: Pressure Volume Relationship is Related to Coronary Flow Reserve in Non-Ischemic Dilated Cardiomyopathy
Authors: Ciampi Quirino , Pratali Lorenza , Rigo Fausto , Gerardi Sonia , Villari Bruno , Picano Eugenio , Sicari Rosa
Published: April 2024

Background.
Coronary flow reserve (CFR) on left anterior descending (LAD) can be reduced in non-ischemic dilated cardiomyopathy (DCM). Pressure-volume relationship (PVR) is a useful method for evaluating LV myocardial contractility during stress echocardiography (SE). Aim of the study was to assess the relationship between CFR on LAD and PVR in DCM patients.

Methods.
Sixty DCM patients (36 men; 63±13 years, mean value of ejection fraction: 36±7%) underwent dipyridamole stress echo (dypSE, 0.84 mg/kg in 6′). CFR was defined as the ratio between maximal vasodilation and rest peak diastolic flow velocity in LAD. PVR was defined as systolic cuff pressure/end-systolic volume index difference between rest-peak dypSE.

Results.
PVR was inversely related to wall motion score index at rest (r=-.424, p=.001) and at peak dypSE (r=-.528, p<.001), and directly related to E wave deceleration time (r=.365, p=.014). PVR was not related to ejection fraction at rest, and directly related to ejection fraction at peak dypSE (r=.482, p<.001). CFR on LAD was abnormal (<2) in 25/60 (42%) patients. PVR was directly related to CFR on LAD (r=.412, p=.001, Figure).

Conclusions.
In DCM patients, the presence of myocardial contractile reserve is directly related to CFR on LAD.
Abstract 9691: Group X Secretory Phospholipase A
2
in Neutrophils Plays a Pathogenic Role in Abdominal Aortic Aneurysms in Mice
Authors: Watanabe Kazuhiro , Fujioka Daisuke , Saito Yukio , Nakamura Takamitsu , Obata Jun-ei , Kawabata Kenichi , Watanabe Yosuke , Mishina Hideto , Tamaru Shun , Kugiyama Kiyotaka
Published: April 2024

Group X secretory phospholipase A
2
(sPLA
2
-X) is expressed in neutrophils and plays a role in the pathogenesis of neutrophil-mediated tissue inflammation and injury. Neutrophils have a critical role in development of abdominal aortic aneurysms. This study tested the hypothesis that sPLA
2
-X in neutrophils may contribute to the pathogenesis of abdominal aortic aneurysms using sPLA
2
-X knockout (sPLA
2
-X
-/-
) mice.

Methods and Results:
Abdominal aortic aneurysms were created by application of CaCl
2
(0.5M) to the external surface of the aorta. As a result, a half of sPLA
2
-X
+/+
mice had abdominal aortic aneurysm (> 50% increase in aortic diameter from pretreatment) 6 weeks after CaCl
2
treatment, while none of sPLA
2
-X
-/-
mice had it. The aortas of sPLA
2
-X
-/-
mice had smaller diameters (% increase from pretreatment, 26.0 ± 3.7 vs. 42.4 ± 7.0, respectively, p < 0.01), a reduced grade of elastin degradation and lower activities of elastase and gelatinase after CaCl
2
treatment compared with sPLA
2
-X
+/+
mice. In sPLA
2
-X
+/+
mice, immunofluorescence microscopic images showed that the immunoreactivity of sPLA
2
-X was detected only in neutrophils within aortic walls 3 days, 1, 2 and 6 weeks after CaCl
2
treatment, while the immunoreactivity was not detected in macrophages, mast cells or other cells in the aortic walls. Also, sPLA
2
-X immunoreactivity was colocalized in neutrophils expressing MMP-9. Neutrophils isolated from sPLA
2
-X
-/-
mice had lower activities of elastase, gelatinase and MMP-9 in response to PMA or fMLP compared with sPLA
2
-X
+/+
mice. The attenuated release of proteases from sPLA
2
-X
-/-
neutrophils was reversed by the exogenous addition of mouse sPLA
2
-X protein. The aortic diameters and elastin degradation grades were significantly reduced in the lethally irradiated sPLA
2
-X
+/+
mice reconstituted with sPLA
2
-X
-/-
bone marrow compared to irradiated sPLA
2
-X
+/+
mice reconstituted with sPLA
2
-X
+/+
bone marrow. The adoptive transfer of sPLA
2
-X
+/+
neutrophils reversed aortic diameters and elastin degradation grade in the lethally irradiated sPLA
2
-X
+/+
mice reconstituted with sPLA
2
-X
-/-
bone marrow to a similar extent seen in sPLA
2
-X
+/+
mice.

Conclusions:
sPLA
2
-X in neutrophils plays a critical role in the pathogenesis of abdominal aortic aneurysms.
Abstract 9692: A 2D Speckle Tracking Echocardiography Demonstrates Improvement of Left Atrial and Ventricular Strain After Ablation in Patients with Atrial Fibrillation;
Authors: Kato Hiroshi , Kubota Shoichi , Takasawa Yosuke , Kumamoto Teruhiko , Yamamoto Makoto
Published: April 2024

Introduction:
Recent echocardiographic studies have shown that strain analysis of the myocardium is a very sensitive method for detecting various pathophysiological changes before and after cardiovascular interventional procedures. We hypothesized that a 2D speckle tracking imaging can quantify the damage of the left atrial (LA) and left ventricular (LV) myocardium in patients with atrial fibrillation (AF), and demonstrate improvement of atrial and ventricular function after ablation procedure.

Methods:
We performed catheter ablation guided by CARTO navigation (extensive encircling pulmonary vein isolation) in 35 patients with AF (paroxysmal, n=23; persistent, n=12). LA and LV longitudinal strain in systolic phase by 2D speckle tracking echocardiographic imaging and 24-hour Holter ECG were evaluated at baseline before ablation and various follow-up time points (1 day, 1 month, and 3 months after ablation). Those without AF who underwent catheter ablation for other indications served as a control group (n=22).

Results:
Patients with persistent AF had significantly lower LA and LV longitudinal strain at baseline than those with paroxysmal AF and the control (LA, 14.9±6.5% vs 40.4±18.6% and 41.2±21.8%, p<0.001; LV, -15.0±6.4% vs -21.1±3.3% and -21.2±1.7%, p<0.05). In those with persistent AF, LV longitudinal strain returned to the normal value of -20.4±2.6% 1 month after ablation, and subsequently, LA strain was also improved to the value of 40.0±18.9% 3 months after ablation. At the most recent follow-up, 77% of the patients with AF maintained sinus rhythm on Holter ECG.

Conclusions:
Restoration and maintenance of sinus rhythm by catheter ablation in patients with persistent AF improves both LA and LV strain in a time-dependent manner. A 2D speckle tracking imaging can demonstrate improvement of atrial and ventricular function after ablation procedure.G009692
Abstract 9720: Trends In The Prevalence Of Coronary Heart Disease And Congestive Heart Failure Among Adult Population In The U.s.: National Health And Nutrition Examination Survey 2001-2008
Authors: Yoon Sung Sug (Sarah) , Dillon Charles , Illoh Kachi , Carroll Margaret , Wright Jacqueline
Published: April 2024

Objectives:
To evaluate overall trends in the prevalence of coronary heart disease (CHD) and congestive heart failure (CHF) in the U.S. population aged 40 years and older.

Methods:
A total of 13866 individuals aged 40 and older participated in the household interview and of these 13,067 were both interviewed and examined in National Health and Nutrition Examination Survey (2001-2008). Demographic variables (age, gender, race/ethnicity, education and health insurance) and risk factors (hypertension, diabetes, high cholesterol and body mass index) were included. Definition of coronary heart disease, congestive heart failure and undiagnosed angina as follows:

Results:
The prevalence of coronary heart disease significantly decreased from 10.3% in 2001-2002 to 8.7% in 2007-2008 (
P-trend
< 0.05) but no changes were observed in CHF. CHD prevalence among women (
P-trend
= 0.05) and adults with health insurance (
P-trend
< 0.05) significantly decreased. In adults who had a total cholesterol < 240 mg/dl, CHD prevalence significantly decreased in those without hypertension and in adults who did not have diabetes (
p-trend
< 0.05 for all groups). The prevalence of angina significantly decreased from 4.8% in 2001-2002 to 3.2% in 2007-2008 (
P-trend
< 0.05). Meanwhile, the overall prevalence of MI remained unchanged.

Conclusion:
The overall prevalence of CHD significantly decreased in the 8 years survey period. The results suggest that the overall decreased prevalence in CHD may have been primarily driven by the decreased prevalence in angina because the prevalence of the other components of CHD did not change over this 8 year interval.
Abstract 9739: MicroRNA26 Regulation of TRPC3 Subunits Underlies Profibrillatory Fibroblast Activation in a Canine Atrial Fibrillation Model
Authors: Harada Masahide , Luo Xiaobin , Qi Xiao Yan , Xiao Jiening , Shi Yanfen , Tardif Jean-Claude , Nattel Stanley
Published: April 2024

Background:
Cardiac fibroblast (FB) proliferation and differentiation into extracellular matrix (ECM) secreting myofibroblasts contributes to AF-promoting fibrotic remodeling. We previously observed that Ca
2+
entry through transient receptor potential canonical 3 (TRPC3) channels regulates cardiac FB proliferation/differentiation. Here, we examined the potential involvement of TRPC3 in a canine AF model.

Methods:
Dogs kept continuously in AF for 1 week by pacing at 600 bpm (n=11) were compared to controls (CTL, n=11). Echocardiographic, hemodynamic and electrophysiological properties were studied in vivo. Left atrial (LA) FBs were isolated for nonselective cation current (
I
NSC
) recording (patch clamp), cell cycle analysis (flow cytometry), protein (immunoblot) and mRNA (qPCR) expression.

Results:
AF increased LA diastolic area by 13%* (*p<0.05 vs CTL) and LA pressure by 150%* without LV dilation. AF also shortened atrial refractory periods from 98±4 to 79±5 ms* (BCL 150 ms) and prolonged spontaneously maintained AF duration from 26±8 to 937±209 s*. In freshly isolated FBs,
I
NSC
sensitive to a TRPC3 selective blocker, pyrazole3 (Pyr3, 3 μ M) increased in AF by 89%*, indicating increased TRPC3 current. In freshly cultured FBs, the cell number increase-rate, the G2/M cell content (an index of cell division) and α-smooth muscle actin protein expression increased in AF by 185*, 33* and 154* % respectively, indicating increased proliferation and differentiation; in vitro treatment with Pyr3 (3 μ M) decreased these profibrotic indices by 78%*, 12%* and 74%* vs vehicle respectively. In fresh FBs, collagen-1 and -3 gene expression increased in AF by 1210%* and 750%* respectively, indicating increased ECM production. TRPC3 protein expression in fresh FBs increased in AF by 64%*; however, TRPC3 mRNA decreased by 44%*, suggesting epigenetic regulation by microRNA (miR). AF reduced FB expression of miR-26a, predicted to target and suppress TRPC3 translation, by 65%*. In vitro miR-26a knockdown upregulated TRPC3 protein by 54%*, mimicking AF effects.

Conclusions:
AF increases FB proliferation, differentiation and ECM gene expression by increasing TRPC3 subunit expression and current, likely by downregulating the TRPC3-targeting microRNA miR-26.
Abstract 9746: Differential Impact of Dose-Related Chronic Alcohol Ingestion on Action Potential Upstroke, Systolic Myocardial Function and Cardiac Pro-inflammatory Factors mRNA Expression in Male C57BL/6 Mice
Authors: Hung Chung-Lieh , Lai Yu-Jun , Tien Ting-Yi , Tseng Ya-Ming , Lin Cheng-I , Chen Yao-Chang , Yeh Hung-I
Published: April 2024

Background
Cardiomyopathy elicited by ethanol or the toxic metabolites after chronic excessive alcohol intake had been well documented. However, to what extent of such dose-related chronic alcohol (Alc) ingestion on myocardial systolic performance and electrical disturbance remained unclear.

Methods
Totally 40 C57BL/6 male mice of 6 weeks old were fed with a liquid diet containing 4% (n=13) or 6% (n=14) alcohol and normal diet (CTRL, n=13) for 12 weeks. In
vivo
cardiac function was examined by echocardiography at baseline and before animal sacrifice. Optical mapping (Lecia MZ FLIII system, Heidelberg, Germany) and single cardiomyocyte patch clamp were used to assess conduction velocity of ventricular surface and action potential of single cardiomyocyte, respectively. Extent of myocardial macrophage infiltration and fibrosis were examined by immunostaining with the mRNA content of pro-inflammatory factors determined by real-time PCR.

Results
Both 4% and 6% Alc groups had reduced conduction velocity (47±3 cm/s and 28±8 cm/s vs Ctrl: 71±7 cm/s, p<0.05)) and a more perturbated activation spread. Echocardiography demonstrated enlarged cardiac dimension and worsened fractional shortening in both Alc groups while only 6% Alc mice demonstrated a significant decline of systolic myocardial velocity (Ctrl vs 6%: 1.14±0.03 vs 0.97±0.03, p<0.05). Reduced action potential upstroke velocity (Figure) and abnormal resting membrane potential were shown in both Alc groups. Markedly increased macrophage infiltration and fibrosis zone (6% vs Ctrl: 3.1±0.3 vs 1.3±0.1 mm
2
/cm
2
, p<0.05) were accompanied by significantly elevated pro-inflammatory (including TNF-α, ΙL-6, and ΜΜP-2) factors mRNA expression only in 6% Alc mice.

Conclusion
These results showed a differential impact of myocardial electromechanical disturbance in response to dose-specific Alc ingestion and that overt inflammation response may start to take place in more severely damaged myocardium.
Abstract 9779: Nitric Oxide Generated Through Ascorbic Acid Reduction of Nitrogen Dioxide Reduces Pulmonary Vascular Resistance in Hypoxemic Swine with Minimal Inhaled and Exhaled Nitrogen Dioxide
Authors: Lovich Mark A , Bruno Natalie K , Wei Abraham E , Maslov Mikhail Y , Denton Ryan J , Gamero Lucas G , Vasquez Gregory B , Gilbert Richard J
Published: April 2024

Background:
Inhaled nitric oxide (NO) has the capacity to selectively dilate pulmonary blood vessels and improve oxygenation in patients with pulmonary diseases. NO in the presence of oxygen spontaneously converts to nitrogen dioxisw (NO
2
), a toxic byproduct with multiple adverse pulmonary effects. The potential for co-inhalation of NO
2
drives delivery system complexity, gas monitoring and cost. We demonstrate a new method for generating inhaled NO based on reducing NO
2
just prior to inhalation, using ascorbic acid/silica gel reactor cartridges (GeNO, LLC). Ascorbic acid protonates NO
2
, yielding NO, water and dehydroascorbic acid. This reaction occurs within the ventilator hoses, leaving little time for NO
2
reformation.

Methods:
In vivo efficacy was assessed through the inhalation of NO (1, 5, 20, and 80 PPM) in hypoxemic swine (FiO
2
15%). NO
2
in N
2
was mixed with O
2
prior to entry into the hoses of a portable ventilator upstream of two ascorbic acid cartridges in series. Inhaled and exhaled NO and NO
2
were sampled using in-line electrochemical detectors (step response time < 0.8 s, GeNO, LLC).

Results:
Inspired and expired NO
2
was always under 0.3 PPM in 50% and 0.9 PPM in 100% O
2
(Fig. 1). Inhaled NO significantly reduced the hypoxemia elevated mean pulmonary artery pressure and pulmonary vascular resistance at all doses (Fig. 2).

Conclusion:
Inspired and even expired NO
2
levels were low using ultra-fast electrochemical methods. NO supplied by this novel system was capable of reversing hypoxemia induced pulmonary hypertension. The lack of co-delivered toxic NO
2
may allow for a substantial reconsideration of the therapeutic role of inhaled NO in a wide range of respiratory diseases.
Abstract 9790: Endothelin-1 Inhibits Endothelium-Dependent NO-Mediated Dilation of Coronary Arterioles via p38 Kinase Linked Superoxide Production From NAD(P)H Oxidase
Authors: Thengchaisri Naris , Hein Travis W , Ren Yi , Kuo Lih
Published: April 2024

Elevated levels of endothelin (ET)-1, a potent constrictor peptide, are associated with higher risk of cardiovascular diseases by promoting vasoconstriction and oxidative stress. However, it remains unknown whether ET-1, at subvasomotor concentrations, exerts adverse effects on coronary vasomotor function. To address this issue without confounding influences from systemic and local factors, porcine coronary arterioles (50-100 μm) were isolated, cannulated and pressurized without flow for in vitro study. Diameter changes were recorded using a videomicrometer. Dihydroethidium (DHE) staining was used to detect superoxide production. Arterioles developed basal tone (60±3 µm) and dilated dose-dependently to the endothelium-dependent NO-mediated vasodilators serotonin (1 nM to 0.1 µM) and adenosine (1 nM to 10 µM). Extraluminal incubation with a clinically relevant subvasomotor concentration of ET-1 (10 pM, 60 minutes) significantly attenuated arteriolar dilation to adenosine and serotonin but not to endothelium-independent vasodilator sodium nitroprusside. The adverse effects of ET-1 on serotonin- and adenosine-induced dilations were prevented by pretreating the vessels with the ETA receptor antagonist BQ123 (1 μM), the superoxide scavenger TEMPOL (1 mM), the NAD(P)H oxidase inhibitor apocynin (100 μM) or the p38 kinase inhibitor SB203580 (0.1 μM). However, the adverse effects of ET-1 were not prevented by pretreating the vessels with ETB receptor antagonist BQ788 (0.1 μM), H2O2 scavenger catalase (1000 units/ml), xanthine oxidase inhibitor allopurinol (10 μM) or c-Jun N-terminal kinase inhibitor SP600125 (5 μM). DHE immunohistochemical staining showed that ET-1 generated TEMPOL- and SB203580-sensitive superoxide production in the arteriolar endothelium. Collectively, our data indicate that exposure of coronary arterioles to a pathophysiological concentration of ET-1 inhibits endothelium-dependent NO-mediated dilation in coronary arterioles by activation of ETA receptors leading to the production of superoxide from NAD(P)H oxidase, which appears to be linked with p38 kinase activation.
Abstract 9811: Medical Resource Use, Costs and Quality of Life are Similar Between Patients with Acute Decompensated Heart Failure Treated with Nesiritide Versus Placebo
Authors: Reed Shelby D , Kaul Padma , Hernandez Adrian F , Li Yanhong , Eapen Zubin J , Schulman Kevin A , Whellan David J , Westerhout Cindy M , Massie Barry , Howlett Jonathan G , Armstrong Paul W , Starling Randy , O'Connor Christopher M , Califf Robert M
Published: April 2024

Introduction:
In the recent Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure Trial (ASCEND-HF), treatment with nesiritide did not reduce heart failure rehospitalization or mortality at 30 days relative to treatment with placebo. Dyspnea was marginally improved with nesiritide, but did not reach pre-specified levels for statistical significance. Our study reports on a prospective economic and quality of life evaluation that was conducted as part of the trial.

Objective:
Compare medical resource use, costs and quality of life outcomes between patients randomized to nesiritide versus placebo in the ASCEND-HF.

Methods:
Detailed resource use data, including data on length of stay and readmissions within 30 days were collected on the case report form. Quality of life was assessed using the EQ-5D, administered at baseline, 24 hours, discharge, and 30 days. Hospital billing data representing 1253 admissions for US patients were used to develop a cost prediction model (R
2
=0.70), which was used to generate inpatient cost estimates for patients without billing data (US and non-US). To lessen the influence of geographical variations in length of stay when estimating costs, we applied an adjustment in which length of stay was reweighted based on the mean LOS in the US relative to each country. Generalized linear models were used to compare resource use and costs. Responses to the EQ-5D were converted to US utility weights. Patients who died were assigned an EQ-5D value of 0. ANOVA was used to compare EQ-5D utilities between treatment groups.

Results:
Of 7141 patients randomized, 7007 received study drug. Estimates of resource use, direct medical costs and EQ-5D utility weights are reported in the Table.

Conclusions:
Consistent with main study findings, measures of medical resource use, costs, and EQ-5D health utilities were similar between nesiritide and placebo in this trial.
Abstract 9812: Dietary Supplementation of Nitrite Reduces Chronic Cardiotoxicity of Doxorubicin: Role of Activation of Protein Kinase G and Down-Regulation of Endothelial Nitric Oxide Synthase in Heart
Authors: Zhu Shu-Guang , Das Anindita , Durrant David E , Kukreja Rakesh C , Xi Lei
Published: April 2024

Background:
Doxorubicin (DOX) is one of the most effective and commonly used chemotherapeutic agents for cancer. Clinical use of DOX is limited because of its serious dose-dependent cardiotoxicity. We recently demonstrated that oral intake of inorganic nitrate (NaNO3) protects against acute cardiotoxicity of DOX. The present study was designed to further elucidate if dietary supplementation of nitrite (NaNO2) also limits the cardiotoxic effects following chronic, multiple low-dose treatment of DOX.

Methods & Results:
Adult male CF-1 mice were divided into 4 groups (n=6/group): 1)
Saline
[0.2 ml, IP]; 2)
DOX
[3 x weekly IP injection of 5 mg/kg DOX; cumulative dose = 15 mg/kg]; 3)
Nitrite
- NaNO2 was added into drinking water at concentration of 50 mg/L for entire duration of 32 days; 4)
Nitrite+DOX
- mice received nitrite-enriched water 7 days before the first DOX injection and throughout the 32-day period. Five days after the last DOX injection, echocardiography and pressure-volume Millar microtip catheterization were performed to assess left ventricular (LV) contractile function and other hemodynamic indices. As shown in the Table below, LV systolic and diastolic function was significantly improved in
Nitrite+DOX
group as compared with
DOX
group. Oral nitrite intake augmented plasma level of nitrite, but not nitrate or sum of nitrate+nitrite (NOx). Further molecular studies revealed that nitrite intake enhanced cardiac activity of cGMP-dependent protein kinase (PKG) and reduced expression of endothelial nitric oxide synthase (eNOS) as compared with
Saline
or
DOX
(n=3/group).

Conclusion:
We have provided novel evidence showing that dietary nitrite supplementation reduces cardiotoxicity following chronic DOX treatment. The cardioprotective effect of nitrite may be mediated by the enhanced PKG signaling and the decreased expression of likely uncoupled eNOS in the heart. Nitrite could be a promising therapeutic agent in combating chronic DOX cardiotoxicity.
Abstract 9814: Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention Have Higher Levels of On-Treatment Platelet Reactivity
Authors: Gaglia Michael A , Torguson Rebecca , Pakala Rajbabu , Sardi Gabriel , Xue Zhenyi , Suddath William O , Kent Kenneth M , Satler Lowell F , Pichard Augusto D , Waksman Ron
Published: April 2024

Introduction:
High on-treatment platelet reactivity (HOPR) in patients taking clopidogrel is associated with adverse events following PCI. The impact of presentation with an acute coronary syndrome (ACS) upon levels of on-treatment platelet reactivity, however, is not well-understood.

Hypothesis:
We hypothesized that ACS patients, compared to non-ACS patients, would be more likely to have HOPR as measured by the Vasodilator Stimulated Phosphoprotein Phosphorylation (VASP) assay following PCI.

Methods:
Patients received 600 mg of clopidogrel and 325 mg aspirin at the time of PCI and underwent platelet reactivity testing with VASP 6-24 hours following PCI. HOPR was defined as a VASP platelet reactivity index >50%. ACS was defined as ≥2 of the following: 1) symptoms consistent with myocardial ischemia; 2) ST-segment elevation or depression ≥1 mm in ≥2 contiguous leads on EKG; 3) cardiac troponin level above the upper limit of normal. VASP platelet reactivity index and HOPR were compared between groups using the Wilcoxon and Chi-square tests, respectively. Multivariable logistic regression was performed to assess the independent effect of ACS upon HOPR.

Results:
Overall, 377 patients were enrolled; 12.9% presented with ACS, although none presented with cardiogenic shock. Patients with ACS were less likely to have a history of CAD (22.4% v. 59.8%) or previous PCI (12.5% v. 46.6%) and more likely to have a history of congestive heart failure (22.4% v. 11.6%) or a left anterior descending lesion (47.8% v. 30.2%; p <0.001 for all comparisons). Median VASP platelet reactivity index was higher in ACS patients (52.6% v. 38.3%, p=0.02), as was incidence of HOPR (55.1% v. 34.6%, p=0.007). Following multivariable adjustment, ACS remained significantly associated with HOPR (OR 2.18, 95% CI 1.15-4.12, p=0.02; Table).

Conclusion:
Presentation with ACS is a significant risk factor for HOPR. As such, platelet reactivity testing should focus on such high-risk patients.
Abstract 9821: Calcium-Dependent Changes in Myocardial Sheet Mechanics Reveal Reversible Diastolic Dysfunction in Aged Duchenne Muscular Dystrophy (
mdx
) Mice
Authors: Cheng Ya-Jian , Chen Junjie , Caruthers Shelton D , Lanza Gregory M , Wickline Samuel A
Published: April 2024

INTRODUCTION:
The relationship between abnormal sarcoplasmic Ca
2+
handling and cardiac structural mechanics in
mdx
mice has not been defined. Diffusion tensor MRI (DTI) has been used to quantify the contribution of myocardial sheet architecture in ventricular wall thickening mechanics. In this study, DTI was employed to assess altered sheet mechanics due to impaired intracellular calcium homeostasis.

METHODS:
Sixteen-month old
mdx
(n = 10) and age matched wildtype (WT, n = 10) mice were used. Hearts were excised and prepared for Langendorff retrograde perfusion to be sequentially arrested in diastole and systole for DTI. The first group was perfused with regular St. Thomas’ cardioplegic solution containing normal [Ca
2+
] (1.2 mM) to arrest hearts in diastole. To assess the regulatory effect of [Ca
2+
] on diastolic sheet mechanics, the second group was perfused with modified cardioplegic solution containing low [Ca
2+
] (0.078 mM). All hearts were then reperfused with Krebs buffer to resume beating followed by 2.5mM barium-induced systolic arrest for DTI. Magnitude of sheet angle, |β|, of each heart was calculated from the diffusion tensors. MANOVA was used for statistical analysis.

RESULTS:
In diastole,
mdx
hearts exhibited lower |β| in midventricle than WT (Fig. A). Reducing [Ca
2+
] in cardioplegic solution restored diastolic |β| in
mdx
hearts to normal level but had no detectable effect on WT hearts. No significant difference of systolic |β| was observed between
mdx
and WT hearts (Fig. B).

CONCLUSION:
The observed lower diastolic |β| in
mdx
hearts indicated
mdx
cardiomyocytes failed to fully relax at resting state. The regulatory effect of [Ca
2+
] on diastolic |β| of
mdx
hearts suggested sheet structural abnormality is reversible despite the advance age of
mdx
mice. Thus, the disturbed sheet mechanics may reflect functional consequences of abnormal Ca
2+
handling in vivo, which may correlate with membrane calcium channel dysfunction preceding eventual cardiac failure.
Abstract 9834: Impact of Bone Marrow Cell Therapy on Left Ventricular Function, Structure, and Clinical Outcomes in Patients with Ischemic Heart Disease: A Meta-Analysis
Authors: Jeevanantham Vinodh , Butler Matthew , Saad Andre , Abdel-Latif Ahmed , Dawn Buddhadeb
Published: April 2024

Background:
The effects of adult bone marrow cell (BMC) therapy on left ventricular (LV) function, remodeling, and clinical outcomes in patients with ischemic heart disease (IHD) remain controversial. We systematically reviewed the effects of BMC therapy on LV ejection fraction (LVEF), LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), infarct size, and clinical outcomes in patients with IHD.

Methods:
We searched the MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials, and reference lists of retrieved articles for relevant clinical trials through March 2010. Randomized control trials (RCTs) and cohort studies conducted in patients with IHD were included. Weighted Mean Difference (WMD) for changes in LVEF, LVESV, LVEDV and infarct size were estimated using random effects meta-analysis. Peto odds ratio was calculated for clinical outcomes.

Results:
A total of 43 studies (enrolling 2,537 patients) out of 1,554 identified studies were included in the final analysis. Compared with the standard treatment group, BMC-treated patients showed a significant increase in LVEF, and significant decrease in LVESV, LVEDV, and infarct size (Table). These findings were significant irrespective of the study design (RCTs vs. Cohort studies), type of IHD (acute myocardial infarction vs. chronic IHD) and duration of follow up. Compared with patients who received standard therapy, BMC-treated patients showed significant decrease in all-cause mortality, cardiac mortality, recurrent MI, and stent thrombosis (Table).

Conclusions:
The pooled data from this largest meta-analysis of its kind to date show that compared with standard therapy, transplantation of adult BMCs results in significant improvement in LV structure, function and scar size in patients with IHD. In addition, BMC therapy is associated with significant reduction in mortality, recurrent MI and stent thrombosis compared to standard therapy in patients with IHD.
Abstract 9856: Intrinsic Cardiac Nerve Activities and Atrial Arrhythmias in Patients Recovering From Open Heart Surgery
Authors: Shen Mark J , Coffey Arthur C , Ice Daniel S , Miller Steven J , Garlie Jason B , Straka Susan P , Adams David E , Wagner David B , Shen Changyu , Chen Lan S , Lin Shien-Fong , Chen Peng-Sheng
Published: April 2024

Introduction-
Intrinsic cardiac nerve activities (ICNA) are invariable triggers of paroxysmal atrial tachyarrhythmias in ambulatory dogs. We sought to record ICNA in human patients to determine if ICNA are associated with atrial arrhythmias.

Hypothesis-
ICNA are associated with the development of post-operative atrial arrhythmias.

Methods-
The study protocol was approved by the IRB. Five patients (56±10 years old; 4 male and 1 female) undergoing open heart surgery consented for this study. Two temporary pacing electrodes were placed on the epicardial fat pad at the left superior pulmonary vein-left atrium (LSPV-LA) junction during surgery. ICNA were continuously recorded for up to 3 days after surgery. Nerve activities were considered present if there was a 3-fold increase in the amplitude over baseline noise.

Results-
We processed 5440 minutes of recordings (1088±1065 minutes per patient). ICNA were recorded in 10.2% of the time. We identified a total 3914 episodes of high amplitude spike discharge activity (HASDA, Figure A) and 51 episodes of low-amplitude burst discharge activity (LABDA, Figure B). A total of 872 episodes of premature atrial contractions (PACs) were noted. Of those, 308 episodes (35.8%) were preceded by ICNA (Figures A and B). In comparison, among 872 control time segments (3 min prior to the PACs), only 28 episodes (3.2%) were preceded by ICNA (
P
<0.001). The absence of ICNA had high specificity (96.8%) for predicting subsequent occurrence of PACs.

Conclusions-
ICNA can be recorded from human patients in the post-operative period. Both HASDA and LABDA are observed. There is a significant association between ICNA and subsequent PACs.
Abstract 9862: Rearrangement of Myocardial Deformation to Preserve Left Ventricular Ejection Performance in Chronic Aortic Regurgitation
Authors: Seo Yoshihiro , Ishizu Tomoko , Iida Noriko , Aonuma Kazutaka
Published: April 2024

Background:
In chronic aortic regurgitation (AR) patients, rearrangements of left ventricular (LV) wall deformation including contraction and thickening may occur to preserve LV ejection performance in the course of myocardial adaptation to increased systolic wall stress. We assessed transmural rearrangements of myocardial deformation by speckle tracking echocardiography in patients with chronic AR.

Methods:
We enrolled 90 patients with AR and 53 control subjects. On a LV short-axis B-mode image, total-, inner-half -, and outer-half radial strain (RS) and circumferential strain (CS) at inner, mid, and outer layers were calculated. Longitudinal strain (LS) was calculated on an apical 4-chamber image. Three components of end-systolic wall stress (ESS) were calculated: midwall circumferential (ESSc), meridional (ESSm), and inner radial (ESSr). AR severity was classified as moderate in 31 patients, severe with preserved LVEF ≥50% (severe ARpEF) in 42 patients, and severe with depressed LVEF <50% (severe ARdEF) in 17 patients.

Results:
LS was decreased even in the moderate AR group with normal ESSm. Inner-RS progressively decreased with increases of ESSr; however, outer-RS in the moderate and severe ARpEF groups was higher than that in the control group. Consequently, total-RS was preserved even in the severe ARpEF group with increased ESSr. Inner-CS was lower in the severe ARpEF group than in the control and moderate AR groups, however, outer-CS was higher in the severe ARpEF group than in the control group. All strain parameters were lower in the severe ARdEF group with dramatically increased ESS than in other groups. In 29 patients with aortic valve replacement (AVR), total-RS and outer-RS were significantly decreased after AVR. The ratio of inner-RS to outer-RS significantly increased after AVR and did not differ from that in the control group.

Conclusions:
Transmural strain analysis revealed rearrangements of wall deformation in the course of adaptation to increased ESS in patients with AR. As a distinctive rearrangement, subendocardial dysfunction accompanied by increased wall thickening in the subepicardium may indicate vertical compensation of wall thickening to preserve LVEF.
Abstract 99: Placement of Automated External Defibrillators in Denmark: “Free Seating”
Authors: Nielsen Anne M , Rasmussen Lars S
Published: April 2024

Objectives:
According to current guidelines from the American Heart Association and the European Resuscitation Council Automated External Defibrillators (AEDs) should be placed where there is a high incidence of out-of-hospital cardiac arrest. This includes transportation centers, sport facilities, and large shopping malls. In Denmark, all AEDs have had “over-the-counter” status since 2003 thus allowing everyone to purchase an AED without prescription or medical supervision. We investigated how this system influenced AED placement nationally.

Methods:
We collected information on AED placement on September 15th 2010 from a web page used for voluntary registration of AEDs in Denmark.

Results and discussion:
There were 2811 registered AEDs. The majority (29%) was registered at private companies, and another 7% were registered at shops and 4% at hotels. Around 10% were placed in municipal buildings (e.g. town halls) and another 10% were registered in schools, kindergartens, or nursing homes. Nineteen and 3% were registered at sport facilities and at transportation centers, respectively. Healthcare professionals (dentists, GPs, and physiotherapists) had 5% of the registered AEDs. Two percent of the AEDs were purchased by residents' associations and 1% by a private person. The rest were registered at various other locations.

Conclusion:
With nonstrategic initiatives, AEDs are not necessarily placed where there is a high risk of out-of hospital cardiac arrest.