bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12610: Renal Sympathetic Denervation Modulates Ventricular Electrophysiology and Arrhythmogenesis
Authors: Huang Bing , Yu Lilei , He Bo , Lu Zhibing , Wang Songyun , He Wenbo , Yang Kang , Liao Kai , Jiang Hong
Published: July 2021

Introduction:
Previous studies suggest that renal sympathetic nerves can modulate central sympathetic tone. Recently, a beneficial effect of renal sympathetic denervation (RSD) has been seen in patients with different settings of ventricular electrical storm. However, the effect of RSD on ventricular electrophysiology remains unclear.

Methods:
Twenty-eight adult mongrel dogs were included in the present study. Eighteen dogs were subjected to RSD which was performed by ablating the adventitial surface of the renal artery. In Group 1 (n=8), programmed stimulation was performed before and after RSD to determinate ventricular effective refractory period (ERP) and action potential duration (APD) restitution properties. In Group 2 (n=10), acute myocardial ischemia (AMI) was induced by ligating the proximal left anterior descending coronary artery after the performance of RSD and the incidence of ventricular arrhythmia (VA) was calculated during 1-hour recording. In another 10 dogs (Group 3), AMI was induced and VA was measured with sham RSD.

Results:
In Group 1, RSD significantly prolonged ventricular ERP and APD, reduced the maximum slope (Smax) of the restitution curve and suppressed APD alternans at each site (Fig. 1A, C, E). RSD also significantly decreased the spatial dispersions of ERP, APD and Smax (Fig. 1B, D, F). The occurrence of spontaneous VA during 1-h AMI in Group 2 was significantly lower than that in Group 3 (Tab. 1).

Conclusions:
RSD significantly prolongs ventricular ERP and APD, attenuates APD restitution properties and reduces the incidence of ischemia-induced VA, suggesting that RSD may exert an anti-arrhythmic role for VA.
Abstract 12622: Western Diet for One Month Impairs Myocardial Energetics and Both Systolic and Diastolic Pump Function in the Mouse Heart
Authors: Luptak Ivan , Sverdlov Aaron L , Elezaby Aly , Miller Edward J , Pimentel David R , Liesa Marc , Shirihai Orian , Cohen Richard A , Balschi James A , Colucci Wilson S
Published: July 2021

Background and Significance:
Metabolic heart disease(MHD) is common in patients with obesity, type 2 diabetes and/or metabolic syndrome. We found cardiac mitochondrial dysfunction in mice with obesity-related MHD due to consumption of a high fat high sucrose (HFHS) diet. The effects of diet-induced obesity on cardiac energetics and pump function in the intact organ are largely unknown.

Hypothesis:
We tested the hypothesis that cardiac mitochondrial dysfunction due to HFHS diet for one month impairs energetic and contractile reserve in the intact heart.

Methods and Results:
Mice were fed a HFHS or control diet (CD) for 1 month. In isolated cardiac mitochondria from HFHS-fed mice (vs. CD) the maximal rate of ATP synthesis was decreased for complex I (down by 42%; p<0.05) and II (down by 37%; p<0.05) substrates. We measured myocardial energetics in isolated perfused hearts using 31P NMR spectroscopy at baseline (450 bpm, 2 mM Ca++) and high workload (600 bpm, 4 mM Ca++) in HFHS (n=7) and CD (n=8) hearts. In HFHS-fed hearts, myocardial ATP concentration was the same at baseline (10.5±0.4 vs 10.4±0.5 mM) and high workload (7.4±0.9 vs. 7.5±0.5 mM) as that of CD hearts. However, in HFHS-fed hearts the concentration of phosphocreatine, which reflects energy reserve, was decreased at baseline (13±0.7 vs. 17.5±0.8 mM; p<0.01) and decreased further at high workload (down to 7.3±0.7; p<0.01 vs. baseline and p<0.01 vs. CD at 10.5±0.4 mM) - indicating a mismatch between ATP production and utilization. In HFHS hearts, the diastolic pressure-volume relationship was shifted upward and leftward at baseline, indicative of diastolic dysfunction. In HFHS hearts, baseline systolic function was preserved (rate pressure product 41,600±2,200 vs. 41,000±2,000 mmHg/min), but was decreased at high workload (54,800±7,200 vs. 85,300±4,300 mmHg/min; p<0.01 vs. CD), reflecting an impaired contractile reserve.

Conclusion:
Consumption of a HFHS diet for one month causes cardiac mitochondrial dysfunction with reduced ATP synthesis leading to impaired energetic reserve in the intact heart. Diastolic dysfunction at rest and the impaired ability to increase systolic function with increased work demands may result from impaired energetics in MHD.
Abstract 12625: Mechanical Shear Stress Restores Mitochondrial Cytoarchitecture in Human Endothelial Cells Exposed to Angiotensin II by Modulating Activity of the Fission-Inducing Protein Dynamin Related Protein 1
Authors: Durand Matthew J , Gutterman David D
Published: July 2021

Background:
The mitochondria exist in a state of balance between fission (fragmentation) and fusion (joining of mitochondrial segments). Disease is characterized by excessive fission, leading to an overproduction of mitochondrial reactive oxygen species (ROS) which mediate pathological changes in vascular endothelium. Dynamin-related protein-1 (DRP-1) is the primary mediator of mitochondrial fission. The therapeutic benefit of exercise is largely due to increased endothelial shear; however the effects of shear stress on DRP-1 expression and mitochondrial structure are unknown.

Hypothesis:
Shear stress reduces mitochondrial fission in cultured human umbilical vein endothelial cells (HUVECs) exposed to the fission-inducing stimulus angiotensin II (ANG II) by reducing DRP-1 expression and activity.

Methods:
HUVECs were treated with MitoRFP for 24 hours to fluorescently label the mitochondria, then were exposed to ANG II (10 pM; 4 hours), fixed, and 25 random cells/group were imaged with a confocal microscope. Separate groups of cells were sheared (15 dyn/cm2; 24 hours) immediately following ANG II exposure using the Ibidi Pump System. To quantify mitochondrial fission, images were converted to binary color and ImageJ was used to count non-contiguous mitochondrial fragments. This value was divided by the number of pixels in the mitochondrial network and multiplied by 1000 to yield a Mitochondrial Fragmentation Index (MFI). Total DRP-1 expression and phosphorylation of the S616 activator and S637 suppressor sites were analyzed by Western blot.

Results:
ANG II increased MFI (1.13±0.25 vs. 0.75±0.06), DRP-1 expression (+48%) and phosphorylation of the S616 activator site (+141%; p<0.05 for all) compared to static controls. Conversely, ANG II-treated cells sheared for 24 hours showed reduced mitochondrial fission (MFI = 0.50 vs. 0.75±0.06), DRP-1 expression (-24%) and phosphorylation at S616 (-11%) compared to control. ANG II treated cells exposed to shear also showed a robust increase (+528%) in phosphorylation of the S637 suppressor site of DRP-1.

Conclusions:
High shear stress restores mitochondrial network integrity in HUVECs exposed to ANG II, suggesting exercise may promote vascular health by modulating mitochondrial fission.
Abstract 12636: Pro-Atrial Natriuretic Peptide: A Novel Guanylyl Cyclase-A Receptor Activator Which Goes Beyond Carperitide and Nesiritide
Authors: Ichiki Tomoko , Huntley Brenda K , Andersen Ingrid A , Sangaralingham S Jeson , Harty Gail J , Sandberg Sharon M , Heublein Denise M , Burnett John C
Published: July 2021

Introduction:
ProANP is a 108 amino acid (AA) prohormone which is produced in the atria and processed to the mature 28 AA ANP

which activates the guanylyl cyclase receptor-A (GC-A) and its second messenger cGMP. ProANP is found in the human circulation but its bioavailability is undefined.

Hypothesis:
ProANP represents a novel cardiac peptide with more sustained natriuretic actions than either carperitide (ANP) or nesiritide (BNP). ProANP itself can activate GC-A in vitro and the proANP can be processed in human serum from normals and in patients with heart failure (HF).

Methods:
We examined the
in vivo
cardiorenal actions of proANP compared to

ANP, BNP, or placebo in normal canines (667 pmol/kg, n=5/group). We determined cGMP activation of proANP, ANP and BNP in GC-A expressing HEK293 cells. ProANP processing and degradation was also defined in serum from normal subjects (n=13) and patients with HF (n=14) ex vivo.

Results:
ProANP had significantly greater diuretic and natriuretic properties with increased renal blood flow and sustained renal tubular actions compared to ANP or BNP in canines. ProANP also resulted in greater and more prolonged cardiac unloading than ANP, and much less hypotensive effects than BNP. The plasma half-life of proANP was 4.5 times longer than ANP and 3.8 times longer than BNP. ProANP itself stimulated cGMP generation in GC-A expressing HEK cells which was equal to ANP. ProANP was processed to ANP in fresh serum from normals as well as HF patients ex vivo and the processed peptide activated cGMP in GC-A expressing HEK cells.

Conclusions:
ProANP represents a novel GC-A activator with a longer half-life and greater natriuresis and diuresis than ANP and BNP and less hypotensive effects than BNP. The bioactivity of exogenous proANP may be through direct stimulation of GC-A, as well as through processing into ANP, as proANP is processed in the circulation of both normal and HF. As proANP circulates in the human circulation, proANP may represent a key circulating hormone in cardiorenal and blood pressure homeostasis as well as a potential innovative therapeutic beyond ANP (carperitide) or BNP (nesiritide) for cardiorenal diseases including HF.
Abstract 12641: Endothelial Cell Hspa12B Plays a Cardioprotective Role in Sepsis Induced Cardiac Dysfunction via the Release of MicroRNA Containing Exosomes
Authors: Zhang Xia , Wang Xiaohui , Ha Tuanzhu , Liu Li , Kao Race , Kalbfleisch John , Williams David , Li Chuanfu
Published: July 2021

Heat shock protein A12B (HSPA12B) is predominately expressed in endothelial cells and has been reported to contribute to angiogenesis. We hypothesized that HSPA12B plays a protective role in sepsis-induced cardiac dysfunction. Endothelial HSPA12B
-/-
(n=6) and wild type (WT, n=6) mice were subjected to cecal ligation and puncture (CLP)-induced sepsis. Sham surgical operation served as sham control (n=6). Cardiac function was examined by echocardiography before and 6 hour after CLP. In WT septic mice, ejection fraction (EF%) and fractional shortening (%FS) were significantly reduced by 34.8% and 43.1% (p<0.05), compared with control. HSPA12B
-/-
septic mice showed even greater decrements in EF% and FS% values (19.9% and 22.5%), when compared with WT septic mice. Serum levels of TNFα and IL-6 were higher in HSPA12B
-/-
septic mice than in WT septic mice. The expression of ICAM1 and VCAM1 in the myocardium of HSPA12B
-/-
septic mice was greater than in WT septic mice. Exosomes play an important role in cell-cell communication.
In vitro
data showed that exosomes isolated from the serum of HSPA12B
-/-
septic mice induced increased levels of TNFα and IL-6, NF-κB binding activity and TRAF6 ubiquitination in macrophages, when compared with WT septic exosomes. HSPA12B
-/-
septic exosomes contained significantly less microRNA-146a, which negatively regulates NF-κB signaling, when compared with WT septic exosomes. Endothelial cells (HUVEC) treated with HSPA12B
-/-
septic exosomes showed decreased expression of tight junction proteins (ZO-1and Occludin) and miR-126, which regulates the expression of adhesion molecules, when compared with WT septic exosomes treatment. In addition, the amounts of miR-146a and miR-126 in the exosomes from the serum of HSPA12B
-/-
septic mice were less than in the exosomes from WT septic mice. This is the first report that endothelial cell HSPA12B attenuates cardiac dysfunction in sepsis via secretion of exosomes and microRNA expression. We conclude that endothelial HSPA12B plays a cardioprotective role in sepsis via microRNA containing exosomes.
Abstract 12646: Oxidation-Dependent Phosphomimetic Effect of a Human Heart Failure Mutation of Phospholamban
Authors: Abrol Neha , de Tombe Pieter P , Robia Seth L
Published: July 2021

Rationale:
A naturally-occurring, missense Arg9-to-Cys (R9C) mutation of phospholamban (PLB) triggers cardiomyopathy and premature death in humans. However, the fundamental molecular mechanism underlying the cardiotoxic role of R9C-PLB in sarco/endoplasmic reticulum Ca
2+
-ATPase (SERCA) regulation and cardiomyocyte Ca
2+
handling is not clear.

Objective:
The goal of this study was to investigate the acute physiological consequences of R9C-PLB mutation on cardiomyocyte Ca
2+
kinetics and contractility and identify the molecular mechanism underlying R9C pathology.

Methods and Results:
We measured the physiological consequences of R9C-PLB mutation on Ca
2+
transients and sarcomere shortening in adult cardiomyocytes at increasing pacing frequencies. In contrast to studies of chronic R9C-PLB expression in transgenic mice, we found that acute expression of R9C-PLB exerts a positively inotropic and lusitropic effect in cardiomyocytes. Importantly, R9C-PLB exhibited blunted sensitivity to frequency potentiation and β-adrenergic stimulation, two major physiological mechanisms for the regulation of cardiac performance. To identify the molecular mechanism of R9C pathology, we fused fluorescent protein tags to PLB and SERCA, and compared the effect of R9C and pentamer-destabilizing mutation (SSS) on PLB oligomerization and PLB-SERCA interaction. Fluorescence resonance energy transfer (FRET) measurements in live cells revealed that R9C exhibited an increased affinity of PLB oligomerization, and a decreased binding affinity to SERCA due to an oxidative modification which mimics phosphorylation. Real-time FRET analysis in cardiomyocytes revealed that R9C-PLB exhibits enhanced sensitivity to oxidative stress, which is a prevailing condition in heart failure.

Conclusions:
We conclude that the primary mechanism of R9C pathology is a phosphomimetic effect of PLB cysteine oxidation, manifested as increased oligomerization and a change in the structure of the PLB-SERCA regulatory complex.
Abstract 12648: Deletion of 12/15 Lipoxygenase Improves Left Ventricle Function and Survival by Resolving Inflammation Post Myocardial Infarction
Authors: Kain Vasundhara , Ingle Kevin A , Kabarowski Janusz , Prabhu Sumanth D , Halade Ganesh V
Published: July 2021

12/15 lipoxygenase (LOX) is crucial in the inflammatory process leading to diabetes and atherosclerosis. However, the role of 12/15 LOX in myocardial infarction (MI) and left ventricle (LV) remodeling is unclear.

We assessed the role of 12/15 LOX in resolving inflammation in post-MI LV remodeling. 8-12 weeks old C57BL/6J wild-type (WT; n=67) and 12/15 LOX (LOX
–/–
; n=78) male mice were subjected to permanent coronary artery ligation surgery and monitored through day (d)1 and d5. No MI surgery mice were maintained as d0 naïve controls. LOX
-/-
mice showed higher survival rate, improved fractional shortening with reduced remodeling and edema index than WT at d1 and d5 post-MI (all p<0.05). LOX
-/-
mice showed increased Cxcl5 expression at d1 post-MI, consistent with stimulated neutrophil recruitment in the infarct region that was decreased at d5 compared to WT. LOX
-/-
mice infarct had increased expression of Ccl2 and Cxcl1, that stimulated an earlier recruitment of monocytes with increased macrophages population at d5 (all p<0.05) compared to WT. The altered kinetics of immune cells post-MI indicates a rapid resolving phase, through increase in alternative macrophage phenotypes with reduced collagen density in LOX
-/-
mice compared to WT mice at d5 post-MI. LOX
-/-
mice showed a coordinated COX-1 and COX-2 response at d1 post MI, leading to an evident increase in 5-LOX and hemoxygenase-1 (HO-1) at d5 post-MI. 12/15 LOX deletion enhanced the recruitment of alternative macrophages with secretion of HO-1 to resolve inflammation. In-vitro addition of LOX metabolite 12 hydroxyeicosatetraenoic acid to LOX
-/-
fibroblast induced early expression of COX-2 and 5-LOX compared to WT, indicating 5LOX role in resolution of inflammation. Post-MI increased expression of TIMP-1 and decrease in MMP-9 at d1 and α-SMA at d5 in LOX
-/-
mice suggested controlled differentiation of fibroblast-to-myofibroblast which is key event during ventricular tissue repair and resolving phase. This change is supported by increased expression of tgf-βi, ctgf and admats-2 (all P<0.05) at d5 post MI. In conclusion, absence of 12/15 LOX improves post-MI survival rates and attenuates LV dysfunction by resolving inflammation through coordination of 5-LOX and HO-1 as key inflammation resolving enzymes.
Abstract 12660: Model of End-Stage Liver Disease Excluding INR (MELD-XI) Scoring System Provides the Long-Term Prognostic Information in Patients Admitted With Acute Decompensated Heart Failure, Regardless of Reduced or Preserve Left Ventricular Ejection Fraction
Authors: Yamada Takahisa , Morita Takashi , Furukawa Yoshio , Tamaki Shunsuke , Iwasaki Yusuke , Kawasaki Masato , Kikuchi Atsushi , Kondo Takumi , Kawai Tsutomu , Takahashi Satoshi , Ishimi Masashi , Hakui Hideyuki , Ozaki Tatsuhisa , Satoh Yoshihiro , Seo Masahiro , Fukunami Masatake
Published: July 2021

Backgrounds:
Liver dysfunction has a prognostic impact on the outcome of patients with advanced heart failure. A model of end-stage liver disease excluding INR (MELD-XI) is a robust scoring system of liver dysfunction, and a high score has been shown to be associated with poor prognosis in patients with heart failure. However, there is little information available on the long-term prognostic significance of MELD-XI score in patients admitted with acute decompensated heart failure (ADHF), relating to reduced or preserved left ventricular ejection fraction (HFrEF or HFpEF).

Methods and Results:
We studied 303 consecutive patients admitted with ADHF and discharged with survival (HFrEF(LVEF<50%); n=163, HFpEF;n=140). MELD-XI score was calculated by the following formula: 5.11[[Unable to Display Character: ･]]ln(bilirubin)+11.79[[Unable to Display Character: ･]]ln(creatinine)+9.44. During a follow-up period of 5.0±4.3 yrs, 75 patients had cardiovascular death (CVD). Receiver-operator curve analysis revealed that MELD-XI score of 12 was a fair discriminator for CVD (AUC 0.704 (95%CI 0.635-0.772), p<0.0001; sensitivity 67% and specificity 62%). In HFrEF group, MELD-XI score was significantly independently associated with CVD (p=0.0037) at multivariate Cox analysis, and patients with high MELD-XI score (≥12) had a higher risk of CVD than those with low MELD score (46% vs 24%, p=0.0038, hazard ratio: 2.20 (95%CI 1.27-3.79)). In HFpEF group, MELD-XI score was also significantly independently associated with CVD (p=0.005) at multivariate Cox analysis, and patients with high MELD-XI score (≥12) had a higher risk of CVD (34% vs 8%, p<0.0001, hazard ratio: 6.25 (95%CI 2.59-15.05)).

Conclusion:
A MELD-XI scoring system would provide the long-term prognostic information in patients admitted with ADHF, regardless of HFrEF or HFpEF.
Abstract 12673: Placement of Proximal Edge on TCFA and Calcification Correlates With Inadequate Neointimal Coverage of Struts After Drug Eluting Stent Implantation
Authors: Ueda Tomoya , Uemura Shiro , Dote Yoko , Goryo Yutaka , Sugawara Yu , Okayama Satoshi , Watanabe Makoto , Saito Yoshihiko
Published: July 2021

Introduction:
Inadequate neointimal coverage of the stent struts is one of the risks for late stent thrombosis, especially in DES. Using OCT, we studied the morphological characteristics of coronary segment of both proximal and distal edges, and evaluated their influence on the neointimal coverage of the strut in chronic phase.

Methods:
Of 111 culprit coronary lesions in 91 patients, baseline OCT tissue characteristics were evaluated at both proximal and distal edges after DES implantation. The second OCT examination was performed on 9.1 months after implantation, and neointimal coverage of struts was assessed within 5mm inner segments from each stent edge. An uncovered strut was defined as having the signal thickness less than 30 μm from the center of strut.

Results:
Of 10995 apposed stent struts, uncovered struts were detected in 5.3% within distal and 6.8% within proximal edges. For further statistical analysis, edge segments were classified into two categories according to the ratio of uncovered struts, as the poorly-covered group (highest quartile with % uncovered struts), and the well-covered group (the remaining lower quartiles with % uncovered struts). As to OCT tissue characteristic, 1) fibrous plaque was significantly less observed in the poorly-covered group at both distal and proximal edges (p=0.0031 and p=0.0046, respectively). 2) Lipid pool was more frequently observed in the poorly-covered group than the well-covered group at both distal and proximal edges (p=0.0037 and p=0.0061, respectively). 3) Thin-cap fibroatheroma (TCFA) and calcification were also more frequently observed in the poorly-covered group than the well-covered group (p=0.0025 and p=0.0070, respectively) at proximal stent edge. Logistic regression analysis revealed that existence of calcification at proximal edge was an independent predictor for uncovered struts (OR: 5.48, 95%CI: 1.46-23.46, p=0.0119). TCFA at proximal edge was also an independent predictor (p=0.0044).

Conclusions:
TCFA and calcification at proximal edge were predictors of uncovered struts. Although mechanism should be further elucidated, placement of proximal edge on such tissue characteristics should be avoided.
Abstract 12683: Combined Assessment of High-Sensitive Troponin I and N-Terminal Pro-B-Type Natriuretic Peptide Levels Improves the Prediction of Future Admission for Heart Failure in Outpatients With Chronic Kidney Disease
Authors: Ishii Junnichi , Takahashi Hiroshi , Hasegawa Midori , Okuyama Ryuunosuke , Kawai Hideki , Muramatsu Takashi , Naruse Hiroyuki , Motoyama Sadako , Matsui Shigeru , Izawa Hideo , Yuzawa Yukio , Ozaki Yukio
Published: July 2021

Background:
Heart failure (HF) is a common consequence of chronic kidney disease (CKD), and it portends high risk for mortality. We prospectively investigated the predictive value of a combination of high-sensitive troponin I (hsTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for HF admission in outpatients with CKD.

Methods:
Baseline hsTnI and NT-proBNP levels were measured in 451 stable outpatients with CKD (estimated GFR < 60 mL/min/1.73 m
2
) on not dialysis (mean age, 69.7 years). Using echocardiography with tissue Doppler imaging, left ventricular ejection fraction (EF) and E/e’ ratio were estimated. Among these patients, 41% had a history of cardiovascular disease, and 48% had a history of diabetes.

Results:
During a mean follow-up period of 924 days, there were 70 HF admissions. Patients who admitted for HF had higher hsTnI levels (22.4 vs. 10.5 pg/mL, p < 0.0001), NT-proBNP levels (1726 vs. 310 pg/mL, p < 0.0001), and E/e’ ratio (15.3 vs. 10.3, p < 0.0001), and displayed lower values of EF (55 vs. 59%, p < 0.0001) and estimated GFR (23.7 vs. 30.6 mL/min/1.73 m
2
, p = 0.009) than those who did not. Using multivariate Cox regression analysis including 11 clinical variables, increased hsTnI (relative risk, 1.98 per 10-fold increment, p = 0.02) and NT-proBNP (3.18 per 10-fold increment, p = 0.003) levels were shown to be independent predictors of HF admission. When patients were stratified into four groups according to NT-proBNP levels > a median value of 397 pg/mL and/or hsTnI levels > a median value of 11.6 pg/mL, HF admission rates were 3.1%, 7.5%, 11.8%, and 33.1%, respectively (p < 0.0001). Furthermore, when hsTnI and NT-proBNP levels were combined, the predictive values for HF admission were increased, as shown by the C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI; Table 1).

Conclusions:
The combined assessment of hsTnI and NT-proBNP levels can improve the prediction of HF admission in outpatients with CKD.
Abstract 12707: Chads2 and Chads2vasc Scores Predict the Risk for Left Atrial Thrombus in Patients With Atrial Fibrillation
Authors: Jia Fengpeng , Fu Minghuan , Ling Zhiyu , Luo Suxin , Gu Jun , He Quan , Han Lei , Liu Zhenguo
Published: July 2021

Background:
The study was to evaluate the value of CHADS2 and CHADS2VASC scores on predicting left atrial (LA) thrombus in the patients with atrial fibrillation (AF).

Methods and Results:
All the non-valvular AF patients undergoing AF ablation from June 2010 to June 2012 were included and divided into two groups: patients without anticoagulation and with Coumadin anticoagulation for at least 4 weeks. The relationship between CHADS2 and CHADS2VASC scores and LA thrombus as identified on transesophageal echocardiography (TEE) was analyzed prior to ablation. A total of 397 patients underwent pre-ablation TEE: 212 patients without anticoagulation, and 185 with anticoagulation. There were no differences in the CHADS2 and CHADS2VASC scores in the two groups. LA thrombus was present in 15.6% and 5.9% for the patients without anticoagulation and for those with anticoagulation, respectively (p = 0.002). There was a strong association between CHADS2 and LA thrombus, and between CHADS2VASC and LA thrombus in the two groups. No thrombus was identified in patients with CHADS2VASC score of 0 in both groups. However, thrombus was detected in 3.5% of patients with CHADS2 score of 0 in the group without anticoagulation, while no thrombus was present in the ones with anticoagulation. CHADS2VASC score of ≥1 (r=2.03, p = 0.04) was the only factor independently associated with LA thrombus in patients without anticoagulation, while both CHADS2VASC score of ≥2 (r=2.61, p=0.02) and CHADS2 score of ≥2 (r=2.73, p=0.01) were independently associated with LA thrombus. Further analyses showed that CHADS2VASC score was a better predictor for LA thrombus than CHADS2 score in patients without anticoagulation. However, there was no difference between the two scoring systems in predicting LA thrombus in patients with anticoagulation.

Conclusions:
LA thrombus was associated with CHADS2VASC and CHADS2 scores in non-valvular AF patients without anticoagulation. CHADS2VASC score was a better predictor than CHADS2 score for LA thrombus in patients without anticoagulation. The data suggested that it might be unnecessary to undergo a TEE evaluation for LA thrombus in low risk patients identified by CHADS2VASC score regardless anticoagulation therapy prior to cardioversion or ablation.
Abstract 12746: Validation of a New Algorithm for Detection of Coronary Artery Disease Using Carotid and Femoral Vascular Ultrasound
Authors: Alzaeim Nabil , Abdelwahab Amir , Baligh Essam
Published: July 2021

Background:
Atherosclerosis is a systemic disease and patients presenting with atherosclerotic coronary artery disease (CAD) usually have associated vascular disease and the reverse is true. Abdelwahab A. et al study is one of the studies who investigate the relation between the different duplex parameters of the carotid and femoral arteries and the extent of coronary atherosclerosis and they proposed a new algorithm for the detection of significant CAD by using carotid and femoral vascular ultrasound.

Objective:
To assess the validity and applicability of a new algorithm for detection of significant CAD.

Methods:
Peripheral arterial duplex evaluation was performed for 97 consecutive patients (65 men and 32 women; mean age 59±4.5 years) undergoing coronary angiography for a variety of indications. The following duplex parameters were determined in all patients : Common carotid and common femoral intima media thickness (IMT), carotid total plaques dimension product (PDP) and carotid-femoral (CARFEM) index which is a combination index of IMT of carotid artery and common femoral artery and total wall thickness of the superficial femoral artery.

Results:
As the number of affected coronary arteries increased, there was a proportional increase in the mean of Carotid IMT, total PDP and CARFEM Index (P= .025, < 0.001 and 0.017 respectively ). Sensitivity, specificity, positive and negative predictive values of the proposed algorithm were 90.3% 72%, 90.3% and 72% respectively.

Conclusion:
Carotid and femoral duplex provides an easy non-invasive tool for detection of significant CAD. The proposed step-wise algorithm could be a reliable approach for detection of significant CAD.
Abstract 12752: Mortality Risk for Ruptured Abdominal Aortic Aneurysm After Endovascular and Open Intervention in Women
Authors: De Rango Paola , Simonte Gioele , Biello Antonella , Manzone Alessandra , Cieri Enrico , Verzini Fabio , Parlani Giovanbattista , Lenti Massimo
Published: July 2021

Hypothesis:
There may be sex differences in presentation and outcomes of abdominal aortic aneurysms (AAA) with increased mortality rates in women. Aim of this study was to assess mortality risk after repair of ruptured AAA (rAAA) in women in the endovascular repair (EVAR) era.

Methods:
All patients treated in 2006-2014 for rAAA were reviewed. Characteristics at presentation and outcomes were compared between women and men. Multivariable logistic regression and Cox proportional hazards modeling were performed to identify the effect of sex adjusted for other predictors on mortality.

Results:
One-hundred and four patients were identified: 16.3% (17/104) were women. Forty-one procedures (39.4%) were by EVAR, with comparable rates in women (47.1%) and men (37.9%;P=0.59). On admission women and men shared similar comorbidities and presentation (shock rates 43.8% vs. 45.9%; P=1; free rupture rates 58.8% vs. 67.8%; P=0.58 ) and comparable mean aneurysm diameter (76.2mm vs.77.7mm;P=0.8) but women were older (mean age 86.2+5.8 vs. 75.5 +10.3 years; P<0.0001) and octogenarian women were twice as likely as men (88% vs. 40% P<0.0001). Sex-related age difference was more evident within the open surgery group. Perioperative mortality was not different between women and men (35.3% vs. 35.6%) either after EVAR [25.0% vs. 33% in women and men respectively;Odds Ratio(OR) 0.7; 95%Confidence Interval (CI) 0.12-3.9] or after open surgery (44.4% vs. 37.0%; OR 4.7;95%CI 0.98-24.8), even though there was a trend for lower mortality in women with EVAR. In adjusted analyses, female sex was not associated with perioperative mortality as it was for old age (OR 5.5;95%CI 1.7-18.3) and free rupture (OR 3.5;95%CI 1.06- 11.7). At a mean follow-up of 22.3 months late survival was worse in women than in men but only for patients undergoing open surgery and the difference did not attain statistical relevance. After controlling for age, surgical repair, free rupture, cardiac disease, female sex was not predictor of late mortality.

Conclusions:
Despite AAA repair is often delayed in women and applied at older age, women might not show increased perioperative mortality risks from rAAA treatment after the introduction of EVAR. Larger data are required to confirm this hypothesis.
Abstract 12757: The Combination of Dyssynchrony and Global Longitudinal Strain by 3D Speckle Tracking After ST-Elevation Myocardial Infarction is Useful for Prediction of Final Infarct Size and Left Ventricular Remodeling
Authors: Iwahashi Noriaki , Gohbara Masaomi , Kataoka Shunsuke , Akiyama Eiichi , Maejima Nobuhiko , Tsukahara Kengo , Hibi Kiyoshi , Kosuge Masami , Ebina Toshiaki , Umemura Satoshi , Kimura Kazuo
Published: July 2021

Background:
Left ventricular (LV) global strain estimated immediately after ST elevation AMI (STEMI) was reported as a predictor of LV remodeling. Furthermore, LV dyssynchrony estimated by 2D strain is also a prognosticator. However, strain analysis ideally should be assessed by 3D speckle tracking, in order to avoid through plane motion. We explored the usefulness of these two variable assessed by 3D speckle tracking in patients with a first STEMI.

Methods:
Consecutive 190 patients (131 men, age 65 years, peak CPK=3169 IU/l) presenting with a first STEMI who underwent primary PCI within 12 hours of onset were enrolled. Within 24 h of PCI, echocardiography was performed by iE33(Philips). 3D speckle tracking was analyzed by 4D LV-Analysis (TOM-TEC, Germany). Global longitudinal strain was calculated (3D-GLS) and the standard deviation (SD) of time to regional peak 3D longitudinal strain (3D-Long-SD) for all 16 segments was assessed as the parameter of dyssynchrony. Final infarct size was defined using Tc99m-sestamibi as the total area of <50%uptake area at 2 weeks. Echocardiography was repeated 12 months later and LV remodeling was defined as an absolute increase in LVEDV of more than 20%.

Results:
LV remodeling was observed in 52 patients at 12 months. Both 3D-GLS and 3D-Long-SD had significant relationships with infarct size (r2=0.236, 0.169, p<0.0001). Furthermore, both of the worst tertile of them predicted LV remodeling (Odds ratio = 2.634, 95%CI; 1.322-5.308, p<0.001) (Odds ratio = 3.846, 95%CI;1.887-8.011, p<0.001). Table shows logistic regression analysis for LV remodeling and the combination of these indexes was the strongest predictor (Odds ratio = 2.58, 95%CI 1.003-6.723, p=0.04).

Conclusions:
In patients with a first STEMI, GLS and LV dyssynchrony assessed by 3D speckle tracking echocardiography immediately after PCI can predict final infarct size and LV remodeling. The combination of these parameters was especially useful to predict LV remodeling.
Abstract 12766: Long Term Outcome of Patients With Complete Revascularization
Authors: Kang Jeehoon , Park Kyung Woo , Kang Si-Hyuck , Kang Hyun-Jae , Lee Hae-Young , Koo Bon-Kwon , Chae In-Ho , Youn Tae-Jin , Oh Byung-Hee , Park Young-Bae , Kim Hyo-soo
Published: July 2021

Introduction:
Complete revascularization (CR) is considered as a goal for percutaneous coronary intervention (PCI). Previous studies have proved that achieving CR is beneficial compared to incomplete CR. However there has been no research about the long term outcome within CR patients.

Hypothesis:
The SS has predictive value in CR patients.

Methods:
From patients enrolled in the Efficacy of Xience/Promus versus Cypher in rEducing Late Loss after stENTing (EXCELLENT) registry, the SYNTAX score was checked before and after PCI. The primary clinical outcome was 3-year patient-oriented composite endpoint (POCE), which was a composite of all cause death, any myocardial infarction, and any revascularization. Secondary outcomes were the individual components of 3-year POCE and 3-year target lesion failure (TLF). For calculation of the clinical SS, the SS was multiplied with the value of the ‘Age, Creatinine, and Ejection Fraction’ score.

Results:
Among 5102 patients from the EXCELLENT registry, 2112 patients achieved CR by PCI. 3-year POCE was less common in CR patients (10.0% vs. 16.9%, p<0.001) and CR was an independent predictor of adverse outcomes (Hazard ratio (HR) 1.326, 95% Confidence Interval (CI) 1.108-1.587, p=0.002). Patients who achieved CR were divided into 3 groups, according to the pre-PCI SYNTAX score (SS); 1≤low-SS<6: 771 patients, 6≤mid-SS<10: 692 patients, and high-SS≥10: 649 patients. 3-year POCE increased significantly along with increasing baseline SS tertiles (7.5% vs. 8.4% vs. 14.8%, p<0.001) and secondary outcomes also showed similar tendency. Multivariate analysis showed that baseline SS was an independent predictor of 3-year POCE (HR 1.032, 95% CI 1.011-1.053, p=0.003 per SS point). The clinical SS was superior to baseline SS in predicting 3-year POCE (AUC: 0.595 vs. 0.649, p=0.008). In subgroup analysis, baseline SS was a predictor for POCE only in multi-vessel diseases (HR 1.027, 95% CI 1.001-1.054, p=0.042 per SS point).

Conclusions:
CR is an independent predictor of 3-year POCE in patients receiving PCI. However, even after CR is achieved to make the post-PCI SS zero, baseline SS still has predictive value of 3-year clinical outcomes. Moreover, the predictivity is was superior in multi-vessel diseases.
Abstract 12794: Hospital Length of Stay and Readmissions Post Heart Failure Hospitalization in the EVEREST Trial
Authors: Khan Hassan , Kalogeropoulos Andreas P , Ambrosy Andrew P , Maggioni Aldo P , Zannad Faiez , Konstam Marvin , Swedberg Karl , Yancy Clyde W , Fonarow Gregg C , Gheorghiade Mihai , Butler Javed
Published: July 2021

Background:
Previous reports have provided conflicting data regarding the relationship between length of stay (LOS) and subsequent readmissions risk among patients hospitalized for heart failure (HF).

Methods:
We performed a post-hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial to evaluate the differences in LOS overall and between geographical regions (North America, South America, Western Europe, and Eastern Europe) in association with all-cause and cause specific (HF, cardiovascular [CV] non-HF and non-CV) readmissions within 30 days of discharge after HF hospitalization.

Results:
The median (IQR) LOS among the 4,133 patients enrolled from 20 countries across 359 sites was 8 (4-11) days. The 30-day readmissions rates were 15.6% (95% confidence intervals [CI] 14.6-16.8) for all-cause; 5.5% (95%CI 4.9-6.3) for HF; 4.4% (95%CI 3.8-5.1) for CV non-HF and 5.8% (95%CI 5.1-6.6) for non-CV readmissions. Overall there was a positive correlation between LOS and all cause readmissions (r=0.09; 95%CI 0.06-0.12). The adjusted odds ratio for the top (>14 days) versus the bottom (<3 days) quintile for LOS was 1.39 (95%CI 0. 92-2.11) for all-cause; 0.43 (95%CI 0.24-0.79) for HF; 2.99 (95%CI 1.49-6.02) for CV non-HF and 1.72 (95%CI 1.05-2.81) for non-CV readmissions, Figure 1. These findings remained consistent in analyses within patient characteristic subgroups and also largely within regions.

Conclusions:
Longer hospital LOS was associated with a higher risk for all-cause, CV non-HF, and non-CV readmissions, and with a lower risk of HF readmissions. These results may have important bearing in developing clinical and research strategies to reduce readmissions.
Abstract 12822: Increased Expression and Serum Levels of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Patients With Aortic Valve Stenosis
Authors: Yoshiyama Tomotaka , Yunoki Kei , Komatsu Ryushi , Haze Kazuo , Naruko Takahiko , Sugioka Kenichi , Nakagawa Masashi , Inaba Mayumi , Yoshiyama Minoru , Uchida Kagehiro , Sawamura Tatsuya , Ueda Makiko
Published: July 2021

Background:
The development of aortic valve stenosis (AS) involves multiple events, including inflammation and lipid deposition and oxidation. Circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) play an important role in the development and progression of atherosclerosis. The aims of this study were to investigate the serum levels of sLOX-1 in patients with AS and also examine the expression of LOX-1 immunohistochemically in aortic valve specimens from these patients.

Methods:
Serum sLOX-1 levels were measured in patients with AS (n=128), stable angina pectoris (SAP, n=343) and in 53 control subjects using a sandwich ELISA method. Frozen aortic valve samples were also obtained surgically from a cohort of 20 AS patients. In addition, frozen aortic valve specimens were obtained at autopsy from individuals who died of non-cardiovascular causes (n = 11, mean age 68 yr) as a reference. Immunostaining of the samples was performed using antibodies against smooth muscle cells, macrophages, T-lymphocytes, neutrophils, microvessels, and LOX-1.

Results:
Serum sLOX-1 levels were significantly higher in AS patients compared with SAP patients (
P
<0.0005) or control subjects (
P
<0.0001). There were no differences in serum sLOX-1 levels between AS patients with or without coronary artery disease. Immunohistochemical staining showed that the LOX-1-positive area, as a percentage of the total area, was significantly (P<0.01) higher in AS patients compared with reference cases. Double immunostaining for LOX-1 and macrophages revealed that the vast majority of LOX-1-positive cells were macrophages.

Conclusions:
This study demonstrates for the first time that serum sLOX-1 levels are elevated in patients with AS, and AS lesions contain a significantly higher percentage of LOX-1-positive macrophages. These findings suggest that LOX-1, a marker of oxidative stress, may play an important role in the development of aortic valve stenosis.
Abstract 12858: Left Ventricular Dysfunction Switches Cardiac Mesenchymal Stem/Stromal Cells Toward a Pro-Inflammatory Phenotype
Authors: Naftali-Shani Nili , Levin-Kotler La-Paz , Palevski Dahlia , Amit Uri , Holbova Radka , Hochhauser Edith , Leor Jonathan
Published: July 2021

Introduction and Hypothesis:
Mesenchymal stem/stromal cells (MSCs) are appealing candidates for cardiac cell therapy due to their ease of preparation, immunoprivilege properties, reparative potential and safety. We aimed to test the hypothesis that the inflammatory environment following myocardial infarction (MI) and left ventricular (LV) dysfunction could modulate the reparative properties of resident and transplanted MSCs.

Methods and Results:
To test this hypothesis, we isolated and cultured resident cardiac and subcutaneous (SC) fat tissue MSCs from mice, 28 days after MI (LVEF: 27.9%±3.8) or sham operation (LVEF: 54.9%±3.8). Proliferation rate was highest in cardiac MSCs after MI, compared with other groups (p<0.001 after 96 hours). Next, we measured the levels of secreted cytokines in the medium collected from the different cells and found that MI polarized cardiac MSCs toward a pro-inflammatory profile and stimulated secretion of the inflammatory cytokines IL1α, IL1β, IL-12, IL-6 and TNF-α (p<0.05), as well as the monocyte recruitment factors: MIP-1α, RANTES and MCP-1 (p<0.05). In contrast, SC fat MSCs were less affected by MI and LV dysfunction and mainly decreased their macrophage recruitment and anti-inflammatory factors. Surprisingly, transplantation of cardiac and adipose tissue MSCs from both MI and sham operated animals, into mice hearts immediately after MI (n=5-8 per group), did not improve cardiac remodeling and function, compared with saline. To determine the mechanism behind MSC polarization, we stimulated cardiac MSCs from toll-like receptor 4 (
TLR4
) deficient and wild-type mice, with the secretome of LPS-activated macrophages. Significantly, there was less inflammatory cytokine secretion in TLR4-deficient MSCs, compared with control suggesting that cardiac MSC polarization is mediated by
TLR4
activation.

Conclusions:
Post MI inflammatory environment switches resident cardiac and implanted MSCs toward a pro-inflammatory phenotype and impair their reparative properties. This effect is mediated by
TLR4
. Our findings are relevant to the pathogenesis and progression of LV remodeling, and could guide the selection and engineering of MSCs for heart repair.
Abstract 12926: Transition Readiness Assessment in Adolescents and Young Adults With Heart Disease: Can We Improve the Outcome?
Authors: Uzark Karen , Smith Cynthia , Yu Sunkyung , Donohue Janet , Afton Katherine , Norris Mark D , Cotts Timothy B
Published: July 2021

Objective:
Transition is defined as “the process by which adolescents and young adults with chronic childhood illnesses are prepared to take charge of their lives and their health in adulthood”. We previously reported common knowledge deficits and lack of transition readiness (TR) in 13-25 year olds with congenital or acquired heart disease. The aims of this study were to re-evaluate TR in these patients at follow-up (F/U) and to examine the relationship between changes in TR and quality of life (QOL).

Methods:
Patients (n=106) completed the TR Assessment and Pediatric Quality of Life Inventory (PedsQL) utilizing an e-tablet, web-based format at a routine F/U clinic visit. Changes from initial to F/U scores were evaluated.

Results:
Median patient age was 18.7 yrs at a median F/U time of 1.02 yrs. Average perceived knowledge deficit score (% of items with no knowledge) at F/U was 18.0 ± 15.2%, decreased from 24.7 ± 16.5%, p<.0001. On a 100-point scale, the mean score for self-efficacy increased from 71.4 ± 17.0 to 76.7 ± 18.2 (p=.004) and for self-management increased from 47.9 ± 18.4 to 52.0 ± 20.7 (p=.0004). While physical QOL did not change, the mean psychosocial QOL score increased significantly from 80.2 ± 13.3 to 82.5 ± 12.0, p=.02. A decrease in knowledge deficit score at F/U was significantly associated with an increased psychosocial QOL score, p=.03. An increase in self-efficacy score was associated with an increase in psychosocial QOL score (p=.04), especially social QOL (p=.02). Among patients who reported receiving specific information after initial TR assessment, knowledge deficits decreased related to medication (p=.002), symptoms to call for (p=.02), how to contact heart doctor (p=.02), and health insurance (p=.10). Self-efficacy scores improved in patients reporting receipt of information regarding how to contact the heart doctor (p=.06) and how to communicate with healthcare team (p=.05).

Conclusion:
While deficits in knowledge and self-management skills persist, TR assessment and recognition of deficits can improve transition readiness with improved psychosocial QOL. Routine TR assessment is important to identify transition needs. Further studies are needed to examine the relationship between TR and outcomes in young adults with heart disease.
Abstract 13013: The Impact of Prolonged Clopidogrel Beyond 12 Months After Coronary Stenting in Patients with Acute Coronary Syndromes
Authors: Wimmer Neil J , Smoot Kyle , Cho Kelly , Sokolovskaya Galina , Gagnon David , Ly Samantha , Temiyasathit Sara , Do Jacquelyn , Nava Adrianna , Ostrowski Simon , Gaziano J. M , Faxon David P , Kinlay Scott
Published: July 2021

Introduction:
Clopidogrel up to 12 months after an acute coronary syndrome (ACS) lowers the risk of major adverse coronary events. Guidelines recommend clopidogrel for 12 months after coronary intervention (PCI) with bare-metal (BMS) or drug-eluting (DES) stents. The value of prolonging clopidogrel beyond 12 months in PCI patients with ACS is unknown.

Hypothesis:
We hypothesize that prolonged clopidogrel differentially reduces adverse events in patients receiving DES compared with those receiving BMS for an ACS.

Methods:
We linked all PCIs in the national Veterans Affairs (VA) health system from 2002-2006 with the VA pharmacy database. VA and non-VA clinical outcomes were identified by ICD9 codes from the VA and CMS/Medicare databases. All patients who were event free at 12 months were followed for death, myocardial infarction (MI), and recurrent target vessel revascularization (TVR). The hazard ratio for prolonged clopidogrel use (more than 12 months) versus clopidogrel for less than or equal to 12 months was assessed for each outcome within each stent type, using Cox proportional hazards models. Multivariable models and propensity models were also used to adjust for confounding related to the propensity for prolonged clopidogrel treatment.

Results:
After exclusions, 28,507 patients had PCI and were event free at 12 months. Of these, 18,279 (64%) had an ACS at their index PCI including 9,336 (51%) who received a DES and 8,447 (46%) who received prolonged clopidogrel. Events occurring up to 4 years after PCI in these ACS patients included 1358 deaths, 1885 death or MIs, and 1335 TVRs. Prolonged clopidogrel was associated with lower risk of death (interaction p=0.04) and death or MI (interaction p=0.001) only in patients receiving DES (Table). Similar results were seen in multivariable and propensity models.

Conclusions:
Prolonging clopidogrel more than 12 months after PCI for ACS may lower the risk of death or MI in patients receiving DES but not in patients receiving BMS.