bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13076: Lipid-lowering Therapy Stabilizes the Complexity of Non-culprit Plaques in Human Coronary Artery: A Quantitative Assessment Using OCT Bright Spot Algorithm
Authors: Minami Yoshiyasu , Hoyt Taylor , Phipps Jennifer E , Milner Thomas E , Xing Lei , Yu Bo , Feldman Marc D , Jang Ik-Kyung
Published: July 2021

Introduction:
Recent studies using optical coherence tomography (OCT) reported that statin therapy increases the thickness of fibrous cap in human coronary plaques. However, the efficacy on the stabilization of plaque complexity remains unknown.

Aim:
To quantitatively evaluate the statin efficacy on the change of plaque complexity using an OCT bright spot algorithm.

Methods:
From a randomized trial (NCT01023607), we identified 59 lipid-rich coronary plaques in non-culprit lesions from 40 patients who were randomized to receive atorvastatin 60mg (AT60), rosuvastatin 10mg (RT10) or atorvastatin 20mg (AT20), and had serial image acquisition at baseline, 6-month, and 12-month by time-domain OCT. We applied an OCT algorithm which is able to identify bright spots representing variety of plaque components including macrophage. The density of bright spots was measured within superficial 250μm of the vessel wall as the number of bright pixels divided by the number of pixels in each frame through the entire plaque length.

Results:
Significant reduction of bright spot density was observed from baseline to 12-month, particularly during the second 6 months (Figure). All three types of statin demonstrated the marked reduction of bright spot density from the baseline to 12-month (-0.61% [-0.93, -0.34], P<0.001, -0.45% [-0.99, -0.34], P=0.001 and -0.41% [-0.98, -0.19], P<0.001, in AT60 (n=22), RT10 (n=15) and AT20 (n=22), respectively) without significant difference among the groups (P=0.76). There was no significant difference in the reduction of bright spot density from baseline to 12-month between patients with acute coronary syndrome (n=47) and those with stable angina (n=12) (-0.49% [-0.97, -0.28] vs. -0.41% [-0.89, -0.21], P=0.62).

Conclusions:
Coronary plaque complexity evaluated by a quantitative OCT algorithm was significantly improved by 12-month statin therapy irrespective of the statin type and baseline clinical presentation.
Abstract 13092: Cardiac MRI Practice: An Analysis of 2012 and 2013 Medicare Provider Utilization and Payment Data
Authors: Goldfarb James W
Published: July 2021

Introduction:
The Centers for Medicare and Medicaid Services (CMS) recently released detailed information on services provided to Medicare beneficiaries by physicians for 2012 and 2013. The information provides individual provider information based on HCPCS code, number of services and payment. Additionally, demographic information is provided for each physician. We analyzed these databases to determine the number of cardiac MRI services provided, physician payment, characteristics of providers and changes over time to provide insight into the practice of cardiac MRI in the United States.

Methods:
The 2012 and 2013 Medicare Provider Utilization and Payment Data: Physician and other Supplier Public Use File (PUF) was downloaded and searched for cardiac MRI HCPCS codes (75557-75564). Statistics were calculated for the number of providers, number of services, payment, geographic location and type of facility. Additionally, provider degree, gender and clinical specialty were analyzed. Changes from 2012 to 2013 were statistically compared.

Results:
In 2012, there were 311 (84% male) providers with 11,473 cardiac MR scans. The number of MRI scans per provider (36.9±39.2; range: 11-260) varied widely. In 2013, the number of providers increased to 337 (85% male) with 12,076 cardiac MR scans (35.8±36.7; range: 11-246). Physician identified specialty was 48% Cardiology and 46% Diagnostic Radiology. Payment (2013) was less (p<0.001) in facilities ($125.8±8.6; n=10,107) compared to non-facilities ($451.75±123.3; n=1,969). In Figure 1, the number of MR scans (2013) are displayed geographically and by HCPCS code.

Conclusions:
Cardiac MR utilization slightly increased and payment decreased from 2012 to 2013. Usage was split evenly between Cardiology and Diagnostic Radiology, but providers were predominantly male.
Abstract 13097: Novel Interaction of Antioxidant-1 With NADPH Oxidase p47phox and TRAF4: Role in TNFα-Induced Inflammation and Atherosclerosis
Authors: Das Archita , Varadarajan Sudhahar , Chen Gin-Fu , Surenkhuu Bayasgalan , Tian Jun , Ushio-Fukai Masuko , Fukai Tohru
Published: July 2021

Tumor necrosis factor-TNFα plays a key role in atherosclerosis via NADPH oxidase-derived reactive oxygen species (ROS) and its downstream redox-sensitive inflammatory responses. Copper (Cu) has been implicated in atherosclerosis and inflammation with unknown mechanism. Bioavailability of Cu is controlled by transport-proteins including Cu-chaperone Atox1 which obtains Cu via Cu-importer CTR1 localized at plasma membrane. We recently found that Atox1 also functions as a Cu-dependent transcription factor for NADPH oxidase p47phox. However, role of Atox1 in atherosclerosis is unknown. Here we show that ApoE-/-Atox1-/- mice with 16 weeks high-fat-diet (HFD) showed decreased atherosclerotic lesion (40%, Oil-O-red staining). inflammatory cell recruitment (50% decrease, Mac3+) and extracellular matrix deposition (Masson’s Trichrome) compared to ApoE-/-HFD. Mechanistically, in cultured endothelial cells (ECs), Atox1 knockdown with siRNA, or Cu-chelator BCS inhibited TNFα-induced ROS production (70%) at later phase (16hrs) and its downstream VCAM1/ICAM1 expression and monocyte adhesion by reducing transcription of p47phox. Unexpectedly, TNFα stimulation rapidly promoted Atox1/p47phox binding in a PKCδ-dependent and Cu-“independent” manner, which is required for p47phox membrane translocation involved in early phase of (5min) ROS production and subsequent Cys oxidation of Cu-importer CTR1 detected by a biotin-labeled Cys-OH trapping reagent. This was followed by CTR1/Cu-dependent Atox1 binding to TNFα receptor associated factor (TRAF)4, which promoted Atox1 nuclear translocation to increase p47phox expression leading to late-phase of ROS production, facilitating further monocyte adhesion to ECs. In summary, Atox1 plays an important role in activating p47phox-based NADPH oxidase and inflammatory responses in ECs by binding to p47phox that induces early phase of ROS to promote CTR1 oxidation in Cu-independent manner. This is followed by Cu-dependent Atox1/TRAF4 binding required for Atox1 nuclear translocation to function as a transcription factor for p47phox, leading to late-phase of ROS production, which contributes to acceleration of atherosclerosis in vivo.
Abstract 13131: Impact of Exercise Training on Cardiac Structure and Function in Patients With Type-2 Diabetes or Obesity: A Meta-analysis of Randomized Control Trials
Authors: Anand Vidhu , Pandey Ambarish , Garg Sushil Kumar
Published: July 2021

Background:
Type 2 Diabetes mellitus (T2DM) and obesity are associated with subclinical abnormalities in left ventricular structure and function and an increased downstream risk for heart failure. Exercise training has been associated with significant improvement in cardiorespiratory fitness among these patients. However, its impact of cardiac structure and function is not well established. In this meta-analysis, we evaluated the effect of exercise training on the LV systolic and diastolic function in patients with T2DM or obesity.

Methods:
We included all randomized control trials (RCTs) that evaluated the effect of exercise training on cardiac structure and function among obese or T2DM patients. Primary outcome of interest was change in cardiorespiratory fitness (peak oxygen uptake, ml/kg/min) and measures of left ventricular systolic (global longitudinal strain) and diastolic function (early diastolic velocity, e`).

Results:
The study included 484 patients who were enrolled in 8 RCTs. In the pooled data analysis, patients with T2DM or obesity undergoing exercise training had significant improvements in peak oxygen uptake [Weighted Mean Difference (WMD): 1.30 (95%CI: 0.55 to 2.04)]. Among echocardiographic outcomes, exercise training participants had modest but statistically significant improvements in early diastolic velocity [WMD (95% CI): 0.46 (0.01 to 0.09)], and global longitudinal strain [WMD (95% CI): 0.62 (0.04 to 0.09)] as compared with control group participants (Figure).

Conclusion:
Exercise training in patients with T2DM or obesity is associated with a significant improvement in cardiorespiratory fitness and modest improvements in echocardiographic measures of systolic and diastolic function. These findings suggest that exercise training may improve subclinical systolic and diastolic dysfunction in patients at risk for HF in later life.
Abstract 13158: Impact of Enhancing Fetal Lung Vascular and Alveolar Development by Slow-release Novel Synthetic Prostacyclin Agonist for Treatment of Fetal Lung Hypoplasia
Authors: Umeda Satoshi , Miyagawa Shigeru , Fukushima Satsuki , Harada Akima , Saito Atsuhiro , Sakai Yoshiki , Sawa Yoshiki , Okuyama Hiroomi
Published: July 2021

Background:
Lung hypoplasia and persistent pulmonary hypertension associated with critical pathologies, such as congenital diaphragmatic hernia (CDH), is the major cause of mortality in the neonates. Although prostaglandins pathway is known to play a pivotal role in the lung development, effectiveness of postnatal treatment by prostaglandin agonists was reported to be suboptimal. We hypothesized that prenatal treatment by ONO-1301SR, slow-release form of a novel synthetic prostacyclin agonist with thromboxane inhibitory activity, might promote development of lungs having hypoplasia in the fetal period.

Methods:
On embryonic day (E) 9.5, nitrofen was given to pregnant Sprague-Dawley rats to produce a CDH-relating lung hypoplasia model, while normal rats (n=4) received vehicle only. At the same day, either ONO-1301SR or placebo was randomly given to the nitrofen-treated rats (placebo; n=7, ONO; n=5). On E21.5, the normal fetuses, and the fetuses having CDH were analyzed.

Results:
Prenatal ONO-1301SR administration had no influence on incidence of nitrofen-induced CDH. One-seventh of maternal blood concentration of ONO-1301 was transferred to fetal blood at E21.5, warranting efficient placental permeability of this molecule. Prostacyclin receptor was expressed in pulmonary arterial smooth muscle cells in the fetus. Lung-to-body weight ratio (%) in the ONO group (1.88±0.07) was greater than that in the placebo group (1.60±0.04, p<0.01). Histologically, medial wall thickness in the ONO group was two-third thinner than that in the placebo group (p<0.01). In addition, the number of Ttf-1-positive cells and capillary density were 1.5 times or more greater in the ONO group than that in the placebo group (p<0.05), associated with a greater expression of VEGF and SDF-1 in the ONO group, suggesting enhanced development of the alveolar and capillary network.

Conclusions:
Prenatal ONO-1301SR administration promoted efficient development of hypoplastic lungs associated with CDH in the nitrofen-induced rat model, indicating potential of this treatment for pathologies having lung hypoplasia.
Abstract 13174: Sex Differences in Clinical Characteristics, Management and Prognosis in Patients With Heart Failure With Preserved Ejection Faction: Insights From the CHART-2 Study
Authors: Tsuji Kanako , Sakata Yasuhiko , Miura Masanobu , Tadaki Soichiro , Ushigome Ryoichi , Yamauchi Takeshi , Sato Kenjiro , Onose Takeo , Abe Ruri , Nochioka Kotaro , Takahashi Jun , Miyata Satoshi , Shimokawa Hiroaki
Published: July 2021

Background:
The number of the patients with heart failure with preserved ejection fraction (HFpEF) has been rapidly increasing worldwide. However, sex differences in patients with HFpEF remain to be elucidated.

Methods and Results:
We examined sex differences in 3,124 consecutive patients with HFpEF (EF≥50%, mean 69.4years, 34.7% female) registered in our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (N=10,219). Female patients, as compared with male patients, were characterized by higher age (72 vs. 68 years, P<0.01), higher LVEF (67 vs. 64%, P<0.01), higher heart rate (74 vs. 70bpm, PNYHA class III (14.1 vs. 7.0%, P<0.01), higher BNP levels (106 vs. 73pg/mL, P<0.01), lower prevalence of coronary artery disease (30 vs. 53%, P<0.01) and lower prescription rates of renin angiotensin system inhibitors (64.7 vs. 71.8%, P<0.01) and beta-blockers (37.8 vs. 43.9%, P<0.01). During the median 3.2-year follow-up, 147 female patients and 245 males died. Although there was no sex difference in all-cause mortality (13.6 vs. 12.0%, P=0.11), female patients more frequently died due to cardiovascular causes (53.7 vs. 39.2%, hazard ratio (HR): 1.62, 95% CI 1.20-2.18, P<0.01), and experienced more HF admissions (12.6 vs. 9.8%, HR: 1.35, 95% CI 1.08-1.68, P<0.01). Use of beta-blockers or renin-angiotensin system inhibitors was not associated with decreased incidence of death or HF admission in both sexes. In contrast, use of statins was associated with reduced incidence of all-cause death in both sexes (males and females; adjusted HR, 0.59 and 0.57; 95% CI 0.46-0.77 and 0.47-0.70, respectively, both P<0.01) and was also associated with reduced incidence of HF admission in males (adjusted HR: 0.67, 95%CI 0.53-0.85, P<0.01) but not in females (adjusted HR: 0.83, 95% CI 0.63-1.10, P=0.19).

Conclusions:
As compared with males, female patients with HFpEF were characterized by severer condition of HF and increased risk of cardiovascular death and HF admission. Although statin use was equally associated with improved mortality in both sexes, female patients with HFpEF may benefit from statins less than males in terms of reduction of HF admission.
Abstract 13288: Higher Non-High Density Lipoprotein Cholesterol is Associated With Arterial-Ventricular Stiffening in Childhood Obesity
Authors: Harada Kenji , Harada Yukiko , Toyono Manatomo
Published: July 2021

Background:
Serum non-high density lipoprotein cholesterol (HDLC) is known to be a good predictor of cardiovascular events. However, few studies have examined non-HDLC and cardiovascular function in overweight/obese children. The purpose of this study is to assess the relationship between non-HDLC and cardiovascular function in children.

Methods:
Echocardiography was performed in 243 children aged 7 to 15 years (BMI 18 to 34 kg/m2). Left ventricular (LV) end-diastolic volume, LV mass, transmitral peak flow velocity (E), and mitral annular myocardial velocity (Em) were measured. LV mass/volume ratio was calculated. Stroke volume (SV) was measured using aortic diameter and pulsed Doppler velocity profile. SV was indexed for body surface area (SVI). Effective arterial elastance (Ea) was estimated by end-systolic pressure/SVI. End-systolic elastance (Ees) was calculated by a modified single-beat method. End-diastolic elastance (Ed) was calculated from Doppler indices reflective of atrial pressures (E/Em) and the diastolic filling volume (SV). Lipids, uric acid, fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and high sensitive C-reactive protein (hs-CRP) were also assessed.

Results:
Ea, Ees, and Ed all increased significantly with BMI(r = 0.30, 0.26, and 0.18, p < 0.01, respectively). There were significant relationships between BMI and non-HDLC, HDLC, uric acid, triglycerides, HOMA-IR, and hs-CRP (r = 0.21, -0.32, 0.48, 0.37, 0.37, 0.52, and 0.39, p < 0.01, respectively). Ea correlated significantly with non-HDLC, HDLC, uric acid, triglycerides, HOMA-IR, and hs-CRP (r = 0.20, -0.15, 0.18, 0.23, 0.22, and 0.14, p < 0.05, respectively). There were significant relationships between Ees and non-HDLC, uric acid, triglycerides, and HOMA-IR (r = 0.25, 0.20, 0.16, and 0.17, p < 0.05, respectively). Ed correlated significantly with non-HDLC (r = 0.18, p < 0.05). In multiple regression analysis, non-HDLC was independent determinants of Ea, Ees, and Ed. Conclusions: Higher non-HDLC and combined arterial-ventricular stiffening may contribute to the increased prevalence of later cardiovascular disorder.
Abstract 13498: Reperfusion Therapy With Rapamycin Prevents Myocardial Ischemic Injury, Through Activation of AKT and ERK
Authors: Filippone Scott M , Roh Sean K , Salloum Fadi N , Kukreja Rakesh C , Das Anindita
Published: July 2021

Background:
The selective inhibitor of mammalian target of rapamycin (mTOR), rapamycin (RAPA), has been shown to exert preconditioning-like cardioprotective effects against ischemia/reperfusion (I/R) injury. Two distinct mTOR complexes (mTORC1 and mTORC2) differentially regulate cardiomyocyte apoptosis and tissue damage following myocardial infarction. We hypothesized that reperfusion therapy with RAPA would reduce myocardial infarct size through differential modulation of mTOR complexes and MAP kinases.

Methods and Results:
Adult C57BL mice were subjected to 30 min of ischemia via left anterior descending coronary artery ligation followed by reperfusion for 24 hr. RAPA (0.25 mg/kg) or 10% DMSO (volume-matched control) was administered via intra-cardiac injection at the onset of reperfusion. Post I/R survival (90%) and cardiac function (fractional shortening, FS: 26.9±2.6%) were improved in RAPA-treated mice compared to control (survival: 60%, FS:16.7±3.2%). Additionally, RAPA caused significant reduction in myocardial infarct size (Fig. 1A), measured by tetrazolium chloride staining, and apoptosis (Fig. 1B) in peri-infarct regions, assessed by TUNEL staining. Western blot analysis revealed that RAPA restored Akt473 phosphorylation (target of mTORC2), but reduced ribosomal protein S6 phosphorylation (target of mTORC1) following I/R injury (Fig. 1C). The protective effect of RAPA was associated with increased phosphorylation of ERK1/2 and decreased phosphorylation of P38 (Fig. 1D). RAPA also attenuated pro-apoptotic protein Bax, in concert with increased pro-survival Bcl2 to Bax ratio (Fig. 1E).

Conclusion:
Reperfusion therapy with RAPA protects hearts against I/R injury by selective activation of mTORC2 and ERK with concurrent inhibition of mTOC1 and P38. We propose that RAPA could be a novel treatment strategy to modulate mTOR complexes and MAP kinase signaling for attenuation of reperfusion injury in the heart.
Abstract 13573: Trends, Predictors and Outcomes of Intracranial Hemorrhage in Patients With Left Ventricular Assist Device
Authors: Shahreyar Muhammad , Bhandari Sanjay , Malik Mobin , Muppidi Vijayadershan , Dang Geetanjali , Gupta Navdeep , Sulemanjee Nasir , Downey Francis X , Jahangir Arshad
Published: July 2021

Introduction:
Left ventricular assist device (LVAD) is being increasingly utilized in patients with advanced heart failure both as bridge to heart transplantation and as destination therapy. Intracranial hemorrhage (ICH) is one of major complications associated with LVAD. However, current trends on utilization of LVAD and associated ICH in real world practice are not known.

Methods:
We analyzed patients in the Nationwide Inpatient Sample (NIS) between 2007 and 2011. Heart failure patients with LVAD were identified from the database and patients with discharge diagnosis of ICH were compared to those without ICH. Trends and outcomes of ICH in patients with LVAD were analyzed. In addition, predictors of ICH were identified using a multivariate regression model.

Results:
We identified 20,443 discharges with a primary diagnosis of heart failure with LVAD of which 447 patients had a co-diagnosis of ICH. We saw a significant increase in discharge diagnosis of heart failure with LVAD from 1232 discharges in 2007 to 6308 in 2011 (p<0.001)(Figure). However, the incidence of ICH in this patient population decreased from 3.9% in 2007 to 2.4% in 2011. On multivariate analysis, in-hospital mortality was significantly higher in the ICH group (OR: 9.5, P=0.0001). After adjustment for potential confounders age <35 years (OR: 2.4, P=0.01) and a rising Charlson co-morbidity index score were independent predictors of ICH whereas presence of diabetes (OR: 0.05, P=0.001), chronic lung disease (OR:0.07, P=0.001), renal disease (OR: 0.09, P=0.001) and peripheral vascular disease (OR: 0.12, P=0.002) were found to be protective of ICH.

Conclusions:
Our analysis indicates an increasing trend in utilization of LVAD but a decrease in incidence of ICH over the same period. ICH was found to increase risk of mortality by nearly 10 fold. Increasing comorbidity burden increases the risk of ICH whereas age and certain individual co-morbidities appear to have a paradoxical effect on risk of ICH.
Abstract 13651: Angiotensin-Converting Enzyme Inhibitors Preserve Limb Function and Decrease Myofibrosis and Oxidative Damage in the Calf Muscle of Patients With Peripheral Artery Disease
Authors: Ha Duy , Casale George , Koutakis Panagiotis , Hanna Mina , Swanson Stanley , Zhu Zhen , Papoutsi Evlampia , Pipinos Iraklis
Published: July 2021

Introduction:
A six-month treatment with the Angiotensin-Converting Enzyme Inhibitor (ACEI) Ramipril improved the walking ability of Peripheral Artery Disease (PAD) patients, but the mechanism remains unknown. ACEI have been shown to reduce fibrosis in heart and kidney and improve arterial compliance. We have identified a myopathy in calf muscles of PAD patients, characterized by fibrosis and increased TGF-β1 produced exclusively in smooth muscle cells (SMC) of microvessels. These events were linked to myofiber oxidative damage and reduced myofiber cross-sectional area.

Hypothesis:
The myopathy of PAD patients taking ACEI is improved compared to patients who are not taking ACEI and this improvement is associated with improved walking ability.

Methods:
Calf muscle biopsies, from PAD patients (Fontaine Stage II) taking ACEI (ACEI+) and those who were not (ACEI-), were fixed, embedded in paraffin, sectioned at 4 microns and slide mounted. Oxidative damage (carbonyl groups) (N=13 for ACEI- and 22 for ACEI+) and TGF-β1 (N=13 for ACEI- and 20 for ACEI+) were analyzed by quantitative fluorescence microscopy and expressed as grey scale units (gsu). Myofiber cross-sectional area was determined from fluorescence-labeled sarcolemma. Fibrosis was determined as collagen density (gsu) by multi-spectral analysis of slide specimens (N=13 for ACEI- and 20 for ACEI+) stained with Mason Trichrome. Limb function was assessed by the six-minute walking distance (N=28 for ACEI- and 20 for ACEI+).

Results:
Compared to ACEI- patients, ACEI+ patients had reduced TGF-β1 (4.25 gsu +/- 0.69 vs. 1.51 gsu +/- 0.23; p = 0.001) and decreased collagen density (2067 gsu +/- 88 vs. 1671 gsu +/- 51; p < 0.001). Carbonyl adducts were reduced in myofibers of ACEI+ compared to ACEI- patients (1584 gsu +/- 55 vs. 1779 gsu +/- 58; p = 0.019) and myofiber cross sectional area was increased (4629 μm2 +/- 285 vs. 3816 μm2 +/- 267; p = 0.023). Six-minute walking distance was greater in ACEI+ compared to ACEI- patients (333 m +/- 20 vs. 266 m +/- 16; p = 0.011).

Conclusions:
Improved walking distance of PAD patients taking ACEI is associated with improved calf muscle myopathy, determined as reduced TGF-β1 production, collagen density, and myofiber oxidative damage, and increased myofiber cross-sectional area.
Abstract 13699: Cardiovascular Health Impact of Air Pollution Control in Beijing and Urban China: Projections From the Cardiovascular Disease Policy Model-China
Authors: Huang Chen , Moran Andrew E , Yang Xueli , Cao Jie , Chen Kai , Wang Miao , He Jiang , Goldman Lee , Coxson Pamela G , Zhao Dong , Kinney Patrick L , Gu Dongfeng
Published: July 2021

Background:
Air pollution ranks the 4th among risk factors responsible for China’s avoidable disease burden. We projected the potential cardiovascular health benefits achievable with sustained air quality improvement in Beijing and all of urban China.

Methods:
Coronary heart disease (CHD) and stroke mortality and life years gained were projected in adults aged 35-84 years in Beijing and urban China using the Cardiovascular Disease Policy Model-China. We simulated two air quality improvement scenarios from 2015-2030, each achieved gradually over 10 years: 1) the 2008 Beijing Olympics fine particle matter (PM2.5) level of 55 μg/m3, and 2) the World Health Organization (WHO) recommendation of 10 μg/m3. For comparison, we simulated a 50% reduction in active and secondhand smoking and reduction of systolic hypertension to 140 mmHg, each over 5 years. Relative risks of CHD, stroke and all-cause mortality associated with long term PM2.5 exposure were obtained from a meta-analysis of observational studies. Systolic blood pressure and smoking relative risks were estimated from China Multi-provincial Cohort Study.

Results:
PM2.5 reduction to 2008 Olympic levels in Beijing would reduce stroke deaths by 2.7%, CHD deaths by 7.2% over 2015-2030 and would gain life-years on the order of about a third of that projected for a 50% smoking reduction, and a fourth of that projected for systolic hypertension control (Table). However, achieving more aggressive WHO PM2.5 goal would yield greater life year gains than either tobacco or systolic blood pressure control. Achieving 2008 Olympics levels in urban China would prevent 304,000 stroke deaths, 619,000 CHD deaths, and gain 4.2 million life years over 2015-2030.

Conclusions:
Air pollution is a leading cardiovascular risk factor in Beijing and all urban China. We projected that lowering air pollution to Beijing Olympics level could prevent about 900,000 cardiovascular deaths and gain about 4.2 million life years in urban China by 2030.
Abstract 13794: Serial Brain Metabolism in Term Neonates With Congenital Heart Disease: Association With Clinical Factors and Neurodevelopmental Outcomes
Authors: Harbison Anna L , Votava-Smith Jodie K , Del Castillo Sylvia , Kumar S Ram , Lee Vincent K , Lai Hollie A , O’Neil Sharon H , Bluml Stefan , Paquette Lisa , Panigraphy Ashok
Published: July 2021

Objectives:
Term congenital heart disease (CHD) neonates demonstrate pre-operative (op) abnormal brain metabolism (reduced N-acetylaspartate (NAA), elevated lactate) on long echo MR spectroscopy (MRS). We sought to delineate associations between serial brain metabolism and patient and perioperative clinical factors in term neonates with CHD using short echo MRS. We measured NAA and lactate as well as other metabolites important for brain connectivity such as neurotransmitters glutamate/glutamine and GABA.

Methods:
Subjects were prospectively enrolled to undergo pre and post-op 3T short echo single voxel MRS of parietal white matter with absolute quantitation of 15 metabolites using LCModel. Neurodevelopment (ND) was assessed via 18 month Battelle Developmental Inventory. Linear and logistic regression with false discovery rate correction was used for statistical analysis.

Results:
Eighty subjects were enrolled 2009-2015 and 21 term CHD infants underwent both pre and post-op MRS. Eight infants had at least one MRS and ND. NAA and glutamate were significantly decreased post-op compared to pre-op (p<0.0001), with no significant difference in other metabolites. Pre-op factors including lower Apgar score, birth weight, head circumference and PaO2 and higher arterial pH and serum lactate were associated with lower NAA (p<0.002). Single ventricle anatomy was associated with low NAA, high myo-inositol and low glutamine/glutamate compared to two ventricles (p<0.01). Longer cardipulmonary bypass time, but not deep hypothermic circulatory arrest, was associated with reduced NAA (p<0.001). Post-op, global alteration in multiple serial brain metabolites (NAA, lactate, glutamate/glutamine, GABA, myo-inostol) were associated with longer ICU and hospital stay (p<0.03). In those with ND testing, high GABA correlated with low cognitive domain score, while high glutamine correlated with low motor score (p<0.03).

Conclusion:
In term CHD neonates, serial brain metabolism by MRS demonstrates alterations beyond NAA, including neurotransmitters GABA and glutamate/glutamine. These abnormalities are associated with multiple clinical pre and post-op factors and also predict prolonged hospital stay and 18 month ND.
Abstract 13831: Atrial and Ventricular Cardiac Stem Cells From the Same Heart Exhibit Differential Functional Characteristics for Cardiac Regeneration but Are Superior to the Endothelial Progenitor Cells From the Same Patient
Authors: Dixit Parul , Donnelly Hayden , Edamatsu Midori , Galvin Ivor , Bunton Richard , Katare Rajesh
Published: July 2021

Introduction:
Deciding the best cell type for cardiac regeneration remains a challenge, however, no studies have directly compared the functional efficacy of cardiac stem cells (CSCs) with extra- cardiac SCs isolated from the same patient.

Objective:
To compare the functional characteristics of endothelial progenitor cells (EPCs), right atrial (RAA) CSCs and left ventricular (LV) CSCs isolated from the same patients.

Methods and Results:
Flow-cytometry analysis of CSCs (n=12 patients) revealed higher expression of CD90 (involved in cell adhesion and migration) in RAA CSCs (CD90 & CD105 ++ve cells: 71±15% in RAA vs. 47±27% in LV, P<0.05). However, scratch assay showed superior wound closure in LV CSCs (80±10% in LV vs. 60±5% in RAA, P<0.05) suggesting that LV CSCs have a better migration potential. Moreover, the expansion properties of RAA CSCs were better than LV CSCs in terms of higher cumulative population doublings in culture. To simulate in vivo ischemic environment, cells were subjected to hypoxia (1% O2) and serum starvation for 3 days. RAA and LV CSCs exhibited similar pattern of resistance to apoptotic cell death (evaluated as percentage of annexin +ve cells, n=5) and proliferation under hypoxia. Interestingly, EPCs exhibited highest resistance to apoptotic cell death, but they also showed the lowest proliferation under hypoxia (P<0.05). Secretion of paracrine and pro-angiogenic factors have been thought to be most important mechanisms behind cardiac regeneration. Therefore, to compare the paracrine angiogenic and wound healing potential, HUVECs were cultured in culture supernatant (CS) from all the 3 cell types. RAA-CS showed the highest increase in tube formation capacity (P<0.05, n=6), while the scratch assay showed comparable wound closure with both LV and RAA CS (67.56 ± 7.36% and 70.02 ± 5.70%, n=5), but was lowest in EPC CS (54±7%). The secretion of the angiogenic growth factor VEGF-A (n=5) was lowest in EPCs (0.36± 0.20 ng/mL) and comparable between RAA (3.44±1.94 ng/mL) and LV CSCs (4.33± 1.57 ng/mL).

Conclusion:
Stem cells from different regions exhibit differential functional characteristics within the same patient. The selection of the best cell type should therefore be influenced by the nature of the injury and the type of effect desired.
Abstract 13837: Adrenergic Receptors β2 and β3 Transduce Differential Signals in Cardiac Fibroblasts
Authors: Tonegawa Kota , Nakayama Hiroyuki , Igarashi Hiromi , Matsunami Sachi , Hayamizu Nao , Obana Masanori , Maeda Makiko , Fujio Yasushi
Published: July 2021

Background:
Cardiac fibroblasts (CFs) are the most prevalent cell types in heart and play important roles in cardiac remodeling. While the roles of β-adrenergic receptor (βAR) signaling in cardiomyocytes (CMs) are well characterized, those in CFs remain to be elusive due to lack of convenient method to assess those signaling. There are three subtypes of, βAR β1, β2, β3 and β2AR is reported to be expressed in CFs by which enhances cell proliferation and production of inflammatory cytokines. Clinical efficacy of non-selective β blocker carvedilol for heart failure (HF) surpasses that of β1 selective blocker metoprolol, suggesting critical roles of β2 and β3AR in the pathogenesis of HF.

Objective:
To elucidate the signaling downstream βARs in CFs in heart.

Methods and Results:
Caveolae is an important microdomain for signal transduction, such as βAR, present in CMs or CFs. To elucidate βAR signaling of caveolae in CFs, we generated a fusion protein composed of phospholamban (PLN) and caveolin3 (Cav3) representing PKA activation as phosphorylation at S16 of PLN and CaMKII as that at T17 in caveolae. Thus, activation of PKA or CaMKII is detectable by anti-phospho-S16 or T17 antibody, respectively. In neonatal rat CFs (NRCFs) infected PLN-Cav3 adenovirus, stimulation by isoproterenol (ISO) led to enhanced phosphorylation of both S16 and T17, suggesting PKA and CaMKII activation in caveolae of CFs. RT-PCR analyses showed β2AR and β3AR were present in NRCFs. Stimulation with β2AR selective agonists activated both PKA and CaMKII, while β3AR elicited solely PKA activation, analyzed by using β3AR selective agonist/antagonist. In addition, in order to examine the significance of βAR stimulation for heart failure, we administered ISO continuously for two weeks in β2ARKO mice. As a result, fibrosis was suppressed in β2ARKO mice compared with wild-type mice (0.35% vs 2.37%, p<0.05) suggesting critical roles of β2AR in development of cardiac fibrosis caused by βAR stimulation in mice.

Conclusions:
Both β2 and β3AR are expressed in NRCFs and transduce distinct signaling and β2AR selective stimulation elicit development of cardiac fibrosis via activation of CaMKII signaling. Thus, selective βAR regulation could be potential novel anti-fibrotic therapeutics in HF.
Abstract 13901: Spatial Distribution of the Late Gadolinium Enhancement on Cardiac MRI Strongly Affects Maximal T-wave Alternans Sites on the 12-lead Holter ECG in Hypertrophic Cardiomyopathy
Authors: Sakamoto Naka , Sato Nobuyuki , Talib Ahmed , Otsu Keisuke , Sugiyama Eitaro , Minoshima Akiho , Tanabe Yasuko , Takeuchi Toshiharu , Kawamura Yuichiro , Hasebe Naoyuki
Published: July 2021

[Background]:
Late gadolinium enhancement (LGE) on cardiac MRI (CMR) predicts the mortality in hypertrophic cardiomyopathy (HCM) patients. T-wave alternans (TWA) is a potential cardiac mortality predictor. However, whether LGE localization affects TWA is unclear.

[Purpose]:
To elucidate the localization relationship between the LGE and maximal TWA lead (TWAmax-lead) and maximal TWA voltage (TWAmax) using 12-lead Holter ECGs (Holter12) in HCM.

[Methods]:
Holter12s and CMR were performed in 46 HCM patients. TWA was assessed using a modified moving average method and the TWAmax was determined in each lead. The average transmural LGE extent was scored using a 4 point score (Score 0:no LGE, 1:1-25%, 2:26-50%, 3:51-75%, 4:76-100%) in 12 left ventricular segments and the sum (LGEtotal) was calculated. Left ventricular LGE sites were classified into anterior, septal, inferior, and lateral. Corresponding ECG lead groups were defined as V3-4 for anterior, V1-2 for septal, II, III, aVF for inferior, and I, aVL, and V5-6 for lateral. The TWAmax was analyzed depending on the Score of the 5 stages, and the coincidence between the LGE distribution and TWAmax-lead was investigated. Furthermore, the differences in the TWAmax, LGEtotal, and left ventricular ejection fraction (LVEF) in the presence or absence of ventricular tachycardia (VT) were also studied.

[Results]:
The TWAmax was 50±11μV for Score=0, 54±13μV for Score=1, 61±18μV for Score=2, 67±20μV for Score=3, and 47±16μV for Score=4. The TWAmax for Scores 2 and 3 was significantly greater than for Score=0 (p<0.001, p<0.001, respectively), but there was no significant difference between Scores 1 and 4, and Score=0 (p=0.14, p=0.41). The TWAmax-lead revealed scores ranging from 1 to 3 in all segments. The LGEtotal and TWAmax were significantly greater in patients with VT (n=23) than without (17±7 vs. 10±7 [p<0.01], 83±17μV vs. 64±18μV [p<0.001], respectively). The LVEF did not statistically differ between the two groups (48±16% vs. 54±10%, p=0.21).

[Conclusions]:
The LGE distribution correlated with the TWA, i.e., a 50-75% transmural extent of the LGE yielded the maximal local TWA. The spatial distribution of the LGE strongly affects myocardial repolarization abnormalities indicated by TWA as VT substrates in HCM.
Abstract 13903: Application of
in vivo
Tissue-engineered, Autologous “Biotube” Vascular Grafts, Prepared Using a Less Invasive Device, for Hemodialysis Access in a Canine Model
Authors: Furukoshi Maya , Nakayama Yasuhide
Published: July 2021

Purpose:
When arteriovenous (AV) fistula is not feasible for vascular access in most patients on hemodialysis, the second choice is interposition AV fistula using synthetic graft. However, the grafts pose risks such as infection and low patency. Therefore, we created in vivo tissue-engineered “Biotube” vascular grafts formed with autologous tissue, based on the tissue encapsulation phenomenon. Previously, we confirmed that vascular-like structure was reconstructed in implanted Biotubes with year-ordered patency in vivo. In this study, we evaluated whether Biotubes could replace vascular access grafts for hemodialysis in the cervical vessels of beagles.

Methods and Results:
The mold for Biotube preparation was assembled by inserting a silicone rod (external diameter 4 mm; length 50 mm) into an acrylate tubular cover (internal diameter 6 mm; length 50 mm with several longitudinal slits). The molds were embedded into the dorsal subcutaneous pouches of beagles (n=3) for 4 weeks, after which they were harvested by a minimally invasive technique from the same incision (width ca. 20 mm). After removing the molds, Biotubes formed by tissue migration to a silicone surface through the mold slits (internal diameter 4 mm; length 45 mm; wall thickness ca. 1 mm) were obtained. Biotubes were then bypassed between the carotid artery (side-to-end anastomosis) and jugular vein (end-to-end anastomosis) of anesthetized beagles. Following placement of Biotubes, continuous thrill was felt by palpation and ultrasound showed turbulent blood flow. After one month, angiography showed no stenosis, elongation, or hemorrhage in any Biotubes. Percutaneous puncturing with a needle, blood removal and resupply from the needle, and astirction within several minutes were feasible.

Conclusions:
In our beagle model, Biotubes successfully created an AV shunt that maintained steady blood flow, suggesting that Biotubes have potential clinical use in maintaining vascular access for hemodialysis.
Abstract 13906: Women and ICD: The Influence of Age and Clinical Characteristics on Survival; the Experience of the Italian ClinicalService Multicenter Observational Project
Authors: Fumagalli Stefano , Padeletti Luigi , Marchionni Niccolò , Lunati Maurizio , Proclemer Alessandro , Boriani Giuseppe , Landolina Maurizio , Ricci Renato Pietro , Gasparini Maurizio ,   on behalf of the ClinicalService Cardiological Cntrs
Published: July 2021

Introduction:
The prevalence of heart failure (HF) significantly increases with age especially in women, who are more frequently hospitalized for this condition than men. Despite epidemiological data and the results of some studies showing that implantable cardiac defibrillator (ICD) can be particularly useful in women, undertreatment still represents a significant problem in female gender. Aims of this research were to analyze the age-related characteristics of women who underwent ICD implantation in a large Italian database and to define the predictors of mortality during the follow-up.

Methods:
In the Italian ClinicalService Multicenter Observational Project, 6311 patients receiving an ICD between 2004 and 2011 were included in 117 centers. Women were 1102 (17.5% of the whole population) and were divided into 3 groups (<65: N=413, 65-74: N=416, ≥75 years: N=273). We evaluated age-related differences in baseline clinical characteristics and, then, we compared survival between women < and ≥75 years during a 27-month follow-up.

Results:
Age in the three groups was 55±9, 70±3 and 78±3 years, respectively. Coronary artery disease (CAD; 25, 32, 45%), chronic renal failure (CRF; 5, 6, 11%), COPD, diabetes and hypertension steadily grew with age (all p≤0.001). EF was severely reduced in every group (30±12, 28±7 and 30±10, p=0.008), with NYHA III-IV Class more represented among elderly women (52, 58, 62%, p<0.001). Beta-blockers were less often prescribed at advanced age (87, 81, 79%, p=0.022) and CRT-D more often used in subjects ≥65 years (64, 79, 71%, p=0.002). During the follow-up, mortality was significantly higher in older women (5, 7, 12%, p<0.001). Age-group (HR=1.47, p=0.033), CAD (HR=2.98, p<0.001) and the presence of CRF (HR=2.93, p=0.006) were multivariate predictors of prognosis in our group of women with an ICD. CAD (HR=3.45, p<0.001) and CRF (HR=4.14, p=0.004) were independently associated with prognosis also in <75 years patients, while no predictors were found for elderly women.

Conclusions:
Women presently represent <20% of patients receiving an ICD. Age, CAD and CRF negatively influence survival in this population. However, in older women, traditional risk factors seem to lose their importance.
Abstract 13917: Post-systolic Shortening in the Ischemic Myocardium is Attenuated in Multivessel Disease
Authors: Sakurai Daisuke , Asanuma Toshihiko , Masuda Kasumi , Oka Masamichi , Kotani Koichiro , Inoue Katsuji , Nakatani Satoshi
Published: July 2021

Background:
Post-systolic shortening (PSS) is myocardial shortening that occurs after end-systole and is considered as a sensitive marker of myocardial ischemia. Empirically, PSS in patients with multivessel disease is smaller than that in those with single vessel disease. Although this seems to be due to a decrease of difference in contraction between the ischemic and the surrounding myocardium, no study has elucidated it. We investigated the relationship between PSS and the difference of contraction between the ischemic and surrounding myocardium in an animal model which underwent left anterior descending coronary artery (LAD) occlusion (single vessel disease model) followed by left circumflex coronary artery (LCx) occlusion (multivessel disease model).

Methods:
In 7 open-chest dogs, left ventricular short-axis images (GE Vivid E9) and hemodynamic data were acquired at 3 conditions: (1) at baseline, (2) during LAD occlusion, and (3) during both LAD and LCx occlusion. Circumferential strains were analyzed in 6 segments by speckle tracking software. The amplitude of PSS (ε
PSS
) and end-systolic strain (ε
ES
) were measured and the difference of ε
ES
between a segment perfused by the LAD and the average of the other 5 segments was calculated (Δε
ES
).

Results:
In the LAD segment, dyskinetic motion and PSS occurred during LAD occlusion but they were paradoxically attenuated during both LAD and LCx occlusion. ε
PSS
significantly correlated with Δε
ES
(r=0.95, p<0.05). Although ε
PSS
significantly decreased during both occlusion compared to LAD occlusion, ε
PSS
corrected by Δε
ES
(ε
PSS
/Δε
ES
) did not decrease (figure).

Conclusions:
PSS in the ischemic myocardium was attenuated when the surrounding myocardium also became ischemic. The difference of contraction between the ischemic and the surrounding myocardium at end-systole seems to be a determinant of the amplitude of PSS. A parameter ε
PSS
/Δε
ES
may be useful for assessing ischemia in patients with multivessel disease.
Abstract 13968: Regional Calcified Plaque Score evaluated by Computed Tomographic Angiography for Indicating the Addition of Rotational Atherectomy in Patients With Percutaneous Coronary Intervention
Authors: Sekimoto Teruo , Akutsu Yasushi , Hamazaki Yuji , Tsujita Hiroaki , Tsukamoto Shigeto , Kaneko Kyouichi , Kodama Yusuke , Kobayashi Youichi
Published: July 2021

Introduction:
Rotational atherectomy (Rota) has been proposed as the best strategy relative to all other percutaneous coronary interventions (PCI) in complex and severely calcified lesions, and the examination of calcified plaque conditions is necessary to determine whether Rota is indicated. Multidetector computed tomography coronary angiography (CTA) can provide non-invasive assessment of calcified plaques with obstructive coronary artery disease.

Hypothesis:
We hypothesized that regional coronary artery calcium score (CAC) of the target lesion on CTA would aid in deciding whether subsequent intervention strategies should be pursued, including Rota.

Methods:
Lesion CAC and calcified plaque patterns measured in the target lesion on CTA were evaluated regionally with quantitative coronary analysis (QCA) on angiography for predicting Rota treatment in 116 consecutive patients (168 target lesions) who had undergone their first PCI (mean age ± standard deviations: 68 ± 10 years, females: 19.8%).

Results:
PCI without Rota was performed successfully in 105 patients (154 lesions), and Rota treatment was added in 11 patients (14 lesions). The patients with Rota had significantly higher SYNTAX score (p=0.007) and CAC than those without Rota (p<0.001). Concerning the target lesions, the primary factors associated with the implementation of Rota included a lesion length of ≥20 mm and a diameter stenosis of ≥74% on QCA (indicates a complex lesion), and a lesion CAC ≥453 and one calcification arc ≥270 on cross-section images on CTA (indicates a severely calcified pattern). After adjustment for potential confounding variables, high lesion CAC (≥453) remains a powerful predictor of Rota treatment with odds ratios of 31.3 [95% confidence interval 2.8-345, p=0.005] (sensitivity: 92.9% and specificity: 88.3%).

Conclusions:
The lesion CAC as a simple marker of calcified plaque condition in target lesion is useful for indicating the addition of Rota in patients with PCI.
Abstract 14014: Early Detection of Myocardial Involvement in Idiopathic Inflammatory Myopathies Assessed by Cardiac Magnetic Resonance Imaging
Authors: Buckert Dominik , Rosenbohm Angela , Kassubek Jan , Rottbauer Wolfgang , Ludolph Albert , Bernhardt Peter
Published: July 2021

Background:
Idiopathic inflammatory myopathies are heterogeneous autoimmune systemic diseases characterized by chronic progressive muscle weakness and inflammatory infiltrates in skeletal muscle. The frequency of cardiac involvement varies between 9% and 72%, mainly dependent on patient selection, definition and diagnostic tools applied. Heart failure is the most frequent finding. Cardiac magnetic resonance imaging (CMR) has been shown to provide reliable and valuable information about cardiac function and inflammatory process in one examination.

Hypothesis:
Aim of our prospective study was to characterize cardiac involvement using a comprehensive CMR protocol.

Methods:
Fifty-three consecutive patients with histologically proven idiopathic inflammatory myopathy were enrolled into the study. Blood levels of Creatine kinase (CK) and myocardial CK (CK-MB) were analyzed from each patient. All patients underwent CMR examination in a 1.5-T whole body scanner. 3D short-axis functional steady-state free precession and late gadolinium enhancement (LGE) sequences were acquired in all patients covering the entire left and right ventricle. CMR images were analyzed by two experienced and blinded readers in consensus. Besides functional analysis LGE images were analyzed for hyperenhancement and quantified as LGE percentage of myocardial mass.

Results:
Reduced left ventricular function (ejection fraction < 60%) was present in 9 (17%) patients. These patients exhibited significantly higher blood levels of CK-MB (283±193 vs. 175±221 U/l, p=0.02) than patients with preserved LVEF. Early myocardial enhancement (>45% signal intensity increase) was more often present (6 out of 9 [66.7%] vs. 25 out of 44 [56.8%], p=.014) as well as LGE patterns consistent with myocardial inflammation (9 out of 9 [100%] vs. 24 out of 44 [54.5%], p=.001). LGE was most often observed in the inferior and lateral segments.

Conclusion:
The results of this study show that CMR is able to detect cardiac involvement in idiopathic inflammatory myopathies. Early diagnosis using CMR could result in early therapy of heart failure, leading to beneficial ventricular remodeling and thus improving living quality and survival in these patients.