bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12737: Sex and Race/Ethnic Disparities in the Use of High Potency Statins for Patients With Atherosclerotic Cardiovascular Disease
Authors: Rodriguez Fatima , Lin Shoutzu , Heidenreich Paul A
Published: July 2021

Background:
The November 2013 AHA/ACC prevention guidelines recommend the use of a fixed dose high potency statin (HPS) for patients with established atherosclerotic cardiovascular disease (ASCVD), irrespective of low-density lipoprotein cholesterol levels. We sought to determine how these guidelines are being adopted at the Veterans Affairs (VA) Health System and identify treatment gaps in patient groups.

Methods:
We examined administrative data from the VA 6 months prior to the index dates of 4/1/2013 and 4/1/2014 to identify patients with at least one outpatient visit for a diagnosis of established ASCVD, defined as coronary heart disease, cerebrovascular disease, or peripheral arterial disease. Statin use was assessed 6 months following the index date, and HPS was defined as atorvastatin 40mg or 80mg, rosuvasatin 20mg or 40mg, and simvastatin 80mg. Patient and facility-level predictors of statin use for secondary prevention were analyzed using multivariate logistic regressions.

Results:
Our study sample included 507,072 and 489,754 eligible adults with established ASCVD, in 4/1/2013 and 4/1/2014, respectively. The sample consisted of approximately 190,035 (2%) women and 200,461 (19%) non-white patients. HPS use was lowest in Hispanics and Native Americans, though all groups showed an increase over time (Figure 1). After adjustment for clinical and facility characteristics, there was a 40% increase in the use of HPS during the study period [OR=1.4; 95%CI (1.39-1.42)]. However, the racial differences shown in Figure 1 persisted and women were less likely to receive HPS than men (Odds Ratios [OR]=0.85; 95% CI 0.83-0.87).

Conclusion:
HPS use has increased following release of the ACC/AHA prevention guideline in the VA, though racial and gender disparities persist. Our findings highlight the continued need for targeted efforts to increase HPS use for women and certain minority groups.
Abstract 12770: The Significant Role of Endothelium and Arterial Wall Properties in Patients With Pseudoexfoliative Glaucoma
Authors: Siasou Georgia , Siasos Gerasimos , Moschos Marilita M , Gouliopoulos Nikolaos , Oikonomou Evangelos , Paraskevopoulos Thodoris , Tsalamandris Sotiris , Mourouzis Konstantinos , Dimitropoulos Stathis , Antonopoulos Alexios , Kokkou Eleni , Zaromitidou Marina , Stefanadis Christodoulos , Tousoulis Dimitris
Published: July 2021

Introduction:
Primary open-angle glaucoma (POAG) is one of the most prevalent causes of irreversible blindness and is associated with endothelial dysfunction and arterial stiffness. Pseudoexfoliative glaucoma (PEG) is another type of glaucoma observed in pseudoexfoliation syndrome. It is characterized by the deposition of pseudoexfoliative material not only to the anterior segment of the eye, but also to the vessels, heart and other organs.

Hypothesis:
Endothelial function and arterial stiffness are impaired in patients with POAG and PEG supporting the significant role of vascular function impairment in the progression of the disease.

Methods:
Forty four POAG patients, 22 PEG and 38 healthy subjects (Cl) were included in this study. All subjects were free of cardiovascular or inflammatory diseases. Endothelial function was evaluated by flow-mediated dilatation (FMD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as a measure of arterial wave reflections

Results:
Between the three study groups CL, POAG, PEG there was no difference in age (67±10years vs. 70±9years vs. 66±12yeras, p=0.12) or prevalence of male sex (70% vs. 57% vs. 50%, p=0.21). Importantly, there was a linear impairment of FMD (7.35±2.77% vs. 6.58±3.18% vs. 4.88±3.29%, p=0.006), PWV (7.98±1.56m/sec vs. 9.20±1.84m/sec vs. 9.22±2.16m/sec, p=0.004) and AIx (21.29±8.77% vs. 25.14±5.71% vs. 28.20±8.75%, p=0.002) from CL to POAG and PEG. Interestingly post hoc test after Scheffe correction revealed also that PEG subjects had not only significantly impaired FMD, compared to control subjects, but also compared to POAG subjects (4.88±3.29% vs. 6.58±3.18%, p=0.02).

Conclusions:
Endothelial function and arterial stiffness are significantly impaired in patients with pseudoexfoliative glaucoma. These findings shed some light in the pathophysiology of pseudoexfoliative glaucoma and support the theory that pseudoexfoliative fibrils may also accumulate and damage the arterial wall.
Abstract 12797: A Global Longitudinal Strain in Endocardial Layer Selectively Correlated With Left Ventricular Ejection in Systemic Autoimmune Disorder Patients: A Multi-layer Transthoracic Echocardiography Study
Authors: Ozawa Koya , Funabashi Nobusada , Sugiura Atsushi , Takaoka Hiroyuki , Kobayashi Yoshio
Published: July 2021

Introduction:
In patients with systemic autoimmune disorders (SAD), hemodynamic abnormalities such as pulmonary hypertension occur.

Hypothesis:
Some specific myocardial characteristics in SAD patients may precipitate hemodynamic abnormalities. Using myocardial multi-layer transthoracic echocardiography (TTE) analysis, we determine left ventricular (LV) myocardial characteristics in SAD patients, and compared LV ejection fraction (LVEF), estimated pulmonary arterial systolic pressure (ePASP) on TTE and serum brain natriuretic protein (BNP).

Methods:
Twenty SAD patients (18 female; mean age 49±18 years; systemic lupus erythematosus 35%; vasculitis 20%; scleroderma 5%, rheumatoid arthritis 5%, mixed connective tissue disease 5%) underwent TTE (Vivid E9, GE Healthcare). Apical 2-, 3-, and 4-chamber GLS views and parasternal short axis GCS view at the level of the papillary muscle was acquired. GLS was defined by averaging all 17 LV segments. GCS was defined as averaged LV segments at the level of papillary muscle. Furthermore strain measurements (absolute values) of whole, endocardial, and epicardial layers were performed using Echo PAC version 113 (GE Healthcare).

Results:
There was no significant correlation between GLS (whole, endocardial, and epicardial layers) and LVEF, ePASP, and BNP, respectively. GCS was significantly negatively correlated with serum BNP (R=-0.606 (whole), -0.452 (endocardial) and -0.447 (epicardial layer)). GCS in whole and epicardial layer was significantly negative correlated with ePASP (-0.528 (whole) and -0.457 (epicardial layer)). Only GCS in endocardial layer was significantly positive correlated with LVEF (R=0.466).

Conclusions:
In SAD patients, GCS significantly correlated with cardiac function and, especially in the endocardial layer selectively and positively correlated with LVEF. These specific myocardial characteristics in SAD patients may precipitate hemodynamic abnormalities.
Abstract 12854: Uric Acid In-hospital Change Provides the Additional Long-Term Prognostic Information to Acute Kidney Injury in Patients Admitted for Acute Decompensated Heart Failure
Authors: Yamada Takahisa , Morita Takashi , Furukawa Yoshio , Tamaki Shunsuke , Iwasaki Yusuke , Kawasaki Masato , Kikuchi Atsushi , Kondo Takumi , Ishimi Masashi , Hakui Hideyuki , Ozaki Tatsuhisa , Satoh Yoshihiro , Seo Masahiro , Ikeda Iyo , Fukuhara Eiji , Fukunami Masatake
Published: July 2021

Backgrounds:
Acute kidney injury (AKI) during heart failure treatment is associated with poor outcome in patients admitted with acute decompensated heart failure (ADHF). In patients with ADHF,increased uric acid (UA) level is also a prognostic marker, but there is no information available on the long-term prognostic significance of UA in-hospital change, relating to AKI in patients admitted for ADHF.

Methods and Results:
We studied 237 patients admitted with ADHF and discharged with survival. The measurements of serum UA and creatinine (Cr) levels were repeated during hospitalization, and the change of UA was obtained by subtracting the value at admission or discharge from the maximum value. AKI was defined according to AKI Network criteria (stage 1, ≥0.3mg/dl absolute or 1.5-to 2.0-fold relative increase in Cr; stage 2, >2- to 3-fold increase in Cr; stage 3, >3-fold increase in Cr or Cr≥4.0mg/dl with an acute rise of ≥0.5mg/dl). During a follow-up period of 4.3±3.3 yrs, 59 patients had cardiovascular death (CVD). At multivariate Cox analysis, UA change (p=0.02) and stage 2 or 3 AKI (p=0.01) were significantly associated with CVD, independently of age, systolic blood pressure, serum sodium, hemoglobin, UA and Cr levels, although stage 1 AKI showed no significant association with CVD. Patients with both higher degree of UA change (top quartile:≥4.4 mg/dl) and stage 2 or 3 AKI had a significant increased CVD risk, compared to patients with either higher UA change or stage 2 or 3 AKI (75% vs 34%, p=0.006, hazard ratio 3.8[95%CI 1.4-8.6]). Furthermore, patients with either higher UA change or stage 2 or 3 AKI also had a significant increased CVD risk, compared to patients with none of these two variables (34% vs 19%, p=0.01, hazard ratio 2.0[95%CI 1.1-3.5]).

Conclusion:
Uric acid in-hospital change could provide the additional long-term prognostic information to moderate to severe AKI in patients admitted for ADHF.
Abstract 12941: Gender Differences in Age-Related Aortic Elongation and Dilatation: Longitudinal Results From the Multiethnic Study of Atherosclerosis
Authors: AlGhatrif Majd , Ohyama Yoshiaki , Ambale-Venkatesh Bharath , Vaidya Dhananjay , Teixido-Tura Gisela , Redheuil Alban , Wu Colin , Hundley William G , Bluemke David , Lakatta Edward , Lima Joao
Published: July 2021

Background:
Major aortic remodeling processes ensue with aging. Information on the patterns of the longitudinal changes in aortic geometry is essential to understand the dramatic hemodynamic changes observed with aging.

Methods:
Data from 1396 MESA participants who had aortic magnetic resonance imaging in 2000-02 and 2010-12 were analyzed. Ascending aorta diastolic diameter (Add), strain (Astr), arch length (Alen) and their rates of change (Δ) were determined using the validated automated software (ARTFUN, INSERM LIB). Multivariate analysis was performed to examine the correlates of the changes of these parameters. Least square means of Add and Alen adjusted for body surface area were plotted against age for those not on anti-HTN drugs on either visit (n=590).

Results:
The main correlates of increased ΔAdd, and ΔAlen were male gender, smaller baseline Add, and Alen, lower PP, greater MAP and ΔMAP. Increased ΔAdd was also associated with greater baseline Astr and with not being on anti-HTN drugs, while greater ΔAlen, was associated with smaller ΔPP in women only (P<0.05 for all). Figures.1 shows cross sectional Add, and Alen (upper panels) and their longitudinal changes (lower panels). In men, Add, and Alen increased with aging; ΔAlen was steady but ΔAdd increased significantly after the 7th decade. In women, although Add and Alen increased with aging, ΔAdd decreased linearly with advancing aging while ΔAlen increased after the 7th decade.

Conclusion:
Gender, baseline blood pressure parameters and baseline aortic geometry and elasticity are the main determinants of aortic remodeling. Aortic elongation and dilatation follow different trajectories and vary by gender. In contrast to men, aortic dilation in women was minimal beyond the 7th decade and aortic elongation was the main remodeling process and was inversely associated with changes in PP. Gender differences in aortic remodeling might explain the increased pulsatility observed in women with advancing aging.
Abstract 12987: Annulus Deformity Index Obtained by Using Four-dimension Multidetector Computed Tomography in Patients With Severe Aortic Stenosis is Useful for Predicting Over Moderate Paravalvular Regurgitation Immediately After Transcatheter Aortic Valve Replacement
Authors: Tamura Harutoshi , Iguchi Nobuo , Utanohara Yuko , Mahara Keitaro , Takamisawa Itaru , Seki Atsushi , Suzuki Makoto , Tobaru Tetsuya , Takayama Morimasa , Umemura Jun , Sumiyoshi Tetsuya , Tomoike Hitonobu
Published: July 2021

Background:
Correct assessment of annulus diameter before transcatheter aortic valve replacement (TAVR) using multidetector computed tomography (MDCT) is important to minimize complications such as annulus rupture and paravalvular aortic regurgitation (PVR). The form of the annulus was previously reported to be oval, while the form of the SAPIEN XT valve was circular. However, the association between the ellipsoid degree of annulus and PVR remains unclear. A new technique of measuring variability in a region of interest through a cardiac cycle using voxel tracking for image data obtained by four-dimensional MDCT (4D-MDCT) was recently reported. This technology allows evaluation of changes of the annulus through the cardiac cycle, and detection of the cardiac phase of maximum and minimum annulus area correctly compared with conventional methods. In the present study, we examined whether evaluating the annulus ellipsoid degree obtained by 4D-MDCT is useful for predicting the occurrence of PVR immediately after TAVR.

Methods:
We performed 4D-MDCT in 72 patients with severe aortic valve stenosis before TAVR (mean age, 82 years; mean AVA, 0.61 cm
2
). All patients were implanted SAPIEN XT. The 4D-MDCT image data were analyzed offline on a workstation using a voxel-tracking method (Ziosoft Inc.). We defined the deformity index calculated as the ratio of short axis diameter to large axis diameter of the annulus.

Results:
Mean R-R% of the maximum and minimum annulus area were 14.5% and 46.4%, respectively. Patients with PVR (n=20) had a significantly lower deformity index at maximum, minimum, and R-R 30% annulus area phase compared with no PVR patients. Receiver operating characteristic curve analysis showed that the deformity index at phase of maximum annulus area was an excellent marker for predicting PVR when compared to other cardiac phases (Figure).

Conclusion:
Low deformity index obtained using 4D-MDCT may be a useful marker for predicting PVR immediately after TAVR.
Abstract 13004: The Effect of Vasopressor Agents in the Treatment of Cardiovascular Shock
Authors: Yagi Tsukasa , Tachibana Eizo , Ueki Yasushi , Sakamoto Kazuo , Imamura Hiroshi , Miyamoto Takamichi , Takahashi Hiroshi , Hanada Hiroyuki , Yonemoto Naohiro , Nagao Ken , Hirayama Atsushi
Published: July 2021

Background:
Various vasopressor agents are used for the treatment of cardiovascular shock. According to a randomized double-blind comparison study reported in 2010, norepinephrine is more useful than dopamine for patients in cardiovascular shock. In Japan, although both norepinephrine and dopamine are used as first-line vasopressor agents, the status of use and usefulness of the two agents have not yet been clarified.

Methods:
The Japanese Circulation Society (JCS) Shock Registry was a prospective, observational, multi-center, cohort study between May 2012 and June 2014.Of the patients registered in the JCS-Shock Registry, data of those who received norepinephrine or dopamine as a vasopressor agent, without the use of intra-aortic ballon pumping or cardiopulmonary bypass, were examined. The primary end point of the study was the rate of death at 30 days.

Results:
Of the 980 patients registered in the JCS-Shock Registry, the data of 320 patients were included in this analysis, after exclusion of patients who had not received the two agents and patients meeting the exclusion criteria. Of the 320 patients, 98 had received norepinephrine (N group), 142 had received dopamine (D group), and 80 had received both agents (N+D group). The acute mortality rates were 26.5, 25.4 and 46.2% in the N, D and N+D groups, respectively (p = 0.003). In a stratified analysis according to the renal function (eGFR [median: 43] ≥43 [normal renal function] versus eGFR <43 [reduced renal function]) at the time of admission, the acute mortality rates in the patients of the N, D and N+D groups with normal renal function were 7.8, 21.1 and 41.2%, respectively (p = 0.001), being significantly lower in the N group. On the other hand, the acute mortality rates in the patients of the N, D and N+D groups with reduced renal function were 46.8, 29.6 and 50.0%, respectively (p = 0.049), being significantly lower in the D group.

Conclusion:
Although norepinephrine is recommended as the first-line treatment, a trend towards more frequent use of dopamine was found in Japan. In addition, norepinephrine appeared to contribute to a reduction of the acute mortality in patients with normal renal function, while dopamine appeared to contribute to a reduction of the acute mortality in patients with reduced renal function.
Abstract 13031: A Randomized Trial Comparing the Effects of Ticagrelor versus Clopidogrel on Myocardial Perfusion in Patients With Coronary Artery Disease
Authors: Pelletier-Galarneau Matthieu , Hunter Chad R , Ascah Kathryn J , Beanlands Rob S , Chong Aun Yeong , Chow Benjamin J , Dwivedi Girish , Hessian Renee C , Wells Glenn R , deKemp Robert A , Ruddy Terrence D
Published: July 2021

Introduction:
Ticagrelor is a reversible P2Y12 receptor antagonist used in patients with acute coronary syndrome (ACS). In the PLATO trial, treatment with ticagrelor reduced mortality compared to clopidogrel, to which pleotropic mechanisms may have contributed. In this study, we compared the effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease on myocardial blood flow (MBF) at rest and during intermediate and high dose adenosine infusion.

Methods:
Patients (n=22) were randomized using a double-blind crossover design to ticagrelor 90 mg orally twice a day for 10 days and clopidogrel 75 mg orally once a day for 10 days, with a washout period of at least 5 days between the treatments. MBF was measured using Rb-82 PET-CT at baseline and at intermediate (80 mcg/kg/min) and high dose adenosine (140 mcg/kg/min).

Results:
Global MBF was significantly greater with ticagrelor versus clopidogrel at intermediate dose adenosine (1.28±0.55 versus 1.13±0.47, p=0.002), and not different at baseline (0.65±0.19 versus 0.60±0.15, p=0.4254) nor at high dose adenosine (1.64±0.40 versus 1.61±0.19, p=0.5302). In abnormal segments with low MBF reserve (<2.5), MBF was significantly greater with ticagrelor compared to clopidogrel at intermediate and high dose of adenosine (p<0.0001), with no difference at baseline. For segments with high MBF reserve (≥2.5 and < 3.5), segmental MBF was significantly greater with ticagrelor compared to clopidogrel at baseline (p<0.001) and at intermediate adenosine dose (p<0.0001).

Conclusions:
Global stress MBF was greater with ticagrelor compared to clopidogrel during intermediate dose adenosine infusion. Regional MBF in segments with reduced MBF reserve was greater with ticagrelor compared to clopidogrel during intermediate and high dose adenosine. This suggests that ticagrelor may potentiate adenosine-induced myocardial blood coronary flow increases in patients with stable CAD compared to clopidogrel; an effect that may explain the observed incremental mortality benefit observed with ticagrelor.
Abstract 13080: Electrocardiographic Strain Pattern as a Predictor for New-Onset Heart Failure, Concentric Hypertrophy, Reduced Function, and Scar: MESA (Multi-Ethnic Study of Atherosclerosis)
Authors: Inoue Yuko Y , Soliman Elsayed Z , Yoneyama Kihei , Ambale-Venkatesh Bharath , Wu Colin O , Sparapani Rodney , Bluemke David A , Lima João A , Ashikaga Hiroshi
Published: July 2021

Introduction:
Left ventricular hypertrophy (LVH) is associated with incident heart failure (HF), and ECG strain is a marker of LVH. This study sought to evaluate the relationship of baseline ECG strain to the incidence of HF, longitudinal change of left ventricular (LV) geometry and function by cardiac magnetic resonance imaging (CMR).

Methods:
A total of 4,732 participants (mean age 61 years, 54% women) free of cardiovascular disease (CVD) underwent ECG and CMR. We used univariable and multivariable Cox proportional hazards to evaluate the association of ECG strain with incident HF (n=137). We also examined the association of baseline ECG strain with changes of LV geometry and function in 2,846 participants imaged at baseline and 10 years later using multiple linear regression models. Finally, we evaluated the association between the presence of ECG strain and LV scar defined by late Gadolinium enhancement at year 10 (n=1,650).

Results:
The presence of ECG strain was significantly associated with incident HF (hazard ratio: 2.53; 95% CI: 1.40 to 4.57; p=0.021) during follow-up (median 11.2 years). Longitudinal analysis revealed that the presence of ECG strain at baseline was significantly associated with an increase in the LV mass index (β=5.54g/m2, p<0.001), LV mass-to-volume ratio (β=0.07g/mL, p=0.009), and a decrease in LV ejection fraction (EF) (β=-2.35%, p=0.015), even when coronary heart disease events were excluded. Moreover, ECG strain was independently associated with LV scar (p=0.004).

Conclusions:
In a cohort of middle-aged participants without prior CVD, ECG strain was an independent predictor of new-onset HF. In addition, ECG strain was related to development of LV concentric hypertrophy and decline in EF as well as LV scar.
Abstract 13139: Fasting Triglycerides Are Independently Associated With Subclinical Atherosclerosis: The ELSA-Brasil Study
Authors: Bittencourt Marcio S , Santos Raul D , Staniak Henrique , Santos Itamar S , Pereira Alexandre C , Seshasai Sreenivasa R , Vallejo-Vaz Antonio , Ray Kausik , Duncan Bruce B , Bensenor Isabela M , Lotufo Paulo
Published: July 2021

Introduction:
While triglycerides (TG) are associated with cardiovascular disease, most studies suggests that non-fasting TG drives this effect, whereas the role of fasting TG is less well established.

Hypothesis:
We have evaluated whether triglyceride-derived markers (log-transformed TG [lnTG], non-HDL, TG/HDL ratio) and HDL independently predict subclinical coronary artery disease as measured by the coronary artery calcium score (CAC).

Methods:
We included 2911 (50.3±8.5 years, 54% women) participants from the ELSA-Brasil study who had no prior history of CVD, were not currently using lipid-lowering medications and underwent CAC evaluation. We analyzed the independent association of triglyceride-derived markers (lnTG, non-HDL, TG/HDL ratio) and HDL with CAC using logistic regression.

Results:
Among the 2911 participants, 759 (26%) had a CAC >0, and 247 (8.5%) had a CAC > 100. The median triglycerides level was 112 (IQR: 80 -162). Individuals with CAC>0 had higher TG levels than those with CAC=0 (p<0.001). They also had higher levels of total cholesterol, LDL, non-HDL levels, lower HDL and higher TG/HDL ratios (all p<0.001). After adjustment for clinical risk factors log transformed TG, non-HDL and TG/HDL ratio remained significantly associated with CAC (allp<0.05), while HDL did not. Even after further adjustment for body mass-index (BMI) and for high sensitivity CRP, those predictors remained independently associated with CAC (table).

Conclusions:
In a large cohort of asymptomatic individuals, measures associated with fasting TG were associated with CAC score. Even after adjustment for clinical risk factors, BMI and hsCRP, measures associated with TG (lnTG, non-HDL and TG/HDL ratio) all remained independent predictors of CAC, while HDL did not. This suggests that TG may potentially be an independent target for therapy to reduce residual cardiovascular risk.
Abstract 13141: Cellular Microrna 449b Upregulation Sensitizes Ischemia/reperfusion Injury via Inhibition of Nrf-1, Increasing Ros Production and Apoptosis in the Diabetic Heart
Authors: Wang Hang , Lau Wayne , Gao Erhe , Koch Walter , Ma Xin , Wang Yajing
Published: July 2021

Myocardial ischemic/reperfusion (MI/R) injury is significantly enhanced in diabetes by incompletely understood mechanisms. Recent clinical and experimental studies demonstrate that hypoadiponectinemia during diabetes enhances oxidative stress and exaggerates MI/R injury. However, molecular mechanisms responsible for hypoadiponectinemia-induced oxidative stress remain unknown. In a discovery-driven fashion, we determined the role of cardiac microRNAs in the MI/R response in adiponectin knockout (APNKO) mice. From 68 total miRNAs differentially expressed between APNKO and wild type (WT) mice, miRNA 449b was identified as the microRNA most relevant to oxidative stress and apoptosis. In cultured neonatal cardiomyocytes, miRNA 449b silencing inhibited hypoxia/reoxygenation-induced apoptosis, whereas miR-449b overexpression significantly increased oxidative stress and cardiomyocyte apoptosis. In APNKO mice, administration of anti-miR-449b decreased oxidative stress (-17.2±3.8%, p<0.05), reduced caspase-3 activity (-21.3±4.2%, p<0.05), attenuated myocardial apoptosis (-16.3±4.1%, p<0.05), and improved myocardial function (1.4±0.3 fold). To identify the downstream molecule regulated by miRNA 449b, we integrated transcriptomics and proteomics data with computational annotation data, and identified Nrf-1 as a miRNA 449b target. A luciferase reporter gene assay demonstrated that miRNA 449b inhibited Nrf-1 expression via Nrf-1 mRNA 3’UTR region binding. Finally, we demonstrated that miRNA 449b was significantly upregulated, Nrf-1 expression was significantly decreased, and the anti-oxidative molecule metallothionein (MT) was significantly inhibited in the diabetic heart subjected to MI/R. Administration of anti-miR-449b in diabetic animals upregulated Nrf-1 and MT expression, reduced oxidative stress, and improved cardiac function (P<0.01) after MI/R. Taken together, this study provides the first evidence that hypoadiponectinemia during diabetes causes cardiac miRNA-449b upregulation and subsequent downregulation of Nrf-1 and MT, thus enhancing oxidative stress and MI/R injury. MicroRNA 449b may represent a potential therapeutic target against diabetic heart disease.
Abstract 13191: Acute Renal Injury and Mortality After Transcatheter Aortic Valve Replacement
Authors: Meneguz-Moreno Rafael A , Castro-Filho Antonio D , Jatene Tannas , Silva Guilherme Barreto G , Nunes Mário Barbosa G , Jeronimo Andreia D , Ramos Auristela Isabel d , Siqueira Dimytri , Abizaid Alexandre Antonio C , Sousa Amanda Guerra M , Sousa Jose Eduardo M
Published: July 2021

Introduction:
The presence of acute renal injury (AKI) enhances morbimortality after surgical aortic valve.

Hypothesis:
This prospective observational study aims to determine the incidence of AKI after transcatheter aortic valve replacement (TAVR), its predictors and impact on 30-days and 1-year mortality.

Methods:
We assessed data from 224 consecutive patients with severe symptomatic aortic stenosis submitted to TAVR between January 2009 and February 2015 on two tertiary cardiologic centers, conducted by the same heart team. All patients used an ionic, low-osmolar, low-viscosity contrast. Kidney injury was defined according to VARC criteria, following AKIN system, and data collected until the seventh day post-procedure. Three patients were excluded due to death during the procedure, considering those deaths not related to renal dysfunction, remaining 221 patients analysed separated in two groups: AKI group and non-AKI group. Follow-up was performed on 30 days and after one year.

Results:
Fifty two patients (23.5%) developed AKI until seventh day of procedure. Groups 1 and 2 were similar, except for EuroSCORE II (8.66% ± 5.64% vs 7.34% ± 8.58%, p = 0.02) and glomerular filtration rate (GFR) (39.59 ml/min.1.73m2 ± 13.62 vs. 48.49 ± 19.6, p = 0.002). Overall 30 days-mortality and 1-year mortality was 6.3% and 14.0%, respectively. Both 30-day mortality (23.1% vs 1.2%, p < 0.001) and 1-year mortality (44.2% vs 4.7%, p< 0.001) were higher in group 1. In multivariable-adjusted models, the only independent predictor for AKI after TAVR was baseline GFR [hazard ratio (HR) 1.37, CI 95% 1.08-1.77, p = 0.01]. Regarding long term follow-up, AKI (HR 19.86, CI 95% 7.31-53.98, p <0.001) and COPD (HR 3.14, CI 95% 1.05-9.40, p = 0.04) were independent risk factors for 1-year mortality, whilst hypertension (HR 0.269, CI 95% 0.09-0.80, p = 0.01) was shown to be protective for long term mortality.

Conclusion:
In this TAVR sample, baseline GFR was the only independent predictor of AKI, and patients who developed it had significantly higher mortality at 30 days and 1 year. Acute renal impairment was the strongest risk factor for mortality and adverse cardiovascular events that provided risk information beyond the traditional scores, as EuroSCORE II and STS.
Abstract 13193: Impact of “Off-Peak” Versus “Peak” Hour Coronary Interventions for ST-Elevation Myocardial Infarction on Adverse Outcomes
Authors: Lee Jae S , Redel-Traub Gabriel , Kim Michael , Meraj Perwaiz , Brennan Christina , Vidi Venkatesan
Published: July 2021

Background:
In addition to patient-dependent factors, whether the time of arrival of the patient to the hospital with ST-elevation myocardial infarction (STEMI) might play a role in subsequent adverse outcomes following primary percutaneous coronary interventions (PCI) is not well studied.

Method:
856 PCI procedures for patients presenting with STEMI from two large hospitals in the health system were analyzed. Peak hours were defined as procedures performed between 7 AM and 7 PM on weekdays. Off-peak hours were defined as procedures performed between 7 PM and 7 PM on weekdays and weekends. Unadjusted and propensity score-adjusted analyses were performed to analyze the following inpatient outcomes: composite of death/MI/stroke, composite of bleeding events, composite of death/MI/stroke/bleeding endpoints, and long-term mortality.

Results:
Of 856 PCIs, 407 (47.5%) were performed during the peak hours. In both unadjusted and propensity score-adjusted analyses, no significant differences in adverse outcomes and long-term mortality were observed in patients who had PCIs during off-peak and peak hours (see Table). In addition, a separate analysis performed on patients who underwent primary PCIs between 7 AM-7 PM (“Morning”) versus 7 PM-7 AM (“Evening”) on all days showed no difference in the inpatient adverse outcomes and long-term mortality (Adjusted long term mortality: HR 0.79 (95% CI 0.40-1.56), p=0.49).

Conclusion:
Primary PCIs performed on patients presenting with STEMI during off-peak versus peak hours results in similar inpatient adverse outcomes and long-term mortality.
Abstract 13197: Characteristics and Outcomes of Patients Presenting With Hypertensive Urgency in the Outpatient Setting
Authors: Patel Krishna , Young Laura , Howell Erik H , Hu Bo , Morrison Shannon J , Rutecki Gregory , Thomas George , Rothberg Michael B
Published: July 2021

Background:
Hypertensive urgency is a commonly encountered outpatient problem. Prevalence and short term outcomes of this condition are unknown. JNC VII recommends aggressive BP control over several days. However, a small percentage of patients are sent to the emergency department. It is unknown whether hospital management of these patients is better than outpatient BP management.

Methods:
Retrospective cohort study of all patients presenting to an office in a large health care system from 2008-2013 with SBP ≥180mmHg or DBP ≥ 110mmHg. We excluded pregnant women and patients referred to the hospital for symptoms or treatment of other conditions. Patients were divided into 2 groups: those sent home and those referred to hospital. We recorded baseline demographic and clinical data. Propensity matched outcomes recorded included MACE (acute coronary syndrome, stroke/TIA) uncontrolled hypertension (≥140/90 mmHg) and hospital admissions.

Results:
Of 2,199,019 office visits, 58,583 (5%) had hypertensive urgency. Mean age was 63±15 yrs, 58% were females, 76% Caucasian, mean BMI was 31±8 kg/m2 and mean SBP and DBP were 182±16 and 96±16 mmHg. Only 426 (0.7%) patients were referred to the ED/hospital. On propensity matched analysis between the patients referred to the hospital and sent home, there was no significant difference in MACE events at 7 days (0% vs. 0.13%, p=1), 30 days (0.25% vs. 0%, p=1) or 6 months (0.5% vs. 0.13%, p=0.26). Compared to patients sent home, patients referred to the hospital had less uncontrolled hypertension at 1 month (81% vs. 88%, p=0.001) but not at 6 months (65% vs 69%, p=0.16). They also had higher 7- and 30-day hospital admission rates (8.5% vs. 4.9%, p=0.01; 11.8% vs 7.6%, p=0.02).

Conclusion:
Hypertensive urgency occurs commonly, but the rate of MACE in asymptomatic patients is very low. ED visits increased hospitalizations, but did not improve outcomes. Most patients with hypertensive urgencies still had uncontrolled hypertension at 6 months.
Abstract 13224: Which White Cell Subtypes Predict the Presence of Coronary Artery Disease in High Risk Patients Over 55 Years Old?
Authors: Trakarnwijitr Issada , Li Bobby V , Adams Heath , Layland Jamie , Garlick John , Wilson Andrew M
Published: July 2021

Introduction:
Inflammation has an important role in initiation and progression of coronary artery disease (CAD). Different white cell count (WCC) subtypes may reflect different mechanisms of this complex disease, and may be valuable clinically in risk stratification and detection of patients with CAD. Studies on the correlation between WCC subtypes and CAD have yielded conflicting results.

Hypothesis:
We hypothesized that WCC subtypes are associated with the presence of CAD in high-risk patients over 55 years old.

Methods:
We analyzed 622 patients over the age of 55 from the BRAVEHEART and MINACS cohort who were referred for coronary angiogram at our institution. Univariate and multivariate logistic regression models were used to compare different WCC subtypes as predictors of presence of CAD, defined as ≥50% stenosis of 1 or more coronary arteries. We adjusted for age, sex and conventional cardiac risk factors.

Results:
On univariate analysis, patients with CAD had significantly more CVD risk factors compared to control patients. Markers associated with CAD were lower lymphocytes (tertile 2 OR 0.61, 95% CI 0.39-0.98, p=0.040, tertile 3 OR 0.70, 95% CI 0.44-1.12, p=0.139), and higher monocytes (tertile 3 OR 2.51, 95% CI 1.45-4.34, p=0.001), neutrophil-lymphocyte ratio (NLR) (OR 1.70, 95% CI 1.07-2.68, p=0.024), and monocyte-lymphocyte ratio (MLR) (tertile 3 OR 2.62, 95% CI 1.61-4.26, p<0.001). After adjustment for CVD risk factors, lower lymphocytes (tertile 2 OR 0.40, 95% CI 0.22-0.73, p=0.003, tertile 3 OR 0.50, 95% CI 0.27-0.93, p=0.028), and higher monocytes (tertile 3 OR 2.38, 95% CI 1.23-4.61, p=0.010), NLR (tertile 3 OR 1.91, 95% CI 1.08-3.38, p=0.025), and MLR (tertile 3 OR 2.26, 95% CI 1.23-4.14, p=0.009) were associated with CAD.

Conclusions:
In high-risk patients over 55 years old, lower lymphocytes, and higher monocytes, NLR and MLR were associated with angiographically determined CAD independent of other risk factors. Monocytes and MLR were the strongest correlates of CAD in high-risk patients over 55. Whether these can be used as biomarkers of CAD in high risk patients warrants further study.
Abstract 13236: Coronary Vasospasm Induced in Transgenic Mouse With Overexpression of p122RhoGAP/DLC1
Authors: Kinjo Takahiko , Tanaka Makoto , Osanai Tomohiro , Narita Ikuyo , Tannno Tomohiro , Nishizaki Kimitaka , Shibutani Shuji , Ishida Yuji , Tomita Hirofumi , Homma Yoshimi , Okumura Ken
Published: July 2021

Backgrounds:
We reported that the activity of phospholipase C (PLC)-δ1, a key enzyme for Ca2+ signaling in the artery, was 3-fold enhanced in patients with coronary spastic angina (CSA), and was positively correlated with coronary vasomotility. We recently showed that p122RhoGAP/DLC1 (DLC1) protein, which was discovered as a stimulator of PLCδ-1, was upregulated in CSA patients. We tested the hypothesis that overexpression of DLC1 cause coronary spasm in mice.

Methods and Results:
We generated transgenic (TG) C57BL/6J mice with vascular smooth muscle-specific overexpression of DLC1. The gene and protein expression of DLC1 was enhanced by 11-fold and 4.4-fold, respectively, in the homozygous TG aorta compared with wild type (WT) mice. Systolic blood pressure and heart rate measured by tail-cuff method were similar between TG and WT mice, and no early mortality was found until the age of 30 weeks. PLC enzymatic activities in the plasma membrane and the whole cell were enhanced by 1.4 and 2.0 times, respectively, in cultured aortic vascular smooth muscle cells from homozygous TG compared with those from WT. To induce coronary spasm, ergometrine at 50 mg/kg was injected into the jugular vein of the anesthetized mice, and the ECG in lead II was recorded continuously. Heart rate, PR interval, QRS duration, and QRS morphology at baseline were all similar between TG and WT mice. Immediately after ergometrine injection, ST segment elevation was observed in one of 7 WT (14%), 6 of 7 heterozygous TG (84%), and 7 of 7 homozygous TG mice (100%) (both p<0.05, WT vs TGs). This ST segment elevation in TG was followed by atrioventricular conduction disturbance and wide QRS rhythm, which are suggestive of myocardial ischemia. In the isolated Langendorff hearts, coronary perfusion pressure was increased after ergometrine in homozygous TG mice but not in WT mice despite the fact that the response to prostaglandin F2α was similar between TG and WT mice (n=5). In the group treated with ergometrine, focal narrowing of the coronary artery was documented only in TG mice (2 lesions in 2 hearts).

Conclusion:
Upregulated DLC1 caused enhanced coronary vasomotility after ergometrine injection in mice. Upregulation of DLC1 in the coronary artery can be a cause of coronary spasm in humans.
Abstract 13261: Relationship Between Circulating CD34+ and CD146+ Cells and Change in Infarct Size in Patients With Acute Coronary Syndrome
Authors: Montange Damien , Davani Siamak , Gambert Ségolène , Seronde Marie-France , Schiele Francois , Meneveau Nicolas F
Published: July 2021

Background:
The presence of CD34+ and CD146+ cells in the peripheral blood in response to myocardial ischemia has been advocated as a marker of an organism’s regenerative capacity by late and early progenitor cells respectively. The aim of this study was to evaluate the relationship between circulating CD34+ and CD146+ levels and the change in infarct size, as assessed by magnetic resonance imaging (MRI) in patients (pts) with acute coronary syndrome (ACS including ST and non ST elevation myocardial infarction).

Methods:
Patients <75 years old, admitted with a first ACS within 12 hours of onset of symptoms were enrolled. Peripheral blood samples for cytofluorimetric analysis of CD34+ and CD146+ cells level were drawn at day 0. Initial infarct size was evaluated from peak troponin I levels determined from 5 blood samples over the first 72 hours. MRI measurements of infarct size were performed at day 5 and at 6 months follow-up.

Results:
In total, 34 patients aged 57±10 years were included. Mean ejection fraction was 62±11%. Log-transformed number of CD 34+ and CD146+ were significantly correlated with the relative change in infarct size between day 5 and 6 month follow-up (p=0.01, r=-0;41 and p=0.001, r=-0.52 respectively) (Figure)

Conclusion:
The highest CD34+ and CD146+ cell levels were associated with the greatest relative reduction in infarct size 6 months after ACS. These results support the hypothesis that these cells could be considered as a marker of regenerative capacity in patients with acute coronary syndromes.
Abstract 13262: Right to Left Ventricular Interdependence at Rest and During Exercise Assessed by the Ratio Between Pulmonary Systolic to Diastolic Time in Heart Failure Reduced Ejection Fraction
Authors: Generati Greta , Bandera Francesco , Pellegrino Marta , Labate Valentina , Carbone Francesco , Alfonzetti Eleonora , Guazzi Marco
Published: July 2021

Background:
The ratio between the duration of right ventricular (RV) systole and diastole (S:D ratio) has been proposed as an index of RV performance in a pediatric population with pulmonary arterial hypertension in whom it may predict prognosis and functional capacity. In heart failure (HF) S:D may provide relevant insights in the exercise response. Aim: to analyze the correlation between rest and peak exercise S:D and functional and cardiac parameters in HFrEF.

Methods:
94 HFrEF patients (mean age 66±11 y, male 70%, ischemic etiology 71%, mean LVEF 34±9%) underwent a symptom-limited cardiopulmonary exercise testing (incremental ramp protocol) combined with exercise-echo. RV S:D was assessed by echo at rest and peak exercise.

Results:
A good correlation was found between rest and peak S:D and CPET indexes of exercise capacity, such as peak oxygen consumption (VO2) (Sperman’s rho -0.40 and 0.38 respectively, p= 0.02 and 0.023) and maximal workload (Rho= -0.42 and -0.45, p=0.031 and 0.034). An higher S:D also correlated with more impaired ventilatory efficiency or higher VE/VCO2 slope (Rho 0.49 and 0.32, p=0.019 and 0.024). Looking at echo phenotype, interestingly S:D is associated with parameters of mitral regurgitation (MR) severity, such as effective regurgitant orifice (Rho rest 0.63, peak 0.35, p<0.01) and pulmonary artery systolic pressure (PASP, rho rest 0.53, peak 0.35, p<0.01) particularly at rest. S:D also correlated with right RV fractional area change at rest and peak exercise (-0.39 and -0.39, p=0.035 and 0.04). Conclusions: In HFrEF population the assessment of S:D at rest and peak exercise predicts functional status and is related to more advanced hemodynamic impairment (increased PASP and MR) as expression of more unfavorable ventricular interdependence.
Abstract 13267: Advanced Heart Failure With Reduced Ejection Fraction and Severe Mitral Insufficiency Compensate With a Higher Oxygen Peripheral Extraction to a Reduced Cardiac Output vs Oxygen Uptake Response to Maximal Exercise
Authors: Generati Greta , Bandera Francesco , Pellegrino Marta , Labate Valentina , Carbone Francesco , Alfonzetti Eleonora , Guazzi Marco
Published: July 2021

Background:
in heart failure (HF) the mitral regurgitation (MR) is clinical and prognostic relevant. Cardiopulmonary exercise testing (CPET) allows evaluating functional capacity and provides indexes for HF risk stratification such as peak oxygen consumption (VO2). Since MR determines a severity-related backward flow to left atrium, it may result in an unfavorable central blood flow exercise redistribution that is physiological relevant to VO2 increase. Aim: To evaluate the cardiac output (CO) and VO2 exercise-response in HF reduced ejection fraction (HFrEF) patients according to MR severity to dissect what mechanism may be predominant in the VO2 increase.

Methods:
104 HFrEF patients (mean age 64±11 y, male 72%, ischemic etiology 68%, mean LVEF 34±9%) underwent a maximal CPET (incremental ramp protocol) combined with exercise-echo. CO was non-invasive estimated by echo.

Results:
Population was divided into 2 groups according to the rest MR: group A (n=80) non-severe MR and B (N=24) severe MR. Despite the groups did not differ in rest CO (A vs B 3.8±1 vs 3.4±1.8 L/min, p=ns) and VO2 (0.27±0.06 vs 0.28±0.09 L/min, p=ns) group B showed higher peripheral extraction (C(a-v)O2 8±2 vs 9±4 mL/100 mL, p=0.036) already at rest (Figure). At peak exercise group B had an impaired increase both in CO (7,0±2,0 vs 5,2±3,3 L/min) and VO2 (1,0±0,3 vs 0,8±0,3 L/min, p=0.001) partially compensated by a greater C(a-v)O2 contribution (15±4 vs 18±5 for A vs B, p=0.047). Conclusions: Severe MR and consequent partial abnormal CO redistribution to the pulmonary circulation seems a relevant pathophysiological mechanisms that limits overall exercise performance in HFrEF. In this high risk subset of patients peripheral extraction compensates for the reduced CO and makes the basis for novel perspectives in these patients.
Abstract 13271: Aortic Inflammation Continues in Patients With A History of Kawasaki Disease and Persistent Arterial Aneurysms
Authors: Suda Kenji , Tahara Nobuhiro , Honda Akihiro , Nakamura Tomohisa , Yoshimoto Hironaga , Kishimoto Shintaro , Kudo Yoshiyuki , Iemura Motofumi , Fukumoto Yoshihiro
Published: July 2021

Introduction:
Kawasaki disease (KD) is well known vasculitis that primarily affects small to middle sized arteries such as coronary arteries and/or peripheral arteries. However, little evidence showed inflammation of large vasculature such as the aorta in patients with KD. Measurements of 18F-fluorodeoxyglucose (FDG) uptake evaluated by positron emission tomography (PET) and X-ray computed tomography (CT) could be useful to identify inflammatory activity of the vessel wall.

Hypothesis:
We hypothesized that aortic inflammation continues long after KD.

Methods:
FDG-PET/CT was performed in 19 patients with a history of KD. Of 19 patients, 11 patients still had persistent coronary and/or systemic vascular aneurysms (KD-An) and the remaining 8 revealed regression of arterial aneurysms (KD-Reg). Patients suffered from KD at 2.8 ± 3.2 years old and underwent FDG-PET at 22.2 ± 8.0 years old. FDG-PET was also performed in 5 control with age 14.1 ± 2.6 years old. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR). Also demographic and laboratory data were collected.

Results:
Aortic FDG uptake was distinctly intense in patients with a history of KD and persistent vascular aneurysms. The Aortic TBR was significantly higher in KD-An (1.50 ± 0.30) than KD-Reg (1.11 ± 0.13, p = 0.004) or controls (1.03 ± 0.25, p=0.003). Although Control was significantly younger and had significantly lower body mass index, there was no significant correlation between these values and TBR. Also there was no significant difference in laboratory data including lipid profiles and glycemic status among 3 groups.

Conclusions:
Vascular inflammation of the aortic wall continues long after KD with persistent arterial aneurysms.
Abstract 13300: The Risk of Incident Hypertension According to the Metabolic Health and Obesity: Definition of Metabolic Health Does Not Matter
Authors: Kang Yu Mi , Jung Chang Hee , Jang Jung Eun , Hwang JenieYoonoo , Kim Eun Hee , Park Joong-Yeol , Kim Hong-Kyu , Lee Woo Je
Published: July 2021

Background:
Obesity is considered to be an important risk factor for hypertension. The metabolically healthy obese (MHO) phenotype refers to obese individuals with a favorable metabolic profile. Its prognostic value remains controversial and may partly depend on differences in defining methods. We examined the risk of MHO phenotype with incident hypertension in a Korean population using four representative criteria to define metabolic health status.

Design and methods:
The study population comprised of 31,033 Koreans without hypertension. Participants were stratified by body mass index (BMI) (cut-off value, 25.0 kg/m2) and metabolic health state, according to four defining methods; Adult Treatment Panel (ATP)-III criteria, Wildman criteria, Karelis criteria, and Homeostasis Model Assessment (HOMA) criteria.

Results:
Over the median follow-up period of 35.0 months (range, 4.5-81.4 months), 4,589 of the 31,033 individuals (14.8%) developed incident hypertension. Compared with the metabolically healthy nonobese (MHNO) group, the MHO group showed increased risk of incident hypertension with a multivariate-adjusted hazard ratio (HR) of 1.42 (95% confidence interval [CI], 1.30-1.54), 1.43 (95% CI 1.31-1.57), 1.41 (95% CI 1.27-1.56), and 1.33 (95% CI 1.23-1.45), when defined by ATP-III criteria, Wildman criteria, Karelis criteria, and HOMA criteria, respectively. Metabolically unhealthy obese (MUO) individuals were at the highest risk of incident hypertension.

Conclusions:
MHO subjects showed a substantially higher risk of incident hypertension regardless of the definition for metabolic health. Thus, it is important to consider both metabolic health and obesity when evaluating risk of hypertension.