bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14055: Trend and Predictors of Prolonged Length of Hospital Stay Following Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction in The United States: A 10 Year Perspective
Authors: Panchal Hemang B , Veeranki Sreenivas P , Bhatheja Samit , Abusara Ashraf , Paul Timir
Published: July 2021

Background:
Length of hospital stay (LOS) following percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) significantly affects healthcare utilization and cost. There is paucity of data in the United States on the optimal LOS following PCI for STEMI. Our study objective is to assess the trend and predictors of prolonged LOS following PCI with stent placement for STEMI.

Methods:
Data were obtained from nationwide inpatient sample from 2003-2012, which is a 20% stratified probability sample of all non-federal acute care hospitalizations. Study outcome was prolonged LOS defined as stay in hospital for >4 days following PCI for STEMI. Cochrane-Armitage trend test and multivariable logistic regression models were used to delineate the predictors of prolonged LOS which included patient’s demographics, baseline comorbidities, presenting illnesses and in-hospital complications following PCI for STEMI.

Results:
A total of 223,267 patients with STEMI underwent PCI with stent placement with a mean LOS of 3.3±3.3 days. There were 16.1% patients who had prolonged LOS. The trend analysis showed that incidence of prolonged LOS decreased from 17.1% in year 2003 to 14.3% in year 2012 (p<0.05) (figure 1A). Pneumonia and peri-procedural intra-aortic balloon pump use were the strongest predictors for prolonged LOS. Other significant predictors for prolonged LOS following PCI for STEMI were history of congestive heart failure, anemia, respiratory failure requiring ventilator use; peri-procedural stroke and anemia or hemorrhage requiring blood transfusion (figure 1B).

Conclusions:
Incidence of prolonged LOS has consistently decreased over 10 years. Patient’s baseline comorbidities, illnesses at presentation and in-hospital complications can predict prolonged LOS following PCI for STEMI. Implementing an aggressive standard of care to prevent in-hospital complications can further shorten the LOS following PCI for STEMI.
Abstract 14077: Use of Cardiac Troponin I to Identify Acute Myocardial Infarction in Patients With Impaired Renal Function
Authors: von Jeinsen Beatrice , Tzikas Stergios , Palapies Lars , Zeller Tanja , Bickel Christoph , Lackner Karl J , Baldus Stephan , Blankenberg Stefan , Muenzel Thomas , Zeiher Andreas M , Keller Till
Published: July 2021

Introduction:
Cardiac troponins are the gold standard to diagnose acute myocardial infarction (AMI). Troponin I (TnI) levels are known to be increased in patients with chronic kidney disease (CKD) irrespective of an AMI. The established diagnostic TnI cut-off to detect AMI is calculated based on a healthy reference population and might not be representative for CKD patients.

Hypothesis:
The aim of this study was to investigate TnI levels in patients with and without CKD with suspected AMI and to calculate CKD- optimized diagnostic TnI thresholds.

Methods:
Of 1572 patients enrolled with suspected AMI, 266 patients showed an impaired renal function with estimated glomerular filtration rate (eGFR) of less then 60ml/min and were classified as patients with CKD. N=77 (34%) of patients with CKD and n=278 (24%) without CKD had the final diagnosis AMI. TnI was measured on admission and after 3h. Based on receiver operator characterics curve analyses (AUROC) of the baseline levels CKD optimized TnI threshold were derived. Sensitivity and specifity were calculated for the 99th percentile cut-off (30.0 pg/mL), the optimized cut-off (58.0 pg/mL) and the change in TnI concentration within 3h after admission.

Results:
Patients with CKD had higher TnI levels then patients without CKD (6.0pg/mL vs. 20.9pg/ml; p<0.001). This difference was more pronounced in patients without AMI (median 9.1 vs. 4.4; p<0.001), whereas the difference diminished in AMI patients (median 337.4 vs. 238.6; p=0.83).

In CKD patients TnI remained a strong marker to detect AMI with AUROC of 0.933 compared to 0.969 in patients without CKD.

Applying the 99th percentile threshold it was associated with a relevant loss of specificity in CKD patients with 80% compared to 96% in patients without CKD. This poor specificity could be regained by use of a higher CKD-optimized threshold or use of the change in TnI concentration within 3h leading to specificities of 90% and 96%, respectively.

Conclusions:
Patients presenting with suspected AMI and CKD have higher TnI levels on admission compared to patients without CKD leading to a low specificity detecting AMI in CKD patients. Using an CKD-optimized TnI cut-off level on admission or using the change in TnI concentration within 3h is able to regain this lost specificity.
Abstract 14127: Measures of Patient Activation and Social Support in a Peer-led Support Network for Women With CVD
Authors: Witt Dawn , Benson Gretchen , Sillah Arthur , Campbell Susan , Berra Kathy
Published: July 2021

Introduction:
Social support has been recognized as having a strong impact on health and well-being and has also been shown to have beneficial effects in a wide variety of disease states. Social support from friends, family or peers can augment the care offered in traditional healthcare settings by providing advice, encouragement and education However, there is limited research on the impact of peer-led support programs among women living with cardiovascular disease (CVD).

Objective:
To examine the relationship between patient activation and measures of social support among women who attended a WomenHeart: The National Coalition for Women with Heart Disease peer-led support program in their local community. We hypothesized that high levels of social support would be associated with high levels of patient activation in this study population.

Methods:
Participants were recruited from 50 national WomenHeart Support Network groups. A 70 item, online survey was administered and the main analytic sample for this study included 157 women. Multivariable logistic regression was used to examine the association between patient activation levels (Lower activation levels: 1,2 vs higher activation levels: 3,4) and social support scores (range: lowest 8 to highest 34), adjusting for age.

Results:
Study participants reported high levels of social support and patient activation. Those who were at or above the median for the social support measures (indicating high levels of social support) had greater odds of high levels of patient activation (levels 3 or 4) compared to individuals reporting low levels of social support (OR 2.23 95%CI1.04, 4.76,
p
= 0.012).

Conclusions:
Results of our survey demonstrate that this group of women with coronary heart disease who regularly attended a peer-led support group and indicated a high level of social support report taking a more active role in self-management behaviors.
Abstract 14134: Effects of Statin Plus Ezetimibe versus Statin Alone on Coronary Atherosclerosis in Acute Coronary Syndrome
Authors: Hibi Kiyoshi , Kimura Kazuo , Sonoda Shinjo , Otsuji Yutaka , Murohara Toyoaki , Ishii Hideki , Sato Katsuhiko , Koshida Ryouji , Ozaki Yukio , Sata Masataka , Kawasaki Masanori , Morino Yoshihiro , Miyamoto Tadashi , Amano Tetsuya , Morita Satoshi , Fujiwara Hisayoshi
Published: July 2021

Introduction:
IMPROVE-IT trial showed that ezetimibe plus statin treatment, as compared with statin alone, decreased cardiovascular events in patients with acute coronary syndrome (ACS). However, proir studies have failed to show a beneficial effect of ezetimibe on carotid plaque progression when added to statin treatment.

Hypothesis:
The addition of ezetimibe to statin therapy affects coronary plaque behavior in the non-culprit vessel.

Methods:
We conducted a prospective, randomized open-label parallel group study with blind endpoint evaluation conducted at 10 centers in Japan. A total of 128 statin naïve patients with ACS undergoing intravascular ultrasound (IVUS) guided percutaneous coronary intervention were randomized and nonculprit coronary lesions associated with mild-to-moderate stenosis in 103 patients had evaluable IVUS examinations at baseline and at 8 to 12 months follow-up. Conventional IVUS and integrated backscatter (IB)-IVUS measurements at 1-mm intervals were calculated. Patients were randomly assigned to receive either 2mg/day of pitavastatin plus 10mg/day ezetimibe or 2mg/day of pitavastatin. Primary endpoints were the percentage change in non-culprit coronary plaque volume and percent change in lipid plaque volume.

Results:
Mean low density lipoprotein cholesterol was reduced from 125mg/dl to 65mg/dl in the combination therapy group receiving statin plus ezetimibe (n=50) and 126mg/dl to 87 mg/dl in the statin alone group (n=53)(between group difference of 16.9%, P<0.0001). Length of analyzed segment did not differ between the groups (median 38.0 vs. 41.2 mm, p=0.40). The primary endpoint, percent change in plaque volume, was -5.1% in the combination therapy group and -6.2% in the statin alone group (P=0.66), although both groups resulted in reduction of plaque volume compared with baseline (both p=0.001). The percent change in lipid plaque volume did not differ between the groups (4.3 vs. -3.0%, P=0.37).

Conclusions:
Among patients with acute coronary syndrome, combined therapy with ezetimibe and statin did not result in a significant change in coronary plaque regression or tissue component compared with statin alone.
Abstract 14140: The Weight of the Evidence: Comparison of Operatively Excised Aortic Valve Weights in Patients With High Gradient versus Low Gradient Aortic Stenosis and Overall Survival Following Aortic Valve Replacement
Authors: Negrotto Sara M , Thaden Jeremy J , Suri Rakesh M , Maleszewski Joseph J , Pislaru Sorin V , Eleid Mackram F , Nkomo Vuyisile T
Published: July 2021

Introduction:
Excised aortic valve weight (AVW) correlates with severity of AS. There is some debate about the true severity of AS in low gradient AS (LGAS) compared to high gradient AS (HGAS). We sought to compare patient characteristics and operatively excised AVW in patients with LGAS vs HGAS vs moderate AS.

Methods:
916 patients with EF ≥50% undergoing surgical aortic valve replacement for AS between 2010-2012 were included. Clinical and echocardiographic characteristics of LGAS patients (AVA≤1cm
2
, MnG<40mmHg; N=68) were compared to HGAS patients (AVA≤1cm
2
, MnG≥40mmHg; N=745) and operatively excised AVW were compared to moderate AS (AVA>1cm
2
, MnG<40mmHg; N=102).

Results:
Compared to HGAS, LGAS patients were older (mean age 77 ± 10 vs 73 ± 10 years; p=0.001), often female (56% vs 38%; p=0.006), but without differences in diabetes (26% vs 29%; p=0.78), hyperlipidemia (85% vs 86%, p=0.86), coronary artery disease (49% vs 44%; p=0.53), or hypertension (81% vs 76%; p=0.38). LGAS patients predominantly had trileaflet aortic valves (91% vs 71%; p<0.001), smaller LVOT diameter (2.16 ± 0.15 vs 2.25 ± 0.20 cm; p=0.002), lower stroke volume index (42.1 ± 7.3 vs 49.0 ± 8.8 cc/m
2
; p<0.001), lower systemic compliance (0.77 ± 0.30 vs 0.93 ± 0.33 ; p<0.001), but no difference in valvulo-arterial impedance (3.96 ± 0.76 vs. 3.84 ± 0.80, p=0.24) compared to HGAS. Excised AVW were lower in patients with LGAS vs HGAS (1.77 ± 0.76 vs 2.69 ± 1.26 g, p<0.001), but not different from moderate AS (1.77 ± 0.76 vs 2.04 ± 0.94 g; p=0.1). This relationship held true when AVW was indexed to body surface area. Three-year mortality post-valve replacement was significantly higher in LGAS compared to HGAS (22% vs 11%, p=0.02).

Conclusions:
LGAS occurs mostly in older female patients with trileaflet aortic valves. Excised AVW in LGAS is similar to moderate AS but lower than HGAS. However, systemic compliance is higher in LGAS vs HGAS contributing to increased afterload. Poorer outcomes after surgery in LGAS patients may be attributed to noncompliant vasculature which is not corrected with valve replacement and evaluation of patients with LGAS should include assessment of peripheral resistance.
Abstract 14190: Optimal Peri-endoscopic Management of Anti-thrombotic Therapy in Chinese Elderly Patients: A Retrospective Study
Authors: Wang Hao , Tao Tao , Wang Hai-jun , Guo Yu-tao , Wang Yu-tang
Published: July 2021

Introduction:
To investigate optimal timing of cessation and resumption of anti-thrombotic therapy (ATT) during gastrointestinal endoscopy in Chinese elderly patients.

Methods:
Between January 1st 2008 and December 31st 2014,at Chinese PLA General Hospital, 3747 patients (76.03±10.3 years) hospitalized for elective gastrointestinal endoscopy were retrospectively analyzed. The study population were predominately male(96.1%) and senile(age ≥60, 92.3%).Patients‘ peri-endoscopic management of ATT and adverse events (thromboembolism and bleeding) were recorded. RхC tables were used to compare the differences of peri-endoscopic adverse events among patients with different peri-endoscopic management of ATT.

Results:
the peri-endoscopic thromboembolic incidence in those with discontinuing ATT ≥7 days before procedure was significantly higher (8.12%). No difference of bleeding incidence was found among different cessation time before procedure. The peri-endoscopic thromboembolic incidence increased as the delaying of resuming ATT after procedure. However, the incidence of peri-endoscopic bleeding in patients with resuming ATT 2-7 days after procedure was lowest (0.63%). The reason why bleeding incidences in patients with resuming ATT >7 days, and those without resuming ATT were much higher than those with resuming ATT 2-7 days was that occurrence of bleeding urged physician to postpone or cancel resumption of ATT. When discontinuing ATT, the differences of peri-endoscopic thromboembolic or bleeding events between patients receiving low-molecular-weight heparin bridging therapy and those without bridging therapy were not significant.

Conclusions:
Cessation of ATT <7 days before endoscopic procedure and resumption of ATT in 2-7days after procedure were optimal peri-endoscopic ATT management strategy for Chinese elderly patients.Bridging therapy couldn’t protect elderly patients from peri-endoscopic thromboembolic events.
Abstract 14373: Treatment Trends Among High Cardiovascular Disease Risk Patients Treated With Lipid-lowering Therapies: A United States Real-world Study
Authors: Quek Ruben G , Fox Kathleen M , Wang Li , Li Lu , Gandra Shravanthi R , Wong Nathan D
Published: July 2021

Introduction:
Strong evidence exists linking LDL-C as a causal factor of atherosclerotic CVD. Statins are the cornerstone for lipid lowering therapy (LLT) so it is important to understand treatment trends in light of current guidelines. Objective: To evaluate LLT trends in a US real-world setting.

Methods:
Patients (aged ≥18y) who initiated LLT (statins and/or ezetimibe) from 01/01/2007-06/30/2011 were retrospectively identified from IMS commercial claims. Patients were classified into two cohorts: 1) Prior CVD and 2) Prior CHD RE conditions [Definitions in Figure 1] and stratified by age group (<65 and ≥65y). Eligible patients had continuous health plan enrollment for ≥1 year pre- and post-index date (LLT initiation date). The following were assessed: index statin intensity (defined by ACC/AHA 2013 guidelines), first treatment modification (e.g., switch, re-initiation after temporary discontinuation of >60 days, permanent discontinuation of all LLT) and time-to-first treatment modification.

Results:
A total of 41,934 patients with prior CVD (mean age: 58y) and 170,344 patients with CHD RE (mean age: 57y) were analyzed. From 2007-2011, 66.6-77.8% and 8.8-25.1% of the cohorts were prescribed moderate-intensity and high-intensity statins, respectively, on the index date. Among the CVD and CHD RE cohorts, 18.8% and 26.2% reinitiated index LLT, 11.6% and 13.2% permanently discontinued all LLT and 19.5% and 13.6% switched to a different statin, respectively, as the first treatment modification (Figure 1). A similar trend was observed among patients aged ≥65y. Average number of days to first treatment modification was 130-399 days.

Conclusion:
With 79% of patients modifying their index LLT, of which 12-13% permanently discontinuing all LLT, such treatment modifications may potentially be indicative of index statin intolerability and/or ineffectiveness. High-intensity statin therapy initiation is low, potentially resulting in residual risk of CVD.
Abstract 14599: Long-term Outcomes in Elderly Survivors of Myocardial Infarction With and Without Out-of-Hospital Cardiac Arrest
Authors: Fordyce Christopher B , Wang Tracy Y , Chen Anita Y , Thomas Laine , Granger Christopher B , Scirica Benjamin M , Henry Timothy D , Hansen Carolina M , Kragholm Kristian , Wong Graham C , Ramanathan Krishnan , Peterson Eric D , Anderson Monique L
Published: July 2021

Introduction:
While out-of-hospital cardiac arrest (OHCA) is associated with worse in-hospital outcomes following acute myocardial infarction (MI), post-discharge mortality and health care utilization of elderly patients who survive hospitalization have not been well described. Understanding their long-term prognosis has implications for resource allocation for managing this growing population.

Methods:
Using linked NCDR ACTION-Registry GWTG and Centers for Medicare and Medicaid Services data, we analyzed 54,860 patients (mean age = 76.6) at 545 US hospitals with MI who survived to hospital discharge between April 2011 to December 2012. After excluding hospice patients (n=1,444), rates of observed 1-year mortality post-discharge were computed using the Kaplan-Meier method. Multivariable Cox models were used to examine the associations between OHCA and mortality or all-cause readmission within 1 year post-discharge.

Results:
Compared with elderly MI survivors without OHCA (n=54,219), those with OHCA (n=641) were younger, more likely to be male and smokers, but less likely to have diabetes, heart failure, or prior revascularization. OHCA patients presented to the hospital more often with STEMI and cardiogenic shock, and were more likely to experience adverse in-hospital events compared to patients without OCHA. Despite this, OHCA was associated with similar unadjusted (Figure, p=0.17) and adjusted 1-year post-discharge mortality (adjusted HR 0.87, 95% CI, 0.67 - 1.13) and lower combined unadjusted (44.0% vs. 50.0%, p=0.033) or adjusted 1-year mortality or all-cause readmission (adjusted HR 0.83, 95% CI, 0.71 - 0.96).

Conclusions:
Elderly survivors of MI complicated by OHCA have similar long-term survival and lower rates of healthcare utilization at 1 year post-discharge compared to those without OHCA. These findings support efforts to optimize pre- and intra- hospital processes of care to improve outcomes of elderly OHCA patients.
Abstract 14615: The Preventable Causes of Cardiovascular Diseases in China: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors
Authors: Li Yanping , Hu Frank
Published: July 2021

Background:
fuelled by rapid urbanization and changes in dietary and lifestyle choices, cardiovascular disease (CVD) has emerged as the leading cause of death in China.

Purposes:
to estimate the CVD events that potentially contributed to 9 modifiable dietary, lifestyle, and metabolic risk factors in China.

Methods:
We used data on risk factor exposures in the Chinese population from nationally representative health surveys and CVD morbidity and mortality statistics from the China Health Statistical Yearbook and the National Population Census. We obtained the etiological effects of risk factors on CVD risk, by age, from systematic reviews and meta-analyses of epidemiological studies. We estimated the number of CVD events attributable to all non-optimal levels of each risk factor exposure, by urban/rural, age and sex.

Results:
Based on the exposure distribution estimated by 2009 China Health Nutrition Survey, the population attributable risk (PAR) on CVD events was 47.3% for high blood pressure, 23.2%, for physical inactivity, 18.5% for smoking, 13.5 for high BMI, 13.0% for high LDL cholesterol, 11.8% for high blood glucose, 11.1% for low dietary intakes of fruit and vegetable, 7.1% for high sodium intake and 3.5% for low PUFA intake, which was 78.0%, 18.8%, 20.9%, 21.9%, 8.2%, 16.1%, 12.0%, 20.3% and 2.0%, respectively, based on exposure distribution of 2002 China National Nutrition and Health Survey. In 2009, high blood pressure was responsible for 3.9 million CVD events, including 1.4 million CHD, 1.5 million ischemic strokes and 1 million hemorrhagic strokes. Large gender difference was found for PAR% of smoking (male 27.8%/female 6.5%).

Conclusions:
High blood pressure, smoking and physical inactivity, which all have effective interventions, are responsible for the largest number of CVD events in China. Other dietary, lifestyle, and metabolic risk factors for chronic diseases also cause a substantial number of CVD morbidity and mortality in China.
Abstract 14637: Effects of Dietary Patterns in the Severity of Coronary Artery Disease
Authors: Georgiopoulos George , Siasos Gerasimos , Kokkou Eleni , Oikonomou Evangelos , Dimitropoulos Stathis , Chrysohoou Christina , Mourouzis Konstantinos , Anastasiou Maria , Biri Christina , Zografos Theodoros , Antonopoulos Alexis , Papanikolou Aggelos , Tousoulis Dimitris
Published: July 2021

Introduction:
The impact of diet on atherosclerosis progression is well established. However, the independent predictive value of unhealthy diet in the prognosis and severity of coronary artery disease (CAD) has not been definitely confirmed and clinicians often ignore how to incorporate it in clinical practice.

Hypothesis:
Dietary patterns may impact CAD severity.

Methods:
In this cohort study we included 188 consecutive symptomatic stable CAD patients. The diagnosis of CAD was based on coronary angiography and patients were categorized as having severe CAD and non-severe CAD. The diagnosis of severe CAD was based on the presence of either left main coronary artery disease (stenosis≥50%), or three-vessel coronary artery disease, or two-vessel coronary artery disease marked by stenosis of the proximal left anterior descending artery ≥70%. Among several demographics and clinical characteristics all subjects were tested with a validated semi quantitative food frequency questionnaire.

Results:
Concerning baseline demographic characteristics there was no difference between subjects with severe CAD and non-severe CAD while, the prevalence of severe CAD was higher in current smokers compared to non-smokers. Principal component analysis revealed 8 distinct dietary patterns. The first component-western dietary pattern (increased intake of fat, red meat and carbohydrates and minimal consumption of fruits vegetables and green leafy)- was predictive of severe CAD (AUC:0.73, 95% CIs:0.64-0.83, p<0.001) and more interestingly, can increase the discriminative ability of a multivariate model based on all major risk factors.

Conclusion:
The unhealthy western type of diet is associated with the severity and extent of coronary artery lesions in patients with stable CAD. These findings highlight the importance of accessing dietary patterns when calculating cardiovascular risk and to take into consideration dietary habits in the management of cardiovascular patients.
Abstract 14653: Prevention of Diet-induced Metabolic Dysregulation, Inflammation and Atherosclerosis in Ldlr-/- Mice by Treatment With the ACL Inhibitor ETC-1002
Authors: Samsoondar Joshua P , Sutherland Brian G , Telford Dawn E , Sawyez Cynthia G , Edwards Jane Y , Filippov Sergey , Pinkosky Stephen L , Newton Roger S , Huff Murray W
Published: July 2021

ETC-1002 (8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) is a novel LDL cholesterol-lowering compound. Preclinical studies revealed that ETC-1002 targets the liver where its metabolite, ETC-1002-CoA, inhibits the synthesis of sterols and fatty acids. The primary mechanism of action is through inhibition of hepatic ATP-citrate lyase (ACL). In the current study we tested the ability of ETC-1002 to prevent diet-induced metabolic dysregulation, inflammation and atherosclerosis in LDL receptor deficient (Ldlr-/-) mice. Ldlr-/- mice fed a high-fat high-cholesterol diet (42% kcal fat; 0.2% cholesterol; HFHC) developed hypercholesterolemia, hypertriglyceridemia, hyperglycemia, hyperinsulinemia, fatty liver and obesity over the 12 week study. ETC-1002 supplementation to the HFHC diet at 3, 10 and 30 mg/kg/d significantly attenuated these metabolic abnormalities in a dose-dependent manner. ETC-1002 + HFHC attenuated plasma triglyceride (up to 64%) and plasma cholesterol concentrations (up to 50%), and improved glucose homeostasis compared to HFHC alone as determined by glucose tolerance tests. Adiposity was attenuated up to 48% with treatment. In liver, ETC-1002 dose dependently prevented cholesterol and triglyceride accumulation up to 75% and 90%, respectively. Hepatic gene expression analysis revealed that treatment significantly reduced the expression of the inflammatory genes Tnfa, Il1b, Ccl3 and Nos2 as well as increased the expression of genes involved in mitochondrial (Cpt1a, 1.3-fold) and peroxisomal (Acox1, 4.1-fold) fatty acid beta-oxidation. ETC-1002 reduced aortic cholesterol ester content by up to 63% and robustly attenuated atherosclerotic lesion development in the aortic sinus by 48%. These studies demonstrate that ETC-1002 effectively prevents plasma and tissue lipid elevations and attenuates the onset of inflammation, leading to the prevention of atherosclerotic lesion development in a mouse model of metabolic dysregulation.
Abstract 14690: Microrna-495 Mediates the Angiogenic Potential of iPSC-Derived Endothelial Cells in Infarcted Heart
Authors: Liang Jialiang , Huang Wei , Cai Wenfeng , Xu Meifeng , Paul Christian , Millard Ronald , Wang Yigang
Published: July 2021

Background and Objective:
miR-495 inhibition is known to enhance mesoderm differentiation, but its role in angiogenesis is not clear. The present study seeks to determine whether miR-495 mediates angiogenesis induced by human induced pluripotent stem cells (hiPSCs) in infarcted heart.

Methods:
The miR-495 in hiPSCs was knocked down via lentivirus. ECs were generated from hiPSCs (hiECs) and sorted by MACS using CD144 antibody (Fig. 1A).

In vitro
:

the angiogenic potential of hiEC
Anti-495
(hiEC
Scr
as control) was analyzed by tube formation and expression of angiogenic genes was detected by PCR array.

In vivo
:

hiECs were transplanted into infarcted heart of immunodeficient mice (LAD ligation); after 4 weeks, hearts were harvested for immunostaining and genome PCR to identify implanted cells.

Results:
In vitro
:

The tube length of hiEC
Anti-495
was increased (Fig. 1B) and multiple angiogenic genes (EFNB2, TIE2, IGF1, and JAG1) were upregulated in hiEC
Anti-495
as compared to hiEC
Scr
(Fig. 1C).

In vivo
:

Implantation of hiEC
Anti-495
increased the isolectin-B4
+
capillary density in the infarcted heart (Fig. 1D). hiEC
Anti-495
integrated into mouse vascular networks, whereas the structural integration of hiEC
Scr
was seldom observed. Human DNA derived from hiEC
Anti-495
in infarcted heart was higher as compared to hiEC
Scr
(Fig.1E).

Conclusion:
miR-495 represents a promising mediator for promoting angiogenic potential and functional integration of hiPSC-derived ECs for the treatment of infarcted heart.
Abstract 14697: Novel Assays for Quantification of Lipoprotein-Associated (PCSK9-apoB, PCSK9-Lp(a)) Proprotein Covertase Subtilisin/Kexin Type 9 (PCKS9)
Authors: Yeang Calvin , Choi Yun-Seok , Lee Sang-Rok , Bertoia Monica L , Rimm Eric B , Yang Xiaohong , Witztum Joseph L , Tsimikas Sotirios
Published: July 2021

Background:
PCSK9 is a major regulator of plasma LDL-C. Monoclonal antibodies to PCSK9 lower LDL-C by 45-65% and Lp(a) by 9-38%. The canonical function of PCSK9 is binding of LDL-receptor (LDLR) via its extracellular EGF-A domain, and subsequently mediating LDLR degradation. However, PCSK9 also weakly associates with plasma lipoproteins, with 20-40% of total plasma PCSK9 found on LDL. However, most LDL particles do not contain PCSK9. Whether PCSK9 also associates with other lipoproteins such as Lp(a) are not well described.

Methods:
Sensitive and quantitative sandwich-based ELISA assays were developed to measure PCSK9 associated plasma lipoproteins in both mouse and human plasma. For human plasma, commercial rabbit polyclonal antibodies binding to the C-terminal region of PCSK9 (Abgent, ThermoFisher) or REGN727 human monoclonal antibody were bound to microtiter well plates. Plasma was added and monoclonal antibodies MB47 and LPA4, binding to apoB-100 and apo(a) respectively, were used to detect PCSK9-apoB-100 and PCSK9-Lp(a) complexes with a chemiluminescent ELISA. For mouse assays, REGN727 was used as the capture antibody as it detects mouse PCSK9 and monoclonal antibody LF3 was used to detect mouse apoB.

Results:
PCSK9-apoB and PCSK9-Lp(a) complexes could be detected in both human plasma and in various mouse models expressing apo(a) or Lp(a). The signal to noise ratio was ~20 fold in various clinical samples, including in healthy subjects and in patients with cardiovascular disease. In 536 clinical samples from the Health Professional Follow-Up Study, PCSK9-Lp(a) correlated strongly with Lp(a) (r=0.59, p<0.001, age-adjusted) but not other lipid variables. PCSK9-apoB correlated weakly with PCSK9-Lp(a) (r=0.30, p<0.001, age-adjusted) and LDL-C (r=0.22, p<0.001, age-adjusted). These associations were virtually the same in 526 women in the Nurses’ Health Study.

Conclusions:
Novel ELISAs were generated to quantitate lipoprotein-associated PCSK9 in transgenic mouse and human plasma, including on apoB and Lp(a). Changes in PCSK9-Lp(a) complexes may provide insights into the Lp(a)-lowering effect of PCSK9 antibodies. Whether these assays will predict CVD outcomes waits to be determined in PCSK9 antibody and epidemiological studies.
Abstract 14725: Association of Adipokines With Subclinical Myocardial Dysfunction - The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Ostovaneh Mohammad R , Ambale Venkatesh Bharath , Yoneyama Kihei , Sharma Shishir , Allison Matthew A , Greenland Philip , Wu Colin O , Bluemke David A , Lima João A
Published: July 2021

Background:
Adipokines such as adiponectin, leptin and resistin have been associated with heart failure. We explore the association of adipokines and myocardial fibrosis as MRI-derived measure of subclinical myocardial dysfunction.

Methods:
For the current analysis, we studied MESA subjects who had adiponectin, leptin, resistin and TNF-α measured at second/third follow-up exams (2003-2005) and underwent post gadolinium MRI T1 mapping at 25 minutes for assessment of myocardial fibrosis at the fifth follow-up exam (2010 -2012). Linear regression analysis was used to evaluate the association of log-transformed adipokine levels with T1 time. BMI-stratified analysis was performed when the interaction term of BMI and adipokines was significant. Lower T1 time reflects greater myocardial fibrosis.

Results:
Four hundred and twenty three subjects (mean age: 61.4(8.1), 187 females) were included in the analysis. Median values of adiponectin, leptin, resistin and TNF-α were 16.9 μg/ml (IQR: 11-25), 11.1 ng/ml (IQR:5-25), 14 ng/ml(IQR:11-17) and 4.5 pg/ml(IQR:3.5-5.9). Higher adiponectin was associated with lower degree of myocardial fibrosis in subjects with BMI<25 (p = 0.005). Higher leptin in individuals with BMI≥30 (p<0.001) and higher resistin in those with BMI<25 (p=0.02) was associated with greater myocardial fibrosis.

Conclusion:
Higher adiponectin is associated with lower degree of myocardial fibrosis in normal weight subjects. Leptin in obese individuals and resistin in those with normal BMI are positively associated with myocardial fibrosis.
Abstract 14760: Right Ventricular Function in Preterm Neonates: Reference Values for Longitudinal Strain by Two-dimensional Speckle Tracking Echocardiography From Birth to One Year of Life
Authors: Levy Philip T , Patel Meghna D , Holland Mark R , Sekarski Timothy J , Mathur Amit , Lee Caroline , Hamvas Aaron , Singh Gautam K
Published: July 2021

Introduction:
Right ventricle (RV) systolic function is an important determinant of cardiopulmonary outcomes in premature infants. Two-dimensional speckle tracking echocardiography (2DSTE) derived myocardial strain is a reliable measure of RV systolic function in premature infants, but lacks reference values for clinical application in premature infants. We aimed to determine the maturational (age- and weight- related) changes in RV strain to establish reference values in preterm infants from birth to one year corrected age (CA).

Methods:
RV peak global longitudinal strain (pGLS) and RV free wall longitudinal strain (FWLS) were measured in a prospective longitudinal study in 115 preterm infants (< 29 weeks at birth) at 24 and 72 hours of age (HOA), 32 and 36 weeks postmenstrual age (PMA), and one year (CA) by 2DTSE (GE EchoPac) from a RV-focus apical 4-chamber view using a validated protocol. Premature infants that developed chronic lung disease or had a hemodynamically significant PDA were excluded (n=65) from analysis for the reference values.

Results:
RV pGLS ranged from -16% at birth to -26% by one year CA and RV FWLS ranged from -18% at birth to -27% to one year CA in healthy preterm infants. RV pGLS and FWLS strain correlated with increasing weight (r=0.87, p < 0.001), PMA in weeks (r=0.85, p < 0.001; r=0.83, p < 0.001), but were independent of gestational age at birth (r=0.4, p=0.38; r=0.3, p=0.5). RV strain was significantly lower in preterm infants with bronchopulmonary dysplasia (p=0.004) at 32 and 36 weeks PMA, and one year CA (Figure). RV strain was independent of gender or need for mechanical ventilation.

Conclusions:
This study establishes reference values of RV global and free wall longitudinal strain and tracks their postnatal maturational changes in preterm infants. These measures increase from birth to one year CA and are linearly associated with increasing weight reflecting the postnatal cardiac growth as a contributor to the maturation of RV function.
Abstract 14775: Current Results of Open Repair of Descending Thoracic and Thoracoabdominal Aortic Aneurysms
Authors: Gaudino Mario , Lau Christopher , Munjal Monica , Elsayed Mohamed , Benedetto Umberto , Girardi Leonard N
Published: July 2021

Introduction:
Open repair of thoracic and thoracoabdominal aortic aneurysms (DTA and TAAA respectively) constitutes a benchmark for comparison with endovascular techniques. Hypothesis. To evaluate the current results of the open repair of DTA and TAAA. Methods. Open DTA and TAAA repair was performed on 675 consecutive patients (210 TAA and 465 TAAA). Three surgical techniques were used based on the type of the aneurysm and the risk profile of the patient: clamp and saw, partial bypass or hypothermic circulatory arrest. Spinal drain was used in 82.7% of patients. Regression analysis was performed to identify independent determinants of in-hospital and late outcomes and individual major postoperative complications. Propensity matching (PPM) was used to compare results of the different surgical techniques Results. Operative mortality was 5.6% (38/675); incidence of postoperative spinal cord injury, stroke, need for tracheostomy, myocardial infarction and dialysis were 2.8%, 0.7%, 7.7%, 0.6% and 5.2% respectively. Kaplan Mayer survival at five-year was 57.8%. Female gender, urgent operation and preoperative dialysis were independent predictors of adverse in-hospital adverse events. Preoperative renal and respiratory failure were associated with follow-up death. Female gender and preoperative chronic pulmonary disease were associated with postoperative need for tracheostomy, whereas preoperative renal failure, urgent operation and peripheral vascular disease predicted the need for postoperative dialysis. Due to the low number of events, logistic regression analysis was not possible for predictors of spinal cord injury. In the PPM groups no difference was found in the early and late outcome between patients treated with different techniques (see table).

Conclusion:
In the current era open TAA and TAAA repair allows excellent outcomes.
Abstract 14804: Time-Course and Influencing Factors of Ventricular Tachy-Arrhythmias After Initiation of Steroid Therapy in Patients With Cardiac Sarcoidosis
Authors: Segawa Masato , Fukuda Koji , Nakano Makoto , Kondo Masateru , Hirano Michinori , Shimokawa Hiroaki
Published: July 2021

Introduction:
It is widely known that ventricular tachy-arrhythmias (VTs) are often observed in patients with cardiac sarcoidosis (CS) as one of the presentations of poor prognosis. However, the time-course and influencing factors of VTs after the introduction of corticosteroid therapy in CS patients remain to be elucidated.

Methods and Results:
We examined the influence of steroid therapy on VTs in 68 consecutive CS patients in Tohoku University Hospital from October 1998 until September 2014 (57±11 years-old, M/F 18/50). CS was diagnosed based on the original guidelines for diagnosis of CS from the Japanese Ministry of Health and Welfare. Corticosteroid therapy was performed in all CS patients. VTs were defined as sustained ventricular tachycardia/fibrillation or appropriate ICD therapy events. During a mean follow-up of 5.5 years, 20 out of 68 patients (29%) experienced VTs after the initiation of corticosteroid therapy, and 14 (70%) of them had VTs in the first 12 months (Figure A). Multivariable analysis showed that the positive gallium scintigraphy was an independent risk factor for VTs (odds ratio, 17.4; 95% CI, 1.03-294, P=0.047). Survival free from VTs events was significantly lower in the Ga-positive group than in the Ga-negative group (P<0.001), where most of the events were developed in the early phase in the Ga-positive group (Figure B). Furthermore, electrical storm (ES) of VTs was noted in 10 patients (14.7%), and most of them (8 out of the 10 patients) had ES in the first 12 months, whereas the recurrence of ES was relatively low (Figure C).

Conclusions:
VTs or ES in CS patients was frequently noted in the first 12 months after initiation of corticosteroid therapy, possibly representing inflammatory conditions, for which Ga scintigraphy is useful diagnostic strategy and Ga-positive is an independent prognostic factor in CS.
Abstract 14816: Twelve-month Outcomes of Stenting versus Standard Balloon Angioplasty for the Below-the-Knee Arterial Disease Patients Underwent Percutaneous Transluminal Angioplasty
Authors: Rha Seung Woon , Choi Byoung Geol , Choi Se Yeon , Byun Jae Kyeong , Na Jin Oh , Choi Cheol Ung , Lim Hong Euy , Kim Jin Won , Kim Eung Ju , Park Chang Gyu , Seo Hong Seog , Oh Dong Joo
Published: July 2021

Background:
Although percutaneous transluminal angioplasty (PTA) is considered as an effective treatment strategy in patients (pts) with critical limb ischemia (CLI), below-the-knee (BTK) lesions with CLI is particularly challenging. This study sought to compare the 12-month outcomes following stenting versus standard plain old balloon angioplasty (POBA) alone in BTK lesions.

Method:
This study consisted of 339 consecutive lower extremity arterial disease pts (394 limbs, 1026 lesions included 716 BTK lesions) with BTK lesions from Sep 2004 to Dec 2013. All the enrolled pts were treated by stenting (bare metal stents, primary or provisional, 78 limbs in 73 pts) or POBA (316 limbs in 266 pts) with PTA. Procedural success, complications and clinical outcomes were compared between the two groups up to 12 months. To adjust potential confounders, a propensity score matched (PSM) analysis was performed using the logistic regression model.

Results:
After PSM analysis, 2 propensity-matched groups (56 pairs in pts, n= 112; 61 pairs in limbs, n=122, C-statistic=0.808) were generated, and the baseline & angiographic characteristics of the two groups were balanced. Procedural success, complication incidences were similar between the two groups. Six to 9-month CT or angiographic follow-up, there were similar incidence of binary restenosis, primary, and secondary patency. At 12 months, there were similar incidence of individual hard endpoints including mortality, myocardial infarction, limb salvage, and any extremity amputations except the target lesion and extremity revascularization. Repeat PTA incidence was higher in the stenting group than POBA group (table).

Conclusion:
Although the repeat PTA risk was increased with BTK stenting, other major individual clinical outcomes and limb salvage rates were similar between the POBA and stenting for the BTK lesions.
Abstract 14820: Sirt7 Deficiency in Blood Vessel Components Impairs Vascular Function by Inhibiting Cell Cycle- and Inflammatory-Related Protein Expression
Authors: Kimura Yuichi , Izumiya Yasuhiro , Araki Satoshi , Yamamura Satoru , Onoue Yoshiro , Hanatani Shinsuke , Ogawa Hisao
Published: July 2021

Introduction:
Aging is a well-established cardiovascular risk factor and associated with vascular dysfunction. Sirt7, one of the members of mammalian sirtuin family, is thought to be involved in age-related diseases. However, little is known about the relative contribution of Sirt7 in vascular dysfunction.

Hypothesis:
Sirt7 maintains vascular cell functions and its deficiency plays a critical role in vascular diseases.

Methods:
Sirt7 loss- and gain-of-function experiments were performed with human aortic smooth muscle cells (HAoSMCs) and human umbilical vein endothelial cells (HUVECs). In vivo, blood flow recovery was evaluated by hindlimb ischemia model in homozygous Sirt7 deficient (Sirt7-/-) and wild-type (WT) mice. Irradiated WT mice were intravenously received bone marrow (BM) cells from WT or Sirt7 -/- mouse to achieve BM transfer.

Results:
An RNAi-medicated Sirt7 knockdown resulted in a significant inhibition of HAoSMCs proliferation following serum or Platelet-derived growth factor BB (PDGF-BB) stimulation as determined by cell count, BrdU cell proliferation assay and MTS proliferation assay. Knockdown of endogenous Sirt7 also reduced cell migration as revealed by Boyden chamber migration assay. The Cyclin D1 and Cyclin dependent kinase 2 (CDK2) protein levels were significantly decreased in Sirt7 siRNA-treated HAoSMCs in response to serum or PDGF-BB stimulation. In endothelial cells, knockdown of Sirt7 attenuated tube formation, proliferation and migration. These changes were accompanied by reduced ERK activation and VCAM-1 mRNA and protein expression in Sirt7 siRNA-treated HUVECs. Conversely, overexpression of Sirt7 by adenovirus enhanced tube formation and cell proliferation. In vivo, blood flow recovery in response to hindlimb ischemia was significantly attenuated in Sirt7-/- mice compared with WT mice. There was no difference in blood flow recovery between WT mice transplanted with WT or Sirt7-/- BM cells suggesting that Sirt7 deficiency in vascular cells have a predominant effect on attenuated blood flow recovery in response to hindlimb ischemia.

Conclusions:
Sirt7 in blood vessel components have an important role in maintenance of vascular function. Sirt7 could be a promising therapeutic target for vascular diseases.
Abstract 14854: Optimal Cut-off Points of Waist Circumference for Detecting Central Obesity and Severe Central Obesity in Chinese Adults
Authors: Wen Xiaoxiao , Mai Jinzhuang , Gao Xiangmin , Guo Min , Wu Yong , Liu Xiaoqing , Zhao Liancheng
Published: July 2021

Introduction:
Given that no consensus has yet been reached over the optimal cut-off points of waist circumference (WC) for Chinese, this study aimed to determine the appropriate cut-off points of WC for detecting central obesity and severe central obesity in a Chinese adult population.

Methods:
Data from the cross-sectional survey of the PRC-USA Collaborative study of Cardiovascular and Cardiopulmonary Epidemiology in 1993-1994 was used, including 10265 subjects (4921 men and 5344 women) aged 35-69 years. Each integer of WC in centimeters was used as the cut-off point to detect clustering of cardiovascular risk factors, which was defined as the presence of two or more risk factors among hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia and low levels of high-density lipoprotein cholesterol. Based on the Receiver operating characteristic (ROC) curve analysis, the WC value corresponding to the point on the ROC curve nearest to the upper left corner of the ROC graph was considered the optimal cut-off for central obesity and the value corresponding to the point with specificity of 90% or more was considered the optimal cut-off for severe central obesity.

Results:
The optimal cut-off value of WC to detect clustering of risk factors was ≥84 cm for men and was ≥80 cm for women with the shortest distance to the upper left corner being 0.4304 and 0.4504, respectively. The cut-off values of WC with specificity above 90% were ≥93 cm and ≥91 cm for men and women respectively.

Conclusions:
These results were equal or similar to the WC cut-off points proposed by the Guidelines for Prevention and Control of Overweight and Obesity in Chinese Adults, i.e., ≥85/80 cm (men/women) for increased risk for obesity related diseases and ≥95/90 cm (men/women) for much higher risk. For practical reasons, WC≥85/80 cm and ≥95/90 cm (men/women) could be the optimal cut-off values for detecting central obesity and severe central obesity, respectively, in Chinese adult population.
Abstract 14895: Catheter-Based Treatment for Pulmonary Embolism With Concomitant Use of Intrapulmonary Thrombolysis Improves In-Hospital Mortality Rates
Authors: Kalra Rajat , Bajaj Navkaranbir S , Guichard Jason L , Ather Sameer , Lancaster William J , Raman Fabio , Arora Pankaj , Clark Donald T , McGiffin David C , Ahmed Mustafa I
Published: July 2021

Introduction:
In-hospital mortality rates after catheter-based treatment (CBT) of high-risk pulmonary embolism (PE) are variable. Use of intrapulmonary thrombolytics with other CBT may result in rapid clearance of obstruction, prevent extremis and lead to improved mortality rates.

Hypothesis:
We hypothesized that the concomitant use of intrapulmonary thrombolysis in conjunction with CBT may affect mortality and explain the heterogeneity among in-hospital mortality rates.

Methods:
We searched SCOPUS since inception to November 2014 using predefined criteria. Studies reporting in-hospital mortality in patients with massive PE or a combination of massive and submassive PE, as defined by the American Heart Association, were included. In-hospital all-cause mortality rates were estimated in these high-risk patients using standard meta-analytic methods. Heterogeneity in mortality rates was explored with meta-regression.

Results:
In 54 eligible studies with 1,333 patients, 1357 CBT procedures were performed. All CBT modalities were studied. In-hospital mortality rates varied widely amongst studies (Figure, Panel A). On meta-regression with Logit-in hospital mortality rate as the dependent variable, studies that had a higher proportion of patients who received concomitant intrapulmonary thrombolysis had lower Logit in-hospital mortality rate (β = - 0.01, p <0.001; Figure, Panel B).

Conclusions:
Concomitant use of intrapulmonary thrombolytics is associated with lower in-hospital mortality rate in patients undergoing CBT for high-risk PE.