bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13290: GDF-15 at One Month After an Acute Coronary Syndrome is Associated With Increased Risk of Major Bleeding - A PLATO Biomarker Substudy
Authors: Lindholm Daniel , Hagström Emil , James Stefan K , Becker Richard C , Cannon Christopher P , Himmelmann Anders , Husted Steen , Katus Hugo A , Maurer Gerald , Lopez-Sendon Jose , Steg Philippe Gabriel , Storey Robert F , Siegbahn Agneta , Wallentin Lars
Published: July 2021

Introduction:
Levels of Growth Differentiation Factor-15 (GDF-15) are associated with major bleeding events in acute coronary syndromes (ACS), when measured at the time of initial presentation. We hypothesized that an additional measurement of GDF-15 at 1 month after ACS provides additional information regarding risk of major bleeding.

Methods:
In the PLATO trial, levels of GDF-15 were determined in 4049 ACS patients at both baseline and at 1 month, using an immunoassay (Roche). The primary endpoint was non-CABG related major bleeding. A 1-month landmark analysis was performed, in relation to GDF-15 elevation status at baseline and 1 month, using a cutoff of 1800 ng/L. The relation between GDF-15 at 1 month and the primary endpoint from 1 month onward was evaluated using a Cox proportional hazards model; adjusting for baseline GDF-15, age, anemia (hemoglobin <130 g/L in men, <120 g/L in women), impaired renal function (eGFR <50 mL/min/1.73m2), and history of gastrointestinal bleeding.

Results:
In the unadjusted analysis, patients with GDF-15 >1800 ng/L at 1 month had increased bleeding rates during follow-up, irrespective of the baseline value. Patients with GDF-15 ≤1800 ng/L at 1 month had lower bleeding risk regardless of initial level (see figure). In the adjusted analysis, GDF-15 >1800 ng/L at 1 month was independently associated with the outcome, hazard ratio 3.39 (95% CI 1.89-6.09).

Conclusions:
The level of GDF-15 at 1 month after ACS is related to the risk of bleeding during dual antiplatelet treatment. Assessment of GDF-15 level at 1 month provides additional information on the subsequent bleeding risk, regardless of the patient’s index GDF-15 level in the acute phase, and may therefore be helpful for decision-making on continued dual antiplatelet treatment.
Abstract 13382: Urgent Control of Rapid Atrial Tachyarrhythmia Using Landiolol in Patients With Heart Failure With Severely Reduced Ejection Fraction : An Ultra-Short-Acting β-blocker for Emergency ADHF
Authors: Iwahashi Noriaki , Gohbara Masaomi , Kataoka Shunsuke , Minamimoto Yugo , Akiyama Eiichi , Maejima Nobuhiko , Tsukahara Kengo , Hibi Kiyoshi , Kosuge Masami , Kosuge Masami , Ebina Toshiaki , Umemura Satoshi , Kimura Kazuo
Published: July 2021

Backgounds:
To control heart rate(HR) of atrial tachyarrhythmia is important in patients with acute decompensated heart failure(ADHF) in their critical phase. Landiolol is newly developed an ultra-short-acting β-blocker. We explored the hemodynamic effect of Landiolol treatment for atrial tachyarrhythmia in patients with ADHF in their critical phase.

Hypothesis:
Landiolol is useful to control HR of atrial tachyarrhythmia without any adverse events and it can make their status better.

Methods:
Consecutive 35 ADHF patients were enrolled(74 years, 25 men, EF25%, HR137/min, BNP837pg/ml). 34 out of 35 patients had atrial fibrillation (AF) or atrial flutter (AFL), and one patient had atrial tachcardia (AT). We treated them with low dose landiolol immediately after admission. Among them, 17 patients were monitored by Swan-Ganz (S-G) catheterization to explore the hemodynamic effect of Landiolol.

Results:
The average maximum dose of Landiolol was 3.3γ. No patients had serious adverse events. HR (93/min, p<0.0001) and BNP (618pg/ml, p<0.05 ) decreased after treatment and

In S-G data, PCWP and PAP decreased after Landiolol treatment, on the other hand CO increased. Three patients out of 17 patients with S-G could not achieve adequate HR decrease (110<min) even with their maximum dose, their ΔHR were -28, -28, +1/min.. They had higher PCWP (32 vs 20, p<0.05) and relatively lower CO (2.7 vs 3.0, NS) compared with responders. One patient had AT and his HR didn’t decrease (ΔHR= +1/min) and hemodynamic condition didn't improve.

Conclusions:
Low dose Landiolol that is an ultra-short-acting β-blocker, was effective for controlling rapid HR in AF/AFL patients with LV dysfunction despite being in the critical state. The patients with extremely severe condition and atrial tachycardia might not be suitable for Landiolol treatment in their critical states.
Abstract 13557: Regulation of PBEF Release by NAD Glycohydrolase CD38
Authors: Zhu Xiangdong , Meliton Angelo , Li Jing , Wang Youhua , Zhu Mengqi , Leff Alan R , Vanden Hoek Terry L
Published: July 2021

Introduction:
Our previous work suggests that PBEF is an early blood marker inversely related to hypothermia protection and resuscitation survival in a mouse model of hemorrhagic shock. Given that neutrophils are a potential high-concentration source of blood PBEF, we studied mechanisms of PBEF release from isolated human neutrophils that could help design novel resuscitation strategies.

Methods:
Human blood neutrophils were isolated by Percoll density gradient. PBEF secretion into neutrophil supernatant was measured by ELISA.

Results:
Non-stimulated neutrophils (i.e. exposed to serum-starved conditions) released PBEF. PBEF in supernatant was observed at 5 min and plateaued after 30 min at 37oC. This release was not due to cell injury since LDH was unchanged, nor was it blocked by the classical secretion inhibitors, brefeldin A (blocks ER-Golgi transport) or nocodazole (blocks microtubule polymerization). As PBEF product NAD+ is consumed by multiple intra- and ecto-NADases, we determined whether inhibition of NADase activity impairs PBEF release. Nicotinamide, a global inhibitor of all NADases, blocked PBEF secretion by 73%, suggesting NADases promote PBEF secretion. To identify the specific NADase in PBEF secretion, neutrophils were treated with inhibitors for PARP, sirtuin, CD38 or mono-ADP-ribosyltransferase. We found that inhibition of CD38 by tannic acid or apigenin was able to block PBEF secretion in neutrophils (10.2 ± 2.8 ng/ml for control vs 1.8 ± 0.2 ng/ml for tannic acid at 100 μM, P < 0.01), but not by inhibitors of the other NADases. This observation indicated that CD38 glycohydroase activity is required for PBEF secretion. To further support the role of tannic acid in CD38 inhibition, tannic acid was shown to inhibit ε-ADP ribose production when neutrophils were treated with ε-NAD+. Finally, PBEF secretion was significantly enhanced by oxidative stress using H2O2 exposure.

Conclusions:
PBEF is constitutively released from neutrophils and this release is regulated by CD38 NAD glycohydrolase activity. Changes in human neutrophil microenvironment, especially oxidative stress, result in significant PBEF release within a timeframe that could account for the blood changes seen during mouse cardiovascular resuscitation.
Abstract 13576: Concomitant Valve Intervention During Left Ventricular Assist Device Implantation Improves Mid-term Hemodynamics and Survival
Authors: Tanaka Akiko , Onsager David , Cozadd Daniel , Kim Gene , Adatya Sirtaz , Sarswat Nitash , Sayer Gabriel , Fedson Savitri , Uriel Nir , Jeevanandam Valluvan , Ota Takeyoshi
Published: July 2021

Introduction:
This is a retrospective single-institutional study to investigate safety and efficacy of concomitant valve procedures in patients undergoing left ventricular assist device (LVAD) implantation.

Methods:
From July 2008 to December 2014, 254 patients underwent LVAD implantation. 165 patients had concomitant valve intervention (aortic valve [A], N=3; mitral valve [M], N=78; tricuspid valve [T], N=131; multiple valve intervention, N=67, A+M=3, A+T=11, M+T=44, A+M+T=9). Patients were divided into two groups: Group D, with residual diseased valve, N=97; and Group C, with no-diseased valve, N=157) (see details in figure) and short-/mid-term outcomes were compared.

Results:
Intraoperative and postoperative outcomes did not differ in two groups except for significantly more concomitant valve procedures (Group D=54 [56%], Group C=111 [70%], P<.0001) and longer cardio-pulmonary bypass time (Group D=125 min vs Group C=148min, P = 0.003) in Group C compared to Group D. There was no statistically significant difference in two groups in In-hospital mortality with a tendency to be favorable to Group C (Group D=19.6% vs Group C=11.6%, P=0.09). Concomitant valve intervention did not increase in-hospital mortality (LVAD+valve=15.7%, isolated LVAD=14.1%, P=0.73). During mid-term follow up, mean pulmonary artery pressure (mmHg)(Group D=27, Group N=22, P=0.012) and wedge pressure (Group D=15, Group C=12,P=0.038) were significantly lower in Group C compared to Group D. Post-LVAD implant survival and freedom from heart failure readmission rate at 1 year were significantly higher in Group C compared to Group D (survival, Group D=59 ± 5%, Group C=72 ± 3%, P=0.035; admission, Group D=79 ± 5%, Group C=88±3%, P=0.034)

Conclusions:
Concomitant valve procedure during LVAD implantation did not increase operative morbidity and mortality. Aggressive valve intervention during LVAD implantation may contribute to improved mid-term hemodynamics and survival.
Abstract 13614: Prognostic Value of Cardiorespiratory Fitness in Patients With Chronic Renal Dysfunction: The FIT (Henry Ford Exercise Testing) Project
Authors: Ahmed Amjad , Qureshi Waqas T , Brawner Clinton A , Keteyian Steven J , Ehrman Jonathan K , Blumenthal Roger S , Nasir Khurram , Blaha Michael J , Al-Mallah Mouaz H
Published: July 2021

Background:
Chronic kidney disease (CKD) is associated with high morbidity and mortality. We tested the hypothesis that cardiorespiratory fitness (CRF) retains incremental prognostic value over renal function, as measured by estimated glomerular filtration rate (eGFR).

Methods:
Our analysis included 50,121 patients (mean age 55 ± 12.6 years and 47.5% females) from The Henry Ford Exercise Testing Project (FIT project), who underwent exercise stress testing between 1991 and 2009. Patients with heart failure or missing relevant covariate data were excluded. The mean duration between stress testing and creatinine measurement was 30 days and eGFR was estimated using the Modification of Diet in Renal Disease equation. Treadmill stress testing used the standard Bruce protocol and CRF was estimated using metabolic equivalent of task units (MET). Patients were followed-up for all-cause mortality. Multiple nested Cox models were used to determine the incremental prognostic value of CRF over eGFR.

Results:
The magnitude of renal dysfunction was inversely associated with (level of CRF (mean METs achieved 9.1, 9.0, 7.5, 5.5 METS for Stage I, II, III and more than III CKD respectively, p<0.0001). Over a median follow-up duration of 6.7 yr, (IQR 3.9 to 10 yr), 6,308 (12.6%) patients died. CRF was a strong, independent predictor of mortality (p <0.001) and at every stage of renal function, improved CRF was associated with improved survival. (figure). Using Cox analysis, CRF added improved discriminatory ability beyond traditional risk factors and renal function: Area under the curve (AUC) 0.837 (95% CI 0.832 - 0.842) vs. 0.814 (95% CI 0.809 - 0.8198), respectively, p-value <0.0001. Renal function did not add incremental prognostic value once CRF was accounted for.

Conclusion:
Regardless of renal function, CRF is an independent predictor of mortality. Fitness adds incremental prognostic value over renal function in this large diverse clinical cohort.
Abstract 13741: Clinical Value of the Detection of Autoantibodies Against β1, β2 and α1 Adrenergic Receptors in Patients With Heart Failure
Authors: Hou Dongyan , Liang Yanhong , Zhang Lin
Published: July 2021

Background:
Metoprolol and carvedilol are the β-blockers most often used in the management of patients with heart failure (HF), and the choice of drug is still unclear. Autoantibodies against β1, β2 and α1 adrenergic receptors (anti-β1-AR, anti-β2-AR and anti-α1-AR) participate in the pathology of HF. The purpose of the current study is to determine anti-β1-AR, anti-β2-AR and anti-α1-AR may be association with carvedilol treatment in HF patients.

Methods:
Synthetic β1, β2 and α1 adrenoreceptors peptides served as the target antigen. ELISA was used to screen the sera of 267 HF patients, which were divided into different groups based on their autoantibodies reactively. Echocardiography was performed between carvedilol therapy.

Results:
Final analysis covered 137 patients, including 65 patients with three autoantibodies and 72 negative. The frequency and geometric mean titer of anti-β1-AR, anti-β2-AR and anti-α1-AR were significantly lower in the positive group after 6 months of carvedilol (all P<0.01, from 100% to 57%, 50%, 49% and from 1:118, 1:138, 1:130 to 1:72, 1:61,1:67 respectively). Of these, 28 patients showed no autoantibodies. Both groups showed improvement left ventricular remodeling and function by carvedilol in combination with standard treatment regime for six months (all P<0.01). However, the 68 patients with three antibodies improved more obviously than 72 negative patients (P<0.01).

Conclusion:
Carvedilol treatment significantly decreased the frequency and geometric mean titer in patients with three autoantibodies, even to complete ablation, and with more improvement in cardiac function and remodeling. Three autoantibodies may be useful biomarker of over-activation of the sympathetic nerves system for clinical medication.
Abstract 13813: Intravascular Vagal Nerve Stimulation in Acute Myocardial Infarction Markedly Reduced Infarct Size and Improved Cardiac Function in the Long Term
Authors: Arimura Takahiro , Saku Keita , Kakino Takamori , Nishikawa Takuya , Tohyama Takeshi , Akashi Takuya , Murayama Yoshinori , Kishi Takuya , Ide Tomomi , Sunagawa Kenji
Published: July 2021

Backgrounds:
In acute myocardial infarction (AMI), the extent of myocardial damage governs the progression to heart failure in the long-term. Therefore, reducing the myocardial damage is prerequisite to prevent chronic heart failure. Although vagal nerve stimulation (VNS) has been repeatedly demonstrated to have the powerful anti-infarct effect, technical difficulties preclude its clinical applications. Recently we developed an new percutaneous, intravascular VNS (iVNS). In this study, we investigated whether iVNS reduces the infarct size and prevents heart failure one month after ischemia reperfusion (IR).

Methods:
In mongrel dogs, we ligated the left anterior descending coronary artery for 3 hours and reperfused. We transvascularly stimulated the right vagal nerve with a pacing catheter in the superior vena cava. We maximized the intensity of iVNS that did not deteriorate hemodynamics (amplitude; 5.1±2.1 V, pulse width; 0.2ms, frequency; 10 Hz). We started iVNS at the onset of ischemia (iVNS0, n=7) or 90 min after the onset of ischemia (iVNS90, n=7) and continued to 60 min after reperfusion. One month after IR, we compared the infarct size, left ventricular (LV) function and hormonal responses among 3 groups including the no treatment group (IR, n=10).

Results:
Both iVNS0 and iVNS90 significantly reduced the infarct size (IR: 11.6±3.1, iVNS0: 2.4±2.1, iVNS90: 4.5±1.9%, p<0.05, Figure), improved LV ejection fraction (IR: 50±7, iVNS0: 61±6, iVNS90: 60±5.1%, p<0.05) and decreased LV end-diastolic pressure (IR: 14.6±1.9, iVNS0: 4.2±1.0, iVNS90: 5.0±2.8mmHg, P<0.05). The benefits were larger in iVNS0 than iVNS90.

Conclusion:
Short term iVNS delivered prior to coronary reperfusion markedly reduced the infarct size and preserved LV function one month after ischemia. Since we can transvascularly deliver iVNS, it may serve as a new non-pharmacological therapeutic strategy and contribute to improve the long term survival in patients with AMI.
Abstract 13864: Associations Between the Amount and Intensity of Physical Activity and Major Cardiovascular Events in Patients With Stable Coronary Heart Disease: Results From the STABILITY Trial
Authors: Stewart Ralph A , Held Claes , Armstrong Paul W , Cannon Christopher P , Hadziosmanovic Nermin , Hagström Emil , Hochman Judith S , Koenig Wolfgang , Lonn Eva , Nicolau Jose , Steg Philippe Gabriel , Watson David , Wallentin Lars , White Harvey D
Published: July 2021

Introduction:
Secondary preventive guidelines recommend patients with stable coronary heart disease (CHD) take at least 30 min of moderate or vigorous physical activity (PA) on at least 5 days/week.

Hypothesis:
Lower levels of PA may be beneficial for cardiovascular (CV) prognosis.

Aim:
To evaluate associations between self-reported PA, including mild intensity exercise and outcomes in a global cohort of patients with stable CHD.

Methods:
A lifestyle questionnaire was completed at baseline by 15,486 (97.8%) STABILITY participants. Total PA was estimated from individual subject self-reports of hours spent each week on mild, moderate and vigorous exercise, 2, 4 and 8 METS respectively. Associations between the total amount of PA and MACE (CV mortality, non-fatal myocardial infarction or non-fatal stroke), CV and non-CV mortality were evaluated using Cox proportional hazard models adjusting for age, gender, treatment allocation, markers of disease severity and CV risk factors during a median follow-up of 3.7 yrs.

Results:
For all subjects, a greater proportion of MET.hours was spent taking mild (50.4%) compared to moderate (39.7%) and vigorous (10.0%) PA. The mean (±SD) PA reported for the ‘sedentary’ (t1, n=5281), ‘mildly active’ (t2, n=5055) and ‘moderately active’ (t3, n=5151) tertiles were t1 12.1±7.4, t2 39.6±7.4 and t3 104.3±45.9 MET.hours/week. Compared to ‘sedentary’ subjects the ‘mild’ and ‘moderate’ PA tertiles had a lower risk of MACE HR 0.96 (95% CI 0.85-1.08) and 0.79 (0.70-0.91), p=0.0019, CV death 0.89 (0.75-1.06) and 0.69 (0.57-0.85), p=0.0019, and non-CV death 0.54 (0.41-0.72) and 0.72 (0.55-0.95), p<.0001. See Figure.

Conclusions:
In patients with stable CHD there is a strong inverse association between self-reported PA and MACE, CV mortality and non-CV mortality. Even modest amounts of mild intensity exercise are associated with lower mortality.
Abstract 13898: Atrial Fibrillation And Persistence With Anticoagulant Treatment
Authors: Forslund Tomas , Wettermark Björn , Hjemdahl Paul
Published: July 2021

Introduction:
Treatment with oral anticoagugulants (OACs) effectively reduces the risk for ischemic stroke, but undertreatment with warfarin has since long been a problem. Three non-vitamin K antagonist oral anticoagulants (NOACs) now provide alternatives to warfarin. The main aim of this study was to assess the overall persistence with OACs and to compare the persistence with different types of OACs in patients with atrial fibrillation and a risk score indicating anticoagulant treatment.

Methods:
All individuals with non-valvular atrial fibrillation and CHADSVASc scores of 2-9 who had a first claim of either warfarin (n=9916 ), dabigatran (n= 2678), rivaroxaban (n= 2062), or apixaban (n= 1340) from April 2011 until December 2014 were identified in the administrative health data register (VAL) of the Stockholm region (2.1 million inhabitants). VAL contains anonymized data regarding diagnoses, age, sex, prescription claims, hospitalizations and other healthcare consultations (including primary care), migration and death. Multivariate analysis was performed adjusting for age, sex, prior anticoagulant treatment, prescriber category, and the total numbers of drugs claimed by the patients.

Results:
The overall persistence with any OAC was 88% (CI 0.87-0.89 ) at one year and 83 % (CI 0.82-0.84) at two years. After one year the crude persistence was 85% with warfarin (CI 0.84-0.86), 86% with apixaban (CI 0.82-0.90), 74% with dabigatran (CI 0.72-0.76), and 77% with rivaroxaban (CI 0.75-0.80). Multivariate analysis confirmed statistically significant differences, with warfarin and apixaban having higher persistence than dabigatran or rivaroxaban .

Conclusions:
The long-term overall persistence to anticoagulant treatment was high in patients with non-valvular atrial fibrillation in the Stockholm region. The results indicate better persistence with warfarin and apixaban than with dabigatran or rivaroxaban in actual care.
Abstract 13957: TNF-α/MiR-133a Involved in Myocardial Leukocytes Infiltration and Cardiac Dysfunction on the Early Phase of Coronary Microembolization
Authors: Chen Zhangwei , Cao Yuanyuan , Qian Juying , Ma Jianying , Zou Yunzeng , Ge Junbo
Published: July 2021

Objectives:
MicroRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level by either degradation or translational repression of a target mRNA. It has been demonstrated that miR-133a plays a critical role on inflammatory response after acute myocardial infarction. However, it is unknown about myocardial expression of miR-133a after coronary microembolization (CME) in mini-pigs.

Methods:
Ten mini-pigs were enroll in this study, including sham-operation group (n=5), CME group (n=7) and adalimumab pre-treatment group (n=6) (TNF-α antibody, 2mg/kg intracoronary injection before CME). Magnetic resonance imaging (3.0-T) was performed at baseline, 6th hour and one week after procedure. Serum TNF-α and troponin T were also detected. Myocardial expressions of miR-133a were detected by realtime-PCR method. Myocardium specimens were embedded in paraffin for hematoxylin and eosin (HE) staining, while number of leukocytes infiltration were analyzed by Leica DFC 320 digital soft.

Results:
Compared with sham-operation group, serum level of troponin T and TNF-α were increased significantly in CME group, while leukocyte infiltration on microembolization associated myocardium was also increased. Interestingly, myocardial expression of miR-133a was increased significantly after CME (2.33±0.62 vs. 1.28±0.68, P<0.05). Cardiac function detected by MRI was decreased in CME group (LVEF at 6th hour: 55.2% vs. 61.4%, P<0.05; LVEF at one week: 56.4% vs. 62.8%, P<0.05). We found that pre-treatment with adalimumab not only significantly improved LVEF after CME (6th hour: 59.3% vs. 55.2%, P<0.05; one week: 60.2% vs. 56.4%, P<0.05), but also decreased myocardial expression of miR-133a (1.36±0.58 vs. 2.33±0.62, P<0.05), which had a positive relation with the average number of leukocytes infiltration on microembolization area (r=0.364, P<0.05) .

Conclusions:
TNF-α/miR-133a expression might be involved in cardiac dysfunction after CME, which was associated with the process of leukocytes infiltration.
Abstract 13962: Large Exome Data Questions the Role of 14 Genes Previously Associated With Dilated Cardiomyopathy
Authors: Nouhravesh Nina , Alhberg Gustav , Weeke Peter E , Olesen Morten S
Published: July 2021

Background:
Dilated cardiomyopathy (DCM) has been associated with hundreds of genetic variants across 62 genes. These associations are now being questioned by large control populations in which these variants are found with high allele frequencies.

Hypothesis:
We hypothesized that genetic variants previously associated with DCM are overrepresented in the population-based ExAC database when taking the prevalence of the disease into account. Hence, we aimed to identify potentially false-positive variants previously associated with DCM.

Methods:
We identified all previously DCM associated variants in The Human Gene Mutation Database (HGMD). We then systematically searched for these in the ExAC database containing exome data on 61.000 individuals. In addition, we performed a PolyPhen-2 prediction on all variants, including those not found in the ExAC database.

Results:
We identified 148 (31%) out of 473 variants previously associated with DCM in ExAC. These variants included eight stop-gain variants, eight splice variants and 132 missense variants. The 148 variants affected 7.928 alleles corresponding to a genotype prevalence of 1:7 in the ExAC population. Thirty-five variants were found in 25 or more alleles, corresponding to a DCM genotype prevalence of 1:8 Furthermore, we identified all variants previously associated with DCM in 14 genes; hereof 4 genes only contained variants above our estimated allele frequency (25:61000). Polyphen-2 analysis predicted 53 (36%) variants to be benign in the ExAC population compared with 53 (16%) among variants not found in ExAC (p<0.001).

Conclusion:
In conclusion, we identified much higher genotype prevalence of previously DCM associated variants than expected in the exome data from ExAC. More importantly we found 4 genes in which all previously identified variants were found with relative high allele frequencies, questioning the association of these genes with the monogenic form of DCM.
Abstract 14026: The Impact of Hemoglobin Drop, Bleeding Events and Blood Transfusion on Long Term Mortality Following Transcatheter Aortic Valve Implantation
Authors: Konigstein Maayan , Havakuk Ofer , Finkelstein Ariel , Ben shoshan Jeremy , Keren Gad , Banai Shmuel
Published: July 2021

Background:
Despite the minimally invasive nature of trans-catheter aortic valve implantation (TAVI), the procedure is associated with several complications. We analyzed the individual impact of bleeding events, hemoglobin (Hb) drop, and Red Blood Cells (RBC) transfusions on prognosis.

Methods and results:
Consecutive patients (n=597) undergoing trans-femoral TAVI were prospectively enrolled. Peri-procedural Hb levels, RBC transfusions and major/life threatening bleeding events were documented and analyzed. To study the relationship between Hb drop, RBC transfusions and long-term mortality, the entire cohort was divided into 4 groups according to Hb drop (less or ≥ than 3 g/dl), and receiving RBC transfusion (yes /no). In the entire cohort mean Hb level decreased following TAVI (11.8±1.4 to 9.5 ±1.3 g/dl; p<0.001). Major/ life threatening bleedings occurred in 66 (10.1%) patients, and 179 (30%) patients received RBC transfusions. Major/life threatening bleedings were not independently associated with mortality when adjusted to Hg drop and RBC transfusion. Among patients with Hb drop of < 3 g/dl, those who received blood transfusion had higher mortality (HR 1.9 CI 1.2-2.9; p=0.004). Among patients with Hb drop of ≥ 3 g/dl, the Hb drop had no significant impact on survival (HR 1.5 CI 0.7-2.9; p=0.2), however, patients that received blood transfusions had a significantly higher mortality (HR 4.1 CI 2.2-7.7; p<0.001).

Conclusion:
Hb drop is frequently observed following TAVI. RBC transfusion is strongly associated with increased long-term mortality in these patients, regardless of the degree of Hb drop.
Abstract 14058: Transvascular Total Left Ventricular Unloading for Acute Myocardial Infarction Strikingly Reduced Myocardial Oxygen Consumption, Limited the Infarct Size and Prevented Heart Failure in the long term
Authors: Arimura Takahiro , Saku Keita , Kakino Takamori , Akashi Takuya , Murayama Yoshinori , Tohyama Takeshi , Nishikawa Takuya , Kishi Takuya , Ide Tomomi , Sunagawa Kenji
Published: July 2021

Backgrounds:
Despite the latest progresses of early reperfusion, myocardial infarction (MI) remains a leading cause of chronic heart failure (CHF). Left ventricular (LV) assist device (VAD) mechanically unloads LV, thus myocardial oxygen consumption (MVO2). Theoretical analysis indicates that the partial VAD (p-VAD) where LV remains ejecting decreases preload (EDV) while increases afterload (ESV), thereby marginally decreases MVO2. In contrast, total LVAD (t-VAD) where LV no longer ejects, markedly decreases ESV as well as EDV, thus markedly reduces MVO2. We examined whether t-VAD in ischemia reperfusion (IR) could reduce the infarct size and prevent heart failure in the long term.

Methods:
First, in normal dogs, we examined the impact of p-VAD and t-VAD on MVO2 by Fick principle (coronary flow and arterial venous O2 difference). Second, we occluded the left anterior descending coronary artery for 3 hours and reperfused. We started transvascular LVAD (Impella®) from 1 hour after ischemia to 1 hour after reperfusion. We compared cardiac function, infarct size and hormones 1 month after ischemia among 3 groups, control group (IR, n=8), p-VAD (n=6), and t-VAD (n=6).

Results:
t-VAD markedly decreased MVO2 (p<0.05, Figure 1). 1 month after ischemia, t-VAD normalized LV end-systolic elastance (IR: 6.5±3.2, p-VAD: 9.7±1.3, t-VAD: 12.8±5.1 mmHg/ml, p<0.05) and reduced LV end-diastolic pressure (16.5±2.7, 6.4±2.9, 4.4±1.5 mmHg, p<0.05), and NT proBNP (3391±1364, 2084±348, 1632±228 pg/ml, p<0.05) indicating the successful prevention of heart failure. t-VAD markedly reduced the infarct size by more than 80% relative to IR (p<0.05, Figure 2) despite the fact that it started 1 hour after the onset of ischemia.

Conclusions:
Transvascular total left ventricular unloading for acute myocardial infarction strikingly reduces the MI size and prevents heart failure in the chronic phase. It might serve as a new therapeutic strategy in the management of patients with acute MI.
Abstract 14103: Lipoprotein (a) is an Important Factor to Determine Myocardial Viability and Left Ventricular Functional Recovery After Acute Myocardial Infarction
Authors: Hayasaka Kazuto , Hikita Hiroyuki , Shigeta Takatoshi , Misawa Toru , Mizusawa Takafumi , Yamakami Yosuke , Kojima Keisuke , Sagawa Yuichirou , Ohtani Hirofumi , Hishikari Keiichi , Yamao Kazuya , Nakashima Emiko , Sugiyama Tomoyo , Nakajima Jun , Takigawa Masateru , Tanaka Yasuaki , Ohkubo Kenji , Kimura Shigeki , Takagi Katsumasa , Kuwahara Taishi , Takahashi Atsushi , Isobe Mitsuaki
Published: July 2021

Introduction:
High serum levels of lipoprotein (a) (Lp(a)) are associated with adverse outcomes after acute myocardial infarction (AMI). Lp(a) exerts its atherogenic and thrombogenic properties, which suggests greater lipid component of plaque and thrombi at the culprit lesion of AMI with elevated Lp(a). The risk of coronary artery disease is increased with a threshold serum Lp(a) level of 25 mg/dl.

Purpose:
We sought to evaluate impact of Lp(a) on myocardial viability and left ventricular function after AMI.

Methods:
The study included 156 patients (66±10.7 yrs, mean±sd, men 122, LAD/LCX/RCA 80/16/60) with first AMI within 24 hours from the onset who underwent emergent PCI. Serum Lp(a) was measured at admission. Serum CPK values were measured at admission and at intervals of 4 hours. Peak CPK value was determined. Within 2 weeks, Tl/BMIPP SPECT was performed to measure perfusion-metabolism mismatch score, an indicator of viable myocardium, from each total defect score of Tl/BMIPP using 17-segment model and semiquantitative visual score (0:normal, to 4:no uptake). Left ventricular ejection fraction (LVEF) was measured by two-dimensional echocardiography (2D trace) within 1 week (baseline LVEF) and at 6 months to 1 year (follow-up LVEF).

Results:
The study patients were divided into the group with serum Lp(a)≧25mg/dl at admission (n=42, Lp(a) 44.0±19.4mg/dl) and the group with Lp(a)<25 (n=114, Lp(a) 10.8±6.5). There were no significant differences between the two groups with respect to age, gender, peak CPK (2732±2060 IU/L (Lp(a)≧25), 2971±2254 (Lp(a)<25)). The mismatch score was significantly lower in Lp(a)≧25 group than in Lp(a)<25 (4.4±3.3 vs 5.9±3.9, p<0.05, respectively). Δ%LVEF (100*(follow-up LVEF - baseline LVEF)/ baseline LVEF) was significantly lower in Lp(a)≧25 than Lp(a)<25 (-2.0±11.0 vs 7.4±13.0, p<0.05, respectively).

Conclusions:
Elevated Lp(a) was associated with less myocardial viability and less LVEF recovery after AMI.
Abstract 14122: Myeloid Cell mPGES-1 Depletion Attenuates Mortality After Myocardial Infarction in Mice
Authors: Chen Lihong , Yang Guangrui , FitzGerald Garret
Published: July 2021

Selective depletion of microsomal PGE2 synthase (mPGES) -1 in myeloid cells retards atherogenesis and suppresses the vascular proliferative response to injury, while it does not predispose to thrombogenesis or hypertension. However, studies using bone marrow transplants from irradiated mice suggest that myeloid cell mPGES-1 facilitates cardiac remodeling and prolongs survival after experimental myocardial infarction (MI). Here we addressed this question using mice lacking mPGES-1 in myeloid cells, particularly macrophages (Mac-mPGES-1 KO), generated by crossing mPGES-1 floxed mice with LysMCre mice, and subjecting them to coronary artery ligation. Cardiac structure and function were assessed by morphometric analysis, echocardiography, and invasive hemodynamics 7 and 28 days after MI. Despite a similar infarct size, in contrast to the prior report, the post-MI survival rate was markedly improved in the Mac-mPGES-1 KO mice compared to WT controls (92.9% vs. 55.6%, p=0.03). Left ventricular systolic (reflected by ejection fraction, fractional shortening, end systolic pressure, and +dP/dt) and diastolic function (reflected by end diastolic pressure, -dP/dt, and Tau), cardiac hypertrophy (reflected by LV dimensions) and staining for fibrosis did not differ between the groups. In conclusion, Cre-loxP mediated deletion of mPGES-1 in myeloid cells has favorable effects on post-MI survival, with no detectable adverse influence on post-MI remodeling. These results add to evidence that targeting macrophage mPGES-1 may represent a safe and efficacious approach to the treatment and prevention of cardiovascular inflammatory disease.
Abstract 14226: Physicians Speak up About Heart Health Awareness and Action: A Women’s Heart Alliance Research Report
Authors: Andersen Holly , Bairey-Merz Noel C , Burns Adam , Walsh Mary N , Greenberger Phyllis , Campbell Susan , Pollin Irene , Brown Nancy , Jenkins Majorie , Redberg Rita , Johnson Paula , Robinson British
Published: July 2021

Introduction:
Cardiovascular disease is the number one killer of women in the US. In November 2014, the Women’s Heart Alliance (WHA) launched a nationwide campaign to increase physician awareness and action toward women’s heart risk.

Methods:
Survey data collection from May 6-12, 2014 used the ERI (Research Now) Physician and Healthcare Professional Panel (HCP), an online invitation-only database based on AMA data and verified. The survey included 200 Primary Care Physicians (PCPs) and 100 cardiologists, currently in practice ≥3 yrs. Overall; ≥33% of PCPs and OB/GYN patients, and ≥21% of cardiologists’ patients were female.

Results:
Heart disease was a top concern for 39% PCPs. Among the AHA guideline-recommended heart risk assessment items for women, 16% of PCPs and 22% cardiologists implemented all eight. Only 22% of PCPs and 42% of cardiologists feel well prepared to assess heart disease risk in women. While a majority of cardiologists and PCPs are aware of the ASCVD Risk Assessment Calculator, current usage is below 50%s in both groups (Figure). A majority of PCPs (87%) and cardiologists (82%) were favorable towards a national campaign.

Conclusions:
Heart disease in women is not a top-tier concern for PCPs or cardiologists. Physician awareness and use of heart risk assessment is low, and a majority are supportive of a national campaign Strategies to improve healthcare provider awareness and action for heart risk assessment practice gaps are needed.
Abstract 14565: Comparative Transcriptomic Analysis of Multiple Cardiovascular Fates From Embryonic Stem Cells Predicts Regulatory Genes, Alternative Splicing and Long Non-coding RNAs in Human Cardiogenesis
Authors: Li Yang , Lin Bo , Yang Lei
Published: July 2021

Introduction:
Dissecting the gene expression programs which control the early stage cardiovascular development is essential for understanding the molecular mechanisms of human heart development and heart disease. Many lineage-specific genes are involved in the differentiation into specific cell fate.

Hypothesis:
The lineage-specificity of the genes may predict regulatory potential during human cardiovascular differentiation.

Methods:
Here, we performed transcriptome sequencing (RNA-seq) of highly purified human Embryonic Stem Cells (hESCs), hESC-derived Multipotential Cardiovascular Progenitors (MCPs) and MCP-specified three cardiovascular lineages. A novel algorithm, named as Gene Expression Pattern Analyzer (GEPA), was developed to obtain a refined lineage-specificity map of all sequenced genes, which reveals dynamic changes of transcriptional factor networks underlying early human cardiovascular development.

Results:
The GEPA predictions captured ∼90% of top-ranked regulatory cardiac genes that were previously predicted based on chromatin signature changes in hESCs, and further defined their cardiovascular lineage-specificities, indicating that our multi-fate comparison analysis could predict novel regulatory genes. Furthermore, GEPA analysis revealed the MCP-specific expressions of genes in ephrin signaling pathway, positive role of which in cardiomyocyte differentiation was further validated experimentally. By using RNA-seq plus GEPA workflow, we also identified stage-specific RNA splicing switch and lineage-enriched long noncoding RNAs during human cardiovascular differentiation.

Conclusions:
Overall, our study utilized multi-cell-fate transcriptomic comparison analysis to establish a lineage-specific gene expression map for predicting and validating novel regulatory mechanisms underlying early human cardiovascular development.
Abstract 14619: Ultrasound-stimulated Microbubbles for Drug/gene Delivery: Microbubble-generated Shear Stress Induces Pores in Cellular Membranes
Authors: Helfield Brandon , Qin Bin , Chen Xucai , Villanueva Flordeliza
Published: July 2021

Background:
Ultrasound (US)-stimulated microbubbles (MBs) are emerging as novel target-specific non-viral gene/drug delivery vectors for treatment of vascular disease, e.g. to deliver VEGF plasmid DNA to promote arteriogenesis. The nature of the MB-target cell interactions that facilitate nucleic acid delivery across cell membranes, and hence strategies to optimize the efficiency of this platform, are poorly understood. The objective of this study was to gain mechanistic insight into MB-mediated increases in cell membrane permeability.

Methods:
Phospholipid coated MBs were allowed to lay adjacent to cultured human umbilical vein endothelial cells (HUVEC) at 37C. Propidium iodide (PI) was put into the media before US exposure to assess membrane permeability (sonoporation). Individual MB-cell pairs (n=351) were exposed to a single US pulse at 0.5, 1, or 2 MHz, with a duration of 4, 8 or 16 μs and pressures 0.1-0.8 MPa. Ultrafast microscopy recorded MB oscillations (Fig. 1a); a second camera simultaneously recorded fluorescence (PI uptake, Fig. 1b). US-induced MB radius change (excursion) was measured and used to calculate shear stress. HUVEC membranes were fluorescently labeled to visualize pore features.

Results:
Absolute MB excursion distance and associated shear stress were strong threshold indicators of sonoporation (PI uptake). For an 8 μs pulse, the oscillation (shear stress) threshold above which HUVECs porate was 3.9, 2.6, and 1.4 μm (7.8, 14.5, 22.7 kPa) at 0.5, 1 and 2 MHz respectively. At a given US frequency, increases in pulse duration decreased the required excursion and shear stress. Cell membrane imaging showed that MBs can induce apical and basal pores (sub-μm to μm sizes) that reseal (Fig. 1c).

Conclusions:
Sonoporation is related to absolute MB excursion distance and its associated shear stress and can occur with various US parameters and MB sizes. This data has implications on intelligent US-MB design for their use as payload delivery vehicles.
Abstract 14621: Whole Body Periodic Acceleration (pGz) Induces Anti-Inflammatory Signaling in Brain After Hypoxic Injury
Authors: Adams Jose A , Pastuszko Anna , Pastuszko Peter , Wilson David , Nadkarni Vinay
Published: July 2021

Introduction:
Asphyxia is the most common cause of cardiac arrest in children, with devastating complications. Asphyxia Cardiac Arrest (ACA) is associated with a generalized systemic inflammatory response, in addition brain injury after cardiac arrest (CA) has been shown to have an inflammatory component. Effective neuroprotective strategies are desperately needed. pGz is a method which moves the body in a repetitive head to foot motion increasing pulsatile shear stress, inducing endothelial nitric oxide (eNO) and increasing microvascular flow to brain, heart and other vital organs. We have shown that pGz applied as a preconditioning (pre-treatment) prior to brain hypoxia ischemia, induces increase in brain anti-apoptotic proteins, and modulated the inflammatory response.

Hypothesis:
The objective of this study was to determine whether pGz post-treatment after ACA, also modifies pro inflammatory brain regulatory proteins.

Methods:
Twelve anesthetized neonatal piglets (weight 2.5-3 kg) were subjected to 30 min of 7% FiO2, followed by 7 min of Apnea and resuscitation with recovery in 21% FiO2. Animals were randomly assigned to; recovery for 3 hr (Hyp-Cont) or recovery with pGz beginning 30min after hypoxia for 3 hr (pGz). Another group(Sham) had surgery and anesthesia but no hypoxia. Protein expression of IL-1β, IL-6, TNFα, eNOS, and p-eNOS in cortex were meassured.

Results:
Hypoxia induced a 38%, 74% and 10% increase from Sham in IL-1β, IL-6, TNFα respectively. In contrast pGz treated animals only had a 4%, 21% increase in IL-1β, IL-6, and a 14% decrease in TNFα from Sham. Activation of eNOS (p-eNOS/eNOS) doubled in pGz treated. Figure [Mean (± SD)*p< 0.01].

Conclusion:
pGz post resuscitation in a piglet model of ACA decreases brain pro-inflammatory regulatory proteins. The latter, taken together with pGz’s induction of anti-apoptotic signaling proteins, suggest that pGz can be a simple, novel neurotherapeutic strategy when applied after cardiac arrest.
Abstract 14749: Extra-cardiac Mitral Valve Repair - Experience With the Adjustable BACE Device
Authors: Raman Jaishankar , Beaver Thomas , Talluri Krishna
Published: July 2021

Introduction:
Functional mitral regurgitation (MR) is primarily due to abnormalities of the ventricular muscle in the presence of normal mitral leaflets. Present surgical treatment, repair or replacement, address the mitral valve annulus and leaflets, not the ventricular muscle. We describe our early and mid-term clinical experience with extra-cardiac treatment of MR with a novel, device that is implanted on a beating heart and can be adjusted remotely.

Hypothesis:
Evaluation of efficacy and outcomes

Methods:
Between Dec, 2008 and June, 2015, thirty one patients (mean age 59 years) with functional and ischemic MR were evaluated at 9 multi-national centers. All patients had severe MR (Mean MR grade 3.1) on trans-thoracic and/or trans-esophageal echocardiography, and impaired LV function (Mean EF 33.6%). Risk assessment by Logistic Euroscore was16.58%. Patients underwent implantation of a custom made BACE (Basal Annuloplasty of the Cardia Externally) device, along with CABG (mean 2.5 grafts per patient). The device was placed at the base of the heart, overlapping the atrial and ventricular surfaces of the atrio-ventricular groove circumferentially. All procedures were performed on a beating heart with the majority of them performed off-pump. Intra-operative trans-esophageal echocardiography allowed customized inflation of specific chambers to selectively deform the annulus and sub-annular myocardium. Two patients required delayed peri-operative adjustment of the BACE device.

Results:
The degree of MR improved from a mean of 3.1 to 0.9. This >2 class improvement in MR was sustained over the 12 month follow up period in all patients. Moderately severe TR in 3 patients went down to trivial. There was one peri-operative death associated with balloon related leg ischemia. One device was explanted early at re-exploration for bleeding. There were no device related complications.

Conclusions:
Ischemic functional mitral valve regurgitation can be treated by epicardial implantation and dynamic adjustment of the BACE device. This technique has significant implications in the treatment of ischemic functional MR without entering the heart, with the added ability to remotely adjust the device.
Abstract 14757: Prognostic Significance of Tissue Oxygen Saturation Using Near Infrared Spectroscopy in Patients Undergoing Therapeutic Hypothermia After Cardiac Arrest
Authors: Bell Adrian , Qureshi Ataul , Awuor Stephen O , Nair Sanjeev , Enoh Agei , Makowski Daniel , Curtis Charity , Patel Nainesh C , Feldman Bruce A
Published: July 2021

Background:
Near infrared spectroscopy is a noninvasive method for assessing regional tissue oxygenation (StO2), a parameter influenced by microvascular perfusion. Normal StO2 values recorded from the thenar eminance are 87% ± 6%. In critically ill patients, low StO2 levels (<70%) have been associated with a poor prognosis. We evaluated the prognostic significance of StO2 in patients undergoing therapeutic hypothermia (TH) after cardiac arrest (CA).

Hypothesis:
After resuscitation from CA, an initial StO2 ≥70%, or an initial StO2 <70% followed by an upward trend, is associated with a good neurologic outcome.

Methods:
We conducted a retrospective analysis of CA patients who underwent TH between August, 2005 and June, 2013. StO2 levels at the thenar eminence were collected at the onset and hourly during TH. Neurological outcome was assessed by the Cerebral Performance Category (CPC) at hospital discharge. Good outcome was defined as survival to hospital discharge with a CPC ≤2. Univariate and multivariate analyses were performed.

Results:
Among 160 patients, 18% (n=29) survived with a CPC ≤2. Survival with a CPC ≤2 was associated with witnessed CA (p=0.04; OR 11.6; 95% CI 1.1-118.0), shockable rhythm (p=0.02; OR 3.4; 95% CI 1.2-9.3), time to return of spontaneous circulation (ROSC) ≤15 minutes (p=0.02; OR 4.5; 95% CI 1.2-16.6) and age <65 (p=0.001; OR 7.6; 95% CI 2.3-25.5). However, an initial StO2 ≥70% was not associated with a CPC ≤2 (P=0.7; OR 0.82; 95% CI 0.29-2.2). For patients with an initial St02 <70%, there was no difference in outcome between those with an upward trend vs downward trend in St02 (p=0.98).

Conclusions:
Similar to previous trials documenting the value of TH witnessed CA, shockable rhythm, short time to ROSC, and younger age were associated with a good neurologic outcome. StO2 levels recorded from the thenar eminence were not associated with neurologic outcome. These StO2 levels are influenced by regional perfusion and tissue oxygenation but may not reflect cerebral microvascular perfusion. Identifying alternative technologies to assess cerebral microvascular perfusion may help determine patients for whom a good neurologic outcome can be predicted.