bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11776: The Questionable Clinical Impact of Routine Pre-operative Cardiology Consultation Prior to Vascular Surgical Procedures
Authors: Henke Peter , Park Yeo Jung , Eliassen Anna , Mansour Ash , Jain Krishna , Nypaver Tim , Grossman Paul , Gurm Hitinder
Published: July 2021

Objective:
No significant evidence basis exists for who and when a preoperative cardiac consultation should be obtained. We sought to define the variation in preoperative cardiology for patients requiring a vascular surgical procedure and determine whether this was associated with differences in perioperative myocardial infarction (poMI) or death.

Methods:
A 29 hospital statewide QI collaborative were queried for open aortic aneurysm repair, EVAR, and open vascular bypass procedures. Preprocedure documented cardiac consultation as well as stress testing was determined as part of the database. The primary outcome was poMI and death.

Results:
Among 5191 patients, 48% had a documented preoperative cardiac cardiology consultation, with the poMI rate of 2.1% and a 1.3% death rate. Across hospitals, preoperative cardiac consultation varied from <10% to over 85%, and was not dependent on the procedural volume, academic versus community status , or hospital size. Cardiology consultation rates correlated with stress test usage (Pearson ρ = 0.6; p < .001). Stratification of patients by the Revised Cardiac Risk Index (RCRI) categories showed consultation varied significantly by classification; RCRI=1; 38% had preoperative cardiology consult rate versus an RCRI =4; 66% had a cardiology consult. After stratification by RCRI, there was no association between cardiac consultation use and lower postoperative MI rate (Table) or death rate. Moreover, use of preoperative cardioprotective medications was not more common in those hospitals with high (> 50%) cardiology consultation rates as compared to lower consultation hospitals.

Discussion:
Preoperative cardiology consultation for vascular surgical patients varies greatly between institutions. Cardiology consultation was not associated with better utilization of cardioprotective medications nor was it associated with a lower incidence of death or myocardial infarction.

MI Frequency by Cardiac Consultation
Abstract 11816: Sustained Ventricular Fibrillation During CPR as the Strongest Predictor for the Favorable Neurological Outcomes in Out-of-hospital Cardiac Arrest Patients; The Multicenter Prospective Study of SAVE-J
Authors: Nakashima Takahiro , Tahara Yoshio , Yasuda Satoshi , Morimura Naoto , Nagao Ken , Asai Yasufumi , Yokota Hiroyuki , Hase Mamoru , Atsumi Takahiro , Sakamoto Tetsuya ,   SAVE-J Study Group
Published: July 2021

Introduction:
Extracorporeal cardiopulmonary resuscitation (ECPR) has been reported to be effective in out-of-hospital cardiac arrest (OHCA) patients in whom ventricular fibrillation (VF) as an initial rhythm were refractory to conventional cardiopulmonary resuscitation (CPR). However, it remains unclear whether ECPR is effective even though cardiac rhythm would change from VF to non-VF during CPR.

Methods:
This multicenter prospective observational study was conducted in 46 hospitals. A total of 457 patients with OHCA aged 20-74 years in whom initial rhythm was VF and the duration from collapse to hospital arrival was within 45 minutes were originally registered. After given CPR for more than 15 minutes in hospital, these patients received combination therapy with ECPR including therapeutic hypothermia (TH), or not received. The patients underwent ECPR (n=250) were classified into the following 2 groups according to rhythm changes during CPR; Group-A (sustained VF; n=127) and Group-B (changing from VF initially to non-shockable rhythm; n=123). The endpoint was a favorable outcome defined as Cerebral Performance Category 1-2 at 6 months after collapse.

Results:
There were no significant differences of age, sex, time from collapse to ECPR start and the rate of TH between the 2 groups. The rate achieving favorable outcome was significantly higher in Group-A than Group-B. (19.7% vs. 3.3%, p<0.001) (Figure1). When focusing on sustained VF (Group-A), the rate achieving favorable outcome improved about 5.5-fold by ECPR (ECPR, n=127; 19.7% vs. non-ECPR, n=55; 3.6%, p<0.001) (Figure2). In the multivariate logistic-regression analysis, sustained VF during CPR was the strongest predictor for the favorable outcomes among the pre-hospital parameters including age, bystander CPR and time from collapse to ECPR (Odds ratio 4.43, p=0.018).

Conclusions:
These findings indicates that the patients with sustained VF seem to be a particular population that could merit ECPR.
Abstract 11878: Bendavia, a Novel Mitochondria Targeting Peptide, Improves Mitochondrial Function in Circulating Blood Monocytes From Dogs With Chronic Heart Failure
Authors: Sabbah Hani , Sing-Gupta Vinita , Gupta Ramesh C
Published: July 2021

Introduction:
We previously showed that mitochondrial (MITO) function of the failing heart is abnormal as evidenced by reduced MITO respiration and reduced MITO ATP synthesis. We also showed that this abnormality extends to MITO of circulating blood monocytes (MCs). Therapy with Bendavia, a novel MITO targeting peptide, has been shown to normalize MITO function of failing cardiomyocytes.

Hypothesis:
Bendavia will also normalize abnormalities of MITO function of MCs of dogs with chronic heart failure (HF).

Methods:
Peripheral blood samples were obtained from 6 normal (NL) dogs and 6 dogs with coronary microembolizations-induced HF (LV ejection fraction ~30%) and used to isolate MCs by sequential Ficoll and Percoll density gradients. An XFe/XF96 analyzer (Seahorse Bioscience) was used to measure oxygen consumption rates (OCR) in MCs in the presence and absence of 1 μM oligomycin, 0.5 μM FCCP, or 1 μM each rotenone and antimycin. MITO proton leak, maximal respiration (MAXresp), and spare respiratory capacity (SRC) were measure in the presence and absence of 0.1, 1.0 and 10 μM concentrations of Bendavia and results expressed in pmols OCR/min/μg protein.

Results:
Proton leak, MAXresp and SRC were abnormal in MCs of HF dogs compared to NL dogs. Incubation with Bendavia had no effect on any of the measures of MCs MITO function of NL dogs (Table). In contrast, MITO function of MCs from HF dogs was nearly normalized after treatment with Bendavia (Table).

Conclusions:
MITO function is abnormal in circulating blood MCs of dogs with HF. Bendavia had no effect on MITO function of MCs from NL dogs. Treatment with Bendavia of MCs from HF dogs elicited a dose-dependent correction/normalization of MITO function. These findings support the use of circulating blood MCs as means of assessing MITO dysfunction in HF and as a marker of potential benefits derived from treatment with MITO targeted therapies.
Abstract 11900: Influence of Competing Risks on the Association Between Warfarin and Ischemic Stroke in Atrial Fibrillation: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study
Authors: Ashburner Jeffrey M , Go Alan S , Chang Yuchiao , Fang Margaret C , Fredman Lisa , Applebaum Katie M , Singer Daniel E
Published: July 2021

Introduction:
Studies examining the association between warfarin therapy and incidence of ischemic stroke in adults with atrial fibrillation (AF) have not accounted for patients who die of non-stroke causes.

Hypothesis:
Accounting for the competing risk of death may provide greater understanding of the “real world” impact of warfarin on stroke risk during multiyear follow-up in a large, diverse cohort of AF patients.

Methods:
We assessed this association in the ATRIA community-based cohort of AF patients (n=13,559; study years 1996-2003), with thromboembolic (>90% ischemic stroke) events (TEE) being clinician-adjudicated. Extended Cox proportional hazards regression with time-varying warfarin exposure estimated the cause-specific hazard ratio (HR) for TEE while adjusting for stroke risk factors. Fine and Gray subdistribution regression was used to estimate this association while also accounting for competing death events.

Results:
Patients using warfarin were younger, more likely to have had a prior stroke, and to have known diabetes, coronary disease, and heart failure, and also had higher mean CHA2DS2VASc scores (3.68 vs. 3.22). The death rate was much higher in the non-warfarin group (8.1 deaths/100 person-years; 2637 deaths vs. 5.5 deaths/100 person-years; 1777 deaths on warfarin). The cause-specific HR indicated a large reduction in TE with warfarin use (adjusted HR: 0.57, 95% CI: 0.50-0.65). In subdistribution hazard models accounting for competing death events over the full follow-up of 6 years, this association was substantially attenuated (adjusted HR: 0.87, 95% CI: 0.77-0.99). In analyses limited to 1-year follow-up with only 648 competing death events, the results without accounting for competing risks (adjusted cause-specific HR: 0.55, 95% CI: 0.43-0.71) were similar to the results that did account for competing risks (adjusted subdistribution HR: 0.59, 95% CI: 0.46-0.75).

Conclusions:
By accounting for competing death events, our results reflect a more realistic estimate of the multi-year stroke prevention benefits of warfarin for patients with AF. Many old/frail individuals with AF will not live long enough to gain substantial benefit from warfarin.
Abstract 11973: Clinical Outcome and Predictors of Short-term Mortality in Cardiogenic Shock Treated With Venous-arterial Extracorporeal Membrane Oxygenation: Results From the Japanese Circulation Society Cardiovascular Shock Registry
Authors: Ueki Yasushi , Imamura Hiroshi , Miyamoto Takahiro , Yagi Tsukasa , Sakamoto Kazuo , Takahashi Hiroshi , Hanada Hiroyuki , Tachibana Eizo , Yonemoto Naohiro , Nagao Ken
Published: July 2021

Introduction:
Venous-arterial extracorporeal membrane oxygenation (ECMO) should be considered as a means of rescuing patients with refractory cardiogenic shock and cardiac arrest. Few data are available regarding predicting the outcome of patients with cardiogenic shock treated with ECMO. The aim of this study was to investigate the outcomes of patients with cardiogenic shock assisted by ECMO and to identify the predictors of 30-day mortality.

Methods:
The Japanese Circulation Society Cardiovascular Shock registry is a prospective, observational, multi-center, cohort study. Between May 2012 and June 2014, a total of 980 patients with cardiovascular shock were enrolled from 82 centers in Japan. Finally, 162 patients (mean age 60.2±14.7 years, 81.5% male) required ECMO and completing 30-day follow-up were analyzed. The primary endpoint was all-cause death at 30 days.

Results:
Of 162 patients, 80 (49.7%) were shock after return of spontaneous circulation (ROSC) and 102 (63%) had acute coronary syndrome (ACS). The 30-day mortality overall, the non-shock after ROSC group, and the ACS group were 69.1%, 59.3%, and 68.6%, respectively. The causes of death were heart failure in 30 patients (26.8%), multiple organ failure in 49 (43.8%), respiratory failure in 2 (1.8%), sepsis in 2 (1.8%), arrhythmia in 12 (10.7%), neurological death in 8 (7.1%), and others in 9 (7.6%). On multivariate analysis, neurological status on admission (odds ratio 2.188, 95% confidence interval 1.23-3.66, p=0.007) was an independent predictor of all cause death at 30-days.

Conclusion:
Patients with cardiovascular shock who required ECMO demonstrated high mortality. Neurological status was an independent predictor of 30-day mortality.
Abstract 12000: Altered Vascular Elasticity Reflected Vascular Endothelial Dysfunction and Elevated Galectin-3 Using Novel Brachial Artery Vascular Volume Elastic Modulus With Automated Oscillometric Approach
Authors: Yoshinaga Keiichiro , Tomiyama Yuuki , Fujii Satoshi , Nishio Saori , Ochi Noriki , Katoh Chietsugu , Inoue Mamiko , Nishida Mutumi , Takeuchi Keisuke , Ito Yoichi M , Tamaki Nagara
Published: July 2021

Introduction:
Simple vascular function measurements are desirable for atherosclerosis risk assessments. Recently, we developed a novel modality of automated oscillometric method to measure a brachial artery’s vascular elastic modulus (V
E
) and reported that V
E
is uninfluenced by blood pressure. Galectin-3 (Gal-3) expressed in endothelial cells regulates vascular fibrosis and is a molecular determinant of vascular stiffness.

Hypothesis:
We aimed to clarify whether V
E
selectively correlates with marker of vascular stiffness in chronic kidney disease (CKD).

Methods:
12 moderate-to-severe CKD pts (mean eGFR 25.9±23.5 mL/min/1.73m
2
) and 15 controls were studied. Rest V
E
in brachial artery was measured by new automated oscillometric detector. V
E
was defined as follows [VE =ΔPressure/ (100XΔarea/Area) mmHg/%]. Using ultrasound, the brachial artery diameter at rest and during reactive hyperemia [flow mediated dilatation (FMD) with endothelial-dependent dilatation] was measured. Gal-3 and interleukin-6 (IL-6), a representative inflammatory marker, were measured by enzyme-linked immune assay.

Results:
CKD had lower FMD (4.86±3.37 vs 9.05±2.98 %, P=0.003) and had attenuated V
E
than control (1.08±0.26 vs 0.83±0.17 mmHg/%, P=0.002). CKD had higher IL-6 (0.67±0.29 vs 0.29±0.33 pg/mL, P=0.003) and higher Gal-3 (20.0±12.4 vs. 5.84±2.83 pg/mL, P<0.001). V
E
was negatively correlated with %FMD (r=-0.46, P=0.015) and correlated with Gal-3 (r=0.40, P=0.036) but not in IL-6 (r=0.21, P=0.28).

Conclusions:
Attenuated vascular elasticity detected by this novel approach closely correlated with increase in Gal-3 and reduced FMD in CKD. This may indicate that the attenuated vascular elasticity selectively reflects vascular fibrosis as evidenced by Gal-3 and subsequent endothelial responses to vascular stiffness. Thus, this oscillometric measurement may be useful for detecting vascular fibrosis information and dysfunction in endothelium level.
Abstract 12059: Incidental Findings in Cardiomyopathy and Channelopathy Genes Among 5891 Individuals Undergoing Whole-exome Sequencing. What Should be Reported?
Authors: Mastantuono Elisa , Wieland Thomas , Berutti Riccardo , Lichtner Peter , Strom Tim , Meitinger Thomas , Crotti Lia
Published: July 2021

Background:
Whole-exome-sequencing (WES) is becoming a common molecular diagnostic test for patients with genetic disorders. However, this technique allows the identification not only of mutations responsible for the disease under investigation, but also of variants potentially causing other diseases, the so called “incidental findings” (IFs).

The American College of Medical Genetics and Genomics (ACMG) stated that IFs should be reported based on clinical validity and utility and indicated a list of 56 actionable genes. Among these, nearly half (20/56) are major genes associated with channelopathies and cardiomyopathies. Despite these recommendations, most of the studies so far published, reported also mutations in minor genes among the actionable findings.

Methods:
WES was performed in 5891 individuals without known channelopathies or cardiomyopathies. Exome data were first filtered based on genotype quality. Subsequently, a frequency filter was applied, considering 1000 Genomes, ExAC and our internal exome database. Variants reported as pathogenic in ClinVar or novel but expected to be pathogenic (nonsense, frameshift and splice) were further investigated, following the ACMG guidelines. Major (20) and minor (73) genes associated with channelopathies and cardiomyopathies were evaluated.

Results:
We identified 3514 variants in the 93 genes under investigation, after applying the quality and frequency filters. Eight variants were classified as pathogenic and 52 as likely pathogenic and they were detected in around 1% of the individuals. The vast majority (85%) of pathogenic or likely pathogenic variants were located in the 20 actionable genes indicated by ACMG. The inclusion of minor genes increased the number of variants of unknown significance (VUS), from 865 to 3454.

Conclusion:
Our data support the ACMG recommendations in reporting only IFs identified in the 20 major cardiac actionable genes. Indeed, the inclusion of minor genes is mainly increasing the number of VUS, without significantly impacting the number of pathogenic and likely pathogenic variants. The percentage of individuals with potentially clinical relevant variants in these genes is too high in relation to the disease-prevalence: a cardiologic evaluation is warranted.
Abstract 12162: Association of Symptom Clusters With Mode of Transportation to Emergency Department in Patients Diagnosed With Acute Coronary Syndrome
Authors: Davis Leslie L , McCoy Thomas P , Riegel Barbara , McKinley Sharon , Doering Lynn , Dracup Kathleen , Moser Debra
Published: July 2021

Background:
Prompt treatment of acute coronary syndrome (ACS) has been shown to reduce mortality and morbidity; yet many patients delay seeking care. In order to receive timely care, symptoms of ACS need to be recognized, interpreted, and acted upon. Patients who experience symptoms matching their expectations and those with correct symptom attribution are more likely to use emergency medical services (EMS) as a means of transportation to the hospital. The connection between symptom type and EMS use has not been fully explored.

Purpose:
To assess if clusters of presenting symptoms are associated with EMS transportation to the emergency department (ED) in patients with ACS and to evaluate if EMS transportation or symptom clusters are associated with prehospital delay time.

Methods:
A secondary analysis was conducted from the PROMOTION trial, a randomized controlled trial to reduce patient prehospital delay in ACS.

Results:
Of the 3,522 subjects with coronary artery disease enrolled, 3,087 completed 2-year follow-up. Of these, 331 subjects visited an ED for ACS symptoms during follow-up. Among the 331, 84% (278) had mode of transportation documented; 44% arrived by EMS. Having classic ACS symptoms (chest pain, pressure, or discomfort) in combination with pain symptoms (AOR=2.66, p = 0.011), classic ACS symptoms in combination with stress symptoms (AOR=2.61, p = 0.007) or classic ACS symptoms in combination with both pain and stress symptoms (AOR=3.90, p = 0.012) were associated with higher odds of arriving to the ED by EMS compared to classic ACS symptoms alone. Among 260 patients with prehospital delay time available, arriving by EMS decreased median delay time by 68.5 minutes compared to those with other transportation, after accounting for symptom clusters, patient and study characteristics (p = 0.002). Symptom clusters did not predict delay time in adjusted modeling (p = 0.952).

Conclusion:
While chest pain was the most prevalent symptom of ACS for most (85%), these findings suggest that it is the cluster of classic ACS symptoms with other types of symptom that motivate patients to use EMS. With less than half of patients using EMS, further research is needed to better understand how symptom clusters influence care-seeking behavior.
Abstract 12208: Microrna-181b Inhibits Thrombin-mediated Activation of Endothelial Cells and Arterial Thrombosis by Targeting Card10
(Best of Basic Science Abstract)
Authors: Sun Xinghui , Lin Jibin , He Shaolin , Franck Gregory , Wara AKM , Icli Basak , Li Dazhu , Feinberg Mark W
Published: July 2021

Objective:
Thrombogenic and inflammatory mediators such as thrombin induce NF-kB-mediated EC activation and dysfunction, which contribute to the pathogenesis of arterial thrombosis. The role of the anti-inflammatory microRNA-181b (miR-181b) on thrombosis remains unknown.

Methods and Results:
It has been demonstrated that miR-181b inhibits downstream NF-kB signaling in response to TNF-a. Herein, we reveal that miR-181b can inhibit upstream NF-kB signaling uniquely in response to thrombin. Overexpression of miR-181b inhibited thrombin-induced activation of NF-kB signaling demonstrated by the reduction of phospho-IKK-b, -IkB-a, and p65 nuclear translocation in ECs. MiR-181b also reduced the expression of NF-kB target genes VCAM-1, ICAM-1, E-selectin, PAI-1, and tissue factor. Mechanistically, miR-181b targets Card10, an adaptor protein that participates in the activation of the IKK complex in response to signals transduced from G-protein coupled receptors such as PAR-1. MiR-181b reduced the expression of Card10 mRNA and protein, but not PAR-1. In addition, miR-181b inhibited Card10 3’-UTR luciferase reporter activity, and Argonaute-2 miRNP-IP studies revealed 4-fold enrichment of Card10 mRNA in the RNA-induced silencing complex in the presence of miR-181b, indicating that Card10 is a bona fide direct target. SiRNA-mediated knockdown of Card10 expression phenocopied miR-181b’s effects on NF-kB signaling and targets. Interestingly, knockdown of Card10 does not affect TNF-a-induced activation of NF-kB signaling and target gene expression, suggesting stimulus-specific regulation of NF-kB signaling and endothelial responses by miR-181b in ECs. Finally, in response to photochemical injury-induced arterial thrombosis, systemic delivery of miR-181b reduced thrombus formation by 73% in carotid arteries, and prolonged the time to occlusion by 1.6-fold.

Conclusions:
MiR-181b is an important regulator of thrombin-induced EC activation and arterial thrombosis. These studies highlight the relevance of miRNA-dependent targets in response to ligand-specific signaling in ECs. Delivery of miR-181b or Card10 inhibition may represent a new therapeutic approach to reduce arterial thrombosis by improving vascular EC function.
Abstract 12231: PECAM1 is Essential for Flow-mediated Gab1 Tyrosine Phosphorylation and Signaling
in vitro
and
in vivo
Authors: Xu Suowen , Koroleva Marina , Fujiwara Keigi , Jin Zheng Gen
Published: July 2021

Introduction:
Impaired activation of endothelial nitric oxide (NO) synthase (eNOS) and ensued NO production is a common mechanism of various cardiovascular pathologies, including hypertension and atherosclerosis. Specific signaling cascades, generated by vascular endothelial cells (ECs) in response to laminar flow, modulate EC structure and functions, NO production in particular. We have previously shown that flow-stimulated Gab1 (Grb2-associated binder-1) tyrosine phosphorylation mediates eNOS activation. However, the upstream mechanism that regulates Gab1 tyrosine phosphorylation remains unclear.

Hypothesis:
We hypothesized that platelet endothelial cell adhesion molecule-1 (PECAM1), a key molecule in an endothelial mechanosensing complex, specifically mediates Gab1 tyrosine phosphorylation and its downstream Akt and eNOS activation in ECs upon flow rather than hepatocyte growth factor (HGF) stimulation.

Methods:
Western blot,
en face
staining and voluntary wheel running.

Results:
Small interfering RNA (siRNA) targeting PECAM1 abolished flow- but not HGF-induced Gab1 tyrosine phosphorylation and Akt, eNOS activation as well as Gab1 membrane translocation. Protein-tyrosine phosphatase SHP2, which has been shown to interact with Gab1, was involved in a flow signaling pathway as well as HGF-induced signaling, as SHP2 siRNA diminished the flow- and HGF-induced Gab1 tyrosine phosphorylation, membrane localization and downstream signaling. Pharmacological inhibition of PI3K by LY294002 decreased flow, but not HGF-mediated Gab1 phosphorylation and membrane localization as well as eNOS activation. Finally, we observed that flow-mediated Gab1 and eNOS phosphorylation
in vivo
induced by voluntary wheel running was reduced in PECAM1 knockout mice.

Conclusions:
These results demonstrate a specific role of PECAM1 in flow-mediated Gab1 tyrosine phosphorylation and eNOS signaling in ECs
Abstract 12274: Endothelium-specific Deletion of Epsins Attenuates Atherosclerosis Through Maintaining ER Homeostasis
Authors: Dong Yunzhou , Rahman Ashiqur , Liu Xiaolei , Wu Hao , Brophy Megan , Chen Hong
Published: July 2021

Epsins are endocytotic proteins for the internalization of plasma membrane receptors. Our previous studies have suggested that epsins play an important role in tumorigenesis and lymphatic development by modulating VEGFR2, VEGFR3 or Wnt signaling. Whether epsins affect atherosclerosis remains unknown. In an ApoE-deficient murine model, endothelial-specific double knockout mice (EC-iDKO/ApoE-/-) significantly attenuated atherosclerotic lesion and macrophage infiltration in aortic root and aortic arch compared to ApoE-/- mice fed Western diet for ten weeks. Endothelium-dependent relaxation is significantly improved in epsin-deficient mice. Mechanistically, the expression of epsins is upregulated in atheroma and mouse endothelial cells in a pro-inflammatory condition, mirrored in human atherosclerotic specimen. Proteomics study using Mass spectrometry revealed that epsins bind IP3R1 and facilitate its degradation in endothelium under inflammatory condition. Downregulation of IP3R1 by athero-prone substances augmented ER stress and NFkB signaling, reversible by ER stress inhibitor 4-PBA. In line with the findings from mouse studies, IP3R1 is dramatically downregulated in human atherosclerotic endothelium. Loss of epsins stabilized IP3R1, and attenuated ER stress-dependent NFkB activation and inflammatory signaling as evidenced by the reduced expression of P-selectin, adhesion molecules, and chemoattractant MCP-1 in primary mouse aortic endothelial cells (MAEC), and reflected by in vitro rolling analysis between isolated MAEC and macrophage from mouse. Molecular modeling and mapping analysis revealed that epsin UIM is critical to facilitate the degradation of IP3R1. In conclusion, we have identified a novel molecular mechanism regarding epsins in the regulation of atherosclerosis, and our data suggest that epsins are a potential target to treat atherosclerosis.
Abstract 12322: Physical Symptoms and Depression Interact in Predicting Quality-of-Life in Heart Failure
Authors: Denfeld Quin E , Mudd James O , Hiatt Shirin O , Gelow Jill M , Chien Christopher V , Lee Christopher S
Published: July 2021

Introduction:
Quality-of-life (QOL) is an important patient-oriented outcome in heart failure (HF). The interaction effect of physical symptoms and depression in predicting QOL in HF, however, is not well understood.

Hypothesis:
There is a strong interaction effect between physical symptom and depression in predicting QOL among adults with moderate to advanced HF.

Methods:
This was a secondary analysis of combined data collected during two prospective cohort studies of symptoms among adults with moderate to advanced HF. Physical symptoms were measured with the Heart Failure Somatic Perception Scale subscale (HFSPS), and depression was measured with the Patient Health Questionnaire-9 (PHQ-9). QOL was measured with the visual analog scale (VAS) of the EQ-5D.

Results:
The average age of the sample (n=291) was 56.7±13.3 years, and most were male (61.9%). A majority of subjects were classified as New York Heart Association Class III HF (56.4%), and most had non-ischemic etiology (65.2%). Average VAS score on the EQ-5D was 54.27±22.54. Both HFSPS scores (β = -0.58 ± 0.12, p<0.001) and PHQ9 scores (β = -1.77 ± 0.38, p<0.001) were significantly related to VAS scores. There was a significant interaction effect of HFSPS scores and PHQ9 scores in predicting VAS scores (Figure 1; interaction effect: β = 0.02 ± 0.01, p<0.05; model: R2 = 0.28, F(3,265) = 35.18, p<0.001).

Conclusions:
Physical symptoms and depression have strong independent and interactive effects in predicting QOL in HF, indicating that both should be considered concurrently when managing QOL among adults with HF.
Abstract 12360: Coronary Stent Information via Smartphone: A New Application Improving Health-care Quality of Patients Having Undergone Percutaneous Coronary Intervention
Authors: Imagawa Hiroshi , Yagi Takayoshi , Taniguchi Hirokatsu
Published: July 2021

Introduction:
There are a huge number of patients who have been treated by percutaneous coronary intervention (PCI) with stenting. For PCI two types of stent are used commonly; bare-metal stent and drug-eluting stent. Although choice of the stent has high clinical importance, the information is usually hard to obtain because of onset of unexpected pathological events in emergency cases, the needs to concentrate on treatment of urgent disorders resulting in not enough attention paid to the information itself, and so on. The lack of the information may, however, lead to inadequate decision, i.e. interruption of antiplatelet therapy. Many studies have reported that cessation of antiplatelet medications produces in-stent thrombosis in patients, especially those with drug-eluting stent during early post-operative period. This complication might lead to a lethal condition in clinical practice.

Hypothesis:
Smartphone based ubiquitous system of recording coronary stent information would be useful in managing patients, who underwent percutaneous coronary intervention.

Methods and Results:
We developed a smartphone application archiving PCI data. The operation date and type of coronary stent are recorded in the memory of smartphone. The information will enable an optimal decision about continuation or discontinuation of medications including antiplatelet in the emergency setting. The time-series record about of PCI data can be accessed anytime and anywhere in the world. Feasibility and usefulness were evaluated by both volunteer patients and cardiologits. Eighty-six percent of PCI patients satisfied with and the 80% of cardiologists espoused this application.

Conclusions:
Coronary stent data recording system using smartphone technology is a simple and valuable method in managing coronary artery disease patients after interventional stent deployment. This ubiquitous application would improve health-care quality of patients who have undergone PCI.
Abstract 12440: Global Longitudinal Strain With 2D-Speckle Tracking Predicts Chemotherapy-related Systolic Dysfunction Independenty of Basal Assessment in Patients With Breast Carcinoma
Authors: Guerra Federico , Marchesini Marco , Contadini Daniele , Menditto Alessio , Morelli Marco , Piccolo Elisa , Tagliavento Marco , Battelli Nicola , Berardi Rossana , Cascinu Stefano , Capucci Alessandro
Published: July 2021

Introduction:
Recent developments in anticancer therapies for breast carcinoma allowed an improvement in patient survival, notwithstanding a parallel increase of cardiovascular morbidity. Systolic dysfunction and heart failure represent a relevant problem in these patients due to insidious onset and the potential irreversible nature of cardiac damage. Therefore, strong and early predictors of chemoteraphy-realted systolic dysfunction are been sought.

Hypothesis:
To investigate global longitudinal strain (GLS) assessed by 2D-speckle tracking as a potential early marker of systolic dysfunction in chemoteraphy-treated breast cancer patients.

Methods:
Population include sixty-nine patients, referred to our unit for cardiologic assessment prior to neo-adjuvant or adjuvant chemotherapy for breast cancer. Patients with prior heart failure and atrial fibrillation were excluded. The protocol included a baseline echocolorDoppler and 2D-strain evaluation before the beginning of chemotherapy and subsequent serial controls every 3 months. In patients developing systolic dysfunction, further unscheduled assessment were made at the cardiologist discretion.

Results:
Nineteen (27.5%) patients were classified as having cardiotoxicity according to CREC and ESMO criteria. ROC curve analysis showed that a 3-month GLS <-16% predicted subsequent development of systolic dysfunction with good sensitivity and specificity (80% and 90% respectively), with a negative predictive value of 92%. Cardiotoxicity occurred in 8 patients at 6 months and in 11 patients within 9 months; among all of those, 84% of patients already showed a GLS <-16% at 3-month, and 100% at 6-month, confirming the early diagnostic potential of GLS. After chemotherapy suspension and introduction of cardioprotective drugs, GLS remained depressed longer than left ventricular ejection fraction (LVEF) over 1-year follow-up.

Conclusions:
Strain imaging with 2D-speckle tracking allows the identification of patients at high risk of developing systolic dysfunction. An absolute cut-off value of -16% can provide a useful, time-independent clinical tool to improve follow-up management and concentrate resources on high-risk patients.
Abstract 12509: Initial Reports on the Safety of Intravenous Tissue Plasminogen Activator in Acute Ischemic Stroke Patients Taking Novel Oral Anticoagulants (NOACs)
Authors: Xian Ying , Federspiel Jerome J , Hernandez Adrian F , Lytle Barbara , Schwamm Lee H , Bhatt Deepak L , Smith Eric E , Fonarow Gregg C , Peterson Eric D
Published: July 2021

Background:
Intravenous tissue plasminogen activator (IV tPA) improves outcomes in ischemic stroke when given early; however, there is limited information on the safety of giving IV tPA to those already on a novel oral anticoagulants (NOACs, dabigatran, rivaroxaban, and apixaban). Given this, the current stroke guidelines warn against use of IV tPA in patients on a NOAC.

Methods:
We analyzed data from 42,887 ischemic stroke patients treated with IV tPA within 4.5 hours from 1,289 Get With The Guidelines-Stroke hospitals between October 2012 and March 2015.

Results:
A total of 1751 patients treated with tPA were receiving one of the oral anticoagulants prior to admission (warfarin with INR<1.7 1500, dabigatran 87, rivaroxaban 129, and apixaban 35). Patients taking oral anticoagulants were older (median 79, 74, 71 for warfarin, any NOACs, and no oral anticoagulant, respectively), had more comorbid conditions, and more severe strokes (median NIHSS 13, 12, and 9). Compared with those not on any oral anticoagulant (3.9%), the unadjusted symptomatic intracranial hemorrhage (sICH) rates were higher in warfarin (4.9%) and NOAC (4.8%) patients. These differences were not statistically significant after adjusting for potential confounders in multivariable logistic regression model: adjusted odds ratio 0.85 (95 CI 0.66-1.10) for warfarin and 0.92 (0.51-1.65) for NOACs. Life-threatening or serious systemic hemorrhage, in-hospital mortality, discharge to hospice, and modified Rankin Score at discharge were similar among those on vs not on an oral anticoagulant (Table). Patients receiving NOACs appeared to have higher likelihood of discharge home and being able to ambulate independently at discharge, although the number of NOACs receiving tPA is small and may reflect potential treatment selection.

Conclusion:
This preliminary experience supports the potential safety of giving IV tPA to selected patients with acute ischemic stroke who were receiving chronic NOACs therapy.
Abstract 12513: Poorer Cognitive Function is associated With Objectively Monitored Medication Adherence in Patients With Heart Failure
Authors: Dolansky Mary A , Hawkins Misty A , Schaefer Julie T , Sattar Abdus , Gunstad John , Redle Joseph D , Josephson Richard , Moore Shirley M , Hughes Joel W
Published: July 2021

Introduction:
Cognitive impairment is prevalent in heart failure (HF); however, its role in HF treatment adherence is unclear. Given the complex polypharmacy in HF treatment, cognitive deficits may be especially important in predicting medication management. Thus, the objective of the current study was to examine the impact of cognitive function on medication adherence among patients with HF using gold standard, objective assessments: neuropsychological testing and electronic pill-box monitoring.

Hypothesis:
Diminishing cognitive functioning will be associated with poorer medication adherence.

Methods:
Participants were 372 patients with HF (59.7% male, 68.7±9.7 years) who completed a full neuropsychological battery. Medication adherence was objectively measured for 21 days using the Medisgnals pillbox. Regression analyses tested whether baseline attention, executive function, or memory predicted 21-day medication adherence.

Results:
In unadjusted analyses, lower scores on all three cognitive domains predicted poorer medication adherence (β = .52-85, p = .001-.009). After adjusting for demographic, clinical, and psychosocial variables, only memory continue to predict medication adherence (β = 0.51, p = .008), whereas executive function trended toward significance (β = 0.24 p = .075) and attention was no longer a predictor (β = 0.34, p = .131).

Conclusions:
Poorer cognitive function, especially in regards to memory, predicted reduced medication adherence among patients with HF. This effect remained after adjustment for factors known to predict adherence, such as depression, social support, and disease severity level. Our findings emphasize that cognitive deficits are not only prevalent in HF but that they also predict clinical outcomes (i.e., adherence to medication).
Abstract 12515: Enhanced Transforming Growth Factor β Signaling Rescues Defective Differentiation of Smooth Muscle Cell in Bicuspid Aortic Valve With Thoracic Aortic Aneurysm
Authors: Yang Bo , Jiao Jiao , Xiong Wei , Wang Lunchang , Chen Eugene
Published: July 2021

Individuals with bicuspid aortic valves (BAV) are at a high risk to develop a thoracic aortic aneurysms (TAA) than patients with trileaflet aortic valves (TAV), most commonly involving ascending aorta and sparing the descending aorta. Smooth muscle cells (SMCs) in the ascending and descending aorta arise from neural crest and paraxial mesoderm, respectively. We hypothesize the aortopathy associated with BAVs is due to aberrant differentiation of neural crest stem cells (NCSCs) to SMCs. Induced pluripotent stem cell (iPSC) lines were established from a patient with BAV/TAA, and control patients with TAV and a normal aorta. The iPSCs pluripotency was verified by standard stem cell markers and teratoma formation in SCID mice. iPSCs were differentiated into NCSCs and paraxial mesoderm cells (PMCs) separately, and verified by specific neural crest markers and paraxial mesoderm markers. Both NCSCs and PMCs were differentiated into SMCs, NCSC-SMCs and PMC-SMCs, by treating with TGFβ1 and PDGF-bb. With differentiation, both SMCs lines expressed SMC specific markers including MYH11, CNN1, ACTA2, and TAGLN by quantitative RT-PCR and immunohistochemical staining. However, NCSC-derived SMCs from BAV/TAA patient demonstrated significantly decreased expression and protein levels of MYH11 and ACTA2 and impaired contraction by gel contraction assay compared to NCSC-SMCs derived from control. In contrast, the PMC-derived SMCs from BAV/TAAD patient had similar or higher expression and levels of contractile proteins, including MYH11, CNN1, ACTA2, and TAGLN, and contractile response to carbacol treatment when compared with control PMC-SMCs. The defective differentiation of NCSC-SMC from the BAV/TAA patient was coupled with the decreased TGFβ signaling as assessed by decreased gene expression of TGFβ1 and connective tissue growth factor (CTGF) when compared to control cells. Increasing the concentration of TGFβ1, rescued the gene expressions of TGFβ1, CTGF, MYH11 and ACTA2 in the NCSC-SMCs from the BAV/TAA. Taken together, our data demonstrate that defective TGFβ signaling and differentiation of specifically NCSC-derived SMCs contributes to aortopathy in BAV with ascending aortic aneurysm.
Abstract 12665: Remodeling of Nuclear Ca
2+
Disposition in Atrial Fibrillation Associated Remodeling
Authors: Qi Xiao- Y , Villeneuve Louis , Xiong Feng , Sun Yiguo , Dobrev Dobromir , Nattel Stanley
Published: July 2021

Introduction:
Atrial fibrillation (AF) induces substantial self-promoting remodeling related to the rapid atrial rate. There is evidence that changes in nuclear Ca
2+
content alter ion channel gene expression and thereby effect electrophysiological changes that increase AF vulnerability and maintenance. However, the ways in which AF affects atrial cardiomyocyte (ACM) nuclear Ca
2+
disposition are unknown. Here, we studied the effects of AF-related remodeling on ACM nuclear structure and Ca
2+
handling.

Methods and Results:
ACMs were isolated from control (CTL) dogs and dogs subjected to 1 week of AF maintained by atrial tachypacing at 600 bpm (n=7, 6 respectively). We used nuclear imaging with Fluo-5N AM and nucleoplasmic and cytoplasmic calcium transient (CaT) recordings from intact ACMs loaded with Fluo-4 AM. AF significantly decreased the number of nuclear invaginations (NIV) normalized to nuclear envelope (NE) circumference, and increased nuclear length and perimeter in ACMs (Figure A). Diastolic [Ca
2+
]
nuc
and [Ca
2+
]
cyto
increased in AF vs CTL (Figure B, by 110%*, 89%* respectively, *P<0.05). Nucleoplasmic Ca
2+
transient amplitude decreased significantly with AF, but simultaneously measured cytoplasmic transient amplitude did not change (Figure C). Relaxation time from peak of the Ca
2+
transient to 50% decline (TD
50
) of nucleoplasmic and cytoplasmic CaTs were significantly prolonged in AF. The addition of a physiological nuclear Ca
2+
transient enhancer, endothelin (200 nM), increased diastolic [Ca
2+
]
nuc
and [Ca
2+
]
cyto
in both CTL (by 25±6%, 21±6%) and AF (by 40±4%, 31±2 ) ACMs. The IP3 receptor blocker 2-aminoethoxydiphenyl borate (2-APB, 5 μM) abolished endothelin effects on [Ca
2+
]
nuc
.

Conclusions:
AF-related remodeling alters atrial cardiomyocyte nuclear structure and nucleoplasmic [Ca
2+
] handling. These alterations may play an important role in associated gene-expression changes that produce the AF substrate.
Abstract 12678: Clinical Utility of Echocardiographic Epicardial Adipose Tissue Thickness Measured Using a High-frequency Linear Probe in Patients With Coronary Artery Disease
Authors: Hirata Yukia , Yamada Hirotsugu , Kusunose Kenya , Nishio Susumu , Bando Mika , Yamaguchi Koji , Iwase Takashi , Soeki Takeshi , Wakatsuki Tetsuzo , Sata Masataka
Published: July 2021

Introduction:
Epicardial adipose tissue(EAT), which is thought to be an ectopic adipose tissue, has been paid attention in association with coronary artery disease (CAD).

Hypothesis:
We hypothesized that EAT in anterior interventricular groove (AIG) obtained by echocardiography can be an additional marker over classical risk factors for prediction of CAD.

Methods:
We enrolled 311 patients (mean age 67±11 yrs, 208 men) who underwent coronary angiography between December 2011 and December 2013 at our hospital. We measured EAT thickness on the AIG and right ventricular free wall (EAT-RV) using high-frequency linear probe. Subjects were divided into 2 groups with and without significant coronary stenosis (≧75%) from coronary angiography. The performance of clinical risk factors (including age, male gender, body mass index (BMI), diabetes mellitus, hypertension, dyslipidemia, and smoking) plus various combinations of EAT thickness measurements for predicting CAD was assessed using the area under the curve (AUC) in ROC analysis.

Results:
The EAT-AIG thickness was significantly greater in the CAD group than that in the non-CAD group (8.3±3.0 vs. 6.3±2.5 mm, p<0.001), and there as also significant difference in the EAT-RV between the two groups (5.0±2.1 vs. 4.4±2.3 mm, p=0.009). Adding the EAT-AIG thickness over classical risk factors improved prediction of presence CAD (AUC 0.692 vs. 0.788, p<0.001), while the EAT-RV did not (AUC 0.692 vs. 0.704, p=0.343).

Conclusions:
Echocardiographic EAT-AIG thickness was greater in the CAD group than the non-CAD group. This non-invasive index may have clinical potential as a maker for predicting coronary atherosclerosis.
Abstract 12702: A Novel Human S10F-Hsp20 Mutation Induces Lethal Peripartum Cardiomyopathy
(Best of Basic Science Abstract)
Authors: Liu Guansheng , Jiang Min , Cai Wenfeng , Adly George , Gardner George , Lam Chi Keung , Rubinstein Jack , Kranias Evangelia G.
Published: July 2021

Background:
Heat shock protein 20 (Hsp20) has emerged as a novel cardioprotector against stress-induced injury. In this study, we investigated the functional significance of a novel human Hsp20 mutation (S10F) in peri-partum cardiomyopathy.

Methods and Results:
We identified a human S10F-Hsp20 mutant with a frequency of 2.8% in dilated cardiomyopathy patients (470 screened), while we did not find any normal subjects carrying this mutation (282 screened). To determine the functional significance of S10F-Hsp20, transgenic mice with cardiac-specific overexpression of this mutant were generated. We observed that female TGs were fertile, and delivered normal litter sizes, but they invariably died after 2, 3 or 4 pregnancies (Fig. 1a). However, overexpression of WT-Hsp20 to similar levels as S10F was not associated with any deaths following multiple pregnancies. Further histological examination of S10F females revealed significantly dilated hearts and increased heart weight/tibia length after the third delivery, compared to WT (non transgenic) mice. (Fig. 1b,c). Echocardiography assessment showed that this dilation (Fig. 1d) is associated with increased left ventricular end-systolic volume (Fig. 1e), increased left ventricular end-diastolic volume, depressed ejection fraction (Fig. 1f) and decreased fractional shortening. Further studies revealed that cardiomyocyte apoptosis was increased by 4 fold in S10F hearts after the third delivery(Fig. 1g,h). The mechanisms associated with the detrimental remodelling in S10F females included decreased Akt (Fig. 1i) and ERK phosphorylation under both baseline and pregnancy conditions. As a result, the activities of Akt and ERK were reduced, contributing to increased cell death in the S10F hearts of pregnant females.

Conclusion:
The human S10F mutation may compromise the heart’s coping with pregnancy induced stress conditions mainly through increased apoptosis by reduction of Akt and ERK activities.
Abstract 12750: Exercise Ventilatory Power in Heart Failure. Definition of Functional and Hemodynamic Patterns by Cardiopulmonary Exercise Testing and Stress Echocardiography
Authors: Labate Valentina , Generati Greta , Pellegrino Marta , Bandera Francesco , Guazzi Marco
Published: July 2021

Exercise Ventilatory Power (EVP; peak systolic blood pressure/exercise ventilation to CO2 production slope) is a new powerful prognostic marker that combines ventilator abnormalities with systemic hemodynamic during exercise. The phenotype and clinical relevance of patients with a worse EVP is broadly undefined and we aimed at this definition across a population of heart failure reduced ejection fraction (HFrEF) of different severity.

Methods:
77 HFrEF patients (mean age 65±11; male 70%; ischemic etiology 59%; NYHA class I, II, III and IV 23%, 33%, 31% and 13%, respectively; mean LVEF 34±9 %) underwent cardiopulmonary exercise test (CPET) evaluation (ramp protocol on performed on a tilt-table cycleergometer) combined with simultaneous echocardiographic assessment.

Results:
Patients were divided in 2 EVP classes (cutoff 3) focusing on peak exercise echocardiographic variables.

Conclusions:
A low EVP translates in a very unfavorable phenotype characterized by a lower peak VO2 and CO response at peak exercise. Remarkable impairment in right heart function and pulmonary hemodynamics were also peculiar of a low EVP. All the LV-pulmonary circulation- RV apparatus is abnormally involved in the exercise response of the EVP HFrEF phenotype.