bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16458: Paracrine Crosstalk Between Paltelets And Vascular Endothelial Cell is Mediated via MicroRNAs
Authors: Dangwal Seema , Stratmann Bernd , Bang Claudia , Tschoepe Diethelm , Thum Thomas
Published: July 2021

Majority of extracellular miRNAs constituting plasma miRNA pool are released by platelets. This study investigated the miRNA signature of leukocyte depleted platelets (LDP) isolated from T2DM or healthy subjects and explored the mechanism of miRNA mediated vascular crosstalk.

LDPs, obtained by leukocyte filtration of platelet rich plasma (PRP), were isolated from blood withdrawn from 6 T2DM patients (male, age: 54.8±7.6 yrs; HbA1c: 8.9±0.6%; BMI: 30.9±2.8kg/m2) and 10 healthy volunteers (male, age: 49.2±6.8yrs; HbA1c: 5.3±0.2%; BMI: 26.6±3.8kg/m2). Total RNA isolated from diabetic or healthy LDPs was subjected to PCR based miRNA profiling. Matrigel capillary formation and genomic BrdU incorporation were measured as readouts of angiogenesis and cell proliferation respectively. Cellular metabolic activities were measured by WST-1 assay. Student t-test was applied to compare groups and p<0.05 considered significant.

Total 735 (97%) miRNAs were detected (threshold< 29 Ct) in all LDPs. Levels of 19.5% miRNAs were decreased in T2DM platelets, whereas 7.5% miRNAs showed increase at 2-50 fold cutoff value. Compared to healthy LDPs (n=10), decreased levels of 14 highly platelet enriched miRNAs candidates including miR-21 and miR-22 were confirmed by RTPCR validation of individual T2DM LDPs irrespective of aspirin intake or presence of coronary heart disease (n=11).

Thrombin stimulation of washed healthy platelets increased miRNA release into cell supernatant and confocal microscopy confirmed the cellular uptake of platelet released micro-particles into human coronary artery endothelial cells within 2-24h. In addition, endothelial overexpression of miR-21 or miR-22 decreased cell proliferation and metabolic activity, whereas miR-22 also attenuated capillary formation capacity. MiR-21 and miR-22 modulation inversely regulated expression of cell-cycle regulator gene CDK-6 at mRNA and protein levels.

Diabetic platelets show distinct miRNA signature compared to healthy platelets and lower levels of miRNAs in diabetic platelets may represent their active secretion during diabetes. Released miRNAs may mediate crosstalk with vascular cells by influencing cellular gene expression and function upon their uptake.
Abstract 16469: One Hundred Consecutive Patients With Perceval Sutureless Valve: A Good Alternative to Standard Avr and Tavr
Authors: Piccoli Paolo , Moggi Annalisa , Camurri Nicola , Fiorani Vinicio , Manfredi Jacopo , Pederzolli Nicola , Rambaldini Manfredo
Published: July 2021

Introduction:The recently introduced sutureless prostheses for aortic valve replacement allow short cross-clamp and CPB times with good clinical and haemodynamic performances. It is arguable that these factors can positively impact on post-operative morbidity and mortality, in particular in those patients with a medium- high risk profile. This study shows the mid-term results of a single center experience in patients undergoing AVR. with the Perceval sutureless bioprosthesis (Sorin Group, Saluggia, Italy)

Methods:One hundred patients (64 female; mean age 78.2±4.7 years) with aortic valve stenosis (mean gradient of 51.3±14,2 mmHg) underwent aortic valve implantation with the sutureless Perceval bioprosthesis. High-thoracic epidural analgesia was used in 31 patients (31%). Associated CABG surgery was performed in 29 patients (29,%). The mean logistic EuroSCORE was 14.9±9.4% and the STS score was 3,3±1,7.

Results:Thirty-day mortality was 2% (n=2). Mean CPB and cross-clamp times for isolated AVR were 38,1±18,6 and 24,2±9,8 minutes respectively. Perioperative echocardiography revealed significant paravalvular leakage in three patients (3%). Postoperative mean trans-valvular gradient was 13.6±5.2 mmHg. AV block requiring PM implantation occurred in 2 patients (2%). No thrombosis and no post-operative strokes were observed. At a mean follow-up of 13±6.7 months, no significant paravalvular leakage or valvular regurgitation was observed, and no migration or dislodgement of the prosthesis occurred.

Conclusions:This study shows that sutureless implantation of the Perceval aortic valve bioprosthesis provides a simple and reproducible alternative for standard AVR and TAVR in medium-high risk patients eligible for AVR. The use of this self-anchoring valve was also associated in our patients with absence of embolic events and a very low incidence of AV blocks requiring PM implantation. These findings encourage the use of this valve in a broader spectrum of patients A control randomized trial is needed to confirm these promising findings.
Abstract 16480: Characteristics and Outcomes of Patients With Papillary Muscle Ventricular Arrhythmias
Authors: Gianni Carola , Di Biase Luigi , Mohanty Sanghamitra , Trivedi Chintan , Gökoglan Yalçin , Günes Mahmut F , Bai Rong , Al-Ahmad Amin , Burkhardt J D , Gallinghouse Joseph G , Horton Rodney , Hranitzky Patrick M , Sanchez Javier E , Natale Andrea
Published: July 2021

Introduction:
We sought to investigate the characteristics and outcomes of patients who underwent RF ablation of PM ventricular arrhythmias (VA) in our center.

Results:
26 patients were included, median age was 66 years (16 to 85), 46% female, all with normal LVEF. PM VAs were PVCs in 68% patients, and PVC + VT in 32%. Site of origin was the LV infero-septal PM in 73%, LV antero-lateral PM in 15% and right ventricular RV septal PM in 12%.

46% of patients showed other VAs in addition to the one originating from the PMs; in 33% of these patients, additional VAs were 2 or more. These VAs were mostly PVCs (92%), localized in the LVOT (64% - 56 % in the basal LV and 44% in the aortic cusps) and the septal RVOT (36%). The only additional VT was fascicular.

All the PMs and mappable additional VAs were ablated with RF energy through an irrigated catheter and the aid of ICE; a remote magnetic navigation system (RMS) was used in half of the procedures. In one case, PVC suppression required additional epicardial ablation.

Major complications occurred in 2 patients (8%): 1 pericardial effusion (the patient underwent ablation of a crista terminalis premature atrial complex in the same procedure) and 1 pseudoaneurysm.

Acute success (PM VA suppression/non-inducibility) was achieved in 96% of patients (the patient with pericardial effusion could be anticoagulated further and the procedure was stopped). After a median follow-up period of 8 (4-14) months, long-term success (no PM VT recurrence or PVC burden reduced by 80% off antiarrhythmic drugs) was 92% after a single procedure, 96% after repeat procedures. When considering additional VAs, the only recurrence was a parahisian RVOT PVC.

No difference in acute or overall long-term success was observed when comparing RMS-guided vs standard procedures (respectively 92% vs 100 % and 100% vs 92%; P = NS).

Conclusion:
PM VAs are most commonly PVCs originating from the LV infero-septal PM and are frequently (48%) associated with an additional ventricular focus (LVOT > RVOT >> fascicular VT).

RF ablation is safe and effective in eliminating or significantly reduce the burden of PM VAs, as well the extra-PM foci that are commonly encountered in this population. RMS guided ablation is not inferior to standard ablation in this subset of patients.
Abstract 16486: Safely Removing the Brakes on Fibrinolysis: Inactivation of α2-Antiplasmin Dissolves Pulmonary Emboli Without Causing Bleeding
Authors: Singh Satish , Houng Aiilyan K , Reed Guy L
Published: July 2021

Introduction:
Venous thromboembolism affects millions of patients per year and pulmonary embolism (PE) is a leading cause of hospital mortality. PE activates the fibrinolytic system, but regulatory molecules such as α2-antiplasmin (a2AP) appear to prevent thrombus dissolution. Pharmacologic tissue plasminogen activator (tPA) dissolves pulmonary emboli, relieves right heart strain and improves mortality in high risk patients, but tPA has unacceptable bleeding risks. We examined whether inactivation of a2AP may prove to be a safer and more effective method for dissolving experimental pulmonary emboli.

Methods:
Pulmonary embolism was examined in a humanized model. Anesthetized, a2AP
-/-
mice, supplemented with physiological levels of a2AP, were infused with
125
I-labeled human thrombi via the jugular vein. Then mice were treated with tPA, no agent (control), a humanized chimeric monoclonal antibody inactivator of a2AP (a2AP-I) or the combination of low dose tPA and a2AP-I. Thrombus dissolution was determined by gamma counting and surgical bleeding was measured.

Results:
Clinical dose tPA dissolved pulmonary emboli more effectively than no therapy (control, p<0.001). However, mice treated with a2AP-I showed greater thrombus dissolution than tPA (p<0.001) or controls (p<0.001). Alone, low doses of tPA did not dissolve thrombi, but in combination with a2AP-I, low dose tPA increased thrombus dissolution more than clinical dose tPA alone (p<0.001) or a2AP-I alone (p<0.001). Clinical dose tPA therapy was associated with a significant increase in bleeding (p<0.01). Though more potent than tPA in dissolving pulmonary emboli, a2AP-I alone, or in combination with low dose tPA, did not increase bleeding risk vs. controls and caused less bleeding than tPA (p<0.01).

Conclusion:
In experimental pulmonary embolism a2AP plays a critical regulatory role in blocking fibrinolysis. Inactivation of a2AP was more potent than tPA in dissolving thrombi in PE, but unlike tPA, it did not cause bleeding. This suggests that a2AP inactivation may be a safer strategy for treating venous thromboembolism.
Abstract 16525: Left Ventricular Unloading Before, Not After, Reperfusion Limits Infarct Size and Improves Survival in Acute Myocardial Infarction: A Bench to Bedside Study
Authors: Kapur Navin K , Paruchuri Vikram , Qiao Xiaoying , Morine Kevin , Buiten Lyanne , Josephy Noam , Hout Mariah , Karas Richard H
Published: July 2021

Ischemia-reperfusion injury (IRI) is a major determinant of myocardial damage in acute myocardial infarction (AMI). We explored the hypothesis that reducing left ventricular wall stress (LV unloading) with an axial flow catheter (Impella) before, not after, coronary reperfusion reduces infarct size and improves survival.

Methods:
We first employed a model of AMI. After 90 minutes of LAD occlusion, adult, male swine (n=4/group) were randomized to: 1) 120 minutes of reperfusion alone (IRI), 2) 30 minutes of LV unloading before 120 minutes of reperfusion (Impella to Balloon Group; ITB) or 3) 30 minutes of reperfusion followed by LV unloading and an additional 120 minutes of reperfusion (Balloon to Impella Group; BTI). Infarct size, myocardial kinase activity, and mitochondrial integrity were quantified. To explore the clinical utility of LV unloading before reperfusion we retrospectively studied all patients in the USPella registry presenting with ST-segmentc elevation AMI and cardiogenic shock who received an Impella within 120 minutes before (n=41; STEMI-ITB) or within 120 minutes after (n=76; STEMI-BTI) percutaneous reperfusion between 2009 and 2014.

Results:
Compared to IRI alone, infarct size was reduced in the ITB group, not the BTI group (62±2% vs 33±6% vs 58±15%, IRI vs ITB vs BTI, p<0.01 for IRI vs ITB; p<0.05 for ITB vs BTI). Levels of phosphorylated Akt, Erk-1/2, and GSK3b were increased within the infarct zone in the ITB, not BTI group. Mitochondrial numbers and markers of integrity were higher within the infarct zone in the ITB, compared to IRI or BTI. In the registry, in-hospital (51% vs 28%, p=0.02) and 30-day survival (42% vs 20%, p=0.03) were higher in the STEMI-ITB than the STEMI-BTI group. A STEMI-ITB time of less than 60 minutes (n=38) was associated with higher in-hospital survival than a STEMI-BTI time of less than 60 minutes (n=40) (50% vs 25%, p=0.02).

Conclusion:
Primary LV unloading before, not after, coronary reperfusion reduces infarct size, increases cardioprotective signaling, and improves mitochondrial integrity. These findings are supported by improved survival among patients treated with an Impella before, not after reperfusion in AMI. Future studies are required to explore the clinical utility of primary LV unloading in AMI.
Abstract 16530: Post-exercise Flow-mediated Dilation is augmented in Highly Trained Female Athletes
Authors: Andaku Daniela K , Archiza Bruno , Caruso Flavia C , Zangrando Katiany T , Lanzotti Humberto , Amaral André C , Bonjorno Jr José Carlos , de Oliveira Cláudio R , Phillips Shane A , Arena Ross , Borghi-Silva Audrey
Published: July 2021

Background:
Recent evidence has indicated a ceiling to the benefits of exercise training that, if chronically surpassed, may have a negative effect on cardiac function. Conversely, improvements in peripheral arterial function may respond positively to chronic high volume training. Recent studies have shown that flow-mediated dilation (FMD) is decreased immediately after maximal exercise in sedentary subjects and is unaltered in subjects who participate in moderate volume exercise. We investigated the acute effects of maximal exercise on vascular function of elite female athletes with a high-volume training history.

Methods:
Fifteen elite female soccer players (mean age: 22.1 ± 4.4 years; BMI: 20.76 ± 1.75 kg/m2), with a high volume/intensity training history (4-6 hours per day) were evaluated. Subjects underwent maximal cardiopulmonary exercise testing (CPX) on a treadmill (VO2max 41.1 ± 3.9 mLO2•kg-1•min-1). Brachial artery FMD was determined using high-resolution ultrasound before and immediately after CPX. Flow velocity were measured at baseline (BSL) and during reactive hyperemia (RH) both prior to and following exercise.

Results:
Brachial artery diameter increased during RH before (3.42 ± 0.38mm vs. 3.03 ± 0.28mm, p<0.001) and after CPX (3.61 ± 0.44mm vs. 3.10 ± 0.37mm, p<0.001). Importantly, FMD was increased following CPX compared to BSL (16.86 ± 9.04% vs. 12.95 ± 7.03%, p=0.027). There was significant increase in peak flow velocity during RH before (135.28 ± 42.19cm/s vs. 79.19 ± 28.14cm/s, p=0.001) and after CPX (139.15 ± 41.07cm/s vs. 87.64 ± 21.23cm/s, p<0.001) (Table).

Conclusion:
The results of the current study indicate that arterial function is improved following acute aerobic exercise in elite female athletes with a chronic high volume training history. These findings deviate from the emerging literature suggesting chronic high volume training may be detrimental to cardiovascular function in the long term.
Abstract 16535: Conditional Knockout of the Mitochondrial 18-kDa Translocator Protein Limits Heart Failure
Authors: Thai Phung , Lu Xiyuan , Daugherty Daniel , Deng Wenbin , Bers Donald M , Schaefer Saul
Published: July 2021

Introduction:
Heart failure results in myocyte and mitochondrial death, and is characterized by abnormalities in mitochondrial calcium handling, energy production, and opening of the mitochondrial permeability transition pore (mPTP). The 18-kDa mitochondrial translocator protein (TSPO) has been shown to be significantly upregulated by heart failure in animals and in explanted hearts from patients, suggesting a vital role for this protein. Hypothesis: In the current experiments, we tested the hypothesis that conditional knockout of the TSPO using Cre inducible TSPO-floxed C57BL/6J mice would limit heart failure resulting from transverse aortic constriction (TAC).

Methods:
Mice in 4 groups_wild-type (WT) sham, WT TAC, KO sham, and KO TAC_were monitored by weekly echocardiography for 8 weeks, followed by downstream experiments.

Results:
TAC caused a 46±13% reduction in ejection fraction in WT mice, which was significantly lower in the KO mice (14±10%, P < 0.01, Figure). Strain analysis revealed a significant improvement in radial, longitudinal, and circumferential strain in KO TAC mice, supported by tissue histology finding of significantly less collagen in KO TAC mice. KO TAC mice showed lower heart to body weight and lung to body weight ratios, with no KO TAC mice showing signs of pulmonary edema. Calcium uptake experiment using Rhod-2 AM in isolated cells revealed that KO TAC mice had higher mitochondrial calcium uptake, a crucial finding since mitochondrial calcium uptake has been shown to play a role in energetics and mPTP opening.

Conclusion:
Genetic modulation of the TSPO limits heart failure due to pressure overload, likely mediated by preserving mitochondrial calcium uptake and energy production, and possibly limiting mPTP opening. These data suggest that pharmacologic interventions that inhibit TSPO expression or function can limit heart failure at the sub-cellular level.
Abstract 16538: The Impact of Institutional Design on Transcatheter Aortic Valve Replacement Complication Rates in the United States
Authors: Pant Sadip , Patel Samir , Golwala Harsh , Patel Nilesh , Badheka Apurva , Deshmukh Abhishek , Agnihotri Kanishk , Patel Nilay , Savani Chirag , Grubb Kendra , Flaherty Michael
Published: July 2021

Introduction:
With the technical advancements and expanding indications, utilization of TAVR is on the rise among various institutions in the United States .While appropriate patient selection and better techniques are essential to improving outcomes, the impact of institutional design (or hospital setting) on outcomes with TAVR has yet to be examined.

Objective:
The objective of our study is to compare TAVR complication rates among teaching vs non-teaching centers in the United States

Methods:
We used Healthcare Cost and Utilization Project - National Inpatient Sample (NIS) data , the largest all payer database of hospital inpatient stay available in United States, to identify patients (age ≥18 years) who underwent TAVR from Jan-Dec 2012. We constructed multivariable models to determine independent predictors (age, sex, race, Charlson’s comorbidity index, hospital size, hospital location and TAVR approach) of TAVR-associated complications. Statistical analysis was performed using Stata IC 11.0 (Stata-Corp, College Station, TX).

Results:
We identified 7,405 TAVR procedures performed in the United States in 2012. 88% of TAVR were performed in teaching centers. There was no difference in mortality following TAVR between teaching and non-teaching centers. The occurrence of any in-hospital complication was lower in teaching centers as compared to non-teaching centers (42% vs. 50%, p<0.001). Rates of individual complications in teaching vs. non-teaching centers are illustrated in the figure. In adjusted analysis, hemorrhage requiring transfusion (13.2% vs. 20.8%, p<0.001), renal complications requiring dialysis (1.2% vs. 2.3%, p=0.009), respiratory complications (7.5% vs. 11%, p<0.001) and complications requiring open-heart surgery (2% vs. 4.6%, p<0.001) were lower in teaching centers as compared to non-teaching centers. Vascular access site complications, pacemaker insertion, pericardial and neurological complications were similar between teaching and non-teaching centers (Figure).

Conclusion:
Institutional design impacts TAVR complication rates albeit no difference in mortality. In general, complication rates are lower in teaching centers compared to non-teaching centers.
Abstract 16572: Association of Atrial Fibrosis With Major Adverse Cardiac Events in Patients With Non-valvular Atrial Fibrillation
Authors: King Jordan B , Singhal Mukul , Kaur Gagan , Johnson Kara , Pacchia Christina , Biskupiak Joseph , Marrouche Nassir
Published: July 2021

Background:
Extensive of atrial fibrosis has been demonstrated to significantly predict success of catheter ablation. However, impact of extensive fibrosis on other aspects of patient care and long-term prognosis is unknown.

Methods:
We conducted a historical cohort study to assess the hypothesis that increased degree of atrial fibrosis is independently associated with major adverse cardiac events (MACE). We reviewed 853 patients with non-valvular atrial fibrillation (NVAF) and quantified fibrosis. Logistic regression models were used to evaluate the association of percent fibrosis on experiencing a MACE. Linear splines were utilized to allow the functional form of the exposure to vary at high (>15%) and low (<15%) fibrosis scores. The outcome of interest was a composite of MACE: myocardial infarction (MI), ischemic stroke (IS), or venous thromboembolism (VTE).

Results:
The mean age of the cohort was 66.2±12.4 with 66% male and 79% white. During a median follow-up of 2.9 years, 69 (8.1%), 46 (5.4%), 52 (6.1%), and 156 (18.3%) of patients experienced an MI, IS, VTE, or MACE, respectively. High fibrosis patients were more likely to be older, male, and have a higher CHA2DS2-VASc score. In the unadjusted analysis, increased fibrosis was associated with increased odds of a MI (OR [95% CI] P-Value: 1.30 [1.00, 1.68] 0.05) or any MACE (1.28 [1.06, 1.56] 0.01), but not with IS or VTE. After adjusting for potential confounders, increasing fibrosis levels had significantly increased odds of MI (1.53 [1.02, 2.28] 0.04) and VTE (1.52 [1.17, 2.86] <0.01) when fibrosis levels were above 15%. There was no significant association below 15%. The odds of a MACE was significant above 15% (1.64 [1.18, 2.27] <0.01) and across all fibrosis scores (1.23 [1.01, 1.49] 0.04), but was insignificant when only fibrosis levels below 15% were examined.

Conclusions:
Advanced degree of atrial fibrosis in patients with NVAF is independently associated with increased risk of MI, VTE and a composite of MACE.
Abstract 16598: The Role of Paraoxonase 2 in Myocardial Ischemia/Reperfusion Injury
Authors: Li Jingyuan , Grijalva Victor R , Reddy Srinivasa T , Eghbali Mansoureh
Published: July 2021

Objectives:
Paraoxonases (PON) gene family consists of three proteins PON1, PON2, and PON3. PON2 is an intracellular membrane-associated protein that is widely expressed in vascular cells and many tissues. At the subcellular level, PON2 is localized to both the ER and mitochondria, and protects against oxidative stress.

Hypothesis:
The aim of this study was to investigate the role of PON2 in myocardial ischemia reperfusion injury.

Methods:
PON2 deficient (PON2-/-) and WT male mice were subjected to in-vivo ischemia/reperfusion injury. The left anterior descending coronary artery was occluded for 30 min followed by 24 hr of reperfusion. The infarct size, mitochondrial calcium retention capacity (CRC) and reactive oxygen species (ROS) generation were measured. The expression of C/EBP homologous protein (CHOP), GSK3b and phosphate GSK3b protein were examined by Western Blot. The number of animals was 5-7/group and data were expressed as mean±SEM. T test were used for statistical analysis. Probability values <0.05 were considered statistically significant.

Results:
The infarct size was ~2 fold larger in PON2 deficient mice compared to WT mice (p<0.05). The threshold for opening of mitochondrial permeability transition pore (mPTP) in response to calcium overload was much lower in PON2-/- mice compared with WT mice (173±19 in PON2-/-, 250±41 in WT, nmol/mg-mitochondrial protein, p<0.05). The ROS production was ~2 fold higher in isolated cardiac mitochondria from PON2-/- mice compared with WT mice (p<0.05). ER stress protein CHOP increased significantly in PON2-/- mice compared to WT mice (normalized to WT: 1±0.05 in WT, 1.66±0.08 in PON2-/-, p<0.001). Phospho-GSK3b level was significantly downregulated in in PON2-/- mice compared to WT mice (pGSK3b/GSK3b normalized to WT: 1±0.06 in WT 0.67±0.08 in PON2-/-, p<0.05).

Conclusions:
PON2 regulates myocardial ischemia/reperfusion injury via inhibiting the opening of mPTP, which is associated with reduced mitochondria ROS production, deactivation of ER stress signaling CHOP and GSK3b.
Abstract 16600: Unraveling Outcomes in Medically Managed Patient With Acute Coronary Syndromes (ACS): The Alberta COntemporary Acute coronary syndrome Patients invasive Treatment Strategies (COAPT) Study
Authors: Welsh Robert C , Bainey Kevin R , Norris Colleen , Knudtson Merril , Traboulsi Dean , Brass Neil , Savu Anamaria , Ali Imtiaz , O'Neill Blair , Armstrong Paul W , Kaul Padma
Published: July 2021

Objectives:
Limited “real world” data exists on characteristics and outcomes of ACS patients managed without revascularization (REVASC). Accordingly, we assessed an inclusive cohort of ACS patients grouped by catheterization and REVASC status.

Methods:
ACS pts in Alberta, Canada (n=3.7M) were assessed using population health database linkages (April 2010 - March 2013) and categorized into 3 groups: no CATH, CATH no REVASC and CATH REVASC (excluding pts with previous CATH - 6 m or ACS - 3 m). Baseline characteristics, in-hospital death, one year death and readmission were compared (logistic regression modelling).

Results:
Of 14, 661 ACS pts, 20.6% were not referred for CATH, 17.7% had CATH no REVASC and 61.7% had CATH REVASC (table). The pts not referred for CATH pts were older had more comorbidities, less frequent STEMI and were more likely admitted to a non-CATH hospital. They had prolonged hospital stay and 11.9% in-hospital death; 4-fold higher comparing no CATH vs. REVASC (adjusted OR 4.37, 95% CI 3.4-5.6). After excluding pts with in-hospital death within 2 days from admission and/or non-obstructive CAD (n=712), pts not referred for CATH had a 3-fold risk of in-hospital death (OR 3.28, 95% CI 2.5-4.4). Compared to REVASC, CATH no REVASC did not have increased in-hospital death (OR 1.2, 95% CI 0.86 - 1.1), however if pts without obstructive CAD were excluded, CATH no REVASC had a trend for increased in-hospital death (OR 1.4, 95% CI 0.99 - 1.96). Cath no REVASC was associated with increased 1 yr death (adjusted OR 1.97 (1.54-2.5)).

Conclusion:
Patients with ACS managed medically represent a diverse patient population. Once receiving CATH, pts managed medically have similar risk of death as those receiving REVASC. However those not referred for CATH have multiple comorbidities, are more likely managed in non-cardiac CATH hospitals and have a marked increase in both of in-hospital and 1 year death and rehospitalizaiton.This substantial cohort deserves further investigation.
Abstract 16639: Low Yield of Additional Non-invasive Testing in Moderate Worst Stenosis by cCTA in Acute Chest Pain Patients - Results From a Clinical ED cCTA Registry
Authors: Janjua Sumbal A , Vadvala Harshna V , Staziaki Pedro V , Takx Richard A , Prabhakar Anand M , Nagurney John T , Neilan Tomas G , Hoffmann Udo , Ghoshhajra Brian B
Published: July 2021

Introduction:
Coronary computed tomography angiography (cCTA) allows efficient triage of low-intermediate risk patients with suspected acute coronary syndrome (ACS); appropriate management of patients with moderate stenosis by cCTA is unknown. We evaluated the yield of downstream testing in moderate stenosis patients in a clinical ED cCTA registry.

Methods:
All consecutive ED patients with acute chest pain undergoing cCTA as part of routine care between October 2012 and July 2014 were screened. Patients with moderate as their worst stenosis (50-69% stenosis) on cCTA were included. Plaque characteristics, resting left ventricular function (by cCTA), results of any functional downstream non-invasive testing, invasive coronary angiography (ICA) and interventions, and discharge diagnosis were reported. ACS was defined as acute myocardial infarction (MI) or unstable angina pectoris (UAP) and adjudicated by an independent committee. Ischemia was defined as clear, territorial abnormality by myocardial perfusion scintigraphy imaging (MPI) or rest or stress echocardiogram, significant dynamic ST-T shift by exercise treadmill test (ETT) and stenosis >70% on ICA or fractional flow reserve (FFR) <0.75.

Results:
586 patients underwent cCTA, with 7.2% (n=42) deemed moderate stenosis. Rate of ACS was 14.2% (n=6) with all adjudicated as UAP. Of these, 83% had stenosis caused by lipid-rich plaque; 33% had wall motion abnormalities on cCTA. The majority (n=28; 66%) underwent downstream non-invasive testing. Overall, n=2 (6%) of the non-invasive tests were positive for ischemia while n=3 (42%) of the invasive tests were diagnosed as positive for ischemia (all revascularized) (Figure 1).

Conclusions:
Unstable angina but not myocardial infarction is frequent among acute chest pain patients with moderate stenosis by cCTA. cCTA findings of lipid-rich plaque and resting functional abnormalities had a relatively higher yield vs. other non-invasive tests to detect ischemia.
Abstract 16668: Long-term Outcomes After Endo-epicardial Catheter Ablation of Ventricular Tachycardia in Nonischemic Cardiomyopathy
Authors: Zado Erica S , Santangeli Pasquale , Marchlinski Francis E
Published: July 2021

Introduction:
Endo-epicardial catheter ablation of ventricular tachycardia (VT) in patients (pts) with nonischemic cardiomyopathy (NICM) has been reported to have satisfactory results at the short- and mid-term follow-up. We sought to determine the outcomes at the long-term follow-up of endo-epicardial ablation of VT in NICM.

Hypothesis:
Catheter ablation provides satisfactory long term outcome

Methods:
We prospectively enrolled 128 pts (age 59±13 years, 116 [91%] males) with NICM who underwent endo-epicardial radiofrequency catheter ablation at our Institution. After substrate mapping, all critical sites for the clinical or induced VT(s), identified with activation, entrainment or pace-mapping, together with late, split and fractionated potentials were targeted with focal and/or linear ablation. The procedural endpoint was noninducibility of sustained monomorphic VT. Pts were followed with ICD interrogation.

Results:
A total of 108 (73%) pts had idiopathic dilated NICM. The remaining 20 (14%) pts had hypertrophic CM (n=11), suspected inflammatory CM (n=6), or valvular CM (n=3). The mean LV ejection fraction was 33±15%. After a mean follow-up of 19 months (max 97 months), a total of 36 (28%) pts died and 17 (13%) underwent heart transplant. Cumulative survival free from any recurrent VT was 53% (68/128 patients) (Figure A). In the remaining 60 (47%) patients with VT recurrences, catheter ablation still resulted in a significant beneficial clinical impact on VT burden, with 25/60 (42%) having only isolated (1-2) VT episodes over follow-up, and a striking reduction of VT storm in the remaining pts (Figure B).

Conclusions:
In patients with NICM and VT, endo-epicardial substrate-based ablation is effective in achieving long-term freedom from any VT in 53% of patients, with a substantial improvement in VT burden in many of the remaining patients.
Abstract 16673: Intramyocardial Injection of MSC-derived Extracellular Vesicles Confers Superior Cardiac Repair After a Reperfused Myocardial Infarction
Authors: Cheng Guangming , Labedz-Maslowska Anna , Berdecka Dominika , Xuan Yu-Ting , Samanta Anweshan , Girgis Magdy , Wang Ou-Li , Kedracka-Krok Sylwia , Davani Arash , Vincent Robert J , Yang Yanjuan , Karnas Elzbieta , Sarna Michal , Hauptman Jeryl , Madeja Zbigniew , Dawn Buddhadeb , Zuba-Surma Ewa
Published: July 2021

Introduction:
Stem cell-derived extracellular vesicles (EVs) are known to facilitate cell-to-cell communication. The potential of mesenchymal stem cell (MSC)-derived EVs for cardiac repair when compared with MSC whole cell injection remains unknown.

Hypothesis:
We hypothesized that therapy with MSC-EVs after a reperfused myocardial infarction (MI) will result in greater improvement in LV structure and function compared with injection of MSCs.

Methods:
EVs were collected by sequential centrifugation from culture supernatants of murine bone marrow MSCs. We used tunable resistive pulse sensing technology (TRPS), flow cytometry, real-time qRT-PCR and mass spectrometry to analyze MSC-EVs. Wild-type (C57BL/6) mice underwent a 30-min coronary occlusion followed by reperfusion, and 48 h later received intramyocardial injection of vehicle (PBS, n=14), MSCs (n=14), or MSC-EVs (n=14). Echocardiography was performed 4 d prior to MI (BSL) and at 48 h and 30 d after injection. Mice were sacrificed after 30 d.

Results:
MSC-EVs were noted to be small vesicles with average size of 233.0 ± 70.2 nm (Fig), and expressed MSC-specific markers, including CD29, CD90.2, CD105, Sca-1 and CD49e (Fig). MSC-EVs were enriched in mRNAs, miRNAs and proteins from donor MSCs; and carried transcripts of genes regulating cardiac/vascular differentiation, such as GATA-4, Nkx2.5, Tie-2, and GATA-2. In vivo, LV ejection fraction (EF) was significantly and similarly reduced in all groups at 48 h after MI (Fig). At 30 d after MI, mice injected with MSC-EVs exhibited significantly higher EF (Fig) and smaller LV end-diastolic volume compared with vehicle-treated and MSC-injected mice.

Conclusions:
We conclude that MSC-EVs represent natural nanocarriers capable of transferring bioactive contents and inducing cardiac repair following intramyocardial injection after MI in vivo. The use of MSC-EVs may potentially improve the outcomes of cell therapy in humans.
Abstract 16689: Smartphone-enabled Device for the Monitoring of Blood Volume Variations Using Magnetohydrodynamic Voltages
Authors: Wu Kevin J , Gregory T. Stan , Reeder Charles , Leitmann Bobby , Huffines Augustus , Donovan Sheila , Mosteller Luke , Murrow Jonathan R , Tse Zion Tsz Ho
Published: July 2021

Background:
Blood volume assessment is a valuable clinical metric, which can diagnostically be used to assess tissue health, monitor patient rehabilitation, and track the progression of wound healing. Currently there exists several methods to assess flow (MRI, US), but are either limited in cost or portability, and may require injection of contrast agents. Magnetohydrodynamic voltages (VMHD) are induced through blood flow interactions with an external magnetic field, and have been successfully measured using a modified ECG recorder and software package [1]. We hypothesize that a portable device capable of measuring induced VMHD could be used to rapidly quantify changes in blood flow.

Objectives:
Develop a portable device capable of monitoring of variations in blood volumes using induced VMHD.

Methods:
A portable smartphone-based ECG monitor was developed to use methods proposed in [1] to extract a metric proportional to blood flow from acquired ECGs (Fig. 1a). ECGs were acquired in two healthy volunteers, the second being a trained athlete. VMHD was induced in the carotid artery while in the presence of 0.4T static magnetic field generated by a neodymium magnet embedded in the monitor (Fig. 1b). VMHD signal extraction was performed to isolate the voltage induced by the magnet. Integrating over the VMHD yielded a metric proportional to blood volume [1,2]. Trials were performed at rest and at an elevated heart rate (HR) from exercise stress.

Results:
Induced VMHD was shown to increase from the baseline during exercise by 59% and 106% for the healthy subject and the athlete, respectively; resulting in a 47% difference in VMHD variations between the trained athlete and the healthy subject (Fig. 1c).

Conclusions:
A stand-alone device capable of quickly assessing blood volumes in the field using custom hardware and smartphone technology was developed. The ability of the device to quantify VMHD-derived blood flow was demonstrated.

Ref: [1] Tse, MRM, 2013. [2] Gregory, JCMR, 2015.
Abstract 16700: Mineralocorticoid Receptor Antagonist Utilization in Eligible Patients Post St-elevation Myocardial Infarction
Authors: Nazzari Hamed , Ramanathan Krishnan , Taylor Carolyn , Deyell Marc , Grewal Jasmine , Tang Jonathan , Largy Wendy , Perry-Arnesen Michele , Wong Graham , Toma Mustafa
Published: July 2021

Background:
Mineralocorticoid receptor antagonists (MRAs) have been shown to reduce the morbidity and mortality in patients with reduced left ventricular ejection fraction (LVEF) post myocardial infarction (MI). Canadian guidelines recommend a MRA in patients post MI with an LVEF of ≤40% and documented heart failure or diabetes before hospital discharge, in the absence of any contraindications. We sought to examine if discrepancies between guideline-based therapy and actual prescribing rates exists in the use of MRAs in acute ST-elevation myocardial infarction (STEMI) patients.

Methods:
Retrospective analysis of utilization rates of MRAs in eligible patients enrolled in the Vancouver Coastal Health Authority STEMI database between October 2007 and October 2014. Inclusion criteria were based on the EPHESUS trial, which included an LVEF <40% and documented heart failure or history of diabetes. Patients on dialysis or with a serum Cr >221 were excluded.

Results:
2583 patients had a STEMI during the study period. 192 (7.4%) patients were determined to be eligible for MRA prescription at discharge, 32 were excluded due missing discharge prescription information. Of the remaining 160 patients, the mean age was 67.9, 71.3% were male, 72.5% had an anterior MI and the mean LVEF was 30.4%. During hospitalization 51.6% had clinical evidence of HF and 21.3% were diagnosed with cardiogenic shock. PCI was performed in 75.6% of those eligible and 11.3% underwent CABG, 11.9% were medically managed and 1.25% underwent thrombolysis as a final revascularization strategy. On discharge 98% were on ASA, 81.3% on a second anti-platelet agent, 96% were on a beta-blocker, 75.6% were on an ACEi, 15.6% were on an ARB, 99.4% were on a statin. Only 22 (13.8%) of eligible patients were discharged on an MRA. No significant clinical difference existed amongst those that received an MRA compared to those that did not.

Conclusions:
Despite a Class IA recommendation for the use of MRAs in this patient population, our study demonstrates that the majority of patients are not prescribed an MRA after STEMI. This demonstrates a large care gap between evidence based guidelines and clinical practice. The reasons for this discrepancy in practice patterns are unclear and will be the focus of further study.
Abstract 16704: Role of Statins in Heart Transplant Recipients: A Meta-analysis
Authors: Vallakati Ajay , Reddy Siddharth , Dunlap Mark , Taylor David
Published: July 2021

Introduction:
Statins, through their immunomodulatory effects, may prevent cardiac allograft dysfunction in heart transplant recipients. Current International Society of Heart and Lung Transplantation (ISHLT) guidelines recommend the use of statins in these patients. Though several studies have demonstrated significant survival benefit with statin use, a pooled analysis evaluating the role of statins in heart transplant recipients has not been performed to date. We conducted a meta-analysis to study the effect of statins on outcomes in heart transplant recipients.

Methods:
We searched PubMed for all published studies comparing statins with controls in heart transplant recipients. Outcomes studied included all-cause mortality and hemodynamically significant / fatal rejection. All studies reporting these outcomes were included in the pooled analysis. Random effects model with Mantel-Haenszel method was used to analyze the outcomes.

Results:
We identified 9 studies (n = 2062) which compared outcomes in heart transplant recipients receiving statins (n = 1449) with that of those not receiving statins (n = 613). Of the 9 studies, 4 were randomized controlled trials and 5 were retrospective studies. There was no heterogeneity across the studies (mortality - I2 = 0%, rejection - I2 = 19%). The use of statins was associated with a significant reduction in all-cause mortality (OR 0.28, 95% CI 0.21-0.37, p < 0.0001). Statins also significantly decreased hemodynamically significant / fatal rejections (OR 0.41, 95% CI 0.25-0.69, p < 0.0001)

Conclusion:
Statins provide significant survival benefit and reduce cardiac allograft rejection in heart transplant recipients.
Abstract 16708: Increasing Age and the Benefit From Higher-intensity Lipid Lowering With Ezetimibe/Simvastatin vs. Simvastatin Alone: Results From the IMPROVE-IT Trial
Authors: Bach Richard G , Cannon Christopher , Giugliano Robert , White Jennifer , Lokhnygina Yuliya , Tershakovec Andrew , Musliner Thomas , Braunwald Eugene , Blazing Michael
Published: July 2021

Introduction:
While lipid lowering reduces cardiovascular (CV) events, evidence supporting high-intensity lipid lowering among elderly pts is more limited, and recent guidelines recommend moderate rather than high-intensity therapy for pts >75 yrs. We explored age subgroups within the IMPROVE-IT trial to evaluate whether age modified the benefit of adding ezetimibe (EZ) to statin therapy.

Methods and Results:
The IMPROVE-IT trial demonstrated the combination of EZ and simvastatin (EZ/S) significantly reduced major CV events vs. simvastatin (S) alone in pts with acute coronary syndrome (ACS) and LDL-C between 50 and 125 mg/dL. The primary composite endpoint was CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, and coronary revascularization >30 days. Outcomes according to age were compared in pre-specified subgroups using Kaplan-Meier (KM) analysis and Cox proportional hazards models using age as a continuous variable. Of the 18,144 pts enrolled, 7971 (44%) were 65 yrs or older and 2798 (15%) were 75 yrs or older at randomization. As age increased, event rate increased with KM rates at 7 yrs in the S arm of 30.8% for pts <65 yrs, 39.9% for pts ≥65 yrs, and 47.6% for pts ≥75 yrs. Treatment with EZ/S compared with S resulted in lower event rates in all age groups with an absolute reduction for pts <65 yrs of 0.85% (HR 0.98 CI 0.90-1.05), for pts ≥65 yrs of 3.6% (HR 0.89 CI 0.82-0.96), and for pts ≥75 yrs of 8.7% (HR 0.80 CI 0.70-0.90), with interaction P values of 0.09 and 0.005, respectively. Using age as a continuous variable found event rates for EZ/S vs. S were always lower, but the test for interaction between age and treatment effect for the primary endpoint was non-significant (P=0.15). The rate of gallbladder, liver, and muscle-related adverse events was not increased with EZ/S vs. S among older pts or younger pts.

Conclusions:
In the IMPROVE-IT trial, pts 65 yrs or older and especially pts 75 yrs or older after ACS derived substantial benefit from higher-intensity lipid lowering therapy with EZ/S compared with S alone, with no increase in safety issues among older age subgroups. These results may have implications for guideline recommendations regarding more intensive lipid lowering in the elderly.
Abstract 16718: Energy Induced Vasodilation in a Model of Endothelial Dysfunction Requires Nitric Oxide
Authors: Lindemer Brian , Weihrauch Dorothee , Keszler Agnes , Lohr Nicole
Published: July 2021

Introduction:
Over 8 million Americans are treated for peripheral artery disease (PAD), i.e. intermittent claudication, impaired wound healing, and critical limb ischemia. Endothelial dysfunction of the microcirculation is a potential mechanism for the pathogenesis of PAD because risk factors for PAD- age, hypertension, atherosclerosis, diabetes mellitus, and active tobacco use, have been directly related to a reduction in NOS expression and NO production. These reductions in NO bioavailability impair flow mediated dilation of the brachial artery and acetylcholine induced vasodilation. We have shown energy (670 nm (R/NIR)) can increase NO independent of NOS through release of NO from nitrosyl-heme stores. We hypothesized R/NIR can stimulate vasodilation, and serve as a potential therapy to recover vasodilation in a model of endothelial dysfunction (db/db mice).

Methods:
Human dermal microvascular endothelial cells (HMVEC) loaded with DAF-2 were stimulated with R/NIR 100mW/cm2 up to 6J. NO was measured using HPLC of DAF-2T. To test vasodilation, facial arteries from C57Bl/6 and db/db mice were isolated, pressurized to 60mmHg, and pre-constricted with U46619. The vessels were irradiated with 670 nm light (10mW/cm2) for 5 min with 10 min dark period between irradiation.

Results:
HMVEC stimulated with R/NIR increased NO 28.3% (±11.2, p<0.05). The NO scavenger c-PTIO inhibited R/NIR (17.0%±5.9, p<0.05) but was unchanged by pre-incubation with NOS inhibitor L-NAME (1mM) (13.1% ± 5.6). Vessel diameter increased up to 17.8% (±3, p<0.05) after 5 min with R/NIR. L-NAME did not affect dilation (13.74% ±2.2), however c-PTIO (100μM) could attenuate dilation (-.51% ± 1.1, p<0.001). R/NIR vasodilation was abolished with vessel denudation (1.2%± 2.21, p<0.001), suggesting R/NIR dilation was endothelial dependent. Impaired dilation in db/db mice was reversed, as R/NIR could significantly dilate db/db vessels after 5 min [(13.7% ± 2.8) vs. control (17.8% ±3)].

Conclusion:
R/NIR vasodilation requires intact endothelium and NO, but does not require NOS. In an obesity model of endothelial dysfunction, R/NIR can significantly restore vasodilation. Therefore, R/NIR as a source for therapeutic NO should be strongly considered in the treatment of ischemic wounds.
Abstract 16722: Comparison of Tricuspid Annular Plane Systolic Excursion to Fractional Area Change for Evaluation of Right Ventricular Systolic Function: Systematic Review and Meta-analysis
Authors: Lee Justin Z , Low See-Wei , Yun Seongseok , Dherange Parinita , Desai Ankit A , Juneman Elizabeth , Lee Kwan S , Suryanarayana Prakash
Published: July 2021

Introduction:
Right ventricular (RV) systolic function is prognostically important, but its assessment by echocardiography remains challenging. Tricuspid annular plane systolic excursion (TAPSE) and fractional area change (FAC) have been evaluated as echocardiographic indices for RV ejection fraction (RVEF), but their correlation with the gold-standard cardiac magnetic resonance imaging (CMRI) remains unclear. The aim of this meta-analysis is to pool and compare data from all studies that evaluated reliability of TAPSE and FAC in comparison to CMRI-derived RVEF.

Hypothesis:
We assessed the hypothesis that FAC is superior to TAPSE as an echocardiographic index for measurement of RV systolic function.

Methods:
A systematic literature search of 4493 potentially relevant citations from PubMed, and EMBASE databases yielded 25 eligible studies. The means of TAPSE and FAC, CMRI-derived RVEF, and correlation coefficients were pooled from each study for analysis.

Results:
A total of 25 studies were included in the final analysis, with a total of 1,858 patients who underwent 2D-echocardiography and cardiac MRI. FAC, compared to TAPSE, exhibited numerically superior correlation to CMRI RVEF (R2 = 0.63, and R2 = 0.15 respectively). Subgroup analysis revealed that FAC’s correlation was also numerically superior in patients with reduced right ventricular ejection fraction of less than 45% (R2 = 0.4 and R2 = 0.17, respectively). In patients with pulmonary hypertension (PH), TAPSE and FAC had mean correlation coefficients of 0.57±0.1 and 0.60±0.13, and were not statistically different (p=0.85).

Conclusions:
FAC is superior to TAPSE as an echocardiographic index for measurement of RV systolic function, even in patients with reduced right ventricular ejection fraction, but not in patients with PH. The adaptation to increased afterload of PH likely culminates in distinct and asymmetric patterns of RV dysfunction, which are not well assessed by FAC or TAPSE.