bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16055: Lipoprotein Subclasses, Size, and Statin-Associated Incident Diabetes: An Analysis From the JUPITER Trial
Authors: Dugani Sagar , Akinkuolie Akintunde O , Glynn Robert J , Ridker Paul M , Mora Samia
Published: July 2021

Statins reduce CVD events, LDL cholesterol (LDL-C) and triglycerides, with an increased risk of diabetes. The underlying predictors of statin-associated diabetes are unclear. We evaluated lipoprotein subclass and size changes in response to rosuvastatin to identify predictors of diabetes on statin therapy Among 11,918 non-diabetic participants in JUPITER (NCT00239681), lipoprotein subclasses and size were quantified by NMR spectroscopy (LipoScience, NC) prior to and 1 year after randomization to placebo or rosuvastatin (total 370 incident diabetes). Cox regression models were adjusted for diabetes risk factors Compared to baseline, rosuvastatin lowered LDL-C and particles by lowering cholesterol-enriched large LDL (58%) and IDL (46%), with less relative lowering of cholesterol-poor small LDL (22%), resulting in smaller LDL size (1.5%). Rosuvastatin lowered (15%-20%) triglycerides, VLDL triglycerides, and VLDL particles by lowering large (15%), medium (7%), and small (27%) particles, and increasing VLDL size (3%) (all p<0.0001). Among statin-allocated individuals, after adjusting for typical risk factors, incident diabetes was inversely associated with baseline levels of LDL-C, HDL-C, large LDL particles, and LDL size, and positively associated with baseline triglycerides, non-HDL-C, ApoB, LDL particles, VLDL particles, VLDL triglycerides and size (Table). Similar associations were seen in on-treatment rosuvastatin and placebo groups In JUPITER, random allocation to rosuvastatin altered the lipoprotein subclass profile in a manner associated with the development of diabetes Adjusted Hazard Ratios (95% CI) and Risk of Incident Diabetes with Rosuvastatin

Baseline parameters HR per 1-SD p value

LDL-C .86 (0.76-0.98) .02

HDL-C .69 (0.54-0.87) .002

Triglycerides 1.62 (1.41-1.86) <.0001

Non-HDL-C 1.20 (1.04-1.39) .01

ApoB 1.35 (1.18-1.55) <.0001

Total LDL* 1.32 (1.15-1.51) <.0001

Large LDL* .79 (0.71-0.87) <.0001

Small LDL* 1.71 (1.40-2.08) <.0001

IDL* .97 (0.85-1.11) .69

LDL size .66 (0.58-0.75) <.0001

Total VLDL* 1.16 (1.00-1.34) .046

Large VLDL* 1.78 (1.51-2.10) <.0001

Medium VLDL* 1.35 (1.15-1.58) .0002

Small VLDL* .93 (0.82-1.06) .30

VLDL size 1.58 (1.39-1.80) <.0001

VLDL triglycerides 1.51 (1.31-1.73) <.0001

*particles
Abstract 16128: Vascular Healing Response After Everolimus Eluting Stent Implantation in Patients With or Without Diabetes Mellitus -Evaluation With Optical Coherence Tomography
Authors: Goryo Yutaka , Uemura Shiro , Dote Yoko , Sugawara Yu , Ueda Tomoya , Okayama Satoshi , Watanabe Makoto , Saito Yoshihiko
Published: July 2021

Introduction:
Clinical introduction of percutaneous coronary intervention (PCI) with drug eluting stent has substantially decreased the rate of in-stent restenosis (ISR). However, it is reported that patients with diabetes mellitus (DM) still have higher incidence of restenosis and secondary cardiovascular events than patients without DM. Using intravascular optical coherence tomography (OCT), we evaluated the effect of DM on healing process of coronary artery after everolimus eluting stents (EES) implantation in the comparison with non-DM patients.

Methods and Results:
We studied 26 DM patients (65.1±11.9y/o) and 59 non-DM patients (68.1±9.4y/o) who received OCT-guided EES implantation. The second OCT examination was performed on 296±71.1 days after implantation (291±74.2days vs. 298±70.3days, p=0.51). OCT cross-sectional images of the second study were examined to determine the condition of neointimal coverage over every strut in 1mm interval (DM; 725 cross-sections and 5742 struts, non-DM; 1482 cross-sections and 12098 struts). In addition, neointimal thickness (NIT) over each strut measured and tissue characteristics were examined. One in-stent restenosis with clinical manifestation was observed in each group. Average NIT was significantly thicker in DM group than in non-DM group (107±99.2μm vs. 92±74.6μm, p<0.01). The incidence of malapposed struts without neointimal coverage were very low and similar in both groups (0.22±0.54 vs. 0.13±0.72%, p=0.43). The frequency of OCT-defined unstable neointimal characteristics was significantly higher rate in DM than non-DM group (14.5±18.9% vs. 6.67±14.5%, p=0.03).

Conclusions:
EES implanted in DM patients showed acceptable neointimal proliferation and uncovered stent struts similar to non-DM patients, suggesting the mid-term efficacy and safety of EES in DM patients. However, long-term follow-up should be necessary because of the high incidence of unstable neointimal characteristics which might be a substrate for the future development of neoatherosclerosis.
Abstract 16129: Feasibility and Safety of Treatment With an Intracoronary Infusion of Adipose Derived Regenerative Cells (ADRC) in Patients With an Acute ST-Elevation Myocardial Infarction (ADVANCE study)
Authors: Duckers Henricus J , Musialiek Piotr , Dudek Daiusz , Kochman Janusz , Kesten Steven , Pompilio Giuilo
Published: July 2021

Objectives:
The ADVANCE clinical trial sought to define the safety, feasibility and efficacy of an intracoronary infusion of adipose derived regenerative cells in patients admitted with an acute ST-elevation myocardial infarction (STEMI) within 24 hours of successful primary PCI.

Methods:
In this randomized, double-blind, placebo-controlled trial (n=23, 2:1 randomization), within 24 hours of successful primary PCI following STEMI, a small volume liposuction was performed for fat harvest and ADRC isolation by an automated Celution® System, and intracoronary infusion within 12 hours of the liposuction.

Results:
23 patients were enrolled to date (all male, age 58 years, BMI 28 kg/m
2
). The liposuction procedure data are shown in the table TEMI patients were routinely treated with dual anti platelets and heparin. The decline in hemoglobin following the liposuction procedure from baseline over the 10 hours following the procedure was 10.2% ±7.6 (mean
±
SD) Although two patients had >20% of Hb decline at anytime (maximum 20.8%), one of these patients returned to within 10% of baseline by 10 hours without transfusion. The liposuction procedure was completed in all but one patient (terminated early due to hypotension - resolved with termination of procedure).

IC infusion of the ADRC suspension was performed successfully in all patients. No impediment of coronary TIMI flow was observed during or following cell infusion of these mesenchymal-like cells. No ventricular arrhythmias were observed during cell infusion. No major adverse cardiac or cerebral events (MACCE) occurred within 30 days of the procedures.

Conclusion:
Limited liposuction to harvest fat for ADRC stem cell isolation and subsequent intracoronary infusion of these autologous ADRCs can be performed safely in patients with acute STEMI under dual antiplatelets therapy, demonstrating feasibility of the therapeutic application of point-of-care cell therapy using ADRCs.
Abstract 16248: Comparison of a Non-Invasive Respiratory Volume Monitor to End-Tidal CO2 in Measuring Changes in Minute Ventilation
Authors: Williams George , Fleming Eamon , Voscopoulos Christopher
Published: July 2021

Introduction:
Monitoring respiratory performance is a challenge. Use of secondary indicators like oxygen saturation (SpO
2
) and capnography (EtCO
2
) have introduced delay in diagnosis and can produce false alarms. EtCO
2
in non-intubated patients has been problematic. We compared performance of an EtCO
2
monitor to a respiratory volume monitor (RVM), which provides accurate (error <10%) measurements of minute ventilation (MV), tidal volume & respiratory rate, to assess changes in respiratory status in non-intubated subjects.

Methods:
Continuous RVM (ExSpiron, Respiratory Motion, Waltham, MA) and capnography data (Capnostream 20, SmartCapnoLine Plus & Filterline Set, Covidien, Mansfield, MA) were collected from 39 subjects. The relationship between EtCO
2
& MV for each patient was quantified & EtCO
2
sensitivity to MV changes and mean EtCO
2
values were compared across the two EtCO
2
sampling techniques (paired t-test).

Results:
A strong negative correlation between MV changes and EtCO
2
changes was found (similar between nasal sampling (NS) and in-line sampling (IS) ( -0.6 ±0.1 v -0.7±0.1 mmHg/(L/min), p>0.1, Fig 1A)). IS readings were higher than NS for each patient. In the same patients (normal breathing) the average IS EtCO
2
was 36.7 ±0.7 vs 33.7±0.6 mmHg for NS (p<0.01) despite larger MV (8.74 ±0.5 vs 7.0±0.5 L/min). Similar disparity was present during hypo & hyperventilation (Fig 1B&C). Regardless of sampling methodology, EtCO
2
displayed poor resolution in response to large swings in MV (13 & 14 mmHg in response to 17 & 21 fold increase in MV; IS & NS, respectively).

Conclusions:
Under controlled experimental conditions & with an in-line sensor capable of capturing 100% of exhaled air, EtCO
2
did not report large swings in MV with fidelity. Commonly used nasal sampling introduced a systematic bias that could further delay informing clinicians of dangerously low MV. RVM provides a direct measure of MV, eliminating the lag between a change in MV and secondary measurements.
Abstract 16328: Residual Pulmonary Hypertension Persist Even in Patients With Successful MitraClip and Adversely Affect Heart Failure Events
Authors: Saji Mike , Ailawadi Gorav , Dent John , Lim David S
Published: July 2021

Background:
Pulmonary hypertension (PH) is common among patients requiring mitral valve treatment, and even mild PH adversely affect outcome. The aim of the study was to investigate the response of pulmonary artery pressure (PAP) in patients undergoing MitraClip and determine the prognostic effect of residual PH.

Methods:
From 2007 to 2013, 121 consecutive patients undergoing the MitraClip were retrospectively reviewed. Patients were categorized into two groups according to residual PH defined by post-procedural PAP obtained by transthoracic echocardiography. The primary endpoint was combined endpoints of all-cause mortality, left ventricular assist device implantation, shock, mitral valve surgery, New York Heart Association III-IV, re-hospitalization due to heart failure, new onset atrial fibrillation requiring hospitalization, ventricular arrhythmia, mechanical ventilation more than 48 hours, admission longer than two weeks. Patients with existing pulmonary disease or systemic disease affecting PAP were excluded.

Results:
Forty seven of 86 had residual PH. Patients with residual PH had higher pre-procedural PAP, and higher six months PAP than those without residual PH (pre-procedural, 50.3±13.4 vs 42.2±9.8 mmHg, p=0.003; at six months, 45.4±14.0 vs 34.7±9.9 mmHg, p<0.001, respectively). Patients without residual PH had an immediate decrease in PAP (42.2±9.8 vs 31.5±5.9 mmHg, p<0.001), while patients with residual PH had a decrease in PAP at a month, but not a significant change immediate post-procedure (pre- to post-procedure, 50.3±13.4 to 49.7±7.2 mmHg p=0.808; post-procedure to a month, 49.7±7.2 to 43.3±10.3 mmHg, p<0.001). Primary combined endpoint at two years met 26.5%. The Kaplan-Meier Curve (Log rank method) showed patients with residual PH had poorer outcome on primary endpoint (p=0.017). The independent predictor of the primary endpoint evaluated by multivariate analysis (Cox proportional hazard) was post-procedural PH [hazard ratio 2.9, 95% confidence interval 1.1-7.9].

Conclusion:
Patients with residual PH have higher rate of adverse events associated with heart failure even with successful MR reduction, and additional medical intervention, such as pulmonary vasodilator, should be considered.
Abstract 16680: Lipoprotein(a) and Progression Rate of Aortic Valve Stenosis - A Pooled-Analysis of Two Prospective Studies
Authors: Capoulade Romain , Tastet Lionel , Mahmut Ablajan , Chan Kwan L , Guauque-Olarte Sandra , Arsenault Marie , Bedard Elisabeth , Arsenault Benoit J , Gaudreault Nathalie , Dumesnil Jean G , Teo Koon K , Tam James W , Després Jean-Pierre , Mathieu Patrick , Bossé Yohan , Pibarot Philippe
Published: July 2021

BACKGROUND:
Recent studies have reported a single nucleotide polymorphism (i.e. rs10455872) at the LPA gene locus, encoding the lipoprotein(a) [Lp(a)], is associated with the presence of aortic valve calcification and clinical aortic stenosis (AS). The objectives of this study were to examine the association of Lp(a) plasma levels and rs 10455872 with the progression rate of AS.

METHODS:
Lp(a) plasma levels were measured in 203 patients with AS included in the ASTRONOMER (NCT00800800) trial and 246 patients in the PROGRESSA study (NCT01679431). The polymorphism rs10455872 was genotyped in the PROGRESSA cohort. Hemodynamic progression rate of AS severity was assessed by measuring the annualized increase in peak aortic jet velocity (Vpeak) by Doppler-echocardiography.

RESULTS:
Twenty-seven (13%) patients of the ASTRONOMER trial and 47 (19%) of the PROGRESSA study had high Lp(a) plasma levels (i.e. >50mg/dL). Baseline AS severity was similar in patients with high vs. low Lp(a) levels (p>0.10). In the pooled-analysis of both cohorts (a total of 449 patients with mean follow-up: 3.0 ±1.4 yrs), AS progression rate was similar in patients with Lp(a)>50 mg/dL compared to those with Lp(a)≤50 mg/dL (annualized change in Vpeak: +0.17±0.21 vs. +0.17±0.21 m/s/yr; p=0.97). Stratified analyses by cohort provided consistent results (ASTRONOMER: +0.20±0.21 vs. +0.25±0.19 m/s/yr; p=0.20; and PROGRESSA: +0.12±0.21 vs. +0.14±0.20 m/s/yr; p=0.46). In the PROGRESSA study, 38 (16%) patients carried at least one rs10455872 risk allele. Carriers of the risk allele had higher Lp(a) levels (58±24 vs. 20±38 mg/dL; p<0.0001). Baseline AS severity was similar in carriers and non-carriers whereas there was a borderline significant association for lower AS progression rate in carriers compared to non-carriers (+0.07±0.17 vs. +0.15±0.21 m/s/yr; p=0.05). Similar results were obtained for baseline and annualized progression rate assessed by aortic valve area.

CONCLUSION:
This prospective study shows that neither LPA gene variant nor Lp(a) plasma levels are associated with faster AS progression rate. Our findings do not support the notion that Lp(a) levels are related to AS progression rate in patients with AS.
Abstract 16892: Beneficial Effect of miR-25 Decoy Overexpression in a Murine Model of Heart Failure
Authors: Jeong Dongtak , Oh Jae Gyun , Baccarini Alessia , Brown Brian , Mercola Mark , Hajjar Roger J
Published: July 2021

Introduction:
Recently, our group found that miR-25 is a key microRNA that regulates SERCA2a and we showed anti-miR25 treatment enhanced cardiac contractility and function through SERCA2a restoration in murine heart failure model. However, the strong and stable suppression of specific microRNA activity would be essential to evaluate the therapeutic potential of such an approach. In this study, we constructed a miR-25 decoy t using TuD RNA (tough decoy RNAs) and miR-25 decoy activity was evaluated in various settings.

Methods:
First, miR-25 decoy construct was applied to both isolated adult cardiomyocytes and H9C2 cardiomyoblasts. A pMirTarget vector containing SERCA2a 3’-UTR under luciferase was used to evaluate this decoy specificity. Second, we generated pressure-overload heart failure models in mouse by TAC operation. In the HF mice, AAV9-GFP (control) and AAV9-miR-25 decoy were delivered by tail vein injection. Two months following gene transfer, cardiac function was evaluated by echocardiography and invasive hemodynamics. Protein and RNA expression levels of SERCA2a and miR-25 expression level were confirmed by qRT-PCR analysis.

Results:
First, we observed that we were able to achieve about 2-3 fold increase of SERCA2a expression by miR-25 decoy transfection in both H9C2 and in isolated adult cardiomyocytes. Also, similar expression pattern was confirmed in the heart of miR-25 decoy injected normal mice. Second, the HF model by TAC surgery was confirmed with echocardiography. Overall average FS (%) in HF was 37.77+/- 8.75 (n=10) and in non-surgery control mice was 62.51 +/- 3.42(n=4). After AAV9 injection, cardiac function of AAV9-miR-25 decoy injected mice was enhanced but AAV9-GFP injected mice showed severe cardiac dysfunction and dilation (AAV-GFP (n=6) vs AAV-miR-25 decoy (n=4)). Third, western blot analysis showed that SERCA2a expression was significantly restored in miR-25 decoy injected mice. In addition, we confirmed that miR-25 expression level was kept low by qRT-PCR analysis. Taken together, our data would indicate that using miR-25 decoy is an effective strategy for the long-term suppression of miR-25 and it may be a promising therapeutic target to restore SERCA2a and reverse the HF phenotype.
Abstract 16899: Neutralization of Bleeding Induced by Direct Factor Xa and Thrombin Inhibitors by Prothrombin Complex Concentrates Alone and in Combination with Antifibrinolytic Agents
Authors: Jeske Walter , Escalante Vicki , McGeehan Elizabeth , Walenga Jeanine , Fareed Jawed , Bakhos Mamdouh
Published: July 2021

Introduction:
Concerns remain over bleeding with direct factor Xa and thrombin inhibitors in cases of overdose or medical emergency. This study tested the ability of PCCs to reverse bleeding induced by apixaban, rivaroxaban or dabigatran in a standardized rat tail resection model.

Methods:
Individual groups of anesthetized rats (8-10) were anticoagulated with apixaban, rivaroxaban or dabigatran and subsequently treated with vehicle, 3-factor (Profilnine), 4-factor (Beriplex) or activated 4-factor PCC (FEIBA). Five minutes post-PCC administration, a tail snip was performed and bleeding time was measured. Upon cessation of bleeding, a blood samples were collected for ex vivo analysis and the rat was humanely euthanized.

Results:
In comparison to saline control (6.8 + 1.1 sec) apixaban (300μg/kg) prolonged bleeding time (17.1±5.6; p=0.024). Beriplex at doses ≤10U/kg did not shorten bleeding time while 10U/kg Profilnine did. FEIBA prolonged bleeding beyond that seen with apixaban alone (22.6±11.4 and 37.5±5.2 min for 5 and 10U/kg doses; p<0.001 apixaban + 10U/kg FEIBA vs. apixaban). 100 and 300μg/kg rivaroxaban prolonged bleeding time (20.8±2.5, p=0.002 vs. saline; 25.0±10.0 min, p<0.001 vs. saline). Profilnine was more effective than Beriplex or FEIBA in reversing rivaroxaban-induced bleeding. Dabigatran-induced bleeding was prevented by Beriplex or Profilnine but enhanced by FEIBA (50.3±8.3 vs. 15.9±1.2 min; p<0.001). Treatment of apixaban or rivaroxaban anticoagulated rats with FEIBA + 10mg/kg epsilon aminocaproic acid, produced bleeding times comparable to those of non-anticoagulated rats (apixaban: 6.7±5.0 min; rivaroxaban: 7.7±6.4 min). Ex vivo analysis of blood samples did not show any relevance with the observed bleeding or its modulation.

Discussion:
PCCs appear useful for neutralizing bleeding induced by direct factor Xa and thrombin inhibitors, but each PCC exhibits a distinct neutralization profile. Co-administration of a fibrinolytic inhibitor may enhance effectiveness of hemorrhage reversal by PCCs.
Abstract 16905: Fluorescence Resonance Energy Transfer Reveals that Cardiac Calcium ATPase Dimerizes and Forms a Complex with Phospholamban in a 2:1 Stoichiometry
Authors: Blackwell Daniel , Robia Seth L
Published: July 2021

The sarco/endoplasmic reticulum calcium ATPase (SERCA) has been proposed to form functional dimers in vitro. In order to investigate whether SERCA forms homo-dimers in live cells, we fused canine SERCA2a to cerulean (Cer) or yellow fluorescent protein (YFP), and quantified SERCA-SERCA interactions by fluorescence resonance energy transfer (FRET). SERCA-SERCA FRET efficiency was dependent on the labeling position of the fluorescent protein tags, with the highest FRET efficiency achieved when the respective fluorescent proteins were fused to SERCA N-termini. FRET was reduced by competition with unlabeled SERCA, suggesting that the observed FRET was due to specific protein-protein interactions. Progressive photobleaching of YFP showed that Cer intensity increased linearly with decreasing YFP intensity, suggesting that the stoichiometry of the SERCA complex is a dimer. In contrast, a control experiment with phospholamban (PLB) oligomer showed a non-linear YFP/Cer relationship, consistent with its well-known pentameric stoichiometry. We also investigated whether SERCA dimers could interact with PLB, the regulatory binding partner of SERCA. Interestingly, while average maximal FRET was 28% between SERCA and PLB, fluorescence lifetime measurements revealed two different lifetimes, consistent with two different populations of FRET donors. One population showed very low FRET, while the other population exhibited high FRET- approximately double the measured average maximal FRET efficiency. The data are consistent with a single PLB bound to each SERCA homo-dimer; in this regulatory complex one SERCA protomer is in close proximity to PLB (50 Å), while the other is too far away to participate in FRET with PLB.
Abstract 17132: Risk Factors for Anthracycline And/or Herceptin-induced Left Ventricular Systolic Dysfunction
Authors: Hamirani Yasmin S , El Sayed Ali , Dillon Patrick , Wong Andrew , Mehra Pooja , Kramer Christopher M , Salerno Michael
Published: July 2021

Introduction:
Anthracyclines (ANT) and Herceptin (HER) are known to cause left ventricular (LV) systolic dysfunction and congestive heart failure (CHF). We aimed to identify the clinical risk factors associated with reduced LV function caused by one or both agents.

Methods:
We retrospectively examined our electronic records for patients that received ANT and/or HER from 2000-2013 and identified 3253 patients. 2704 were excluded for lack of a follow-up EF assessment (2699) or development of CAD (5) after the start of chemotherapy. Of the remaining 216 patients, 27 (12.5%) had a drop in EF after chemotherapy of >10% to below 50% and 185 (86.6%) did not. Kruskal Wallis test and Fisher exact test were utilized to estimate the difference between groups, and logistic regression model was used to predict a fall in EF.

Results:
More patients with a fall in EF had hypertension (HTN), hyperlipidemia (HL) and CAD (Table). A higher % of patients with a fall in EF received both HER and ANT as compared to ANT alone (36% vs 9.5% p=0.001). Higher use of liposomal doxorubicin was seen in the group with no reduction in EF. The median (IQR) time difference (days) between start of chemotherapy and reduced EF was 213 (76-761) and the doxorubicin dose in this group was 240 (128.5-254) mg/m2. On multivariate analysis hypertension and use of Herceptin remained independent predictors of EF fall.

Conclusion:
HTN, HL, CAD and concomitant HER use were univariate predictors of EF decline, while only HTN and HER were independent multivariate predictors. Given the prevalence of reduced EF at follow-up, late assessment of EF is indicated to avoid missing chemotherapy-induced cardiotoxicity.
Abstract 17241: Impaired Left Atrioventricular Coupling Compromises Cardiac Performance in Heart Failure With Preserved Ejection Fraction
Authors: Zakeri Rosita , Takahama Hiroyuki , Araoz Philip A , Lee Hon-Chi , Redfield Margaret M
Published: July 2021

Background:
In heart failure with preserved ejection fraction (HFpEF), left ventricular (LV) systolic elastance (Ees) increases in tandem with increases in arterial elastance (Ea), which maintains ejection fraction but limits systolic reserve and precipitates volume sensitivity. The left atrium (LA) lies in series with the LV and contributes to LV stroke volume. We hypothesized that HFpEF is associated with increased LA systolic elastance (E
LA
) and deranged atrioventricular (AV) coupling which may additionally compromise cardiac performance.

Methods:
HFpEF was modeled by experimental hypertension (bilateral renal wrap + DOCA) in elderly dogs (n=9). LA and LV structure, function (echo, MRI) and invasively assessed pressure-volume relationships (PVR, open-chest; pericardiotomy; admittance catheter) were compared to sham-operated young dogs (control; n=13).

Results:
As compared to controls, HFpEF dogs displayed concentric remodeling, with increased diastolic stiffness, Ea and Ees (p<0.05 for all) and reduced Ea/Ees (p=0.03). LA maximum volume (28±3 vs 23±3mL, p=0.007), LA stroke volume (4±1 vs2±1mL, p=0.006), LA active emptying fraction (18±6 vs 12±2%, p=0.03) and LA ejection rate (51±14 vs 30±16mL/s) were higher in HFpEF versus controls, suggesting increased LA stroke work and inotropy. At matched heart rate and LA pressure, E
LA
was steeper in HFpEF than control (2.7±0.9 vs 1.5±0.6mmHg/mL, p=0.01) and positively correlated with Ees (r=0.6, p=0.005) and Ea (r=0.66, p=0.002). However AV mismatch occurred as increases in E
LA
were not proportionate to increases in Ees (Ees/E
LA
1.3±0.4 HFpEF vs 0.8±0.4 control, p<0.05). On linear regression, worse AV coupling (i.e. higher Ees/E
LA
) was associated with lower LV stroke volume (
Figure
).

Conclusion:
In experimental HFpEF, despite enhanced LA contractility, AV coupling was deranged. Worse AV coupling may further contribute to reserve dysfunction, LA pressure rise, and susceptibility to pulmonary edema in HFpEF.
Abstract 17406: Association of Post-operative Complications with Clinical Outcomes and Hospital Costs following the Norwood Operation
Authors: McHugh Kimberly E , Pasquali Sara K , Hall Matthew A , Scheurer Mark A
Published: July 2021

Introduction:
Patients undergoing the Norwood operation consume considerable healthcare resources. However, data are limited regarding factors impacting hospitalization costs for these patients. We evaluated the association of post-operative complications with hospital costs.

Methods:
We utilized a unique dataset consisting of prospectively collected clinical outcomes and complications data from the Pediatric Heart Network Single Ventricle Reconstruction trial linked at the patient level with cost data for hospitals (n=10) participating in the Children’s Hospital Association administrative databases during the trial period. Probabilistic matching of indirect identifiers was used to link records. Cost-to-charge ratios were used to estimate costs, which were adjusted for regional differences and inflation. The relationship between complications and cost was modeled using linear regression, accounting for the skewed distribution of cost, and adjusting for within-center clustering and patient characteristics.

Results:
A total of 334 eligible Norwood records (95%) were matched between datasets. Overall, 82% suffered at least one complication (median 2; range 0-33). The most common complications associated with increased hospital costs included: cardiopulmonary resuscitation (22%), arrhythmia (22%), sepsis (15%), and extracorporeal membrane oxygenation (11%). Those with complications had longer post-operative length of stay (25d vs. 12d, p<0.0001), more total ventilator days (7d vs. 5d, p<0.0001), and higher in-hospital mortality (17.6% vs. 3.4%, p<0.01). Adjusted hospital costs in those with a complication were $113,505 (95% CI $99,326 - $129,707) vs. $71,453 (95% CI $59,200 - $86,243) in those without a complication, p=0.0001, and costs increased with the number of complications (1-2 complications = $117,137 vs. 3-4 complications = $155,500 [p<0.01] vs. ≥5 complications $266,386 [p< 0.0001]).

Conclusions:
This unique dataset of merged clinical trial and cost data demonstrated that postoperative complications are common following the Norwood operation and are associated with worse clinical outcomes and higher costs. Efforts to reduce complications in this population may lead to both improved outcomes and cost savings.
Abstract 17480: Safety and Efficacy of Continuous Anticoagulant and Antiplatelet Combination Therapy during Implantation of Cardiac Rhythm Devices
Authors: Ishibashi Kohei , Miyamoto Koji , Wada Mitsuru , Nakajima Ikutaro , Okamura Hideo , Noda Takashi , Aiba Takeshi , Takaki Hiroshi , Kamakura Shiro , Ishihara Masaharu , Anzai Toshihisa , Yasuda Satoshi , Ogawa Hisao , Kusano Kengo
Published: July 2021

Introduction:
Previous studies showed that continuous anticoagulation during implantation of cardiac rhythm device (CRD) was safe. However, the safety and efficacy of continuous anticoagulant and antiplatelet combination therapy in patients undergoing CRD interventions has not been clearly defined.

Hypothesis:
We sought to evaluate the safety and efficacy of this therapy during implantation of CRD.

Methods:
A total of consecutive 300 patients (mean 68.7 years old, 171 males) underwent CRD implantation were enrolled from April 2012 to December 2012. We divided patients into Non-drug (patients without antithrombotic therapy), Single-drug (patients with anticoagulant or antiplatelet therapy), and Combination-drug (patients with anticoagulant and antiplatelet therapy) group, and evaluated the clinical outcome among 3 groups. Clinically significant hematoma was defined as device-pocket hematoma that needed prolonged hospitalization, interruption of antithrombotic therapy, surgical intervention, or blood products transfusion.

Results:
The number of Non-drug, Single-drug, and Combination-drug groups was 129, 139, and 32, respectively. Clinical outcome was shown in Table. Hematoma occurred significantly more in Combination-drug than Non-drug group, but occurrence of clinically significant hematoma was not different among 3 groups. Cardiac tamponade was none and thrombo-embolic event was rare.

Conclusions:
Continuous anticoagulant and antiplatelet combination therapy was safe and effective during implantation of CRD.
Abstract 17649: Inhibition of Src Homology 2 Domain-containing Phosphatase 1 (SHP-1) Increases Insulin Sensitivity in High-fat Diet-induced Insulin Resistant C57black6 Mice
Authors: Krüger Janine , Dagnell Markus , Stawowy Philipp , Caglayan Evren , Östman Arne , Kintscher Ulrich , Kappert Kai
Published: July 2021

Background:
Insulin resistance plays a crucial role in the development of type 2 diabetes, and exerts great impact on vascular inflammation and remodeling. At the molecular level a post-insulin receptor (IR) defect in insulin signaling has been suggested to contribute to insulin resistance. IR signaling is antagonized and tightly controlled by protein tyrosine phosphatases (PTPs). The precise role of PTPs in insulin resistance, however, has not been explored.

Results:
Male C57BL/6J mice were fed a high-fat diet (HFD, 60% kcal from fat) to induce insulin resistance, or a low-fat diet (LFD, 10% kcal from fat) for 10 weeks. Afterwards, HFD mice were treated with PTP-inhibitors for additional 6 weeks. Mice under HFD exhibited a significant increase in body weight as well as decreased respiratory quotient and adiponectin levels, and were characterized by impaired insulin- and glucose tolerance. Organ-based gene expression analyses in insulin-resistant mice demonstrated upregulation of SHP-1, PTP1B, LAR, and DEP-1 in insulin-sensitive organs. SHP-1 was further explored in vitro. Insulin stimulation in murine liver cells induced site-selective hyper-phosphorylation at IR tyrosine-sites Y1158, and Y1361 after inhibition of SHP-1. Furthermore, SHP-1 impairment time-dependently enhanced insulin-induced Akt- and Erk-phosphorylation, and resulted in elevated glucose uptake in skeletal muscle cells. Administration of a SHP-1 inhibitor (Sodium Stibogluconate) and a brought pan-PTP inhibitor (BMOV) in HFD mice led to improvement of both insulin- and glucose tolerance. In accordance, PTP-activity was significantly impaired in epididymal fat, skeletal muscle, and liver under BMOV treatment, being confirmed by reduced ex vivo dephosphorylation of a radioactive labelled peptide (AEEEIYGEFEAKKKK). Finally, BMOV- and SHP-1 treatment also resulted in reduced body weight.

Conclusions:
IR-antagonizing PTPs were organ-specifically regulated in insulin resistance. The results indicate a central role of PTPs and, in particular, of SHP-1 as endogenous antagonists of the IR. Taken together targeting PTPs led to beneficial effects in insulin resistance, and may thus improve metabolic diseases as well as cardiovascular morbidity and mortality.
Abstract 17875: Translating 3D Printing into Clinical Practice: Do Patient-Specific Models Aid in Communicating with Parents of Children with Congenital Heart Disease?
Authors: Biglino Giovanni , Capelli Claudio , Schievano Silvia , Wray Jo , Leaver Lindsay-Kay , Khambadkone Sachin , Giardini Alessandro , Derrick Graham , Jones Alex , Taylor Andrew M
Published: July 2021

Introduction:
Communication in medical consultations is recognised as an important factor in optimising patient satisfaction and health outcomes. Patient-specific (PS) plastic models of congenital heart lesions may offer benefits for education and communication purposes. This study aimed to quantitatively test the translational potential of PS models in a systematic manner.

Methods:
Parents of children with congenital heart defects (n=97), matched for age, sex and level of education, were divided into Group I (n=52) for normal consultations/follow-up visits, and Group II (n=45) where PS models generated from magnetic resonance imaging and printed in white nylon with rapid prototyping machine model were additionally used. Participants and cardiologists completed rating scales (scored from 0-10) to assess parents’ knowledge of their child’s condition before and after the consultation and to provide feedback on any tools used, including the 3D model.

Results:
Clinicians reported that the models were very useful (8.8±1.1/10), encouraged parent interaction (9.1±1.4/10), and did not lengthen consultation (93% cases), although these lasted 5 minutes longer (p=0.02). Parents rated PS models as very useful (9.5±0.7/10) and more informative than medical images, with 73% explicitly asking to keep their model. Parents in both groups equally felt their understanding improved following their visit, although when their questionnaires were rated blindly by two cardiologists only 5 participants per group were actually found to demonstrate improved understanding. In 40% of cases the cardiologists were not able to gather even the primary diagnosis based on the information provided by parents after their consultation.

Conclusions:
Patients’ parents and clinicians found PS models to be useful communication tools, although parents’ understanding appears to be mainly related to their prior level of knowledge. Clinicians found PS models useful in explaining congenital heart defects and encouraging parent interaction. Use of such a modality during the first interactions with parents may have benefits for improving parents’ participation in their child’s management.
Abstract 18307: Prevalence, Predictors and Prognostic Impact of High On-treatment Platelet Reactivity to Aspirin and Clopidogrel in Patients With Symptomatic Peripheral Artery Disease in Japanese Population
Authors: FUKINO KEIKO , Hozawa Koji , Matsumoto Takahiro , Ishiguro Hisaaki , Nakamura Sunao
Published: July 2021

Introduction:
High on-treatment platelet reactivity (HPR) is associated with increased risk of ischemic events and therapeutic failure in patients with coronary artery disease, whereas its role in patients with peripheral artery disease is not widely reported.

Purpose:
This study aims to investigate the prevalence of HPR in patients with symptomatic peripheral artery disease and its possible predictors in Asian population.

Methods:
Among patients who underwent endovascular therapy at our institution during September 2013 to April 2014, 125 patients who received aspirin and/or clopidogrel were included. Residual platelet reactivity was assessed with VerifyNow aspirin and P2Y12 assays. HPR was defined as aspirin reaction units (ARU) ≧ 550 for aspirin and P2Y12 reaction units (PRU) ≧ 235 for clopidogrel.

Results:
The prevalence of HPR to aspirin was not significantly different between patients with intermittent claudication (IMC) and critical limb ischemia patients (22.2% and 23.2%, respectively), whereas the prevalence of HPR to clopidogrel was higher in CLI patients, especially in patients with tissue loss compared to IMC patients (39.3% and 62.5%, respectively, p<0.05). 7.7% of IMC patients and 12.5% of CLI patients showed HPR to both aspirin and clopidogrel. Multivariate analysis revealed that age and diabetes were independent predictors for HPR to clopidogrel.

Conclusion:
HPR to aspirin and/or clopidogrel was highly prevalent in symptomatic PAD patients in Japanese population. The prevalence of HPR was significantly higher in patients with tissue loss compared with those without. Optimizing antiplatelet regimen according to residual platelet reactivity in CLI patients would be indispensable to avoid repeat revascularization and unexpected amputation.
Abstract 18666: What are Key Factors to Achieve Better Stent Apposition at Left Main Bifurcation by Culottes Stenting Technique? Micro-CT Analysis Using Bifurcated Elastic Coronary Artery Models
Authors: Hikichi Yutaka , Ohba Takafumi , Inukai Tsuyoshi , Kishigami Sho , Arai Jun , Umezu Mitsuo , Node Koichi , Iwasaki Kiyotaka
Published: July 2021

Introduction:
We hypothesize that restenosis or stent thrombosis at left main (LM) bifurcation after two-stenting are caused by incomplete stent apposition to coronary artery which may be affected by bifurcation angles, stent design, stent size, and stenting techniques. We investigated influences of those factors on stent apposition using bifurcated elastic coronary artery models (CAMs) to understand better two-stenting with culottes technique.

Methods:
Based on CT angiography of 209 patients, three LM bifurcated CAMs were manufactured. Focusing on magnitude of the angles between LMT and LCx, the angle data were divided into three groups. Each average model such as the LMT-LCx, LAD-LCx, and LMT-LAD angles of 143°, 59.1°, and 144.3° (mild model: MiM), 121.9°, 70.6°, and 141.4° (moderate model: MoM), and 99.1°, 86.2°, and 143.6° (severe model: SM) was manufactured. Each model has 60% stenosis along with LMT to LAD, and 50% stenosis at LCx ostium. Diameters of LMT, LAD, and LCx were 4.5mm, 3.5mm, and 3.0mm. Two-link Nobori (N) and 3-link Xience V (X) stent were employed for comparison. Moreover, differences in selection of 3.5mm-diameter (3.5D) or 3.0D stent for LCx on stent apposition were investigated, because stent expansion capability differs between the two sizes. When 3.5D stents were used for LCx, stents were deployed at balloon inflation pressure of 4atm for N and 5 or 6atm for X, respectively. Then, additional stent expansion with a 3D balloon was performed. Culottes stenting and final kissing balloon inflation were performed by a single doctor. Stent incomplete apposition volume (SIAV) was quantitatively assessed using micro-CT.

Results:
When 3D stents were used for LCx, there were no differences in SIAV among MiM, MoM, and SM, both for N and X. Interestingly, when 3.5D stents were used for LCx, SIAV of N were smaller in SM than that in MiM and MoM, respectively (p<0.05), and SIAV of X in SM were larger than that in MiM (p<0.05). When 3D stents were used for LCx, SIAV were comparable between N and X, regardless of the bifurcation angles. When 3.5D stents were used for LCx, SIAV of N were smaller than that of X in MoM and SM (p<0.05).

Conclusions:
The bifurcation angle between LMT and LCx, stent design, and stent size for LCx were key factors to reduce SIAV in culottes stenting.
Abstract 18910: Angiotensin Converting Enzyme 2 Deficiency Results in Cardiac Insulin Resistance in Response to High-Fat Diet
Authors: Patel Vaibhav B , Mori Jun , McLean Brent A , Lopaschuk Gary D , Oudit Gavin Y
Published: July 2021

Background:
Activation of the renin-angiotensin system (RAS) can alter the cardiac energy substrate preference, thereby contributing to the progression of heart failure. Angiotensin converting enzyme (ACE) 2 is a key negative regulator of the RAS where it metabolizes angiotensin (Ang) II into Ang (1-7).

Hypothesis:
Myocardial ACE2 was upregulated in response to high-fat diet in wildtype (WT) mice. We hypothesize that ACE2 upregulation is a compensatory response and loss of ACE2 will worsened obesity and its associated cardiomyopathy.

Methods and Results:
ACE2-null (ACE2-/y; ACE2KO) and WT litter-mate control mice were fed with high-fat diet (HFD; 45 kcal%) or control diet (10 kcal%) and studied at 6-months of age. In contrast to our hypothesis, loss of ACE2 resulted in decreased obesity in response to HFD compared to WT mice (body weight at 6-months: 45.9±4.3 in ACE2KO-HFD vs 51.4±1.55 in WT-HFD; p<0.05). Conversely, ACE2KO-HFD mice showed increased fasting plasma glucose levels (6.76±0.7 in ACE2KO-HFD vs 5.11±0.6 in WT-HFD; p<0.05) with worsened whole-body insulin resistance. We subjected hearts to ex vivo aerobic perfusions to measure cardiac energy metabolism. ACE2KO-HFD hearts showed markedly decreased cardiac work along with reduced insulin response suggesting increased myocardial insulin resistance. ACE2KO-HFD hearts relied predominantly on fat metabolism as the energy source, a feature observed in cardiomyopathy. Pressure-volume analysis showed worsened diastolic dysfunction in the ACE2KO hearts compared to WT hearts in response to HFD, which was primarily due to impaired active relaxation (Tau(Weiss): 7.41±0.4 in ACE2KO-HFD vs 6.26±0.52 in WT-HFD; p<0.05). Metabolic and functional changes in the ACE2KO-HFD were associated with impaired insulin signaling (decreased p-Akt) and decreased phosphorylation of AMPK. ACE2KO-HFD hearts also showed increased pyruvate dehydrogenase kinase 4 expression and phosphorylation of pyruvate dehydrogenase.

Conclusions:
Renin-angiotensin system plays an important role in cardiac metabolism. We found a novel role of ACE2 in cardiac insulin signaling, where ACE2 negatively regulates obesity and hyperglycemia induced cardiac insulin-resistance and alterations in cardiac metabolism.
Abstract 19066: Quantifying the Years of Life Gained From Myocardial Infarction Admission Process-of-Care Measures
Authors: Bucholz Emily M , Butala Neel M , Normand Sharon-Lise T , Krumholz Harlan M
Published: July 2021

Background:
Studies evaluating process of care measures for acute myocardial infarction (AMI) have generally demonstrated improved 30-day survival for patients receiving these therapies; however, almost no studies have followed patients beyond 1 year. As a result, there is considerable uncertainty as to whether the early survival benefits persist over the long-term.

Methods:
We analyzed data from the Cooperative Cardiovascular Project, a study of Medicare beneficiaries hospitalized for AMI between 1994 and 1995, to examine the relationship between 5 AMI admission measures (aspirin, beta-blockers, acute reperfusion therapy, time to percutaneous coronary intervention (PCI) ≤90 minutes, and time to fibrinolysis ≤30 min) and life expectancy after AMI. Patient eligibility for each measure was determined using AHA/ACC guidelines, and vital status over 17 years of follow-up was ascertained through the Medicare Denominator files. Cox proportional hazards regression with extrapolation using exponential models was used to calculate life expectancy after AMI.

Results:
Our study cohort consisted of 147,429 patients who were eligible for at least one measure. Survival curves for recipients and non-recipients of each core measure separated within the first year and remained distinct over the remainder of follow-up. This pattern was consistent across all five therapies and resulted in significantly longer life expectancies for patients receiving these therapies (Table 1). Differences in life expectancy between recipients and non-recipients decreased but remained significant after adjustment for patient and hospital characteristics.

Conclusions:
Receipt of 5 AMI admission therapies was associated with significant gains in life expectancy after AMI, lending further support for AMI process of care measures, which can be delivered rapidly at the time of hospitalization.
Abstract 19096: D-dimer Profile and Prognostic Implication in Different Classes of Acute Aortic Syndromes
Authors: Gorla Riccardo , Janosi Rolf A , Kahlert Philipp , Tsagakis Konstantinos , Jacob Heinz , Bossone Eduardo , Erbel Raimund
Published: July 2021

Background:
D-dimer has been reported to be elevated at presentation in acute aortic dissection (AAD). However, little is known about D-dimer in the setting of intramural hematoma (IMH) and penetrating aortic ulcer (PAU) as well as its time course during hospitalization.

Methods:
Clinical and laboratory data of 300 patients with acute aortic syndromes (208 AAD, 45 IMH and 47 PAU) were prospectively collected from 2000 to 2014. D-dimer blood levels were measured at presentation and daily during hospitalization with a latex-enhanced turbidometric test (250 μg/l upper limit of normal; D-dimer Plus - Dade Behring) until 2009 and with a microparticle-enhanced immunoassay (0,55 mg/l upper limit of normal; Innovance - Dade Behring) from 2010. Analysis of variance with Bonferroni post hoc analysis and Student T test were applied as appropriate.

Results:
At presentation, AAD and IMH showed significantly higher D-dimer levels than PAU (p<0,01). Similarly, D-dimer levels during hospitalization were found significantly higher in AAD and IMH, as compared to PAU (p<0,001).

From a subgroup analysis according to in-hospital outcome, D-dimer levels were significantly increased in patients complicated with major adverse events (a composite of extension/new dissection, aortic rupture and death) as compared to others (n=86, 29% and n=214, 71%; D-dimer: 1432 ± 855 μg/l vs. 787 ± 215 μg/l, p<0,001; 10,5 ± 6,3 mg/l vs. 8,3 ± 2,1 mg/l, p<0,05 respectively). (Table 1)

Conclusions:
D-dimer levels were found markedly increased both at presentation and during hospitalization in AAD and IMH, but not in PAU. Interestingly, higher values during hospital stay were associated with in-hospital major adverse events. Further studies are needed to integrate D-dimer testing in AAS clinical diagnostic and prognostic risk stratification scoring tools.
Abstract 19105: Basis for Biochemical Discordance Between Activated Partial Thromboplastin Time and Anti-factor Xa in Patients with Continuous Flow Left Ventricular Assist Device on Unfractionated Heparin Infusion
Authors: Yarmohammadi Hirad , Feng Amy J , Alraies Chadi M , Thenappan Thenappan , Colvin Monica , John Ranjit , Eckman Peter , Pritzker Marc , Adatya Sirtaz
Published: July 2021

Introduction:
Unfractionated Heparin (UFH) has been the mainstay of therapy for bridging and treatment of suspected device thrombosis/hemolysis in Continuous Flow Left Ventricular Assist Device (CF-LVAD), however the optimal monitoring test has not been prospectively evaluated. We previously reported that that Activated Partial Thromboplastin Time (aPTT) and anti-Xa levels measured simultaneously are frequently discordant in these patients.

Hypothesis:
Warfarin administration and hemolysis might be the biochemical basis for discordance between aPTT and anti-Xa in patients with CF-LVAD requiring UFH.

Methods:
A prospective observational study consisting of 38 patients with HeartMateII, consecutively admitted for UFH therapy with simultaneous measurements of aPTT and anti-factor Xa levels. Patients were stratified based on requirement of UFH for either sub-therapeutic INR or suspected device thrombosis. Patients were grouped according to whether the paired values fell within or outside the concordant therapeutic range, when discordant thromboelastography and factor analysis were performed.

Results:
Anti-Xa and aPTT were concordant 41.9% of the time in those getting treated for sub-therapeutic INR and only 18.8% in the group that getting treated for hemolysis/ device thrombosis. Data pairs with a supratherapeutic aPTT values were most likely to be associated with an INR ≥1.5, (p<0.001) (figure). On logistic regression analysis, high LDH was found to be a significant predictor of discordance (95% CI: 1.47-3.84). There was no consistent relationship between thromboelastography and factor analysis in the incidence of discordance.

Conclusions:
The relationship between aPTT and anti-factor Xa is not consistent in patients with CF-LVAD and the most common pattern was a supra-therapeutic aPTT relative to anti-factor Xa . Elevated LDH which is the sign for hemolysis and warfarin administration might contribute to an increased incidence of discordance.