bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2777: Optimal Expansion of the Stent is a Major Contributor to the Neointimal Coverage Following Sirolimus-eluting Stent Implantation: A Combined Study of Angioscopy and Intravascular Ultrasound
Authors: Sera Fusako , Kotani Jun-ichi , Awata Masaki , Nanto Shinsuke , Uematsu Masaaki , Morozumi Takakazu , Watanabe Tetsuya , Onishi Toshinari , Iida Osamu , Minamiguchi Hitoshi , Akahori Hirokuni , Yano Masamichi , Ikeoka Kuniyasu , Okamoto Shin , Tanaka Nobuaki , Yasui Haruyo , Nagata Seiki
Published: July 2021

Background:
Although sirolimus-eluting stent (SES) has significantly reduced in-stent restenosis by inhibiting neointimal hyperplasia, insufficient neointimal coverage after stenting may result in adverse outcomes. Determinants of neointimal coverage following SES, however, are poorly understood.

Methods:
We evaluated 28 SES lesions using both angioscopy and intravascular ultrasound (IVUS). Degree of neointimal coverage was judged by angioscopy at follow-up (11 ± 6 months):
complete/incomplete
coverage, based on whether the stent struts were embedded by the neointima. Minimal stent area (MSA), external elastic membrane (EEM), lumen cross-sectional area (CSA) and plaque burden (EEM minus lumen/EEM CSA) were measured by IVUS at stent implantation. Both proximal and distal references were used. Stent expansion was assessed by stent expansion index (SEI) as MSA/reference EEM CSA. Under-expansion was defined as SEI < 0.4. Incomplete apposition was defined as the lack of contact between any strut and the underlying vessel wall.

Results:
Complete
coverage was identified in 10 (36%), and
incomplete
coverage in 18 (64%). Time from the stenting to angioscopy (10 ± 5 versus 11 ± 7 months, p=0.8) as well as the lesion and procedural characteristics was similar between the
complete/incomplete
coverage groups. IVUS parameters were also similar, except for the final MSA (7.0±1.8mm
2
in
complete
versus 5.3±1.9mm
2
in
incomplete
, p=0.02) and lumen CSA at the distal reference site (6.1±1.4mm
2
in
complete
versus 4.9 ±1.2mm
2
in
incomplete
, p= 0.02). The frequency of incomplete apposition was similar between the groups (20% in
complete
versus 39% in
incomplete
, P= 0.4); however, SEI was significantly larger in the
complete
coverage than in the
incomplete
coverage group (0.52 ± 0.11 versus 0.39 ± 0.09, p=0.002). Stent under-expansion was identified only in 2 (20%) of the
complete
coverage, as compared to 67% of the
incomplete
coverage group (P=0.046). By multivariate logistic regression analysis, large SEI was strongly associated with
complete
neointimal coverage (P=0.04).

Conclusion:
Optimal expansion of the stent is a major contributor to the complete neointimal coverage following sirolimus-eluting stent implantation.
Abstract 2779: Two- Dimentional Imaging Of Lipids Deposited In The Coronary Plaques By Near-infrared Fluorescence Angioscopy
Authors: Uchida Yasumi
Published: July 2021

Background: The lipids deposited deep in the vascular wall are hardly detectable by any available imaging modalities including IVUS and OCT. Since near-infrared (NIR) light penetrates relatively deeply into the tissues, we devised a near-infrared fluorescence angioscope (NIRFA) for two dimensional imaging of lipids deposited even in deep layers of vascular wall.

Aim: To examine feasibility of NIRFA for imaging of lipids in coronary arterial wall in man.

Methods: NIRFA is composed of a quartz fiberscope incorporated in 5F balloon catheter, fluorescence exciter, fluorescence emitter, ICCD and recorder. NIR exciter filter of 710nm and emitter filter of 780nm were employed since among the major 30 substances composing atherosclerotic plaques, free cholesterol and cholesteryl esters alone exhibit NIR autofluorescence while oxLDL and TG not.

In vitro study: Coronary artery removed from human cadaver was perfused with saline and an angioscope was introduced into it for imaging of lipids and the obtained NIR images were compared with histology.

Clinical study: During routine coronary angiography, lipid deposition in the coronary artery was surveyed by NIRFA in 7 patients with coronary artery disease.

Results:

In vitro study. Coronary segments without lipid deposition by histology did not exhibit autofluorescence. Those with lipid deposition by histology, the lipids deposited within 700μm in depth from luminal surface exhibited autofluorescence. Deposited lipids not forming lipid pool exhibited strong and homogenous autofluorescence. Lipid pool exhibited no or weak autofluorescence surrounded by strong ones, indicating it is filled with oxLDL and/or TG.

Clinical study. Autofluorescence was frequently detected not only in yellow plaques but also in white plaques by conventional angioscopy and hard plaques by IVUS.

Also, autofluorescence was frequently detected in apparently normal coronary segments.

Conclusion: The results indicate that this NIRFA is feasible for two dimensional imaging of lipids deposited even in deep layers of coronary arterial wall which are not detectable by conventional angioscopy, OCT and IVUS.
Abstract 2780: A First-in-Class Oligonucleotide Drug-Antidote Pair Efficiently Modulates Factor IXa Activity in Human Subjects - A Nascent Platform for Antidote-Controlled Periprocedural Anticoagulation
Authors: Chan Mark Y , Cohen Mauricio G , Rusconi Christopher P , Alexander John H , Myles Shelley K , Aberle Laura G , Lin Min , Melloni Chiara , Tonkens Ross M , Harrington Robert A , Becker Richard C
Published: July 2021

Background:
Safe and active reversibility of anticoagulation is highly desirable. Factor IXa, critical for rapid thrombin generation on platelet surfaces, is a novel target for regulating coagulation. The REG1 System comprises RB006 (drug) and RB007 (antidote). RB006, a ribonucleic acid aptamer, selectively binds and inhibits IXa. RB007, the complementary oligonucleotide antidote, binds to RB006 by Watson-Crick base pairing, neutralizing its anti-factor IXa activity.

Methods:
To explore the feasiblity of testing the REG1 system in catheter-based intervention trials, we analyzed data from 2 randomized dose-escalation studies of REG1: phase 1a with 84 healthy subjects and phase 1b with 50 patients with stable coronary artery disease taking aspirin and/or clopidogrel.

Results:
An intravenous (IV) bolus of RB006 produced a similar dose-dependent activated partial thromboplastin time (aPTT) increase in both populations; a weight-adjusted dose of 1mg/kg RB006 consistently achieved 100% factor IXa inhibition (figure 1

), a level effectively eliminating artifical surface thrombosis in animal models. IV bolus RB007 in a 2:1 antidote:drug ratio reversed the aPTT to <10% above the upper limit of normal within a median of 1 min (IQR 1–2), with no rebound increase up to 7 days. Despite dual antiplatelet use in 19 subjects, no major bleeding or other serious adverse events occurred.

Conclusions:
These exploratory data support the safe regulation of coagulation with a factor IXa-specific drug-antidote system. The pharmacodynamic response elicted by a 1mg/kg RB006 dose and 2:1 antidote:drug ratio appears suitable for catheter-based intervention studies.

Figure 1.

Relative APTT and % Factor IXa inhibition versus RB008 Dose (mg/kg)
Abstract 2789: Evaluation of Risk of Cerebral Infarction by Tissue Characterization of Carotid Artery Plaques using Integrated Backscatter Ultrasound
Authors: Yamada Kiyofumi , Yoshimura Shin-ichi , Kawasaki Masanori , Enomoto Yukiko , Minatoguchi Shinya , Iwama Toru
Published: July 2021

Background:
Although carotid plaques with large lipid pools may be more likely to cause cerebral infarction (CI), there is little clinical evidence supporting this hypothesis. The purpose of this study was to elucidate whether three dimensional (3D) IB color-coded mapping methods could stratify the risk of CI.

Methods:
IB values of plaques were measured in 63 carotid plaques (>50% stenosis) in 63 patients [acute CI (<2 days after onset): n=14, old CI (>60 days after onset): n=15, asymptomatic: n=34]. IB images were acquired using an ultrasonic system (Philips Medical, Sonos7500). We set regions of interest (0.6 x 0.6mm) on the echo tomography. Our definition of IB values for each tissue type was determined by comparing the histology reported in our previous study (7<lipid pool ≤ 13; 13<fibrosis ≤ 18; 18<dense fibrosis ≤ 27; 27<calcification ≤ 33dB). The % lipid volume (%LV: lipid volume/plaque volume) was automatically calculated in each plaque. We also characterized lipid-rich plaques using a magnetic resonance imaging (MRI) at the same sites.

Results:
% lipid volume of acute CI, old CI and asymptomatic were 80±14, 22±15 and 37±24%, respectively. Receiver-operating-characteristic curve analysis showed that a cutoff point of 51% was the most reliable predictor of the CI risk [sensitivity: 93%, specificity: 93%, positive predictive value (PPV): 93%, negative predictive value (NPV): 93%]. These diagnostic accuracies were higher than those of MRI (sensitivity: 85%, specificity: 71%, PPV: 75%, NPV: 83%).

Conclusion:
Carotid plaques with greater volume of lipid pool are more likely to cause CI. The 3D IB method is more useful to predict CI rather than depending on MRI.
Abstract 390: VLDL Exits From The Endoplasmic Reticulum In A Specialized VLDL-transporting-vesicle (VTV) In Rat Primary Hepatocytes.
Authors: Siddiqi Shadab A
Published: July 2021

Transport of very low-density lipoprotein (VLDL) from its site of synthesis, the endoplasmic reticulum (ER), to the Golgi is required for its eventual secretion from hepatocytes. This step represents a potential therapeutic target in controlling VLDL export and thus control of its metabolic derivative, LDL, the major carrier of cholesterol and determinant of atherosclerosis. The present study was designed to understand how VLDL exits from the ER at the molecular level. We developed an
in vitro
ER-budding assay in which rat liver ER (500 ug) was pre-loaded with
14
C-triacylglycerol (TAG) to mark VLDL and
3
H-proteins to mark newly synthesized proteins. The ER was incubated with rat liver cytosol (1 mg), GTP, and ATP at 37
o
C for 30 min. The reaction mix was fractionated on a continuous sucrose gradient and the distribution of
14
C-TAG and
3
H-protein across the gradient was determined.
14
C-TAG was found in the light density region of the gradient, the expected place for TAG-rich VLDL carrying vesicles whereas
3
H-proteins appeared in the mid portion, the expected place in the gradient for protein vesicles. We examined the distribution of apolipoprotein B100 (apoB100), a marker for VLDL and albumin (a typical liver secretory protein) across the same gradient by Western blotting. As expected, apoB100 was distributed in light fractions whereas albumin was mainly in the mid portion of the gradient. These data show that VLDL and albumin are transported in vesicles of differing density. We hypothesize that a specialized vesicle is utilized for VLDL transport, which we name the VLDL-transporting-vesicle (VTV). Our results show that the release of VTV from rat liver ER requires cytosol, GTP, Sar1 (a GTPase), ATP, and incubation at 37
o
C. VTV was sealed as judged by apoB100 signal post proteinase K treatment. VTVs concentrate ApoB100, Sar1, and exclude ER-resident protein calnexin. VTV fuses with liver
cis
-Golgi and delivers its cargo, VLDL, to the Golgi lumen. 2D-gels and electron microscopy data reveal that VTVs are different in their protein composition and are larger in size when compared to albumin carrying vesicles. In conclusion, we have identified and characterized a new ER-derived vesicle, VTV, which transports nascent VLDL from the ER to the Golgi in primary hepatocytes.
Abstract 2804: Early Invasive Management of Acute Coronary Syndromes without ST-elevation: Relation between Rate of Invasive Therapies and Very Long-term Mortality in the Randomized Trials
Authors: Verheugt Freek W , Brouwer Marc A
Published: July 2021

Background

Randomized trials evaluating an early invasive against a conservative strategy show a benefit over a conservative approach in the composite of death, MI and revascularisation/recurrent ischemia. However, the rate of invasive therapies differed significantly in the trials. Moreover, there were also large differences in the rate of invasive therapies in the invasive versus the conservative arms (
cross-over rate)
in the different studies. Therefore we studied the differences in rate of invasive therapy in the study arms of the above trials, and correlated them with the benefit of the invasive therapy with regard to the very long-term mortality as recently published.

Methods and Results

We analyzed very long-term mortality (30,932 patient-years) in the 9 trials carried out between 1996 and 2004, which randomized 10,558 patients with non-ST-elevation acute coronary syndromes to an early invasive or an ischemia-guided conservative strategy. Differences in the revascularization rate between the invasive and conservative strategies in the trials ranged between 10% and 39%. There was no relation of the differences in revascularization between invasive and conservative strategies and the benefit on mortality whatsoever (see figure

).

Conclusion

Although most trials on non ST-elevation ACS reported a reduction in the composite of death, MI and revascularisation/ recurrent ischemia, an early invasive strategy does not lead to improved survival on the very long-term. There seems no relation between the difference in revascularisation rate and benefit on the very long term, which may explain the lack of efficacy of early intervention on very long-term mortality.
Abstract 2809: Absence of Flow-Limiting Coronary Artery Disease Among Patients Undergoing Emergent Cardiac Catheterization For ST Segment Elevation Myocardial Infarction in the National Cardiovascular Data Registry CathPCI Registry: Implications for Primary Angioplasty Programs
Authors: Ho Kalon K , Anderson H. V , Shaw Richard E , Klein Lloyd W , Beachy James H , Cannon Christopher P , Krumholz Harlan M , Fitzgerald Susan , Hermann Anthony , Mitchell Kristi , Rumsfeld John , Brindis Ralph G
Published: July 2021

Background
: Many hospitals have established primary angioplasty programs with a goal of providing consistently timely reperfusion for patients with suspected acute ST segment elevation myocardial infarction (STEMI). As the locus of control for activation of the cardiac catheterization laboratory moves from the cardiologist to the emergency department and even to pre-hospital activation by emergency medical services, concerns have been raised about ``false positive” activations of the primary angioplasty team, yet there has been little data on the frequency of this occurence.

Objective
: We sought to estimate how often flow-limiting coronary artery disease (CAD) was NOT found among patients undergoing emergent cardiac catheterization in a large multi-center registry.

Methods and Results
: The National Cardiovascular Data Registry (NCDR) CathPCI Registry is a cardiac catheterization and angioplasty quality improvement and outcomes database with over 800 participating institutions. Among 131,211 patients undergoing emergent or salvage coronary angiography from 1/1/2005 -12/31/2006, 9.8% had no lesions of ≥50% diameter stenoses in the major epicardial coronary arteries. No angiographically visualized coronary stenoses at all were reported in 5.2% of these cases. Detailed data were not readily available on whether the primary indication for the procedure was suspected acute STEMI vs. other reasons such as hemodynamic instability or refractory arrhythmia.

Conclusions
: Among patients undergoing emergent or salvage diagnostic catheterizations nationwide in the NCDR CathPCI Registry, finding NO angiographically-apparent flow-limiting CAD was uncommon (<10%). While no clinical finding or test will perfectly discriminate STEMI from ``STEMI mimics”, current clinical practice appears to activate primary angioplasty teams with reasonable specificity.
Abstract 2812: Predictors of Reinfarction Following PCI or Medical Management in Patients With Persistent Total Occlusion After Myocardial Infarction: Results from the Occluded Artery Trial (OAT)
Authors: White Harvey D , Steg P G , Dzavik Vladimir , Menon Venu , Reynolds Harmony R , Carvalho Antonio C , Barton Bruce A , Cantor Warren J , Kruk Mariusz , Martin C E , Pearte Camille A , Knatterud Genell L , Lamas Gervasio A , Hochman Judith S
Published: July 2021

Background
: The Occluded Artery Trial (OAT) randomized 2201 patients (up to 28 days post MI) with an occluded infarct-related artery to either percutaneous coronary intervention (PCI) or medical treatment alone (MED). There was no difference in five-year life table event rates for the primary end point of death, reinfarction (ReMI) or heart failure. However in patients randomized to PCI there was a trend for an increase in adjudicated ReMI: 7.0% vs. 5.1%, HR 1.35 (95% CI: 0.92–1.99, p=0.12) and investigator-reported ReMI: 10.9% PCI vs 7.9% MED, HR 1.36, (95% CI: 0.98 –1.86, p=0.05).

Aim
: To determine independent predictors of ReMI.

Methods
: ReMIs were adjudicated and required two of the following: ischemic symptoms ≥30 min, ECG changes and marker elevation [creatinine kinase elevation 2x upper limit of normal (ULN), CKMB >ULN or troponin 2x ULN; after PCI, CK or CK-MB 3x ULN and after surgery, CK or CK-MB 5x ULN]. Cox multivariable regression models were developed including baseline demographics, angiographic data, and discharge medications. P<0.01 was considered significant for this secondary analysis.

Results: Conclusions
: In the OAT trial predictors of adjudicated ReMI were prior MI (before qualifying MI) and diabetes. The predictors were similar for both treatment groups and no single angiographic factor or effect of medication was identified.

Adjudicated ReMI
Abstract 2815: Validation of Rapid Automated Tissue Synchronisation Imaging Techniques for Assessment of Cardiac Dyssynchrony in both Sinus and Non-Sinus Rhythm
Authors: McCormack Cameron , Wai Bryan , Muir Tracey , Ord Michelle , Anavekar Nagesh , Kearney Leighton G , Srivastava Piyush M
Published: July 2021

Background: Intraventricular dyssynchrony predicts left ventricle remodelling and clinical response following cardiac resynchronisation therapy. Currently, no consensus exists as to the most appropriate methodology for assessing dyssynchrony. Tissue Velocity Imaging (TVI) based septal to lateral delay (SLD) >65ms (Bax et al) and 12 segment dyssynchrony index (DI) (Yu et al) are most commonly used. These methods are time consuming and involve multiple manual calculations. Automated dyssynchrony assessment with Tissue Synchronisation Imaging (TSI) may provide a more rapid estimation of dyssynchrony.

Aims: To assess the validity of automated TSI (TSI auto) based dyssynchrony measures in comparison to established TVI techniques.

Methods: We randomly selected echocardiograms of 51 subjects (Sinus rhythm (SR) n=35, AF/paced n=16) from our heart failure service and compared TSI auto to conventional TVI methods (SLD and DI). For TSI auto, 6 basal and 6 mid segments were defined and dyssynchrony parameters calculated with the Echopac 6 software.

Results: The mean age of the group was 66±11 years, 86% were male. The majority had ischaemic aetiology (69%) and the mean LVEF was 35.2±1.3%. Mean QRS duration was 138±6ms (LBBB 54%) and 69% were in SR. Bland-Altman analysis of TVI and TSI auto DI showed excellent agreement (Limits of agreement (LOA): -8.7 to 15.9, p=0.16) (Figure

). Agreement between SLD techniques was acceptable (LOA: -169 to 137 p=0.9). ROC curves were constructed for TSI auto (AUC SR 0.9, non-SR 0.917).

Conclusions: Automated TSI provides an accurate and efficient means of measurement of intraventricular dyssynchrony in both sinus and non sinus rhythm.
Abstract 2819: Cross-correlation Analysis of Myocardial Velocity is Superior to Conventional Time-to-Peak Parameters for Quantifying Left Ventricular Dyssynchrony
Authors: Fornwalt Brandon K , Arita Takeshi , Bhasin Mohit , Voulgaris George , Merlino John D , León Angel R , Fyfe Derek A , Oshinski John N
Published: July 2021

Background-

A recent study showed that the most commonly used Tissue Doppler imaging (TDI) parameters to diagnose left ventricular dyssynchrony agree only 50% of the time. Most of these parameters require calculation of the ``time-to-peak” myocardial velocity. This ``time-to-peak” based analysis utilizes only one of >100 data points collected per heart cycle.

Methods-

We developed and tested a new dyssynchrony parameter, cross-correlation delay (XCD), that utilizes all velocity data points from 3 consecutive beats (~420 points). We
hypothesized
that XCD would be superior to existing methods at diagnosing dyssynchrony. We tested XCD on 11 members of a positive control group (echocardiographic responders to cardiac resynchronization therapy) and 12 members of a negative control group (normal echocardiogram and 12-lead ECG). We compared XCD to septal-to-lateral delay in time-to-peak (SLD), maximum difference in the basal 2- or 4-chamber times-to-peak (MaxDiff) and standard deviation of the 12 basal and mid-wall times-to-peak (Ts-SD).

Results-

An XCD threshold of 31ms discriminated between positive and negative controls with 100% sensitivity and specificity (Figure 1

). SLD, MaxDiff and Ts-SD showed sensitivities of 36, 55 and 100% and specificities of 50, 42 and 50%, respectively. ROC analysis showed XCD and Ts-SD were superior to SLD and MaxDiff in discriminating between positive and negative controls (p<0.01). XCD was the
only
parameter which decreased after resynchronization in the positive controls (from 160±88ms to 69±61ms, p=0.003).

Conclusion-

XCD is superior to existing parameters at discriminating patients with LV dyssynchrony from those with normal function.

Figure 1.

XCD shows the greatest discrimination between positive and negative controls. Dyssynchrony values for each positive control are shown as x’s and values for each negative control are shown as circels. Different dyssynchrony parameters are shown in each subplot (A-D). Threshold values to diagnose dyssynchrony are plotted as horizontal lines in each figure. Note that x’s above the threshold line represent false positives while circles below the threshold line represent false negatives.
Abstract 2821: Clinical and Echocardiographic Determinants of Left Ventricular Synchrony
Authors: Ng Arnold , Tran Da T , Newman Mark , Allman Christine , Vidaic Jane , Touzel Kim , Lo Sidney T , Hopkins Andrew P , Leung Dominic Y
Published: July 2021

Background
: Current research on predicting response to cardiac resynchronization therapy suggests quantification of left ventricular (LV) dyssynchrony. However, impact of age, gender and other variables on LV synchrony in healthy individuals is unknown.

Methods
: Echocardiography with color tissue Doppler was performed on 122 healthy volunteers (age 19 – 68 years, 64 men). LV systolic and diastolic synchrony were measured as the absolute basal lateral to septal wall delay (LSD) in peak myocardial Sm and Em velocities respectively. Systolic and diastolic synchrony were also measured as the standard deviation of time to 12 regional peak Sm (SDTs) and Em (SDTe) velocities. Mean Sm and Em velocities were calculated from 6 basal segments.

Results
: Mean QRS duration was 87 ± 12msec. Mean systolic LSD and SDTs were 57.5 ± 39.7msec and 37.1 ± 17.4msec respectively. Women had significantly higher systolic LSD (74.1 ± 40.2 vs 42.2 ± 32.8msec, p < 0.001) and SDTs (44.5 ± 16.1 vs 30.2 ± 15.7msec, p < 0.001) than men. SDTs was correlated with LV wall stress (r = 0.23, p = 0.01) and mean Sm (r = 0.40, p < 0.001). Gender (p < 0.001) and mean Sm (partial r = -0.31, p < 0.001) independently predicted SDTs (multiple R = 0.51, p < 0.001) whereas only gender independently predicted systolic LSD. Mean diastolic LSD and SDTe were 15.3 ± 15.6msec and 17.3 ± 6.7msec respectively. There were no gender differences in diastolic LSD or SDTe. Diastolic LSD was correlated with mean Em (r = -0.20, p = 0.03), isovolumic relaxation time (IVRT, r = 0.24, p = 0.01), mitral E/A ratio (r = -0.21, p = 0.02), pulmonary S/D ratio (r = 0.23, p = 0.01) and systolic blood pressure (r = 0.22, p = 0.02). Only IVRT independently predicted diastolic LSD. SDTe correlated with age (r = 0.42, p < 0.001), mean Em (r = -0.73, p <0.001), mitral E/A ratio (r =0.40, p <0.001), pulmonary S/D ratio (r =0.42, p <0.001), IVRT (r = 0.51, p < 0.001), systolic blood pressure (r = 0.25, p = 0.005) and LV mass (r = 0.21, p = 0.019). Mean Em (partial r = -0.34, p < 0.001) and IVRT (partial r = 0.31, p = 0.001) independently predicted SDTe (multiple R = 0.58, p < 0.001).

Conclusions
: In healthy individuals, 1) women have higher systolic but not diastolic synchrony indices than men; 2) systolic function impacts on systolic synchrony, diastolic function impacts on diastolic synchrony.
Abstract 397: Perivascular Fat Tissue Plays An Atheroprotective Role In Neointimal Formation After Angioplasty
Authors: Takaoka Minoru , Sata Masataka , Nagai Ryozo
Published: July 2021

Background:
Obesity is associated with chronic inflammation and increases risk for cardiovascular disease and type 2 diabetes. Recently visceral, as opposed to subcutaneous, fat tissue confers the most cardio-metabolic risk. The aim of the present study is to determine whether perivascular fat tissue contributes to neointimal formation after angioplasty.

Methods and Results:
An endovascular injury was induced in the femoral arteries of wild-type mice without or with removal of perivascular adipose tissue. Neointimal area and Neointima/Media ratio were markedly enhanced by removal of perivascular adipose mice (P=0.05). Visceral fat tissue (VAT) or subcutaneous fat tissue (SAT) were harvested from GFP-transgenic mice and transplanted around the injured femoral without endogenous perivascular fat. Neointimal formation was markedly enhanced in the VAT-transplantation group compared with the SAT-transplantation group (P=0.05). Real-time PCR analysis showed that the transplanted VAT had significantly higher proinflammatory cytokines, TNF alpha, IL-6, MCP-1, and PAI-1, mRNA levels than the SAT (P=0.05). Next, the effects of VAT and SAT on smooth muscle cell proliferation were investigated in vitro. Conditioned medium was prepared from extracts of VAT and SAT. Cell proliferation was measured by MTS assay. VAT stimulated smooth muscle cell proliferation compared with SAT (P=0.05).

Conclusions:
The present study demonstrates that perivascular adipose tissue protects neointimal formation after angioplasty. VAT stimulates neointimal formation and smooth muscle cell proliferation, probably by secreting proinflammatory cytokines, at least in part. Adipocytokines, particularly secreted from perivascular fat tissue, may play a role in the pathogenesis of neointimal formation after angioplasty.
Abstract 2848: Medication Knowledge And Assistance In Older Chronic Heart Failure Patients.
Authors: Gallagher Robyn , Donoghue Judith , Chenoweth Lynn , Stein-Parbury Jane
Published: July 2021

Medication knowledge and assistance in older chronic heart failure (CHF) patients. Medication adherence is central to the optimal management of CHF. Little is known about older patients’ knowledge of their medications or the factors that contribute to this knowledge.

Aim: To describe and identify the predictors of medication knowledge in older CHF patients.

Method: Subjects (
n
= 62) aged over 55 years with moderate heart failure (New York Heart Association Class II and III) who identified as self-managing were recruited from hospital or rehabilitation.

Interviews occurred at home four weeks post-discharge using a medication checklist and the Self-Efficacy in Chronic Illness Scale (Lorig et al, 2001). Multiple regression analysis determined the predictors of medication knowledge.

Results: Patients were aged mean 78.4 years (sd 8.54 years), mostly male (57%) and had an average 8 (median, range 3–22) medications to take daily, of which 6 (median, range 3–14) were for CHF. Most managed their own medications (54%) but more than a quarter (28%) were assisted by reminding, dispensing and supervision. Compliance with medications was high (84%), although only half (53%) knew the name, main purpose and side effect of their medications. Patients with better self-efficacy (β = 2.88) and no help with medication (β = -21.05) had better medication knowledge (model
F
= 13.6,
p
= .000,
R
= .61,
r
2
= .37).

Conclusion: Older CHF patients have poor knowledge of their medications, which may be improved by promoting overall self-efficacy for disease management. Less knowledgeable patients received appropriate assistance with medications, but the consequence may be less knowledge and thus warrants further investigation.
Abstract 2853: The Prevalence of Ion Channel Disorders in Victims of Sudden Adult Death Syndrome
Authors: Chlebinska Agnes C , Basavarajaiah Sandeep , O’Sullivan Ann , Sharma Sanjay
Published: July 2021

Objectives: Sudden adult death syndrome (SADS) accounts for at least 4% of all sudden cardiac deaths in the United Kingdom and is often attributed to an ion channel disorder. The precise prevalence of and hence efficacy of effectiveness for screening for ion channel disorders utilising non-invasive cardiac tests in first degree relatives of victims of SADS is unknown. The aim of this study was to identify the prevalence of ion channel disorders in victims of SADS.

Methods: Between March 2006 and March 2007, 17 families of victims of SADS were evaluated in a tertiary inherited cardiac clinic. A total of 46 individuals underwent 12-lead ECG, echocardiography, exercise stress testing, 24 hour Holter and, when applicable, an Ajmaline provocation test and/or cardiac magnetic resonance scan.

Results: All family members had a structurally normal heart. An ion channel disorder was identified in 7 out of 17 (41%) families. Of these, 5 (71%) families exhibited the Brugada phenotype and 2 families manifested the long QT syndrome phenotype. A total of 11 of 46 (24%) asymptomatic family members were identified with an ion channel disorder.

Conclusions: Non-invasive cardiac evaluation of first-degree family members of victims of SADS in a tertiary inherited cardiac diseases clinic suggests that ion channel disorders, particularly Brugada’s syndrome, account for at least 40% of all SADS deaths in the UK.
Abstract 2859: Baseline Values and Drug-induced Changes of the Ventricular Repolarization Morphology in the Electrocardiograms of Patients with a History of Drug-induced Torsades de Pointes.
Authors: Couderc J-Philippe , Kaab Sefan , Hinterseer Martin , McNitt Scott , Fossa Anthony , Xia J , Zareba Wojciech , Moss Arthur
Published: July 2021

Background:
Assessing propensity to torsades de pointes (TdP) when exposed to QT-prolonging drug is challenging because baseline QT-prolongation has limited predictive value for identifying risk of TdP. The aim of this study was to determine whether computer-based repolarization morphology parameters could identify individuals who developed drug-induced TdP.

Method:
Five-minute standard digital 12-lead ECGs were acquired at baseline and after a controlled sotalol challenge (2 mg/kg BW, i.v.) in 34 cardiac patients of whom 17 had a history of TdP (+TdPs) in the context of a QT prolonging drug and 17 had no history of TdP (-TdPs).Computerized ECG parameters including QT, TpTe (T peak to T end interval) and a morphological measure of the duration of the early part of the repolarization interval (ERD) were implemented. All parameters were corrected for the effect of heart rate (HR).

Results:
There were 9 females among the + TdP patients and 12 females in the -TdP group (p = 0.8). The drugs triggering TdPs were: antidepressant, antibiotics, antiarrhythmic and anti-migraine. They included sotalol, amiodarone, bisacodyl, erythromycin, imipramime, cipramil and sumatriptan. The table

below shows the comparison of baseline values and the on-sotalol changes of the repolarization parameters after HR correction. The analysis revealed a longer QT interval duration at baseline in patient +TdPs. This prolongation was only present in the early part of the T-wave (ERD, p = 0.02). On sotalol, the patients with a history of TdPs have longer QT prolongation associated with a significant increased late part of the repolarization (TpTe, p = 0.01).

Conclusion
: Our results revealed that specific repolarization features are present at baseline and on sotalol challenge in patients with and without history of TdPs. These parameters could complement the role of the QT prolongation as a proarrhythmic surrogate marker.

Baseline values and sotalol-induced changes in ECG parameters
Abstract 2861: Amiodarone, in Contrast to Sotalol, Equally Decreases Epicardial and Endocardial Atrial Fibrillation Inducibility, Despite a Steep Transmural Concentration Gradient
Authors: Bolderman Robert W , Hermans Rob J , Rademakers Leonard M , Jansen Tim S , van der Veen Frederik H , Maessen Jos G
Published: July 2021

Background:
Amiodarone causes less ventricular transmural dispersion of repolarization (TDR) and proarrhythmia than sotalol. Effects of both drugs on atrial TDR, however, have not yet been well defined. We applied intrapericardial (IPC) drug delivery to produce in vivo transmural concentration gradients. We assessed the hypotheses that IPC amiodarone causes less atrial TDR than IPC sotalol and that IPC amiodarone is more effective than IPC sotalol in lowering atrial fibrillation (AF) inducibility.

Methods:
Goats (n = 25) were randomised into 5 groups receiving either IPC dextrose, amiodarone (IV or IPC) or d,l-sotalol (IV or IPC). Drugs were infused for 3 hours at a constant rate of 2 mg/kg per hour. Quadripolar catheters were placed on the epi- and endocardial surfaces of the right atrium. Atrial effective refractory period (AERP) and AF inducibility were measured by single premature stimuli at 4 times the diastolic threshold. Atria were freeze-microtomed parallel to the epicardial surface and analysed by HPLC.

Results:
IPC drug delivery produced high epicardial concentrations (fig.1a

) with significantly decreased epicardial AF inducibility. A similar decrease in endocardial AF inducibility was only observed in the IPC amiodarone group (fig.1b

). TDR (defined as endo-minus epicardial AERP) became negative after IPC sotalol (from 13.0 ± 3.2 to -30.7 ± 7.3 ms, p < 0.05). In the other groups TDR did not change significantly and remained positive.

Conclusions:
IPC delivery boosts epicardial drug concentration and efficacy. For amiodarone, this also increases endocardial efficacy. IPC sotalol, however, inverts TDR, which may explain its inferior endocardial efficacy.

Figure 1a.

Concentrations in right atrium (mean + SD)

Figure 1b. Chang in AF inducibility (mean + SD)
Abstract 2867: Adrenergic Receptor Polymorphisms and Prevention of Atrial Fibrillation with Bucindolol in Patients with Heart Failure
Authors: Sauer William , Lowery Christopher M , Budhathoki Chakra , Lowes Brian D , Bristow Michael R
Published: July 2021

Background:
β-blockers have been shown to prevent atrial fibrillation (AF) in patients with low left ventricular ejection fraction (LVEF) and chronic heart failure (CHF). We hypothesized that there may be genotype specific responses to β-blocker therapy for prevention of AF.

Methods:
The β-blocker Evaluation of Survival Trial (BEST) was a randomized trial of bucindolol in patients with NYHA Class III–IV CHF and LVEF ≤0.35. From a substudy of genotyped subjects, we identified those with the high functioning Arg389 β1 adrenergic receptor polymorphism and the loss of function 322–325 α2c adrenergic receptor deletion polymorphism. The incidence of AF was prospectively recorded as an adverse event during the trial.

Results:
Of the 1040 subjects in the genotyped cohort, there were a total of 493 Arg389 β1 receptor homozygotes vs. 547 Gly389 carriers and 207 α2c deletion carriers vs. 833 wild-types. The diplotypes included 418 subjects with both Arg/Arg389 β1 receptors and wild type α2c, 484 with one of these, and 134 carrying both the α2c deletion and the β1 Gly389 polymorphisms. For the genetic substudy, bucindolol was associated with a lower incidence of AF (7.0% vs. 10.7%; p = 0.03). There was a significant drug-gene interaction for prevention of AF with both polymorphisms (β-1 overall p = 0.04; α2c overall p = 0.04). Arg389 homozygotes randomized to bucindolol had a lower incidence of new onset AF during the trial than those randomized to placebo (5.1% vs. 11.9%; p < 0.01) as for wild type α2c homozygotes (7.1% vs. 11.2%; p = 0.04). This reduction in AF incidence was not seen in β-1 Gly389 carriers (8.9% vs. 9.7%; p = 0.77) and α2c deletion carriers (6.8% vs. 8.7%; p = 0.79). Subjects with the Arg/Arg389 β-1/wild-type α2c receptor diplotype randomized to bucindolol had a lower rate of AF occurrence than those with only one or neither of these genotypes (both: 5.2% vs. 11.7%; p = 0.02; one: 8.2% vs. 11.2%; p = 0.28; neither: 8.5% vs. 6.7%; p = 0.75).

Conclusion:
Subjects with CHF and Arg/Arg389 β1 or wild type α2c adrenergic receptors treated with bucindolol had a lower rate of new onset AF than those randomized to placebo. This treatment effect was not observed in the population of β-1 Gly389 or the α2c deletion carriers, indicating a pharmacogenetic interaction.
Abstract 2872: Interleukin-18/interleukin-10 Ratio is an Independent Predictor of Cardiovascular Events in Patients with Stable Coronary Artery Disease
Authors: Camargo Paulo V , Roman Raquel M , Rossini Ana Paula W , Dedonelli Anderson , Stella Steffan F , Meotti Carolina , Giaretta Thiane , Gasparin Andressa , Polanczyk Carisi A
Published: July 2021

Background: The balance between pro-inflammatory cytokine IL-18 and anti-inflammatory cytokine IL-10 has been suggested to play a role in atherogenesis and in the prognosis of acute coronary syndrome (ACS). We hypothesized that stable coronary artery disease (CAD) patients have a pro-inflammatory profile prior to an acute event.

Methods
: A case-control study nested in a cohort of stable CAD patients was performed. Patients were consecutively included and blood samples collected at 3-months intervals. Cases were patients who presented any vascular event (death, ACS, ischemic stroke, peripheral arterial occlusion and revascularization) and controls were retrieved from a sequential list, in a 1:2 ratio, after 22 ± 9 months of follow-up. Serum hs-CRP, interleukin (IL)-10, IL-18 were measured in two serial samples, collected before the events.

Results
: Among 176 CAD patients, 42 developed a vascular event (cases) and 76 were selected to the control group. Serum levels of IL-18 were significantly higher among cases (411 ± 185 vs. 340 ± 133pg/ml;
p
= 0.037). Hs-CRP levels (5.4 vs. 5.1mg/l), IL-10 (7.4 vs. 7.2pg/ml), and IL-18/IL-10 ratio (66 vs. 61) were not different between cases and controls in both samples. Cox regression analysis showed that IL-18 levels (HR 1.75 (0.89 –3.5;p = 0.11) and IL-18/IL-10 ratio (HR 1.97; 1.0 –3.8) were predictors of worse prognosis (Figure

).

Conclusion:
In this study, IL-18 and IL-18/IL-10 ratio were associated with clinical outcomes and support the hypothesis that the balance between pro-inflammatory and anti-inflammatory cytokines may be an important determinant of vascular events in stable CAD patients.
Abstract 398: Apolipoprotein CIII (apoCIII) Inhibits Insulin-dependent Endothelial Nitric Oxide Synthase (eNOS) Function In Endothelial Cells Through Protein Kinase C (PKC) βII
Authors: Kawakami Akio , Tani Mariko , Osaka Mizuko , Sacks Frank M , Shimokado Kentaro , Yoshida Masayuki
Published: July 2021

Objective
Apolipoprotein (apo) CIII, a prominent component of atherogenic dyslipidemia, is elevated in patients with type2 diabetes and insulin resistance, and independently predicts cardiovascular disease (CVD). Endothelial dysfunction is an important component of the pathophysiology of atherosclerosis, and is associated with insulin resistance. We previously reported that apoCIII has a direct effect on vascular endothelium, activating endothelial cells to recruit monocytes through PKCβ and NF-κB-dependent mechanisms. In the present study, we investigated the effect of apoCIII on insulin-dependent endothelial nitric oxide synthase (eNOS) function in endothelial cells and in the aortas of C57BL/6J mice.

Methods and Results
ApoCIII treatment (100μg/ml, 30 minutes) inhibited insulin-induced ISR-1/phosphatidylinositol 3-kinase (PI3K)/Akt activation in human umbilical vein endothelial cells (HUVECs). Furthermore, apoCIII reduced insulin-stimulated eNOS activation and NO release into the media. ApoCIII induced PKCβII activation in HUVECs, resulting in IRS-1 phosphorylation at pSer
616
and ERK activation. Impaired insulin-stimulated eNOS activation and NO production were restored by PKCβ inhibitor and MEK1 inhibitor to a lesser extent. In addition, treatment of C57BL/6J mice with apoCIII resulted in impaired insulin-dependent activation of PI3K/Akt/eNOS pathway in the aorta. Pretreatment with PKCβ inhibitor attenuated inhibitory effects of apoCIII. ApoCIII resides on VLDL fraction in the plasma, especially in the postprandial state. Injection of apoCIII-rich VLDL, but not apoCIII-deficient VLDL, also impaired these processes.

Conclusion
Our data suggest that apoCIII impairs insulin stimulation of NO production by vascular endothelium. This adverse effect of apoCIII is mediated by its activation of PKCβII which inhibits the IRS-1/PI3K/Akt/eNOS pathway. These results indicate that apoCIII not only modulates lipoprotein metabolism, but also may directly contribute to the development of diabetic complications through endothelial dysfunction. Finally, our results may point to a novel mechanism that links dyslipidemia, insulin resistance and endothelial dysfunction.
Abstract 2886: Angiotesin-Converting Enzyme Inhibitors Attenuate Age-related Progression of Cardiac Allograft Vasculopathy - A Serial Volumetric Intravascular Ultrasound Study
Authors: Moon Keon-Woong , Sipahi Ilke , Nicholls Stephen J , Schoenhagen Paul , Kalidindi Srinivasa R , Kapadia Samir R , Starling Randall C , Hobbs Robert E , Erinc Kursad , Magyar William A , Nissen Steven E , Tuzcu E. M
Published: July 2021

Background
: The development of cardiac allograft vasculopathy (CAV) portends an adverse clinical outcome in heart transplant recipients. Previous studies of clinical predictors of CAV have investigated small cohorts and have not evaluated the volumetric extent of disease. This study determined predictors of progression of the volumetric severity of vasculopathy in a large cohort of heart transplant recipients.

Methods
: Serial intravascular ultrasound examinations were performed in 119 heart transplant recipients at 1 month and 1 year following transplantation. Clinical predictors of serial changes in atheroma volume were determined. In particular, the impact of donor and recipient age stratified according to the median was investigated.

Results
: Patients ( donor age 33.3 ± 14.2 years, recipient age 54.5 ± 12.6 years, 71.9 % male) demonstrated an increase in atheroma volume (64.2 ± 41.7 mm
3
at 1 month vs. 78.1 ± 53.4 mm
3
at 1 year,
p
< 0.001) and a decrease in lumen volume (334.2 ± 197.3 mm
3
at 1 month vs. 321.6 ± 187.8 mm
3
at 1 year,
p
= 0.001). Greater increases in atheroma volume were observed in the setting of older donor age (r = 0.24,
p
= 0.008), older recipient age (r = 0.23,
p
= 0.01) and recipients not treated with an angiotensin-converting enzyme (ACE) inhibitor (without ACE inhibitor, 21.1 ± 33.3 mm
3
vs. with ACE inhibitor, 9.1 ± 27.6 mm
3
,
p
= 0.03). In multivariate analysis, donor age (
p
= 0.01) and the lack of treatment with an ACE inhibitor (
p
= 0.02) remained independent predictors of increases in atheroma volume. Increased disease progression with age was attenuated with the use of ACE inhibitors (table

).

Conclusion
: Donor age and ACE inhibitor treatment are major determinants of CAV progression. This analysis suggests that treatment with ACE inhibitors would attenuate age-related progression of CAV. Large randomized clinical trials are warranted to ascertain such a beneficial effect.
Abstract 2892: Inhibition of Toll-like Receptor-2 May Limit Cardiac Dysfunction After a Myocardial Infarction by Reducing Apoptosis via a p38 MAPK-dependent Pathway
Authors: Su Brenda B , Sun Zhuo , Fujii Hiroko , Wu Jun , Li Zhihong , Weisel Richard D , Yau Terrence , Li Ren-Ke
Published: July 2021

Background:
Inhibition of toll-like receptors (TLRs) may be a new treatment to prevent congestive heart failure during post-myocardial infarction (MI) surgical interventions. TLR2 knockout (KO) mice provide an opportunity to predict the effects of inhibitors and to establish the mechanisms responsible for their beneficial effects. This study was performed to establish the pathways responsible for myocardial protection in the absence of TLRs after MI.

Methods and Results:
In vivo study:
MI was induced in TLR2 KO and wild-type (WT) C56B/6J mice by anterior coronary artery ligation. Cardiac function was preserved in the KO mice compared to the WT mice (echocardiography demonstrated higher fractional shortening and fractional area change, p<0.05) at 3, 7 and 28 days after the MI. To evaluate the mechanisms responsible for the functional improvements, cardiac cytokine production was measured. TNF-α, IL-1β and IL-6 were significantly decreased in the infarct region of KO compared to WT mice at 3 days post-MI. On day 7, IL-6 production was significantly decreased in the infarct region and TNF-α was decreased in the non-infarcted region of KO compared to WT mice. Phosphorylation of p38 MAPK was prevented, and the number of TUNEL positive nuclei was reduced in the infarct region of KO compared to WT mice. Phosphorylation of Akt was upregulated in the non-infarcted region of KO mice at 3 days after MI. There were no differences in the phosphorylation of ERK or JNK at the same time point.
In vitro study:
Myocardial fibroblasts were isolated from KO and WT mice, cultured, and then exposed to hydrogen peroxide. Compared to cells from WT mice, cells from KO mice exhibited greater protection (less cell death) and reduced p38 phosphorylation as early as 5 and 15 minutes after hydrogen peroxide stimulation.

Conclusions:
TLR2 KO mice allow the assessment of the potential benefits of TLR inhibitors. Reducing TLR2 after an infarction will decrease cytokine production and cell death in a p38 MAPK-dependent manner, which in turn will contribute to the preservation of cardiac function. Early inhibition of TLR2 function may represent a new target to prevent heart failure after MI.
Abstract 2922:
KCNQ1
Gain-of-function Mutation Associated With Familial Atrial Fibrillation
Authors: Darbar Dawood , Abraham Robert , Kucera Gayle , Stubblefield Tanya , Yang Tao , Roden Dan M
Published: July 2021

Background

: Family history is a risk factor for atrial fibrillation (AF). We report here a 3-generation Caucasian family with familial AF and a highly dysfunctional mutation in
KCNQ1
.

Methods and Results:

In the proband, there was a 9-bp duplication resulting in insertion of the amino acids IAP (IAP54 –56) in the N-terminus of the protein. The kindred included 4 other family members with AF or palpitations. Each affected family member presented with early onset paroxysmal lone AF and no QT prolongation. This variant has previously been reported in presumed healthy African-American individuals (minor allele frequency 1.3%), but has not been studied
in vitro
. In transfected CHO cells, coexpression of IAP54 –56 with
KCNE1
generated currents that were much larger and activated much earlier that wild-type I
Ks
(

Figure

); e.g. at +20 mV, peak current was 75±8 [IAP54 –56] vs 25±5 [wt] pA/pF after 5-sec pulses (n=7 each, P<0.001). Computational simulations of human atrial action potential (AP) that incorporated Markov models of wt or IAP54 –56-I
Ks
were performed. At a cycle length of 400ms, accelerated activation of IAP54 –56-I
Ks
resulted in open state accumulation and increased maximum I
Ks
amplitude ~40-fold (351 vs 9 pA/pF), resulting in ~6-fold AP duration shortening (44 vs 259 ms).

Conclusions:

We have identified a
KCNQ1
indel in a moderate sized Caucasian kindred with familial AF and normal QT intervals. This variant results in an I
Ks
gain-of-function and the resulting shortening of atrial action potentials may predispose to AF. This variant has been reported in 1.3% of African-Americans, suggesting it may be a common risk allele in some populations.