bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15165: A Green Tea Catechin, (-)-epicatechin-3-gallate, Suppresses Early After-depolarization in Long-term Cultured Cardiomyocytes
Authors: Wu Adonis Z , Wu Sheng-Nan , Lin Cheng-I , Lin Shien-Fong
Published: July 2021

Introduction:
Our previous study verified (-)-epicatechin-3-gallate (ECG), a green tea polyphenol, can act as a sodium channel agonist. However, the treating effects of ECG on the arrhythmic disorders, such as early after-depolarization (EAD) remain uncertain.

Hypothesis:
We hypothesize that ECG alters the rate of spontaneous action potential (sAP) and suppresses EAD through its action on voltage-gated sodium current (
I
Na
).

Methods:
By using patch-clamp technique, we characterized the alterations of sAP in cultured neonatal rat ventricular myocytes (NRVMs). We further examined the effects of ECG on the firing rate and morphology of sAP.

Results:
The sAP alterations were investigated in two stages. The early stage, 3-4 days post cell isolation, involved a gradual suppression of amplitude (~36.9%) and frequency (~72%) in the early culture periods, followed by about two folds APD
90
prolongation in the late culture stage, > 7 days post cell isolation. These changes of sAP were strongly correlated with dysfunction of
I
Na
(r
2
=0.99) but not with
I
K
or
I
to
. With an increment in the incubating period, the
I
Na
properties were also observed in the decrease of
I
Na
density (~44%), negative shift of steady-state inactivation curve (
V
h
, -73.4±4.2 vs. 83.1±4.7 mV, p<.05), and prolongation of the recovery time constant (
τ
, 65.8±4.1 vs. 82.5±4.6 ms, p<.05). The dysfunction of
I
Na
appeared to result in an increased incidence of the bradycardia-dependent EAD. Treatment with ECG suppressed EAD via accelerating the
I
Na
recovery time to normal, resulting in fast firing rate of the sAP as in early culture period.

Conclusions:
Long-term culture of myocytes leads to retardation of automaticity, APD prolongation, EAD occurrence, and concomitant
I
Na
suppression. ECG restores
I
Na
and cellular automaticity in long-term cultured NRVMs.
Abstract 15181: Predictors of Mortality and Morbidity in Patients With Chronic Heart Failure - Analysis of Red-HF Trial
Authors: Anand Inder S , Yu Changhong , Pfeffer Marc A , McMurray John J , Desai Akshay S , Solomon Scott D , Veldhuisen Dirk J , Cheng Sunfa , Olson Kurt , Maggioni Aldo P , Swedberg Karl , Young James B
Published: July 2021

Background:
A number of prognostic models have been developed to risk stratify patients with heart failure (HF) and reduced ejection fraction (EF). However, few have included medications, device therapy and natriuretic peptides.

Methods and Results:
We analyzed data from 2278 patients in Reduction of Events with Darbepoetin Alfa in Heart Failure (RED-HF) trial that tested the effects raising hemoglobin in high-risk anemic patients with HF (median age 72 years; Hg 11.2 g/dL; EF 31%; and GFR 46 ml/min/1.73m2; annualized mortality 14.1%). Multivariable Cox regression models were developed to predict the primary endpoint of all-cause mortality or hospitalization for HF, and all-cause mortality, starting with 43 baseline demographic, clinical, treatment and biochemical variables including NT-proBNP. Nonlinear relationships with continuous variables were examined using restricted cubic splines. Final predictor variables were selected using backward stepwise selection in 1000 bootstrap samples. For the primary outcome, NT-proBNP, hospitalization for HF in past 6-months, heart rate, diastolic BP and bilirubin were the strongest of the 12 final predictors that provided good discrimination (Harrell’s C=0.74) with excellent calibration (Figure). Surprisingly, age, diabetes and EF were not selected. Forcing them in the model did not change discrimination (Harrell’s C=0.74). For all-cause mortality, NT-proBNP, diastolic BP, beta-blocker use, bilirubin and albumin were among the strongest of the 11 final predictors (Harrell’s C=0.71). Again, diabetes and EF were not in the model and forcing them in the model did not improve the C-statistics.

Conclusions:
In a contemporary well-treated population of severe HF with reduced EF, a multivariable risk model that included medications, devices and natriuretic peptide provided good discrimination and prediction of the primary outcome and all-cause mortality. NT-proBNP was the strongest predictor of both outcomes.
Abstract 152: Impact of Shock Timing During Mechanical CPR on Defibrillation Efficacy
Authors: Walker Robert G , Esibov Alexander , Chapman Fred W
Published: July 2021

Background:
Mechanical CPR (mCPR) devices enable defibrillation shock delivery during ongoing chest compressions, without the pause required during manual CPR. It is unknown whether shock delivery during ongoing mCPR, vs. during a pause, affects VF termination efficacy. Animal studies suggest that during ongoing mCPR, timing a shock to a specific phase of the compression cycle may significantly affect shock efficacy.

Methods:
We retrospectively analyzed electronic defibrillator recordings from the Amsterdam Resuscitation Study (ARREST), a prospective out-of-hospital cardiac arrest registry. We identified cases with LUCAS mCPR and at least one shock delivered after mCPR initiation. Shocks were sorted by energy level, and the most prevalent (360 J) was selected for the present analysis. Continuous ECG and impedance signals were analyzed to determine VF termination (defined as absence of VF at 5 sec after shock) for each shock after mCPR initiation, and whether the shock was delivered during a pause or during mCPR. For shocks delivered during a pause we measured pre-shock pause duration; for shocks delivered without pausing we measured the exact timing of the shock during the compression cycle.

Results:
In 153 cases meeting analysis criteria, 509 360J shocks occurred after mCPR initiation; VF termination outcome could be determined for 460. VF termination for first eligible shock during mCPR in each case was 84/97 (87%) during a pause, and 79/93 (85%; p=0.74) during ongoing mCPR; for all eligible shocks, VF termination was 203/242 (83.9%) and 155/196 (79.1%; p=0.20) respectively. For shocks during mCPR, there were no statistically significant differences in VF termination rate for shocks during four equal length phases beginning with LUCAS piston upstroke: 39/44 (89%), 39/49 (80%), 35/51 (69%), 40/50 (80%) (p = 0.12). For shocks during a pause, VF termination rate did not differ for pre-shock pauses ≤5 sec (75/91, 82.4%) vs. >5 sec (128/151, 84.8%; p=0.63).

Conclusions:
Our results indicate that shocks can be delivered during ongoing mCPR without reducing defibrillation efficacy. The exact shock timing during the mCPR compression cycle did not significantly alter shock efficacy. VF termination rate was not affected by pre-shock pause duration during mCPR.
Abstract 15237: Serum Galectin-3 Level Predicts Late Recurrence Following Cryoballoon-based Pulmonary Vein Isolation in Lone Atrial Fibrillation Patients
Authors: Gurses Kadri M , Yalcin Muhammed U , Kocyigit Duygu , Canpinar Hande , Evranos Banu , Ates Ahmet H , Yorgun Hikmet , Sahiner Mehmet L , Kaya Ergun B , Guc Dicle , Oto Mehmet A , Aytemir Kudret
Published: July 2021

BACKGROUND:
Left atrial(LA) interstitial fibrosis is known to be a key contributor to atrial fibrillation(AF) development and maintenance. The role of galectin-3 in the pathogenesis of cardiac fibrosis has been demonstrated in previous studies. We aimed to determine whether serum galectin-3 level is an independent predictor for the late AF recurrence in patients with lone AF who underwent cryoballoon- based pulmonary ven isolation(PVI).

METHODS:
100 patients (43.80% male, 56.95± 11.36 years) with lone AF who underwent cryoballoon-based PVI were included in the study. Pre-procedural galectin-3 levels were measured with ELISA.

RESULTS:
At a follow-up of 12 months, 76 (76%) patients were free of late AF recurrence. Body mass index(BMI) ( 25.04± 1.54 vs. 23.93± 2.08 kg/m2, p=0.002), AF duration [7 (3- 20) vs. 5 (1- 24) months, p=0.024], serum galectine-3 levels [11.10 (4.20- 33.80) vs. 5.70 (2.60- 12.40) ng/mL, p<0.001], left atrial diameter(LAD) (4.30± 0.40 vs.3.79± 0.42 cm, p<0.001) and incidence of early recurrence (60 vs 2%, p<0.001) were found to be significantly higher in patients with late AF recurrence. Serum galectin-3 levels (HR: 1.16, p<0.001), LAD (HR: 3.38, p= 0.042) and early recurrence (HR: 10.92, p<0.001) were found to be independent predictors of late AF recurrence in the multivariate Cox regression analysis. A cut-off level for serum galectin-3 level of 7.9 ng/mL predicted late AF recurrence in lone AF patients with a sensitivity of 93.33% and specificity of 87.76% (AUC: 0.910, p<0.001).

CONCLUSION:
Pre-procedural serum galectin-3 level is an independent predictor of late AF recurrence following cryoballoon-based PVI in patients with lone AF. Galectin-3 may serve as a novel biomarker to identify patients with high recurrence risk following AF ablation.
Abstract 15248: Comparison of the Effects of Two Low-Density Lipoprotein Cholesterol Goals on Secondary Prevention After Acute Myocardial Infarction: ≥50% Reduction From Baseline versus <70 mg/dL
Authors: Cho Kyung Hoon , Lee Kyoung Jin , Kim Kyung Hwan , Kim Woo-Jin , Kim Min Chul , Kim Cheol Hwan , Jun Seung Jin , Kim Hyun Kuk , Jeong Hae-Chang , Park Keun-Ho , Sim Doo Sun , Park Kyung Woo , Lee Sang Rok , Hong Young Joon , Ahn Youngkeun , Chae Jei Keon , Kim Hyo-Soo , Cho Jeong Gwan , Park Jong Chun , Jeong Myung Ho
Published: July 2021

Background:
There haven’t been well-designed studies conducted to know an optimal goal for low-density lipoprotein cholesterol (LDL-C) after acute myocardial infarction (AMI).

Methods:
Of 2,409 consecutive patients (62.7 ± 12.4 years, 74.1% men) with AMI who had baseline LDL-C levels ≥70mg/dL and received discharge statin prescriptions after successful percutaneous coronary intervention, 1,305 patients (61.0 ± 11.8 years, 77.0% men) who had LDL-C levels tested at 1 year (mean baseline LDL-C, 126.5 ± 33.5 mg/dL; mean LDL-C reduction at 1 year, 53.1 ± 29.3 mg/dL) were analyzed in this study. Patients were categorized into 2 groups according to the values of LDL-C at 1 year in two different ways using percent change from baseline (≥50% reduction, n=428 versus <50% reduction, n=877) and fixed levels (<70 mg/L, n=625 versus ≥70 mg/dL, n=680). The primary endpoint was the composite of major cardiac events (MCEs) including cardiac deaths, non-fatal myocardial infarctions and coronary revascularizations (angioplasty or bypass grafting) after hospital discharge. A median follow-up duration was 2.0 years (interquartile range, 1.9 to 2.1 years).

Results:
At 2 years, MCEs occurred in 139 patients (10.7%). Kaplan-Meier estimates of the MCEs rates at 2 years revealed that patients with ≥50% LDL-C reduction from baseline had fewer MCEs compared with <50% LDL-C reduction (8.2% versus 11.9%; Log rank
P
=0.026), while those with LDL-C levels <70 mg/dL at 1 year did not (<70 mg/L, 10.7% versus ≥70 mg/dL, 10.6%; Log rank
P
=0.998). In a multivariable Cox proportional hazard model, patients with ≥50% LDL-C reduction from baseline had a 39% reduction in the risk of MCEs compared with <50% LDL-C reduction (adjusted hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.41 to 0.90;
P
=0.012). But, compared with LDL-C levels ≥70 mg/dL at 1 year, patients with LDL-C levels <70 mg/dL didn’t have a significant reduction in the risk of MCEs (adjusted HR, 0.98; 95% CI, 0.69 to 1.37;
P
=0.975).

Conclusions:
Obtaining a ≥50% reduction in LDL-C was associated with a significant reduction in the risk of MCEs after AMI, whereas achieving a <70 mg/dL was not. Our study suggests that obtaining a ≥50% reduction from baseline could be an optimal goal for LDL-C after AMI, not achieving a <70 mg/dL.
Abstract 15253: A Paradoxical Rise in Serum Copeptin After Non-Pulsatile LVAD: a New SIADH?
Authors: Statz Cara M , Ras Aleksandra M , Ballard Kevin D , Gluck Jason A , Wencker Detlef
Published: July 2021

Introduction:
Hyponatremia (Na< 136 mmol/L) is prevalent (~28%) among hospitalized heart failure (HF) patients and a marker of advanced/end-stage HF(AHF) with increased mortality. Treatment of hyponatremia has no survival benefit in this population. In a prospective study of AHF patients, we sought to define the prevalence, pathophysiology and role of V2 vasoreceptor activity in the development of hyponatremia. Serum copeptin (S-COP), a surrogate marker for AVP activity, was assessed during AHF therapies (AHFT) which included axial-non-pulsatile left ventricular assist device (LVAD) and/or heart transplant (HTx).

Methods:
Serum samples were collected from AHF patients pre and post AHFT and compared with normal controls. S-COP levels were assessed using an enzyme linked immunosorbant assay and correlated to clinical variables, serum Sodium (S-Na) and glomerular filtration rate (eGFR).

Results:
Among 89 consecutive (mean age 56.2±15.35; M=69) patients awaiting AHFT, 54 (60%) were hyponatremic. Preop S-COP was elevated compared to controls (0.68±0.50 vs 0.53±0.13 ng/ml, P=.02) and inversely correlated to S-Na and eGFR (r=-0.23, P<.05, r=-0.23, P<.05; N=81); conversely, eGFR and S-Na were uncorrelated. AHFT (n=42) normalized S-Na (133.2±4.1 vs 136.1±3.5 mmol/l; P=.001) and improved eGFR (47.7±13.6 vs 52.7±9.7 mL/min/1.73sqm; P=.001); however, post LVAD (n=34) S-COP rose (0.67±0.21 vs 1.84±0.76 ng/ml; P<.0001) with incomplete normalization of S-NA (132.9±4.3 vs 135.9±3.8 mmol/l; P<.01). In contrast, post HTx (n=9) S-COP was unchanged to pre-AHFT (0.59±0.32 vs 0.65±0.16 ng/ml; P>.1) and was lower compared to post LVAD (0.65±0.16 vs 1.84±0.76 ng/ml; P<.0001). Elevated S-COP with LVAD as bridge to transplant (n=3) showed a marked decrease post HTx (2.7±0.50 vs 1.0±0.29 ng/ml; P<.01).

Conclusions:
In AHF, the prevalence of hyponatremia is double compared to acute hospitalized HF and associated with S-COP surge prior to AHFT. Unexpectedly, LVAD but not HTx was associated with rising S-COP and incomplete S-Na recovery despite clinical improvement, suggesting inappropriate antidiuretic hormone release. The association of S-COP rise with non-pulsatile LVAD and potential benefit of long-term AVP inhibition post LVAD merits further studies.
Abstract 15258: The Association of Genetic Polymorphism of rs2106261 in ZFHX3 and ‘Super-responder’ to Catheter Ablation Among the Patients With Long-standing Persistent Atrial Fibrillation
Authors: Park Jin kyu , Park Junbeom , Uhm Jae-Sun , Joung Boyoung , Lee Moon-Hyong , Pak Hui-Nam
Published: July 2021

Introduction:
The radiofrequency catheter ablation (RFCA) is challenging in patients with long-standing persistent atrial fibrillation (PeAF) and its clinical outcome is highly variable. Genome-wide association studies (GWAS) have identified that the rs2106261 polymorphism in ZFHX3 is associated with non-valuvluar AF.

Hypothesis:
We tested the association between the “super-responder” to the radiofrequency catheter ablation (RFCA) and the rs2106261 polymorphism among the patients with long-standing persistent AF.

Methods:
We included consecutive 207 patients with long-standing PeAF (79.2% male, age 58.0±9.7 years and follow-up interval 21 (16-34) months) who underwent RFCA for symptomatic long-standing PeAF. The super-responders were defined as the patients without early or clinical recurrence of AF at least for 12 months of post-procedural follow-up period without taking anti-arrhythmic drug. We looked for the characteristics of super-responders in clinical profiles, ECG in sinus rhythm, 3D-left atrial (LA) CT, or genotypes of the rs2106262.

Results:
1. Fifty two patients (25.1%) were categorized as super-responders. Super-responders were younger (55.5±9.6 vs. 58.9±9.6 years old, p=0.028) and had shorter AF duration (44.9 [25.4-73.1] vs. 65.1 [34.1-113.6] month, p=0.010), shorter QTc (435.1±27.8 vs. 447.3±29.1 msec, p=0.007), lower negative P wave amplitude in lead V1 (0.07±0.03 vs. 0.08±0.04, p=0.034), and smaller LA volume index (CT) (75.2±21.0 vs. 88.2±24.1, p=0.001) than recurred patient group. 2. In additive model, the minor allele frequency of the rs2106261 was higher in super-responders (52.2%) than in recurred group (40.9%, p=0.058). 3. In multivariate analyses, LA volume index (adjusted OR=0.973, 95% CI 0.955-0.992, p=0.006) and genetic polymorphism of the rs2106261 (adjusted OR=1.808, 95% CI 1.034-3.163, p=0.038) were independently associated with super-responder to RFCA among the patients with long-standing persistent AF.

Conclusion:
Although the recurrence rate after catheter ablation for long-standing persistent AF is still high, pre-procedural LA volume index or the rs2106261 polymorphism may be helpful for the selection of good candidate for RFCA.
Abstract 15280: Comparisons of Action Potentials and Ionic Currents Between Neonatal Rat Ventricular Myocytes and Adult Zebrafish Ventricular Myocytes
Authors: Wu Adonis Z , Lin Shien-Fong , Wu Sheng-Nan
Published: July 2021

Introduction:
Zebrafish heart is established as a model to investigate cardiac electrical abnormalities. However, electrical properties of adult zebrafish cardiomyocytes are not sufficiently characterized.

Hypothesis:
In this study, by comparing the electrical properties between neonatal rat ventricular myocytes (NRVMs) and adult zebrafish ventricular myocytes (AZVMs), we intended to characterize the action potential (AP), action current (AC) and the properties of Na
+
current (
I
Na
) in AZVMs.

Methods:
We used patch-clamp technique to characterize the electrical properties, including AP, AC and
I
Na
, in cultured NRVMs and freshly isolated AZVMs.

Results:
NVRMs showed larger AP amplitude (119±6 vs. 79±4mV, p<.05) but shorter AP duration (APD
90
, 136±11 vs. 213±19 ms, p<.05) than those of AZVMs. The AP duration exhibited marked frequency-dependent alterations in AZVMs. Under the slow pacing rate, early after-depolarizations (EAD) emerged under slow pacing rate with 0.05 Hz. In cell-attached voltage-clamp recordings made from AZVMs, ACs could be elicited by +10 mV steps. As the depolarization step increased to +70 mV, the latency for appearance of ACs was progressively reduced from >123 ms to 9.8 ms. The presence of spontaneous ACs was monitored in spontaneously beating NRVMs and AZVMs. The AC amplitude in NRVMs was larger compared to that in AZVMs (17.3±2.1 vs. 11.6±1.1 pA, p<.05), although firing frequency of AC in NRVMs is higher than in AZVMs (1.13±0.09 vs. 0.38±0.03 Hz, p<.05). The lowering effect of ranolazine, a
I
Na
antagonist, on firing frequency was significantly larger in NRVMs (1.13±0.09 to 0.31±0.02 Hz, p<.05) than in AZVMs (0.38±0.03 to 0.27±0.02 Hz). There was a hyperpolarizing shift of peak
I
Na
in AZVM compared to NRVM.

Conclusions:
Our results demonstrated major differences in the cellular electrical behavior between AZVMs and NRVMs.
Abstract 15288: Conductive Polymer Hydrogel for Enhancement of Electrical Propagation in Border Zone Myocardium after Myocardial Infarction
Authors: Mihic Anton , Miyagi Yasuo , Wu Jun , Vlacic Goran , Lam Martin , Cui Zui , Li Shu-hong , Sun Lu , Weisel Richard D , Li Ren-Ke
Published: July 2021

Introduction:
After myocardial infarction (MI), cardiomyocyte death results in a non-contractile fibrotic scar and altered electrical properties, including delayed impulse propagation across the scar region which may contribute to ventricular dysfunction. Hydrogels such as chitosan have been used clinically to stabilize the LV free wall and prevent dilation. We chemically modified chitosan with the charge-carrying conductive polymer polypyrrole (PPy), yielding a biomaterial with more than 100X the conductivity of chitosan alone. Chitosan-PPy is capable of carrying electrical impulses and may enhance synchronous contraction.

Methods:
Biomaterials were synthesized under sterile conditions and were thoroughly characterized
in vitro
. Myocardial infarction was created by coronary artery ligation in Sprague-Dawley rats (n = 36), and 1 week later chitosan, chitosan-PPy or saline were injected into the border zone regions. Animals were followed for 8 or 16 weeks (n = 6/treatment/time-point) and cardiac conduction and function were assessed with ECG, echocardiography, impedance catheter analysis and finally Langendorff-perfused epicardial optical mapping.

Results:
Eight weeks post-injection, QRS duration was increased in saline and chitosan treated hearts, but was maintained in chitosan-PPy hearts until 16 weeks (
p
< 0.01), suggesting less maladaptive ventricular remodeling associated with slowing of depolarizing conduction in the chitosan-PPy group. Echocardiography revealed that fractional shortening was enhanced in chitosan-PPy treated hearts at both 8 and 16 weeks (
p
< 0.01). At 16 weeks, chitosan-PPy hearts had increased stroke work capacity, and better maintained (lower) end systolic volume (
p
< 0.05). Optical mapping demonstrated that chitosan-PPy-treated hearts had faster transverse conduction velocities measured along the border zone epicardial surface (
p
< 0.01).

Conclusions:
We synthesized and characterized a novel conductive polymer hydrogel that may be used therapeutically to enhance favorable cardiac recovery at the LV border zone following an MI. Chitosan-PPy enhanced heart function by augmenting synchronized contraction.
Abstract 15298: A New Scoring System for the Prediction of Paroxysmal Atrial Fibrillation Progression and Relationship with Clinical Outcomes
Authors: Park Hyung Wook , Lee Ki Hong , Yoon Nam Sik , Cho Jeong Gwan , Kim Sung Soo , Kim Cheol Hwan , Kim Kyung Hwan , Jun Seung Jin , Kim Woo Jin , Kim Min Chul , Cho Kyung Hoon , Lee Kyoung Jin , Jeong Hae Chang , Cho Jae Yeong , Park Keun-Ho , Sim Doo Sun , Yoon Hyun Joo , Kim Kye Hun , Hong Young Joon , Kim Ju Han , Ahn Youngkeun , Park Jong Chun , Jeong Myung Ho
Published: July 2021

Background:
The progression of paroxysmal atrial fibrillation (AF) to persistent, long lasting persistent AF is often associated with poor clinical outcomes. Although some factors were known to be useful, their accuracy and clinical relationship are not good enough to predict the progression.

Hypothesis:
We aimed to construct a new predictive scoring system for the progression of paroxysmal AF. Also, we aimed to evaluate the relationship of a new predicting system with clinical outcomes.

Methods:
We analyzed 2,047 patients (61.2±13.2 years old, 1158 males) who were newly diagnosed as AF from January 2006 to January 2013. Progression of AF and clinical outcomes were analyzed after at least one-year follow-up. Clinical outcomes were defined as the composite of death, hospitalization due to heart failure, and new onset stroke. Independent predictors of AF progression were analyzed and incorporated into a new predictive scoring system. Its predictive accuracy was compared with CHADS
2
, CHA
2
DS
2
-VASc, and HATCH scoring system.

Results:
Paroxysmal AF was diagnosed in 449 (21.6%) patients. Among them, 78 (17.4%) patients progressed to persistent AF. Multivariate analysis showed congestive heart failure (LVEF <45%), hypertension, older age (≥65 years old), chronic renal disease, previous history of stroke, COPD, left atrial enlargement (≥43mm), high NT-pro BNP serum levels (≥1,000 pg/mL) were independently associated with the progression. A new scoring system was calculated with the sum of 1 point at each independent risk factor. It showed better predictive accuracy for AF progression (area under curve (AUC): 0.754, 95% confidence interval [CI] 0.69-0.83, p<0.001) than CHADS
2
(AUC 0.643; 95% CI 0.58-0.71), CHA
2
DS
2
-VASc (AUC 0.647; 95% CI 0.58-0.71), and HATCH score (AUC 0.675; 95% CI 0.61-0.74). Also, it showed better predictive accuracy for the composite of clinical outcomes (AUC 0.764, 95% CI 0.68-0.83, p<0.001) with linear correlation (linear p<0.001) than the other scoring systems. More than 60% of patients with paroxysmal AF progressed into sustained AF if the score by a new system was more than 3.

Conclusions:
A new scoring system may help to the prediction of AF progression and prognosis for clinical outcomes in patients with paroxysmal AF.
Abstract 15312: Genetic Deletion of Toll-like Receptor 9 Accelerates Blood Flow Recovery after Hindlimb Ischemia
Authors: Nishimoto Sachiko , Fukuda Daiju , Higashikuni Yasutomi , Tanaka Kimie , Hirata Yoichiro , Yagi Shusuke , Soeki Takeshi , Sakaue Hiroshi , Shimabukuro Michio , Sata Masataka
Published: July 2021

Background:
Peripheral artery disease causes significant functional disability and results in impaired quality of life. Toll-like receptor (TLR)-2, 3 and 4 are suggested to participate in blood flow recovery in ischemic limb by modulating inflammation and angiogenesis, however, the role of TLR9 remains unknown. TLR9 recognizes bacterial unmethylated DNA and plays a role in innate defense, although it can also provoke inflammation in response to fragmented DNA released from regenerated mammalian cells. This study tested the hypothesis that genetic deletion of TLR9 accelerates blood flow recovery after femoral artery ligation by inhibiting inflammation and improving endothelial cell function.

Methods and Results:
Unilateral femoral artery ligation was performed in TLR9-deficient (TLR9KO) mice and wild type (WT) mice. Femoral artery ligation significantly increased RNA expression of TLR9 (20-times) in WT mice and plasma levels of single-stranded DNA and double-stranded DNA, endogenous ligands for TLR9, in both strains of mice compared with each sham-operated group (P<0.05). Laser Doppler perfusion imaging demonstrated that TLR9KO mice significantly improved the ratio of the blood flow in the ischemic to non-ischemic limb compared with WT mice at 2 weeks after ligation (P<0.05). TLR9KO mice showed less accumulation of macrophages and less expression of inflammatory molecules (e.g., TNF-α, MCP-1 and IL-1β in ischemic muscle compared with WT mice (P<0.05, respectively). In vitro experiments using thioglycolate-stimulated peritoneal macrophages demonstrated that CpG ODN, agonistic oligonucleotide for TLR9, promoted the expression of pro-inflammatory molecules (e.g., MCP-1 and TNF-α) in WT macrophages (P<0.05, respectively) but not in TLR9 KO macrophages. Furthermore, activation of TLR9 by CpG ODN inhibited migration and proliferation of endothelial cells as determined by scratch-wound assay and MTS assay, respectively (P<0.05).

Conclusion:
Our results suggested that TLR9 enhances inflammation and affects migration and proliferation of endothelial cells, leading to impaired blood flow recovery in ischemic limb. TLR9 may serve as a potential therapeutic target for ischemic limb disease.
Abstract 15362: Pre-participation Screening of Young Competitive Athletes for the Prevention of Sudden Cardiac Death Using a New Electrocardiographic Device
Authors: Cho Jae Hyung , Selen Mats A , Kocheril Abraham G
Published: July 2021

Introduction:
Routine 12-lead electrocardiogram screening for the prevention of sudden cardiac death in young athletes is not recommended due to the enormous cost per life saved. The application of less expensive electrocardiographic devices has not been investigated.

Hypothesis:
The purpose of this pilot study was to investigate the utility of a new 3-lead wireless electrocardiographic device for the pre-participation screening of young competitive athletes.

Methods:
Twenty-seven college football players were enrolled in this study. During the pre-participation screening sessions, each player underwent evaluation using a conventional 12-lead electrocardiogram and a new 3-lead electrocardiogram coupled to our wireless electrocardiographic device. The new 3-lead electrocardiography is a compact device that yields high quality electrocardiographic signals. We compared several electrocardiographic parameters (QRS duration, QRS amplitude, left ventricular hypertrophy, ST deviation and corrected QT interval) using Pearson’s correlation coefficient.

Results:
The QRS duration, QRS amplitude and corrected QT interval values exhibited significant correlation between the two types of electrocardiograms (correlation coefficient 0.723, 0.537 and 0.734, respectively with P value of 0.01, 0.004 and 0.01, respectively). ST deviation in V1 was weakly correlated with ST deviation in lead Z without statistical significance (correlation coefficient 0.227 with P value of 0.256). Assessment of left ventricular hypertrophy using the Cornell voltage or Sokolow-Lyon criteria and average QRS amplitude also revealed weak correlation without statistical significance (correlation coefficient 0.221 and 0.246, respectively with P value of 0.268 and 0.216, respectively).

Conclusions:
Our newly developed 3-lead electrocardiogram results correlated well with those of a conventional 12-lead electrocardiogram in terms of QRS duration, QRS amplitude and corrected QT interval. Thus, the 3-lead electrocardiogram might represent a useful screening tool for the prevention of sudden cardiac death in young competitive athletes.
Abstract 15392: Inflammation and Ischemic Heart Failure: Monocyte-Mediated Cardiac Fibroblast Activation and Matrix Remodeling Through a Direct Cell-Cell Contact Mechanism
Authors: Mewhort Holly E , Lipon Brodie D , Svystonyuk Daniyil A , Guzzardi David G , Fedak Paul W
Published: July 2021

BACKGROUND:
Following myocardial infarction (MI), activated cardiac myofibroblasts facilitate extracellular matrix (ECM) remodeling to prevent mechanical complications. However, prolonged myofibroblast activity leads to dysregulation of the ECM, maladaptive remodeling, fibrosis and heart failure (HF). Chronic inflammation is believed to drive persistent myofibroblast activity, however, the mechanisms are unclear. In this study, we explored the effects of peripheral blood monocytes on human cardiac fibroblast activation in a 3D ECM microenvironment.

METHODS/RESULTS:
Human cardiac fibroblasts isolated from surgical human heart biopsies were seeded into 3D collagen matrices. Peripheral blood monocytes isolated from healthy human donors were co-cultured with fibroblasts. Monocytes increased fibroblast activation measured by collagen ECM contraction (17.9±11.1% increase; p<0.01) and resulted in local ECM remodeling observed by confocal microscopy. Under co-culture conditions that prevent cell-cell contact but allow interaction via paracrine factors, monocytes had minimal effects on fibroblast activation (6.4±7.0 vs.17.9±11.1% increase, respectively; p<0.01). Multiplex analysis of the co-culture media revealed an increase in the paracrine factors Transforming Growth Factor-beta 1 (TGF-β1) and Matrix Metalloproteinase 9 when monocytes and fibroblasts were cultured under cell-cell contact conditions (162.2±11.7pg/mL and 17.5±0.5ng/mL, respectively, vs. 21.8±5.7pg/mL and 4.9 ±0.4ng/mL; p<0.001). TGF-β1 blockade abolished monocyte induced cardiac fibroblast activation, as did β1-integrin. These data suggest direct cell-cell interaction between monocytes and cardiac fibroblasts through β1-integrin results in TGF-β1 release facilitating fibroblast activation and matrix remodeling.

CONCLUSION:
For the first time, we demonstrate that peripheral blood monocytes stimulate human cardiac fibroblast activation through a mechanism involving TGF-β1 release as a consequence of direct cell-cell interaction through β1-integrin. These data implicate inflammation as a driver of cardiac fibrosis post-MI, highlighting potential novel therapeutic targets for the treatment of ischemic HF.
Abstract 15454: Inhibition of Mechanistic Target of Rapamycin by Heterozygous Deletion of Raptor Ameliorates Pressure-overload Induced Heart Failure and the Associated Proteomics Remodeling
Authors: Dai Dao Fu
Published: July 2021

Background:
We reported that inhibition of mechanistic target of rapamycin (mTOR) by short-term rapamycin or caloric restriction ameliorates age-dependent cardiac hypertrophy and diastolic dysfunction. Although inhibition of mTOR signaling is well known to regulate metabolism and suppress protein synthesis, the mechanisms of beneficial effect of mTOR inhibition in cardiac hypertrophy and failure are not fully understood.

Method:
To investigate the mechanisms underlying beneficial effect of mTOR inhibition, we used the transverse aortic constriction (TAC)-induced heart failure model and examined the effect of heterozygous deletion of Raptor (Raptor het), a component of mTOR complex 1, and transgenic overexpression of cardiac specific wild type or mutant 4EBP1, one of the main downstream target of mTOR complex 1. Global proteomics analysis was performed using an improved label-free quantitative shotgun approach, followed by Ingenuity Pathway analysis.

Results:
In wild-type mice with TAC-induced heart failure, global proteomics analysis revealed decreased abundance of proteins involved in mitochondrial function, electron transport chain, citric acid cycle and fatty acid metabolism and increased abundance of proteins involved in several signaling pathways (RhoA, actin, integrin) as well as oxidative stress response and protein ubiquitin pathways. Raptor het attenuate TAC induced heart failure, accompanied by better preservation of proteomics remodeling, especially the proteins involved in mitochondrial function, citric acid cycle and protein ubiquitination pathways. In contrast, either transgenic overexpression of wild type 4EBP1 or mutant 4EBP1 abolish the adaptive hypertrophy in response to TAC by suppressing protein translation, and thereby aggravate heart failure, in parallel with adverse remodeling of left ventricular proteomes. Neonatal cardiomyocyte experiments reveal that PGC1-α and Sirt3 are among the candidate signaling mechanisms linking the mTOR inhibition and mitochondrial metabolism.

Conclusion:
mTOR inhibition by Raptor heterozygous deletion, but not overexpression of 4EBP1, ameliorates TAC-induced heart failure and associated with better preservation of mitochondrial proteome.
Abstract 15486: Intramyocardial Gene Therapy With a Novel Angiogenic Molecule, Pellino-1 Preserves Functions and Increases Cell Survivability in a Mouse Myocardial Infarction Model
Authors: Coca-Soliz Vladimir , Tapias Leonidas , Selvaraju Vaithinathan , Thirunavukkarasu Mahesh , Palesty J.Alexander , Maulik Nilanjana
Published: July 2021

Introduction:
Our present study attempted to evaluate the effect of Pellino1 (Peli1) overexpression on angiogenesis and myocardial function by intramyocardial administration of adenovirus encoding Peli1 (Ad.Peli1) following myocardial infarction (MI) in mice.

Methods:
CD-1/ICR mice were divided into six groups: Control Sham (CS); Control MI (CMI); Adeno-LacZ Sham (Ad.LacZS); Adeno-LacZ MI (Ad.LacZMI); Adeno-Pellino1 Sham (Ad.Peli1S) and Adeno-Pellino1 MI (Ad.Peli1MI). MI was induced by permanent ligation of left anterior descending coronary artery (LAD). Following LAD ligation or sham surgery Ad.LacZ or Ad.Peli1 was injected at 4 border zone sites to either Ad.LacZS/Ad.LaczMI or Ad.Peli1S/Ad.Peli1MI groups respectively. Heart tissue was collected 24 hours post MI for Western blot analysis,4 days for gap junction protein and 30 days later for immunohistochemistry after echocardiographic analysis.

Results:
Echocardiographic analysis revealed increased ejection fraction [48±0.75 vs. 33±0.98% (n=10-11);p<0.05] and fractional shortening [24±0.49 vs. 16±0.51% (n=10-11) p<0.05] along with decreased LVIDs [3.74±0.14 vs. 5.21±0.19(mm) (n=10-11); p<0.05] in the Ad.Peli1MI as compared to the Ad.LacZMI group. Immunohistochemical analysis for fibrosis with picrosirius red staining exhibited a decrease in collagen deposition in Ad.Peli1MI group [16±1.05 vs. 29±2.05% (n=8); p<0.0001] as compared to Ad.LacZMI group. Connexin-43, a major ventricular gap junction protein was found to be significantly expressed in Ad.Peli1MI group compared to Ad.LacZMI. Ad.Peli1 gene therapy after MI increased capillary density [2342±122 vs. 1776±54 counts/mm2 (n=6);p<0.05] as compared to the Ad.LacZMI group. Western blot analysis 24h after MI revealed increased phosphorylation of Akt (3.4 fold), eNOS (1.9fold) and MK2 (1.7fold) with Ad.Peli1 treatment compared to Ad.LacZ. Similar experiments conducted with Peli1KO mice also revealed decreased DNA binding activity of NFκB activity by Gel-shift analysis 8 h after MI.

Conclusion:
Taken together, these data shows the potential of Peli1 gene therapy in inducing angiogenesis and reducing ventricular remodeling in the infarcted myocardium.
Abstract 15499: Children After Fontan have the Strength, Body Composition, and Daily Moderate-to-Vigorous Physical Activity Required for Successful Participation with Peers
Authors: Longmuir Patricia E , Corey Mary , Faulkner Guy , Russell Jennifer L , McCrindle Brian W
Published: July 2021

Introduction:
This cross-sectional study evaluated the healthy, active lifestyle capacity (daily physical activity, strength, flexibility, body composition) of children after Fontan, which was hypothesized to be lower than healthy peers.

Methods:
Participants (n=64, 25 female) were 9 ± 2 years of age. Fontan completion occurred at 3 ± 1 years of age. Canadian Health Measures Survey protocols assessed aerobic endurance (walking up/down steps at set pace), strength (handgrip dynamometry), flexibility (sit and reach), body composition (body mass index) and daily moderate-to-vigorous physical activity (7-day accelerometry). Participant versus published norm differences were evaluated with t-tests. Linear regression evaluated associations with age/gender/demographic factors.

Results:
Children after Fontan had strength scores similar (mean difference 1 kg) to their peers, were less likely to be obese (mean difference of body mass index = 1.1 ± 2.5, p=.001) and performed 50 minutes of moderate-to-vigorous activity per day. Estimated maximal aerobic endurance (mean difference = 21 ± 3 ml/kg/min or 61% of expected) and flexibility (mean difference = 9 ± 8 cm or 64% of expected) were lower than peers(p<.001). Participants performed fewer minutes of daily activity (mean difference from normal 12 ± 17 minutes/day, p<.001), but almost all (60/63) demonstrated the capacity for at least 20 minutes per day. Daily activity was higher with Fontan completion at a younger age (4 ± 2 mins/year) and for those taking antithrombotic medication (7 ± 18 and 22 ± 17 fewer minutes/day for those taking/not taking antithrombotics, respectively).

Conclusions:
Children after Fontan demonstrate the capacity to successfully perform the daily physical activity associated with optimal health. They have similar levels of strength and good body composition. We recommend that children after Fontan be counselled to expect that they can successfully participate in physically active peer play.
Abstract 15503: Reasons for Incomplete Decongestion at Heart Failure Discharge from a Tertiary Center and Community Hospital
Authors: Gilstrap Lauren G , Desai Akshay S , Ghazinouri Roya , Carr Christina , Small Roy , Mehra Mandeep , Stevenson Lynne
Published: July 2021

Introduction:
Standardized Clinical Assessment and Management Plans (SCAMPs) are a novel tool forthe prospective auditing of clinical outcomes and quality improvement in areas of practice variation. Using the SCAMP methodology to address heart failure (HF) discharges, two sites collaborated to investigate adherence to guideline-recommended achievement of optimal volume status and reasons for deviation in clinical practice.

Methods:
Consecutive patients hospitalized for chronic HF at a tertiary referral center (Brigham and Women’s Hospital, Boston MA, n=108, 55.3%) and community hospital with a dedicated heart failure program (Lancaster General Hospital, Lancaster PA, n=87, 44.6%) were enrolled in a HF SCAMP which recommended discharge only after complete decongestion (defined by jugular venous pressure <8cmH20 and absence of lower extremity edema, orthopnea and rales). Reasons for deviation from were documented by the attending physician. 90 day readmission rates were recorded.

Results:
There were 195 patients enrolled. The average age at BWH was 64 years compared to 79 year at LGH. Overall, 57 (29%) patients had residual congestion at discharge, 37% of patients at BWH and 20% at LGH (p=0.01). However, the average weight change was -4.3kg at BWH and -3.8Kg at LGH. At BWH, the most common reason for inadequate decongestion was renal dysfunction (34% BWH vs. 6% LGH, p=0.04). At LGH, non-cardiac/chronic edema (“edema resistant”) was the most common reason (44% LGH vs. 17% BWH (p=0.08). Plan for continued diuresis at home was more common at LGH (LGH 19% vs. BWH 0%, p=0.03). At 90 days, 37% of congested patients and 23% of completely decongested patients had been readmitted (p=0.08).

Conclusions:
Nearly 1 in 3 patients admitted for worsening HF were discharged with residual congestion, which was more common at the tertiary care center and trended with higher readmission rates. The reasons for inadequate decongestion were different between sites.
Abstract 15515: Sexual Dimorphism in Cardiac Response to Intrauterine Growth Restriction (IUGR)
Authors: Maloyan Alina , Muralimanoharan Sribalasubashini , Nijland Mark , Nathanielsz Peter W
Published: July 2021

Background:
Poor fetal nutrient availability predisposes to adult cardiovascular disease (CVD). We have developed a fetal baboon model of maternal undernutrition resulting in Intrauterine Growth Restriction (IUGR) in both male and female fetuses (Li, et al, J Endocrinol, 2013). MicroRNAs are small non-coding RNAs that regulate gene expression through mRNA degradation and translational repression.

Hypothesis:
We hypothesized that IUGR is accompanied by cardiac dysfunction and dysregulation of cardiac miRNAs.

Methods:
Six control pregnant baboons ate ad libitum, and six nutrient restricted pregnant baboons ate a globally reduced diet (70% of control feed) from 0.16 gestation (G) through pregnancy resulting in fetal IUGR compared to controls (p<0.05). No differences in heart weight were observed. Fetuses (3 males and 3 females per group) were euthanized at C-section at 0.9G. Cardiac sections were studied for morphological changes and fibrosis using H&E and Masson’s trichrome staining respectively. Total left ventricular RNA was isolated and miRNA array was performed.

Results:
While no differences in myofiber orientation were observed, IUGR male but not female fetuses showed a reverse correlation between birth weight and accumulation of fibrotic tissue in the heart (r=-0.831, p=0.01). We next investigated the expression of the extracellular matrix proteins thrombospondin-1 (TSP-1) and connective tissue growth factor (CTGF). A reverse correlation between birth weight and cardiac TSP-1 levels (r=-0.77, p=0.03) was found in male but not female fetuses. No changes in CTGF were observed.

Sexual dimorphism was observed in fetal cardiac miRNA expression within both IUGR and control groups. In male IUGR group, the increase in levels of TSP-1 was associated with more than 50% reduction in expression of its targeting miRNA-19a, reduction in which has been implicated in CVD. Other CVD-related and differentially expressed miRNAs in male IUGR included miRNA-23b, 27b, 99b, 143, 181a, and 378-3p.

Summary:
IUGR resulting from decreased maternal nutrition is associated with sexual dimorphism in cardiac structure and miRNA expression. If the changes observed in male IUGR fetuses persists postnatally they may program offspring for higher CVD risk later in life.
Abstract 15573: Impact of Coronary Calcification on Different Culprit Lesion Morphology in Acute Coronary Syndrome
Authors: Miura Katsuya , Dote Keigo , Kato Masaya , Sasaki Shota , Oda Noboru , Kagawa Eisuke , Nakano Yoshinori
Published: July 2021

Background:
Previous studies have reported plaque rupture and erosion were the most common causes of acute coronary syndrome (ACS) and spotty calcifications was identified as a marker of plaque rupture. Optical coherence tomography (OCT) offers a high-resolution imaging to assess the plaque morphology and coronary calcification.

Purpose:
The aim of this study was to evaluate the relationship between the distribution of coronary calcification and the culprit lesion morphology in patients with ACS.

Methods:
We enrolled consecutive 183 patients with ACS (mean age: 68 ± 11 years, 148 males). Culprit lesion was assessed by OCT and patients were divided into the rupture and non-rupture group according to the OCT findings. Maximum radial thickness, cross-sectional area of calcification and radial depth from the lumen and longitudinal length of calcification were compared between 2 groups.

Results:
Plaque rupture was detected at culprit site in 105 patients and coronary calcification was identified in 58 patients. There were no significant differences in age and gender between 2 groups.

Maximum thickness, area and longitudinal length of calcification were smaller in rupture group (457.4 ± 284.9 μm vs. 722.1 ± 384.1 μm, p < 0.01, 0.7 ± 0.4 mm
2
vs. 1.8 ± 1.4 mm
2
, p < 0.01, 2.2 ± 1.1 mm vs. 5.6 ± 5.3 mm, p[[Unsupported Character - Codename ­]] < 0.01, respectively). Radial depth of calcification from the lumen was significantly geater in rupture group (150.0 ± 65.3 μm vs. 83.1 ± 63.3 μm, p<0.001).

Conclusions:
Distribution of coronary calcification could be associated with morphological etiology of ACS.
Abstract 15609: Plasma Fibrin Clot Properties Measured Ex-vivo Are Associated With Intracoronary Thrombus Ultrastructure
Authors: Zalewski Jaroslaw , Bogaert Jan , Sadowski Marcin , Woznicka Olga , Doulaptsis Constantinos , Ntoumpanaki Maria , Zabczyk Michal , Nessler Jadwiga , Undas Anetta
Published: July 2021

Introduction:
Fibrin is a major component of intracoronary thrombus obtained during ST-elevation myocardial infarction (STEMI). Apart of the time of ischemia determinants of intracoronary thrombus composition are largely unknown.

Hypothesis:
We sought to investigate whether ex-vivo measured plasma fibrin clot properties are associated with intracoronary thrombus ultrastructure.

Methods:
In the intracoronary thrombus aspirated from 80 of the 156 consecutive STEMI patients within 12 hours since symptom onset, we assessed the content of fibrin, erythrocytes and platelets and thrombus heterogeneity by scanning electron microscopy. On admission plasma fibrin clot permeability (Ks), which indicates pore size, clot lysis time (t50%), platelet reactivity index (PRI) and aggregation induced by 5 μM of adenosine diphosphate (ADP) were correlated with intracoronary thrombus composition.

Results:
All patients received 300 mg of aspirin and 45 (56.3%) 600 mg of clopidogrel, 70 (41-120) min prior to aspiration. PRI inversely correlated (r=-0.24, P=0.035) with the time elapsed since clopidogrel pretreatment. The median content of fibrin, erythrocytes and platelets in intracoronary thrombus was 49.1 (25.0-72.6)%, 29.0 (4.8-57.7)% and 6.8 (1.0-15.1)%, respectively. Fibrin content was correlated with baseline Ks (r=-0.45, P<0.0001), t50% (r=0.32, P<0.0001), fibrinogen (r=0.32, P<0.0001), the time to opening of infarct-related artery (r=0.24, P<0.001), reference lumen diameter of infarct-related artery (r=0.15, P<0.001), but not with PRI and ADP-induced platelet aggregation. Fibrin content was higher in patients without pre-hospital loading with clopidogrel (58 vs. 43%, P<0.0001), treated with aspirin prior to STEMI (62 vs. 47%, P<0.0001) or with positive family history of coronary artery disease (62 vs. 46%, P=0.0004). Multiple regression analysis adjusted for age and fibrinogen showed that Ks, time of ischemia and clopidogrel pretreatment independently predicted fibrin content in intracoronary thrombus (R2=0.44, P<0.0001).

Conclusion:
Formation of denser fibrin clots displaying resistance to lysis, and clopidogrel pretreatment contributed to fibrin content within the intracoronary thrombus during an acute phase of STEMI.