bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13991: Acute Procedural and Clinical Outcome Comparison Using the First and Second-Generation Cryoballoon: Inside a Large Cohort of Data Derived From Real World Multicentric Experience
Authors: Padeletti Luigi , Arena Giuseppe , Tondo Claudio , Fumagalli Stefano , Lunati Maurizio , Porcellini Stefano , Catanzariti Domenico , Sciarra Luigi , Leoni Loira , Senatore Gaetano , Curnis Antonio ,   on behalf of 1STOP Cardiological Cntrs
Published: July 2021

Introduction:
Limited data are available on safety and efficacy of second-generation cryoballoon (CB2) for cryoablation of atrial fibrillation (CBA).

Hypothesis:
To evaluate in a large cohort of patients treated in real world clinical settings, demographics, procedural data and outcomes comparing CB2 to first-generation cryoballoon (CB1).

Methods:
Between 2012 and 2014, 581 patients (74% men, 59±10 years, 78% paroxysmal AF, LA diameter: 41±6 mm) suffering from AF and undergoing pulmonary veins (PV) CBA were prospectively enrolled in ClinicalService® framework One Shot TO Pulmonary vein isolation (1STOP) project. The cohort was divided into 2 groups according to the cryoballoon used in standard clinical practice: 120 (21%) CB1 and 461 (79%) CB2.

Results:
Clinical and demographic characteristics were similar in the two cohorts; procedure, fluoroscopy and ablation time were significantly lower in CB2 respect to CB1 (141±40 vs 166±50 min, p<.001; 35±15 vs 41±15 min, p<.001; 27±17 vs 41±26 min, p<.001) with comparable acute success rate (97.8 vs 97.4%, p=ns); 22 patients (3.8%) experienced procedural complications. The most frequent acute procedural complication was transient diaphragmatic paralysis, significantly lower in CB2 vs CB1 (0.7 vs 3.3%, p=.016). Data at a minimum FU of 6 months were available for 237 (41%) patients: annual rate of follow-up complications was significantly lower in CB2 vs CB1 (Rate*100 pt/years: 5.74 vs 17.92, Incidence Rate Ratio - IRR: 0.32; 95% CI 0.17- 0.60; p<.001) as well as CB2 was associated with lower PV reconnection rate causing redo ablation (Rate*100 pt/years: 0.64 vs 4.98; IRR: 0.13; 95% CI 0.05-0.30; p<.001); 25 complications in 16 patients have been reported during FU, 21 (84%) of which for AF recurrence.

Kaplain Meier analysis showed that freedom from AF at 12 months for patients with paroxysmal indication, considering a blanking period of 3 months, was 67.8% (95% CI 53.1-78.8%) in CB1 group and 77.8% (95% CI 68.6-84.7%) in CB2.

Conclusions:
The novel cryoballoon Arctic Front Advance (CB2) has proven to achieve, in a large clinical standard setting, significantly faster CBA times in comparison with the first-generation balloon, results also in lower acute procedural complication rates and a 78% 1-year freedom from AF.
Abstract 14043: Enhanced Integrin α4β1-mediated Adhesion Contributes to a Mobilization Defect of Endothelial Progenitor Cells in Diabetes
Authors: O'Toole Timothy , Abplanalp Wesley , Conklin Daniel , Cantor Joe , Ginsberg Mark , Bhatnagar Aruni
Published: July 2021

While previous studies have identified a deficit of circulating endothelial progenitor cells (EPCs) in diabetic conditions (diabetic “mobilopathy”), the basis for these deficits are not completely understood. To model the adhesive properties of EPCs in diabetic conditions, we cultured these cells in high glucose and found that they had stronger adhesion to bone marrow stromal cells. This enhanced adhesion was associated with decreased expression of protein kinase A regulatory subunit 1β (PRKAR1β), consequent activation of protein kinase A (PKA), and phosphorylation of the α4 integrin on serine 988. The potentiating effects of high glucose on adhesion were mimicked by direct PKA activation and reversed by treatment with a PKA inhibitor, overexpression of PRKAR1β or expression of a phosphorylation-defective α4 integrin (α4-S988A). Using the STZ model of type I diabetes, we show that α4-S988A-expressing mice have more circulating EPCs than do their wild type counterparts (2.6 ± 0.5 fold). Furthermore, the diabetic α4-S988A mice demonstrate enhanced revascularization (1.50 ± 0.3 fold vs. WT) and tissue repair after hind limb ischemia. Thus, hyperglycemic conditions potentiate the adhesion of EPCs to bone marrow stromal cells which results in an in vivo mobilization defect. Mutational reversal of this increased adhesion liberates EPCs and promotes re-endothelialization in ischemic tissues, suggesting a potential therapeutic target to treat diabetic vascular complications.
Abstract 14045: Reperfusion Therapy With Recombinant Human Relaxin (Serelaxin) Attenuates Myocardial Inflammasome Formation and Ischemic Injury in Mice via eNOS-dependent Mechanism
Authors: Valle Raleigh Juan , Mauro Adolfo G , Marchetti Carlo , He Jun , Toldo Stefano , Abbate Antonio , Salloum Fadi N
Published: July 2021

Background:
The preconditioning-like infarct-sparing and anti-inflammatory effects of the peptide hormone relaxin following ischemic injury have been studied in the heart. Whether reperfusion therapy with recombinant human relaxin (serelaxin, SRLX) reduces myocardial infarct size and attenuates NLRP3 inflammasome formation/caspase-1 activation and subsequent loss of functional myocardium following ischemia/reperfusion (I/R) injury is unknown.

Methods and Results:
After baseline echocardiography, adult male C57BL (WT) or eNOS knockout (KO) mice underwent myocardial infarction (MI) by coronary artery ligation for 30 minutes followed by 24 h reperfusion. Mice were treated with either SRLX (10 μg/Kg; sc) or saline 5 minutes before reperfusion. SRLX improved survival at 24 h post MI in WT mice (79%) as compared with controls (42%), whereas there was no difference in survival between SRLX- and saline-treated eNOS KO mice. Moreover, SRLX significantly reduced infarct size, measured with TTC staining, and preserved LV fractional shortening (FS) and end-systolic diameter (LVESD) in WT mice as compared with controls. Interestingly, cardiac caspase-1 activity was markedly reduced in SRLX-treated mice compared with controls at 24 h post MI (Figure A-D). Genetic deletion of eNOS abolished the infarct-sparing and anti-inflammatory effects of SRLX as well as functional preservation. SRLX plasma levels were assessed 5 min. after treatment using ELISA and the results demonstrate therapeutic levels comparable to plasma relaxin during the first trimester of pregnancy (Figure E).

Conclusion:
Reperfusion therapy with SRLX attenuates myocardial I/R injury and NLRP3 inflammasome formation via eNOS-dependent mechanism. We propose that SRLX possesses an anti-inflammatory effect preventing caspase-1 activation and inflammatory complications following MI, which may shed some light on the mechanism behind the survival benefit observed in the RELAX-AHF trial.
Abstract 14069: Subclinical Impairment of Left Ventricular Function in Stage A Subjects in a Community-based Population
Authors: Hasegawa Takuya , Asakura Masanori , Kanzaki Hideaki , Asanuma Hiroshi , Takashio Seiji , Amaki Makoto , Takahama Hiroyuki , Ohara Takahiro , Sugano Yasuo , Yasuda Satoshi , Ogawa Hisao , Anzai Toshihisa , Kitakaze Masafumi
Published: July 2021

Introduction:
Stage A heart failure (HF) is defined as an asymptomatic state with HF risk factors of hypertension, diabetes, obesity, metabolic syndrome, and atherosclerotic disease in the absence of obvious left ventricular (LV) structural changes including LV hypertrophy (LVH). ACC/AHA guidelines recommend us to treat these risk factors of Stage A HF patients to prevent the progression of HF, hinting us to investigate the prevalence of subclinical impairment of LV function in Stage A subjects in general populations.

Methods:
We studied 1162 community-dwelling subjects without obvious heart diseases (mean age, 63±11 years; 448 men, 714 women, 63% with hypertension and 11% with diabetes) in the annual health checkup in a rural community, Arita-cho, Saga, Japan. The population was divided into 3 groups; the subjects without either LVH or the HF risk factors ("Stage 0"), the subjects with the HF risk factors in the absence of LVH (Stage A) , and the subjects in the presence of LVH (Stage B). LV systolic and diastolic function were estimated by mitral annular velocity in systole (s'), and the waves of transmitral flow (E) and mitral annular velocity (e'), respectively. LVH was defined as the top quintile of LV mass index.

Results:
The subjects in Stage A had the lower and higher values of s' and E/e', respectively, and the higher prevalence of LV diastolic dysfunction than those in Stage 0, while 45% of Stages A subjects showed LV diastolic dysfunction (Table). In multivariate logistic analyses, age, systolic blood pressure and LV mass were independent determinants of s', whereas either overlapped or different risk factors, such as age, sex, systolic blood pressure, and body mass index emerged as the determinants for E/e'.

Conclusions:
Even without obvious LV remodeling, subclinical LV systolic and diastolic impairment was observed in Stage A subjects. The disparity of the risk factors between LV systolic and diastolic dysfunction may indicate their pathophysiological differences.
Abstract 14079: Diagnostic Impact of the Finding From Study of Coronary Images in Acute Coronary Syndrome Patients With Out-of-Hospital Cardiac Arrest
Authors: Tateishi Kazuya , Abe Daisuke , Iwama Toru , Sassa Tatsuro , Ohashi Kouichi , Kaneko Masakazu , Harunari Tomohiko , Yui Yoshiaki , Kuroki Norihiro , Yuba Takao , Suzuki Ko , Hamabe Yuichi
Published: July 2021

Background:
Acute coronary syndrome (ACS) is the major cause of out-of-hospital-cardiac-arrest (OHCA). The patients with ventricular fibrillation (VF) have more chance to get the return of spontaneous circulation (ROSC) and favorite neurological outcome by using defibrillator compared with pulseless electrical activity (PEA) and asystole.

The duration from collapse to ROSC is important in ACS patients with OHCA, but the relationship between the finding from study of coronary images and ROSC interval is still unknown.

Objective:
We investigated the association between the finding from study of coronary images and ROSC interval in ACS patients with OHCA.

Methods:
A cohort of 2779 patients was admitted to our emergency center due to cardiopulmonary arrest (CPA) from April 2011 to March 2015. We included the ACS patients who had CPA with VF as an initial rhythm, successfully resuscitated, underwent coronary angiography (CAG), had a culprit lesion, and needed percutaneous coronary intervention (PCI) (n=58, 63.7±12.0 years old, 93.1% male ).

We divided the 58 patients into 2 groups; early ROSC group (ROSC ≦20min: E-ROSC n=24) and late ROSC group (ROSC >20min: L-ROSC n=34), and analyzed their characteristics, respectively.

Results:
Age was no significant difference between 2 groups (E-ROSC vs. L-ROSC; 64.8±14.3 vs. 63.0±10.2, p=0.54). E-ROSC group had higher incidence of female (17% vs. 0%), successful resuscitation by defibrillator (96% vs. 21%), and higher 30 days survival rate (96% vs. 41%) compared with L-ROSC group (all p<0.05).

The finding of collateral artery for the culprit lesion: Rentrop I-III and TIMI III flow in CAG on arrival were no significant differences between 2 groups (Rentrop I-III : 45.8% vs. 55.9% P=0.45; TIMI III: 33% vs. 59% P=0.88). Incidence of multi-vessel disease was lower in E-ROSC than L-ROSC (16.7% vs. 58.9% P=0.001).

Conclusion:
Collateral and TIMI flow were not associated with ease of resuscitation, but multi-vessel disease may have a negative impact on resuscitation especially VF.
Abstract 14104: Replacement of Infarct Myocardium by Large Scale-Expanded Human Induced Pluripotent Stem Cell-Derived Cardiac Cell-Sheet in a Porcine Chronic Myocardial Infarction Model
Authors: Domae Keitaro , Miyagawa Shigeru , Fukushima Satsuki , Saito Atsuhiro , Imanishi Yukiko , Takeda Maki , Ito Emiko , Ishikawa Tsuyoshi , Miyagawa Nobu , Matsuura Katsuhisa , Kino-oka Masahiro , Toda Koichi , Sawa Yoshiki
Published: July 2021

Introduction:
It has been shown that transplanted induced pluripotent stem cell (iPSC)-derived cardiac cells in the myocardial infarction (MI) heart synchronously contract with native myocardium to mechanically contribute to functional recovery in rodent models. We herein hypothesized that large scale cardiac cell-sheets generated by human iPSCs may induce a greater functional recovery than small scale ones after transplantation in chronic MI heart.

Methods:
Bioreactor-based three-dimensional suspension culture system was used for generating large scale-expanded human iPSC-derived cardiomyocytes, of which cardiac troponin T positivity was constantly 75-85%. Scaffold-free cell-sheets containing several cell number (1.0х10^6, 10^7, 10^8) were transplanted over the cardiac surface in porcine chronic MI heart (n=5 each). Tacrolimus and prednisolone were daily given in all pigs against xeno-transplantation-inducing immune reaction.

Results:
Echocardiographically, left ventricular systolic and diastolic dimensions were significantly decreasing and ejection fraction was significantly increasing in the 10^8 cell group. In addition, global myocardial structure was better preserved in the 10^8 cell group with presence of the graft in the infarct area macroscopically (Figure). Moreover, there were significantly less accumulation of interstitial fibrosis in the infarct-remote area and greater vascular density and expression of VEGF, bFGF, and SDF-1 in the infarct-border area in the 10^8 cell group than the other groups at 3 months after the transplantation.

Conclusions:
Large scale human iPSC-derived cardiac cells were engrafted in the infarct myocardium, showing substantial functional recovery in a porcine chronic MI heart, indicating that artificial cell-based myocardial replacement therapy may be achieved. In contrast, small scale cardiac cells induced modest functional recovery, suggesting paracrine mechanisms of this treatment.
Abstract 14106: Assessment of Right Ventricular to Pulmonary Circulation Uncoupling at Peak Exercise in Heart Failure Patients by the Relationship Between Pulmonary Systolic Pressure vs Right Ventricular Longitudinal Strain
Authors: Donghi Valeria , Carbone Francesco , Labate Valentina , Generati Greta , Pellegrino Marta , Alfonzetti Eleonora , Bandera Francesco , Guazzi Marco
Published: July 2021

Background:
Speckle tracking analysis is an emerging technique that can be useful to assess abnormalities in cardiac contractility before traditional echo parameters.

Purpose:
To investigate whether right ventricular (RV) 2D speckle tracking analysis at peak exercise could stratify a heart failure reduced ejection fraction (HFrEF) population in different functional phenotypes, with particular emphasis on RV to pulmonary circulation relationship.

Methods:
36 HFrEF patients (mean age 69±12; male 69%; NYHA I-II-III-IV 19-17-25-5 %) underwent a maximal cardiopulmonary exercise testing evaluation (bike, incremental ramp protocol) combined with Echo-Doppler and off-line speckle tracking analysis. Study population was divided in two groups according to median value of 2D right ventricle longitudinal strain at peak exercise (Group A RVLG at peak < -16, 17 patients vs Group B ≥ -16, 19 patients). In all patients we performed traditional echo and 2D longitudinal speckle tracking analysis at rest and peak exercise.

Results:
Despite similar left ventricle ejection fraction (Group A 36± 9% vs Group B 32±9%, p=ns) and global right ventricle longitudinal strain (RVLG) at rest (Group A -18.6±5.6% vs Group B -14.5±8.2%, p=ns), Group B patients showed a similar exercise performance (Peak VO
2
Group A 31.6±7.4 vs Group B 11.6±3.4 mlO
2
/Kg/min, p=ns) but more impaired ventilation (VE/VCO2 slope Group A 31.6±7.4 vs Group B 37.4±8.8, p<0.05), and a clear RV to PC uncoupling at peak exercise as assessed by the relationship between pulmonary systolic pressure vs RVLG (see figure below).

Conclusions:
In HFrEF RV speckle tracking analysis at peak exercise seems a useful technique for unmasking RV to PC uncoupling and the unfavorable gas exchange and ventilatory phenotypes.
Abstract 14331: Role for HDAC6 in Pulmonary Arterial Hypertension
Authors: Chabot Sophie , Ruffenach Grégoire , Breuils-Bonnet Sandra , Tremblay Eve , Boucherat Olivier , Bonnet Sébastien , Provencher Steeve
Published: July 2021

Background:
Pulmonary arterial smooth muscle cells (PASMCs) from pulmonary arterial hypertension (PAH) patients exhibit a pro-proliferative, pro-migratory and anti-apoptotic phenotype mediated, at least in part, by survivin overexpression, leading to the development of progressive pulmonary artery (PA) remodeling. This results in right ventricle (RV) hypertrophy and failure. For many years, the cytoplasmic class IIb histone deacetylase 6 (HDAC6), which mainly functions as a α-tubulin deacetylase has been understudied. Several cancer studies have demonstrated that HDAC6 cooperates with the Heat Shock Protein 90 (HSP90) and regulates many signaling pathways involved in cancer and PAH development. In the cardiovascular field, HDAC6 upregulation has been associated with heart failure. We hypothesized that specific HDAC6 inhibition corrects the abnormal phenotype of PAH-PASMCs and improves RV function.

Method/Results:
Using a multidisciplinary and translational approach, we demonstrated that both HDAC6 and HSP90 are upregulated (Wb; p<0.01) in the lungs, distal PAs, and PASMCs from PAH patients (n=5) compared to controls (n=5). HDAC6 inhibition using Tubastatin A dose-dependently increased α-tubulin acetylation and decreased PAH-PASMC migration (scratch test; p<0.05), apoptosis resistance (Annexin-V; p<0.05) and proliferation (Ki67; p<0.01). Tubastatin A also reduced the expression of survivin in PAH-PASMCs (Wb). Similar effects were observed after HSP90 inhibition with AT13387, which also reduced HDAC6 expression in PAH-PASMCs (Wb) suggesting that a HSP90-dependent mechanism may account for HDAC6 upregulation. Within the heart, HDAC6 was exclusively expressed in human decompensated RV from PAH patients (n=5) and not in control RV (Wb, p<0.01).

Conclusion:
We provide evidence that HSP90 and HDAC6 are upregulated in human PAH and contribute to the proliferative, migratory and anti-apoptotic phenotype of PAH-PASMCs. Moreover, HDAC6 is specifically increased in the RV of PAH patients, suggesting that specific HDAC6 inhibition may represent a novel and attractive target in PAH for the treatment of both PA remodeling and RV failure. The therapeutic potential of HDAC6 inhibition in a PAH rat model is currently under investigation.
Abstract 14366: T-lymphocytes May Contribute to Thrombus Formation in Patients With Acute Coronary Syndrome via Expression of Tissue Factor
Authors: Cimmino Giovanni , Ciccarelli Giovanni , Conte Stefano , Pellegrino Grazia , Insabato Luigi , Calì Gaetano , Cirillo Plinio , Golino Paolo
Published: July 2021

Background:
Activation of T-cells plays an important role in the pathophysiology of acute coronary syndromes (ACS). We have previously shown that plaques from ACS patients are characterized by a selective oligoclonal expansion of T-cells, indicating a specific, antigen-mediated recruitment of T-cells within the unstable lesions. We have also previously reported that activated T-cells in vitro express functional Tissue Factor (TF) on their surface. At the moment, however it is not known whether expression of TF by T-cells may contribute to thrombus formation in vivo.

Methods:
Blood was collected from the aorta and the coronary sinus of 13 NSTEMI and 10 stable CAD patients. CD3+ cells were selectively isolated and TF gene expression (real time PCR)and protein levels (western blot) were evaluated. In additional 7 STEMI patients, thrombotic formation material was obtained from the occluded coronary artery by catheter aspiration during primary PCI. TF expression in CD3+ cells was evaluated by immunohistochemistry and confocal microscopy.

Results:
Transcardiac TF expression in CD3+ cells was significantly higher in NSTEMI patients as compared to CD3+ cells obtained from stable CAD patients. Interestingly, thrombi aspirated from STEMI patients resulted enriched in CD3+cells, which expressed TF on their surface as shown in the figure.

Conclusions:
Our data demonstrate that in patients with ACS, T-lymphocytes may express surface TF, thus contributing to the process of thrombus formation. This finding may shed new light into the pathophysiologyof ACS.
Abstract 14579: Peak Myocardial Blood Flow versus Noninvasive Coronary Flow Reserve for Prediction of Future Events
Authors: Al-Mallah Mouaz H , Aljizeeri Ahmed , Ahmed Dalia , Alfaris Mousa , Suleiman Abdulbaset , Suliman Ihab
Published: July 2021

Background:
Impaired coronary flow reserve (CFR) is an early manifestation of coronary artery disease (CAD), even in vessels free of angiographic stenosis. The aim of this analysis is to determine the differential role peak myocardial blood flow (MBF) or noninvasive CFR in predicting future events.

Methods:
We included 3,003 consecutive patients with known or suspected CAD (mean age 61±11years, 42% females) who underwent rubidium-82 rest/stress positron emission tomography (PET) for clinical indications. Rest and peak MBF were calculated with factor analysis and a 2-compartment kinetic model and were used to calculate CFR. Patients were followed up for a median duration of 1.4 years (interquartile range, 0.5-1.8 years) for the incidence of cardiac death or myocardial infarction. (CDMI). Multiple Cox regression models were used to determine the prognostic value of peak MBF and CFR and the incremental value of peak MBF over CFR.

Results:
The included cohort has prevalence of CAD risk factors: Diabetes (60%), hypertension (87%) and dyslipidemia (85%). A total of 40% patients had evidence of perfusion defects (Sum stress score>3). After a median follow up duration of 1.4 years, 140 patients (4.7%) experienced CD/MI. In multivariate Cox regression adjusted for Duke clinical risk score, resting ejection fraction and SSS, both CFR (Hazard Ratio 0.70, 95% CI 0.54 -0.89, p=0.005) and peak MBF (Hazard Ratio 0.71, 95% CI 0.57 -0.89, p=0.003) were independent predictors of CDMI. (Adding peak MBF added incremental prognostic value over CFR. (Area under the curve increased from 0.776 to 0.793, p=0.021).

Conclusion:
Noninvasively measured MBF and CFR are independent predictors of CDMI in patients with known or suspected CAD. Peak MBF adds incremental prognostic value over noninvasive CFR.
Abstract 14632: Effect of Obesity on Myocardial Strain Determined by Speckle Tracking Imaging
Authors: Zhu Meihua , Streiff Cole , He Tao , Ashraf Muhammad , Zhang Jiahui , Tam Lydia , Sahn David J
Published: July 2021

Introduction:
Obesity may affect cardiac function, which is hard to detect by traditional echocardiography in the early stages. Speckle tracking imaging (STI) is sensitive to subtle myocardial dysfunction. The aim of this study was to determine the influence of obesity on left ventricular (LV) myocardial function in diet-induced obesity (DIO) mice using two-dimensional (2D) speckle tracking echocardiography (STE).

Hypothesis:
2D STE is useful to detect obesity-caused myocardial dysfunction.

Methods:
Twenty newborn mice were divided into two groups: a DIO group (high-fat diet) and a control group (regular-fat diet). 2D image loops were acquired at the end of each month for 6 months. Global longitudinal strain (GLS) and global circumferential strain (GCS) were analyzed at feeding periods over 3 months and 6 months, and compared between the two groups.

Results:
The control group gained 64% of its initial weight, while the DIO group gained 82% of its initial weight at the 3 month feeding period; and the two groups gained 88% (control) and 125% (DIO) respectively at 6 months. STE analysis revealed an insignificant decrease in strain values in the DIO mice after 3 months; however, after 6 months, the DIO group demonstrated a significant decrease in strain values (P<0.05) despite normal ejection fractions in both groups.

Conclusions:
2D STE is highly feasible to detect the myocardial dysfunction caused by obesity in earlier stage. These strain values appear to be related to the severity of obesity.
Abstract 14648: Interleukin-18 Blockade Prevents Diastolic Dysfunction in a Mouse Model of Heart Failure With Preserved Ejection Fraction
Authors: Regan Jessica A , Mauro Adolofo G , Carbone Salvatore , Marchetti Carlo , Mezzaroma Eleonora , Krauskaus Donatas , Salloum Fadi N , Dinarello Charles A , Van Tassel Benjamin , Abbate Antonio , Toldo Stefano
Published: July 2021

Background:
Heart failure with preserved ejection fraction (HFpEF) is characterized by elevated left ventricular (LV) filling pressures due to impaired LV diastolic function. Low-dose infusion of angiotensin 2 (AT2) in the mouse induces a HFpEF phenotype without increasing blood pressure. AT2 infusion induces expression of Interleukin-18 (IL-18) in the heart. We therefore tested whether IL-18 mediated AT2-induced LV diastolic dysfunction in this model.

Methods:
We infused subcutaneously AT2 (0.2 mg/Kg/day) or a matching volume of vehicle via osmotic pumps surgically implanted in the interscapular space in adult wild-type (WT) male mice and IL-18 knock-out mice (IL-18KO). We also treated WT mice with daily intraperitoneal injections of recombinant murine IL-18 binding protein (IL-18bp, a naturally occurring IL-18 blocker) at 3 different doses (0.1, 0.3 and 1.0 mg/kg) or vehicle for 25 days starting on day 3. We performed a Doppler-echocardiography study before implantation and at 28 days to measure LV dimensions, mass, and systolic and diastolic function in all mice. LV catheterization was performed prior to sacrifice to measure LV end-diastolic pressure (LVEDP) using a Millar catheter.

Results:
AT2 induces a significant increase in isovolumetric relaxation time (IRT) and myocardial performance index (MPI) at Doppler echocardiography and elevation of LVEDP at catheterization, indicative of impaired LV diastolic function, in absence of any measurable effects on systolic blood pressure nor LV dimensions, mass, or systolic function. Mice with genetic deletion of IL-18 (IL-18 KO) or WT mice treated with IL-18bp had no significant increase in IRT, MPI or LVEDP with AT2 infusion.

Conclusion:
Genetic or pharmacologic IL-18 blockade prevent diastolic dysfunction in a mouse model of HFpEF induced by low dose AT2 infusion, suggesting a critical role of IL-18 in the pathophysiology of HFpEF.
Abstract 14660: Effect of PR Interval on Mortality Reduction With Cardiac Resynchronization Therapy - A Secondary Analysis of the COMPANION Trial
Authors: Lin Jeffrey , Buhr Kevin A , Kipp Ryan
Published: July 2021

Introduction:
Prolonged PR intervals may impair atrioventricular mechanical coupling and adversely affect cardiac performance. We hypothesize that patients with advanced systolic heart failure, wide QRS complexes, and prolonged PR intervals will have improved survival from cardiac resynchronization therapy with defibrillator (CRT-D) regardless of whether left bundle branch block (LBBB) or non-LBBB is present.

Methods:
Patients enrolled in the optimal pharmacologic therapy (OPT) and CRT-D arms of the COMPANION trial were included in a multivariable Cox model of all-cause mortality as a function of presence of LBBB and value of PR interval at baseline. Hazard ratios representing the mortality reduction for CRT-D versus OPT were estimated together with pointwise 95% confidence intervals (CIs).

Results:
A total of 308 OPT and 595 CRT-D patients were included in the analysis. In both the LBBB (n=648) and non-LBBB (n=255) subgroups, the mortality reduction associated with CRT-D compared to OPT was greater with increasingly prolonged baseline PR interval (Figure 1, p=0.02 for each subgroup). Hazard ratios for CRT-D versus OPT (with 95% CIs) for PR intervals of 200ms and 250ms were 0.51 [0.35,0.74] and 0.30 [0.18,0.50] respectively for the LBBB subgroup, and 0.86 [0.50,1.5] and 0.39 [0.18,0.86] respectively for the non-LBBB subgroup. For non-LBBB patients with PR interval ≤200ms, there was no evidence of mortality benefit with CRT-D (p=0.60).

Conclusions:
In patients with advanced systolic heart failure, wide QRS complexes, and prolonged PR intervals, restoration of atrioventricular mechanical coupling with CRT-D may improve survival in both LBBB and non-LBBB recipients. In patients with non-LBBB, a benefit from CRT-D may occur in patients with prolonged PR intervals.

Figure 1:
Risk for all-cause mortality by hazard ratios stratified according to PR interval quartiles.
Abstract 14698: Does Autologous Stem Cell Transplantation Improve Cardiac Function in Patients With Systemic AL amyloidosis?
Authors: Pun Shawn , Landau Heather J , Yu Anthony , Verma Shivani , Bello Christina , Mara Elton , Hassoun Hani , Steingart Richard M , Liu Jennifer
Published: July 2021

Introduction:
Autologous stem cell transplantation (ASCT) is an effective therapy for prolonging survival in patients with systemic AL amyloidosis (ALA). Cardiac dysfunction due to amyloid involvement is a strong determinant of mortality. Whether ASCT can improve cardiac function is not well understood.

Hypothesis:
To assess changes in conventional echocardiographic parameters and global longitudinal strain (GLS) at baseline and 1 year post-ASCT and to determine predictors of 1 year mortality post-ASCT.

Methods:
Our study included fifty-one patients with newly diagnosed, biopsy-proven systemic AL amyloidosis undergoing ASCT. Cardiac biomarkers and echocardiographic measurements were obtained in all patients at baseline and at 1 year post-ASCT in 1 year survivors. Speckle-tracking global longitudinal strain (GLS) was retrospectively analyzed using vendor neutral software (TomTec Imaging Systems GmbH).

Results:
The mean age was 56.4 +/- 7.9 and 47.1% were female. Cardiac involvement was present in 68.6% based on consensus criteria. The mean baseline EF was 64.9 +/- 8.3. Complete hematologic response at 1 year was 55.8%. Mortality was 15.7% at 1 year. Long-term mortality was 27.5% (mean follow-up 4.0 +/- 2.6 years). Predictors of 1 year mortality were baseline GLS, troponin, BNP, septal thickness and E/A ratio. Age, gender and creatinine were not predictive. Among survivors at 1 year post-ASCT, there was no significant change in the biomarker or echocardiographic indices compared to baseline, regardless of hematologic response.

Conclusions:
Markers of cardiac dysfunction at baseline are predictive of 1 year mortality in patients with systemic ALA. Among those who survived to 1 year post-ASCT, there was no change in cardiac function assessed by echocardiography or biomarkers compared to baseline.
Abstract 14713: Coronary Dominance and Risk of Ventricular Fibrillation in Coronary Artery Disease
Authors: Narayanan Kumar , Uy-Evanado Audrey , Teodorescu Carmen , Reinier Kyndaron , Chugh Harpriya , Gunson Karen , Jui Jonathan , Chugh Sumeet S
Published: July 2021

Introduction:
Recent studies have suggested a link between coronary dominance and overall prognosis in patients with coronary artery disease (CAD). A specific association with sudden cardiac arrest (SCA) has not been investigated.

Hypothesis:
Coronary dominance pattern is associated with SCA risk.

Methods:
From a large, prospective, population-based study of SCA in a Northwestern US metro region (approx. one million residents), we identified SCA cases who underwent coronary angiogram at cardiac arrest and compared the coronary dominance pattern to a geographically-matched control population without history of SCA, undergoing angiograms for acute coronary syndromes (ACS) over the same time period.

Results:
Angiographic data were compared between a total of 203 SCA cases and 173 control subjects. Cases and controls respectively were not significantly different in age (62.3± 12.4 vs 64.3 ± 10.9 years; p=0.09), sex (males 69.8% vs 71.7%, p=0.69), body mass index (29.0 ± 7.7 vs 29.1 ± 6.6; p=0.89), diabetes (33.5% vs 27.9%; p=0.24), hypertension (62.5% vs 65.7%; p=0.52) and previous history of myocardial infarction (36.0% vs 34.9%; p=0.82) or coronary revascularization (18.7% vs 25.4%; p=0.12). Ventricular tachycardia or fibrillation (VT/VF) was the presenting arrest rhythm in the majority (86.9%) of cases. Compared to controls, a right dominant coronary system was
less
likely to be seen in cases (78.4% vs 86.7%) and a co-dominant system was
more
likely to be present (9.9% vs 1.9%) with nearly equal left dominance (11.7% vs 11.4%) (p for between group comparisons = 0.04). A co-dominant system was associated with an increased odds of SCD [OR 5.6 (1.2-26.2); p=0.01].There was no difference in the proportion of cases and controls with significant stenosis (≥ 50%) in the posterior descending artery (4.4% vs 8.7%; p=0.10).

Conclusions:
In this community-based study, we identified specific patterns of coronary dominance associated with VF. Mechanisms related to the area of myocardium at risk or vascular supply to the inferior (vagal) surface of the heart may be involved and warrant further focused evaluation.
Abstract 14729: Weight Loss Reduces Atrial Fibrillation Inducibility and Burden in Severe Obesity Induced by Either High-Fat Diet or Genetic Hyperphagia in Mice
Authors: Savio-Galimberti Eleonora , Kannankeril Prince , Wasserman David , Darbar Dawood
Published: July 2021

Introduction:
Atrial fibrillation (AF), the most common sustained arrhythmia worldwide, is associated with increased morbidity and mortality. Obesity is increasingly recognized as an important risk factor to develop AF and heart disease with a diet rich in fats leading to morbid obesity. Melanocortin-4 receptor (MC4R) gene is a critical regulator of energy homeostasis, and homozygous loss-of-function mutations cause hyperphagia and morbid obesity.

Hypothesis:
We hypothesized that obesity and its comorbidities can create a profibrillatory substrate for AF in high fat diet-induced obese (DIO) and MC4R knock-out (MC4R-KO) mice, and that this substrate can be reversed by weight loss.

Methods:
Transesophageal rapid pacing was performed using atrial burst pacing (cycle length: 50-15 ms, for 15 s) to determine AF inducibility (% of mice that develop AF) and AF burden (number of AF episodes and total AF duration/mouse) in lightly anesthesized normotensive mice (C57bl6 mice [LEAN], DIO, and MC4R-KO), with continuous ECG monitoring. Transthoracic echocardiography was performed to assess right (R) and left (L) atrial appendage (AA) sizes.

Results:
Atrial burst pacing induced AF in 91% of DIO and 100% of MC4R-KO vs. 50% of LEAN (P<0.01, N=8 mice/group). Compared to LEAN, both DIO and MC4R-KO exhibited greater number of inducible AF episodes (0.7±0.2 vs. 1.8±0.2 vs. 1.8±0.1, P<0.01, N=15 mice/group) with longer duration (17.9±3 vs. 196±22 vs. 244±34 s, P<0.0001, N=15 mice/group; Figure). Both DIO and MC4R-KO had greater LAA volumes as compared with LEAN (5.2±0.2 vs. 6.7±0.4 vs. 4.1±0.1 μl, P<0.01, N=8 mice/group). RAA volume was similar across groups. After 20% weight loss, both AF burden and LAA volumes were significantly reduced to those seen in LEAN (22±5 s, 4.5±0.1 μl, P<0.001, N=8 mice/group).

Conclusions:
High-fat diet or genetic hyperphagia-induced obesity increases LAA volume and creates a profibrillatory substrate for AF that can be reversed with weight loss.
Abstract 14845: Masquerading Bundle Branch Block: An Electrocardiographic Marker of Poor Prognosis
Authors: Schroder e Souza Thiago G , Almeida Rômulo L , Targueta Gabriel P , Felicioni Sandro P , Cerutti Pinto Virginia B , Moretti Marcelo P , de Marchi Mariana F , França Francisco Faustino A
Published: July 2021

Introduction:
Masquerading bundle branch block (MBBB) is a rare cardiac conduction anomaly characterized in the Electrocardiogram (EKG) by Right Bundle Branch Block in the precordial leads and Left Bundle Branch Block in frontal leads. The available evidence indicates that it carries poor prognosis and that it is often underdiagnosed. We studied epidemiological peculiarities, electrocardiographic features and prognosis of this rare kind of ventricular conduction delay.

Methods:
In a review of over 600,000 EKGs from the database of Tele-Electrocardiography department of Dante Pazzanese Institute of Cardiology during the last seven years, we found twenty-five cases of MBBB. Diagnostic criteria were presence of QRS ≥ 0.12 s, dominant positive waves in V1, left axis deviation and absent or minimal S wave in DI and aVL. Epidemiological data was collected for each EKG and the follow-up of patient′s health status was assessed by telephone contact. Kaplan-Meier survival curves were based on the following endpoints: mortality, pacemaker implantation and the composite of both.

Results:
We identified twenty-five cases (21 males and 4 females) of MBBB. The average age was 69 (±14) years. Sinus rhythm was present in 17 patients (68%), atrial fibrillation in 7 (28%) and atrial flutter in one (4%). Average heart rate, PR interval, QRS length, QTc and QRS axis were, respectively: 70 (±17) bpm, 205 (±50) ms, 159 (±24) ms, 463 (±37) ms and -76° (±6) degrees. Follow-up data was successfully obtained from 15 patients: 4 (26.6%) had a pacemaker implanted, 7 (46.6%) died and 9 had combined endpoints (60%). According to the Kaplan-Meier survival curve, at 48 months, the estimated ratios of death, pacemaker implantation or combined endpoints were 41.4%, 38.9% and 80.2%, respectively.

Conclusions:
MBBB represents a high-risk condition and, although rare, this EKG pattern should be taken into consideration due to the poor prognosis associated with its presence.
Abstract 14907: Clinically Feasible Electronic Health Record Tool for Stratification of 1- to 3-Year Post-Myocardial Infarction Risk of Cardiovascular Events: The Intermountain Acute Coronary Syndromes Risk Scores
Authors: Horne Benjamin D , Muhlestein Joseph B , Bhandary Durgesh , Hoetzer Greta L , Khan Naeem D , Bair Tami L , Lappé Donald L
Published: July 2021

Background:
Randomized trials report that prolonged (>1 year) use of P2Y12 inhibitors with aspirin after myocardial infarction (MI) reduces stent thrombosis and cardiovascular (CV) events, including new MI, stroke, and CV death. Post-MI patients may benefit to a differing extent from long-term dual anti-platelet therapy (DAPT); thus, a method is needed to identify those at higher risk of CV events.

Hypothesis:
A low-cost, easy-to-use, and highly predictive risk stratification tool can be created to differentiate risk of CV events 1-3 years after MI.

Methods:
Patients surviving ≥1 year after an index MI who had ≥1 additional risk factor for MI were studied. Cox regression models were used to derive sex-specific Intermountain Acute Coronary Syndromes (IMACS) risk scores in 70% of patients (N=1,342 females; 3,047 males). Validation of IMACS scores was performed in the other 30% of patients (N=576 females; 1,290 males). Variables used in model creation were age, troponin I, B-type natriuretic peptide, hemoglobin A1c, and all components of the lipid panel, complete blood count, and comprehensive metabolic panel. The primary end point was a composite of CV death, MI, or stroke.

Results:
Age averaged 68.7±12 and 69.8±12 for females in the derivation and validation groups, respectively, and 63.6±12 and 63.9±12 for males. IMACS scores ranged from 0-11 for females (grouping scores of 0-2, 3-6, and 7-11 into low-, moderate-, and high-risk) and 0-14 for males (0-2, 3-7, 8-14). In the validation groups, IMACS categories stratified CV event risk (Figure). IMACS c-statistics for females were c=0.675 and c=0.734 in derivation and validation groups, respectively, and for males c=0.715 and c=0.672.

Conclusion:
Sex-specific IMACS risk scores strongly stratified 1- to 3-year post-MI risk of CV events. IMACS is an inexpensive electronic health record tool that empowers the evaluation of which post-MI patients may be the best candidates for more aggressive therapeutic management.
Abstract 14950: Meta-analysis of Oral Anticoagulants With Dual vs Single Antiplatelet Therapy in Patients After Coronary Intervention
Authors: Briasoulis Alexandros , Sharma Shikha , Mallikethi-Reddy Sagar , Papageorgiou Nikolaos , Palla Mohan , Tousoulis Dimitris
Published: July 2021

Background:
Combined use of dual antiplatelet therapy with oral anticoagulation (OAC) is required in some patients with after coronary artery stenting or acute coronary syndrome (ACS).

Methods:
We performed a meta-analysis of the comparative effects of triple antithrombotic therapy (TT) vs OAC with single antiplatelet therapy (DT) on all-cause mortality, stroke, cardiovascular death, myocardial infarction, target vessel revascularization and major bleeding. We conducted an EMBASE and MEDLINE search for prospective controlled trials and cohort studies of patients requiring anticoagulation after coronary stenting.

Results:
We identified 3 prospective controlled studies and 5 cohort studies, which compared TT vs dual therapy (DT). We identified 4 prospective controlled and 6 cohort studies with 4564 patients on TT and 1848 on DT with an average follow up duration of 10.1 months. TT is associated with similar rates of all-cause mortality, stroke and major bleeding but significantly lower rates of myocardial infarction compared to DT (mainly OAC plus clopidogrel).

Conclusion:
Triple antithrombotic therapy is associated with similar mortality and bleeding rates but less myocardial infarctions compared with OAC and single antiplatelet therapy.
Abstract 15016: Calcifications of Aortic Valve, Coronary Arteries and Aorta in 500 Consecutive Patients
Authors: Galas Anna , Michalowska Ilona , Kepka Cezary , Abramczuk Elzbieta , Orlowska-Baranowska Ewa , Hryniewiecki Tomasz
Published: July 2021

Introduction:
Diseases presenting with cardiac and vascular calcification are well known and a variety of diagnostic modalities enable detection of calcifications. However, the relationship between calcification of arteries and the aortic valve together with corresponding pathophysiological processes have not been yet unequivocally elucidated.

Purposes of the study:
An assessment of correlation between presence and severity of calcifications in the aortic valve, coronary arteries, aorta and influence of cardiovascular disease risk factors on prevalence of calcifications in this locations.

Material and Methods:
The study included consecutive patients over 60 years of age referred for computed tomography imaging of coronary artery disease. A total number of included patients reached 500 subjects. Besides coronary artery calcification (CAC), we evaluated aortic valve calcification (AVC) and ascending aorta calcification (AAC). Computed tomography examinations were performed with a dual-source, 64-slice scanner. Exclusion criteria encompassed: diagnosed aortic valve disease, history of coronary artery angioplasty, bypass grafting or heart valve surgery.

Results:
AVC was diagnosed in 163 patients (32.6%). Prevalence of CAC and AAC was higher than AVC and amounted to 78.8% and 59.8%, respectively. Aortic valve calcification was more often observed in men than women. Degree of AVC severity was significantly lesser than that of CAC and AAC (p=0.0001, p=0.0001). In our study population, we did not find a significant dependence between presence and severity of AVC and CAC or AAC. However, we did observe a statistically significant relationship between presence and severity of CAC and AAC. In contrast to coronary arteries and the aorta, we did not find significantly increased prevalence of AVC among patients with arterial hypertension, dyslipidemias, diabetes, smokers or patients with elevated BMI. Only sex and age exerted significant influence on development of AVC.

Conclusions:
Despite some similarities between the process of aortic valve calcification and that involving coronary arteries and aorta, these phenomena are not interrelated. It seems that process of calcification of the aortic valve is significantly different from atherosclerosis.
Abstract 15060: Protein-Engineered Hydrogels for Improved Efficacy of Stem Cell-Based Injection Therapy in a Murine Model of Peripheral Arterial Disease
Authors: Cai Lei , Dewi Ruby , Strassberg Zachary , Hou Luqia , Foster Abbygail , Heilshorn Sarah C , Huang Ngan F
Published: July 2021

Introduction:
Stem cell injection is a minimally invasive approach for treatment of cardiovascular diseases including peripheral arterial disease (PAD), which affects over 8 million patients in the US. However, poor cell survival and low cell retention at injection site are critical bottlenecks to the efficacy of stem cell therapy. We developed a shear-thinning and self-healing hydrogel system with controllable rigidity for stem cell encapsulation so as to enhance transplant cell viability.

Hypothesis:
The injectable hydrogel system will prolong cell survival under ischemic conditions and maintain cellular phenotype, in comparison to cell injection in saline.

Methods:
We developed a hydrogel comprised of two complementary engineered proteins that self-assemble upon simple mixing. The hydrogel network incorporates a polyethylene glycol physical crosslinker that modulates hydrogel stiffness and degradation. Bioluminescently-labeled human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) were encapsulated within the hydrogel with controllable stiffness (G'~10-800 Pa) under conditions of hypoxia (1% O2). The cells within hydrogel were then subjected to an in vitro model of injection and assayed for cell survival, proliferation, and endothelial phenotype for up to 14 days. To verify these results in an experimental model of PAD, 10^6 cells were injected in saline or in 400 Pa hydrogel into the ischemic limb in SCID mice.

Results:
Acutely after injection, the survival of iPSC-ECs in saline was 65%, whereas survival of iPSC-ECs in hydrogels with stiffnesses of 10, 100, 400, and 800 Pa was 94%. Bioluminescence imaging of cell viability in hypoxia for 14 days demonstrated the highest proliferation in the hydrogel with 400 Pa stiffness. In the 400 Pa hydrogel, iPSC-ECs maintained elongated morphology with robust expression of endothelial phenotypic marker, CD31. In the ischemic hindlimb, iPSC-EC retention was markedly increased with hydrogel encapsulation, compared to saline delivery.

Conclusions:
These findings demonstrate that stem cell encapsulation within this protein hydrogel improves cell viability, which may have therapeutic benefit for treatment of PAD and broadly to myocardial ischemia.