bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2003: More Chest Compressions and Fewer Shocks Are Given During Out-of-Hospital Cardiac Arrest Resuscitation With the 2005 AHA Guidelines
Authors: White Lynn J , Cantrell Sarah A , Cronin Robert , Koser Shawn , Keseg David , Sayre Michael R
Published: July 2021

Introduction
Long pauses without chest compressions (CC) have been identified in CPR provided by EMS professionals for out-of-hospital cardiac arrest (OOHCA). The 2005 AHA ECC CPR guidelines emphasize CC. The 2005 AHA Basic Life Support (BLS) for Healthcare Professionals (HCP) course introduced a training method with more CPR skills practice during the DVD based course. The purpose of this before/after study was to determine whether CC rates increased after introduction of the 2005 course.

Methods
This urban EMS system has 400 cardiac etiology OOHCA events annually. A convenience sample of 49 continuous electronic ECG recordings of VF patients was analyzed with the impedance channel of the LIFEPAK 12 (Physio-Control, Redmond WA) and proprietary software. A trained researcher verified the automated analysis. Each CC during the resuscitation attempt and pauses in CC before and after the first defibrillation shock were noted. The time of return of spontaneous circulation (ROSC) was determined by medical record review and onset of regular electrical activity without CC. Medical records were reviewed for outcome to hospital discharge. The EMS patient care protocol for VF was changed on July 1, 2006 to comply with the 2005 AHA ECC guidelines. Cases were grouped by the OOHCA date: 9/2004 to 12/31/2006 (pre) and 7/1/2006 to 4/21/2007 (post). EMS personnel began taking the 2005 BLS for HCP course during spring 2006. Monthly courses over 3 years will recertify 1500 personnel.

Results
29 cases were analyzed from the pre group and 20 from the post group. Compressions per minute increased from a mean (±SD) of 47 ± 16 pre to 75 ± 33 post (P < 0.01). The mean count of shocks given per victim decreased from 4.5 ± 4.0 pre to 2.8 ± 1.8 post (P < 0.04). The CC pause before the first shock was unchanged (23.6 ± 18.4 seconds to 22.1 ± 17.9). but the CC pause following that shock decreased significantly from 48.7 ± 63.2 to 11.8 ± 22.5 (p=0.008). Rates of ROSC (55% pre, 50% post) and survival to discharge (15% pre, 13% post) were similar.

Conclusion
Following introduction of the 2005 BLS for HCP course and the EMS protocol change, the quality of CPR delivered to victims of OOHCA improved significantly compared with pre-2006 CPR. The sample size was too small to detect differences in survival rates.
Abstract 2009: Matching the Transthoracic Defibrillation Vector to the Fibrillation Vector Improves Shock Success
Authors: Brooks Leonard A , Zhang Yi , Dendi Raghuveer , Anderson Roger H , Kerber Richard E
Published: July 2021

Background:
Depolarization of myocytes requires less energy when electrical current flows along the longitudinal axis compared to the transverse axis of myocytes. Since ventricular fibrillation (VF) amplitude in ECG leads reflects the functional electrical orientation of the majority of myocytes, we hypothesized that a defibrillation shock would be more effective if the shock vector was oriented along the functional electrical axis of the majority of myocytes, and this axis could be determined in real time from the relative amplitudes of the VF signal measured in three orthogonal ECG leads.

Methods:
In closed-chest, anesthetized, swine (22.0 ± SE0.8 kg, n=9), a new directional defibrillation device was used to simultaneously measure the VF amplitude through three orthogonal pairs of defibrillation electrodes: anterior-posterior, lateral-lateral, and superior-inferior. VF was electrically induced and persisted for 15 seconds. During defibrillation, the device identified the electrode pair that measured the largest or smallest peak amplitudes (+ or −) within the previous 100msec through which to deliver the shock. Defibrillation success for the electrodes measuring the largest or smallest VF amplitude was evaluated by delivering four 50J shocks for VF through each of these electrode pairs (in random order). The electrode pair measuring the largest VF signal amplitude was considered to be most closely aligned with the functional VF vector.

Results:
Fifty J shocks (n=37) delivered through the electrode pair measuring the largest VF signal amplitude had higher defibrillation success than 50J shocks (n=37) delivered through the electrodes measuring the smallest VF signal amplitude (62 ± 10% vs.19 ± 8%, p<0.05). Impedance and current were not different.

Conclusions:
By using a directional defibrillation device which instantaneously measures the peak VF signal amplitude in three pairs of orthogonally oriented defibrillation electrodes, it is feasible to determine which set of electrodes is oriented more favorably to the functional VF vector and to direct the shock through that set of electrodes. Matching the defibrillation vector to the fibrillation vector improves shock success.
Abstract 2010: A Pre-hospital Percutaneous Cardiopulmonary Bypass Order Treatment Strategy Significantly Improves Neurological Function in Patients with Out-of-Hospital Cardiogenic Cardiopulmonary Arrest
Authors: Kano Hitoshi , Satou Tomoyuki , Yamazaki Kei , Saitou Tomoyo , Endou Akio , Matsui Toshihisa , Henzan Naomi , Okada Masaki , Makise Hiroshi , Igarashi Yasumi , Makino Takao , Iwakiri Naoki , Fukuda Hiroyuki , Katou Noriyoshi , Togashi Masaki , Yoshida Tetsunori
Published: July 2021

Objectives:
Percutaneous cardiopulmonary bypass (PCPB) is a powerful tool for rescuing the emergency patients (pts) with out-of-hospital cardiogenic cardiac arrest (OHCCA), who are not responding to advanced cardiovascular life support (ACLS). But the system under which the decision to apply PCPB is made at the hospital and preparations then made could exceed the time limitations imposed for cerebral resuscitation. Thus, we have collaborated with the physician-manned ambulance system, and we introduced a pre-hospital PCPB order treatment strategy for patients with out-of-hospital cardiogenic cardiopulmonary arrest, who do not respond to drug administration or electrical cardioversion.

Methods:
In 174 pts with OHCA treated with PCPB in a single institution, from April 1991 to May 2007. 135 consecutive pts with cardiogenic cardiac arrest refractory to ACLS, who had been treated with PCPB, were included. 135 Pts were divided into two groups. Pre-hospital order groups (n=42) were treated under the pre-hospital PCPB order system, and in-hospital order groups (n=93) were treated under the decision to initiate PCPB was made at the hospital. Rate of return of spontaneous circulation (ROSC), weaning of PCPB, survival to discharge, and favorable neurological recovery were assessed.

Results:
Pre-hospital order groups showed increases in ROSC, weaning of PCPB, survival to discharge, and significant increases in favorable neurological recovery compared to in-hospital order groups.

Conclusions:
These results suggest that a pre-hospital PCPB order treatment strategy for patients after CPA significantly improves the neurological function in pts with OHCCA.

Table
Abstract 2022: Feasibility of Dynamic Substrate Mapping: Insights from an Animal Infarction Model and Comparison with Bipolar Voltage Mapping in Patients
Authors: Reents Tilko , Geller Johann Cristoph , Mittag Jörg , Schneider Ralf , Deisenhofer Isabell , Zrenner Bernhard , Klein H.U. , Reek Sven
Published: July 2021

Background:
Different substrate based ablation strategies have been developed for ablation of ventricular tachycardia (VT) after myocardial infarction (MI). We investigated the “Dynamic Substrate Mapping (DSM)”, a tool integrated into the noncontact mapping (NCM) system.

Methods:
An electrophysiologic study (EPS) was performed 96 ± 10 days after experimental anteroseptal MI in 19 female sheep. Scar was defined by NCM during sinus rhythm. The area of scar was determined using the DSM tool with a cut-off of 50 %, 40%, 30% and 20% of the largest deflection of the unipolar electrogram. The scar was determined by either magnetic resonance imaging (MRI, n=9) or pathology (n=10). Areas determined by MRI or pathology and by DSM were compared. In 11 patients referred for ablation of VT simultaneous electroanatomical mapping and NCM was performed. The location of the low voltage area in the bipolar voltage map and the DSM were compared.

Results:
For all 19 animals a low voltage area was delineated with a cut off of 50% of the largest unipolar deflection. The low voltage area determined with DSM was greater then the scar determined by pathology or MRI (29,32 ± 28,83 cm
2
vs 8,52 ± 3,48 cm
2
. p < 0,05). Infarct scar determined by MRI or pathology was always located within the low voltage area determined by DSM. There was no correlation between the sizes of the low voltage area determined by pathology/MRI and DSM. Delineation of a low voltage area was not possible in all animals with a cut off of 40%, 30%, and 20%. In 11 patients, locations of the low voltage areas determined by bipolar voltage maps and DSM corresponded well. The area defined by DSM was larger then the area defined by bipolar voltage map. there was a good correlation between the size of the low voltage areas determined by bipolar voltage map and DSM for cut off values of 50% and 40% (r
2
= 0,66 and r
2
= 0,61; p<0,05). With a cut off of 30% and 20% of the largest unipolar deflection a low voltage area could not be defined for all patients.

Conclusion:
Sizes of abnormal myocardium defined by DSM do not correlate with scar areas determined by pathology or MRI. Areas of abnormal myocardium delineated by DSM are greater then areas defined with bipolar voltage map. A detailed description of the scar border zone with DSM during sinus rhythm alone is not feasible.
Abstract 313: KLF5 Plays an Important Role in Endoplasmic Reticulum Stress Response in both Cardiovascular and Metabolic System
Authors: Eguchi Kosei , Manabe Ichiro , Shen Hua , Ohishi Yumiko , Fujiu Katsuhito , Takeda Norifumi , Nagai Ryozo
Published: July 2021

We have previously shown that the transcription factor KLF5 plays an important role in cardiovascular diseases. KLF5 heterozygous knockout (
KLF5
+/−
) mice exhibited much less neointima formation in vascular injury models and less severe cardiac hypertrophy and fibrosis in the angiotensin II-loading model. We have also found that KLF5 is expressed in metabolic tissues, such as adipose tissue, pancreatic β-cell, and skeletal muscle. When
KLF5
+/−
mice were fed with high-fat diet, they were protected from metabolic syndrome. These findings demonstrate that KLF5 plays important roles in stress response in both cardiovascular and metabolic systems. To better understand how KLF5 responds to metabolic and inflammatory stress, we analyzed signaling pathways that activate KLF5. One such pathway was the unfolded protein response (UPR). Indeed, in
KLF5
+/−
mice fed with high-fat diet exhibited much less severe pancreatic islets remodeling, in which endoplasmic reticulum (ER) stress and UPR have been shown to play an essential role. To further analyze KLF5’s role in ER stress responses, we treated mouse MIN6 pancreatic β cells with palmitate as a model of lipotoxicity. Palmitate induced ER stress markers, CHOP, Bip and phosphor-eIF2α. The increases in ER stress markers were accompanied by induction of KLF5, while insulin expression was decreased. When ER stress was attenuated by 4-phenylbutyrate and tauroursodeoxycholate, the induction of KLF5 and the down regulation of insulin expression were significantly inhibited. When the KLF5 was knocked down with siRNA, the down regulation of insulin mRNA expression in response to palmitate was suppressed. These results demonstrate that KLF5 is a downstream effecter protein of ER stress in β-cells and is involved in insulin expression. We then analyzed it in the cardiovascular system. We found that KLF5 was also induced by ER stress in smooth muscle cells (SMCs). Moreover, interleukin-1, which is known to induce inflammatory genes in SMCs, activated KLF5 via ER stress. Results of the present study suggest that KLF5 responds to ER stress in both cardiovascular and metabolic systems and that this signaling pathway plays important roles in pathogenesis and progression of metabolic syndrome as well as cardiovascular diseases.
Abstract 2092: Effect Of Recipient Genotype On Donor Cardiac Allograft Function In Children And Young Adults
Authors: Auerbach Scott R , Manlhiot Cedric , Reddy Sushma , Richmond Marc , Gruber Dorota , McCrindle Brian , Chen Jonathan M , Addonizio Linda J , Chung Wendy K , Mital Seema
Published: July 2021

Background
The renin-angiotensin-aldosterone (RAAS) and adrenergic receptor (ADR) genotypes affect cardiac function in heart failure. It is not known if recipient genotype affects function of the transplanted heart. We investigated the influence of recipient RAAS or ADR genotype on cardiac function and outcomes after transplant (Tx).

Methods
Patients (Pts) < 25 yrs old, post cardiac Tx, were enrolled (2003–06) and genotyped for polymorphisms in genes associated with RAAS upregulation (ACE-D, AGTR1-C, AGT-G, CYP11B2-G and CMA1-A) and β-ADR downregulation (β1Arg389 and β2Gly16). Hetero- or homozygosity for the high risk allele was considered a high-risk genotype. Univariate associations between genotypes and incidence of rejection, cardiac dysfunction (hemodynamic/echocardiographic), graft vasculopathy (GV), death and reTx were assessed via logistic or linear regression models with time dependent models as needed.

Results
Of 222 pts transplanted, 107 pts were studied. Age at Tx was 8.4±6.8 yrs (follow-up, 6.3±5.3 yrs; 42% male). The high risk allele frequency was: ACE 51%, AGTR1 23%, AGT 59%, CYP 35%, CMA 42%, β1Arg389 74% and β2Gly16 37% (in Hardy-Weinberg equilibrium). During follow-up, 81% pts had rejection, 51% graft dysfunction, 13% developed GV, 7% died and 8% were re-transplanted. 24% pts were receiving ACE/Angiotensin receptor inhibitors and 5% were receiving β-blockers at 5 yrs post-Tx. The presence of a high risk AGT or AGTR genotype was associated with greater severity of graft dysfunction at last follow-up (p=0.05), elevated CVP and PA pressures (p<0.001) and higher mortality. ADR genotype had no effect on outcomes. Cumulatively, a higher number of homozygous high risk RAAS genotypes was associated with a higher incidence of rejection (Hazard ratio/HR,1.3), graft dysfunction (HR,1.5) and higher probability of death (HR,2.5) (p<0.05).

Conclusion
RAAS polymorphisms in the recipient are associated with higher mortality after cardiac Tx possibly related to greater impairment of graft function with rejection. Whether wider use of RAAS inhibitors in this high risk cohort can improve outcomes after Tx requires further investigation. The lack of effect of the ADR genotype may relate to sympathetic denervation of the transplanted heart.
Abstract 2103: Prevention of Pulmonary Hypertension by ACE2 Gene Transfer to Lungs
Authors: Yamazato Yoriko , Hong KwonHo , Jang Dae Song , Ferreira Anderson J , Yamazato Masanobu , Oh S Paul , Raizada Mohan K
Published: July 2021

Pulmonary hypertension (PH) is characterized by increase in pulmonary vascular resistance, and narrowing and loss of pulmonary microvasculare. There is an indispensable need to develop innovative approaches for its control since PH becomes refractory to current therapies in later stages. Recent discovery of angiotensin converting enzyme 2 (ACE2), its involvement in cardiac remodeling, coupled with the limited success of ACE inhibitors in PH has led us to hypothesize that shifting the balance of renin-angiotensin system (RAS) to vasoprotective ACE2-Ang1–7-
mas
receptor axis would result the beneficial outcome in PH. We tested this hypothesis with the use of ACE2 overexpression in lungs by lentiviral vector-mediated gene transfer. Lentiviral vector particle(3x10^8 TU) containing murine ACE2 (letni-ACE2) were injected into 6 weeks old C57BL/6 mice prior to induction of PH by administration of weekly 600 mg/kg of monocrotaline (MCT) for 8 weeks for prevention studies. In addition, lenti-ACE2 was delivered following 6 weeks MCT treatment in reversal studies. Right ventricle systolic pressure (RVSP), Real-time RT-PCR, immunohisitochemistory of ACE2 and Ang (1–7) and histology of lungs in control and lent-ACE2 treated mice were carried out to evaluated the outcome on PH. Delivery of lenti-ACE2 resulted in a long-term increase in ACE2 expression in the lungs. A 60% and 100 % increases in protein and mRNA levels for ACE2 were observed. ACE2 and Ang (1–7) immunoreactivity were observed in epithelial and alveolar cells and alveolar macrophages. MCT treatment increased in RVSP (MCT 44.5+/−5.7 mmHg, control 24+/−1.0mmHg), RV hypertrophy (RV/LV+Sp ratio; 0.31+/−0.01), and wall thickness of pulmonary vessels. ACE2 gene transfer prevented increases in RVSP (26.1+/− 1.1mmHg), and RV hypertrophy (0.26+/−0.1), and reduced vessel wall thickness. In addition, ACE2 overexpression resulted in a significant reversal of RVSP (23.5+/−0.6mmHg). Futhermore, ACE2 overexpression in mice exhibited better general appearance and gained weight compared to MCT-treated mice. ACE2 gene transfer to lungs prevents and reverses vascular remodeling and PH in MCT model of PH. These observations suggest that targeting of pulmonary ACE2 holds novel therapeutic potential for PH.
Abstract 321: Cardiac Function Improvement Following In vivo Intracoronary Adeno-Associated Virus Type 1 Vector Gene Transfer of SERCA2a in a Pre-Clinical Model of Heart Failure
Authors: Ly Hung Q , Kawase Yoshiaki , Prunier Fabrice A , Lebeche Djamel , Shi Yafen , Yoneyama Ryuichi , Hoshino Kozo , Takewa Yoshiaki , Peluso Richard , Zsebo Krisztina , Tardif Jean-Claude , Tanguay Jean-Francois , Hajjar Roger J
Published: July 2021

Background:
Reduced activity and expression of sarcoplasmic reticulum Ca
2+
ATPase (SERCA2a) is known to occur in HF.

Method:
Our 4-month study examined the effects of SERCA2a gene transfer in a swine volume-overload HF (VO-HF) model. Using Yorkshire-Landrace swine, HF was created by severing mitral apparatus chordae to induce mitral regurgitation.

Results:
At 2 months (M), a compensated state of VO-HF was found: prolongation of the rate of isovolumic relaxation (Tau), increased left ventricular internal diameter diastolic and systolic diameters (LVIDd, LVIDs). At 2M, intracoronary injection of adeno-associated virus serotype 1 vector carrying SERCA2a under a cytomegalovirus promoter (AAV1.SERCA2a) (n = 10) vs. saline (n = 6) was performed. At 4M, gene transfer resulted in (A) positive LV inotropic effects: (dP/dt)/P, 15.5 ± 3.0 sec
− 1
SERCA2a-group vs. 21.2 ± 3.2 sec
− 1
controls; p < 0.01; (B) a favorable trend in LV lusitropic effects: Tau, 0.037 ± 0.019 vs. 0.051 ± 0.01 msec, p = 0.09; (C) improvement in LV geometry: % change in LVIDs, +15 ± 11% controls vs. −3.0 ± 10% SERCA2a-group, p < 0.01. At 4M, BNP levels remained stable in post- SERCA2a gene transfer, in contrast to the progressive rising levels among controls. Further, cardiac SERCA2a expression was significantly decreased in controls whereas it was restored to normal levels in the SERCA2a group (Figure

). Lastly, there was no histopathological evidence of myocardial inflammatory reaction or necrosis.

Conclusion:
Overexpression of SERCA2a by in vivo AAV1-mediated intracoronary gene transfer preserved systolic function, potentially prevented diastolic dysfunction and improved ventricular remodeling.
Abstract 2150: A European and Canadian Multicenter Randomized, Double-Blind Trial of the Sirolimus-Eluting Stent (SES) in Patients with De Novo Native Coronary Artery Lesions (NEW-SIRIUS): 5-Year Clinical Outcomes
Authors: Schampaert Eric , Schofer Joachim , Breithardt Guenther , Cohen Eric A. , Schlüter Michael , Wichter Thomas , Wittebols Kristel , Stoll Hans-Peter
Published: July 2021

Background
: NEW-SIRIUS is the pooled analysis of the E-SIRIUS (n=352) and C-SIRIUS (n=100) studies, respectively, performed in Europe and Canada. Identical in design, these are multicenter randomized, double-blind trials examining the safety and efficacy of the sirolimus-eluting stent (SES) vs. an identical bare-metal stent (BMS) in 452 patients to treat de novo native long lesions in small coronary arteries, with adjunctive clopidogrel for only 2 months.

Methods
: The primary endpoint was in-stent minimum lumen diameter (MLD) at 8-month follow-up. Among the secondary endpoints were major adverse cardiac events(MACE) at 1, 6, 9 and 12 months, and annually up to 5 years post-procedure, as well as target lesion revascularization (TLR), target vessel revascularization (TVR) and protocol-defined stent thrombosis.

Results
: At 8 months, the MLD was 2.27±0.47mm in the SES vs. 1.36±0.66 mm in the BMS (p < 0.001). The binary in-lesion restenosis rate was 5.1% in the SES vs. 44.2% in the BMS (p < 0.001). At 4 years, there was a significantly lower incidence of MACE (SES: 15.1% vs BMS: 33.9%, p < 0.001), primarily driven by a significant difference in clinically-driven TLR rates (SES: 7.1% vs. BMS: 26.0%, p < 0.001). A subgroup analysis in diabetic patients (45 SES, 60 BMS) demonstrated that the in-stent MLD was larger in SES than in BMS (2.20±0.47 vs 1.14±0.64 mm, p < 0.001) and the binary in-lesion restenosis rate was reduced from 56.1% (BMS) to 10.0% (RRR: 82.2%, p < 0.001) at 8 months. At 4 years, the freedom from MACE in diabetic patients was 80.0% in the SES vs. 61.7% in the BMS (p = 0.031), again mainly driven by an improved freedom from clinically driven-TLR (SES: 90.8% vs. BMS: 66.9%, p=0.005), with no evidence of a late catch-up effect.

Conclusion
: Up to 4 years, SES were superior to BMS in the total cohort as well as in the diabetic subgroup without evidence of a late catch-up. Five-year follow-up data, including antiplatelet therapies utilization and a diabetic subgroup analyses will be available by July 2007 and presented.
Abstract 2178: Sonic Hedgehog In Adult Hypoxic Cerebellum
Authors: Straface Giuseppe , Flex Andrea , Biscetti Federico , Gaetani Eleonora , Pecorini Giovanni , Angelini Flavia , Pola Paolo , Pola Roberto
Published: July 2021

Background:
Cerebellar hypoxia is responsible for important aspects of cognitive deterioration and motor disturbances in neurological disorders, such as stroke, vascular dementia, and neurodegeneration. In the cerebellum, VEGF is significantly upregulated after hypoxia and is able to induce angiogenesis, reduce neuronal apoptosis, and regulate neuronal differentiation, proliferation, and migration. But, VEGF is not sufficient to provide neuroprotection. A crucial role is played by growth associated protein-43 (GAP43), for which important activities have been described. The purpose of this study was to investigate the role of the developmental Sonic hedgehog (Shh) signaling pathway in postnatal hypoxic cerebellum and its relationship with VEGF and GAP43 expression.

Methods:
We used adult C57BL/6J mice, ptc1-lacZ mice, and GAP43−/− mice for these experiments. Ptc1-lacZ mice carry a non-disruptive insertion of the lacZ gene under the control of the ptc1 promoter. Ptc1 is a downstream-transcriptional target of Shh and its upregulation indicates activation of the Shh pathway. Mice were exposed to systemic normobaric hypoxia (6%O
2
) for 6 hours and the expression of Shh, Ptc1, VEGF, and GAP43 were investigated.

Results:
After exposure to hypoxia, Shh-positive staining was detected in Purkinje cells (PCs). The same cells were also lacZ(ptc1)-positive, indicating that PCs are both Shh-producing and -responding elements. Also the cells of the internal granular layer (IGL) were lacZ(ptc1)-positive, indicating that these cells are Shh-responsive. LacZ(ptc1)-positive IGL cells were also immunopositive for VEGF and GAP-43. We also found that ptc1 expression is lost in PCs of GAP43−/− mice, indicating that Shh requires GAP43 to activate its downstream target genes in PCs. Finally, when cultures enriched in granular cells were stimulated with Shh recombinant protein, GAP43 phosphorylation was increased. This effect was inhibited by Shh-inhibitor cyclopamine.

Conclusions:
This is the first time that hypoxia is reported to activate the Shh pathway in the adult. Our data suggest that the Shh pathway might be important for the cerebellar response to hypoxia, through interactions with VEGF and GAP43.
Abstract 329: Discovery of a Novel Paracrine Angiogenic Factor from Akt-Transduced Mesenchymal Stem Cells for Cell/Protein-based Therapy in angiogenesis
Authors: Guo Jian , Huang Jing , Mirotsou Maria , Mu Hui , Zhang Lunan , Loiselle David , Haystead Timothy , Pratt Richard E , Dzau Victor J
Published: July 2021

Previously we have shown that injection of mesenchymal stem cells overexpressing the survival gene Akt (Akt-MSCs) into infarcted rodent hearts dramatically reduced the infarct size and improved ventricular function as early as 72 hours after treatment. Furthermore, injection of conditioned medium isolated from these cells reproduced the similar effects. These data strongly suggest that the observed beneficial effects are due to paracrine factors released from the Akt-MSCs. Since angiogenesis has been shown previously to reduce ischemia injury, we reasoned that part of the protective effects include an angiogenic component. To help identify potential paracrine factors, we performed microarray analysis of Akt-MSCs and identified 46 novel differentially expressed transcripts, and among these, 5 novel transcripts potentially encoding secreted proteins were identified. The open reading frames of these novel transcripts were cloned and expressed in E.
coli
as maltose binding protein (MBP) fusion proteins. These 5 novel MBP fusion proteins (10nM) were tested in an endothelial tube formation assay using Human Umbilical Vein Endothelial Cells (HUVECs). Compared to MBP control or fresh serum free media, one of the MBP-novel fusion proteins has a pronounced tube forming ability (n = 8, p < 0.001). Bioinformatic analysis reveals that this novel angiogenic factor contains two fibronectin type III domains and a short hydrophobic ~20 amino acid as the signal peptide at amino-terminus. Full-length human cDNA (1704 base pairs) of this novel angiogenic factor was cloned into pcDNA-DEST40 plasmid without the stop codon, in the translational frame fused with V5-epitope at the carboxyl terminus. Upon transient transfection into HEK293 cells with this expression construct, this novel angiogenic factor secreted into culture medium as ~63 KDa protein evidenced by western blotting using anti-V5 antibody. Further studies will dissect the signaling mechanisms of this novel factor and our ongoing
in vivo
studies will further explore the possibilities of using protein and/or cell-based approach for novel therapeutic angiogenesis for the injured heart.
Abstract 2209: Impaired Diastolic Filling During Exercise Negatively Impacts Exercise Capacity in Children Who Have Undergone the Fontan Operation
Authors: Border William L , Mays Wayne A , Hambrook John T , Madueme Peace C , Knecht Sandy K , Gerdes Yvette M , Moore Vicky , Witt Sandra A , Glascock Betty J , Michelfelder Erik C , Knilans Timothy K , Kimball Thomas R
Published: July 2021

Background:
Increased cardiac output during exercise relies on synergy between forward pumping of the heart and a peripheral pump, comprised of skeletal muscle function and arteriolar dilation, which augments venous return. The critical component of this two-pump system is the maintenance of normal filling pressures, by enhancing diastolic filling. We hypothesized that children with normal systemic ventricular function, who have undergone the Fontan operation, have impaired diastolic filling during exercise which may negatively impact exercise capacity.

Methods:
Stress echocardiography was performed during upright cycle ergometry in a group of Fontan patients with normal systolic function (n=14) and a group of normal controls (n=17). Echo parameters obtained at each stage of exercise included early myocardial velocity at the systemic atrioventricular valve lateral annulus (Em), continuous wave Doppler velocity of ventricular inflow (E), calculation of the E/Em ratio (index of ventricular filling pressures), diastolic filling time (DFT), stroke volume (SV) and cardiac output (Q). Heart rate (HR) and maximal aerobic capacity (MVO2) were recorded. All data were normalized to percentage of MVO2.

Results:
The mean age was 14 years in both groups (p=0.8). The gender distribution was similar (p=0.1). The mean body mass index was slightly lower in the Fontan group (23 vs 19, p=0.05). All studies were judged to be maximal. Exercise and echo data are provided below:
Abstract 2213: Characteristics of Aspirin Non-Responders: Results from the Aspirin Resistance Testing and Initial Strategy for Treatment (ARTIST) Multicenter Trial
Authors: Daniels Lori B , Clopton Paul , Peacock W. F , Nowak Richard , Harrison Alex , Wu Alan , Kirk J. D , Maisel Alan S
Published: July 2021

Introduction:
Aspirin (ASA) therapy reduces the risk of thrombotic events by inhibiting platelet aggregation, however some individuals have a diminished response to ASA. The ability to predict ASA non-responsiveness has important therapeutic implications. We studied patients with suspected acute coronary syndrome (ACS) to determine the characteristics of patients with ASA non-responsiveness.

Methods:
We enrolled 1010 patients with suspected ACS in the emergency departments (ED’s) of 5 sites. All subjects were on outpatient ASA therapy or received ASA in the ED, and were excluded if on clopidogrel. Blood was tested for ASA non-responsiveness (defined as ASA reactive units ≥ 550) on a VerifyNow® (Accumetrics) device.

Results:
Overall prevalence of ASA non-responsiveness was 10.3% (95% C.I. 8.6–12.3%). Responsiveness to ASA did not differ by age or sex, but varied significantly by race. Hispanics had a higher prevalence of ASA non-responsiveness, while whites and Asians had a lower prevalence (

Figure

). Other factors associated with increased prevalence of ASA resistance included outpatient ASA therapy (p<0.001), a history of alcohol (p=0.045) or drug abuse (p=0.02), a history of heart failure (p=0.01), and renal insufficiency (p=0.003). Patients with ASA non-responsiveness had lower BMI (p=0.006) and hemoglobin (p<0.001), and higher BNP levels (p<0.001), prothrombin time (p=0.01), and partial thromboplastin time (p<0.001).

Conclusions:
Among suspected ACS patients, the prevalence of ASA non-responsiveness varies by race and is highest in Hispanics. ASA resistance is also more prevalent in patients with clinical characteristics consistent with poorer health.

Prevalence of ASA Non-Responsiveness by Race
Abstract 2218: Impact of Low Molecular Weight Heparin on Bleeding, Need for Transfusion and 6-month Survival in Elderly Patients (75 years of age or older) with Acute Myocardial iInfarction. Data from the FAST-MI Registry of the French Society of Cardiology.
Authors: Durand Eric , Schiele François , Simon Tabassome , Godenir Jean-Philippe , Cambou Jean-Pierre , Tabone Xavier , Mulak Geneviève , Danchin Nicolas
Published: July 2021

There are conflicting results as regards the impact of low molecular weight heparin (LMWH) on bleeding and mortality in elderly patients.

Aim: to compare in-hospital mortality in pts with AMI according to type of heparin used.

Methods: FAST-MI is a nationwide French registry carried out over a one-month period in the fall 2005, including consecutive pts with AMI admitted to CCUs =75 years and had received heparin therapy. Of those, 301 received unfractionated heparin (UFH) only, 398 LMWH only and 185 both UFH and LMWH. UFH only patients were slightly older (83 vs 82 years, p<0.01) and patients on LMWH only more often had NSTEMI: 65% vs 55% (UFH) and 50% (UFH+LMWH), p<0.01). Major bleeding was found in 6.3% (UFH), 2.3% (LMWH) and 2.7% (UFH+LMWH) (p<0.02). Blood transfusion was used in 10% (UFH), 4.8% (LMWH) and 4.3% (UFH+LMWH) (p<0.01). After x-variate adjustment, compared with UFH only, the need for transfusion was significantly lower (p<0.03) for LMWH OR=0.45 (95%CI: 0.25–0.85) and for UFH+LMWH OR=0.44 (0.19–1.01) and major bleeding was also reduced (OR=0.39; 95%CI: 0.17–0.89, for LMWH and OR=0.47; 95%CI: 0.17–1.31, for UFH+LMWH). Six-month survival was 73% for UFH, 85% for LMWH and 82% for UFH+LMH (p<0.001, Figure

). Using Cox x-variate analysis, use of LMWH remained associated with improved 6-month survival: OR=0.65 (95%CI: 0.46–0.92) for LMWH alone, and OR=0.69 (95%CI: 0.45–1.05) for UFH+LMWH, in comparison with UFH alone.

Conclusion: in a “real world” population hospitalised for AMI, the use of LMWH was associated with a reduced risk of bleeding complications and improved survival.
Abstract 2222: Long-term Outcomes of Acute Coronary Syndrome Patients with Chronic Renal Insufficiency treated with Bivalirudin vs Heparin plus a Glycoprotein IIb/IIIa Inhibitor: One Year Results from the Randomized ACUITY Trial
Authors: Mehran Roxana , Kirtane Ajay J , Dangas George D , Ohman E. M , Pocock Stuart , Gersh Bernard J , Bertrand Michel E , Hamon Martial , Manoukian Steven V , Hoekstra James , Pollack Charles V , Desmet Walter , Feit Frederick , Stella Joseph , Cequier Angel R , Stuckey Thomas , Cohen David J , Lansky Alexandra J , Stone Gregg W
Published: July 2021

Background:
In the ACUITY Trial, patients (pts) with chronic renal insufficiency (CRI) had significantly higher rates of ischemic events and major bleeding compared to pts without CRI at 30 days. Bivalirudin (Biv) monotherapy provided similar protection from ischemic events but with significantly less bleeding compared to heparin + a GPIIb/IIIa inhibitor (Hep+GPI). The impact of a Biv alone strategy on one year mortality is unknown.

Methods:
Pts with moderate and high risk acute coronary syndromes (ACS) were randomized to Hep + GPI, Biv + GPI, or Biv monotherapy. CRI was defined as baseline creatinine clearance (CrCl) <60 mL/min. We evaluated the impact of CRI and antithrombotic strategy on composite ischemia (death, MI, or revascularization) and mortality at one year.

Results:
Of the pts enrolled, 12,933 had baseline CrCl data: 2468 (19.1%) pts had CrCl ≥60 mL/min and 10,465 (80.9%) pts had CrCl <60 mL/min. Rates of major bleeding at 30 days in pts with CRI were significantly lower with Biv alone vs Hep+GPI (6.2% vs 9.8%, p<0.01). Pts with CRI had higher mortality at one year compared to those without CRI (8.7% vs 3.0%, p<0.001). There was no difference in composite ischemia for pts who received Biv monotherapy vs Hep + GPI (23.0% vs 21.4%, p=0.10). One year mortality by antithrombin strategy is shown in the Figure

.

Conclusions:
CRI in pts with ACS is associated with higher rates of one year mortality. In these high risk pts, Biv monotherapy improved early clinical outcomes compared to Hep + GPI by reducing major bleeding, and resulted in similar rates of one year mortality.

Cumulative Mortality at One Year, Patients with CRI
Abstract 2227: Results of Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction Patients Following Cardiac Arrest
Authors: Henry Timothy D , Duval Sue , Mooney Michael R , Menssen Katie M , Kapsner Christopher E , Page David I , Parham William , Unger Barbara T , Burke M N , Chavez Ivan J , Traverse Jay H , Larson David M
Published: July 2021

Background: Patients with cardiac arrest associated with STEMI are routinely excluded from clinical trials and therefore, almost no data exist regarding their outcomes with primary PCI. Patients with out of hospital cardiac arrest (OOHCA) are a particularly high-risk cohort and the appropriate reperfusion strategy for these patients is controversial.

Methods/Results: We determined the outcomes of patients who sustained a cardiac arrest prior to primary PCI in 1,500 consecutive patients with STEMI admitted to or transferred to a regional PCI center. Overall 159(10.6%) STEMI patients sustained a cardiac arrest prior to PCI, including 47 (3.1%) with OOHCA. The in-hospital, 30-day and 1-year mortality for patients without cardiac arrest, cardiac arrest excluding OOHCA and patients with OOHCA are included in table

. 53.3% of the deaths in OOHCA were related to anoxic brain injury compared to 9.1% of the deaths in patients with in-hospital cardiac arrest (p<0.003). Thirty-six percent of patients with OOHCA underwent a cooling protocol (return of spontaneous circulation and persistent neurologic impairment) with a 41% in-hospital mortality.

Conclusions: Cardiac arrest prior to PCI (including both OOHCA and in-hospital) in patients with STEMI is a major predictor for in-hospital mortality. Patients with cardiac arrest who survive to discharge subsequently do well. OOHCA has a higher mortality than in-hospital cardiac arrest and the majority of deaths are due to anoxic brain injury. Still, nearly 70% of OOHCA survived to discharge without neurological impairment.
Abstract 2241: Direct Visualization Of The Fossa Ovalis For Transeptal Puncture:
In Vivo
Evaluation Of The IRIS Catheter In A Porcine Model
Authors: Thiagalingam Aravinda , d’Avila Andre , Foley Lori , Miller David , Rothe Chris , Saadat Vahid , Ruskin Jeremy N , Reddy Vivek Y
Published: July 2021

Introduction:
Transeptal puncture is required for many interventional procedures but has a serious complication rate of ~1%. The primary risk of the procedure is related to mis-identification of the interatrial septum resulting in inadvertant puncture of the aorta or the atrial wall into the pericardium. We have investigated the utility of a catheter that allows direct visualization of the fossa ovalis to correctly position the transseptal needle at the interatrial septum.

Methods:
This study included 6 swine. The IRIS catheter (Voyage Medical, Campbell, CA) enables direct visualization using a cone-shaped hood into which saline is infused to exclude blood. In 4/6 animals, intracardiac echocardiography was used to visualize, but not guide, the transeptal puncture; there was no visible tenting of the septum. After transeptal puncture was performed the IRIS catheter was used to directly visualize and cannulate the puncture sites.

Results:
In 5 animals, transeptal puncture was successfully performed repeatedly (2–4 punctures/animal), and a .035 guidwire passed into the left atrium. IRIS could also guide cannulation of previous puncture in these animals. In 1 animal, visualization could not be performed because the atrial septum was lacerated during an attempt at left atrial visualization via a patent foramen ovale. Pericardial effusion was only observed in this latter animal on post-mortem exam. IRIS visualization of the atrial septum correlated well with the pathological specimen (see Figure

).

Conclusion:
The IRIS catheter allows direct
in vivo
visualization of the interatrial septum to guide
de novo
transeptal puncture or cannulation of previous punctures.

Top: A cascade of
in vivo
IRIS images of transeptal puncture holes (arrows) and a PFO

Bottom: Corresponding post mortem speciman
Abstract 2256: Predictors of “Life-Threatening” Fast VT or VF in Arrhythmogenic Right Ventricular Dysplasia
Authors: Laidlaw Douglas W , Lucier David , Daubert James P , Marcus Frank I , Scheinman Melvin M , Zareba Wojciech , Estes N.A. Mark
Published: July 2021

Introduction: The Multidisciplinary Study of Right Ventricular Dysplasia is an NIH-funded, multicenter, prospective registry of patients meeting Task-Force criteria for arrhythmogenic right ventricular dysplasia (ARVD). Previous studies have used the occurrence of “life-threatening” fast VT or VF as a surrogate for sudden cardiac death in patients with an ICD, however the patient characteristics associated with sudden cardiac death in ARVD remain poorly defined.

Methods: All patients in the ARVD registry that underwent implantation of an ICD were studied. Baseline characteristics of patients who received ICD therapy for fast VT/VF (with a cycle length of <250msec) were compared to those patients who did not receive ICD therapy. The cumulative risk of appropriate ICD therapy for fast VT/VF was determined by the Kaplan-Meier method for patients receiving an ICD for primary or secondary prevention.

Results: 80 patients in the ARVD registry underwent implantation of an ICD. Of those, 61 patients (76%) had an ICD implanted for secondary prevention and 19 patients (24%) for primary prevention. Over a mean follow-up of 1.7 years, 17.5% of patients experienced appropriate ICD therapy for fast VT/VF, including 18% of patients with an ICD implanted for secondary prevention and 15.8% of patients with and ICD implanted for primary prevention. Among all baseline imaging, echocardiographic, and electrcardiographic characteristics, none were significantly associated with the occurance of fast VT/VF during follow-up. In a Kaplan-Meier analysis, there was no significant diffference in the cumulative risk of ICD therapy for fast VT/VF between primary or secondary prevention cohorts (log rank p-value = 0.69).

Conclusions: In this registry of patients meeting the current Task Force criteria for ARVD, there is a high incidence of “life-threatening” fast VT/VF during follow-up, and the probability of fast VT/VF is similar in patients with an ICD for secondary prevention compared to those with an ICD for primary prevention. Furthermore, baseline characteristics do not reliably predict a future risk of life threatening arrhythmias in this cohort.
Abstract 2281: Mitral E Wave Deceleration Time to Peak E Velocity Ratio And Cardiovascular Outcome in Hypertensive Patients During Anti-Hypertensive Treatment: the LIFE Echo-Substudy.
Authors: Chinali Marcello , Mishra Rakesh K , de Simone Giovanni , Aurigemma Gerard P , Gerdts Eva , Wachtell Kristian , Boman Kurt , Dahlof Bjorn , Devereux Richard B
Published: July 2021

Background:
Early mitral flow deceleration time (DTE) is a prognostically validated marker of LV chamber stiffness. However, for any given LV stiffness, a higher E peak velocity (E) is associated with longer DTE, suggesting that the prognostic relevance of DTE might be influenced by variations in cardiac preload (e.g. during anti-hypertensive treatment). It is not known whether normalization of deceleration time for E-velocity (DTE/E) might be a more stable diastolic index for prediction of incident cardiovascular (CV) events in hypertensive patients during treatment, as compared to DTE.

Methods:
We evaluated 770 hypertensive patients (66±7 years; 42% women) with ECG-LV hypertrophy enrolled in the LIFE echo-substudy. Echocardiographic exams were performed annually for 5 years during anti-hypertensive treatment. Prognostic value of basal DTE/E was preliminary evaluated. Variation over time of both DTE/E and DTE were therefore analyzed in relation to incident combined fatal and non-fatal CV events.

Results:
During follow-up, 69 CV events occurred (9% of study population). Mean basal DTE/pE was 3.55±1.55 sec
2
/cm*10
−3.
In univariate analysis baseline DTE/E was associated positively with age (r=0.10; p<0.01), relative wall thickness (r=0.13; p<0.01) and isovolumic relaxation time (r=0.26; p<0.001) and negatively with heart rate (r=−0.20; p<0.001); no association was found with systolic blood pressure, diastolic blood pressure, LV mass or ejection fraction. Unadjusted Cox regression showed a positive association between baseline DTE/E and CV events [(HR=1.21 (95%CI= 1.07–1.37); p=0.002]. In time-varying Cox model, independently of age, gender, type of anti-hypertensive treatment and in-treatment heart rate, higher in-treatment DTE/E was associated with higher rate of CV events [(HR=1.26 (95%CI= 1.04 –1.80); p<0.026], whereas no association was found for in-treatment DTE (p=NS).

Conclusions:
In a population of treated hypertensive patients with ECG-LV hypertrophy, the ratio of in-treatment DTE/E, but not DTE alone, independently predicts incident CV events. In high-risk hypertensive patients, normalization of DTE for E peak velocity might be preferred to DTE in evaluating diastolic function during anti-hypertensive treatment.
Abstract 2302: Adeno-associated Virus-mediated Prostaglandin I Synthase Gene Transfer Improved The Hypoxia-induced Pulmonary Hypertension In Mice
Authors: Kawakami Takashi , Kanazawa Hideaki , Satoh Toru , Ieda Masaki , Ieda Yasuyo , Kimura Kensuke , Mochizuki Hideaki , Yokoyama Chieko , Ogawa Satoshi , Fukuda Keiichi
Published: July 2021

Background:
Although prostaglandin I
2
and its derivatives are clinically used for the treatment of pulmonary hypertension, continuous intravenous administration is required for the effective treatment. Prostaglandin I
2
synthase (PGIS) is one of the most powerful therapeutic genes against pulmonary hypertension (PH). The purpose of this study was to investigate whether the human PGIS (hPGIS) gene transfer using adeno-associated virus (AAV) vector into the skeletal muscle was effective to the hypoxia induced-pulmonary hypertension in mice.

Methods and Results:

PH was induced in the mice subjected to hypoxic chamber (O2 10%) for 8 weeks. Right ventricular systolic pressure (RVSP) significantly increased in PH group compared with control group.

In the gene transferred group (AAV1-hPGIS), the AAV type1-hPGIS (2.0×10
11
v.g./body) vector was injected into the left thigh muscle at 24 hour after exposure to hypoxia. Saline injected mice were served as control group.

After 8 weeks, hemodynamics and histological analysis was performed. AAV1-PGIS significantly decreased right ventricular systolic pressure to 26±5 mmHg compared with PH group (40±4 mmHg). Systemic blood pressure did not significantly decrease AAV-hPGIS treated group.

QT-PCR revealed that PH group increased BNP mRNA in RV by 6-fold higher, while AAV1-hPGIS group decreased to 1.3-fold compared with the control group.

Histological analysis revealed that PH group showed severe medial thickening of the pulmonary artery, and increased %wall thickness to 33.3±7.3%, while AAV1-hPGIS decreased to 17±3.6 %.

RT-PCR revealed that the hPGIS gene expression was detected only at the injected side, but not in the liver, kidney, heart, and the other organs. Histological analysis showed no pathological changes at the injected skeletal muscles.

Finally, Kaplan-Mayer analysis revealed that PH group showed 47% survival at 12 weeks wile AAV1-hPGIS group showed 73%, indicating that AAV1-hPGIS treatment significantly increased the survival of PH.

Conclusions:
Our study demonstrated that the AAV1-mediaqted gene transfer of PGIS was effective to treat the hypoxia-induced pulmonary hypertension in mice, and can prolong the survival of these animals.