bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3860: Arrhythmia Vulnerability of Aged Haploinsufficient Cx43 Mice is Determined by Heterogeneous Downregulation of Cx43 Combined with Increased Fibrosis
Authors: Jansen John A , van Veen Toon A , Bosch Astrid A , van der Nagel Roel , Vos Marc A , de Bakker Jacques M , van Rijen Harold V 
Published: July 2021

Background: Reduced gap junction expression and increased collagen deposition are commonly found in ventricles of electrically remodeled diseased hearts. Their interactive contribution to slow conduction and increased arrhythmogeneity is, however, unclear. In this study, we investigated the effect of increased fibrosis with normal or reduced levels of the ventricular gap junction protein Cx43 on impulse propagation and arrhythmogeneity.
Methods: 11 Cx43fl/fl (Control) and 13 Cx43CreER(T)/fl mice (expressing only 50% of Cx43 protein compared to control; Cx43HZ) were aged to 20 months. Epicardial activation mapping (208 electrode terminals) of right (RV) and left (LV) ventricle was performed on Langendorff perfused hearts. Effective refractory period (ERP) was determined by premature stimulation and arrhythmia inducibility was tested by 1–3 premature stimuli and burst pacing. Epicardial conduction velocity longitudinal (CVL) and transverse (CVT) to fiber orientation and inhomogeneity of conduction was determined during S1S1 pacing (150 ms). Cx43, N-cadherin expression, and tissue collagen content was determined by (immuno)histology and Western blotting.
Results: Sustained ventricular arrhythmias were induced in 0/11 control and 8/13 Cx43HZ mice (p<0.01). CVL and CVT were unchanged, except for CVT in RV, which was decreased from 48.2±2 to 39.3±1.8 cm/s (Control vs Cx43HZ, p<0.05). In RV, ERP was decreased from 78.2±6.0 to 53.1±3.3 ms (Control vs Cx43HZ, p<0.05). In both RV and LV, inhomogeneity of conduction was significantly higher in Cx43HZ mice with arrhythmias (VT+), compared to both Control and Cx43HZ mice without arrhythmias (VT−). Cx43 expression levels were comparable between VT+ and VT- Cx43HZ mice, though strongly reduced compared to Control. However, Cx43 distribution was very heterogeneous in VT+ mice with large areas devoid of Cx43 while N-cadherin was unaffected, indicating the presence of intact intercalated disks. Compared to Control interstitial fibrosis was increased in Cx43HZ mice, but more pronounced in VT+ Cx43HZ mice when compared to Cx43HZ VT- mice.
Conclusions: Combined heterogeneous reduction of Cx43 and increased fibrosis strongly enhance arrhythmogenic vulnerability in aged haploinsufficient Cx43 mice.
Abstract 5509: Arginase Activity Mediates Vascular Inflammation
Authors: Caldwell Ruth B , Zhang Wenbo , Baban Babak , Rojas Modesto , Virmani Suvika , Patel Chintan , Smith Sylvia B , Romero Maritza , Caldwell Robert W 
Published: July 2021

We have shown before that activity of NOX2 NADPH oxidase has a critical role in causing vascular inflammation. We have also shown that diabetes-induced vascular endothelial cell (EC) dysfunction is mediated by increases in arginase activity which decreases availability of L-arginine to EC nitric oxide synthase (eNOS). While the specific role of arginase activity in vascular inflammation is not yet clear, increases in arginase I levels have been described in conditions of elevated oxidative stress and inflammation. We have now used a model of endotoxin-induced retinal inflammation to assess the hypothesis that increased arginase activity is involved in the development of vascular inflammation. Mice were injected with lipopolysaccharide (LPS, 4 mg/kg, ip, 3–16 hrs). Measurement of urea formation showed that retinal arginase activity was increased in the LPS-treated mice (1.9±0.3-fold, n=5). Quantitative PCR showed that arginase I (AI) mRNA was also increased with a peak at 12 hrs (2.2±0.1-fold, n=3). Expression of the AII isoform was unchanged. Western blotting, immunohistochemistry and flow cytometry confirmed an increase in AI protein expression, which was localized to vascular cells, glia and microglia. AI expression and arginase activity were also increased in LPS-treated glia and microglia. The LPS-induced increases in AI expression were correlated with increases in mRNA for MCP-1 (575.1±84.8-fold, n=5), TNF-alpha (55.6±10.3-fold, n=4) and iNOS (103.3±1.5-fold, n=3) and with increased leukocyte adhesion to the vessel wall (5.5±1.5 fold, n=3–5). Studies using knockout mice deficient in one copy of the AI gene and both copies of AII or mice treated with the selective arginase inhibitor ([S]-[2-boronoethyl]-L-cysteine-HCl, 20 mg/kg, iv) showed that LPS-induced increases in inflammatory gene expression and leukostasis were blocked by knocking down or inhibiting arginase. Furthermore, the LPS-induced increase in AI was abrogated by NOX2 deletion or apocynin treatment, indicating involvement of NADPH oxidase activity. In conclusion, LPS-induced vascular inflammation is mediated by NADPH oxidase-dependent increases in arginase activity.
This research has received full or partial funding support from the American Heart Association, AHA Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).
Abstract 5569: Paracrine Effects of Cardiomyocyte STAT3 Determine the Vasculogenic Differentiation Potential of Cardiac Progenitor Cells: Potential Role of Endogenous Erythropoietin
Authors: Fischer Philipp , Hoch Melanie , Stapel Britta , Drexler Helmut , Hilfiker-Kleiner Denise 
Published: July 2021

Mice with a cardiomyocyte-restricted knock out of STAT3 (αMHC-Cretg/+; STAT3flox/flox, STAT3-KO) show a continuous decrease of cardiac vascularization and develop heart failure beyond the age of 9 months. We investigated the role of cardiomyocyte STAT3-driven paracrine effects on Sca-1+ cardiac progenitor cells (CPC) in the mouse heart. CPC were immunomag-netically isolated from KO and wildtype (STAT3flox/flox, WT) hearts (age: 3 months). PCR and Western blot confirmed deletion of STAT3 in cardiomyocytes of KO mice, while CPC from KO showed normal expression of STAT3. The total number of CPC per heart was similar between WT and KO mice. FACS analysis revealed a reduced number of endothelial progenitor cells (defined by co-expression of Sca-1, CD31 and CD38, −25%, P<0.05) in CPC from KO compared to CPC from WT. In vitro culture for 4 weeks on fibronectin-coated plates of CPC from KO revealed reduced proliferation (−33%, p<0.01), impaired endothelial cell (EC) tubeformation (monitored with Tie2, eNOS and CD31 immunohistochemistry (IHC), p<0.01) and enhanced adipocyte differentiation (oil red staining and RT-PCR, p<0.05) compared with CPC from WT. Microarray of freshly isolated CPC reflected this differences in EC and adipocyte differentiation on the mRNA level (i.e. EC marker Prostaglandin E Rezeptor-3: 2.3-fold lower; adipocyte marker Lipocalin-2 2.7-fold higher in CPC from KO hearts). Microarray results from whole left ventricular tissue showed a decrease in gene expression of Erythropoietin (Epo) in KO hearts (-9,25-fold). ELISA, IHC and methylcellulose assay confirm expression of active EPO by cardiomyocytes. CPC express high levels of EPO receptor (IHC, RT-PCR). Epo enhanced tube formation and sprouting of EC and attenuated adipocyte differentiation of CPCs from KO. In vivo treatment with Epo rescued impaired proliferation, promoted EC differentiation and attenuated adipocyte differentiation of CPC from KO hearts.
Conclusion: STAT3-dependent paracrine factors from cardiomyocytes regulate proliferation, differentiation and vasculogenic properties of CPCs. Cardiomyocyte derived EPO is an important paracrine mediator that promotes differentiation into EC and attenuates differentiation into adipocytes from CPCs in the adult heart.
Abstract 566: Critical Role of Ghrelin in Ventricular Remodeling after Acute Myocardial Infarction
Authors: Kondo Hideyuki , Hojo Yukihiro , Nishimura Yoshioki , Takahashi Nozomu , Ikemoto Tomokazu , Dezaki Katsuya , Katsuki Takaaki , Yada Toshihiko , Shimada Kazuyuki 
Published: July 2021

Background: Ghrelin is a novel growth hormone (GH)-releasing peptide, originally isolated from the stomach, which has been identified as an endogenous ligand for the GH secretagogues receptor (GHS-R). Previous studies revealed that chronic administration of ghrelin suppresses cardiac sympathetic activity and prevents left ventricular (LV) remodeling after acute myocardial infarction (AMI). However clinical role of ghrelin after AMI is still not clear. We examined the role of ghrelin in LV remodeling after AMI.
Objectives: To elucidate the role of ghrelin in LV remodeling after AMI.
Subjects and methods: We employed patients with the first AMI (n=41, mean age 61.9±8.9 years old). We obtained peripheral blood on 1, 7, 14 days and 6 months after the onset. Plasma total ghrelin levels were measured by enzyme-linked immunosorbent assay. Patients were treated by percutaneous coronary intervention within 12 hours after onset. Successful myocardial reperfusion (TIMI flow grade 2 or 3) was accomplished in all patients. To analyze LV remodeling, all patients submitted to two serial left ventriculographies carried out on the day of admission and 6 months after the onset (mean 199±13 days). LV volume index (LVEDVI) was calculated by QCA-CMS software.
Results: Plasma total ghrelin levels increased after the onset of AMI (day 0: 28.4±6.4, day 7: 75.1±12.2, day 14: 89.9±14.8 pg/ml, 6months: 46.5±6.6 fmol/ml, p<0.001). There was a significant positive correlation between plasma ghrelin levels on day 14 after the onset and changes in LVEDVI (r=+0.53, p<0.001). The stepwise multivariate regression analysis showed that the plasma ghrelin level on day 14 is a significant explanatory variable for the changes in LVEDVI (F=8.77, p<0.01, β=+0.40).
Conclusions: The elevation of Ghrelin levels might be a compensatory mechanism to prevent LV remodeling. These results first indicate that ghrelin has a critical role in the progression of left ventricular remodeling after AMI.
Abstract 751: Retrograde Acute Type A Aortic Dissection: Are Outcomes Worse Than Classic Acute Aortic Dissection?
Authors: Estrera Anthony L , Miller Charles C , Azizzadeh Ali , Lee Taek-Yeon , Abdullah Saad , Walkes Jon-Cecil , Safi Hazim J 
Published: July 2021

Introduction: Recent reports of retrograde acute type A aortic dissection (RTAAD) following thoracic aortic endovascular repair have been associated with poor outcomes. This raises concerns about outcomes with RTAAD in general. We report and compare outcomes of retrograde acute Type A aortic dissection repair with classic acute aortic dissection (CAAD).
Methods: Between 8/1991 and 5/2008, we repaired 322 patients with acute type A dissection. This cohort was divided into two groups: RTAAD Group (52 cases), and CAAD Group (270 cases). RTAAD was defined as the presence of a dissection tear originating distal to the arch as identified intra-operatively. Tears in the ascending aorta denoted dissection as classic. Repairs using circulatory arrest were similar between groups, p>0.33. Preoperative, operative, and post-operative variables were analyzed retrospectively.

Results: Retrograde type A aortic dissection occurred in 16.1% (52/322) of patients. RTAAD differed from CAAD in the median time from initial symptoms to operation (75+−87 hours vs. 47+−61 hours) and specific presenting conditions. (See Table 1

) Outcomes (stroke: RTAAD, 2.1% vs. CAAD, 3.6%, bleeding: 4% vs. 9%, myocardial infarction: 6% vs. 6%, and mortality: 11% vs. 18%) did not differ significantly between the groups, p>0.05.

Conclusions: RTAAD presented later for repair and less frequently with redo-sternotomy and aortic valvular insufficiency. Despite these differences, outcomes from surgical repair did not differ significantly. Acceptable outcomes may be achieved with timely intervention.

Table 1:

Preoperative Variables
Abstract 857: Systolic Blood Pressure of 115 mmHg and Above is Associated with Worsening Cardiac Risk Profile in Normotensive Individuals
Authors: Rafey Mohammed A , Butt Saud , Hila Sorana , Butler Robert , Pohl Marc A , Poggio Emilio , Schreiber Martin J 
Published: July 2021

Aim: To explore whether a systolic blood pressure (SBP) cut-off of ≥115 mmHg is associated with worsening in the cardiac risk profile of healthy, normotensive individuals.
Background: Data from population based trials demonstrates an increase in cardiovascular events beginning with a SBP of 115mmHg. We sought to study the cardiac risk profile of healthy, normotensive individuals with SBP ≥115 mmHg.
Methods: A retrospective chart review was performed on all 391 consecutive live donors who were found healthy and eventually donated kidney between April 1997 and December 2005 at our institution. Pre-kidney donation profile collected included age, gender, race, body mass index [BMI], office blood pressure readings, fasting glucose (FBS), uric acid (UA), lipid profile and iothalamate GFR [iGFR]. We stratified patients into two groups based on systolic blood pressure cut-off value of ≥115mmHg. Continuous variables were compared between groups using independent samples t test, categorical variables were compared using chi square and Fisher’s exact tests utilizing a 2 sided p value < 0.05.
Results: The sample included 230 women (59%), 361 white patients (81%). Mean age was 41±9 years, SBP was 115.6 ± 15 mmHg, BMI 26.7 ± 4.24, UA 5.0 mg/dl ± 1, FBS of 87 ± 9 mg/dl and iGFR 106.47 ± 16.47 ml/min. Each of these risk factor variables was significantly elevated in the subgroup with SBP ≥115 mmHg when compared to those with lower SBP.
Conclusion: These data suggest that in otherwise healthy living donors a SBP of ≥115 mmHg is associated with a more adverse cardiac risk profile in comparison to those with a SBP less than 115 mmHg. Further studies are needed to see if instituting early interventions would improve cardiac profile and prevent cardiovascular events.
Abstract 2083: Five-Year Follow-Up of Quality of Life in Randomized Patients to Receive Coronary Bypass Surgery, Percutaneous Coronary Intervention or Medical Treatment: The Medicine Angioplasty or Surgery Study (MASS-II) Trial
Authors: Takiuti Myrthes E , Girardi Priscyla , Nogueira Celia R , Nakano Teryo , Paulitsch Felipe S , Garzillo Cibele L , Lopes Neuza , Stolf Noedir A , Hueb Whady 
Published: July 2021

Background: Although coronary bypass surgery (CABG), percutaneous coronary intervention (PCI) are used for the relief of symptoms and for a better tolerance to exercises, there is no conclusive evidence showing that these methods offer more benefits than the medical treatment (MT) to the quality of life (QoL) in patients with symptomatic coronary artery disease (CAD). This study sought to compare the QoL scores during 5-year in patients with stable multivessel CAD, who underwent one of the 3 therapeutic approaches.
Methods: From May 2000 and May 2005 a total of 611 patients were randomly assigned to a CABG (n=203), PCI (n=205) or MT (n=203). Of these patients, 546 (89%) were followed for assessments of QoL and demographic profile questionnaire for a 5-year period. 187 (34%) underwent CABG, 181 (33 %) PCI and 178 (33%) underwent MT. The Short Form Health-Related QoL Questionnaire (SF-36) was used to assess the patients, before randomization, six months, and 12months and annually until the end of study. The SF-36 comprises 36 items that can be combined into the following eight multi-item summary scores: physical functioning, vitality, bodily pain, mental heath, social functioning, and role limitation due to physical health, emotional problems and general health perceptions.
Results: At baseline, we found no difference relating to overall mortality between three groups. The eight domains of QoL showed improvement in all groups at 6-month follow-up visit compared with the baseline evaluation (p<0.001). Surgical therapy, PCI and MT showed improvements over baseline in most domains of quality of life (p<0.001). The improvements was observed mainly in surgical group and especially in physical role functioning. On the other hand medical therapy group showed fewer changed in their rating of general health. PCI group showed significant superiority over medical group in terms of physical functioning, vitality and general health after randomization.
Conclusion: All patients had improvement in QoL detected at 6 months persisting until 60 months. Moreover, CABG patients had better improvement of QoL compared with other groups. Furthermore, the QoL of PCI patients was better than MT patients at the end of follow-up.
Abstract 2128: Predictive Value of Short-term Deceleration Capacity
Authors: Schmidt Georg , Bauer Axel , Barthel Petra , Müller Alexander 
Published: July 2021

Background: Deceleration Capacity (DC) derived from 24-hour Holter recordings is a strong predictor of mortality in patients after acute myocardial infarction (MI). This prospective cohort study investigates the predictive power of DC derived from short-term recordings.
Methods: 938 survivors of acute MI (age ≤80 years, sinus rhythm) were included. Within one week after index infarction, 30-min high resolution ECGs (1600Hz, supine position and resting conditions) as well as 24h-Holter recordings were performed. Short-term DC (DCs) and long-term DC (DCl) were calculated according to the previously published technology. Primary endpoint was death from any cause at two years. Multivariate Cox-regression analyses were adjusted for LVEF ≤30% and clinical covariates.

Results: During the 2-year follow-up, 36 patients (3.8%) died. Both, DCs and DCl were strong predictors of death with areas under the receiver-operator characteristics curves of 76.3% and 77.8%, respectively (p<0.0001). DCs was significantly correlated with DCl (r=0.7, p<0.0001). After adjustment for LVEF, presence of diabetes mellitus, advanced age and history of a previous MI, DCs (≤2.5ms) remained a highly significant predictor of death (Table

).

Conclusion: DC derived from high-resolution short-term ECGs is a strong and significant predictor of death in post-infarction patients.

Multivariate Cox regression analysis for Prediction of 2y-Mortality
Abstract 2154: Paroxysmal Atrial Tachyarrhythmia (AT) as a Trigger for Heart Failure Exacerbations: Assessment by Implanted Trans-pulmonary Impedance Sensor
Authors: Jhanjee Rajat , Templeton Grant , Nguyen John , Sakaguchi Scott , Lu Fei , Lurie Keith G , Milstein Simon , Van Heel Laura , Benditt David G 
Published: July 2021

Introduction: From clinical experience, it is known that worsening of heart failure (HF) is often associated with a seemingly greater susceptibility to atrial tachyarrhythmias (AT), particularly atrial fibrillation. However, it is not clear whether it is the HF or the AT that is the sentinel event, and triggers the other. recently, certain contemporary implantable pulse generators (IPGs) are able to estimate intra-thoracic fluid status by means of detecting alterations of trans-pulmonary electrical impedance (OptiVol® [OV], Medtronic Inc). This capability permits long-term assessment of HF in pts. Employing this tool (i.e., OV) this study examined the temporal relationship between HF as assessed by OV method and AT events.
Methods: Fourteen patients (pts: males, 71%, mean age 70±6.7 years) with OV-capable IPGs were enrolled. At each patient visit, OV index values since last follow-up, and AT duration (hours) were collected. OV Index >60 based on Medtronic Impedance Diagnostics in Heart Failure Trial (MID-HeFT) data was used as a cutoff to signify HF. Devices were interrogated to ascertain the temporal relationship of OV Index >60 and incidence of AT. Results are presented as mean ± SD.
Results: Eighty-five pt visits were analyzed (mean=6.1 visits per pt, average follow-up, 21.7±5.7 months). Left-ventricular ejection fraction was 40±10%, with ischemic cardiomyopathy accounting for 57% pts. In 23 of 85 visits the OV index exceeded threshold and episodes of AT were detected by the device. Of these 23 instances in which there was AT-HF concordance, AT onset preceded the increase of OV index above threshold in 21/23 cases (91% of the time), comprising 9 of 14 pts (64%).
Conclusions: In patients with both systolic HF and paroxysmal AT, our findings suggest that AT tends to precede worsening of heart failure and may act as the trigger event.
Abstract 2314: Insulin is the Protective Component of Glucose-Insulin-Potassium Solutions during Coronary Artery Bypass Graft Surgery in Patients with Diabetes
Authors: Lazar Harold L , McDonnell Marie , Chipkin Stuart , Bao Yusheng , Fitzgerald Carmel , Hunter Curtis , Shapira Oz , Shemin Richard , Cabral Howard 
Published: July 2021

Maintaining glycemic control(120 –180mg/dl)with GIK solutions in patients with diabetes undergoing CABG decreases perioperative morbidity and enhances long-term survival. The mechanism by which GIK exerts its protective effects is unknown. This study was undertaken to determine whether it is substrate enhancement with glucose, glycemic control with insulin, or the combination of glucose + insulin + potassium which contributes to improved outcomes with GIK in CABG patients with diabetes. One hundred-twenty diabetic patients undergoing isolated CABG surgery were prospectively randomized to achieve glycemic control(120 –180mg/dl)using an INSULIN infusion(100units/100mlNS),LOW GIK(500mlD5W + 80units insulin + 40mEqKCL), and HIGH GIK(D20W + 200units insulin + 80mEqKCL) beginning on anesthetic induction and continuing for 18 hours after surgery. Variables assessed included Major Adverse Events(MAE=death, MI, CVA, atrial fibrillation, infection, ventilation > 24 hours, inotropic usage > 24hours,lenght of stay > 7days), serum glucose, the amount of insulin infused, and serum free fatty acids(ffa).Values are mean+/− standard deviation. HIGH GIK delivered more insulin and resulted in significantly lower levels of glucose and ffa. However, it had no effect on the incidence of MAEs compared to INSULIN infusions without glucose and potassium. Insulin, rather than substrate enhancement with glucose and potassium, is the key element in GIK used in CABG patients with diabetes. Augmenting insulin delivery results in lower levels of glucose and ffa, but has no effect on clinical outcomes as long as gylcemic control(120 –180mg/dl) is achieved.
This research has received full or partial funding support from the American Heart Association, AHA National Center.

RESULTS
Abstract 2514: Endovascular Imaging Causes Significant But Temporary Endothelial Injury
Authors: Van Der Giessen Willem J , Krabbendam Stefan C , van Beusekom Heleen M 
Published: July 2021

Coronary Imaging e.g. IVUS and OCT to assess vascular size, plaque morphology and composition are useful tools in clinical trials as well as in routine practice. It is unclear whether imaging catheters induce acute endothelial cell damage (ECD) and how this heals over time.
Methods. Normal porcine coronary arteries were subjected to intravascular imaging (Raman, IVUS, OCT), guidewire-only placement or no manipulation (control). ECD was assessed acute or at 5 days (chronic) with an Evans Blue dye-exclusion test and planimetry followed by scanning electron microscopy (SEM).
Results. Acute injury (% staining of the area exposed to imaging) was considerable, but similar for the 3 imaging catheters. Guidewire-only induced less ECD. One-way ANOVA showed that only OCT- and RAMAN induced more ECD than control. Analysis with SEM showed that staining was associated with either EC denudation or injured but present EC. At 5 days staining was reduced to background levels.
Conclusion. Vascular imaging and guide wire manipulation both induce acute ECD, but this injury heals within 5 days following imaging. Planimetry of endothelial injury