bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 8544: Axillary Vein is a Better Access than Subclavian Vein or Cephalic Vein with Respect to Long-Term Pacemaker Lead Survival
Authors: Chan Ngai Y , Cheong Yan Y , Kwong Nim P , Law Tin C , Mok Ngai S , Tsui Ping T , Choy Chi C , Lau Chun L , Lo Ying K , Chu Pui S , Yuen Ho C , Chow Hoi F , Lau Suet T
Published: April 2024

Purpose:
To investigate the relationship between venous access and long-term pacemaker lead failure (PLF)

Methods:
This is a retrospective cohort study. Case records of 409 patients (221 women, mean age 72.2±10.5 years) undergoing pacemaker implantation in 2 hospitals in the period between January 2000 and December 2004 were reviewed. PLF was defined as abnormal impedance and/or high pacing threshold and/or low sensing threshold leading to replacement or abandonment of the lead.

Results:
A total of 682 (274 atrial and 408 ventricular) leads were implanted with contrast-guided axillary vein puncture (AP, 252), subclavian vein puncture (SP, 212) or cephalic vein cutdown (CP, 218). Over a mean follow-up of 73.7±33.2 months, 25 PLF were documented. Three (1.2%) were in AP group, 9 (4.1%) were in CP group and 13 (6.1%) were in the SP group. Using Cox regression, only the use of AP (RR=0.25, 95% CI 0.07-0.92; p=0.037), but not the other variables (age, sex, aetiology of bradycardia, cardiac chamber of lead implantation, lead size, lead material and lead fixation mechanism) was an independent predictor of PLF. With Kaplan-Meier analysis, AP results in significantly less PLF than SP (p=0.013) or CP (p=0.047).

Conclusions:
The use of AP is an independent predictor of PLF. AP results in less PLF than SP or CP.
Abstract 8562: Lower Survival after Drug-eluting Stents than Coronary Artery Bypass Grafting for Unprotected Left Main and/or Multivessel Disease: A Meta-analysis of Randomized Trials and Risk-adjusted Observational Comparative Studies
Authors: Goto Shin-nosuke , Takagi Hisato
Published: April 2024

Backgrounds:
Previous meta-analyses of raw data from randomized trials and observational comparative studies have demonstrated no significant difference in survival between drug-eluting stents (DES) and coronary artery bypass grafting (CABG) for patients with unprotected left main (ULMD) and/or multivesssel disease (MVD) (double-vessel [2VD] and triple-vessel disease [3VD]). Raw data from observational studies, however, are unadjusted and susceptible to confounding.

Methods:
To attempt to control for confounding in observational studies, we performed a meta-analysis of randomized trials and risk-adjusted observational comparative studies (providing adjusted hazard ratios [HRs] using propensity score and/or multivariate Cox proportional hazards regression analyses) of DES versus CABG for survival in patients with ULMD and/or MVD. Study-specific estimates were combined in a random-effects model.

Results:
Our comprehensive search identified 3 randomized trials and 21 risk-adjusted observational comparative studies. Pooled analysis of 32 HRs for all-cause death from all studies (36,574 patients) demonstrated a significantly higher mortality with DES than CABG (HR, 1.22; 95% confidence interval [CI], 1.04-1.42; P=0.01). Exclusion of any single HR from the analysis did not substantively alter the overall results of our analysis. When data were pooled separately in MVD (both 2VD and 3VD)-studies (31,325 patients) and ULMD-studies (4,214 patients), DES were associated with a significantly higher mortality than CABG for MVD (HR, 1.34; 95% CI, 1.11-1.61; P=0.002), not for ULMD (HR, 0.93; 95% CI, 0.69-1.25; P=0.74). Separately pooled analysis of 3VD-studies (14,196 patients) and 2VD-studies (15,137 patients) demonstrated a significantly higher mortality with DES than CABG for 3VD (HR, 1.49; 95% CI, 1.17-1.89; P=0.001), not for 2VD (HR, 1.25; 95% CI, 0.82-1.89; P=0.29).

Conclusions:
The present meta-analysis of randomized trials and risk-adjusted observational comparative studies suggests that DES are associated with lower survival than CABG for high-risk (ULMD and/or MVD) patients, mainly due to lower survival for patients with 3VD.
Abstract 8567: Combination of Active Targeting Erythropoietin-Liposome with Sialyl Lewis X and G-CSF, is Markedly Protective against Ischemia Reperfusion Injury via EPCs Mobilization and Upregulation of p-Akt and p-ERK
Authors: Yamada Yoshihisa , Kobayashi Hiroyuki , Yasuda Shinji , Iwasa Masamitsu , Sumi Shohei , Ushikoshi Hiroaki , Nishigaki Kazuhiko , Takemura Genzou , Fujiwara Takako , Fujiwara Hisayoshi , Minatoguchi Shinya
Published: April 2024

Purpose:
We previously reported that erythropoietin(EPO)-containing nano-size liposome with Sialyl Lewis X (SLX) and G-CSF prevent cardiac remodeling and improve cardiac function, respectively. Then we hypothesized that combination of EPO-liposome with SLX and G-CSF might be more protective against ischemia reperfusion injury than EPO-liposome with SLX or G-CSF alone.

Methods:
Japanese white rabbits (n=40) were subjected to 30-minute coronary occlusion followed by 14 days of reperfusion. Rabbits were administered saline (control group, i.v., n=10), G-CSF (G group, 10μ g/kg/day, i.c., for 5days, n=10), EPO-liposome with SLX (LE group, i.v., 5000IU/ml of EPO, 1ml, n=10), G-CSF + EPO-liposome with SLX (LE+G group, n=10) after reperfusion. Myocardial infarct size was calculated as a percentage of the risk area of the left ventricle. Western blot-analysis examined phosphorylation of Akt and ERK, and expression of E- and P-selectin in the ischemic myocardium at 14days of reperfusion. We also performed fluorescence-activated cell sorter (FACS) analysis of endothelial progenitor cells (EPCs) to evaluate CD34
+
/CXCR4
+
cell mobilization at 7 days after reperfusion.

Results:
The infarct size was significantly smaller in the LE+G group (14.0±2.5%) than in the control group (29.0±5.4%), G group (20.3±5.6%) or LE group (18.7±3.7%). Western blot-analysis showed a higher expression of phosphorylated(p)-Akt and p-ERK and expression of E- and P-selectin in the infarct area of the LE+G group than the others. Serum SDF-1 level at 2 days after reperfusion was higher in the G group and the LE+G group than in the Control group or the LE group. The percentages of CD34
+
/CXCR4
+
cells among total peripheral blood mononuclear cells of G group and LE+G group were higher than the others.

Conclusions:
Combination of post-infarct treatment with G-CSF and EPO-liposome with SLX markedly reduced the infarct size via EPCs mobilization and upregulation of p-Akt and p-ERK in the ischemic myocardium. This combination therapy may provide a new strategy for the treatment of myocardial infarction.
Abstract 8577: Multidisciplinary Care of Patients Receiving Cardiac Resynchronization Therapy Improves Clinical Outcomes
Authors: Altman Robert K , Orencole Mary , Parks Kimberly A , Moore Stephanie A , Park Mi Young , Kumar Prabhat , Deeprasertkul Peerawut , Truong Quynh A , Schlett Christopher L , Lewis Gregory D , Heist E. Kevin , Picard Michael H , Singh Jagmeet P
Published: April 2024

Background:
Although cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with heart failure, a substantial minority of patients do not respond adequately to this therapy. The objective of this study was to examine the impact of a ‘multidisciplinary care approach’ on clinical outcome.

Methods:
The clinical outcome in patients prospectively receiving multidisciplinary care (MC, n=254) was compared with a control group of patients who received conventional care (CC, n=173). The MC group was followed prospectively in an integrated clinic setting by a team of subspecialists from the heart failure, electrophysiology and echocardiography service at 1, 3 and 6 months post-implant. All patients had echocardiographic-guided optimization at their 1-month visit. Proportional hazard models (adjusting for all potential confounders) and Kaplan-Meier estimates for time to first event curves were compared between the 2 groups, over a 2-year follow up. Outcome was measured as a combined endpoint of heart failure hospitalization, cardiac transplantation or all-cause mortality.

Results:
The clinical characteristics between the MC and CC groups at baseline were comparable (age, 68+13 vs. 69+12; NYHA III, 90% vs. 82%; ischemic cardiomyopathy 55% vs. 64%, p=NS, respectively). The event free survival was significantly higher in the multidisciplinary vs. conventional care group (Figure, p=0.0015). A significant reduction in clinical events was noted in the MC versus the CC group ( 0.62, 95%CI 0.47-0.84, p = 0.002) and remained significant after adjustment (HR 0.67, p=0.03).

Conclusion:
Integrated multidisciplinary care improves 2-year event free survival in patients receiving cardiac resynchronization therapy.
Abstract 86: CPR Parameters as Predictors of Return of Spontaneous Circulation Following Inpatient Cardiac Arrest
Authors: Sell Rebecca E , Husa Ruchika D , Ludington Morgan C , Davis Daniel P
Published: April 2024

Background:
The quality of cardiopulmonary resuscitation (CPR) parameters, including chest compression fraction (CCF) and compression depth, appear to be associated with return of spontaneous circulation (ROSC) in out-of-hospital cardiopulmonary arrest (CPA). In addition, end tidal carbon dioxide (EtCO2) may be useful as a marker for ROSC during low flow states such as CPA.

Objective:
To explore the relationship between CCF, compression depth, and EtCO2 for inpatient CPA.

Methods:
This study was conducted in two urban university hospitals. Defibrillator data are exported for analysis following all CPA events. Inpatient medical records were reviewed to determine baseline characteristics and outcomes. CPR data were analyzed in 1-min intervals over the entire CPA resuscitation. The pattern of CCF, compression depth, and EtCO2 were explored in ventricular fibrillation (VF) and non-VF patients and in those with and without ROSC.

Results:
A total of 23 CPAs were analyzed between 5/31/09 and 4/23/11. There were 14 with ROSC and 9 without ROSC. The majority of arrests were non-VF (87%). The mean values were calculated for code duration (13 min), CCF (92%), compression depth (2.8 inches), and EtCO2 (20.3 mm Hg). Code duration was shorter (8.8 vs. 19.8 min) and CCF values higher (93.1% vs. 89.5%) in patients with ROSC. EtCO2 values were higher in VF patients with ROSC (17 vs. 11 mmHg) but not for all rhythms. In addition, terminal EtCO2 values were higher when compared to mean EtCO2 values in ROSC patients than for non-ROSC patients.

Conclusion:
For this small sample of inpatient cardiac arrests, patients with ROSC had shorter code durations, higher CCF values, deeper compressions, and higher terminal EtCO2 values. These data support the importance of optimal CPR in the inpatient setting.
Abstract 8603: Expression of Human Interleukine-37 Protects Mouse Heart Against Ischemic Injury Through Suppression of Monocyte Chemoattractant Protein-1-Mediated Mononuclear Cell Accumulation
Authors: Yousif Nasser G , Li Jilin , Yousif Fadhil , Ao Lihua , Jin Chunhua , Fullerton David A , Dinarello Charles A , Meng Xianzhong
Published: April 2024

Myocardial inflammatory response to ischemia, involving up-regulated chemokine expression and leukocyte accumulation, contributes to the mechanism of myocardial injury and cardiac dysfunction. IL-37 is a new human cytokine and has an anti-inflammatory function. Currently, it is unknown whether IL-37 suppresses myocardial inflammatory response to ischemia. We tested the
hypothesis
that expression of human IL-37 in mouse protects the heart against ischemic injury and LV dysfunction through suppression of the myocardial inflammatory response. The
purposes
of this study were to determine: 1) the effect of expression of human IL-37 transgene on myocardial injury in mice after coronary artery ligation, 2) whether IL-37 suppresses myocardial chemokine expression and leukocyte accumulation following ischemia and 3) whether IL-37 modulates the inflammatory response of cardiac vascular endothelial cells (CVECs) to in vitro pro-inflammatory stimulation.

Methods and results:
IL-37 Tg and WT mice were subjected to left anterior descending coronary artery ligation. In addition, CVECs isolated from IL-37 Tg and WT mice were stimulated with TLR2 and TLR4 agonists. Expression of IL-37 markedly reduced infarct size and improved LV function. The protective effects of IL-37 were associated with reduced IKK phosphorylation, NF-κB intranuclear translocation, MCP-1 production and mononuclear cell accumulation in the ischemic myocardium. In WT mice, neutralization of MCP-1 or MCP-1 KO reduced mononuclear cell accumulation, infarct size and LV function deficit. Further, prior depletion of monocytes resulted in infarct size reduction and LV function improvement in WT mice. In vitro studies in mouse CVECs found that expression of IL-37 suppressed NF-κB activation and MCP-1 production induced by stimulation of TLR2 or TLR4.

Conclusion:
This study demonstrates that IL-37 protects the heart against ischemic injury and LV dysfunction through suppression of MCP-1 production and the resultant mononuclear cell accumulation. These findings suggest that this novel anti-inflammatory cytokine has a therapeutic potential for the regulation of myocardial inflammatory response to ischemia and for protection against ischemic myocardial injury.
Abstract 8621: Factors Associated with Superior Cavopulmonary Connection Timing and Outcomes in Infants with Single Ventricle: A Report from the Pediatric Heart Network's Infant Single Ventricle Trial
Authors: Cnota James , Allen Kerstin , Colan Steven , Covitz Wesley , Graham Eric M , Hehir David , Levine Jami , Margossian Renee , McCrindle Brian , Minich LuAnne , Natarajan Shobha , Richmond Marc , Hsu Daphne ,   Pediatric Heart Network Investigators
Published: April 2024

Background:
Factors that influence the timing of the superior cavopulmonary connection (SCPC) have not been well characterized. Studies identifying outcome predictors following the SCPC are contradictory. This analysis aims to identify factors associated with SCPC timing and surgical outcomes.

Methods:
The Pediatric Heart Network's Infant Single Ventricle trial database was used to identify participants who underwent SCPC. Age at SCPC, length of stay (LOS) and death by age 14 months were evaluated. Potential associated factors included patient demographics, measures from neonatal hospitalization and pre-SCPC visit, SCPC type, and the number of concurrent cardiac surgical procedures. Age at SCPC was analyzed by Cox proportional hazards regression. Natural log LOS was analyzed by multiple linear regression. Models were determined by stepwise selection methods adjusting for clinical site.

Results:
SCPC was performed in 193 subjects at a median age of 5.2 (IQR 4.2, 6.2) months and weight of 5.9 (IQR 5.3, 6.6) kg. Median LOS was 7 days (IQR 6, 10). There were 3 early deaths (during hospitalization) and 3 late deaths (between SCPC discharge and final 14 month study visit). Factors independently associated with age at SCPC and log LOS include: Other commonly cited factors including type of SCPC, valve regurgitation, ventricular ejection fraction and ventricular end-diastolic pressure were not independently associated with age at SCPC or log LOS.

Conclusions:
Significant variation among centers, independent of patient factors, highlights the controversy about optimal timing of SCPC. Earlier timing appears to be associated with case complexity and interim morbidities. Factors associated with LOS may offer insights for improving pre-SCPC care and surgical outcome. The risks and benefits of elective SCPC at younger age require further study.
Abstract 8648: Human Macrophage Regulation via Interaction with Pericardial Adipose Tissue-Derived Mesenchymal Stromal Cells
Authors: Adutler-Lieber Shimrit , Ben-Mordechai Tamar , Naftali-Shani Nili , Asher Elad , Loberman Dan , Itzhaki-Alfia Ayelet , Raanani Ehud , Leor Jonathan
Published: April 2024

Background:
While mesenchymal stromal cells (MSCs) were found to improve tissue repair, their mechanism of action is not fully understood. We aimed to test the hypothesis that MSCs may act via macrophages and that specifically, human pericardial adipose tissue-derived MSCs can polarize human macrophages into reparative, anti-inflammatory (M2)-like phenotype.

Methods and Results:
MSCs were isolated and expanded from pericardial adipose tissue of patients undergoing cardiac surgery. Monocytes isolated from human blood using Ficoll and MACS positive selection of CD14+ cells were cultured 5-7 days, washed, and co-cultured with MSCs 1-14 days directly or through a transwell membrane restricting cell contact. Supernatant was collected on different days for cytokine analysis by ELISA. M2 macrophage markers (CD206, CD163 and CD16) and phagocytic ability of fluorescent latex beads were examined using flow cytometry. We found that human MSCs increased the percentage of macrophages expressing alternative macrophage (M2) markers CD206+CD163+ (1.5 fold) and CD16+ (9 fold). MSCs also increased macrophage secretion of anti-inflammatory and reparative cytokines IL-10 (Fig; 9 fold, p<0.001), VEGF (3 fold, p<0.01), IL-13 (2 fold, p<0.05) and IL-4 (2 fold, P<0.05), and decreased IL-1 (2 fold, p<0.01), TNF-α (1.5 fold, p<0.001), IL-12 (1.5 fold, p<0.001), IL-17 (3 fold, p<0.001), IL-23 (16 fold, p<0.01) and IFN-γ (2 fold, p<0.001). In addition, co-culturing induced a star-shaped morphology of macrophages and decreased their phagocytic ability (2 fold).

Conclusions:
Our findings suggest, for the first time, that human pericardial adipose tissue-derived MSCs can polarize human macrophages towards anti-inflammatory, reparative phenotype. Our findings could be relevant for the mechanism of atherosclerosis and the development of novel immune-modulation therapy for the treatment of MI, atherosclerosis and other inflammatory diseases.
Abstract 8696: Assessment of Time-Left Atrial Volume Curve and Left Atrial Emptying Function by Speckle Tracking Echocardiography is Useful to Evaluate Left Ventricular Diastolic Function in Patients with Preserved Ejection Fraction
Authors: Fujii Tomoko , Tanaka Ryuhei , Ono Koji , Watanabe Takatomo , Nagaya Maki , Onishi Noriyuki , Matsuoka Reiko , Tokoro Fumitaka , Abe Shintaro , Goto Yoshiaki , Yoshizane Takashi , Kato Takashi , Warita Syunichiro , Kojima Tai , Iwama Makoto , Hirose Takeshi , Tanihata Shintaro , Noda Toshiyuki , Iida Mami , Watanabe Sachiro , Kawasaki Masanori , Minatoguchi Shinya
Published: April 2024

Background:
Left atrial (LA) volume is proposed to evaluate left ventricular (LV) filling pressure and E/e' is used to estimate LV diastolic function instead of invasive measurement. However, it is difficult to measure LA volume accurately and quickly using routine echocardiography and E/e' from 8 to 15 is classified as a gray zone to estimate LV filling pressure. Thus, we assessed the hypothesis that evaluation of time-LA volume curve and LA emptying function (EF) measured by speckle tracking may be more useful to estimate LV diastolic function as a noninvasive method in the clinical settings than E/e' .

Methods
: LA phasic volume and EF were measured in 34 patients (age 69±8, 14 men) with LV ejection fraction ≥50% by speckle tracking echocardiography that can provide time-LA volume curve automatically, and E/e' was also obtained just before cardiac catheterization, and these parameters were compared with pulmonary capillary wedge pressure (PCWP).

Results
: LA max. and min. volume had significant positive correlations with PCWP (r=0.72, P<0.01 and r=0.80, P<0.01, respectively). LA total, passive and active EF had significant negative correlations with PCWP (r=-0.82, p<0.01, r=-0.56, p<0.05 and r=-0.66, P<0.01, respectively). There was a significant but weak positive correlation between E/e' and PCWP (r=0.52, p<0.05). As PCWP was elevated, LA max. and min. volume were increased and pre-atrial contraction volume was closer to min. volume, and total and active EF were decreased (Figure). Using 33% of LA total EF as a cutoff, the sensitivity and the specificity in predicting elevated LV filling pressure >12mmHg were 89% and 88%, while using 15 of E/e' those values were 53% and 79%, using 40ml/m
2
of LA volume those values were 48% and 82%.

Conclusions
: In noninvasive estimation of LV diastolic function, assessment of time-LA volume curve and LA EF may be a novel and more useful method and have an incremental value compared with measurement of LA volume and E/e' in the clinical settings .
Abstract 8717: A Significant Reduction in Air Kerma with A Simple Radiation Quality Initiative
Authors: Prabhu William , Mueller Enkhtuyaa L , Dauerman Harold , Gogo Prospero B
Published: April 2024

Background:
Minimizing exposure to ionizing radiation in the cardiac catheterization laboratory reduces the risk of both deterministic and stochastic injury to patients as well as lab personnel. We hypothesize that a Radiation Quality Improvement (RQI) program of education and feedback could modify operator behavior to decrease radiation use.

Methods:
We performed a single center prospective registry from March 2010 to March 2011 incorporating all consecutive coronary diagnostic and interventional procedures. Both air kerma (AK) and fluoroscopic time (FT) values were documented. RQI consisted of mandatory physician training of all staff and operators with 2 follow up educational sessions. Intervention included a mandatory warning system for excessive FT (>25min) during procedures as well as regular e-mail tips on c-arm settings associated with lower radiation use. Feedback tools were developed to provide quarterly individual operator FT and AK. We compared the use of radiation in the 4 month period before and the 6 month period after RQI.

Results:
A total of 1,838 patients were enrolled across 9 PCI operators. Pre-RQI (N=704) and Post-RQI (N=1,134) procedures were similar in terms of indication, clinical characteristics, level of urgency and operator representation. FT per case was similar pre and post RQI: 9.98±0.70 min vs. 10.48±0.53 min; p=0.26. There was a significant decrease in the average AK per case (1652±116 mGy vs. 1515±78 mGy, p=0.047). There was heterogeneity in the response to our intervention amongst the operators (p=0.001 for the interaction) but no heterogeneity in response based on diagnostic versus interventional cases.

Conclusions:
Radiation quality improvement is feasible and an intervention consisting of physician/staff education and rapid individualized feedback significantly reduces the use of radiation in the cardiac catheterization laboratory. This simple intervention has potential to improve patient and lab personnel safety.
Abstract 8728: Nitric Oxide Delivery During Cardiopulmonary Bypass Reduces Postoperative Morbidity in Children - A Randomized Trial
Authors: Checchia Paul A , Muenzer Jared , Bronicki Ronald , Raithel Steven , Dixon David , Gandhi Sanjiv , Huddleston Charles
Published: April 2024

Background:
Cardiac surgery leads to reperfusion injury and endothelial dysfunction causing fluid retention, coagulopathy, and myocardial dysfunction. Gaseous nitric oxide (gNO) has been demonstrated to have a myocardial protective effect and anti-reperfusion properties. We hypothesized that gNO administration during CPB would have similar beneficial effects.

Methods:
A prospective, randomized, blinded, placebo controlled study in which children undergoing repair of Tetralogy of Fallot received either 20 ppm of gNO or placebo delivered to the membrane oxygenator during CPB.

Results:
16 children consented and randomized into 2 equal groups. There were no differences in age, cross clamp time, CPB time, or methemoglobin. The NO group had a shorter time on vent (8.4 +/- 7.6 vs 16.3 +/- 6.5 hrs, p<0.05) and CICU LOS (53.8 +/- 19.7 vs 79.4 +/- 37.7 hrs, p=0.05). The NO group had lower troponin values at 12, 24, and 48 hours (p<0.05) and lower BNP at 12 and 24 hours (p<0.05) (graphs). There was a trend toward less positive fluid balance in the first 48hrs post op (+187mL vs +317mL) with significantly less diuretic usage (1.6 +/- 0.9 vs 4.0 +/- 1.0 of furosemide, and 0 vs 6.3 +/- 7.4 of chlorothiazide, both mean total dose (mg/kg) in first 48 hrs, both p<0.05). NO patients had a higher mean Hgb at 48 hrs (11.8 vs 9.8, p<0.05) despite no differences in chest tube output, PRBC transfusion, platelet counts or transfusion, FFP transfusion, or pT/pTT in the first 48hrs. There were no differences in IL6, IL8, TNF, or lactate.

Conclusions:
The delivery of gNO to the CPB circuit in children undergoing cardiac surgery results in myocardial protection, improved fluid balance, and improved postoperative ICU course.
Abstract 8734: The Utility of Troponin I in Two Cohorts of Cardiac Patients: Implications for Clinical Practice
Authors: Sayeed Sameer , Petrini Joann R , Copen David
Published: April 2024

Background:
Minor elevations in troponin I are common among patients with chronic coronary artery disease (CAD) and those with new supraventricular tachyarrhythmia (SVT). These troponin I elevations are often attributed to an acute coronary syndrome (ACS). However, minor elevations in troponin I may be present for other reasons, such as demand ischemia. Our aim was to observe the prevalence of troponin I elevations in patients with: 1) new onset atrial fibrillation (A-fib), flutter (A-flutter) or SVT and 2) known CAD following exercise, and to assess the hypothesis that troponin I elevations in these settings would not be indicative of ACS.

Methods:
This study included two components. First, a retrospective review of 740 charts of patients with new onset A-fib, A-flutter or ectopic SVT presenting to the Danbury Hospital Emergency Department between July 2009 and July 2010. Excluded were 45 patients with symptoms and EKG changes indicating ACS on admission. Second, a separate sample of 75 patients with known CAD presenting to the Danbury Hospital Cardiology Clinic for follow-up imaging stress tests were recruited. Eligible patients underwent a stress test and perfusion imaging and had one troponin I sample drawn prior to the stress test and a second at the completion of all imaging four hours later.

Results:
Among patients with new A-fib, A-flutter and SVT, 31.9% had minor elevations in troponin I levels (values ranged from 0.05-1.0 ng/mL). In those with elevation, 64% had no documented CAD. In addition, for those with elevation, 78.4% had new onset A-fib, 11.3% had new onset A-flutter and 10.4% had new onset SVT. In the separate cohort of patients with CAD who underwent stress testing, 38.7% had troponin elevation following exercise. A total of 50.7% of these patients had no evidence of ischemia by EKG and perfusion and 54.7% had a Duke Treadmill score greater than or equal to 5.

Conclusion:
For patients with chronic CAD subject to physical stress or those with new onset A-fib, flutter or SVT, small elevations in troponin I are fairly common, and often do not indicate ACS. In a cost containment environment, expensive therapy and testing of these patients may be unnecessary.
Abstract 8742: Deletion of CIKS (Act1 or traf3ip2) Abrogates Angiotensin-II-induced Cardiac Hypertrophy
in vitro
and
in vivo
Authors: Shanmugam Prakashsrinivas , Valente Anthony J , Delafontaine Laurent , Gardner Jason D , Siebenlist Ulrich , Chandrasekar Bysani
Published: April 2024

Chronic elevation of Angiotensin-II (Ang-II) can lead to cardiac hypertrophy and heart failure. Ang-II activates NF-κB and AP-1, and induces pro-inflammatory cytokines and pro-growth factors. The adapter molecule CIKS (connection to IKK and SAPK/JNK; also known as Act1 or traf3ip2) lies upstream of IKK and JNK, and mediates both autoimmune and inflammatory diseases. We hypothesized that CIKS plays a causal role in Ang-II-induced cardiac hypertrophy. The heart and body weights were similar in both wild type (WT; C57Bl/6) and CIKS null mice (C57Bl6 background). However, continuous infusion of Ang-II (1.5 μg/kg/min for 7 days; n=8/group) led to cardiac hypertrophy (heart wt/tibial length, 38% increase
vs
saline,
P
<0.01) and upregulation of CIKS mRNA (2-fold,
P
<0.05) and protein (3.1-fold,
P
<0.01) in WT, but not CIKS null mice (
P
<0.001 vs WT+Ang-II). Ang-II increased heart rate and systolic blood pressure in both, but levels trended higher in the CIKS null (not significant). Ang-II increased NF-κB and AP-1 DNA binding activities, and induced ANP, cytokine (TNF-α, IL-18), growth factor (WISP1), and MMP (MMP-2, -9, and -14) expression/activity in WT, but not CIKS null mice. Ang-II treatment of adult cardiomyocytes from WT resulted in significant hypertrophy (increased cell surface area and protein without DNA synthesis; both at least
P
<0.01), PI3K, Akt, p70
S6K
and ribosomal S6 protein activation, and ANP, TNF-α, IL-18, WISP1, and MMPs expression. Moreover, Ang-II induced CIKS mRNA (at 1 h, 5.1-fold,
P
<0.001) and protein (at 2 h, 3.78-fold,
P
<0.01) in a time- and dose-dependent manner. Importantly, CIKS knockdown (lentiviral shRNA) blunted Ang-II induced IKKβ and JNK activities, p65 and c-Jun phosphorylation, and NF-κB and AP-1 DNA binding and reporter gene activities, cytokine, WISP1, and MMPs in WT-cardiomyocytes. These results were recapitulated in CIKS null cardiomyocytes. Our results demonstrate that CIKS plays a critical role in Ang-II-mediated cardiac hypertrophy
in vivo
and cardiomyocyte hypertrophy
in vitro
thorough induction of IKK/NF-κB and JNK/AP-1-dependent cytokine, growth factor, and MMP expression. CIKS is a potential therapeutic target in cardiac hypertrophy and congestive heart failure.
Abstract 8771: Asialoerythropoietin, a Nonerythropoietic Derivative of Erythropoietin, Displays Broad Anti-Heart Failure Activity
Authors: Takeyama Toshiaki , Takemura Genzou , Kanamori Hiromitsu , Ogino Atsushi , Kawaguchi Tomonori , Watanabe Takatomo , Morishita Kentaro , Tsujimoto Akiko , Goto Kazuko , Fujiwara Takako , Fujiwara Hisayoshi , Minatoguchi Shinya
Published: April 2024

Accumulating evidence suggests cardioprotective effect of erythropoietion (EPO) in experiments, but EPO has some unwanted effects. We investigated effect of asialoerythropoietin (AEPO), a nonerythrogenic derivative of EPO, on 3 different models of heart failure: doxorubicin (DOX)-induced cardiomyopathy, post-large myocardial infarction (MI), and dilated cardiomyopathy in δ-sarcoglycan deficient mouse (Sgcd-null). Accoding to echocardiography and cardiac catheterization, a single intraperitoneal injection of DOX (15 mg/kg) induced an established heart failure in mice 2 weeks later, to which AEPO (1500 U/kg, twice a week, for 2 weeks) was administered. Left ventricular dysfunction was attenuated in the AEPO-treated group (ejection fraction: 71±3% vs. 50±1% in controls). The AEPO-treated heart showed less myocardial fibrosis, inflammatory cell infiltration, and atrophic degeneration of cardiomyocytes accompanying restored expression of GATA-4 and sarcomeric proteins. Among downstream signals of EPO receptor, DOX inactivated ERK in the heart, of which activity AEPO restored. Next, in the mice with large sized, 6-week-old MI, a marked left ventricular dysfunction with adverse remodeling was apparent. AEPO treatment for the subsequent 4 weeks mitigated the further progression of dysfunction and remodeling (ejection fraction: 37±2% vs. 26±3% in controls), accompanying reduced myocardial fibrosis. ERK and Akt were activated in the MI bearing hearts, which were furthermore augmented by AEPO. AEPO activated STAT3, too. Finally, AEPO was administered to 25 weeks old Sgcd-null mice with decreased left ventricular contractility, for the subsequent 5 weeks. Left ventricular dysfunction and dilatation were mitigated (ejection fraction: 71±1% vs. 52±0.4% in controls), accompanying reduced myocardial fibrosis and furthermore compensative hypertrophy. ERK was inactivated, and Akt was activated in the heart of Sgcd null mice. AEPO restored the ERK activity, and furthermore activated Akt. Neither polycythemia nor splenomegaly was noted in any groups. In conclusion, AEPO displays broad anti-heart failure activity regardless of the etiology of heart failure through distinct molecular signals.
Abstract 8791: Novel ECG Criteria Identifying Posteroseptal Right Ventricular Outflow Tract Arrhythmia
Authors: Sasaoka Taro , Hachiya Hitoshi , Nakamura Tomofumi , Sugiyama Koji , Yagishita Atsuhiko , Tanaka Yasuaki , Sasano Tetsuro , Kawabata Mihoko , Hirao Kenzo , Isobe Mitsuaki
Published: April 2024

Background:
Some studies have shown ECG characteristics of outflow tract ventricular arrhythmia (OT-VA), however, most of the studies mainly focused on prediction of LVOT or RVOT origin. The detail of 12-lead ECG characteristics of septal right ventricular outflow tract arrhythmia (RVOT-VA) remains unknown.

Purpose:
The purpose of this study is to elucidate the predictability of the site of origin in septal RVOT-VA by 12-lead ECG characteristics.

Method:
A total of 56 consecutive patients underwent radiofrequency catheter ablation (RFCA) in our institution from 2006 to 2009. Among them, 32 patients (59%) with septal RVOT-VA were retrospectively reviewed. They were divided into 3 groups according to the ablation success site, anteroseptal RVOT (Group A, n=9), posteroseptal RVOT (Group P, n=9), and midseptal RVOT (Group M, n=14).

Result:
Baseline characteristics such as age, sex, etc. did not show significant difference in each group. Compared with other groups, Group P showed significantly higher rate of R or rS pattern in lead I (Group P: 100%, Group A: 11%, Group M:36%, p<0.0001). Existence of r-wave (>0.1mV) in V1 was recognized more frequently in Group P than Group A and Group M (89%, 33%, 50%, respectively, p<0.05). Also, the ratio of V1/V2 Q-wave amplitude was significantly higher in Group P (0.75, 0.51, 0.58, p<0.01). We could predict the site of origin was posteroseptal RVOT if the 12-lead ECG met those 3 criteria of R or rS pattern in lead I, existence of r-wave (>0.1mV) in V1, and ratio of V1/V2 > 0.6 (sensitivity 89%, specificity 100%).

Conclusion:
In this study, we could predict the posteroseptal RVOT origin among septal RVOT-VAs if the 12-lead ECG satisfied these 3 criteria (
Figure
).
Abstract 8811: Pheochromocytoma Cardiomyopathy: The Extreme Effect of Catecholamines on the Heart
Authors: Gupta Rajat M , Desai Akshay S
Published: April 2024

A previously healthy 19-year-old man was admitted with nausea, vomiting and labile blood pressures after several months of headaches and palpitations. Though normotensive on presentation, his blood pressure rose to 240/160 mmHg after administration of IV metoclopramide. He then developed dyspnea, acute pulmonary edema, and became hypotensive. Echocardiogram revealed an LV ejection fraction of 10% without cavity dilation. Coronary angiography revealed no coronary artery disease, and ventriculography revealed no regional wall motion abnormalities or apical ballooning. Given the concern for myocarditis, an RV endomyocardial biopsy was performed, which revealed necrotic myocytes, but no inflammatory infiltrate. CT scan of the abdomen revealed a 4.0 x 3.5 cm mass within the right adrenal gland and plasma normetanephrine levels were markedly elevated at 28.8 nmol/L. In the context of a presumptive diagnosis of pheochromocytoma complicated by catecholaminergic cardiomyopathy, plans were made for surgical resection of the tumor following alpha-adrenergic blockade. Continued hypotension prompted urgent implantation of a percutaneous ventricular assist device (pVAD). With pVAD support, hemodynamics improved over 2 weeks, serial echocardiograms showed improvement in LV ejection fraction to 60%, and laparoscopic removal of the adrenal mass was safely undertaken. Pathology confirmed a pheochromocytoma. Pheochromocytoma-induced cardiogenic shock is a rare syndrome described after adrenergic storm triggered by mechanical compression, tumor hemorrhage, or administration of dopaminergic agonists, such as metoclopromide in this case. The pathophysiology of acute myocardial stunning during catecholamine surge remains unclear. Postulated mechanisms include coronary vasospasm, direct toxic effects of catecholamines on cardiomyocytes, and a newly proposed hypothesis of Gi-receptor-coupled catecholamine signaling (stimulus trafficking). Our patient illustrates that the inhibitory effects of catecholamine excess on myocardial function may be reversible with early clinical recognition, aggressive hemodynamic support, appropriate pre-operative preparation, and surgical resection by a specialized team.
Abstract 8816: Comparison of Prognostic Values of Contemporary Contrast-Induced Nephropathy Definitions in Patients with Acute Myocardial Infarction Undergoing Emergency Coronary Angiography
Authors: Kiyokuni Masayoshi , Kosuge Masami , Endo Tsutomu , Ebina Toshiaki , Hibi Kiyoshi , Tsukahara Kengo , Iwahashi Noriaki , Endo Mitsuaki , Maejima Nobuhiko , Umemura Satoshi , Kimura Kazuo
Published: April 2024

Background:
Previous studies have shown that contrast-induced nephropathy (CIN) defined in several ways is associated with poor outcomes. However, there is no consensus on the optimal definition of CIN. Objective: We examined the prognostic significance of 3 contemporary definitions of CIN with respect to long-term major adverse cardiac and cerebrovascular event (MACCE) and mortality after emergency coronary angiography for acute myocardial infarction (AMI).

Methods:
We measured serum creatinine (SCr) at admission and each day for the following 3 days in 733 patients with AMI who underwent emergency coronary angiography within 12 h after symptom onset. CIN was defined as SCr increase ≥0.5 mg/dl, SCr increase ≥25%, or estimated glomerular filtration rate (eGFR) decrease ≥25%.

Results:
Of 733 patients (age 64 ± 12 years), 47% were anterior AMI, 31% had renal dysfunction defined as admission eGFR <60 ml/min/1.73m2, and 81% underwent primary percutaneous coronary intervention. The mean volume of contrast medium used was 155 ± 57 ml. The incidence of CIN ranged widely depending on the definition used; 7.8% (SCr increase ≥0.5 mg/dl), 37.4% (SCr increase ≥ 25%), and 29.2% (eGFR decrease ≥ 25%). There were significant differences of 5-year MACCE (all-cause death, non-fatal myocardial infarction, or stroke) and all-cause mortality between patients with and without CIN by the 3 definitions (especially SCr increase ≥0.5 mg/dl). In multivariate analysis, only SCr increase ≥0.5 mg/dl was independently and significantly associated with 5-year MACCE and all-cause mortality; but the other 2 definitions were not.

Conclusions:
In patients with AMI undergoing emergency coronary angiography, of the 3 contemporary definitions of CIN, only SCr increase ≥0.5 mg/dl strongly predicts 5-year adverse outcomes, suggesting the prognostic importance of this definition.
Abstract 8823: Abnormal Cardiac Innervation in Ventricular Fibrillation Patients with and Without Brugada Syndrome
Authors: Nakano Yukiko , Oda Noboru , Suenari Kazuyoshi , Makita Yuko , Kajihara Kenta , Sairaku Akinori , Tokuyama Takenori , Motoda Chikaaki , Fujiwara Mai , Toshitaka Iwasaki , Watanabe Yoshikazu , Yamazato Ryo , Sumida Hiroomi , Kihara Yasuki
Published: April 2024

Abnormal cardiac innervation in patients with ventricular fibrillation (VF) has been reported. We investigated autonomic function in 48 successfully resuscitated VF patients using heart rate variability (HRV) as measured by Holter ECG and
123
I-metaiodobenzylguanidine (
123
I-MIBG) scintigraphy. Eight patients were excluded because of hypertrophic cardiomyopathy (N = 2), arrhythmogenic right ventricular cardiomyopathy (N = 3), catecholamine-sensitive ventricular tachycardia (N = 1), and long QT syndrome (N = 2). Patients who could not discontinue internal remedies (N = 5) were also excluded. Fifteen patients (42 ± 14 years, 15 males) were diagnosed with Brugada syndrome (BS), and the remaining 20 patients (47 ± 6 years, 8 males) were diagnosed with idiopathic VF (IVF). QTc time was longer in the IVF patients than in the BS patients (450.1 ± 10.1 ms vs. 389.4 ± 21.0 ms, P < 0.05). RMS40 was lower in the BS patients than in the IVF patients (13.9 ± 2.2 mV vs. 20.9 ± 3.6 mV, P < 0.05). Parameters of HRV were similar in both groups, but abnormal circadian variations of HRV were observed in 53.3% of BS patients and 13.3% of IVF patients. The washout ratio was higher in the IVF patients than in the BS patients (36.3 ± 4.3 vs. 26.0 ± 2.1). The
123
I-MIBG uptake was increased in lateral regions in BS patients. Regionally reduced
123
I-MIBG uptake was observed with many variations in all patients, but no significant difference was observed between groups. These results demonstrated impairment of sympathetic innervation or enhanced activity of the sympathetic nervous system in patients with VF, particularly indicating sympathetic hypertonia in IVF and imbalance of circadian HRV in BS. These findings may have an impact on the arrhythmogenesis of such patients.
Abstract 8837: Markers of Extracellular Matrix Turnover and the Development of Right Ventricular Failure After Ventricular Assist Device Implantation in Patients with Advanced Heart Failure
Authors: Kato Tomoko S , Chokshi Aalap , Singh Parvati , Khawaja Tuba , Cheema Faisal , Yang Jonathan , Takayama Hiroo , Naka Yoshifumi , Farr Maryjane , Mancini Donna , Schulze P. Christian
Published: April 2024

Background.
The development of right ventricular failure (RVF) is one of major causes of morbidity and mortality of patients following LVAD placement. The cardiac extracellular matrix (ECM) is a dynamic and metabolically active collagenous network that responds to mechanical strain.

Hypothesis.
We assessed the hypothesis that there would be an association between ECM turnover and development of RVF after LVAD implantation in patients with advanced heart failure (HF).

Methods.
Circulating levels of osteopontin (OPN), metalloproteinases (MMP)-2 and -9 and tissue inhibitor of MMP (TIMP)-1 and -4 were measured in 61 patients at the time of LVAD implantation and explantation. Serum ECM markers were also measured in 10 normal control subjects. RVF was defined as the need for right ventricular assist device, nitric oxide inhalation>48 hours and/or inotropic support >14 days or re-starting after 14 days.

Results.
All ECM markers were elevated in patients with HF compared to controls (all p<0.05). 23 patients (37.7%) developed RVF on LVAD support. All ECM markers decreased on LVAD support in patients without RVF (all p<0.05), but serum MMP-2, TIMP-1 and -4 and OPN remained elevated in patients with RVF. Post-LVAD OPN and TIMP-1 was higher in patients with RVH than those without RVF (316.4±84.6 vs. 202.4±69.1 ng/mL, p<0.01, 210.7±62.4 vs. 164.3±45.2, p<0.01, respectively). Multivariate analysis showed right ventricular stroke work index (RVSWI) [odds ratio (OR) 0.41, 95%confidence interval (CI) 0.207-0.670, p<0.01], pre-LVAD circulating BNP (OR 1.02, 95%CI 1.00-1.04, p<0.05) and OPN (OR 1.32, 95%CI, 1.01-1.61, p<0.05) were significantly associated with RVF. OPN correlated inversely with RVSWI (r=-0.44, p<0.001). OPN levels of >260 ng/mL could discriminate patients developing RVF from those without RVF (83% sensitivity and 82% specificity).

Conclusions.
Elevated levels of OPN before LVAD placement are associated with the development of RVF. Persistent elevation of circulating ECM markers after LVAD implantation characterizes patients who develop RVF. These novel biomarkers would have a potential role in the pathogenesis of RVF development in patients undergoing LVAD implantation.
Abstract 8839: Acute Heart Failure: Canadian Perspectives from an RCT and a Registry
Authors: Ezekowitz Justin A , Virani Sean , Leader Rolland , White Michael , Zieroth Shelley , Delgado Diego , Proulx Guy , Hu Jia , Hernandez Adrian F , Westerhout Cynthia M , O'Connor Christopher M , Armstrong Paul W
Published: April 2024

Background/Objectives:
Randomized controlled trials (RCT) are limited by their generalizability to the broader non-trial population. The recently completed ASCEND-HF RCT provides the first substantive evaluation of care patterns in Canadian patients with acute heart failure (AHF). In order to provide a context for this RCT we designed a complementary registry at the same RCT sites to characterize practice patterns, baseline characteristics and in-hospital outcomes.

Methods:
Patients with a principal diagnosis of AHF (ICD-9-CM 402 and 428; ICD-10 I50.x, I11.0, I13.0, I13.2) admitted to 7 hospitals participating in ASCEND-HF (n=697 patients, 2007 to 2010; total of 57 one-month sampling periods) were evaluated and compared to ASCEND-HF RCT patients (n=465, 31 sites, 2007 to 2010). Key inclusion criteria for ASCEND-HF were signs and symptoms of HF, <24 hours from admission to emergency or acute care, and if known, and elevated BNP or LVEF<40%. Values are medians with interquartile range (IQR).

Results:
Patients in the Registry were older, more likely female and have chronic respiratory disease, less likely to have diabetes, and had a similar incidence of ischemic HF, atrial fibrillation and similar BNP levels.(See Table) Median systolic BP and LVEF was higher in Registry vs. RCT patients. Although Registry patients arrived more often via ambulance, they had longer time from triage to 1
st
physician consult but a similar total length of stay as RCT patients. In-hospital mortality was much higher in the Registry compared to the RCT patients: 9.3% vs. 1.3%, p<0.001.

Conclusions:
Patients in a large RCT are typically younger but have a lower LVEF compared with the patients in a Registry from the same Canadian sites. Despite this, the observed in-hospital mortality is higher in unselected Registry as compared to RCT patients highlighting the need for novel strategies applicable to a generalizable AHF population to improve clinical outcomes.
Abstract 8880: Senescence Marker Protein 30 Inhibits Angiotensin II-induced Cardiac Remodeling
Authors: Misaka Tomofumi , Suzuki Satoshi , Miyata Makiko , Kobayashi Atsushi , Saitoh Shu-ichi , Takeishi Yasuchika
Published: April 2024

Backgrounds:
Aging is a major risk factor of cardiovascular diseases including heart failure. Senescence marker protein 30 (SMP30) is originally identified as an important aging marker protein, which the expression decreases androgen-independently with aging. SMP30 may act as an anti-aging factor in various organs, but the functional role of SMP30 in the heart has not been investigated.

Purpose:
We tested the hypothesis that SMP30 functions as cardio-protective by anti-aging effects in angiotensin II (Ang II) -induced cardiac remodeling.

Methods and Results:
SMP30 knockout mice (KO) and wild-type mice (WT) were subjected to continuous Ang II infusion (800 ng/kg/min). After 14 days, the extent of cardiac hypertrophy and myocardial fibrosis were significantly higher in SMP30 KO mice than in WT mice (P<0.01, respectively). Echocardiography revealed that SMP30 KO mice had more severely impaired systolic and diastolic function with remarkably enlarged left ventricular dimension compared to WT mice (Table). Generation of reactive oxygen species related with activation of NADPH oxidase was greater in SMP30 KO mice than in WT mice (P<0.01). The numbers of TUNEL positive nuclei were markedly increased in SMP30 KO mice compared to WT mice (P<0.01). In addition, activation of signaling pathways leading to apoptosis such as increases in caspase-3 activity, Bax/Bcl-2 ratio and phosphorylation of c-Jun N-terminal kinase were observed in SMP30 KO mice compared with WT mice (P<0.01, for each). The numbers of senescence-associated β-galactosidase-positive cardiomyocytes were increased via upregulation of p21 gene expression in SMP30 KO mice compared to WT mice (P<0.01).

Conclusions:
This study demonstrates the first evidence that deficiency of SMP30 exacerbates Ang II-induced cardiac hypertrophy, dysfunction and remodeling. These findings suggest that SMP30 has a cardio-protective role as anti-aging factor by anti-oxidative and anti-apoptotic effects in the heart.