bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 232: Out-of-Hospital Airway Management and Cardiac Arrest Outcomes: A Propensity Score Matched Analysis
Authors: Shin Sang Do , Ahn Ki Ok , Song Kyoung Jun , Park Chang Bae , Lee Eui Jung
Published: April 2024

Objective:
This study aimed to determine whether EMT-intermediate ETI or LMA comparing with bag-valve mask ventilation is associated with improved OHCA outcomes in Korea.

Methods:
We used a Korean national OHCA cohort database composed of hospital and ambulance data. We included all EMS-treated OHCA with presumed cardiac etiology for the period Jan. 2006 to Dec. 2008. We excluded cases not receiving continued resuscitation in the emergency department (ED), as well as those without available hospital outcome data. The primary exposure was airway management technique during ambulance transport (endotracheal tube (ETI), laryngeal mask airway (LMA) or bag-valve-mask (BVM)). The primary outcomes were survival to admission and hospital discharge. We compared outcomes between each airway management group using multivariable logistic regression, adjusting for sex, age, witnessed, prehospital defibrillation, bystander cardiopulmonary resuscitation (CPR), call to ambulance arrival time to the scene, call to ambulance arrival time to ED, initial ECG, metropolitan, and level of ED. We repeated the analysis using propensity-score matched subsets.

Results:
Of 54,496 patients with OHCA, we included 5,278 (9.7%). Overall survival to admission and to discharge was 20.2% and 6.9%, respectively. ETI and LMA was performed in 250 (4.7%) and 391 (7.4%), respectively. In the full multivariable models using total patients, adjusted survival to admission and discharge were similar for ETI and BVM; OR 0.91 (0.66-1.27) and 1.00 (0.60-1.66), respectively. Adjusted survival to admission and discharge were significantly lower in LMA than BVM: OR 0.72 (0.54-0.95) and 0.52 (0.32-0.85), respectively. In the full multivariable models using propensity matched samples, adjusted survival to admission and discharge were similar for ETI and BVM; OR 1.32 (0.81-2.16) and 1.44 (0.66-3.15), respectively. Adjusted survival to admission was similar for LMA and BVM: OR 0.72 (0.50-1.02). However, survival to discharge was significantly lower for LMA than BVM: OR 0.45(0.25- 0.82).

Conclusions:
In Korea, EMT-I placed LMA during ambulance transport was associated with worsened OHCA survival to discharge than BVM. Outcomes were similar between EMT-I ETI and BVM ventilation.
Abstract 244: A Prospective Randomized Study of the Efficacy of Rectilinear and Truncated Exponential Biphasic Waveforms in the Elective Cardioversion of Atrial Fibrillation
Authors: Deakin Charles D , Connelly Stephanie , Yuen Brian
Published: April 2024

INTRODUCTION:
Several different biphasic waveforms are now available for clinical use. Few studies have compared differences in the efficacy of these waveforms. We compared biphasic rectilinear (BR) and biphasic truncated exponential (BTE) waveforms in their efficacy to cardiovert patients undergoing elective cardioversion for atrial fibrillation.

METHODS:
In a prospective randomised study, sequential adult patients undergoing elective cardioversion for atrial fibrillation were recruited. Patients were randomised to receive synchronised defibrillation using either a BR or BTE waveform, both using a 50J, 100J, 150J, 200J, 200J selected energy escalating protocol. Successful cardioversion was defined as a return to sinus rhythm immediately after a given shock. Failure to cardiovert after a second 200J shock was classed as failed defibrillation. The power of this study was 80% with 5% significance level to detect a difference of 20% or greater between groups. Survival analysis was used to assess the total energy delivered (and number of shocks) to achieve successful cardioversion between groups.

RESULTS:
A total of 202 patients were recruited over a four-year period, of which data was complete for 199 (100 BR waveform; 99 BTE waveform). There was no major difference in demographic data (Median age; BR 65.5 yrs, BTE 68.0 yrs: Median weight; BR 90.2 kg, BTE 88.9 kg; Median duration of AF; BR 7.0 months, BTE 6.0 months: Amiodarone; BT 23.8%, BTE 18.2%). Cardioversion rates and associated energy delivered are shown below. Median number of shocks to achieve cardioversion was 2 for the BR waveform and 3 for the BTE waveform (Log rank test, P=0.059).

CONCLUSIONS:
BR and BTE waveforms show similar efficacy in the elective cardioversion of atrial fibrillation.
Abstract 246: The Impact of ECG Filtration Software on Minimizing the Interval to Defibrillation for Inpatient Cardiopulmonary Arrest
Authors: Husa Ruchika D , Sell Rebecca , Davis Daniel P
Published: April 2024

Background:
Minimizing pre- and post-shock compression pauses improves the likelihood of successful defibrillation. However, rhythm analysis prior to and immediately following defibrillation attempts may prolong these intervals. ECG filtration software may decrease pre- and post-shock pause intervals.

Objective:
To describe the impact of ECG filtration software in minimizing pre- and post-shock pauses for inpatient cardiopulmonary arrest (CPA).

Methods:
This study was conducted in two urban university hospitals following implementation of ECG filtration software in May 2009. We routinely export defibrillator data from all CPAs. For this analysis, pre- and post-shock compression pauses were quantified. In addition, two physicians independently evaluated the pre-shock rhythm. This data was reported descriptively.

Results:
A total of 98 defibrillation attempts in 38 patients were included. Pre-shock intervals ranged from 0-39 seconds; the majority (75%) were <5 sec. The vast majority (94%) of post-shock intervals were <5 sec. The majority (63%) of pre-shock rhythms were ventricular fibrillation/ventricular tachycardia; 23% were pulseless electrical activity (PEA); 3% were asystole; and 10% could not be determined. For PEA defibrillation attempts, 74% had a pre-shock pause <2 sec, and 26% were administered at the end of prolonged codes. Mean chest compression fraction (CCF) were 89%.

Conclusions:
ECG filtration software appears to minimize pre- and post-shock intervals. A small but measurable incidence of PEA defibrillation was observed with very brief pre-shock intervals. This may warrant a brief pause to confirm VF/VT prior to defibrillator charge.
Abstract 266: Ethnic Differences in Patient Characteristics but Not Implantable Cardioverter-Defibrillator (ICD) Utilization Rates for Primary Prevention of Sudden Cardiac Death (SCD)
Authors: Singh Narendra , Kaleka Preetinder , Song David , Chandra Sandeep , Suh David , Yan Linda , Dorsey Anthony , Ramamurthy Suresh
Published: April 2024

Background:
Underutilization of ICD's for primary prevention of SCD has been previously reported. Whether ethnic differences in utilization play a role in this is unclear.

Method:
Retrospective chart review of consecutive heart failure (HF) pts in a suburban outpatient cardiology practice from Jan 2006-Dec 2010.

Results:
Of the 2813 HF pts, 533 (19/%) had an ejection fraction of <35%, of whom 170 (32%) received an ICD device. Of the 533 pts, 23% were Caucasian (C), 67% African American (AA), 6% Southeast Asian (SEA), 3% East Indian (EI), 2% Hispanic (H). The mean age was 63+18 yrs, with AA (60 yrs) being youngest and C (72 yrs) the oldest (p<0.001). Mean EF (23%) ranged from 21% in EI to 25% in C (p<0.04). EI pts had more CAD (71%, p=<0.01) while AA pts had more hypertension (91%, p<0.001). No sig differences in smoking (16%) diabetes (39%), PVD (24%) hyperlipidemia (62%) or family history (37%) was seen. In those pts without an ICD (n=363) no documentation of a discussion was noted in 55% of charts. Documented pt refusal of an ICD trended higher in EI pts (29% p>0.057) Although males made up 62% of the group and were younger (62 vs 65 yrs,p<0.05) no gender differences in ICD implantation rates were seen. Pts were well treated for HF with no ethnic differences noted for use of diuretics (81%), ACEI/ARB (79%), beta-blockers (89%), digoxin (28%) warfarin 22% and aspirin (59%) Only statins were used more commonly in EI vs AA (71% vs 50%, p<0.05)

Conclusions:
Our findings suggest that ICD's for primary prevention of SCD are underutilized in multiple ethnic groups. Lack of a documented discussion re ICD's is too common. There are significant ethnic differences in pt characteristics for HF etiology but not for HF pharmacotherapy utilization. Patient refusal rates for ICD's also vary among ethnic groups and require further evaluation to see if these differences can explain the observed underutilization of device therapy.
Abstract 272: Intralipid Protects Late Pregnant Mouse Heart Against Ischemia/Reperfusion Injury More Efficiently than Cyclosporine-A
Authors: Li Jingyuan , Amjedi Marjan , Nadadur Sandhya , Eghbali Mansoureh
Published: April 2024

Introduction
Recently, we found that hearts of late pregnant (LP) mice have higher vulnerability to ischemia/reperfusion (I/R) injury compared to hearts of non-pregnant mice. We also found intralipid (ITLD), a clinically safe compound protects the male rodent hearts against I/R injury if administrated at reperfusion. Here we explored whether ITLD can protect the function of LP mouse hearts against I/R injury, and compared its action with cyclosporine-A (CsA), a potent inhibitor of mithochondrial permeability transition pore (mPTP) opening.

Methods
Isolated LP mouse hearts were subjected to 20 min ischemia followed by reperfusion with i) Krebs Henseleit buffer (CTRL), ii) additional 1% ITLD or iii) 1.5µM CsA. The duration of reperfusion was 40 min for heart functional measurements and infarct size assessment and 10 min for measurements of mitochondrial calcium retention capacity (CRC). Two way ANOVA was used for statistical analysis. P<0.05 were considered statistically significant. Values are expressed as mean± SEM.

Results
The heart functional recovery of LP mice after ischemia was very poor. Postischemic administration of ITLD significantly improved the cardiac function of LP mice; the rate pressure product (RPP) at the end of reperfusion was improved from 1614±438 mmHg*beats/min (n=4) to 11556±784 mmHg*beats/min (n=3) with addition of ITLD. The infarct size was also significantly reduced by ITLD to 17±2% (n=3) from 59±5% (n=4) in CTRL (P<0.01). Interestingly, ITLD was even more efficient than CsA in protecting the hearts of LP mice against ischemia reperfusion injury as in CsA group the RPP was significantly lower at the end of reperfusion (5960±1332, n=4) and the infarct size was larger (25±3%, n=4) compared to ITLD(P<0.05). ITLD-induced cardioprotection of LP mouse hearts against I/R was associated with a delay in the opening of the mPTP similar to CsA. The calcium load required for triggering the opening of the mPTP increased from 180±7 nM/mg (n=6) protein in CTRL to 290±12 nM/mg (n=6) protein in ITLD (P<0.01), which was not significantly different than 276±20 nM/mg protein in CsA group.

Conclusion
ITLD protects late pregnant mouse hearts against I/R injury more efficiently than CsA by inhibiting the mPTP opening.
Abstract 275: VF Characteristics and ICD Shock Success: Differences Between Ischemic and Nonischemic Heart Disease
Authors: Bonnes Judith L , Jaspers Focks Jeroen , Westra Sjoerd W , Brouwer Marc A , Smeets Joep L
Published: April 2024

Introduction:
From animal studies we know that signal characteristics of ventricular fibrillation (VF) are affected by the presence of myocardial scarring. The impact of the underlying etiology of scar formation, ischemic or nonischemic, is unknown. Whether the origin of scar formation is correlated to shock success has not been thoroughly studied either. Therefore, our aim is to compare signal characteristics of VF and shock success in ICD-patients, with either ischemic or nonischemic heart disease.

Methods:
Consecutive patients undergoing Medtronic ICD implantation between 2005 and 2011 were studied. After ICD implantation VF was induced to test the device. A first ICD shock of 15J was delivered to terminate VF. Signal analysis was performed on the first 4 seconds of the induced VF. The frequency content of the signal was determined using the Fourier Analysis. In addition, the success rate of the first ICD shock was scored.

Results:
A total of 229 patients were studied of whom 149 (65%) had ischemic heart disease. The dominant, fundamental and median frequency were significantly lower in patients with ischemic heart disease (Table). Also the organization index was lower. In the ischemic heart disease group 83% (124/149) had a successful first ICD shock compared to 89% (71/80) in patients with nonischemic heart disease (p=0.26).

Conclusion:
Signal characteristics of induced VF are markedly different between patients with ischemic and nonischemic heart disease. VF in ischemic heart disease is slower, less regular and less organized. Shock success was not affected by the underlying etiology, but in 10-20% of cases a first shock was not sufficient. Identification of patients with a lower shock success is subject to further study.
Abstract 35: Clinical Characteristics and Outcomes of Out-of-Hospital Cardiac Arrest Patients in Areas of Tremendous Snowfall
Authors: Hase Mamoru , Akasaka Hiroshi , Hanada Hiroyuki , Kokubu Nobuaki , Nishida Junichi , Tsuchihashi Kazufumi , Miura Tetsuji , Yonemoto Naohiro , Nonogi Hiroshi , Kimura Takeshi , Nagao Ken
Published: April 2024

Backgrounds:
The snow removal is a hard work in the tremendous snowfall area. Because it is difficult to limit to light work in consideration for the physical condition, the heart attacks are often experienced during the snow removal. Little information is available with regard to the severe heart attacks such as out-of-hospital cardiac arrest (OHCA) during the snow removal. The purpose of this study was to evaluate the characteristics and clinical outcomes of OHCA patients in the tremendous snowfall area.

Methods:
A prospective, nationwide, population-based registry of out-of-hospital cardiac arrests has been conducted by the Fire and Disaster Management Agency of Japan between January 2005 and December 2009. We enrolled all OHCA patients of presumed cardiac etiology. The tremendous snowfall area was defined as the prefectures including the city which five-year average annual cumulative snowfall depth was over 50 cm. We compared the clinical characteristics and the neurological outcomes between the tremendous snowfall area (group S) and the other area (group N).

Results:
During the five years, 297,111 patients had OHCA of presumed cardiac etiology. Though the time interval from emergency call to arrival of emergency life-saving technician in group S was longer (7.36 min) than that in group N (7.12 min), the time intervals from emergency call to restoration of spontaneous circulation in group S (19.87 min) and group N (19.72 min) were the same. The one-month survival rate in group S (5.06%) was lower than group N (5.28 %). The favorable neurological recovery rates in group S (2.67 %) and group N (2.77 %) were the same. Comparing the monthly outcomes, the one-month survival rate in group S (6.03 %) was lower than that in group N (7.02 %) in June. Though the large number of OHCA was occurred, there were no significant differences in the one-month survival and favorable neurological recovery rates between two groups in winter.

Conclusion:
This study suggested that tremendous snowfall didn’t affect the outcomes of OHCA patients much.
Abstract 9721:
Tmem100
, a Novel BMP9/10-dependent Endothelial Gene Essential for Arterial Development and Morphogenesis
Authors: Somekawa Satoshi , Hayashi Hisaki , Sakabe Masahide , Ioka Tomoko , Sato Genki , Inada Ken , Uemura Shiro , Nakagawa Osamu , Saito Yoshihiko
Published: April 2024

Satoshi Somekawa, 2011 Finalist and Presenting Author
Abstract 11543: Matrix Metalloproteinase-9 Deletion Attenuates Myocardial Fibrosis and Diastolic Dysfunction in Aging Mice
Authors: Chiao Ying Ann , Jin Yu-Fang , Shamhart Patricia , Zamilpa Rogelio , Dai Qiuxia , Ramirez Trevi A , Zhang Jianhua , Lindsey Merry L
Published: April 2024

Ying Ann Chiao, 2011 Finalist and Presenting Author
Abstract 13899: Radiation Exposure to Staff and the Public Following Myocardial Perfusion Imaging
Authors: Tsao Connie W. , Frost Lauren E. , Palmer Matthew R. , Fanning Kim , Manning Warren J. , Hauser Thomas H.
Published: April 2024

Connie W. Tsao, 2011 Finalist and Presenting Author
Abstract 58: An Intrathoracic Pressure Regulation Device Improved Cardiac Output in Porcine Peritonitis
Authors: Goldfarb Roy D , Jaffe J Douglas , Torjman Marc D , Mitrev Ludmil , Metzger Anja , Lurie Keith , Parrillo Joseph E , Dellinger R Phillip
Published: April 2024

Background:
Septic shock initiates multiple pathophysiologic pathways manifesting as microvascular hypoperfusion, cellular dysfunction and ultimately tissue death. Septic shock is characterized by reduced cardiac output. To improve cardiac output in septic shock, we tested an Intrathoracic Pressure Regulator (IPR), a novel, non-invasive therapy which decreases intrathoracic pressure during passive exhalation in mechanically ventilated patients. By creating a more negative intrathoracic pressure during exhalation, IPR enhances venous return and thereby increases cardiac output. We hypothesized that intermittent IPR therapy will transiently improve cardiac output without fluid resuscitation in porcine peritonitis.

Materials and Methods:
9 female Yorkshire pigs (30-40kg) were anesthetized with isofluorane, intubated, mechanically ventilated, instrumented with a Swan-Ganz and a femoral artery catheter. Animals were assigned to either a treatment group (n=4) or a control group (n=5). Following a one hour period of hemodynamic monitoring, a fibrin clot containing 4x109 cfu.kg-1 E. coli O11.B4 was implanted into the peritoneum. Two hours after implantation, IPR was applied for cycles of 30 minutes on and 15 minutes off. This treatment regimen was performed for six hours in total or until the animal met euthanasia criteria. The control group was monitored without the IPR for 6 hours or until meeting euthanasia criteria. The primary outcome measurement was maximum change in cardiac index during IPR.

Results:
During ITP therapy, cardiac index rose 0.125 L/minute/m2 in treated animals whereas in time matched controls, cardiac index rose 0.011L/minute/m2 (P<0.05). In treated animals, ITP therapy caused pulmonary vascular resistance (PVR) to drop significantly when compared to before therapy or after therapy; whereas in time matched control animals, PVR increased over time.

Conclusions:
This study demonstrated that IPR treatment for septic shock caused significant increases in cardiac output and decreases in pulmonary vascular resistance. Further studies are needed to determine the potential clinical benefit of this non-invasive circulatory enhancement technology.
SAK Three for All
Authors:   Sak Comedy Lab
Published: April 2024

Dr. William J. Rashkind and his family established this lecture in 1986 shortly before his death. Dr. Rashkind was an internationally known pediatric cardiologist credited for developing balloon atrial septostomy, also known as the Rashkind procedure. Dr. Rashkind was an active volunteer for the American Heart Association at the national and state levels. This lecture is made possible by a grant from the late Dr. Rashkind and his family.

In honor of the 25
th
anniversary of the Rashkind Lecture, the SAK Comedy Lab from Orlando, Florida, is pleased to present a special performance at the CVDY Council Dinner this year. The SAK “Three for All” is a hilarious and fast-paced improv comedy show, jam- packed with the group's favorite games, scenes and songs. This classic SAK show features audience participation and is guaranteed to have the entire audience engaged and laughing.

SAK alumni can be seen regularly in television, film and stage productions, including Lauren Pritchard (MadTV, True Blood), Paul Vogt (MadTV), Jonathan Mangum (Let's Make a Deal) and most notably, Wayne Brady (the Wayne Brady Show, Whose Line is it Anyway, Let's Make a Deal). SAK shows have been enjoyed by over 2 million people worldwide.
Abstract 8090: Identification Of
Rcn2
As A Novel Regulator Of Cytokine Expression
Authors: Shi Weibin , Wang Qian , Manichaikul Ani
Published: April 2024

Background-
Ath29
is an atherosclerosis susceptibility locus on chromosome 9 identified in an intercross between C57BL/6 (B6) and C3H/HeJ (C3H) apolipoprotein E-deficient (apoE
−/−
) mice. This locus was subsequently replicated in two separate intercrosses that developed early or advanced atherosclerotic lesions. The objective of this study was to characterize
Ath29
through construction and analysis of a congenic strain and identify underlying candidate genes.

Methods and Results-
Congenic strain was constructed by introgressing the chromosomal segment harboring
Ath29
from C3H.apoE
−/−
into B6.apoE
−/−
mice. Congenic mice developed significantly smaller early and advance atherosclerotic lesions than B6.apoE
−/−
mice. Microarray analysis revealed 317 genes to be differentially expressed in the aorta of congenic mice compared with B6.apoE
−/−
mice. Pathway analysis of these genes suggested the calcium signaling pathway to be implicated in regulating atherosclerosis susceptibility.
Rcn2
is located underneath the linkage peak of
Ath29
and involved in calcium signaling. Multiple SNPs between B6 and C3H mice were detected within and surrounding
Rcn2
with one SNP falling within an upstream cAMP response element. Immunostaining demonstrated its expression in atherosclerotic lesions. Knockdown of
Rcn2
with siRNAs resulted in significant reductions in both baseline and oxidized phospholipid-induced VCAM-1 and MCP-1 expression by endothelial cells.

Conclusions-
Ath29
is confirmed to be a major atherosclerosis susceptibility locus affecting both early and advanced lesion formation in mice, and
Rcn2
is identified as a novel regulator of cytokine expression.
Abstract 8165: The Association of Vascular Calcification and All Cause Mortality in Diabetes: Diabetes Heart Study
Authors: Agarwal Subhashish , Herrington David M , Cox Amanda J , Morgan Timothy M , Xu Jianzhao , Carr John J , Freedman Barry I , Bowden Donald W
Published: April 2024

Background
Coronary artery calcium (CAC), carotid artery calcium (CAAC), and abdominal aorta calcium (AAC) are noninvasive measures of atherosclerosis that predict mortality and are increasingly being utilized in risk prediction models. In a prior study we demonstrated that CAC is a powerful independent factor for mortality in type 2 diabetes affected subjects with odds of death six fold higher in CAC greater than thousand compared to CAC lower than ten. The objective of the current study was to determine which vascular bed is a better predictor of mortality in diabetes.

Methods
A total of 854 participants, ages 39-86, with complete data on diabetes, vascular imaging and covariates in the Diabetes Heart Study (DHS) were followed for an average of 7.4 years. Atherosclerosis imaging was performed utilizing fast-gated helical computed tomography scan at baseline to obtain measures of coronary, carotid, and abdominal aorta Agatston calcium scores. Seven-year risk estimates for all-cause mortality were obtained using logistic regression models adjusted for age, gender, smoking, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity including log transformed (CAC+1), (CAAC+1), and (AAC+1).

Results
Overall, 15% (129/854) of participants died during follow-up. Coronary artery calcium was associated more strongly than either carotid or abdominal calcium with mortality. After adjusting for potential confounders, and each other (CAC, CAAC, and AAC), the odds ratio of all-cause mortality increased 2.08 fold (95% CI, 1.46-3.01) for each 1-standard deviation (SD) increment of log transformed CAC score, 1.38 fold (95% CI, 1.02-1.89) for each 1-SD increment of log CAAC, and 0.9 fold (95% CI, 0.60-1.40) for each 1-SD increment of log AAC. A receiver operating characteristic curve analysis also suggested that CAC score was a better predictor of mortality than was CAAC and AAC, with areas under the curve of 0.77, 0.76, and 0.75, respectively.

Conclusion
Atherosclerosis imaging is becoming widely available and is now utilized to predict future risk for clinical events. This study found that CAC score is a better predictor of mortality than carotid or abdominal aorta vascular beds in diabetes.
Abstract 8256: Timing of Perioperative Methylprednisolone and Outcome in Infants Undergoing Heart Surgery
Authors: Pasquali Sara K , Jacobs Jeffrey P , He Xia , Jacobs Marshall L , O'Brien Sean M , Hall Matthew , Jaquiss Robert D , Welke Karl F , Peterson Eric D , Shah Samir S , Gaynor J. W , Li Jennifer S
Published: April 2024

Background:
Prior studies suggested peri-operative corticosteroids may reduce the post-bypass inflammatory response after congenital heart surgery, particularly regimens involving 2 doses (most often 1 dose given the night before surgery, and 1 in the operating room). More recent studies have called this into question, including a trial of methylprednisolone (MP) showing no benefit of 2 doses vs. 1 in infants. Lack of a placebo group and power to assess mortality or risks of treatment (infection) have limited prior analyses. In the present study we evaluated outcomes across MP regimens vs. no steroids in a large cohort.

Methods:
Clinical data from the Society of Thoracic Surgeons Database were linked to medication data from the Pediatric Health Information Systems Database for 25 participating centers. All infants (≤30d) undergoing heart surgery from 2004-2008 were included. Multivariable analysis adjusting for patient and center characteristics, surgical risk category, and within center clustering was used to evaluate the association of MP regimen with outcome.

Results:
A total of 3180 infants were included: 22% received MP on both the day before and day of surgery, 12% on the day before surgery, 28% on the day of surgery, and 38% did not receive any peri-operative steroids. In multivariable analysis (Table), there was no significant mortality or length of stay benefit associated with any MP regimen (vs. no steroids), and no difference in infection (sepsis, mediastinitis, wound infection). In subgroup analysis by surgical risk group there was a significant association of MP with infection consistent across all regimens (overall OR 2.6, 95% CI 1.3-5.2) in the lower surgical risk group.

Conclusions:
This multicenter observational analysis did not find any benefit associated with MP in infants undergoing heart surgery and suggested increased infection in certain subgroups. These data reinforce the need for a large randomized trial in this population.
Abstract 8300: SkM1 Gene Transfer Into Canine Ventricular Myocardium Decreases the Threshold Potential for Action Potential Initiation
Authors: Sosunov Eugene A , Boink Gerard J , Shlapakova Iryna N , Kryukova Yelena , Danilo Peter , Anyukhovsky Evgeny P , Cohen Ira S , Robinson Richard B , Rosen Michael R
Published: April 2024

Introduction:
We have previously shown that combined HCN2/SkM1 gene expression in canine left bundle branch (LBB) results in a biological pacemaker having a faster rate than that based on HCN2 alone. We now tested the hypothesis that expressing Nav1.4 channels (encoded by the SkM1 gene) decreases the threshold potential (TrP) for action potential (AP) initiation. Thus, in the LBB expressing Nav1.4, the same slope of phase 4 depolarization should bring membrane potential to TrP faster, resulting in a more rapid automatic rate. We now tested this hypothesis in left ventricular subepicardial (LV) preparations suitable for current injection and TrP measurement.

Methods:
Adenoviral constructs of HCN2, SkM1 or HCN2/SkM1 were implanted into canine anterior LV. At 7d, myocardial fascicles (~0.5 mm diameter, 6-10 mm long) were isolated from injected sites and transferred to a tissue bath having 2 compartments separated by a plastic membrane with a hole permitting passage of the preparation. Transmembrane potential was recorded by microelectrodes. Preparations were driven at 1 Hz and every 10th stimulus was substituted by a 30 ms pulse of extracellular depolarizing current. The magnitude of depolarizing current was gradually increased until AP was initiated and TrP recorded.

Results:
For regularly paced AP, there were no differences in maximum diastolic potential (MDP) among groups whereas maximum upstroke velocity (V
max
) was higher in SkM1 and HCN2/SkM1 than in HCN2 (Table, *
P
<0.05 vs HCN2). TrP was significantly more negative and V
max
 at TrP was higher in SkM1 and HCN2/SkM1 than in HCN2 (Table, *
P
<0.05 vs HCN2).

Conclusions:
Expression of Nav1.4 Na+ channels can accelerate the rate of HCN2 based biological pacemakers by decreasing TrP for AP initiation.
Abstract 8393: IL-18 Binding Protein (IL-18BP) Inhibits β-AR Induced Cardiomyocyte Hypertrophy
in vitro
and Myocardial Hypertrophy i
n vivo
Authors: Murray David R , Mummidi Srinivas , Valente Anthony J , Dinarello Charles A , Delafontaine Patrice , Chandrasekar Bysani
Published: April 2024

Crosstalk between the sympathetic nervous system and proinflammatory cytokines such as interleukin-18 (IL-18) plays a key role in the pathophysiology of the hypertrophied failing heart. Importantly, IL-18 can directly promote cardiomyocyte hypertrophy. IL-18 binding protein (IL-18BP) is a natural inhibitor of IL-18, and counters its biological effects. While β-AR stimulation induces IL-18, it is not known whether it also regulates IL-18BP. Here we demonstrate that the β-AR agonist isoproterenol (ISO) upregulates IL-18BP mRNA and protein expression in adult mouse cardiomyocytes in β
2
-AR/Gi-dependent manner. We cloned mouse
Il18bp
5’
cis
-regulatory region, and identified several putative transcription factor-binding sites, including CREB, C/EBP, NF-
k
B, and Sp1. While forced expression of dnp65 or kdIKKβ, or pre-treatment with mithramycin (Sp1 inhibitor) had no significant effect, forced expression of dnCREB or C/EBPβ knockdown markedly attenuated ISO-induced
Il18bp
transcription. ISO induced
Il18bp
promoter-reporter activity, and the deletion or mutation of CREB and C/EBP motifs reduced the response. ISO induced CREB and C/EBPβ DNA-binding activity, reporter gene activation, and
in vivo
binding to
Il18bp
promoter. ISO induced CREB and C/EBPβ activation via PI3K/Akt and ERK1/2. Importantly, ISO-induced hypertrophy (increased cell surface area and protein and not DNA synthesis) was blunted in cardiomyocytes isolated from IL-18BP Tg mice, by the forced expression of IL-18BP, and IL-18 neutralizing Ab. Further, ISO treatment
in vivo
was associated with Akt and ERK1/2 phosphorylation, CREB and C/EBPβ activation, and IL-18BP expression. Notably, ISO-induced myocardial hypertrophy was markedly attenuated in IL-18BP Tg mice. These data provide the first evidence that ISO induces mouse IL-18BP expression in cardiomyocytes via β
2
-AR/Gi-mediated Akt and ERK1/2-dependent CREB and C/EBPβ activation. Moreover, IL-18BP inhibits ISO-induced cardiomyocyte hypertrophy both
in vitro
and
in vivo
, likely via prevention of the biologic effects of IL-18. Thus, catecholamine induced expression of IL-18BP may play a protective role in the hypertrophied failing heart, a disease state characterized by sustained β-AR activation and IL-18 signaling.
Abstract 8445: Outcomes from Symptom and Economic Evaluation of Fluid Restriction in Persons with Heart Failure
Authors: Reilly Carolyn M , Higgins Melinda , Smith Andrew , Culler Steven D , Dunbar Sandra B
Published: April 2024

Introduction:
Fluid restrictions (FR) are routinely prescribed for persons with heart failure (HF), yet little is known regarding patient adherence and outcomes from this self-care behavior.

Purpose:
To evaluate adherence and outcomes in persons with HF randomized to receive attention control (AC) or an education and behavioral intervention (EBI) consisting of FR education, rationale, skill building for quantifying fluid intake, strategies, and goal setting.

Methods:
25 NYHA Class II-IV persons (age 44-83 years, 56% male, 20% minority, mean EF 23.0 +11.7%, on standard HF medications) were evaluated at baseline, 3 and 6 months. Measures included adherence with the prescribed FR, physical measures [BNP, congestion score, and intrathoracic impedance (IIM)], and patient reported outcomes (thirst distress, HF symptoms, and HRQL), analyzed using multi-level mixed models, RM-ANCOVA, and time series analyses.

Results:
Relationships between self-reported fluid status, fluid congestion, symptom distress, and HRQL were observed. While the sample size was small, moderate effect sizes were noted in all measures that trended toward significance (
p
<.10). Patients randomized to the EBI group demonstrated decreased total fluid consumption (
paired t
(11)= 2.243,
p
< .05, large effect size (ES) 0.56), less frequency of HF symptoms (
t(24.720)
= -2.048,
p
= .05, moderate ES 0.38), less severity of symptoms (
t(24.335)
= -1.914,
p
= .07, moderate ES 0.36), and less interference of HF symptoms with physical activity (
t(25.647)
= -2.032,
p
= .05, moderate ES 0.37). Thirst distress was noted to worsen in this group (
t(27.424)
= 1.993,
p
= .06, moderate ES 0.36) while HRQL did not change in the EBI group but improved in the AC (
t(22.880)
= -1.755,
p
= .09). Time series indicated a negative relationship between weight & IIM, positive correlation between weight & daily fluid intake, and a potential negative association between fluid intake & IIM.

Conclusion:
This pilot and feasibility study demonstrated that adherence with a prescribed FR is possible and may lead to improved typical HF symptoms, but may also increase symptoms of thirst. More research into the effects and benefits of FR including the level of FR that confers the best outcomes for the least patient distress, is warranted.
Abstract 8449: Evaluation of Atrial Remodeling and Fibrillation Vulnerability Using Molecular Imaging of Matrix Metalloproteinases
Authors: Lin Ben A , Akar Joseph G , Mukherjee Rupak , Purushothaman Kailasnath , Eckhouse Shaina R , Liu Chi , Papademetris Xenophon , Dione Donald P , Spinale Francis G , Sinusas Albert J
Published: April 2024

INTRODUCTION:
Heart failure after myocardial infarction (MI) leads to atrial remodeling and fibrosis, thereby increasing vulnerability to atrial fibrillation (AF). While matrix metalloproteinase (MMP) activity is known to be an important mediator of left ventricular (LV) remodeling after MI, atrial MMP activation in this setting has not been well studied.

HYPOTHESIS:
We hypothesized that atrial structural remodeling and fibrillation vulnerability occurring early after MI can be noninvasively assessed using targeted molecular imaging of MMP activation.

METHODS:
In vivo
and
ex vivo
SPECT/CT images were obtained in control pigs (n=7) and in pigs 1 week (n=2) or 4 weeks (n=6) after surgical induction of MI. Hybrid 64-slice SPECT/CT scans were performed at 2 hours after intravenous injection of a Tc99m-labeled radiotracer targeted to activated MMPs (RP805; Lantheus Medical Imaging, North Billerica, MA). Myocardial RP805 retention was quantified by gamma well counting after sacrifice. AF vulnerability was assessed in control pigs (n=3) and in pigs 4 weeks post-MI (n=4) using atrial burst pacing for 10 seconds with cycle lengths ranging from 300 to 180 ms.

RESULTS:
SPECT/CT images demonstrated increased uptake in the MI region and both atria compared to control pigs.
In vivo
images at 1 week post-MI are shown. RP805 retention at 1 week post-MI was 762±75% in the MI region compared to normal LV and 339±52% in the left atrium (LA) compared to normal LA (p<0.01 each). At 4 weeks post-MI, these values were 351±51% in the MI region and 174±27% in the LA (p<0.01 each). AF was inducible in 4 of 4 post-MI pigs and 0 of 3 controls (p=0.03).

CONCLUSIONS:
MMP-targeted SPECT/CT imaging may provide valuable noninvasive assessment of atrial remodeling and allow early identification of arrhythmogenic substrates prior to the onset of irreversible fibrosis. This approach may have significant implications regarding AF risk stratification as well as preventive and interventional AF treatment.
Abstract 8470: Conditional Deletion of Cardiac Connexin45 Results in Impaired Av-Nodal Conduction Properties
Authors: Schrickel Jan W , Frank Marina , Offermanns Stefan , Wirth Angela , Nickenig Georg , Lickfett Lars , Willecke Klaus
Published: April 2024

Introduction:
Cx45 has been proposed to maintain basal AV-nodal conduction. The exact function of Cx45 in the adult heart has not yet been identified as Cx45 deficient mice are embryonic lethal.

Methods:
We generated a transgenic mouse line by breeding floxed Cx45 mice with inducible cardiomyocyte-specific Cre-recombinase-expressing mice. Cardiac Cx45 was conditionally deleted by intraperitoneal administration of tamoxifen in adult mice (Cx45 fl/fl:aMHC-CreERt2). In these mice and control littermates (Cx45 fl/fl), we performed telemetric ECGs (n=5) and in vivo electrophysiological investigations (EPI) using transvenous catheterization to assess standard EPI-parameters (n=10).

Results:
Holter ECGs showed similar heart rates in the genotypes (590±65 in Cx45 fl/fl:aMHC-CreERt2 vs. 571±72 in Cx45 fl/fl). PQ-intervals were prolonged in Cx45 fl/fl:aMHC-CreERt2 (41.0±2.2ms vs. 36.4±3.1ms; p<0.05) and the P-wave was shorter (8.9±1.6ms vs. 6.6±1.0ms; p<0.05). Under inhalative ansthesia, heart rate was significantly lower in both genotypes (382±43 in Cx45 fl/fl:aMHC-CreERt2; 419±10 in Cx45 fl/fl; p<0.05 vs. spontaneous heart rate), but PQ remained significantly prolonged in the conditional knock-out mice (41.2±4.7ms vs. 37.5±3.5ms; p<0.05). Evaluation of intracardiac electrograms showed no measurable alterations of supra- or infra-Hisian conduction at comparable AH- and HV-intervals. Sinus-nodal recovery period and Wenckebach periodicity were not significantly different among the groups.

Conclusions:
Our mouse mutants with conditional cardiac deletion of Cx45 represent the first model for evaluation of Cx45 function in the adult heart. Our data show prolonged AV-intervals and no impaired AV-nodal conduction under fast heart rates. These findings support the thesis of Cx45 as a provider of basal AV-nodal conductivity, potentially as a backup system for maintaining AV-nodal conduction under pathological conditions, but with minor importance for AV-nodal conductivity when Cx30.2 and Cx40 are present.
Abstract 8489: Study Modifications & Primary Endpoint Reinterpretations Prior to Food & Drug Administration Approval of High-Risk Cardiovascular Devices
Authors: Dhruva Sanket S , Liu Lucy H , Bero Lisa A , Redberg Rita F
Published: April 2024

Introduction:
It is known that post-hoc analysis is less reliable and reduces the certainty of research findings. The most rigorous Food & Drug Administration (FDA) review process, for novel and high-risk devices, is called Premarket Approval (PMA). It is unknown to what extent post-hoc analysis is used in PMA applications.

Hypothesis:
We hypothesized that the PMA review process would involve studies of the highest methodological rigor and that all studies of approved cardiovascular devices would meet their pre-specified primary endpoints.

Methods:
We examined the Summary of Safety and Effectiveness Data, a document which is intended to present an objective critique of the scientific evidence which the FDA reviews for each device, for all PMA cardiovascular devices approved from 2000 through 2010. Any study modification or post-hoc primary endpoint reinterpretation was recorded by one author and confirmed by at least one additional author.

Results:
Of the 96 cardiovascular PMAs between 2000-2010 containing a study with at least one primary endpoint, 18 (19%) had some form of study modification or post-hoc primary endpoint reinterpretation. In 10 of these PMAs, a study did not meet at least one pre-specified primary endpoint, but the device was approved on the basis of a post-hoc data review. Pre-specified statistical analyses were changed after study initiation in 3 PMAs. Two PMAs were approved on qualitative merits rather than quantitative data after the FDA deemed the study characteristics no longer applicable at the time of review. Pre-specified controls were changed in 2 PMAs. In 1 PMA each, study design was modified after study initiation, a primary endpoint was redefined after study initiation, or new patients were added to a study after completion of initial enrollment.

Conclusions:
The most rigorous FDA review process includes numerous forms of study modification and post-hoc primary endpoint reinterpretation. More consistent requirements for pre-specified clinical trial outcomes will help improve the quality and consistency of the approval process and ensure that cardiovascular devices are safe and effective.
Abstract 8490: End Stage Heart Failure: Are We Missing Patients Who May Benefit from Left Ventricular Assist Device Support?
Authors: Cowger Jennifer A , Kittleson Michelle , Patel Chetan , Stewart Garrick , Rame J Eduardo , Mountis Maria , Patel Parag , Johnson Frances , Teuteberg Jeffrey , Guglin Maya , Aaronson Keith D
Published: April 2024

Introduction:
Heart failure (HF) is associated with tremendous morbidity and mortality and presents a significant social and financial burden to the U.S and abroad. Prior studies of left ventricular assist device (LVAD) support focused mainly on inotrope requiring patients (INTERMACS levels 1-3). Given improvements in survival following LVAD implant, we hypothesize that there is a “less ill” cohort of HF patients whose estimated 1 year mortality may justify LVAD therapy.

Methods:
This was a prospective multicenter observational study of patients (n=150) 18-80 years of age with non-inotrope dependent, chronic (>12 months) advanced HF who were not listed for cardiac transplant. All patients had an LVEF <30% and either two HF admissions in 1 year or one HF admission and at least one other high risk feature (peak oxygen consumption (pVO2) <55% predicted, 6-min walk (6MW) distance <300 m, BNP > 800 pg/mL, sodium <135 mg/dL, an ER/clinic visit for IV diuretic therapy). Baseline demographics, laboratories, and functional capacity were assessed. Seattle Heart Failure Model (SHFM) survival estimates following medical management of HF were calculated. Lietz-Miller (LMS) and HeartMate II Risk (HMIIR) scores were then calculated for estimation of survival following LVAD therapy.

Results:
Mean±standard deviation patient age was 57±13 years, 71% were male, and mean HF duration was 7±5 years with a mean LVEF of 17±6%. Within 6 months, patients had a mean 2.3±1.0 HF hospitalizations and 18% had had an ICD shock. The mean BNP was 1074±1099 pg/mL and 85% and 15% were NYHA class III and IV, respectively. Mean pVO2 and 6MW values were 12.9±4.0 ml/kg min (54±35% predicted) and 251±127 m, respectively. A SHFM score >1.5 (17% estimated 1-yr mortality) was present in 36%, and 7% had a score >2.5 (39% estimated 1-yr mortality). Yet, HMIIR (mean score 0.28±0.51, 7% high risk) and LMS (mean score 7.9±4.7, 6% high risk) scores predicted good LVAD outcomes.

Conclusion:
Within referral centers, we have identified a group of HF outpatients without inotropic therapy predicted to have high mortality on medical management but low risk following LVAD. This suggests there is a sizeable cohort of ambulatory patients not currently receiving LVAD therapy who could derive benefit.
Abstract 8493: Lack of Association between Discharge Prescription of Aldosterone Antagonists and Outcomes in Medicare Beneficiaries with Heart Failure and Preserved Ejection Fraction: A Propensity-Matched Study of the OPTIMIZE-HF
Authors: Ahmed Ali , Zhang Yan , Mujib Marjan , Arora Tarun , Kilgore Meredith , Aban Inmaculada , Love Thomas , Levesque Raynald , Kitzman Dalane , Gheorghiade Mihai , Allman Richard , Fonarow Gregg
Published: April 2024

Background:
Aldosterone antagonists reduce mortality in systolic heart failure (HF). However, their effect in HF patients with preserved ejection fraction (HF-PEF) remains unclear. Propensity-matched studies can assemble balanced cohorts while remaining blinded to outcomes, and are suitable when RCTs are difficult or unethical. We examined the association of aldosterone antagonist with outcomes in a propensity-matched cohort of older HF-PEF patients.

Methods:
Of the 26,376 OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) patients linked to Medicare outcomes data (through Dec 2008), 10429 patients age ≥65 years with HF-PEF (LVEF ≥40%) were discharged alive. Of these, 866 (8.3%) received a discharge prescription for aldosterone antagonists. Propensity scores for aldosterone antagonist use, estimated for each of the 10429 patients, were used to assemble a cohort of 864 pairs of patients receiving and not receiving these drugs who were balanced on 116 baseline characteristics.

Results:
Patients (n=1728) had a mean (±SD) age of 80 (±8) years, a mean (±SD) LVEF of 54% (±9%), 63% were women, and 8% African American. During ∼6 years of follow-up, all-cause mortality occurred in 71% and 70% of matched patients receiving and not receiving aldosterone antagonists (hazard ratio, 1.01; 95% CI, 0.90-1.24; p=0.929; Figure). A similar propensity-adjusted association was observed in the 10429 pre-match patients (hazard ratio, 0.99; 95% CI, 0.91-1.08; p=0.800). Aldosterone antagonist use also had no significant association with HF or all-cause hospitalization.

Conclusions:
Discharge prescription of aldosterone antagonists had no association with mortality or hospitalization in a propensity-matched balanced cohort of older HF-PEF patients. Whether these results differ from younger RCT-eligible patients will await results of the ongoing TOPCAT trial.
Abstract 8521: Early Extracorporeal Membrane Oxygenator-Assisted Primary Percutaneous Coronary Intervention Improved 30-Day Clinical Outcomes in Patients with STEMI Complicated with Profound Cardiogenic Shock
Authors: Sheu Jiunn-Jye , Tsai Tzu-Hsien , Chua Sarah , Yip Hon-Kan
Published: April 2024

Objectives:
This study tested the hypothesis that early extracorporeal membrane oxygenator (ECMO) offered additional benefits in improving 30-day outcomes in patients with acute ST-segment elevation myocardial infarction (STEMI) complicated with profound cardiogenic shock undergoing primary percutaneous coronary intervention (PCI).

Methods:
Between May 1993 and July 2002, 920 acute STEMI patients underwent primary PCI. Of these patients, 12.5% (115) with cardiogenic shock were enrolled into this study (Group 1). Between August 2002 and December 2009, 1650 acute STEMI patients underwent primary PCI. Of these patients, 13.3% (219) complicated with cardiogenic shock were enrolled (Group 2).

Results:
Incidence of profound shock [defined as systolic blood pressure remained ≤ 75 mmHg after intra-aortic balloon pump and inotropic agent supports] was similar in both groups (21.7% vs. 21.0%, p>0.5). ECMO support, which was only available for group 2 patients, was performed at catheterization room. The results demonstrated that final thrombolysis in myocardial infarction (TIMI)-3 flow in infarct-related artery was similar between the two groups (p=0.678). However, total 30-day mortality and the mortality of profound shock patients were lower in group 2 than in group 1 (all p <0.04). Additionally, the hospital-survival time was remarkably longer in group 2 than in group 1 patients (p=0.0005). Moreover, multivariate analysis demonstrated that unsuccessful reperfusion, presence of advanced congestive heart failure, profound shock, and age were independent predictors of 30-day mortality (all p<0.02).

Conclusion:
Early ECMO-assisted primary PCI improved 30-day outcomes in STEMI patients complicated with profound cardiogenic shock (The following figure is the detailed schematic presentation of the enrollment status of the patients and their clinical outcome).