bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 72: Verbalization of the Phrase “There's No Pulse---Start Compressions” Is Associated with Faster Initiation of Chest Compressions
Authors: Hunt Elizabeth A , Bradshaw Jamie H , Nelson-McMillan Kristen L , Duval-Arnould Jordan M , Shilkofski Nicole A
Published: April 2024

Introduction:
When a patient is pulseless, chest compressions (CC) must be started immediately. Our research group has observed when in-hospital providers note a loss of pulse, many focus on advanced rather than basic life support. Human factors components in team resuscitation may be optimized to improve performance.

Hypothesis:
We hypothesize that residents who verbalize the phrase “There's no pulse” directly followed by “start compressions” will: 1) be more likely to perform CC and 2) initiate CC more quickly than those that do not utter this phrase.

Methods:
We performed a retrospective review of videos from an observational study of pediatric residents managing a high-fidelity manikin simulator programmed to develop pulseless ventricular tachycardia (PVT). We measured the proportion of residents that started CC, time to starting CC, words uttered in recognition of pulselessness and phrases and/or actions that followed.

Results:
Seventy of eighty residents participated and data from 68/80 (85%) was reviewed. Once the manikin developed PVT, 42/68 (62%) stated “there's no pulse” during their initial assessment, 9/68 (13%) assessed pulses but did not make any verbal comment. The remaining 17/68 (25%) did not feel the pulse initially, focusing on the rhythm.Of the 42 residents who stated “there's no pulse”, only 16/42 (38%) followed that by stating “start compressions”. Other plans verbalized included: “defibrillation” 19/42 (45%), “intubation” 2/42 (5%), “blood pressure” 2/42 (5%), “IV” 1/42 (2%), “call the code team” 1/42 (2%) and “epinephrine” 1/42 (2%). A higher proportion of residents who stated “there's no pulse, start compressions” ultimately started CC vs. those that did not [16/16 (100%) vs. 30/52 (58%), p = 0.002]. Of those that ultimately started CC, residents uttering this phrase had a faster median time (Interquartile range - IQR) to starting CC than all others [30 seconds (IQR: 19-42) vs. 150 (51-242), p < 0.001].

Conclusions:
In conclusion, residents who speak out loud and verbalize the phrase “There's no pulse, start compressions” are more likely and faster to start CC than those that do not. Further investigation into whether training providers to use this technique will be consistently associated with faster time to starting CC is warranted.
Abstract 73: Improving Teamwork Perceptions and Cardiopulmonary Resuscitation Performance by High-Fidelity Simulation-Based Teamwork Training
Authors: Chou Eric H , Yang Chih-Wei , Chong Kah-Meng , Yeh Huang-Fu , Huang Edward P , Wu Cheng-Yi , Wang Hui-Chih , Liu Yueh-Ping , Chiang Wen-Chu , Ko Patrick C , Ma Matthew H
Published: April 2024

Introduction:
The quality of cardiopulmonary resuscitation (CPR) performance influences patient's outcome. Besides individual technical knowledge and skills, teamwork perceptions have an impact on team performance, and consequently on resuscitation quality. This study aimed to investigate the impacts of high-fidelity simulation (HFS)-based teamwork training on team perceptions and CPR performance.

Methods:
This was a prospective, case-controlled study. A four-scenario, HFS-based teamwork training program was developed and implemented from November 2007 to February 2008. In addition to resuscitation skills, the program focused on teaching teamwork competencies, including leadership, communication, situation monitoring, and mutual support. Case scenarios were simulated using a high-fidelity mannequin simulator in a simulated emergency department (ED) setting. Audio-visual assisted feedback was given by facilitators after each scenario. A standardized questionnaire for assessment of teamwork performance was developed, using 5-point Likert scales. All participants completed the questionnaires immediately after each scenario, according to their performance during that simulation session. Both the first and last case scenarios were patients of out-of-hospital cardiac arrest. CPR performance including compression rate, no-flow ratio, and initiation time of defibrillation was measured by reviewing the videos.

Results:
A total of 83 ED staffs, including 24 residents and 59 nurses, were enrolled. Teamwork perceptions improved significantly after the simulation training course (
p
<0.001). For CPR performance, there was a trend toward decreased hyperventilation rate (19.1±5.6 vs. 14.8±8.2 min
-1
,
p
=0.10), increased chest compression rate (102.4±17.1 vs. 110.4±15.2 min
-1
,
p
=0.12), and faster initiation of defibrillation (93.4±26.9 vs. 69.1±39.0 secs,
p
=0.09) after the training course. No-flow fraction (0.23±0.07 vs. 0.17±0.08,
p
=0.01), initiation of intubation (99.1±40.6 vs. 77.0±37.0 secs,
p
=0.02) and intravenous access (86.9±37.7 vs. 63.4±33.8 secs,
p
=0.02) were significantly improved.

Conclusion:
HFS-based teamwork training is effective in improving teamwork perceptions and some aspects of CPR performance.
Abstract 77: Predictive Power of Early Lactate Clearance Regarding 30-Day Neurological Outcome After Cardiac Arrest with Cardiopulmonary Bypass
Authors: Hayashida Kei , Suzuki Masaru , Shiroshita-Takeshita Akiko , Hori Shingo
Published: April 2024

Objective:
Early lactate clearance has been reported to be associated with improved mortality in patients with post cardiac arrest syndrome (PCAS). Recently, cardiopulmonary bypass (CPB) has significantly improved prognosis of those patients, however, it has been still unknown whether early lactate clearance could predict for neurological outcome in PCAS with CPB. We aimed to investigate the usefulness of the early lactate clearance in a cardiac arrest of patients resuscitated and treated with CPB.

Methods:
Retrospective observational study. Between January 2000 and March 2011, 46 cardiac arrest patients with cardiac causes underwent CPB in a university hospital in Tokyo. Of those, serial arterial lactate concentrations (at ICU admission and 6 hours after ICU admission) were obtained from 21 patients (19 Males, median 61 y/o). Lactate clearance was defined as the percent change after 6 hours from baseline. The patients were divided into two groups (high lactate clearance group or low lactate clearance) by median lactate clearance.

Results:
The lactate clearance in the high lactate clearance group was 50.3±13.1% (mean±SD) and the low lactate clearance group -14.7±23.9%. There were no significant differences between the groups for demographics, laboratories (except platelets, baseline PaO
2
), baseline lactate (the high lactate clearance group: 11.3±3.5mg/dl, the low lactate clearance group:10.8±4.2mg/dl), baseline arterial pressure (99.9±41.1mmHg, 96.1±26.7mmHg), use of catecholamine. In the high clearance group, there was significantly higher for favorable CPC (<=2) rate (44%
vs
0%, OR 2.8, 95%CI [1.48-5.40]) and Kaplan-Meier survival analysis showed a survival benefit over 30 days (log-rank; p=0.02). Cut-off points with 95% specificity in predicting favorable outcome was 67.4% for early lactate clearance (sensitivity 75%).

CONCLUSIONS:
Early lactate clearance is specific but only moderately sensitive markers of 30-day neurological outcome. These findings suggest that post arrest tissue hypoperfusion during CPB contributes lactate clearance, regardless CPB.
Abstract 78: 30:2 vs 15:2 Compression-Ventilation Ratio by Emergency Medical Services Responders in Patients with Out-of-Hospital Nonshockable Cardiac Arrest
Authors: Nagao Ken , Tachibana Eizo , Nishikawa Kei , Yagi Tsukasa , Yonemoto Naohiro , Takayama Morimasa , Nonogi Hiroshi , Shirai Shinichi , Kimura Takeshi
Published: April 2024

BACKGROUND
The 2010 AHA guidelines for CPR recommended that emergency medical services (EMS) responders should use minimal interruptions in chest compressions using a 30:2 compression-ventilation ratio in adult victims. However, it is unclear whether this CPR by EMS responders can improve survival for adults with non-shockable cardiac arrest (CA) including pulseless electrical arrest (PEA) and asystole.

METHODS
We compared the effects of a 30:2 compression-ventilation ratio CPR by EMS responders recommended in the 2005 CPR guidelines with those of a 15:2 compression-ventilation ratio CPR recommended in the 2000 CPR guidelines from the data of the All-Japan Utstein Registry, a prospective, nationwide, observational registry. The study endpoints were return of spontaneous circulation (ROSC) on hospital arrival and 30-day favorable neurological outcome after CA.

RESULTS
Of the 58,448 adult patients with bystander-witnessed out-of-hospital CA due to presumed cardiac etiology in the year 2005, 2008 and 2009, 24,250 with non-shockable cardiac arrest who did not receive bystander CPR were included; 16,091 received a 30:2 CPR by EMS responders, and 8,159 received a 15:2 CPR by EMS responders. The 30:2 group had significantly higher rates of ROSC and favorable neurological outcome than the 15:2 group in the whole cohort (ROSC; 6.6% vs. 4.2%, p<0.001, favorable neurological outcome; 1.3% vs. 0.8%, p<0.001), and in the subgroups of patients with PEA (ROSC; 9.8% vs. 5.8%, p<0.001, favorable neurological outcome; 2.4% vs. 1.6%, p=0.002). Although the 30:2 group had a significantly higher ROSC rate than the 15:2 group (4.3% vs. 3.3%, p=0.002), favorable neurological outcome did not differ between the 30:2 group and the 15:2 group (0.5% vs. 0.3%, p=0.28) in the subgroups of patients with asystole. The adjusted odds ratios after a 30:2 CPR was 1.62 (95% CI, 1.43-1.84) for ROSC and 1.56 (95% CI, 1.18-2.05) for favorable neurological outcome, and other independent predictor of each study endpoint was PEA.

CONCLUSION
A 30:2 compression-ventilation ratio CPR by EMS responders improved ROSC and favorable neurological outcome in adult patients with bystander-witnessed out-of-hospital PEA CA, but this CPR had not neurological benefits for adult patients with asystole CA.
Abstract 8087: Association of Left Ventricular Mechanical Dyssynchrony with Outcomes in Ischemic Cardiomyopathy: A Follow-up Study of 587 Patients Undergoing Gated Positron Emission Tomography
Authors: Aljaroudi Wael , Alraies M Chadi , Jaber Wael A , Popovick Zoran , Brunken Richard , Cerqueira Manuel D , Marwick Thomas
Published: April 2024

Background:
We sought to assess the independent contribution of left ventricular (LV) dyssynchrony to prognosis in patients with ischemic cardiomyopathy (ICM).

Methods and Results:
Stress/rest Rb-82 gated PET imaging was performed in consecutive patients with ICM and LV ejection fraction (EF) ≤35% (age 66±11 years, 83% men) between 2006 and 2010. Excluding those with CRT, 587 patients were followed for cardiac and all-cause mortality for 1.9±1.4 years. The mean phase dyssynchrony index (standard deviation [SD] 50±21°) was higher than that of a normal group (13±4°, P<0.0001). Of 95 cardiac deaths (16%), 70% were from pump failure, 18% from arrhythmias and 12% from coronary artery disease. Using a SD cut-off of 43° to define dyssynchrony, patients with SD≥43° (n=339) had poorer outcomes than those with SD<43° (cardiac death 19% vs. 12%, p=0.02). However, Cox analysis showed survival to be independently associated with age (HR 1.05 [95%CI 1.03-1.07]), diabetes (1.7[1.14-2.57]), mitral regurgitation (1.39[1.11-1.75]), EF (0.95[0.92-0.98]), and fixed perfusion defect size (PDS) (1.15 [1.05-1.25] per 10% increase), but not SD. Similarly, only age, diabetes, heart failure class, EF and fixed PDS were independently associated with all-cause death. Using nested Cox models, LVEF and fixed PDS added significant information for the prediction of outcome while phase SD did not (Figure 1). Finally, patients with large scar burden (fixed PDS ≥40%) had worse outcome independent of SD (Figure 2).

Conclusion:
In patients with ICM, the association of LV dyssynchrony with cardiac death appears to derive from advanced age, diabetes, mitral regurgitation, scar burden and lower LVEF, but not SD.
Abstract 8126: ST-Segment Elevation in Lead aVR Strongly Predicts Adverse Outcomes at 1 Year in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome
Authors: Kosuge Masami , Ebina Toshiaki , Hibi Kiyoshi , Iwahashi Noriaki , Maejima Nobuhiko , Endo Mitsuaki , Tsukahara Kengo , Morita Satoshi , Uchino Kazuaki , Ishikawa Toshiyuki , Umemura Satoshi , Kimura Kazuo
Published: April 2024

Background:
In patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), ST-segment depression on admission ECG is recognized to strongly predict poor outcomes; however, lead aVR is not considered. Lead aVR is referred to as a “cavity lead,” and ST-segment elevation in lead aVR (ST↑aVR) may reflect global subendocardial ischemia in NSTE-ACS.

Methods:
We studied 585 patients with NSTE-ACS who underwent coronary angiography during initial hospitalization. Patients were divided into the 3 groups according to the degree of ST↑aVR on admission ECG: no ST↑aVR (n=422, G-A); ST↑aVR <1.0 mm (n=84, G-B); and ST↑aVR ≥1.0 mm (n=79, G-C). TIMI risk score, summed ST-segment depression in all leads except aVR (ΣST↓), troponin T (TnT), hemoglobin (Hb), high-sensitivity C-reactive protein (hsCRP), estimated glomerular filtration rate (eGFR), and brain natriuretic peptide (BNP) were also measured on admission.

Results:
There were no differences in sex or coronary risk factors except for diabetes mellitus in the 3 groups. In G-A, G-B, and G-C, age was 66±11, 70±10, and 70±11 years; TIMI risk core was 2.6±1.4, 3.5±1.2, and 4.1±1.2; the rates of diabetes mellitus were 29%, 41%, and 53%; Killip class ≥2 was 5%, 14%, and 28%; positive TnT was 28%, 42%, and 57%; the levels of Hb were 14±2, 13±2, and 13±2 g/dl; hsCRP was 0.329±0.574, 0.540±1.100, and 0.664±1.340 mg/dl; eGFR was 68±25, 62±29, and 58±24 ml/min/1.73 m
2
; BNP was 157±284, 282±415, and 386±334 pg/ml; ΣST↓ was 1.8±2.4, 6.0±4.0, and 12.3±6.0 mm; the rates of left main or 3-vessel disease were 6%, 42%, and 72%; and major adverse events (death, [re]infarction, urgent revascularization, or congestive heart failure) at 1 year were 11%, 37%, and 46%, respectively (all p<0.01). Multivariate analysis showed that as compared with no ST↑aVR, the hazard ratios (95% CI) for 1-year adverse events associated with ST↑aVR <1.0 mm and ST↑aVR ≥1.0 mm were 2.66 (1.18-5.89; p<0.001) and 4.20 (1.48-10.9; p<0.001), respectively.

Conclusions:
ST↑aVR on admission ECG is a strong predictor of 1-year adverse outcomes in patients with NSTE-ACS, even after adjusting for traditional risk factors, biomarker profiles, and ST-segment depression in other leads. Our findings suggest the importance of ST↑aVR in early risk stratification.
Abstract 8146: Gene Delivery of Suppressor of Cytokine Signaling 1 Decreases Myocardial Inflammation in Experimental Autoimmune Myocarditis
Authors: Tajiri Kazuko , Imanaka-Yoshida Kyoko , Hiroe Michiaki , Naka Tetsuji , Aonuma Kazutaka , Yasutomi Yasuhiro
Published: April 2024

Introduction:
Myocarditis and subsequent dilated cardiomyopathy are major cause of heart failure. Recent reports indicate that a subgroup of myocarditis patients may benefit from immune-targeted therapies. Suppressor of cytokine signaling 1 (SOCS1) plays a key role in the negative regulation of immune responses. We therefore hypothesized that overexpression of SOCS1 may have therapeutic effects in the treatment of myocarditis.

Methods and Results:
Myocarditis was induced by subcutaneous immunization with cardiac specific peptides derived from α myosin heavy chain (MyHC-α) in BALB/c mice. Plasmid DNA encoding SOCS1 (pSOCS1) or empty plasmid was injected intraperitoneally into mice on days 0, 5 and 10 after induction of myocarditis. The heart-to-body weight ratios in pSOCS1-treated mice were significantly decreased compared with control plasmid-received mice (4.8±0.2 mg/g vs 6.2±0.5 mg/g; n=5, P<0.05). pSOCS1-treated mice had fewer infiltrating CD45+ cells in the heart than control plasmid-injected mice analyzed by flow cytometry (4.0±0.6 % of total cells vs 36.4±10.6 % of total cells; n=5, p<0.05). Echocardiography showed preserved contractile function in pSOCS1-treated mice compared with control plasmid-treated mice (fractional shortening: 36±3 % vs 22±1 %; n=9, p<0.01). Western blot analysis of DCs from pSOCS1-treated mice revealed decreased phosphorylation of STAT1. In the culture supernatant of DCs from pSOCS1-treated mice, the amount of proinflammatory cytokines was decreased (IL-6: 472±11 pg/ml vs 762±20 pg/ml, p<0.01; TNF-α: 1.9±0.0 ng/ml vs 3.9±0.1 ng/ml, p<0.01). MyHC-α-specific CD4+ T cells were isolated from myocarditis mice and co-cultured with MyHC-α-pulsed DCs from pSOCS1- or control plasmid-treated mice. The proliferative responses of CD4+ T cells co-cultured with DCs from pSOCS1-treated mice were much lower than with DCs from control plasmid-received mice assessed by measuring [3H]-thymidine uptake (1,401±393 cpm vs 2,584±213 cpm, p<0.05).

Conclusion:
SOCS1 gene therapy reduced cardiac inflammation and improved cardiac performance in experimental autoimmune myocarditis. Our data suggested that in vivo gene delivery of SOCS1 suppresses the functional capacity of DCs to prime and expand autoreactive CD4+ T cells.
Abstract 8158: Prior Incidence of Ventricular Tachyarrhythmias Predict Subsequent Episodes of Ventricular Tachyarrhythmias and Increased Mortality in Subjects with Mildly Reduced Ejection Fraction on Cardiac Resynchronization Therapy -A MADIT study analysis
Authors: Chatterjee Saurav , Barsheshet Alon , Mukherjee Debabrata , Lichstein Edgar , Goldenberg Ilan
Published: April 2024

Background:
An incidence of ventricular tachyarrhythmia (VA)(including ventricular tachycardia and ventricular fibrillation) in a patient with reduced ejection fraction is a marker of increased all-cause mortality. We aimed to assess the impact of prior VAs on clinical outcomes in patients with mild heart failure symptoms who received cardiac resynchronization therapy with a defibrillator (CRT-D).

Methods:
We evaluated benefit of CRT-D vs. ICD-only therapy in the reduction of ventricular tachyarrhythmias or death by the presence of a history of VA among 1820 patients enrolled in the MADIT-CRT trial.

Results:
A history of VA was a significant risk factor for the occurrence of VT/VF or death during the trial (HR 2.06, 95% CI 1.55-2.74, p<0.001). Multivariate analysis showed that CRT-D therapy was associated with a significant reduction in the risk of ventricular tachyarrhytmias among patients without a history of VA, whereas risk-reduction associated with CRT-D therapy was not statistically significant among patients with a history of prior VA (Table).

Conclusions:
Our findings suggest that a history of prior VA is a powerful risk factor for the development of subsequent ventricular tachyarrhythmias and mortality among patients with mild CHF symptoms who receive device therapy. The benefit of CRT-D therapy appears to be attenuated among patients with prior VA.
Abstract 8166: Elevated N-Terminal Pro-Brain Natriuretic Peptide Increases the Risk of Recurrent Thromboembolic Events After Acute Pulmonary Embolism
Authors: Wang Yong , Liu Zhinghong
Published: April 2024

Introduction:
N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) is a predictor of short-term clinical adverse outcome in patients with acute pulmonary embolism (APE), but its long-term prognostic value remains largely undefined.

Hypothesis:
We assessed the hypothesis that elevated plasma NTproBNP level is associated with recurrent venous thromboembolism (VTE).

Methods:
On admission, NTproBNP levels were measured in 224 consecutive patients with the first episode of acute pulmonary embolism occurring from January 2005 through October 2010. Patients were categorized to two groups by NTproBNP reference range and followed up at 3, 6, and 12 months and yearly thereafter. The primary end point was symptomatic, recurrent fatal or nonfatal VTE.

Results:
NTproBNP was elevated in 158 (71%) patients and not elevated in 66 (29%) patients. After a mean follow-up period of 31.0±19.4 months, patients with elevated NTproBNP showed an increased risk of recurrent VTE (20 patients, 12.7%) compared with those not elevated (only 1 patient, 1.5%) (
P
=0.009). 6 of 7 deaths related to pulmonary embolism occurred in patients with NTproBNP elevated, compared with patients with NTproBNP normal (1 of 7 deaths, P=0.64). At multivariate analysis stratified by oral anticoagulant treatment duration, elevated NTproBNP was an independent predictor of recurrent VTE (hazard ratio; 10.50;
P
=0.02).

Conclusions:
Elevated NTproBNP is associated with the increased risk of VTE recurrence in acute pulmonary embolism patients.
Abstract 8197: Serum Dickkopf-1 Level Predicts Cardiac Events in Chronic Heart Failure Patients
Authors: Niizeki Takeshi , Kaneko Kazuyoshi , Sasaki Toshiki , Sugawara Shigeo , Kubota Isao
Published: April 2024

Background:
The Wnt signaling pathway is an important regulator of adult tissue maintenance and homeostasis. Disorder in Wnt signaling pathway causes cancer, human degenerative disease, and aging-associated heart disorders such as diastolic dysfunction. Dickkopf-1 (DKK-1) is negative regulator protein of the Wnt signaling pathway and is associated with a variety of organic diseases. Chronic heart failure (CHF) is characterized by systemic abnormalities and the myocardium is continually exposed to various stressors such as anoxia, ischemia, inflammation, and free radicals. Increasing age had been reported to increase mortality of CHF patients. Under the hypothesis that DKK-1 as a regulator protein is involved in ventricular remodeling, ongoing myocardial damage, and aging-associated disorders, we aimed to examine the prognostic value of serum DKK-1 in patient with CHF.

Methods and Results:
Serum DKK-1 level was measured in 210 CHF patients and 62 control subjects by the competitive enzyme-linked immunosorbent assay. Patients were prospectively followed with endpoints of cardiac death or re-hospitalization for worsening CHF during a median follow-up period of 720 days. Serum DKK-1 level was higher in CHF patients than in control subjects and increased with advancing NYHA functional class (P < 0.0001). Furthermore, serum DKK-1 level was significantly increased with aging. There were 88 cardiac events during follow-up period (42%). Serum DKK-1 level was significantly higher in patients with cardiac events than those in event free patients. Kaplan-Meier analysis clearly demonstrated that the high DKK-1 group had a significantly higher incidence of cardiac events than the low DKK-1 group (P < 0.0001). Patients were divided into 3 groups based upon DKK-1 level, and the highest 3
rd
tertile was associated with the highest risk of cardiac events (8.68-fold compared to the 1
st
tertile). In the multivariate Cox analysis, DKK-1 level was an independent risk factor for cardiac events (hazard ratio 3.66, 95% confidence interval 1.49-4.76, P = 0.0015).

Conclusion:
Elevated serum DKK-1 level, a major antagonist of the Wnt signaling pathway, is associated to increased cardiac events and provides prognostic information in CHF patients.
Abstract 8244: Inhibition of Ca2+ Entry Mode of Na+/Ca2+ Exchanger Improves Survival Rate of Rat Model for Heart Failure with Preserved Ejection Fraction
Authors: Kamimura Daisuke , Ohtani Tomohito , Sakata Yasushi , Mano Toshiaki , Takeda Yasuharu , Tamaki Shunsuke , Omori Yosuke , Tsukamoto Yasumasa , Furutani Kazuharu , Komiyama Yutaka , Yoshika Masamichi , Takahashi Hakuo , Matsuda Toshio , Baba Akemichi , Umemura Satoshi , Miwa Takeshi , Komuro Issei , Yamamoto Kazuhiro
Published: April 2024

Background:
Heart failure with preserved ejection fraction (HFPEF) has a poor prognosis as well as heart failure with reduced ejection fraction and its therapeutic strategy has not been established. Left ventricular (LV) fibrosis and stiffening play crucial roles in the development of HFPEF. Plasma level of digitalis-like factors (DLFs) is increased in about a half of patients with hypertension, a principal underlying cardiovascular disease of HFPEF. DLFs inhibit ion-pumping function of Na+/K+-ATPase and activate the Ca2+ entry mode of Na+/Ca2+ exchanger (NCX). It is also known that DLFs promote collagen production in fibroblasts.

Objective:
The objective of this study was to explore whether the pharmacological inhibition of the NCX entry mode is effective in preventing LV fibrosis and the development of HFPEF.

Methods and Results:
(1) Dahl salt-sensitive rats fed 8% NaCl diet from age 6 weeks served as hypertensive HFPEF model. In this model, 24-hour urine excretion of DLFs was greater than that in the age-matched control at compensatory hypertrophic and heart failure stages. (2) Continuous administration of ouabain for 14 weeks developed LV fibrosis without the changes in blood pressure in Sprague-Dawley rats irrespective of NaCl loading. (3) Ouabain elevated intracellular Ca2+ concentration through the entry of extracellular Ca2+, increased the phosphorylation level of p42/44 mitogen-activated protein kinases, and enhanced 3H-proline incorporation in cardiac fibroblast, and SEA0400, the inhibitor of the NCX entry mode, suppressed these in vitro effects of ouabain. (4) In the HFPEF model, chronic administration of SEA0400 at subdepressor dose prevented the elevation of LV filling pressure and improved the survival rate in association with the attenuation of LV fibrosis and stiffening.

Conclusion:
DLFs and the subsequently activated NCX entry mode may play an important role in the development of hypertensive HFPEF, and the blockade of the NCX entry mode may be a new therapeutic strategy for this phenotype of heart failure.
Abstract 8268: Sickness Behavior Predicts Event Free Survival in Adults with Heart Failure
Authors: Riegel Barbara , Ratcliffe Sarah J
Published: April 2024

Stimulation of the immune system produces a non-specific cluster of symptoms referred to as sickness behavior. Numerous and diverse systemic conditions stimulate the immune system and produce this response, including heart failure (HF).

Purpose:
The purpose of this study was to explore the ability of the sickness behavior symptom cluster to predict event-free survival 6 months later in adults with HF.

Methods:
A sample of 280 adults with stage C HF was enrolled from 3 sites in the Northeastern US. Those with dementia, terminal illness, a recent history of drug or alcohol abuse, and night shift workers were excluded. NYHA functional class was measured at baseline. Sickness behaviors, defined as an aggregate of fatigue, sleepiness, and depression, were measured at baseline, aggregated using factor analysis. Hospitalizations were measured by self-report and validated in the medical record. Deaths were confirmed in the medical record or the US death records. The influence of sickness behavior on event free survival (hospitalization, death) was analyzed with multivariable Cox proportional hazards regression.

Results:
A total of 97 events (6 deaths) occurred during the 6-months of follow-up in the 274 subjects with follow-up data available. When the analysis was stratified by NYHA class, sickness behavior was a significant predictor of the risk for death or hospitalization for subjects in NYHA class IV (n=48, RR=1.67, p=0.011) but not in the other NYHA classes.

Conclusion:
Adults with NYHA class IV HF who manifest sickness behavior are more likely to be hospitalized or die than those without the sickness behavior symptom cluster. Study of the factors associated with sickness behavior may suggest targets for intervention. Further study of this indicator of immune dysfunction may help integrate disparate observations regarding fatigue, sleepiness, and depression in HF patients.
Abstract 8274: Resveratrol Brings About Reverse Remodeling In The Heart With A Large Old Myocardial Infarction Through Autophagy Activating amp Kinase Pathway
Authors: Kanamori Hiromitsu , Takemura Genzou , Goto Kazuko , Maruyama Rumi , Tsujimoto Akiko , Ogino Atsushi , Takeyama Toshiaki , Kawaguchi Tomonori , Watanabe Takatomo , Morishita Kentaro , Fujiwara Takako , Fujiwara Hisayoshi , Seishima Mitsuru , Minatoguchi Shinya
Published: April 2024

We previously reported that autophagy is activated during postmyocardial infarction and compensates for the lack of energy in cardiomyocytes by digesting and recycling own constituents. Resveratrol is a popular natural polyphenolic compound, abundantly contained in the skin of grapes and red wine, and is recently reported to have not only an anti-oxidant property but also autophagy-accelerating action. We here investigated the effect of resveratrol on established heart failure due to a large old myocardial infarction. Myocardial infarction was induced in mice by the left coronary artery ligation. Four weeks post-infarction, the surviving mice were assigned to four groups: control (saline, n=15); resveratrol (50 mg/kg/day, n=15); chroloquine (an autophagy inhibitor, 10 mg/kg/day, n=15); and combination (resveratrol, 50 mg/kg/day plus chroloquine, 10 mg/kg/day, n=15). The agents were administered for 2 weeks using osmotic mini pump. Resveratrol significantly attenuated and partially reversed left ventricular dilatation (reverse remodeling) and improved function: left ventricular end-diastolic diameter, 4.1±0.2 mm vs. 4.9±0.3 mm in controls; and ejection fraction, 46.9±3.3 % vs. 35.8±3.3 % in controls (p<0.05), accompanying reduction of ventricular expression of atrial natriuretic peptide. In those hearts, autophagic findings were augmented as shown by upregulation of microtubule-associated protein-1 light chain 3-II (LC3-II) and by electron microscopic findings of autophagic vacuoles. The activation of AMP-activated protein kinase was enhanced in the hearts treated with resveratrol while the activation of mammalian target of rapamycin complex 1 (mTORC1) and p70S6 kinase (a direct down-stream target of mTORC1) was suppressed compared to vehicle. Chroloquine brought about an opposite result, including aggravation of cardiac dysfunction and remodeling progression, where autophagic activity was diminished. A combined treatment with resveratrol and chroloquine offset each effect on the postinfarction heart. Any treatment did not affect apoptosis in the infarcted heart. The present findings suggest that resveratrol is new pharmacological strategy -i.e., manipulation of autophagy, against postinfarction cardiac remodeling.
Abstract 8284: Brain-Derived Neurotrophic Factor Protects Against Cardiac Dysfunction After Myocardial Infarction via a Central Nervous System-Mediated Pathway
Authors: Okada Sho , Minamino Tohru , Yokoyama Masataka , Tateno Kaoru , Moriya Junji , Shimizu Ippei , Nojima Aika , Ito Takashi , Ogasawara Yoko , Komuro Issei , Kobayashi Yoshio
Published: April 2024

The central nervous system (CSN) is thought to influence regulation of the cardiovascular system in response to humoral and neural signals from peripheral tissues, but our understanding of the molecular mechanisms involved is still quite limited. Here we demonstrate a novel CNS-mediated mechanism by which brain-derived neurotrophic factor (Bdnf) has a protective effect against cardiac remodeling after myocardial infarction (MI). We generated conditional Bdnf knockout (CKO) mice, in which expression of Bdnf was systemically reduced, by using the inducible Cre-loxP system. Two weeks after MI was induced surgically in these mice, systolic function was significantly impaired and cardiac size was markedly increased in CKO mice compared with controls. Cardiomyocyte death was increased in these mice, along with decreased expression of survival molecules. Deletion of the Bdnf receptor (TrkB) from the heart also led to exacerbation of cardiac dysfunction after MI. The plasma levels of Bdnf were markedly increased after MI and this increase was associated with up-regulation of Bdnf expression in the brain, but not in the heart. Ablation of afferent nerves from the heart or genetic disruption of neuronal Bdnf expression inhibited the increase of plasma Bdnf after MI and led to exacerbation of cardiac dysfunction. Peripheral administration of Bdnf significantly restored the cardiac phenotype of neuronal Bdnf-deficient mice, suggesting that Bdnf expression is up-regulated by neural signals from the heart after MI and then protects the myocardium against ischemic injury. These findings also suggest that activation of neuronal Bdnf may become a therapeutic strategy for cardiac disease.
Abstract 8309: Adiponectin Deficiency Exacerbates Endothelial Dysfunction By Increasing Inflammation In High-fat Diet Induced Obese Mice
Authors: Lee Sewon , Zhang Cuihua
Published: April 2024

Adiponectin (APN) is a 30-kDa protein exclusively secreted by adipose tissue. Clinical data show obese and type 2 diabetic patients have decreased APN levels in the circulation. Previously, we showed that APN is deficient in the serum and in aorta protein expression in type 2 diabetic mice (
db/db
, Lepr

db

), which suggests APN may play an important role in vascular dysfunction and the development of type 2 diabetes. Accordingly, we hypothesized that APN deficiency will impair endothelial function in aortas in high fat diet (HF) induced obese mice. To test this hypothesis, we fed HF diet (60% calories from fat) in wild type (WT) and APN knock-out (APNKO) mice for 18 weeks and studied vascular function of aorta ex vivo. Endothelium-dependent vasodilator acetylcholine (Ach)-induced vasodilation was blunted in APNKO+HF compare to WT+HF, but sodium nitroprusside (SNP)-induced endothelium-independent vasodilation was identical. Previously, we showed that adenoviral delivery of APN (Ad-APN) improved endothelial function in diabetic mice compare to control virus treatment (Ad-βgal). Real-time PCR results showed that mRNA gene expression of TNFα, IL-6 and intercellular adhesion molecule-1(ICAM-1) was higher in
db/db
aortas compared to control mice, suggesting that inflammation and recruitment of immune cells may contribute to endothelial dysfunction. However, Ad-APN treatment decreased TNFα, IL-6 and ICAM-1 suggesting APN may suppress inflammation and adhesion molecules. This suggests that APN may contribute to an increase in nitric oxide bioavailability by decreasing inflammation and recruitment of immune cells in the aorta. APN appears to play an important role in the prevention of vascular dysfunction in the aortas by preventing inflammation and immune response the animal and infers a similar role may occur is in obese/diabetic patients.
Abstract 8377: Cathepsin K Deficiency Suppresses the Development of Experimental Intimal Hyperplasia in Response to Injury
Authors: Hu Lina , Cheng Xian Wu , Shi Guo-Ping , Song Haizhen , Unno Kazumasa , Jiang Haiying , Okumura Kenji , Murohara Toyoaki , Kuzuya Masafumi
Published: April 2024

Background.
Cathepsin K (Cat K), a potent elastinolytic and collagenolytic cysteine protease, is considered likely to participate in the development and destabilization of atherosclerotic plaques. In order to define the role of Cat K in arterial remodeling, we evaluated the influence of the targeted deletion of the Cat K gene (Cat K−/−) on vascular remodeling after flow cessation in murine carotid arteries.

Methods and Results.
Male Cat K+/+ and Cat K−/− mice receiving normal chow underwent ligation or ligation/polyethylene cuff-placement injuries to the left common carotid artery just proximal to its bifurcation, and were then processed for morphological and biochemical studies at specific time points. There were no changes in the expression of Cat K mRNA or protein in the basal or injured arteries. Histological analysis revealed that there was significantly less intimal hyperplasia in Cat K−/− mice than in control mice at 28 days after surgery. At Day 4 after surgery, the amounts of mRNA for MMP-9, MMP-14, toll-like receptor-4 (TLR-4), chemokine ligand 12 (CCL12) and the contents of macrophages were significantly lower in both the single- and double-injured arteries of Cat K−/− mice than in corresponding model of Cat K+/+ mice. At Day 7, gelatin zymography showed that MMP-9 activity increased in the injured arteries of both types in Cat K+/+ mice. An ex vivo migration assay showed that Cat K deficiency impaired smooth muscle cell migration from aortic explants. Although there were no differences in SMC adhesion or apoptosis in mice of either genotype, Cat K deficiency impaired chemoattractant-directed SMC and macrophage invasions. Synthetic cathepsin inhibitor E64d inhibited ligation-induced neointima formation in Cat K+/+ mice but a deficiency of endogenous inhibitor cystatin C deteriorated the neointima in apoliporotein E deficiency mice. ELISA demonstrated that Cat K−/− mice had lower levels of plasma stromal-derived factor-1 and interleukin-1β.

Conclusions.
This study demonstrates an essential role of Cat K in atherosclerotic lesion formation in response to injury, possibly via the reduction of inflammation and SMC formation, suggesting a novel therapeutic strategy for the control of atherosclerosis by regulating Cat K activity.
Abstract 8396: A Novel Lamin Interactor (MLIP) is Critical for Cardiac Development and its Potential Role in DCM
Authors: Burgon Patrick G , Lockwood Julia , Wells Glenn , Ahmady Elmira , Blais Alexandre , Stewart Alexandre F
Published: April 2024

A-type lamins have been implicated in the maintenance of cellular commitment and differentiation. Mutations in the LMNA gene are associated with cardiac conduction disease and dilated cardiomyopathy (DCM) in humans. The molecular mechanisms that relate mutations in LMNA with different human diseases are poorly understood and its interactions become of prominence. Using protein:protein interaction assays against Lamin A/C we discovered a novel muscle enriched lamin interacting protein (MLIP) from human heart. MLIP (C6orf142 & 2310046A06rik) is a unique single copy gene that is an innovation of amniotes (reptiles, birds and mammals). The MLIP gene encodes alternatively spliced protein variants (23 to 57kDa) that possess several novel structural motifs not found in other proteins. Like Lamin A/C, MLIP is ubiquitously expressed with tissue specific isoforms found most abundantly in heart, skeletal and smooth muscle. MLIP interacts directly and co-localizes with Lamin A and C in the nuclear envelope. Down-regulation of Lamin A/C expression by shRNA results in the up-regulation and mis-localization of MLIP. In the developing mouse heart MLIP is differentially expressed from E9 to adulthood. Conditional MLIP homozygous null mice die
in utero
, while hemizygous MLIP null mice develop DCM by 8 weeks of age (Table 1). Ongoing longitudinal studies combining echo with microSPECT-CT will further define the DCM phenotype. In addition to interacting with Lamin, MLIP also binds to genomic DNA within close proximity of genes encoding transcription factors (including Foxc1/c2, Foxa2, Gata4, Mef2c, Pitx2, Rxra and Tbx2) as determined by chromatin immmunoprecipitation and gel mobility shift assays. In conclusion, MLIP is a newly discovered lamin interacting protein that may serve as a tanscriptional regulator that impact genes involved in cardiac development and provides a new direction to study.
Abstract 8397: Action Registry Guideline Adherences Differ Between ST-Elevation and Non-ST Elevation Myocardial Infarction Patients
Authors: Weiss Jeffrey , Fleming Jennifer , Levy Nancy , Gortych Patricia , Casey Donald , Cohen Barry
Published: April 2024

Background:
Based on the ACC/AHA 2008 Performance Measures for Adults with Acute Myocardial Infarction, the ACTION Registry-GWTG (Get with the Guidelines) Outcomes Report examines a given site's performance on acute and discharge guideline metrics used in treating heart attacks. We reviewed our data from the Outcomes Report to compare guideline adherences between ST Elevation myocardial infarction (STEMI) and non-ST Elevation myocardial infarction (NSTEMI) patients.

Methods:
There were 76,493 STEMI and 117,440 NSTEMI ACTION Registry participants between the 4
th
quarter of 2007 through the 3
rd
quarter of 2010 (i.e., 2008-2010). Acute guideline metrics included aspirin (ASA) on arrival and evaluation of left ventricular systolic function (LVSF). Discharge guideline metrics included aspirin (ASA), beta-blocker (BB), angiotensin-converting enzyme inhibitor (ACE) or angiotensin-receptor blocker (ARB) if ejection fraction <40%, statin, adult smoking cessation advice (ASCA), and cardiac rehabilitation referral (CRR). We analyzed adherences to guidelines in STEMI and NSTEMI patients over three years - nationally (NAT), at our center (MMH), and at the nation's top 10% centers (TOP). Chi square and Fischer's exact test were used to compare the two groups.

Results:

Conclusions:
We found statistically significant discrepancies in metric guideline adherences between STEMI and NSTEMI patients over three years. Adherences were higher in the STEMI compared with NSTEMI groups in nearly all metrics measured. This may reflect the presence of timely and comprehensive “Code STEMI” guidelines in place. Perhaps “Code NSTEMI” guidelines or diagnosis-based (eg, NSTEMI-based) medication reconciliation forms could further improve NSTEMI guideline adherences.
Abstract 8401: Switching of Hif-α Isoforms is Critical in the Resolution of Inflammation
Authors: Takeda Norihiko , Abe Hajime , Senba Hiroaki , Johnson Randall , Manabe Ichiro , Nagai Ryozo
Published: April 2024

Hypoxia is a pathological condition in which the tissue is deprived of adequate oxygen supply. It occurs in myocardial ischemia, cardiac hypertrophy and atherosclerosis, and accelerates the inflammatory processes in cardiac tissues. Each cell exerts its own responses to hypoxia, and most of them are mediated through a pair of transcription factors, hypoxia inducible factors- 1α (HIF- 1α) and HIF- 2α. Macrophages, key mediators of inflammation, are activated and accumulate in hypoxic area. Macrophages are currently classified into M1 (pro-inflammatory) and M2 (anti-inflammatory). However, the molecular mechanisms of M1 and M2-specific activations remain elusive. Here we revealed M1 and M2 specific functions of HIF-1α and HIF-2α, which play essential roles in the initiation and resolution of inflammation. HIF-1α was acutely induced in M1 activation, whereas HIF-2α was exclusively expressed in M2, but not in M1 macrophages. Th1 cytokines such as IFNγ induced HIF-1α, but strongly suppressed HIF-2α. In contrast, Th2 cytokine, including IL-4 increased HIF-2α level. We identified inducible NO synthase (iNOS, a M1 marker gene) as a HIF-1α target, and arginase1 (arg1, a M2 marker gene) as a HIF-2α target gene, respectively. These two enzymes compete for the common substrate, l-arginine, and inhibit each other's function. HIF-1α elicits NO production in M1, however, HIF-2α suppresses NO production through arginase1 induction in M2 macrophages. The balance between HIF-1α and HIF-2α determine that of iNOS/arg1, resulting in the regulation of NO production. To verify the roles of HIF-α in vivo, we generated macrophage specific HIF-1α knockout mice (mHIF-1α KO) and HIF-2α knockout (mHIF-2α KO). Intraperitoneal injection of lipopolysaccaride (LPS) induces plasma NO rises acutely (6hr), and it normalizes within 24 hours. In mHIF-1α KO mice, peak NO rise was attenuated. In contrast, mHIF-2α KO mice exhibited delayed recovery of NO level after LPS injection. Those results implied the essential role of HIF-1α in initiating NO production, whereas HIF-2α is critically important in the resolution. The switching of HIF-α isoforms could account for the functional diversity between M1 and M2, and contribute to the initiation and resolution of the inflammation.
Abstract 8428: Percutaneous Intrapericardial Echocardiographic Imaging with CMUT Based Imaging Catheters: First In Vivo Results
Authors: Stephens Douglas N , Truong Uyen T , Seo Chi H , Nikoozadeh Amin , Oralkan Omer , Khuri-Yakub Butrus (Pierre) T , de la Rama Alan , Dentinger Aaron , Lin Feng , Thomenius Kai , Shivkumar Kalyanam , Mahajan Aman , O'Donnell Matthew , Sahn David J
Published: April 2024

Background:
The standard approach for the catheter ablation of arrhythmias and the accompanying guidance of intracardiac echocardiography (ICE) is performed from the endocardial aspect of the heart. This approach may now also include percutaneous epicardial mapping which has been developed and utilized in several electrophysiology (EP) laboratories. Previous research using percutaneous pericardial procedures has been safely and effectively applied to a range of supraventricular arrhythmia substrates.

Methods:
Our family of ICE devices now includes a new 9F forward-looking catheter which is constructed with a silicon based capacitive micromachined ultrasonic transducer (CMUT) technology. Several CMUT ML catheters have been tested in 3 porcine experiments. The percutaneous epicardial approach was tested with successful imaging of heart chambers from the oblique sinus of the pericardial space.

Results:
This micro-linear (ML) catheter provides high-resolution, real-time, 2D ultrasound images at 14 MHz, and is capable of both electrical mapping and electroanatomical guidance. Although the 24 element array aperture is small (1.6 mm), the imaging depth of penetration is considerable (> 3 cm). A thin metalized cap can be placed over the array for performing radiofrequency ablation without distorting imaging.

Conclusions:
This silicon based technology has the unique prospect of enhancing both miniaturization and multiple modalities of operation.
Abstract 8436: Depression and Mortality in Older Adults Undergoing Percutaneous Coronary Intervention
Authors: Gharacholou S. M , Roger Veronique L , Lennon Ryan J , Frye Mark A , Rihal Charanjit S , Singh Mandeep
Published: April 2024

Background:
Depression is prevalent in adults with cardiovascular disease; however, the association between depression and death in older adults treated with percutaneous coronary intervention (PCI) is not known.

Method:
We prospectively studied 596 patients 65 years of age or older undergoing PCI at Mayo Clinic (Rochester, MN and Franciscan Skemp Hospital in La Crosse, WI) from October 2005 through September 2008. Depression was assessed using the validated and reliable Center for Epidemiological Studies Depression (CES-D) scale. Patients were categorized into groups by depression symptom severity: none/mild (CES-D <16; referent), moderate (CES-D 16-21), or moderate/severe (CES-D>21). Patients were followed annually for death.

Results:
Mean age of patients was 75.0±6.4 years; 31% were women, 98.0% were white. There were 461 patients (77.3%) that were not depressed and 135 patients (22.7%) that were depressed; 67 patients (11.3%) had moderate depressive scores (CES-D 16-21) and 68 patients (11.4%) had moderate/severe scores (CES-D >21). Groups were similar with respect to baseline characteristics. After a median follow-up of 36 months, there were 74 deaths, and patients with moderate/severe depressive symptom scores had a higher cumulative incidence of mortality (p = 0.036 by log-rank) (Figure). In multivariable analysis, CES-D score >21 was independently predictive of all-cause mortality (HR 1.90; 95% CI 1.02-3.53; p = 0.043), along with other covariates, including age (HR 1.88; 95% CI 1.31-2.68), comorbidity (Charlson Index) (HR 1.08; 95% CI 1.02-1.15), and diabetes mellitus (HR 2.04; 95% CI 1.26-3.30).

Conclusion:
Over one-fifth of older adults undergoing PCI met criteria for depression and those with high depressive scores reflecting greater self-perceived depressive symptoms had worse survival. Recognition of depressive symptoms in older adults treated with PCI identifies a cohort at higher risk of adverse outcomes.